A randomized, single blind comparative trial of norethindrone enanthate and depo-medroxyprogesterone acetate in Bangladesh

A randomized, single blind comparative trial of norethindrone enanthate (NET-ENT) and depo-medroxyprogesterone acetate (DMPA) was conducted in the Model Clinic, Decca, Bangladesh, to determine if there were differences in reported side effects, reasons for discontinuation and discontinuation rates of these two injectables. On all follow-up visits the proportion of women reporting no bleeding (amenorrhea) was higher for the DMPA clients compared to the NET-ENT clients. Concurrent with these findings, the proportion of women reporting irregular bleeding was consistently higher for the NET-ENT clients. Concurrent with these findings, the proportion of women reporting irregular bleeding was consistently higher for the NET-ENT clients compared to those receiving DMPA. By the fourth injection, less than 15% of the clients in both drug groups still reported having regular cyclic bleeding (4 of the 26 DMPA clients and 4 of the 28 NET-ENT clients). Five of the 133 women on DMPA and 6 of the 106 women on NET-ENT became pregnant while using the injectables. At the end of one year of follow-up, 14 of the 133 DMPA and 14 of the 106 NET-ENT clients were still continuing (came back for a fifth injection).     

Hyperacute therapy of ischemic stroke: intravenous thrombolysis

Stroke is the third most common cause of death in the United States following heart disease and cancer. Following the success of thrombolysis for myocardial infarction in the early 1990s, major trials for evaluation of this new therapeutic approach for ischemic stroke were initiated. The majority of ischemic strokes are due to occlusion of a cerebral vessel by a blood clot. Occlusion of a cerebral blood vessel leads to a core of infracted tissue surrounded by a relatively hypoperfused but viable brain tissue (the ischemic penumbra), which can be potentially salvaged by rapid recanalization of the target vessel. The underlying rationale for introduction of thrombolytic drugs is the lysis of an obliterating thrombus and reestablishment of blood flow. In this article we review the major intravenous thrombolysis trials leading to approval of intravenous recombinant tissue plasminogen activator, the only FDA approved treatment available today for acute ischemic stroke.     

Event-based prospective memory in schizophrenia

Although memory deficits have been well documented in schizophrenia, so far, there is dearth of literature about prospective memory (PM), that is memory for future events, in this disorder. The present study investigated event-based PM in schizophrenia. Additionally, the relationship of event-based PM with clinical variables of schizophrenia was also assessed. Task incorporating event-based prospective memory was administered on 42 schizophrenia patients and 42 nonpsychiatric comparison subjects. Patients with schizophrenia were additionally rated on The Scale for the Assessment of Positive Symptoms, The Scale for the Assessment of Negative Symptoms and The Brief Psychiatric Rating Scale. Results showed schizophrenia patients to have poor event-based prospective memory. However, no significant correlation was observed between the clinical variables and PM.     

Emergence of methicilllin resistant Staphylococcus aureus (MRSA) associated with wound infections

In a hospital setting antimicrobial resistant organisms especially Methicillin resistant Staphylococcus aureus (MRSA) has emerged as an important variable influencing patients' outcome and overall resource utilisation. The present study was undertaken to find out the proportion of MRSA and other organisms and their antimicrobial resistance pattern in admitted cases with postoperative wound infections. A total of 50 wound swabs were collected irrespective of age and sex of the patients from National Institute of Traumatology and Orthopaedics Rehabilitation (NITOR). The laboratory work was performed in the department of microbiology of National Institute of Cardiovascular Diseases (NICVD). Isolation, identification and susceptibility testing was done according to the guideline of the National Committee for Clinical Laboratory Standards (NCCLS, 1998). Out of the 50 samples 34 yielded growths of which 15 had growth of single organism and 19 had mixed growth of 2 to 3 organisms. Four different types of organisms were identified. Highest percentage was Escherichia coli 55.9%, followed by Pseudomonas sp. 52.9%, Proteus sp. 38.2%, and Staphylococcus aureus 17.6%. Of the 6 isolates of S aureus 5 (83.3%) were MRSA. Therefore it can be concluded that MRSA is existing in the hospital premises of NITOR, which can endanger the life of many. This study emphasises that susceptibility testing of all clinical isolates is essential to reduce the morbidity, mortality and longer duration of hospital stay. In addition proper management of the cases can decrease the spread of multiple drug resistant organisms in the community.     

Assessment of the patient with hyperacute stroke: imaging and therapy

Neuroimaging is an important part of the assessment of patients with hyperacute stroke. As new treatments that may reverse cerebral ischemia have been developed, the role of neuroimaging has changed from simply anatomic depiction of early infarction to identification, by means of physiologic (rather than simply anatomic) information, of regions that are at risk for infarction. The goal of such imaging techniques is to monitor successes and complications of recently developed treatments such as thrombolysis.     

High fat diet containing cholesterol induce aortic aneurysm through recruitment and proliferation of circulating agranulocytes in apoE knock out mice model

We studied and compared the efficiency of induction aneurysm in apo E mice by using high fat diet and Ang II. Aneurysm induced in 6 week old male apo E −/− mice by subcutaneous release of Ang II injection for 45 days. Also, aneurysm was induced in three month old male apo E by administration of high fat diet for a period of three months. No difference in body weight in Ang II treated mice. But, increase in body weight and mean arterial blood pressure observed in high fat diet group animals. Highly significant increase in total cholesterol, TG, LDL and significant decrease in HDL level were observed in Ang II treated animals. Significant increase in total cholesterol, but no changes in TG, LDL, HDL levels were observed in high fat diet group. Higher percentage of circulating monocytes was observed in ang II treated group but more number of circulating lymphocytes were observed in high fat diet group in FACS analysis. In histopathology, intimal layer of abdominal aorta was completely replaced by chronic inflammatory cells particularly macrophages (80%) which appeared as foam cells and lymphocytes (20%) in ang II treated animals. Degradation of elastin, infiltration of lymphocytes, chondrocytes and cellular migration towards media were observed in the abdominal aorta of high fat diet group. Real time analysis and immunofluorescence assay supports over expression of Vcam 1 Icam1, MCP 1and MMP2 genes were observed in Ang II treated animals. In immunofluorescence assay, over expression of Mac 3 protein specific for macrophages was observed in abdominal aorta of ang II treated animals, but over expression of CD45.1 & 45.2 proteins specific to lymphocytes were observed in high fat diet group. Based on our observations, Ang II induced aortic aneurysm by recruiting/ proliferating circulating monocytes by up regulating Icam-1, Vcam -1 and MCP-1. Also, ang II involved in degradation of elastin in the abdominal aorta by up regulation of MMP2 to promote agranulocytes migration in the intimal layers. Epithelial cell hyperplasia with accumulation of fatty fluids (cyst) was observed in seminal vesicle and ventral prostate of high fat treated animals. Fatty degeneration, germ cell apoptosis and infiltration giant cells were observed in the testes of high fat diet group. As per available literature these observations were not reported with high fat diet treatments with apo E models. High fat diet induced aneurysm prominently in abdominal, thoracic aorta and extensive plaque formation was observed in femoral and renal arteries. Administration of high fat diet containing cholesterol induced aneurysm in apo E mice model also efficient method to rule out the pathogenesis of aortic aneurysm when compared with angiotensin.     

Dual behavior of HCV Core gene in regulation of apoptosis is important in progression of HCC

Hepatitis C virus (HCV) causes acute and chronic hepatitis which can lead to HCC (Hepatocelluar carcinoma) via oxidative stress, steatosis, insulin resistance, fibrosis and liver cirrhosis. Apoptosis is essential for the control and eradication of viral infections. In acute HCV infection, enhanced hepatocyte apoptosis is significant for elimination of viral pathogen. In case of chronic HCV, down regulation of apoptosis and enhanced cell proliferation not only causes HCV infection persistency in the majority of patients. However, the impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. Regulation of apoptosis in hepatocytes by HCV Core is so important in progression of HCC. This review focuses on the dual character of HCV Core on regulation of apoptosis and progression of HCC.     

Mechanistic studies on the drug metabolism and toxicity originating from cytochromes P450

Abstract

Cytochromes P450 are oxidizing enzymes; a few families of cytochromes P450 are implicated in drug metabolism. These enzymatic reactions involve many processes including (i) prodrug to drug conversion, (ii) easy excretion of drug, (iii) generation of reactive metabolites, many of which cause toxicity. In this review, the fundamental biochemical mechanisms associated with the conversion of drugs into the useful or toxic metabolites have been discussed. The mechanisms can be established with the help of many experimental methods like mass spectral analysis, NMR and in vitro analysis etc. Computational methods provide detailed atomic level information, which is generally not available from experimental studies. Thus, the in silico efforts in elucidating the molecular mechanisms are complementary to the known experimental methods and are often clearer (especially in providing 3D information about the metabolites and their reactions). Quantum chemical methods and molecular docking become especially very useful. This review includes five case studies, which explain how the atomic level details were obtained to explore the reaction mechanisms of drug metabolism by cytochromes P450.