Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials.

Neurodegenerative diseases are caused by the gradual loss of neurons' function. These neurological illnesses remain incurable, and current medicines only alleviate the symptoms. Given the social and economic burden caused by the rising frequency of neurodegenerative diseases, there is an urgent need for the development of appropriate therapeutics. Natural compounds are gaining popularity as alternatives to synthetic drugs due to their neuroprotective properties and higher biocompatibility. While natural compounds' therapeutic effects for neurodegenerative disease treatment have been investigated in numerous in vitro and in vivo studies, only few have moved to clinical trials. This article provides the first systematic review of the clinical trials evaluating natural compounds' safety and efficacy for the treatment of the five most prevalent neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease.

Drug Delivery Systems as a Strategy to Improve the Efficacy of FDA-Approved Alzheimer's Drugs.

Alzheimer's disease (AD) is the most common form of dementia, with a high impact worldwide, accounting for more than 46 million cases. The continuous increase of AD demands the fast development of preventive and curative therapeutic strategies that are truly effective. The drugs approved for AD treatment are classified into acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The therapeutic effectiveness of those drugs is hindered by their restricted access to the brain due to the blood-brain barrier, low bioavailability, and poor pharmacokinetic properties. In addition, the drugs are reported to have undesirable side effects. Several drug delivery systems (DDSs) have been widely exploited to address these issues. DDSs serve as drug carriers, combining the ability to deliver drugs locally and in a targeted manner with the ability to release them in a controlled and sustained manner. As a result, the pharmacological therapeutic effectiveness is raised, while the unwanted side effects induced by the unspecific distribution decrease. This article reviews the recently developed DDSs to increase the efficacy of Food and Drug Administration-approved AD drugs.

Mitochondrial dysfunction on Leishmania (Leishmania) amazonensis induced by ketoconazole: insights into drug mode of action.

BACKGROUND: Leishmania parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase. OBJECTIVE: The present study aimed to better understand the biological response of Leishmania (Leishmania) amazonensis promastigotes at the cellular level after ketoconazole treatment. METHODS: Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment. FINDINGS: The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8 strain). MAIN CONCLUSIONS: Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in in vitro models.

Polymeric Nanoparticles-Loaded Hydrogels for Biomedical Applications: A Systematic Review on In Vivo Findings.

Clinically available medications face several hurdles that limit their therapeutic activity, including restricted access to the target tissues due to biological barriers, low bioavailability, and poor pharmacokinetic properties. Drug delivery systems (DDS), such as nanoparticles (NPs) and hydrogels, have been widely employed to address these issues. Furthermore, the DDS improves drugs' therapeutic efficacy while reducing undesired side effects caused by the unspecific distribution over the different tissues. The integration of NPs into hydrogels has emerged to improve their performance when compared with each DDS individually. The combination of both DDS enhances the ability to deliver drugs in a localized and targeted manner, paired with a controlled and sustained drug release, resulting in increased drug therapeutic effectiveness. With the incorporation of the NPs into hydrogels, it is possible to apply the DDS locally and then provide a sustained release of the NPs in the site of action, allowing the drug uptake in the required location. Additionally, most of the materials used to produce the hydrogels and NPs present low toxicity. This article provides a systematic review of the polymeric NPs-loaded hydrogels developed for various biomedical applications, focusing on studies that present in vivo data.

Mitochondrial dysfunction on Leishmania (Leishmania) amazonensis induced by ketoconazole: insights into drug mode of action

BACKGROUND Leishmania parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase. OBJECTIVE The present study aimed to better understand the biological response of Leishmania (Leishmania) amazonensis promastigotes at the cellular level after ketoconazole treatment. METHODS Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment. FINDINGS The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8 strain). MAIN CONCLUSIONS Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in in vitro models.

Comunicação Alternativa para Alunos com Autismo na Escola: uma Revisão da Literatura / Alternative Communication for Students with Autism at School: a Literature Review

RESUMO: Estudos meta-analíticos e descritivos conduzidos nas últimas décadas têm demonstrado a efetividade da Comunicação Alternativa e Ampliada (CAA) para pessoas com Transtorno do Espectro Autista (TEA). A maior parte dessas investigações tem focado, contudo, na efetividade clínica da CAA sem atentar para os aspectos pragmáticos da comunicação assistida em contextos não estruturados, como a escola. O objetivo desta investigação foi ampliar, por meio de uma revisão integrativa da literatura, o acervo de pesquisas tratadas em revisões anteriores e, assim, analisar os contextos em que a CAA foi utilizada com educandos com TEA na escola regular. Para isso, foi realizada uma busca no portal de periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e no catálogo eletrônico de teses e dissertações dessa mesma agência com termos previamente definidos. As oito pesquisas encontradas, publicadas entre 2015 e 2018, incluíram participantes entre 3 e 12 anos de idade que utilizavam sistemas assistidos de comunicação, sendo predominantes as pranchas/álbuns de CAA ou pictogramas avulsos. Todos os estudos foram conduzidos na sala de aula regular e/ou nas Salas de Recursos Multifuncionais, mas dois deles incluíram o ambiente domiciliar. A despeito do uso da CAA em contextos naturais envolver interlocutores conhecidos, foram identificadas lacunas em aspectos pragmáticos da comunicação dos educandos. Observou-se a predominância da comunicação imperativa, a qual focava primordialmente nos comportamentos pragmáticos de solicitação. Embora limitações tenham sido identificadas, os estudos revelaram resultados positivos sobre o uso da CAA para alunos com TEA.

ABSTRACT: Meta-analytical and descriptive studies conducted in recent decades have demonstrated the effectiveness of Augmentative and Alternative Communication (AAC) for people with Autism Spectrum Disorders (ASD). Most of these investigations have focused, however, on the clinical effectiveness of AAC without considering pragmatic aspects of assisted communication in unstructured contexts, such as schools. Te aim of this investigation was to expand, through an integrative literature review, the current body of research, analyzing the contexts where AAC was used with students with ASD in regular schools. In this sense, a search was carried out on the Coordination for the Improvement of Higher Education Personnel (CAPES) journals portal and on the electronic catalog of theses and dissertations of this same agency with previously defined terms Te eight studies found, published between 2015 and 2018, included participants between 3 and 12 years of age who used assisted communication systems, primarily AAC boards and picture cards. All studies were conducted in the regular classroom and / or Multifunctional Resource Rooms, but two included the home environment. Despite the use of AAC in natural contexts, involving known interlocutors, gaps were identified in pragmatic aspects of student communication. Tere was a predominance of imperative communication, focusing primarily on pragmatic solicitation behaviors. Despite the limitations identified, the studies revealed positive results on the use of AAC for students with ASD.

First epidemiological description of tegumentar and visceral Leishmaniasis in Patrocínio municipality, Minas Gerais (2000-2017) / Primeira descrição epidemiológica de leishmaniose tegumentar e visceral no município de Patrocínio, Minas Gerais (2000-2017)

Leishmaniasis is a disease that can affect visceral organs (visceral leishmaniasis; VL) or mucous membranes and skin, causing lesions of different forms and levels of severities (tegumentary leishmaniasis; TL). Like several others, leishmaniasis is a neglected disease, as the pharmaceutical industry seems to show little to no interest in developing new drugs targeting the disease. This study aims to trace the epidemiological profile of leishmaniasis in the Municipality of Patrocínio, State of Minas Gerais, over a period of time. Secondary data of reported cases from 2000 to 2017 were analyzed as provided by the Patrocinio Health Department. As no literature was found on the status of such a disease in Patrocinio, it is important to trace the epidemiological profile of leishmaniasis in the area. The findings pointed out that the disease affected predominantly male in the economically active population, mainly from the urban area, and that it had no relationship with professional activity. Twenty-two cases of leishmaniasis (15 of TL and 7 of VL) were reported, all of which were treated and cured. Five cases of TL and 1 case of VL were autochthonous, and confirmed cases of canine infection took place in 2011, 2016 and 2017.KEYWORDS: Alto Paranaíba. Autochthonous. Human leishmaniasis. Triângulo Mineiro. INTRODUCTION Leishmaniasis is a parasitic disease caused by protozoa of the Leishmania genus, which are transmitted from one host to another by phlebotomine sandflies (NAGLE et al., 2014). It may affect both visceral organs and skin surfaces (HANDLER et al., 2015) and lead to four major clinical syndromes: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), visceral leishmaniasis or kala-azar (VL) and post-kala-azar dermal leishmaniasis (PKDL) (ANVERSA et al., 2018). Leishmaniasis is treated as a public health problem due to its high incidence and the disorders it can cause to the affected individuals. TL is characterized by ulcers on the face and/or extremities and nasal/oral/pharyngeal mucous (HANDLER et al, 2015), which can cause deformities such as disfiguring and permanent scars with partial or total mutilation of the nasopharyngeal mucosa, with further social, economic and psychological implications (ANVERSA et al., 2018, SUNYOTO; BOELAERT; MEHEUS, 2019). The mortality rate for VL, a more severe form, is 10%, making it the second most deadly tropical parasitic infection in the world after malaria (HANDLER et al., 2015). Updated regional information on the disease is important for epidemiological surveillance. However, the actual number of leishmaniasis cases is unknown due to underreporting, lack of epidemiological surveillance system or adequate diagnostic methods. Most data on incidence rates are based on estimates (PACE, 2014). Around 1.5 to 2 million new cases of leishmaniasis are estimated to occur annually worldwide: 500,000 are VL; 1 to 1.5 million cases are related to cutaneous or mucocutaneous leishmaniasis. Both forms commonly occur in Brazil (ANVERSA et al., 2018; WHO, 2020). Silva (2017) reported that the highest incidence rates of VL in the State of Minas Gerais, Brazil, from 2002 to 2013 were concentrated in the mesoregions in the North (Noroeste de Minas, Norte de Minas, and Jequitinhonha), in the East (Vale do Rio Doce) and in the center of the state (Central Mineira and Metropolitana de Belo Horizonte). The other mesoregions (Campo das Verentes, Oeste de Minas, Sul/Sudoeste de Minas, Triângulo Received: 08/04/19 Accepted: 20/12/19

A leishmaniose é uma doença que pode afetar órgãos viscerais (leishmaniose visceral; LV) ou as mucosas e a pele, provocando lesões de diferentes formas e gravidades (leishmaniose tegumentar; LT). Como várias outras moléstias, a leishmaniose é uma doença negligenciada, já que a indústria farmacêutica parece mostrar pouco ou nenhum interesse em desenvolver novos medicamentos direcionados à enfermidade. O estudo teve como objetivo traçar o perfil epidemiológico da leishmaniose no município de Patrocínio, estado de Minas Gerais, ao longo de um período de tempo. Dados secundários de casos registrados no período de 2000 a 2017 foram analisados, conforme fornecido pelo Departamento de Saúde de Patrocínio. Como não foi encontrada literatura sobre a situação dessa doença em Patrocínio, é importante traçar o perfil epidemiológico da leishmaniose na região. Os achados apontaram que a doença afetou predominantemente o sexo masculino da população economicamente ativa, principalmente da área urbana, e que não tinha relação com a atividade profissional. Foram notificados 22 casos de leishmaniose (15 de LT e 7 de LV), todos tratados e curados. Cinco casos de LT e 1 de LV foram considerados autóctones, e houve casos confirmados de infecção canina nos anos de 2011, 2016 e 2017.

Increased ROS generation causes apoptosis-like death: Mechanistic insights into the anti-Leishmania activity of a potent ruthenium(II) complex.

Some metallodrugs that exhibit interesting biological activity contain transition metals such as ruthenium, and have been extensively exploited because of their antiparasitic potential. In previous study, we reported the remarkable anti-Leishmania activity of precursor cis-[RuIICl2(dppm)2], where dppm = bis(diphenylphosphino)methane, and new ruthenium(II) complexes, cis-[RuII(η2-O2CC10H13)(dppm)2]PF6 (bbato), cis-[RuII(η2-O2CC7H7S)(dppm)2]PF6 (mtbato) and cis-[RuII(η2-O2CC7H7O2)(dppm)2]PF6 (hmxbato) against some Leishmania species. In view of the promising activity of the hmxbato complex against Leishmania (Leishmania) amazonensis promastigotes, the present work investigated the possible parasite death mechanism involved in the action of this hmxbato and its precursor. We report, for the first time, that hmxbato and precursor promoted an increase in reactive oxygen species production, depolarization of the mitochondrial membrane, DNA fragmentation, formation of a pre-apoptotic peak, alterations in parasite morphology and formation of autophagic vacuoles. Taken together, our results suggest that these ruthenium complexes cause parasite death by apoptosis. Thus, this work provides relevant knowledge on the activity of ruthenium(II) complexes against L. (L.) amazonensis. Such information will be essential for the exploitation of these complexes as future candidates for cutaneous leishmaniasis treatment.

Multidisciplinary approach for patients with nephropathic cystinosis: model for care in a rare and chronic renal disease / Abordagem multidisciplinar para pacientes com cistinose nefropática: modelo para atendimento em uma doença renal rara e crônica

Abstract Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case.

Resumo A assistência a pacientes com doenças crônicas e raras é complexa, principalmente pela falta de disseminação de conhecimento sobre a doença, o que dificulta o diagnóstico preciso e precoce, além da necessidade da realização de exames específicos, por vezes de alta complexidade e custo. Somam-se a esses fatores dificuldades na obtenção de tratamento adequado quando disponível, na conscientização do paciente e da família sobre a doença e na aderência ao tratamento. A cistinose nefropática está entre essas doenças. Após mais de 20 anos como centro de atendimento a esses pacientes, os autores propõem um protocolo de seguimento, o qual vem sendo empregado com melhora na qualidade da assistência e consiste de uma abordagem multidisciplinar, incluindo, principalmente, atendimento prestado por médico, enfermeiro, psicólogo, nutricionista e assistente social. Neste artigo, cada área expõe de maneira objetiva como abordar pontos que envolvem as etapas do diagnóstico e sua comunicação ao paciente e a seus familiares ou responsáveis, abrangendo as particularidades da doença e do tratamento, o impacto na vida do paciente e de sua família, a abordagem das questões psicológicas e sociais e orientações quanto a medicamentos e dietas. Considera-se que este protocolo poderia ser adaptado ao seguimento de pacientes portadores de outras doenças raras, incluindo aquelas com envolvimento renal. Com essa proposta, espera-se alcançar o maior número de profissionais envolvidos no seguimento desses pacientes, fortalecendo as bases para a criação de um protocolo nacional, observando-se as particularidades de cada caso.

Multidisciplinary approach for patients with nephropathic cystinosis: model for care in a rare and chronic renal disease.

Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case.

Increased ROS generation causes apoptosis-like death: mechanistic insights into the anti-Leishmania activity of a potent ruthenium(II) complex

Some metallodrugs that exhibit interesting biological activity contain transition metals such as ruthenium, and have been extensively exploited because of their antiparasitic potential. In previous study, we reported the remarkable anti-Leishmania activity of precursor cis-[RuIICl2(dppm)2], where dppm=bis(diphenylphosphino)methane, and new ruthenium(II) complexes, cis-[RuII(n2-O2CC10H13)(dppm)2]PF6 (bbato), cis-[RuII(n2-O2CC7H7S)(dppm)2]PF6 (mtbato) and cis-[RuII(n2-O2CC7H7O2)(dppm)2]PF6 (hmxbato) against some Leishmania species. In view of the promising activity of the hmxbato complex against Leishmania (Leishmania) amazonensis promastigotes, the present work investigated the possible parasite death mechanism involved in the action of this hmxbato and its precursor. We report, for the first time, that hmxbato and precursor promoted an increase in reactive oxygen species production, depolarization of the mitochondrial membrane, DNA fragmentation, formation of a pre-apoptotic peak, alterations in parasite morphology and formation of autophagic vacuoles. Taken together, our results suggest that these ruthenium complexes cause parasite death by apoptosis. Thus, this work provides relevant knowledge on the activity of ruthenium(II) complexes against L. (L.) amazonensis. Such information will be essential for the exploitation of these complexes as future candidates for cutaneous leishmaniasis treatment.

Increased ROS generation causes apoptosis-like death: mechanistic insights into the anti-Leishmania activity of a potent ruthenium(II) complex

Some metallodrugs that exhibit interesting biological activity contain transition metals such as ruthenium, and have been extensively exploited because of their antiparasitic potential. In previous study, we reported the remarkable anti-Leishmania activity of precursor cis-[RuIICl2(dppm)2], where dppm=bis(diphenylphosphino)methane, and new ruthenium(II) complexes, cis-[RuII(n2-O2CC10H13)(dppm)2]PF6 (bbato), cis-[RuII(n2-O2CC7H7S)(dppm)2]PF6 (mtbato) and cis-[RuII(n2-O2CC7H7O2)(dppm)2]PF6 (hmxbato) against some Leishmania species. In view of the promising activity of the hmxbato complex against Leishmania (Leishmania) amazonensis promastigotes, the present work investigated the possible parasite death mechanism involved in the action of this hmxbato and its precursor. We report, for the first time, that hmxbato and precursor promoted an increase in reactive oxygen species production, depolarization of the mitochondrial membrane, DNA fragmentation, formation of a pre-apoptotic peak, alterations in parasite morphology and formation of autophagic vacuoles. Taken together, our results suggest that these ruthenium complexes cause parasite death by apoptosis. Thus, this work provides relevant knowledge on the activity of ruthenium(II) complexes against L. (L.) amazonensis. Such information will be essential for the exploitation of these complexes as future candidates for cutaneous leishmaniasis treatment.

Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction.

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The many complications presented by the current treatment - including high toxicity, high cost and parasite resistance - make the development of new therapeutic agents indispensable. The present study aims to evaluate the anti-Leishmania potential of new ruthenium(II) complexes, cis­[RuII(η2-O2CR)(dppm)2]PF6, with dppm=bis(diphenylphosphino)methane and R=4-butylbenzoate (bbato) 1, 4-(methylthio)benzoate (mtbato) 2 and 3-hydroxy-4-methoxybenzoate (hmxbato) 3, in promastigote cytotoxicity and their effect on parasite-host interaction. The cytotoxicity of complexes was analyzed by MTT assay against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Leishmania) infantum promastigotes and the murine macrophage (RAW 264.7). The effect of complexes on parasite-host interaction was evaluated by in vitro infectivity assay performed in the presence of two different concentrations of each complex: the promastigote IC50 value and the concentration nontoxic to 90% of RAW 264.7 macrophages. Complexes 1-3 exhibited potent cytotoxic activity against all Leishmania species assayed. The IC50 values ranged from 7.52-12.59µM (complex 1); 0.70-3.28µM (complex 2) and 0.52-1.75µM (complex 3). All complexes significantly inhibited the infectivity index at both tested concentrations. The infectivity inhibitions ranged from 37 to 85%. Interestingly, the infectivity inhibitions due to complex action did not differ significantly at either of the tested concentrations, except for the complex 1 against Leishmania (Leishmania) infantum. The infectivity inhibitions resulted from reductions in both percentage of infected macrophages and number of parasites per macrophage. Taken together the results suggest remarkable leishmanicidal activity in vitro by these new ruthenium(II) complexes.

A fourteen-year retrospective of clinic-epidemiological aspects of cutaneous and visceral leishmaniasis in Uberlândia, Minas Gerais, Brazil / Uma retrospectiva de 14 anos dos aspectos clínico-epidemiológicos da leishmaniose cutânea e visceral em Uberlândia, Minas Gerais, Brasil

The purpose of this study was to describe clinic-epidemiological characteristics of leishmaniasis cases attended at the Clinical Hospital of Federal University of Uberlândia (CHU), state of Minas Gerais, from January 2000 to December 2013. This is a descriptive and retrospective review of medical records of patients diagnosed with leishmaniasis and treated at the CHU. 168 cases of leishmaniasis were analyzed and most patients were male, aged 23 to 60 years. For cutaneous and mucosal leishmaniasis, single lesions, located mainly in lower limbs and head (CL) and nasal mucosa (ML), were the most common clinical presentation. Regarding the diagnosis, the most performed methods for CL and ML were biopsy plus histopathology and biopsy plus immunohistochemistry; biopsy plus direct parasitological examination methods were the most frequent for VL. Most patients (84%) received treatment, mainly glucantime for both CL and ML; VL treatment was based on amphotericin B or glucantime. According to data from Sistema de Informações de Agravos de Notificação (SINAN), the Brazilian information system to notify and investigate cases of diseases and their aggravations, no case has been confirmed as autochthonous. It is noteworthy the underreporting of cases and the lack of complete information in medical records. Our results may contribute to a better understanding of the real situation in Uberlândia region concerning to leishmaniasis.

O propósito desse estudo foi descrever as características clínico-epidemiológicas dos casos de leishmaniose atendidos no Hospital de Clínicas da Unversidade Federal de Uberlândia (HCU), Minas Gerais, de janeiro de 2000 a dezembro de 2013. Trata-se de uma revisão descritiva e retrospectiva de registros médicos de pacientes diagnosticados com leishmaniose e tratados no HCU. 168 casos diagnosticados com leishmaniose foram analisados e os pacientes, em sua marioria, foram homens, com idade entre 23 e 60 anos. Para a leishmaniose cutânea e mucosa, lesões únicas, localizadas principalmente nos membros inferiores e na cabeça (LC) e mucosa nasal (LM), foram as apresentações clínicas mais comuns. Em relação ao diagnóstico, os métodos mais realizados para LC e LM foram biópsia mais histopatologia e biópsia mais imunohistoquímica; biópsia mais parasitológico direto foi o mais frequente para LV. A maioria dos pacientes (84%) recebeu tratamento, principalmente glucantime tanto para LC quanto para LM; o tratamento para LV foi atribuido à anfotericina B ou glucantime. De acordo com os dados do Sistema de Informação de Agravos de Notificação (SINAN), o sistema de informação brasileiro para notificar e investigar casos de doenças e seus agravamentos, nenhum caso foi confirmado como autóctone. Ressalta-se a subnotificação dos casos e a informação incompleta nos prontuários médicos. Nossos resultados podem contribuir para um melhor entendimento da real situação da leishmaniose na região de Uberlândia.

In vitro additive interaction between ketoconazole and antimony against intramacrophage Leishmania (Leishmania) amazonensis amastigotes.

Leishmaniasis is a group of diseases caused by protozoa of Leishmania genus. The currently available treatments for this disease are expensive, present high toxicity and are associated to difficulties of healing and parasite resistance. Therefore, the development of strategies for leishmaniasis treatment is indispensable and includes reposition of existing drugs, as well as drug combination therapy. The aim of this study was to assess the nature of ketoconazole and antimony association on the cytotoxic effect against Leishmania (Leishmania) amazonensis amastigotes. The calculated mean sum of fractional 50% inhibitory concentration ([Formula: see text]ΣFIC50) was 2.54 and 1.43 for free and intracellular amastigotes, respectively, values that suggest an additive interaction between ketoconazole and antimony concerning to Leishmania toxicity only in the intramacrophage parasite form. Despite the clinical efficacy of ketoconazole-antimony combination has been shown in the literature, our study is the first to describe the nature of ketoconazole-antimony interaction against L. (L.) amazonensis amastigotes. Moreover, our results point out the need for future in vivo studies to confirm the nature of ketoconazole-antimony interaction and also to determine possible effective dosage regimens related to ketoconazole administration in association with the optimal lower dose of antimony.

Processos de Leitura em Educandos com Autismo: um Estudo de Revisão / Literacy Process in Students with Autism Spectrum Disorder (ASD): a Review Study

RESUMO: dois objetivos são identificados no presente artigo: (a) contrastar o processo de desenvolvimento da leitura em pessoas com desenvolvimento típico e Transtorno do Espectro do Autismo (TEA) e (b) relatar os resultados de um estudo de revisão de pesquisas, publicadas em periódicos científicos, no período 2009-2015, sobre práticas interventivas em leitura, utilizadas no atendimento de indivíduos com TEA. Os resultados das pesquisas revelam que esses indivíduos, tipicamente, evidenciam déficits no processo de aquisição de competências em leitura. Assinale-se que os prejuízos na integração de informações, para fins de compreensão textual é prevalente, sendo apontado como um dos fatores críticos a serem tratados. Os problemas de leitura identificados nessa população podem, no entanto, ser remediados por meio de adaptações de estratégias empregadas com educandos com desenvolvimento típico. O artigo discute, por fim, a escassez de estudos nacionais que abordam essa temática e a carência de políticas educacionais que prezem pela adoção de modelos interventivos respaldados em pesquisas científicas.

ABSTRACT: Two objectives were identified in this article: (a) to contrast the reading development process in people with typical development and Autism Spectrum Disorder (ASD) and (b) to report the results of a review study focused on interventional practices published in scientific journals between 2009 and 2015. The results showed that individuals with ASD typically show deficits in reading development. Failure to integrate written information for textual understanding is prevalent and considerate a critical factor to be addressed. Reading problems identified in this population may, however, be remedied by adapting strategies commonly used with typically developing peers. The article further discusses the limited number of published national studies that address this issue and the lack of educational policies that support the use scientifically based practices.

Outcome of renal transplantation from a donor with polycystic kidney disease.

Faced with the long waiting list for a kidney transplant, the use of donors with expanded criteria, like polycystic kidneys, is an option that aims to increase in a short time the supply of kidneys for transplant. This report of two cases of transplants performed from a donor with polycystic kidneys showed promising results, and the receptors evolved with good renal function, serum creatinine measurements within the normal range and with adequate glomerular filtration rate, evaluated over a period of four years post transplant. This fact confirms that the option of using donors with polycystic kidneys is safe and gives good results.

Resumo Diante da longa fila de espera por um transplante renal, a utilização de doadores com critério expandido, a exemplo de rins policísticos, torna-se uma opção que visa aumentar a oferta de rins para transplante a curto prazo. O presente relato de dois casos de transplantes realizados a partir de um doador com rins policísticos apresentou resultado promissor, tendo os receptores evoluído com boa função renal, dosagens de creatinina sérica dentro da faixa de normalidade e com taxa de filtração glomerular adequada, avaliados num período de quatro anos pós-transplante. Isto confirma que a opção da utilização de doadores com rins policísticos é segura e apresenta bons resultados.