Resumo Atrofia muscular espinhal ligada ao cromossomo 5 (AME-5q) é uma doença genética de herança autossômica recessiva causada por mutações no gene SMN1. A AME-5q cursa com degeneração progressiva dos motoneurônios medulares e bulbares, acarretando grave comprometimento motor e respiratório com redução da sobrevida, especialmente nas suas formas clínicas mais graves. Nos últimos anos, terapias modificadoras da doença altamente eficazes, ou que atuam regulando o splicing do exon 7 do gene SMN2 ou adicionando uma cópia do gene SMN1 via terapia gênica, têm surgido, proporcionando uma mudança drástica na história natural da doença. Dessa forma, o desenvolvimento de guias terapêuticos e de consensos de especialistas torna-se importante no sentido de direcionar o uso dessas terapias na prática clínica. Este consenso, preparado por especialistas brasileiros, teve como objetivos revisar as principais terapias modificadoras de doença disponíveis, analisar criticamente os resultados dos estudos clínicos dessas terapias e prover recomendações para seu uso na prática clínica para pacientes com AME-5q. Aspectos relativos ao diagnóstico, aconselhamento genético e seguimento dos pacientes em uso das terapias também são abordados nesse consenso. Assim, esse consenso promove valiosas informações a respeito do manejo atual da AME-5q auxiliando decisões terapêuticas na prática clínica e promovendo ganhos adicionais nos desfechos finais. AME5q AMEq AME 5q q (AME-5q SMN bulbares sobrevida graves anos eficazes gênica surgido forma tornase torna se brasileiros disponíveis AME5q. 5q. diagnóstico Assim finais

Abstract Spinal muscular atrophy linked to chromosome 5 (SMA-5q) is an autosomal recessive genetic disease caused by mutations in the SMN1. SMA-5q is characterized by progressive degeneration of the spinal cord and bulbar motor neurons, causing severe motor and respiratory impairment with reduced survival, especially in its more severe clinical forms. In recent years, highly effective disease-modifying therapies have emerged, either acting by regulating the splicing of exon 7 of the SMN2 gene or adding a copy of the SMN1 gene through gene therapy, providing a drastic change in the natural history of the disease. In this way, developing therapeutic guides and expert consensus becomes essential to direct the use of these therapies in clinical practice. This consensus, prepared by Brazilian experts, aimed to review the main available disease-modifying therapies, critically analyze the results of clinical studies, and provide recommendations for their use in clinical practice for patients with SMA-5q. This consensus also addresses aspects related to diagnosis, genetic counseling, and follow-up of patients under drug treatment. Thus, this consensus provides valuable information regarding the current management of SMA-5q, helping therapeutic decisions in clinical practice and promoting additional gains in outcomes. SMA5q SMAq SMA 5q q (SMA-5q SMN neurons survival forms years diseasemodifying modifying emerged therapy way experts studies SMA5q. 5q. diagnosis counseling followup follow up treatment Thus SMA5q, 5q, outcomes

Abstract INTRODUCTION: Chagas disease (CD) is an important public health problem in Brazil and worldwide. Aging and obesity are important matters in patients with CD, as is hypovitaminosis D3, which can decrease the quality of life of these patients. Immunomodulation mediated by vitamin D3, especially the production of antimicrobial peptides such as cathelicidin LL-37, might be related to the severity and symptoms of CD. This study aimed to determine the serum levels of vitamin D and LL-37 and VDR gene polymorphisms in patients with chronic CD. METHODS: This study included male patients with cardiac and indeterminate clinical forms of CD. Clinical, anthropometric, and blood parameters were obtained. Serum levels of 25(OH)D3 and LL-37 were determined by chemiluminescence and enzyme-linked immunosorbent assay respectively. Fok (rs731236), Bsm (rs1544410), Apa (rs7975232), and Taq (rs731236) polymorphisms of the VDR gene were investigated by PCR-RFLP. RESULTS: Sixty-four patients were included in the study: 18 of the cardiac form and 46 of the indeterminate form. No differences in age, ethnicity, BMI, arterial hypertension, diabetes mellitus, or dyslipidemias were observed between groups. However, the serum levels of 25(OH)D3, but not of LL-37, were lower in the cardiac form group. The association among polymorphisms, vitamin D, and clinical form was not significant. CONCLUSIONS: Decreased levels of vitamin D suggest an association with the cardiac form of CD. Studies investigating the roles of vitamin D and LL-37 in the immune response and their associations with VDR polymorphisms and disease susceptibility are necessary.

Abstract Background: Background: Tuberculosis (TB) is an infectious lung disease with high worldwide incidence that severely compromises the quality of life in affected individuals. Clinical tests are currently employed to monitor pulmonary status and treatment progression. The present study aimed to apply a three-dimensional (3D) reconstruction method based on chest radiography to quantify lung-involvement volume of TB acute-phase patients before and after treatment. In addition, these results were compared with indices from conventional clinical exams to show the coincidence level. Methods: A 3D lung reconstruction method using patient chest radiography was applied to quantify lung-involvement volume using retrospective examinations of 50 patients who were diagnosed with pulmonary TB and treated with two different drugs schemes. Twenty-five patients were treated with Scheme I (rifampicin, isoniazid, and pyrazinamide), whereas twenty-five patients were treated with Scheme II (rifampicin, isoniazid, pyrazinamide, and ethambutol). Acute-phase reaction: Serum exams included C-reactive protein levels, erythrocyte sedimentation rate, and albumin levels. Pulmonary function was tested posttreatment. Results: We found strong agreement between lung involvement and serum indices pre- and posttreatment. Comparison of the functional severity degree with lung involvement based on 3D image quantification for both treatment schemes found a high correlation. Conclusions: The present 3D reconstruction method produced a satisfactory agreement with the acute-phase reaction, most notably a higher significance level with the C-reactive protein. We also found a quite reasonable coincidence between the 3D reconstruction method and the degree of functional lung impairment posttreatment. The performance of the quantification method was satisfactory when comparing the two treatment schemes. Thus, the 3D reconstruction quantification method may be useful tools for monitoring TB treatment. The association with serum indices are not only inexpensive and sensitive but also may be incorporated into the assessment of patients during TB treatment.

RESUMO O objetivo do estudo foi avaliar os efeitos da desnutrição protéico-calórica em camundongos isogênicos da linhagem BALB/c inoculados com Lacazia loboi, empregando parâmetros nutricionais e histopatológicos. Foram constituídos quatro grupos: G1- inoculados com restrição dietética; G2- não inoculados com restrição dietética; G3- inoculados sem restrição dietética; G4- não inoculados sem restrição dietética. Após instalada a desnutrição, os animais foram inoculados via intradérmica no coxim plantar e após quatro meses foram sacrificados para remoção do coxim plantar, fígado e baço. A infecção não exerceu grande influência no peso corporal dos camundongos. O peso do fígado e baço apresentou redução nos grupos desnutridos em comparação aos grupos nutridos. A lesão macroscópica, a viabilidade e o número total de fungos dos coxins plantares dos camundongos inoculados revelaram aumento no G3 quando comparado com o G1. Em relação à análise histopatológica dos coxins plantares observou-se aumento da celularidade global na composição do granuloma no G3 em relação ao G1, com grande número de macrófagos e células gigantes multinucleadas, discretos números de linfócitos estavam presentes em G3 e aumentados no G1. Os resultados sugerem que existe grande interação entre nutrição e doença de Jorge Lobo.

SUMMARY The aim of this study was to evaluate the effects of the protein-calorie malnutrition in BALB/c isogenic mice infected with Lacazia loboi, employing nutritional and histopathological parameters. Four groups were composed: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. Once malnutrition had been imposed, the animals were inoculated intradermally in the footpad and after four months, were sacrificed for the excision of the footpad, liver and spleen. The infection did not exert great influence on the body weight of the mice. The weight of the liver and spleen showed reduction in the undernourished groups when compared to the nourished groups. The macroscopic lesions, viability index and total number of fungi found in the footpads of the infected mice were increased in G3 when compared to G1. Regarding the histopathological analysis of the footpad, a global cellularity increase in the composition of the granuloma was observed in G3 when compared to G1, with large numbers of macrophages and multinucleated giant cells, discrete numbers of lymphocytes were present in G3 and an increase was observed in G1. The results suggest that there is considerable interaction between Jorge Lobo's disease and nutrition.

AbstractBackground Jorge Lobo’s disease, also known as lacaziosis, is a cutaneous-subcutaneous mycosis with chronic evolution. It is caused by the fungus Lacazia loboi. Herein we report a study that relates the genotoxicity caused by L. loboi in isogenic mice with nutritional status, through a normal or restricted diet.Methods DNA damage was assessed in the peripheral blood by the comet assay (tail intensity).Results The results for leukocytes showed increases in the mean tail intensity in mice under dietary restriction, in infected mice under dietary restriction and in infected mice ingesting a normal diet.Conclusion These results indicate that dietary restriction and L. loboi infection may increase DNA damage levels in mice, as detected by the comet assay.

Introduction Visceral leishmaniasis (VL) is caused by the intracellular protozoan Leishmania donovani complex. VL may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. The nutritional status of the patients with VL is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. Changes in lipoproteins and plasma proteins may have major impacts in the host during infection. Thus, our goal was evaluate the serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose, albumin, globulin and total protein levels, as well as the body composition, of VL patients before and after treatment. Methods Nutritional evaluation was performed using the bioelectrical impedance analysis (BIA) to assess body composition. Biochemical data on the serum total cholesterol, HDL, LDL, triglycerides, glucose, albumin, globulin and total protein were collected from the medical charts of the patients. Results BIA indicated that both pre-treatment and post-treatment patients exhibited decreased phase angles compared to the controls, which is indicative of disease. Prior to treatment, the patients exhibited lower levels of total body water compared to the controls. Regarding the biochemical evaluation, patients with active VL exhibited lower levels of total cholesterol, HDL, LDL and albumin and higher triglyceride levels compared to patients after treatment and the controls. Treatment increased the levels of albumin and lipoproteins and decreased the triglyceride levels. Conclusions Our results suggest that patients with active VL present biochemical and nutritional changes that are reversed by treatment.

This study isolated and quantified intestinal bacteria of children with cleft palate before and after palatoplasty. A prospective study was conducted from May 2007 to September 2008 on 18 children with cleft palate, aged one to four years, of both genders, attending a tertiary cleft center in Brazil for palatoplasty, to analyze the effect of surgical palate repair on the concentration of anaerobes Bacteroides sp, Bifidobacterium sp and microaerophiles Lactobacillus sp in feces of infants with cleft palate before and 24 hours after treatment with cefazolin for palatoplasty. There was significant reduction of Lactobacillus sp (p < 0.002), Bacteroides sp (p < 0.001) and Bifidobacterium sp (p = 0.021) after palatoplasty, revealing that surgery and utilization of cefazolin significantly influenced the fecal microbiota comparing collections before and after surgery. However, due to study limitations, it was not possible to conclude that other isolated factors, such as surgical stress, anesthetics and other medications used in palatoplasty might have a significant influence on the microbiota. Considering the important participation of the intestinal microbiota on both local and systemic metabolic and immunological activities of the host, professionals should be attentive to the possible influence of these changes in patients submitted to cleft repair.

RESUMO Este estudo teve como objetivo estimar o número de casos de reações sorológicas não-negativas para doença de Chagas em doadores de sangue do Hemocentro de Botucatu, São Paulo - Brasil de 2003 a 2010 e, relaciona-las com as suas cidades de origem. Quinhentos e setenta e quatro reações sorológicas não-negativas para doença de Chagas foram avaliados. Destes, 371 eram reagentes (64,8%), e 203 inconclusivos (35,4%). A prevalência da doença de Chagas nos doadores de sangue foi de 0,05%. Houve, em média, 72 casos/ano, e uma prevalência do sexo masculino foi observada (64,8%). Quarenta e três indivíduos (7,49%) tinham entre 18 e 30 anos, 92 (16,02%) de 31 a 40; 147 (25,61%) 41 a 50, e 292 (50,87%) tinham mais de 50 anos. Observou-se que 29.3% das mulheres com sorologia reagente estavam em idade fértil (18 e 45 anos). A maioria dos doadores eram naturais de cidades das regiões sudoeste e central da cidade de São Paulo, mas os indivíduos de outros estados contribuíram com 20%. A procedência da maioria dos doadores era a cidade de Botucatu/SP, seguido pela cidade de Taquarituba/SP. Portanto, o perfil de doadores de sangue neste hemocentro favorece a ocorrência de um número maior de reações sorológicas não-negativas. Embora tenha havido uma redução significativa no número de casos novos/ano para esta doença, ainda é um problema de saúde pública, e os resultados sugerem a necessidade de novas avaliações epidemiológicas na região estudada.

SUMMARY This study aimed at estimating the number of cases of non-negative serological reactions to Chagas disease in blood donors at the Blood Center of Botucatu, São Paulo, Brazil, from 2003 to 2010 and at relating them to their cities of origin. Five hundred and seventy-four non-negative results for Chagas disease were evaluated. Of these, 371 (64.8%) were reagent, and 203 (35.4%) were inconclusive. The prevalence of Chagas disease in blood donors was 0.05%. There were, on average, 72 cases/year, and a prevalence of males was observed (64.8%). Forty-three (7.49%) individuals were 18 to 30 years old; 92 (16.02%) were 31 to 40; 147 (25.61%) 41 to 50, and 292 (50.87%) were older than 50 years. It was observed that 29.3% of females with reagent serology were at their fertile age (18 and 45 years). The majority of donors were originally from cities in the southwestern and central regions of São Paulo, but individuals from other states contributed with 20%. The provenance of most donors was the city of Botucatu/SP, followed by the city of Taquarituba/SP. Therefore, the profile of donors at this blood center favors the occurrence of a larger number of non-negative serological reactions. Although there has been a significant reduction in the number of new cases/year for this disease, it is still a public-health problem, and results suggest the need for new epidemiological assessments in the studied region.

Chagas disease (CD), also known as American trypanosomiasis, is caused by the flagellated protozoan Trypanosoma cruzi, and affects an estimated 8 to 10 million people worldwide. In Latin America, 25 million people live in risk areas, while in 2008 alone, 10,000 CD-related deaths were reported. This review aimed to evaluate the challenges of CD control, future perspectives, and actions performed worldwide to control expansion of the disease and its impact on public health in Latin America.

Neste trabalho, foi determinada a estrutura da variabilidade espacial da emissão de CO2, temperatura e umidade de solos desprovidos de vegetação em duas localidades sob cultivo da cana-de-açúcar, em sistemas de manejos de cana crua e de cana queimada, no nordeste do Estado de São Paulo. A emissão de CO2 e a temperatura do solo foram registradas utilizando-se de câmara de fluxo portátil e sensor de temperatura do sistema LI-6400. A umidade foi avaliada utilizando sistema portátil TDR. A maior emissão foi observada no local sob manejo de cana queimada, com valor médio de 2,05 μmol m-2 s-1, porém a dependência espacial na emissão de CO2 foi encontrada somente na área sob manejo de cana crua. Os mapas de krigagem da emissão de CO2, temperatura e umidade do solo sob manejo de cana queimada mostraram correspondência à declividade do terreno, com as maiores emissões e temperaturas localizadas na parte mais alta, sendo as maiores umidades do solo encontradas na parte mais baixa do local estudado. Os resultados indicam correlação linear positiva da emissão de CO2 com a temperatura, e negativa com a umidade do solo somente no local com manejo de cana queimada, e não no sistema de cana crua, onde a presença de palhada certamente impede a ação direta da radiação solar e o escoamento de chuvas.

In this work, it was determined the spatial variability structure of soil CO2 emission, the temperature and the soil moisture in two locations currently cultivated with sugar cane and submitted to different management systems: slash/burn and no-till, in the northeast of São Paulo State. The soil CO2 emission and the soil temperature were registered by using a portable chamber and a temperature sensor of LI-6400 system. Soil moisture was measured by a portable TDR system. The highest emission was observed in the slash and burn plot, with an average value of 2.05 μmol m-2 s-1, but spatial variability structure was observed just for the CO2 emission under the no-till management systems. In the slash and burn system, the kriging maps of soil CO2 emission, the temperature and the moisture shown to be related to the land declivity, as the higher emissions and temperatures were located in the highest level, and the smaller moisture values located in the lowest parts of the studied area. Results indicate a positive linear correlation between soil emission and temperature and also a negative correlation regarding soil moisture, for the slash and burn plot only, but not in the no-till plots, where crop residues were left in soil surface and certainly modified the direct incidence of the solar radiation and the action of rain drainage.

Avaliar a microbiota intestinal de indivíduos que sofreram acidente ocupacional com materiais biológicos e receberam anti-retrovirais foi o objetivo deste estudo. O grupo de estudo constou de 23 indivíduos com idade entre 18-45 anos, sendo 13 doadores de sangue e 10 que sofreram acidente ocupacional. Foram avaliados a microbiota intestinal, antropometria e exames laboratoriais pré, pós e 30 dias após o término da medicação. Zidovudina mais lamivudina foi utilizada em 70% dos indivíduos associado ao nelfinavir, 20% ao efavirenz e 10% ao ritonavir. As alterações nutricionais e dietéticas-laboratoriais e de microbiota intestinal foram analisadas em três momentos. M1: até dois dias do início da profilaxia; M2: no último dia da profilaxia e M3: 30 dias após o término da profilaxia. Náuseas, vômitos e diarréia estiveram presentes em 50% no segundo momento do estudo. Sobrepeso em 70%, desnutrição e eutrofia em 10%, dos indivíduos, não se modificaram durante o estudo. Transaminases, triglicérides, LDL-colesterol se elevaram no segundo momento e normalizaram 30 dias após término da medicação. Houve redução significativa dos Lactobacillus, Bifidobacterium e Bacteróides nos três momentos. Uso de anti-retrovirais provocou impacto significativo na microbiota intestinal dos indivíduos, sem recuperação em 30 dias.

The aim of this study was to evaluate the intestinal microbiota of individuals who had suffered occupational accidents and had received antiretrovirals. The study group consisted of 23 individuals between 18 and 45 years old, of whom 13 were blood donors and 10 had suffered occupational accidents. Intestinal microflora, anthropometry and laboratory tests were evaluated before, after and 30 days after discontinuation of the medication. Zidovudine plus lamivudine was used in association with nelfinavir for 70% of the individuals, with efavirenz for 20% and with ritonavir for 10%. Nutritional, diet, laboratory and intestinal microbiota abnormalities were analyzed at three times: M1, not more than two days after starting prophylaxis; M2, on the last day of prophylaxis; and M3, 30 days after ending prophylaxis. Nausea, vomiting and diarrhea were present in 50% at M2. Overweight in 70%, malnutrition and eutrophy in 10% of the individuals remained unchanged during the study. Transaminases, triglycerides and LDL-cholesterol because elevated at M2 and normalized 30 days after discontinuation of the medication. There were significant reductions in Lactobacillus, Bifidobacterium and Bacteroides at the three times. The use of antiretrovirals caused a significant impact on the individuals’ intestinal microbiota, without recovery after 30 days.

Chagas disease (CD), caused by the protozoan Trypanossoma cruzi, affects approximately 18 million individuals in the Americas, 5 million of which live in Brazil. Most chronic sufferers have either the indeterminate form of the disease, without organic compromise, or the cardiac or digestive forms. Despite the importance of this disease, there is no information on the effect of nutrition on CD evolution. We evaluated the clinical-nutritional profile of individuals with CD treated at the Tropical Diseases Nutrition Out-Patient Clinic of the Botucatu School of Medicine, UNESP. A retrospective cohort study was performed between 2002 and 2006, on 66 patients with serum and parasitological diagnosis of CD. Epidemiological, clinical, nutritional, and biochemical data were collected, including gender, age, skin color, smoking, alcoholism, physical activity, weight, stature, body mass index, abdominal circumference, glycemia, and lipid profile. Fifty-three percent were male and 47% female; 96% were white skinned. Mean age was 49.6±6.36 years. The predominant form was indeterminate in 71%; smoking and drinking were recorded in 23% and 17%, respectively. Sedentariness predominated in 83%, and 55% presented increased abdominal circumference. Most, 94%, were overweight or obese. The biochemical exams revealed hyperglycemia in 12% and dyslipidemia in 74%. These findings suggest that the Chagas population presents co-morbidities and risk factors for developing chronic non-transmissible diseases, including cardiovascular diseases, making CD evolution even worse.

The use of highly active antiretroviral therapy (HAART) in HIV-infected patients has been associated with the development of risk factors for cardiovascular diseases (CD) including dyslipidemia and insulin resistance, hypertriglyceridemia being the most frequent metabolic disturbance in these patients. Fibrates are indicated when hypertriglyceridemia is accentuated and persists for over six months. We evaluated the efficacy and safety of bezafibrate for the treatment of hypertriglyceridemia in HIV-infected individuals on HAART. All patients received 400mg/day of bezafibrate and were evaluated three times: Mo (pre-treatment), M1 (one month after treatment), and M2 (six months after treatment). Fifteen adult individuals, eight males and seven females with mean age = 41.2 ± 7.97 years and triglyceride serum levels > 400mg/dL were included in the study. Smoking, alcohol ingestion and sedentarism rates were 50%, 6.66% and 60%, respectively. Family history of CD, hypertension and diabetes mellitus was reported in 33.3%, 40% and 46.7% of the cases, respectively, while dyslipidemia was reported by only 13.3%. More than half of the patients were using a protease inhibitor plus a nucleotide analog transcriptase inhibitor. Eutrophy and tendency toward overweight were observed at all three study time points. There were significant reductions in triglyceride serum levels from Mo to M1 and from Mo to M2. No significant changes were observed in the serum levels of creatine phosphokinase, hepatic enzymes, CD4+, CD8+ and viral load. Therefore, bezafibrate seems to be safe and effective for the reduction of hypertriglyceridemia in HIV-infected patients on HAART.

The intestinal tract harbors a huge diversity of metabolically-active aerobic and anaerobic bacteria that interact, forming a complex ecosystem. This microbiota has an important role in human metabolism, nutrition, immunity, and protection against colonization by pathogenic microorganisms. Several factors can influence the intestinal microbiota; these include age, diet, inflammatory and infectious processes, and the use of antimicrobials. We investigated the influence of bacterial infection of the respiratory tract and of amoxicillin therapy on the normal intestinal microbiota of patients. Bacterial infectious processes affecting the respiratory tract were found to influence the intestinal microbiota, significantly decreasing the number of colony-forming units (CFUs) of Bacteroides spp. and Lactobacillus spp. per gram of feces. The use of amoxicillin also influenced the intestinal microbiota, significantly decreasing the CFU of Bifidobacterium spp. and Lactobacillus spp. /g of feces. Changes in the composition of the intestinal microbiota need to be observed, since a decrease in the normal microorganisms can pose a number of hazards for hosts, including decreased resistance to colonization. With proper follow-up, health-care teams can minimize such hazards by implementing suitable therapy- and diet-related measures, thus reducing the occurrence of detrimental effects on the gastrointestinal ecosystem.

Foram avaliadas a função plaquetária e os níveis séricos de fibrinogênio em 14 doentes picados por serpentes do gênero Bothrops, sendo 10 do sexo masculino e 4 do sexo feminino, com idades compreendidas entre 13 e 59 anos. Houve diferença estatística (p < 0,05) entre os níveis séricos defibrinogênio avaliados 24 e 48 horas após o acidente. Houve tendência à normalização após 48 horas do tratamento. A plaquetopenia foi evidente nas avaliações de 24 e 48 horas. Houve tendência à nomalização no 8o dia após o tratamento (p <0,05). Os níveis de produtos de degradação defibrina (PDF) mostraram-se alterados em 83,33 % dos pacientes avaliados. Os autores sugerem que a hipoagregação esteja relacionada com níveis baixos de fibrinogênio e elevados de PDF.

Platelet function and plasma fibrinogen levels were evaluated in 14 patients, 10 males and 4females, aged 13-59years bitten by Bothrops genus snakes. There was a statistical difference (p < 0.05) among plasma fibrinogen levels evaluated 24 and 48 hours after envenomation. There was a tendency towards normalization after 48 hours of treatment. The low platelet number was clear in 24-48 hour evaluations with a tendency towards normalization after 48 hours of treatment (p<0.05). Fibrinogen levels and fibrin degradation product (FDP) levels appeared to be altered in 83.33% of patients evaluated. The authors suggest that platelet hypoaggregation is related to decreased fibrinogen and increased FDP levels.</