Avaliação da ingestão alimentar e excreção de metabólitos na nefrolitíase / Evaluation of food intake and excretion of metabolites in nephrolithiasis

Introdução: A nefrolitíase é uma patologia frequente, com alta taxa de prevalência e recorrência, ocorrendo por processo multifatorial e complexo. Objetivo: Analisar as principais características dietéticas e metabólicas de pacientes com nefrolitíase e compará-los com grupo controle. Métodos: Estudo observacional, transversal, com 31 pacientes com nefrolitíase (NE) e 18 saudáveis. Na ingestão dietética, foram verificados sódio, cálcio, proteína, potássio, vitamina C, oxalato e a ingestão hídrica em ambos os grupos. Na avaliação metabólica, foi analisada excreção urinária de citrato e oxalato. Também foi avaliada presença de hipertensão arterial e Índice de Massa Corporal (IMC). Resultados: Quanto ao grupo NE, verificou-se que 45,2% apresentou alta ingestão de sódio e 100% de oxalato. Foi também observada baixa ingestão de cálcio em 93,5%, potássio em 100% e vitamina C em 94,9%. Com relação à proteína, apenas 12,5% apresentou ingestão normoproteica. Quanto à ingestão hídrica, 12,9% apresentou ingestão menor que 1 litro, 54,8% entre 1 a 2 litros, e 32,3% maior que 2 litros. Foi observada hipertensão arterial sistêmica em 64,5% desses pacientes e excreção adequada de citrato e oxalato em 90,5% deles. Não foi verificada diferença estatística significativa na ingestão alimentar, IMC, e excreção de oxalato entre os grupos. No entanto, o grupo NE apresentou maior excreção de citrato. Conclusão: Verificou-se nos dois grupos elevada prevalência de pacientes com sobrepeso, alta ingestão de oxalato e sódio, além de inadequação nas ingestões de cálcio, potássio e vitamina C. No grupo NE, foi observada ...

Introduction: Nephrolithiasis is a common condition with high prevalence and recurrence, occuring by a complex and multifactorial process. Objective: To analyze the main dietary and metabolic characteristics of patients with nephrolithiasis and compare them with a control group. Methods: A crosssectional study with 31 patients with nephrolithiasis (NE) and 18 healthy. By the dietary intake it were observed sodium, calcium, protein, potassium, vitamin C, oxalate and water intake in both groups. Metabolic assessment were analyzed in urinary excretion of oxalate and citrate. The presence of hypertension and body mass index (BMI) was also evaluated. Results: In the NE group, it was found that 45.2% had a high intake of sodium and 100% a high intake of oxalate. It was also observed a low calcium, potassium and vitamin C intake by 93.5%, 100% and 94.9% respectively. Regarding protein, only 12.5% had normal protein intake. Concerning water intake, 12.9% had an ingestion less than 1 liter, 54.8% between 1 and 2 liters and 32.3% higher than 2 liters. Hypertension was observed in 64.5% of patients and adequate excretion of oxalate and citrate in 90.5% of them. There was no statistically difference in food intake, BMI and oxalate excretion between groups. However, the NE group showed higher urinary citrate. Conclusion: It was found in both groups a high prevalence of overweight patients, a high intake of oxalate and sodium, in addition to inadequate intakes of calcium, potassium and vitamin C. The NE group showed high protein intake and increased excretion of citrate. .

MSX1 gene and nonsyndromic oral clefts in a Southern Brazilian population

Nonsyndromic oral clefts (NSOC) are the most common craniofacial birth defects in humans. The etiology of NSOC is complex, involving both genetic and environmental factors. Several genes that play a role in cellular proliferation, differentiation, and apoptosis have been associated with clefting. For example, variations in the homeobox gene family member MSX1, including a CA repeat located within its single intron, may play a role in clefting. The aim of this study was to investigate the association between MSX1 CA repeat polymorphism and NSOC in a Southern Brazilian population using a case-parent triad design. We studied 182 nuclear families with NSOC recruited from the Hospital de Clínicas de Porto Alegre in Southern Brazil. The polymorphic region was amplified by the polymerase chain reaction and analyzed by using an automated sequencer. Among the 182 families studied, four different alleles were observed, at frequencies of 0.057 (175 bp), 0.169 (173 bp), 0.096 (171 bp) and 0.67 (169 bp). A transmission disequilibrium test with a family-based association test (FBAT) software program was used for analysis. FBAT analysis showed overtransmission of the 169 bp allele in NSOC (P=0.0005). These results suggest that the CA repeat polymorphism of the MSX1 gene may play a role in risk of NSOC in populations from Southern Brazil.

HOXB5 expression in oral squamous cell carcinoma

Human HOX genes encode transcription factors that act as master regulators of embryonic development. They are important in several processes such as cellular morphogenesis and differentiation. The HOXB5 gene in particular has been reported in some types of neoplasm, but not in oral cancer. OBJECTIVE: The present study investigated the expression of HOXB5 in oral squamous cell carcinoma (SCC) and in non-tumoral adjacent tissues, focusing on verifying its possible role as a broad tumor-associated gene and its association with histopathological and clinical (TNM) characteristics. MATERIAL AND METHODS: RT-PCR was performed to amplify HOXB5 mRNA in 15 OSCCs and adjacent non-tumoral epithelium. A possible association with TNM and histopathologic data was verifed by the chi-square and post-hoc t-test. RESULTS: HOXB5 was amplifed in 60 percent non-tumoral epithelium and in 93.3 percent carcinomas. No statistically signifcant differences were found regarding the HOXB5 mRNA expression and TNM or histological grade. CONCLUSION: HOXB5 is expressed in OSCCs and its role in cancer progression should be further investigated.

Estudo clínico e molecular em uma coorte de portadores de deficiência de hormônio de crescimento na Bahia / Clinical and molecular study in a cohort of patients with growth hormone deficiency in Bahia

A deficiência de hormônio do crescimento (DGH) tem incidência estimada entre 1/4.000 a 1/10.000 nascidos vivos e pode ser isolada ou associar-se a outras deficiências hormonais. Como não há exame “padrão-ouro”, o seu diagnóstico baseia-se em critérios antropométricos associados a pico diminuído de GH após testes de estímulos farmacológicos. Mais recentemente, a presença de ectopia do lobo posterior hipofisário (ELP) à ressonância nuclear magnética de hipófise (RNMH) tem sido considerada marcador de DGH e mutações em genes associados à embriogênese hipofisária têm sido descritas nesse pacientes. O objetivo do trabalho foi descrever as características clínicas, moleculares e radiológicas de uma coorte de portadores de DGH, acompanhada num mesmo centro de referência (Centro de Diabetes e Endocrinologia da Bahia), entre dezembro de 1998 e dezembro de 2009. Métodos: todos os pacientes realizaram avaliação da função hipofisária e RNMH. O estudo foi dividido em duas partes. Na primeira, foram incluídos apenas pacientes com DGH e ELP (n=130), sendo realizada a caracterização fenotípica da população. Além disso, mutações nos genes HESX1, LHX4 e OTX2 foram avaliadas em 104 pacientes, pelos métodos de PCR e SSCP ou PCR e sequenciamento. Na segunda parte do estudo, foi comparada a resposta terapêutica no primeiro ano de tratamento com hormônio do crescimento nos pacientes com (n=58) e sem (n=26) ELP. Resultados: No subgrupo de pacientes com ELP observou-se grande variabilidade fenotípica. Deficiência hormonal hipofisária combinada foi descrita em 61,5% dos pacientes, sendo mais frequente naqueles nos quais a haste hipofisária não foi visualizada. Malformações cerebrais ocorreram em 9,2% dos pacientes. Trinta pacientes apresentaram mutações, não descritas anteriormente, em genes associados à embriogênese hipofisária, sendo 26 no LHX4 e cinco no HESX1. Mutações no OTX2 não foram identificadas nessa população. A segunda parte do estudo evidenciou que a velocidade de crescimento durante o tratamento com GH foi similar nos pacientes com e sem ELP. Conclusões: o estudo, que avaliou a maior casuística de pacientes com DGH associada à ELP já descrita, confirma a heterogeneidade fenotípica da população, além da baixa prevalência de mutações na mesma. Além disso, ao contrário de estudos prévios, demonstra que a presença de ELP não se associou a melhor resposta ao tratamento com GH.

Baixa estatura por haploinsuficiência do gene SHOX: do diagnóstico ao tratamento / Short stature caused by SHOX gene haploinsufficiency: from diagnosis to treatment

Estudos realizados em pacientes portadores de deleções parciais dos cromossomos sexuais permitiram a caracterização do SHOX, gene localizado na região pseudoautossômica no braço curto dos cromossomos sexuais, fundamental na determinação da altura normal. A perda de uma cópia deste gene na síndrome de Turner (ST) explica dois terços da baixa estatura observada nesta síndrome. A haploinsuficiência do SHOX é detectada em 77 por cento dos pacientes com discondrosteose de Leri-Weill, uma forma comum de displasia esquelética de herança autossômica dominante e em 3 por cento das crianças com baixa estatura idiopática (BEI), tornando os defeitos neste gene a principal causa monogênica de baixa estatura. A medida da altura sentada em relação à altura total (Z da AS/AT para idade e sexo) é uma forma simples de identificar a desproporção corpórea e, associada ao exame cuidadoso do paciente e de outros membros da família, auxilia na seleção de pacientes para o estudo molecular do SHOX. O uso de hormônio de crescimento (GH) está bem estabelecido na ST e em razão da causa comum da baixa estatura com o de crianças com defeitos isolados do SHOX o tratamento destes pacientes com GH é também proposto. Neste artigo será revisado os aspectos clínicos, moleculares e terapêuticos da haploinsuficiência do SHOX.

Studies involving patients with short stature and partial deletion of sex chromosomes identified SHOX gene in the pseudoautosomal region of the X and Y chromosomes. SHOX haploinsufficiency is an important cause of short stature in a diversity of clinical conditions. It explains 2/3 of short stature observed in Turner syndrome (TS) patients. Heterozygous mutations in SHOX are observed in 77 percent of patients with Leri-Weill dyschondrosteosis, a common dominant inherited skeletal dysplasia and in 3 percent of children with idiopathic short stature, indicating that SHOX defects are the most frequent monogenetic cause of short stature. The sitting height/height ratio (SH/H) standard deviation score is a simple way to assess body proportions and together with a careful exam of other family members, effectively selected a group of patients that presented a high frequency of SHOX mutations. Growth hormone treatment of short stature due to TS is well established and considering the common etiology of short stature in patients with isolated defects of SHOX gene, this treatment is also proposed for these patients. Here, we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.

Análisis mutacional del gen Homeobox de segmento muscular 1 (MSX1) en chilenos con fisuras orales / Mutational analysis of the muscle segment homeobox gene 1 (MSX1) in Chilean patients with cleft lip/palate

Background: Mutations of the MSX1 gene may contribute to nonsyndromic forms of cleft lip and/or cleft palate. Aim: To search for mutations of MSX1 coding regions, including one highly conserved non-coding region in the single intron, among Chilean patients with cleft lip/palate. Patients and Methods: We studied 45 patients with cleft lip/palate and their parents. Oral mucosa samples were obtained with a swab. DNA was extracted and amplified by PCR. Results: Two missense mutations (G16D and G34A) were identified in this study that may be useful for future admixture studies. The G16D mutation appears to disrupt a possible splicing site and may contribute to clefting in this population. Conclusions: Rare MSX1 mutations are found in some cases of cleft lip and/or cleft palate but others remain to be found most likely in other regulatory regions of the gene.

Expression of Cdx-2 Homeobox Gene in Intestinal Metaplasia and Gastric Adenocarcinoma / 대한소화기학회지

BACKGROUND/AIMS: The Cdx-1 and Cdx-2 genes are intestinal transcription factors that may be involved in the regulation of proliferation and differentiation of intestinal epithelial cells. The Cdx-1 and Cdx-2 are expressed in the epithelium of the small intestine and colon but not in the normal epithelium of the esophagus and stomach. Conversely, aberrant Cdx-2 expression is often observed in the esophagus and stomach. We investigated the expression and role of Cdx-2 in intestinal metaplasia and gastric adenocarcinoma. METHODS: The gastric tissues obtained endoscopically were analyzed by the reverse transcriptase-polymerase chain reaction and histology. The Cdx-1 and Cdx-2 mRNA expression was confirmed and analyzed according to updated Sydney classification. Then, immunohistochemical study with monoclonal anti-Cdx-2 antibody was performed with gastric adenocarcinoma obtained by surgical resection. RESULTS: The prevalence of Cdx-1 and Cdx-2 mRNA expression was significantly higher in mucosa with intestinal metaplasia than mucosa without intestinal metaplasia. In immunohistochemical study, nuclear staining of Cdx-2 was strong in metaplastic mucosa, but weak in adjacent normal gastric mucosa (p<0.001). The expression of Cdx-2 in gastric adenocarcinoma was lower than in metaplastic mucosa (p<0.001). The Cdx-2 expression was also detected in 97% of intestinal type gastric adenocarcinoma and 61.5% of diffuse type gastric adenocarcinoma (p=0.003). CONCLUSIONS: Aberrant expression of Cdx-2 is observed in intestinal metaplasia and a subset of gastric adenocarcinoma, which is predominant in intestinal-type gastric adenocarcinoma. Therefore, Cdx-2 may play an important role in gastric carcinogenesis, especially in intestinal type adenocarcinoma.