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Drug-resistant epilepsy has been explained by different mechanisms. The most accepted one involves overexpression of multidrug transporters proteins at the blood brain barrier and brain metabolizing enzymes. This hypothesis is one of the main pharmacokinetic reasons that lead to the lack of response of some antiseizure drug substrates of these transporters and enzymes due to their limited entrance into the brain and limited stay at the sites of actions. Although uncontrolled seizures can be the cause of the overexpression, some antiseizure medications themselves can cause such overexpression leading to treatment failure and thus refractoriness. However, it has to be taken into account that the inductive effect of some drugs such as carbamazepine or phenytoin not only impacts on the brain but also on the rest of the body with different intensity, influencing the amount of drug available for the central nervous system. Such induction is not only local drug concentration but also time dependent. In the case of valproic acid, the deficient disposition of ammonia due to a malfunction of the urea cycle, which would have its origin in an intrinsic deficiency of L-carnitine levels in the patient or by its depletion caused by the action of this antiseizure drug, could lead to drug-resistant epilepsy. Many efforts have been made to change this situation. In order to name some, the administration of once-daily dosing of phenytoin or the coadministration of carnitine with valproic acid would be preferable to avoid iatrogenic refractoriness. Another could be the use of an adjuvant drug that down-regulates the expression of transporters. In this case, the use of cannabidiol with antiseizure properties itself and able to diminish the overexpression of these transporters in the brain could be a novel therapy in order to allow penetration of other antiseizure medications into the brain.

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La artritis reumatoide es una enfermedad autoinmune, sistémica, crónica, que afecta con más frecuencia a mujeres que a hombres, y se observa predominantemente en ancianos. El propósito de este trabajo es presentar el resultado de una revisión bibliográfica sobre aspectos generales relacionados con la patogenia de la artritis reumatoide y el manejo terapéutico actual, así como perspectivas futuras de nuevos enfoques terapéuticos. Existen dos subtipos principales de artritis reumatoide según la presencia o ausencia de anticuerpos antiproteína citrulinada. La citrulinación es catalizada por la enzima peptidilarginina-deiminasa dependiente de calcio, que cambia una arginina cargada positivamente a una citrulina polar, pero neutra como resultado de una modificación postraduccional. Este estudio se enfoca en el subconjunto de artritis reumatoide positivo para anticuerpos antiproteína citrulinada y se divide la progresión del proceso de artritis reumatoide en varias etapas. Cabe mencionar que estas etapas pueden ocurrir de forma secuencial o simultánea. Se requiere con urgencia una mejor comprensión de cómo los mecanismos patológicos impulsan el deterioro del progreso de la artritis reumatoide en los individuos con el fin de desarrollar terapias que tratarán eficazmente a los pacientes en cada etapa del progreso de la enfermedad(AU)

Rheumatoid arthritis is a chronic systemic autoimmune disease that arises more frequently in women than in men, and is predominantly observed in the elderly. To present the result of a bibliographic review on general aspects related to the pathogenesis of rheumatoid arthritis and current therapeutic management, as well as future perspectives of new therapeutic approaches. There are two main subtypes of rheumatoid arthritis according to the presence or absence of anti-citrullinated protein antibodies. Citrullination is catalyzed by the calcium-dependent enzyme peptidylarginine deiminase, which changes a positively charged arginine to a polar but neutral citrulline as a result of post-translational modification. This work focuses on the anti-citrullinated protein antibodies -positive rheumatoid arthritis subset and divides the progression of the rheumatoid arthritis process into several stages. It should be mentioned that these stages can occur sequentially or simultaneously. A better understanding of how pathological mechanisms drive the deterioration of rheumatoid arthritis progression in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of disease progression(AU)

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Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an emergent infectious disease that has caused millions of deaths throughout the world. COVID-19 infection's main symptoms are fever, cough, fatigue, and neurological manifestations such as headache, myalgias, anosmia, ageusia, impaired consciousness, seizures, and even neuromuscular junctions' disorders. In addition, it is known that this disease causes a series of systemic complications such as adverse respiratory distress syndrome, cardiac injury, acute kidney injury, and liver dysfunction. Due to the neurological symptoms associated with COVID-19, damage in the central nervous system has been suggested as well as the neuroinvasive potential of SARS-CoV-2. It is known that CoV infections are associated with an inflammation process related to the imbalance of the antioxidant system; cellular changes caused by oxidative stress contribute to brain tissue damage. Although anti-COVID-19 vaccines are under development, there is no specific treatment for COVID-19 and its clinical manifestations and complications; only supportive treatments with immunomodulators, anti-vascular endothelial growth factors, modulating drugs, statins, or nutritional supplements have been used. In the present work, we analyzed the potential of antioxidants as adjuvants for the treatment of COVID-19 and specifically their possible role in preventing or decreasing the neurological manifestations and neurological complications present in the disease.

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La insuficiencia cardiaca aguda (ICA) se define como la aparición rápida o el empeoramiento de los síntomas o signos de IC. Es una entidad potencialmente mortal que requiere evaluación y tratamiento urgentes y típicamente conlleva la hospitalización urgente. La descompensación de la insuficiencia cardiaca crónica puede ocurrir sin que existan factores desencadenantes conocidos. Se produce una disfunción endotelial que puede deberse a un desequilibrio en el medio neuro-hormonal, inflamatorio, y oxidativo en la circulación y en las células endoteliales. Se produce clínicamente hipoperfusión miocárdica, reducción del flujo coronario, disfunción isquémica, aumento de la rigidez vascular y deterioro de la distensibilidad arterial que agravan en mayor medida la lesión miocárdica. La evaluación inicial y la monitorización no invasiva continua de las funciones vitales cardiorrespiratorias son esenciales. Los diuréticos son la piedra angular del tratamiento de los pacientes con ICA y signos de sobrecarga de fluidos y congestión. La terapia de reemplazo renal se debe reservar para pacientes que no responden al tratamiento con diuréticos. Los vasodilatadores intravenosos son los segundos fármacos más utilizados en la ICA para el alivio de los síntomas; sin embargo, no existen pruebas definitivas que confirmen su efecto beneficioso. El uso de inotrópicos debería estar reservado a los pacientes con disfunción sistólica que afecta a la perfusión de órganos vitales. Los dispositivos de asistencia ventricular y otras formas de asistencia mecánica circulatoria pueden emplearse como tratamiento puente en pacientes seleccionados(AU)

Acute heart failure (AHF) is defined as the rapid onset or worsening of the symptoms or signs of heart failure. It is a potentially fatal entity that requires urgent evaluation and treatment and typically involves urgent hospitalization. Decompensation of chronic heart failure can occur without known triggers. An endothelial dysfunction occurs that may be due to an imbalance in the neuro-hormonal, inflammatory, and oxidative environment in the circulation and in the endothelial cells. Myocardial hypoperfusion is clinically produced, coronary flow reduction, ischemic dysfunction, increased vascular rigidity and deterioration of arterial compliance that aggravate myocardial injury to a greater extent. Initial evaluation and continuous non-invasive monitoring of vital cardiorespiratory functions are essential. Diuretics are the cornerstone of the treatment of patients with AHF and signs of fluid overload and congestion. Renal replacement therapy should be reserved for patients who do not respond to treatment with diuretics. Intravenous vasodilators are the second most used drugs in the AHF for the relief of symptoms; however, there is no definitive evidence to confirm its beneficial effect. The use of inotropics should be reserved for patients with systolic dysfunction that affects the perfusion of vital organs. Ventricular assist devices and other forms of mechanical circulatory assistance can be used as a bridge treatment in selected patients(AU)

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Fungal peritonitis is frequent on peritoneal dialysis, with rare cases by Exophiala dermatitidis. A 25-month-old female admitted to the pediatric ICU with acute renal failure was submitted to peritoneal dialysis. After 10 days patient presented fever. Peritoneal fluid culture showed yeast colonies molecularly identified as E. dermatitidis. Patient was treated with voriconazole and hemodialysis. The literature was reviewed. Disseminated infections are frequently fatal, but appropriate diagnose and therapeutic led to cure in this case.

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INTRODUCTION: The hepatitis C virus (HCV) is recognized as one of the hepatic viruses most often associated with extrahepatic manifestations (EHMs). It is currently accepted that cryoglobulinemic vasculitis (CV) is the key autoimmune extrahepatic disease associated with HCV infection. Therapeutic approaches have mainly been based on the use of old antiviral interferon (IFN)-based regimens and immunosuppressive therapies, often with an inadequate balance between therapeutic benefits and excess side effects. Areas covered: Therapeutic management of HCV patients with EHMs, including both non-autoimmune (cardiovascular, hematological, general features) and autoimmune complications (organ-specific and systemic autoimmune diseases). Therapies included antiviral (IFN, ribavirin, direct-acting antivirals - DAAs-) and non-antiviral (immunosuppressive agents, rituximab, plasma exchanges) options. The review analyses the current evidence for proposing a treat-to-target (T2T) approach for HCV-related autoimmune EHMs based on an organ-by-organ strategy. Expert commentary: Eradication of HCV must be considered the key T2T in the therapeutic approach to HCV-related EHMs, as there has been a disruptive change due to the appearance of direct-acting antivirals (DAAs) as game-changers in HCV therapy, with an efficacy reaching nearly 100%. In this scenario, the central role played until now by IFN and ribavirin is not currently supported and they will not be used in the future.

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Bruxism is a rhythmic masticatory muscle activity, characterized by teeth grinding and clenching. This is a phenomenon mainly regulated by the central nervous system and peripherally influenced. It has two circadian manifestations, during sleep (sleep bruxism) and awake states (awake bruxism). Bruxism is much more than just tooth wearing. It is currently linked to orofacial pain; headaches; sleep disorders; sleep breathing disorders, such as apnea and hypopnea sleep syndrome; behavior disorders, or those associated with the use of medications. It is also influenced by psycho-social and behavior factors, which means that oromandibular parafunctional activities, temporomandibular disorders, malocclusion, high levels of anxiety and stress, among others, may precipitate the occurrence of bruxism. Nowadays, its etiology is multifactorial. The dentist and the pediatrician are responsible for its early detection, diagnosis, management, and prevention of its possible consequences on the patients. The aim of this review is to update the concepts of this disease and to make health professionals aware of its early detection and its timely management.

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El bruxismo es una actividad muscular mandibular repetitiva, caracterizada por apriete y rechinamiento dentario. Se considera un fenómeno regulado por el sistema nervioso central, principalmente, e influido por factores periféricos. Tiene 2 manifestaciones circadianas distintas: puede ocurrir durante el sueño -indicado como bruxismo de sueño- o durante la vigilia -indicado como bruxismo despierto-. El bruxismo es mucho más que solo el desgaste que podemos observar en los dientes: de hecho, se asocia con dolor orofacial, cefaleas, trastornos del sueño, trastornos respiratorios durante el sueño como el síndrome de apnea e hipoapnea del sueño, trastornos del comportamiento o asociados al uso de fármacos. Además, se ve influido por factores psicosociales y posturales, lo que indica que parafunciones oromandibulares, los trastornos temporomandibulares, la maloclusión, los altos niveles de ansiedad y de estrés, entre otros, podrían influir en la ocurrencia de bruxismo. Su etiología es considerada hoy como multifactorial. Su detección temprana, diagnóstico, tratamiento y la prevención de sus posibles consecuencias en los pacientes es responsabilidad del pediatra y del odontólogo. El objetivo de esta revisión es actualizar los conceptos sobre esta patología y alertar a los profesionales de la salud sobre su detección precoz y su manejo oportuno.

Bruxism is a rhythmic masticatory muscle activity, characterized by teeth grinding and clenching. This is a phenomenon mainly regulated by the central nervous system and peripherally influenced. It has two circadian manifestations, during sleep (sleep bruxism) and awake states (awake bruxism). Bruxism is much more than just tooth wearing. It is currently linked to orofacial pain; headaches; sleep disorders; sleep breathing disorders, such as apnea and hypopnea sleep syndrome; behavior disorders, or those associated with the use of medications. It is also influenced by psycho-social and behavior factors, which means that oromandibular parafunctional activities, temporomandibular disorders, malocclusion, high levels of anxiety and stress, among others, may precipitate the occurrence of bruxism. Nowadays, its etiology is multifactorial. The dentist and the pediatrician are responsible for its early detection, diagnosis, management, and prevention of its possible consequences on the patients. The aim of this review is to update the concepts of this disease and to make health professionals aware of its early detection and its timely management.

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Corrimento vaginal é a queixa mais frequente em Ginecologia, em toda e qualquer idade. A atenção em ginecologia infanto puberal apresenta características específicas que a diferenciam do atendimento ginecológico a mulheres de outras faixas etárias. A busca pelo médico, nas crianças e adolescentes, em geral é acompanhada de preocupação de pais e responsáveis. Objetivo: Avaliar a relevância do diagnóstico clínico frente a queixas sugestivas de vulvovaginite em crianças e adolescentes. Identificar sintomas, diagnósticos, terapêuticas e desfechos em crianças e adolescentes atendidas em um hospital universitário. Métodos: Estudo retrospectivo de análise de prontuários de crianças e adolescentes até 15 anos de idade, atendidas no Ambulatório de Ginecologia Infanto Puberal do HUAP de 01/01/2002 a 31/12/2012. Foram estudadas as seguintes variáveis: município de origem das pacientes, forma como foram encaminhadas, idade, status com ou sem menarca, queixas, tempo das queixas, presença de comorbidades, diagnóstico, tratamentos efetuados e desfecho. Foi utilizado teste não paramétrico para verificação das hipóteses estabelecidas para as variáveis contínuas. Resultados: Do universo de 203 pacientes incluídas no estudo, 46 apresentavam cuidados de higiene deficientes; 76, hábitos de vestuário inadequado; 67, ambos; 11 pacientes tiveram o diagnóstico de candidíase; 1 era portadora de coalescência de pequenos lábios e apenas 2 apresentavam, de fato, vulvovaginite. Conclusão: É alta a relevância do adequado diagnóstico, frente a queixas sugestivas de vulvovaginite, já que a quase totalidade do grupo em estudo não apresentou qualquer tipo de doença.

Vaginal discharge is the most frequent complaint in Gynecology at any age. Pediatric and Adolescent Gynecology has specific features that differentiate it from gynecological care of women from other age groups. The search for a doctor, for children and adolescents, is generally accompaniedby concern of parents and guardians. Objective: To evaluate the relevance of the clinical diagnosis face to the complaints suggestive of vulvovaginitisin children and adolescents. To identify symptoms, diagnoses, treatments, and outcomes in the study population. Subjects and Methods: Children andadolescents up to the of age of 15 years were selected for this retrospective study. They were looked after at the Pediatric and Adolescent Gynecology Ambulatory of the Hospital Universitário Antonio Pedro from 01/01/2002 to 31/12/2012. The following variables were studied: the city of origin of the patients, the way they were routed, age, status with or without menarche, complaints, while complaints, co morbidities, diagnosis, treatments performed,and outcome. Nonparametric test was used to verify the hypotheses established for the continuous variables. Results: From the pool of 203 patientsincluded in the study, 46 had lack of hygiene care; 76, inappropriate clothing habits; 67, both; 11 patients were diagnosed with candidiasis; one was a carrierof the coalescence of the labia minora, and only two showed, vulvovaginitis. Conclusions: The relevance of the clinical diagnosis was proved, face to the complaints suggestive of vulvovaginitis, as 93.1 % of the study group did not show any kind of pathology.

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O Acompanhamento Terapêutico (AT) vem se constituindo em um novo dispositivo clínico que percorre os espaços comunitários possíveis, como forma de atenção psicossocial. Será discutida a relação entre a ação clínica do AT e a interdisciplinaridade em saúde, imiscuída ao campo da atenção psicossocial. O objetivo é cooperar no processo de proposições de novas práticas que tenham em vista o sujeito atendido em saúde mental, valorizada a produção de sentido das ações desenvolvidas no AT em favor das demandas subjetivas. A abordagem metodológica foi qualitativa, em que quatro (4) sujeitos foram acompanhados em estudos de casos clínicos, por um período aproximado de um ano. Considera-se que favorecer a inclusão e a reabilitação dos acompanhados no AT é compreendê-los como sujeitos do próprio tratamento, reconhecendo a totalidade desafiante da natureza humana implicada nesse contexto, em que a reflexão sobre cada caso solicita a ampliação do campo de saber das várias especialidades profissionais envolvidas.

Therapeutic accompaniment (TA) has become a new clinical device that goes through potential community spaces as a means of psychosocial support. This paper addresses the relation between clinical action of TA and interdisciplinarity in health services, linked with psychosocial support initiatives. The purpose of this paper is to provide suggestions regarding the proposition of new practices targeting mental health patients, by appraising production of meaning of initiatives carried out in TA in favor of subjective demands. This paper adopts a qualitative approach, in which four (4) subjects were supervised on clinical case surveys during one year, approximately. It is believed that, by promoting inclusion and rehabilitation, TA patients can be understood as subjects of the treatment itself, thus acknowledging the challenging entirety of human nature implied, in which the reflection upon each case asks for expanding the realm of knowledge of the many professional specialties involved.

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O Acompanhamento Terapêutico (AT) vem se constituindo em um novo dispositivo clínico que percorre os espaços comunitários possíveis, como forma de atenção psicossocial. Será discutida a relação entre a ação clínica do AT e a interdisciplinaridade em saúde, imiscuída ao campo da atenção psicossocial. O objetivo é cooperar no processo de proposições de novas práticas que tenham em vista o sujeito atendido em saúde mental, valorizada a produção de sentido das ações desenvolvidas no AT em favor das demandas subjetivas. A abordagem metodológica foi qualitativa, em que quatro (4) sujeitos foram acompanhados em estudos de casos clínicos, por um período aproximado de um ano. Considera-se que favorecer a inclusão e a reabilitação dos acompanhados no AT é compreendê-los como sujeitos do próprio tratamento, reconhecendo a totalidade desafiante da natureza humana implicada nesse contexto, em que a reflexão sobre cada caso solicita a ampliação do campo de saber das várias especialidades profissionais envolvidas.(AU)

Therapeutic accompaniment (TA) has become a new clinical device that goes through potential community spaces as a means of psychosocial support. This paper addresses the relation between clinical action of TA and interdisciplinarity in health services, linked with psychosocial support initiatives. The purpose of this paper is to provide suggestions regarding the proposition of new practices targeting mental health patients, by appraising production of meaning of initiatives carried out in TA in favor of subjective demands. This paper adopts a qualitative approach, in which four (4) subjects were supervised on clinical case surveys during one year, approximately. It is believed that, by promoting inclusion and rehabilitation, TA patients can be understood as subjects of the treatment itself, thus acknowledging the challenging entirety of human nature implied, in which the reflection upon each case asks for expanding the realm of knowledge of the many professional specialties involved.(AU)

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