Counter effects of Vitamin E against Outcomes of Alcohol Toxicity in Pancreatic Acini: Histomorphometric Study

Aim: To evaluate the effects of alcohol on the microscopic morphology of the exocrine pancreas and blood serum amylase and to explored that if vitamin E has a protective role against alcohol-induced damage in the pancreas of rabbits. Study design: Analytical experimental study Place and duration of study: Departments of Anatomy, Pathology and Pharmacology in Peshawar Medical College Pakistan from 1st January 2019 to 30th June 2019. Methodology: Eighteen healthy adult male domestic rabbits weighing 1-1.5 kg were chosen (oryctolaguscuniculus). The control group A received proper food and normal saline as drinking water, experimental group B received proper diet and 30 percent ethanol solution (30ml/kg/day) orally daily with normal saline, and experimental group C received proper diet, 30 percent ethanol solution (30ml/kg/day), vitamin E (50mg/kg/day) orally daily with normal saline. Each rabbit's blood was taken for serum amylase. Morphology of acinar cells included: 1) number of cells, (10 acini/field, 2) size of acini, 3) size of acinar cells, and 4) size of acinar nuclei. Results: Normal value of serum amylase in rabbits was found. The difference in serum amylase levels between the control and experimental groups for both E4 and E8 animals was not statistically significant. There was no significant difference in the number of pancreatic acinar cells, size of pancreatic acini, the pancreatic acinar cell size, and pancreatic acinar cells nuclear size in the control and experimental groups for both E4 and E8 animals. Conclusion: Alcohol consumption had no influence on the histomorphology of the rabbits' pancreatic acini in a short period (4-8 weeks). No significant variation was noted in the pancreatic acinar cells count & size, pancreatic acinar cells nuclear count and size, and pancreatic acini size. Therefore, protective role of vitamin E was not usefully identified. Keywords: Alcohol, Pancreas, Histomorphology, Vitamin E, Serum amylase

Evaluation of Avian Reovirus S1133 Vaccine Strain in Neonatal Broiler Chickens in Gastrointestinal Integrity and Performance in a Large-Scale Commercial Field Trial

Avian reovirus (ARV) is the principal cause of several diseases. The vaccination of breeders allows for the control of viral arthritis and delivery of maternal-derived antibodies to the progeny. The vaccination of broiler chickens with ARV strain S1133 is used to prevent viral arthritis. However, the post-vaccination enteric effects have not been well-characterized. The purpose of this study was to evaluate the effect of vaccination with the S1133 strain on the weight gain and feed conversion of broiler chickens and to characterize the gastric, enteric, and pancreatic lesions that the strain could induce. A total of 672,000 chickens were divided into two groups: a group vaccinated with ARV strain S1133 (S1133ARV) and a control group (not vaccinated). Upon histological analysis, the vaccine group showed less proventricular glandular tissue and atrophy of the pancreas and duodenal villi, as well as having a lower average daily profit. The conclusion based on the results of this investigation is that neonatal vaccination with S1133ARV causes atrophy of the pancreatic acini, proventricular glands, and intestinal villi, leading to an increased diameter of the glandular lumen and atrophy of the enteric villous, as well as weight loss, in broiler chickens.

The effects of ammonia and glutamine on mitochondrial respiration of rat pancreatic acinar cells

During glutamine catabolism is produced ammonia, which can be toxic to cells. In hepatic encephalopathy neuron mitochondria ammonia causes the formation of free radicals, the opening of the mitochondrial permeability transition pore, oxidative phosphorylation disruption and swelling. It is still unknown whether the utilization of glutamine in the mitochondria of acinar cells of the pancreas produces toxic concentrations of ammonia. The experiments were performed on male Wistar rats weighing 250–300 g. Pancreatic acini were isolated using collagenase. Cells were incubated for 30 min with glucose (10 mM) in the control and additionally NH4Cl (5 mM) or glutamine (2 mM) in the experiment. Acetylcholine (10 μM) or cholecystokinin (0.1 nM) was used to stimulate secretion. Respiration rate of isolated rat pancreatic acini was measured using a Clark electrode. Maximum respiration rate was stimulated by addition to the FCCP. Statistical significance (P) of difference between the groups was determined with two-way repeated-measures ANOVA followed by a Holm-Bonferroni corrected post-hoc t tests. The secretagogues acetylcholine and cholecystokinin did not affect basal and FCCP-stimulated respiratory rate. The basal respiratory rate of pancreatic acinar cells decreased with NH4Cl compared to the basal respiratory rate with glucose oxidation, and this decrease was observed both at normal condition and under the action of secretagogues. Glutamine did not affect basal respiratory rate. During glutamine oxidation, the maximum respiratory rate increased compared to the control, regardless of the effect of acetylcholine or cholecystokinin. NH4Cl reduced the maximum rate of FCCP-stimulated respiration in rest or upon stimulation with secretagogues compared to glucose control. Therefore, NH4Cl causes a negative effect mitochondrial respiration regardless of secretory stimulation with acetylcholine or cholecystokinin. The toxic amount of ammonia required for inhibition of mitochondrial respiration is apparently not formed due to glutamine oxidation even when stimulated by acinar cells by secretagogues.

Giant Calculus with More than 100 Small Calculi in Choledochal Cysts

Giant biliary calculus in the common bile duct (CBD) is rare. Giant calculus of choledochal cyst (CC) is even rarer, and no case of giant calculus of CC with more than 100 calculi has been reported in the indexed literature. We present the case of a 8.0 × 4.5 × 4.0 cm sized giant calculus with >100 small calculi in type IVa CCs with heterotopic pancreas in a 45-year-old male, which is a surprisingly rare occurrence. Magnetic resonance cholangiopancreatography showed multifocal irregular dilatation of intrahepatic biliary radicles with multiple filling defects with a giant calculus in CC with cholelithiasis. The case was successfully managed with open cholecystectomy and choledochotomy with retrieval of 1 giant and more than 100 small calculi with excision of CC with Roux-en-Y hepaticojejunostomy. Histopathological examination (HPE) showed inflamed CC identified with focal areas of surface ulceration with increased fibrosis areas in the wall and few pancreatic acini. A bile duct calculus is defined as “giant” when the size is 5 cm or more. Stone formation within is the most frequent complication of CC. Most intracystic calculi have been described as soft, earthy, and pigmented in appearance, supporting bile stasis as a primary etiologic factor. The only treatment for giant calculus of CBD or CC is surgical. Endoscopic treatment is mostly unsuccessful and open surgery is the treatment of choice due to giant size, increased load of calculus, and presence of calculi in the left and right hepatic ducts.

Heterotopic Pancreas in the Gallbladder: Case Report and Literature Review

Introduction. Heterotopic pancreas (HP) is the congenital presence of pancreatic tissue outside its normal location in the absence of vascular and anatomical connection with the main pancreas. HP can affect any part of the gastrointestinal tract, and it is mostly encountered in the stomach. The gallbladder is a rare site of HP, and our literature review revealed that only 38 cases were reported. We present a case of HP in the gallbladder that was presented with a picture of acute cholecystitis. After the case presentation, we will discuss HP in the gallbladder by reviewing the literature. Case Presentation. A 49-year-old male presented to the emergency department complaining of progressively worsening right upper abdominal pain for the last 24 hours. After thorough history and physical examination, a provisional diagnosis of acute cholecystitis was made. Abdominal ultrasonography revealed a rim of edema surrounding the gallbladder wall with two stones impacted at the gallbladder neck. Laparoscopic cholecystectomy was performed with an uneventful postoperative course, and the patient was discharged the next day. Microscopic examination of the gallbladder showed that a heterotopic pancreatic tissue, composed of a large number of pancreatic acini and few ducts with the absence of islets of Langerhans, was found around the cystic duct. The patient was asymptomatic at the regular follow-up six months postoperatively. Conclusion. HP in the gallbladder is an extremely rare finding. Its clinical presentation is not different from other cholecystopathic diseases. Most cases were accompanied by cholelithiasis. Preoperative laboratory and imaging modalities are usually not helpful in the diagnosis of HP in the gallbladder. The definitive diagnosis is made by histological examination of the gallbladder specimen. Laparoscopic cholecystectomy is sufficing treatment.

Effects of insulin on adaptive capacity of rat pancreatic acinar cells mitochondria

Insulin increases the basal and agonist-stimulated secretion of pancreatic acinar cells, which leads to increase of energy demand and requires sufficient oxidative substrates supply. Cholecystokinin substantially increases the respiration rate of pancreatic acinar cells upon pyruvate oxidation. However, it is not clear how insulin affects mitochondrial oxidative processes at rest and upon secretory stimulation. Experiments were carried out on male Wistar rats (250–300 g) kept on standard diet. Animals were fasted 12 h before the experiment. Pancreatic acini were isolated with collagenase. Basal and FCCP-stimulated respiration of rat pancreatic acini was measured with Clark electrode. Adaptive capacity of mitochondria was assessed by the maximal rate of uncoupled respiration. Statistical significance (P) of differenced between the means was assessed either with a paired t-test or with repeated measures two-way ANOVA and post-hoc Turkey test. Adaptive capacity of pan­creatic acinar mitochondria was significantly higher when pyruvate (2 mM) was used as oxidative substrate comparing with glucose (10 mM). Incubation with insulin (100 nM) for 20 minutes elevated the basal respiration and adaptive capacity of pancreatic acinar mitochondria upon glucose, but not pyruvate, oxidation. Cholecystokinin (0.1 nM, 30 min) stimulated the rate of basal and maximal uncoupled respiration of acinar cells upon pyruvate oxidation, but insulin completely negated this increase of mitochondrial adaptive capacity. Thus, insulin increases the glucose oxidation in pancreatic acinar cells at resting state, but suppresses pyruvate oxidation upon secretory stimulation with cholecystokinin. The mechanisms of insulin action of pyruvate metabolism in pancreatic acinar cells require further elucidation.

Immunoproteasome deficiency leads to sustained pancreatic injury and delayed recovery from experimental pancreatitis

Background & AimsUncovering potential new targets involved in pancreas recovery may permit the development of new therapies and improvement of pancreatitis treatment. One disease mechanism comprises the endoplasmic reticulum stress response and a key regulator to prevent proteotoxic stress in an inflammatory context is the immunoproteasome, an induced form of the constitutive proteasome. Our aim was therefore to investigate the role of the immunoproteasome in acute pancreatitis.MethodsAcute pancreatitis was induced in wild type and LMP7−/− mice and several biochemical parameters for disease severity were addressed, including protease activities and histology of pancreatic damage. Real-time PCR was used to measure pro-inflammation and unfolded protein response. Serum IL-6 was detected by cytometric bead assay. Western blotting was used to quantify the ratio of ubiquitin-protein conjugates as well as unfolded protein response activation. Immunofluorescence identified leukocytes infiltration as well as ubiquitin-protein conjugates in the pancreas.ResultsIn this study, we demonstrate that the β5i/LMP7-subunit deletion correlates with persistent pancreatic damage. Interestingly, immunoproteasome-deficient mice unveil increased activity of pancreatic enzymes as well as higher secretion of Interleukin-6 and transcript expression of the Interleukin IL-1β, IFN-β cytokines and the CXCL-10 chemokine. Thereafter, acinar cell death was increased, which appears to be due to the greater accumulation of ubiquitin-protein conjugates and prolonged unfolded protein response.ConclusionsOur findings suggest that the immunoproteasome plays a protective role in acute pancreatitis via its role in the clearance of damaged proteins and the balance of ER-stress responses in pancreatic acini as well as in macrophages cytokine production.

Effects of Kombucha Tea on Side Effects of High Cholesterol Diet in Rabbits

Background: This research aimed to assess the effect of kombucha tea on reducing cholesterol (HCH) uptake and ameliorating biochemical and physiological side effects of high cholesterol diets. Objectives: The aim of this research was evaluate the effectiveness of Kombucha tea in reducing cholesterol uptake as well as pathological and immunological side effects from high cholesterol diets in Rabbit. Methods: A total of 32 rabbits were assigned into four groups: 1. Control, fed with standard pellets; 2. HCh+St, fed with high cholesterol diet; 3. HCh+Kom, fed with high cholesterol diet and orally received kombucha beverage; and 4. Kom+St, orally received kombucha beverage along with standard diet. Then, the blood Cholesterol (CHO), Triglycerides (TG), Low-density Lipoprotein (LDL), Malondialdehyde (MDA), ferritin, Creatine Phosphokinase (CPK), Interleukin-1 (IL-1), interleukin-6 (IL-6), and liver enzymes (alanine transaminase [ALT], and aspartate transaminase [ AST]), as well as liver histopathological features, were evaluated in all groups. Results: CHO and TG showed the highest level in the blood of the HCh+St group, whereas those gavaged with HCh+Kom displayed no change in TG and LDL. Conversely, the HCh+Kom group showed a significant increase in HDL when compared with HCh+St and Kom+St groups. MDA ferritin and CPK in the Kom+St group was significantly higher than the other groups, followed by HCh+Kom. No significant difference was observed in the values of IL-1 and IL-6 as well as ALT and AST between the experimental groups and the control group. Histopathological observations of the liver tissues revealed foam cells with an acidophilic appearance in the HCh+St group and hyperemia in the sinusoid of HCh+Kom and Kom+St groups. Degradation in pancreatic acini was observed in the HCh+St rabbits. Conclusion: The data suggest that kombucha consumption is effective in preventing problems caused by high cholesterol diets.