Exploration of NMI-MsCl mediated amide bond formation for the synthesis of novel 3,5-substituted-1,2,4-oxadiazole derivatives: synthesis, evaluation of anti-inflammatory activity and molecular docking studies.

We herein report the facile synthesis of a series of 3,5-substituted-1,2,4-oxadiazole derivatives 9a-e and 10a-e in good to excellent yields by employing NMI-MsCl mediated amide bond formation reaction. The anti-inflammatory potential of the newly synthesized compounds were evaluated by anti-denaturation assay using diclofenac sodium as the reference drug. The compounds 9a and 9d demonstrated promising activity profile when compared to the reference standard. The SAR and molecular docking studies were also carried out for obtaining more details about the profound activity profile of the synthesized molecules. The synthesized compounds were docked against two target proteins TGF-ß and IL-1 by AutoDock vina and Auto Dock 4.2.

Design, synthesis and molecular docking studies of some 1-(5-(2-fluoro-5-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-3-yl)piperazine derivatives as potential anti-inflammatory agents.

We herein report the facile synthesis of a series of 3,5-substituted-1,2,4-oxadiazole derivatives in good to excellent yields. The anti-inflammatory potential of the newly synthesized compounds was evaluated by anti-denaturation assay using diclofenac sodium as the reference standard. Some of the compounds exhibited profound activity profile when compared to the standard drug. The molecular docking and SAR studies were carried out at the later stage for gaining more insights about the promising activity profile of the synthesized molecules.

Rare coagulation factor deficiencies: a countrywide screening data from India.

As compared to haemophilia, although the clinical features and the management strategies for rare coagulation factor deficiencies are discussed, little is known about them. This study was undertaken to assess the distribution, clinical presentation and treatment of patients with rare coagulation factor deficiency disorders in a cross-sectional population of India. Blood samples and other clinical details from patients suspected of rare coagulation factor deficiencies were collected by the Haemophilia Treatment Centers across India and were diagnosed at National Institute of Immunohaematology, Mumbai. A total of 321 cases of rare clotting factor deficiencies were diagnosed, of which 88% were severe, 10% moderate and 2% mild. Commonest deficiency encountered was factor XIII (FXIII) (30%) followed by FX (15.6%), FVII (15%), fibrinogen (12.1%), FXI (9%), combined V and VIII deficiency (5.6%) and congenital multiple vitamin K-dependent coagulation factor deficiency (MCFD, 2.1%). Major representation of these deficiencies was from Southern and Western India (82%). Mucocutaneous bleeding was the commonest clinical presentation (59%); intracranial (IC) haemorrhage was seen in 18% of the patients; menorrhagia was an important clinical pointer in women in the reproductive age group (78%); 8% of the severe cases had no history of bleeding and 73% of the FXIII deficiency cases had umbilical stump bleeding. The major therapeutic products used was fresh frozen plasma (64%), cryoprecipitate (15%), whole blood (15%), antifibrinolytics (5%) and recombinant FVIIa (1%). A distinct pattern in the distribution of rare clotting factor deficiencies was observed which was based on multiple factors that include ethnicity and the available diagnostic facilities in different regions of this vast country.

Socio-economic position and cardiovascular risk in rural Indian adolescents: evidence from the Andhra Pradesh children and parents study (APCAPS).

OBJECTIVES: This study examined association between socio-economic position and cardiovascular risk factors in adolescents to investigate whether childhood socio-economic position is a risk factor for future cardiovascular disease, independently of adult behaviours. STUDY DESIGN AND METHODS: Participants (n = 1128, 46% girls, aged 13-18 years) were members of a birth cohort (Andhra Pradesh Children and Parents Study or APCAPS) established to investigate long-term effects of a pregnancy and childhood nutritional supplementation trial conducted in 29 villages near Hyderabad in South India. Cross-sectional associations between socio-economic position and cardiovascular risk factors were examined using linear regression models. RESULTS: The mean BMI was 16.7 kg/m(2) for boys and 17.8 kg/m(2) for girls. Socio-economic position was positively associated with fat mass index (0.15 kg/m(2); 95% CI: 0.05-0.25) and inversely associated with central-peripheral skinfold ratio (-0.04; 95% CI: -0.06 to -0.01) and, in boys, fasting triglycerides (-0.05; 95% CI: -0.09 to -0.01). Association of socio-economic position with other risk factors (blood pressure, arterial stiffness, fasting glucose, insulin and cholesterol) was weak and inconsistent, and did not persist after adjustment for potential confounders, including age, sex, pubertal stage, height, adiposity and nutrition supplementation. CONCLUSIONS: The study thus showed that lower socio-economic position may be associated with greater central adiposity and higher triglyceride levels in these settings. Socio-economic gradient in cardiovascular risk may strengthen in future with later economic and lifestyle changes. Cardiovascular disease prevention strategies should therefore focus on the youth from the low income group.

Erythrocyte fatty acids and desaturase indices in early pregnancy are associated with risk of preeclampsia.

Preeclampsia (PE) is a pregnancy disorder that may be associated with inadequate maternal nutrition. Fatty acids are vital for placental and fetal growth. Fatty acid desaturases, key enzymes influencing the metabolism of polyunsaturated fatty acids, are reported to be associated with cardiometabolic risk. Any imbalance in the levels of omega-3 and omega-6 fatty acids can result in increased inflammatory response. The current study reports the levels of erythrocyte fatty acids and desaturase index across gestation in women who develop PE (n = 108) and compares them with non-PE women (n = 216). Maternal erythrocyte fatty acids were measured at 4 time points during pregnancy (i.e., 11-14, 18-22, 26-28 weeks and at delivery) using gas chromatography. Maternal total erythrocyte saturated fatty acids and omega-6/omega-3 fatty acid ratio was higher in the PE group as compared to the non-PE group at 11-14 weeks and 18-22 weeks respectively. Maternal Δ5 desaturase index was lower while Δ6 desaturase index was higher in the PE group at 11-14 and 18-22 weeks. Maternal stearoyl CoA desaturase-18 (SCD-18) index was lower at 11-14 weeks and at delivery. These changes were mainly observed in the early onset PE (EOP) group. Δ6 desaturase index at 11-14 weeks predicted the risk of EOP. Imbalance in fatty acid levels and desaturase indices predate the clinical diagnosis of PE, indicating their role in its pathophysiology. Measurement of fatty acids and desaturase indices in early pregnancy merits evaluation as predictors of risk of PE.

Drivers of food acquisition practices in the food environment of peri-urban Hyderabad, India: A qualitative investigation.

This study investigates drivers of food acquisition practices in the food environment of peri-urban Hyderabad, India. We used a multi-method qualitative methodology that included in-depth interviews (n = 18) and an innovative qualitative geographical information systems (Q-GIS) approach, featuring participatory photo mapping and follow-up graphic-elicitation interviews (n = 22). Secondary data from eight focus group discussions (n = 94) was used to corroborate findings related to fruits and vegetables. Thematic analysis identified three primary drivers of food acquisition practices among adults: 1) Food prices and affordability; 2) Vendor and product properties, including (a) quality and freshness, and (b) adulteration and contamination; and 3) Social capital. Drivers of food acquisition and consumption among children and adolescents were a key concern for our participants, and included food availability and accessibility, desirability, and convenience. Findings reveal a need for targeted interventions in external and personal food environments to improve diets, nutrition, and health in this setting.

Study of short term memory status in adult bipolar disorder patients in south Indian population.

The present study was undertaken to establish short term memory status in bipolar disorder cases as compared with normal age and sex matched control group in Bijapur (Karnataka). Results showed that a significant decrease in short term memory status in bipolar disorder cases as compared to their control group .Loss of attention, decreased processing speed and executive function patterns may be the probable causes of such observations.

Histopathological alterations in hepatopancreas of Gafrarium divaricatum exposed to xylene, benzene and gear oil-WSF.

Gafrarium divaricatum were exposed to xylene (4.25 and 8.50 mg l(-1)), benzene (4.35 and 8.70 mg l(-1)) and gear oil-WSF (1 and 2%) for 30 days. Chronic exposure of clams to the pollutants resulted in loss of bubbling epithelium, reduction in cytoplasm volume and density, fusion of cell membranes and nuclei forming darkly stained area at basal part of the cells. Disintegration of basement membrane due to damaged epithelial cells, disruption of inner lining of tubule, formation of necrotic spaces, separation of epithelial cells from basement membrane, increase in internal luminar area, complete necrosis of epithelial cells as well as occurrence of cell debris in between the tissue were also observed in the clams due to chronic exposure of the toxicants.

Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA).

In order to identify new metabolic abnormalities in patients with complex neurodegenerative disorders of unknown aetiology, we performed high resolution in vitro proton nuclear magnetic resonance spectroscopy on patient cerebrospinal fluid (CSF) samples. We identified five adult patients, including two sisters, with significantly elevated free sialic acid in the CSF compared to both the cohort of patients with diseases of unknown aetiology (n = 144; P < 0.001) and a control group of patients with well-defined diseases (n = 91; P < 0.001). All five patients displayed cerebellar ataxia, with peripheral neuropathy and cognitive decline or noteworthy behavioural changes. Cerebral MRI showed mild to moderate cerebellar atrophy (5/5) as well as white matter abnormalities in the cerebellum including the peridentate region (4/5), and at the periventricular level (3/5). Two-dimensional gel analyses revealed significant hyposialylation of transferrin in CSF of all patients compared to age-matched controls (P < 0.001)--a finding not present in the CSF of patients with Salla disease, the most common free sialic acid storage disorder. Free sialic acid content was normal in patients' urine and cultured fibroblasts as were plasma glycosylation patterns of transferrin. Analysis of the ganglioside profile in peripheral nerve biopsies of two out of five patients was also normal. Sequencing of four candidate genes in the free sialic acid biosynthetic pathway did not reveal any mutation. We therefore identified a new free sialic acid syndrome in which cerebellar ataxia is the leading symptom. The term CAFSA is suggested (cerebellar ataxia with free sialic acid).

Prenatal sonographic diagnosis of fetal persistent urogenital sinus with congenital hydrocolpos.

We report a case of persistent urogenital sinus with hydrocolpos and associated renal anomalies diagnosed prenatally at 30 weeks' gestation. The prenatal findings were confirmed on postnatal ultrasonography and genitogram with voiding urethrogram. The imaging features and a review of the literature are discussed. The possibility of hydrometrocolpos secondary to urogenital sinus should be considered on prenatal sonography in the presence of a presacral cystic mass with clear urine or turbid contents and a fluid-debris level (cervical or vaginal secretions). Because the prognosis and neonatal management of isolated hydrocolpos (which usually resolves spontaneously) differ greatly from those of hydrocolpos associated with a cloacal malformation, it is important to diagnose prenatally any associated anomalies in order to allow optimal postnatal management.

Infant limbus: an immunohistological study.

All published literature to date has identified the human corneo-scleral limbus as the site within which stem cells of the ocular surface reside. Recently we described a unique anatomical structure at the limbus, termed the Limbal Epithelial Crypt (LEC) that has features of a putative stem cell niche. In this study we examined infant limbus tissue (donor age 4 months) for evidence of LEC and performed immunohistological comparison between infant limbus and adult LEC. No defined LEC were detected in the infant limbus. However, the entire infant limbus has characteristics resembling adult LEC. Both infant limbus and LEC demonstrated negative expression for desmoglein 3. p63 and integrin beta1 expressions were located to the distal region of the infant limbus and to the basal region of the LEC. ABCG2 expression was positive throughout most of the infant limbus as was connexin 43. Infant limbus and in particular the distal region, appeared to house cells that are more "stem-like" in nature. The LEC may be a result of normal physiological developmental in order to protect and maintain stem cells at the ocular surface.

Antiphospholipid antibodies in haemophilia patients with severe bleeding tendency: cause, consequence or a consequential cause?

The prevalence, cause and the impact of antiphospholipid antibodies (APAs) on the clinical severity in haemophilia patients is poorly studied. We studied 72 severe seronegative (negative for HIV, HBsAg, HCV) haemophilia patients for the presence of four common APAs. Twenty-six (36.1%) were positive for any one of the APAs studied of which eight were positive only for anticardiolipin antibodies, three for beta2 glycoprotein (beta2GP1), four for prothrombin (PT) and six for anti annexin antibodies. Remaining six patients showed multi-specific antibodies. Further, clinically severe haemophilia patients (n = 37) showed higher prevalence of APAs as compared with the clinically milder group (n = 35) suggesting that these antibodies do not contribute in alleviating the clinical severity in haemophilia patients as has been observed with other inherited thrombophilia markers. The study of in vitro thrombin generation showed a higher endogenous thrombin potential (ETP) i.e. almost normal, in case of beta2GP1-positive patients as compared with patients with other types of APAs. High prevalence of APAs in clinically severe haemophilia patients may be a consequence of continuing tissue damage in the clinically severe group; as in India, clotting factor concentrates cannot be used ad lib because of financial constraints. Higher thrombin-generating potential in case of patients positive for beta2GP1 did not seem to have any impact on the clinical severity of haemophilia patients.

Antiplatelet antibodies in cases of Glanzmann's thrombasthenia with and without a history of multiple platelet transfusion.

Antiplatelet antibodies are known to be present in a wide spectrum of patients, which include chronic Idiopathic Thrombocytopenic Purpura (ITP), infections, etc., including Glanzmann's thrombasthenia (GT) patients who receive multiple platelet transfusions. The presence of natural antibodies to platelet receptors is not studied in cases of GT. We studied the antiplatelet antibodies in 23 patients with GT, 15 of which had received multiple transfusions and eight that had not received transfusions, along with 50 cases of chronic ITP. The prevalence and specificity of platelet-bound antibodies were detected by inhibition assays using O-group platelets on flow cytometry. The mean antiplatelet antibodies in 15 patients of GT who had not received transfusions and eight patients with multiple transfusions was 8427 + 2131.88 and 9038 + 2856 antibodies/platelet, respectively, while in case of the 50 ITP patients studied, it was 22166 + 5616 antibodies/platelet (Normal Range 1500-3200 antibodies/platelet). We conclude that GT patients who have not received transfusions may develop antiplatelet antibodies to the missing/abnormal receptor. Whether this is due to a molecular mimicry or due to some other mechanism needs to be explored.

Environmental impacts of dietary shifts in India: A modelling study using nationally-representative data.

Food production is a major driver of environmental change, and unhealthy diets are the leading cause of global disease burden. In high-income countries (HICs), modelling studies suggest that adoption of healthy diets could improve population health and reduce environmental footprints associated with food production. We assessed whether such benefits from dietary change could occur in India, where under-nutrition and overweight and obesity are simultaneously prevalent. We calculated the potential changes in greenhouse gas (GHG) emissions, blue and green water footprints (WFs), and land use (LU), that would result from shifting current national food consumption patterns in India to healthy diets (meeting dietary guidelines) and to "affluent diets" (those consumed by the wealthiest quartile of households, which may represent future purchasing power and nutritional trajectories). Dietary data were derived from the 2011-12 nationally-representative household expenditure survey, and we assessed dietary scenarios nationally and across six Indian sub-regions, by rural or urban location, and for those consuming above or below recommended dietary energy intakes. We modelled the changes in consumption of 34 food groups necessary to meet Indian dietary guidelines, as well as an affluent diet representative of those in the highest wealth quartile. These changes were combined with food-specific data on GHG emissions, calculated using the Cool Farm Tool, and WF and LU adapted from the Water Footprint Network and Food and Agriculture Organization, respectively. Shifting to healthy guidelines nationally required a minor increase in dietary energy (3%), with larger increases in fruit (18%) and vegetable (72%) intake, though baseline proportion of dietary energy from fat and protein was adequate and did not change significantly. Meeting healthy guidelines slightly increased environmental footprints by about 3-5% across GHG emissions, blue and green WFs, and LU. However, these national averages masked substantial variation within sub-populations. For example, shifting to healthy diets among those with dietary energy intake below recommended guidelines would result in increases of 28% in GHG emissions, 18 and 34% in blue and green WFs, respectively, and 41% in LU. Decreased environmental impacts were seen among those who currently consume above recommended dietary energy (-6 to -16% across footprints). Adoption of affluent diets by the whole population would result in increases of 19-36% across the environmental indicators. Specific food groups contributing to these shifts varied by scenario. Environmental impacts also varied markedly between six major Indian sub-regions. In India, where undernutrition is prevalent, widespread adoption of healthy diets may lead to small increases in the environmental footprints of the food system relative to the status quo, although much larger increases would occur if there was widespread adoption of diets currently consumed by the wealthiest quartile of the population. To achieve lower diet-related disease burdens and reduced environmental footprints of the food system, greater efficiency of food production and reductions in food waste are likely to be required alongside promotion of healthy diets.

Immobilization of Candida rugosa lipase on poly(allyl glycidyl ether-co-ethylene glycol dimethacrylate) macroporous polymer particles.

Macroporous polymer particles containing surface epoxy groups were synthesized for immobilization of Candida rugosa lipase (CRL). The effect of incorporation of two different sets of monomers [allyl glycidyl ether (AGE) and glycidyl methacrylate (GMA)] and the effect of crosslinking density on immobilization of lipase were studied. AGE-co-EGDM polymers gave higher binding and expression of lipase than GMA-co-EGDM polymers. Optimization of immobilization parameters was done with respect to immobilization time and enzyme loading. Amongst AGE-co-EGDM polymer series, AGE-150 polymer found to give maximum lipase activity yield and therefore evaluated for temperature, pH and storage stability. Under optimum conditions, AGE-150 polymer gave 78.40% of activity yield. Immobilized lipase on AGE-150 showed a broader pH, higher temperature and excellent storage stability.

Immunoprofile of Hodgkin's lymphoma in India.

AIMS AND BACKGROUND: The immunoprofile of the Reed Sternberg cell with respect to immunoreactivity for CD20 and lack of CD15 has been described as a poor prognostic factor. Large scale studies analyzing the immunoprofile of Hodgkin's lymphoma (HL) from India are lacking. The aim of this study was to obtain baseline information on relative frequencies and immunoprofiles of the two major types of HL and comparing reports from developed and developing countries. MATERIALS AND METHODS: 451 cases of HL were classified as per the WHO into classical (n= 397) HL (cHL) and nodular lymphocyte predominant HL (NLPHL) (n=54). Cases of cHL were divided into 5 immunophenotypic groups; Group A (CD15+,CD30+,CD20-), Group B (CD15-,CD30+,CD20-), Group C (CD15+,CD30+,CD20+), Group D (CD15-,CD30+,CD20+)and Group E (CD15-,CD30-,CD20+). In cases of NLPHL, the immunophenotype of lymphocytes in the background, whether T(CD3) or B(CD20) rich was observed. RESULTS: Most cases of cHL belonged to Group A (44.58%) followed by Group B (40.05%), C(5.54%), D(9.57%) and E(0.25%). Half, (50.89%) the cases of cHL were immunonegative for CD15, whereas CD20 was expressed by 15.61% of the cases. Three (5.55%) cases of NLPHL showed a CD3 (T) cell rich background. Significant differences were also observed with respect to the age distribution of cHL as compared to the west. CONCLUSION: Our study demonstrates that India has a high number of CD15 negative and a relatively higher number of CD20 positive cHL cases as compared to the western population. Favorable treatment response and good cure rates that one sees in western cHL may not apply to India.

Perinuclear Antineutrophil Cytoplasmic Antibody Positive Glomerulonephritis in a Case of Limited Cutaneous Scleroderma.

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis in a patient of scleroderma is very rare. Very few cases have been reported in English literature. We report a case of a 58-year-old male with long-standing limited cutaneous scleroderma (Scl-70 positive) presenting with normotensive scleroderma renal crisis. Perinuclear ANCA with antimyeloperoxidase antibody was found to be strongly positive. Renal biopsy showed pauci immune-necrotizing crescentic glomerulonephritis. We believe that this case report will be helpful in understanding clinical features of normotensive ANCA-associated glomerulonephritis in scleroderma patients.

Variation in skin hydration on the basis of Deha Prakriti (body constitution): A cross-sectional observational study.

BACKGROUND: Prakriti (body constitution) is an important concept of Ayurveda which is decided at the time of birth. It shows differences in physical, physiological and psychological characteristics of an individual. Variation in skin characteristics is found as per Prakriti. AIM: The aim of the present work was to study hydration of skin over volar forearm in people with different Prakriti with the help of skin diagnostic SD 27 instrument. SUBJECTS AND METHODS: This was a cross-sectional study conducted at Cosmetic Technology Department in unmarried healthy female students of (18-30 years). A total of 904 volunteers were screened, of which 621 volunteers were further examined for Deha Prakriti for screening of single Dosha dominant Prakriti. 58 Vata, 70 Pitta and 61 Kapha dominant Prakriti were eligible for further study, but on actual day of skin examination, 50 volunteers in each group completed the study. Skin hydration was measured by skin diagnostic SD 27 instrument. RESULTS: It was found that maximum people with Vata (92%) and Pitta dominant Prakriti (70%) had less hydration while (48%) Kapha dominant Prakriti volunteers had normal to dehydrated skin. Chi-square test was used for analysis. The Chi-square value is 45.9 and P = 0.0001, which is highly significant. CONCLUSION: The skin of Vata and Pitta dominant Prakriti had less hydration while hydration was well maintained in Kapha dominant Prakriti than that of Vata and Pitta Prakriti people.