Rs4862705 in the melatonin receptor 1A gene is associated with renal function decline in type 1 diabetes individuals.

Aim: The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A (MTNR1A). Methods: Eight SNPs in MTNR1A were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated. Results: The group of individuals with a renal function decline ≥ 5 mL min-1 1.73 m-2 year-1 presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82; p = 0.0046). No other significant associations were found. Conclusions: This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.

Variants in HSD11B1 gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes.

BACKGROUND AND AIM: 11ß-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association of HSD11B1 SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. MATERIALS AND METHODS: Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). RESULTS: The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96; P = .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37; P = .028). A follow-up study revealed that 29% of the individuals lost ≥5 mL min-1 × 1.73 m2 per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89; P = .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42; P = .004). CONCLUSION: SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals.

Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes.

AIMS/INTRODUCTION: Epigenetics participate in the pathogenesis of metabolic memory, a situation in which hyperglycemia exerts prolonged deleterious effects even after its normalization. We tested the hypothesis that genetic variants in an epigenetic gene could predispose to diabetes complications. MATERIAL AND METHODS: We assessed the frequency of five single-nucleotide polymorphisms in the gene encoding deoxyribonucleic acid methytransferase 1 (DNMT1; rs8112895, rs7254567, rs11085721, rs17291414 and rs10854076), and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy in 359 individuals with long-term type 1 diabetes. RESULTS: None of the single-nucleotide polymorphisms studied was significantly associated with the presence of chronic complications in the overall population. However, after sex stratification, the minor allele C of rs11085721 conferred risk for cardiovascular neuropathy in women after adjustment for confounding variables (odds ratio 2.32; 95% confidence interval 1.26-4.33; P = 0.006). CONCLUSIONS: The fact that heterozygous mutations in DNMT1 are associated with hereditary sensory autonomic neuropathy provides plausibility to the present finding. If confirmed in independent samples, it suggests that genetic variants in epigenetic genes might predispose to more or fewer epigenetic changes in the face of similar metabolic derangements triggered by hyperglycemia, constituting the "genetics of epigenetics" for microvascular diabetes complications.

A importância da imunofenotipagem no diagnóstico da leucemia aguda bifenotípica: estudo de prontuários de dois casos / The importance of the imunophenotyping in the diagnosis of the biphenotypic acute leukemia: charts study of two cases

análise de dois casos de leucemia aguda bifenotípica (LAB) ilustrando a importância da imunofenotipagem no diagnóstico diferencial das leucemias agudas mais freqüentes. Método: estudo analítico de dois casos de LAB de clínica particular associado à revisão de literatura sobre o tema. Conclusão: os casos estudados ratificam a impossibilidade de estabelecer o diagnóstico de LAB com base apenas na citologia sanguínea, tornandoimpreterível a solicitação da imunofenotipagem nos casos de suspeita de leucemia aguda

analysis of two cases of biphenotypic acute leukemia (BAL), presenting the importance of the imunophenotyping in the different diagnosis of the most frequent acute leukemias. Method: analytic study of two BAL cases from a private practice, associated to the review of articles related. Conclusion: the cases studied reaffirm the impossibility of establishing the diagnosis of BAL based only in the blood cytology. The request ofimunophenotyping becomes essential in the cases of acute leukemia suspicion.

Infecções em pacientes com HIV/AIDS de Hospital de Referência, em Belém / Infections in pacients with HIV/AIDS from a reference hospital, in Belém

Objetivo: investigar a freqüência de infecções oportunistas ou não, presentes nos portadores de infecção pelo HIV/Aids internados no Hospital Universitário João de Barros Barreto HUJBB, Belém-PA, de janeiro a dezembro de 2007, assim como, seus aspectos sócio-demográficos.Método: realizou-se um estudo tipo transversal, a partir dos dados obtidos pela revisão dos respectivos prontuários da Divisão de Arquivo Médico e Estatística do HUJBB. Nesse período foram internados 498 pacientes com diagnóstico de HIV/Aids, dos quais, 260 foram incluídosneste estudo. Resultados: do sexo masculino 68% (177/260) e 32% (83/260) do sexo feminino; 83,8% (218/260) já havia apresentado alguma infecção oportunista ou não, sendo mais prevalentes a candidíase oral (30,3%); tuberculose pulmonar (28,9%); pneumonia bacteriana(20,6%); neurotoxoplasmose (23,8%); candidíase esofagiana (15,59) e tuberculose extrapulmonar (14,2%). Outras infecções estiveram presentes, como: herpes simples, pneumocistose,herpes zoster, isosporíase, neurocriptococose, criptosporidiose, histoplasmose e sarcoma de Kaposi. A média ponderada do período de internação foi de 14,05 dias. Conclusão: no grupo investigado foram mais freqüentes as infecções consideradas oportunistas. A tuberculosecontinua sendo um evento expressivo, seja na forma pulmonar, seja na extra-pulmonar, fato para o qual os profissionais de saúde devem estar sempre atentos.

Objective: the aim of this study was to investigate the frequency of opportunist or not oportunist infections in the patients interned with HIV/Aids in the University Hospital João de Barros Barreto, Belém - PA, from january to december of 2007, as well as demographic-partneraspects. Methods: a transversal study based on prontuaries review of handbooks filed in theHospital?s Division of Medical Archive and Statistic. During the studied period, 498 patients were admitted into the hospital with diagnose of HIV/Aids, among whom 260 were included in the study. Results: 68% (177/260) were male and 32% (83/260) were female in the studiedgroup; 83,8% (218/260) had already presented some opportunist or not oportunistic infection, being the most frequent ones the oral candidiasis (30,3%), pulmonary tuberculosis (28,9 %), bacterial pneumonia (20,6 %), neurotoxoplasmosis (23,8 %) and extra-pulmonary tuberculosis(19,2 %) Other infections were present as: esofagic cadidiasis, herpes simplex, Pneumocystis carinii pneumonia, herpes zoster, isosporiasis, neurocriptococosis, cryptosporidiosis, histoplasmosis, Kaposi´s sarcoma. The weigthed average found for the period of admission wasequal to 14,05 days. Conclusion: in the investigated group the most frequent infections were the opportunists one. Tuberculosis remains as an expressive event, in the pulmonary form, as well as in the extra-pulmonary one, which deserves special attention from health professionals envolved.