Nailfold capillaroscopy and microvascular involvement in Diabetes Mellitus / Capilaroscopia de leito ungueal e envolvimento microvascular em Diabetes Mellitus

Objective: to study the relationship between microvascular lesions of Diabetes Mellitus and alterations in the nailfold capillaroscopy. Subjects and Methods: cross-sectional study including 140 individuals (70 with Diabetes Mellitus and 70 controls). Epidemiological and clinical variables were collected from patient's charts. Fundus ophthalmoscopy, nailfold capillaroscopy, analysis of microalbuminuria and renal clearance as well as fasting glycaemia and HbA1c values were studied simultaneously. Results: capillary density was reduced, and vascular dilatation was increased in Diabetes Mellitus patients when compared to controls (both with p<0.0001). In diabetic individuals the number of dermal papillary capillaries/mm3 correlated negatively with microalbuminuria (p=0.02), patient's age (p=0.03), values of HbA1c (p=0.03). Patients with diabetic retinopathy and using antiplatelet agents had lower capillary density (p<0.0001 and 0.04 respectively). Capillary dilatation was associated with disease duration (p=0.04). Conclusion: microvascular disease in Diabetes Mellitus is reflected in nailfold capillaroscopy. Decreased capillary density, increased number of ectasias and increased presence of avascular areas were observed in patients with diabetes when compared to controls. In the present study, capillary density correlated/associate with age, retinopathy, use of antiplatelet medication, HbA1c, microalbuminuria and diabetes duration. Ectasias or dilatations were related to retinopathy, glomerular filtration rate and longer disease duration.

Objetivo: estudar a relação entre lesões microvasculares do Diabetes Mellitus e alterações na capilaroscopia ungueal. Sujeitos e Métodos: estudo transversal incluindo 140 indivíduos (70 com Diabetes Mellitus e 70 controles). Variáveis epidemiológicas e clínicas foram coletadas dos prontuários dos pacientes. A oftalmoscopia de fundo, capilaroscopia ungueal, análise de microalbuminúria e depuração renal, bem como glicemia de jejum e valores de HbA1c foram estudados simultaneamente. Resultados: a densidade capilar foi reduzida e a dilatação vascular aumentada em pacientes com Diabetes Mellitus quando comparados aos controles (ambos com p <0,0001). Em indivíduos diabéticos, o número de capilares papilares dérmicos/ mm3 correlacionou-se negativamente com microalbuminúria (p = 0,02), idade do paciente (p = 0,03), valores de HbA1c (p = 0,03). Pacientes com retinopatia diabética e em uso de antiagregante plaquetário apresentaram menor densidade capilar (p <0,0001 e 0,04 respectivamente). A dilatação capilar foi associada ao tempo de doença (p = 0,04). Conclusão: a doença microvascular no Diabetes Mellitus reflete-se na capilaroscopia ungueal. Diminuição da densidade capilar, aumento do número de ectasias e aumento da presença de áreas avasculares foram observados em pacientes com diabetes quando comparados aos controles. No presente estudo, a densidade capilar se correlacionou/ se associou com idade, retinopatia, uso de antiagregante plaquetário, HbA1c, microalbuminúria e tempo de diabetes. Ectasias ou dilatações foram relacionadas à retinopatia, à taxa de filtração glomerular e a maior duração da doença.

Transcriptomic profiling of gamma ray induced mutants from the CGL1 human hybrid cell system reveals novel insights into the mechanisms of radiation-induced carcinogenesis.

BACKGROUND: Somatic cell hybrid systems generated by combining cancerous with non-cancerous cells provide useful model systems to study neoplastic transformation. Combined with recent advances in omics-based technologies, novel molecular signatures that drive radiation-induced carcinogenesis can be analyzed at an exceptional global level. METHODS: Here, we present a complete whole-transcriptome analysis of gamma-induced mutants (GIM) and gamma irradiated control (CON) segregants isolated from the CGL1 (HeLa x normal fibroblast) human hybrid cell-system exposed to high doses of radiation. Using the Human Transcriptome Array 2.0 microarray technology and conservative discrimination parameters, we have elucidated 1067 differentially expressed genes (DEGs) between tumorigenic and non-tumorigenic cells. RESULTS: Gene ontology enrichment analysis revealed that tumorigenic cells demonstrated shifts in extracellular matrix (ECM) and cellular adhesion profiles, dysregulation of cyclic AMP (cAMP) signaling, and alterations in nutrient transport and cellular energetics. Furthermore, putative upstream master regulator analysis demonstrated that loss of TGFß1 signaling due to reduced SMAD3 expression is involved in radiation-induced carcinogenesis. CONCLUSIONS: Taken together, this study presents novel insights into specific gene expression and pathway level differences that contribute to radiation-induced carcinogenesis in a human cell-based model. This global transcriptomic analysis and our published tumor suppressor gene deletion loci analyses will allow us to identify and functionally test candidate nexus upstream tumor suppressor genes that are deleted or silenced after exposure to radiation.