DISPOSITION KINETICS AND DOSAGE REGIMEN OF TAMOXIFEN IN ADULT HEALTHY FEMALE VOLUNTEERS

Breast cancer is the second most pervasive cause of mortalities in the world and Tamoxifen is the hormone therapy of choice in pre-menopausal estrogen receptor positive breast cancer women and sometimes in post-menopausal women. The pharmgeonetics factors widely affect the pharmacokinetic parameters. Information regarding this anti breast cancer drug shows that bio disposition of Tamoxifen has not been widely studied in local healthy adult female subjects. Disposition kinectics and dosage regimen were investigated in eight healthy adult females of a specific age group 35-55 years. Blood samples were collected at various intervals after oral administration 20mg Tamoxifen tablet. Plasma concentrations were determined with HPLC. Plasma concentration versus time curve was analyzed with one compartment pharmacokinetic model to calculate the kinetic parameters such as Cmax and volume of distribution etc. The pharmacokinetic analysis revealed Cmax of 28.11 ± 2.11 ng/mL at mean Tmax of 7.7 hours.The mean ± SE volume of distribution was 306.6 ± 3.681 L/kg ,respectively while extrapolated zero time drug concentration of elimination phase 0.037 ± 0.005ng/mL. Mean ± SE rate constant for elimination phase was 0.12 ± 0.002 hr-1. Due to decrease in Cmax attained after single oral dose, it is recommended that dosing interval of Tamoxifen should be decreased as to attain steady state levels for pharmacotherapeutic results in breast cancer females. However, 5-10ng/mL change is due to the changes of environment, epigenetic and genetic variation between Pakistan and drug manufacturing foreign countries

RENAL CLEARANCE AND URINARY EXCRETION OF CIPROFLOXACIN IN GOATS

The renal clearance and urinary excretion of ciprofloxacin were investigated in eight healthy female goats. In each animal, ciprofloxacin was administered intramuscularly at the rate of 5 mg/kg body weight. Following drug administration, blood and urine samples were collected at different time intervals and analyzed for ciprofloxacin and creatinine. High performance liquid chromatography (HPLC) was used to determine the drug concentration in the plasma and urine. The value of diuresis after single administration of ciprofloxacin was 0.073 ± 0.014 ml/min/kg. Mean (± SE) values for renal clearance of creatinine and ciprofloxacin were 1.870 ± 0.385 and 0.982 ± 0.166 ml/min/kg, respectively. The ratio between the renal clearance of ciprofloxacin and that of creatinine remained less than one, which was indicative of back diffusion. The mean (± SE) value for the cumulative percent of ciprofloxacin dose excreted at 10 hours following its intramuscular administration was 13.03 ± 2.07. Based on these results, it was evident that besides glomerular filtration, renal handling of drug involved back diffusion also. It was concluded that in local goats glomerular filtration rate (GFR) was lower than that reported for their foreign counterparts

Factors influencing farmers' participation in water management: a community development perspective

Participation is believed to a systematic involvement of the significant number of people, in diverse activities to manage their own problems, carrying the concept of togetherness, which enhance the advantages. It always oscillates and depends on the background in which it occurs. Farmers' participation is critical to improve on-farm water management and crop productivity. The study was conducted to identify the factors involved in the fluctuation of participation. This paper reports the results, in which, farmer participation through planning, implementation, monitoring and evaluation of water-user associations were measured, and it was linked to various socioeconomic, demographic, and farm and irrigation characteristics. Multiple linear regression analysis reveals that the participation was positively influenced by age, education, residential locality, house type, lack of on-farm facilities, underground water use for irrigation purpose and location of watercourses on the canal network. However, residential locality and on-farm facilities have significantly negative relationships with the dependent variable in Sindh province of Pakistan

Lipid Lowering Efficacy of Pennisetum glaucum Bran in Hyperlipidemic Albino Rats

The objective of the study was to determine lipid lowering efficacy of Pennisetum (P) glaucum (Pearl millet, locally known as bajra), bran in hyperlipidemia albino rats. Simvastatin, (Tablet survive®), was used as cholesterol lowering synthetic drug. The period of 0-15 days was considered as a lead-in period to induce hyperlipidemia with atherogenic diet in albino rats. P. glaucum bran at dose rate of 2, 4 and 6 g/kg BW showed lipid lowering efficacy in hyperlipidemic rats at post-treatment days 30, 45 and 60. At the level of 6 g/kg, P. glaucum bran was able to produce a significant (P<0.05) increase in HDL- cholesterol (47%) and fall in other lipid profile parameters i.e. total lipids (41%), triglycerides(48%), total cholesterol (39%) and LDL- cholesterol (55%). P. glaucum 6 g/kg also reduced total cholesterol in liver tissue and increased fecal bile acid secretion. The results of present study suggest that 6 g/kg P. glaucum bran and 0.6 mg/kg Simvastatin were equally effective in treating hyperlipidemia in albino rats. Moreover, the potency of P. glaucum for stimulating fecal bile acid secretion in albino rats may safely be conceived, at least, as a part of mechanisms for its antihyperlipidemic efficacy

Discovery and Characterization of Iron Sulfide and Polyphosphate Bodies Coexisting in Archaeoglobus fulgidus

Inorganic storage granules have long been recognized in bacterial and eukaryotic cells but were only recently identified in archaeal cells. Here, we report the cellular organization and chemical compositions of storage granules in the Euryarchaeon, Archaeoglobus fulgidus strain VC16, a hyperthermophilic, anaerobic, and sulfate-reducing microorganism. Dense granules were apparent in A. fulgidus cells imaged by cryo electron microscopy (cryoEM) but not so by negative stain electron microscopy. Cryo electron tomography (cryoET) revealed that each cell contains one to several dense granules located near the cell membrane. Energy dispersive X-ray (EDX) spectroscopy and scanning transmission electron microscopy (STEM) show that, surprisingly, each cell contains not just one but often two types of granules with different elemental compositions. One type, named iron sulfide body (ISB), is composed mainly of the elements iron and sulfur plus copper; and the other one, called polyphosphate body (PPB), is composed of phosphorus and oxygen plus magnesium, calcium, and aluminum. PPBs are likely used for energy storage and/or metal sequestration/detoxification. ISBs could result from the reduction of sulfate to sulfide via anaerobic energy harvesting pathways and may be associated with energy and/or metal storage or detoxification. The exceptional ability of these archaeal cells to sequester different elements may have novel bioengineering applications

Size-Resolved Fluorescence Underscores Negligible Interaction of Dissolved Organic Matter During Conservative Mixing in a Large Boreal River

Although river mixing occurs widely in nature, the corresponding evolution of dissolved organic matter (DOM) composition remains poorly understood. Here, surface water samples were collected at multiple transects in the lower Athabasca River (LAR) under base-flow conditions. Asymmetric flow field-flow fractionation (AF4) coupled to online excitation-emission measurements (EEMs) and parallel factor analysis (PARAFAC) were utilized to investigate the size distribution of fluorescent DOM components during river mixing and the corresponding variation in size-resolved fluorescence. The majority of fluorescent components occurred at 0.810 and 1.170 kDa, reflecting the small size of the DOM molecules with maximum fluorescence. The loadings of fluorescence normalized to absorbance at 254 nm (A254) were highest for most terrestrial humic-like components, followed by the microbial humic-like component, and the protein-like components. Differences in size-resolved fluorescence were observed between DOM in humic-rich tributaries and in the mainstem of the LAR upstream of tributary inputs. The trend of variations in the A254-normalized PARAFAC loadings of terrestrial humic-like components also illustrates conservative mixing of aromatic-rich terrestrial DOM across size fractions in the LAR. From a molecular point of view, the mixing of fluorescent DOM occurred linearly and simultaneously across sizes without any evidence of aggregation, sedimentation, or changes in the fluorescence or concentration of any size fraction over the &gt;60 km required for complete mixing of the river and its tributaries. Overall, this study provides insights into the size characteristics of fluorescent components of DOM and their conservative mixing behavior in large boreal rivers

Prevalence and demographics of anxiety disorders: a snapshot from a community health centre in Pakistan

<p>Abstract</p> <p>Background</p> <p>The developing world is faced with a high burden of anxiety disorders. The exact prevalence of anxiety disorders in Pakistan is not known. There is a need to develop an evidence base to aid policy development on tackling anxiety and depressive disorders in the country. This is the first pilot study to address the prevalence of anxiety disorders and their association with sociodemographic factors in Pakistan.</p> <p>Methods</p> <p>A cross-sectional study was conducted among people visiting Aga Khan University Hospital (AKUH), a tertiary care facility in Karachi, Pakistan. The point prevalence of anxiety amongst the sample population, which comprised of patients and their attendants, excluding all health care personnel, was assessed using the validated Urdu version of the Hospital Anxiety and Depression Scale (HADS). The questionnaire was administered to 423 people. Descriptive statistics were performed for mean scores and proportions.</p> <p>Results</p> <p>The mean anxiety score of the population was 5.7 ± 3.86. About 28.3% had borderline or pathological anxiety. The factors found to be independently predicted with anxiety were, female sex (odds ratio (OR) = 2.14, 95% CI 1.36–3.36, p = 0.01); physical illness (OR = 1.67, 95% CI 1.06–2.64, p = 0.026); and psychiatric illness (OR = 1.176, 95% CI 1.0–3.1, p = 0.048). In the final multivariate model, female sex (adjusted odds ratio (AOR) = 2, 95% CI 1.28–3.22) and physical illness (AOR = 1.56, 95% CI 0.97–2.48) were found to be significant.</p> <p>Conclusion</p> <p>Further studies via nationally representative surveys need to be undertaken to fully grasp the scope of this emerging public health issue in Pakistan.</p

Cellular community detection for tissue phenotyping in colorectal cancer histology images

Classification of various types of tissue in cancer histology images based on the cellular compositions is an important step towards the development of computational pathology tools for systematic digital profiling of the spatial tumor microenvironment. Most existing methods for tissue phenotyping are limited to the classification of tumor and stroma and require large amount of annotated histology images which are often not available. In the current work, we pose the problem of identifying distinct tissue phenotypes as finding communities in cellular graphs or networks. First, we train a deep neural network for cell detection and classification into five distinct cellular components. Considering the detected nuclei as nodes, potential cell-cell connections are assigned using Delaunay triangulation resulting in a cell-level graph. Based on this cell graph, a feature vector capturing potential cell-cell connection of different types of cells is computed. These feature vectors are used to construct a patch-level graph based on chi-square distance. We map patch-level nodes to the geometric space by representing each node as a vector of geodesic distances from other nodes in the network and iteratively drifting the patch nodes in the direction of positive density gradients towards maximum density regions. The proposed algorithm is evaluated on a publicly available dataset and another new large-scale dataset consisting of 280K patches of seven tissue phenotypes. The estimated communities have significant biological meanings as verified by the expert pathologists. A comparison with current state-of-the-art methods reveals significant performance improvement in tissue phenotyping