Endocannabinoids-related compounds in gastrointestinal diseases

The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases

N-terminal Pro B-type Natriuretic Peptide and the Evaluation of Cardiac Dysfunction and Severity of Disease in Cirrhotic Patients

Purpose: Cardiac dysfunction and hyperdynamic systemic circulation may be present in patients with cirrhosis. The purpose of this study was to identify relations between plasma levels of N-terminal-proBNP (NT-proBNP), reflecting early ventricular dysfunction, and the severity of liver disease and cardiac dysfunction in cirrhotic patients. Materials and Methods: Sixty-three cirrhotic patients and 15 controls (group 1) were enrolled in this study. Plasma levels of NT-proBNP were determined in echocardiographically examined patients, which were allocated to 1 of 3 groups according to Child-Pugh classification or into 2 groups, i.e., a compensated group without ascites (group 2) and decompensated group with ascites (group 3). Results: Plasma NT-proBNP levels were significantly higher in cirrhotic patients (groups 2 and 3) than in age-matched controls (155.9 and 198.3 vs. 40.3 pg/mL

In vivo and ex vivo effects of propofol on myocardial performance in rats with obstructive jaundice

BACKGROUND: Responsiveness of the 'jaundiced heart' to propofol is not completely understood. The purpose of this study was to evaluate the effect of propofol on myocardial performance in rats with obstructive jaundice. METHODS: Male Sprague-Dawley rats (n = 40) were randomly allocated into two groups, twenty underwent bile duct ligation (BDL), and 20 underwent a sham operation. Seven days after the surgery, propofol was administered in vivo and ex vivo (Langendorff preparations). Heart rate, left ventricular end-systolic pressure (LVESP) left ventricular end-diastolic pressure (LVEDP), and maximal rate for left ventricular pressure rise and decline (+/- dP/dtmax ) were measured to determine the influence of propofol on the cardiac function of rats. RESULTS: Impaired basal cardiac function was observed in the isolated BDL hearts, whereas in vivo indices of basal cardiac function (LVESP and +/- dP/dt) in vivo were significantly higher in rats that underwent BDL compared with controls. With low or intermediate concentrations of propofol, these indices of cardiac function were within the normal physiologic range in both groups, and responsiveness to propofol was unaffected by BDL. When the highest concentration of propofol was administrated, a significant decline in cardiac function was observed in the BDL group. CONCLUSIONS: In rats that underwent BDL, basal cardiac performance was better in vivo and worse ex vivo compared with controls. Low and intermediate concentrations of propofol did not appear to impair cardiac function in rats with obstructive jaundice.published_or_final_versio

Role of endocannabinoid system in development of cardiac dysfunction in cirrhosis

Bibliography: 146-15

A new model for the assessment of nonpoint source pollution using GIS and virtual intelligence.

Today, nonpoint source (NPS) pollution remains as the leading cause of water quality problems in the United States (USEPA, 1996). The most common NPS pollutants are sediment (i.e. total suspended solids, TSS) and nutrients (i.e. total nitrogen, TN). These wash into water bodies from agricultural land, construction sites, and other areas of disturbance. To develop the virtual non-point source assessment system (VNPSAS) model, monitoring gauges were selected for data extraction from West Virginia and also the western part of Virginia. A geographic information system (GIS) was used as a productive environment for data extraction and spatial analysis. The information for each watershed was extracted from digital databases based on the coordinates of an imaginary grid over the watershed boundary. Different data sets were extracted based on the type of the pollutant and number of the cells in the grid (one, two, and four-cell). The VNPSAS model was developed based on artificial neural network technology. A three-layer backpropagation neural network was used as the main engine for the VNPSAS model. Four sets of training data from each dataset were used to test the VNPSAS model (cross-validation runs). It was found that the VNPSAS model provides relatively accurate estimates of NPS pollution concentration. The average R2, between actual and virtual measurements of TSS for one, two, and four-cell grids were 0.939, 0.910 and 0.408 for verification datasets, and 0.954, 0.993, and 0.888 for the training datasets, respectively. The average R2, between actual and virtual measurements of TN for one and two-cell grids were 0.845 and 0.244 for verification datasets, and 0.929 and 0.875 for the training datasets, respectively. The high values of the R2 for most of the cases demonstrated the high performance of the VNPSAS for NPS pollution assessment. This research showed that by increasing the number of cells in the grid, the accuracy of the predictions declines. It was demonstrated that this behavior is a function of data availability and not the inability of the model to predict the NPS pollution. This research is one of the first attempts made to model the NPS pollution assessment using GIS and artificial intelligence

Effects of internal marketing on employees performance: Effect of Mediator Organizational Innovation (Case study: departments within The AGHAJARI Oil and Gas Operation Company)

The present study examines the role and mechanisms of internal marketing variables on employee performance through the mediator role of organizational innovation. Statistic population included 770 experts and managers, 43 departments within the Agha-Jari oil and gas Operation Company; using stratified random sampling and Cochran formula 257 were selected as the sample size. Three questionnaires were used, the validity of which was confirmed by the experts. Internal marketing with the validity of 0.70, organizational innovation with the validity of 0.76 and employee performance with the validity of 0.80 were used; validity of faculty members and reliability was confirmed. Data analysis was conducted using structural equation modeling (SEM) with partial least squares (PLS approach and Smart PLS software. The results indicated a direct, significant and positive effect of internal marketing intensity, (0.659) and the indirect effect with mediating role of organizational innovation intensity (0.065) on employee performance and mediating role of organizational innovation intensity (0.474) on organizational innovation. In addition, organizational innovation intensity (0.137) has a significant and positive effect on employee performance