Laser de CO2 fracionado no tratamento da síndrome geniturinária da menopausa

Introdução: A Síndrome Genitourinária da Menopausa (SGM) é um conjunto de sinais e sintomas que compreende dispareunia, perda da lubrificação vaginal, sangramentos, incontinência urinária e infecções genitourinárias recorrentes. Mais da metade das mulheres experimenta alguns desses sintomas na senescência, cujo tratamento envolve o uso contínuo de terapia hormonal e/ou lubrificantes e hidratantes vaginais. No entanto, esses tratamentos têm baixa adesão, seja pela necessidade de uso regular, seja pela contraindicação de hormônios. O uso intra-vaginal do laser de CO2 tem sido aventado como tratamento alternativo com baixo índice de efeitos adversos ou contraindicações, mas faltam substratos que endossem seu uso, como a correlação clínica com histologia e imunohistoquímica. Objetivo: Avaliar os benefícios do laser de CO2 Femilift® (Alma Lasers, Israel) no tratamento da SGM; esclarecer provável mecanismo de ação, correlacionando a melhora clínica às alterações microscópicas encontradas; e investigar efeitos adversos. Materiais e Métodos: Quatorze mulheres sintomáticas para a SGM e sexualmente ativas, participaram do estudo. Aplicou-se questionários de função sexual (Female Sexual Function Index - FSFI) e incontinência urinaria (International Consultation on Incontinence Questionnaire Short Form - ICIQ-SF) antes e 1 mês após o término do protocolo de tratamento, constituído por 3 sessões do laser de CO2 com intervalo médio de 30 dias. Nesses dois momentos foram realizados exames especulares ginecológicos com avaliação clínica pelo Índice de Saúde Vaginal (VHIS), análise do pH, e biópsia da parede vaginal. O material foi avaliado nas técnicas hematoxicilina/eosina (HE), ácido periódico Schiff (PAS), picrosirius, orceína e imunohistoquímica (IHQ) para colágenos I e III. Efeitos colaterais e segurança foram investigados. Resultados: Após o tratamento, houve melhora significativa no FSFI (de 12,36 ± 10,74 para 18,82 ± 11,87, p<0,01), no ICIQ-SF (11,50 ± 6,52 para 4,77 ± 6,04, p<0,01) e no VHIS das pacientes (13,14 ± 2,77 para 17,42 ± 3,14 com p < 0,01). Ao HE, observou-se aumento no número de camadas epiteliais totais (11,33 ± 1,67 para 13,67± 1,49, p=0,015) e superficiais (de 1,39 ± 0,84 para 3,25 ± 1,41, com p=0,01). O PAS não mostrou aumento no número de camadas de células epiteliais ricas em glicogênio, mas houve melhor distribuição em camadas mais superficiais após o tratamento. À análise do picrosirius, houve aumento de fibras colágenas do tipo III (10.86 ± 7,66 para 16.87 ± 3,96, com p<0,05) e diminuição na proporção de fibras tipo I (de 68.29 ± 9,57 para 61,4 ± 7,66, p<0,05). Além disso, as fibras colágenas sofreram um rearranjo estrutural, tornando-se mais finas, homogêneas e paralelamente distribuídas. Não houve diferença na contagem das fibras elásticas. O estudo imunohistoquímico confirmou apenas o aumento do colágeno III (de 26 ± 8,98 para 36,05 ± 5,8, p<0,01), com diminuição da proporção colágeno I:III (de 1,85 ± 0,43 para 1,26 ± 0,14, p=0,001). Conclusão: A eficácia do laser de CO2 Femilift® no tratamento da SGM pode estar relacionada à renovação epitelial e ao remodelamento do tecido conjuntivo que ele promove, com reversão da atrofia vaginal e neocolagênese. A segurança pôde ser inferida com a ausência de efeitos adversos graves.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorIntroduction: Genitourinary Syndrome of Menopause (GSM) is a group of signs and symptoms such as dyspareunia, vaginal dryness, bleeding, discharge, urinary incontinence and recurrent genitourinary infections, experimented by half of women after ovarian failure. The treatment involves hormone therapy, vaginal lubricants and moisturizers, with low compliance due to the need of frequent use and possible side effects of hormones, especially among women with thromboembolic events or estrogen-dependent neoplasias. Therefore, recent vaginal use of CO2 lasers has shown interesting results, with low side effects, but still low research on its effect in the tissue and the possible mechanism of action to achieve the benefits. Objective: Evaluate the effects of the Femilift CO2 Laser (Alma Lasers, Israel) in treating the GSM, correlating the subjective symptom improvement with the objective clinical aspects of the vaginal tissue, establishing possible mechanisms of action and side-effects. Methods: Fourteen women symptomatic for the GSM and sexually active were included in the research. They answered the Female Sexual Function Index (FSFI) questionnaire and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) before and 1 month after three monthly laser sections, as well as samples from their vaginal wall were biopsied in the same time frames, when they were submitted to specular examination. The clinical parameters used were the local pH and the Vaginal Health Index Score (VHIS). Histologic samples were stained with hematoxylin/eosin(HE), periodic acid Schiff (PAS), picrosirius, orcein and Immunohistochemistry (IHQ) for collagens I and III. Side-effects were investigated. Results: There were significant improvement in the FSFI (from 12,36 ± 10,74 to 18,82 ± 11,87, p<0,01), ICIQ-SF (11,50 ± 6,52 to 4,77 ± 6,04, p<0,01), and VHIS (13,14 ± 2,77 to 17,42 ± 3,14, p < 0,01). Histologic samples showed increase in total epithelial cell layers (11,33 ± 1,67 to 13,67± 1,49, p=0,015) and superficial epithelial layers (1,39 ± 0,84 to 3,25 ± 1,41, p=0,01). PAS didn’t show significant alterations in glycogen-rich epithelial cell layers, but revealed that more superficial cells appeared PAS + after treatment. Picrosirius stain revealed increase in type IIII collagen fibers (10.86 ± 7,66 to 16.87 ± 3,96, p<0,05) and decrease in type I collagen fibers (68.29 ± 9,57 to 61,4 ± 7,66, p<0,05). Structurally, the fibers became thinner, more homogeneous and parallelly distributed, without the rough lumps observed before the treatment. Orcein stain didn’t show significant changes in elastic fibers. IHQ confirmed only the increase in collagen III (26 ± 8,98 to 36,05 ± 5,8, p<0,01), with no significant alteration of collagen I, lowering the proportion between fibers I:III (from 1,85 ± 0,43 to 1,26 ± 0,14, p=0,001). Conclusion: The efficacy of the CO2 laser Femilift® in treating GSM was demonstrated, and the benefits could be attributed to the epithelial renovation and connective tissue remodeling, reverting the vaginal atrophy and promoting neocollagenesis. Safety could be inferred by the lack of severe side effects101

Cerebrospinal fluid levels of chemokines in HIV infected patients with and without opportunistic infection of the central nervous system

Chemokines are chemoattractant cytokines involved in the immune response of a wide variety of diseases. There are few studies assessing their role in opportunistic infections in HIV-infected patients. In this study, we measured CC and CXC chemokines in cerebrospinal fluid (CSF) samples obtained from 40 HIV-infected patients with or without opportunistic infections of the central nervous system (CNS). CSF samples were also analyzed for quantification of total protein, cell count and HIV-1 RNA. HIV+ patients with cryptococcal meningitis had higher levels of CCL2, CCL3, CCL5, CXCL9 and CXCL10 when compared to patients without opportunistic neurological infections. Furthermore, HIV+ patients with associated cryptococcal meningitis had higher levels of CCL3, CXCL9 and CXCL10 when compared to HIV+ patients with associated toxoplasmic encephalitis. CCL3 and CXCL9 levels were positively correlated with CSF HIV-1 RNA levels, CSF protein concentration, and CSF cell count. CXCL10 level was correlated with the CSF viral load and the CSF cell count and CCL5 level was correlated with the CSF cell count. In conclusion, the profile of chemokines in CSF of HIV patients may differ according to the modality of the presented opportunistic infection and according to other biological markers, such as viral load in CSF. These differences are probably related to different patterns of neuroinflammatory responses displayed by patients with different opportunistic neurological infections. (C) 2009 Elsevier B.V. All rights reserved.Rede Instituto Brasileiro de Neurociencia (IBNet/Finep)Fundacao de Amparo A Pesquisa do Estado de Minas Gerais (Fapemig), Brazi

Study of the profile of the neurotrophin BDNF in new leprosy cases before, during and after multidrug therapy

Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in the survival of neurons and growth and differentiation of dendrites and axons. The purpose of the present study was to evaluate plasma levels of BDNF of leprosy patients at different stages of multidrug therapy (MDT) in comparison with non-infected individuals. Plasma levels of BDNF were measured by ELISA in 30 healthy controls and 37 leprosy patients at diagnosis, during and after MDT. Plasma levels of BDNF tended to be higher in control subjects in comparison with leprosy patients, but this difference does not reach statistical significance. Interestingly, BDNF levels changed following MDT, achieving statistical difference only at the 2nd dose of MDT. These results indicate that BDNF may not be a surrogate marker of leprosy infection and/or related neuropathy. Further research is needed to investigate the meaning of BDNF level changes following leprosy treatment