Selection of autochthonous lactic acid bacteria from goat dairies and their addition to evaluate the inhibition of Salmonella typhi in artisanal cheese.

This study aimed to select autochthonous lactic acid bacteria (LAB) with probiotic and functional properties from goat dairies and test their addition to artisanal cheese for the inhibition of Salmonella typhi. In vitro tests, including survival in the gastrointestinal tract (GIT), auto- and co-aggregation, the hemolytic test, DNase activity, antimicrobial susceptibility, antibacterial activity, tolerance to NaCl and exopolysaccharide (EPS), gas and diacetyl production were conducted for sixty isolates. Based on these tests, four LAB isolates (UNIVASF CAP 16, 45, 84 and 279) were selected and identified. Additional tests, such as production of lactic and citric acids by UNIVASF CAP isolates were performed in addition to assays of bile salt hydrolase (BSH), ß-galactosidase and decarboxylase activity. The four selected LAB produced high lactic acid (>17 g/L) and low citric acid (0.2 g/L) concentrations. All selected strains showed BSH and ß-galactosidase activity and none showed decarboxylase activity. Three goat cheeses (1, 2 and control) were produced and evaluated for the inhibitory action of selected LAB against Salmonella typhi. The cheese inoculated with LAB (cheese 2) decreased 0.38 log10 CFU/g of S. Typhy population while in the cheese without LAB inoculation (cheese 1) the pathogen population increased by 0.29 log units. Further, the pH value increased linearly over time, by 0.004 units per day in cheese 1. In the cheese 2, the pH value decreased linearly over time, by 0.066 units per day. The cocktail containing selected Lactobacillus strains with potential probiotic and technological properties showed antibacterial activity against S. typhi in vitro and in artisanal goat cheese. Thus, goat milk is important source of potential probiotic LAB which may be used to inhibit the growth of Salmonella population in cheese goat, contributing to safety and functional value of the product.

Concurrent Loss of Heterozygosity and Mosaic Deletion of 12p13.32pter.

Deletions in the short arm of chromosome 12 are the rarest subtelomeric imbalances. Less than 20 patients have been reported to date, and their microdeletions were identified either by FISH or array-CGH without SNP data. Here, we report a patient with a 12p13.32pter mosaic deletion detected by chromosome microarray analysis with loss of heterozygosity (LOH) of the deleted segment in addition to the adjacent distal segment. LOH is indicative of a complex rearrangement, suggestive of mitotic microhomology-mediated break-induced replication.

Partial 1q Duplications and Associated Phenotype.

Duplications of the long arm of chromosome 1 are rare. Distal duplications are the most common and have been reported as either pure trisomy or unbalanced translocations. The paucity of cases with pure distal 1q duplications has made it difficult to delineate a partial distal trisomy 1q syndrome. Here, we report 2 patients with overlapping 1q duplications detected by G-banding. Array CGH and FISH were performed to characterize the duplicated segments, exclude the involvement of other chromosomes and determine the orientation of the duplication. Patient 1 presents with a mild phenotype and carries a 22.5-Mb 1q41q43 duplication. Patient 2 presents with a pure 1q42.13qter inverted duplication of 21.5 Mb, one of the smallest distal 1q duplications ever described and one of the few cases characterized by array CGH, thus contributing to a better characterization of distal 1q duplication syndrome.

Craniofacial and dental features in kabuki syndrome patients.

Objective : To describe oral manifestations in Brazilian individuals with Kabuki syndrome, a multiple congenital anomaly/mental retardation syndrome. Study Design : A total of 16 Kabuki syndrome individuals, aged between 8 to 24 years and of both sexes, were referred by the Department of Clinical Genetics for oral treatment and follow-up to the Oral Care Center for Inherited Diseases, University Hospital of Brasília, Brasília, Brazil. Each individual underwent complete physical examination, as well as intraoral and radiographic examinations. Results : Craniofacial and dental alterations were observed in all Kabuki syndrome patients examined. In addition, atypical shape of the molars' crowns, occlusal convergence of the premolars' crowns, and root dilaceration were also observed. Enamel diffuse opacities were observed in permanent dentition (n  =  10). Conclusion : A great clinical heterogeneity was observed in Kabuki syndrome individuals in line with previous studies in the literature. Further clinical and molecular studies are necessary in order to better understand the presence of dental anomalies in this syndrome.

Transient neonatal hypothyroidism in a boy with unbalanced translocation t(8;16) / Hipotireoidismo neonatal transitório em um menino com translocação não balanceada t(8;16)

Genetic defects resulting in deficiency of thyroid hormone synthesis can be found in about 10% of the patients with permanent congenital hypothyroidism, but the identification of genetic abnormalities in association with the transient form of the disease is extremely rare. We report the case of a boy with transient neonatal hypothyroidism that was undiagnosed in the neonatal screening, associated with extrathyroid malformations and mental retardation. The boy carries an unbalanced translocation t(8;16), and his maternal uncle had a similar phenotype. Chromosomal analysis defined the patient's karyotype as 46,XY,der(8)t(8;16)(q24.3;q22)mat,16qh+. Array-CGH with patient's DNA revealed a ~80 kb terminal deletion on chromosome 8q24.3qter, and a ~21 Mb duplication on chromosome 16q22qter. ZNF252 gene, mapped to the deleted region on patient's chromosome 8, is highly expressed in the thyroid, and may be a candidate gene for our patient's transient neonatal thyroid dysfunction. This is the first report on the association of a chromosomal translocation with the transient form of congenital hypothyroidism. This description creates new hypothesis for the physiopathology of transient congenital hypothyroidism, and may also contribute to the definition of the unbalanced translocation t(8;16)(q24.3;q22) phenotype, which has never been described before. Arq Bras Endocrinol Metab. 2012;56(8):564-9.

Defeitos genéticos resultando em deficiência hormonal tireoidiana podem ser encontrados em cerca de 10% dos pacientes com hipotireoidismo congênito permanente, porém a identificação de anormalidades genéticas associadas à forma transitória da doença é extremamente rara. Relatamos o caso de um menino com hipotireoidismo neonatal transitório não diagnosticado no teste de triagem neonatal, associado a malformações extratireoidianas e retardo mental. O paciente é portador de translocação não balanceada t(8;16), e seu tio materno tinha fenótipo similar. A análise cromossômica definiu o cariótipo do paciente como 46,XY,der(8)t(8;16)(q24.3;q22)mat,16qh+. A análise cromossômica array-CGH com o DNA do paciente revelou deleção terminal de ~80 kb no cromossomo 8q24.3qter, e duplicação de ~21 Mb no cromossomo 16q22qter. O gene ZNF252, mapeado na região da deleção no cromossomo 8 do paciente, é altamente expresso na tireoide e pode ser um gene candidato no hipotireoidismo neonatal transitório do paciente. Esse é o primeiro relato de associação de uma translocação cromossômica com a forma transitória do hipotireoidismo congênito. Essa descrição descortina novas hipóteses para a fisiopatologia do hipotireoidismo congênito transitório e também pode contribuir para a definição do fenótipo da translocação não balanceada t(8;16)(q24.3;q22), nunca descrito anteriormente. Arq Bras Endocrinol Metab. 2012;56(8):564-9.

Does celiac disease occur in Afro-derived Brazilian populations?

BACKGROUND: Celiac disease is an autoimmune disorder that occurs in genetically susceptible individuals in whom the ingestion of dietary gluten induces intestinal mucosa inflammation. Previous studies suggest that celiac disease may either be very rare or underdiagnosed in African and/or African-derived population. AIM: Determine the prevalence of celiac disease in Sub-Saharan African-derived Brazilian communities using serological screening. SUBJECTS AND METHODS: Inhabitants from 10 African-derived communities from Northeastern of Brazil were screened for celiac disease. All sera were tested for endomysial class IgA antibody using indirect immunofluorescence. RESULTS: No positive test for IgA-endomysial was observed in the 860 individuals tested. CONCLUSION: Our data suggests a low prevalence of celiac disease in African-derived Brazilian populations.

Transient neonatal hypothyroidism in a boy with unbalanced translocation t(8;16).

Genetic defects resulting in deficiency of thyroid hormone synthesis can be found in about 10% of the patients with permanent congenital hypothyroidism, but the identification of genetic abnormalities in association with the transient form of the disease is extremely rare. We report the case of a boy with transient neonatal hypothyroidism that was undiagnosed in the neonatal screening, associated with extrathyroid malformations and mental retardation. The boy carries an unbalanced translocation t(8;16), and his maternal uncle had a similar phenotype. Chromosomal analysis defined the patient's karyotype as 46,XY,der(8)t(8;16)(q24.3;q22)mat,16qh+. Array-CGH with patient's DNA revealed a ~80 kb terminal deletion on chromosome 8q24.3qter, and a ~21 Mb duplication on chromosome 16q22qter. ZNF252 gene, mapped to the deleted region on patient's chromosome 8, is highly expressed in the thyroid, and may be a candidate gene for our patient's transient neonatal thyroid dysfunction. This is the first report on the association of a chromosomal translocation with the transient form of congenital hypothyroidism. This description creates new hypothesis for the physiopathology of transient congenital hypothyroidism, and may also contribute to the definition of the unbalanced translocation t(8;16)(q24.3;q22) phenotype, which has never been described before.

Aspectos clínicos da leucemia mieloide crônica em pacientes do Hospital de Base do Distrito Federal / Clinical features of chronic myeloid leukemia in patients at the Hospital de Base do Distrito Federal

Objetivo. Descrever aspectos clínicos, hematológicos e de sobrevida de pacientes com leucemia mieloide crônica em hospital especializado de Brasília, Brasil. Método. Estudo descritivo e retrospectivo de 223 pacientes atendidos no período de maio de 2002 a abril de 2009. Resultados. A mediana de idade foi 45 anos. Aproximadamente, 92% dos pacientes foram classificados como tendo doença em fase crônica, 5% em fase acelerada e 3% em crise blástica. Observou-se esplenomegalia em64,7% de 150 pacientes, inclusive as de grandes dimensões (29,3%), além de hiperleucocitose, com mediana 120.200/mm3, e elevada proporção de pacientes (67,5%) em grupos de risco intermediário e de alto risco de acordo com escore prognóstico de Sokal. A sobrevida global foi 84,7% aos oito anos, com intervalo de confiança de 95%:75,5% a 90,7%, e a sobrevida livre de progressão foi 73,5% no mesmo período com intervalo de confiança de 95%: 61,9% a 82%, embora diversas modalidades de tratamento tenham sido usadas. A sobrevida global aos oito anos foi significativamente maior em doentes do grupo de baixo risco no escore de Sokal (p = 0,017). Conclusão. Os pacientes se apresentaram com características de doença avançada ao diagnóstico, quando analisados em conjunto e foram seguidos em desfechos de longo prazo com resultados inferiores aos observados na literatura médica.

Objective. The authors described clinical, hematological and survival features of patients with chronic myeloid leukemia in a specialized hospital of Brasília, Brazil. Method. This is a retrospective and descriptive study which included 223 patients treated from May 2002 to April 2009.Results. The median age was 45 years. Approximately, 92% of patients were classified as having chronic phase, 5% accelerated phase and 3% in blast crisis. Splenomegaly was observed in a significant proportion of them, 64.7 % out of 150, and it was large in 29.3%. Hyperleucocytosis, median 120.200/mm3, was observed and a high proportion of patients(67.5%) were classified as having intermediate and high risk group according to Sokal prognostic score. The at eight years overall survival was 84.7%, with 95% confidence interval of 75.5% to 90.7%, and progression free survival was 73.5%, with 95% confidence interval of 61.9% to 82%, in the same period, although several treatment protocols were employed. Overall survival was significantly better in patients with low risk Sokal score (p = 0,017). Conclusion. The patients presented features of advanced disease at diagnosis and long-term outcomes were worse than those from published data in the medical literature.

Genotoxic effects of white fluorescent light on human lymphocytes in vitro.

Sources of light beams such as white fluorescent light, are present in our daily life to meet the needs of life in the modern world. This study was conducted with the objective of determining the possible genotoxic, cytotoxic and aneugenic effects caused by this agent in different stages of the cell cycle (G0/early G1, S, and late G2), using different cytogenetic parameters (sister chromatid exchanges--SCE, chromosome aberrations--CA, and detection of aneugenic effects) in lymphocytes from temporary cultures of human peripheral blood. WFL showed a genotoxic effect in vitro, expressed by an increase in the frequency of SCE's, regardless of the cell cycle stage. However, no increase in the frequency of CAs was observed. In addition, disturbances in cell cycle kinetics and chromosomal segregation were also observed. Taken together, such data may contribute to a better understanding and a different management in the use of phototherapy for some pathological conditions.

GATA1 mutations in acute leukemia in children with Down syndrome.

It has been reported that somatic mutations in the X-linked GATA1 gene are present in hematological clonal disorders in children with Down syndrome (DS). We analyzed retrospective samples of DS children with acute myeloid leukemia, transient leukemia (TL), and myelodysplastic syndrome (MDS) to test whether the specificity of GATA1 mutations can be helpful in distinguishing these hematopoietic disorders. A total of 49 samples were subjected to GATA1 mutation screening by direct sequencing and denaturing polyacrylamide gel electrophoresis (PAGE). Mutations in exon 2 of GATA1 were detected in six of eight DS-AML M7 samples and in four of six DS-TL; no mutation was detected in 13 children with acute lymphoblastic leukemia (DS-ALL), 6 with DS-AML (M0, M2, and M5), 6 with DS-MDS and in 8 DS infants without hematological disorders and 2 children with AML M7 without DS. Blast cells proportion in the sample represented a critical aspect on the sensitivity of mutation detection in GATA1, and a combination of sequence analysis and PAGE is necessary to detect mutations when blast percentage is low. The absence of detected mutations in any of the DS-MDS cases raises the question whether MDS in DS children is an intermediate stage between TL and AML M7, as previously suggested.

Analysis of genetic susceptibility to mercury contamination evaluated through molecular biomarkers in at-risk Amazon Amerindian populations

We investigated Individual differences in susceptibility to methylmercury (MeHg) contamination and its relationship with polymorphisms of the detoxifying enzyme glutathione S-transferase (GST). In Brazil, some Amerindian tribes from the Amazon region have an increased level of mercury in their hair. Samples of hair and blood were taken from inhabitants of two villages in the Kayabi and Munduruku Amerindian communities to investigate mercury levels in association with genetic polymorphism of GSTs. Other molecular biological markers were also studied, such as hemoglobin, haptoglobin and glucose 6-phosphate dehydrogenase (G-6-PDH). Higher levels of mercury contamination were found in the Kayabi villagers, who had a null genotype (GSTM1 0/0, also denominated GSTM1 null) frequency of 26%, than in the Munduruku villagers, for which the null genotype frequency was 0%. Individuals with the GSTM1 null phenotype had higher concentrations of mercury in their hair than individuals with GSTM1+/+ phenotypes (F = 21.51, p < 0.0001). No association with other markers studied was observed. This study suggests that GSTM1 may be involved in the biotransformation of mercury in humans

Fish consumption (hair mercury) and nutritional status of Amazonian Amer-Indian children.

Fish are abundant and important dietary items for the Amer-Indians, and total hair-Hg (HHg) concentration is a reliable marker of fish consumption. We studied the impact of fish consumption (HHg) on the nutritional status of Indian children of Eastern Amazonia. Weight-for-height Z score (WHZ) was measured, and HHg was determined in 203 children younger than 10 years of age in three villages. There was significantly higher fish consumption in Kayabi children (16.55 microg Hg/g; SD, 11.44) than in children of the Munduruku villages of Missão-Cururu (4.76 microg Hg/g; SD, 2.09) and Kaburua (2.87 microg Hg/g; SD, 2.13). Anthropometric indices showed WHZ means of -0.27, -0.22, and 0.40, respectively, for Kayabi, Missão-Cururu and Kaburua villages. Despite a different pattern of fish-protein consumption between tribes, there was no significant correlation between WHZ and HHg concentrations (r2 = 0.0079; P < 0.2021). Dietary differences among Amazonian tribes can be traced and used in measuring health outcomes. Higher fish consumption, although important for Kayabis, was compensated by other protein sources by the Kaburua villagers.

Distribution of glutathione S-transferase GSTM1 and GSTT1 null phenotypes in Brazilian Amerindians

The distribution of glutathione S-transferase (GST) GSTM1 and GSTT1 null phenotype frequencies in two Brazilian Amerindian tribes, the Munduruku tribe from Missão Cururu village (79 individuals) and the Kayabi tribe (41 individuals), was analyzed by polymerase chain reaction (PCR) amplification. The GST null phenotype frequencies for the Munduruku sample were 0 percent for GSTM1 and 27 percent for GSTT1 while for the Kayabi sample the null phenotype frequencies were 27 percent for GSTM1 and 29 percent for GSTT1. This is the first report of the absence of the GSTM1 null phenotype in any ethnic group.

Transient neonatal myeloproliferative disorder without Down syndrome and detection of GATA1 mutation.

Transient myeloproliferative disorder is a form of self-limited leukemia that occurs almost exclusively in neonates with Down syndrome. The authors report an unusual case of a newborn without constitutional trisomy 21 who developed undifferentiated leukemia and subsequently achieved clinical and molecular remission without chemotherapy. Cytogenetics and molecular analysis have shown trisomy 21 and GATA1 mutation restricted to leukemic cells. G-to-T transversion was detected, which is predicted to result in a premature stop codon (c.119G>T; pGlu67X) in diagnosis samples. These findings emphasize that there must be a powerful interaction between GATA1 and trisomy 21 in leukemogenesis process.

Hair mercury (signature of fish consumption) and cardiovascular risk in Munduruku and Kayabi Indians of Amazonia.

Fish is an important natural resource in the diet of inhabitants of the Amazon rain forest and a marker of its consumption (hair Hg) was used to compare selected cardiovascular risk parameters between tribes of Eastern Amazonia. Three Munduruku (Terra Preta, Kaburua, Cururu) villages and one Kayabi village at the banks of head rivers (Tapajos, Tropas, Kabitutu, Cururu, Curuzinho, Teles Pires) of the Tapajos Basin were studied in relation to fish Hg concentrations, mercury in hair (fish consumption) and erythrocytes, body mass index (height/weight, kg/cm2), and blood pressure. The mean fish Hg concentrations were higher in predatory (578.6 ng/g) than in nonpredatory species (52.8 ng/g). Overall only 26% of fish Hg concentrations were above 500 ng/g, and only 11% were above 1000 ng/g. There was no systematic trend in fish Hg concentrations from rivers with a history of gold-mining activities. The biomarker of fish consumption (hair Hg) was significantly associated with erythrocyte-Hg (r=0.5181; P=0.0001) and was significantly higher in Kayabi (12.7 microg/g) than in the Munduruku (3.4 microg/g). Biomarker-assessed fish consumption rate was higher in the Kayabi (110 g/day) than in the Munduruku villages (30 g/day). Although no significant differences in body mass index (BMI) were observed between tribes, there was a trend of lower increase in blood pressure with age among the higher fish consumers (Kayabi). Summary clinical evaluation did not detect neurologic complaints compatible with Hg intoxication (paraparesis, numbness, tremor, balancing failure), but endemic tropical diseases such as clinical history of malaria showed a high prevalence (55.4%). Fish is an abundant natural resource, important in the Indian diet, that has been historically consumed without perceived problems and can easily be traced through hair Hg. The exposure to freshwater fish monomethyl mercury is less of an issue than endemic infectious diseases such as malaria and lack of basic medical services.