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1.
Ravikanth Bhamidipati P Venkatesh Prajakta V Dravid Prasad C Narasimhulu Sastry Tvrs Jagattaran Das Ramesh Mullangi Nuggehally R Srinivas 《European journal of drug metabolism and pharmacokinetics》2005,30(3):187-193
The aim of this study was to determine the bioavailability of a novel oxazolidinone, DRF-6196, in mice and rats following intravenous (i.v) and oral dosing and to compare the pharmacokinetics with those obtained following linezolid dosing. Blood samples were drawn at predetermined intervals up to 24 h post-dose after either DRF-6196 or linezolid administration. The concentrations of DRF-6196 and linezolid in various plasma samples were determined by a HPLC method. Following oral administration maximum concentrations of DRF-6196 were achieved within 0.5 h irrespective of the species. While the doses increased in the ratio of 1 : 3 : 10, mean Cmax and AUC(0-infinity) values in mice for DRF-6196 increased in the ratio of 1 : 3.87 : 8.53 and 1 : 2.51 : 9.24, respectively. Both the Cmax and AUC(0-infinity) values increased almost proportional to the dose administered in mice. Following i.v administration, the concentration of DRF-6196 declined in a bi-exponential fashion with terminal elimination half-life of 1.5 h irrespective of the species. The systemic clearance and volume of distribution of DRF-6196 in mice were 1.14 L/h/kg and 0.66 L/kg, respectively after i.v administration, while the respective values in rats were 0.61 L/h/kg and 0.41L/kg, respectively. Elimination half-life ranged between 0.8-1.5 h. Absolute oral bioavailability of DRF-6196 was found to be 80-96% across the test dose range. Although plasma levels of DRF-6196 were lesser compared to linezolid in the initial hours, it may not have any consequences on the clinical effectiveness of the molecule. 相似文献
2.
Rajeswara Reddy Saddala Lavanya Thopireddy Narasimhulu Ganapathi Sathyavelu Reddy Kesireddy 《Experimental and toxicologic pathology》2013,65(1-2):15-19
Plants with antidiabetic activities provide important source for the development of new drugs in the management of diabetes mellitus. The main aim of this study was to evaluate the protective effect of aqueous extract (AE) of Pimpinella tirupatiensis (Pt) tuberous root on cardiac oxidative stress and lipid peroxidation (LPO) in non-diabetic and streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar rats by a single administration of STZ (40 mg/kg intraperitoneal (i.p). AE (750 mg/kg/b.w./day) and glibenclamide (GLB) (20 mg/kg/b.w./day) were administrated orally by intra oral gastric tube for 30 days. After 4 weeks of hyperglycaemia the enzymatic and non-enzymatic factors were measured in cardiac tissue of diabetic and control groups. Xanthine oxidase activity (XOD), Uric acid (UA) and malondialdehyde (MDA) content were significantly (p < 0.01) elevated by 48, 48 and 50% respectively and the contents of glutathione (GSH), ascorbic acid (AA) were significantly (p < 0.01) diminished by 45 and 42% respectively in diabetic rats when compared to normal. Treatment with AE and GLB normalized the content of UA, GSH, AA, MDA and the activity of XOD. No significant changes were observed in control rats treated with AE. This data suggests that hyperglycemia induces oxidative stress in the heart, but the oxidative stress defense mechanisms in the heart tissue are fairly efficacious against oxidative injury by the treatment with AE and GLB. The present study reveals that AE may provide a useful therapeutic option in the reversal of oxidative stress induced cardiac dysfunction in diabetes mellitus. 相似文献
3.
Bommena Hanumantha Rao Inti Venkata Subramanyeswara Rao Vysyaraju Ravi Kanth Korrapati Venkata Vara Prasada Rao K. Balamurali Krishna Bethanabatla Syama Sundar 《Scientia pharmaceutica》2015,83(3):465-478
Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the preparation of Olmesartan Medoxomil with 99.9% purity in an overall 62% yield. The synthesis includes three isolations and one purification with easy plant operations. This process describes the formation and control of each individual impurity in all stages. This process for Olmesartan Medoxomil and its intermediates is competent for industrial production in very short reaction time intervals with an appreciable yield and high purity. 相似文献
4.
Chandrakala Aluganti Narasimhulu Krithika SelvarajanMatthew Brown Sampath Parthasarathy 《Atherosclerosis》2014
Objective
Apolipoprotein A1 (ApoA1) and apolipoprotein E (ApoE) mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties. In this study, we tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins and whether they would counteract and neutralize the negatively charged modified lipoproteins, inhibit their uptake and inflammation by macrophages.Methods and results
5F-mimetic peptide of ApoA1, LL27 derived from the anti-microbial peptide hCAP, and a human glycodelin derived peptide were commercially synthesized. We noted that these three distinct cationic lysine-rich peptides, two of which were unrelated to any known apolipoproteins, inhibited copper-mediated oxidation of lipoproteins and reduced lipid peroxides in a lysine dependent manner. The peptides also retarded the electrophoretic mobility of previously oxidized LDL and acetylated LDL by virtue of their net positive charge. Pre-incubation of peptides with modified lipoproteins reduced the uptake of the latter by macrophages, thus preventing the formation of foam cells. The cationic peptides inhibited oxidized LDL (Ox-LDL)-induced inflammatory response both in vitro and in vivo.Conclusion
Based on these results, we suggest that in addition to the well known mimetic peptides, other suitable cationic peptides may be of use for controlling Ox-LDL mediated inflammation and atherosclerotic progression. 相似文献5.
6.
Kurt D. Piggott Anne Liu Jessica Monczka Harun Fakioglu Sukumar Suguna Narasimhulu Kamal Pourmoghadam William DeCampli 《The Journal of thoracic and cardiovascular surgery》2018,155(5):2104-2109
Objective
Nutrition is vital for maintaining optimal cellular and organ function, particularly in neonates who undergo cardiac surgery. Achieving nutritional goals preoperatively can be challenging because of fluid restrictions, suboptimal oral intake, and concerns for inadequate gastrointestinal circulation. We examined preoperative caloric intake and its effects on postoperative course in neonates who underwent cardiac surgery.Methods
We retrospectively reviewed records of neonates (younger than 30 days) who underwent congenital heart surgery requiring cardiopulmonary bypass from 2008 to 2014 at Arnold Palmer Hospital for Children. Data on multiple nutritional and postoperative variables were collected. Study outcomes included hospital length of stay, duration of mechanical ventilation, and acute kidney injury (AKI).Results
Records of 95 neonates were reviewed. Sixty-six patients (69.5%) with a median age of 5 days did not achieve preoperative caloric goal, whereas 29 patients (30.5%) with a median age of 11 days did. Of those who achieved caloric goal, 6 (20.6%) achieved it via total parental nutrition, 9 (31.1%) with a combination of total parental nutrition and enteral feeds, and 14 (48.3%) via enteral route. There was a significant difference in peak lactate (P = .002), inotropic score (P = .02), and duration of mechanical ventilation (P = .013) between those who did and did not achieve caloric goal. In multivariable analysis we found that failure to achieve caloric goal preoperatively was independently associated with stage 2 or 3 AKI (P = .04; odds ratio, 4.48; 95% confidence interval, 1.02-19.63) and younger age at the time of surgery (P < .001; odds ratio, 0.12; 95% confidence interval, 0.04-0.33).Conclusions
Failure to achieve preoperative caloric goal might contribute to development of AKI and might be associated with greater severity of illness postoperatively. 相似文献7.
Singh A Guidry L Narasimhulu KV Mai D Trombley J Redding KE Giles GI Lancaster JR Steyn AJ 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(28):11562-11567
A fundamental challenge in the redox biology of Mycobacterium tuberculosis (Mtb) is to understand the mechanisms involved in sensing redox signals such as oxygen (O2), nitric oxide (NO), and nutrient depletion, which are thought to play a crucial role in persistence. Here we show that Mtb WhiB3 responds to the dormancy signals NO and O2 through its iron-sulfur (Fe-S) cluster. To functionally assemble the WhiB3 Fe-S cluster, we identified and characterized the Mtb cysteine desulfurase (IscS; Rv3025c) and developed a native enzymatic reconstitution system for assembling Fe-S clusters in Mtb. EPR and UV-visible spectroscopy analysis of reduced WhiB3 is consistent with a one-electron reduction of EPR silent [4Fe-4S]2+ to EPR visible [4Fe-4S]+. Atmospheric O2 gradually degrades the WhiB3 [4Fe-4S]2+ cluster to generate a [3Fe-4S]+ intermediate. Furthermore, EPR analysis demonstrates that NO forms a protein-bound dinitrosyl-iron-dithiol complex with the Fe-S cluster, indicating that NO specifically targets the WhiB3 Fe-S cluster. Our data suggest that the mechanism of WhiB3 4Fe-4S cluster degradation is similar to that of fumarate nitrate regulator. Importantly, Mtb DeltawhiB3 shows enhanced growth on acetate medium, but a growth defect on media containing glucose, pyruvate, succinate, or fumarate as the sole carbon source. Our results implicate WhiB3 in metabolic switching and in sensing the physiologically relevant host signaling molecules NO and O2 through its [4Fe-4S] cluster. Taken together, our results suggest that WhiB3 is an intracellular redox sensor that integrates environmental redox signals with core intermediary metabolism. 相似文献
8.
9.
Chilakapati J Korrapati MC Hill RA Warbritton A Latendresse JR Mehendale HM 《Toxicology》2007,230(2-3):105-116
Thioacetamide (TA) is bioactivated by CYP2E1 to TA sulfoxide (TASO), and to the highly reactive sulfdioxide (TASO2), which initiates hepatic necrosis by covalent binding. Previously, we have established that TA exhibits saturation toxicokinetics over a 12-fold dose range, which explains the lack of dose–response for bioactivation-based liver injury. In vivo and in vitro studies indicated that the second step (TASO → TASO2) of TA bioactivation is less efficient than the first one (TA → TASO). The objective of the present study was to specifically test the saturation of the second step of TA bioactivation by directly administering TASO, which obviates the contribution from first step, i.e. TA → TASO. Male SD rats were injected with low (50 mg/kg, ip), medium (100 mg/kg) and high (LD70, 200 mg/kg) doses of TASO. Bioactivation-mediated liver injury that occurs in the initial time points (6 and 12 h), estimated by plasma ALT, AST and liver histopathology over a time course, was not dose-proportional. Escalation of liver injury thereafter was dose dependent: low dose injury subsided; medium dose injury escalated upto 36 h before declining; high dose injury escalated from 24 h leading to 70% mortality. TASO was quantified in plasma by HPLC at various time points after administration of the three doses. With increasing dose (i.e., from 50 to 200 mg/kg), area under the curve (AUC) and Cmax increased more than dose proportionately, indicating that TASO bioactivation exhibits saturable kinetics. Toxicokinetics and initiation of liver injury of TASO are similar to that of TA, although TASO-initiated injury occurs at lower doses. These findings indicate that bioactivation of TASO to its reactive metabolite is saturable in the rat as suggested by previous studies with TA. 相似文献
10.
Drug interaction with hepatic microsomal cytochrome 总被引:11,自引:0,他引:11