SYNTHESIS AND ANTICONVULSANT ACTIVITY (CHEMO SHOCK) OF N-1(SUBSTITUTED-N-4[(4-OXO-3-PHENYL-3, 4-DIHYDRO-QUINAZOLINE-2-YLMETHYL) SEMICARBAZONES

Objective: This work is designed at finding new structure leads with potential anticonvulsant activities of 4(3H)-quinazolinone pharmacophore scaffold.Methods: A new series of 4(3H)-quinazolinone pharmacophore was designed with substituted moieties possesses different electronic environment in the hope of developing potent and safe new effective compounds. In such fashion, in this paper, we report the synthesis and anticonvulsant activity (Chemo shock) of N-1(substituted-N-4[(4-oxo-3-phenyl-3, 4-dihydro-quinazoline-2-ylmethyl) semicarbazones 3A-d (1-7), 3B-d (1-7), 3C-d (1-7), their chemical structure were characterized using IR,  H-H NMR, and elemental analysis techniques. Their anticonvulsant activity was evaluated using chemicals strychnine, thiosemicarbazide and 4-aminopyridine induced seizure models at a dose of 30, 100, 300 mg/kg unto 2 hrs tests in mice. The rotarod assay was performed in mice to evaluate the neurotoxicity of the compounds. 1Results: Compounds 3C (d-4), 3B (d-4), and 3A (d-4) were observed to be most feasible to act against glutamate receptor for anticonvulsant activity.Conclusions: The results obtained revealed that numbers of novel quinazolinone semicarbazone derivatives are effective in chemical to induce (chemo shock) model and showing good anticonvulsant activity.Keywords: Quinazolinone, Semicarbazones, Strychnine, Thiosemicarbazide, 4-aminopyridine, Anticonvulsant activity, Chemo shock

Milk Production and Nutrient Efficiency of Lactation Goats on Diet Containing Linseed Cake, Mustard Cake and Guar Korma with Urea in Concentrates

Protein supplements, those conventionally used in goat feeding includes oil meals of ground nut, soybean meal, linseed and til etc., which are very costly and their availability is limited for ruminant feeding as these are most used in pig and poultry rations. However, mustard (Brassica juncea) oil meal is available in plenty at cheaper prices but their utilization in goat feeding is limited due to its bitterness (Pailan and Singhal, 2007), which arises upon degradation of glucosinolate contents of mustard (Tripathi and Mishra, 2007). Ruminant animals have unique capability of bioconversion of nonprotein nitrogen substances into microbial protein, which can also substitute organic protein supplement. Guar korma is another high protein feed resource available at cheaper prices, which can also be used in animal feeding in limited quantities. The use of mustard cake in replacement of linseed cake upto 75% in concentrates of lactating Jamunapari goats have been demonstrated earlier. However, information of guar korma use in goat feeding is in scanty. The level and quality of dietary protein and fat have influence on milk production and quality (Tripathi, 2014) Therefore, present experiment aimed to utilized mustard oil meal, urea and guar korma in replacement of conventional linseed oil cake as protein supplement in concentrate mixture of lactating goats feeding and assess the nutrient utilization efficiency for milk production

Bio-efficacy of phytoextracts and oil cakes on Macrophomina phaseolina (Tassi) causing stem rot disease of jute, Corchorus spp.

In the present study efforts were made to explore the efficacy of various plant extracts and oil cakes against Macrophomina phaseolina. The efficacy of eight different plant species, Zingiber officianale, Aloe indica, Lawsonia inermis, Chenopodium album, Allium cepa, Piper betel, Murraya koenigii, Parthenium hysterophorus aqueous extracts including oil cakes of mustard and neem were evaluated by using of poisoned food technique in vitro for their inhibitory effect on mycelial growth of M. phaseolina causing stem rot of jute (Corchorus olitorius and C. capsularis). The rhizome extract of Z. officinale produced maximum growth inhibition (74.59%) of the pathogen followed by leaf extracts of A. indica (63.57%), and leaf extract of L. inermis (60.17%) at the concentration of 10%. The maximum mycelial growth inhibition (52.40%) was recorded with neem cake (Azadirachta indica) at the concentrations of 20% followed by 42.61% and 29.60% with concentration of 15% and 10%, respectively. However, maximum mycelial growth inhibition (19.42%) was recorded with mustard cake (Brassica juncea) at the concentration of 20% followed by 16.64% and 12.20% at the concentration of 15% and 10% respectively. In general mycelial growth inhibition was dose dependent and it was maximum in case of neem cake than mustard cake. The present study revealed that, these plant extracts and oilcake extracts could be exploited for the possible control of deadly pathogen M. phaseolina. Accordingly, this is an important proactive measure in preventing the spread of the stem rot disease through a more ecofriendly approach

A Method: Fornix Depth Measurement in Ophthalmic Socket

Several methods have been publicized to measure the fornix depth but the error in the measurement makes them inconvenient for the correct diagnosis of fornix depth in the eye. In view of the cruelty of disease the precise method is needed to correctly evaluate the fornix depth measurement. In this report, a novel approach is being addressed, to solve the depth measuring issue with the logical experimental design. The explanation with the proposed hypothesis is described here with the relevant scientific approach, the emphasis of certain advantages of the present invention over the conventional measurement approaches. In this case the diagnosis and the process of diagnosis should be accurate, but in the field of ophthalmology an accurate measurement of fornix depth without committing any error was a challenging task. So far in the development of the measurement of fornix depth is concern. Currently, we discussed a novel method for the measurements of fornix depth in ophthalmic eye, which will be beneficial to get the accurate value, however it was not possible in the previously reported methods. It will have many advantages over the existing methods

Prediction of severe adverse maternal outcome in women admitted in obstetric ward using physiological and biochemical parameters

Background: To study physiological and biochemical parameters to predict serious adverse maternal outcomes and to develop risk score using above parameters.Methods: This prospective study was conducted in 500 high risk pregnant women attending tertiary care teaching hospital. We noted physiological and biochemical parameters as soon as they were available .The primary outcome measures was “severe adverse maternal outcome(SAMO)” in form of one or more among  mortality, near miss morbidity and ICU admissions.Results: Out-off 500 women, severe adverse maternal outcomes were seen in 158 (31.6%) women. Most common cause of near miss maternal morbidity was hypertensive disease of pregnancy (62.7%) followed by major obstetric hemorrhage (18.9%). There were 33(6.6%) ICU admission, 23 (4.6%) maternal death and 153 (30.6%) near miss maternal morbidity. The most common cause of maternal death in our study was obstetric hemorrhage. The significant variables after multivariate analysis [temp, pulse, urine protein] were used  to devise a Maternal early warning score (MEWS) based on physiological parameters at score value of  ≥1/6 was found to have  sensitivity of 70% and specificity of 82% in predicting SAMO with AUROC of 0.76. The significant laboratory parameters after multivariate analysis were blood urea, serum creatinine, serum bilirubin and liver enzymes. The obstetric risk score (Maternal risk prediction score MRPS) which incorporated of these laboratory parameters in addition to physiological parameters has sensitivity of 82% and specificity of 75% with AUROC 0.79 value ≥ 2/18.Conclusions: The addition of laboratotory parameters to physiological variables improves performance of risk score to predict SAMO

Mucin MUC13 and YAP1 correlate with poor survival in colorectal cancer

Background: Metastatic disease contributes to over 90% of cancer-associated deaths. Colorectal cancer (CRC), the second lethal malignancy, has the greatest incidence and mortality rates in the Southern United States. Over 40-50% of CRC patients acquire metastasis at some point throughout their disease\u27s progression. CRC survival rate drops from 90%-14% when the disease is confined within the colon and therefore “early diagnosis” becomes imperative to determine timely and quality treatments. We have identified that MUC13 protein translocate to nucleus along with transcription factor Yes-Associated Protein 1 (YAP1) during anchorage independent conditions (metastatic phenotype). YAP1 is known to be overexpressed in CRC which promotes proliferation and survival of CRC cells. This study will provide information regarding MUC13 and YAP1 correlation and their role in CRC patient outcomes. Methods: The comparative analysis of MUC13 and YAP1 expression in CRC samples (Tissue Microarrays (TMA) of CRC patients (39 cases and 95 cores)) with Pathology grade, TNM Classification, Clinical stage, and Survival information were investigated using Immunohistochemistry (IHC) staining, followed by digital scanning by 3D-Histech scanner, and analysis using QuantCenter image analysis software. Results: IHC analysis revealed increased MUC13 expression in colon adenocarcinoma and metastatic adenocarcinoma compared to normal colon tissues. MUC13 expression was observed in nucleus, cytoplasm and membrane associated with mostly with poorly differentiated adenocarcinomas, while YAP1 was localized in the nucleus. The correlation of MUC13/YAP1 expression with patient outcome is in progress. Conclusion: This study will potentially establish a correlation between MUC13 and YAP1 with CRC patient outcome

Chemical composition, in-vitro fermentation and methane production potential of unconventional feed resources in goats

Unconventional feed resources namely Aloe barbadensis (ALB), Musa paradisiaca (MUP), Punica granatum (PUG), Murraya koenigii (MUK), Lawsonia inermis (LOI) and Boehravia diffusa (BOD) were assessed for in- vitro methane production potential and fermentation with whole goat rumen flora. Nutrient content of all the bio- resources were different, and the gas production varied from 57.7 to 161.7 ml/ g DM, with the highest gas in ALB and the lowest in BOD. Although, gas production was different among all feed resources, however gas production for each gram DM fermented was similar in MUP, PUG, MUK and LOI leaves. Methane production ranged from 6.7 to 18.9 g and 10.5 to 22.83 g/ kg DM and g/ kg fermented DM respectively. The energy loss in the form of methane also followed the trend of gas production, which ranged from 11.4 to 17.1% of digestible energy. Therefore, feed resources with varying nutrient contents have significant variations in fermentability and methane production potential

Protein kinase D1 regulates subcellular localisation and metastatic function of metastasis-associated protein 1

Background: Cancer progression and metastasis is profoundly influenced by protein kinase D1 (PKD1) and metastasis-associated protein 1 (MTA1) in addition to other pathways. However, the nature of regulatory relationship between the PKD1 and MTA1, and its resulting impact on cancer metastasis remains unknown. Here we present evidence to establish that PKD1 is an upstream regulatory kinase of MTA1. Methods: Protein and mRNA expression of MTA1 in PKD1-overexpressing cells were determined using western blotting and reverse-transcription quantitative real-time PCR. Immunoprecipitation and proximity ligation assay (PLA) were used to determine the interaction between PKD1 and MTA1. PKD1-mediated nucleo-cytoplasmic export and polyubiquitin-dependent proteosomal degradation was determined using immunostaining. The correlation between PKD1 and MTA1 was determined using intra-tibial, subcutaneous xenograft, PTEN-knockout (PTEN-KO) and transgenic adenocarcinoma of mouse prostate (TRAMP) mouse models, as well as human cancer tissues. Results: We found that MTA1 is a PKD1-interacting substrate, and that PKD1 phosphorylates MTA1, supports its nucleus-to-cytoplasmic redistribution and utilises its N-terminal and kinase domains to effectively inhibit the levels of MTA1 via polyubiquitin-dependent proteosomal degradation. PKD1-mediated downregulation of MTA1 was accompanied by a significant suppression of prostate cancer progression and metastasis in physiologically relevant spontaneous tumour models. Accordingly, progression of human prostate tumours to increased invasiveness was also accompanied by decreased and increased levels of PKD1 and MTA1, respectively. Conclusions: Overall, this study, for the first time, establishes that PKD1 is an upstream regulatory kinase of MTA1 status and its associated metastatic activity, and that the PKD1-MTA1 axis could be targeted for anti-cancer strategies