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1.
Hit, Lead & Candidate Discovery
A variety of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl)phenyl) quinazolin-4(3H)-ones have been synthesized by treating 3-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)-2-(methyl/phenyl)-quinazolin-4(3H)-one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N-methyl-d -aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects. The title compounds were tested for its antiepileptic potency by MES and scPTZ model. Rotorod test is used to assess its neurotoxicity. In the preliminary test it was found that in MES test, analogs 6d , 6e , 6f, and 6l were potent; whereas in scPTZ test analogs 6d , 6e , 6f, and 6k displayed potent antiepileptic activity. Additionally these five derivatives were tested in rats orally at a dose of 30 mg/kg and found that compounds 2-methyl-3-(4-(5-morpholino-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6e and 2-methyl-3-(4-(5-(piperidin-1-yl)-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6f exhibited superior activity than reference Phenytoin. In MES test, these derivatives 6e and 6f showed activity at 30 mg/kg i.p. dose after 0.5 hr and 4.0 hr. In scPTZ test these derivatives 6e and 6f showed activity at 100 and 300 mg/kg i.p. dose after 0.5 hr and 4.0 hr, respectively.  相似文献   
2.
Klinefelter syndrome (KFS) is the most common non-heritable sex chromosome anomaly caused by nondisjunction during cell division and contains two or more X chromosomes. More than two third of all cases are homogenous (47XXY) and the remaining are mosaic (46XY/47XXY). Lower limb ulcers are frequently observed and attributed to impaired fibrinolysis. A case of KFS with post acne scars and leg ulcers is presented. The rarity of acne in this syndrome is explained by the phenomenon of mosaicism.  相似文献   
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4.
Bronchogenic carcinoma, the commonest lung tumor occurs more frequently in the elderly with typical symptoms of cough, haemoptysis, weight loss, dyspnoea or chest pain. These symptoms mimic common respiratory infections in en-demic areas like pulmonary tuberculosis. Also, metastasis at presentation itself is common, the favoured sites being liver, contra-lateral lungs, bones, brain, etc., although unusual and rare sites like heart also are known. We herein report a rare association of both carcinoma with active pulmonary tuberculosis in the same lobe associated with intracardiac metastasis. Very few cases have been published describing lung carcinoma with intracardiac metastasis. We hope the documentation of this rare case will shed further light into the subject area and improve clinical education.  相似文献   
5.
There is a growing interest in the design and synthesis of the quinoxaline-2,3-dione derivatives and hydrazones due to their neuroprotective activity, anticancer, anti-inflammatory, analgesic, anticonvulsant, antiviral, antibacterial and antifungal activity, and hydrazone-based coupling methods are used in medical biotechnology to couple drugs and also to target antibodies. Different series of α-amino-3-hydroxy-5-methylisoxazole propionate receptor antagonists are described to be effective in the therapy of neurodegenerative disorders in the literature, one of which is based on the quinoxaline-2,3-dione structure, which has a high affinity and selectivity over receptors. Quinoxaline-2,3-bis hydrazone(s) were prepared by the nucleophilic addition reaction at the second and third position of quinoxaline-2,3-dione using different hydrazines (a–f) in conventional and microwave oven methods successfully with the good percentage of yields. The six synthesized compounds showed satisfactory analytical results. The oral administration of the synthesized drugs (20 mg/kg body weight) showed its curative and preventive effect against intracranial administration of ethidium bromide-induced demyelination in rats proved by the battery of behavioral and histological studies. The synthesized drugs are useful to counteract various demyelinating disorders which will be a great relief for our society. Further studies are needed on the molecular mechanisms of these compounds with neuroprotective activity.  相似文献   
6.
Purpose:The aim of this study was to measure blur thresholds before and after refractive surgery.Methods:In this prospective cohort study conducted in a tertiary eye hospital in South India. Blur thresholds were measured for 30 young adult myopic patients 1 month prior to and after refractive surgery. Patients were asked to report three stages of blur, namely Detectable Blur (DB), Bothersome Blur (BB), and Non-resolvable Blur (NB). Blur was created by adding plus lenses (in steps of 0.12D) over their optimal subjective refraction. The blur judgments were made both monocularly and binocularly when looking through a 3 mm artificial pupil at one line above the best-corrected visual acuity.Results:A total of 30 participants were included in this study (mean age = 25.5 ± 3.8 (20–36) years; 77% female). The mean binocular preoperative blur of this group was: DB = 0.39 ± 0.26D, BB = 0.74 ± 0.28D and NB = 1.04 ± 0.42D. The corresponding mean binocular blur one-month post-operatively was DB = 0.46 ± 0.28D, BB = 0.83 ± 0.35D, and NB = 1.21 ± 0.44D. Although there was a marginal increase in the blur thresholds postoperatively, the difference was not statistically significant (DB: P = 0.320; BB: P = 0.229; NB: P = 0.054).Conclusion:All three blur thresholds showed an insignificant minimal increase at 1 month post-operatively suggesting that patients adapt to the induced blur following refractive surgery. A longer follow up would reveal how the adaptation to blur would change with time.  相似文献   
7.
Mutations in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS). Accumulating evidence implicates astrocytes as important non-cell autonomous contributors to ALS pathogenesis, although the potential deleterious effects of astrocytes on the function of motor neurons remains to be determined in a completely humanized model of C9orf72-mediated ALS. Here, we use a human iPSC-based model to study the cell autonomous and non-autonomous consequences of mutant C9orf72 expression by astrocytes. We show that mutant astrocytes both recapitulate key aspects of C9orf72-related ALS pathology and, upon co-culture, cause motor neurons to undergo a progressive loss of action potential output due to decreases in the magnitude of voltage-activated Na+ and K+ currents. Importantly, CRISPR/Cas-9 mediated excision of the C9orf72 repeat expansion reverses these phenotypes, confirming that the C9orf72 mutation is responsible for both cell-autonomous astrocyte pathology and non-cell autonomous motor neuron pathophysiology.  相似文献   
8.
The present study emphasizes the role of engineered protein (gallic acid engineered gelatin [GEG]) on the closure of wound gaps of different shapes assessed under in vitro (fibroblast cell line) and in vivo (rat) experimental models. Circular, triangle, rectangle, and square are the shapes selected for the study. Intending engineered protein (GEG) augments the cell migration in rectangle and triangle shapes and reduces the gap space significantly compared with circular and square shapes. Similar observations were made with in vivo model study, and it was observed that the wound closure starts along the wound edges. In circular and square shapes, the cell movement follow a purse‐string mechanism/the mixed pattern. Thus, the present study suggested that for faster wound healing, the cell migration along the wound edge may be found beneficial, and the external healing agent in the form of engineered protein hydrogel accelerate the healing accordingly.  相似文献   
9.
IntroductionLatarjet procedure is commonly performed for recurrent anterior shoulder instability with glenoid side bone loss. Classic Latarjet procedure can be performed using specially designed drill guides, jigs, or by freehand technique. Here we have described a technical note on classic Latarjet procedure performed with freehand technique utilizing simple rulers and caliper. The functional and radiological outcomes of our patients have also been analysed.Material and Methods149 open classic Latarjet procedures were performed using our technique between March 2015 and July 2018. The mean age of the patients was 32.95 years (Range 22–59 years). The functional outcome of the patients was measured using Western Ontario Shoulder Instability (WOSI) and Oxford Shoulder Instability Score (OSIS) at 2 years of follow-up. Screw and graft positioning were studied in 24 consecutive patients with a postoperative computed tomography (CT) scan.ResultsThere was no incidence of recurrent subluxation or dislocation post-surgery. Mean OSIS score increased from 15.63 ± 3.20 preoperatively to 42.44 ± 3.88 postoperatively (p value < 0.05). WOSI score decreased significantly from 62.54% ± 8.24 to 10.26 ± 6.33 postoperatively at 2-year follow-up (p value < 0.05). Postoperative CT scan also showed satisfactory screw placement in all patients.ConclusionOpen Latarjet procedure performed using freehand technique provides good functional and radiological outcomes in patients with recurrent anterior shoulder instability with glenoid side bone loss.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43465-021-00385-7.  相似文献   
10.
Inflammation Research - CRP gene polymorphism is common in inflammatory diseases, but such association has not been reported in periodontitis. Our objective was to interrogate SNPs of crp in...  相似文献   
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