Adeno-associated virus type 2 infection activates caspase dependent and independent apoptosis in multiple breast cancer lines but not in normal mammary epithelial cells

<p>Abstract</p> <p>Background</p> <p>In normal cells proliferation and apoptosis are tightly regulated, whereas in tumor cells the balance is shifted in favor of increased proliferation and reduced apoptosis. Anticancer agents mediate tumor cell death via targeting multiple pathways of programmed cell death. We have reported that the non-pathogenic, tumor suppressive Adeno-Associated Virus Type 2 (AAV2) induces apoptosis in Human Papillomavirus (HPV) positive cervical cancer cells, but not in normal keratinocytes. In the current study, we examined the potential of AAV2 to inhibit proliferation of MCF-7 and MDA-MB-468 (both weakly invasive), as well as MDA-MB-231 (highly invasive) human breast cancer derived cell lines. As controls, we used normal human mammary epithelial cells (nHMECs) isolated from tissue biopsies of patients undergoing breast reduction surgery.</p> <p>Results</p> <p>AAV2 infected MCF-7 line underwent caspase-independent, and MDA-MB-468 and MDA-MB-231 cell lines underwent caspase-dependent apoptosis. Death of MDA-MB-468 cells was marked by caspase-9 activation, whereas death of MDA-MB-231 cells was marked by activation of both caspase-8 and caspase-9, and resembled a mixture of apoptotic and necrotic cell death. Cellular demise was correlated with the ability of AAV2 to productively infect and differentially express AAV2 non-structural proteins: Rep78, Rep68 and Rep40, dependent on the cell line. Cell death in the MCF-7 and MDA-MB-231 lines coincided with increased S phase entry, whereas the MDA-MB-468 cells increasingly entered into G2. AAV2 infection led to decreased cell viability which correlated with increased expression of proliferation markers c-Myc and Ki-67. In contrast, nHMECs that were infected with AAV2 failed to establish productive infection or undergo apoptosis.</p> <p>Conclusion</p> <p>AAV2 regulated enrichment of cell cycle check-point functions in G1/S, S and G2 phases could create a favorable environment for Rep protein expression. Inherent Rep associated endonuclease activity and AAV2 genomic hair-pin ends have the potential to induce a cellular DNA damage response, which could act in tandem with c-Myc regulated/sensitized apoptosis induction. In contrast, failure of AAV2 to productively infect nHMECs could be clinically advantageous. Identifying the molecular mechanisms of AAV2 targeted cell cycle regulation of death inducing signals could be harnessed for developing novel therapeutics for weakly invasive as well as aggressive breast cancer types.</p

Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer

Formularam-se comprimidos de liberação imediata à base de cefuroxima axetil, pelo método de compressão direta, com diferentes percentagens de lauril sulfato de sódio (LSS), tais como 0,5, 1,0, 1,5, e também sem SLS. Os lotes resultantes dos comprimidos foram avaliados por ambos os métodos da farmacopeia e não farmacopeicos para determinar as propriedades físico-mecânicas. O teste de dissolução foi realizado em meios diferentes, como HCl 0,07 M, água destilada, HCl 0,1 M com pH 1,2 e os tampões fosfato (pH 4,5 e 6,8) para observar a liberação do fármaco contra a correspondente concentração de LSS utilizado. Em seguida, as formulações de teste foram comparadas por fatores f1 (dissimilaridade) e f2 (similaridade), utilizando uma marca de referência de cefuroxima axetil. Diferenças significativas (pCefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS) such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1 (dissimilarity) and f2 (similarity) factors using a reference brand of cefuroxime axetil. Significant differences (

Anorexic behaviour and attitudes among female medical and nursing students at a private university hospital

Objective: To study the anorexic behaviour and attitude among female medical and nursing students in a tertiary care hospital.SUBJECTS AND Methods: A cross-sectional survey to determine the proportion of anorexic behaviour among female medical and nursing students at The Aga Khan University Hospital Karachi was conducted. A multistaged sampling technique was utilized in which our study population was first divided according to field of enrollment (medical or nursing school) and then stratified by class. Within each stratum, we used convenience sampling due to time and availability constraints. We utilized a modified Eating Attitudes Test (EAT-26) to collect data. The Eating Attitude Test is probably the most widely used standardized measure of symptoms characteristic of eating disorders, including anorexia nervosa.Results: A total of 180 female students were interviewed. Ninety-four (52.2%) were medical students and 86 (47.8%) were nursing students. Among the 94 medical students, 26 (27.7%) were from first year, 14 (14.9%) from second year, 15 (16.0%) from third year, 20 (21.3%) from fourth year and 19 (20.2%) from the final year of medical college. Among the 86 nursing students 34 (39.5%) were from first year, 23 (26.7%) from second year, 27 (31.4%) from third year and 2 (2.4%) from fourth year. The proportion of anorexic behaviour among medical students was 8.0%, 7.1% and 20.0% in first, third and fourth years respectively. No individuals with anorexic behaviour were found in second and fifth years. The total proportion of anorexic behaviour among female health care students was 21.7%.CONCLUSION: Results showed a 21.7% prevalence of anorexic behaviour, a figure much higher than that reported in similar studies conducted in Asia. We also found that the proportion was much higher among female nursing students as compared to female medical students. A previous visit to a psychiatrist for reasons other than eating disorders was found to be associated with anorexic behaviour

Heat transfer augmentation and entropy generation analysis of Microchannel Heat Sink (MCHS) with symmetrical ogive-shaped ribs

This study proposes the use of symmetrical ogive-shaped ribs on the walls of microchannel heat sinks (MCHS) to improve their thermal performance with minimal pressure drop. The ribs are arranged in three different configurations: ribs attached to all channel walls (MC-SAWR), ribs attached to side channel walls (MC-SSWR), and ribs attached to the bottom channel wall (MC-SBWR). Numerical investigations are conducted using the laminar conjugate heat transfer model to study the flow and heat transfer characteristics of the MCHS. The augmentation entropy generation number and thermal enhancement factor criterion are used to quantify the overall hydrothermal performance of the MCHS. The results show that the inclusion of symmetrical ogive-shaped ribs improves the Nusselt number of MCHS. The MC-SAWR configuration shows the highest Nusselt number improvement of 13–50% compared to the smooth MCHS over the Reynolds number range of 100–1000. Additionally, the MC-SAWR configuration shows a maximum reduction of 58% in the total entropy generation rate as it has the smallest augmentation entropy generation number value of 0.42. In terms of the thermal enhancement factor criterion, the MC-SSWR configuration shows the highest performance at Reynolds numbers below 400, but the MC-SAWR configuration outperformed the MC-SSWR configuration at Reynolds numbers above 400. Therefore, the MC-SAWR configuration is the best configuration that provides high cooling performance

Medicinal plants used for veterinary diseases by the local inhabitants of the Teshil Tangi, District Charsadda, Pakistan

Therapeutic plants ethnically utilized for the cure of various aliments of animals have an important part in the rural veterinary healthcare system because allopathic medicines remain inaccessible, particularly in the third world countries. This work was carried out in Teshil Tangi District Charsadda, Pakistan, in 2016-18, aiming for conserving the ethnic medicinal plants knowledge about veterinary illnesses. Information was collected from older people, herbalists and pansaris (herbal sellers) via semi-structured questionnaire and open ended interviews. Quantification of the result was done by Relative Frequency Citation (RFC) and Use Value (UV).The result of current study comprises of the 118 therapeutic plant species’ collection which belong to forty-six families by interviewing 233 native informants. Among the 46 botanical families, Leguminosae with 14 species was the leading family. The most dominant growth habit was herbs constituted (68%). Leaves (42%) were the main morphological parts used for ethnoveterinary medicine. The highest UV was obtained for 0.52 for Silybum marianum (L.) and RFC (0.33) for Silybum marianum (L.). Most of the therapeutic plants have been utilized for curing digestive illnesses, followed by promote lactation and wounds healing. Due to the dense and diverse vegetation, the study area is rich in ethnobotanical knowledge and the people still use medicinal plants to cure animal diseases

Hepatitis B virus infection among different sex and age groups in Pakistani Punjab

<p>Abstract</p> <p>Background</p> <p>Hepatitis B virus (HBV) infection is a serious health problem in the developing countries including Pakistan. Various risk factors are responsible for the spread of this infectious disease. Prevalence of HBV infection in apparently suspected individual of Punjab province of Pakistan was analyzed during January 2008 to December 2010. Current study was aimed to investigate the epidemiology and risk factors of HBV infection.</p> <p>Methodology</p> <p>Four thousand eight hundred and ninety patients suffering from chronic liver disease were screened for the presence of HBV DNA using qualitative Real Time PCR methodology to confirm their status of infection. A predesigned standard questionnaire was filled for all the patients that included information about the possible risk factors.</p> <p>Results</p> <p>A total of 4890 ELISA positive patients were screened for Hepatitis B virus infection. Of these 3143 were positive for HBV, includes 68.15% males and 31.85% females. Male were observed to be more frequently infected as compared to the female with a positivity ratio of 2.14: 1. The rate of infection increases with the passage of time in the course of three years. Highest frequency of infection was found in the age of 21-30 was 34.93% followed by 23.83% in 31-40. Only (13.39%) were belonging to the age group 11-20 year. The rate of infection declines with increasing age as shown by age groups 41-50 (16.13%) and 51-60 (7.09%). While children aged 0-10 and very old >60 age groups were very less frequently 1.49% and 1.65% infected respectively. Important risk factors contributing to HBV spread include barber risk (23.60%), blood transfusion (4.04%), History of injection 26.19%, Reuse of syringes 26.60%, dental risk (11.20%) and surgical procedure (4.26%). Among the entire respondents trend sharing personal items was very common. History of injection, barber risk, surgery and dental procedure and reuse of syringes appear as major risk factors for the transmission.</p> <p>Conclusion</p> <p>Male were more frequently exposed to the risk factors as compared to female. Similarly the younger age group had high rate of infection as compared to the children's and the older age groups. Reuse of syringes', barber risk and History of injection were main risk identified during the present study. To lower HBV transmission rate Government should take aggressive steps towards massive awareness and vaccination programs to decrease the burden of HBV from the Punjab province of Pakistan.</p

Anorexic behaviour and attitudes among female medical and nursing students at a private university hospital

Objective: To study the anorexic behaviour and attitude among female medical and nursing students in a tertiary care hospital.SUBJECTS AND Methods: A cross-sectional survey to determine the proportion of anorexic behaviour among female medical and nursing students at The Aga Khan University Hospital Karachi was conducted. A multistaged sampling technique was utilized in which our study population was first divided according to field of enrollment (medical or nursing school) and then stratified by class. Within each stratum, we used convenience sampling due to time and availability constraints. We utilized a modified Eating Attitudes Test (EAT-26) to collect data. The Eating Attitude Test is probably the most widely used standardized measure of symptoms characteristic of eating disorders, including anorexia nervosa.Results: A total of 180 female students were interviewed. Ninety-four (52.2%) were medical students and 86 (47.8%) were nursing students. Among the 94 medical students, 26 (27.7%) were from first year, 14 (14.9%) from second year, 15 (16.0%) from third year, 20 (21.3%) from fourth year and 19 (20.2%) from the final year of medical college. Among the 86 nursing students 34 (39.5%) were from first year, 23 (26.7%) from second year, 27 (31.4%) from third year and 2 (2.4%) from fourth year. The proportion of anorexic behaviour among medical students was 8.0%, 7.1% and 20.0% in first, third and fourth years respectively. No individuals with anorexic behaviour were found in second and fifth years. The total proportion of anorexic behaviour among female health care students was 21.7%.CONCLUSION: Results showed a 21.7% prevalence of anorexic behaviour, a figure much higher than that reported in similar studies conducted in Asia. We also found that the proportion was much higher among female nursing students as compared to female medical students. A previous visit to a psychiatrist for reasons other than eating disorders was found to be associated with anorexic behaviour

Bioinformatics Analysis of Envelope Glycoprotein E epitopes of Dengue Virus Type 3

The E glycoprotein of dengue virus is responsible for the viral binding to the receptor. The crystal structure of envelope glycoprotein has already been determined. However, where the well-defined Bcell and T-cell epitopes are located is still a question. Because of the large variations among the four dengue genotypes, it is very hard to design conserved epitopes for all of them. Therefore, we selected only one genotype (DENV3). The conserved regions were found in more than 600 DENV E glycoprotein sequences. Both the B-cell and T-cell epitopes were predicted and the hydrophobicity, antigenicity, accessibility and flexibility of the highly conserved E glycoprotein were further predicted by using different bioinformatics algorithms. The secondary structure was obtained and the predicted epitopes were pointed out in it. Binding sites on glycoprotein of DENV-3 for attachment of virus to the receptor was identified, while keeping those attachments in which new drugs for dengue related infections could not be designed.Key words: Glycoprotein, DENV3, epitopes, antigenecity, B-cell, T-cell, vaccine