Treatment of variola major with cytosine arabinoside.

A controlled study of the efficacy of cytosine arabinoside in the treatment of patients with variola major was performed. Cytosine aravinoside was given intravenously at a dose approximating 3 mg/kg of body weight every 24 hr for up to seven days. All nine patients receiving cytosine arabinoside and four of the 11 patients receiving placebo died. In three of the patients receiving cytosine aravinoside, death occurred late in the illness at a time when the patient's lesions began to dry up, the patient's temperature became normal, and the patient's general condition appeared to improve. The virus could be isolated from the blood at day 7 from three of four patients treated with cytosine arabinoside as compared with zero of six control patients. Hematologic data showed a depression in the number of circulating granulocytes. It is possible that the drug lowered the resistance to infection either through direct suppression of granulocytes or through interference with other immune mechanisms. Cytosine arabinside administered in the doses used in this study is not effective in the treatment of variola major.     

Building small dams can decrease malaria: a comparative study from Sundargarh District, Orissa, India

The adverse health effect of environmental changes brought about with the construction of large and small dams has often been reported. Here, we present results of a 5-year (2001-2005) study documenting the positive effect of such developmental projects in reducing malaria in an area where malaria transmission is mainly due to the highly efficient anthropophagic vector Anopheles fluviatilis with some contribution from Anopheles culicifacies. The former breeds exclusively in the slow-flowing streams and the latter breeds in a variety of habitats. The study was conducted in San Dulakudar village and comparisons were made with two control villages situated near the stream with similar topography and malaria transmission pattern. Epidemiological data was collected through longitudinal weekly surveillance and cross-sectional surveys in all the study villages. The mean annual malaria incidence rates due to Plasmodium falciparum in children of 1-5 years age group during 2001 before construction of dam was 1304.3 and 785.7 cases/1000 population in dam site village and control villages, respectively. However, after construction of dam, there was gradual reduction in the malaria cases in dam site village and during 2005 the incidence was significantly reduced to 181.8 (P<0.01) whereas it was increased to 1000 in control villages without any significant change in comparison to baseline year (P>0.05). A significant reduction in malaria incidence and parasite rate was also recorded in all the age groups in dam site village without registering any significant change in control villages. The construction of a small dam in the study village altered the water flow above and below the dam thereby making it unfavourable for the breeding of A. fluviatilis which in turn brought about significant impact on malaria transmission.     

Occurrence of virulence genes, 16S rRNA methylases,and plasmid-mediated quinolone resistance genes in CTX-M-producing Escherichia coli from Pakistan

The aim of the study was to conduct a comprehensive molecular characterization of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli collected from Pakistan. Genetic relatedness among 98 ESBL-producing E. coli was measured by pulsed-field gel electrophoresis (PFGE). The presence of genes encoding ESBLs, virulence factors (VFs), 16S rRNA methylases, plasmid-mediated quinolone resistance (PMQR) encoding elements, plasmid replicon types, phylogenetic groups of E. coli, prevalence of the worldwide disseminated clone E. coli ST131, and phylogrouping of CTX-M enzymes was investigated by polymerase chain reaction (PCR). All isolates carried bla _CTX-M genes and, except for one isolate from CTX-M phylogroup 9, they all belonged to CTX-M phylogroup 1. The isolates were genetically diverse with PFGE. Phylogenetic group D (36 %) was most abundant in this collection of E. coli, whereas isolates belonging to B2 (22 %) had the highest content of virulence genes. PMQR genes were found in 84.6 % of the isolates; among them, 93 % isolates were positive for variants of acetyltransferases (aac(6′)-lb-cr), whereas qnrB, qepA, and qnrS were present in 11 %, 5 %, and 4 % of the isolates, respectively. Only 3 % of the isolates contained genes encoding 16S rRNA methylases. The most abundant replicon type was IncF (96 %), and 18 % of the isolates belonged to the ST131 clone. Out of 34 investigated VFs, 24 genes encoding different types of adhesins, protectins, toxins, siderophores, and other VFs were found. Although the isolates in this collection were highly resistant to many antimicrobials, susceptibility to amikacin and meropenem was retained.     

Renin angiotensin system modulates mTOR pathway through AT2R in HIVAN

Mammalian target of rapamycin (mTOR) has been reported to contribute to the development of HIV-associated nephropathy (HIVAN). We hypothesized that HIV may be activating renal tissue mTOR pathway through renin angiotensin system (RAS) via Angiotensin Receptor Type II receptor (AT2R). Renal tissues of Vpr transgenic and Tg26 (HIVAN) mice displayed enhanced phosphorylation of mTOR and p70S6K. Aliskiren, a renin inhibitor attenuated phosphorylation of both mTOR and p70S6K in renal tissues of HIVAN mice. Interestingly, Angiotensin Receptor Type I (AT1R) blockade did not modulate renal tissue phosphorylation of mTOR in HIVAN mice; on the other hand, AT2R blockade attenuated renal tissue phosphorylation of mTOR in HIVAN mice. In vitro studies, both renin and Ang II displayed enhanced mouse tubular cell (MTC) phosphorylation of p70S6K in a dose dependent manner. HIV/MTC also displayed enhanced phosphorylation of both mTOR and p70S6K; interestingly this effect of HIV was further enhanced by losartan (an AT1R blocker). On the other hand, AT2R blockade attenuated HIV-induced tubular cell phosphorylation of mTOR and p70S6K, whereas, AT2R agonist enhanced phosphorylation of mTOR and p70S6K. These findings indicate that HIV stimulates mTOR pathway in HIVAN through the activation of renin angiotensin system via AT2R.     

Emblica officinalis improves glycemic status and oxidative stress in STZ induced type 2 diabetic model rats

Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P0.07)but reduced glutathione content was found to be increased significantly(P0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.     

Evidence of a Major Reservoir of Non-Malarial Febrile Diseases in Malaria-Endemic Regions of Bangladesh

In malaria-endemic regions any febrile case is likely to be classified as malaria based on presumptive diagnosis largely caused by a lack of diagnostic resources. A district-wide prevalence study assessing etiologies of fever in 659 patients recruited in rural and semi-urban areas of Bandarban district in southeastern Bangladesh revealed high proportions of seropositivity for selected infectious diseases (leptospirosis, typhoid fever) potentially being misdiagnosed as malaria because of similarities in the clinical presentation. In an area with point prevalences of more than 40% for malaria among fever cases, even higher seroprevalence rates of leptospirosis and typhoid fever provide evidence of a major persistent reservoir of these pathogens.     

Management of Occluded Metal Stents in Malignant Biliary Obstruction: Similar Outcomes with Second Metal Stents Compared to Plastic Stents

Background

Covered or uncovered self expandable metallic stents (SEMS) placed in patients with malignant biliary obstruction can occlude in 19–40?%, but optimal management is unclear.

Aim

We sought to summarize current evidence regarding management of occluded SEMS in patients with malignant biliary obstruction.

Methods

Two investigators independently searched Pubmed, Embase, and Web of Science using pre-defined search criteria, and reviewed bibliographies of included studies. Data were independently abstracted by two investigators, and analyzed using RevMan. We compared strategies of second SEMS versus plastic stents with respect to the following outcomes: rate of second stent re-occlusion, duration of second stent patency, and survival.

Results

Ten retrospective studies met inclusion criteria for the systematic review. Management options described were placement of an uncovered SEMS (n?=?125), covered SEMS (n?=?106), plastic stent (n?=?135), percutaneous biliary drain (n?=?7), mechanical cleaning (n?=?18), or microwave coagulation (n?=?7). Relative risk of re-occlusion was not significantly different in patients with second SEMS compared to plastic stents (RR 1.24, 95?% CI 0.92, 1.67, I²?=?0, p 0.16). Duration of second stent patency was not significantly different between patients who received second SEMS versus plastic stents (weighted mean difference 0.46, 95?% CI ?0.30, 1.23, I²?=?83?%). Survival was not significantly different among patients who received plastic stents versus SEMS (weighted mean difference ?1.13, 95?% CI ?2.33, 0.07, I² 86?%, p = 0.07).

Conclusions

Among patients with malignant biliary obstruction and occluded SEMS, available evidence suggests a strategy of placing a plastic stent may be as effective as second SEMS. Limitations of these findings were that all studies were retrospective and heterogeneity between studies was detected for two of the outcomes.