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1.
Haiyung Cheng Jules I. Schwartz Charles Lin Raju D. Amin James R. Seibold Kenneth C. Lasseter David L. Ebel Dominick J. Tocco J. Douglas Rogers 《Biopharmaceutics & drug disposition》1994,15(5):409-418
MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD4-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg 14C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative. 相似文献
2.
Sajja Lokeswara Rao Mannam Gopichand Sompali Sriramulu Reddy Karri Venkata Ravirala Bala Raju Raju Bhupathiraju Soma Raju Penmetcha Krishnam 《Indian Journal of Thoracic and Cardiovascular Surgery》2004,20(4):173-177
Background Cardiopulmonary bypass (CPB) may contribute to the complications and it is assumed that eliminating cardiopulmonary bypass
has the potential of reducing post operative morbidity after coronary artery bypass grafting (CABG). The study was carried
out to compare mortality and morbidity in the off-pump and on-pump CABG groups.
Methods We prospectively analysed 200 patients undergoing CABG. Group A consists of 100 patients underwent multi-vessel off-pump CABG
and group B consists of 100 patients underwent CABG with CPB. The incidence of complications (mortality, re-exploration for
bleeding, myocardial infarction, atrial fibrillation, neurological events, new onset renal failure (s. creatinine>1.6 mg/dL)
pulmonary complications, length of ICU stay and hospital stay were recorded, analysed and compared.
Results OPCAB patients received 2.73±0.61 grafts/patient and on-pump CABG patients received 3.39±0.75 grafts/patient (p value<0.00001). There was no significant statistical difference in mortality, incidence of stroke between OPCAB and CABG
with CPB patients. Length of ICU stay was 32.84±4.22 vs 44.85±7.18 hrs (p value<0.00001) and hospital stay was 6.52±0.69 vs 7.94±0.92 days (p value<0.00001) between group A and group B respectively. Incidence of atrial fibrillation was less in OPCAB group 7% vs 12%
although it was statistically not significant (p value 0.33). It was observed in our study that there was no significant deference in worsening of existing renal failure
between on-pump CABG and OPCAB 6% vs 2% (P value 0.28). Blood utilization was significantly less in OPCAB group (p value<0.001).
Conclusion There was no statistically significant difference in terms of mortality, incidence of stroke and new onset renal failure in
both groups. But there was lesser incidence of post operative atrial fibrillation, worsening of existing renal failure in
off-pump group though statistically not significant. There was significant reduction in blood utilization, length of ICU and
hospital stay in OPCAB group. 相似文献
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Seventy patients with abnormal vaginal bleeding were examined with a Storz hysteroscope. The examination took an average of only 5 min. Sixty patients had the examination under general anaesthesia, five under paracervical block and five had no form of anaesthesia. All tolerated the procedure well. There were no complications directly related to the hysteroscopic examination. There was complete correlation between the histology of the endometrium obtained at subsequent curettage and the hysteroscopic findings. 相似文献
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Frequency receptive fields (RFs) were determined before and after pairing iontophorectic administration of acetylcholine (ACh) with a repeated single-frequency stimulus in the auditory cortex of barbiturate-anesthesized cats. In 58% of the cells, the paired ACh + tone treatment produced subsequent alterations of frequency RFs. In half of these cases, the RF modifications were highly specific to the frequency that had been paired with ACh. Atropine antagoized the frequency-effects of ACh, suggesting that they were mediated via muscarinic cholinergic receptors. 相似文献
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Charles I. Cox Raju Metherate Norman M. Weinberger John H. Ashe 《Brain research bulletin》1992,28(3):401-410
Neurons of in vitro guinea pig and rat auditory cortex receive a complex synaptic pattern of afferent information. As many as four synaptic responses to a single-stimulus pulse to the gray or white matter can occur; an early-EPSP followed, sequentially, by an early-IPSP, late-EPSP, and late-IPSP. Paired pulse stimulation and pharmacological studies show that the early-IPSP can modify information transmission that occurs by way of the early-EPSP. Each of these four synaptic responses differed in estimated reversal potential, and each was differentially sensitive to antagonism by pharmacological agents. DNQX (6,7-dinitroquinoxaline-2,3-dione), a quisqualate/kainate receptor antagonist, blocked the early-EPSP, and the late-EPSP was blocked by the NMDA receptor antagonist APV (D-2-amino-5-phosphonovalerate). The early-IPSP was blocked by the GABA-a receptor antagonist bicuculline, and the late-IPSP by the GABA-b receptor antagonists 2-OH saclofen or phaclofen. Presentation of stimulus trains, even at relatively low intensities, could produce a long-lasting APV-sensitive membrane depolarization. Also discussed is the possible role of these synaptic potentials in auditory cortical function and plasticity. 相似文献