Ozlem Elpek

Differential changes in Substance P, VIP as well as neprilysin levels in patients with gastritis or ulcer

The protective effect of capsaicin-sensitive sensory nerve (CSSN) activation was recently demonstrated in human gastric mucosa. We here examined changes in neuropeptides, specifically Substance P (SP), calcitonin-gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) in patients with chronic gastritis or ulcer. Furthermore changes in neprilysin levels, which hydrolyse these neuropeptides, were determined. Gastric biopsies were obtained from both lesion- and normal-appearing mucosa of 57 patients. The presence of H. pylori infection was verified with rapid urease assay. Neuronal and non-neuronal levels of SP, VIP, CGRP and neprilysin activity were determined in freshly frozen biopsies. Immunohistochemical localization of neprilysin was performed in 30 paraffin embedded specimens. We here found that neuronal SP levels decreased significantly in normally appearing mucosa of patients with gastritis while levels of non-neuronal SP increased in diseased areas of gastritis and ulcer. The presence of H. pylori led to further decreases of SP levels. The content of VIP in both disease-involved and uninvolved mucosa, and expression of neprilysin, markedly decreased in patients with gastritis or ulcer. Since VIP, as well as SP fragments, formed following hydrolysis with neprilysin is recognized to have gastroprotective effects, decreased levels of VIP, SP and neprilysin may predispose to cellular damage.

Pentoxifylline therapy attenuates intestinal injury in rat pups with hypoxic ischemic encephalopathy

Abstract Aim: The aim of this study was to evaluate the effects of post-ischemic pentoxifylline (PTX) therapy on the gut injury in neonatal rat model of hypoxic ischemic encephalopathy (HIE). Methods: Seven-day-old Wistar rat pups (n = 24) of either sex, delivered spontaneously, were used in this experimental study. Seven-day-old rat pups were randomly divided into three groups. Control group (n = 8): after median neck incision was made, neither ligation nor hypoxia was performed. Hypoxia group (n = 8): 0.5 ml of saline was injected intraperitoneally immediately after hypoxia. Pentoxifylline + Hypoxia group (n = 8): the rat pups were administered intraperitoneally 60 mg/kg of PTX immediately after hypoxia. Eight rats from all groups were sacrificed 24 h after drug administration. The ischemic injury was scored at least six sections at three different levels using histopathologic injury scores (HIS). Results: Induction of hypoxia/reoxygenation (H/R) increased mean HIS levels significantly at 24 h in the intestinal tissue samples in the hypoxia group as compared with the control group. Induction of H/R decreased means HIS levels significantly at 24 h in the intestinal tissue samples in the PTX + hypoxia group as compared with the hypoxia group. Conclusion: In this experimental study, PTX significantly attenuated H/R-induced intestinal injury in neonatal rat model of HIE. These findings indicate that PTX can reduce the intestinal H/R injury.

Diclofenac induced gastrointestinal and renal toxicity is alleviated by thymoquinone treatment

The aim of this study was to investigate whether thymoquinone (TQ) could alleviate diclofenac (DCLF)-induced gastrointestinal and renal toxicity in rats. Diclofenac was administered via intramuscular injection twice daily for 5 days and TQ was given by gavage for the same period. Hematological and biochemical profiles were measured with autoanalyzers while reactive oxygen/nitrogen species (ROS/RNS) generation and total antioxidant capacity (TAC) were assayed by standard kits. Tissue injuries were evaluated by microscopy and histopathological scoring. Diclofenac treatment caused kidney and liver function test abnormalities, reduced hematocrit and hemoglobin levels but increased WBC and platelet counts. Histopathological findings showed renal tubular damage, gastrointestinal lesions and increased fibrosis in DCLF treated rats. Thymoquinone administration, along with DCLF treatment, attenuated hematological test abnormalities and DCLF induced renal functional impairment as evident by significantly restored serum creatinine and blood urea nitrogen levels. Similarly, TQ treatment significantly alleviated liver function test abnormalities and decreased tissue injury in the stomach and duodenum. Diclofenac treatment caused increased ROS/RNS formation and decreased TAC in the kidney, stomach and duodenal tissue. Thymoquinone administration increased gastrointestinal and renal TAC in DCLF treated rats. These results indicate that TQ could ameliorate gastrointestinal and renal toxicity induced by high dose DCLF treatment.

The repair of a large duodenal defect by a pedicled gastric seromuscular flap

PurposeThe aim was to evaluate the efficacy of a pedicled gastric seromuscular flap for the closure of a large duodenal defect.MethodsA large defect of the second duodenal part was repaired by a gastric seromuscular flap. Of 35 rats, 9 rats were euthanized at 2 weeks, 12 rats at 2 months, and 14 rats at 4 months for the histopathological evaluation of the patch and normal duodenum (control) adjacent to the patch.ResultsAll rats survived. The patch was completely covered by neomucosa in all of the 4-month rats, and in 8 of the 12 2-month rats. The villous height of the neomucosa was significantly higher in the 4-month rats in comparison to the other rats (P < 0.001). However, a normal duodenum had higher villi than in that of the patches (P < 0.001). The crypt density of the neomucosa was significantly increased in the 4-month rats in comparison to the 2-week and the 2-month rats (P < 0.001 and P < 0.05 group, respectively). The crypt density was higher in the controls than in the neomucosa covered patch of the 2-week and the 2-month rats (P < 0.001 and P < 0.05, respectively). The crypt depth of the neomucosa increased significantly in the 4-month rats and in the controls versus the 2-week rats (P < 0.05).ConclusionThe new mucosal barrier overlaying the patch appeared to be satisfactory. This technique, which has not been described previously, is likely to be useful for the repair of the large duodenal defect.

ADAM proteases involved in inflammation are differentially altered in patients with gastritis or ulcer

ADAM metallopeptidase domain (ADAM)9, 10 and 17 have α-secretase activity that regulates ectodomain shedding of factors involved in inflammation, cell proliferation, angiogenesis, and wound healing. The secretase activity of ADAM proteins is known to induce an inflammatory response. However, under certain conditions, a lack of secretase activity may induce inflammation suggesting differential roles of ADAM proteins with secretase activity. To the best of our knowledge, the present study evaluated the changes in α-secretase activity and expression of associated ADAM proteases (ADAM9, 10 and 17) in the gastric mucosa of patients with gastritis and ulcers, for the first time. Gastroduedonal mucosal samples from 42 patients were snap-frozen to determine changes in α-secretase activity. Twenty-four of these patients had gastritis, 9 patients had duedonal ulcers and 9 patients did not have any pathological changes. Paraffin-embedded gastric specimens (n=32) were used for immunohistochemical detection of ADAM9, ADAM10 and ADAM17. α-secretase activity of the gastric mucosa of healthy subjects was significantly higher compared with the uninvolved mucosa of patients with gastritis or ulcer. These results were associated with the immunohistochemical staining results, which demonstrated that ADAM10 expression markedly decreased in glandular epithelial cells and ADAM9 expression was lost in foveolar epithelial cells of gastric mucosa adjacent to ulcer. However, ADAM17 expression was increased in the normal gastric mucosa of patients with bleeding peptic ulcers and in the gastric mucosa adjacent to the ulcer suggesting a counteracting role of ADAM17. Decreased ADAM9 and 10 expression, and an associated decrease in α-secretase activity may predispose to chronic gastritis and ulcer. Further studies are required to determine the possible etiological role of increased ADAM17 expression.