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51.
Anand Swaroop Manashi Bagchi Pawan Kumar Harry G. Preuss Kiran Tiwari Palma Ann Marone 《Toxicology mechanisms and methods》2014,24(7):495-503
Safety and anti-diabetic efficacy of a novel, proprietary Trigonella foenum-graecum seed extract [novel fenugreek extract (FE), Fenfuro?, CR0010810) enriched in furostanolic saponins (>60% w/w, HPLC) were assessed. Concerning safety, we undertook studies dealing with acute oral toxicity, 28-d sub-chronic toxicity and Ames’ bacterial reverse mutation assay that revealed no toxicity. Concerning efficacy, we examined beneficial effects of the extract on rats with type 2 diabetes (T2D). Male Sprague–Dawley rats received a high-fat diet for 2 weeks followed by streptozotocin (STZ, 35?mg/kg i.p.) to produce T2D. Seven days post-STZ, rats showing ≥300?mg/dl fasting plasma glucose level (PGL) were included in the study. FE (150- or 450- mg/kg p.o.) and glipizide (5?mg/kg p.o.) were administered once daily for 20?d and then twice daily for another 10?d (total 30?d). Blood samples were collected at 0, 10, 20 and 30?d of treatment and estimated for fasting plasma triglyceride (PTG), total cholesterol and insulin levels. After 30?d, FE and glipizide-treated diabetic animals were treated in combination with or without metformin (100?mg/kg) twice daily for another 10?d. FE did not influence body weight, feed and water intake. FE (150?mg/kg p.o.) reduced PTG levels in T2D rats by 22%, 24.6% and 29% at 10, 20 and 30?d of treatment, respectively, while glipizide (5?mg/kg p.o.) reduced the PTG levels by 57.4%, 46.2% and 39.4% at these time points. FE (450?mg/kg) treatment in STZ-induced diabetic rats produced significant hypoglycemic activity (approximately 31.5%) as compared to insulin (48.2% with 1 U/kg i.p.). FE (150?mg/kg p.o.) and metformin (100?mg/kg p.o.) combined produced significant reduction (20.7%) of PGL in T2D rats. No adverse effects were observed. We conclude after extensive in vitro and in vivo safety and efficacy studies that FE is safe and effective in treating T2D. 相似文献
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Percy H. Carter GregoryD. Brown RobertJ. Cherney Douglas G. Batt Jing Chen Cheryl M. Clark Mary Ellen Cvijic John V. Duncia Soo S. Ko Sandhya Mandlekar Ruowei Mo DavidJ. Nelson Jian Pang Anne V. Rose Joseph B. Santella III AndrewJ. Tebben Sarah C. Traeger Songmei Xu Qihong Zhao JoelC. Barrish 《ACS medicinal chemistry letters》2015,6(4):439-444
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UFLC method development and validation of a novel triethylamine containing thiophene S006‐830 ‐ an antitubercular molecule and its application to pharmacokinetic and bioavailability studies in SD rats 下载免费PDF全文
Yeshwant Singh Anamika Misra H.N. Kushwaha Ashish Tiwari Ashok Kumar Sharma Shio Kumar Singh 《Drug testing and analysis》2015,7(8):721-726
A sensitive and selective ultra fast liquid chromatography (UFLC) method has been developed and validated for the determination of a potent and novel antitubercular compound S006‐830 in Sprague Dawley (SD) rat plasma. Samples were extracted and processed by protein precipitation method using acetonitrile. Chromatographic separation was achieved on a Phenomenex, Luna C‐18 column (3μm, 100mm x 2mm i.d.) under isocratic condition. Detection was performed on UFLC‐NEXERA system (LC‐30AD, Shimadzu, Kyoto, Japan) with a degasser (DGU‐20A), auto‐injector (SIL‐30AC), fixed with a 100‐μL loop. Method was found sensitive and reproducible over a linearity range of 15.6‐2000 ng/mL. Recovery of S006‐830 and internal standard was found >90% for spiked matrix control and standard quality control plasma samples. This validated method was successfully applied to generate pharmacokinetic profile of S006‐830 in SD rats. Oral dose proportionality studies were conducted at 100, 50, 25 mg/Kg dose levels, while an IV study was conducted at 25 mg/Kg dose. There was dose dependent increase in AUC and Cmax indicating S006‐830 to exhibit linear pharmacokinetics. S006‐830 exhibited favorable bioavailability in the range of 45‐55%. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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Srivastava Sharad Tiwari Surabhi Srivastava Nishi Verma Shikhar Rawat Ajay Kumar Singh 《Proceedings of the National Academy of Sciences, India. Section B.》2019,89(3):1057-1066
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Centella asiatica (L.) Urb. (Apiaceae) with high commercial value is an important herb in traditional Indian... 相似文献
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H G Güllner F C Bartter J R Gill P S Dickman C B Wilson J L Tiwari 《Archives of internal medicine》1983,143(8):1534-1540
A new syndrome, characterized by hypokalemic alkalosis, hyperreninemia, aldosterone, high urinary prostaglandin E2 excretion, normal BP, and resistance of BP to angiotensin II is described in three of four siblings. Histologic examination of tissue obtained by biopsy from the kidneys showed an intense staining of the proximal tubular cells, as well as an extreme hypertrophy of the proximal tubular basement membranes, features that previously have not been observed. On electron microscopic examination, the characteristic changes of the tubular cells consisted of very dense cytoplasm, compact mitochondria, and pyknotic nuclei. In contrast to Bartter's syndrome, the juxtaglomerular apparatus were of normal appearance. Glomerular filtration rate and renal plasma flow were within normal limits. Fractional distal delivery of proximal tubular solute and fractional chloride reabsorption in the thick ascending limb of the loop of Henle were normal. The findings of a genetic linkage between the syndrome and the major histocompatibility system suggests that this familial tubulopathy is an inherited disorder. 相似文献
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Jennie G. Pouget Tahireh A. Shams Arun K. Tiwari Daniel J. Müller 《Dialogues in clinical neuroscience》2014,16(4):555-566
Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. 相似文献