Discriminative Stimulus, Reinforcing, Physical Dependence, and Antinociceptive Effects of Oxycodone in Mice, Rats, and Rhesus Monkeys.

Despite oxycodone's (4,5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one) history of clinical use and the attention it has received as a drug of abuse, few reports have documented its pharmacology's relevance to its abuse or its mechanism of action. The purposes of the present study were to further characterize the analgesic effects of oxycodone, its mechanism of action, and its effects in terms of its relevance to its abuse liability. The results indicate that oxycodone had potent antinociceptive effects in the mouse paraphenylquinone writhing, hot-plate, and tail-flick assays, in which it appeared to be acting as a μ-opioid receptor agonist. It generalized to the heroin discriminative stimulus and served as a positive reinforcer in rats and completely suppressed withdrawal signs in morphinedependent rhesus monkeys. These results suggest that the analgesic and abuse liability effects of oxycodone are likely mediated through μ-opioid receptors and provide the first laboratory report of its discriminative stimulus, reinforcing, and morphine cross-dependency effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lateral hypothalamic syndrome in rats: a comparison of the behavioral and neurochemical effects of lesions placed in the lateral hypothalamus and nigrostriatal bundle

The effects of total (T-NSB) and subtotal (S-NSB) destruction of the nigrostriatal bundle were compared with the effects of large lateral hypothalamic (LH) lesions on various aspects of the lateral hypothalamic syndrome. The T-NSB and LH lesions produced equivalent decreases in caudate and telencephalic contents of dopamine and norepinephrine, while with the exception of telencephalic dopamine, S-NSB lesions had consistently smaller effect. The T-NSB and LH lesions produced equivalent effects on duration of aphagia and adipsia (Stages 1 to 3) and on long-term decreases in body weight and ad lib water consumption, and these effects were always greater than those produced by the S-NSB lesion. These aspects of the lateral hypothalamic syndrome appeared to be related to the interruption of the nigrostriatal bundle and consequent decrease in caudate dopamine. The T-NSB and S-NSB lesions produced equivalent long-term deficits in water regulation as measured by drinking in the absence of food or in response to intra- and extracellular dehydration, but these deficits were always significantly less than those produced by the LH lesion. It was concluded that these regulatory deficits were not related to destruction of catecholamine pathways. All three lesions totally blocked eating in response to a glucoprivic challenge. This aspect of the lateral hypothalamic syndrome, therefore, results from destruction of a small portion of the lateral diencephalon and may be related to the interruption of the dopaminergic mesolimbic system.     

Discovery of systematic responses and potential biomarkers induced by ochratoxin A using metabolomics

Ochratoxin A (OTA) is known to be nephrotoxic and hepatotoxic in rodents when exposed orally. To understand the systematic responses to OTA exposure, GC-MS- and ¹H-NMR-based metabolomic techniques together with histopathological assessments were applied to analyse the urine and plasma of OTA-exposed rats. It was found that OTA exposure caused significant elevation of amino acids (alanine, glycine, leucine etc.), pentose (ribose, glucitol, xylitol etc.) and nucleic acid metabolites (pseudouridine, adenosine, uridine). Moreover, myo-inositol, trimethylamine-oxide (TMAO), pseudouridine and leucine were identified as potential biomarkers for OTA toxicity. The primary pathways included the pentose phosphate pathway (PPP), the Krebs cycle (TCA), the creatine pathway and gluconeogenesis. The activated PPP was attributed to the high requirements for nicotinamide adenine dinucleotide phosphate (NADPH), which is involved in OTA metabolism through cytochrome P450. The elevated gluconeogenesis and TCA suggest that energy metabolism was involved. The up-regulated synthesis of creatinine reveals the elevated catabolism of proteins. These findings provide an overview of systematic responses to OTA exposure and metabolomic insight into the toxicological mechanism of OTA.     

维生素D3补充对大鼠免疫细胞功能影响的实验研究

目的：维生素D（VD）对机体免疫功能作用已引起广泛关注,本实验研究补充不同剂量VD,对大鼠免疫细胞活性的影响。方法：将30只Wistar大鼠随机分为3组,分别为VD,1（对照组）、VD,2和VD,3组,每组10只,雌雄各半。VD,l组大鼠每天摄入VD,20IU／kg（生理剂量,相当于成人每天摄入5txg维生素D,）、VD2组和VD3组分别补充200IU／（kg·d）（10倍量）和1000IU／（kg·d）（50倍量）的VD,;补充时间为4周。实验结束时麻醉无痛处死,取血样（约5mL）离心,采用LC-Ms／MS测定血清VD,浓度、CCK-8法检测淋巴细胞增殖活性、流式细胞术测单核细胞吞噬功能。结果：经过4周VD,补充后,结果显示,VD,1、VD,2和VD。3组大鼠血清VD,浓度分别为14．8ng／mL、34．7n【g／mL和60．7ng／mL,随着补充剂量的增加,机体VD,吸收水平也显著提高;VDl补充后,VD,2组淋巴细胞增殖活性的OD值达到3．04,明显高于VD,1组的2．64（P〈0．05）,但VD33组与VD31组相比淋巴细胞增殖活性无显著性差异（P〉0．05）。采用流式细胞术观察单核细胞吞噬活性（荧光强度）,结果显示VD,2组大鼠单核细胞吞噬活性荧光强度到达19．98,明显高于VD,1组的15．48,而高剂量VD,补充的VD,3组大鼠单核细胞吞噬活性未见明显增强。结论：适宜剂量VD,[200IU／（kg·d）]补充可增强淋巴细胞增殖和单核细胞吞噬活性,而过高剂量（50倍生理剂量）未观察到明显免疫调节作用。     

Antihypertensive properties of aqueous extracts of vegetable leaf‐fortified bread after oral administration to spontaneously hypertensive rats

This study investigated the potential cardiovascular health benefits of leavened bread produced from wheat flour that contained 1%, 2% and 3% additions of leafy vegetable powders obtained from Amaranthus viridis (AO), Solanum macrocarpon (SM) or Telfairia occidentalis (TO). Dried breads were extracted with water at 60 °C followed by analysis for total polyphenolic content (TPC), as well as in vitro inhibitions of angiotensin‐converting enzyme and renin activities. HPLC analysis of the bread extracts indicated the presence of mainly rutin, gallic acid, myricetin and caffeic acid. TPC of the vegetable‐fortified breads was significantly (P < 0.05) higher (5.8–7.6 mg gallic acid equivalent, GAE/g) than that of control bread (5.5 mg GAE/g). Oral administration of 100 mg dried extract/kg body weight to spontaneously hypertensive rats led to reductions (up to 42 mmHg) in systolic, diastolic and mean arterial blood pressure in comparison with 20 mmHg for the control bread.     

Effect of guar gum on the serum lipid profile of Sprague Dawley rats

The aim of the study was to probe the hypocholesterolemic effect of legumes dietary fiber through “chapaties” a staple diet of the South Asia. Commercial wheat flour (atta) was blended with legumes i.e. lentil, chickpea and guar gum in various combinations to make composite flour for the preparation of chapaties. Maximum dietary fiber (8.85%) was observed in composite flour with 3g/100 g guar gum, which also gave whiter look and puffiness to the end product. Highest percent increase in dietary fiber (35.3%) was in flour with 3g/100 g guar gum followed by guar gum 2g/100 g (24.1%). The diets prepared from three best selected compositions along with control, were fed to male Sprague Dawley rats for 8 weeks. Lowest serum cholesterol (82.46 mg/dl) was observed in rats fed on guar gum 3g/100 g which showed a significant reduction (17.2%) as compared to control. Similarly, in case of LDL and triglycerides, guar gum 3 g/100 g showed highest decline i.e., 29.7% and 28.4% with reference to control, respectively. The present investigation suggests that five chapaties per day prepared from selected compositions provides an extra 5-8 g of dietary fiber that is helpful in lowering cholesterol in hypercholesterolemic individuals.     

红景天提取物抗疲劳作用的研究

目的探讨蔷薇红景天提取物的抗疲劳作用。方法随机将健康Wistar大鼠分为4组,分别为红景天低剂量组(0.01 g/kg)、中剂量组(0.1 g/kg)、高剂量组(0.3 g/kg)和空白对照组(蒸馏水),连续灌胃给药15 d后,进行负重游泳实验,记录大鼠力竭性游泳时间,随后测定血乳酸、血清尿素氮、肌糖原以及肝糖原。结果与空白对照组比较,低、中、高3个剂量组大鼠游泳时间分别延长了50.9%,73.5%和53.7%;血乳酸分别下降了27.5%,23.1%和25.4%;血清尿素氮分别下降了16.5%,20.4%和20.0%;肝糖原分别提高了38.2%,65.4%和53.8%;肌糖原分别提高了46.9%,81.9%和83.1%。以上结果均有统计学意义(P<0.01)。结论红景天具有良好的抗疲劳作用。     

茶树花对大鼠肥胖病和高脂血症预防作用研究

目的:研究茶树花对大鼠肥胖病和高脂血症的预防作用.方法:将40只大鼠分为5组,即:基础饲料组、高脂饲料组、茶树花2.5％、5％、7.5％3个剂量组.每两天测量体重和摄食量1次,24d后断头取血,测定总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C).取体脂(肾及睾丸周围脂肪)称重.结果:与基础饲料组相比,高脂饲料组大鼠体重、脂肪系数、TC、TG、LDL-C、动脉粥样硬化指数(AI)显著增加;3个剂量茶树花添加组大鼠体重、脂肪系数、TC、TG、LDL-C、AI均低于高脂饲料组,且呈显著或极显著差异;中、高剂量组大鼠体重、脂肪系数、TC、TG、LDL-C、HDL-C、AI与基础饲料组无明显差异.结论:茶树花对大鼠肥胖病和高脂血症有一定的预防作用,3个剂量组中添加5％茶树花效果最好,可开发为降脂减肥的纯天然保健食品.     

Hypotensive effect of a sweetpotato protein digest in spontaneously hypertensive rats and purification of angiotensin I-converting enzyme inhibitory peptides

We have investigated angiotensin I-converting enzyme (ACE) inhibitory activity in an enzyme digest of sweetpotato protein, the antihypertensive effect of the digest in spontaneously hypertensive rats (SHR), and the identification of an ACE inhibitory peptide. Protein was prepared from squeezed juice of sweetpotato by isoelectric focusing precipitation. Three kinds of proteases were selected for effective protein digestion. The digest, sweetpotato peptide (SPP), exhibited strong ACE inhibitory activity (IC₅₀: 18.2 μg/ml). SPP was orally administered by gavage to SHR at a dose of 100 mg/kg or 500 mg/kg. The systolic blood pressure and the diastolic blood pressure were measured at 0 (before administration), 2, 4, 8, and 24 h after administration. A dose-dependent decrease in systolic blood pressure in SHR was observed after oral administration of SPP. Significant differences between SPP-administered rats and control rats were observed 4 and 8 h after administration in the 500 mg/kg-administered group and 8 h after administration in the 100 mg/kg-administered group. Diastolic blood pressure also decreased in the SPP-administered groups, although the difference between SPP-administered rats and control rats was not significant. These results suggest that SPP may be useful in the prevention or treatment of hypertension. Peptides with ACE inhibitory activity were purified from SPP by absorption chromatography and preparative HPLC using an ODS column. The amino acid sequences of isolated peptides were I-T-P, I-I-P, G-Q-Y and S-T-Y-Q-T; their ACE inhibitory activities (IC₅₀) were 9.5 μM, 80.8 μM, 52.3 μM and 300.4 μM, respectively. In conclusion, I-T-P is a novel, strong ACE inhibitory peptide.