A NOVEL APPROACH TOWARDS DEVELOPMENT OF QUINAZOLINE DERIVATIVES IN PAIN MANAGEMENT

ABSTRACT-   Objective: To synthesis evaluation of the analgesic and anti-inflammatory activities of pyrazoline bearing 4(3H)-quinazolinone derivatives. Methods: Synthesis of Chalcone (3a-3j) involves the Claisen-Schmidt condensation of equimolar quantities of substituted acetophenone with aromatic aldehyde in the presence of aqueous alkali (10%). Comp. (3a-3j) undergoes cyloaddition reaction with semicarbazide HCl in the presence of suitable solvent to yield comp. (4a-4j). It undergoes addition cyclization reaction with anthranillic acid to yield final comp. (6a-6j). Acute toxicity study of synthesized compound was found according to OECD guidelines 423. The test compound do not showed any toxicity up to 200mg/kg dose. Mortality was not observed during the course of study. The analgesic and anti-inflammatory activity of all synthesized compounds were carried by using hot plate method and Carrageenan induced Rat Paw Edema Method respectively. Results: All compounds synthesized are obtained in crystalline form with good practical yield. The purity and homogeneity of compounds synthesized were determined by sharp melting points and TLC method. The chemical structures were confirmed by FTIR, 1HNMR, and Mass spectrum. Conclusion: The synthesized compound 6b, 6d, 6e, 6i and 6j showed good analgesic and anti-inflammatory activities whereas others showed significant activities. Keywords: Quinazoline, pyrazole, analgesic and anti-inflammatory activity

Preliminary Parametric Investigations into Macro-Laser Polishing of Laser-Directed Energy Deposition of SS 304L Bulk Structures

The higher surface roughness of laser-directed energy deposition (LDED)-built components necessitates advanced and sustainable surface quality enhancement techniques like laser polishing. In the present work, a parametric study involving experimental investigation and numerical analysis is conducted to determine the effect of macro-laser polishing on LDED-built SS 304L structures. A thermophysical model is developed to simulate the effect of laser power and scan speed on the melt pool depth of the LDED-built samples. The simulated melt pool depth is compared with experimental results and is found to be in good agreement. Further, the correlation between the melt pool depth and surface behaviour is studied based on shallow surface melting and shallow over-melting mechanisms. A maximum reduction in surface roughness from 21.3 µm to 9 µm (~57%) is achieved with laser polishing, and process parameters’ effect on the surface roughness is investigated. Scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS) mapping, and X-ray diffraction (XRD) are used to further characterize the laser-polished surface. SEM-EDS analysis shows that the segregation is more evident in laser-polished samples, while the XRD results indicate the absence of phase change during the process. This study paves the way to a greater understanding of the effect of macro-laser polishing on LDED-built SS 304L structures

Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA

Co-existence of gastric adenocarcinoma and neuroendocrine carcinoma: a rare entity

A mixed adenoneuroendocrine carcinoma is a tumor composed of both adenocarcinoma and neuroendocrine carcinoma components, with each comprising  at least one-third of the lesion, as defined by the World Health Organization classification of neuroendocrine neoplasms in 2010.. A 67-years-old male was admitted to the hospital with symptoms suggesting gastric cancer. Histopathology examination from endoscopic biopsy revealed adenocarcinoma. Later partial gastrectomy specimen examination the lesion show presence of well differentiated adenocarcinoma along with neuro endocrine carcinoma.</p

Development and Evaluation of Active Case Detection Methods to Support Visceral Leishmaniasis Elimination in India.

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case's knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 via ACD (15 (0.8%) via house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with =90 days compared to the referent of <30 days for ACD vs PCD were 0.88, 0.56 and 0.42 respectively. These ACD strategies not only reduce time to diagnosis, and thus risk of transmission, but also ensure that there is a double check on the proportion of cases actually getting captured. Such a process can supplement passive case detection efforts that must go on, possibly perpetually, even after elimination as a public health problem is achieved

In-Situ Stress Measurement in Raniganj Coalfield and Its Applications in Mine Stability Analysis

The in situ stresses have significant effects on the stability of openings, support requirements, parting stability, pillar strength, etc. In order to analyze the stability of underground structures, the measurement of magnitude and direction of horizontal stress is necessary in addition to knowing other geomining parameters and rock properties. In this direction, this paper presents a systematic determination of in situ stresses in three mines of the southern Raniganj coalfield of India, using single sleeve fracturing technique. Based on the analysis of field test results, the gradients of major, minor and average horizontal stresses are established for the southern Raniganj coalfield. The determined in situ stress values are used in numerical modeling for stability evaluation of known case histories of parting between contiguous seams and pillars of this coalfield. The numerical modeling results analyzed in this paper validated that the in situ stresses determined in the Raniganj coalfield are acceptable for the stability analysis of coal pillars, parting and underground roadways

Techno-economic Feasibility of Resin Bolts as a System of Roof Support in a Bord-&-Pillar Development Panel - A Case Study

The primary sources of energy consist of coal, lignite, oil, natural gas, hydro power, nuclear power and wind power. The projected demand of coal in tenth and eleventh five year plans are 446.59 Tonnes (2006-07) and 620 Million Metric Tonnes (2011-12) respectively. Till now 63.7 per cent of energy-need of India are met by the coal sector. In this context, the production plan of coal has to be revised to meet the demand of our country. To reduce the gap between demand and supply we need to have a careful planning of existing mines as well as of new mines so that we can produce economic coal in difficult geo-mining conditions, day by day our mining horizon is shifting deeper, hence more strata related problems to be encountered and an application of high strength resisting support would be most important requisite in that circumstances. This paper deals with the technical suitability and economical viability of the resin boting as a system of support in a development Bord-&Pillar panel. A case study is discussed where it is applied with consideration of support efficacy and support cost

Monitoring of Rock Movements Using Multipoint Borehole Extensometer from Surface for safety of structures above stowed goaf of an underground coal mine – a case study

Monitoring of rock movement for ground control initiative for the safety of existing surface features is a prime motto of any mining activity. It becomes a daunting task if the monitoring has to be done for inaccessible area from the surface. The multipoint borehole extensometer (MPBX) has been found very suitable in this regard. An extensometer should be selected on the basis of its intended use, the preciseness of measurement required, the anticipated range of deformation, and the details accompanying installation. In this paper a case study has been discussed here elaborating the modus operandi for the selection of compatible type of MPBX, according to the uses. Also, there is one case study presented depicting the real time monitoring of a coal mine constituted important surface features over under coal pillar extraction panel

Framing of design of support for lip and drift of a new underground coal mine - a case study

During opening of a new underground coal mine through inclines, some times it is very difficult to make first opening in the rocks even at some depth if the strata is not competent, especially in the case of poorly cemented medium to coarse grained sandstone. Support of the lip (mouth of the opening) in loose strata is very complex job. When the opening is made and prolonged at some distance, the problem is minimized. Resin bolting, which has been used during this study, is very important support system in bad ground conditions due to its fast setting nature and very good load bearing capacity. For permanent assessment of rock mass it is very important to study the amount of rock load coming around the openings. Hence an attempt has been made in this paper to throw some light on design of support system for driffts of a newly opened underground coal mines after detailed geotechnical studies of roof rocks, which is composed of poorly cemented strata

Instrumentation as first line of defense for prediction of rock movement in power house drift - a case study

Today instrumentation is a basic need for prediction of rock strata behaviour. There are many instruments, which are being used for ground control measures and monitoring of strata movement. The most important factor during excavation is to control the movement of strata and stress developed. Problems regarding strata movement are prominent in underground coal mines and tunnels as the overlying rock above the immediate roof most of the times are composed of weak sedimentations. After excavation process these weak overlying rocks get associated with strata movement if proper support system has not been provided. In underground mines and tunnels roof fall is the major reason of casualties. By instrumentation it gets much easier to monitor the rock movement, which enables management to enhance their support system. Continuous monitoring of strata helps to envisage the excessive rock movement and stress which may create big problem during excavation. Hence an attempt has been made in this paper to throw some light on continuous monitoring of rock using Borehole extensometer and tape extensometer in power house drift of NHPC (Subansiri project, Assam) to study the movement of strat