Pituitary network connectivity as a mechanism for the luteinising hormone surge.

Ovulation in vertebrates is caused by a surge of luteinising hormone (LH) from the pituitary. The LH surge is initiated by rising oestradiol concentration, although the precise mechanism of oestradiol action in humans and primates is not yet understood. Recent advances in labelling and three-dimensional imaging have revealed a rich pituitary structure of interwoven networks of different cell types. In the present study, we develop a mathematical model to test the hypothesis that oestradiol modulation of connectivity between pituitary cells can underlie the LH surge. In the model, gonadotrophin-releasing hormone (GnRH) pulses stimulate LH secretion by two independent mechanisms. The first mechanism corresponds to the well known direct action of GnRH on gonadotrophs, which is inhibited by the rising oestradiol concentration. The second mechanism of GnRH action is to stimulate a recurrent network of pituitary cells; in this case, the folliculostellate cells, which in turn stimulate LH secretion from the gonadotrophs. The network activity is modelled by a one-dimensional ordinary differential equation. The key to the LH surge in the model lies in the assumption that oestradiol modulates network connectivity. When the circulating oestradiol concentration is low, the network is barely connected, and cannot maintain a recurrent signal. When the oestradiol concentration is high, the network is highly connected, and maintains a high level of activity even after GnRH stimulation, thereby leading to a surge of LH secretion.

Drug utilization pattern of Chinese herbal medicines in a general hospital in Taiwan.

PURPOSE: Drug utilization studies are important for the optimization of drug therapy and have received a great attention in recent years. Most of the information on drug use patterns has been derived from studies in modern Western medicines; however, studies regarding the drug utilization of traditional Chinese medicine (CM) are few. The present study was the first clinical research to evaluate the drug utilization patterns of Chinese herbal medicines in a general hospital in Taiwan. METHODS: Data were collected prospectively from the patients attending the Traditional Medicine Center of Taipei Veteran General Hospital under CM drug treatments. The study was carried out over a period of 1 year, from January 2002 to December 2002. Core drug use indicators, such as the average number of drugs per prescriptions, the dosing frequency of prescriptions, and the most common prescribed CM herbs and formulae were evaluated. The primary diagnosis and the CM drugs prescribed for were also revealed. All data were analyzed by descriptive statistics. RESULTS: A total of 10 737 patients, representing 52 255 CM drugs, were screened during the study period. Regarding the prescriptions, the average number of drugs per prescription was 4.87 and 37.21% of prescriptions were composed by five drugs. Most of prescriptions (91.38%) were prescribed for three times a day. The most often prescribed Chinese herb was Hong-Hwa (5.76%) and the most common Chinese herbal formula was Jia-Wey-Shiau-Yau-San (3.80%). The most frequent main diagnosis was insomnia (15.58%), followed by menopause (5.22%) and constipation (5.09%). CONCLUSION: The survey revealed the drug use pattern of CMs in a general hospital. The majority of CM prescriptions were composed by 3-6 drugs and often prescribed for three times a day. Generally, the rational drug uses of CM drugs were provided with respect to the various diagnoses.

Rational pharmacotherapy in the diabetic hypertension: analysis-prescribing patterns in a general hospital in Taiwan.

OBJECTIVES: To examine prescribing at a 2800-bed hospital, also providing ambulatory services for 9000 visits per day, with a view to assessing the extent to which it followed international guidelines for treating diabetic hypertension. METHOD: Patients receiving antidiabetic and antihypertensive drugs concomitantly during the 4-week study period were included. RESULT: Of the 5015 eligible patients, most received combination antidiabetic therapy. Oral antidiabetic agents used alone or in combination included (in descending order) metformin, glibenclamide, gliclazide, glipizide, glimepiride and alpha-glucosidase inhibitors. Gliclazide accounted for most of the oral antidiabetic drug expenditure. Sulfonylurea plus metformin was the most popular regimen. Prescriptions for long-acting sulfonylureas did not differ between elderly and younger patients. For blood pressure control, calcium-channel blockers were most commonly used alone and overall, although current guidelines suggest that they should be second-line treatments. Inappropriate use of immediate-release nifedipine was noted. The combination, atenolol >100 mg/day and hydrochlorothiazide 50 mg/day (or an equivalent) were extensively used. Among 54.7% patients treated with combination antihypertensives, calcium-channel blockers and an angiotensin-converting enzyme inhibitor were most commonly used. CONCLUSION: Most diabetic hypertensive patients were treated with combination therapy for glucose and blood pressure control. Prescriptions for antihypertensive drugs often differed from current guidelines, especially in the choice of agents and their combinations.

Transdermal-controlled administration of oxycodone.

The permeability of hairless mouse skin membrane to the weak base narcotic analgesic oxycodone (pKa = 8.53) was investigated. The effects of pH on the solubility and skin permeation rate were also studied. The results of the study of skin permeation of drug through hairless mouse skin suggest that the permeability of oxycodone base is approximately 7.4 times higher than that of protonated oxycodone. The nonionic species of oxycodone, at various drug loadings, was then incorporated in a Dow-Corning silicone elastomer for the evaluation of the release rate and skin permeation rate. It was found that Q/t1/2 is directly proportional to the square root of the drug loading dose, as expected by Higuchi's equation (where Q is the cumulative amount released and t is time). However, the skin permeation rate was observed to increase initially with drug loading and level off at the loading dose of 60 mg/cm3.