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BACKGROUND Flupirtine is a nonopioid, central analgesic without antipyretic or antiphlogistic properties. Flupirtine-MR is an oral modified-release formulation with a 100 mg fast-input and a 300 mg portion with slow protracted release. METHODS Single- (D01) and repeated-dose (D03-D09) pharmacokinetics of 400 mg flupirtine-MR were investigated in patients with severe renal dysfunction (REN: N: 12; 21 50 years of age; creatinine clearance (CLCr)≤30 mL/min per 1.73 m2 body surface area (BSA)) and healthy older subjects (EN1: N: 8; 60-69 years; CLCr≥80 mL/min and EN2: N: 8; ≥70 years, CLCr≥60 mL/min) vs. young healthy control subjects (YN: N: 12; 21-40 years; CLCr≥90 mL/min). RESULTS Renal dysfunction led to a relatively small average increase in systemic exposure to flupirtine: on D09, the REN : YN-ratios were 1.37 (95% confidence interval (CI): 1.03-1.82), 1.21 (CI: 1.01-1.45), and 1.34 (CI: 1.09-1.64) for Css,0, Css,max, and Css,av, respectively. A similar increase in exposure was observed in older subjects: the respective EN1:YN-ratios were 1.30 (CI: 0.95-1.79), 1.23 (CI: 1.01-1.49), and 1.23 (CI: 0.98-1.54); the EN2:YN-ratios were 1.50 (CI: 1.10-2.04), 1.16 (CI: 0.85-1.41), and 1.41 (CI: 1.12-1.79), respectively. Neither age nor renal function was a predominant factor of pharmacokinetic variability. Single and repeated doses of flupirtine-MR were very well tolerated. CONCLUSIONS The average renal and age effects were small, but the use of a lower starting dose (1/2 tablet) is recommended since some of these subjects might have relatively high exposure levels.

8. D. Svintsov, V. Vyurkov, V. Ryzhii, and T. Otsuji, Voltage-con-trolled surface plasmon-polaritons in double graphene layer struc-tures, J Appl Phys 113 (2013), 053701.9. M. Tamagnone, J.S. Gomez-Diaz, J.R. Mosig, and J. Perruisseau-Carrier, Reconfigurable terahertz plasmonic antenna concept using agraphene stack, Appl Phys Lett 101 (2012), 214102.10. R. Filter, M. Farhat, M. Steglich, R. Alaee, C. Rockstuhl, and F.Lederer, Tunable graphene antennas for selective enhancement ofTHz-emission, Opt Express 21 (2013), 3737–3745.11. J.S. Gomez-Diaz and J. Perruisseau-Carrier, Graphene-based plas-monic switches at near infrared frequencies, Opt Express 21 (2013),15490–15504.12. M. Liu, X. Yin, and X. Zhang, Double-layer graphene optical modu-lator, Nano Lett 12 (2012), 1482–1485.13. R.E. Collin, Field theory of guided waves, McGraw-Hill Book Co.,New York, 1960.14. D. Lioubtchenko, S. Tretyakov, and S. Dudorov, Millimeter-wavewaveguides, Kluwer Academic Publishers, Boston, MA, 2003.

This multicenter, placebo-controlled, double-blind, randomized parallel-group trial was conducted to investigate the efficacy and tolerability of myrtol standardized (MYS, Gelomyrtol forte, 3 x 300 mg) in the long-term treatment of patients with chronic bronchitis during the winter. 246 patients received the investigational treatments (MYS: 122, placebo: 124) for at least 1 month; 215 subjects (110 under MYS and 105 under placebo) were evaluable in terms of efficacy (exacerbation rate, the need for antibiotics, symptom scores and general well-being) for the protocol-defined 6 months of treatment. Statistically significantly (p 7 days. Well-being (assessed in terms of general health and health impairment by cough and expectoration) was significantly better under treatment with MYS. The overall therapeutic efficacy evaluation scored higher for MYS. Therefore, it is concluded that long-term treatment with MYS is equally well tolerated as placebo but is clearly superior in efficacy in terms of protecting against acute exacerbations in patients with chronic bronchitis: it reduces the frequency and intensity of acute exacerbations, the need of antibiotics for them and the health impairment by cough and expectoration.

Tem sido objeto de preocupação da literatura médica e, mais recentemente, da psicológica, a alta prevalência do câncer de mama nas mulheres. O diagnóstico precoce muito favorece na redução dos índices e, entre os meios de detecção, o "auto-exame da mama" se caracteriza como uma prevenção secundária, sem custos e segura. Pesquisas demonstram, contudo, que a prática do auto-exame da mama é insatisfatória, principalmente em mulheres de escolaridade e nível sócio-econômico baixos. Segundo a Teoria da Ação Racional (TRA), a maioria dos comportamentos humanos pode ser explicada em termos de crenças comportamentais ou normativas. Nesse sentido, a presente pesquisa teve por objetivo investigar as crenças modais salientes desse estrato populacional, desprovido de informações claras e serviços de saúde efetivos, através de um levantamento em uma amostra de 40 mulheres entrevistadas em ambulatórios públicos de João Pessoa (PB). As entrevistas continham itens sobre as vantagens e desvantagens do auto-exame da mama, conhecimentos e dados sócio-demográficos. A média de idade da amostra foi de 32,5 anos (DP = 11,37). As entrevistas indicaram um total de 132 crenças comportamentais, que foram categorizadas em nove dimensões e 166 crenças normativas, categorizadas em quatro dimensões. Estes resultados demonstraram que as crenças influenciam a adesão à prática do auto-exame da mama e servirão de base para que os profissionais que lidam com campanhas públicas de prevenção voltem sua atenção para esses aspectos e abordem conteúdos que promovam não só a prática do auto-exame da mama, mas outras estratégias preventivas nesta significativa população.

Erectile function in man depends upon a complex interaction of psychogenic, neurologic, hormonal and vascular factors, and therefore the management of erectile dysfunction (ED) reflects this complexity of control. Therapeutic options include psychological and non-pharmacological approaches as well as drug treatments. The effectiveness of the type-5 cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra) confirms the pivotal role of the NO-cGMP axis in promoting and maintaining erection. Although widely acclaimed, sildenafil leaves many questions unanswered, especially regarding its susceptibility to pharmacokinetic drug interactions, and its safety in patients with ischaemic heart disease and those taking nitrates. In view of the epidemiological link between erectile dysfunction and cardiovascular disease in the elderly, this limitation might have much broader implications. The presently available scientific documentation, although less extensive, indicates that NO donors, such as topically applied nitroglycerin (GTN; for example, 1-2 puffs of an ordinary GTN spray applied to the shaft of the penis), might be a reasonable alternative. Further larger-scale research on the efficacy and tolerability of topical GTN is needed to establish its full therapeutic potential in the treatment of erectile dysfunction.

Objective. Our objective was to investigate the potential for relevant pharmacotherapeutic interaction between cytochrome P4503A4 (CYP3A4)-inhibiting agents such as erythromycin and the dopamine agonist alpha -dihydroergocryptine (DHEC). Methods. The study was carried out as a single-center, controlled, nonblinded, 2-way crossover clinical trial with randomly allocated period-balanced sequences investigating two treatments of a single oral dose of 10 mg DHEC (on the morning of day 1), once administered alone (reference), once along with a 4-day treatment (days -2 to 1) of 500 mg erythromycin 3 times daily. Periods were separated by a washout of at least 14 days. Nine healthy white male volunteers, 22 to 42 years old, with a body weight range of 58 to 90 kg (body mass index, 20.2-25.1 kg (.) m(-2)) began the study. One subject discontinued prematurely, and 8 concluded the study in accordance with the study protocol. Results. The plasma and urinary pharmacokinetics of DHEC and its metabolites were characterized by a large variability Concomitant treatment with erythromycin led to respective increases of 9.5 (95% confidence interval [CI], 6.5 to 13.9) and 16.5 (95% CI, 8.7 to 31.5) times the maximum observed plasma drug concentration and the a-rea under the time course of the plasma concentrations up to the last quantifiable concentration after dosing of unchanged DHEC (determined by radioimmunoassay). The 24-hour urinary excretion was on average 11 times larger (95% CI, 5.9 to 20.7). Qualitatively similar findings were recorded for the total of DHEC plus metabolites (as determined by enzyme immunoassay). Conclusions. The concomitant use of erythromycin or similarly CYP3A4-inhibiting agents along, vith direct dopaminergic agonists such as the ergoline DHEC may cause a clinically relevant increase in pharmacokinetic; exposure, which may induce exaggerated dopaminergic effects.

Randomised controlled trials (RCTs) provide the best available external evidence for the use of alpha1-blockers in treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Placebo-controlled and actively-controlled RCTs evidenced the efficacy of alpha1-blockers in augmenting urine flow, relieving symptoms, reducing bother and improving quality of life in patients with LUTS. This improvement involves both filling (irritative) and voiding (obstructive) symptoms, occurs promptly and is well-maintained over time. Treatment benefit is independent of prostate size and baseline prostate specific antigen (PSA). There is no evidence of relevant differences between the different alpha1-blockers in this regard and all alpha1-blockers can be accepted as appropriately efficacious at the presently recommended doses. The best available external evidence for relevant differential properties of alpha1-blockers relates to their clinical selectivity in terms of the absence/presence of ancillary cardiovascular, i.e. anti-hypertensive effects. Anti-hypertensive alpha1-blockers (terazosin and doxazosin in particular) are more likely to cause dizziness and other cardiovascular untoward effects, eventually leading to premature treatment discontinuation. Alfuzosin (although primarily developed as an anti-hypertensive agent) and tamsulosin in contrast, are better tolerated; the former nevertheless carries a more distinct risk of symptomatic impairment of blood pressure control. Although indirect comparisons between different studies suggest a higher risk of retrograde ejaculation with tamsulosin, this hypothesis failed to be confirmed in direct comparative RCTs.

Red vine leaf extract (RVLE) is a herbal medicine containing several flavonoids, with quercetin-3-O-beta-glucuronide and isoquercitrin (quercetin-3-O-beta-glycoside) as the main components.To assess the efficacy and safety of once-daily doses of 360 and 720 mg RVLE (pharmaceutical extract code AS 195; Antistax Venenkapseln) compared to placebo in patients with stage I and incipient stage II chronic venous insufficiency (CVI).A 12-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center study.Male and female outpatients aged 25 to 75 years with stage I to stage II CVI (i.e. without extensive trophic changes), not having any other significant medical conditions and not treated with compression stockings, diuretics or other drugs affecting fluid balance.Patients were randomly assigned to a double-blind treatment with placebo, 360 mg AS 195 or 720 mg AS 195 once daily for 12 weeks, preceded and followed by a single-blind 2-week placebo treatment for baseline run-in and end-of-trial washout, respectively. Study criteria were evaluated at baseline, after 6 and 12 weeks of treatment and 2 weeks after discontinuation of treatment.Of the 260 patients enrolled and randomized, 219 completed the study in accordance with the protocol. In the intention-to-treat analysis (N = 257), the mean (+/- SD) lower leg volume (measured by water displacement plethysmography) of the patients treated with placebo (N = 87) increased by 15.2 +/- 90.1 g (displaced water mass) and by 33.7 +/- 96.1 g after 6 and 12 weeks compared to baseline. In contrast, for patients treated with AS 195, lower leg volume decreased, and after 12 weeks of treatment, the difference in mean lower leg volume between the active treatment groups and the placebo group was -75.9 g (95% CI: -106.1 to -45.8 g) and -99.9 g (95% CI: -130.3 to -69.6 g) for the group treated with 360-mg AS 195 (N = 86) and 720-mg AS 195 (N = 84), respectively. The changes in calf circumference showed a similar pattern: in patients treated with AS 195, both the higher dose (720 mg) and, albeit to a lesser extent, the lower dose (360 mg) resulted in a clear reduction in circumference over time, whereas, circumference remained largely unchanged in patients treated with the placebo (95% CI of the estimated treatment effects vs. placebo after 12 weeks: -1.40 to -0.56 cm and -1.73 to -0.88 cm for 360 and 720 mg AS 195, respectively). These differences were statistically significant (p0.001). The reductions in ankle circumference were qualitatively similar but quantitatively less marked. Subjectively, there was an improvement in key CVI symptoms (VAS) at 6 weeks with all treatments, but a further improvement at week 12 was seen only in the active treatment groups; at 12 weeks, the changes compared to baseline were significantly greater (p0.001) in both active treatment groups than in the placebo group. The treatments were well tolerated; Adverse events were rare and usually mild. Two adverse events (AEs) during treatment with the placebo led to hospitalization and were hence labeled as 'serious'. Three further patients were withdrawn because of AEs which occurred during treatment with the placebo.Once-daily doses of 360 and 720 mg AS 195 were confirmed to be safe and effective in the treatment of mild CVI, reducing significantly lower leg edema and circumference whilst improving key CVI-related symptoms to a clinically relevant extent. The edema reduction is at least equivalent to that reported for compression stockings and/or other edema-reducing agents. The higher dose was as well tolerated as the lower dose but resulted in a slightly greater and more sustained improvement.

Tem sido objeto de preocupação da literatura médica e, mais recentemente, da psicológica, a alta prevalência do câncer de mama nas mulheres. O diagnóstico precoce muito favorece na redução dos índices e, entre os meios de detecção, o "auto-exame da mama" se caracteriza como uma prevenção secundária, sem custos e segura. Pesquisas demonstram, contudo, que a prática do auto-exame da mama é insatisfatória, principalmente em mulheres de escolaridade e nível sócio-econômico baixos. Segundo a Teoria da Ação Racional (TRA), a maioria dos comportamentos humanos pode ser explicada em termos de crenças comportamentais ou normativas. Nesse sentido, a presente pesquisa teve por objetivo investigar as crenças modais salientes desse estrato populacional, desprovido de informações claras e serviços de saúde efetivos, através de um levantamento em uma amostra de 40 mulheres entrevistadas em ambulatórios públicos de João Pessoa (PB). As entrevistas continham itens sobre as vantagens e desvantagens do auto-exame da mama, conhecimentos e dados sócio-demográficos. A média de idade da amostra foi de 32,5 anos (DP = 11,37). As entrevistas indicaram um total de 132 crenças comportamentais, que foram categorizadas em nove dimensões e 166 crenças normativas, categorizadas em quatro dimensões. Estes resultados demonstraram que as crenças influenciam a adesão à prática do auto-exame da mama e servirão de base para que os profissionais que lidam com campanhas públicas de prevenção voltem sua atenção para esses aspectos e abordem conteúdos que promovam não só a prática do auto-exame da mama, mas outras estratégias preventivas nesta significativa população. It has been object of concern to the medical literature and, more recently, to psychology, the high prevalence of breast cancer in women. The early diagnosis helps to decrease the index, and among the methods for detection, the "breast self-examination" appears as a secondary prevention, secure and without costs. Researches have shown, however, that the practice of breast self-examination is not satisfactory, mainly to women of a low schooling as well as a low social-economic level. According to the Theory of Reasoned Action (TRA), most of human behavior can be explained in terms of behavioral or normative beliefs. So, the present research aims to investigate the prominent modal beliefs of low income women, who lack clear information and effective health services, by using a sample of 40 women interviewed at a public hospital in João Pessoa (PB, Northeast of Brazil). The interviews contained items about the advantages and disadvantages of the breast self-examination, knowledge and sociodemographic data. The average age of the sample was 32,5 years (DP = 11,37). Results indicate a total of 132 behavioral beliefs, which were classified into 9 dimensions and 166 normative beliefs, classified into 4 dimensions. These results demonstrate that beliefs do influence adherence to a practice of breast self-examination, and might make public prevention campaigns to turn their attention to these aspects, promoting not only the practice of breast self examination, but other preventive strategies for this significant portion of the population.