Cognitive effects of onabotulinumtoxinA in chronic migraine.

BACKGROUND: Chronic migraine is a disabling condition, often associated with comorbidities including cognitive dysfunction, anxiety and depression. It is unclear whether cognitive complaints are associated with the underlying migraine pathophysiological process or related to drugs or comorbidities of depression and anxiety. OBJECTIVE: To evaluate cognitive changes in chronic migraine and assess reversibility of cognitive dysfunction following effective migraine treatment using onabotulinumtoxinA. METHODS: This was a prospective real-world study of 60 patients with chronic migraine treated with onabotulinumtoxinA. Headache diaries recorded total headache days at baseline and duration of 12 weeks post-treatment. Computerised cognitive tests of reaction time and working memory (WM) speed and accuracy using a purpose-specific website was implemented at baseline, 6 weeks and 12 weeks. The Patient Health Questionnaire (PHQ-9) and Penn State Worry Questionnaire-Past Week (PSWQ-PW) were administered for depression and anxiety levels. Associations between clinical response, cognitive parameters, PHQ-9 and PSWQ-PW were analysed. RESULTS: At 6 weeks post-treatment, 88% patients achieved good response (≥50% reduction in headache frequency) with improvement of PHQ-9, PSWQ-PW, cognitive speed tests and WM accuracy compared with baseline (all p<0.05). There was no overall correlation between good headache response and improved cognitive measures and no association between good headache response and improved PHQ-9 and PSWQ-PW scores. Improved WM accuracy correlated with reduced PSWQ-PW (p=0.047). There was no correlation between improved WM accuracy and reduced PHQ-9. CONCLUSIONS: OnabotulinumtoxinA treatment for chronic migraine improved anxiety, depression and cognitive performances but these improvements did not correlate with reduction in headache and migraine frequency. Improved WM accuracy was significantly associated with reduced anxiety level.

The radiographic and functional outcome of bilateral mandibular condylar head fractures: a comparison between open and closed treatment.

UNLABELLED: Bilateral mandibular condylar fractures accounts for 24% to 33% of condylar fractures but the indications of open reduction of bilateral condylar fracture are still controversial. It is generally accepted that displaced subcondylar fractures are indicated for open reduction, but the proper treatment of condylar head fractures are still variable. This retrospective study compares the radiographical and functional outcomes of bilateral condylar head fractures between open and closed reduction groups. MATERIALS AND METHODS: From February 1994 to June 2012, a total of 85 patients with bilateral condylar head fractures were retrospectively reviewed. Among this group, 41 cases underwent open reductions while the other 44 cases had closed reductions. Only adult patients with adequate follow-up and complete radiographic study were included in this study: consisting of 20 patients in the open group and 18 patients in the closed group.The subjective symptoms including temporomandibular joints (TMJ) symptoms, complications or adverse sequelae, and functional results, such as maximal mouth opening, were recorded. The outcome of patient's satisfaction was individually assessed by an independent reviewer. The computed tomographic results after treatment were evaluated between both groups. RESULTS: The mean follow-up period was 25.5±13.3 months. The open reduction group had better postoperative chewing functions, less malocclusion rates, less degree of TMJ pain (p=0.046), better radiographic outcome (p=0.036), and an overall satisfaction rate (p=0.039).There were 4 cases of failure in the closed reduction group. Subsequent open reduction (n=2) and redo closed reduction with intermaxillary fixation (n=2) were performed. Eleven patients in the close reduction group presented persistent malocclusion through objective evaluation. The subsequent treatment included further orthognathic surgery (n=1) and orthodontic treatment (n=7). Three of the patients refused further treatment. CONCLUSIONS: Open reduction for bilateral condylar head fractures presented an overall better functional and radiographic outcome, with higher patient satisfaction if condylar fracture segments were still feasible for rigid fixation.

Resveratrol and cardiovascular health--promising therapeutic or hopeless illusion?

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural polyphenolic compound that exists in Polygonum cuspidatum, grapes, peanuts and berries, as well as their manufactured products, especially red wine. Resveratrol is a pharmacologically active compound that interacts with multiple targets in a variety of cardiovascular disease models to exert protective effects or induce a reduction in cardiovascular risks parameters. This review attempts to primarily serve to summarize the current research findings regarding the putative cardioprotective effects of resveratrol and the molecular pathways underlying these effects. One intent is to hopefully provide a relatively comprehensive resource for clues that may prompt ideas for additional mechanistic studies which might further elucidate and strengthen the role of the stilbene family of compounds in cardiovascular disease and cardioprotection. Model systems that incorporate a significant functional association with tissues outside of the cardiovascular system proper, such as adipose (cell culture, obesity models) and pancreatic (diabetes) tissues, were reviewed, and the molecular pathways and/or targets related to these models and influenced by resveratrol are discussed. Because the body of work encompassing the stilbenes and other phytochemicals in the context of longevity and the ability to presumably mitigate a plethora of afflictions is replete with conflicting information and controversy, especially so with respect to the human response, we tried to remain as neutral as possible in compiling and presenting the more current data with minimal commentary, permitting the reader free reign to extract the knowledge most helpful to their own investigations.

An outcomes-based approach to curriculum development in pharmacy.

OBJECTIVE: To implement an outcomes-based approach to pharmacy curriculum development. DESIGN: Desired learning outcomes were identified; course content, learning activities, and assessment instruments were designed; and evaluation was conducted and feedback obtained to refine the curriculum. ASSESSMENT: All professional skills, 4 generic capabilities, and the coherence of the curriculum scales showed significant improvement compared to graduates' performance under both the old and transitional curriculum. CONCLUSION: An outcomes-based approach to pharmacy curriculum development provided convincing evidence of enhancement to the curriculum. Such an approach should be considered when implementing or revising pharmacy curriculum.

Chronic hypoxia inhibits the antihypertensive effect of melatonin on pulmonary artery.

Exposure of animals to chronic hypoxia induces pulmonary vascular remodeling leading to pulmonary hypertension. Melatonin, the principal hormone of the pineal gland, is known to have an inhibitory effect on rat vascular reactivity. This study examined the effect of chronic hypoxia on the influence of melatonin on the vasoreactivity of the pulmonary artery. The inhibitory effect of melatonin on the phenylephrine-induced constriction in normoxia-adapted rings (101.5+/-4% versus 82.2+/-4%) in the presence or absence of melatonin, respectively) was lost following chronic hypoxic treatment (100.2+/-4% versus 102.2+/-2%) and this effect was independent of the endothelium. Melatonin also significantly enhanced the relaxant response to acetylcholine of the pulmonary arterial rings from normoxic rats (34.76+/-5.67% versus 53.82+/-4.736%) in the absence or presence of melatonin, respectively). In contrast, melatonin had no significant effect (21.71+/-1.37% versus 23.51+/-6.891%) on the relaxant response to acetylcholine of the pulmonary arterial rings from chronic hypoxia-adapted rats. Pre-treatment with melatonin (10(-4) M) showed no significant effect on the vasorelaxation by the nitric oxide donor; sodium nitroprusside (10(-7)-10(-5) M). The melatonin-induced changes were blocked by the melatonergic-receptor antagonist luzindole (2x10(-6) M). The results from our study confirm the presence of melatonergic receptors on the pulmonary trunk of rats and also suggest that the modulatory role of melatonin on the vasoreactivity of pulmonary trunk does not involve the nitric oxide pathway. Most importantly, our results show that development of pulmonary hypertension in rats is associated with the loss of the vasorelaxant influence of melatonin.

Soy isoflavone supplementation and fasting serum glucose and lipid profile among postmenopausal Chinese women: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Long-term effects of soy-derived isoflavones on lipids remain uncertain, and few data are available on their effects on glycemic control. We examined the effects of isolated soy germ isoflavones on the changes in fasting glucose (FG) and lipids. DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in 203 postmenopausal Chinese women aged 48 to 62 years. They were randomly assigned to receive daily doses of 500 mg calcium, and 0 mg isoflavones (placebo, n=67), 40 mg isoflavones (n=68), and 80 mg isoflavones (n=68). Serum FG, triglycerides, high-density lipoprotein, low-density lipoprotein, total cholesterol, and lipoprotein cholesterol were measured at baseline and 1 year after treatment. The primary data analysis was performed on the 203 randomized women according to the intent-to-treat principle. The last value carried forward was used for any missing data at follow-up. RESULTS: We observed moderate but significant favorable effects of soy isoflavones on the changes (P=0.012) and percentage of changes (P=0.031) in FG (analysis of variance). The 1-year mean (SD) differences of FG changes were -5.2 (-9.4 to -1.0) mg/dL (P=0.010) and -3.3 (-7.5 to 0.9) mg/dL (P=0.18) in the 40- and 80-mg isoflavone groups compared with the placebo group. We also noted a significant interaction between the treatment and baseline FG on the changes in FG (P=0.004). The isoflavone effects were much more significant in women with baseline FG 100 mg/dL or more than in those with FG less than 90 mg/dL. We observed little effect of soy isoflavones on changes in serum lipids among the treatment groups. CONCLUSIONS: One-year of soy isoflavone supplementation might have a favorable effect on FG in women, but has no significant effect on serum lipids.

Prevalence of amiodarone-related hepatotoxicity in 720 Chinese patients with or without baseline liver dysfunction.

BACKGROUND: The prevalence of hepatotoxicity after longterm oral amiodarone therapy in Chinese patients with or without elevated liver enzymes at baseline is unknown. HYPOTHESIS: Amiodarone may still be safely prescribed for Chinese patients who have baseline liver dysfunction. METHODS: This is a retrospective cross-sectional study. Significant liver dysfunction (SLD) was defined as alanine aminotransferase (ALT) > 2 times upper limit of normal range. RESULTS: Baseline liver function was checked in 628 of the 720 Chinese patients identified. The mean duration of amiodarone use was 615.9 +/- 703.1 days. Ninety patients (14.3%) had elevated baseline ALT. The prevalence of SLD was 3.7% (confidence interval [CI] 2.1-5.3%) and 4.4% (CI 0.2-8.6%) in patients with normal (n = 538) and elevated (n = 90) baseline ALT, respectively (p = 0.765). Therapy was continued in 42 patients with elevated baseline ALT until final follow-up. Eight of these (19.0%) had elevated ALT upon final follow-up, but the derangement was mild (mean ALT 134.8 +/- 145.9 IU/l, median 76 IU/l). During follow up, 24 patients developed SLD and half of these subsequently withdrew from therapy. The ALT levels at final follow-up had improved over time in both groups, but the mean difference was not significant (255.1 +/- 706.4 vs. 131.0 +/- 207.5 IU/l, p = 0.312). CONCLUSION: The prevalence of SLD in Chinese patients taking oral amiodarone with or without elevated baseline ALT was similar (4.4 vs. 3.7%). It seems that amiodarone may be safely prescribed in patients with elevated baseline ALT.

Beneficial effect of soy isoflavones on bone mineral content was modified by years since menopause, body weight, and calcium intake: a double-blind, randomized, controlled trial.

OBJECTIVE: Many studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss, but no data reported whether such an effect could be influenced by other important factors affecting bone loss. This study examines whether the associations between isoflavone supplementation and rates of change in bone mineral content (BMC) could be modified by years since menopause (YSM), body weight (BW), and dietary calcium intake in postmenopausal Chinese women aged 48 to 62 years. DESIGN: A group of 203 eligible women were randomly assigned to three treatment groups: placebo (daily dose of 0 mg isoflavones + 500 mg calcium, n = 67), mid-dose (40 mg isoflavones + 500 mg calcium, n = 68); and high-dose (80 mg isoflavones + 500 mg calcium, n = 68). Bone mineral density (BMD) and BMC at the whole body, spine, and hip were measured by dual-energy x-ray absorptiometry at baseline and posttreatment after 1 year. YSM, BW, and dietary calcium intake stratified analyses were performed to evaluate whether the associations between isoflavones supplementation and BMC change rates were varied with these factors. RESULTS: Both univariate and multivariate analyses observed significant favorable effect of isoflavone supplementation on rates of change in BMC at the total hip and trochanter among later postmenopausal women (> 4 y), in women with lower BW (< or =median, 55.5 kg), or among women with lower level of calcium intake (< or =median, 1095 mg/d). CONCLUSIONS: The independent effect of soy on the maintenance of hip BMC is more marked in women in later menopause or those with lower BW or calcium intake.

Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial.

Animal studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss, but few data are available in humans, especially in the Asian populations. This double-blind, placebo-controlled, randomized trial examines the effects of soy isoflavones on bone loss in postmenopausal Chinese women, aged 48-62 yr. Two hundred and three eligible subjects were randomly assigned to three treatment groups with daily doses of placebo (1 g starch; n = 67), mid-dose (0.5 g starch, 0.5 g soy extracts, and approximately 40 mg isoflavones; n = 68), and high dose (1.0 g soy extracts and approximately 80 mg isoflavones; n = 68). All were given 12.5 mmol (500 mg) calcium and 125 IU vitamin D(3). Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, spine, and hip were measured using dual energy x-ray absorptiometry at baseline and 1 yr post treatment. Both univariate and multivariate analyses showed that women in the high dose group had mild, but statistically significantly, higher favorable change rate in BMC at the total hip and trochanter (P < 0.05) compared with the placebo and mid-dose groups, even after further adjustments for the potential confounding factors. Further stratified analyses revealed that the positive effects of soy isoflavone supplementation were observed only among women with lower initial baseline BMC (median or less). In conclusion, soy isoflavones have a mild, but significant, independent effect on the maintenance of hip BMC in postmenopausal women with low initial bone mass.

Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms.

Analyses of gene expression profiles at five different stages of mouse submandibular salivary gland development provide insight into gland organogenesis and identify genes that may be critical at different stages. Genes with similar expression profiles were clustered, and RT-PCR was used to confirm the developmental changes. We focused on fibroblast growth factor receptor 1 (FGFR1), as its expression is highest early in gland development. We extended our array results and analyzed the developmental expression patterns of other FGFR and FGF isoforms. The functional significance of FGFR1 was confirmed by submandibular gland organ culture. Antisense oligonucleotides decreased expression of FGFR1 and reduced branching morphogenesis of the glands. Inhibiting FGFR1 signaling with SU5402, a FGFR1 tyrosine kinase inhibitor, reduced branching morphogenesis. SU5402 treatment decreased cell proliferation but did not increase apoptosis. Fgfr, Fgf and Bmp gene expression was localized to either the mesenchyme or the epithelium by PCR, and then measured over time by real time PCR after SU5402 treatment. FGFR1 signaling regulates Fgfr1, Fgf1, Fgf3 and Bmp7 expression and indirectly regulates Fgf7, Fgf10 and Bmp4. Exogenous FGFs and BMPs added to glands in culture reveal distinct effects on gland morphology. Glands cultured with SU5402 were then rescued with exogenous BMP7, FGF7 or FGF10. Taken together, our results suggest specific FGFs and BMPs play reciprocal roles in regulating branching morphogenesis and FGFR1 signaling plays a central role by regulating both FGF and BMP expression.

Coriolus versicolor: a medicinal mushroom with promising immunotherapeutic values.

Coriolus versicolor (CV) is a medicinal mushroom widely prescribed for the prophylaxis and treatment of cancer and infection in China. In recent years, it has been extensively demonstrated both preclinically and clinically that aqueous extracts obtained from CV display a wide array of biological activities, including stimulatory effects on different immune cells and inhibition of cancer growth. The growing popularity of aqueous CV extracts as an adjunct medical modality to conventional cancer therapies has generated substantial commercial interest in developing these extracts into consistent and efficacious oral proprietary products. While very limited information is available on the physical, chemical, and pharmacodynamic properties of the active principles present in these extracts, there has been sufficient scientific evidence to support the feasibility of developing at least some of these constituents into an evidence-based immunodulatory agent. In this article, the background, traditional usage, pharmacological activities, clinical effects, adverse reactions, active constituents, and regulatory aspects of CV are reviewed. Presented also in this review are the current uses and administration, potential drug interactions, and contraindication of aqueous extracts prepared from CV.