Endocrinology: Comparative pharmacokinetics of two urinary human follicle stimulating hormone preparations in healthy female and male volunteers

These studies were designed to compare the pharmacokinetic characteristicsof a very highly purified urinary human follicle stimulatinghormone (FSH-HP) preparation (sp. act. 9000 IU FSH/mg of protein),Metrodin HP^®, with a standard urinary FSH preparation Metrodin^®(FSH). The two preparations were administered in a balanced,random-order, cross-over sequence as single doses of 150IU,separated by 1 week of washout to 12 female volunteers by i.v.injection and to 12 male volunteers by i.m. and s.c. routes.FSH concentrations were measured by immunoradiometric assayand by an in-vitro rat granulosa cell aromatase bioassay. Afteran i.v. bolus, the pharmacokinetics of the two FSH preparationswere identical. Total clearance was 0.5 and 0.15 1/h respectivelyfor immunoassay and bioassay data. Immunoassay showed that thetwo preparations were similar for renal clearance (0.1 1/h),volumes of distribution at steady state (9 1), distributionand terminal half-lives (2 and 17 h, respectively). After parenteraladministrations, the absorption half-life of FSH was 3 h andthe apparent terminal half-life was 1.5 days. Both preparationshad relative bio-availabilities close to 100% for i.m. and s.c.administrations. Immunopurification, which results in a veryhighly purified FSH-HP, does not modify the pharmacokineticproperties of FSH. This study also confirmed that s.c. and i.m.doses of FSH-HP are equivalent from the pharmacokinetic andpharmacodynamic points of view.     

Chronic Intake of Energy Drinks and Their Sugar Free Substitution Similarly Promotes Metabolic Syndrome

Energy drinks containing significant quantities of caffeine, taurine and sugar are increasingly consumed, particularly by adolescents and young adults. The putative effects of chronic ingestion of either standard energy drink, Mother^TM (ED), or its sugar-free formulation (sfED) on metabolic syndrome were determined in wild-type C57BL/6J mice, in comparison to a soft drink, Coca-Cola (SD), a Western-styled diet enriched in saturated fatty acids (SFA), and a combination of SFA + ED. Following 13 weeks of intervention, mice treated with ED were hyperglycaemic and hypertriglyceridaemic, indicating higher triglyceride glucose index, which was similar to the mice maintained on SD. Surprisingly, the mice maintained on sfED also showed signs of insulin resistance with hyperglycaemia, hypertriglyceridaemia, and greater triglyceride glucose index, comparable to the ED group mice. In addition, the ED mice had greater adiposity primarily due to the increase in white adipose tissue, although the body weight was comparable to the control mice receiving only water. The mice maintained on SFA diet exhibited significantly greater weight gain, body fat, cholesterol and insulin, whilst blood glucose and triglyceride concentrations remained comparable to the control mice. Collectively, these data suggest that the consumption of both standard and sugar-free forms of energy drinks induces metabolic syndrome, particularly insulin resistance.     

受体－A蛋白融合蛋白制备抗P物质受体血清及其特性

受体－Ａ蛋白融合蛋白制备抗Ｐ物质受体血清及其特性ＷａｌｔｅｒＫ．Ｋ．Ｈｏ（何国强）；ＡｌｅｘｉｓＰ．Ｋ．Ｃｈｅ，郑德枢（香港中文大学；香港生物化学系，香港沙田；广州医学院神经科学研究所，广州５１０１８２）本文报告了用直肠杆菌表达Ｐ物质受体－Ａ蛋白融合...     

Endocrinology: Presence and possible function of activin-like substance in human follicular fluid

We assessed the presence of an activin-like substance in humanfollicular fluid that was obtained from women undergoing in-vitrofertilization using a bioassay for activin A. Activin activitywas not detected in crude follicular fluids; the bioactivityof standard activin A was inhibited by the addition of follicularfluid. After the follistatin (binding protein of activin A)was removed from follicular fluid using a purification procedure,activin activity was detected in the follicular fluids (meanconcentration: 131 ± 40 ng/ml). Activin activity wasinhibited by the addition of follistatin to fluid. The concentrationof activin activity was substantially higher (100-fold) thanthat reported in serum. The concentration negatively and significantlycorrelated with the number of developed follicles in the ovary(r = 0.501, P < 0.01). These results suggest that activinA and its binding protein are present in follicular fluid inlarge amounts and that they may have a role in local ovarianregulation.     

头孢克肟胶囊在健康志愿者的生物等效性研究

目的:研究头孢克肟胶囊在健康人体内的生物等效性。方法:20名健康男性志愿者双周期、随机交叉、自身对照,口服单剂量试验和对照头孢克肟胶囊200 mg。用HPLC-UV检测法和微生物法测定血药浓度,所得数据用3P97软件处理,按一室模型计算药代动力学参数。结果:试验及对照制剂HPLC法测定的C_(max)分别为2.317±0.536和2.87±0.492 mg·L~(-1);t_(max)分别为4.1±0.7和4.3±0.7 h;AUC_(0-16)分别为17.251±5.087和16.954±4.536 mg·L~(-1)·h;AUCO_(0-∞)分别为18.386±4.559和18.138±3.931 mg·h·L~(-1)。微生物法测定的C_(max)分别为2.437±0.495和2.361±0.435 mg·L~(-1);t_(max)分别为4.13±0.65和3.90±0.45 h;AUC_(0-16)分别为18.741±3.931和18.064±3.350 mg·h·L~(-1);AUCO_(0-∞)分别为20.109±4.497和19.403±3.693 mg·h·L~(-1)。对AUCO_(0-16)、AUC_(0-∞)、C_(max)进行双向单测检验,无显著性差异。HPLC法和微生物法测定的试验品相对生物采利用度分别为(101.53±18.21)％,(103.30±15.78)％,结论:试验头孢克肟胶囊和对照制剂具有生物等效性。HPLC法与微生物法呈相关性。     

Implication of brevetoxin B1 and PbTx-3 in neurotoxic shellfish poisoning in New Zealand by isolation and quantitative determination with liquid chromatography-tandem mass spectrometry.

Brevetoxin B1 (BTX-B1) was isolated from Austrovenus stutchburyi following the 1992-1993 outbreak of neurotoxic shellfish poisoning (NSP) in New Zealand. We report here the first isolation of PbTx-3 from the same shellfish and the development of a procedure for quantitative determination of PbTx-3 and BTX-B1. PbTx-3 was isolated by chromatography on columns of SiO2, ODS, and LH-20, followed by reverse-phase HPLCs. In mass spectrometry (MS) with an electrospray ionization (ESI) interface operating in the positive or negative ion mode, the abundant protonated ion [M+H]+ of PbTx-3 (m/z 897) and the de-sodiated ion [M-Na]- of BTX-B1 (m/z 1016) were generated, respectively. These served as precursor ions for collision-induced dissociation, and the product ions of m/z 725 from PbTx-3 and m/z 80 from BTX-B1 were identified, allowing unambiguous confirmation of these toxins by selected reaction monitoring liquid chromatography-tandem mass spectrometry (SRM LC-MS/MS) analysis. The determination limits were 0.4 and 2 ng/g for BTX-B1 and PbTx-3 at a signal-to-noise ratio of five, respectively. This LC-MS/MS method was successfully applied to determine BTX-B1 and PbTx-3 in the NSP-associated toxic shellfish. BTX-B1 was found in both A. stutchburyi and Perna canaliculus, but not in Crassostrea gigas, while PbTx-3 was found in all three.     

The use of Lepidium sativum in a plant bioassay system for the detection of microcystin-LR.

Toxin-producing cyanobacteria pose a worldwide health threat to humans and animals due to their increasing presence in both drinking and recreational waters. Detection of microcystins in water generally relies on specialised equipment and a delay of several days for transport and analysis. Little work has, however, been done on establishing a simple, cost-effective and sensitive plant bioassay for the detection of microcystin-LR (MCLR) in water at the WHO Tolerable Daily Intake guideline level of 1 microg/l. We investigated the effect of a MCLR extract at 1 and 10 microg/l on the growth of Lepidium sativum over 6 days. Exposure to 10 microg/l MCLR resulted in a significant decrease in root and leaf lengths and fresh weights of seedlings when compared to the controls. These results were consistent with seedlings exposed to pure MCLR at 10 microg/l. Seedlings exposed to 1 microg/l MCLR showed a significant decrease in root development from day 2 to day 6. Glutathione S-transferase and glutathione peroxidase activities were also significantly raised in plants from days 5 and 4, respectively, at both toxin levels investigated.     

The 1.5 GHz Electromagnetic Near-field Used for Cellular Phones Does Not Promote Rat Liver Carcinogenesis in a Medium-term Liver Bioassay

We have recently established that local exposure to a 929.2 MHz electromagnetic near-field, used for cellular phones, does not promote rat liver carcinogenesis in a medium-term bioassay system. In the present study, a 1.439 GHz electromagnetic near-field (EMF), another microwave band employed for cellular phones in Japan, was similarly investigated. Time division multiple access (TDMA) signals for the Personal Digital Cellular (PDC) Japanese cellular telephone standard system were directed to rats through a quarter-wavelength monopole antenna. Numerical dosimetry showed that the peak SARs within the liver were 1.91–0.937 W/kg, while the whole-body average specific absorption rates (SARs) were 0.680–0.453 W/kg, when the time-averaged antenna radiation power was 0.33 W. Exposure was for 90 min a day, 5 days a week, over 6 weeks, to male F344 rats given a single dose of diethylnitrosamine (200 mg/kg, i.p.) 2 weeks previously. At week 3, all rats were subjected to a two-thirds partial hepatectomy. At week 8, the experiment was terminated and the animals were killed. Carcinogenic potential was scored by comparing the numbers and areas of the induced glutathione S-transferase placental form (GST-P)-positive foci in the livers of exposed (48) and sham-exposed rats (48). Despite increased serum levels of corticosterone, adrenocorticotropic hormone (ACTH) and melatonin, the numbers and the areas of GST-P-positive foci were not significantly altered by the exposure. These findings clearly indicated that local body exposure to a 1.439 GHz EMF, as in the case of a 929.2 MHz field, has no promoting effect on rat liver carcinogenesis in the present model.     

地红霉素片的人体药代动力学及生物利用度研究

目的　考察国产与进口地红霉素片的药代动力学及生物等效性。方法　采用随机单剂二交叉试验设计,18名健康男性志愿者单剂口服国产与进口地红霉素片 75 0mg,微生物法测定地红霉素血浓度。对二种制剂的主要药代动力学参数进行方差分析、双向单侧t检验,评价试验制剂与参比制剂的生物等效性。结果　国产和进口地红霉素片主要药代动力学参数t1/2ke分别为 19 77± 4 5 1h和 18 5 7± 3 39h,Tpeak分别为 3 89± 0 76h和 3 83± 0 5 1h,Cmax分别为 1 6 12± 0 176 μg·ml-1和1 6 85± 0 10 8μg·ml-1,AUC0～ 96h分别为 11 4 0± 1 88μg·ml-1·h和 11 0 5± 1 84 μg·ml-1·h,AUC0～∞ 分别为 12 14± 2 11μg·ml-1·h和 11 6 6± 1 88μg·ml-1·h,国产地红霉素片相对生物利用度F为 10 3 79%± 10 5 2 %。结论　国产与进口地红霉素片为生物等效制剂。