Anti-tubercular and antioxidant activities of C-glycosyl carbonic anhydrase inhibitors: towards the development of novel chemotherapeutic agents against Mycobacterium tuberculosis.

During the treatment of tuberculosis infection, oxidative stress due to anti-tubercular drugs may result in tissue inflammation. It was suggested that treatment with antioxidant drugs could be beneficial as an adjunct to anti-tuberculosis drug therapy. Recently our group has shown that several C-glycosides are inhibitors of Mycobacterium tuberculosis ß-carbonic anhydrases (CAs, EC 4.2.1.1). In an effort to develop novel chemotherapeutic agents against tuberculosis, the anti-tubercular and antioxidant activities of a series of C-glycosides containing the phenol or the methoxyaryl moiety were studied. Many compounds showed inhibition of growth of M. tuberculosis H37Rv strain and good antioxidant ability. A glycomimetic incorporating the 3-hydroxyphenyl moiety showed the best activity profile and therefore this functionality represents lead for the development of novel anti-tubercular agents with dual mechanisms of action.

Cross-sectional survey of the prevalence of reduced estimated glomerular filtration rate, albuminuria and cardiovascular risk in a native Spanish population.

OBJECTIVES: HERMEX is a population-based study which tries to evaluate the relative weight of cardiovascular risk factors in inhabitants of Extremadura, Spain. This report presents the data about chronic kidney disease (CKD) in a Spanish population sample. METHODS: For an observational cross-sectional population-based study, 3,402 subjects were randomly selected from health care system records. The final sample included 2,813 participants (mean age 51.2 years, 53.5% women). Renal function was estimated from serum creatinine using the 4-variable Modification of Diet in Renal Disease (MDRD-4) Study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Individual renal risk was calculated using the Kidney Disease Improving Global Outcomes (KDIGO) table. RESULTS: Using the CKD-EPI formula, 3.6% of participants had a glomerular filtration rate (GFR) <60 ml/min. MDRD-4 gave a result of 4.0%. Prevalence of albuminuria was 5.5%. Taken together, in patients with albuminuria and/or reduced GFR, the prevalence of renal disease was 8.1%. The KDIGO renal risk table suggested that 0.05% of patients were at high or very high risk of CKD progression and 1.6% at medium risk. CKD was more common in those who were obese, hypertensive, dyslipidemic or had diabetes. Multivariate analysis showed an independent negative association of CKD as dependent variable with systolic blood pressure and body mass index, but a positive correlation with diastolic blood pressure and male sex. CONCLUSIONS: A low frequency of abnormal GFR was detected in a randomly selected sample of the Spanish general population. This finding agreed with the low rates of cardiovascular mortality and morbidity observed in Spain in spite of a high prevalence of classic cardiovascular risk factors.

Prevalence of abnormal urinary albumin excretion in a population-based study in Spain: results from the HERMEX Study.

BACKGROUND: HERMEX is a population-based study which try to evaluate the relative weight of cardiovascular risk factors in the population of Extremadura. This report provides the data obtained about microalbuminuria in a large Spanish population. DESIGN AND METHODS: Observational, cross-sectional, population-based study. A total of 3402 subjects were randomly selected from the Health Care System of Extremadura. The final sample included 2813 subjects (mean age 51·2 years, 53·5% female). Urinary albumin excretion rate (UAER) in first morning urine sample was analysed. Microalbuminuria was diagnosed when UAER was ≥ 22 in men or ≥ 31 mg/g in women. RESULTS: Prevalence of abnormal UAER in general population was 5·5% (microalbuminuria: 4·7%; proteinuria 0·8%). Microalbuminuria grew slightly in patients between 65 and 74 years and showed a dramatic increase in subject older than 75 years (P < 0·001). Men showed a high prevalence of microalbuminuria (5·8% vs. women 3·6%; P = 0·006 chi-squared test). Increased UAER was more common in obese subjects (6·7% vs. 2·3%, P < 0·001), hypertensive patients (8·3% vs. 2·3%, P < 0·001) and diabetic ones (10·9% vs. 3·7%, P < 0·001). The multivariate analysis showed a positive correlation of abnormal UAER with body mass index (BMI), systolic blood pressure, plasma creatinine and triglyceride levels. CONCLUSIONS: A low frequency of abnormal UAER was detected in a randomly selected sample of Spanish general population. This finding agreed with the low rates of cardiovascular mortality and morbidity observed in Spain in spite of a high prevalence of classic cardiovascular risk factors.