Bioconjugate based on cisplatin and bacterial exopolysaccharide with reduced side effects: A novel proposal for cancer treatment.

BACKGROUND: In the search for alternatives that attenuate the toxicity associated to oncologic treatment with cisplatin (CDDP) and considering the potential health-beneficial properties of exopolysaccharides (EPS) produced by lactic acid bacteria, it was aimed on this study to evaluate the cytotoxic, toxicologic and antitumoral efficacy of a bioconjugate based on CDDP and EPS, on the experimental tumor of sarcoma 180. METHODS: After the synthesis of the cis-[Pt(NH3)2(Cl)2] complex and of the conjugate containing Lactobacillus fermentum exopolysaccharide was tested both in vitro and in vivo for evaluating the acute toxicity. RESULTS: The antitumoral study was performed using mice transplanted with sarcoma 180. The bioconjugate showed low to medium cytotoxicity for the cell lines tested, as well moderated acute toxicity. After determining the LD50, the following experimental groups were established for the antitumor assay: Control (NaCl 0,9%), CDDP (1 mg/kg), EPS and bioconjugate composition (200 mg/kg). The bioconjugate promoted a 38% regression in tumor mass when compared to the control, and a regression of 41% when compared to CDDP. Liver histopathological analysis revealed discrete alterations in animals treated with (CDDP + EPS) when compared to control. The bioconjugate also minimized changes in the renal parenchyma resulting from the tumor. CONCLUSION: Our results indicate that when CDDP is associated with EPS, this composition was more biocompatible, showing itself as a potent chemotherapeutic agent and lower tissue toxicity.

Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy.

Limb-girdle muscular dystrophies (LGMD) are a group of genetically heterogeneous disorders characterized by predominantly proximal muscle weakness. We aimed to characterize epidemiological, clinical and molecular data of patients with autosomal recessive LGMD2/LGMD-R in Brazil. A multicenter historical cohort study was performed at 13 centers, in which index cases and their affected relatives' data from consecutive families with genetic or pathological diagnosis of LGMD2/LGMD-R were reviewed from July 2017 to August 2018. Survival curves to major handicap for LGMD2A/LGMD-R1-calpain3-related, LGMD2B/LGMD-R2-dysferlin-related and sarcoglycanopathies were built and progressions according to sex and genotype were estimated. In 370 patients (305 families) with LGMD2/LGMD-R, most frequent subtypes were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related, each representing around 30% of families. Sarcoglycanopathies were the most frequent childhood-onset subtype, representing 21% of families. Five percent of families had LGMD2G/LGMD-R7-telethonin-related, an ultra-rare subtype worldwide. Females with LGMD2B/LGMD-R2-dysferlin-related had less severe progression to handicap than males and LGMD2A/LGMD-R1-calpain3-related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. We have provided paramount epidemiological data of LGMD2/LGMD-R in Brazil that might help on differential diagnosis, better patient care and guiding future collaborative clinical trials and natural history studies in the field.

Permanencia y deserción versus autoeficacia de estudiantes universitarios: un desafío de la calidad educativa

Introducción. La deserción estudiantil a nivel universitario sigue siendo un problema vigente que desencadena pérdidas financieras además de tipo social y familiar, cuando no se alcanzan las metas de la formación académica que garantice trabajadores competentes para el mundo laboral actual. Objetivo. Analizar la permanencia y deserción versus la autoeficacia de estudiantes universitarios en el marco de la calidad educativa. Materiales y métodos. La población estuvo constituida por los estudiantes de una universidad de la ciudad de Barranquilla en Colombia. Se tomó, del registro para el período 20151, una muestra de 322 estudiantes, de los cuales 195 estaban activos y 127 en deserción. El trabajo fue descriptivo y transaccional de diseño no experimental. El instrumento de recolección de datos fue la Escala de Autoeficacia General (EAG), apoyada por el sistema de información institucional del Departamento de Admisiones y Registro. Resultados. Se demostró que no existe una correlación significativa entre autoeficacia y permanencia, así como tampoco entre la autoeficacia y la deserción. Sin embargo, un hallazgo significativo fue demostrar que la media de autoeficacia en desertores resultó mayor que la de los estudiantes que permanecieron en la institución. Conclusiones. Se obtuvo que no se presenta una correlación significativa entre las variables autoeficacia, deserción y permanencia.

Introduction. The student dropout at university level continues being a current problem that unleashes financial loss besides social and familiar ones, when academic formation goals are not achieved, which assures skillful workers for the current labor world. Objective. To analyze the permanence and dropout versus self-sufficiency of university students in the quality educative framework. Materials and methods. Population was composed by university students in the city of Barranquilla, Colombia. The registry of 2015-1 term, a sample of 322 students, from which 195 were active and 127 on dropout was taken. The work was descriptive and transactional of non-experimental design. Data collection instrument was the General Self-sufficiency scale (GSS), supported by the institutional information system of the Admissions and Registration Department. Results. It was proved that there is not a significant correlation between self-efficiency and permanence, as neither between self-sufficiency or dropout; however, a significant finding was to prove that the average of dropout's self-sufficient students resulted greater than the one of students staying in the institution. Conclusions. It was obtained that there is not a significant correlation among self-efficiency, dropout, and permanence variables.

Introdução. A deserção estudantil a nível universitário segue sendo um problema vigente que desencadeia perdas financeiras ademais de tipo social e familiar, quando não se alcançam as metas da formação acadêmica que garante trabalhadores competentes para o mundo laboral atual. Objetivo. Analisar a permanência e deserção versus a auto eficácia de estudantes universitários no marco da qualidade educativa. Materiais e métodos. A população foi constituída pelos estudantes de uma universidade da cidade de Barranquilla na Colômbia. Se tomou, do registro para o período 2015-1, uma amostra de 322 estudantes, dos quais 195 estavam ativos e 127 em deserção. O trabalho foi descritivo e transacional de desenho não experimental. O instrumento de recolhimento dos dados foi a Escala de Auto eficácia General (EAG), apoiada pelo sistema de informação institucional do Departamento de Admissões e Registro. Resultados. Se demostrou que não existe uma correlação significativa entre auto eficácia e permanência, assim como tampouco entre a auto eficácia e a deserção. Embora, um descobrimento significativo foi demostrar que a média de auto eficácia em desertores resultou maior que a dos estudantes que permaneceram na instituição. Conclusões. Se obteve que não se apresenta una correlação significativa entre as variáveis auto eficácia, deserção e permanência.

Guidelines for the diagnosis, treatment and clinical monitoring of patients with juvenile and adult Pompe disease / Diretriz para o diagnóstico, tratamento e acompanhamento clínico de pacientes com doença de Pompe juvenil e do adulto

ABSTRACT Pompe disease (PD) is a potentially lethal illness involving irreversible muscle damage resulting from glycogen storage in muscle fiber and activation of autophagic pathways. A promising therapeutic perspective for PD is enzyme replacement therapy (ERT) with the human recombinant enzyme acid alpha-glucosidase (Myozyme®). The need to organize a diagnostic flowchart, systematize clinical follow-up, and establish new therapeutic recommendations has become vital, as ERT ensures greater patient longevity. A task force of experienced clinicians outlined a protocol for diagnosis, monitoring, treatment, genetic counseling, and rehabilitation for PD patients. The study was conducted under the coordination of REBREPOM, the Brazilian Network for Studies of PD. The meeting of these experts took place in October 2013, at L’Hotel Port Bay in São Paulo, Brazil. In August 2014, the text was reassessed and updated. Given the rarity of PD and limited high-impact publications, experts submitted their views.

RESUMO A doença de Pompe (DP) é uma doença grave, potencialmente letal, devida ao depósito de glicogênio na fibra muscular e ativação de vias autofágicas. Tratamento promissor para a DP é a reposição enzimática com a enzima recombinante humana alfa-glicosidase ácida (rhAGA -Myozyme®). A necessidade de organizar uma propedêutica diagnóstica, sistematizar o seguimento clínico e sedimentar as novas recomendações terapêuticas tornaram-se vitais à medida que o tratamento permite uma maior longevidade aos pacientes. Uma força-tarefa de clínicos experientes no manejo da DP foi constituída para elaborar um protocolo para o diagnóstico, acompanhamento clínico, tratamento, aconselhamento genético, entre outras considerações voltadas ao paciente adulto. O estudo foi realizado sob a coordenação da Rede Brasileira de Estudos da Doença de Pompe (REBREPOM). Diante da raridade da DP e escassez de trabalhos de alto impacto de evidência científica, os especialistas emitiram suas opiniões.

Guidelines for the diagnosis, treatment and clinical monitoring of patients with juvenile and adult Pompe disease.

Pompe disease (PD) is a potentially lethal illness involving irreversible muscle damage resulting from glycogen storage in muscle fiber and activation of autophagic pathways. A promising therapeutic perspective for PD is enzyme replacement therapy (ERT) with the human recombinant enzyme acid alpha-glucosidase (Myozyme®). The need to organize a diagnostic flowchart, systematize clinical follow-up, and establish new therapeutic recommendations has become vital, as ERT ensures greater patient longevity. A task force of experienced clinicians outlined a protocol for diagnosis, monitoring, treatment, genetic counseling, and rehabilitation for PD patients. The study was conducted under the coordination of REBREPOM, the Brazilian Network for Studies of PD. The meeting of these experts took place in October 2013, at L'Hotel Port Bay in São Paulo, Brazil. In August 2014, the text was reassessed and updated. Given the rarity of PD and limited high-impact publications, experts submitted their views.

The sensory territory of the lateral cutaneous nerve of the thigh as determined by anatomic dissections and ultrasound-guided blocks.

BACKGROUND AND OBJECTIVES: A femoral block sometimes fails to provide complete sensory anesthesia of the anterior aspect of middle and distal thigh, and a block of the lateral cutaneous nerve of the thigh (LCN) is often necessary to supplement it. The goal of this study was to demonstrate, both in the anatomy laboratory and in the clinical setting, a possible contribution of the LCN to the innervation of the anterior thigh. METHODS: This was a prospective, observational study, including anatomic dissections and a clinical section in which 22 patients received an ultrasound-guided block of the LCN. The resulting area of anesthesia was determined 15 minutes later using pinprick examination. RESULTS: In 1 of 3 thigh dissections, we found a dominant LCN innervating most of the anterior aspect of the middle and distal thigh, areas that are usually attributed to the femoral nerve. In the clinical part of the study, 10 patients (45.5%) developed an area of anesthesia that extended to the medial aspect of the thigh and distally to the patella. CONCLUSIONS: Our results, coming from a small sample, seem to indicate that the LCN may contribute to the innervation of the anterior thigh in some cases. A block of the LCN could be considered when a femoral block has failed to produce the expected area of anesthesia.

Opioid system manipulation during testicular development: resultson sperm production and sertoli cells population / Manipulação do sistema opioidérgico durante o desenvolvimento testicular: consequência sobre a produção espermática e a população de células de sertoli

The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal periodthrough-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1) during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.(AU)

As células de Sertoli têm fundamental importância para o desenvolvimento e manutenção da espermatogênese, bem como possuem uma relação numérica diretamente proporcional com a produção espermática. O período proliferativo destas células em ratos ocorre entre 13 dias pré-natal e 21 dias pós-natal, resultando na definição da população de células de Sertoli nos animais adultos. As células de Leydig podem modular a proliferação das células de Sertoli durante o período fetal e neonatal por meio da -endorfina. A manipulação do sistema opioidérgico durante esta fase pode promover alterações em parâmetros relacionados com o desenvolvimento dos sistemas nervoso, endócrino e reprodutivo. Em virtude disto, o objetivo do presente trabalho foi comparar os efeitos do bloqueio de receptores opioides nas células de Sertoli, utilizando o naltrexone (50 mg kg-1), durante o período proliferativo destas células em ratos Wistar. De acordo com nossos resultados, a manipulação do sistema opioidérgico durante o período pré-natal reduziu o comprimento total de túbulos seminíferos e a população de células de Sertoli em ratos adultos, porém, a produção espermática foi normal pela resposta compensatória desta célula na capacidade de suporte para espermatozoides.(AU)

Opioid system manipulation during testicular development: results on sperm production and sertoli cells population / Manipulação do sistema opioidérgico durante o desenvolvimento testicular: consequência sobre a produção espermática e a população de células de sertoli

The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1) during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.

As células de Sertoli têm fundamental importância para o desenvolvimento e manutenção da espermatogênese, bem como possuem uma relação numérica diretamente proporcional com a produção espermática. O período proliferativo destas células em ratos ocorre entre 13 dias pré-natal e 21 dias pós-natal, resultando na definição da população de células de Sertoli nos animais adultos. As células de Leydig podem modular a proliferação das células de Sertoli durante o período fetal e neonatal por meio da -endorfina. A manipulação do sistema opioidérgico durante esta fase pode promover alterações em parâmetros relacionados com o desenvolvimento dos sistemas nervoso, endócrino e reprodutivo. Em virtude disto, o objetivo do presente trabalho foi comparar os efeitos do bloqueio de receptores opioides nas células de Sertoli, utilizando o naltrexone (50 mg kg-1), durante o período proliferativo destas células em ratos Wistar. De acordo com nossos resultados, a manipulação do sistema opioidérgico durante o período pré-natal reduziu o comprimento total de túbulos seminíferos e a população de células de Sertoli em ratos adultos, porém, a produção espermática foi normal pela resposta compensatória desta célula na capacidade de suporte para espermatozoides.

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations.

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Molecular analyses identified 71 mutant alleles from the probands, nine of which are novel (five missense mutations c.136T > G, c.650C > T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A > G, two deletions c.18_25del and c.2185delC, and one nonsense mutation c.643G > T). Interestingly, the c.1905C > A variant was detected in four unrelated patients and may represent a common Brazilian Pompe mutation. The c.2560C > T severe mutation was frequent in our population suggesting a high prevalence in Brazil. Also, eight out of the 21 infantile-onset patients have two truncating mutations predicted to abrogate protein expression. Of the ten late-onset patients who do not carry the common late-onset intronic mutation c.-32-13T > G, five (from three separate families) carry the recently described intronic mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation c.1781G > C in combination with known severe mutation c.1941C > G. The association of these variants (c.1781G > C and c.-32-3C > A) with late-onset disease suggests that they allow for some residual activity in these patients. Our findings help to characterize Pompe disease in Brazil and support the need for additional studies to define the wide clinical and pathological spectrum observed in this disease.

Miopatias distais: análise clínica, laboratorial, eletromiográfica, histológico-histoquímica de oito casos / Distal myopathies: clinical, laboratorial, electromyographic, histologic-histochemical analysis of 8 cases

As miopatias distais säo entidades raras e de dificil classificaçäo. Descrevemos oito casos de miopatias distais, cinco do sexo masculino e três do feminino, em que o início dos sintomas ocorreu aos 10 anos em cinco e aos 20 em três. O início dos síntomas se deu na musculatura distal dos membros inferiores e a seguir dos membros superiores, posteriormente afetando as porçöes proximais dos quatro membros. As enzimas séricas de origem muscular mostraram discreta elevaçäo em cinco casos, moderada em um e importante em dois. As eletromiografias sugeriram miopatia primária em quatro, desinervaçäo em dois e era de tipo neuromiopático em outro. As biópsias musculares revelaram sinais de envolvimento misto (miopatia e desinervaçäo) em dois casos, miopatia crônica ativa em cinco e miopatia crônica em um. Quatro casos apresentavam vacúolos com conteúdo positivo na fosfatase ácida, em dois do tipo marginado. Seis casos mostraram importante aumento focal da fosfatase ácida sugerindo patogenia com importante participaçäo lisosomal. Dois dos casos foram classificadoscomo miopatia distal autossômica recessiva variante de Welander; dois, como autossômica recessiva tipo Miyoshi; dois, como autossômica recessiva com vacúolos marginados (Myzuzawa e Nonaka); e dois, na classificaçäo de miscelânia