Response of pulse phenol injection on an anaerobic-anoxic-aerobic system

The performance of a three-stage suspended growth continuous system consisting of anaerobic-anoxic-aerobic reactors was evaluated after injection of a pulse phenol shock load in the anaerobic reactor. The synthetic feed contained phenol, cyanide, thiocyanate and ammonia-nitrogen. Anaerobic reactor required 22 days to regain its previous cyanide removal efficiency and the reactor achieved a new steady state in terms of phenol removal. The anoxic reactor achieved its previous phenol and the thiocyanate removal efficiency in seven to nine days. In the aerobic reactor, nitrification was severely inhibited due to the washout of nitrifying bacteria. The aerobic reactor was the most sensitive in terms of phenol shock load in the three-stage system.     

Endogenous thioredoxin is required for redox cycling of anthracyclines and p53-dependent apoptosis in cancer cells

Apoptosis is a major mechanism of cancer cell destruction by chemotherapy and radiotherapy. The anthracycline class of antitumor drugs undergoes redox cycling in living cells producing increased amounts of reactive oxygen species and semiquinone radical, both of which can cause DNA damage, and consequently trigger apoptotic death of cancer cells. We show here that MCF-7 cells overexpressing thioredoxin (Trx) were more apoptotic in response to daunomycin. Trx overexpression in MCF-7 cells increased the generation of superoxide anion (O2*-) in anthracycline-treated cell extracts. Enhanced generation of O2- in response to daunomycin inTrx-overexpressing MCF-7 cells was inhibited by diphenyleneiodonium chloride, a general NADPH reductase inhibitor, demonstrating that Trx provides reducing equivalents to a bioreductive enzyme for redox cycling of daunomycin. Additionally Trx increased p53-DNA binding and expression in response to anthracyclines. MCF-7 cells expressing mutant redox-inactive Trx showed decreased superoxide generation, apoptosis, and p53 protein and DNA binding. In addition, down-regulation of endogenous Trx expression by small interfering RNA resulted in decreased expression of caspase-7 and cleaved poly(ADP-ribose) polymerase expression in response to daunomycin. These results suggest that endogenous Trx is required for anthracycline-mediated apoptosis of breast cancer cells. Taken together, our data demonstrate a novel pro-oxidant and proapoptotic role of Trx in anthracycline-mediated apoptosis in anthracycline chemotherapy.     

Electrostatic potential surfaces of 5-HT(3)R agonists suggest accessory cation-pi site adjacent to agonist binding domain

Electrostatic potential surface mapping of various aromatic ring systems contained in 5-HT(3)R agonists indicate that some agonists contain an aromatic moiety capable of a favorable cation-pi interaction next to the e-face of pyridine (or its bioisostere). A pharmacophore model has been proposed based on superimposition of two distinct 'aryl' interactions.     

Distribution of Candida species in different clinical sources in Delhi, India, and proteinase and phospholipase activity of Candida albicans isolates

Eighty-five isolates of Candida recovered from three hundred and fifty diverse clinical sources, viz. respiratory tract (sputum, bronchial washing,bronchoalveolar lavage, tracheal aspirate), blood, urine, high vaginal swab, skin and plastic devices, were studied in detail for their morphological and biochemical characters. Seven species of Candida were identified, viz., C. albicans (45.8%), C. tropicalis (24.7%), C. parapsilosis (10.5%), C. krusei (7.0%), C. kefyr (7.0%), C. guilliermondii (3.5%), and C. glabrata (1.1%). C. albicans was the predominant species isolated from all clinical specimens, except blood from which C. krusei was most frequently (38.4%) recovered. Out of 39 isolates of C. albicans, 26 (66.6%) and 19 (48.7%) exhibited strong proteinase and phospholipase activity respectively. There was a higher prevalence of proteinase producing strains amongst the vaginal and skin isolates than that in urinary and respiratory isolates. Also a greater number of phospholipase producing strains was observed in the vaginal and urinary isolates than that in the respiratory and skin isolates.     

Ovary specific immune response during Plasmodium yoelii yoelii infection in malaria vector Anopheles stephensi (Diptera:Insecta)

Innate immune related polypeptides expression during three gonotrophic cycles in the ovaries of major disease vector mosquito A. stephensi has been analyzed following infection by malaria parasite, P. yoelii yoelii. Seventeen polypeptides were induced in the ovaries of various stages due to parasitic infection. Most of proteins were induced systemically during early stages of infection suggesting the possibility of immune related signalling process. The reduction in the quantity of protein contents in infected mosquitoes has been ascribed to the repression of seven polypeptides and in turn correlated with the fecundity reduction. The mechanism of these responses and their significance for malaria transmission and fecundity reduction are discussed.     

Expression,purification, and biochemical characterization of Mycobacterium tuberculosis aspartate decarboxylase,PanD

Like all bacteria, Mycobacterium tuberculosis (Mtb) possesses the genes necessary for coenzyme A biosynthesis and metabolism. In the present work, the Mtb panD gene was PCR amplified, overexpressed, and purified by metal affinity chromatography. The recombinant Mtb panD was found to exist as a tetramer in solution. Incubation of Mtb panD at 37 degrees C for several hours resulted in a complete cleavage of the inactive (pi) form into the two subunits (alpha and beta). The cleavage was confirmed by Western blot analysis as well as by N-terminal sequencing. Cleaved Mtb panD was assayed for decarboxylase activity with L-aspartate as substrate. The kinetic parameters K(m) and k(cat) were found to be 219 microM and 0.65s(-1), respectively. These results provide the means for further studies based on the identification of the Mtb panD as well as other components of pantothenate metabolism as potential drug targets.     

Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats

Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.     

Design, synthesis, and SAR studies of some 5-aliphatic oximino esters of thiophene as potential anti-inflammatory leads: comparative biological activity profile of aliphatic oximes vs aromatic oximes

A series of novel tetra substituted thiophenes were synthesized, characterized, and evaluated for their anti-inflammatory activity in carrageenin induced rat paw edema model-an acute in vivo model. Compounds V1, V3, V11, V12, V17, and V18 showed good anti-inflammatory activity, indicating the importance of oxime moiety in modulating the activity. The structure-activity relationship studies explore "the aliphatic oxime esters" attached via a ketone bridge to fifth position of the thiophene, and indicate that this feature may enhance the anti-inflammatory activity as compared to aromatic oximes. Since free radicals are implicated in various inflammatory disorders, the free radical scavenging activity of some of the synthesized candidates was assessed using 1,1-diphenyl-2-picryl hydrazyl assay. The oxime containing analogs exhibited weak to moderate activity as free radical scavengers in DPPH assay. A plausible reasoning for its free radical scavenging ability is discussed. All the compounds were also screened in nitro blue tetrazolium model, to assess them as superoxide anion radical scavengers. A direct correlation between anti-inflammatory activity and free radical scavenging activity was not seen. The results disclose a new class of anti-inflammatory agents designed and synthesized for the first time wherein the utility of aliphatic oxime esters in modulating the anti-inflammatory activity profile is apparent. This will give us potential anti-inflammatory leads.     

Short duration of elevated vIRF-1 expression during lytic replication of human herpesvirus 8 limits its ability to block antiviral responses induced by alpha interferon in BCBL-1 cells

Human herpesvirus 8 (HHV-8) encodes multiple proteins that disrupt the host antiviral response, including viral interferon (IFN) regulatory factor 1 (vIRF-1). The product of the vIRF-1 gene blocks responses to IFN when overexpressed by transfection, but the functional consequence of vIRF-1 that is expressed during infection with HHV-8 is not known. These studies demonstrate that BCBL-1 cells that were latently infected with HHV-8 expressed low levels of vIRF-1 that were associated with PML bodies, whereas much higher levels of vIRF-1 were transiently expressed during the lytic phase of HHV-8 replication. The low levels of vIRF-1 that were associated with PML bodies were insufficient to block alpha IFN (IFN-alpha)-induced alterations in gene expression, whereas cells that expressed high levels of vIRF-1 were resistant to some changes induced by IFN-alpha, including the expression of the double-stranded-RNA-activated protein kinase. High levels of vIRF-1 were expressed for only a short period during the lytic cascade, so many cells with HHV-8 in the lytic phase responded to IFN-alpha with increased expression of antiviral genes and enhanced apoptosis. Furthermore, the production of infectious virus was severely compromised when IFN-alpha was present early during the lytic cascade. These studies indicate that the transient expression of high levels of vIRF-1 is inadequate to subvert many of the antiviral effects of IFN-alpha so that IFN-alpha can effectively induce apoptosis and block production of infectious virus when present early in the lytic cascade of HHV-8.