LC-MS/MS methods for determination of unstable pivmecillinam and mecillinam in acidified human plasma: Application to a pharmacokinetic study.

Pivmecillinam, the ester of biologically active antibiotic mecillinam, is an effective oral preparation to treat urinary tract infections. To study pharmacokinetics in humans, LC-MS/MS methods were developed to quantify pivmecillinam and mecillinam in human plasma, respectively. Considering cephalexin as internal standard, analytes were separated on UltimateXB-C18 columns after protein precipitation by acetonitrile. The mobile phase was composed of water containing 0.1% formic acid and methanol. The multiple reactions monitoring transitions of m/z 440.2→167.1, 326.1→167.1, and 348.1→158.1 were selected to inspect pivmecillinam, mecillinam, and the internal standard in positive ion mode. No apparent matrix effect was perceived. Linearities were obtained over calibration ranges of 0.0500-12.0 and 10.0-15,000 ng/mL, respectively. The intraday precisions were below 5.5%, the interday precisions were below 6.1%, and accuracies were within -8.1 to 13.0%. Stability tests were conducted and an acidification step was explored to enhance the stability of pivmecillinam and mecillinam. Further stability was validated under various storage and processing conditions. Both methods were applied to a pharmacokinetic study of pivmecillinam and mecillinam after oral administration of 400 mg pivmecillinam hydrochloride tablets in healthy Chinese subjects.

Corosolic acid and its structural analogs: A systematic review of their biological activities and underlying mechanism of action.

BACKGROUND: The corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature. PURPOSE: This systematic review aims to summarize the medical applications of CA and its analogues. METHODS: A systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. 'corosolic acid', 'ursolic acid', 'oleanolic acid', 'maslinic acid', 'asiatic acid', 'betulinic acid', 'extraction', 'pharmacokinetic', 'pharmacological' were used to extract relevant literature. The PRISMA guidelines were followed. RESULTS: At the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared. CONCLUSION: CA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.

The Effects of Mindfulness-Based Movement on Parameters of Stress.

The Mindfulness-Based Stress Reduction program (MBSR) of Kabat-Zinn includes a combination of sitting meditation, yoga, and walking; thus, movement is not emphasized primarily to induce a state of awareness. The purpose of this study was to investigate the effects of a Mindfulness-Based Movement Program (MBM) in women on parameters of stress and coping; that is, in contrast to MBSR, MBM primarily emphasized yoga to cultivate awareness. This study investigated: (a) an objective measure of stress (the cortisol response to a laboratory stressor) following an 8-week MBM in year 1 participants only (n = 17; MBM group = 9; Control group = 8); (b) subjective measures of stress following an 8-week MBM in years 1 and 2 (n = 32; MBM = 16; C = 16); and (c) changes in coping style following an 8- week MBM in years 1 and 2 (n = 32; MBM = 16; C = 16). A mixed plot 2 (Group: TC or MBM) by 5 (Trial: Baseline, Stressor, Recovery 1, Recovery 2, and Recovery 3) repeated measures ANOVA was run for cortisol. Preliminary results indicated a strong trend towards a lowered cortisol response for the MBM group compared to the control group. A mixed plot 2 (Group: TC or MBM) by 2 (Time: Pretest, Post-test) repeated measures ANOVA was run for Spielberg's State Anxiety, the Perceived Stress Scale, and the Problem Focused Style of Coping Scale for the Suppressive, Reflective, and the Reactive Coping Style. There were significant main effects for time, group, and an interaction of time and group for Spielberg's State Anxiety and the Perceived Stress Scale. Significant differences were also found for time and the interaction of time and group for the Problem Focused Style of Coping for the Reflective Coping Style (p < 0.05). In conclusion, results indicate positive effects of the MBM program on perceived measures of stress and coping style in women.

Neuroendocrine responses to psychological stress in eumenorrheic and oligomenorrheic women.

Neuroendocrine adaptive responses to psychological stress include activation of the hypothalamic-pituitary-adrenal (HPA) axis and sometimes suppression of the hypothalamic-pituitary-gonadal (HPG) axis. In women who experience chronic stress, these responses are probably responsible for disturbances in the menstrual cycle. In the present experiment, we investigated the effect of an acutely stressful situation on the physiological and neuroendocrine responses in college age women. We hypothesized that females who are experiencing some degree of abnormal menstrual function or women who have less-robust cycles (oligomenorrheic females) would exhibit differences in gonadotropin secretion from eumenorrheic females when exposed to psychological stressors. Fifteen women completed this study: eumenorrheic (n = 5) and oligomenorrheic women (n = 5) who experienced a series of psychological stressors, and eumenorrheic controls (n = 5). Blood samples were taken at 10 min intervals for 8 h (09:00-17:00) in each woman during the mid-follicular phase of the menstrual cycle. The psychological stressors were administered for 1 h beginning at 13:00 h. Luteinizing hormone (LH), growth hormone (GH) and cortisol were measured in each sample to assess the effect of stress on secretion of these hormones. Deconvolution analysis was used to analyze pulsatile hormone secretion and the approximate entropy (ApEn) statistic analyzed the regularity of release of each hormone. Although, there were significant changes in heart rate (HR), skin resistance (SR) and cortisol levels in the stressed women during the psychological stressor compared to resting baseline values but not in the controls, there was no difference in either LH or GH secretion between women who experienced stress and those who did not. Furthermore, there were no differences in the LH or GH secretion patterns in the oligomenorrheic and eumenorrheic women exposed to the psychological stressor.