Transcriptome meta-analysis of peripheral lymphomononuclear cells indicates that gestational diabetes is closer to type 1 diabetes than to type 2 diabetes mellitus.

We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diabetes to evaluate similarities and dissimilarities among these diabetes types. cRNA samples obtained from peripheral blood lymphomononuclear cells (PBMC) of 56 diabetes mellitus patients (type 1 = 19; type 2 = 20; gestational = 17) were hybridized to the same whole human genome oligomicroarray platform, encompassing 44,000 transcripts. The GeneSpring software was used to perform analysis and hierarchical clustering, and the DAVID database was used for gene ontology. The gene expression profiles showed more similarity between gestational and type 1 diabetes rather than between type 2 and gestational diabetes, a finding that was not influenced by patient gender and age. The meta-analysis of the three types of diabetes disclosed 3,747 differentially and significantly expressed genes. A total of 486 genes were characteristic of gestational diabetes, 202 genes of type 1, and 651 genes of type 2 diabetes. 19 known genes were shared by type 1, type 2 and gestational diabetes, highlighting EGF, FAM46C, HBEGF, ID1, SH3BGRL2, VEPH1, and TMEM158 genes. The meta-analysis of PBMC transcription profiles characterized each type of diabetes revealing that gestational and type 1 diabetes were transcriptionally related.

Interferon-γ +874 polymorphism in the first intron of the human interferon-γ gene and kidney allograft outcome.

BACKGROUND: Despite advances in immunosuppressive therapy in the past decade, allograft rejection remains an important cause of kidney graft failure. Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcomes. Several studies have shown that the production of cytokines varies among individuals. These variations are determined by genetic polymorphisms, most commonly within the regulatory region of cytokine genes. The aim of the present study was to assess the effect of allelic variation on acute rejection episodes (ARE) or chronic allograft nephropathy (CAN) after kidney transplantation. METHODS: To determine a possible correlation between the interferon (INF)-γ +874 polymorphism and kidney allograft outcome, we isolated genomic DNA from 74 patients who underwent isolated kidney allografts and were classified into 2 groups--a rejection and a nonrejection group--for comparison with a control group of 163 healthy subjects. RESULTS: We genotyped INF-γ +874 polymorphisms in all groups. The transplant group showed a significantly increased homozygous genotype T/T (P = .0118) compared with healthy controls. Similarly, considering only patients with CAN, the homozygous genotype T/T (P = .0067) was significantly increased compared with the healthy controls. The rejection group indicated a significant increased homozygous genotype T/T compared with the control group (P = .0061). CONCLUSION: Homozygous genotype T/T was associated with increased levels of INF-γ and greater numbers among the rejection and CAN cohorts.

Interleukin-17 and kidney allograft outcome.

UNLABELLED: Acute rejection episodes (ARE) are important complications that involve the interplay between mechanisms that maintain graft tolerance and promote rejection. The proinflammatory cytokine interleukin-17 (IL-17) has been implicated in many conditions in humans and mice. In kidney transplant patients, the evaluation IL-17 levels has been performed in only a few patients. We performed a cross-sectional study correlating quantitative IL-17 levels and clinical outcomes. PATIENTS AND METHODS: We studied 19 specimens from biopsies performed in patients (n = 19) who received isolated kidney grafts. ARE signs were present in 9 (47%) patients who provide specimens; whereas, 10 (53%) others showed no signs of rejection. Eighteen healthy control sample IL-17 underwent measurement, all of which were performed by an enzyme-linked immunosorbent assay method. We assessed other factors, such as the recipients demographic data, cold ischemia time, HLA mismatches, time elapsed from transplantation to the biopsy, posttransplantation status, antibody panel, donor type, and immunosuppressive treatment. RESULTS: IL-17 levels were clearly increased among samples derived from patients with ongoing rejection (125.7 +/- 27.06 pg/mL) in contrast, to the nonrejection group, (30 +/- 13.32 pg/mL) (P < .05). Healthy controls showed no detectable IL-17 levels. CONCLUSIONS: These findings suggested that IL-17 was important in the pathophysiology of acute kidney rejection.

HLA polymorphisms as incidence factor in the progression to end-stage renal disease in Brazilian patients awaiting kidney transplant.

Chronic renal failure (CRF) leads in the majority of instances to end-stage renal disease (ESRD) requiring renal replacement therapy. Age, gender, genetics, race, hypertension, and smoking among others are factors associated with ESRD. Our interest was to evaluate the possible associations of class I and II HLA antigens with ESRD renal disease independent of other factors, among patients with CRF, having various diagnoses in the Brazilian population of the São Paulo state. So 21 HLA-A, 31 HLA-B, and 13 HLA-DR were detected in 105 patients who were compared with 160 healthy controls of both sexes who were not related to the patients evaluated until 2005. We calculated allelic frequencies, haplotypes frequencies, etiological fractions (EF), preventive fractions, and relative risks (RR). We compared demographic data of patients and controls. The antigens positively associated with ESRD were: HLA-A78 (RR = 30.31 and EF = 0.96) and HLA-DR11 (RR = 18.87 and EF = 0.65). The antigens HLAB14 (RR = 29.90 and EF = 0.75) was present at a significantly lower frequency among patients compared with controls. In contrast, no haplotype frequency showed statically significant associations. Further molecular studies may clarify types and subtypes of alleles involved with ESRD progression.

Tratamento das dermatomicoses com ketoconazole por via oral - estudo multicentrico. / Treatment of dermatomycosis with ketoconazole by oral route - multicenter study

Neste estudo foram incluidos 148 doentes, sendo 65 com pitiriase versicolor e 83 com dermatofitoses, submetidos a tratamento com ketoconazole por via oral. A dose diaria foi de 200mg (um comprimido) durante duas a quatro semanas para os casos de pitiriase versicolor e de quatro a oito semanas para os de dermatofitoses. O tratamento determinou, nos doentes de pitiriase versicolor, cura clinica e micologica em 50 (78,1%), apenas cura clinica em dois (3,1%) e cura micologica em um (1,6%). Nos doentes com dermatofitoses, em 69 (84,1%) houve cura clinica e micologica, quatro (4,9%) apresentaram cura micologica e cinco (6,1%) tiveram apenas cura clinica. Efeitos colaterais foram observados em 11 doentes (7,4%), sendo que dois necessitaram abandonar o tratamento por intolerancia (um teve nauseas de grau moderado e outro, nauseas, vomitos e tonturas de grau moderado, ambos no 1o. dia de tratamento).O ketoconazole por via oral demonstrou ser bastante eficaz no tratamento de pitiriase versicolor e de dermatofitoses

Note on the classification of the Leishmania sp. responsible for cutaneous leishmaniasis in the East Central Region of Brazil.

The authors studied a species of Leishmania which is the causative agent of cutaneous leishmaniasis in Mato Grosso, Brazil. The parasite displays unusual characteristics which do not fit exactly into either the L. mexicana or L. brasiliensis complexes. The buoyant density DNA resembles that of the L. mexicana complex but the culture and hamster inoculation results resemble those of the L. brasiliensis complex. Further comparative studies are required to elucidate the relationship of the Mato Grosso Leishmania to the L. mexicana complex.