A Retrospective Study of Mucopolysaccharidosis Type II in Brazil - Data from Brazilian Health System (DATASUS)

Abstract Data on Mucopolysaccharidosis type II (MPS II) in Latin America are scarce. This retrospective database study, using data from the Informatics Department of the Brazilian Health System (DATASUS), aimed to estimate the prevalence of MPSII in Brazil from 2008 to 2020 and to describe demographic and clinical profiles from patients under treatment. The study population was derived from DATASUS records of MPS II (ICD-10 E76.1) diagnosed in Brazil. Initially 455 patients were found, but only 181 patients who were receiving idursulfase treatment were included in this study. Among these cases, as expected in a X-linked disease, all were males and 40% of the cases were recorded in the Southeast region, and another 34% in the Northeast region. The biggest proportion of patients (39%) were diagnosed when they were 10-19 years old. There are 212 clinical conditions associated with MPS II, although the main comorbidities related to MPSII include: abdominal/inguinal hernia, respiratory complications, and carpal tunnel syndrome. Respiratory disorders were the fifth most frequent comorbidity recorded in these patients. The healthcare professionals in Brazil more involved in the diagnosis of MPS II were radiologists, followed by geneticists and cardiologists. Despite some limitations, DATASUS is a relevant database to provide information on rare diseases such as MPS II. Most cases were reported in southeast and northeast regions, respectively. This information is crucial to help design targeted public policies.

Histomorphometry of Bone Microarchitecture in Rats Treated with Vitamin D and Bisphosphonate in the Management of Osteoporosis / Histomorfometria da microarquitetura óssea em ratas tratadas com vitamina D e bisfosfonato no manejo da osteoporose

Abstract Objective To verify how the combined administration of alendronate (ALN) and vitamin D3 (VD) acts on the bone microarchitecture in rats with glucocorticoid-induced osteoporosis. Methods The experiment used 32 90-day-old female Wistar rats weighing between 300 and 400g. The induction of osteoporosis consisted of intramuscular administration of dexamethasone at a dose of 7.5 mg/kg of body weight once a week for 5 weeks, except for the animals in the control group. The animals were separated into the following groups: G1 (control group without osteoporosis), G2 (control group with osteoporosis without treatment), G3 (group with osteoporosis treated with ALN 0.2 mg/kg), G4 (group with osteoporosis treated with VD 10,000UI/500μL), and G5 (group with osteoporosis treated with ALN þ VD). The right femurs of the rats were fixed in 10% buffered formaldehyde, decalcified, and processed for inclusion in paraffin. Histological sections were stained with hematoxylin-eosin for histomorphometric analysis. Cortical thickness and medullary cavity were measured in cross-sections. Results There was a statistical difference (p< 0.05) between groups G3 and G5 compared with the positive control group (G2), both related to the measurement of cortical thickness and to the total diameter of the bone. In the evaluation of the spinal area, only the G3 group has shown to be statistically different from the G2 group. Conclusion Concomitant treatment with daily ALN and weekly VD is effective in preventing glucocorticoid-induced bone loss. However, there was no difference between the therapy tested and treatment with ALN alone.

Resumo Objetivo Verificar como a administração conjunta de alendronato de sódio (ALN) e vitamina D3 (VD) atua na microarquitetura óssea em ratas com osteoporose induzida por glicocorticoide. Métodos O experimento utilizou 32 ratas da linhagem Wistar, com peso médio de 300 a 400g, com 90 dias de vida. A indução da osteoporose consistiu na administração de dexametasona na dose de 7,5 mg/kg de peso corporal, por via intramuscular, 1 vez por semana durante 5 semanas, à exceção dos animais do grupo controle. Os animais foram distribuídos nos seguintes grupos: G1 (grupo controle sem osteoporose), G2 (grupo controle com osteoporose sem tratamento), G3 (grupo com osteoporose tratado com ALN 0,2 mg/kg), G4 (grupo com osteoporose tratado com VD 10.000UI/500μL) e G5 (grupo com osteoporose tratado com ALN þ VD). Os fêmures direitos das ratas foram fixados em formol a 10% tamponado, descalcificados e processados para inclusão em parafina. Os cortes histológicos foram corados com hematoxilina-eosina para análise histomorfométrica. A espessura cortical e a cavidade medular foram medidas em cortes transversais. Resultados Houve diferença estatística (p< 0,05) entre os grupos G3 e G5 em relação ao grupo controle positivo (G2), tanto em relação à medida da espessura cortical quanto em relação ao diâmetro total do osso. Na avaliação da área medular, apenas o grupo G3 se mostrou estatisticamente diferente do grupo G2. Conclusão O tratamento concomitante com ALN diário e VD semanal é eficaz para prevenir a perda óssea induzida por glicocorticoide. No entanto, não houve diferença entre esta terapia testada e o tratamento apenas com o ALN.

Clinical and diagnostic aspects of Fabry disease management: a narrative review with a particular focus on Brazilian experts' perspectives

ABSTRACT Research on the genetics, epidemiology, and clinical manifestations of Fabry disease (FD) has increased significantly in recent years. However, some relevant clinical questions still need to be answered to develop better approaches to patient management. This review focuses on answering specific questions raised by Brazilian experts based on their experience in diagnosing and managing patients with FD. The questions are as follows: What is the role of globotriaosylsphingosine in diagnosis? How does one proceed with the diagnosis if there is a variant of unknown significance? What are the earliest and most reliable markers of renal, cardiac, and neurological impairment? What is the prevalence of FD in patients with cryptogenic stroke? What is the average delay in diagnosis in patients with FD? Based on these questions, our objective was to highlight epidemiological, diagnostic, and clinical aspects relating to the literature in the FD field.

Transtorno do espectro autista e a suplementação por ácido fólico antes e durante a gestação / Autism spectrum disorder and folic acid supplementation before and during pregnancy

RESUMO Objetivo Elucidar se a suplementação com ácido fólico pouco antes da concepção e/ou durante a gestação pode estar realmente atrelado ao desenvolvimento do transtorno do espectro autista (TEA). Metódos Foi realizada uma revisão de literatura em base de dados, nos idiomas português e inglês, durante o período de novembro de 2017 até abril de 2018, com ênfase nas publicações mais recentes. Resultados Do total de 174 artigos, 87 compuseram este trabalho. Pesquisas apontam que o aumento dos casos de TEA se deve ao fato de que mais fatores genéticos estejam implicados na etiopatogênese neural. No entanto, a grande maioria dos artigos ressalta com maior precisão que há mais efeitos benéficos do uso de ácido fólico antes da concepção e durante a gestação na prevenção do TEA, assim como de outras anormalidades relacionadas aos defeitos do tubo neural. Conclusão Quando se analisa o risco-benefício da suplementação com ácido fólico nas doses recomendadas, 0,4 a 0,8 mg/dia, conclui-se que os benefícios sobrepujam os possíveis riscos de desenvolver o TEA.

ABSTRACT Objective Elucidating whether supplementation with folic acid shortly before conception and/or during pregnancy may actually be linked to the development of Autistic Spectrum Disorder (ASD). Methods A literature review was conducted in the Portuguese and English languages during the period from November 2017 to April 2018, with emphasis on the most recent publications. Results Of the total of 174 articles, 87 compose this work. Research indicates that the increase in ASD cases should take into account the fact that more genetic factors are implicated in neural pathogenesis. However, a large majority of articles point out that there are more beneficial effects of using folic acid before application and during pregnancy in the prevention of ASD, as well as other abnormalities related to neural tube defects. Conclusion When analyzing the risk-benefit of folic acid supplementation at the recommended doses, 0.4 to 0.8 mg/day, it is concluded that the benefits outweigh the possible risks of developing ASD.

Correlations of condition factor and gonadosomatic, hepatosomatic and lipo-somatic relations of Leptodactylus macrosternum (ANURA: Leptodactylidae) in the Brazilian Semi-arid

ABSTRACT The objective of this study was to assess variations of the condition factor (K1) in relation to the gonadosomatic- RGS and energy reserves (hepatosomatic - RWL and liposomatic - RFB relations) of Leptodactylus macrosternum and their relationship to climate variation in the Northeast of Brazil, Caatinga area, state of Paraiba. The animals were captured fortnightly through active collecting, between January and December 2013. Significant differences were observed in the monthly variations of K1, RGS and RFB indices in male and female L. macrosternum over the months of collection. In males, K1 showed no significant relationship with the other variables. In females, RGS values only show notable correlations with RWF and K1 values. K1 values showed significant correlations with all other weight and length ratios. Climate change in the HFOB region showed significant relationships with the variation of the indexes evaluated, with the exception of RWF. The variation of K1, RGS, RWL and RFB values over the months of collection as well as their relation with the local climatic variation, showed a brief reproductive activity for the species.

Effects of melatonin and prolactin in reproduction: review of literature / Efeitos da melatonina e da prolactina na reprodução: revisão de literatura.

Summary The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

Resumo A glândula pineal é responsável pela produção do hormônio melatonina (MEL), sendo aceita como a glândula reguladora da reprodução em mamíferos. A prolactina (PRL) também exibe atividade reprodutiva em animais, em resposta ao fotoperíodo. Sabe-se que as concentrações de PRL são elevadas durante o verão e baixam durante o inverno, ocorrendo o oposto com os níveis do hormônio melatonina nessas estações. Nos mamíferos placentários, tanto a melatonina quanto a prolactina influenciam a implantação, que é considerada o ponto crítico da gravidez, pois o sucesso da gestação requer o desenvolvimento de uma interação sincronizada entre o endométrio e o blastocisto para o desenvolvimento da placenta. Sabe- -se ainda que os níveis de PRL durante a gestação são essenciais para a manutenção da gravidez, pois esse hormônio induz o corpo lúteo a produzir progesterona, além de estimular a implantação do blastocisto, mantendo a prenhez e o desenvolvimento placentário. Em contrapartida, tem-se demonstrado também que os níveis de melatonina no plasma aumentam durante a gestação, atingindo valores elevados no fim desse período, sugerindo que esse hormônio desempenhe um importante papel na manutenção da gestação. Dessa forma, fica claro que o tratamento com prolactina ou melatonina interfere nos processos responsáveis pelo desenvolvimento e pela manutenção da gestação.