Pharmacokinetics of valerenic acid after single and multiple doses of valerian in older women

Insomnia is a commonly reported clinical problem with as many as 50% of older adults reporting difficulty in falling and/or remaining asleep. Valerian (Valeriana officinalis) is a commonly used herb that has been advocated for promoting sleep. Valerenic acid is used as a marker for quantitative analysis of valerian products with evidence of pharmacological activity relevant to the hypnotic effects of valerian. The objective of this study was to determine the pharmacokinetics of valerenic acid in a group of elderly women after receiving a single nightly valerian dose and after 2 weeks of valerian dosing. There was not a statistically significant difference in the average peak concentration (C(max)), time to maximum concentration (T(max)) area under the time curve (AUC), elimination half-life (T(1/2)) and oral clearance after a single dose compared with multiple dosing. There was considerable inter- and intra-subject variability in the pharmacokinetic parameters. C(max) and AUC deceased and T(1/2) increased with increased body weight. The variability between the capsules was extremely low: 2.2%, 1.4% and 1.4%, for hydroxyvalerenic acid, acetoxyvalerenic acid and valerenic acid, respectively. In conclusion, large variability in the pharmacokinetics of valerenic acid may contribute to the inconsistencies in the effect of valerian as a sleep aid.     

The patient-physician relationship and medical utilization

Objective: The goal of this study was to (1) explore the relationship between medical utilization and characteristics of the patient-physician relationship and (2) evaluate the relationship between physician perception of patient difficulty, chronic medical problems, and patient somatizing tendencies.Method: Patients in an academic family practice center were asked to complete a demographic data sheet, the PRIME-MD Patient Questionnaire, and the Barrett-Lennard Relationship Inventory regarding their relationship with their physicians. Their physicians completed the Difficult Doctor-Patient Relationship Questionnaire. Patient charts were examined for number of office visits and phone calls in the previous year, as well as number of chronic problems and medications. The study was conducted from September 2000 to November 2001.Results: Forms were completed by 165 patients and 20 physicians. Forty-three patients who were approached refused to participate. Patient ratings on the Barrett-Lennard Relationship Inventory were not related to utilization measures. Physician ratings of difficulty were significantly related to phone calls and visits (p < .05), as well as PRIME-MD Patient Questionnaire somatization tendencies (p < .05) but not to number of chronic problems. Patient and physician ratings were not significantly correlated. Gender (p < .001), marital status (p < .04), education (p < .03), and employment status (p < .002) were all related to utilization measures.Conclusion: Medical utilization was associated with somatizing tendencies of patients and the physicians' perception of patient difficulty. Physicians rated patients as difficult if they tended to somatize but not if they had a number of chronic problems.     

BARIATRIC SURGERY IN AUSTRALIA: WHO,WHY AND HOW?

A review of published reports was conducted to identify gaps in the research regarding bariatric surgery. Much of the research that has been conducted is clinical outcome based; however, little research has been conducted in many key areas. Data on the demographics of the bariatric surgery group are patchy at best. The role of best practice and evidence-based medicine in bariatric surgery seems to be poorly understood, and equity issues and the role of clinical pathways in bariatric surgery need to be clarified. Significant gaps were identified in the published reports regarding pathways to bariatric surgery and multidisciplinary team use. Additionally, much of the published report and research data were from US studies, as few Australian studies have been conducted. Further research and policy and practice developments in bariatric surgery are needed, especially with regard to the Australian context.     

Comparison of monounsaturated fat with carbohydrates as a replacement for saturated fat in subjects with a high metabolic risk profile: studies in the fasting and postprandial states

BACKGROUND: In subjects with a high prevalence of metabolic risk abnormalities, the preferred replacement for saturated fat is unresolved. OBJECTIVE: The objective was to study whether carbohydrate or monounsaturated fat is a preferred replacement for saturated fat. DESIGN: Fifty-two men and 33 women, selected to have any combination of HDL cholesterol < or = 30th percentile, triacylglycerol > or = 70th percentile, or insulin > or = 70th percentile, were enrolled in a 3-period, 7-wk randomized crossover study. The subjects consumed an average American diet (AAD; 36% of energy from fat) and 2 additional diets in which 7% of energy from saturated fat was replaced with either carbohydrate (CHO diet) or monounsaturated fatty acids (MUFA diet). RESULTS: Relative to the AAD, LDL cholesterol was lower with both the CHO (-7.0%) and MUFA (-6.3%) diets, whereas the difference in HDL cholesterol was smaller during the MUFA diet (-4.3%) than during the CHO diet (-7.2%). Plasma triacylglycerols tended to be lower with the MUFA diet, but were significantly higher with the CHO diet. Although dietary lipid responses varied on the basis of baseline lipid profiles, the response to diet did not differ between subjects with or without the metabolic syndrome or with or without insulin resistance. Postprandial triacylglycerol concentrations did not differ significantly between the diets. Lipoprotein(a) concentrations increased with both the CHO (20%) and MUFA (11%) diets relative to the AAD. CONCLUSIONS: In the study population, who were at increased risk of coronary artery disease, MUFA provided a greater reduction in risk as a replacement for saturated fat than did carbohydrate.     

A cyclic peptide derived from alpha-fetoprotein inhibits the proliferative effects of the epidermal growth factor and estradiol in MCF7 cells

A cyclic peptide derived from the active domain of alpha-fetoprotein (AFP) significantly inhibited the proliferation of MCF7 cells stimulated with the epidermal growth factor (EGF) or estradiol (E2). The action of these three agents on cell growth was independent of the presence of calf serum in the culture medium. Our results demonstrated that the cyclic peptide interfered markedly with the regulation of MAPK by activated c-erbB2. The cyclic peptide showed no effect on the E2-stimulated release of matrix metalloproteinases 2 and 9 nor on the shedding of heparin-binding EGF into the culture medium. We propose that the AFP-derived cyclic peptide represents a valuable novel antiproliferative agent for treating breast cancer.     

Urine and Plasma Pharmacokinetics of Lofexidine after Oral Delivery in Opiate-Dependent Patients

Objectives: The objective of this study was to investigate lofexidine urine and plasma pharmacokinetics using three different dosing regimens in opioid dependent subjects. To date, there have been no published studies on lofexidine appearance and excretion in urine of opioid dependent subjects. Methods: Subjects were stabilized with 100 mg morphine sulphate on days 3–8 of the study. The dosing regimens of lofexidine hydrochloride were .8 mg twice a day (BID), 1.2 mg BID, or .8 mg three times a day (TID) on days 9 through 16 of the study. Plasma and urine samples were collected at appropriate time points. Area under the concentration-time curve (AUC), maximum concentration in plasma (C_max), time when maximum concentration was reached (T_max) and fraction excreted unchanged in urine (Fe) were calculated. Results: The average half-life obtained from all profiles was 12.1 ± 6.3 hr. Steady-state (SS) was reached by study day 15. The plasma pharmacokinetic parameters for 1.2 mg BID and .8 mg TID dosing regimens did not seem to be different at steady state (day 15). T_max was not statistically significantly different across dosing regimens. Fe values ranged between .01% and 34% with high variability within the same dosing regimen. For the total dose of 2.4 mg/day the two dosing regimens that were evaluated, namely 1.2 mg BID and .8 mg TID, did not show a significant statistical difference in plasma and urine pharmacokinetic parameters. Conclusion: Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine urine pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis.