Abstract Background: obesity can influence vitamin D levels, which in turn might be associated with cardiometabolic risk factors. Objectives: this study assessed the association between 25-hydroxyvitamin D [25(OH)D] levels and cardiometabolic risk factors in adolescents with overweight living in a region of northeastern Brazil. Material and methods: a cross-sectional study was carried out by non-probabilistic sampling in adolescents diagnosed with overweight or obesity. The subjects were divided according to their 25(OH) D status into two groups: sufficient vitamin D and hypovitaminosis D. Biodemographic, lifestyle, cardiometabolic, and biochemical factors were evaluated. A logistic regression model was applied to determine the predictors of hypovitaminosis D. Results: we found a high frequency of hypovitaminosis D (45.6 %) in adolescents. Weekly sun exposure was negatively associated with hypovitaminosis D (OR = 0.96; 95 % CI: 0.92-0.99), while significant positive associations were observed between hypovitaminosis D and blood pressure above the 95th percentile (OR = 4.00; 95 % CI: 1.19-13.37), body weight (OR = 1.04; 95 % CI: 1.01-1.07), and fasting insulin (OR = 1.13; 95 % CI: 1.05-1.22). Conclusion: hypovitaminosis D showed a high prevalence in adolescents with overweight living in a sunny region of northeastern Brazil, and cardiometabolic risk factors such as systemic arterial hypertension, high body weight, and hyperinsulinemia are predictors of hypovitaminosis D.

Resumen Introducción: la obesidad puede influir en los niveles de vitamina D, lo que a su vez podría estar asociado con factores de riesgo cardiometabólico. Objetivos: este estudio evaluó la asociación entre los niveles de 25-hidroxivitamina D [25(OH)D] y los factores de riesgo cardiometabólico en adolescentes con sobrepeso que viven en una región del noreste de Brasil. Material y métodos: se realizó un estudio transversal mediante muestreo no probabilístico con adolescentes diagnosticados de sobrepeso u obesidad. Los sujetos se dividieron según su estado de 25(OH) D en dos grupos: suficiente vitamina D e hipovitaminosis D. Se evaluaron factores biodemográficos, de estilo de vida, cardiometabólicos y bioquímicos. Se aplicó un modelo de regresión logística para determinar los predictores de la hipovitaminosis D. Resultados: encontramos una alta frecuencia de hipovitaminosis D (45,6 %) en los adolescentes. La exposición semanal al sol se asoció negativamente a la hipovitaminosis D (OR = 0,96; IC 95 %: 0,92-0,99), mientras que se observaron asociaciones positivas significativas entre hipovitaminosis D y presión arterial por encima del percentil 95 (OR = 4,00; IC 95 %: 1,19-13,37), peso corporal (OR = 1,04; IC del 95 %: 1,01-1,07) e insulina en ayunas (OR = 1,13; IC del 95 %: 1,05-1,22). Conclusión: la hipovitaminosis D mostró una alta prevalencia entre los adolescentes con sobrepeso que viven en una región soleada del noreste de Brasil, y los factores de riesgo cardiometabólico, como hipertensión arterial sistémica, peso corporal elevado e hiperinsulinemia, son predictores de hipovitaminosis D.

Resumo Introdução: As fendas orofaciais não sindrômicas possuem uma etiologia complexa devido à contribuição de fatores de risco genéticos e ambientais, assim como a interação entre eles. Dentre os mais de 15loci de susceptibilidade para as fendas orofaciais não sindrômicas com considerável suporte estatístico e biológico, o IRF6 é o gene mais validado pela maioria dos estudos. Apesar disso, em populações geneticamente heterogêneas como a brasileira, a confirmação da associação entre as fendas orofaciais não sindrômicas e as variantes mais comuns do IRF6 ainda não é um fato consolidado e outras variantes não tão conhecidas IRF6 são pouco investigadas. Objetivo: O objetivo deste estudo foi investigar a associação de variados polimorfismos do IRF6 com o desenvolvimento das fendas orofaciais não sindrômicas em uma população do nordeste do Brasil. Método: Amostras de sangue de 186 pacientes com fendas orofaciais não sindrômicas e 182 controles do estado do Rio Grande do Norte, Brasil, foram obtidas para analisar os polimorfismos do IRF6 (rs2235371, rs642961, rs2236907, rs861019 e rs1044516) por reação em cadeia da polimerase em tempo real. Os pacientes com fendas orofaciais não sindrômicas foram classificados em fenda labiopalatina, fenda palatina isolada e fenda labial isolada. Resultados: As frequências genotípica e alélica do polimorfismo de único nucleotídeo rs2235371 no IRF6 mostraram-se significativamente diferentes em pacientes com fenda palatina isolada quando comparadas às dos controles, enquanto que nenhuma associação foi encontrada entre rs642961, rs2236907, rs861019 e rs1044516 e risco para o desenvolvimento das fendas orofaciais não sindrômicas. Conclusão: A associação encontrada entre rs2235371 e fenda palatina isolada deve ser interpretada com cautela devido ao baixo número de indivíduos investigados, sendo necessários mais estudos com um tamanho amostral maior para confirmar essa associação. Além disso, não foram encontradas associações significativas entre os demais polimorfismos do IRF6 rs642961, rs2236907, rs861019 e rs1044516 e a susceptibilidade às fendas orofaciais não sindrômicas.

Abstract Introduction: Non-syndromic orofacial clefts have a complex etiology due to the contribution from both genetic and environmental risk factors, as well as the interaction between them. Among the more than 15 susceptibility loci for non-syndromic orofacial clefts with considerable statistical and biological support, the IRF6 is the most validated gene by the majority of studies. Nonetheless, in genetically heterogeneous populations such as Brazilian, the confirmation of association between non-syndromic orofacial clefts and IRF6 common variants is not a consolidated fact and unrecognized IRF6 variants are poorly investigated. Objective: The aim of this study was to investigate the association of IRF6 polymorphisms with non-syndromic orofacial clefts development in a population from northeast Brazil. Methods: Blood samples of 186 non-syndromic orofacial clefts patients and 182 controls from Rio Grande do Norte, Brazil, were obtained to analyze IRF6 polymorphisms (rs2235371, rs642961, rs2236907, rs861019, and rs1044516) by real-time polymerase chain reaction. Non-syndromic orofacial clefts patients were classified in cleft lip and palate, cleft palate only and cleft lip only groups. Results: The genotype and allele frequencies of single nucleotide polymorphism rs2235371 in IRF6 showed significant differences in patients with cleft palate when compared to the controls, whereas no association was shown between rs642961, rs2236907, rs861019, and rs1044516 and non-syndromic orofacial clefts. Conclusion: The association found between rs2235371 and isolated cleft palate should be interpreted with caution due to the low number of individuals investigated, and more studies with larger sample size are needed to confirm these association. In addition, there is a lack of association of the rs642961, rs2236907 and rs861019 polymorphisms with non-syndromic orofacial clefts susceptibility.

Diabetes Mellitus (DM) is a metabolic syndrome characterized by hyperglycemia. Chronic complications affect a number of organs, including the lungs. Cissampelos sympodialis Eichl (Menispermaceae) is a plant used to treat respiratory diseases. The aim of this study was to evaluate the effect of Cissampelos sympodialis extract (CSE) in lungs of diabetic rats. We used 30 Wistar rats divided into three groups: control group (CG), diabetic group (DG) and diabetic Cissampelos sympodialis treatment group (DTG). Diabetes was induced by streptozotocin (40 mg/kg i.v.). The CSE (400 mg/kg, po) was administered daily, during four weeks, beginning one week after the onset of DM. The treatment with CSE was not able to reduce blood glucose levels after streptozotocin injection. However, it was able to decrease cholesterol and triglycerides and prevent damage on pancreatic islets morphology. Additionally, morphological alterations such as alveolar septa loss, inflammatory infiltrate and fibrosis were seen in lung tissue of rats with DM, and treatment with CSE apparently reversed these histopathological findings. Thus, CSE treatment reduced the lipid profile and restored the lung architecture of diabetic animals by a mechanism independent of glycemia and which might be associated with the reduction of the damage on the pancreatic islets.

ABSTRACT Objective: The present study has investigated the association between low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism and type 1 diabetes mellitus (T1DM) susceptibility in a Brazilian population. Subjects and methods: A total number of 134 T1DM patients and 180 normoglycemic individuals (NG) aged 6-20 years were studied. Glycated hemoglobin and glucose levels were determined. Genotyping of LRP5 4037C>T (rs3736228) was performed. Results: T1DM patients showed poor glycemic control. Genotypes in the codominant (CT: OR = 2.99 [CI 95%: 1.71-5.24], p < 0.001; TT: OR = 5.34 [CI 95%: 1.05-2702], p < 0.001), dominant (CT + TT: OR = 3.16 [CI 95%: 1.84-5.43], p < 0.001) and log-additive (OR = 2.78 [CI 95%: 1.70-4.52], p < 0.001) models, and LRP5 4037T allele (OR = 2.88, [CI 95%: 1.78-4.77], p < 0.001) were associated with an increased risk of developing T1DM. LRP5 4037CT and CT+TT carriers in T1DM group showed higher concentrations of serum glucose and glycated hemoglobin when compared with CC carriers. Conclusion: The LRP5 4037C>T may represent a candidate for T1DM susceptibility, as well as poor glycemic control.

Abstract: Considering that environmental risk factors substantially contribute to the etiology of orofacial clefts and that knowledge about the characteristics and comorbidities associated with oral clefts is fundamental to promoting better quality of life, this study aimed to describe the risk factors, main characteristics, and comorbidities of a group of patients with cleft lip and/or cleft palate (CL/P) from Rio Grande do Norte (RN), Brazil. Data were obtained from 173 patients with CL/P using a form from the Brazilian database on Orofacial Clefts. Most patients were male with cleft lip and palate and had a normal size and weight at birth; presented few neonatal intercurrent events; and had anemia and respiratory and cardiovascular diseases as main associated comorbidities. They also required timely surgical rehabilitation and multidisciplinary care to stimulate their neuropsychomotor development. In addition, a high frequency of familial recurrence and of parental consanguinity was evidenced in the studied population, especially for the cleft lip and cleft palate type. Other relevant findings were the considerable maternal exposure to alcohol, infections, smoking, and hypertension, as well as low supplementation with vitamins and minerals and deliberate consumption of analgesics, antibiotics, and antihypertensives during pregnancy. Characterization of the CL/P patient profile is essential for the planning of health services and integration among the health professionals involved in the diagnosis and treatment of these malformations. Our results reinforce the need for additional research to confirm the association between environmental factors and the development of orofacial clefts.

ABSTRACT The aim of the present study was to investigate the bone mineral density (BMD) of patients with type 1 Diabetes mellitus (T1DM). We also assessed the association between osteoprotegerin (OPG) genetic polymorphisms and BMD. Genotyping was performed for 1181G>C and 163A>G OPG polymorphisms by allelic discrimination in 119 patients with T1DM and 161 normoglycemic (NG) individuals, aged 6 to 20 years old. Glycemic control, serum parameters of bone metabolism and BMD were evaluated. T1DM patients showed low BMD, poor glycemic control and decreased total calcium values when compared to controls (p < 0.05). For all the polymorphisms studied, the genotype and allele frequencies in patients with T1DM were not significantly different from the controls. In patients with T1DM, carriers of OPG 1181CC showed higher concentrations of ionized calcium compared to patients with GG+GC genotypes. These results suggest that low BMD is associated with poor glycemic control in T1DM. Despite the lack of a detected association between OPG polymorphisms and BMD in these patients, the increased ionized calcium in those carrying OPG 1181CC suggests a possible increase in osteoclastogenesis, a conclusion that may be supported by the lower BMD observed in these subjects.

As metaloproteinases participam do reparo das úlceras venosas de membros inferiores. Até o momento, estudos de atividade enzimática utilizaram, em sua maior parte, biópsia das úlceras. Objetivamos avaliar a viabilidade da mensuração da atividade enzimática de metaloproteinases 2 e 9, extraídas por swab, em amostras de exsudato de úlcera venosa, através de zimografia. O método de processamento da amostra coletada mostrou-se viável, visto que foi possível obter concentração proteica adequada para análise. Através de zimografia, observamos que as quantidades de proteína total das amostras carregadas nos géis entre 0,125 e 0,5 μg, além do tempo de ativação enzimática de 19 horas (a 37 °C), foram parâmetros adequados e de melhor resultado para a análise da atividade gelatinolítica. A coleta através de swab mostrou-se um método simples, rápido e eficaz para a coleta de fluido de úlcera venosa com o objetivo de mensuração da atividade gelatinolítica com grau mínimo de invasividade.

Metalloproteinases play a role in repair of venous ulcers of the lower limbs. The great majority of studies of metalloproteinase enzyme activity conducted to date have employed material from biopsies of ulcers. We evaluated the viability of using zymography to measure the enzyme activity of metalloproteinases 2 and 9 in samples of venous ulcer exudate collected on swabs. The method chosen for processing the samples proved viable in terms of its ability to provide adequate protein concentrations for analysis. Using zymography, we observed that the parameters that provided the best results for analysis of gelatinolytic activity were 0.125 to 0.5 μg of total protein content in the gels and enzymatic activation time of 19 hours (at 37 °C). Collection of venous ulcer fluid using swabs proved to be a simple, rapid and effective method for obtaining samples for measurement of gelatinolytic activity with a minimum degree of invasivity.

A relação entre peroxidação lipídica, defesa antioxidante e osteopenia diabética permanece obscura. Este estudo avaliou a associação entre índice de peroxidação lipídica, parâmetro de defesa antioxidante e metabolismo ósseo em um modelo diabético pré-menopausa através de medidas como a concentração de substâncias reativas ao ácido tiobarbitúrico (SRAT) e conteúdo de glutationa reduzida (GSH) no homogenato cerebral, análises histomorfométricas, teste biomecânico e densidade mineral óssea (DMO). Ratos Wistar fêmeas com ciclo estral regular foram distribuídos em dois grupos: Grupo 1 - ratas controle (n = 15) e Grupo 2 - ratas diabéticas (n = 15). O diabetes foi induzido pela aloxana e confirmado pela glicemia >250 mg/dL. O índice de peroxidação lipídica, medido pela concentração de SRAT, demonstrou um aumento significativo (p<0.05) nos animais diabéticos, em relação aos animais controle. Entretanto, o parâmetro de defesa antioxidante, mensurado pelo conteúdo de GSH, foi reduzido significativamente (p<0.05) nos animais diabéticos. As análises histomorfométricas mostraram um aumento significativo (p<0.05) da separação trabecular do fêmur, associado à diminuição significativa da espessura trabecular (p<0.05) e volume ósseo trabecular reduzido nas ratas diabéticas. Além disso, o teste biomecânico, medido pela força máxima, e valores de DMO foram reduzidos significativamente (p<0.05) no grupo diabético. Dessa maneira, nossos resultados demonstraram que a peroxidação lipídica aumentada e defesa antioxidante modificada podem estar relacionadas ao desenvolvimento do estresse oxidativo e osteopenia diabética em ratas pré-menopausadas.

The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship among lipid peroxidation index, antioxidant defense parameters and bone metabolism in a premenopausal diabetic model using measures including thiobarbituric acid-reactive substances concentration (TBARS) and reduced glutathione (GSH) content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD). Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15) and Group 2: diabetic rats (n = 15). Diabetes was induced by alloxan and confirmed by glycemia >250 mg/dL. The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (p<0.05) in diabetic animals in comparison to control animals. However, the antioxidant parameter measured by GSH content, was significantly lower (p<0.05) in diabetic animals. Histomorphometric analysis showed a significant increase (p<0.05) in femoral trabecular separation together with a significant decrease (p<0.05) in trabecular thickness, and reduced trabecular bone volume in diabetic rats. Moreover, biomechanical testing and BMD values were significantly lower (p<0.05) in the diabetic group. Thus, our results demonstrated that increased lipid peroxidation and altered antioxidant defense could be related to the development of oxidative stress and diabetic osteopenia in premenopausal rats.

OBJETIVO: avaliar o efeito do tamoxifeno no perfil lipídico e renal de ratos controles e diabéticos. MÉTODOS: Foram utilizados 40 ratos fêmeas Wistar (180-220g peso corporal), divididos randomicamente em 4 grupos: C (n=10, receberam veículo), T (n=10, tratados com tamoxifeno, 0,3mg/kg/dia), D (n=10, diabéticos induzidos por estreptozotocina, 45mg/Kg) e DT (n=10, diabéticos tratados com tamoxifeno). Foram dosados os analitos, glicose, colesterol total, triglicérides, proteínas totais, albumina, uréia e creatinina utilizando Kits Labtest através do analisador Cobas Mira (Alemanha,1996). RESULTADOS: o grupo T apresentou diminuição do colesterol total e triglicérides em relação ao C, e o grupo D um aumento em relação aos demais. Para as proteínas totais foi observado um aumento no Grupo T em relação ao C. A albumina diminuiu nos grupos D e DT em relação aos grupos C e T. Nos níveis de uréia houve um aumento no grupo D e DT em relação aos grupos C e T. CONCLUSÃO: Em relação ao perfil lipídico foi constatado que durante o período de 60 dias o tratamento com tamoxifeno promoveu uma diminuição dos níveis séricos de colesterol e triglicérides, mesmo associado a condição de Diabetes mellitus.

OBJECTIVE: To evaluate the effect of tamoxifen in the lipidic and renal profile in diabetic and control rats. METHODS: 40 female Wistar rats had been used (180-220g corporal weight), divided randomly in 4 groups: C (n=10, received vehicle), T (n=10, treated with tamoxifen, 0.3mg/kg/day), D (n=10, diabetic induced by streptozotocin, 45mg/Kg) and DT (n=10, diabetic treated with tamoxifen). Glucose, total cholesterol, triglyceride, total proteins, albumin, urea and creatinin were analyzed using Labtest Kits through the Cobas Mira analyzer (Germany, 1996). RESULTS: Group T presented a reduction of total cholesterol and triglyceride in relation to C, and group D an increase in relation to the other ones. About the total proteins it was observed an increasing in Group T in relation to C. The albumin diminished in groups D and DT in relation to C and T. The urea levels increased in groups D and DT in relation to C and T. CONCLUSION: In relation to the lipidic profile it was evidenced that during the period of 60 days the treatment with tamoxifen promoted a reduction in cholesterol and triglyceride levels in the serum, even associated to the condition of Diabetes mellitus.

OBJETIVO: Estudo comparativo foi realizado entre a bolsa jejunal de Fernando Paulino (FP) e uma bolsa jejunal (JP) interposta entre o esôfago e duodeno, para substituir o estômago após gastrectomia . Foi investigado o efeito dos dois procedimentos na histologia do esôfago, estado nutricional e gastrinemia sérica em ratos. MÉTODOS: Quarenta e seis ratos Wistar pesando 282±17g foram aleatoriamente submetidos a sham operation (S), FP e JP após gastectomia total. Decorridas 8 semanas, foi colhido sangue por punção cardíaca para dosagem de proteínas totais, albumina, ferro, transferrina, folato, cobalamina, calcio, e gastrina. Os animais receberam dose letal de anestésico e tecido do esôfago terminal foi retirado para histologia. Foi observada a mortalidade operatória dos animais. RESULTADOS: Quarenta e seis ratos foram operados e 30 sobreviveram por 8 semanas. Cinco (33,3 %) morreram após FP e 11 (52,3%) após JP (p<0.05). Esophagitis pós-operatória ocorreu em 6 ratos JP. Na 8ª semana o peso corporal foi maior nosratos submetidos a FP do que JP (p>0.05). Os ratos submetidos a JP tiveram uma diminuição significativa na albumina, glucose, transferrina, ferro, folato e cálcio, comparado com o sham (p<0.05). Os níveis de gastrina sérica, ferro e calcio mostraram-se significantemente maiores nos ratos submetidos a JP do que nos FP (p<0.05). Nos ratos FP a transferrina e a cobalamina estiveram significantemente diminuídas comparando-se os níveis do pré-operatório com a 8ª semana (p<0.05). CONCLUSÃO: A bolsa jejunal de F. Paulino, em ratos, resultou em mortalidade operatória e incidência de esofagite de refluxo menor do que a interposição de JP. A JP não afetou a dosagem sérica de gastrina, ferro e cálcio, provavelmente devido à preservação da passagem dos alimentos pelo duodeno.

PURPOSE: A comparison was done between the F. Paulino jejunal pouch (FP) and a jejunal pouch (JP) as esophagus-duodenum interpositional graft, for replacing the stomach after total gastrectomy. It was investigated the effect of the two procedures on esophagus histology, nutritional state and serum gastrin in rats. METHODS: Male Wistar rats weighing 282±17g were randomly submitted to sham operation (S), FP and JP after total gastrectomy. After eight weeks the rats were killed with overdose of anesthetic and tissue was taken from the distal esophagus for histology. Serum levels of total proteins, albumin, iron, transferring, folate, cobalamine, calcium, as well as serum gastrin were determined. Survival was considered. RESULTS: Fourty six rats were operated and thirty survived for eight weeks. Five (33.3%) died after FP and 11 (52.3%) after JP (p<0.05). Postoperative esophagitis occurred in 6 JP rats. At 8th week, no difference was observed on body weight when compared FP and JP rats (p>0.05). The JP rats had a significant decrease in serum albumin, glucose, transferrin, iron, folate and calcium, compared to sham (p<0.05). Serum gastrin, iron and calcium were significantly higher in JP rats than in FP rats (p<0.05). In FP rats, transferrin and cobalamine showed significant decrease comparing the preoperative with 8th week levels (p<0.05). CONCLUSION: F. Paulino pouch in rats had lower mortality than JP, and esophagitis was not detected in it. JP rats had serum gastrin, iron and calcium unaffected, possibly because of preservation of duodenal passage.