Epigenetic Alterations in Fanconi Anaemia : Role in Pathophysiology and Therapeutic Potential

Fanconi anaemia (FA) is an inherited disorder characterized by chromosomal instability. The phenotype is variable, which raises the possibility that it may be affected by other factors, such as epigenetic modifications. These play an important role in oncogenesis and may be pharmacologically manipulated. Our aim was to explore whether the epigenetic profiles in FA differ from non-FA individuals and whether these could be manipulated to alter the disease phenotype. We compared expression of epigenetic genes and DNA methylation profile of tumour suppressor genes between FA and normal samples. FA samples exhibited decreased expression levels of genes involved in epigenetic regulation and hypomethylation in the promoter regions of tumour suppressor genes. Treatment of FA cells with histone deacetylase inhibitor Vorinostat increased the expression of DNM3Tβ and reduced the levels of CIITA and HDAC9, PAK1, USP16, all involved in different aspects of epigenetic and immune regulation. Given the ability of Vorinostat to modulate epigenetic genes in FA patients, we investigated its functional effects on the FA phenotype. This was assessed by incubating FA cells with Vorinostat and quantifying chromosomal breaks induced by DNA cross-linking agents. Treatment of FA cells with Vorinostat resulted in a significant reduction of aberrant cells (81% on average). Our results suggest that epigenetic mechanisms may play a role in oncogenesis in FA. Epigenetic agents may be helpful in improving the phenotype of FA patients, potentially reducing tumour incidence in this population

Redução do uso da Cannabis Sativa nas pessoas com deficiência motora em treino de basquete em cadeiras de rodas: ensaio clinico randomizado

Introdução: as pessoas com deficiências têm anormalidade de estrutura ou função anatômica, fisiológica ou psicológica. Sendo que nas lesões crônicas e deficiências permanentes aumenta as taxas de prevalência de alterações mentais ou comportamentais. O uso de cannabis sativa nos esportes tornou-se questão polêmica proeminente e debatida pelas autoridades governamentais e por movimentos esportivos que lutam contra o doping no esporte. Objetivos: analisar o uso de Cannabis Sativa  e aspectos saúde no Treino de Basquete em Cadeiras de Rodas (BCR) das Pessoas com Deficiência Motora (PCD-M). Métodos: estudo experimental tipo ensaio clínico randomizado. A amostra foi triada da população do sexo masculino PCD-M, em  idade igual e superior a 18 anos até 55 anos, residentes na Baixada Cuiabana-MT, Brasil, sendo  recrutadas por sorteio (n=100), e randomizadas para avaliação (n=48), alocados em dois braços sendo experimental (GE n=21) e controle (GC n=27).  A coleta foi realizada por entrevista estruturada e avaliação clínica incluindo os aspectos sociodemográficos, hábitos de estilo de vida, autorrelatos de álcool e drogas. O treino de basquete foi feito duas vezes da semana às 2º e 4º feiras das 19h as 21h com @ 2 horas de tempo de duração. Para análise de dados foi utilizada a teste quiquadrado e cálculo estimativo do efeito da intervenção, com significância em p<0.05 e 95% de intervalo e confiança. Resultados: A idade média foi de 35 (±8,8) anos.  O tempo de prevalência das deficiências por etiologia Poliomielite foram superiores a 20 anos.  Foram encontrados eventos de aspecto mental e comportamental com uso (Cannabis sativa, 25%); alterações no aspecto físico (úlcera de pressão=21%, infecção de urina=40%); previdência social pública (zero auxílio percapita, 10%). Houve  melhora e o Número Necessário para Tratamento com Ulcera Pressão (NTT 3,0 e p=0.03); e redução de usuários de Cannabis Sativa (NNT= 5,50 e p=0.02) neste ensaio clínico. Conclusão:  houve melhora dos aspectos da clínica pós intervenção no GE denotando redução do uso de Cannabis Sativa melhora da condição de saúde na PCD-M. Então, as técnicas de preleção com motivação de equipe, dinâmicas de grupo, a compreensão das regras antidoping nos campeonato de BCR corroborou no equilíbrio do comportamento mental reduzindo consumo de Cannabis Sativa. Assim programas de esportes coletivos para PCD-M podem contribuir no tratamento redução de consumo de Cannabis Sativa e ser estratégia de equilíbrio comportamental e de ressignificação da vida

Effect of a gel containing pilocarpine on vaginal atrophy in castrated rats

OBJECTIVES: To evaluate the effect of Carbopol gel formulations containing pilocarpine on the morphology and morphometry of the vaginal epithelium of castrated rats. METHODS: Thirty-one female Wistar-Hannover rats were randomly divided into four groups: the control Groups I (n=7, rats in persistent estrus; positive controls) and II (n=7, castrated rats, negative controls) and the experimental Groups, III (n=8) and IV (n=9). Persistent estrus (Group I) was achieved with a subcutaneous injection of testosterone propionate on the second postnatal day. At 90 days postnatal, rats in Groups II, III and IV were castrated and treated vaginally for 14 days with Carbopol gel (vehicle alone) or Carbopol gel containing 5% and 15% pilocarpine, respectively. Next, all of the animals were euthanized and their vaginas were removed for histological evaluation. A non-parametric test with a weighted linear regression model was used for data analysis (

The effects of Pilates vs. aerobic training on cardiorespiratory fitness, isokinetic muscular strength, body composition, and functional tasks outcomes for individuals who are overweight/obese: a clinical trial

Background Some studies have been conducted to verify the effects of Pilates for individuals who are obese, but conclusive results are not yet available due to methodological concerns. The present study aims to verify and compare the effects of Pilates and aerobic training on cardiorespiratory fitness, isokinetic muscular strength, body composition, and functional task outcomes for individuals who are overweight/obese. Methods Of the sixty participants, seventeen were allocated to the control group, since the intervention protocol (Pilates or walking sessions) was during their working hours. The remaining 44 participants were randomly allocated to one of two experimental groups (Pilates (n = 22)) or aerobic groups (n = 21).The Pilates and aerobic groups attended 60-min exercise sessions, three times per week for 8 weeks. The aerobic group performed walking training at a heart rate corresponding to the ventilatory threshold. The Pilates group performed exercises on the floor, resistance apparatus, and 1-kg dumbbells. The control group received no intervention. All volunteers were evaluated at the beginning and end of the intervention. The following assessments were conducted: food intake, cardiorespiratory maximal treadmill test, isokinetic strength testing, body composition and anthropometry, abdominal endurance test, trunk extensor endurance test, flexibility test and functional (stair and chair) tests. Results There was no significant difference pre- and post-intervention in calorie intake [F(2, 57) = 0.02744, p = 0.97)]. A significant improvement in oxygen uptake at ventilatory threshold (p = 0.001; d = 0.60), respiratory compensation point (p = 0.01; d = 0.48), and maximum effort (p = 0.01; d = 0.33) was observed only in the Pilates group. Isokinetic peak torque for knee flexor and extensor muscles did not change for any groups. Lean mass (p = 0.0005; d = 0.19) and fat mass (p = 0.0001; d = 0.19) improved only in the Pilates group. Waist and hip circumference measurements decreased similarly in both experimental groups. Abdominal test performance improved more in the Pilates group (p = 0.0001; d = 1.69) than in the aerobic group (p = 0.003; d = 0.95). Trunk extensor endurance and flexibility improved only in the Pilates group (p = 0.0003; d = 0.80 and p = 0.0001; d = 0.41, respectively). The Pilates group showed greater improvement on the chair and stair tests (p = 0.0001; d = 1.48 and p = 0.003; d = 0.78, respectively) than the aerobic group (p = 0.005; d = 0.75 and p = 0.05; d = 0.41, respectively). Conclusion Pilates can be used as an alternative physical training method for individuals who are overweight or obese since it promotes significant effects in cardiorespiratory fitness, body composition, and performance on functional tests