Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil.

Tetrahydrobiopterin (BH4) is a cofactor that participates in the biogenesis reactions of a variety of biomolecules, including l-tyrosine, l-3,4-dihydroxyphenylalanine, 5-hydroxytryptophan, nitric oxide, and glycerol. Dihydropteridine reductase (DHPR, EC 1.5.1.34) is an enzyme involved in the BH4 regeneration. DHPR deficiency (DHPRD) is an autosomal recessive disorder, leading to severe and progressive neurological manifestations, which cannot be exclusively controlled by l-phenylalanine (l-Phe) restricted diet. In fact, the supplementation of neurotransmitter precursors is more decisive in the disease management, and the administration of sapropterin dihydrochloride may also provide positive effects. From the best of our knowledge, there is limited information regarding DHPRD in the past 5 years in the literature. Here, we describe the medical journey of the first patient to have DHPRD confirmed by molecular diagnostic methods in Brazil. The patient presented with two pathogenic variants of the quinoid dihydropteridine reductase (QDPR) gene-which codes for the DHPR protein, one containing the in trans missense mutation c.515C>T (pPro172Leu) in exon 5 and the other containing the same type of mutation in the exon 7 (c.635T>C [p.Phe212Ser]). The authors discuss their experience with sapropterin dihydrochloride for the treatment of DHPRD in this case report.

(In)-Segurança alimentar de famílias residentes em um município do interior da Paraíba, Brasil / Food (in)security of families living in a city of Paraíba, Brazil / (In)Seguridad alimentaria de familias residentes en un municipio del interior de Paraíba, Brasil

RESUMO Objetivo Determinar a prevalência de insegurança alimentar entre famílias residentes no município de Queimadas e sua associação com as características socioeconómicas e demográficas. Métodos Estudo transversal, envolvendo 204 famílias residentes no município de Queimadas, interior da Paraíba, atendidas em serviços públicos de atenção básica à saúde e com crianças pequenas no núcleo familiar. A segurança alimentar foi avaliada pela Escala Brasileira de Insegurança Alimentar. Foi estudada a associação da insegurança alimentar com as características socioeconômicas e demográficas das famílias, usando modelo de regressão logística. Resultados A aplicação da escala revelou que 65,4 % das famílias sofriam com insegurança alimentar, sendo 8,4 % leve; 18,5 % moderada e 38,5 % grave. Maiores prevalências de insegurança alimentar foram encontradas nas famílias não beneficiárias de programa social e com precariedade em condições relacionadas ao saneamento ambiental (sem sanitário no domicílio, sem descarga no sanitário, consumo de água não tratada, escoamento sanitário a céu aberto). Conclusões Os resultados do presente estudo mostram que mais da metade das famílias atendidas em serviços públicos de atenção básica à saúde e com crianças pequenas residentes na cidade de Queimadas vive em estado de insegurança alimentar e que as características socioeconômicas são determinantes importantes desse estado.(AU)

ABSTRACT Objective To determine the prevalence of food insecurity among families living in the municipality of Queimadas and its association with socioeconomic and demographic characteristics. Methods Cross-sectional study involving 204 families living in the municipality of Queimadas, state of Paraíba, Brazil, attended at public primary health care services and with small children in the family core. Food security was assessed by the Brazilian Scale of Food Insecurity. The association between food insecurity and socioeconomic and demographic characteristics of families was studied using a logistic regression model. Results The application of the scale revealed that 65.4 % of families suffered from food insecurity, being 8.4 % mild, 18.5 % moderate and 38.5 % severe. High prevalences of food insecurity were found in families not receiving social program and in precarious conditions related to sanitation (no toilet inside houses, without toilet flushing, consumption of untreated water, open sewage). Conclusions The present study shows that more than half of the families with young children living in the city of Queimadas, served in public primary health services, live in a state of food insecurity and that socioeconomic characteristics are determinant of this state.(AU)

RESUMEN Objetivo Determinar la prevalencia de inseguridad alimentaria entre familias residentes en el municipio de Queimadas y su asociación con las características socioeconómicas y demográficas. Métodos Estudio transversal que involucro a 204 familias residentes en el municipio de Queimadas, interior de Paraíba, atendidas en servicios públicos de atención básica de salud y con niños pequeños en el núcleo familiar. La seguridad alimentaria fue evaluada por medio de la Escala Brasileña de Inseguridad Alimentaria. Fue estudiada la asociación de la inseguridad alimentaria con las características socioeconómicas y demográficas de las familias, usando modelo de regresión logística. Resultados La aplicación de la escala reveló que 65,4 % de las familias estaban con inseguridad alimentaria, siendo 8,4 % leve; 18,5 % moderada y 38,5 % grave. Mayores prevalencias de inseguridad alimentaria se encontraron entre familias no beneficiadas por el programa social y con precariedad en condiciones relacionadas con el saneamiento ambiental (sin baño en el domicilio, baño sin descarga, consumo de agua no tratada, desagüe sanitario a cielo abierto). Conclusiones El presente estudio muestra que más de la mitad de las familias con niños pequeños, residentes en la ciudad de Queimadas, que son atendidas en servicios públicos de atención primaria de salud, viven en estado de inseguridad alimentaria y que las características socioeconómicas son determinantes de ese estado.(AU)

[Food (in)security of families living in a city of Paraíba, Brazil]. / (In)-Segurança alimentar de famílias residentes em um município do interior da Paraíba, brasil.

OBJECTIVE: To determine the prevalence of food insecurity among families living in the municipality of Queimadas and its association with socioeconomic and demographic characteristics. METHODS: Cross-sectional study involving 204 families living in the municipality of Queimadas, state of Paraíba, Brazil, attended at public primary health care services and with small children in the family core. Food security was assessed by the Brazilian Scale of Food Insecurity. The association between food insecurity and socioeconomic and demographic characteristics of families was studied using a logistic regression model. RESULTS: The application of the scale revealed that 65.4 % of families suffered from food insecurity, being 8.4 % mild, 18.5 % moderate and 38.5 % severe. High prevalences of food insecurity were found in families not receiving social program and in precarious conditions related to sanitation (no toilet inside houses, without toilet flushing, consumption of untreated water, open sewage). CONCLUSIONS: The present study shows that more than half of the families with young children living in the city of Queimadas, served in public primary health services, live in a state of food insecurity and that socioeconomic characteristics are determinant of this state.

Reducing occurrence of Giardia duodenalis in children living in semiarid regions: impact of a large scale rainwater harvesting initiative.

BACKGROUND: In Brazil, about two million people living in rural semiarid regions were benefited with the construction of rainwater cement cisterns, as an initiative from the program "One Million Cisterns" (P1MC). Nevertheless, few epidemiological studies have been conducted to assess health risks or protection effects associated with consumption of this water source. The aim of this study was to evaluate whether access to rainwater harvesting cisterns is associated with the decrease in the occurrence of Giardia duodenalis infections in children, compared to other children living in households supplied by other water sources. METHODOLOGY/PRINCIPAL FINDINGS: A quasi-experimental study with two concurrent cohorts was developed in two rural municipalities of the semiarid region of Brazil. A sample of 664 children, aged between 4 months and 5 years old, was followed up, of which 332 had access to rainwater cisterns (cistern group) and 332 did not, having water supplied from alternative sources (comparison group). In a period of approximately one year (2010) intestinal parasites were investigated in feces three times. The prevalence of G. duodenalis in children from the cistern group ranged from 4.8 to 10.5%, while the prevalence in the comparison group ranged from 7.6 to 16.7%. Multivariate analysis (GEE) showed a higher risk of G. duodenalis infection in children who did not have access to rainwater cisterns, when compared to children who did (OR 1.72; 95% CI 1.14-2.59). The other variables associated with G. duodenalis infection were: number of rooms per house (OR 0.89; 95% CI 0.80-0.99); family income (OR0.48; 95% CI 0.26-0.88); birth order (OR 1.72; 95% CI 1.17-2.51); preterm children (OR 1.70; 95% CI 1.19-2.43); and improper hand hygiene prior to food preparation (OR 4.78; 95% CI 1.95-11.76). CONCLUSIONS/SIGNIFICANCE: Ownership of a rainwater cistern is associated with a lower prevalence of G. duodenalis infection in children after adjustment for environmental and family-related factors. Nevertheless, the study suggests the necessity to complement physical interventions with actions related to personal and domestic hygiene to enable further reductions in parasite infections affecting mainly the underprivileged populations.

Instability of a class a G protein-coupled receptor oligomer interface.

The quaternary structure of G protein-coupled receptors (GPCRs) can influence their trafficking and ability to transduce signals. GPCR oligomers are generally portrayed as long-lived entities, although the stability of these complexes has not been studied. Here we show that D2 dopamine receptor protomers interact transiently at a specific oligomer interface. Selective immobilization of cyan fluorescent protein-D2 receptors (C-D2Rs) in the plasma membrane failed to completely immobilize coexpressed D2-venus receptors (D2R-Vs), suggesting that the two did not form stable oligomers with each other. Oxidative cross-linking stabilized C-D2R-D2R-V oligomers such that immobilization of C-D2R also immobilized D2R-V. This stabilization required the presence in both C-D2R and D2R-V of a cysteine residue in transmembrane domain 4 (TM4), a region identified as a putative oligomer interface in these and other class A GPCRs. These results suggest that the interaction of D2 receptor protomers at TM4 is transient unless stabilized and that the quaternary structure of these receptors may thus be subject to physiological or pharmacological regulation.

[Clinical and histological features of duodenal ulcer in children and adolescents]. / Aspectos clínicos e histológicos da úlcera duodenal em crianças e adolescentes.

OBJECTIVE: To evaluate clinical and histological features of duodenal ulcer in children and adolescents. METHODS: Forty-three children with duodenal ulcer were prospectively and consecutively evaluated in a 6-year period (7.2 patients per year). Evaluation included clinical questionnaire focused on dyspeptic symptoms, physical examination, and digestive endoscopy with gastric biopsies for histological examination and Helicobacter pylori detection. RESULTS: Diagnostic age ranged from 4 years and 8 months to 17 years and 4 months (mean age: 12 years and 4 months). Abdominal pain was the main symptom (39/43, 90.7%), which was epigastric in 31/39, periumbilical in 7/39, and nocturnal in 27/39. Other symptoms were loss of appetite (32/43, 74.4%), vomiting (30/43, 69.8%), postprandial fullness (23/43, 53.5%), weight loss (22/43, 51.2%), and abdominal tenderness (19/43, 44.2%). Upper gastrointestinal bleeding occurred in 19/43 (44.2%), whereas anemia occurred in (21/43, 48.8%). Helicobacter pylori infection was detected in 41/43 (95.3%). All infected patients presented acute chronic gastritis in antrum, with lymphomononuclear infiltrate predominance in 92% of them. Eradication of the bacterium occurred in 68.3%. Ulcer healing occurred in all eradicated patients and in 89% of non-eradicated patients. CONCLUSION: Duodenal ulcer was associated with chronic gastritis due to Helicobacter pylori in the majority of patients. Many complications occurred, especially upper digestive bleeding.

Aspectos clínicos e histológicos da úlcera duodenal em crianças e adolescentes / Clinical and histological features of duodenal ulcer in children and adolescents

OBJETIVO: Avaliar as características clínicas e histológicas de crianças e adolescentes com úlcera duodenal. MÉTODOS: Foram avaliadas prospectiva e consecutivamente 43 pacientes com úlcera duodenal ao longo de 6 anos (7,2 pacientes por ano). A avaliação consistiu de questionário clínico de sintomas dispépticos, exame físico e endoscopia digestiva com biópsias gástricas para exame histológico e detecção do Helicobacter pylori. RESULTADOS: A idade no diagnóstico variou de 4 anos e 8 meses a 17 anos e 4 meses (mediana = 12 anos e 4 meses). O sintoma mais freqüente foi dor abdominal (39/43, 90,7 por cento): no epigástrio em 31/39, periumbilical em 7/39 e noturna em 27/39. Outros sintomas freqüentes foram: diminuição do apetite (32/43, 74,4 por cento), vômitos (30/43, 69,8 por cento), plenitude pós-prandial (23/43, 53,5 por cento), perda de peso (22/43, 51,2 por cento) e sensibilidade abdominal (19/43, 44,2 por cento). Hemorragia digestiva alta ocorreu em 19/43 pacientes (44,2 por cento), e anemia em 21/43 (48,8 por cento). H. pylori foi detectado em 41/43 (95,3 por cento), e todos esses pacientes apresentaram gastrite crônica ativa de antro, 92 por cento deles com predomínio do infiltrado linfomononuclear. A erradicação da bactéria ocorreu em 68,3 por cento dos pacientes infectados, mas houve cicatrização da lesão em 100 por cento dos pacientes erradicados e em 89 por cento dos não-erradicados. CONCLUSAO: Ulcera duodenal foi associada à gastrite crônica por H. pylori na grande maioria dos pacientes. Houve grande freqüência de complicações, especialmente hemorragia digestiva alta.

Tratamento de endometriomas ovarianos com implantes subcutâneos de ST-1435 (Elcometrina) / Treatment of ovarian endometriomata with subcutaneous implants of ST-1435 (Elcometrine)

Objetivos: avaliar o efeito do progest¡nico ST 1435 (elcometrina) sobre a evoluçäo de endometriomas ovarianos. Métodos: implantes subcutâneos contendo 50 mg da medicaçäo foram administrados a 51 portadoras de endornetriornas ovarianos, cujos volumes foram documentados por ultra-sonografia endovaginal antes e a cada intervalo de três meses ap¢s o in¡cio do tratamento. Um novo implante foi inserido ao fim de seis meses sempre que houvesse necessidade de continuaçäo do tratamento.Resultados: na admissäo, 74 por cento das pacientes apresentavam dismenorréia, 57 por cento dor pélvica crônica e 31 por cento dispareunia. A intensidade da dor foi considerada incapacitante ou forte por 82 por cento das pacientes. Um total de 924 meses de observaçäo foi registrado durante os quatro anos de duraçäo do estudo. O al¡vio da dor foi observado desde o primeiro mês de tratamento e, ao final do primeiro trimestre, nenhuma paciente referia dor incapacitante ou forte. O volume dos endometriomas foi reduzido em 86 por cento das pacientes. Em 45 por cento o volume normal do ovário foi restabelecido. Em 41 por cento a reduçäo de volume foi incompleta e em 14 por cento das pacientes näo houve reduçäo do volume ovariano. Setenta e sete por cento das pacientes apresentaram amenorréia durante o tratamento. Os efeitos adversos mais comuns foram reduçäo da libido (21 por cento) e peso nos membros inferiores (14 por cento). Um ano ap¢s a suspensäo do tratamento, 33 por cento das pacientes mantinham-se assintomáticas, ao passo que 28 por cento tiveram recidivas com menos de três meses ap¢s a suspensäo. Trinta e nove por cento optaram pela continuidade no use do implante para prolongar a amenorréia. Conclusäo: elcometrina é eficiente em provocar a regressäo e reabsorçäo de endometriomas ovarianos sem apresentar alguns dos efeitos colaterais dos outros tratamentos