The effect of rosa damascena Mill hydro-alcoholic extract on the ileum contraction in rat

Background and purpose: Rosa damascena Mill in Iranian folk medicine is used for treating digestive disorders. We assessed the antispasmodic effects of extract of the leaves of this plant on ileum contractions in Wistar rats; possible mechanisms were investigated, too. Materials and methods: In this experimental study, 48 male Wistar rats (150-200 g) were divided randomly into six groups of eight members, including control group and the groups received extracts of Rosa damascena Mill, propranolol, naloxone, L-nitro-arginine methyl ester (L-NAME), and calcium chloride. To evaluate the effectiveness mechanisms, ileum was placed adjacent to antagonist drugs of β-adrenergic receptors, opioid and inhibitor of the synthesis of nitric oxide, and also under the influence of different doses of calcium chloride. The observed effects were recorded. Then, the percent changes were calculated. Statistical analysis was done using parametric tests of repeated measuring design, ANOVA and t tests. Results: Cumulative extract of Rosa damascena Mill (100, 500 and 1000 mg/k) decreased ileum contractions induced by KCl (P < 0.0001). Propranolol and naloxone significantly decreased the inhibitive effect of the extract on contractions induced by KCl (P < 0.0010), but L-NAME was ineffective. Also, calcium led to the contraction of depolarized tissue through KCI and this contractile effect decreased significantly by the cumulative concentration of Rosa damascena Mill (P < 0.0010). Conclusion: Extract of Rosa damascena Mill probably decreases ileum movements of the rat through stimulating the β-adrenergic and opioid receptors and voltage-dependent channels, and it may be used to treat digestive disorders

ENSO forcing on climate change in Iran: Precipitation analysis

An investigation was conducted to detect the change-point years in the Southern Oscillation Index (SOI) and precipitation time series in Iran for the period 1951-1999 (49 years). Due to the unavailability of data, the record length of the precipitation time series was not consistent for all stations, varying from 34 to 49 years. The Pettitt- Mann-Whitney and Mann-Whitney-Wilcoxon tests were applied to determine the significance of the detected changes. The difference in SOI and precipitation amounts for the period before and after the change years was investigated. The coincidence of change-point years in the SOI time series and precipitation data was explored to evaluate the possible forcing effects of the El Niño-Southern Oscillation (ENSO) phenomenon on the suppression or enhancement of Iran's hydrological cycle. The results indicated that the mid 1970s are the most probable change- point years in the time series of Southern Oscillation Index (SOI) data. The frequency and intensity of El Niño events have increased since then. Consistent with this finding, precipitation data from both south-western and northern parts of Iran have also shown significant change years in or around the mid 1970s. Compared to the period before 1975, annual precipitation over most of the studied regions has increased. This increase was found to be more considerable in southern rather than northern districts. Seasonal precipitation amounts in southern regions have generally increased during autumn and winter and decreased in spring. On the other hand, for northern regions, precipitation has increased during summer and autumn and decreased throughout winter and spring. The most enhanced portions of the hydrological cycle in the southern and northern regions were centred on March and May, respectively

Molecular dynamics simulation study of the effect of hesperetin on pre-apoptotic factors of bad, bak, and bim

Background and Aim: Many compounds derived from medicinal plants, such as antioxidants and polyphenols have significant roles in prevention and treatment of various cancers. Activation of apoptosis related pathways is one of the mechanisms for inhibition of cancer progression. In this study, we investigated the effect of molecular dynamics simulation of hesperetin on the pre-apoptotic factors of Bad, Bak, and Bim. Material and Methods: In this study we collected data about 3 dimensional structure and Protein Data Bank (PDB) files of three apoptotic factors of Bad, Bak, and Bim from Protein Data Bank (http://www.rscb.org /pdb). Using VMD v1.9.2, AutoDock v.4.2, and Gromacs v.4.5.4 softwares, we started processes such as optimization, simulation, molecular docking and molecular dynamics calculations. Results: Binding of Bad molecule to hesperetin led to release of the highest amount of energy and reduced changes in the radius of gyration of Bad protein. But after binding of Bim and Bak proteins to hesperetin, changes in the radius of gyration, increased. The most frequent change in the secondary protein structure was related to increased amount of Bent structure and decreased amount of β-sheet structure in Bim molecule. Conclusion: Hesperetin can affect the activities of pre-apoptotic factors of Bad, Bak, and Bim by influencing their molecular dynamics. It seems that hesperetin has the highest effect on the activation of Bad molecule. Also, it can activate Bim protein and induce apoptosis via inducing alternations in the secondary structure of the protein

Rationale and design of the PRognostic Importance of MIcrovascular Dysfunction in asymptomatic patients with Aortic Stenosis (PRIMID-AS): a multicentre observational study with blinded investigations

Introduction: Aortic stenosis (AS) is the commonest valve disorder in the developed world requiring surgery. Surgery in patients with severe asymptomatic AS remains controversial. Exercise testing can identify asymptomatic patients at increased risk of death and symptom development, but with limited specificity, especially in older adults. Cardiac MRI (CMR), including myocardial perfusion reserve (MPR) may be a novel imaging biomarker in AS. Aims (1) To improve risk stratification in asymptomatic patients with AS and (2) to determine whether MPR is a better predictor of outcome than exercise testing and brain natriuretic peptide (BNP). Method/design Multicentre, prospective observational study in the UK, comparing MPR with exercise testing and BNP (with blinded CMR analysis) for predicting outcome. Population 170 asymptomatic patients with moderate-to-severe AS, who would be considered for aortic valve replacement (AVR). Primary outcome Composite of: typical symptoms necessitating referral for AVR and major adverse cardiovascular events. Follow-up: 12–30 months (minimum 12 months). Primary hypothesis MPR will be a better predictor of outcome than exercise testing and BNP. Ethics/dissemination The study has full ethical approval and is actively recruiting patients. Data collection will be completed in November 2014 and the study results will be submitted for publication within 6 months of completion. ClinicalTrials.gov identifier NCT01658345

Synthesis and Evaluation of 11C-Labeled Triazolones as Probes for Imaging Fatty Acid Synthase Expression by Positron Emission Tomography

Cancer cells require lipids to fulfill energetic, proliferative, and signaling requirements. Even though these cells can take up exogenous fatty acids, the majority exhibit a dependency on de novo fatty acid synthesis. Fatty acid synthase (FASN) is the rate-limiting enzyme in this process. Expression and activity of FASN is elevated in multiple cancers, where it correlates with disease progression and poor prognosis. These observations have sparked interest in developing methods of detecting FASN expression in vivo. One promising approach is the imaging of radiolabeled molecular probes targeting FASN by positron emission tomography (PET). However, although [11C]acetate uptake by prostate cancer cells correlates with FASN expression, no FASN-specific PET probes currently exist. Our aim was to synthesize and evaluate a series of small molecule triazolones based on GSK2194069, an FASN inhibitor with IC50 = 7.7 ± 4.1 nM, for PET imaging of FASN expression. These triazolones were labeled with carbon-11 in good yield and excellent radiochemical purity, and binding to FASN-positive LNCaP cells was significantly higher than FASN-negative PC3 cells. Despite these promising characteristics, however, these molecules exhibited poor in vivo pharmacokinetics and were predominantly retained in lymph nodes and the hepatobiliary system. Future studies will seek to identify structural modifications that improve tumor targeting while maintaining the excretion profile of these first-generation 11C-methyltriazolones

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity

Hydrology and hydrobiological study of the Persian Gulf in the Bushehr region

In order to investigate some ecological condition of the waters of Bushehr province in the Persian gulf between 50~'-01 E to 52~'-47 E and 26~'-39 N to 29~'-03 N, 18 major and 16 minor stations have been studied from Nayband bay to Kharg Island, using R.V. Ferdows 1. There have been a preliminary survey in winter 2001, 4 seasonal surveys in 2001-2 and a complementary one in summer 2002. During this period the seasonal environmental conditions, physico-chemical parameters, zoo and phytoplankton concentrations in water layers, macrobenthoses and sediments were studied. Sea bed swelling in the Motaf region has resulted in division of the area in two parts and in a such away that the climatic and chemico-physical conditions in the southeast area are different from the northwest area. In the southeast area the termocline, halocline, picnocline and oxycline are generated in spring, increased in summer, moved down to the deeper layers in fall and disappeared in the winter. In the Northwest area the clines are only formed in spring and summer but disappear in fall and winter due to almost perfect water column mixing resulted from climatological conditions. During survey period the water temperature ranged from 18 34.1~'C, salinity 37.9 41.3 ppt, conductivity 51.3 70.4 ms/cm, sigmaT 23.1 30.2 g/cm3, dissolved oxygen 0.2 8 ppm, and chlorophyll a 0.1 3.6 mg/m3. It is observed that salinity, conductivity and sigmaT have increased from surface to depeer layer, while oxygen and chlorophyll a had a pick in mean layers but temperature have decreased from surface to the depth. Temperature and conductivity decreased from southeast to the northwest and from costal to offshore. Salinity and sigmaT increased from southeast to the northwest. Dissolved oxygen and chlorophyll-a did not show any trend. The concentration of nutrients including ortho silicate (Si-SiO4- 4), ortho phosphosphate (P PO4-4), nitrate (N NO3- ) and nitrite (N NO2- ) varied between 0.4 13.3, 0.05 1.6, 0.1 12.3 and 0.1 1.4 ~kmol/l, respectively. The overall nutrient concentrations increased from surface to depth. 61 genuses of 5 phytoplankton groups and 8 branches, 12 classes of zooplankton were identified. The identified phytoplanktons included 42 Diatom, 16 Dinophyceae, 3 Cyanophyceae, one Chrysophyceae and one Euglenaphyceae geneses. The highest intensity of phytoplanktons was recorded in summer, while in the case of zooplankton, was recorded in spring. Diatoms had the highest variety in all seasons and the maximum abundance in fall and winter. Cyanophyceaes were predominant group in the spring and summer. On the contrary to zooplanktons, the intensity of phytoplanktons decreased from coastal to the offshore waters. The highest intensity of all planktons (zoo and phyto) was in 10-20 m layer. The intensity of phyto plankton increased from southeast towards northwest. The zooplankton concentration didn t follow any particular trend. The identified macrobenthoses were 69 families including 34 polychaets, 22 gastropods, 10 of bivalvs, 1 crustacean, 1 scaphopoda, 1 foraminifera, 5 classes and 6 orders of crustacea, 1 order of echinodermata, 1 fish larva and 6 branches of other benthoses. Intensity and biomass of all groups were determined. The polychaets and malacostraca had the most abundance in contrast to the other groups. Macrobenthosis intensity decreased from coast to the offshore in southeast of Motaf region, while the middle stations of northwest of Motaf had a better intensity. The mean abundance and biomass of total area decreased from coast to the offshore, and the slope of decrease in biomass was more than abundance. Seasonal minimum and maximum abundance ranged from 1457 to 1903 per square meter in spring and winter, and the biomass ranged between 7.8-10.8 g/m2 in summer and spring, respectively. In spite of high abundance of macrobenthose in the transect no: 13, the estimated biomass was lower than other transects. This might be due to prolonged exposition to more pollutant. The grain size of sediments was classified as gravel, sand, silt and clay. The organic matter of sediments ranged from 1.12 3.3% with annual average of 1.6%. The grain size of sediments in southeastern point was coarser than other areas. The middle stations of northwestern area had fine grain and more organic matter in contrast to the offshore and coastal stations

Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus

Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte– endothelial cell adhesion and vascular inflammation. We also associate PROCR-219Gly with an increased pro- thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR-219Gly to CAD through anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides a framework to reveal the mechanisms underlying similar cross-phenotype associations