Cleto Álvarez-Aguilar

Rosuvastatina y metformina reducen la inflamación y el estrés oxidativo en pacientes con hipertensión y dislipemia

Introduccion y objetivos La hipertension arterial (HTA) y la dislipemia incrementan el riesgo de enfermedad cardiovascular a traves de los efectos proinflamatorios y el estres oxidativo. Nuestro objetivo fue estimar el efecto de la rosuvastatina y la metformina en la inflamacion y el estres oxidativo en pacientes con HTA y dislipemia. Metodos En un ensayo clinico abierto paralelo, se estudio a 48 pacientes con HTA y dislipemia. Se trato a 16 pacientes con rosuvastatina 10 mg/dia, 16 con metformina 1.700 mg/dia y 16 con 10 mg de almidon como control. Las variables analizadas durante el estudio fueron edad, peso, indice de masa corporal (IMC), presion arterial, glucosa, colesterol total (CT), de las lipoproteinas de baja densidad (cLDL) y de las lipoproteinas de alta densidad (cHDL), trigliceridos (TG), interleucina 6 (IL-6), factor de necrosis tumoral alfa (TNFα), glutation reductasa (GSH), glutation peroxidasa (GPx) y superoxido dismutasa (SOD). Resultados Con 10 mg/dia de rosuvastatina, disminuyeron el CT (41,7%), el cLDL (63%) y los TG (10,7%) y se incremento el cHDL (6,3%). Despues del tratamiento farmacologico con rosuvastatina o metformina, se encontro disminucion e interaccion entre grupos en la IL-6, el TNFα, la GSH y la GPx e incremento en la SOD. Conclusiones La rosuvastatina mejoro el perfil de lipidos. Ambos farmacos reducen la inflamacion y el estres oxidativo. Estos resultados demuestran un efecto adicional cardioprotector, como un mecanismo de accion direc-to o a traves de sus efectos pleiotropicos. Son necesarios estudios adicionales a largo plazo para determinar si la rosuvastatina o la metformina seran farmacos utiles para disminuir el riesgo cardiovascular causado por el estres oxidativo y la inflamacion.

Association between angiotensin-1 converting enzyme gene polymorphism and the metabolic syndrome in a Mexican population

Metabolic Syndrome (MS) is recognized as a cluster of cardiovascular risk factors. All components of MS have a genetic base. Genes of the renin angiotensin system are potential candidate genes for MS. We investigated whether angiotensin converting enzyme (ACE) gene polymorphism increases susceptibility to MS as an entity in a Mexican population. In a cross-sectional study, 514 individuals were studied including 245 patients with MS and 269 subjects without MS criteria. ACE gene polymorphism was detected using PCR. MS was defined according to The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria, except that the raised fasting plasma glucose ≥ 100 mg/dl criterion for identification of intolerance fasting glucose was modified in accordance with the suggestion of the American Diabetes Association. Patients with MS were significantly different from subjects without MS in relation to mean body mass index (BMI), waist circumference (WC), systolic blood pressure, diastolic blood pressure, glucose, total cholesterol (C), triglycerides, HDL-C, and LDL-C (P<0.0001). The differences in the mean BMI, WC, glucose, total cholesterol, triglycerides, LDL-C, and HDL-C were maintained in patients with the MS and DD genotypes (P<0.01). The DD genotype was strongly associated with MS (adjusted OR=5.48, 95% CI 3.20-9.38, P<0.0001). We concluded that the DD genotype increases susceptibility to MS in a Mexican population. These results indicate that pharmacological and non-pharmacological treatment and a reduction in body fat will have important therapeutic implications in this disease.

Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study

Patients with chronic kidney disease (CKD) have signs of genomic instability and, as a consequence, extensive genetic damage, possibly due to accumulation of uraemic toxins, oxidative stress mediators and other endogenous substances with genotoxic properties. We explored factors associated with the presence and background levels of genetic damage in CKD. A cross-sectional study was performed in 91 CKD patients including pre-dialysis (CKD patients; n = 23) and patients undergoing peritoneal dialysis (PD; n = 33) or haemodialysis (HD; n = 35) and with 61 healthy subjects, divided into two subgroups with the older group being in the age range of the patients, serving as controls. Alkaline comet assay and cytokinesis-block micronucleus assay in peripheral blood lymphocytes were used to determine DNA and chromosome damage, respectively, present in CKD. Markers of oxidative stress [malondialdehyde (MDA), advanced glycation end products (AGEs), thiols, advanced oxidation protein products and 8-hydroxy-2′-deoxyguanosine] and markers of inflammation (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were also measured. Micronucleus (MN) frequency was significantly higher (P < 0.05) in the CKD group (46±4‰) when compared with the older control (oC) group (27.7±14). A significant increase in MN frequency (P < 0.05) was also seen in PD patients (41.9±14‰) versus the oC group. There was no statistically significant difference for the HD group (29.7±15.6‰; P = NS) versus the oC group. Comet assay data showed a significant increase (P < 0.001) of tail DNA intensity in cells of patients with CKD (15.6±7%) with respect to the total control (TC) group (11±1%). PD patients (14.8±7%) also have a significant increase (P < 0.001) versus the TC group. Again, there was no statistically significant difference for the HD group (12.5±3%) compared with the TC group. Patients with MN values in the upper quartile had increased cholesterol, triglycerides, AGEs and MDA levels and lower albumin levels. Multiple logistic regression analysis showed that male gender, diabetes and treatment modality were independently associated with higher levels of DNA damage. Our results suggest that oxidative stress, diabetes, gender and dialysis modality in CKD patients increased DNA and chromosome damage. To confirm these data, prospective clinical trials need to be performed.

Hiperleptinemia como factor de riesgo en hipertensión arterial asociada a obesidad

FUNDAMENTO Y OBJETIVO Algunas observaciones otorgan un papel relevante al hongo Alternaria alternata como desencadenante de crisis de asma de riesgo vital (ARV). El objetivo de este trabajo fue determinar si las crisis de ARV de los pacientes sensibilizados a Alternaria cursan con un perfil clinico diferencial. Pacientes y metodo Estudio descriptivo y multicentrico (33 hospitales espanoles) de 194 pacientes incluidos de forma prospectiva por padecer una crisis de ARV. Se recogieron las caracteristicas y el curso clinico de la crisis, y cuando alcanzaron la estabilidad clinica se les practicaron una espirometria, pruebas cutaneas de alergia y determinacion de IgE a Alternaria. Se establecio la sensibilizacion a Alternaria cuando la prueba cutanea o bien la IgE especifica resultaron positivas. Resultados En 20 de los pacientes (10%) se pudo constatar sensibilizacion a Alternaria. En comparacion con el grupo de pacientes no sensibilizados, los sensibilizados a Alternaria resultaron ser significativamente mas jovenes, con una media (DE) de edad de 35 (15) frente a 50 (21) anos (p Conclusiones Las caracteristicas clinicas constatadas en las crisis de ARV de los pacientes sensibilizados a Alternaria parecen distinguirlos como fenotipo particular. Una conducta de evitacion especifica podria comportar efectos beneficiosos al prevenir crisis de ARV en los pacientes sensibilizados.

Efecto de la pentoxifilina sobre la evolución de la nefropatía diabética

BACKGROUND AND OBJECTIVE Diabetic nephropathy (DN) is the principal cause of end-chronic kidney disease. Metabolic and hemodynamic components are directly involved. However, convincing data have shown that inflammation participates in the diabetic complications. The aim of this study was to investigate whether the inhibition of the inflammation and pro-inflammatory cytokines with pentoxifylline (PXF) attenuate the progression of the DN. SUBJECTS AND METHOD In a prospective, randomized, double-blind, placebo- controlled study, we evaluated the effect of PXF (1200 mg daily) during 12 months, in 34 patients with incipient or established DN. Evaluated parameters were inflammation, pro-inflammatory cytokines and urinary albumin excretion (UAE). RESULTS PXF treatment had a reno-protective effect determined by a significant reduction in the UAE in both incipient and established (p<0,01) DN patient. This effect was attributed to a reduction in the C-reactive protein, interleukin-6, tumor necrosis factor-alpha and leptin serum levels (p<0,01). CONCLUSIONS PXF treatment caused regression and prevented the progression of renal damage. Thus, PXF should be used in the preventive treatment of DN. These results showed that inflammation and pro-inflammatory cytokines are related to the progression of diabetic nephropathy.

OriginalEfecto de la pentoxifilina sobre la evolución de la nefropatía diabéticaEffect of pentoxifylline on the evolution of diabetic nephropathy

BACKGROUND AND OBJECTIVE Diabetic nephropathy (DN) is the principal cause of end-chronic kidney disease. Metabolic and hemodynamic components are directly involved. However, convincing data have shown that inflammation participates in the diabetic complications. The aim of this study was to investigate whether the inhibition of the inflammation and pro-inflammatory cytokines with pentoxifylline (PXF) attenuate the progression of the DN. SUBJECTS AND METHOD In a prospective, randomized, double-blind, placebo- controlled study, we evaluated the effect of PXF (1200 mg daily) during 12 months, in 34 patients with incipient or established DN. Evaluated parameters were inflammation, pro-inflammatory cytokines and urinary albumin excretion (UAE). RESULTS PXF treatment had a reno-protective effect determined by a significant reduction in the UAE in both incipient and established (p<0,01) DN patient. This effect was attributed to a reduction in the C-reactive protein, interleukin-6, tumor necrosis factor-alpha and leptin serum levels (p<0,01). CONCLUSIONS PXF treatment caused regression and prevented the progression of renal damage. Thus, PXF should be used in the preventive treatment of DN. These results showed that inflammation and pro-inflammatory cytokines are related to the progression of diabetic nephropathy.

Polimorfismo inserción/deleción del gen de la enzima de conversión de la angiotensina en una población mexicana con nefropatía diabética

BACKGROUND AND OBJECTIVE Diabetic nephropathy is a polygenic and multifactorial disease. Studies of familial clustering and genetic predisposition suggest that genetic factors are involved. Among candidate genes, the coding for angiotensin-converting enzyme (ACE) polymorphism has been described. Our objective was to investigate the association ACE gene insertion/deletion (I/D) polymorphism with the development of diabetic nephropathy in a Mexican population. PATIENTS AND METHOD In a cross-sectional study, we evaluated 204 patients with type 2 diabetes: 43 with incipient diabetic nephropathy, 45 with established diabetic nephropathy and 116 without diabetic nephropathy. Diabetic nephropathy was defined according the American Diabetes Association criteria. The ACE I/D gene polymorphism was detected by polymerase chain reaction. RESULTS Patients with type 2 diabetes with both incipient diabetic nephropathy and established diabetic nephropathy significantly differed from controls with respect to variables that determined kidney damage (P<.0001) and serum lipids ( P<.01). The genotype DD was strongly associated with the development of incipient diabetic nephropathy (odds ratio [OR] adjusted = 2.83; 95% confidence interval, 1.74-4.59; P<.0001) and established diabetic nephropathy (OR adjusted = 2.95; 95% CI, 1.83-4.73; P<.0001). CONCLUSIONS The ACE DD genotype is associated with the development of incipient diabetic nephropathy and established diabetic nephropathy in a Mexican population.Fundamento y objetivo La nefropatia diabetica es una enfermedad de etiologia poligenica y multifactorial. Estudios de ligamiento familiar indican que estan involucrados factores geneticos. Un gen candidato es el que codifica la enzima de conversion de la angiotensina (ECA), en el que se ha identificado un polimorfismo insercion/delecion (I/D). El objetivo del presente trabajo ha sido analizar la asociacion del polimorfismo I/D del gen de la ECA con la nefropatia diabetica incipiente y establecida en una poblacion mexicana. Pacientes y metodo Se estudio a 204 pacientes con diabetes mellitus tipo 2, de los que 43 presentaban ademas nefropatia diabetica incipiente y 45 nefropatia diabetica establecida; los 116 restantes no tenian nefropatia diabetica (controles). La nefropatia diabetica se definio de acuerdo con los criterios de la American Diabetes Association. El polimorfismo I/D del gen de la ECA se detecto por reaccion en cadena de la polimerasa. Resultados Los pacientes con diabetes mellitus tipo 2 y nefropatia diabetica incipiente o establecida presentaron diferencias significativas respecto a los controles en las variables que determinan el dano renal (p Conclusiones El genotipo DD del gen de la ECA se asocio con el desarrollo de nefropatia diabetica incipiente y nefropatia diabetica establecida en una poblacion mexicana

Cardiovascular and Renal Effects of Bromocriptine in Diabetic Patients with Stage 4 Chronic Kidney Disease

Objective. The objective of this study was to investigate the effect of bromocriptine (BEC) on left ventricular mass index (LVMI) and residual renal function (RRF) in chronic kidney disease (CKD) patients with type 2 diabetes (T2D). Research Design and Methods. A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day) and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day). Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP) plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels. Results. Both BEC and PBO groups decreased blood pressure—but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC (0.54 ± 0.15 to 0.32 ± 0.17 pg/mL) and increased in PBO (0.37 ± 0.15 to 0.64 ± 0.17 pg/mL). Creatinine clearance did not change in the BEC group and decreased in the PBO group. Conclusions. BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged.

Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients

Background A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients. Methods Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 μmol/L), NE (1.0 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L), and from five nonobese and normotensive controls treated with DA (1 μmol/L), NE (1 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L). Results A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. Conclusion These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.