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Küper MA, Trütschel S, Weinreich J, Königsrainer A, Beckert S. Growth hormone abolishes the negative effects of everolimus on intestinal wound healing. World J Gastroenterol 2016; 22:4321-4329. [PMID: 27158200 PMCID: PMC4853689 DOI: 10.3748/wjg.v22.i17.4321] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2016] [Revised: 02/10/2016] [Accepted: 03/02/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic healing.
METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3 mg/kg po; III: everolimus 3 mg/kg po + hGH 2.5 mg/kg sc). Animals were pre-treated with hGH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical (Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological (cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.
RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with hGH resulted in considerably higher values (I: 134 ± 19 mmHg, II: 85 ± 25 mmHg, III: 114 ± 25 mmHg; P < 0.05, I vs II; P = 0.09, I vs III and II vs III) Hydroxyproline concentration was significantly increased by hGH compared to everolimus alone (I: 14.9 ± 2.5 μg/mg, II: 8.9 ± 3.6 μg/mg, III: 11.9 ± 2.8 μg/mg; P < 0.05, I vs II/III and II vs III). The number of MPO-positive cells was reduced significantly by hGH compared to everolimus alone (I: 10 ± 1 n/mm², II: 15 ± 3 n/mm², III: 9 ± 2 n/mm²; P < 0.05, I vs II and II vs III), while the number of PCNA-positive cells were increased by hGH (I: 28 ± 3 /mm², II: 12 ± 3 /mm², III: 26 ± 12 /mm²; P < 0.05, I vs II and II vs III). Corresponding to these biochemical findings, HE-histology revealed significantly increased amount of granulation tissue in hGH-treated animals.
CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with hGH. Both inflammation as well as collagen deposition is influenced by hGH.
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Øines MN, Krarup PM, Jorgensen LN, Ågren MS. Pharmacological interventions for improved colonic anastomotic healing: A meta-analysis. World J Gastroenterol 2014; 20:12637-12648. [PMID: 25253969 PMCID: PMC4168102 DOI: 10.3748/wjg.v20.i35.12637] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 04/10/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify pharmaceuticals for the prophylaxis of anastomotic leakage (AL), we systematically reviewed studies on anastomosis repair after colorectal surgery.
METHODS: We searched PubMed and EMBASE for articles published between January 1975 and December 2012. We included studies in English with the primary purpose of promoting healing of anastomoses made in the colon or rectum under uncomplicated conditions. We excluded studies on adverse events from interventions, nutritional interventions or in situ physical supporting biomaterials. The primary outcome was biomechanical strength or AL. We performed meta-analyses on therapeutic agents investigated by three or more independent research groups using the same outcome. The DerSimonian-Laird method for random effects was applied with P < 0.05.
RESULTS: Of the 56 different therapeutic agents assessed, 7 met our inclusion criteria for the meta-analysis. The prostacyclin analog iloprost increased the weighted mean of the early bursting pressure of colonic anastomoses in male rats by 60 mmHg (95%CI: 30-89) vs the controls, and the immunosuppressant tacrolimus increased this value by 29 mmHg (95%CI: 4-53) vs the controls. Erythropoietin showed an enhancement of bursting pressure by 45 mmHg (95%CI: 14-76). The anabolic compound growth hormone augmented the anastomotic strength by 21 mmHg (95%CI: 7-35), possibly via the up-regulation of insulin-like growth factor-1, as this growth factor increased the bursting pressure by 61 mmHg (95%CI: 43-79) via increased collagen deposition. Hyperbaric oxygen therapy increased the bursting pressure by 24 mmHg (95%CI: 13-34). Broad-spectrum matrix metalloproteinase inhibitors increased the bursting pressure by 48 mmHg (95%CI: 31-66) on postoperative days 3-4. In the only human study, the AL incidence was not significantly reduced in the 103 colorectal patients treated with aprotinin (11.7%) compared with the 113 placebo-treated patients (9.7%).
CONCLUSION: This systematic review identified only one randomized clinical trial and seven therapeutic agents from pre-clinical models that could be explored further for the prophylaxis of AL after colorectal surgery.
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Donmez R, Oren D, Ozturk G, Kisaoglu A, Ozogul B, Atamanalp SS. The combined effects of glutamine and growth hormone on intestinal anastomosis in the rat intra-abdominal sepsis model. J Surg Res 2012; 182:142-5. [PMID: 23474304 DOI: 10.1016/j.jss.2012.08.033] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2012] [Revised: 07/15/2012] [Accepted: 08/17/2012] [Indexed: 12/17/2022]
Abstract
AIM Intestinal anastomoses are always risky in patients who develop intra-abdominal sepsis. In this study, the effects of combined glutamine and growth hormone (GH) on healing of intestinal anastomosis following intestinal repair in the rat intra-abdominal sepsis was induced. MATERIAL AND METHODS Forty Sprague Dawley Albino rats at 10 weeks weighing between 180 and 240 g were included in the study. All the animals were divided into five groups comprising eight rats each. In the control group, no treatment was given in addition to the routine oral nutrition before and after surgery. In the other groups, following surgery, oral glutamine was given at a dose of 1 mg/kg/d in the glutamine group, subcutaneous GH was given at a dose of 1 mg/kg/d in the GH group, and combined glutamine and GH were administered at the same doses in the glutamine + GH group. In rats, a clinical model mimicking intestinal fistula was generated and fistula repair was performed, and the bursting pressure of the repair area and tissue hydroxyproline level of the repair area were calculated. RESULTS Compared with the control group, glutamine, GH, and combined groups displayed significantly higher mean bursting pressures and tissue hydroxyproline levels. CONCLUSION In order to decrease the risks originating from impaired mechanisms due to intra-abdominal sepsis, and to make anastomosis safer, combined use of glutamine and GH increases the bursting pressure of anastomosis. While the use of either of these two substances alone is effective, combined use makes this effect more prominent.
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Affiliation(s)
- Ramazan Donmez
- Department of General Surgery, Memorial Atasehir Hospital, Istanbul, Turkey
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Effects of oxidative stress on mitochondrial content and integrity of human anastomotic colorectal dehiscence: a preliminary DNA study. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2011; 25:433-9. [PMID: 21912768 DOI: 10.1155/2011/741073] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Anastomotic dehiscence is one of the most severe complications of colorectal surgery. Gaining insight into the molecular mechanisms responsible for the development of anastomotic dehiscence following colorectal surgery is important for the reduction of postoperative complications. OBJECTIVE Based on the close relationship between surgical stress and oxidative stress, the present study aimed to determine whether a correlation exists between increased levels of reactive oxygen species and colorectal anastomotic dehiscence. METHODS Patients who underwent surgical resection for colorectal cancer were divided into three groups: patients with anastomotic dehiscence (group 1); patients without dehiscence who underwent neoadjuvant radiochemotherapy (group 2); and patients without anastomotic dehiscence who did not undergo neoadjuvant radiochemotherapy (group 3). Quantitative polymerase chain reaction and real-time polymerase chain reaction assays were performed to measure nuclear DNA and mitochondrial DNA (mtDNA) content, and possible oxidative damage to nonmalignant colon and rectal tissues adjacent to the anastomoses. RESULTS mtDNA content was reduced in the colon tissue of patients in groups 1 and 2. Rectal mtDNA was found to be more damaged than colonic mtDNAs in all groups. The 4977 bp common deletion was observed in the mtDNA of tissues from both the colon and rectum of all patients. DISCUSSION Patients in groups 1 and 2 were more similar to one another than to group 3, probably due to higher levels of reactive oxygen species in the mitochondria; the greater damage found in the rectum suggests that dehiscence originates primarily from the rectal area. CONCLUSIONS The present study of mtDNA analyses of normal human colon and rectal tissues from patients with colorectal cancer is among the first of its kind.
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Intraperitoneally applied gentamicin increases collagen content and mechanical stability of colon anastomosis in rats. Int J Colorectal Dis 2009; 24:433-40. [PMID: 19050902 DOI: 10.1007/s00384-008-0614-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/12/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND Anastomotic leakage remains a serious complication in colorectal surgery, and is being caused by a multitude of factors. Recent reports reveal changes of the extracellular matrix as risk factors as well as gentamicin as a potential agent to influence wound healing. This experimental study was initiated to investigate the influence of intraperitoneally applied gentamicin on colonic anastomotic wound healing and in particular on mechanical stability, overall collagen content and collagen type I/III ratio. MATERIALS AND METHODS Sixty Sprague Dawley rats were randomized to one of two groups. In each animal, a standard transverse colonic end-to-end anastomosis was performed. Immediately postoperative, either 5 ml gentamicin (1 ml/kg bodyweight) or NaCl 0.9% was applied intraperitoneally. On postoperative days 3, 5, and 14, ten of the animals in each group were sacrificed. Measurements of the anastomosis bursting pressure were performed on postoperative days 3 and 5. At each explantation time, the collagen per protein ratio, the collagen types I/III ratio, and both the expression of MMP-2, -9, and Ki67 were analyzed. RESULTS None of the animals died. None of the rats exhibited clinical evidence of anastomotic leakage. The bursting strength in the gentamicin group was significantly elevated on postoperative day 5. Both the overall collagen content and the collagen type I/III ratio in the gentamicin group were significantly increased 3, 5, and 14 days postoperatively compared to the control group. The expression of MMP-9 was significantly elevated in the gentamicin group both 3 and 5 days postoperatively. In contrast, there were no significant differences in the expression of MMP-9 14 days postoperatively. All investigated samples demonstrated positive staining for MMP-2 and Ki67 without statistically significant differences at any term, respectively. CONCLUSIONS The present data confirm that intraperitoneally applied gentamicin is able to enhance healing and stability of colonic anastomosis due to an increase of both the overall collagen content and collagen type I/III ratio.
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Tei TM, Kissmeyer-Nielsen P, Christensen H, Flyvbjerg A. Growth hormone treatment increases transmural colonic growth in GH-deficient dwarf rats. Growth Horm IGF Res 2000; 10:85-92. [PMID: 10931746 DOI: 10.1054/ghir.2000.0144] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Growth hormone (GH) has been implicated as an important factor in the growth regulation of several visceral organs including the gastrointestinal tract. Our aim was to study the effects of GH administration on colonic growth in dwarf rats with an isolated GH deficiency. Dwarf rats were treated with recombinant human growth hormone (rhGH; 2.0 mg/kg/day) for four weeks and compared with saline treated dwarf rats and rats with normal pituitary function. The colonic wall composition was measured by means of stereological techniques. RhGH treatment of the dwarf rats increased body weight by 80% and proximal and distal colon weight by 63% and 90%, when compared with placebo treated dwarf rats (P< 0.01). The weight of the proximal colonic mucosa increased by 83% (P< 0.01), submucosa by 78% (P< 0.05), and the muscularis propria by 51% (P< 0.001) in rhGH treated dwarf rats compared with dwarf controls. The weight of the distal colonic mucosa increased by 88% (P< 0.01), submucosa by 88% (P< 0.05) and the muscularis propria by 58% (P< 0.05) compared with dwarf controls. The growth of mucosa involved all mucosal layers, with a 73 and 92% increase in the proximal and distal colon luminal surface area respectively (P< 0.001, P< 0.01). The food consumption, expressed as g/day/100 g BW was 13% higher in dwarf rats receiving rhGH than in placebo treated rats (P< 0.05) and normal control rats (P< 0.05). When weights of the GI tract compartments are corrected for the increase in body weight the effects of GH treatment were small or non-significant. RhGH administration in GH deficient dwarf rats induces visceral growth with a pronounced increase in colonic luminal surface area and growth of all layers of the colonic wall. These findings confirm the important role of GH in the regulation of intestinal growth.
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Affiliation(s)
- T M Tei
- Department of Surgery L Amtssygehuset, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
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Ziegler TR, Estívariz CF, Jonas CR, Gu LH, Jones DP, Leader LM. Interactions between nutrients and peptide growth factors in intestinal growth, repair, and function. JPEN J Parenter Enteral Nutr 1999; 23:S174-83. [PMID: 10571452 DOI: 10.1177/014860719902300602] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Several lines of evidence demonstrate that general nutritional status, specific nutrients (eg, zinc, glutamine), and certain trophic growth factors (eg, growth hormone, insulin-like growth factor I, keratinocyte growth factor, and glucagon-like peptide-2) have important interactions relevant for intestinal growth and function. Adequate nutritional status is critical for endogenous growth factor synthesis in the gut and other tissues and is an important mediator of organ responsiveness to exogenous growth factor administration. Both endogenously synthesized and exogenously administered growth factors upregulate nutrient uptake and utilization by gut mucosa, skeletal muscle, and other organs. Emerging data from both animal and human studies indicate that combinations of selected growth factors and specific nutrients may improve the growth, adaptation, and repair of the intestinal mucosa. Additional studies to determine basic mechanisms of nutrient-growth factor interactions and the safety and efficacy of treatment with combinations of specific nutrients and recombinant growth factors are needed. Results of these investigations should define new methods for support of the intestinal tract during short bowel syndrome (SBS), catabolic illness, and malnutrition.
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Affiliation(s)
- T R Ziegler
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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Silver DF, Simon A, Dubin NH, Wheeless CR. Recombinant growth hormone's effects on the strength and thickness of radiation-injured ileal anastomoses: a rat model. J Surg Res 1999; 85:66-70. [PMID: 10383839 DOI: 10.1006/jsre.1999.5611] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND Small bowel resections following radiotherapy for gynecologic cancers have resulted in significant rates of morbidity and mortality. The objective of this study was to evaluate the effect of rGH on the breaking strength and thickness of radiation-injured ileal anastomoses in an animal model. MATERIALS AND METHODS Sprague-Dawley rats were treated with 1800 cGy of pelvic irradiation in a single fractionation. Seventeen weeks following pelvic teletherapy an ileo-ileostomy was performed. The rats were randomized to receive 2.0 mg/kg/day of rGH for 7 days or placebo. On the seventh postoperative day a segment of ileum surrounding the anastomosis was resected. The segments were tested for breaking strength or were histologically measured for anastomotic thickness. RESULTS The ileal anastomotic breaking strength in the rGH group was 181 +/- 8.4 g (mean +/- standard error). The breaking strength of ileal anastomoses in the placebo group was 133 +/- 6.9 g (P < 0.05). The rGH group demonstrated a greater anastomotic thickness (1.65 +/- 0.116 mm) than the placebo group (1.17 +/- 0.113 mm, P < 0.05). Of placebo rats 14.7% developed anastomotic leaks compared to 0% of rGH-treated animals (P < 0.05). CONCLUSIONS RGH increased the ileal anastomotic breaking strength by 36% in radiated rats. The anastomotic leak rate was reduced from 14.7% in the placebo group to 0% in the rGH group. These findings correlated with a 41% increase in the thickness of the anastomotic connective tissue in the rGH group. Clinical investigation in selected patients is warranted.
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Affiliation(s)
- D F Silver
- Department of Gynecology and Obstetrics, The Union Memorial Hospital, Baltimore, Maryland, USA
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Karahasanoglu T, Altinli E, Hamzaoglu I, Paksoy M, Yeşildere T, Alemdaroglu K. Effect of growth hormone treatment on the healing of left colonic anastomoses in protein-malnourished rats. Br J Surg 1998; 85:931-3. [PMID: 9692566 DOI: 10.1046/j.1365-2168.1998.00696.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Malnutrition is known to affect wound healing but it is not known with certainty whether or not postoperative hyperalimentation can reverse this defect. The present study was designed to examine the effects of recombinant human growth hormone (hGH) on left colonic anastomoses in malnourished rats. METHODS Experimental animals were allocated randomly into four groups. In groups 1 and 2 animals were fed with normal diet for 10 days before surgery. In groups 3 and 4 animals were fed with a low-protein diet. Left colonic anastomoses were performed in all animals. Following surgery, rats in groups 1 and 3 received hGH whereas rats in groups 2 and 4 were injected with saline as control. Bursting pressure and hydroxyproline levels on day 4 after operation were used to determine anastomotic healing. RESULTS Bursting pressure was lower in the malnourished rats than those fed with normal diet (P< 0.05). Bursting pressure was higher in normally fed rats which were given hGH. No significant differences could be noted between malnourished control rats and those receiving hGH. CONCLUSION These results suggest that hGH strengthened the left colonic anastomoses in rats fed a normal diet, but could not reverse the negative effects of malnutrition on colonic anastomoses.
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Affiliation(s)
- T Karahasanoglu
- Department of Surgery, Istanbul University Cerrahpasa Medical School, Istanbul University Veterinary Faculty, Turkey
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Türkçapar AG, Demirer S, Sengül N, Ersöz S, Kuterdem E, Renda N, Kuzu I. The adverse effects of octreotide on the healing of colonic anastomoses in rats. Surg Today 1998; 28:279-84. [PMID: 9548309 DOI: 10.1007/s005950050121] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Octreotide, a long-acting somatostatin analogue, is widely used in gastrointestinal hypersecretory states and also for endocrine tumors in an attempt to inhibit the paracrine hormones. Although it is well known that octreotide inhibits trophic and anabolic hormones, no research has been conducted on its adverse effects on wound healing. In the present study, groups of rats were given 20 mcg/kg/day octreotide and 100 mg/kg/day hydrocortisone, the latter being the negative control group, starting 5 days preoperatively. The colonic anastomoses were assessed for healing on postoperative days (PODs) 5 and 8 by determining the bursting pressure of the anastomoses, performing histopathological analysis, and measuring the hydroxyproline content of the anastomotic tissues. Octreotide was found to affect anastomotic healing negatively on both PODs 5 and 8, but the negative effect of hydrocortisone was significant only on POD 8. No significant difference was found between the adverse effects of the two agents on POD 8. These findings indicated that octreotide has an adverse effect on the healing of colonic anastomoses in rats.
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Affiliation(s)
- A G Türkçapar
- Department of General Surgery, Ankara University Medical School, Sihhiye, Turkey
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Abstract
Healing in the GI tract is rapid when free of complications: Unlike cutaneous healing, in which progress can be observed on a daily basis and intervention instituted early if necessary, healing of the intestinal anastomosis is anatomically obscured from inspection, allowing the surgeon only the patient's parameters of general well-being to judge the success of the operation. For the same reason, complications usually require re-operation, with the associated morbidity of a laparotomy and additional general anesthetic. This places a great responsibility on the surgeon to be cognizant of all the preoperative, intraoperative, and postoperative factors relating to anastomotic healing that might compromise the healing process. Bearing these in mind, along with attention to technical detail, should limit complications to an acceptable level. Patients most at risk are (1) those who perioperatively develop physiologic problems that lead to shock, hypoxia, and resultant anastomotic ischemia, (2) those with radiation-induced tissue injury, (3) those with sepsis, and (4) those with preoperative bowel obstruction. Malnourishment, malignancy, diabetes, steroids, and age also influence outcome to varying degrees. Future advancement in the field of GI healing lies in our ability to manipulate the early struggle between collagen synthesis and collagen breakdown. A profound understanding of the molecular and biochemical pathways and the factors that control them will bring us closer to this goal. Clinically, this may be accomplished by the introduction of wound healing enhancers into the anastomotic site, possibly by incorporating them into suture materials, biofragmentable anastomotic rings, or staple materials. Already much is known about the influence of different cytokines and growth factors on collagen regulation, knowledge that will help resolve many of the long-standing problems associated with GI surgery.
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Affiliation(s)
- F J Thornton
- Department of Surgery, Sinai Hospital of Baltimore, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
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Chen K, Nezu R, Inoue M, Wasa M, Iiboshi Y, Fukuzawa M, Kamata S, Takagi Y, Okada A. Beneficial effects of growth hormone combined with parenteral nutrition in the management of inflammatory bowel disease: an experimental study. Surgery 1997; 121:212-8. [PMID: 9037234 DOI: 10.1016/s0039-6060(97)90292-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Growth hormone (GH) improves net protein anabolism and stimulates wound healing. Although GH is also known to exert the trophic effect on the intestinal tract, its role in the healing of intestinal ulceration is not known. The aim of this study was to evaluate the effects of exogenous GH coinfused with parenteral nutrition (PN) in an experimental model of inflammatory bowel disease in rats. METHODS All rats underwent central venous cannulation and were randomized to two groups after induction of small intestinal ulceration with indomethacin. Both groups received the same PN formula. In addition, the GH group (n = 10) received subcutaneous injections of human GH at a dose of 1.0 IU/kg daily for 4 days, whereas the control group (n = 10) received injections of normal saline solution. Nitrogen balance, macroscopic inflammation score, intestinal myeloperoxidase activity, DNA content, and mucosal permeability were determined for each rat. Insulin-like growth factor-I (IGF-I) mRNA was detected by reverse transcription and polymerase chain reaction. RESULTS Administration of GH significantly improved the cumulative nitrogen balance, ameliorated the gross inflammation score, and decreased intestinal myeloperoxidase activity. Similarly, intestinal permeability was significantly decreased in the GH group as compared with the control group. GH treatment resulted in increased plasma concentration of IGF-I and IGF-I mRNA expressions in both the liver and the small intestine compared with those in the control group. CONCLUSIONS Exogenous GH plays an important role in accelerating intestinal healing in an experimental model of small bowel ulceration in rats. The mechanisms may include the stimulated IGF-I production, which thereafter augments intestinal epithelial cell growth.
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Affiliation(s)
- K Chen
- Department of Pediatric Surgery, Osaka University Medical School, Japan
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Petersen TI, Kissmeyer-Nielsen P, Flyvbjerg A, Laurberg S, Christensen H. Effect of insulin-like growth factor I (IGF-I) administration on the healing of colonic anastomoses in rats. Int J Colorectal Dis 1996; 11:19-24. [PMID: 8919336 DOI: 10.1007/bf00418850] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The gastrointestinal tract is highly responsive to the tropic effect of growth hormone (GH). GH stimulates the healing of colonic anastomoses either directly or through insulin-like growth factor I (IGF-I) since specific GH receptor as well as IGF-I receptor have been demonstrated in colon. AIM To determine whether exogenous treatment with IGF-I could stimulate the healing of left colonic anastomoses in rats. METHODS After colonic anastomotic operations adult rats were randomised to treatment with either IGF-I (500 mu g per day) or vehicle (controls). Anastomotic breaking strength and collagen deposition were determined at day after surgery. RESULTS IGF-I treatment increased the anastomotic collagen content by 23% compared with controls. This resulted in a lower extensibility of the anastomosis (P < 0.05), whereas the anastomotic breaking strength did not differ between groups. The treatment resulted in a 3 fold increase in serum IGF-I of IGF-I treated rats, compared to controls. The postoperative body weight increased by 5% in the IGF-I rats from day 0 to day 3, while the control group had a weight loss of 2% in the same period (P < 0.001). CONCLUSION Treatment of colon-operated rats with IGF-I increased the postoperative body weight and stimulates the collagen deposition of left colonic anastomoses, whereas the anastomotic strength may be unaffected by IGF-I treatment.
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Affiliation(s)
- T I Petersen
- Department of Surgery, University Hospital of Aarhus, Denmark
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Ziegler TR. Molecular Mechanisms of Intestinal Injury, Repair, and Growth. UPDATE IN INTENSIVE CARE AND EMERGENCY MEDICINE 1996. [DOI: 10.1007/978-3-642-80224-9_3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Kissmeyer-Nielsen P, Christensen H, Laurberg S. Trophic effects of biosynthetic growth hormone on normal and defunctioned left colon in rats. Scand J Gastroenterol 1995; 30:246-51. [PMID: 7770714 DOI: 10.3109/00365529509093272] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND In rats with diverting colostomies the effects of growth hormone can be differentiated from the actions of fecal passage. METHODS After sham operation or diverting colostomy rats were treated with biosynthetic growth hormone (b-hGH) for 4 weeks. RESULTS In defunctioned colon of b-hGH-treated rats there were increases in mucosal surface area and the weight of mucosa and muscularis propria compared with the atrophic colon of saline-treated rats. The breaking strength of defunctioned colon rings was greater and the defatted dry weight and hydroxyproline content of these specimens were also increased. In intact colon b-hGH stimulated luminal surface area, the weight of mucosal and submucosal layers, and the hydroxyproline content compared with controls. The breaking strength was highest in specimens from saline-treated rats. CONCLUSIONS B-hGH has a growth-promoting role throughout the whole thickness of the colonic wall in rats also in the absence of fecal passage.
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Christensen H, Flyvbjerg A, Orskov H, Laurberg S. Effect of growth hormone on the inflammatory activity of experimental colitis in rats. Scand J Gastroenterol 1993; 28:503-11. [PMID: 8391716 DOI: 10.3109/00365529309098257] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The effect of daily treatment with 2.0 mg biosynthetic human growth hormone per kilogram body weight or isotonic NaCl (controls) on experimental colitis was investigated in rats. Colonic inflammation was induced by instillation of trinitrobenzene sulfonic acid (TNB) intraluminally into the left colon. Untreated NaCl-instilled rats were used for comparison with intact colon. Four days after TNB instillation the growth hormone-treated rats had lower macroscopic and microscopic damage scores and less infiltration of neutrophils, measured as myeloperoxidase activity (MPO), than controls. The biomechanical properties of the colon showed that the breaking strength and energy absorption were reduced in the control rats with colitis compared with intact colon, whereas the rats treated with growth hormone had unchanged strength and energy absorption. The differences in MPO activity, damage scores, and biomechanical properties were associated with a higher concentration of insulin-like growth factor I in serum from growth hormone-treated rats after 4 days than controls. Finally, the growth hormone-treated rats regained their initial body weight after 7 days, in contrast to the body weight of control rats, which remained 11% lower than their initial body weight.
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Affiliation(s)
- H Christensen
- Dept. of Connective Tissue Biology, University of Aarhus, Denmark
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