Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.     

Alcohol consumption of patients attending two accident and emergency departments in north-west England.

The impact of alcohol use on the workload of two accident & emergency departments in north-west England was assessed by blood alcohol concentration (BAC) measurement, inspection of clinical records and interview of all patients aged 16 and over attending throughout a two-week period. The frequency of intoxication was similar to the previous reported rate in Scotland: 13.2% of all patients had a positive BAC. Inebriated injured patients arrived at all times of the day--varying in frequency from 2.5% of midday attenders to 78% of those presenting after midnight. The incidence of alcohol-related industrial accidents was low, but 60% of all assaulted patients were inebriated, many having sustained head injuries. Of patients attending within 2 hours of an accident at home, 19% also had a positive BAC, but 92% of those with ankle sprains were sober. Patients in lower social classes reported higher rates of alcohol consumption. The popularity of beer in comparison to wines and spirits was inversely related to age and unrelated to social class. Alcohol abuse is commonly associated with injuries sustained at home and with assaults occurring in public places. Prevention campaigns directed at the reduction of these types of incidents should be as concerned with the inebriation of the patient as with the architectural, environmental and legal framework within which the 'accident' occurs.     

Endothelial and smooth muscle properties of coronary and mesenteric resistance arteries in spontaneously hypertensive rats compared to WKY rats

Summary— To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level, in vitro experiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15–25-week-old SHR and age-matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D₁₀₀) were determined and vessels were set up to a normalized internal diameter (0.9 D₁₀₀). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro-L-arginine (NOLA, 100 μM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L-arginine (100 μM) but not D-arginine (100 μM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 μM] in MRA; serotonin, 5-HT [10 μM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA-precontracted MRA and 5HT-precontracted coronary arteries in the presence of indomethacin (10 μM), the magnitude of acetylcholine-induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30-min incubation period, NOLA (100 μM) completely inhibited relaxations induced by acetylcholine (0.01–10 μM) in all types of precontracted arteries. Subsequent additions of sodium nitroprusside, (SNP, 10 μM) induced complete relaxations in all preparations. These results show that a basal release of NO or NO-like compound by endothelial cells is present in isolated mesenteric resistance and coronary arteries of WKY rats and SHRs. The contribution of endothelium-derived relaxing factor-nitric oxide (EDRF-NO) to arterial tone was lower in MRA compared to coronary arteries in both strains and in SHR compared to WKY arteries. In the SHR preparations, the impaired relaxation induced by acetylcholine appeared to be due to a functional alteration of the endothelium in the presence of normal reactivity of the smooth muscle cells.     

The effects of a 0.12% chlorhexidine-digluconate-containing mouthrinse versus a placebo on plaque and gingival inflammation over a 3-month period

Abstract Several previous studies have evaluated the effects of 0.12% chlorhexidine digluconate (ChD) mouthrinses on plaque and gingival inflammation. However, previously, none have been based in general dental practices. The aim of this study was to evaluate the potential to conduct controlled periodontal clinical trials in co-operation with general dental practitioners (gdps). The project took place in 5 general dental practices in the South of England. 121 healthy subjects (24 at 4 sites and 25 at the 5th). aged 18-65 years, mean 35 ± 12) years participated in a double-blind, randomised study during which they received full mouth assessments for plaque and gingival bleeding at baseline, 6 and 12 weeks. 60 subjects were randomly asigned to use the 0.12% ChD mouth wash and 6i the placebo. The assessments were carried out by 5 gpds, who had previously achieved inter-examiner κ scores of 0.78–0.85 (mean 0.81) for the plaque index (PlI), and of 0.73–0.94 (mean 0.87) for a modified gingival index (mGI), and who maintained κ scores of 0.51–0.90 for PII and of 0.73–1.00 for mGI during the 12 months required to complete the study. 98 subjects (48 ChD and 50 placebo) completed the study. Even though the baseline levels of plaque and gingivitis were low, by week 12, mean whole mouth piaque score of the ChD mouthwash users had fallen from 1.33 at baseline to 0.96 and was significantly lower (p < 0.001) than for the placebo users, 1.31 at baseline to 1.13. Whole-mouth gingival bleeding score fell from 0.56 to 0.42 in the ChD mouthwash group but was unchanged (0.54–0.55) in the placebo group. A subsidiary data analysis which considered the effects at sites indicated that within these overall differences, the ChD users experienced almost 2× the reduction from plaque score 2 at baseline at proximal molar sites over a 12-week period (50.6% ChD versus 27.6% placebo). It was concluded that 0.12% ChD mouthwash reduced plaque accumulation fay 28% and gingival inflammation by 25% over a 12–week period, that it is feasible for a group of gdps to maintain high levels of inter–examiner consistency in the use of PlI and mGI, that it is also feasible to carry out such a multicentre study in general dental practice, and that the use of mean mouth scores per subject to analyse the effects of mouthrinses may well mask variations in response throughout the mouth.     

麦冬类中药组织切片计算机三维重建图鉴

利用计算机技术实现麦冬类中药组织连续切片三维重建与动态显示,为计算机辅助生药学鉴定和教学提供了新的三维图像技术和研究资料。     

Multiple Cranial Nerve Palsies in a Patient 15 Years after Curative Therapy for a Pituitary Adenoma

Over a 3-year period, a 31-year-old man developed multiple cranial nerve palsies consisting of diplopia, left-sided facial numbness and weakness, and loss of the left corneal reflex. Fifteen years prior to presentation, he had undergone curative therapy for a prolactin-secreting pituitary macroadenoma. The imaging studies were helpful in localizing the disease process, which correlated well with the clinical examination, and for focusing the differential diagnosis.     

表小檗碱对α受体的作用

表小檗碱(epiberberine,EB)是从湖北产黄连(Coptis chinensis Franch)中提取的一种生物碱,属苯喹嗪类原小檗碱,对其药理作用的研究资料甚少,未见其对α肾上腺素体作用的报道。资料表明,许多原小檗碱类化合物有α受体阻滞作用,为从该类化合物中选择     

Establishing new principles for nutrient reference values (NRVs) for food labeling purposes

Many countries such as The Republic of Korea have established their own nutritional standards, collectively termed Nutrient Reference Values(NRVs), and they vary due to the science which was reviewed, the purposes for which they are developed, and issues related to nutrition and food policy in the country. The current effort by the Codex Alimentarius Committee on Nutrition and Foods for Special Dietary Uses (CNFSDU) to update the NRVs that were established following the Helsinki Consultation in 1988 represents an opportunity to develop a set of reference values reflecting current scientific information to be used or adapted by many countries. This paper will focus on possible approaches to selecting or developing reference values which would serve the intended purpose for nutrition labeling to the greatest extent possible. Within the United States, the Food and Drug Administration (U.S. FDA) is currently reviewing regulations on nutrition labeling to better address current health issues, and is expected to enter into a process in the next few months to begin to explore how best to update nutrient Daily Values (DVs), most of which are still based on the Recommended Dietary Allowances (RDAs) of the Food and Nutrition Board, U.S. National Academy of Sciences, last reviewed and revised in 1968. In this presentation, I review the current purposes in the U.S. for nutrition labeling as identified in the 1938 Food, Drug, and Cosmetic Act as amended, the scientific basis for current nutrition labeling regulations in the United States, and the recommendations made by the recent Committee on Use of Dietary Reference Intakes in Nutrition Labeling of the Institute of Medicine (2003) regarding how to use the DRIs in developing new DVs to be used on the label in the United States and Canada. Based on these reviews, I then provide examples of the issues that arise in comparing one approach to another. Much of the discussion focuses on the appropriate role of nutrient labeling within the Nutrition Facts panel, one of the three major public nutrition education tools in the United States (along with MyPyramid and Dietary Guidelines for Americans).