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1.
Abrahim I. Orabi Kamaldeen A. Muili Dong Wang Shunqian Jin George Perides Sohail Z. Husain 《Journal of visualized experiments : JoVE》2013,(77)
The pancreatic acinar cell is the main parenchymal cell of the exocrine pancreas and plays a primary role in the secretion of pancreatic enzymes into the pancreatic duct. It is also the site for the initiation of pancreatitis. Here we describe how acinar cells are isolated from whole pancreas tissue and intracellular calcium signals are measured. In addition, we describe the techniques of transfecting these cells with adenoviral constructs, and subsequently measuring the leakage of lactate dehydrogenase, a marker of cell injury, during conditions that induce acinar cell injury in vitro. These techniques provide a powerful tool to characterize acinar cell physiology and pathology. 相似文献
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Husain SZ Orabi AI Muili KA Luo Y Sarwar S Mahmood SM Wang D Choo-Wing R Singh VP Parness J Ananthanaravanan M Bhandari V Perides G 《American journal of physiology. Gastrointestinal and liver physiology》2012,302(12):G1423-G1433
Biliary pancreatitis is the most common etiology for acute pancreatitis, yet its pathophysiological mechanism remains unclear. Ca(2+) signals generated within the pancreatic acinar cell initiate the early phase of pancreatitis, and bile acids can elicit anomalous acinar cell intracellular Ca(2+) release. We previously demonstrated that Ca(2+) released via the intracellular Ca(2+) channel, the ryanodine receptor (RyR), contributes to the aberrant Ca(2+) signal. In this study, we examined whether RyR inhibition protects against pathological Ca(2+) signals, acinar cell injury, and pancreatitis from bile acid exposure. The bile acid tauro-lithocholic acid-3-sulfate (TLCS) induced intracellular Ca(2+) oscillations at 50 μM and a peak-plateau signal at 500 μM, and only the latter induced acinar cell injury, as determined by lactate dehydrogenase (LDH) leakage. Pretreatment with the RyR inhibitors dantrolene or ryanodine converted the peak-plateau signal to a mostly oscillatory pattern (P < 0.05). They also reduced acinar cell LDH leakage, basolateral blebbing, and propidium iodide uptake (P < 0.05). In vivo, a single dose of dantrolene (5 mg/kg), given either 1 h before or 2 h after intraductal TLCS infusion, reduced the severity of pancreatitis down to the level of the control (P < 0.05). These results suggest that the severity of biliary pancreatitis may be ameliorated by the clinical use of RyR inhibitors. 相似文献
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Assessment of heat tolerance and production performance of Aardi,Damascus, and their crossbred goats
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There is a relationship between the normal progress of digestion and the retention or elimination of the proteins ingested with the meal by Aedes aegyti females. The addition of soybean trypsin inhibitor (STI) to a protein meal prevented digestion and resulted in a rapid elimination of the undigested proteins. The addition of a mix of free amino acids to a protein meal together with STI resulted in a significant increase in the retention of the undigested proteins during the first 10-15 hrs after feeding. The effect of the free amino acids on the retention of the proteins was concentration-dependent between 250 microg/ml and 5 mg/ml. Free amino acids were also important for the retention of non-protein meals. When females were fed a meal containing FITC-dextran (20 kD), most of this compound was eliminated into the feces by 10 hrs; the addition of free amino acid resulted in a significant increase in the retention of the FITC-dextran by the midgut during the first 15 hrs after feeding. The presence of free amino acids in the midgut lumen seems to be an important signal used by the mosquito to regulate the retention of the meal. 相似文献
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Orit Abrahim Erika Linnander Halima Mohammed Netsanet Fetene Elizabeth Bradley 《PloS one》2015,10(10)
Background
Primary healthcare systems in sub-Saharan Africa have undergone substantial development in an effort to expand access to appropriate facilities through a well-functioning referral system. The objective of this study was to evaluate the current patterns of seeking prior care before arriving at a health center or a hospital as a key aspect of the referral system of the primary health care unit (PHCU) in three regions in Ethiopia. We examined what percentage of patients had either sought prior care or had been referred to the present facility and identified demographic and clinical factors associated with having sought prior care or having been referred.Methods and Findings
We conducted a cross-sectional study using face-to-face interviews in the local language with 796 people (99% response rate) seeking outpatient care in three primary health care units serving approximately 100,000 people each and reflecting regional and ethnic diversity; 53% (N = 418) of the sample was seeking care at hospital outpatient departments, and 47% of the sample was seeking care at health centers (N = 378). We used unadjusted and adjusted logistic regression to identify factors associated with having been referred or sought prior care. Our findings indicated that only 10% of all patients interviewed had been referred to their current place of care. Among those in the hospital population, 14% had been referred; among those in the health center population, only 6% had been referred. Of those who had been referred to the hospital, most (74%) had been referred by a health center. Among those who were referred to the health center, the plurality portion (32%) came from a nearby hospital (most commonly for continued HIV treatment or early childhood vaccinations); only 18% had come from a health post. Among patients who had not been formally referred, an additional 25% in the hospital sample and 10% in the health center sample had accessed some prior source of care for their present health concern. In the adjusted analysis, living a longer distance from the source of care and needing more specialized care were correlated with having sought prior care in the hospital sample. We found no factors significantly associated with having sought prior care in the health center sample.Conclusions
The referral system among health facilities in Ethiopia is used by a minority of patients, suggesting that intended connections between health posts, health centers, and hospitals may need strengthening to increase the efficiency of primary care nationally. 相似文献7.
The aim of this study was to investigate the effects of the dietary supplementation of mannan oligosaccharides (MOS) extracted from yeast Saccharomyces cerevisiae, acidifiers -calcium formate (CF), calcium propionate (CP)- and their combination on the caecal microflora of Japanese quail (Coturnix japonica). Four hundred and fifty 1-day old quail where divided in six groups with three replicates each. One group that served as control received the basal diet. The five experimental diets consisted of the basal diet to which either 1 g MOS/kg, or 6 g CF/kg, or 6 g CP/kg, or 1 g MOS plus 6 g CF/kg or 1 g MOS plus 6 g CP/kg were added. The body weight was examined at weekly intervals and mortality was recorded daily. At days 21 and 42 of age, the total count of aerobic bacteria, lactic acid bacteria, enterobacteriaceae and coliforms in the caecal content of one bird of each replicate was determined. Also, at day 42 of age, two birds of each replicate were slaughtered and their carcass weight was determined. The results showed that MOS significantly (P ≤ 0.050) increased the total aerobic plate and lactic acid bacteria counts on day 21. Furthermore, CP significantly (P ≤ 0.050) decreased the total aerobic plate and lactic acid bacteria counts compared to controls on day 21. Significant interaction between MOS and acidifiers was noticed on total aerobic plate count on day 21. No significant (P > 0.050) difference was found in the caecal microflora on day 42. Finally, no significant (P > 0.050) difference was noticed on mortality, body and carcass weight. 相似文献
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Kamaldeen A. Muili Shunqian Jin Abrahim I. Orabi John F. Eisses Tanveer A. Javed Tianming Le Rita Bottino Thotalla Jayaraman Sohail Z. Husain 《The Journal of biological chemistry》2013,288(29):21065-21073
Biliary pancreatitis is the most common etiology of acute pancreatitis, accounting for 30–60% of cases. A dominant theory for the development of biliary pancreatitis is the reflux of bile into the pancreatic duct and subsequent exposure to pancreatic acinar cells. Bile acids are known to induce aberrant Ca2+ signals in acinar cells as well as nuclear translocation of NF-κB. In this study, we examined the role of the downstream Ca2+ target calcineurin on NF-κB translocation. Freshly isolated mouse acinar cells were infected for 24 h with an adenovirus expressing an NF-κB luciferase reporter. The bile acid taurolithocholic acid-3-sulfate caused NF-κB activation at concentrations (500 μm) that were associated with cell injury. We show that the NF-κB inhibitor Bay 11-7082 (1 μm) blocked translocation and injury. Pretreatment with the Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, the calcineurin inhibitors FK506 and cyclosporine A, or use of acinar cells from calcineurin Aβ-deficient mice each led to reduced NF-κB activation with taurolithocholic acid-3-sulfate. Importantly, these manipulations did not affect LPS-induced NF-κB activation. A critical upstream regulator of NF-κB activation is protein kinase C, which translocates to the membranes of various organelles in the active state. We demonstrate that pharmacologic and genetic inhibition of calcineurin blocks translocation of the PKC-δ isoform. In summary, bile-induced NF-κB activation and acinar cell injury are mediated by calcineurin, and a mechanism for this important early inflammatory response appears to be upstream at the level of PKC translocation. 相似文献
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Bradbeer Stephanie J. Harrington Jack Watson Henry Warraich Abrahim Shechonge Asilatu Smith Alan Tamatamah Rashid Ngatunga Benjamin P. Turner George F. Genner Martin J. 《Hydrobiologia》2019,832(1):257-268
Hydrobiologia - Hybridization between introduced and indigenous species can lead to loss of unique genetic resources and precipitate extinction. In Tanzania, the Nile tilapia (Oreochromis... 相似文献
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Abrahim I. Orabi Yuhuan Luo Mahwish U. Ahmad Ahsan U. Shah Zahir Mannan Dong Wang Sheharyar Sarwar Kamaldeen A. Muili Christine Shugrue Thomas R. Kolodecik Vijay P. Singh Mark E. Lowe Edwin Thrower Ju Chen Sohail Z. Husain 《PloS one》2012,7(11)
Acute pancreatitis is a painful, life-threatening disorder of the pancreas whose etiology is often multi-factorial. It is of great importance to understand the interplay between factors that predispose patients to develop the disease. One such factor is an excessive elevation in pancreatic acinar cell Ca2+. These aberrant Ca2+ elevations are triggered by release of Ca2+ from apical Ca2+ pools that are gated by the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3. In this study, we examined the role of IP3R type 2 (IP3R2) using mice deficient in this Ca2+ release channel (IP3R2−/−). Using live acinar cell Ca2+ imaging we found that loss of IP3R2 reduced the amplitude of the apical Ca2+ signal and caused a delay in its initiation. This was associated with a reduction in carbachol-stimulated amylase release and an accumulation of zymogen granules (ZGs). Specifically, there was a 2-fold increase in the number of ZGs (P<0.05) and an expansion of the ZG pool area within the cell. There was also a 1.6- and 2.6-fold increase in cellular amylase and trypsinogen, respectively. However, the mice did not have evidence of pancreatic injury at baseline, other than an elevated serum amylase level. Further, pancreatitis outcomes using a mild caerulein hyperstimulation model were similar between IP3R2−/− and wild type mice. In summary, IP3R2 modulates apical acinar cell Ca2+ signals and pancreatic enzyme secretion. IP3R-deficient acinar cells accumulate ZGs, but the mice do not succumb to pancreatic damage or worse pancreatitis outcomes. 相似文献