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Modi R, Storozuk T, Setia N. Genetic Mutations and Small Bowel Ulcerating Disease: Role in Diagnosis? Curr Gastroenterol Rep 2025; 27:33. [PMID: 40399663 PMCID: PMC12095398 DOI: 10.1007/s11894-025-00978-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/02/2025] [Indexed: 05/23/2025]
Abstract
PURPOSE OF REVIEW This review examines the role of genetic variations in the pathogenesis of small bowel (SB) ulcers associated with Crohn's disease (CD), NSAID enteropathy, and Cryptogenic Multifocal Ulcerous Stenosing Enteritis (CMUSE)/Chronic Non-Specific Ulcers of the Small Intestine (CNSU), aiming to address current diagnostic challenges. RECENT FINDINGS Advances in molecular genetics have revealed significant genetic contributors to SB ulceration. In CD, the NOD2 gene on chromosome 16 and several additional risk variants identified through genome-wide association studies (GWAS)-with key insights from the International Inflammatory Bowel Disease Genetics Consortium-have enhanced our understanding of the pathobiology of the disease. In NSAID enteropathy, polymorphisms in CYP enzymes have been associated with altered drug metabolism and gastrointestinal complications. However, the genetic mechanisms underlying deep ulcers in NSAID enteropathy, as well as CMUSE/CNSU, remain poorly understood. Genetic insights are crucial for understanding SB ulcerative diseases. Future research should focus on identifying specific genetic determinants to improve diagnostic accuracy and therapeutic strategies.
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Affiliation(s)
- Rangesh Modi
- Department of Internal Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, 60637, USA
| | - Tanner Storozuk
- Department of Pathology, University of Chicago, 5841 S Maryland Ave, E607, Chicago, IL, 60637, USA
| | - Namrata Setia
- Department of Pathology, University of Chicago, 5841 S Maryland Ave, E607, Chicago, IL, 60637, USA.
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Jing B, Zhao JJ, Chen ZN, Si WM, Chang SQ, Zheng YC, Zhuang ZF, Zhao GP, Zhang D. ( +)-Catechin Alleviates CCI-Induced Neuropathic Pain by Modulating Microglia M1 and M2 Polarization via the TLR4/MyD88/NF-κB Signaling Pathway. J Neuroimmune Pharmacol 2025; 20:33. [PMID: 40195186 DOI: 10.1007/s11481-025-10202-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 03/22/2025] [Indexed: 04/09/2025]
Abstract
The aim of this research endeavor was to explore the therapeutic potential of ( +)-catechin in mitigating neuropathic pain. A total of thirty-two Sprague‒Dawley rats were randomly allocated into four groups: the sham group, the chronic constriction injury (CCI) group, the CCI + ibuprofen group, and the CCI + ( +)-catechin group. The results of the in vivo experiment show that ( +)-catechin has the potential to improve mechanical hyperalgesia induced by CCI and reduce the infiltration of inflammatory cells in the injured sciatic nerve. CCI induces the upregulation of nNOS, iNOS, IL-1β, and COX-2 within the rat sciatic nerve and leads to an elevation in the levels of IL-1β, PGE2, and TNF-α in the serum of rats, while simultaneously diminishing the secretion of IL-10. Moreover, immunofluorescence analysis reveals that CCI enhances the expression of CD32 (an M1 polarization marker) in the rat spinal cord, while diminishing the expression of CD206 (an M2 polarization marker). However, the administration of ( +)-catechin effectively counteracts these effects. Western blot analysis further demonstrates that ( +)-catechin significantly reduces the protein expression of IBA-1, IL-1β, MyD88, p-NF-κB, p-JNK, p-ERK, p-p38MAPK, COX-2, and TLR4 within the spinal cord. The findings of the BV2 cell experiment revealed the attenuating effects of ( +)-catechin on M1 polarization markers (such as IL-1β, TNF-α, iNOS, and CD32), while concurrently boosting the levels of M2 polarization markers (including CD206, IL-10, and Arg-1). Notably, administration of LPS significantly heightened the accumulation of IBA-1, IL-1β, MyD88, p-NF-κB, p-JNK, p-ERK, p-p38MAPK, TLR4, COX-2, and iNOS, while concurrently suppressing Arg-1 expression. However, the administration of ( +)-catechin effectively reversed these alterations. Overall, these findings suggest that ( +)-catechin alleviates neuropathic pain by modulating the M1 and M2 phenotypes of microglia through the TLR4/MyD88/NF-κB pathway.
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Affiliation(s)
- Bei Jing
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Jia-Ji Zhao
- Chemistry & Chemical Engineering, Guangdong Pharmaceutical University, Guangzhou, China
| | - Zhen-Ni Chen
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Wai-Mei Si
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Shi-Quan Chang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Ya-Chun Zheng
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Zi-Feng Zhuang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Guo-Ping Zhao
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
| | - Di Zhang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
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Chaudhary K, Singh L, Rai PD. Innovative nanocarriers in arthritis therapy: the role of herbal cubosomes. Inflammopharmacology 2025; 33:1833-1860. [PMID: 40122993 DOI: 10.1007/s10787-025-01714-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 02/21/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND Both osteoarthritis (OA) and rheumatoid arthritis (RA) are long-lasting inflammatory disorders that impact the joints. While conventional treatments like NSAIDs and DMARDs are effective, they often have adverse side effects. OBJECTIVE The aim of this review is to explore the possibilities of using herbal treatments in treating the symptoms of arthritis, their stability and bioavailability. Traditional therapies often lead to adverse side effects, prompting a search for safer alternatives, particularly in herbal medicines. This review explores the innovative use of herbal cubosomes as advanced nanocarriers for arthritis therapy. Cubosomes, a type of self-assembled lipid nanoparticle, exhibit unique structural characteristics that enhance the delivery and bioavailability of encapsulated herbal compounds. METHOD Access was gained to PubMed, Scopus database, Google Scholar and Web of Science for the literature search. The results were later screened according to the titles, abstracts, and availability of full texts. RESULTS The expository evaluation of the literature revealed that Key herbal components, such as Withania somnifera (Ashwagandha), Curcuma longa (Turmeric) and Boswellia serrata (Frankincense) are emphasized for their anti-inflammatory characteristics and possible advantages in managing arthritis. The herbal cubosomes enhance drug absorption, retention, and release kinetics in arthritic conditions. The difficulties in delivering and maintaining herbal substances are also discussed, with a focus on how nanotechnology can help get over these obstacles. CONCLUSION Overall, the integration of herbal cubosomes in arthritis therapy presents a promising approach that could result in safer and more efficient treatment alternatives, warranting further research and clinical exploration.
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Affiliation(s)
- Kajal Chaudhary
- Research Scholar, Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, 250005, India.
| | - Lubhan Singh
- Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, 250005, India
| | - Pallavi Dinanath Rai
- Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, 201310, India
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Xu L, Xiao Y, Yu K, Pan H, Xu J, Guan Y, Wang M, Xu X, Wang H. Machine Learning-Assisted Chemical Tongues Based on Dual-channel Inclusion Complexes for Rapid Identification of Nonsteroidal Anti-inflammatory Drugs in Food. ACS Sens 2025; 10:1833-1843. [PMID: 39992799 DOI: 10.1021/acssensors.4c02806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
The improper application of nonsteroidal anti-inflammatory drugs (NSAIDs) presents significant health hazards via vector food contamination. A critical limitation of these traditional existing approaches is their inability to concurrently discern and distinguish among diverse NSAIDs, presenting a notable gap in the analytical capabilities within this domain. Herein, a creative dual-channel fluorescence sensor array was developed for the rapid discrimination and determination of NSAIDs, utilizing complexes of cucurbit[8]uril (CB[8]) with three distinct modified poly(ethylenimines) (PEIs) to address this challenge. The array successfully differentiated and identified 19 NSAIDs with 97% accuracy at a concentration of 1 mM. In addition, it also achieved analyses of individual NSAIDs across a range of concentrations, NSAID mixtures, and impurities of aspirin using statistical analysis methods. More importantly, the approach effectively detected NSAIDs in complex matrices, such as milk and urine, demonstrating its potential for real-world applications.
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Affiliation(s)
- Lian Xu
- School of Life Sciences, Xiamen University, Xiamen 361102, PR China
| | - Yan Xiao
- College of Medical Engineering, Jining Medical University, Jining 272067, PR China
| | - Kun Yu
- Lianyungang Clinical College, Jiangsu University & The Second People's Hospital of Lianyungang, Lianyungang 222006, PR China
| | - Hongshuo Pan
- College of Clinical Medicine, Jining Medical University, Jining 272067, PR China
| | - Jiayi Xu
- College of Clinical Medicine, Jining Medical University, Jining 272067, PR China
| | - Yiyun Guan
- College of Clinical Medicine, Jining Medical University, Jining 272067, PR China
| | - Mengke Wang
- College of Medical Engineering, Jining Medical University, Jining 272067, PR China
| | - Xiangyu Xu
- College of Basic Medical, Jining Medical University, Jining 272067, PR China
| | - Hao Wang
- College of Medical Engineering, Jining Medical University, Jining 272067, PR China
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Zhou J, Zhu F, Liang H, Sun L. Network Pharmacology and Experimental Validation Reveal Sishen Pill's Efficacy in Treating NSAID-Induced Small Intestinal Ulcers. Drug Des Devel Ther 2025; 19:2035-2050. [PMID: 40124554 PMCID: PMC11930021 DOI: 10.2147/dddt.s502193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 03/01/2025] [Indexed: 03/25/2025] Open
Abstract
Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used but often cause small intestinal ulcers (SIUs), for which effective therapies are lacking. Sishen Pill (SSP), a traditional Chinese medicine, shows therapeutic promise, yet its mechanisms remain unclear. This study integrates network pharmacology, molecular docking, and experimental validation to systematically investigate SSP's protective mechanisms against NSAID-induced SIUs. Patients and Methods Active SSP ingredients were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Encyclopedia of Traditional Chinese Medicine (ETCM) databases. SIU-related targets were retrieved from GeneCards and DisGeNET. Protein-protein interaction (PPI) networks were constructed via STRING and Cytoscape, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking (AutoDock Vina, PyMOL) validated ligand-target interactions. In vivo validation employed an indomethacin-induced SIU rat model to assess SSP's effects on ulcer severity, inflammation, oxidative stress, and PI3K/AKT signaling. Results We identified 66 bioactive SSP ingredients, 222 drug targets, and 144 SIU-related targets. Molecular docking revealed high binding affinity of SSP components (quercetin, bavachinin, rutaecarpine, evodiamine) to key targets (AKT1, HSP90AA1, IL6, MAPK1, BCL2). KEGG analysis highlighted the PI3K/AKT pathway as central. In vivo, SSP reduced ulcer indices, suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and attenuated oxidative stress. SSP also downregulated PI3K and AKT1 mRNA expression, confirming pathway modulation. Conclusion This study elucidates SSP's multi-target mechanism against NSAID-induced SIUs, emphasizing its role in suppressing inflammation, oxidative stress, and PI3K/AKT signaling. These findings provide a scientific foundation for SSP's clinical application and highlight its potential as a safe, effective alternative to conventional therapies.
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MESH Headings
- Network Pharmacology
- Anti-Inflammatory Agents, Non-Steroidal/adverse effects
- Animals
- Drugs, Chinese Herbal/pharmacology
- Drugs, Chinese Herbal/chemistry
- Drugs, Chinese Herbal/administration & dosage
- Rats
- Molecular Docking Simulation
- Intestine, Small/drug effects
- Intestine, Small/pathology
- Intestine, Small/metabolism
- Ulcer/drug therapy
- Ulcer/chemically induced
- Ulcer/metabolism
- Ulcer/pathology
- Male
- Rats, Sprague-Dawley
- Humans
- Dose-Response Relationship, Drug
- Intestinal Diseases/drug therapy
- Intestinal Diseases/chemically induced
- Medicine, Chinese Traditional
- Anti-Ulcer Agents/pharmacology
- Disease Models, Animal
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Affiliation(s)
- Jiaying Zhou
- Department of Gastroenterology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, People’s Republic of China
| | - Fengting Zhu
- Department of Gastroenterology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, People’s Republic of China
| | - Huixian Liang
- Department of Gastroenterology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, People’s Republic of China
| | - Leimin Sun
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
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Wierzba K, Chmielewski M, Błeszyńska-Marunowska E, Jagiełło K, Wierucki Ł, Zdrojewski T. Regular Use of Oral Nonsteroidal Anti-inflammatory Drugs in a Population of Polish Seniors: Findings from the PolSenior2 Cross-Sectional Survey. Drugs Aging 2025; 42:245-255. [PMID: 39873974 DOI: 10.1007/s40266-025-01180-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2025] [Indexed: 01/30/2025]
Abstract
INTRODUCTION Older adults represent a growing proportion of the general population. Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a group of medicines that are both necessary, owing to their anti-inflammatory, analgesic, and cardioprotective abilities, and potentially harmful, owing to their side effects. OBJECTIVES This study provides a comprehensive analysis of NSAID usage patterns among Polish adults aged 60 years and older. It focused on the regular use (≥ three times per week) of two types of NSAIDs: acetylsalicylic acid (ASA) and non-ASA NSAIDs, examining consumption on the basis of age, sex, educational level, and place of residence. METHODS Data were collected from the PolSenior2 study, a national cross-sectional survey of 5987 Polish individuals aged 60-106 years, conducted from 2018 to 2019. RESULTS The study found that 30.7% [95% confidence interval (CI) 28.8-32.7)]of Polish seniors regularly used NSAIDs, with 26.2% (95% CI 24.5-28.0) regularly using ASA, 6.3% (95% CI 5.3-7.2) regularly using non-ASA NSAIDs, and 1.9% (95% CI 1.4-2.3) reporting regular use of both. An age-related increase in regular NSAID use, including ASA, was observed. Women were more likely than men to use non-ASA NSAIDs regularly, whereas men in the 70-79 age group were more likely to use ASA. A lower level of education was associated with more frequent NSAID use. CONCLUSIONS The findings have implications for healthcare practitioners and policymakers, emphasizing the need for careful management of NSAID use. The study contributes to a more nuanced understanding of NSAID usage and underscores the necessity for tailored healthcare strategies to ensure safe and effective medication use among older adults.
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Affiliation(s)
- Karol Wierzba
- Department of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine Medical, University of Gdansk, Smoluchowskiego 17, 80-214, Gdańsk, Poland.
| | - Michał Chmielewski
- Department of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine Medical, University of Gdansk, Smoluchowskiego 17, 80-214, Gdańsk, Poland
| | | | - Kacper Jagiełło
- Department of Preventive Medicine and Education, Medical University of Gdansk, Gdańsk, Poland
| | - Łukasz Wierucki
- Department of Preventive Medicine and Education, Medical University of Gdansk, Gdańsk, Poland
| | - Tomasz Zdrojewski
- Department of Preventive Medicine and Education, Medical University of Gdansk, Gdańsk, Poland
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Shirakawa M, Yokoe S, Nakagawa T, Moriwaki K, Takeuchi T, Asahi M. Rapamycin and Starvation Mitigate Indomethacin-Induced Intestinal Damage through Preservation of Lysosomal Vacuolar ATPase Integrity. J Pharmacol Exp Ther 2024; 390:108-115. [PMID: 38834354 DOI: 10.1124/jpet.123.001981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 03/07/2024] [Accepted: 04/19/2024] [Indexed: 06/06/2024] Open
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, antipyretic, and analgesic properties and are among the most commonly used drugs. Although the cause of NSAID-induced gastric ulcers is well understood, the mechanism behind small intestinal ulcers remains elusive. In this study, we examined the mechanism through which indomethacin (IM), a prominent NSAID, induces small intestinal ulcers, both in vitro and in vivo. In IEC6 cells, a small intestinal epithelial cell line, IM treatment elevated levels of LC3-II and p62. These expression levels remained unaltered after treatment with chloroquine or bafilomycin, which are vacuolar ATPase (V-ATPase) inhibitors. IM treatment reduced the activity of cathepsin B, a lysosomal protein hydrolytic enzyme, and increased the lysosomal pH. There was a notable increase in subcellular colocalization of LC3 with Lamp2, a lysosome marker, post IM treatment. The increased lysosomal pH and decreased cathepsin B activity were reversed by pretreatment with rapamycin (Rapa) or glucose starvation, both of which stabilize V-ATPase assembly. To validate the in vitro findings in vivo, we established an IM-induced small intestine ulcer mouse model. In this model, we observed multiple ulcerations and heightened inflammation following IM administration. However, pretreatment with Rapa or fasting, which stabilize V-ATPase assembly, mitigated the IM-induced small intestinal ulcers in mice. Coimmunoprecipitation studies demonstrated that IM binds to V-ATPase in vitro and in vivo. These findings suggest that IM induces small intestinal injury through lysosomal dysfunction, likely due to the disassembly of lysosomal V-ATPase caused by direct binding. Moreover, Rapa or starvation can prevent this injury by stabilizing the assembly. SIGNIFICANCE STATEMENT: This study elucidates the largely unknown mechanisms behind small intestinal ulceration induced by indomethacin and reveals the involvement of lysosomal dysfunction via vacuolar ATPase disassembly. The significance lies in identifying potential preventative interventions, such as rapamycin treatment or glucose starvation, offering pivotal insights that extend beyond nonsteroidal anti-inflammatory drugs-induced ulcers to broader gastrointestinal pathologies and treatments, thereby providing a foundation for novel therapeutic strategies aimed at a wide array of gastrointestinal disorders.
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Affiliation(s)
- Makoto Shirakawa
- Department of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (M.S., S.Y., K.M., M.A.); Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan (T.N.); and The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (T.T.)
| | - Shunichi Yokoe
- Department of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (M.S., S.Y., K.M., M.A.); Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan (T.N.); and The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (T.T.)
| | - Takatoshi Nakagawa
- Department of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (M.S., S.Y., K.M., M.A.); Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan (T.N.); and The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (T.T.)
| | - Kazumasa Moriwaki
- Department of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (M.S., S.Y., K.M., M.A.); Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan (T.N.); and The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (T.T.)
| | - Toshihisa Takeuchi
- Department of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (M.S., S.Y., K.M., M.A.); Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan (T.N.); and The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (T.T.)
| | - Michio Asahi
- Department of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (M.S., S.Y., K.M., M.A.); Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan (T.N.); and The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan (T.T.)
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Won H, Kim E, Chae J, Lee H, Cho J, Jang I, Chung J, Kim M, Lee S. Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males. Clin Transl Sci 2024; 17:e13798. [PMID: 38700290 PMCID: PMC11067709 DOI: 10.1111/cts.13798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 03/01/2024] [Accepted: 03/19/2024] [Indexed: 05/05/2024] Open
Abstract
Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration-time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.
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Affiliation(s)
- Heejae Won
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
- Department of Biomedical SciencesSeoul National University College of MedicineSeoulKorea
| | - Eunwoo Kim
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Jihye Chae
- Daewoong Pharmaceutical Co., Ltd.SeoulKorea
| | | | - Joo‐Youn Cho
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
- Department of Biomedical SciencesSeoul National University College of MedicineSeoulKorea
| | - In‐Jin Jang
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Jae‐Yong Chung
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and Bundang HospitalSeongnamKorea
| | - Min‐Gul Kim
- Department of Pharmacology, School of MedicineJeonbuk National UniversityJeonjuKorea
| | - SeungHwan Lee
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
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9
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Jalal A, Ahmad S, Shah AT, Hussain T, Nawaz HA, Imran S. Preparation of celecoxib loaded bioactive glass chitosan composite hydrogels: a simple approach for therapeutic delivery of NSAIDs. Biomed Mater 2024; 19:035031. [PMID: 38518368 DOI: 10.1088/1748-605x/ad3706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 03/22/2024] [Indexed: 03/24/2024]
Abstract
Arthritis causes inflammatory damage to joints and connective tissues. In the treatment of arthritis, precise and controlled drug delivery to the target site is among the frontline research approaches. In the present research work, celecoxib drug and bioactive glass incorporated chitosan hydrogels were fabricated by the freeze gelation method. Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis/differential scanning calorimetry techniques were used to characterize the hydrogels. Different kinetic models were applied to study the drug release kinetics. The celecoxib release was mainly controlled by a Fickian diffusion process followed by the Higuchi model. Maximum 86.2% drug entrapment was observed in 20 mg drug-loaded hydrogel and its swelling ratio was 115.5% in 28 d. Good hydrophilicity, good drug entrapment efficiency, and moderate drug release patterns of hydrogels can make them suitable for sustained drug release. The cytocompatibility of hydrogels was established by performing an MTT assay on the BHK-21 fibroblast cell line. The promising results have proved that hydrogels can be considered potential material for the slow release of anti-inflammatory drug at the target site in arthritis.
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Affiliation(s)
- Azra Jalal
- Department of Chemistry, Lahore College for Women University, Lahore, Pakistan
| | - Sana Ahmad
- Department of Chemistry, Lahore College for Women University, Lahore, Pakistan
| | - Asma Tufail Shah
- Interdisciplinary Research Centre in Biomedical Materials, COMSATS, Lahore, Pakistan
| | - Tousif Hussain
- Centre for Advanced Studies in Physics, GC University, Lahore, Pakistan
| | - Hafiz Awais Nawaz
- Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Saleha Imran
- Department of Chemistry, Lahore College for Women University, Lahore, Pakistan
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Ozer T, Henry CS. Recent Trends in Nanomaterial Based Electrochemical Sensors for Drug Detection: Considering Green Assessment. Curr Top Med Chem 2024; 24:952-972. [PMID: 38415434 DOI: 10.2174/0115680266286981240207053402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 01/02/2024] [Accepted: 01/12/2024] [Indexed: 02/29/2024]
Abstract
An individual's therapeutic drug exposure level is directly linked to corresponding clinical effects. Rapid, sensitive, inexpensive, portable and reliable devices are needed for diagnosis related to drug exposure, treatment, and prognosis of diseases. Electrochemical sensors are useful for drug monitoring due to their high sensitivity and fast response time. Also, they can be combined with portable signal read-out devices for point-of-care applications. In recent years, nanomaterials such as carbon-based, carbon-metal nanocomposites, noble nanomaterials have been widely used to modify electrode surfaces due to their outstanding features including catalytic abilities, conductivity, chemical stability, biocompatibility for development of electrochemical sensors. This review paper presents the most recent advances about nanomaterials-based electrochemical sensors including the use of green assessment approach for detection of drugs including anticancer, antiviral, anti-inflammatory, and antibiotics covering the period from 2019 to 2023. The sensor characteristics such as analyte interactions, fabrication, sensitivity, and selectivity are also discussed. In addition, the current challenges and potential future directions of the field are highlighted.
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Affiliation(s)
- Tugba Ozer
- Department of Bioengineering, Faculty of Chemical-Metallurgical Engineering, Yildiz Technical University, 34220, Istanbul, Türkiye
- Health Biotechnology Joint Research and Application Center of Excellence, 34220, Esenler, Istanbul, Türkiye
| | - Charles S Henry
- Department of Chemistry, Colorado State University, Fort Collins, CO80523, United States
- School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, 80523, United States
- Metallurgy and Materials Science Research Institute, Chulalongkorn University, Bangkok, Thailand
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11
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Carvajal-Gutiérrez W, Cisneros-Cisneros MA, Calixto OJ, Meneses-Toro MA, Rueda AJP, Vega-Báez MA, Álvarez-Vargas DA, Uscátegui-Ruiz AC, Romero-Sanchez C, Bello-Gualtero JM. Low Frequency of Upper Gastrointestinal Bleeding Despite Non-Steroidal Anti-Inflammatory Drugs and Corticosteroids in Patients with Rheumatoid Arthritis. Curr Rheumatol Rev 2024; 20:555-562. [PMID: 38362696 DOI: 10.2174/0115733971290285240207080745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/19/2024] [Accepted: 01/25/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB). OBJECTIVE This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB. METHODS A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression. RESULTS Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (AOR) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an AOR of 6.17 (95% CI 1.79- 21.24). CONCLUSION This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.
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Affiliation(s)
| | | | - Omar-Javier Calixto
- Rheumatology and Immunology Department, Hospital Militar Central, Bogotá, Colombia
- Clinical Immunology Group-Hospital Militar, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia
- Cellular and Molecular Immunology Group / INMUBO, Universidad El Bosque, Bogotá, Colombia
| | - Maria-Alejandra Meneses-Toro
- Rheumatology and Immunology Department, Hospital Militar Central, Bogotá, Colombia
- Clinical Immunology Group-Hospital Militar, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia
| | | | | | | | | | - Consuelo Romero-Sanchez
- Clinical Immunology Group-Hospital Militar, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia
- Cellular and Molecular Immunology Group / INMUBO, Universidad El Bosque, Bogotá, Colombia
| | - Juan-Manuel Bello-Gualtero
- Rheumatology and Immunology Department, Hospital Militar Central, Bogotá, Colombia
- Clinical Immunology Group-Hospital Militar, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia
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12
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Geczy QE, Thirumaran AJ, Carroll PR, McLachlan AJ, Hunter DJ. What is the most effective and safest Non-steroidal anti-inflammatory drug for treating osteoarthritis in patients with comorbidities? Expert Opin Drug Metab Toxicol 2023; 19:681-695. [PMID: 37817419 DOI: 10.1080/17425255.2023.2267424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 10/03/2023] [Indexed: 10/12/2023]
Abstract
INTRODUCTION Understanding what the most effective and safe non-steroidal anti-inflammatory drug (NSAID) is for managing osteoarthritis (OA) is complicated. OA is prevalent worldwide and people living with OA commonly have multiple comorbidities. The efficacy and safety of NSAIDs in a patient are influenced by their intrinsic and extrinsic factors. Current guidelines recommend the lowest dose for the shortest duration, monitoring patients for risk factors and comorbidities but generally do not specify, which NSAID is most suitable for a patient with specific comorbidities. AREAS COVERED This paper looks at the mechanism of action of all NSAIDs and reviews the current literature concerning their safety in patients with and without comorbidities. Relevant publications were identified by searching PubMed and Cochrane Library using key terms. The search was conducted from inception to 18 July 2023 and included results published before 18 July 2023. The search results and their references were then manually reviewed. EXPERT OPINION In the paper, we determine whether the current practice of 'lowest dose for shortest duration' is in fact the best approach for prescribing NSAIDs and identify which NSAIDs are most suitable given a patient's risk factors and comorbidities. Our aim is to help guide health professionals in recommending the most suitable NSAID for each patient.
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Affiliation(s)
- Quentin E Geczy
- Sydney Medical Program, The University of Sydney, Sydney, NSW, Australia
| | | | - Peter R Carroll
- School of Medicine Sydney, University of Notre Dame, Darlinghurst, NSW, Australia
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Andrew J McLachlan
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - David J Hunter
- Sydney Musculoskeletal Health, Arabanoo Precinct, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
- Rheumatology Department, Royal North Shore Hospital, St Leonards, NSW, Australia
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13
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Bordin DS, Livzan MA, Gaus OV, Mozgovoi SI, Lanas A. Drug-Associated Gastropathy: Diagnostic Criteria. Diagnostics (Basel) 2023; 13:2220. [PMID: 37443618 PMCID: PMC10341309 DOI: 10.3390/diagnostics13132220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/30/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
Drugs are widely used to treat different diseases in modern medicine, but they are often associated with adverse events. Those located in the gastrointestinal tract are common and often mild, but they can be serious or life-threatening and determine the continuation of treatment. The stomach is often affected not only by drugs taken orally but also by those administered parenterally. Here, we review the mechanisms of damage, risk factors and specific endoscopic, histopathological and clinical features of those drugs more often involved in gastric damage, namely NSAIDs, aspirin, anticoagulants, glucocorticosteroids, anticancer drugs, oral iron preparations and proton pump inhibitors. NSAID- and aspirin-associated forms of gastric damage are widely studied and have specific features, although they are often hidden by the coexistence of Helicobacter pylori infection. However, the damaging effect of anticoagulants and corticosteroids or oral iron therapy on the gastric mucosa is controversial. At the same time, the increased use of new antineoplastic drugs, such as checkpoint inhibitors, has opened up a new area of gastrointestinal damage that will be seen more frequently in the near future. We conclude that there is a need to expand and understand drug-induced gastrointestinal damage to prevent and recognize drug-associated gastropathy in a timely manner.
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Affiliation(s)
- Dmitry S. Bordin
- A.S. Loginov Moscow Clinical Scientific Center, Department of Pancreatic, Biliary and Upper Digestive Tract Disorders, 111123 Moscow, Russia
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
- Department of Outpatient Therapy and Family Medicine, Tver State Medical University, 170100 Tver, Russia
| | - Maria A. Livzan
- Department of Faculty Therapy and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Olga V. Gaus
- Department of Faculty Therapy and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Sergei I. Mozgovoi
- Department of Pathological Anatomy, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Angel Lanas
- Digestive Diseases Service, Aragón Health Research Institute (IIS Aragón), University Clinic Hospital, University of Zaragoza, 50009 Zaragoza, Spain
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14
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Brzozowska M, Całka J. Acetylsalicylic Acid Supplementation Affects the Neurochemical Phenotyping of Porcine Duodenal Neurons. Int J Mol Sci 2023; 24:9871. [PMID: 37373019 DOI: 10.3390/ijms24129871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 06/03/2023] [Accepted: 06/04/2023] [Indexed: 06/29/2023] Open
Abstract
Aspirin (ASA) is a popular nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic properties through the inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA results in the formation of gastrointestinal side effects. Due to the fact that the enteric nervous system (ENS) is involved in the regulation of digestive functions both in physiological and pathological states, the aim of this study was to determine the influence of ASA on the neurochemical profile of enteric neurons in the porcine duodenum. Our research, conducted using the double immunofluorescence technique, proved an increase in the expression of selected enteric neurotransmitters in the duodenum as a result of ASA treatment. The mechanisms of the visualized changes are not entirely clear but are probably related to the enteric adaptation to inflammatory conditions resulting from aspirin supplementation. A detailed understanding of the role of the ENS in the development of drug-induced inflammation will contribute to the establishment of new strategies for the treatment of NSAID-induced lesions.
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Affiliation(s)
- Marta Brzozowska
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego Str. 13, 10-718 Olsztyn, Poland
| | - Jarosław Całka
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego Str. 13, 10-718 Olsztyn, Poland
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15
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Sha'aba RI, Chia MA, Gana YA, Alhassan AB, Gadzama IMK. The growth, biochemical composition, and antioxidant response of Microcystis and Chlorella are influenced by Ibuprofen. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:13118-13131. [PMID: 36123556 DOI: 10.1007/s11356-022-22837-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 08/29/2022] [Indexed: 06/15/2023]
Abstract
Non-steroidal anti-inflammatory drugs like ibuprofen (IBU) are extensively used, causing substantial amounts to end up in aquatic ecosystems. Unfortunately, little research has been done on how these medications influence the physiology of phytoplankton. This study aimed to investigate the toxicological and physiological effects of IBU on the cyanobacteria Microcystis aeruginosa LE3 and Microcystis aeruginosa EAWAG 198, and the chlorophyte Chlorella sorokiniana. Exponential growth phase cultures were exposed to IBU at 10 to 10,000 μg/L for 96 h. The medium effect concentrations revealed varied sensitivity to IBU in the order Chlorella sorokiniana > Microcystis aeruginosa LE3 > Microcystis aeruginosa EAWAG 198. The drug caused a significant difference from control in cell density and chlorophyll-a of the three strains, except for chlorophyll-a in M. aeruginosa EAWAG 198 cultures where a significant difference occurred at 100 μg/L. The cell density of M. aeruginosa LE3 cultures exposed to 10 μg/L IBU increased 24 h post-exposure. Increasing concentrations of IBU induced higher total microcystins content of the Microcystis aeruginosa. Intracellular hydrogen peroxide content, peroxidase, and glutathione S-transferase activities, and lipid peroxidation increased as a function of IBU exposure. Total lipid, carbohydrate, and protein content of Chlorella sorokiniana were stimulated following IBU exposure. We conclude that the increasing presence of IBU in aquatic ecosystems could significantly alter the population dynamics of the investigated and other phytoplankton species.
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16
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Oh DJ, Yoon H, Kim HS, Choi YJ, Shin CM, Park YS, Kim N, Lee DH, Ha YJ, Kang EH, Lee YJ, Kim N, Kim KJ, Liu F. The effect of rebamipide on non-steroidal anti-inflammatory drug-induced gastro-enteropathy: a multi-center, randomized pilot study. Korean J Intern Med 2022; 37:1153-1166. [PMID: 36375487 PMCID: PMC9666262 DOI: 10.3904/kjim.2021.216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 02/19/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND/AIMS Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly-used medications, and ailments such as arthritis or heart disease, require long-term use of these drugs, which can induce gastroenteropathy with bleeding and ulcers. This study investigated the associations between efficacy, safety, and gastrointestinal symptoms linked to rebamipide and proton pump inhibitor administration in patients requiring long-term NSAID use. METHODS This study was a multi-center, randomized, open-labeled, pilot design. RESULTS Thirty-three patients were included. Of these, 15 were included in the study group and 18 were in the control group. NSAID-induced gastric ulcers, which were the primary outcome of this study, did not occur in either the study or control group. Changes in the number of small bowel erosions and ulcers were -0.6 ± 3.06 in the study group and 1.33 ± 4.71 in the control group. The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) was three (20%) in the study group and six (40%) in the control group (p = 0.427). No serious adverse events occurred in either group. However, dyspepsia and skin rashes occurred in six patients (31.58%) in the study group and 13 (65%) in the control group (p = 0.036). CONCLUSION Although statistically significant differences were not generated, possibly as a result of the small sample size, mucosal breaks observed via capsule endoscopy revealed that rebamipide was likely to be more effective than lansoprazole in preventing small intestine damage caused by NSAIDs. Furthermore, fewer side-effects emerged with rebamipide.
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Affiliation(s)
- Dong Jun Oh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyun Soo Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - You-Jung Ha
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eun Ha Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yun Jong Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ki-Jeoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Fei Liu
- Deptartment Gastroenteroloy, Shanghai East Hospital Affiliated Tongji University, Shanghai, China
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17
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Stiller CO, Hjemdahl P. Lessons from 20 years with COX-2 inhibitors: Importance of dose-response considerations and fair play in comparative trials. J Intern Med 2022; 292:557-574. [PMID: 35585779 DOI: 10.1111/joim.13505] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzyme cyclooxygenase (COX), which forms prostaglandins involved in pain and inflammation. COX inhibitors have analgesic and anti-inflammatory effects, but also increase risks for gastrointestinal ulcers, bleeding, and renal and cardiovascular adverse events. Identification of two isoforms of COX, COX-1 and COX-2, led to the development of selective COX-2 inhibitors, which were launched as having fewer gastrointestinal side effects since gastroprotective prostaglandins produced via COX-1 are spared. The balance between COX-1 mediated prothrombotic thromboxane and COX-2 mediated antithrombotic prostacyclin is important for thrombotic risk. An increased risk of suffering myocardial infarction and death with COX-2 inhibitor treatment is well established from clinical trials and observational research. Rofecoxib (Vioxx) was withdrawn from the market for this reason, but the equally COX-2 selective etoricoxib has replaced it in Europe but not in the United States. The "traditional" NSAID diclofenac is as COX-2 selective as celecoxib and increases cardiovascular risk dose dependently. COX inhibitor dosages should be lower in osteoarthritis than in rheumatoid arthritis. Randomized trials comparing COX-2 inhibitors with NSAIDs have exaggerated their gastrointestinal benefits by using maximal NSAID doses regardless of indication, and/or hidden the cardiovascular risk by comparing with COX-2 selective diclofenac instead of low-dose ibuprofen or naproxen. Observational studies show increased cardiovascular risks within weeks of treatment with COX-2 inhibitors and high doses of NSAIDs other than naproxen, which is the safest alternative. COX inhibitors are symptomatic drugs that should be used intermittently at the lowest effective dosage, especially among individuals with an increased cardiovascular risk.
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Affiliation(s)
- Carl-Olav Stiller
- Department of Medicine Solna, Clinical Epidemiology Unit/Clinical Pharmacology, Karolinska Institutet and Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden
| | - Paul Hjemdahl
- Department of Medicine Solna, Clinical Epidemiology Unit/Clinical Pharmacology, Karolinska Institutet and Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden
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18
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Tanigawa H, Suzuki N, Suzuki T. Application of ionic liquid to enhance the nose-to-brain delivery of etodolac. Eur J Pharm Sci 2022; 178:106290. [PMID: 36058500 DOI: 10.1016/j.ejps.2022.106290] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 08/09/2022] [Accepted: 08/31/2022] [Indexed: 11/28/2022]
Abstract
The purpose of this study was to enhance the delivery of Etodolac (ETD) to the brain through intranasal administration using an ionic liquid (IL) consisting of ETD and proline ethyl ester. The IL of ETD was prepared by mixing ETD with proline ethyl ester as a counterion in a molar ratio of 1:2.The formation of the IL was confirmed by differential scanning calorimetry (DSC), infrared spectroscopy (IR) and proton nuclear magnetic resonance (1H-NMR).The solubility of ETD in simulated nasal fluids was improved by approximately 200-fold due to the formation of IL. The intranasal administration of ETD-containing IL, which is viscous, increased the nose-to-brain delivery by approximately 7-fold 30 min after an administration of the ETD solution alone. The enhancement of ETD delivery to the brain from the nose was attributed to the enhanced retention of ETD in the nasal mucosal surface due to the viscosity of IL. The induction of prostaglandin E2 in the brain inflammation that was induced by lipopolysaccharides was significantly suppressed by up to 40% in the IL-treated group compared with the drug-untreated group. Therefore, ETD-containing IL were suggested to be useful in designing intranasal formulations for the nasal delivery of ETDs to the brain.
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Affiliation(s)
- Hiroaki Tanigawa
- Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan
| | - Naoto Suzuki
- Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
| | - Toyofumi Suzuki
- Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
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19
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Azhari H, King JA, Coward S, Windsor JW, Ma C, Shah SC, Ng SC, Mak JWY, Kotze PG, Ben-Horin S, Loftus EV, Lees CW, Gearry R, Burisch J, Lakatos PL, Calvet X, Bosques Padilla FJ, Underwood FE, Kaplan GG. The Global Incidence of Peptic Ulcer Disease Is Decreasing Since the Turn of the 21st Century: A Study of the Organisation for Economic Co-Operation and Development (OECD). Am J Gastroenterol 2022; 117:1419-1427. [PMID: 35973143 DOI: 10.14309/ajg.0000000000001843] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 05/27/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = -3.9%; 95% CI: -4.4, -3.3) and morality rates (AAPC = -4.7%; 95% CI: -5.6, -3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021. DISCUSSION PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.
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Affiliation(s)
- Hassan Azhari
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - James A King
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
- Alberta SPOR Support Unit Data Platform, Alberta Health Services, Calgary, Alberta, Canada
| | - Stephanie Coward
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Joseph W Windsor
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Christopher Ma
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Shailja C Shah
- Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA
- GI Section, Veterans Affairs San Diego Healthcare System, San Diego, California, USA
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Joyce W Y Mak
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Paulo G Kotze
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Charlie W Lees
- The University of Edinburgh, Western General Hospital, Edinburgh, Scotland
| | - Richard Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Johan Burisch
- Gastrounit, medical division, Hvidovre University Hospital, Hvidovre, Denmark
| | - Peter L Lakatos
- Division of Gastroenteorlogy, McGill University, Montreal, Canada
- 1st Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Xavier Calvet
- Gastroenterology Department, Hospital Universitari Parc Taulí. Sabadell, Catalonia
- Centro de investigación e red de Enfermedades Hepaticas y Digestivas (CiberEHD)
| | - Francisco Javier Bosques Padilla
- Department of Gastroenterology, University Hospital, Autonomous University of Nuevo Leon, Hospital San José Tecnológico de Monterrey
| | - Fox E Underwood
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Gilaad G Kaplan
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
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20
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Park J, Lim YC, Hwang DS, Ha IH, Lee YS. Analysis of Healthcare Utilization for Primary Dysmenorrhea in Korea: A Retrospective, Cross-Sectional Study. Int J Womens Health 2022; 14:1015-1027. [PMID: 35959202 PMCID: PMC9359788 DOI: 10.2147/ijwh.s366386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 07/23/2022] [Indexed: 11/28/2022] Open
Abstract
Purpose This study is a retrospective, cross-sectional study aiming to present basic data on the treatment modalities and cost of care for primary dysmenorrhea (PD) by analyzing healthcare utilization and patient distributions using the 2010 to 2018 Health Insurance Review and Assessment Service (HIRA) data. Patients and Methods We used the HIRA-National Patient Sample (NPS) data to analyze medical service utilization for PD (ICD-10 code: N94.4, N94.6) in Western medicine (WM) or Korean medicine (KM) care between January 2010 and December 2018. Results There were 41,139 patients diagnosed with PD who utilized Western medicine (WM) or Korean medicine (KM) care at least once during the study period. The number of claims and patients steadily rose over the years from 7430 claims for 3989 patients in 2010 to 11,523 claims for 6226 patients in 2018. The predominant age group was 15 to 24 years. Regarding the frequency of service categories for PD in the claims, consultation was the most common and costly service category in WM (72,120 cases, 47.89%; 631,912 USD, 69.74%), while injection and analogous treatments was the most common and costly service category in KM (97,157 cases, 72.41%; 314,696 USD, 55.86%). Regarding the drug prescriptions, nonsteroidal anti-inflammatory drugs (NSAIDs) (26,617 cases, 40.47%) were the most frequently prescribed drug for PD in pharmacies and hospitals. Conclusion The result shows an annual increase in healthcare utilization for PD with the fastest rate in individuals aged 15 to 24 years. This study provides data on the current utilization of WM and KM care for PD for policymakers. Furthermore, we analyzed the frequency and cost of common treatment modalities in WM and KM, which would be useful data for clinicians and researchers.
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Affiliation(s)
- Jinhun Park
- Department of Internal Medicine, Jaseng Hospital of Korean Medicine, Seoul, Republic of Korea
| | - Yu-Cheol Lim
- Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea
| | - Deok-Sang Hwang
- Department of OB & GY in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - In-Hyuk Ha
- Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea
- Correspondence: In-Hyuk Ha; Ye-Seul Lee, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 2F, 540 Gangnam-daero, Gangnam-gu, Seoul, 06110, Republic of Korea, Tel +82-2-2222-2740, Fax +82-2-2222-2737, Email ;
| | - Ye-Seul Lee
- Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea
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Liu Z, Yuan Z, Hu W, Chen Z. Electrochemically deposition of metal-organic framework onto carbon fibers for online in-tube solid-phase microextraction of non-steroidal anti-inflammatory drugs. J Chromatogr A 2022; 1673:463129. [DOI: 10.1016/j.chroma.2022.463129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 05/04/2022] [Accepted: 05/05/2022] [Indexed: 10/18/2022]
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Otoo BA, Amoabeng IA, Darko G, Borquaye LS. Antibiotic and analgesic residues in the environment – Occurrence and ecological risk study from the Sunyani municipality, Ghana. Toxicol Rep 2022; 9:1491-1500. [DOI: 10.1016/j.toxrep.2022.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/03/2022] [Accepted: 07/06/2022] [Indexed: 10/17/2022] Open
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Canbay HS. Spectrophotometric determination of acid dissociation constants of some arylpropionic acids and arylacetic acids in acetonitrile-water binary mixtures at 25ºC. BRAZ J PHARM SCI 2022. [DOI: 10.1590/s2175-97902022e20740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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25
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Bayram D, Aydin V, Sanli A, Abanoz MN, Sibic B, Pala S, Atac O, Akici A. Comparison of paracetamol and diclofenac prescribing preferences for adults in primary care. Prim Health Care Res Dev 2021; 22:e78. [PMID: 34852871 PMCID: PMC8724224 DOI: 10.1017/s1463423621000797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 09/15/2021] [Accepted: 10/24/2021] [Indexed: 12/05/2022] Open
Abstract
INTRODUCTION The most frequently prescribed analgesic drugs in primary care centers in Turkey are diclofenac and paracetamol, respectively. In this study, we aimed to compare paracetamol-included prescriptions (PIP) and diclofenac-included prescriptions (DIP) generated for adult patients in primary care. METHODS In this cross-sectional study, PIPs (n = 280 488) and DIPs (n = 337 935) created for adults by systematic sampling among primary care physicians working in Istanbul in 2016 (n = 1431) were examined. The demographic characteristics, diagnoses, and additional drugs in PIPs and DIPs were compared. RESULTS Women constituted the majority in both groups (69.8% and 67.9%, respectively; P < 0.05), and mean age at PIP (52.6 ± 18.8 years) was lower compared to DIP (56.3 ± 16.1 years), (P < 0.05). In single-diagnosis prescriptions, 11 of the 15 most common diagnoses in PIP were respiratory tract infections (47.9%); three pain-related diagnoses formed 4.6% of all these prescriptions. In DIP, the number of pain-related diagnoses, mostly of musculoskeletal origin, was eight (28.5%); four diagnoses (7.8%) were upper respiratory tract infections. While hypertension was the third most common diagnosis in PIP (6.1%), it was ranked first in DIP (8.0%). The percentage of prescriptions with additional analgesic (14.0% versus 18.3%, P < 0.001), proton-pump inhibitor (13.8% versus 18.4%; P < 0.001), and antihypertensive (22.0% versus 24.8%, P < 0.001) was lower in PIP compared to DIP. However, the percentage of prescriptions with antibiotics (31.3% versus 14.7%, P < 0.001) was higher in PIP. CONCLUSION Paracetamol appears to be preferred mostly in upper respiratory tract infections compared to the preference of diclofenac rather in painful/inflammatory musculoskeletal conditions. The presence of hypertension among the most commonly encountered diagnoses for these analgesic drugs points to challenges in establishing the diagnosing-treatment match and indicates potential irrational prescribing practice, especially for interactions.
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Affiliation(s)
- Dilara Bayram
- Department of Pharmacology, Faculty of Pharmacy, Acibadem Mehmet Ali Aydinlar University, İstanbul, Turkey
| | - Volkan Aydin
- Department of Medical Pharmacology, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey
| | - Abdullah Sanli
- School of Medicine, Marmara University, Istanbul, Turkey
| | | | - Busra Sibic
- School of Medicine, Marmara University, Istanbul, Turkey
| | - Sedat Pala
- School of Medicine, Marmara University, Istanbul, Turkey
| | - Omer Atac
- Department of Public Health, School of Medicine, Medipol University, Istanbul, Turkey
| | - Ahmet Akici
- Department of Medical Pharmacology, School of Medicine, Marmara University, Istanbul, Turkey
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Jayakar S, Shim J, Jo S, Bean BP, Singeç I, Woolf CJ. Developing nociceptor-selective treatments for acute and chronic pain. Sci Transl Med 2021; 13:eabj9837. [PMID: 34757806 PMCID: PMC9964063 DOI: 10.1126/scitranslmed.abj9837] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Despite substantial efforts dedicated to the development of new, nonaddictive analgesics, success in treating pain has been limited. Clinically available analgesic agents generally lack efficacy and may have undesirable side effects. Traditional target-based drug discovery efforts that generate compounds with selectivity for single targets have a high rate of attrition because of their poor clinical efficacy. Here, we examine the challenges associated with the current analgesic drug discovery model and review evidence in favor of stem cell–derived neuronal-based screening approaches for the identification of analgesic targets and compounds for treating diverse forms of acute and chronic pain.
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Affiliation(s)
- Selwyn Jayakar
- F.M. Kirby Neurobiology, Boston Children’s Hospital, and Department of Neurology, Harvard Medical School; Boston, MA 02115, USA
| | - Jaehoon Shim
- F.M. Kirby Neurobiology, Boston Children’s Hospital, and Department of Neurology, Harvard Medical School; Boston, MA 02115, USA
| | - Sooyeon Jo
- Department of Neurobiology, Harvard Medical School; Boston, MA 02115, USA
| | - Bruce P Bean
- Department of Neurobiology, Harvard Medical School; Boston, MA 02115, USA
| | - Ilyas Singeç
- National Center for Advancing Translational Sciences (NCATS), Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH); Bethesda, MD 20892, USA
| | - Clifford J Woolf
- F.M. Kirby Neurobiology, Boston Children’s Hospital, and Department of Neurology, Harvard Medical School; Boston, MA 02115, USA
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Schulte CA, Deaton DN, Diaz E, Do Y, Gampe RT, Guss JH, Hancock AP, Hobbs H, Hodgson ST, Holt J, Jeune MR, Kahler KM, Kramer HF, Le J, Mortenson PN, Musetti C, Nolte RT, Orband-Miller LA, Peckham GE, Petrov KG, Pietrak BL, Poole C, Price DJ, Saxty G, Shillings A, Smalley TL, Somers DO, Stewart EL, Stuart JD, Thomson SA. A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors. Bioorg Med Chem Lett 2021; 47:128113. [PMID: 33991628 DOI: 10.1016/j.bmcl.2021.128113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 05/04/2021] [Accepted: 05/08/2021] [Indexed: 10/21/2022]
Abstract
Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.
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Affiliation(s)
- Christie A Schulte
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States.
| | - David N Deaton
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Elsie Diaz
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Young Do
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Robert T Gampe
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Jeffrey H Guss
- GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, United States
| | - Ashley P Hancock
- GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom
| | - Heather Hobbs
- GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom
| | - Simon T Hodgson
- GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom
| | - Jason Holt
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Michael R Jeune
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Kirsten M Kahler
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - H Fritz Kramer
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Joelle Le
- GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom
| | - Paul N Mortenson
- Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom
| | - Caterina Musetti
- GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, United States
| | - Robert T Nolte
- GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, United States
| | - Lisa A Orband-Miller
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Gregory E Peckham
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Kim G Petrov
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Beth L Pietrak
- GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, United States
| | - Chuck Poole
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Daniel J Price
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Gordon Saxty
- Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom
| | - Anthony Shillings
- GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom
| | - Terrence L Smalley
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Don O Somers
- GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom
| | - Eugene L Stewart
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - J Darren Stuart
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
| | - Stephen A Thomson
- GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States
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Zhang S, Qu X, Tang H, Wang Y, Yang H, Yuan W, Yue B. Diclofenac Resensitizes Methicillin-Resistant Staphylococcus aureus to β-Lactams and Prevents Implant Infections. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2021; 8:2100681. [PMID: 34258168 PMCID: PMC8261494 DOI: 10.1002/advs.202100681] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/12/2021] [Indexed: 05/25/2023]
Abstract
Implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) can cause major complications during the perioperative period. Diclofenac, one of the most widely used nonsteroidal anti-inflammatory drugs, is often used to relieve pain and inflammation. In this study, it is found that high-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. However, low-doses diclofenac can resensitize bacteria to β-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Further, low-dose diclofenac in combination with β-lactams inhibit MRSA associated biofilm formation in implants. Transcriptomic and proteomic analyses indicate that diclofenac can reduce the expression of genes and proteins associated with β-lactam resistance: mecA, mecR, and blaZ; peptidoglycan biosynthesis: murA, murC, femA, and femB; and biofilm formation: altE and fnbP. Murine implant infection models indicate that diclofenac combined with β-lactams, can substantially alleviate MRSA infections in vivo. In addition, it is investigated that low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. The synergistic effect of diclofenac and β-lactams might have promising applications for preventing perioperative infection, considering its multitarget effects against MRSA.
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Affiliation(s)
- Shutao Zhang
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of MedicineShanghai Jiaotong UniversityShanghai200127China
| | - Xinhua Qu
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of MedicineShanghai Jiaotong UniversityShanghai200127China
| | - Haozheng Tang
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of MedicineShanghai Jiaotong UniversityShanghai200127China
| | - You Wang
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of MedicineShanghai Jiaotong UniversityShanghai200127China
| | - Hongtao Yang
- Department of Plastic & Reconstructive SurgeryThe Ohio State UniversityColumbusOH43210USA
- School of Medical Science and EngineeringBeihang UniversityBeijing100191China
| | - Weien Yuan
- Engineering Research Center of Cell & Therapeutic AntibodyMinistry of EducationSchool of PharmacyShanghai Jiao Tong UniversityShanghai200240China
| | - Bing Yue
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of MedicineShanghai Jiaotong UniversityShanghai200127China
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McEvoy L, Carr DF, Pirmohamed M. Pharmacogenomics of NSAID-Induced Upper Gastrointestinal Toxicity. Front Pharmacol 2021; 12:684162. [PMID: 34234675 PMCID: PMC8256335 DOI: 10.3389/fphar.2021.684162] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/11/2021] [Indexed: 12/19/2022] Open
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug reactions (ADRs) including peptic ulcer disease and gastrointestinal bleeding. A few clinical and genetic predisposing factors have been identified; however, genetic data are contradictory. Further research is needed to identify clinically relevant genetic and non-genetic markers predisposing to NSAID-induced peptic ulceration.
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Affiliation(s)
- L McEvoy
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| | - D F Carr
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| | - M Pirmohamed
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
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Bajaj S, Fuloria S, Subramaniyan V, Meenakshi DU, Wakode S, Kaur A, Bansal H, Manchanda S, Kumar S, Fuloria NK. Chemical Characterization and Anti-Inflammatory Activity of Phytoconstituents from Swertia alata. PLANTS (BASEL, SWITZERLAND) 2021; 10:1109. [PMID: 34072717 PMCID: PMC8229181 DOI: 10.3390/plants10061109] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 05/18/2021] [Accepted: 05/28/2021] [Indexed: 01/17/2023]
Abstract
Swertia alata C.B Clarke (Gentianaceae) is a well-reported plant in the traditional system of medicine. The present study was intended to isolate the phytoconstituents from the ethanolic extract of the aerial parts of S. alata; and evaluate for in vitro COX-1/COX-2 inhibition activity, in vivo anti-inflammatory and ulcerogenic activity. Phytoisolation involved partitioning of S. alata ethanolic extract into petroleum ether and chloroform soluble fractions using silica gel-based column chromatography. The isolation afforded two phytoisolates, namely oleanolic acid (SA-1) and 3-hydroxylup-12-(13)-ene-17-carboxylic acid (SA-4). Phytoisolates structures were established by melting point, ultraviolet (UV), attenuated total reflection-Fourier-transform infrared (ATR-FTIR), nuclear magnetic resonance (1H-NMR, 13C-NMR and HMBC) and mass spectrometry. Phytoisolates were further evaluated for in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity, in vivo anti-inflammatory and ulcerogenic activity. The study revealed SA-4 (COX-1/COX-2 inhibition activity of 104/61.68 µM with % inhibition of 61.36) to be more effective than SA-1 (COX-1/COX-2 inhibition activity of 128.4/87.25 µM, with % inhibition of 47.72). SA-1 and SA-4, when subjected to ulcerogenic study, exhibited significant gastric tolerance. The current study reports chromatographic isolation and spectrometric characterization of SA-1 and SA-4. The present study concludes that compound SA-4 possess significant anti-inflammatory activity and less irritant property over gastric mucosa with no significant ulcerogenicity in comparison to indomethacin.
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Affiliation(s)
- Sakshi Bajaj
- Delhi Institute of Pharmaceutical Science and Research, Pushp Vihar, New Delhi 110017, India; (S.B.); (S.W.); (H.B.); (S.M.); (S.K.)
| | | | | | | | - Sharad Wakode
- Delhi Institute of Pharmaceutical Science and Research, Pushp Vihar, New Delhi 110017, India; (S.B.); (S.W.); (H.B.); (S.M.); (S.K.)
| | - Avneet Kaur
- SGT College of Pharmacy, SGT University, Budhera, Gurugram 122505, India;
| | - Himangini Bansal
- Delhi Institute of Pharmaceutical Science and Research, Pushp Vihar, New Delhi 110017, India; (S.B.); (S.W.); (H.B.); (S.M.); (S.K.)
| | - Satish Manchanda
- Delhi Institute of Pharmaceutical Science and Research, Pushp Vihar, New Delhi 110017, India; (S.B.); (S.W.); (H.B.); (S.M.); (S.K.)
| | - Sachin Kumar
- Delhi Institute of Pharmaceutical Science and Research, Pushp Vihar, New Delhi 110017, India; (S.B.); (S.W.); (H.B.); (S.M.); (S.K.)
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Zhou Y, Xu J, Lu N, Wu X, Zhang Y, Hou X. Development and application of metal-organic framework@GA based on solid-phase extraction coupling with UPLC-MS/MS for the determination of five NSAIDs in water. Talanta 2021; 225:121846. [DOI: 10.1016/j.talanta.2020.121846] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 10/22/2020] [Accepted: 10/28/2020] [Indexed: 01/01/2023]
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Acupoints for Tension-Type Headache: A Literature Study Based on Data Mining Technology. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5567697. [PMID: 33777156 PMCID: PMC7979293 DOI: 10.1155/2021/5567697] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/13/2021] [Accepted: 03/01/2021] [Indexed: 02/05/2023]
Abstract
Objectives This study aimed to explore the characteristics and principles of acupoints, which were applied for treating tension-type headache (TTH). Methods Four databases were searched for the literature studies of treating TTH with acupuncture and moxibustion up to September 1, 2020. Titles, journals, authors, key words, interventions, main acupoints, and outcomes of the included literature studies were extracted and inputted into the self-established Data Excavation Platform of Acupoint Specificity for analysis. Results In total, 128 papers containing 137 prescriptions, 89 meridian acupoints, and 7 extraordinary acupoints of treating TTH with acupuncture and moxibustion were included. The total frequency of acupoints' application was 763 times. Fengchi (GB20), Baihui (GV20), Taiyang (EX-HN5), Hegu (LI4), and Taichong (LR3) were used most frequently. The acupoints in Yang meridians were utilized more than those in Yin meridians (66.1% vs. 17.8%), and the acupoints in the Gallbladder Meridian of Foot Shaoyang were applied most commonly. 59.9% (457/763) of the applied acupoints were on the head, face, and neck, and 31.7% (242/763) were on the four limbs. Additionally, the proportion of specific acupoints' application was 78.2% (597/763). Conclusions The prescription of Fengchi (GB20), Baihui (GV20), Taiyang (EX-HN5), Hegu (LI4), and Taichong (LR3) might be relatively reasonable in clinical practices of treating TTH with acupuncture, which should be verified in further studies.
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Memon A, Kim BY, Kim SE, Pyao Y, Lee YG, Kang SC, Lee WK. Anti-Inflammatory Effect of Phytoncide in an Animal Model of Gastrointestinal Inflammation. Molecules 2021; 26:molecules26071895. [PMID: 33810618 PMCID: PMC8037037 DOI: 10.3390/molecules26071895] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 03/23/2021] [Accepted: 03/24/2021] [Indexed: 01/08/2023] Open
Abstract
Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.
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Affiliation(s)
- Azra Memon
- Department of Biomedical Sciences, School of Medicine, Inha University, Incheon 22212, Korea; (A.M.); (Y.P.)
| | - Bae Yong Kim
- Research Institute, Phylus Co., LTD., Danyang-gun 27000, Korea;
- Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si 17104, Korea; (S.-e.K.); (Y.-G.L.); (S.C.K.)
| | - Se-eun Kim
- Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si 17104, Korea; (S.-e.K.); (Y.-G.L.); (S.C.K.)
| | - Yuliya Pyao
- Department of Biomedical Sciences, School of Medicine, Inha University, Incheon 22212, Korea; (A.M.); (Y.P.)
| | - Yeong-Geun Lee
- Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si 17104, Korea; (S.-e.K.); (Y.-G.L.); (S.C.K.)
| | - Se Chan Kang
- Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si 17104, Korea; (S.-e.K.); (Y.-G.L.); (S.C.K.)
| | - Woon Kyu Lee
- Department of Biomedical Sciences, School of Medicine, Inha University, Incheon 22212, Korea; (A.M.); (Y.P.)
- Correspondence: ; Tel.: +82-10-4607-3871
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Jiang Y, Qi L, Liu J, Wu H, Li Y, Zou L, Guo Z, Wang J, Li H. Analgesic efficacy of imrecoxib for postoperative pain following oral surgery: a prospective randomized, active-controlled, non-inferiority trial. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:469. [PMID: 33850866 PMCID: PMC8039693 DOI: 10.21037/atm-21-264] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Imrecoxib, a novel cyclooxygenase (COX-2) selective non-steroidal anti-inflammatory drug (NSAID), has been approved in China for more than 9 years. This study aimed to assess the efficacy and safety of imrecoxib compared with celecoxib for patients with moderate or severe acute pain following oral surgery. Methods Patients with moderate or severe pain within 6 hours following surgery were enrolled in this randomized, active-control trial. Patients were randomly assigned (1:1) to receive either imrecoxib or celecoxib. Pain assessments on the visual analog scale, verbal rating scale, and pain relief were conducted at 0.5, 1, 2, 4, 6, 9, 12, and 24 hours after the first dose. Adverse events were also recorded. Results Eighty-seven patients were approached from November 2018 to August 2019. Of these, 60 were eligible for randomization. Ultimately, 56 patients (imrecoxib group, n=27; celecoxib group, n=29) were included in the analysis. The difference in total pain relief (TOTPAR) between the imrecoxib and celecoxib groups was 1.03 [95% confidence interval (CI): −1.31–3.77], with the lower bound of the CI above the specified non-inferiority boundary. No perioperative complications were observed in the imrecoxib group during the 24-hour period after the first dose. Conclusions Imrecoxib could significantly relieve pain and has a non-inferior analgesic efficacy compared to celecoxib with good tolerance following oral surgery.
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Affiliation(s)
- Yu Jiang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Lili Qi
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Jie Liu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Heming Wu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Yi Li
- Jiangsu Hengrui Pharmaceutical Co., Ltd., Lianyungang, China
| | - Linhu Zou
- Jiangsu Hengrui Pharmaceutical Co., Ltd., Lianyungang, China
| | - Zhiwei Guo
- Jiangsu Hengrui Pharmaceutical Co., Ltd., Lianyungang, China
| | - Jinqiang Wang
- Jiangsu Hengrui Pharmaceutical Co., Ltd., Lianyungang, China
| | - Huaiqi Li
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
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35
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Tang KS, Shah AD. Nonsteroidal anti-inflammatory drugs in end-stage kidney disease: dangerous or underutilized? Expert Opin Pharmacother 2021; 22:769-777. [PMID: 33467933 DOI: 10.1080/14656566.2020.1856369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a popular class of analgesic and anti-inflammatory medications, but their use is often avoided in end-stage kidney disease (ESKD) patients due to their reputation for nephrotoxic side effects. This removes a useful agent from the analgesic arsenal, even as ESKD patients suffer from proportionally more severe chronic pain than the general population as well as from a large reliance on opioid medications. Areas Covered: This paper reviews the current literature to comprehensively define the pharmacologic mechanisms and adverse effects of NSAIDs and reassesses the viability of their use in ESKD patients. Expert opinion: The evidence directly examining the impact of NSAIDs on long-term outcomes in ESKD is limited. Further study quantifying the risk of NSAID use - especially in dialysis-dependent patients - is warranted. Given the difficulty in achieving adequate pain control in ESKD patients, limited use of NSAIDs in these patients may yet be justified.
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Affiliation(s)
- Kevin S Tang
- Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Ankur D Shah
- Warren Alpert Medical School of Brown University, Providence, RI, USA.,Division of Nephrology, Rhode Island Hospital, Providence, RI, USA.,Division of Nephrology, Medical Service, Veterans Affairs Medical Center, Providence, RI, USA
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Wang X, Tang Q, Hou H, Zhang W, Li M, Chen D, Gu Y, Wang B, Hou J, Liu Y, Cao H. Gut Microbiota in NSAID Enteropathy: New Insights From Inside. Front Cell Infect Microbiol 2021; 11:679396. [PMID: 34295835 PMCID: PMC8290187 DOI: 10.3389/fcimb.2021.679396] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 06/10/2021] [Indexed: 12/15/2022] Open
Abstract
As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.
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Affiliation(s)
- Xianglu Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Qiang Tang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Huiqin Hou
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Wanru Zhang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Mengfan Li
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Danfeng Chen
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yu Gu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Jingli Hou
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China
- *Correspondence: Hailong Cao, ; Jingli Hou, ; Yangping Liu,
| | - Yangping Liu
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China
- *Correspondence: Hailong Cao, ; Jingli Hou, ; Yangping Liu,
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
- *Correspondence: Hailong Cao, ; Jingli Hou, ; Yangping Liu,
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Rahaman M, Ali MS, Jahan K, Belayet JB, Rahman AFMT, Hossain MM. Chemistry of 3-hydroxy-2-aryl acrylate: syntheses, mechanisms, and applications. Org Chem Front 2021. [DOI: 10.1039/d0qo01157f] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
3-Hydroxy-2-aryl acrylate is important scaffold which is widely used for the synthesis of pharmacologically active compounds. This review summarises the synthetic methods of the 3-hydroxy-2-aryl acrylate including mechanisms and applications.
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Affiliation(s)
- Mizzanoor Rahaman
- Department of Chemistry and Biochemistry
- University of Wisconsin–Milwaukee
- Milwaukee
- USA
| | - M. Shahnawaz Ali
- Department of Chemistry and Biochemistry
- University of Wisconsin–Milwaukee
- Milwaukee
- USA
| | - Khorshada Jahan
- Department of Chemistry and Biochemistry
- University of Wisconsin–Milwaukee
- Milwaukee
- USA
| | - Jawad Bin Belayet
- Department of Chemistry and Biochemistry
- University of Wisconsin–Milwaukee
- Milwaukee
- USA
| | | | - M. Mahmun Hossain
- Department of Chemistry and Biochemistry
- University of Wisconsin–Milwaukee
- Milwaukee
- USA
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38
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Fan J, Li BR, Zhang Q, Zhao XH, Wang L. Pretreatment of IEC-6 cells with quercetin and myricetin resists the indomethacin-induced barrier dysfunction via attenuating the calcium-mediated JNK/Src activation. Food Chem Toxicol 2021; 147:111896. [PMID: 33276066 DOI: 10.1016/j.fct.2020.111896] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 11/22/2020] [Accepted: 11/28/2020] [Indexed: 12/11/2022]
Abstract
This study investigated the protective effect of two flavonols quercetin and myricetin on barrier function of rat intestinal epithelial (IEC-6) cells with indomethacin injury. When the cells were pretreated with the heated or unheated flavonols of 2.5-10 μmol/L for 24-48 h and then injured by 300 μmol/L indomethacin for 24 h, they showed reduced lactate dehydrogenase release (LDH) but increased cell viability; however, the flavonols of 20 μmol/L exerted a little effect to increase cell viability or decrease LDH release. Cell pretreatment with 5 μmol/L flavonols also resisted cell barrier dysfunction by increasing transepithelial resistance, reducing paracellular permeability, and promoting mRNA and protein expression of three tight junction proteins zonula occluden-1, occludin, and claudin-1. Although indomethacin injury increased intracellular Ca2+ concentration ([Ca2+]i) and consequently caused JNK/Src activation, the flavonols could decrease [Ca2+]i and attenuate the calcium-mediated JNK/Src activation. Quercetin with less hydroxyl groups was more efficient than myricetin to resist barrier dysfunction, while the unheated flavonols were more active than the heated counterparts to perform this effect. It is thus proposed that quercetin and myricetin could resist barrier dysfunction of the intestine once injured by indomethacin, but heat treatment of flavonols had a negative impact on barrier-protective function of flavonols.
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Affiliation(s)
- Jing Fan
- School of Biology and Food Engineering, Guangdong University of Petrochemical Technology, 525000, Maoming, PR China; Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, 150030, Harbin, PR China
| | - Bai-Ru Li
- School of Mechanical and Electrical Engineering Guangdong University of Petrochemical Technology, 525000, Maoming, PR China
| | - Qiang Zhang
- School of Biology and Food Engineering, Guangdong University of Petrochemical Technology, 525000, Maoming, PR China
| | - Xin-Huai Zhao
- School of Biology and Food Engineering, Guangdong University of Petrochemical Technology, 525000, Maoming, PR China; Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, 150030, Harbin, PR China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong University of Petrochemical Technology, 525000, Maoming, PR China.
| | - Li Wang
- School of Biology and Food Engineering, Guangdong University of Petrochemical Technology, 525000, Maoming, PR China.
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Summer K, Browne J, Liu L, Benkendorff K. Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease. Mar Drugs 2020; 18:md18110570. [PMID: 33228163 PMCID: PMC7699502 DOI: 10.3390/md18110570] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/16/2020] [Accepted: 11/16/2020] [Indexed: 12/26/2022] Open
Abstract
Respiratory diseases place an immense burden on global health and there is a compelling need for the discovery of new compounds for therapeutic development. Here, we identify research priorities by critically reviewing pre-clinical and clinical studies using extracts and compounds derived from molluscs, as well as traditional molluscan medicines, used in the treatment of respiratory diseases. We reviewed 97 biomedical articles demonstrating the anti-inflammatory, antimicrobial, anticancer, and immunomodulatory properties of >320 molluscan extracts/compounds with direct relevance to respiratory disease, in addition to others with promising bioactivities yet to be tested in the respiratory context. Of pertinent interest are compounds demonstrating biofilm inhibition/disruption and antiviral activity, as well as synergism with approved antimicrobial and chemotherapeutic agents. At least 100 traditional medicines, incorporating over 300 different mollusc species, have been used to treat respiratory-related illness in cultures worldwide for thousands of years. These medicines provide useful clues for the discovery of bioactive components that likely underpin their continued use. There is particular incentive for investigations into anti-inflammatory compounds, given the extensive application of molluscan traditional medicines for symptoms of inflammation, and shells, which are the principal molluscan product used in these preparations. Overall, there is a need to target research toward specific respiratory disease-related hypotheses, purify bioactive compounds and elucidate their chemical structures, and develop an evidence base for the integration of quality-controlled traditional medicines.
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Affiliation(s)
- Kate Summer
- Marine Ecology Research Centre, School of Environment, Science and Engineering, Southern Cross University, GPO Box 157, Lismore, NSW 2480, Australia;
| | - Jessica Browne
- School of Health and Human Sciences, Southern Cross University, Terminal Drive, Bilinga, QLD 4225, Australia;
| | - Lei Liu
- Southern Cross Plant Science, Southern Cross University, GPO Box 157, Lismore, NSW 2480, Australia;
| | - Kirsten Benkendorff
- National Marine Science Centre, Southern Cross University, 2 Bay Drive, Coffs Harbour, NSW 2450, Australia
- Correspondence: ; Tel.: +61-429-520-589
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40
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Lee MW, Katz PO. Nonsteroidal Antiinflammatory Drugs, Anticoagulation, and Upper Gastrointestinal Bleeding. Clin Geriatr Med 2020; 37:31-42. [PMID: 33213773 DOI: 10.1016/j.cger.2020.08.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Advanced age, history of peptic ulcer disease, Helicobacter pylori, coadministration of nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, anticoagulation, and antiplatelets are risk factors for gastrointestinal bleeding in the elderly. Awareness of these risks and appropriate use of NSAIDs, particularly in those needing antiplatelet or anticoagulant therapy, is critical to optimal management. Careful selection of elderly patients requiring antiplatelet, anticoagulation, or chronic NSAID therapy for cotherapy with proton pump inhibitors can significantly reduce morbidity and mortality from gastrointestinal bleeding.
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Affiliation(s)
- Mindy Winghin Lee
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, 1315 York Avenue, First Floor, New York, NY 10021, USA
| | - Philip O Katz
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, 1315 York Avenue, First Floor, New York, NY 10021, USA.
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41
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Jebali J, Zakraoui O, Aissaoui D, Abdelkafi-Koubaa Z, Srairi-Abid N, Marrakchi N, Essafi-Benkhadir K. Lebecetin, a snake venom C-type lectin protein, modulates LPS-induced inflammatory cytokine production in human THP-1-derived macrophages. Toxicon 2020; 187:144-150. [PMID: 32918926 DOI: 10.1016/j.toxicon.2020.09.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/11/2020] [Accepted: 09/07/2020] [Indexed: 10/25/2022]
Abstract
The excessive production of inflammatory mediators results in an overactive immune response leading to the worsening of various human diseases. Thus, there is a still need to identify molecules able to regulate the inflammatory response. Lebecetin, a C-type lectin protein isolated from Macrovipera lebetina snake venom, was previously characterized as a platelet aggregation inhibitor and antitumor active biomolecule. In the present work, we investigated its effect on the production of some cytokines linked to inflammatory response and the underlying mechanisms in lipopolysaccharide (LPS)-induced THP1 macrophages. Interestingly, we found that lebecetin reduced the levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while it partially increased LPS-induced secretion of the immunomodulatory cytokine IL-10. Furthermore, this modulatory effect was accompanied by decreased activation of ERK1/2, p38, AKT kinases and NF-κB along with reduced expression of αvβ3 integrin. Thus, this study highlights the promising role of lebecetin as a natural biomolecule that could manage the inflammatory response involved in the development and progression of inflammatory diseases.
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Affiliation(s)
- Jed Jebali
- Institut Pasteur de Tunis, LR11IPT08/LR16IPT08 Laboratoire des Venins et Molécules Thérapeutiques, 1002, Tunis, Tunisia; Université de Tunis El Manar, 1068, Tunis, Tunisia.
| | - Ons Zakraoui
- Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002, Tunis, Tunisia; Université de Tunis El Manar, 1068, Tunis, Tunisia
| | - Dorra Aissaoui
- Institut Pasteur de Tunis, LR11IPT08/LR16IPT08 Laboratoire des Venins et Molécules Thérapeutiques, 1002, Tunis, Tunisia; Université de Tunis El Manar, 1068, Tunis, Tunisia
| | - Zaineb Abdelkafi-Koubaa
- Institut Pasteur de Tunis, LR11IPT08/LR16IPT08 Laboratoire des Venins et Molécules Thérapeutiques, 1002, Tunis, Tunisia; Université de Tunis El Manar, 1068, Tunis, Tunisia
| | - Najet Srairi-Abid
- Institut Pasteur de Tunis, LR11IPT08/LR16IPT08 Laboratoire des Venins et Molécules Thérapeutiques, 1002, Tunis, Tunisia; Université de Tunis El Manar, 1068, Tunis, Tunisia
| | - Naziha Marrakchi
- Institut Pasteur de Tunis, LR11IPT08/LR16IPT08 Laboratoire des Venins et Molécules Thérapeutiques, 1002, Tunis, Tunisia; Université de Tunis El Manar, 1068, Tunis, Tunisia; Faculté de Médecine de Tunis, Tunis, Tunisia
| | - Khadija Essafi-Benkhadir
- Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002, Tunis, Tunisia; Université de Tunis El Manar, 1068, Tunis, Tunisia.
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42
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Silva M, Feijão E, da Cruz de Carvalho R, Duarte IA, Matos AR, Cabrita MT, Barreiro A, Lemos MFL, Novais SC, Marques JC, Caçador I, Reis-Santos P, Fonseca VF, Duarte B. Comfortably numb: Ecotoxicity of the non-steroidal anti-inflammatory drug ibuprofen on Phaeodactylum tricornutum. MARINE ENVIRONMENTAL RESEARCH 2020; 161:105109. [PMID: 32871462 DOI: 10.1016/j.marenvres.2020.105109] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/28/2020] [Accepted: 08/05/2020] [Indexed: 06/11/2023]
Abstract
Emerging pollutants such as pharmaceuticals are continuously released to aquatic environments posing a rising threat to marine ecosystems. Yet, monitoring routines and ecotoxicity data on biota worldwide for these substances are lacking. Non-steroidal anti-inflammatory drugs are among the most prescribed and found pharmaceuticals in aquatic environments. The toxicity effects of environmentally relevant concentrations of ibuprofen on primary productivity, oxidative stress and lipid metabolism of the diatom Phaeodactylum tricornutum were assessed. Diatom cultures were exposed to 0, 0.8, 3, 40, 100 and 300 μg L-1 ibuprofen concentrations, usually found in the vicinity of wastewater treatment plants and coastal environments. Higher concentrations (100 and 300 μg L-1) had a negative impact in P. triconutum growth, inhibiting the chloroplastic energy transduction in the electron transport chain resulting in lower energy reaching the PS I (r2 = -0.55, p < 0.05). In contrast, the mitochondrial electron transport and available energy increased (r2 = 0.68 and r2 = 0.85, p < 0.05 respectively), mostly due to enhancements in lipid and protein contents as opposed to reduction of carbohydrates. A general up-regulation of the antioxidant enzymes could contributed to alleviate oxidative stress resulting in the decrease of lipid peroxidation products (r2 = 0.77, p < 0.05). Canonical analysis of principal components was performed and successfully discriminated exposure groups, with optical data excelling in classifying samples to different ibuprofen concentrations, being potentially used as environmental indicators. Finally, the identified mild to severe effects of ibuprofen on diatoms are likely to be exacerbated by the sustained use of this drug worldwide, underpinning the urgency of evaluating the impacts of this pharmaceutical on coastal and marine trophic webs.
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Affiliation(s)
- Marisa Silva
- MARE - Marine and Environmental Sciences Centre, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal.
| | - Eduardo Feijão
- MARE - Marine and Environmental Sciences Centre, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal
| | - Ricardo da Cruz de Carvalho
- MARE - Marine and Environmental Sciences Centre, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal
| | - Irina A Duarte
- MARE - Marine and Environmental Sciences Centre, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal
| | - Ana Rita Matos
- BioISI - Biosystems and Integrative Sciences Institute, Plant Functional Genomics Group, Departamento de Biologia Vegetal, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal
| | - Maria Teresa Cabrita
- Centro de Estudos Geográficos (CEG), Instituto de Geografia e Ordenamento do Território (IGOT), Universidade de Lisboa, Rua Branca Edmée Marques, 1600-276, Lisboa, Portugal
| | - Aldo Barreiro
- Interdisciplinary Center of Marine and Environmental Research-CIMAR/CIIMAR, University of Porto, Novo Edificio do Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, 4450-208, S/N Matosinhos, Portugal
| | - Marco F L Lemos
- MARE - Marine and Environmental Sciences Centre, ESTM, Polytechnic of Leiria, Avenida do Porto de Pesca, 2520-630, Peniche, Portugal
| | - Sara C Novais
- MARE - Marine and Environmental Sciences Centre, ESTM, Polytechnic of Leiria, Avenida do Porto de Pesca, 2520-630, Peniche, Portugal
| | - João Carlos Marques
- MARE - Marine and Environmental Sciences Centre, c/o Department of Zoology, Faculty of Sciences and Technology, University of Coimbra, 3000, Coimbra, Portugal
| | - Isabel Caçador
- MARE - Marine and Environmental Sciences Centre, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal; Departamento de Biologia Vegetal, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal
| | - Patrick Reis-Santos
- MARE - Marine and Environmental Sciences Centre, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal; Southern Seas Ecology Laboratories, School of Biological Sciences, The University of Adelaide, SA, 5005, Australia
| | - Vanessa F Fonseca
- MARE - Marine and Environmental Sciences Centre, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal; Departamento de Biologia Vegetal, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal
| | - Bernardo Duarte
- MARE - Marine and Environmental Sciences Centre, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal; Departamento de Biologia Vegetal, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal
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Chlorogenic Acid Potentiates the Anti-Inflammatory Activity of Curcumin in LPS-Stimulated THP-1 Cells. Nutrients 2020; 12:nu12092706. [PMID: 32899726 PMCID: PMC7551420 DOI: 10.3390/nu12092706] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 08/27/2020] [Accepted: 08/30/2020] [Indexed: 02/03/2023] Open
Abstract
The anti-inflammatory effects of curcumin are well documented. However, the bioavailability of curcumin is a major barrier to its biological efficacy. Low-dose combination of complimentary bioactives appears to be an attractive strategy for limiting barriers to efficacy of bioactive compounds. In this study, the anti-inflammatory potential of curcumin in combination with chlorogenic acid (CGA), was investigated using human THP-1 macrophages stimulated with lipopolysaccharide (LPS). Curcumin alone suppressed TNF-α production in a dose-dependent manner with a decrease in cell viability at higher doses. Although treatment with CGA alone had no effect on TNF-α production, it however enhanced cell viability and co-administration with curcumin at a 1:1 ratio caused a synergistic reduction in TNF-α production with no impact on cell viability. Furthermore, an qRT-PCR analysis of NF-κB pathway components and inflammatory biomarkers indicated that CGA alone was not effective in reducing the mRNA expression of any of the tested inflammatory marker genes, except TLR-4. However, co-administration of CGA with curcumin, potentiated the anti-inflammatory effects of curcumin. Curcumin and CGA together reduced the mRNA expression of pro-inflammatory cytokines [TNF-α (~88%) and IL-6 (~99%)], and COX-2 (~92%), possibly by suppression of NF-κB (~78%), IκB-β-kinase (~60%) and TLR-4 receptor (~72%) at the mRNA level. Overall, co-administration with CGA improved the inflammation-lowering effects of curcumin in THP-1 cells.
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GİŞİ K, İSPİROĞLU M, KANTARÇEKEN B. NSAID Kullanan Her Hastada Gastrik Profilaksi Gerekli mi? KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNIVERSITESI TIP FAKÜLTESI DERGISI 2020. [DOI: 10.17517/ksutfd.671049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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45
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Broughton-Neiswanger LE, Rivera-Velez SM, Suarez MA, Slovak JE, Piñeyro PE, Hwang JK, Villarino NF. Urinary chemical fingerprint left behind by repeated NSAID administration: Discovery of putative biomarkers using artificial intelligence. PLoS One 2020; 15:e0228989. [PMID: 32053695 PMCID: PMC7018043 DOI: 10.1371/journal.pone.0228989] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 01/28/2020] [Indexed: 02/07/2023] Open
Abstract
Prediction and early detection of kidney damage induced by nonsteroidal anti-inflammatories (NSAIDs) would provide the best chances of maximizing the anti-inflammatory effects while minimizing the risk of kidney damage. Unfortunately, biomarkers for detecting NSAID-induced kidney damage in cats remain to be discovered. To identify potential urinary biomarkers for monitoring NSAID-based treatments, we applied an untargeted metabolomics approach to urine collected from cats treated repeatedly with meloxicam or saline for up to 17 days. Applying multivariate analysis, this study identified a panel of seven metabolites that discriminate meloxicam treated from saline treated cats. Combining artificial intelligence machine learning algorithms and an independent testing urinary metabolome data set from cats with meloxicam-induced kidney damage, a panel of metabolites was identified and validated. The panel of metabolites including tryptophan, tyrosine, taurine, threonic acid, pseudouridine, xylitol and lyxitol, successfully distinguish meloxicam-treated and saline-treated cats with up to 75–100% sensitivity and specificity. This panel of urinary metabolites may prove a useful and non-invasive diagnostic tool for monitoring potential NSAID induced kidney injury in feline patients and may act as the framework for identifying urine biomarkers of NSAID induced injury in other species.
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Affiliation(s)
- Liam E. Broughton-Neiswanger
- Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States of America
| | - Sol M. Rivera-Velez
- Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States of America
| | - Martin A. Suarez
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States of America
| | | | - Pablo E. Piñeyro
- Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, Ames, IA, United States of America
| | - Julianne K. Hwang
- Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States of America
| | - Nicolas F. Villarino
- Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States of America
- * E-mail:
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46
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Dinçer D, Ulukal Karancı E, Akın M, Adanır H. NSAID, antiaggregant, and/or anticoagulant-related upper gastrointestinal bleeding: Is there any change in prophylaxis rate after a 10-year period? TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:505-510. [PMID: 31199288 DOI: 10.5152/tjg.2019.19057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND/AIMS Using proton-pump inhibitor (PPI) is a protective option for patients who require long-term non-steroidal anti-inflammatory drugs (NSAIDs) and antiaggregants. In our previous study, the rate of PPI use in prophylaxis was found to be 2%. Here we aimed to investigate whether there is a change in PPI use in prophylaxis in a similar patient group after 10 years. MATERIALS AND METHODS The patients who followed up with upper gastrointestinal (GI) bleeding diagnosis between January 01, 2016 and December 31, 2017 were retrospectively evaluated. Patients who had malignancy or variceal hemorrhage were excluded. Ninety-six patients, who had taken NSAIDs, antiaggregants, or anticoagulants that were considered as the possible cause of bleeding, were included in the study. Risk groups for NSAID GI toxicity and PPI use rates in these patients were evaluated. RESULTS Twenty (21%) of all patients with upper GI bleeding were using PPI. According to the pre-bleeding risk factor assessment, 86% of the patients were found to have moderate to high risk for NSAID-related GI bleeding, and 81% of these patients were not using PPI. PPI prophylaxis was not provided to 15 (75%) of the 20 patients with previous history of peptic ulcer bleeding. CONCLUSION Despite many studies and recommendations on risk factors and prophylaxis for NSAID-related bleeding, prophylactic PPI use is still largely ignored by physicians. The rate of PPI use in the patient group of this study was found still quite insufficient.
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Affiliation(s)
- Dinç Dinçer
- Department of Gastroenterology, Akdeniz University School of Medicine, Antalya, Turkey
| | - Ece Ulukal Karancı
- Department of Internal Medicine, Akdeniz University School of Medicine, Antalya, Turkey
| | - Mete Akın
- Department of Gastroenterology, Akdeniz University School of Medicine, Antalya, Turkey
| | - Haydar Adanır
- Department of Gastroenterology, Akdeniz University School of Medicine, Antalya, Turkey
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Walker J, Cattaneo M, Badimon L, Agnelli G, Chan AT, Lanas A, Rocca B, Rothwell P, Patrignani P, Langley R, Vilahur G, Cosentino F. Highlights from the 2019 International Aspirin Foundation Scientific Conference, Rome, 28 June 2019: benefits and risks of antithrombotic therapy for cardiovascular disease prevention. Ecancermedicalscience 2020; 14:998. [PMID: 32153653 PMCID: PMC7032943 DOI: 10.3332/ecancer.2020.998] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Indexed: 12/16/2022] Open
Abstract
At the 2019 International Aspirin Foundation Scientific Conference 'Benefits and Risks of Antithrombotic Therapy for Cardiovascular Disease Prevention', held in Rome, Italy, international experts sought to discuss and debate the optimal antithrombotic strategy for the secondary prevention of cardiovascular disease (CVD) and to seek agreement around dosing and target populations for aspirin use in primary disease prevention. Getting the best evidence to support real-life decisions in the clinic can be complex, and individualising management in order to balance both the risks and benefits of different disease prevention strategies appears to be the best approach. It is hoped that future decision-making tools and biomarkers will help direct treatments at those most likely to benefit.
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Affiliation(s)
- Jaqui Walker
- International Aspirin Foundation, 34 Bower Mount Road, Maidstone, Kent ME16 8AU, UK
| | - Marco Cattaneo
- Medicina 2, ASST Santi Paolo e Carlo, Milan, Italy - Dipartimento di Science della Salute, Università degli studi di Milano, 20122 Milan, Italy
| | - Lina Badimon
- Cardiovascular Program-ICCC, IR-Hospital de la Santa Creu, I Sant Pau and CiberCV, 08041 Barcelona, Spain
| | - Giancarlo Agnelli
- Internal Vascular and Emergency Medicine-Stroke Unit, University of Perugia, 06123 Perugia, Italy
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School
| | - Angel Lanas
- University of Zaragoza, 50009 Zaragoza, Spain
| | - Bianca Rocca
- Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy
| | - Peter Rothwell
- Centre for the Prevention of Stroke and Dementia and Professor of Clinical Neurology, Oxford, UK
| | - Paola Patrignani
- Department of Neuroscience, Imaging and Clinical Sciences, and CeSI-MeT, 'G.d'Annunizio' University, School of Medicine, Chieti, Italy
| | - Ruth Langley
- MRC Clinical Trials Unit at UCL, WC1V 6LJ London, UK
| | - Gemma Vilahur
- Cardiovascular Program ICCC-Research Institute Hospital de la Santa Creu I Sant Pau, IIB-Sant Pau, 08041 Barcelona, Spain and CiberCV, Institute Carlos III, 28903 Madrid, Spain
| | - Francesco Cosentino
- Unit of Cardiology, Department of Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden
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48
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Tasneem S, Saleem M, Saeed SA. Nonsteroidal anti-inflammatory drugs as potential ecto-nucleotide phosphodiesterase inhibitors. BRAZ J PHARM SCI 2020. [DOI: 10.1590/s2175-97902019000318271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Shumaila Tasneem
- University of Karachi, Pakistan; Dow University of Health Sciences, Pakistan
| | - Muhammad Saleem
- University of Karachi, Pakistan; University of Education, Pakistan
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49
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Lee SH, Park YW, Choe JY, Shin K, Kwon SR, Cha JH, Kim YJ, Lee J, Kim TH. Gastrointestinal risk factors and patient-reported outcomes of ankylosing spondylitis in Korea. Int J Rheum Dis 2019; 23:342-349. [PMID: 31885217 PMCID: PMC7065053 DOI: 10.1111/1756-185x.13758] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 11/06/2019] [Accepted: 11/07/2019] [Indexed: 12/17/2022]
Abstract
Aim This study examined the degree of gastrointestinal (GI) risk and patient‐reported outcomes including GI‐related symptoms, adherence to non‐steroidal anti‐inflammatory drugs (NSAIDs), disease activity and quality of life (QoL) in patients with ankylosing spondylitis (AS). Methods Cross‐sectional, observational study conducted at six nationwide, university‐based hospitals of Korea. AS patients treated with NSAIDs for at least 2 weeks were included between March and September 2016. Demographic and clinical data were gathered through a medical chart review and patient survey. GI risk was estimated using Standardized Calculator of Risk for Events (SCORE). NSAIDs adherence was investigated with Morisky Medication Adherence Scale‐8 (MMAS‐8). Disease activity and QoL were examined with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and EuroQol‐3L (EQ‐5D, EQ‐visual analog scale [EQ‐VAS]), respectively. Path analysis was implemented to estimate pathways of GI risk, GI symptoms and NSAIDs adherence to QoL. Results A total of 596 patients (age: 38.9 ± 12.6 years, male: 82.1%) participated in the study, of which 33.2% experienced GI symptoms during NSAID treatment, and 34.2% of them showed ongoing GI symptoms upon enrollment. According to SCORE, 37.1% of patients showed moderate to very high GI risk. No patient showed high adherence according to MMAS‐8, so 55.3% of patients with moderate adherence were considered adherent. BASDAI and QoL of the total patients were 3.5 ± 2.0, 0.6 ± 0.3 (EQ‐5D), and 67.4 ± 19.8 (EQ‐VAS), respectively. From path analyses, higher GI risk significantly lowered QoL. Conclusion This study suggests timely therapeutic strategies should be implemented to manage GI risk during NSAID treatment in order to effectively manage AS.
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Affiliation(s)
- Sang-Hoon Lee
- Department of Rheumatology, Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Yong-Wook Park
- Department of Rheumatology, Chonnam National University Hospital, Gwangju, Korea
| | - Jung-Yoon Choe
- Department of Rheumatology, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Kichul Shin
- Department of Rheumatology, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Seong-Ryul Kwon
- Department of Rheumatology, Inha University Hospital, Incheon, Korea
| | - Jin-Hye Cha
- Pfizer Pharmaceuticals Korea Limited, Seoul, Korea
| | | | - Juneyoung Lee
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - Tae-Hwan Kim
- Department of Rheumatology, The Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
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50
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Han X, Chen J, Li Z, Qiu H. Combustion fabrication of magnetic porous carbon as a novel magnetic solid-phase extraction adsorbent for the determination of non-steroidal anti-inflammatory drugs. Anal Chim Acta 2019; 1078:78-89. [DOI: 10.1016/j.aca.2019.06.022] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 06/06/2019] [Accepted: 06/08/2019] [Indexed: 01/06/2023]
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