Publications by authors named "Ernesto Cardona-Muñoz"

61 Publications

Donor-specific antibodies development in renal living-donor receptors: Effect of a single cohort.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211000545

Department of Physiology, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, México.

Minimization in immunosuppression could contribute to the appearance the donor-specific HLA antibodies (DSA) and graft failure. The objective was to compare the incidence of DSA in renal transplantation (RT) in recipients with immunosuppression with and without steroids. A prospective cohort from March 1st, 2013 to March 1st, 2014 and follow-up (1 year), ended in March 2015, was performed in living donor renal transplant (LDRT) recipients with immunosuppression and early steroid withdrawal (ESW) and compared with a control cohort (CC) of patients with steroid-sustained immunosuppression. All patients were negative cross-matched and for DSA pre-transplant. The regression model was used to associate the development of DSA antibodies and acute rejection (AR) in subjects with immunosuppressive regimens with and without steroids. Seventy-seven patients were included (30 ESW and 47 CC). The positivity of DSA class I (13% vs 2%;  < 0.05) and class II (17% vs 4%,  = 0.06) antibodies were higher in ESW versus CC. The ESW tended to predict DSA class II (RR 5.7; CI (0.93-34.5,  = 0.06). T-cell mediated rejection presented in 80% of patients with DSA class I ( = 0.07), and 86% with DSA II ( = 0.03), and was associated with DSA class II, (RR 7.23; CI (1.2-44),  = 0.03). ESW could favor the positivity of DSA. A most strictly monitoring the DSA is necessary for the early stages of the transplant to clarify the relationship between T-cell mediated rejection and DSA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/20587384211000545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020398PMC
March 2021

Assessment of serum macrophage migration inhibitory factor (MIF), adiponectin, and other adipokines as potential markers of proteinuria and renal dysfunction in lupus nephritis: a cross-sectional study.

Biomark Res 2020 28;8:55. Epub 2020 Oct 28.

Programa de Doctorado en Farmacología del Departamento de Fisiología y Programa de Doctorado en Salud del Pública Depatamento de Salud Pública, Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Sierra Mojada 950, Colonia Independencia, 44340 Guadalajara, Jalisco Mexico.

Background: To date, the association of serum macrophage migration inhibitory factor (MIF) and serum adipokines with lupus nephritis is controversial.

Objective: To assess the utility of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritis.

Methods: Cross-sectional study including 196 systemic lupus erythematosus (SLE) patients and 52 healthy controls (HCs). Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal SLE involvement was investigated by renal-SLEDAI. MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed the correlations of quantitative variables by Spearman correlation (r). Multivariable linear regression adjusted the variables associated with the severity of proteinuria.

Results: SLE patients had higher MIF ( = 0.02) and adiponectin ( < 0.001) than HCs. Patients with renal SLE involvement ( = 43) had higher adiponectin (19.0 vs 13.3 μg/mL,  = 0.002) and resistin (10.7 vs 8.9 ng/mL,  = 0.01) than patients with non-renal SLE ( = 153). Proteinuria correlated with high adiponectin (  = 0.19,  < 0.009) and resistin (  = 0.26,  < 0.001). MIF (  = 0.27,  = 0.04). Resistin correlated with increased creatinine (  = 0.18,  = 0.02). High renal-SLEDAI correlated with adiponectin (  = 0.21,  = 0.004). Multiple linear regression showed that elevated adiponectin ( = 0.02), younger age ( = 0.04) and low MIF ( = 0.02) were associated with the severity of proteinuria. Low MIF and high adiponectin levels interacted to explain the association with the severity of proteinuria (R = 0.41).

Conclusions: High adiponectin combined with low MIF concentrations int+eract to explain the severity of proteinuria in renal SLE. These findings highlight the relevance of adiponectin, resistin and MIF as markers of LN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40364-020-00236-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594329PMC
October 2020

Aortic stiffness and central hemodynamics in treatment-naïve HIV infection: a cross-sectional study.

BMC Cardiovasc Disord 2020 10 7;20(1):440. Epub 2020 Oct 7.

Arterial Stiffness Laboratory, Department of Physiology, Universidad de Guadalajara, Sierra Mojada 950, Building Q, Ground Floor, District Independencia, 44340, Guadalajara, Jalisco, Mexico.

Background: Human immunodeficiency virus (HIV) infection is associated with a greater risk of cardiovascular disease (CVD). HIV infection causes a chronic inflammatory state and increases oxidative stress which can cause endothelial dysfunction and arterial stiffness. Aortic stiffness measured by carotid femoral-pulse wave velocity (cfPWV) and central hemodynamics are independent cardiovascular risk factors and have the prognostic ability for CVD. We assessed cfPWV and central hemodynamics in young individuals with recent HIV infection diagnosis and without antiretroviral therapy. We hypothesized that individuals living with HIV would present greater cfPWV and central hemodynamics (central systolic blood pressure and pulse pressure) compared to uninfected controls.

Methods: We recruited 51 treatment-naïve individuals living with HIV (HIV(+)) without previous CVD and 51 age- and sex-matched controls (HIV negative (-)). We evaluated traditional CVD risk factors including metabolic profile, blood pressure (BP), smoking, HIV viral load, and CD4 T-cells count. Arterial stiffness and central hemodynamics were evaluated by cfPWV, central systolic BP, and central pulse pressure (cPP) via applanation tonometry.

Results: HIV(+) individuals presented a greater prevalence of smoking, reduced high-density lipoprotein cholesterol, and body mass index. 65.9% of HIV(+) individuals exhibited lymphocyte CD4 T-cells count < 500 cells/μL. There was no difference in brachial or central BP between groups; however, HIV(+) individuals showed significantly lower cPP. We observed a greater cfPWV (mean difference = 0.5 m/s; p < 0.01) in HIV(+) compared to controls, even after adjusting for heart rate, mean arterial pressure and smoking.

Conclusion: In the early stages of infection, non-treated HIV individuals present a greater prevalence of traditional CVD risk factors, arterial stiffness, and normal or in some cases central hemodynamics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-020-01722-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542972PMC
October 2020

Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy.

Antioxidants (Basel) 2020 Sep 20;9(9). Epub 2020 Sep 20.

Department of Physiology, Health Sciences University Center, Institute of Clinical and Experimental Therapeutics, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico.

Diabetic retinopathy is one of the leading causes of visual impairment and morbidity worldwide, being the number one cause of blindness in people between 27 and 75 years old. It is estimated that ~191 million people will be diagnosed with this microvascular complication by 2030. Its pathogenesis is due to alterations in the retinal microvasculature as a result of a high concentration of glucose in the blood for a long time which generates numerous molecular changes like oxidative stress. Therefore, this narrative review aims to approach various biomarkers associated with the development of diabetic retinopathy. Focusing on the molecules showing promise as detection tools, among them we consider markers of oxidative stress (TAC, LPO, MDA, 4-HNE, SOD, GPx, and catalase), inflammation (IL-6, IL-1ß, IL-8, IL-10, IL-17A, TNF-α, and MMPs), apoptosis (NF-kB, , and caspases), and recently those that have to do with epigenetic modifications, their measurement in different biological matrices obtained from the eye, including importance, obtaining process, handling, and storage of these matrices in order to have the ability to detect the disease in its early stages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox9090891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555116PMC
September 2020

Administration of Herbarium Mixture () on Metabolic Profile in Type 2 Diabetes Mellitus Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

J Med Food 2021 May 21;24(5):527-532. Epub 2020 Sep 21.

Department of Physiology, Health Science University Center, Institute of Experimental and Clinical Therapeutics, University of Guadalajara, Guadalajara, Mexico.

The use of herbarium mixture has been empirical, and the properties are not yet known. The aim of this study was to evaluate the effect of oral administration of herbarium mixture () on metabolic profile in patients with type 2 diabetes mellitus (T2DM). A randomized, double-blind, placebo-controlled, clinical trial was carried out in 40 patients with T2DM. They were between 40 and 65 years of age, with body mass index (BMI) between 25.0 and 34.9 kg/m and HbA1c >7.0%. BMI, waist circumference, fasting glucose, HbA1c, lipids, kidney, and liver function were measured. The patients were randomly assigned to receive the herbarium mixture () 400 mg before each meal, or placebo for 90 days. Herbarium mixture group showed decreased waist circumference (99 ± 14 vs. 98 ± 15 cm;  = .019), fasting glucose (12.0 ± 5.7 vs. 10.3 ± 5.1 mM;  = .019), and HbA1c (9.9% ± 2.7% vs. 8.9% ± 2.5%,  = .002). In conclusion, the administration of herbarium mixture () improved the glycemic profile in patients with T2DM. ClinicalTrial registration: NCT03313856 ClinicalTrials.gov.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jmf.2020.0082DOI Listing
May 2021

The Alteration of Pro-inflammatory Cytokines and Oxidative Stress Markers at Six-Month Post-living Kidney Donation.

Front Med (Lausanne) 2020 29;7:382. Epub 2020 Jul 29.

Department of Physiology, Institute of Experimental and Clinical Therapeutics, University Center of Health Sciences, University of Guadalajara, Guadalajara, Mexico.

Donors have a higher risk of developing chronic kidney disease than the general population. Some mechanisms mediated by pro-inflammatory cytokines and oxidative stress may be involved as risk factors. The objective of the study was to evaluate the behavior of pro-inflammatory cytokines and oxidative stress markers in living renal donors with a 6-month follow-up. A single prospective cohort was performed in 88 renal donors. At the end of the follow-up, the levels of lipoperoxides, 6.52 ± 1.12 mM, and 8-isoprostanes, 63.75 ± 13.28 pg/mL, were lower than before donation, 10.20 ± 3.95 mM ( < 0.001) and 67.54 ± 9.64 pg/mL ( = 0.026), respectively. Initial levels of nitric oxide (NO), 356.09 ± 59.38 μM increased at the end of the follow-up, 467.08 ± 38.74 μM ( < 0.001). It was observed in the final determination of donors decreased activity of antioxidant enzymes superoxide dismutase (SOD), 0.74 ± 0.57 U/L and glutathione peroxidase (GPx), 556.41 ± 80.37 nmol, in comparison with the levels obtained in the initial determination, 1.05 ± 0.57 U/L ( < 0.001) and 827.93 ± 162.78 nmol ( < 0.001), respectively. The pro-inflammatory cytokines, Tumor necrosis factor alpha and interleukin-6 showed no differences at 6 months after donation. The enzyme oxoguanine glycosylase (hOGG1) responsible for repairing oxidative damage to DNA, showed a decrease in its concentration at the end of the study in donor men, 0.40 ± 0.21 ng/mL compared to the initial levels, 0.55 ± 0.32 ng/mL ( = 0.025). The marker, 8-hydroxy-2-deoxyguanosine (8-OHdG) exhibited an increase in donor men at the final determination 2.28 ± 1.99 ng/mL, compared to the concentration before donation, 1.72 ± 1.96 ng/mL ( < 0.001). We found significant changes in the markers of the oxidative state with increased NO and 8-OHdG, as well as a significant decrease in the antioxidant defenses SOD, GPx, and in the DNA repair enzyme in living renal donors after 6 months of follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2020.00382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403208PMC
July 2020

Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson's Disease.

Oxid Med Cell Longev 2020 3;2020:6281454. Epub 2020 Aug 3.

Department of Physiology, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.

Oxidative stress plays a fundamental role in the pathogenesis of Parkinson's disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment's mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme's expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/6281454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424374PMC
June 2021

The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases.

Oxid Med Cell Longev 2020 23;2020:2082145. Epub 2020 Jul 23.

Department of Physiology, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.

Oxidative stress (OS) has the ability to damage different molecules and cellular structures, altering the correct function of organs and systems. OS accumulates in the body by endogenous and exogenous mechanisms. Increasing evidence points to the involvement of OS in the physiopathology of various chronic diseases that require prolonged periods of pharmacological treatment. Long-term treatments may contribute to changes in systemic OS. In this review, we discuss the involvement of OS in the pathological mechanisms of some chronic diseases, the pro- or antioxidant effects of their pharmacological treatments, and possible adjuvant antioxidant alternatives. Diseases such as high blood pressure, arteriosclerosis, and diabetes mellitus contribute to the increased risk of cardiovascular disease. Antihypertensive, lipid-lowering, and hypoglycemic treatments help reduce the risk with an additional antioxidant benefit. Treatment with methotrexate in autoimmune systemic inflammatory diseases, such as rheumatoid arthritis, has a dual role in stimulating the production of OS and producing mitochondrial dysfunction. However, it can also help indirectly decrease the systemic OS induced by inflammation. Medicaments used to treat neurodegenerative diseases tend to decrease the mechanisms related to the production of reactive oxygen species (ROS) and balance OS. On the other hand, immunosuppressive treatments used in cancer or human immunodeficiency virus infection increase the production of ROS, causing significant oxidative damage in different organs and systems without widely documented exogenous antioxidant administration alternatives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/2082145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396016PMC
May 2021

Serum Neuropeptide Y Levels Are Associated with TNF- Levels and Disease Activity in Rheumatoid Arthritis.

J Immunol Res 2020 16;2020:8982163. Epub 2020 Apr 16.

Programa de Doctorado en Farmacología, CUCS, Universidad de Guadalajara, 44340 Guadalajara, Jalisco, Mexico.

Background: Neuropeptide Y (NPY) is a sympathetic neurotransmitter with effects on the regulation of inflammatory cells. The role of NPY on autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is not completely understood. Therefore, we evaluate if NPY levels are markers of disease activity in RA and if there is a correlation between NPY levels and tumor necrosis factor-alpha (TNF-), leptin, and interleukin 6 (IL-6) levels.

Methods: Cross-sectional design, including 108 women with RA. We assessed disease activity by DAS28-ESR (considering active disease a score of ≥2.6). Serum NPY levels and anti-CCP2 antibody, TNF-, IL-6, and leptin levels were quantified (ELISA).

Results: Sixty-eight RA had an active disease (RA-active), and 40 were in remission (RA-remission). RA-active patients had higher NPY levels vs. RA-remission (22.8 ± 13.6 vs. 17.8 ± 10.3; = 0.04). NPY levels correlated with increased TNF- levels ( = 0.32, = 0.001). Leptin or IL-6 did not correlate with NPY levels. In the logistic regression analysis, NPY increased the risk of disease activity (OR: 1.04, 95% CI 1.006-1.09, and = 0.03).

Conclusion: Higher NPY levels are an independent marker of disease activity in RA. This study encourages the quantification of NPY levels as a surrogate marker for RA-active. Future studies evaluating the role of NPY levels interacting with other proinflammatory cytokines are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8982163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182972PMC
February 2021

The Effect of Visceral Abdominal Fat Volume on Oxidative Stress and Proinflammatory Cytokines in Subjects with Normal Weight, Overweight and Obesity.

Diabetes Metab Syndr Obes 2020 8;13:1077-1087. Epub 2020 Apr 8.

Department of Physiology, University Health Sciences Centre, University of Guadalajara, Guadalajara, Jalisco, Mexico.

Purpose: The increase of visceral abdominal fat (VAF) and oxidative stress (OS) are independent predictors for cardiovascular risk. This study aimed to determine the association of VAF with proinflammatory cytokines, oxidants, antioxidants, and oxidative damage to DNA in subjects with normal weight, overweight, and obesity.

Patients and methods: A cross-sectional study that included 21 men and 71 women who attended for a medical check-up was conducted. Dual-energy X-ray absorptiometry (DXA) was used to measure the VAF volume. ELISA and colorimetric techniques were used for chemical analysis.

Results: Low activity of superoxide dismutase (SOD) was found in overweight and obese subjects compared to the normal weight group (=0.005). In contrast, the activity of glutathione peroxidase (GPx) was higher in the overweight and obesity groups compared to the normal weight subjects (=0.017). The total antioxidant capacity (TAC) was also increased in the overweight group compared to the normal weight group (=0.04). According to the volume of VAF, the levels of tumor necrosis factor alfa and interleukin 6 showed no differences between subjects with normal and high VAF. Subjects with high VAF show higher levels of 8-isoprostans compared to normal VAF group (=0.039). Less concentration of 8-oxoguanine-DNA-N-glycosylase-1 (hOGG1) was found in the high VAF group (=0.032) compared to the normal VAF subjects. VAF was positively correlated with lipoperoxides (LPO) (r=0.27, <0.05) and 8-isoprostanes (r=0.25, <0.05). We also found correlations between oxidative stress markers and anthropometric ratios for intra-abdominal fat. The waist-hip ratio was positively correlated with LPO (r=0.30, <0.05) and TAC (r=0.24, <0.05).

Conclusion: These findings suggest that the predominantly oxidative damage associated with VAF in overweight or obesity is lipoperoxidation and oxidative DNA damage. Alterations in endogenous antioxidant defenses may not be linked to the amount of VAF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DMSO.S245494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152535PMC
April 2020

Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation.

Oxid Med Cell Longev 2020 11;2020:3096470. Epub 2020 Mar 11.

Institute of Clinical and Experimental Therapeutics, Department of Physiology, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.

Diabetes mellitus (DM) is a progressive disease induced by a sustained state of chronic hyperglycemia that can lead to several complications targeting highly metabolic cells. Diabetic retinopathy (DR) is a multifactorial microvascular complication of DM, with high prevalence, which can ultimately lead to visual impairment. The genesis of DR involves a complex variety of pathways such as oxidative stress, inflammation, apoptosis, neurodegeneration, angiogenesis, lipid peroxidation, and endoplasmic reticulum (ER) stress, each possessing potential therapeutic biomarkers. A specific treatment has yet to be developed for early stages of DR since no management is given other than glycemic control until the proliferative stage develops, offering a poor visual prognosis to the patient. In this narrative review article, we evaluate different dietary regimens, such as the Mediterranean diet, Dietary Pattern to Stop Hypertension (DASH) and their functional foods, and low-calorie diets (LCDs). Nutraceuticals have also been assessed in DR on account of their antioxidant, anti-inflammatory, and antiangiogenic properties, which may have an important impact on the physiopathology of DR. These nutraceuticals have shown to lower reactive oxygen species (ROS), important inflammatory factors, cytokines, and endothelial damage biomarkers either as monotherapies or combined therapies or concomitantly with established diabetes management or nonconventional adjuvant drugs like topical nonsteroidal anti-inflammatory drugs (NSAIDs).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/3096470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086452PMC
December 2020

Enalapril Influence on Arterial Stiffness in Rheumatoid Arthritis Women: A Randomized Clinical Trial.

Front Med (Lausanne) 2019 29;6:341. Epub 2020 Jan 29.

Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico.

Cardiovascular parameters disruption can be found in patients at early stages of rheumatoid arthritis (RA). The primary endpoint of this study was the reduction of arterial stiffness in RA patients without traditional cardiovascular risk factors or previous comorbidities, measured by cardio-ankle vascular index (CAVI) through the enalapril intervention. The secondary endpoints were the enalapril influence on carotid femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT), carotid artery distensibility (cDistensibility), Young's incremental elastic modulus (Einc)]. Fifty-three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) or placebo (26), both twice a day. The drug was acquired at Victory Enterprises®. The placebo was kindly provided by the Universidad de Guadalajara (UdeG), as well as the blinding into two groups: A and B. Enalapril and placebo were packed into bottles without labeling. Clinical assessment included a structured questionnaire to gather demographic and clinical variables as well as determination of CAVI, cfPWV, cIMT, carotid artery distensibility and Einc. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention. The CAVI measurement at baseline was 7.1 ± 1.4 and increased up to 7.5 ± 1.2 at the end of 12 weeks. Meanwhile, the enalapril group was as follows: 7.4 ± 1.2 and at the of intervention, reduced to 7.1 ± 0.9. A reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP). Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context might be interpreted as a reduction of 6.4 years of arterial aging. The protocol was approved by the Institutional Review Board with the register CI-0117 from UdeG, and 0211/18 from Hospital Civil "Dr. Juan I. Menchaca", Secretaría de Salud Jalisco: DGSP/DDI/D.INV.28/18 and retrospectively registered at ClinicalTrials.gov Protocol Registration and Results System: NCT03667131.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2019.00341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025600PMC
January 2020

The Role of Cardiolipin and Mitochondrial Damage in Kidney Transplant.

Oxid Med Cell Longev 2019 25;2019:3836186. Epub 2019 Nov 25.

Departamento de Química del Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Chronic kidney disease (CKD) is highly incident and prevalent in the world. The death of patients with CKD is primarily due to cardiovascular disease. Renal transplantation (RT) emerges as the best management alternative for patients with CKD. However, the incidence of acute renal graft dysfunction is 11.8% of the related living donor and 17.4% of the cadaveric donor. Anticardiolipin antibodies (ACAs) or antiphospholipid antibodies (APAs) are important risk factors for acute renal graft dysfunction. The determination of ACA or APA to candidates for RT could serve as prognostic markers of early graft failure and would indicate which patients could benefit from anticoagulant therapy. Cardiolipin is a fundamental molecule that plays an important role in the adequate conformation of the mitochondrial cristae and the correct assembly of the mitochondrial respiratory supercomplexes and other proteins essential for proper mitochondrial function. Cardiolipin undergoes a nonrandom oxidation process by having pronounced specificity unrelated to the polyunsaturation pattern of its acyl groups. Accumulation of hydroxyl derivatives and cardiolipin hydroperoxides has been observed in the affected tissues, and recent studies showed that oxidation of cardiolipin is carried out by a cardiolipin-specific peroxidase activity of cardiolipin-bound cytochrome c. Cardiolipin could be responsible for the proapoptotic production of death signals. Cardiolipin modulates the production of energy and participates in inflammation, mitophagy, and cellular apoptosis. The determination of cardiolipin or its antibodies is an attractive therapeutic, diagnostic target in RT and kidney diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/3836186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899302PMC
May 2020

Effect of Telmisartan in the Oxidative Stress Components Induced by Ischemia Reperfusion in Rats.

Oxid Med Cell Longev 2019 2;2019:1302985. Epub 2019 Jul 2.

Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, CUCS, Universidad de Guadalajara, Calle Sierra Mojada 950, Colonia Independencia, CP 44340 Guadalajara, Jalisco, Mexico.

The therapeutic effects of telmisartan, an angiotensin II receptor antagonist and a peroxisome proliferator-activated receptor- (PPAR-) agonist, have been demonstrated in several disorders. It has antioxidant and immune response modulator properties and has shown promising results in the treatment of an ischemia/reperfusion (I/R) lesion. In this study, a skeletal muscle (right gastrocnemius muscle) I/R lesion was induced in rats and different reperfusion times (1 h, 24 h, 72 h, 7-day, and 14-day subgroups) were assessed. Furthermore, levels of oxidative markers such as enzymatic scavengers (catalase (CAT) and superoxide dismutase (SOD)) and metabolites (nitrates and 8-oxo-deoxyguanosine) were determined. The degree of tissue injury (total lesioned fibers and inflammatory cell count) was also evaluated. We observed an increase in CAT and SOD expression levels under telmisartan treatment, with a decrease in injury and oxidative biomarker levels in the 72 h, 7-day, and 14-day subgroups. Telmisartan reduced oxidative stress and decreased the damage of the I/R lesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/1302985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636510PMC
February 2020

Ambulatory blood pressure and arterial stiffness web-based telemonitoring in patients at cardiovascular risk. First results of the VASOTENS (Vascular health ASsessment Of The hypertENSive patients) Registry.

J Clin Hypertens (Greenwich) 2019 08 11;21(8):1155-1168. Epub 2019 Jul 11.

Servicio de Clínica Médica y Sección Hipertensión Arterial, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

The VASOTENS Registry is an international telehealth-based repository of 24-hour ambulatory blood pressure monitorings (ABPM) obtained through an oscillometric upper-arm BP monitor allowing combined estimation of some vascular biomarkers. The present paper reports the results obtained in 1200 participants according to different categories of CV risk. Individual readings were averaged for each recording and 24-hour mean of brachial and aortic systolic (SBP) and diastolic blood pressure (DBP), pulse wave velocity (PWV), and augmentation index (AIx) obtained. Peripheral and central BP, PWV and AIx values were increased in older participants (SBP only) and in case of hypertension (SBP and DBP). BP was lower and PWV and AIx higher in females. PWV was increased and BP unchanged in case of metabolic syndrome. Our results suggest that ambulatory pulse wave analysis in a daily life setting may help evaluate vascular health of individuals at risk for CV disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jch.13623DOI Listing
August 2019

Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.

Lancet 2019 07 9;394(10193):121-130. Epub 2019 Jun 9.

Research Institute, FOSCAL and Medical School, Universidad de Santander UDES, Bucaramanga, Colombia.

Background: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A (HbA) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control.

Methods: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952.

Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001).

Interpretation: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors.

Funding: Eli Lilly and Company.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(19)31149-3DOI Listing
July 2019

Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial.

Lancet 2019 07 9;394(10193):131-138. Epub 2019 Jun 9.

Research Institute, FOSCAL and Medical School, Universidad de Santander UDES, Bucaramanga, Colombia.

Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease.

Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952.

Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p<0·0001), with HRs of 0·89 (0·78-1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39-1·44; p=0·39) for chronic renal replacement therapy.

Interpretation: Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes.

Funding: Eli Lilly and Company.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(19)31150-XDOI Listing
July 2019

Effect of green tea extract on arterial stiffness, lipid profile and sRAGE in patients with type 2 diabetes mellitus: a randomised, double-blind, placebo-controlled trial.

Int J Food Sci Nutr 2019 Dec 14;70(8):977-985. Epub 2019 May 14.

Department of Physiology, Pharmacology, Health Sciences University Center, University of Guadalajara , Guadalajara , Mexico.

Type 2 diabetes mellitus (T2DM) is associated with premature atherosclerosis and arterial stiffening due to the accumulation of advanced glycation end-products in vessel walls. Green tea polyphenols are considered cardio-protective substances. In this randomised double-blind placebo-controlled trial (NCT02627898), we evaluated the effect of Green tea extract on arterial stiffness parameters, lipids, body composition and sRAGE levels. Twenty normotensive patients with T2DM treated with the standard therapy and statins, mean age 53.2 ± 9.4 years and mean BMI 30.1 ± 4.5 kg/m, were randomised to receive a daily dose of 400 mg of green tea extract (polyphenols ≥90%, EGCG ≥45%) or placebo for 12 weeks. Compared to placebo, administration of green tea extract decreased central augmentation index (-3.05 ± 10.8% vs. 6.7 ± 0.1%,  = .04). These findings suggest that green tea extract could be used as an adjunct to the standard therapy to improve arterial stiffness in T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09637486.2019.1589430DOI Listing
December 2019

Subclinical parameters of arterial stiffness and arteriosclerosis correlate with QRISK3 in systemic lupus erythematosus.

PLoS One 2018 5;13(12):e0207520. Epub 2018 Dec 5.

Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Instituto de Terapéutica Experimental y Clínica (INTEC), Guadalajara, Jalisco, México.

It is well known that cardiovascular diseases (CVD) are a major contributor of death in systemic lupus erythematosus (SLE) as well in other rheumatic illness. In the last decades, there has been a growing development of different methodologies with the purpose of early detection of CVD.

Objective: The aim of this study is to correlate the usefulness of subclinical parameters of vascular aging and QRISK 3-2017 score for early detection of CVD in SLE.

Methods: Clinical assessment including systemic lupus erythematosus disease activity index (SLEDAI) and systemic lupus international collaborating clinics / american college of rheumatology damage index (SLICC/ACR DI), laboratory measurements, carotid ultrasound examination, carotid intima media thickness (cIMT) measurement, carotid distention and diameter analysis, arterial stiffness measurement measured by tonometry and QRISK 3-2017 were done. All results were analyzed by SPSS 24 software.

Results: We observed correlation between QRISK3 and mean cIMT (rs = 0.534, P < 0.001), PWV (rs = 0.474, P < 0.001), cfPWV (rs = 0.569, P < 0.001) and distensibility (rs = -0.420, P = 0.006). Consistent with above, SLE patients in middle and high risk QRISK 3-2017 showed increased arterial stiffness versus low risk group.

Conclusions: We encourage to the rheumatology community to assess cardiovascular risk in SLE patients with QRISK 3-2017 risk calculator as an alternative method at the outpatient clinic along a complete cardiovascular evaluation when appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207520PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281193PMC
May 2019

Effect of statins on oxidative DNA damage in diabetic polyneuropathy.

J Circ Biomark 2018 Jan-Dec;7:1849454418804099. Epub 2018 Oct 3.

Department of Health-Disease Sciences as an Individual Process, Tonala University Centre, University of Guadalajara, Jalisco, México.

Oxidative stress induces nerve damage in type 2 diabetes mellitus and leads to diabetic polyneuropathy (DPN) and can affect the DNA and antioxidant status. Statins have pleiotropic, protective effects on the peripheral nerves of patients with diabetes. The aim of this study was to determine the effects of ezetimibe/simvastatin and rosuvastatin on DNA damage in patients with DPN. This randomized, double-blind, placebo-controlled, clinical trial comprised outpatients from Guadalajara, Mexico. The inclusion criteria were either gender, age 35-80 years, type 2 diabetes, glycated hemoglobin ≤10%, diabetic polyneuropathy stage 1/2, and signed informed consent. Patients who were taking antioxidant therapy or statins, had hypersensitivity to drugs, experienced organ failure, were pregnant or breastfeeding, or had other types of neuropathy were excluded. We assigned patients to placebo, ezetimibe/simvastatin 10/20 mg, or rosuvastatin 20 mg, and the primary outcomes were 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, 8-oxoguanine-DNA--glycosilase (hOGG1) for DNA repair, and superoxide dismutase (SOD). Seventy-four patients were recruited. Nine patients were included as negative controls. There were no differences in 8-OHdG between the healthy subjects (4.68 [3.53-6.38] ng/mL) and the DPN patients (4.51 [1.22-9.84] ng/mL), whereas the hOGG1 level was 0.39 (0.37-0.42) ng/mL in the healthy subjects and 0.41 (0.38-0.54) ng/mL in patients with DPN at baseline ( = 0.01). SOD decreased significantly in patients with DPN (5.35 [0.01-17.90] U/mL) compared with the healthy subjects (9.81 [8.66-12.61] U/mL) at baseline ( < 0.001). No significant changes in DNA biomarkers were observed in any group between baseline and final levels. We noted a rise in hOGG1 in patients with DPN, without modifications after treatment. There was a slight, albeit insignificant, increase in SOD in patients who were on statins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1849454418804099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170961PMC
October 2018

[Reliability of an automatic monitor for blood pressure measurement].

Rev Med Chil 2018 Feb;146(2):190-195

Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología del Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.

Background A correct blood pressure (BP) measurement is essential for the diagnosis and control of high BP.

Aim: To evaluate the agreement and repeatability of BP measurements with the OMRON HEM-7320-LA device compared to a mercury sphygmomanometer.

Material And Methods: A cross-sectional study comparing BP measurements made by two randomly selected trained nurses and an automatic oscillometric device. The mercurial sphygmomanometer was connected to the automated device via a "T" type connector and a dual-head stethoscope was used, allowing simultaneous measurements. The results were analyzed with one-factor analysis of variance, Bland-Altman's test, repeatability coefficient (RC), and intra-class correlation coefficient (ICC).

Results: Forty-nine participants aged 56 ± 19 years were included. Nineteen had hypertension (38%). We did not observe a significant difference in either systolic (SBP) or diastolic blood pressure (DBP) pressure measurements between the observers and the device. The mean difference was -0.09 mmHg (95% confidence intervals (CI)-0.9 to 0.7) for SBP and -0.9 mmHg (95% CI -1.7 to -0.13) for DBP. The RC for SBP (6.2, 5.2 and 5.8 mmHg) and DBP (4.7, 4.2 y 5.2 mmHg) was similar between the observers and the device. The ICC for SBP was 0.990 (95% CI 0.983 to 0.995, p < 0.01) and 0.986 (95% CI 0.977 to 0.991, p < 0.01) for DBP.

Conclusions: There was a high level of agreement and similar measurement repeatability in the measurements performed by the automatic device and the mercurial sphygmomanometer. No differences in BP measurements were observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4067/s0034-98872018000200190DOI Listing
February 2018

Efficacy and safety of the combination of isosorbide dinitrate spray and chitosan gel for the treatment of diabetic foot ulcers: A double-blind, randomized, clinical trial.

Diab Vasc Dis Res 2018 07 23;15(4):348-351. Epub 2018 Apr 23.

1 Instituto de terapéutica experimental y clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico.

Aim: To evaluate whether a combination of isosorbide dinitrate spray and chitosan gel (10%) topically applied can have additive benefits for management of diabetic foot ulcers.

Methods: In a randomized, placebo-controlled, double-blinded clinical trial, 68 patients were divided into four groups: Group 1: treated with chitosan gel; Group 2: isosorbide dinitrate spray; Group 3: combination of isosorbide dinitrate spray and chitosan gel; Group 4: placebo.

Results: Histological analyses showed a significant regeneration in all groups ( p < 0.001). On the final assessment of the ulcer, using the combination was found a wound closure percentage of 71 ± 30, 70 ± 27 using isosorbide dinitrate, 58 ± 30 with chitosan and 50 ± 16 with placebo. The number of patients who achieved complete ulcer closure was six using the combination, four with isosorbide dinitrate, three with chitosan and one with placebo. The progression in the healing process of the ulcer showed marked inmunohistochemical differences of Von Willebrand Factor, desmin, vascular endothelial growth factor-A and α-smooth muscle actin in all groups ( p < 0.001), but without notable differences between them.

Conclusion: The combination was better than placebo to reduce the dimensions of the ulcer, accelerate healing and increase the number of patients who achieved complete closure of the ulcer, but the combination was not better than chitosan or isosorbide dinitrate used separately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1479164118769528DOI Listing
July 2018

Effect of Alpha-Lipoic Acid on Clinical and Neurophysiologic Recovery of Carpal Tunnel Syndrome: A Double-Blind, Randomized Clinical Trial.

J Med Food 2018 May 22;21(5):521-526. Epub 2018 Jan 22.

1 Institute of Experimental and Clinical Therapeutics, Health Science University Center, University of Guadalajara , Guadalajara, Jalisco, México .

The objective of our study was to examine the effect of alpha-lipoic acid (ALA) on clinical and neurophysiologic outcomes after surgery for idiopathic carpal tunnel syndrome (CTS). We conducted a randomized, double-blind, placebo-controlled clinical trial in 20 adults diagnosed with idiopathic CTS after clinical and neurophysiologic assessment. Eligible participants took 600 mg ALA or placebo per day for 1 month before surgery, and for 2 months afterward. Further clinical and neurophysiologic assessments were undertaken immediately before surgical decompression, and at 12 weeks postoperatively with additional clinical assessments at the 4th and 8th week after surgery. Clinical outcome measures were taken by Boston Questionnaire score, the presence or absence of Tinel's sign, and Phalen's test findings. Median nerve conduction studies were also undertaken and interpreted according to Dumitru's reference values. Nineteen patients completed the study; one member of the placebo group was lost during follow-up. There were significant improvements in clinical and neurophysiologic variables in the ALA treatment group, present even before surgery. Boston Questionnaire scores had improved significantly in both groups. In the ALA group, none of the participants had positive Phalen's or Tinel's signs at 12 weeks, and motor and sensory fiber latency and amplitude had significantly improved; in the placebo group, only the sensory distal latency had improved significantly. In conclusion, ALA administered 1 month before open decompression and for 2 months afterward improves the clinical and neurophysiologic outcomes after surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jmf.2017.0056DOI Listing
May 2018

Validation of the Omron HEM-7320-LA, upper arm blood pressure monitor with Intelli Wrap Technology Cuff HEM-FL1 for self-measurement and clinic use according to the European Society of Hypertension International Protocol revision 2010 in the Mexican population.

Blood Press Monit 2017 Dec;22(6):375-378

Arterial Stiffness Laboratory, Department of Physiology, University of Guadalajara, Guadalajara, Mexico.

Objective: The aim of this study was to determine the accuracy of the Omron HEM-7320-LA with Intelli Wrap technology cuff HEM-FL1 for self-measurement and clinic blood pressure (BP) measurement according to the European Society of Hypertension International Protocol revision 2010.

Participants And Methods: The evaluation was performed in 39 individuals. The mean age of the participants was 47.9±14 years; systolic BP was 145.2±24.3 mmHg (range: 97-190), diastolic BP was 90.9±12.9 mmHg (range: 68-120), and arm circumference was 30.8±4 cm (range: 25-38.5).

Results: The device successfully fulfilled the established criteria of the validation protocol. The device overestimated systolic BP by 0.6±5.7 mmHg and diastolic BP by 2.2±5.1 mmHg. The specially designed cuff HEM-FL1 to cover a broad range of arm circumferences and self-placement fulfilled the requirements of the International Protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBP.0000000000000290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680989PMC
December 2017

Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities: A STROBE-compliant article.

Medicine (Baltimore) 2017 Aug;96(33):e7862

Instituto de Investigación en Reumatología y del Sistema Musculo Esquelético, Centro Universitario de Ciencias de la Salud Servicio de Reumatología, Especialidad en Reumatología, División de Medicina Interna, Hospital Civil Dr. Juan I. Menchaca Departamento de Fisiología, Centro Universitario de Ciencias de la Salud Departamento de Disciplinas Metodológicas, Filosóficas e Instrumentales, Centro Universitario de Ciencias de la Salud Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Servicio de Cardiología, División de Medicina Interna, OPD Hospital Civil de Guadalajara, Juan I. Menchaca, Guadalajara, Jalisco, Mexico Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.

The aim of this study was to analyze the impact of disease duration on carotid to femoral pulse wave velocity (cfPWV) in rheumatoid arthritis (RA) patients without either known traditional cardiovascular risk factors or previous comorbidities.Patients with RA diagnosis attending the rheumatology outpatient clinic of Hospital Civil Juan I. Menchaca, Guadalajara, Mexico, were analyzed. A total of 106 RA patients without known traditional cardiovascular risk factors were selected. All subjects were evaluated for RA disease duration, RA disease activity score on 28 joints (DAS28), serum lipids, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Arterial stiffness was measured as cfPWV by noninvasive tonometry. A multivariate regression model was used to analyze the contribution of RA disease duration and age on cfPWV. cfPWV was positively correlated with age (r = 0.450, P < .001), RA disease duration (r = 0.340, P < .001), total cholesterol (r = 0.312, P = .002), and low density lipoprotein (LDL-c) cholesterol (r = 0.268, P = .012). Patients with a RA disease duration ≥10 years exhibited significantly increased cfPWV compared with patients with disease duration <2 years (8.4 ± 1.8 vs 7.0 ± 0.8) and ≥2 to <10 years (8.4 ± 1.8 vs 7.8 ± 1.3), respectively. Age, RA disease duration, and triglycerides were predictors of cfPWV in multivariate analyses. According to the β-coefficients, each year of disease duration (β = 0.072) had a greater impact on cfPWV than age (β = 0.054).Each year of life with RA contributes to a higher rate of vascular aging or stiffening than a year of life without RA. The cumulative damage provided by RA was most pronounced in patients with disease duration ≥10 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000007862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571726PMC
August 2017

Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide.

Diabetes Obes Metab 2018 01 14;20(1):42-49. Epub 2017 Jul 14.

Baker Heart and Diabetes Institute, Melbourne, Australia.

The aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.13028DOI Listing
January 2018

Association of adipokines, interleukin-6, and tumor necrosis factor-α concentrations with clinical characteristics and presence of spinal syndesmophytes in patients with ankylosing spondylitis: A cross-sectional study.

J Int Med Res 2017 Jun 23;45(3):1024-1035. Epub 2017 May 23.

2 Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jal., México.

Objective To identify correlations of the serum leptin, adiponectin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations with the clinical characteristics, presence of spinal syndesmophytes, and body composition in patients with ankylosing spondylitis (AS). Methods Forty-eight patients with AS were compared with 41 sex- and age-matched controls. Assessment included clinical characteristics and the presence of spinal syndesmophytes. The serum leptin, adiponectin, TNF-α, and IL-6 concentrations were determined. Body composition was evaluated using dual-energy X-ray absorptiometry. Results Patients with AS and controls had similar fat mass and lean mass. Patients with AS had higher serum TNF-α and leptin concentrations than controls (52.3 vs. 1.5 pg/mL and 17.2 vs. 9.0 µg/mL, respectively). The IL-6 and adiponectin concentrations were not significantly different between the two groups. Patients with syndesmophytes had higher leptin concentrations than those without syndesmophytes (22.1 vs. 10.9 µg/mL); this difference remained after adjustment for the body mass index. Conclusion Elevated leptin concentrations are associated with spinal radiographic damage in patients with AS and can serve as a biomarker. Future studies should evaluate whether leptin might be a potential target for treatments to avoid structural damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300060517708693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536407PMC
June 2017

Identification of beta-Lactamases and beta-Lactam-Related Proteins in Human Pathogenic Bacteria using a Computational Search Approach.

Curr Microbiol 2017 Aug 16;74(8):915-920. Epub 2017 May 16.

Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada #950, colonia Independencia, C.P. 44340, Guadalajara, Jalisco, Mexico.

A systematic analysis of beta-lactamases based on comparative proteomics has not been performed thus far. In this report, we searched for the presence of beta-lactam-related proteins in 591 bacterial proteomes belonging to 52 species that are pathogenic to humans. The amino acid sequences for 19 different types of beta-lactamases (ACT, CARB, CifA, CMY, CTX, FOX, GES, GOB, IMP, IND, KPC, LEN, OKP, OXA, OXY, SHV, TEM, NDM, and VIM) were obtained from the ARG-ANNOT database and were used to construct 19 HMM profiles, which were used to identify potential beta-lactamases in the completely sequenced bacterial proteomes. A total of 2877 matches that included the word "beta-lactamase" and/or "penicillin" in the functional annotation and/or in any of its regions were obtained. These enzymes were mainly described as "penicillin-binding proteins," "beta-lactamases," and "metallo-beta-lactamases" and were observed in 47 of the 52 species studied. In addition, proteins classified as "beta-lactamases" were observed in 39 of the species included. A positive correlation between the number of beta-lactam-related proteins per species and the proteome size was observed (R 0.78, P < 0.00001). This correlation partially explains the high presence of beta-lactam-related proteins in large proteomes, such as Nocardia brasiliensis, Bacillus anthracis, and Mycobacterium tuberculosis, along with their absence in small proteomes, such as Chlamydia spp. and Mycoplasma spp. We detected only five types of beta-lactamases (TEM, SHV, CTX, IMP, and OXA) and other related proteins in particular species that corresponded with those reported in the literature. We additionally detected other potential species-specific beta-lactamases that have not yet been reported. In the future, better results will be achieved due to more accurate sequence annotations and a greater number of sequenced genomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00284-017-1265-3DOI Listing
August 2017

Serum levels of P-glycoprotein and persistence of disease activity despite treatment in patients with systemic lupus erythematosus.

Clin Exp Med 2018 Feb 27;18(1):109-117. Epub 2017 Feb 27.

Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.

Around 25% of patients with systemic lupus erythematosus (SLE) could be refractory to conventional therapies. P-glycoprotein expression on cell surface has been implied on drug resistance, however, to date, it is unknown if P-gp serum levels are associated with SLE disease activity. Evaluate the association of serum P-gp levels and SLE with disease activity despite treatment. A cross-sectional study was conducted on 93 female SLE patients, all receiving glucocorticoids at stable doses for the previous 6 months before to baseline. SLE patients were classified into two groups: (a) patients with active disease [SLE disease activity index (SLEDAI) ≥ 3] despite treatment, and (b) patients with inactive disease (SLEDAI < 3) after treatment. Forty-three healthy females comprised the control group. Serum P-gp, anti-DNA, and both anti-nucleosome antibody levels were measured using ELISA. Active-SLE patients despite treatment had higher P-gp levels compared with inactive-SLE after treatment (78.02 ng/mL ± 114.11 vs. 33.75 ng/mL ± 41.11; p = 0.018) or versus reference group subjects (30.56 ng/mL ± 28.92; p = 0.011). P-gp levels correlated with the scores of SLEDAI (r = 0.26; p = 0.01), Mexican-SLEDAI (MEX-SLEDAI) (r = 0.32; p = 0.002), SLICC/ACR damage index (r = 0.47; p < 0.001), and with prednisone doses (r = 0.33; p = 0.001). In the multivariate model, the high P-gp levels were associated with SLICC/ACR score (p = 0.001), and SLEDAI score (p = 0.014). Our findings support a relationship between serum P-gp levels and SLE with disease activity despite treatment, but it requires further validation in longitudinal studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10238-017-0459-0DOI Listing
February 2018