Identification of 1-[4-Benzyloxyphenyl)-but-3-enyl]-1H-azoles as New Class of Antitubercular and Antimicrobial Agents.

A series of 1-[(4-benzyloxyphenyl)-but-3-enyl]-1H-azoles has been identified as potent antitubercular agents against Mycobacterium tuberculosis. Synthesis of compounds involved acid catalyzed ring-opening of cyclopropyl ring of phenyl cyclopropyl methanols followed by nucleophilic attack of the azoles on the carbocation intermediates. Several of the compounds 26, 34, and 36 exhibited significant antitubercular activities with MIC value as low as 1.

Rapid guiding catheter swapping for management of rupture during percutaneous venoplasty for idiopathic occlusion of superior vena cava.

Treatment for superior vena cava syndrome (SVCS) by percutaneous interventions has become established as a definitive therapy. However, there is a significant risk of rupture during SVC intervention. We describe an uncommon case that developed SVC rupture during percutaneous intervention for idiopathic SVCS.

Regulatory T cells: new keys for further unlocking the enigma of fetal tolerance and pregnancy complications.

The immunological alterations required for successful pregnancy in eutherian placental mammals have remained a scientific enigma since the discovery of MHC haplotype diversity and unique immune signatures among individuals. Within the past 10 years, accumulating data suggest that immune-suppressive regulatory T cells (Tregs) confer essential protective benefits in sustaining tolerance to the semiallogeneic fetus during pregnancy, along with their more established roles in maintaining tolerance to self and "extended self" commensal Ags that averts autoimmunity. Reciprocally, many human pregnancy complications stemming from inadequacies in fetal tolerance have been associated with defects in maternal Tregs.

4-Hydroxy-trans-2-nonenal (4-HNE) induces neuronal SH-SY5Y cell death via hampering ATP binding at kinase domain of Akt1.

Inhibition mechanism(s) of protein kinase B/Akt1 and its consequences on related cell signaling were investigated in human neuroblastoma SH-SY5Y cells exposed to 4-hydroxy-trans-2-nonenal (4-HNE), one of the most reactive aldehyde by-products of lipid peroxidation. In silico data indicate that 4-HNE interacts with kinase domain of Akt1 with the total docking score of 6.0577 and also forms H-bond to Glu234 residue similar to highly potent Akt1 inhibitor imidazopiperidine analog 8b, in which the protonated imidazole nitrogen involves in two hydrogen bonds between Glu234 and Asp292.

Long-term venous access device use in treatment of malignancies: experience from a government hospital in Eastern India.

Long-term venous access catheters are very useful for administration of chemotherapy and other drug infusions in patients with haematological malignancies. But their use in government hospitals is still restricted. This study aimed to audit the surgical and infective complications of the vascular access devices which we have used for last three years in patients of haematological malignancies.

Cutting edge: committed Th1 CD4+ T cell differentiation blocks pregnancy-induced Foxp3 expression with antigen-specific fetal loss.

Pregnancy stimulates induced Foxp3 expression among maternal CD4(+) T cells with fetal specificity. Although sustained maternal regulatory CD4(+) T cell (Treg) expansion is essential for maintaining fetal tolerance during pregnancy, the necessity for Foxp3(+) cells with fetal specificity remains undefined. In this study, we demonstrate that mitigating Treg differentiation among maternal CD4(+) T cells with a single surrogate fetal specificity elicits Ag-specific fetal loss.

Paravalvular leak closure with two large size devices.

Paravalvular leaks (PVL) after valve replacement surgeries are not uncommon. A significant number of these patients need some form of intervention as they commonly present with heart failure or severe hemolysis. Surgical correction is associated with high mortality and morbidity.

Pregnancy-induced maternal regulatory T cells, bona fide memory or maintenance by antigenic reminder from fetal cell microchimerism?

Long-term maintenance of immune components with defined specificity, without antigen is the hallmark feature of immunological memory. However, there are fundamental differences in how memory CD8(+) compared with CD4(+) T cells are maintained. After complete antigen elimination, CD8(+) T cells can persist as a self-renewing numerically stable cell population, and therefore satisfy the most stringent definition of "memory.

Draft Genome Sequences of Human Pathogenic Fungus Geomyces pannorum Sensu Lato and Bat White Nose Syndrome Pathogen Geomyces (Pseudogymnoascus) destructans.

We report the draft genome sequences of Geomyces pannorum sensu lato and Geomyces (Pseudogymnoascus) destructans. G. pannorum has a larger proteome than G.

Development of a simple and rapid method for the specific identification of organism causing anthrax by slide latex agglutination.

Unlabelled: A specific latex agglutination test (LAT) based on anti-PA (protective antigen) antibodies having detection limit of 5 × 10(4) formalin treated Bacillus anthracis cells or 110 ng of PA was optimized in this study. The optimized LAT could detect anthrax toxin in whole blood as well as in serum from the animal models of anthrax infection. The protocol is a simple and promising method for the specific detection of bacteria causing anthrax under routine laboratory, as well as in field, conditions without any special equipments or expertise.

Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection.

Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates.

Double orifice mitral valve in rheumatic heart disease.

A 55-year-old female, presented to our outpatient department with complaints of dyspnea on exertion, NYHA grade II for 7 years, which had progressed to NYHA Grade III in the past 6 months. An echocardiogram done showed severe mitral stenosis with mitral valve fused in the middle to create an appearance of 2 separate valves (complete bridge type) with 2 separate turbulent jets of flow across these valves. No other congenital anomaly was seen.

Effect of body mass index on pregnancy outcomes in nulliparous women delivering singleton babies: observational study.

Objective: To find out the effect of increasing body mass index (BMI) on pregnancy outcomes in nulliparous women delivering singleton babies.

Method: This was a hospital-based observation study, based on 300 nulliparous women delivering singleton babies in June 2009-Sept. 2010.

Protection of mice against lethal rabies virus challenge using short interfering RNAs (siRNAs) delivered through lentiviral vector.

The antiviral potential of small interfering RNAs (siRNAs) targeting rabies virus (RV) polymerase (L) and nucleoprotein (N) genes delivered through lentiviral vector was investigated. For in vitro evaluation, siRNAs expressing BHK-21 cell lines (BHK-L and BHK-N) were developed using transduction with Lenti-L and Lenti-N lentiviruses encoding siRNAs against RV-L and N genes, respectively. When these cell lines were challenged in vitro with RV Pasteur virus-11 (PV-11) strain, there was reduction in number of RV-specific foci and target gene transcripts indicating inhibitory effect on RV multiplication.

Evaluation of single and dual siRNAs targeting rabies virus glycoprotein and nucleoprotein genes for inhibition of virus multiplication in vitro.

Small interfering RNAs (siRNAs) targeting rabies virus (RV) glycoprotein (G) and nucleoprotein (N) genes were evaluated as antiviral agents against rabies virus in vitro in BHK-21 cells. To select effective siRNAs targeting RV-G, a plasmid-based transient co-transfection approach was used. In this, siRNAs were expressed as short hairpin RNAs (shRNAs), and their ability to inhibit RV-G gene expression was evaluated in cells transfected with a plasmid expressing RV-G.

Hematopoietic progenitor cell lines with myeloid and lymphoid potential.

Investigation of immune-cell differentiation and function is limited by shortcomings of suitable and scalable experimental systems. Here we show that retroviral delivery of an estrogen-regulated form of Hoxb8 into mouse bone marrow cells can be used along with Flt3 ligand to conditionally immortalize early hematopoietic progenitor cells (Hoxb8-FL cells). Hoxb8-FL cells have lost self-renewal capacity and potential to differentiate into megakaryocytes and erythrocytes but retain the potential to differentiate into myeloid and lymphoid cells.

Role of Ess1 in growth, morphogenetic switching, and RNA polymerase II transcription in Candida albicans.

Candida albicans is a fungal pathogen that causes potentially fatal infections among immune-compromised individuals. The emergence of drug resistant C. albicans strains makes it important to identify new antifungal drug targets.

Synthesis and biological evaluation of a new class of 4-aminoquinoline-rhodanine hybrid as potent anti-infective agents.

Synthesis of novel 4-aminoquinoline-rhodanine hybrid using inexpensive starting materials via easy to operate methodology, and their biological activity is reported. All the compounds were screened for their in vitro antimalarial activity against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum, and their cytotoxicity toward VERO cell line. Compounds 9, 19, 21 and 23 exhibited excellent antimalarial activity with IC50 value ranging from 13.

Pseudo-aneurysm of mitral aortic intervalvular fibrosa: two case reports.

The fibrous body between the mitral and aortic valve, known as mitral-aortic intervalvular fibrosa (MAIVF) is prone to infection and injury resulting in pseudo-aneurysm formation. Because of its relative rarity, we are far from making any conclusion regarding the natural history and appropriate therapeutic strategy for this condition. We report two cases of this condition with two different and rare etiologies with strikingly different natural courses, providing insight into the natural course and timing of surgery in this rare entity.

An overview of key pretreatment processes employed for bioconversion of lignocellulosic biomass into biofuels and value added products.

The hunt for alternative sources of energy generation that are inexpensive, ecofriendly, renewable and can replace fossil fuels is on, owing to the increasing demands of energy. One approach in this direction is the conversion of plant residues into biofuels wherein lignocellulose, which forms the structural framework of plants consisting of cellulose, hemicellulose and lignin, is first broken down and hydrolyzed into simple fermentable sugars, which upon fermentation form biofuels such as ethanol. A major bottleneck is to disarray lignin which is present as a protective covering and makes cellulose and hemicellulose recalcitrant to enzymatic hydrolysis.

NKT Cell Subsets Can Exert Opposing Effects in Autoimmunity, Tumor Surveillance and Inflammation.

The innate-like natural killer T (NKT) cells are essential regulators of immunity. These cells comprise at least two distinct subsets and recognize different lipid antigens presented by the MHC class I like molecules CD1d. The CD1d-dependent recognition pathway of NKT cells is highly conserved from mouse to humans.

Influence of vehicles used for oral dosing of test molecules on the progression of Mycobacterium tuberculosis infection in mice.

Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters.