FASL polymorphism is associated with response to bacillus Calmette-Guérin immunotherapy in bladder cancer

Objective Deregulation of FAS/FASL system may lead to immune escape and influence bacillus Calmette-Guérin (BCG) immunotherapy outcome, which is currently the gold standard adjuvant treatment for high-risk non–muscle invasive bladder tumors. Among other events, functional promoter polymorphisms of FAS and FASL genes may alter their transcriptional activity. Therefore, we aim to evaluate the role of FAS and FASL polymorphisms in the context of BCG therapy, envisaging the validation of these biomarkers to predict response. Patients and methods DNA extracted from peripheral blood from 125 patients with bladder cancer treated with BCG therapy was analyzed by Polymerase Chain Reaction—Restriction Fragment Length Polymorphism for FAS-670 A/G and FASL-844 T/C polymorphisms. FASL mRNA expression was analyzed by real-time Polymerase Chain Reaction. Results Carriers of FASL-844 CC genotype present a decreased recurrence-free survival after BCG treatment when compared with FASL-844 T allele carriers (mean 71.5 vs. 97.8 months, P = 0.030) and have an increased risk of BCG treatment failure (Hazard Ratio = 1.922; 95% Confidence Interval: [1.064–3.471]; P = 0.030). Multivariate analysis shows that FASL-844 T/C and therapeutics scheme are independent predictive markers of recurrence after treatment. The evaluation of FASL gene mRNA levels demonstrated that patients carrying FASL-844 CC genotype had higher FASL expression in bladder tumors (P = 0.0027). Higher FASL levels were also associated with an increased risk of recurrence after BCG treatment (Hazard Ratio = 2.833; 95% Confidence Interval: [1.012–7.929]; P = 0.047). FAS-670 A/G polymorphism analysis did not reveal any association with BCG therapy outcome. Conclusions Our results suggest that analysis of FASL-844 T/C, but not FAS-670 A/G polymorphisms, may be used as a predictive marker of response to BCG immunotherapy.

Effects of antihypertensive drugs in the differentiation and activation of human bone cells

O osso é um tecido metabolicamente ativo e a sua remodelação é importante para regular e manter a massa óssea. Esse processo envolve a reabsorção do material ósseo por ação dos osteoclastos e a síntese de novo material ósseo mediado pelos osteoblastos. Vários estudos têm sugerido que a pressão arterial elevada está associada a alterações no metabolismo do cálcio, o que leva ao aumento da perda de cálcio e da remoção de cálcio do osso. Embora as alterações no metabolismo ósseo sejam um efeito adverso associado a alguns fármacos antihipertensores, o conhecimento em relação a este efeito terapêutico ligado com os bloqueadores de canais de cálcio é ainda muito escasso. Uma vez que os possíveis efeitos no osso podem ser atribuídos à ação antihipertensiva dessas moléculas, ou através de um efeito direto nas atividades metabólicas ósseas, torna-se necessário esclarecer este assunto. Devido ao facto de que as alterações no metabolismo ósseo são um efeito adverso associado a alguns fármacos antihipertensores, o objetivo deste trabalho é avaliar o efeito que os bloqueadores dos canais de cálcio exercem sobre as células ósseas humanas, nomeadamente osteoclastos, osteoblastos e co-culturas de ambos os tipos celulares. Verificou-se que os efeitos dos fármacos antihipertensores variaram consoante o fármaco testado e o sistema de cultura usado. Alguns fármacos revelaram a capacidade de estimular a osteoclastogénese e a osteoblastogénese em concentrações baixas. Independentemente da identidade do fármaco, concentrações elevadas revelaram ser prejudiciais para a resposta das células ósseas. Os mecanismos intracelulares através dos quais os efeitos foram exercidos foram igualmente afetados de forma diferencial pelos diferentes fármacos. Em resumo, este trabalho demonstrou que os bloqueadores dos canais de cálcio utilizados possuem a capacidade de afetar direta- e indiretamente a resposta de células ósseas humanas, cultivadas isoladamente ou co-cultivadas. Este tipo de informação é crucial para compreender e prevenir os potenciais efeitos destes fármacos no tecido ósseo, e também para adequar e eventualmente melhorar a terapêutica antihipertensora de cada paciente.

A B-learning strategy for Therapeutics at the Bachelor Level

Background Information:The incorporation of distance learning activities by institutions of higher education is considered an important contribution to create new opportunities for teaching at both, initial and continuing training. In Medicine and Nursing, several papers illustrate the adaptation of technological components and teaching methods are prolific, however, when we look at the Pharmaceutical Education area, the examples are scarce. In that sense this project demonstrates the implementation and assessment of a B-Learning Strategy for Therapeutics using a “case based learning” approach. Setting: Academic Pharmacy Methods:This is an exploratory study involving 2nd year students of the Pharmacy Degree at the School of Allied Health Sciences of Oporto. The study population consists of 61 students, divided in groups of 3-4 elements. The b-learning model was implemented during a time period of 8 weeks. Results:A B-learning environment and digital learning objects were successfully created and implemented. Collaboration and assessment techniques were carefully developed to ensure the active participation and fair assessment of all students. Moodle records show a consistent activity of students during the assignments. E-portfolios were also developed using Wikispaces, which promoted reflective writing and clinical reasoning. Conclusions:Our exploratory study suggests that the “case based learning” method can be successfully combined with the technological components to create and maintain a feasible online learning environment for the teaching of therapeutics.

Short- and medium-term effects of manual therapy on cervical active range of motion and pressure pain sensitivity in latent myofascial pain of the upper trapezius muscle: a randomized controlled trial

Objective: The purpose of this study was to investigate effects of different manual techniques on cervical ranges of 17 motion and pressure pain sensitivity in subjects with latent trigger point of the upper trapezius muscle. 18 Methods: One hundred seventeen volunteers, with a unilateral latent trigger point on upper trapezius due to computer 19 work, were randomly divided into 5 groups: ischemic compression (IC) group (n = 24); passive stretching group (n = 20 23); muscle energy technique group (n = 23); and 2 control groups, wait-and-see group (n = 25) and placebo group 21 (n = 22). Cervical spine range of movement was measured using a cervical range of motion instrument as well as 22 pressure pain sensitivity by means of an algometer and a visual analog scale. Outcomes were assessed pretreatment, 23 immediately, and 24 hours after the intervention and 1 week later by a blind researcher. A 4 × 5 mixed repeated- 24 measures analysis of variance was used to examine the effects of the intervention and Cohen d coefficient was used. 25 Results: A group-by-time interaction was detected in all variables (P b .01), except contralateral rotation. The 26 immediate effect sizes of the contralateral flexion, ipsilateral rotation, and pressure pain threshold were large for 3 27 experimental groups. Nevertheless, after 24 hours and 1 week, only IC group maintained the effect size. 28 Conclusions: Manual techniques on upper trapezius with latent trigger point seemed to improve the cervical range of 29 motion and the pressure pain sensitivity. These effects persist after 1 week in the IC group. (J Manipulative Physiol 301 Ther 2013;xx:1-10)