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1.
Dipak K. Das Richard M. Engelman Xuekun Liu Swapna Maity John A. Rousou Joseph Flack Jitendra Laksmipati Randall M. Jones M. Renuka Prasad David W. Deaton 《Molecular and cellular biochemistry》1992,111(1-2):77-86
Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH·). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH·. 相似文献
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M. Renuka Prasad H. S. Dhillon T. Carbary R. J. Dempsey S. W. Scheff 《Journal of neurochemistry》1994,63(2):773-776
Abstract: Regional levels of lactate and inositol 1,4,5-trisphosphate (IP3 ), a cellular second messenger of the excitatory neurotransmitter system, were measured after lateral fluid percussion (FP) brain injury in rats. At 5 min postinjury, tissue lactate concentrations were significantly elevated in the cortices and hippocampi of both the ipsilateral and contralateral hemispheres. By 20 min postinjury, lactate concentrations were elevated only in the cortices and hippocampus of the ipsilateral hemisphere. Whereas the IP3 concentrations were elevated in the hippocampi of the ipsilateral and contralateral hemisphere and in the cortex of ipsilateral hemisphere at 5 min postinjury, no elevation in these sites was found at 20 min postinjury. Histologic analysis revealed neuronal damage in the cortex and CA3 regions of hippocampus ipsilateral to the injury at 24 h postinjury. The present results suggest activation of the phosphoinositide signal transduction pathway at the onset of injury and of a possible requirement of early persistent metabolic dysfunction (>20 min) such as the lactate accumulation in the delayed neuronal damage. 相似文献
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Choudhary Renuka Sharma Anil Kumar Sudarshan Upadhyay Ramesh Chandra Singh Sohan Vir Mohanty Ashok 《Molecular and cellular biochemistry》2020,465(1-2):141-153
Molecular and Cellular Biochemistry - Ultraviolet radiations (UVR) are responsible for a wide variety of acute and chronic effects on the animal skin. However, the effect of UVR-induced oxidative... 相似文献
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The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide‐mediated vasorelaxation in BALB/c mice 下载免费PDF全文
S Gohin A Carriero C Chenu AA Pitsillides TR Arnett M Marenzana 《Cell biochemistry and function》2016,34(2):52-62
There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L‐NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1–34] (80 µg/kg/day) or L‐NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro‐CT, histomorphometry and three‐point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co‐treatment with L‐NAME blocked the action of PTH on blood flow, whereas L‐NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co‐treatment with L‐NAME restricted the PTH‐stimulated increase in cortical bone formation but had no clear‐cut effects in trabecular bone. Co‐treatment with L‐NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO‐mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd. 相似文献
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A. B. Shreya Renuka S. Managuli Jyothsna Menon Lavanya Kondapalli Aswathi R. Hegde Kiran Avadhani 《Journal of liposome research》2016,26(3):221-232
Context: Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM.Objective: The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches.Materials and methods: Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration.Results and discussion: Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0?nm, PDI of 0.232, ZP of??43.7?mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24?h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3?μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p?0.05) increase in bioavailability upon transdermal application compared with oral route.Conclusion: Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM. 相似文献
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The purpose of this study was to determine the factors that influence fill weight and weight variability of capsules produced
on the In-Cap and to assess any differences in terms of capsule defects between gelatin and HPMC (Quali-V) shells. The In-Cap
is an automatic tamping type capsule-filling machine and the low output of ≈3000 capsules/hour makes it ideal for early formulation
development and phase I/IIa clinical supplies manufacture. Four commonly used excipients (Avicel PH101, Avicel PH302, A-Tab,
and Prosolv HD90) and a poorly flowing drug blend were encapsulated at various pin settings and powder bed heights. The average
fill weight and coefficient of weight variation were determined. The percentage of defective capsules formed during encapsulation
was calculated. Results of the study showed that pin setting was critical for controlling the fill weight and the weight variation.
The order of pin setting with pin 1 (closer to the powder chute) set to a relatively higher position and pin 4 (before ejection)
set to a lower position was found to give higher fill weights with relatively lower weight variability. The powder bed height
influenced the fill weight for poorly flowing powders. The capsule machine speed did not appear to significantly influence
the fill weight. The fill weight and weight variation were found to depend on the flow property of the material. A large percentage
of defective capsules was obtained using HPMC shell size #00. Some of the commonly observed defects included split caps and
improperly closed filled capsules. In general, appropriate selection of pin settings and bed height can reduce the weight
variability seen, especially with poorly flowing high-dose formulations. 相似文献