Distribution profile of paraoxonase phenotypes among the Gujaratis

BACKGROUND:

Paraoxonase (PON1) can hydrolyze organophosphate pesticides (OP) and has a key role in the susceptibility of human in OP toxicity. The human-enzyme shows polymorphism and variations in the distribution profile of its phenotypes among different ethnic groups have been observed.

AIMS:

To see the distribution pattern of total PON1 activity in 45 healthy attendants of poisoning cases; 121 healthy unrelated farm-labours and 59 normal subjects of trauma.

MATERIALS AND METHODS:

The PON1 activities from serum/plasma samples of these healthy normal individuals were estimated with/without addition of 1M NaCl in order to determine salt-stimulated and basal activity. The PON 1 phenotypes were determined on the basis of percent activation of enzyme activity.

RESULTS:

Tri-modal distribution of basal PON1 activity was observed among all these individuals. 52.0% of the individuals belonged to Phenotype A, 46.6% to phenotype AB while 1.4% to Phenotype B with gene frequency of allele-A and allele-B being 0.753 and 0.247 respectively in excellent agreement with Hardy-Weinberg equilibrium.

CONCLUSION:

Maximum number of individuals belonged to phenotype-A (low PON1 activity) showing potential vulnerability towards Op-poisoning.     

Kitam Bird Sanctuary,the only low elevation protected area of Sikkim: A conservation hotspot for butterflies in the Eastern Himalaya

The lowland areas of the Himalayan region are subjected to immense anthropogenic pressure because of least representation in the protected area network. Kitam Bird Sanctuary is the only representative protected area that occurs below 1000 m in Sikkim state of India (a part of globally significant biodiversity hotspot of Himalayas) and serves as the refuge for various species of flora and fauna. Here we studied butterfly diversity and community composition in Kitam Bird Sanctuary (a small protected area of 6 km² geographical area) following point count method spread across predetermined transects. Altogether 1674 butterflies belonging to 111 species and six families were recorded after completion of 240 point counts. Among these, 18 species are federally protected under the Wildlife (Protection) Act (1972) of India. Most of the butterflies were forest specialist in terms of habitat preference, whereas based on host plant specificity, the butterfly community was mostly dominated by generalist feeder (Oligophagous II and Polyphagous). Butterfly community parameters showed a strong correlation with habitat variables. While Kitam Bird Sanctuary is primarily designated for conservation of lowland birds, the high diversity of butterflies both in terms of taxonomic richness and trait composition suggests that the sanctuary harbors an ideal habitat for butterflies of the tropical region and invites conservation attention.     

In vivo analgesic,antipyretic, and anti-inflammatory potential in Swiss albino mice and in vitro thrombolytic activity of hydroalcoholic extract from Litsea glutinosa leaves

Background

The study was conducted to evaluate the in vitro thrombolytic activity, and in vivo analgesic, anti-inflammatory and antipyretic potentials of different hydrocarbon soluble extracts of Litsea glutinosa leaves for the first time widely used in the folkloric treatments in Bangladesh. This work aimed to create new insights on the fundamental mechanisms of the plant extracts involved in these activities.

Results

In thrombolytic activity assay, a significant clot disruption was observed at dose of 1 mg/mL for each of the extracts (volume 100 μL) when compared to the standard drug streptokinase. The n-hexane, ethyl acetate, chloroform, and crude methanolic extracts showed 32.23 ± 0.26, 37.67 ± 1.31, 43.13 ± 0.85, and 46.78 ± 0.9% clot lysis, respectively, whereas the positive control streptokinase showed 93.35 ± 0.35% disruption at the dose of 30,000 I.U. In hot plate method, the highest pain inhibitory activity was found at a dose of 500 mg/kg of crude extract (15.54 ± 0.37 sec) which differed significantly (P <0.01 and P <0.001) with that of the standard drug ketorolac (16.38 ± 0.27 sec). In acetic acid induced writhing test, the crude methanolic extract showed significant (P <0.01 and P <0.001) analgesic potential at doses 250 and 500 mg/kg body weight (45.98 and 56.32% inhibition, respectively), where ketorolac showed 64.36% inhibition. In anti-inflammatory activity test, the crude methanolic extract showed significant (P <0.001) potential at doses 250 and 500 mg/kg body weight (1.51 ± 0.04 and 1.47 ± 0.03 mm paw edema, respectively), where ketorolac showed 1.64 ± 0.05 mm edema after 3 h of carrageenan injection. In antipyretic activity assay, the crude extract showed notable reduction in body temperature (32.78 ± 0.46°C) at dose of 500 mg/kg-body weight, when the standard (at dose 150 mg/kg-body weight) exerted 33.32 ± 0.67°C temperature after 3 h of administration.

Conclusions

Our results yield that the crude hydroalcoholic extract has better effects than the other in all trials. In the context, it can be said that the leaves of L. glutinosa possess remarkable pharmacological effects, and justify its traditional use as analgesic, antipyretic, anti-inflammatory, and thrombolytic agent.     

Is One Sputum Specimen as Good as Two during Follow-Up Cultures for Monitoring Multi Drug Resistant Tuberculosis Patients in India?

Background

In India, the Revised National Tuberculosis Control Programme (RNTCP) has adopted the strategy of examining two specimens during follow-up culture examinations to monitor the treatment response of multi-drug resistant tuberculosis (MDR-TB) patients.

Objectives

To determine the incremental yield of the second sputum specimen during follow-up culture examinations among patients with MDR-TB and the effect on case management on changing from two to one specimen follow-up strategy.

Methods

A cross sectional record review of MDR-TB patients registered during 2008–09 under RNTCP was undertaken in three MDR-TB treatment sites of India.

Results

Of 1721 pairs of follow-up sputum culture examinations done among 220 MDR-TB patients, 451(26%) were positive with either of the two specimens; 29(1.7%) were culture positive only on the second specimen indicating the incremental yield. To detect one additional culture positive result on the second specimen, 59 specimens needed to be processed. If we had examined only one specimen, we would have missed 29 culture-positive results. By current RNTCP guidelines, however, a single specimen policy would have altered case management in only 3(0.2%) instances, where patients would have missed a one month extension of the intensive phase of MDR-TB treatment. There is no meaningful advantage in using two specimens for the monitoring of MDR-TB patients. A single specimen policy could be safely implemented with negligible clinical effect on MDR-TB patients and favourable resource implications for RNTCP.     

Somatic Mutations of PIK3R1 Promote Gliomagenesis

The phosphoinositide 3-kinase (PI3K) pathway is targeted for frequent alteration in glioblastoma (GBM) and is one of the core GBM pathways defined by The Cancer Genome Atlas. Somatic mutations of PIK3R1 are observed in multiple tumor types, but the tumorigenic activity of these mutations has not been demonstrated in GBM. We show here that somatic mutations in the iSH2 domain of PIK3R1 act as oncogenic driver events. Specifically, introduction of a subset of the mutations identified in human GBM, in the nSH2 and iSH2 domains, increases signaling through the PI3K pathway and promotes tumorigenesis of primary normal human astrocytes in an orthotopic xenograft model. Furthermore, we show that cells that are dependent on mutant P85α-mediated PI3K signaling exhibit increased sensitivity to a small molecule inhibitor of AKT. Together, these results suggest that GBM patients whose tumors carry mutant PIK3R1 alleles may benefit from treatment with inhibitors of AKT.     

CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial

ABSTRACT: BACKGROUND: Worldwide, over 10 million people are killed or hospitalized because of traumatic brain injury each year. About 90% of deaths occur in low- and middle-income countries. The condition mostly affects young adults, and many experience long lasting or permanent disability. The social and economic burden is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. It has been shown to reduce the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding in elective surgical patients. Methods/design The CRASH-3 trial is an international, multicenter, pragmatic, randomized, double-blind, placebo-controlled trial to quantify the effects of the early administration of TXA on death and disability in patients with traumatic brain injury. Ten thousand adult patients who fulfil the eligibility criteria will be randomized to receive TXA or placebo. Adults with traumatic brain injury, who are within 8 h of injury and have any intracranial bleeding on computerized tomography (CT scan) or Glasgow Coma Score (GCS) of 12 or less can be included if the responsible doctor is substantially uncertain as to whether or not to use TXA in this patient. Patients with significant extracranial bleeding will be excluded since there is evidence that TXA improves outcome in these patients. Treatment will entail a 1 g loading dose followed by a 1 g maintenance dose over 8 h. The main analyses will be on an 'intention-to-treat' basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time from injury to randomization, the severity of the injury, location of the bleeding, and baseline risk. Interaction tests will be used to test whether the effect of treatment differs across these subgroups. A study with 10,000 patients will have approximately 90% power to detect a 15% relative reduction from 20% to 17% in all-cause mortality. Trial registration Current Controlled Trials ISRCTN15088122; Clinicaltrials.gov NCT01402882.     

Hypoxia,a dynamic tool to amplify the gingival mesenchymal stem cells potential for neurotrophic factor secretion

Gingival mesenchymal stem cells (GMSCs) have significant regenerative potential. Their potential applications range from the treatment of inflammatory diseases, wound healing, and oral disorders. Preconditioning these stem cells can optimize their biological properties. Hypoxia preconditioning of MSCs improves stem cell properties like proliferation, survival, and differentiation potential. This research explored the possible impact of hypoxia on the pluripotent stem cell properties that GMSCs possess. We evaluated the morphology, stemness, neurotrophic factors, and stemness-related genes. We compared the protein levels of secreted neurotrophic factors between normoxic and hypoxic GMSC-conditioned media (GMSC-CM). Results revealed that hypoxic cultured GMSC’s had augmented expression of neurotrophic factors BDNF, GDNF, VEGF, and IGF1 and stemness-related gene NANOG. Hypoxic GMSCs showed decreased expression of the OCT4 gene. In hypoxic GMSC-CM, the neurotrophic factors secretions were significantly higher than normoxic GMSC-CM. Our data demonstrate that culturing of GMSCs in hypoxia enhances the secretion of neurotrophic factors that can lead to neuronal lineage differentiation.     

In vitro micropropagation of Acacia nilotica subsp. indica Brenan via cotyledonary nodes

Cotyledonary node explants of Acacia nilotica subspecies indica Brenan, differentiated multiple shoots on Gamborg et al.' s medium (B₅, Gamborg et al. 1968) supplemented with cytokinins like N⁶-benzyladenine, 6-(, -Dimethylallylamino)-purine, kinetin or zeatin. Of the four, BA supported maximum multiple shoot differentiation; the highest average number of shoots (6.3) per expiant was in 1.5 mg/l. The number of shoots was further enhanced by (i) using nodal explants of in vitro regenerated shoots as microcuttings, and (ii) repeated subculture of the original expiants (stumps) on the same medium after excising the shoots. Thus, over seven hundred shoots could be obtained from a single cotyledonary node explant. Individual shoots, when transferred to 2 mg/l indole-3-acetic acid augmented medium organised healthy roots in 100% cultures. Such test tube grown plantlets have been successfully transferred to soil, where they grow well up to eight weeks.Abbreviations 2iP 6-(, -Dimethylallylamino)-purine - AC activated charcoal - B₅ Gamborg et al. 's medium with 0.8% agar + 3 % sucrose - BA,N⁶ benzyladenine - CW coconut water - FAA formalin-aceticacid-alcohol - IAA indole-3-acetic acid - IBA indole-3-butyric acid - Kn kinetin - NAA -naphthaleneacetic acid - NOA -naphthoxyacetic acid     

Inelastic laser light scattering and particle size of detergent-treated microsomes

Using inelastic laser light scattering we have determined the hydrodynamic diameters of a variety of hepatic microsomal preparations. Whole microsomes have a diameter of 3200 Å. Treatment of microsomes with deoxycholate or cholate and chromatography on DEAE-cellulose give three protein fractions: a “non-absorbed” fraction with particles 2650 Å in diameter, cytochrome P-420 1700 Å in diameter and cytochrome c reductase 760 Å in diameter. Preparation of cytochrome P-450 by (NH₄)₂SO₄ precipitation from cholate solution gives particles 640 Å in diameter. All of these sizes are much too large to represent single molecular species, indicating that these fractions are aggregates of membrane proteins with varying concentrations of lipids.