Serum uric acid levels and risk for vascular diseases in patients with metabolic syndrome

OBJECTIVE: Gout and increased serum uric acid (SUA) levels are often seen in patients with components of the metabolic syndrome. Increased SUA levels are associated with increased vascular risk, as is the metabolic syndrome. We investigated the association between SUA levels and the metabolic syndrome in a population of patients with manifest vascular disease to determine whether SUA levels convey an independent risk for vascular disease in patients with the metabolic syndrome. METHODS: A nested case-cohort study of 431 patients with 220 cases with a new vascular event during followup, originating from the Second Manifestations of Arterial Disease (SMART) study. All patients had manifest vascular diseases, consisting of cerebral, coronary, or peripheral artery disease or abdominal aortic aneurysm. The relationship of SUA with the metabolic syndrome was analyzed with linear regression and adjusted for age, sex, creatinine clearance, and alcohol and diuretic use. The relationship of SUA levels with new vascular disease was investigated with Cox regression and adjusted for age and sex. RESULTS: The metabolic syndrome was present in 50% of patients. SUA levels were higher in 214 patients with the metabolic syndrome than in 217 patients without (0.36 +/- 0.08 mmol/l vs 0.32 +/- 0.09 mmol/l). SUA concentrations increased with the number of components of the metabolic syndrome (0.30 mmol/l to 0.38 mmol/l) adjusted for age, sex, creatinine clearance, and alcohol and diuretic use. Increased SUA concentrations were independently associated with risk for vascular events in patients without the metabolic syndrome (age and sex adjusted hazard ratio 2.4, 95% CI 1.0-5.5), in contrast to patients with the metabolic syndrome (adjusted hazard ratio 1.9, 95% CI 1.0-3.9). CONCLUSION: Elevated SUA levels are strongly associated with the metabolic syndrome, yet are not an independent risk factor for vascular disease in patients with the metabolic syndrome. In patients without the metabolic syndrome, elevated SUA levels are associated with increased risk for vascular disease.     

Virological characterization of an infection with a dual-tropic, multidrug-resistant HIV-1 and further evolution on antiretroviral therapy

We studied a case of recent infection with multidrug-resistant (MDR) HIV-1. Over 16 months off-therapy, the CD4 cell count decreased from 419 to 184 cells/mul. Antiretroviral therapy (ART) then led to an incomplete virological response but to an immunological benefit, concurrently with a shift to CCR5-only tropism and a reduction in replication capacity. ART, even if suboptimal, can be of interest in the case of MDR virus infection.     

Revised diagnostic criteria for neuromyelitis optica (NMO)

We analyzed neuromyelitis optica (NMO) IgG in the serum or CSF samples from 46 patients with suspected NMO (28) and limited forms of NMO (18). One hundred and fifteen samples from multiple sclerosis (MS) patients were included as controls. The final clinical diagnosis after follow-up was 16 NMO, 12 MS, 11 transverse myelitis (TM) and seven recurrent optic neuritis (RON). NMO-IgG was detected in 62.5% of NMO, 50% of the recurrent longitudinally extensive TM, 14.3% of the RON but in none of the MS patients. The authors then compared the newly revised diagnostic criteria for NMO with the criteria published in 1999, in the 28 patients with suspected NMO. The revised criteria had higher specificity, and positive and negative predictive value (83.3% vs. 25%; 87.5% vs. 62.5; 83.3% vs. 75%), but slightly lower sensitivity (87.5% vs. 93.7%). Our study confirms NMO-IgG as a highly specific marker of NMO, and the usefulness of the revised diagnostic criteria in predicting a diagnosis of NMO.     

Influence of lipids and obesity on haemorheological parameters in patients with deep vein thrombosis

It is not well established whether haemorheological alterations constitute independent risk factors for deep vein thrombosis (DVT). We have determined in 149 DVT patients and in 185 control subjects the body mass index (BMI), the haemorheological profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen (Fg), erythrocyte aggregation (EA), erythrocyte deformability (ED) and plasma lipids. In the crude analysis BMI, Fg, PV, EA, triglycerides (TG) and ApoB were statistically higher and HDL cholesterol (HDL-Chol) statistically lower in DVT patients than in controls. No differences in BV and ED were observed. After BMI adjustment, Fg, PV and EA remained statistically higher in DVT cases than in controls (P = 0.013; P = 0.012; P = 0.013; P = 0.028, respectively). When the risk of DVT associated with these variables (using cut-offs that corresponded to the mean plus one SD of the control group) was estimated, EA > 8.2 and PV > 1.28 mPa . s were significantly associated with DVT even further adjustment for lipids and obesity (OR = 2.78, P = 0.004; OR = 1.91, P = 0.024, respectively). However, PV did not remain statistically significant after additional adjustment for Fg. When we consider together all the analyzed variables in order to control every variable for each other, TG > 175 mg/dl (OR = 3,2, P = 0.004) and BMI > 30 kg/m(2) (OR = 3.5, P = 0.003), were also independently associated with a greater risk of DVT. Our results suggest that increased EA constitute an independent risk factor for DVT. However, when associated to hyperlipidaemia and obesity it further increases thrombotic risk.     

Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine

Pilocarpine is a cholinergic agonist capable to induce seizures and an epilepticus-like state in rodents. This status epilepticus (SE) is an useful animal model to study the development and understanding of the neuropathology, behavioural and electroencephalographic alterations of human temporal lobe epilepsy. It has been suggested a relationship between SE and reactive oxygen species (ROS) that can result in seizure-induced neurodegeneration. The aim of this study was to evaluate the existence of oxidative damage and the changes in the antioxidant system in cortex after administration of a high pilocarpine dose. Rats were injected with pilocarpine (350 mg/kg i.p.) or with saline as control and 2h after the animals were sacrificed. Malondialdehyde (MDA) levels, as marker of lipid peroxidation, significantly increased (64%) after pilocarpine treatment evidencing oxidative damage. Antioxidant enzyme activities--catalase (CAT), glutathione peroxidase (GP) and superoxide dismutase (SOD)--significantly increased in response to pilocarpine (28%, 28% and 21%, respectively). GP and Mn-SOD gene expression were induced by pilocarpine treatment. Vitamin E concentration in brain cortex decreased (15%) as result of pilocarpine administration. In conclusion, the high dose of pilocarpine, used in the present study, induces oxidative damage and increases antioxidant enzyme activities and expression in brain cortex. Moreover, increased lipid peroxidation produces the consumption of Vitamin E.