Demodex canis targets TLRs to evade host immunity and induce canine demodicosis.

Widespread incidence of Demodex mites throughout the mammalian class and occasional serious and fatal outcomes in dogs warrant an insight into the host-parasite interface especially. Therefore, this study was aimed to unravel the interplay between innate immune response and canine demodicosis. The dogs diagnosed to have natural clinical demodicosis were allocated into two groups; dogs with localized demodicosis (LD) and with generalized demodicosis (GD). The expression of toll-like receptors (TLRs) 2, 4 and 6 genes in peripheral blood mononuclear cells of these dogs was quantified by real-time PCR. Significantly increased TLR2 gene expression, while significantly diminished TLR4 and TLR6 gene expressions were observed in demodicosed dogs (LD and GD) as compared with the healthy ones. Even the expression of TLR2 gene was found to differ significantly between the dogs with LD and GD. Therefore, it can be inferred that clinical demodicosis in dogs is coupled with an up-regulation of TLR2 and down-regulation of TLR4 and TLR6 gene expressions. Overexpression of TLR2 gene might be responsible for Demodex-induced clinical manifestations, while TLR4 and TLR6 gene down-regulations could be the paramount strategy of Demodex mites to elude the host-immune interface.

Inpatient burden of esophageal cancer and analysis of factors affecting in-hospital mortality and length of stay.

Esophageal cancer (EC) continues to be a major source of morbidity and mortality in the United States. However, there has been a relative dearth of research into hospital utilization in patients with EC. This study examines temporal trends in hospital admissions, length of stay (LOS), mortality, and costs associated with EC. In addition, we also analyzed factors associated with inpatient mortality and LOS. We interrogated National Inpatient Sample (NIS), a large registry of inpatient data, to retrieve information about various demographic and factors associated with hospital stay in patients who were admitted for EC between the years 1998 and 2013 in the United States. After examining trends over time, multivariate analysis was performed to identify factors associated with LOS and mortality. During 1998-2013, 538,776 hospital stays with principal diagnosis of EC were reviewed. Number of hospital stays and inpatient charges increased by 397 per year (±67.8; P < 0.0001) and $3,033 per patient per year (±135; <0.0001) respectively. Mortality and LOS decreased by 0.23% per year (±0.03; P < 0.0001) and 0.07 days per year (±0.006; P < 0.0001) respectively. Multiple factors associated with LOS and mortality were outlined. Despite overall increase in hospital utilization with respect to number of admissions and inpatient charges, inpatient mortality and LOS associated with EC declined. Factors associated with inpatient mortality and LOS may help drive clinical decision-making and influence healthcare or hospital policy.

Synthesis of OSL nanophosphor Li3B7O12:Mn and its dosimetric properties.

The present paper reports the structural, morphological and optical properties of nanophosphor Li3B7O12:Mn with an optimised dopant concentration of 0.25 mol% and its surface modification under the irradiation of 250 keV proton beams and gamma photons for ion fluence ranging from 1 × 1013 to 6.25 × 1015 ions cm-2 and doses from 100 mGy-100 Gy, respectively. This nanophosphor has been synthesised by the high temperature solid state reaction method. Its optical properties are characterised by optically stimulated luminescence (OSL) and thermo luminescence (TL) techniques. This nanophosphor is polycrystalline in nature with a grain size of 40-80 nm confirmed by x-ray diffraction (XRD) and transmission electron microscopy (TEM). The OSL decay and TL glow curve response of the proton beam irradiated samples exhibit significant intensity at a fluence of 2.5 × 1014 ions cm-2. Moreover, Li3B7O12:Mn displays a linear response for gamma doses in the range of 100 mGy-50 Gy. We have also investigated the reusability and reproducibility of this material. The above study demonstrates that Li3B7O12:Mn is a robust and promising candidate for medical proton dosimetry.

Isolation of antibacterial protein from Lactobacillus spp. and preparation of probiotic curd.

The study was aimed to isolate antagonistic lactobacilli and the molecules responsible for their antagonistic ability from curd. Preparation of probiotic curd and the ability of the selected lactobacilli to suppress the pathogen therein was also assessed. All the 116 isolates were identified as Lactobacillus spp. based on morphological, biochemical and curdling assays. Five of these lactobacilli (Lb-17, Lb-33, Lb-108, Lb-112, and Lb-N3) were found most promising to inhibit all test pathogens (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi and Shigella sonnei). The cell-free culture supernatants of these five lactobacilli were recorded as thermo-tolerant when subjected to heat treatment at 100 °C for 20 min. The loss in the activity after protease treatment indicated the proteinaceous nature of the antimicrobial molecule present in the culture supernatants. Active protein (19 kDa) produced by lactobacilli was confirmed by SDS-PAGE followed by agar-overlay method. Antibiotic sensitivity assay revealed that the selected Lactobacillus spp. isolates were resistant to methicillin and vancomycin. Probiotic curd prepared by using Lb-108 and Lb-N3 was found to be superior to rest of the three isolates based on organoleptic tests and shelf-life. Complete inhibition of all the test pathogens in curd was shown by Lb-108 and Lb-N3. Inhibition spectrum, production of thermostable protein and preparation of quality curd suggest Lb-108 and Lb-N3 as promising candidates to prepare probiotic curd.

Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

Diabetes and cancer: two diseases with obesity as a common risk factor.

There is a growing body of evidence to support a connection between diabetes (predominantly type 2), obesity and cancer. Multiple meta-analyses of epidemiological data show that people with diabetes are at increased risk of developing many different types of cancers, along with an increased risk of cancer mortality. Several pathophysiological mechanisms for this relationship have been postulated, including insulin resistance and hyperinsulinaemia, enhanced inflammatory processes, dysregulation of sex hormone production and hyperglycaemia. In addition to these potential mechanisms, a number of common risk factors, including obesity, may be behind the association between diabetes and cancer. Indeed, obesity is associated with an increased risk of cancer and diabetes. Abdominal adiposity has been shown to play a role in creating a systemic pro-inflammatory environment, which could result in the development of both diabetes and cancer. Here, we examine the relationship between diabetes, obesity and cancer, and investigate the potential underlying causes of increased cancer risk in individuals with diabetes. Current treatment recommendations for reducing the overall disease burden are also explored and possible areas for future research are considered.

Subcutaneous injection of hyaluronidase with recombinant human insulin compared with insulin lispro in type 1 diabetes.

AIMS: Prandial treatment with human regular insulin for diabetes may result in early postprandial hyperglycaemia and late hypoglycaemia due to its slow onset and long duration of action. This study compared injections of recombinant human insulin (rHI) formulated with recombinant human hyaluronidase [rHuPH20] (INSULIN-PH20) to insulin lispro for prandial treatment in subjects with type 1 diabetes (T1D). METHODS: After a 1-month run-in period using twice-daily insulin glargine (or usual basal insulin therapy for pump users) with prandial lispro, 46 subjects with T1D (42 ± 13 years; body mass index: 26 ± 4 kg/m(2); A1c: 6.8 ± 0.5%) were assigned to INSULIN-PH20 or lispro in a random sequence for two consecutive, 12-week periods as the prandial insulin in an intensive treatment regimen. RESULTS: The mean glycaemic excursion for INSULIN-PH20 (0.96 ± 2.00 mmol/l) was comparable (p = 0.322) to lispro (0.80 ± 1.95 mmol/l). The 8-point self-monitored blood glucose profiles were also comparable in the two groups. Good glycaemic control (A1c) was maintained for both treatments at 12 weeks (INSULIN-PH20: 7.0 ± 0.5%; lispro: 6.9 ± 0.6%). Overall rates of hypoglycaemia (≤ 3.9 mmol/l) were 24 events per patient per 4 weeks for INSULIN-PH20 and 22 events for lispro. There were no significant differences in adverse events or immunogenicity between treatments and both treatments were well tolerated. CONCLUSIONS: Unlike commercially available formulations of regular human insulin, a formulation of rHI with rHuPH20 was comparable to lispro for postprandial glucose excursions in a basal-bolus treatment regimen for T1D patients. Glycaemic control, safety and tolerability profiles were comparable for both treatments.

Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN(®) Basal-Bolus Type 1): 2-year results of a randomized clinical trial.

AIMS: The goal of this study was to compare the long-term safety and efficacy of the basal insulin analogue, insulin degludec with insulin glargine (both with insulin aspart) in Type 1 diabetes, over a 2-year time period. METHODS: This open-label trial comprised a 1-year main trial and a 1-year extension. Patients were randomized to once-daily insulin degludec or insulin glargine and titrated to pre-breakfast plasma glucose values of 3.9-4.9 mmol/l. RESULTS: The rate of nocturnal confirmed hypoglycaemia was 25% lower with insulin degludec than with insulin glargine (P = 0.02). Rates of confirmed hypoglycaemia, severe hypoglycaemia and adverse events, and reductions in glycated haemoglobin and fasting plasma glucose were similar between groups. Despite achieving similar glycaemic control, insulin degludec-treated patients used 12% less basal and 9% less total daily insulin than did insulin glargine-treated patients (P < 0.01). CONCLUSIONS: Long-term basal therapy using insulin degludec in Type 1 diabetes required lower doses and was associated with a 25% lower risk for nocturnal hypoglycaemia than insulin glargine.

Impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes treated with insulin glargine or NPH insulin.

AIM: To compare the impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin glargine or NPH insulin. METHODS: A pooled analysis of 24-week patient level data from randomized controlled studies comparing once-daily insulin glargine with once-daily NPH insulin in insulin-naïve adult patients with T2DM was performed, stratifying patients into quartiles by duration of diabetes: <5.8 years; 5.8 to <9.2 years; 9.2 to <14 years and ≥14 years. Daytime and nocturnal hypoglycaemia events were evaluated. RESULTS: Data from 2330 patients in four randomized controlled trials were included in the analysis; 1258 treated with insulin glargine and 1072 with NPH insulin. The rates of daytime hypoglycaemia were similar for insulin glargine and NPH insulin, irrespective of disease duration. Patients with longer T2DM duration treated with glargine experienced greater glycated haemoglobin A1c (HbA1c) reductions. Rates of severe nocturnal hypoglycaemia and nocturnal hypoglycaemia [self-monitored blood glucose < 70 mg/dl (3.89 mmol/l) and < 50 mg/dl (2.78 mmol/l)] were all significantly and positively correlated with the duration of diabetes for patients treated with NPH insulin but not with insulin glargine. Despite improvements in HbA1c, rates of symptomatic nocturnal hypoglycaemia were significantly lower with insulin glargine than with NPH insulin in patients with longer T2DM duration. CONCLUSION: There is a lower risk for nocturnal hypoglycaemia with insulin glargine than with NPH insulin. When considering diabetes duration, insulin glargine (compared to NPH insulin) may be particularly beneficial in patients with a longer duration of T2DM.

Induced phytoremediation of metals from fly ash mediated by plant growth promoting rhizobacteria.

A study was carried out to observe the impact of a consortium of bacteria isolated from the fly ash on the metal accumulation by T. latifolia. When a consortium of bacteria Bacillus endophyticus NBRFT4 (MTCC 9021), Paenibacillus macerans NBRFTS (MTCC 8912) and Bacillus pumilus NBRFT9 (MTCC 8913) was bioaugmented into the rhizosphere of T. latifolia, it enhanced the metal concentration in root, stem and leaves of the plants through increased bioavailability of metals Fe, Cd, Pb, Cr, Ni, Cu and Zn in the fly ash. Besides, these bacteria also promoted the plant growth perhaps due to utilization of ACC, synthesis of phytoharmones and solubilisation of essential metals found in fly ash. As compared to fly ash alone, the accumulation of Fe was maximally enhanced by 164%, 196%, and 251%, followed by Ni by 92%, 44% and 56%, Zn by 82%, 57% and 91%, Cu by 71%, 53% and 60%, Cr by 96%, 80% and 105%, Pb by 119%, 87% and 140%, Cd by 80%, 109% and 115% in root, stem and leaves, respectively in fly ash with bacteria. Thus, an increased solubilisation of metals coupled with enhanced plant growth stimulated the phytoextraction of metals by T. latifolia from fly ash.

Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes.

OBJECTIVE: Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. DESIGN: Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. SETTING: Antenatal clinics. POPULATION: Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). METHODS: Maternal serum levels of sRAGE (total circulating pool), N(ε)-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. MAIN OUTCOME MEASURES: Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE-). RESULTS: In DM PE+ versus DM PE-, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE:hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE:AGE and sRAGE:CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. CONCLUSIONS: In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM.

Treatment practices in pulmonary tuberculosis by private sector physicians of Meerut, Uttar Pradesh.

BACKGROUND: Majority of the qualified medical practitioners in the country are in the private sector and more than half of patients with tuberculosis (TB) seek treatment from them. The present study was conducted with the objective of assessing the treatment modalities in pulmonary tuberculosis by the private physicians in Meerut City, Uttar Pradesh, India. METHODS: A cross-sectional study was carried out covering all the private physicians (graduates and postgraduates in Medicine and Chest Diseases) registered under the Indian Medical Association, Meerut Branch (n = 154). The physicians were interviewed by a pre-designed and pre-tested questionnaire about the treatment modalities practiced by them. RESULTS: Only 43.5% private physicians had attended any Revised National Tuberculosis Control Programme (RNTCP) training in the past five years. Only 33.1% of them were aware of the International Standards of Tuberculosis Care (ISTC). Fifty-three different regimens were used to treat the patients. Majority of physicians (76%) prescribed daily regimens while 24% administered both daily and intermittent treatment. None of the private physicians prescribed exclusive intermittent regimen. Eighty-seven different treatment regimens were used for the treatment of multidrug-resistant TB (MDR-TB) with none of them prescribing standard treatment under RNTCP. CONCLUSION: As majority of private practitioners do not follow RNTCP guidelines for treating TB, there is an urgent need for their continued education in this area.

Stimulated phytoextraction of metals from fly ash by microbial interventions.

Various combinations of fly ash tolerant bacteria isolated from the rhizospheric zone of Typha latifolia naturally growing on a fly ash dump site were tested for enhanced metal uptake by Brassica juncea grown in fly ash amended with press mud. After enrichment of the bacteria in a nutrient broth, they were subsequently applied to the rhizospheric zone of B. juncea in different combinations. When the metal analysis was done in the plants at their maturity, it was revealed that out of 11 bacterial consortia prepared from the different combinations of four bacterial strains, Micrococcus roseus NBRFT2 (MTCC 9018), Bacillus endophyticus NBRFT4 (MTCC 9021), Paenibacillus macerans NBRFT5 (MTCC 8912) and Bacillus pumilus NBRFT9 (MTCC 8913), a combination of NBRFT5, NBRFT4 and NBRFT9 (ST3) was found to have induced the highest metal accumulations as compared to other consortia. The bioaugmentation of the ST3 consortium enhanced Fe accumulation by 247%, Ni by 231% and Zn by 223% in B. juncea as compared to control plants. These values were found to be significantly higher than the other bacterial consortia. Bacteria were also found to produce siderophores which could enhance the metal uptake by plants through metal mobilization. Besides siderophores, bacteria are also known to produce protons, organic acids and enzymes which enhance the metal mobilization and boost the phytoextraction process. The translocation of metals from root to stem was invariably higher than from stem to leaf. Hence, ST3 was adjudged the best consortium to be used in the field application to accelerate the phytoextraction of metals from fly ash by B. juncea.

Effect of sitagliptin on glucose control in adult patients with Type 1 diabetes: a pilot, double-blind, randomized, crossover trial.

AIMS: Patients with Type 1 diabetes have significantly elevated postprandial glucagon secretion. Dipeptidyl peptidase IV inhibitors improve HbA(1c) by several mechanisms, including increasing glucagon-like peptide 1 and glucose-dependent insulinotropic peptide concentrations, which decreases postprandial rises in glucagon in both Type 1 and Type 2 diabetes. This study evaluates the clinical implications of sitagliptin in adult patients with Type 1 diabetes. METHODS: This investigator-initiated, double-blind, randomized, crossover, 8-week, pilot study enrolled 20 adult subjects with Type 1 diabetes. Subjects received sitagliptin 100 mg/day or placebo for 4 weeks and then crossed over. Outcomes included 2-h postprandial blood glucose and 24-h area under the curve changes in glucose measurements from continuous glucose monitoring, HbA(1c) , fructosamine and insulin dose. RESULTS: Sitagliptin significantly reduced blood glucose (2-h postprandial and 24-h area under the curve) despite reduced total and prandial insulin dose. Based on continuous glucose monitor findings, sitagliptin improved measures of glycaemic control, including mean blood glucose (-0.6 mmol/l; P = 0.012) and time in euglycaemic range 4.4-7.8 mmol/l (0.4 ± 0.2 h; P = 0.046). Significant reductions were also observed in M100, Glycemic Risk Assessment Diabetes Equation (GRADE) and J-index. After controlling for period, treatment and insulin dose, the HbA(1c) was also significantly reduced [-0.27 ± 0.11% (-2.91 ± 1.16 mmol/mol); P = 0.025] when patients were taking sitagliptin. CONCLUSIONS: Sitagliptin significantly improved overall glucose control, including postprandial and 24-h glucose control, in adult patients with Type 1 diabetes, while significantly reducing prandial insulin requirements. Further investigation is warranted in patients with Type 1 diabetes in a larger cohort designed to assess both clinical outcomes and mechanism of action.

Effects of colesevelam on LDL-C, A1c and GLP-1 levels in patients with type 1 diabetes: a pilot randomized double-blind trial.

AIM: colesevelam is indicated to lower low density lipoprotein cholesterol (LDL-C) in hyperlipidaemia and improve glycaemic control in adults with type 2 diabetes. This short-term pilot study evaluates its effects in type 1 diabetes. METHODS: this double-blind, randomized, investigator-initiated, single-centred, 12-week pilot study evaluated 40 adults (age = 36.4 ± 9.4 years) with type 1 diabetes (duration = 20.4 ± 8.5 years) and hyperlipidaemia. It was powered to show a treatment difference of >10% LDL-C reduction. Subjects received 3.75 g/day colesevelam (n = 20) or placebo (n = 20) for 12 weeks. LDL-C and haemoglobin A1c (A1c) levels were assessed at screening (week 2), baseline (week 0) and every 4 weeks throughout the treatment duration. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) levels were measured during 4-h meal (Boost Plus, Nestle HealthCare Nutrition Inc., Florham Park, New Jersey, USA) challenge tests (MCT) at baseline and 12 weeks. RESULTS: colesevelam treatment resulted in a significant reduction in LDL-C values at 4 weeks [-12.1% (95% CI: -20.1 to -4.1), p = 0.004] which was sustained for the study duration (p = 0.005 at 12 weeks). The treatment group also showed a significant change in A1c from baseline at week 4; however, this was not significant for the study duration. There was a significant median increase in GLP-1 levels during the first 2 h of the baseline MCT in the treated group but no difference at 12 weeks. CONCLUSIONS: during this short-term pilot study, colesevelam treatment effectively lowered LDL-C in patients with type 1 diabetes. Improvements in A1c seen at week 4 were not sustained. Effects on glycaemic control in subjects with type 1 diabetes may be related to a postprandial rise in GLP-1 levels and require further clinical study.

Self-monitoring of blood glucose.

Many would argue that the introduction of modern-day diabetes management started 30 years ago with the introduction of self-monitoring of blood glucose (SMBG) at home. While that may be true, it is interesting that many of today's fundamental questions have yet to be answered. Furthermore, the technology itself continues to change, to improve and to better exist with our non-diabetes technology. For example, the first SMBG 'apps' are available now for smart-phones (iPhone), and we can expect the phones themselves to participate more directly with SMBG and diabetes management. Still, both researchers (and payors) continue to ask some fundamental questions. 1. What is the efficacy of SMBG for patients not requiring insulin therapy? 2. What is the optimum frequency of SMBG for patients who do require insulin therapy? 3. What is the role of software to assist in data management for SMBG (for both patients and clinicians)? 4. What is the cost effectiveness of SMBG for all of the different patient populations with diabetes? 5. What is the ideal chemistry which results in the least amount of interfering substances with SMBG? 6. What is an acceptable accuracy for SMBG both at home and in the hospital? The accuracy question is more important than ever since all continuous glucose monitoring (CGM) for now are calibrated with SMBG results. 7 What is the best strategy for teaching patients how best to use their SMBG data? 8. What is the best way to integrate SMBG with insulin pump therapy? 9. What is the role of SMBG with today's CGM devices? 10. What will the role of SMBG be 5-10 years from now with future CGM devices? These are just some of the questions which need more thought and study as we move into 2011. In this chapter we have selected papers that appeared in the PubMed on this topic and chose those we thought were most influential in this area. We have then addressed many of these topics although answers are far from clear for many of them. Although SMBG is not 'new' technology, much research needs to be completed before we fully understand this tool's full impact, particularly as CGM becomes more popular.

Cellular coupling of potassium channels with beta2 adrenoceptors in mediating myometrial relaxation in buffaloes (Bubalus bubalis).

Present study unravels the functional presence of potassium channels and their involvement in mediating beta(2) adrenoceptors-induced myometrial relaxation in buffalo myometrium. Isolated myometrial preparations exhibited rhythmic spontaneity with regular pattern of amplitude and frequency. Levcromakalim produced concentration-dependent inhibitory effect on myometrial spontaneity and relaxant effect and the dose-response curve (DRC) was shifted towards right in the presence of glybenclamaide. In the tissues pretreated with glybenclamide, relaxant effect of albuterol was significantly (P < 0.05-0.001) lower (pD(2) = 6.94, R(max) = 96.8 +/- 3.3%; n = 5) compared with albuterol alone (pD(2) = 8.55, R(max) = 101.1 +/- 6.3%; n = 6) and the DRC was shifted to right. In the presence of tetraethyl ammonium (TEA) also, significant (P < 0.001) rightward shift of DRC of albuterol with decrease in maximal effect (pD(2) = 8.05, R(max) = 71.2 +/- 7.4%; n = 7 vs. control pD(2) = 8.55, R(max) = 101.1 +/- 6.3%; n = 6) was observed. On the other hand, 4-aminopyridine (1 mm) sensitized the myometrial strips and increased the amplitude and frequency/min of myometrial spontaneity but failed to significantly alter the DRC of albuterol. Results of present study suggest the functional presence of K(ATP), BK(Ca) and K(V) channels in buffalo myometrium, but beta(2)-adrenoreceptor agonist-induced myometrial relaxation seems to be K(ATP) and BK(Ca) channel-dependent only. Further, our studies also suggest promising therapeutic potential of potassium channel modulators as tocolytics in buffaloes.

Evaluation of immunogenic potential of 75kDa and 56kDa proteins of newcastle disease virus (NDV).

The R2B strain of virus of new castle disease virus (NDV) was propagated in 9-11 day old embryonated chicken eggs via allantoic cavity route and after seven serial passages virus was purified from allantoic fluid. Purified virus was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis which yielded six major polypeptides ranging from 38-200 kDa. Protein fractions, corresponding to 75 and 56kDa, resembling haemagglutinin-neuraminidase (HN) and fusion (F) proteins were used to ascertain their immunization potential. Immunization of viral proteins was compared with the whole virus vaccine. Among different group of birds, highest haemagglutination inhibition (HI) and enzyme linked immunosorbent assay (ELISA) titers were obtained in birds immunized with whole virus vaccine followed by viral proteins, 75 and 56kDa in combination which was comparable with birds immunized with 56kDa protein alone. Despite lower values of HI and ELISA titers elicited by viral subunits in immunized birds, when challenged with virulent NDV strain, protection accorded by viral proteins in combination (75 +56kDa) or 56kDa alone was comparable with whole virus vaccine.

Studies on in vitro degradability of mixed crude enzyme extracts produced from Pleurotus spp.

A preliminary investigation was conducted to assess lignocellulolytic efficiency of crude extracts from three white-rot fungi, Pleurotus florida PF05 (PF), Pleurotus sajor-caju PS07 (PS) and Pleurotus eryngii PE08 (PE). The activities of CMC-ase, xylanase, beta-glucosidase, beta-xylosidase, laccase and Mn peroxidase in extracts were evaluated. PF produced its highest CMC-ase (317 UL(-1)'), beta-glucosidase (62 UL(-1)), beta-xylosidase (37 UL(-1)) and laccase (347 UL(-1)) activities while, PS produced highest xylanase (269 UL-(1)) and Mn peroxidase (69 UL(-1)) activities. In addition, crude extracts extracted were employed for their in vitro degradability assessment; and were evaluated with mono and mixed extracts separately to corn cob substrate. The losses in cell wall components and dry matter during 5 and 10 days incubations were analyzed after treatments of extracts. Maximum 8.2, 4.4 and 2.8% loss were found respectivelyin hemicellulose (HC), cellulose (C) and lignin (L) with mono extract of PF within 10 days. The influence of mono extract of each strain (PF PS and PE) and their mixed extracts (PF+PS, PF+PE, PS+PE and PF+PS+PE) on degradation of cell wall constituents were remarkably differed. The mixed extract treatment proved maximum 13.6% HC loss by PF+PS+PE extract, 9.2% loss in C by PF+PS extract and 5.2% loss of L by the PF+PS+PE extract treatment. The highest dry matter loss (8.2%) was recorded with PF+PS+PE mixed extract combination.

Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women.

AIMS/HYPOTHESIS: Elevated anti-angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), a soluble form of vascular endothelial growth factor receptor, and endoglin, a co-receptor for TGFbeta1, confer high risk of pre-eclampsia in healthy pregnant women. In this multicentre prospective study, we determined levels of these and related factors in pregnant women with type 1 diabetes, a condition associated with a fourfold increase in pre-eclampsia. METHODS: Maternal serum sFlt1, endoglin, placental growth factor (PlGF) and pigment epithelial derived factor were measured in 151 type 1 diabetic and 24 healthy non-diabetic women at each trimester and at term. RESULTS: Approximately 22% of the diabetic women developed pre-eclampsia, primarily after their third trimester visit. In women with pre-eclampsia (diabetic pre-eclampsia, n = 26) vs those without hypertensive complications (diabetic normotensive, n = 95), significant changes in angiogenic factors were observed, predominantly in the early third trimester and prior to clinical manifestation of pre-eclampsia. Serum sFlt1 levels were increased approximately twofold in type 1 diabetic pre-eclampsia vs type 1 diabetic normotensive women at the third trimester visit (p < 0.05) and the normal rise of PlGF during pregnancy was blunted (p < 0.05). Among type 1 diabetic women, third trimester sFlt1 and PlGF were inversely related (r(2) = 42%, p < 0.0001). Endoglin levels were increased significantly in the diabetic group as a whole vs the non-diabetic group (p < 0.0001). CONCLUSIONS/INTERPRETATION: Higher sFlt1 levels, a blunted PlGF rise and an elevated sFlt1/PlGF ratio are predictive of pre-eclampsia in pregnant women with type 1 diabetes. Elevated endoglin levels in women with type 1 diabetes may confer a predisposition to pre-eclampsia and may contribute to the high incidence of pre-eclampsia in this patient group.