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11.
Pavel Gershkovich Bashir Qadri Avihai Yacovan Shimon Amselem Amnon Hoffman 《European journal of pharmaceutical sciences》2007,31(5):298-305
The aim of this article was to investigate the role of intestinal lymphatic transport in the oral bioavailability of two structurally similar synthetic lipophilic cannabinoids: dexanabinol and PRS-211,220. For this purpose, the long chain triglyceride (LCT) solubility and affinity to chylomicrons ex vivo of both cannabinoids were evaluated. Their oral bioavailability was assessed in rats following administration in a lipid-free and a LCT-based formulation. The intestinal lymphatic transport of these two molecules was also directly measured in a freely moving rat model. LCT solubility of dexanabinol and PRS-211,220 was 7.9 ± 0.2 and 95.8 ± 5.3 mg/g, respectively. The uptake by chylomicrons was moderate (31.6 ± 5.2%) and high (66.1 ± 2.4%), respectively. The bioavailability of dexanabinol (37%) was not affected by LCT solution, whereas administration of PRS-211,220 in LCT improved the absolute oral bioavailability three-fold (from 13 to 35%) in comparison to the lipid-free formulation. The intestinal lymphatic transport of dexanabinol and PRS-211,220 was 7.5 ± 0.8 and 60.7 ± 6.8% of the absorbed dose, respectively. In conclusion, despite structural similarity and similar lipophilicity, dexanabinol and PRS-211,220 exhibited a very diverse pattern of oral absorption, and the lymphatic system played quite a different role in the oral bioavailability of these molecules. The low lymphatic transport of dexanabinol is likely driven by relatively lower affinity to chylomicrons and lower LCT solubility. 相似文献
12.
V. I. Skorik V. V. Shilov A. V. Sudus V. V. Zuev 《Bulletin of experimental biology and medicine》1997,124(4):1042-1045
The apnea model with venovenous perfusion and blood oxygenation in a membrane oxygenator was used to study the gas transport
characteristics of perfluorinated emulsion with the aim to prolong the endurance period in lethal hypoxia. The use of PFOS
emulsion (40 ml/kg) as a hemodilution agent at relatively low rate of assisted perfusion (35 ml/kg×min) produced no improvement
of oxygen supply during the critical period in comparison with conventional plasma substitutes. However, perfusion with oxygenated
perfluorinated emulsion prolonged survival as compared with polyglucin perfusion, mainly due to the maintenance of the vitally
important organs (heart and brain) and due to the improvement of microcirculation.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 477–480, October, 1997 相似文献
13.
利用石英弹簧称重法测定了308.15K时乙醇和苯在含端羟基聚丁二烯(HTPB)和端羟基聚丁二烯/丙烯腈共聚物(HTBN)的嵌段共聚聚氨酯膜中的吸收动力学曲线。结合吸收-络合吸附双模式传递模型,研究了聚氨酯膜的微相分离程度、软硬段的比例和组成以及软段分子量等因素对溶剂在膜中溶解和传递性质的影响。 相似文献
14.
外源性核苷能抵消抗代谢药对肿瘤细胞的杀伤作用;核苷转运抑制剂潘生丁则能阻断核苷的这种抵消作用,从而增强抗代谢药的细胞毒性。本研究证明,胸苷和次黄嘌呤可明显抵消氨甲蝶呤对L1210细胞的杀伤作用,潘生丁则能有效地阻断核苷的抵消作用;潘生丁和两性霉素B合用可明显增强氨甲蝶呤对小鼠S180肉瘤的抑制作用,但不增强氨甲蝶呤对动物的毒性。提示潘生丁有可能应用于肿瘤联合化疗。 相似文献
15.
16.
Lü Zhuo-ren 《中国人民解放军军医大学学报》2006,21(5)
Objective: To compare renal sodium transport, using fractional excretions of lithium(FELi) as a marker of proximal tubule sodium reabsorption, between hypertensive and non-hypertensive ouabain-treated rats and further to elucidate the role of ouabain in pathogenesis of hypertension. Methods: Thirty male Sprague-Dawley rats weighting 180-200 g were randomly divided into normal control group and ouabain treated group. Rats were infused with 1 ml/kg·d normal saline or 27. 8μg/kg·d ouabain in-traperitoneally once a day respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Rats were sacrificed 6 weeks after treatment. Blood and 24-hour urine sample were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate(Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated. Ouabain levels of plasma and renal tissue, plasma renin activity, angiotensin I and aldosterone concentration were determined. Results: 65% of the ouabain-treated rats achieved significantly higher SBP after 4 weeks, compared with that of the saline control groups or self baseline (P<0. 01). But in the other 35% of the ouabain-treated rats, their SBP was similar with control group during the experiment (P>0. 05). The body weight, heart rate and food intake between the 3 groups were no significant differences (P> 0. 05). FELi and FDRNa were significantly lower in ouabain-hypertensive group compared with ouabain-non-hypertensive group and control group(P<0. 01 and P<0. 05). The FEu and FDRn, of ouabain-nonhyper-tensive groups were similar with control group(P>0. 05). Ccr and FENa were comparable between the 3 groups (P>0. 05). Plasma and renal tissue ouabain levels, plasma renin activity, angiotensin I and aldosterone contents in ouabain-hypertensive rats were comparable with ouabain-nonhypertensive rats. Conclusion: Increase of proximal tubule sodium reabsorption play an important role in the pathogenesis of ouabain-hypertensive rats. The change of renal sodium transport may result from regulation to renal Na+ , K + -ATPase by ouabain. 相似文献
17.
99Tcm-DMSA肾皮质显像诊断小儿肾发育不良 总被引:2,自引:0,他引:2
目的 探讨^99Tc^m—二巯基丁二酸(DMSA)肾皮质显像诊断小儿肾发育不良的价值。方法 疑为肾发育不良患儿29例,行常规^99Tc^m—DMSA肾皮质显像和腹部B超检查。图像分析:将发育不良肾分为0~4级。结果 ^99Tc^m—DMSA肾皮质显像示29例患儿中24例为单侧肾发育不良,其中11例1级,7例2级,6例3级,余5例患肾未显影为0级,结合其他:检查诊断为肾发育不良。患肾分肾功能为0~24.9%(平均6.3%)。29例患儿中24例患肾肾皮质显像诊断为肾发育不良,5例患肾未显影,由其他影像学方法确诊,诊断灵敏度为82.76%。29例中19例经手术治疗,病理检查证实为肾发育不良。结论 ^99Tc^m—DMSA肾皮质显像诊断肾发育不良灵敏度高、可靠,可确定发育不良肾部位和判断肾功能。 相似文献
18.
The subdivisions of the sacral intermediolateral nucleus (IML) of the cat have been studied by using a double-labeling technique of retrograde Fluoro-gold (FG) and wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) tracing. The parasympathetic preganglionic neurons (PGNs) that were labeled by the FG injected into the pelvic nerve formed a ‘V’-shaped column known as the sacral parasympathetic nucleus (SPN) in the sacral IML. The neurons that were labeled by the WGA-HRP applied to the lateral parabrachial nucleus (PBL) formed an elongated spindle-shaped column extending throughout the IML of the sacral segments. We designated it by the name of sacral visceral sensory nucleus (SVSN). These findings indicate that the sacral IML of the cat contain two distinct subdivisions, SPN and SVSN. 相似文献
19.
Iwar Klime Antonian Vraana Jaroslav Kune Elena eboUkovaA Zdena Dobe ovaa Pavel tolba Josef Zicha 《Blood pressure》1995,4(3):137-142
Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerrance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na+ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension. 相似文献
20.
STEVEN N. VASLEF LYLE F. MOCKROS KEITH E. COOK RONALD J. LEONARD JEFFREY C. SUNG ROBERT W. ANDERSON 《Artificial organs》1994,18(11):813-817
Abstract: A semiempirical mathematical model of convective oxygen transport is used to design a new, low pressure loss, implantable artificial lung that could be used as a bridge to lung transplantation in patients with advanced respiratory failure. The mass transfer and flow friction relations pertinent to the design of a cross–flow hollow fiber membrane lung are described. The artificial lung is designed to transfer over 200 ml/min of oxygen at blood flow rates up to 5 L/min. A compact design and a blood-side pressure loss of <15 mm Hg allows the device to be implanted in the left chest without the need for a prosthetic blood pump. Surgical implantation of the artificial lung would require the creation of inflow and outflow anastomoses. Oxygen would be supplied via an external source. Blood properties, operating conditions, and empirically determined mass transfer and flow properties are all specified and input into a computer program that numerically solves the design equations. Computer–generated values for the device frontal area, blood path length, and fiber surface area are thereby obtained. The use of this computer–assisted design minimizes the need for extensive trial–and–error testing of prototype devices. Results from in vitro tests of a prototype implantable lung indicate that the mathematical model we describe is an accurate and useful tool in the design of hollow fiber artificial lungs. 相似文献