RESUMEN
BACKGROUND AND OBJECTIVE: Diabetic nephropathy (DN) is the most common cause of end stage renal failure or even death among patients with type 2 diabetes mellitus. Genetic predisposition is widely studied among these patients to identify manageable aspects of the disease pathogenesis. This study was carried out to test the association of engulfment and cell motility 1 (ELMO1) gene polymorphism with DN among Egyptians. ELMO1 is required for phagocytosis of apoptotic cells and cell motility. METHODS: This case-control study was conducted on type 2 diabetic patients who attended Suez Canal University Hospital, Egypt, between November 2016 and October 2017. Peripheral blood was collected from 200 diabetic patients (without nephropathy), 200 patients with DN, and 100 healthy controls for DNA extraction. The single nucleotide polymorphism of ELMO1 (rs741301) was genotyped using real-time polymerase chain reaction and the allele discrimination technique. RESULTS: GG genotype was significantly associated with DN (odds ratio [OR] = 2.7; 95% confidence interval [CI]: 1.4-5.3) (P = .016). The OR for the high-risk allele (G) was 1.9 with 95% CI from 1.5 to 2.9 (P < .001). CONCLUSION: ELMO1 gene (rs741301) polymorphism is a candidate variant in the predisposition to DN.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Biomarcadores/análisis , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Glucemia/análisis , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/patología , Egipto/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
The present study aimed to test the anti-inflammatory and xanthine oxidase inhibitory activities of two synthesized molecules and compare them to routinely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and the serum urate-lowering drug, allopurinol. The anti-inflammatory effects of the designed compounds (A and B) were evaluated in carrageenan (CAR)-induced paw edema in mice. The levels of nitric oxide and myeloperoxidase activity were measured in paw skin using biochemical methods. Additionally, prostaglandin E2 (PGE2), C-reactive protein (CRP), cyclooxygenase-2 (Cox-2), tumor necrosis factor-α (TNFα), interleukin (IL)-1ß, IL-2 and IL-10, and monocyte chemoattractant protein-1 (MCP1) were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of inflammation-related genes was confirmed by real-time qPCR. The expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) were estimated using immunohistochemistry, and xanthine oxidase inhibitory activity was evaluated using an in vitro assay. The results revealed that compounds A and B decreased inflammation, as was observed by a reduction in the elevation of all the tested markers. In addition, the tested compounds markedly decreased paw swelling, mobilization of inflammatory cells, iNOS-, and NF-κB-immunoreactive cells in a mouse model of paw edema. Interestingly, both compounds were potent xanthine oxidase inhibitors as well as Cox inhibitors with higher activity in favor of compound B providing potential dual acting series of anti-hyperuricemic and anti-inflammatory therapeutic agents.
Asunto(s)
Antiinflamatorios/farmacología , Edema/tratamiento farmacológico , Supresores de la Gota/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Proteína C-Reactiva/análisis , Células Cultivadas , Quimiocina CCL2/metabolismo , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Supresores de la Gota/química , Supresores de la Gota/uso terapéutico , Interleucinas/metabolismo , Masculino , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Peroxidasa/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Factor de Necrosis Tumoral alfa/metabolismo , Xantina Oxidasa/antagonistas & inhibidoresRESUMEN
Glomerular filtration rate and/or creatinine are not accurate methods for renal failure prediction. This study tested homocysteine (Hcy) as a predictive and prognostic marker for end stage renal disease (ESRD). In total, 176 subjects were recruited and divided into: healthy normal group (108 subjects); mild-to-moderate impaired renal function group (21 patients); severe impaired renal function group (7 patients); and chronic renal failure group (40 patients) who were on regular hemodialysis. Blood samples were collected, and serum was separated for analysis of total Hcy, creatinine, high sensitive C-reactive protein (CRP), serum albumin, and calcium. Data showed that Hcy level was significantly increased from normal-to-mild impairment then significantly decreases from mild impairment until the patient reaches severe impairment while showing significant elevation in the last stage of chronic renal disease. Creatinine level was increased in all stages of kidney impairment in comparison with control. CRP level was showing significant elevation in the last stage. A significant decrease in both albumin and calcium was occurred in all stages of renal impairment. We conclude Hcy in combination with CRP, creatinine, albumin, and calcium can be used as a prognostic marker for ESRD and an early diagnostic marker for the risk of renal failure.