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101.
102.
Non‐peptide‐based new class of platelet aggregation inhibitors: Design,synthesis, bioevaluation,SAR, and in silico studies
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Pradeep K. Jaiswal Vashundhra Sharma Surendra Kumar Manas Mathur Ajit K. Swami Dharmendra K. Yadav Sandeep Chaudhary 《Archiv der Pharmazie》2018,351(3-4)
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Kyle B. Woodward Hong Zhao Pradeep Shrestha Lalit Batra Min Tan Orlando Grimany‐Nuno Laura Bandura‐Morgan Nadir Askenasy Haval Shirwan Esma S. Yolcu 《American journal of transplantation》2020,20(5):1285-1295
We have previously shown that pancreatic islets engineered to transiently display a modified form of FasL protein (SA‐FasL) on their surface survive indefinitely in allogeneic recipients without a need for chronic immunosuppression. Mechanisms that confer long‐term protection to allograft are yet to be elucidated. We herein demonstrated that immune protection evolves in two distinct phases; induction and maintenance. SA‐FasL‐engineered allogeneic islets survived indefinitely and conferred protection to a second set of donor‐matched, but not third‐party, unmanipulated islet grafts simultaneously transplanted under the contralateral kidney capsule. Protection at the induction phase involved a reduction in the frequency of proliferating alloreactive T cells in the graft‐draining lymph nodes, and required phagocytes and TGF‐β. At the maintenance phase, immune protection evolved into graft site‐restricted immune privilege as the destruction of long‐surviving SA‐FasL‐islet grafts by streptozotocin followed by the transplantation of a second set of unmanipulated islet grafts into the same site from the donor, but not third party, resulted in indefinite survival. The induced immune privilege required both CD4+CD25+Foxp3+ Treg cells and persistent presence of donor antigens. Engineering cell and tissue surfaces with SA‐FasL protein provides a practical, efficient, and safe means of localized immunomodulation with important implications for autoimmunity and transplantation. 相似文献
105.
Andrew John Nicol Pradeep Harkison Navsaria Steve Beningfield Delawir Kahn 《World journal of surgery》2014,38(1):211-214
Background
Detection of a cardiac injury in a stable patient after a penetrating chest injury can be difficult. Ultrasound of the pericardial sac may be associated with a false negative result in the presence of a hemothorax. A filling in of the left heart border inferior to the pulmonary artery, called the straight left heart border (SLHB), is a radiological sign on chest X-ray that we have found to be associated with the finding of a hemopericardium at surgery. The aim of the present study was to determine if this was a reliable and reproducible sign.Methods
This was a prospective study of patients with a penetrating chest injury admitted between 1 October 2001 and 28 February 2009, who had no indication for immediate surgery, and were taken to the operating room for creation of a subxiphoid pericardial window (SPW). The chest X-ray was reviewed by a single trauma surgeon prior to surgery.Results
A total of 162 patients with a possible occult cardiac injury underwent creation of a SPW. Fifty-five of the 162 patients (34 %) were noted to have a SLHB on chest X-ray and a hemopericardium confirmed at SPW. The sensitivity of the SLHB sign was 40 %; specificity, 84 %; and positive predictive value, 89 %. (p = 0.005, Odds ratio 3.48, lower 1.41, upper 8.62).Conclusions
The straight left heart border is a newly described radiological sign that was highly significant in predicting the presence of a hemopericardium and should alert the clinician to a possible occult cardiac injury. 相似文献106.
107.
Pradeep Tyagi Vikas Tyagi Xianggui Qu Hsin-Tzu Lin Hann-Chorng Kuo Yao-Chi Chuang Michael Chancellor 《International urology and nephrology》2014,46(5):871-877
Introduction
Although epidemiology studies consistently report increased prevalence of overactive bladder (OAB) with age, an accurate deciphering of causative links between the two entities remains elusive. Studies on aged rodent bladder have so far yielded contradictory results on age-associated changes in muscarinic receptors, which highlight the challenge posed by species differences in understanding OAB pathology. We hypothesized that age-related biochemical changes in bladder leading to altered bladder function will be reflected in altered urinary proteome of elderly OAB patients.Methods
Single time point urine specimens were obtained from 140 OAB patients in the age range of 25–90 years of either sex coming routinely to the urology clinics. Eight chemokines in urine were measured by MILLIPLEX MAP human cytokine/chemokine multiplex immunoassay and ELISA. Multivariate and univariate statistical analyses were done to determine association of age with urinary chemokines in OAB patients.Results
In agreement with age-dependent higher prevalence of OAB, the logistic regression of the data also revealed the significant association of OAB symptoms with age [odds ratio (OR) 1.12; 95 % CI, (1.072, 1.187), p = 0.0001]. Univariate analysis of 8 urinary proteins revealed an age-associated elevation of NGF (nerve growth factor) in 137 out of 140 OAB patients [Pearson r = 0.274; 95 %CI (0.112–0.422); p = 0.001]. Modest correlation with age was also noted for MCP-1 (monocyte chemoattractant protein-1), which was detected in 115 OAB patients, and the remaining chemokines were undetectable in nearly two-third of OAB patients included in our cohort.Conclusions
Based on our findings, we postulate that age-associated biochemical changes may accentuate the inflammation associated with OAB. Urinary NGF elevation in elderly OAB patients may be a homeostatic response to counter the senescence of bladder nerves and arrest the progression of OAB into detrusor hyperactivity with impaired contractility. Likewise, elevation of MCP-1 may be related to decreased muscle mass and increased content of adipose tissue in bladder of elderly OAB patients. Urinary NGF and MCP-1 can serve as surrogate markers for monitoring age-associated biochemical changes and the effect of therapeutic interventions in OAB patients. 相似文献108.
Andrew H. Kemp Tim Outhred Sasha Saunders Andre R. Brunoni Pradeep J. Nathan Gin S. Malhi 《Psychopharmacology》2014,231(11):2281-2290
Rationale
Black box warnings for young adults under the age of 25 years indicate that antidepressants may increase risk of suicide. While underlying mechanisms for age-related treatment effects remain unclear, vagally mediated cardiovascular function may play a key role. Decreased heart rate (HR) and an increase in its variability (HRV) improve one’s capacity to adapt to environmental stress and attenuate risk for suicide.Objectives
Using a double blind, randomized, placebo-controlled, crossover, experimental study, we examine whether a single dose of escitalopram (20 mg) attenuates cardiovascular responses to stress under experimental conditions and determine whether age moderates these effects.Methods
Forty-four healthy females received a single dose of escitalopram (20 mg) and placebo treatment separated by a 1-week interval (>5 half-lives). HR and high frequency HRV (HF HRV normalized units; 0.15–0.40 Hz) were measured during resting state and stress.Results
While escitalopram attenuated the increase in HR and increased HF HRV, these moderate to large effects were only significant in participants over 25 years of age. No beneficial cardiovascular effects of escitalopram were observed in those under the age of 25.Conclusions
Maturational differences in the development of the prefrontal cortex—a critical region in the central network of autonomic control—may underpin these differential findings. This study provides a theoretical framework on which future research on treatment-emergent suicidality in clinical populations could be based. 相似文献109.
110.
Gagandeep Kaur Walia Simmi Saini Pradeep Vimal Khushboo Bhatia Arun Kumar Ranjana Singh Dorairaj Prabhakaran Vipin Gupta 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2021,15(3):661-665
Background and aimsThe association of melanocortin receptor 4 (MC4R) gene with adiposity measures is widely studied in European populations. Only six studies have investigated the role of MC4R gene with adiposity measures among Indian populations. We have evaluated the role of MC4R (rs17782313) gene polymorphism in influencing adiposity measures in India among children and adults.Materials and methodsThe present population based cross sectional study was conducted among 303 individuals (208 children and 95 adults) of age group 10–30 years, belonging to Rajasthan. Somatometric measurements (standing height, weight, and waist and hip girths) and blood samples were taken after obtaining written informed consent. Genotyping of MC4R rs17782313 single nucleotide polymorphism was done using restriction fragment length polymorphism method for polymerase chain reaction ampli?ed fragments. We examined association between rs17782313 and different adiposity measures (height, weight, BMI, WHR, and waist and hip girths) using linear regression models.ResultsThe MC4R variant (rs17782313) predicted increased body weight (0.15 kg, S.E ± 0.076, P = 0.043) among children. In combined population, the rs17782313 variant was moderately associated with body weight (0.13 kg, S.E ± 0.070, P = 0.057). This variant was not found to be associated with any other adiposity measure.ConclusionFurther studies are needed to evaluate the association of MC4R variants through sequencing and functional genomics with different adiposity measures in Indian populations for understanding the genetic underpinnings of adiposity in India. 相似文献