Effects of Radix Rehmanniae on gastric acid secretion and gastric ulcr formation in rats

ＥｆｅｃｔｓｏｆＲａｄｉｘＲｅｈｍａｎｎｉａｅｏｎｇａｓｔｒｉｃａｃｉｄｓｅｃｒｅｔｉｏｎａｎｄｇａｓｔｒｉｃｕｌｃｒｆｏｒｍａｔｉｏｎｉｎｒａｔｓＷＡＮＧＺｈｕＬｉ１ａｎｄＬＩＬｉｎ２Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｒａｄｉｘｒｅｈｍａｎｎｉａｅ...     

Prospective evaluation of insulin and incretin dynamics in obese adults with and without diabetes for 2 years after Roux-en-Y gastric bypass

Aims/hypothesis

In this prospective case–control study we tested the hypothesis that, while long-term improvements in insulin sensitivity (S_I) accompanying weight loss after Roux-en-Y gastric bypass (RYGB) would be similar in obese individuals with and without type 2 diabetes mellitus, stimulated-islet-cell insulin responses would differ, increasing (recovering) in those with diabetes but decreasing in those without. We investigated whether these changes would occur in conjunction with favourable alterations in meal-related gut hormone secretion and insulin processing.

Methods

Forty participants with type 2 diabetes and 22 participants without diabetes from the Longitudinal Assessment of Bariatric Surgery (LABS-2) study were enrolled in a separate, longitudinal cohort (LABS-3 Diabetes) to examine the mechanisms of postsurgical diabetes improvement. Study procedures included measures of S_I, islet secretory response and gastrointestinal hormone secretion after both intravenous glucose (frequently-sampled IVGTT [FSIVGTT]) and a mixed meal (MM) prior to and up to 24 months after RYGB.

Results

Postoperatively, weight loss and S_I-_FSIVGTT improvement was similar in both groups, whereas the acute insulin response to glucose (AIRglu) decreased in the non-diabetic participants and increased in the participants with type 2 diabetes. The resulting disposition indices (DI_FSIVGTT) increased by three- to ninefold in both groups. In contrast, during the MM, total insulin responsiveness did not significantly change in either group despite durable increases of up to eightfold in postprandial glucagon-like peptide 1 levels, and S_I-MM and DI_MM increased only in the diabetes group. Peak postprandial glucagon levels increased in both groups.

Conclusions/interpretation

For up to 2 years following RYGB, obese participants without diabetes showed improvements in DI that approach population norms. Those with type 2 diabetes recovered islet-cell insulin secretion response yet continued to manifest abnormal insulin processing, with DI values that remained well below population norms. These data suggest that, rather than waiting for lifestyle or medical failure, RYGB is ideally considered before, or as soon as possible after, onset of type 2 diabetes.

Trial registration

ClinicalTrials.gov NCT00433810

     

Effects of Zuogui Wan on neurocyte apoptosis and down-regulation of TGF-β_1 expression in nuclei of arcuate hypothalamus of monosodium glutamate-liver regeneration rats

AIM:To inquire into the effects and mechanism of ZuoguiWan(Pills for Kidney Yin)on neurocyte apoptosis in nucleiof arcuate hypothalamus(ARN)of monosodium glutamate(MSG)-liver regeneration rats,and the mechanism of liverregeneration by using optic microscope,electron microscopeand in situ end labeling technology to adjust nerve-endocrine-immunity network.METHODS:Neurocyte apoptosis in ARN of the experimentrats was observed by using optic microscope,electronmicroscope and in situ end labeling technology.Expression ofTGF-β_1 in ARN was observed by using immunohistochemistrymethod.RESULTS:The expression of TGF-β_1 in rats of model groupwas increased with the increase of ARN neurocyte apoptosisindex(AI)(t=8.3097,12.9884,P<0.01).As comparedwith the rats of model group,the expression of TGF-β_1 inrats of Zuogui Wan treatment group was decreased with thesignificant decrease of ARN neurocyte apoptosis(t=4.5624,11.1420,P<0.01).CONCLUSION:Brain neurocyte calcium ion overexertionand TGF-β_1 protein participate in the adjustment andcontrol of ARN neurocyte apoptosis in MSG-liverregeneration-rats.Zuogui Wan can prevent ARN neurocyteapoptosis of MSG-liver regeneration in rats by down-regulating the expression of TGF-β_1,and influence liverregeneration through adjusting nerve-endocrine-immunenetwork.     

Clinicopathologic significance of expression of nuclear factor-��B RelA and its target gene products in gastric cancer patients

AIM: To assess the prognostic significance of nuclear factor-κB (NF-κB) and its target genes in gastric cancer.METHODS: The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-κB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry.RESULTS: Positive rate of NF-κB RelA was 42.6%. NF-κB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-κB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and overall survival (OS). Multivariate analysis verified that NF-κB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS.CONCLUSION: Increased expression of NF-κB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.     

Effects of Zuogui Wan on neurocyte apoptosis and down-regulation of TGF-β1 expression in nuclei of arcuate hypothalamus of monosodium glutamate -liver regeneration rats

AIM: To inquire into the effects and mechanism of Zuogui Wan (Pills for Kidney Yin) on neurocyte apoptosis in nuclei of arcuate hypothalamus (ARN) of monosodium glutamate (MSG)-Iiver regeneration rats, and the mechanism of liver regeneration by using optic microscope, electron microscope and in situ end labeling technology to adjust nerve-endocrine-immunity network.METHODS: Neurocyte apoptosis in ARN of the experiment rats was observed by using optic microscope, electron microscope and in situ end labeling technology. Expression of TGF-β1 in ARN was observed by using immunohistochemistry method.RESULTS: The expression of TGF-β1 in rats of model group was increased with the increase of ARN neurocyte apoptosis index (AI) (t = 8.3097, 12.9884, P&lt;0.01). As compared with the rats of model group, the expression of TGF-β1 in rats of Zuogui Wan treatment group was decreased with the significant decrease of ARN neurocyte apoptosis (t = 4.5624, 11.1420, P&lt;0.01).CONCLUSION: Brain neurocyte calcium ion overexertion and TGF-β1 protein participate in the adjustment and control of ARN neurocyte apoptosis in MSG-liver regeneration-rats. Zuogui Wan can prevent ARN neurocyte apoptosis of MSG-liver regeneration in rats by downregulating the expression of TGF-β1, and influence liver regeneration through adjusting nerve-endocrine-immunen etwork.     

Extracellular signal-regulated kinase 1- and 2-mediated gastric mucosal injury and repair in gastric ischemia–reperfusion of rats

Background The current study was undertaken to investigate the time course of gastric ischemia–reperfusion (GI-R)-induced gastric mucosal injury and repair and whether extracellular signal-regulated kinase 1/2 (ERK1/2) were involved in GI-R-induced gastric mucosal injury and repair. Methods Immunohistochemistry and Western blot analyses were used. Results Gastric mucosal injury induced by ischemia alone was mild. However, the injury worsened after reperfusion, reaching a maximum at 1 h, and was accompanied by increased apoptotic cells and decreased proliferative cells. Then, the gastric mucosal cells began to repair the injury by enhanced proliferation, which peaked at 24 h after reperfusion, and by 72 h the damaged gastric mucosa was mostly repaired. The ERK1/2 (nonactivated ERK1/2) protein expression level and distribution profile showed no significant changes during the entire reperfusion phase, but the p-ERK1/2 (activated ERK1/2) level changed dramatically. The p-ERK1/2 protein level was decreased at 0.5 h after reperfusion began, and then gradually increased, peaking after 3 h of reperfusion; these changes in p-ERK1/2 occurred simultaneously in the cytoplasm and nucleus. On the other hand, inhibition of the activation of ERK1/2, induced by PD98059, a specific ERK1/2 upstream inhibitor, aggravated the gastric mucosal injury, and apoptosis was increased and proliferation was reduced in the gastric mucosal cells after the same duration of reperfusion. Conclusions Serious gastric mucosal damage involving apoptotic cells occurred rapidly at an early stage of reperfusion and was closely related to the suppression of ERK1/2 activation. The activated ERK1/2 signaling transduction pathway played an important role. Activated ERK1/2 participated in the regulation of gastric mucosal injury and repair induced by GI-R, and might be mediated by the inhibition of apoptosis and the promotion of proliferation in gastric mucosal cells.     

Investigation of the excluded stomach after Roux-en-Y gastric bypass： The role of percutaneous endoscopy

Accessing the bypassed portion of the stomach via conventional endoscopy is difficult following Roux-en-Y gastric bypass surgery. However, endoscopic examination of the stomach and small bowel is possible through percutaneous access into the bypassed stomach （BS） with a combined radiologic and endoscopic technique. We present a case of obscure overt gastrointestinal （GI） bleeding where the source of bleeding was thought to be from the BS. After conventional endoscopic methods failed to examine the BS, percutaneous endoscopy （PE） was used as an alternative to surgical exploration.     

Oxidative stress and hypoxia-induced factor 1α expression in gastric ischemia

AIM: To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia.METHODS:The animal model of gastric ischemia reperfusion was established by placing an elastic rubber band on the proximal part of the bilateral lower limb for ligature for 3 h and reperfusion for 0, 1, 3, 6, 12 or 24 h. Ischemic post-conditioning, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were conducted before reperfusion. Histological and immunohistochemical methods were used to assess the gastric oxidative damageand the expression of HIF1-α in gastric ischemia. The malondialdehyde (MDA) content and superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO) activities were determined by colorimetric assays.RESULTS: Ischemic post-conditioning can reduce post-ischemic oxidativestressand the expression of HIF-1α of gastric tissue resulting from limb ischemia reperfusion injury. MDA, SOD, XOD and MPO were regarded as indexes for mucosal injuries from ROS, and ROS was found to affect the expression of HIF-1α under gastric ischemic conditions.CONCLUSION: ROS affects HIF-1α expression under gastric ischemic conditions induced by limb ischemia reperfusion injury. Therefore, ROS can regulate HIF-1α expression in gastric ischemia.     

Correlation between expression of 1 α-hydroxylase and hypocalcaemia in rats with severe pancreatitis

Objective:To investigate the essential biochemical indices like 1-hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them.Methods:A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups:sham group(SO group) and severe acute pancreatitis group(SAP group).Then they were divided into 1 h,3 h,6 h,and 12 h subgroups according to the killing lime.The severe acute pancreatitis model was established by retrograde injection of 5%sodium taurocholate.Serum calcium,serum creatinine,serum urea nitrogen and serum amylase were measured at different time.Serum 1,25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay.The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location.The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope.Results:Compared with the SO group,rats in the SAP group showed continuous pathological injury as time went by.There was significant increase in serum creatinine,serum urea nitrogen and serum amylase in SAP group compared with the SO group 1,3,6,12 hours after the operation(P0.05).There was significant decrease in serum calcium and 1,25 dihydroxy vitamin D3 3.6,12 hours after the operation(P0.05).It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h.3 h and decreased at 6h,12 h compared with the SO group.The serum calcium,1,25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease.Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h.6 h and 12 h(r=0.976,P0.001;r=0.948.P0.001;r=0.742,P=0.001) and also positive correlation between the 1-hydroxylase expression and serum1,25 dihydroxy vitamin D3 at 1 h,3 h,6 h and 12 h(r=0.935,P0.001;r=0.952,P0.001;r=0.917.P0.001:r=0.874,P0.001).Conclusions:At the early stage of the kidney injury,the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.     

Oxidative stress and hypoxia-induced factor 1α expression in gastric ischemia

AIM:To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia. METHODS:The animal model of gastric ischemia reperfusion was established by placing an elastic rubber band on the proximal part of the bilateral lower limb for ligature for 3 h and reperfusion for 0,1,3,6,12 or 24 h. Ischemic post-conditioning,three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were conducted before reperfusion. Histological and immunohistochemical met...     

Effects of tetrandrine on gastric mucosa and liver in portal hypertensive rats

ＥｆｅｃｔｓｏｆｔｅｔｒａｎｄｒｉｎｅｏｎｇａｓｔｒｉｃｍｕｃｏｓａａｎｄｌｉｖｅｒｉｎｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｖｅｒａｔｓＭＵＹｉ，ＳＨＥＮＹａｏＺｏｎｇａｎｄＣＨＵＹｉＦａｎｇＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒｇａｓｔｒｉｃｍ...     

Cysteamine increases expression and activity of H~1-K~ -ATPase of gastric mucosal cells in weaning piglets

AIM: To determine the in vivo and in vivo effects of cysteamine (CS) on expression and activity of H -K -ATPase of gastric mucosal cells in weaning piglets. METHODS: Eighteen litters of newborn Xinhuai piglets were employed in the in vivo experiment and allocated to control and treatment groups. From 12 d of age (D12), piglets in control group were fed basal diet, while the treatment group received basal diet supplemented with 120 mg/kg CS. Piglets were weaned on D35 in both groups. Six piglets from each group (n = 6) were slaughtered on D28 (one week before weaning), D35 (weaning), D36.5, D38, D42, and D45 (36 h, 72 h, one week and 10 d after weaning), respectively. Semi-quantitative RT-PCR was performed to determine the levels of H -K -ATPase mRNA in gastric mucosa. H -K -ATPase activity in gastric mucosa homogenate was also determined. Gastric mucosal epithelial cells from piglets through primary cultures were used to further elucidate the effect of CS on expression and activity of H -K -ATPase in vivo. Cells were treated for 20 h with 0.001, 0.01, and 0.1 mg/mL of CS (n = 4), respectively. The mRNA expression of H -K -ATPase and somatostatin (SS) as well as the H -K -ATPase activity were determined. RESULTS: in vivo, both mRNA expression and activity of H -K -ATPase in gastric mucosa of control group exhibited a trend to increase from D28 to D45, reaching a peak on D45, but did not show significant age differences. Furthermore, neither the mRNA expression nor the activity of H -K -ATPase was affected significantly by weaning. CS increased the mRNA expression of H -K -ATPase by 73%, 53%, 30% and 39% on D28 (P = 0.014), D35 (P = 0.017), D42 (P = 0.013) and D45 (P = 0.046), respectively. In accordance with the mRNA expression, H -K -ATPase activities were significantly higher in treatment group than in control group on D35 (P = 0.043) and D45 (P = 0.040). In vivo, CS exhibited a dose-dependent effect on mRNA expression and activity of H -K -ATPase. Both H -K -ATPase mRNA expression and activity in gastric mucosal epithelial cells were significantly elevated after 20 h of exposure to the moderate (H -K -ATPase expression: P=0.03; H -K -ATPase activity: P = 0.014) and high concentrations (H -K -ATPase expression: P=0.017; H -K -ATPase activity: P = 0.022) of CS. Significant increases in SS mRNA expression were observed to accompany the elevation of H -K -ATPase expression and activity induced by the moderate (P = 0.024) and high concentrations (P = 0.022) of CS. Low concentration of CS exerted no effects either on expression and activity of H -K -ATPase or on SS mRNA expression in cultured gastric mucosal epithelial cells. CONCLUSION: No significant changes are observed in mRNA expression and activity of H -K -ATPase in gastric mucosa of piglets around weaning from D28 to D45. CS increases expression and activity of gastric H -K -ATPase in vivo and in vivo. SS is involved in mediating the effect of CS on gastric H -K -ATPase expression and activity in weaning piglets.