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Objective: To investigate the beneficial outcomes of intraoperative enteral feeding in free‐flap regeneration after extended head and neck cancer resection and flap reconstruction surgery. Study Design: A pilot randomized, double‐blind, placebo‐controlled clinical trial. Setting: Single tertiary care center. Methods: Patients with advanced head and neck cancers requiring radical tumor resections and free‐flap reconstruction were randomly assigned to receive intraoperative enteral nutrition feeding (100 kcal/100 mL at 10‐20 mL/h) via a nasogastric tube during free‐flap reconstruction (n = 28) or continue fasting (n = 28). The primary outcome was impaired free‐flap regeneration that required surgical reintervention within 90 days after the operation. Participants were enrolled between April 2020 and January 2022; the 90‐day follow‐up ended in April 2022. Results: The incidence of total or partial flap failure was similar between the 2 groups (14.2% or n = 4 in each group), but the rate of wound dehiscence or edge necrosis was significantly reduced in the feeding group (n = 6 vs 0 for fasting vs feeding; absolute risk reduction, 25.0% [95% confidence interval, 6.9‐43.0]%; p = 0.022). Hospital stay length was shorter (p = 0.042) and hand grip strength was better preserved (p = 0.025) in the feeding group. Plasma concentrations of interleukin (IL)‐6 and IL‐8 after the operation increased significantly more in the fasting group. Perioperative adverse events did not differ between the 2 groups. Conclusion: Perioperative enteral feeding is a simple, safe, and effective approach to improve perioperative systemic catabolism and proinflammatory reactions, thereby enhancing early wound regeneration after major operations. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats. Methods and results: Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area. Conclusion: Administration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes. [ABSTRACT FROM AUTHOR]

Objective: The blood flow in the arteriovenous (AV) fistula is significantly reduced in diabetic patients. Statins are known to mediate pleiotropic effects in the vascular endothelium and attenuate inflammatory responses. This study tested the vascular protective effect of rosuvastatin in an experimental model of AV fistula. Methods: One week after the induction of diabetes mellitus (DM) in rats, a fistula was created in the abdominal aorta and inferior vena cava. Rats received placebo or rosuvastatin (15 mg/kg/day) in chow for 2 weeks. The blood flow in the venous segments of the fistula was measured. The expression of proinflammatory genes and the generation of superoxide in the venous fistula were examined. Results: The blood flow and luminal diameter of the AV fistula was significantly enhanced in animals treated with rosuvastatin. Rosuvastatin attenuated the expression of inducible nitric oxide synthase, NADPH oxidase, and monocyte chemotactic protein-1 in the fistula. The levels of superoxide anions and proinflammatory cytokines were also suppressed in rosuvastatin-treated animals. Neointimal formation in the AV fistula was not affected following treatment with rosuvastatin. Conclusions: We demonstrated that rosuvastatin improves luminal dilatation and blood flow in the AV fistula of subjects with DM. These vascular protective effects of rosuvastatin are most likely mediated by the attenuation of proinflammatory activities in the remodeled vasculature. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Polymorphonuclear leucocyte (PMN) numbers are an indicator of the degree of acute lung inflammation. However, there is no standardized system for accurately quantifying their numbers in tissue sections. Also, the effect of lung inflation on the quantification of PMN''s is usually overlooked. Lung specimens obtained from clinical biopsies are usually deflated, while inflated lung tissue is commonly used in experimental studies. We report a method, which is independent of the degree of inflation, for measuring the degree of PMN infiltration in the both inflated and non-inflated lungs. Using light microscopy, we counted the numbers of PMN and non-PMN cells in 240 fields from each of five inflated and five non-inflated lung sections and calculated a ratio of PMN: non-PMN cells (the PMN ratio). The effect on accuracy and precision of number of fields counted was investigated by randomly selecting 200, 160, 80 or 40 readings from the original 240 fields. The mean PMN ratio, its 95% confidence interval (CI) and the coefficient of variation (CV) were calculated for each of the four levels of sampling. Both CI and CV increased as the number of readings decreased. Inflated lung tissue had consistently higher values for CV compared to non-inflated lung. In practice, we recommend that for both inflated and non-inflated lungs, 80–160 fields (approximate 0.23–0.45 mm2 of absolute area evaluated) need to be counted to yield a PMN ratio with acceptable accuracy and precision. The PMN ratio provides a simple and objective way of quantifying the degree of acute inflammation in clinical histopathology and experimental toxicology studies involving lungs. It is suitable for use in research of lung inflammation, and as an accessory diagnostic tool and an objective descriptor for clinical histopathology. [Copyright &y& Elsevier]

Background Diabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. Materials and methods Excisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0.5 μg/kg/d, i.p. ) for 2 wk. The final-to-initial wound area ratio was measured for 14 d. Levels of superoxide anions and proinflammatory cytokines in the wound were determined. Angiogenesis was assessed using the Matrigel assay. Expression levels of proangiogenic factors and extracellular matrix proteins were measured. Results Ex4 restored wound closure in diabetic rats and significantly suppressed the generation of superoxide anions and interleukin-6 in wounds. The number of circulating endothelial progenitor (CD34 + /KDR + ) cells increased significantly in Ex4-treated diabetic rats, which also showed increased capillary tube formation. Protein levels of vascular endothelial growth factor receptor-2, phosphorylated endothelial nitric oxide synthase, matrix metalloproteinase-2, and transforming growth factor-β were increased in diabetic rats receiving Ex4 therapy. Ex4-enhanced vascularity, dermal regeneration, and epidermal regeneration, while it decreased hemorrhaging and increased the number of proliferative cells in the dermis. Conclusions Ex4 accelerated excisional wound healing in subjects with diabetes. Glp-1R activation attenuates inflammatory response and enhances angiogenesis during the early proliferation phase of wound healing in diabetic subjects, while it enhances transforming growth factor-β/matrix metalloproteinase-mediated regeneration during the maturation phase. These results suggest that Ex4 could be used as a standard hypoglycemic agent in diabetic patients with wound injury. [ABSTRACT FROM AUTHOR]

Abstract: Background: The development of warm–cold ischemia–reperfusion (IR) injury of the kidney grafts is inevitable during renal transplantation. However, there is currently no definite renoprotective strategy available in the protection of the graft tissue. In the present study, we compared the renal protection of preconditioning isoflurane with N-acetylcysteine (NAC) in a novel rat model of warm–cold renal IR injury. Materials and methods: Adult Sprague–Dawley rats were randomly assigned to receive inhaled isoflurane (1.5% for 2 h), NAC (1 g/kg, intra-arterial injection) or placebo before the induction of brief warm ischemia (10 min) followed by cold ischemia (45 min) periods. Plasma levels of creatinine and tissue inflammatory reaction in the kidney were analyzed 72 h after reperfusion. Results: Elevated plasma level of creatinine and urea indicated the development of acute renal injury secondary to IR injury. The creatinine levels were reduced in animals pretreated with inhaled isoflurane and NAC, and the level was more significantly decreased in the isoflurane-treated group. Preconditioning with volatile isoflurane also significantly suppressed the tissue myeloperoxidase activity and expression of the inducible nitric oxide synthase. Immunostaining confirmed that myeloperoxidase expression was most significantly attenuated in the glomerulus and peritubular capillaries of rats pre-exposed to isoflurane. Conclusions: We present the first study demonstrating that the administration of volatile isoflurane before induction of experimental warm–cold renal IR injury provides preconditioning renoprotective effect, which is superior to the treatment with NAC. The beneficial renoprotective effect of isoflurane is most likely mediated by attenuation of proinflammatory reaction in the injured kidney. [Copyright &y& Elsevier]