Effects of serum from trypsin inhibitor fed rats on enzyme secretion and protein synthesis by exocrine pancreatic cells

Oral feeding of trypsin inhibitor is known to stimulate rat pancreatic enzyme secretion and cause hypertrophy of the pancreas. In an attempt to detect a possible serum factor(s) responsible, the effects of serum from trypsin inhibitor fed rats on enzyme secretion and protein synthesis by isolated exocrine rat pancreatic cells in suspension were studied.

Serum from trypsin inhibitor fed rats stimulated the secretion of pancreatic enzymes significantly more than serum from control rats. The data suggest that a humoral factor or factors may be involved in the stimulation of pancreatic enzyme secretion by oral trypsin inhibitor.

Serum from trypsin inhibitor fed rats as well as serum from control rats stimulated the ³H-leucine incorporation into protein (protein synthesis) to a significant extent. There was, however, no difference in the effects of the two types of sera in this respect.     

Glucose metabolism parameters during an oral glucose tolerance test in patients with autosomal dominant polycystic kidney disease

Abstract

Objective. The aim of the study was to estimate the pancreatic beta cell function and insulin resistance indexes in a group of Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with normal kidney function and no previous diabetes mellitus diagnosis. Methods. A total of 49 adult patients with ADPKD aged 36 ± 11 years, and 50 healthy controls, all of Caucasian origin, were included in the study. Blood glucose, insulin and C-peptide concentrations were measured during an oral glucose tolerance test (OGTT with 75 g glucose) performed according to WHO recommendations in all subjects. Results. The insulin/glucose ratio at the 30th and 120th minute of the OGTT and the insulinogenic index [(insulin at 30 min – insulin at 0 min)/glucose at 30 min] were significantly lower (p = 0.018, p = 0.031 and p = 0.013, respectively) in the ADPKD group. Four other indexes of beta cell function were lower with the borderline statistical significance (p = 0.054–0.076) than in controls. None of the calculated insulin sensitivity indexes differed between the study and control groups. Conclusions. Presence of ADPKD in patients with normal kidney function is associated with impaired beta cell function after an oral glucose load, without a significant decrease in insulin sensitivity.     

Case report. Laparoscopic pancreatic cystogastrostomy

Summary

Definitive management of pancreatic pseudocysts has traditionally involved surgical drainage via laparotomy. Minimally invasive percutaneous and endoscopic techniques for pseudocyst treatment have recently been described. The advantages of minimally invasive surgical techniques have led to the identification of new therapeutic applications of laparoscopy. We describe the technique we used to perform laparoscopic pancreatic cystogastrostomy. Although long-term predictions of morbidity, mortality and recurrence rates cannot be made based on a single case report, a laparoscopic approach to pancreatic pseudocyst is possible and may become an attractive treatment option.     

The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.     

Elimination of endoplasmic reticulum stress and cardiovascular,type 2 diabetic,and other metabolic diseases

Abstract

Multiple factors including unhealthy living habits influence the life-maintaining functions of the endoplasmic reticulum (ER) and induce ER stress and metabolic abnormalities. The ER responds to the disturbances by activating mechanisms that increase the capacity to eliminate ER stress. This article elucidates the effects of ER activation that eliminates both ER stress and associated cardiovascular, type 2 diabetic (DM2), and other metabolic diseases. ER-activating compounds eliminate ER stress by lowering elevated cholesterol, regress atherosclerosis, decrease cardiovascular mortality, reduce blood glucose and insulin, and, together with the normalization of glucose–insulin homeostasis, remove insulin resistance, pancreatic β-cell failure, and DM2. A deficient cytochrome P450 activity in hepatic ER leads to cholesterol accumulation that induces stress and xanthoma formation, whereas P450-activating therapy up-regulates apolipoprotein AI and LDLR genes, down-regulates apolipoprotein B gene, and produces an antiatherogenic plasma lipoprotein profile. The ER activation reduces the stress also by eliminating hepatic fat and converting saturated fatty acids (FAs) to unsaturated FAs. Cognitive processes require gene expression modification, and preclinical studies indicate that ER-activating therapy improves cognition. Promotion of healthy lifestyle choices and indicated therapies are key factors in the prevention and elimination of ER stress and associated global health problems.     

Hormone-based therapies in the regulation of fuel metabolism and body weight

Background: The integrated central actions of hormones secreted from pancreatic islets, the gut and adipocytes regulate both energy homeostasis and body weight. Dysregulation in these neurohormonal pathways probably contributes to pathogenesis of obesity and type 2 diabetes. Objective: To examine hormone-based therapies targeting these interrelated pathways as potential treatments for obesity and diabetes. Methods: Preclinical and clinical data on therapies based on hormones secreted from the pancreas (glucagon, insulin, amylin and pancreatic polypeptide), gut (glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, cholecystokinin and peptide YY) and adipose tissue (leptin and adiponectin) as potential treatments for diabetes and obesity are reviewed. Results/conclusions: In diabetes, hormone-based treatments have translated into new clinical platforms including insulin analogs, the GLP-1-like peptide receptor agonist exenatide and amylinomimetic pramlintide, which due to their complex interplay and the progressive nature of diabetes, can be utilized in different settings. Various peptide hormones and agonists/antagonists are currently under investigation as new approaches to treatment of obesity and diabetes.     

Human VIP-α: an emerging biologic response modifier to treat primary pulmonary hypertension

Primary pulmonary hypertension (PPH) is a rare life-threatening disorder of unknown etiology manifested by chronic elevation of pulmonary arterial pressure. Given that pulmonary vasoconstriction, endothelial and vascular smooth muscle cell proliferation and in situ thrombosis contribute appreciably to the evolution of PPH, treatment with vasodilators, antiproliferative drugs and anticoagulants, alone or in combination, constitute the pharmacologic standard of care. To this end, long-term administration of oral calcium channel blockers, prostacyclin analogs by various routes and oral endothelin-1 receptor antagonists, alone or in combination, is efficacious in treating patients with PPH. Unfortunately, efficacy is hampered by poor stability, delivery and bioavailability, and by systemic toxicity. Hence, there is an ongoing need to develop and test new drugs to treat patients with PPH. To address this issue, a novel, targeted, long-acting, biocompatible and safe sterically stabilized liposomal and micellar formulation of human vasoactive intestinal peptide (VIP) was developed and tested for human use: the 28-amino acid pleiotropic biologic response modifier, human VIP-α. The long-lasting salutary effects of phospholipid-associated VIP on vasomotor tone and arterial pressure were expressed at low concentrations solely in diseased animals and were independent of its route of administration. Thus, the author proposes that human VIP-α could be developed as a safe long-acting drug to treat patients with PPH.     

血糖紊乱与胰腺癌患者生存时间相关性的研究

目的:探讨血糖紊乱与胰腺癌患者生存时间的关系。方法:回顾性分析44例胰腺癌患者的临床资料,根据血糖水平分成血糖正常组、糖尿病前期组及糖尿病组,观察各组患者的年龄分布、通过随访了解糖代谢紊乱与胰腺癌患者生存时间的关系。结果:本组胰腺癌患者伴糖尿病前期的比例为27.27%,胰腺癌伴糖尿病的比例为31.84%,胰腺癌患者伴有糖耐量异常患者生存时间长于胰腺癌合并糖尿病患者(P<0.05),胰腺癌患者不伴有糖耐量异常的生存时间长于合并糖尿病患者(P<0.05)。结论:胰腺癌患者出现糖代谢紊乱的比例较高,糖代谢紊乱的胰腺癌患者生存时间明显短于无糖代谢异常的患者。     

单纯性胰腺创伤后大鼠胰腺细胞增殖状况的实验研究

目的：构建大鼠单纯性胰腺创伤模型观察胰腺细胞增殖变化特点并探讨胰腺细胞增殖与组织损伤的关系。方法将60只Wistar大鼠分为2组：撞击组（采用BIM‐Ⅲ生物撞击机构建胰腺创伤大鼠模型,40只）和对照组（假手术组,20只）,每组大鼠于建模后6、24、72 h ,7 d处死,采用分光光度法检测各组大鼠血清淀粉酶（AMS）、脂肪酶（LPS）活性,通过TUNEL染色和流式细胞技术测定胰腺组织细胞死亡并分析细胞周期分布特点,Western blot测定胰腺组织Bcl‐2、Bax蛋白的表达。结果撞击组大鼠LPS活性升高时相点晚于AMS且持续时间较长,TUNEL染色、流式细胞检测、Western blot结果揭示胰腺创伤可诱导胰腺组织细胞凋亡和代偿性增生。胰腺细胞增殖变化特点表明胰腺创伤后的最佳治疗时间是发病24 h内。结论同时检测AMS和L PS有助于判定胰腺的外分泌功能受损情况。