壮骨肾宝对实验性小鼠高脂血症的影响

目的观察由黄芪、白术、淫羊藿组成的复方制剂(壮骨肾宝)对实验性小鼠高脂血症的影响。方法用蛋黄乳液快速致小鼠单纯性高胆固醇血症和喂养高脂饲料致高脂血症模型 ,观察预防性给予不同剂量的壮骨肾宝后对血清总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白胆固醇(HDL -ch)的影响。结果壮骨肾宝中、高剂量能使血清TC降低(P<0.05),HDL -ch升高(P<0.01) ,但对TG的影响不大。结论壮骨肾宝有一定降血脂作用 ,并与剂量有关     

姜黄素与辛伐他汀降血脂及抗氧化作用比较

目的:以高脂血症大鼠为模型比较姜黄素、姜黄素固体分散体、辛伐他汀降血脂及抗氧化作用。方法:雄性SD大鼠灌胃给予高脂肪乳剂制备高脂血症大鼠模型。造模的同时,给予姜黄素、姜黄素固体分散体、辛伐他汀,连续给药6周后测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)的含量,超氧化物歧化酶(SOD)的活性。结果:姜黄素与姜黄素固体分散体在降低血清中甘油三酯(TG)的作用明显优于辛伐他汀(P<0.05);而辛伐他汀降低血清中总胆固醇的作用明显优于姜黄素(P<0.01);姜黄素与姜黄素固体分散体能提高血清及肝匀浆中SOD活性,降低MDA含量,姜黄素抗氧化作用明显优于辛伐他汀(P<0.01);姜黄素固体分散体的降血脂及抗氧化能力明显优于姜黄素(P<0.01)。结论:姜黄素固体分散体对高脂血症模型大鼠具有降低血脂及抗氧化的双重作用。     

茯苓醇提取物对高脂血症小鼠的血脂和NO水平的影响

目的 研究茯苓醇提物对高血脂小鼠的降血脂作用.方法 将60只昆明种小鼠,随机均分为正常饲料(空白)组、高脂饲料(模型)组、绞股蓝(对照)组、0.3、0.6、1.2 g·kg~(-1)茯苓醇提物剂量(给药)组,除空白组外,其他组喂以高脂饲料.14 d后,检测小鼠肝脏指数、脾脏指数,小鼠血清中的胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、一氧化氮(NO)和超氧化物歧化酶(SOD)等指标.结果 茯苓醇提物可显著降低高血脂模型小鼠的肝脏指数和血清中TC、TG、LDL-C、NO水平,并显著提高血清中SOD的活性.结论 醇提取物具有降低高脂血症小鼠血脂的作用.     

克脂星胶囊药理实验及疗效观察

研究克脂星胶囊降血脂作用机理和临床疗效;结果高脂血症大鼠血清总胆固醇及甘油三酯明显降低,家兔血清流变学改善,高脂血症病人降低血清总胆固醇和血清甘油三酯有效率超于80%,且无明显毒副作用.     

决明子降血脂有效部位及其量效关系的实验研究

目的研究决明子降血脂的有效部位及其量效关系。方法选用CO超临界、系统溶媒(石油2醚、乙酸乙酯、70%乙醇、水)和水提醇沉的方法分别对决明子进行提取,观察各提取物对腹腔注射蛋黄乳液致高血脂症模型小鼠血清总胆固醇及甘油三酯的影响,初步明确决明子降血脂的有效活性部位,并对该有效部位进行量效关系的评定。结果决明子乙酸乙酯提取物和水提取物均有显著的降低血清总胆固醇和甘油三酯的作用,其中乙酸乙酯提取物的降脂效果优于水提取物,其在0.75～1.00g·kg-1·d-1时降脂效果最佳;决明子70%乙醇提取物和水提醇沉物虽也有一定的降血脂作用,但与对照组相比差异无统计学意义。结论决明子乙酸乙酯提取物为决明子降血脂的有效活性部位,其有效剂量范围在0.50～1.25g·kg-1·d-1之间。     

紫背天葵提取物降血脂及抗凝实验研究

目的 观察紫背天葵提取物的降血脂及抗凝作用.方法 以高脂饲料配方(含猪油、胆固醇等)连续饲养小鼠15 d后制备高血脂动物模型,确认模型成功后,以经典水煮醇沉提取方法对紫背天葵提取物进行降血脂、抗凝药理试验.结果 紫背天葵高剂量组( 15 g/kg)及洛伐他汀均不同程度地降低总胆固醇和甘油三酯水平(P＜0.05),其中以降低胆固醇水平作用最为明显,经过抗凝药理实验发现,经灌胃口服给药紫背天葵高剂量组对降低高脂小鼠血脂水平、降低血液黏滞度有较好作用.结论 15 g/kg紫背天葵具有降低胆固醇和甘油三酯、抗凝作用,本研究为开发成辅助降血脂药物奠定基础.     

野马追对大、小鼠实验性高脂血症的防治作用

目的探讨野马追提取液对大、小鼠实验性高脂血症的防治作用。方法将大鼠和小鼠各60只分别随机分为大、小鼠空白对照组、高脂模型组、阳性对照组及野马追提取液高、中、低剂量组。除空白对照组外,小鼠各组给予相应的药物30d后腹腔注射75%蛋黄乳,大鼠各组喂高脂饲料同时给予相应的药物30d。各组均于末次给药后采血,测血清胆固醇、甘油三酯及高、低密度脂蛋白胆固醇(HDL-C、LDL-C)含量。结果野马追能明显降低实验性血清胆固醇、甘油三酯及LDL-C水平,并明显升高HDL-C水平。结论野马追对实验性大、小鼠高脂血症有明显防治作用。     

栀子黄色素与栀子苷降血脂和体内抗氧化作用的比较

目的 比较栀子中栀子黄色素与栀子苷的降血脂和体内抗氧化作用.方法 饲喂小鼠高脂高胆固醇饲料8周,第5 ～8周分别每日ig给予栀子苷和栀子黄色素(100 mg· kg-1),以辛伐他汀(10 mg·kg-1)为阳性对照;检测小鼠血清中的总胆固醇(TC)、甘油三酯(TG)、低密度蛋白胆固醇(LDL-C)、高密度蛋白胆固醇(HDL-C)和丙二醛(MDA)的水平,测定血清中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活力.结果 栀子黄色素能显著降低高脂血症小鼠血清中TC、TG、LDL-C的水平,升高HDL-C的水平;同时增强SOD和CAT酶的活力,降低MDA的含量;栀子苷虽能显著降低各血脂指标,但对体内抗氧化作用无明显效果.结论 栀子中的栀子黄色素与栀子苷均有降血脂的功能,但栀子黄色素的体内抗氧化作用效果更强.     

克脂星动物实验及临床疗效研究

目的：研究克脂星胶囊降血脂作用机制和临床疗效。方法：对高脂血症大白鼠血清总胆固醇及甘油三酯和家兔血液流变学进行实验观察。结果：本品对高脂血症动物和人均有明显的降低血清总胆固醇和甘油三脂的作用,优于对照组（Ｐ〈０．０１）。结论：本品可用于高脂血症的预防和治疗,无明显毒副作用。     

紫背天葵提取物降血脂及抗凝实验研究

目的观察紫背天葵提取物的降血脂及抗凝作用。方法以高脂饲料配方（含猪油、胆固醇等）连续饲养小鼠15 d后制备高血脂动物模型,确认模型成功后,以经典水煮醇沉提取方法对紫背天葵提取物进行降血脂、抗凝药理试验。结果紫背天葵高剂量组（15 g/kg）及洛伐他汀均不同程度地降低总胆固醇和甘油三酯水平（P〈0.05）,其中以降低胆固醇水平作用最为明显,经过抗凝药理实验发现,经灌胃口服给药紫背天葵高剂量组对降低高脂小鼠血脂水平、降低血液黏滞度有较好作用。结论 15 g/kg紫背天葵具有降低胆固醇和甘油三酯、抗凝作用,本研究为开发成辅助降血脂药物奠定基础。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.     

Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination

The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers.The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml^–1·h, and from 63.4 to 74.6 ng·ml^–1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide.The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril.Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.