Planar bismuth triamides: a tunable platform for main group Lewis acidity and polymerization catalysis.

Geometric deformation in main group compounds can be used to elicit unique properties including strong Lewis acidity. Here we report on a family of planar bismuth(iii) complexes (cf. typically pyramidal structure for such compounds), which show a geometric Lewis acidity that can be further tuned by varying the steric and electronic features of the triamide ligand employed. The structural dynamism of the planar bismuth complexes was probed in both the solid and solution phase, revealing at least three distinct modes of intermolecular association. A modified Gutmann-Beckett method was used to assess their electrophilicity by employing trimethylphosphine sulfide in addition to triethylphosphine oxide as probes, providing insights into the preference for binding hard or soft substrates. Experimental binding studies were complemented by a computational assessment of the affinities and dissection of the latter into their intrinsic bond strength and deformation energy components. The results show comparable Lewis acidity to triarylboranes, with the added ability to bind two bases simultaneously, and reduced discrimination against soft substrates. We also study the catalytic efficacy of these complexes in the ring opening polymerization of cyclic esters ε-caprolactone and rac-lactide. The polymers obtained show excellent dispersity values and high molecular weights with low catalyst loadings used. The complexes retain their performance under industrially relevant conditions, suggesting they may be useful as less toxic alternatives to tin catalysts in the production of medical grade materials. Collectively, these results establish planar bismuth complexes as not only a novel neutral platform for main group Lewis acidity, but also a potentially valuable one for catalysis.

Polymeric nanoparticle formulation of octapeptide (NP-OP): in vitro release and in vivo effect in common marmosets, Callithrix jacchus Linn.

Octapeptide (OP)/FSH-Receptor Binding Inhibitor-8 (FRBI-8), is a synthetic peptide corresponding to N-terminal sequence of purified fraction of Follicle Stimulating Hormone Binding-Inhibitor (FSHBI), isolated earlier from human ovarian follicular-fluid. In order to avoid the repeated drug-administration, OP-loaded, polymeric polylactide (PLA) nanoparticle formulation (NP-OP), was developed using multiple-emulsion technique. This yielded an average particle size of 120 nm with 70% encapsulation-efficiency. In vitro release profile of NP-OP showed sustained release of OP for 21 days. In vivo anti-fertility studies were conducted in marmosets. Results indicated that control animals conceived in the same cycle while two of three treated animals failed to conceive in treatment cycle. The in vivo studies thus corroborate with in vitro release of OP, demonstrating its anti-fertility activity in 66% of animals.

Gene-expression signatures: biomarkers toward diagnosing multiple sclerosis.

Identification of biomarkers contributing to disease diagnosis, classification or prognosis could be of considerable utility. For example, primary methods to diagnose multiple sclerosis (MS) include magnetic resonance imaging and detection of immunological abnormalities in cerebrospinal fluid. We determined whether gene-expression differences in blood discriminated MS subjects from comparator groups, and identified panels of ratios that performed with varying degrees of accuracy depending upon complexity of comparator groups. High levels of overall accuracy were achieved by comparing MS with homogeneous comparator groups. Overall accuracy was compromised when MS was compared with a heterogeneous comparator group. Results, validated in independent cohorts, indicate that gene-expression differences in blood accurately exclude or include a diagnosis of MS and suggest that these approaches may provide clinically useful prediction of MS.

Surface disinfection by exposure to germicidal UV light.

The present study was aimed to design a simple model to check efficacy of germicidal UV tube, to standardise the position, distance and time for UV light and also to find out its efficacy against medically important bacteria, the bacterial spores and fungi. The microbial cultures tested included gram positive and gram negative bacteria, bacterial spores and fungal spores. The microbes streaked on solid media were exposed to UV light. The inactivation of the order of four logs was observed for bacteria. UV light can have efficient inactivation of bacteria up to a distance of eight feet on either side and exposure time of 30 minutes is adequate.

In vitro susceptibility to meropenem and other antimicrobial agents among gram-negative bacilli isolated from hospitalized patients in central India.

BACKGROUND: Growing multiple drug resistance among gram-negative bacilli among hospitalized patients is a serious therapeutic problem, and the aim of the study was to assess the situation in our hospital. METHODS: Antimicrobial susceptibility testing with the disk method was carried out on 1,533 isolates of gram-negative bacilli from urine, pus, body fluid and blood from hospitalized patients. RESULTS: Seventeen percent of isolates were susceptible only to meropenem and either to piperacillin + tazobactam, to cefoperazone + sulbactam or to both. Eleven percent of isolates were susceptible only to meropenem and 6% were resistant to all antimicrobial agents including meropenem. CONCLUSION: Growing multiple drug resistance among gram-negative bacilli in hospital practice demands a rigid antibiotic policy and strict infection control measures.

Bacterial population changes in hospital effluent treatment plant in central India.

Hospital effluent with its high content of multidrug resistant (MDR) enterobacteria and the presence of enteric pathogens could pose a grave problem for the community. It was planned at our tertiary care hospital in central India to study the population changes at various steps of effluent treatment plant (ETP) like collection, aeration, clarification, liquid sludge, dried sludge, high-pressure filter and treated wastewater. The study included viable bacterial counts, coliform counts, staphylococcal, enterococcal, Pseudomonas and multiple drug resistant (MDR) gram negative bacterial counts in the different stages of ETP. In order to study the distribution of bacteria as free floating in liquid and adherent to suspended particles, enumeration of the bacteria in the filterate and the sediment was also carried out. The effluent input showed 55% of the 8.6 x 10(6)/ml bacteria as coliforms and E. coli which was a typical of fecal flora. The prevalence of MDR coliforms was 0.26%. The substantial reduction (> 3log) was seen for the effluent coming from the clarifier. The bulk of the bacteria in the hospital effluent remains firmly adhered to solid particles; aeration and clarification removes bulk of the bacteria by physical processes like flocculation. The treated liquid effluent still contains sizeable loads of MDR bacteria and inactivation by procedure such as chlorination is required. The bacteria get concentrated in sludge and a greater concentration of chlorine is required for decontamination.

Solar disinfection of infectious biomedical waste: a new approach for developing countries.

Poor developing countries cannot afford expensive technologies such as incineration for management of infectious biomedical waste. We assessed solar heating as an alternative technology. We immersed simulated infectious waste with added challenge bacteria in water in a box-type solar cooker, which was left in the sun for 6 h. In 24 sets of observations, the amount of viable bacteria was reduced by about 7 log. We also tested infectious medical waste with a heavy load of bacteria (10(8)-10(9)/g) from our hospital's burn unit for solar heat disinfection in 20 experiments. Our results showed a similar 7 log reduction in the amount of viable bacteria. Solar heating thus seems to be a cheap method to disinfect infectious medical waste in less economically developed countries.

Current status of drug resistance among gram-negative bacilli isolated from admitted cases in a tertiary care centre.

AIMS: To study the prevalence of drug resistance among gram-negative bacilli and susceptibility to the Cefoperazone + Sulbactam and Piperacillin + Tazobactam combination among the hospital isolates resistant to all other antimicrobial agents. METHODS: A total of 367 gram-negative bacilli isolated from various pathological samples were tested for susceptibility to antimicrobial agent by the disc diffusion technique and 300 isolates of gram-negative bacilli which were resistant to all the other antibiotics were checked for sensitivity to piperacillin + tazobactam and cefoperazone + sulbactam combination. RESULTS: Resistance to ampicillin and amoxicillin + clavulanic acid ranged from (72.1-83.8%) which was highest. Resistance to cotrimoxazole, gentamicin, netilmycin, quinolones and all the generation of cephalsporins was often above 50%. piperacillin + tazobactam combination had the lowest incidence of resistance (14 to 20.5%). CONCLUSION: Drug resistance for most of the antimicrobial agents was greater than 50% including the various generations of cephalosporins. Inefficiency of amoxicillin + clavulanic acid (resistance among 72-79.5% isolates) suggests the presence of extended spectrum beta-lactamases among the isolates. Addition of sulbactam to cefoperazone showed increased activity (resistance 27 to 34%) but piperacillin + tazobactam was the most effective combination in vitro.

Treatment of discarded blood units: disinfection with hypochlorite / formalin versus steam sterilization.

Blood bank regulations and bio medical waste rules of India advocate disinfection of contaminated blood units. Incineration is not recommended due to poly-vinyl chloride (PVC) content of blood bags. This study was designed to evaluate the efficacy of chemical disinfection of blood units deliberately contaminated with Staphylococcus aureus and E. coli with 1 and 6 % hypochlorite, 10% formalin and 33% formaldehyde and autoclaving of blood units contaminated with the above mentioned vegetative forms and B. stearothermophilus spores. Only 33 % formaldehyde could bring about 5 log reduction of bacteria but it is highly irritating and toxic. Autoclaving at 15 lbs pressure for 2 hours uniformly inactivated the vegetative forms and B. stearothermophilus spores. Thus, autoclaving of PVC blood bags is a safer and reliable method compared to chemical disinfection.

RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response.

The receptor for advanced glycation end products (RAGE) and its proinflammatory S100/calgranulin ligands are enriched in joints of subjects with rheumatoid arthritis (RA) and amplify the immune/inflammatory response. In a model of inflammatory arthritis, blockade of RAGE in mice immunized and challenged with bovine type II collagen suppressed clinical and histologic evidence of arthritis, in parallel with diminished levels of TNF-alpha, IL-6, and matrix metalloproteinases (MMP) 3, 9 and 13 in affected tissues. Allelic variation within key domains of RAGE may influence these proinflammatory mechanisms, thereby predisposing individuals to heightened inflammatory responses. A polymorphism of the RAGE gene within the ligand-binding domain of the receptor has been identified, consisting of a glycine to serine change at position 82. Cells bearing the RAGE 82S allele displayed enhanced binding and cytokine/MMP generation following ligation by a prototypic S100/calgranulin compared with cells expressing the RAGE 82G allele. In human subjects, a case-control study demonstrated an increased prevalence of the 82S allele in patients with RA compared with control subjects. These data suggest that RAGE 82S upregulates the inflammatory response upon engagement of S100/calgranulins, and, thereby, may contribute to enhanced proinflammatory mechanisms in immune/inflammatory diseases.

A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis.

The macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine and regulates the anti-inflammator effects of glucocorticoids. An important role for MIF within the cytokine cascade is to act in concert with endogenous glucocorticoids to control the set-point and magnitude of the inflammatory response. Elevated expression of MIF in the circulation and in the synovial joint has been documented in rheumatoid arthritis. MIF also has been linked to the development of joint damage and disease pathology in experimental animal models. We describe herein a novel CATT-tetranucleotide repeat polymorphism at position -794 of the human Mif gene and show that it functionally affects the activity of the MIF promoter in gene reporter assays. We describe four genotypes which comprise 5, 6, 7, or 8-CATT repeat units and show that the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients.

Hypochlorite (1%) is inefficient in decontaminating blood containing hypodermic needles.

Infectious biomedical waste and sharps have a potential hazard of transmission of pathogens. Among sharps, used needles form a major share and disinfection by 1 % hypochlorite is recommended in biomedical waste management rules of India. The aim of the present study was to evaluate the efficacy of hypochlorite for the decontamination of needles. Needles (16 g) filled with suspensions of standard strains and clinical isolates of gram positive and gram negative bacteria in plain normal saline and in human blood containing anticoagulant, were exposed to 1% hypochlorite and the surviving bacteria were subjected to viable counts. The observations indicated that 85 - 90 % of the needles filled with bacterial suspensions in saline are disinfected to a level of > 5 log bacterial reduction (standard disinfection) on exposure to hypochlorite but only 15 to 30% needles contaminated with the challenge bacteria suspended in blood showed > 5 log reduction in viable counts. Thus, hypochlorite treatment is inadequate for disinfecting needles contaminated with pathogenic bacteria in presence of blood and should not be recommended as an option for disinfection of the needles.

The role of X-chromosome inactivation in female predisposition to autoimmunity.

We propose that the phenomenon of X-chromosome inactivation in females may constitute a risk factor for loss of T-cell tolerance; specifically that skewed X-chromosome inactivation in the thymus may lead to inadequate thymic deletion. Using a DNA methylation assay, we have examined the X-chromosome inactivation patterns in peripheral blood from normal females (n = 30), female patients with a variety of autoimmune diseases (n = 167). No differences between patients and controls were observed. However, locally skewed X-chromosome inactivation may exist in the thymus, and therefore the underlying hypothesis remains to be disproved.

Induction of autolysis in starved Escherichia coli cells by seminalplasmin, an antimicrobial protein from bovine seminal plasma.

A pair of relA+ and relA E. coli strains, otherwise isogenic, were studied with regard to the susceptibility of starved cells to lysis induced by the natural peptide seminalplasmin. Starved relA cells were more sensitive to seminalplasmin-induced lysis when compared to starved relA+ cells. Nevertheless, pronounced lysis of starved relA+ cells was observed with increase in the concentration of seminalplasmin. In contrast, ampicillin could not lyse starved relA+ cells even at very high concentrations. Further, seminalplasmin could cause loss of viability and degradation of peptidoglycan in starved relA+ cells. These observations suggest that, unlike many other antibiotics, seminalplasmin can induce autolysis under the conditions of a stringent response.

Tendon transfer to restore extension of the thumb using abductor pollicis longus.

20 patients with rupture or division of extensor pollicis longus (EPL) underwent tendon transfer using abductor pollicis longus (APL). All patients except one were reviewed and examined between 6 and 80 months after surgery. The subjective and objective results were satisfactory and are presented with details of the technique and its advantages and limitations.

Seminalplasmin, an antimicrobial protein from bovine seminal plasma, inhibits peptidoglycan synthesis in Escherichia coli.

Seminalplasmin, an antimicrobial protein from bovine seminal plasma, inhibited peptidoglycan synthesis in Escherichia coli in a concentration-dependent manner. The inhibition of peptidoglycan synthesis appears to be a cause rather than a consequence of growth inhibition as it was observed soon after the addition of the antibiotic even in E. coli cells whose growth was totally inhibited by chloramphenicol.