Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders.

OBJECTIVES: The acute manifestations of dengue are well known. The clinical symptoms that present during the convalescent phase of infection are less well characterized, but may be autoimmune-based. This study was undertaken to determine the prevalence of persistent clinical symptoms among individuals infected during the 2006 Cuban epidemic and to evaluate the immunological and genetic factors associated with their occurrence. METHODS: In 2008, clinical data and blood samples were collected from a random sample of adult individuals diagnosed during the 2006 epidemic with dengue fever (DF, n=68), dengue hemorrhagic fever (DHF, n=29), or an asymptomatic infection (AI, n=42). The presence of persistent symptoms was evaluated in all individuals and a psychological assessment was performed. IgG titers and the Fc receptor (FcR) were also evaluated. The following autoimmune markers were assessed in a subset (n=26) of symptomatic individuals: complement factors C3/C4, rheumatoid factor (RF), C-reactive protein (CRP), antinuclear antibodies (ANA), and immune complex (IC). RESULTS: Over half (55/97) the individuals with a prior of diagnosis of DF or DHF had persistent clinical symptoms in the 2 years following infection. The sequelae were unrelated to the initial diagnosis and were more common among women (44/55). No symptoms were reported in the AI group and all study participants had normal mental and cognitive function. Persistent clinical symptoms were associated with HH polymorphic variant (p=0.027) and high IgG titer (p=0.041). Autoimmune marker alterations were common (20/26) in the subset of symptomatic individuals evaluated. CONCLUSIONS: Clinical sequelae after recovery from an acute dengue virus infection are common in the 2 years following infection. The results obtained in this study suggest that persistent symptoms are associated with alterations in some immunological parameters and FcγRIIa gene polymorphism. This could suggest an autoimmune-based disturbance.

Comparison of the efficacy and tolerability of policosanol with atorvastatin in elderly patients with type II hypercholesterolaemia.

BACKGROUND: Hypercholesterolaemia is a risk factor for coronary heart disease (CHD). Clinical studies have shown that lowering elevated serum total cholesterol (TC) levels, and particularly low density lipoprotein-cholesterol (LDL-C) levels, reduces the frequency of coronary morbidity and deaths, whereas high serum levels of high density lipoprotein-cholesterol (HDL-C) protect against CHD. Policosanol is a cholesterol-lowering drug purified from sugar cane wax with a therapeutic dosage range from 5-20 mg/day. Atorvastatin is an HMG-CoA reductase inhibitor which across its dosage range (10-80 mg/day) has shown significantly greater lipid-lowering effects than all previously marketed statins. OBJECTIVE: This study was undertaken to compare the efficacy and tolerability of policosanol with atorvastatin in older patients with type II hypercholesterolaemia. PATIENTS AND METHODS: This randomised, single-blind, parallel-group study was conducted in older patients (60-80 years) with type II hypercholesterolaemia. After 4 weeks on a cholesterol-lowering diet, 75 patients were randomised to policosanol or atorvastatin 10mg tablets taken once daily with the evening meal for 8 weeks. An interim and final check-up were performed at 4 and 8 weeks, respectively, after treatment was initiated. RESULTS: At 4 (p < 0.0001) and 8 (p < 0.00001) weeks, policosanol 10 mg/day significantly lowered serum LDL-C levels by 17.5 and 23.1%, respectively compared with baseline; corresponding values for atorvastatin were 28.4 and 29.8%. At study completion, policosanol significantly (p < 0.0001) reduced serum TC (16.4%), LDL-C/HDL-C ratio (25.5%) and TC/HDL-C ratio (19.3%), as well as (p < 0.001) triglyceride levels (15.4%). Atorvastatin significantly (p < 0.0001) decreased serum TC (22.6%), LDL-C/HDL-C (26.2%) and TC/HDL-C (19.8%) ratios, as well as (p < 0.001) triglyceride levels (15.5%). Atorvastatin was significantly more effective than policosanol in reducing LDL-C and TC, but similar in reducing both atherogenic ratios and triglyceride levels. Policosanol, but not atorvastatin, significantly (p < 0.05) increased serum HDL-C levels by 5.3%. Both treatments were well tolerated. At study completion, atorvastatin mildly, but significantly (p < 0.05) increased creatine phosphokinase (CPK) and creatinine, whereas policosanol significantly reduced AST and glucose (p < 0.01) and CPK (p < 0.05) levels. All individual values, however, remained within normal limits. Three atorvastatin but no policosanol patients withdrew from the study because of adverse events: muscle cramps (1 patient), gastritis (1 patient) and uncontrolled hypertension, abdominal pain and myalgia (1 patient). Overall, no policosanol and seven atorvastatin patients (18.9%) reported a total of nine mild or moderate adverse events during the study (p < 0.01). CONCLUSIONS: This study shows that policosanol (10 mg/day) administered for 8 weeks was less effective than atorvastatin (10 mg/day) in reducing serum LDL-C and TC levels in older patients with type II hypercholesterolaemia. Policosanol, but not atorvastatin, however, significantly increased serum HDL-C levels, whereas both drugs similarly reduced atherogenic ratios and serum triglycerides. Policosanol was better tolerated than atorvastatin as revealed by patient withdrawal analysis and overall frequency of adverse events. Nevertheless, further studies must be conducted in larger sample sizes and using dose-titration methods to achieve target lipid levels in order to reach wider conclusions.

Effects of d-003, a new hypocholesterolaemic and antiplatelet compound, on lipid profile and lipid peroxidation in healthy volunteers.

BACKGROUND: D-003 is a mixture of long-chain aliphatic primary acids purified from sugarcane wax with hypocholesterolaemic effects proven in rabbits and healthy volunteers; it lowers serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) and increases high-density lipoprotein-cholesterol (HDL-C). D-003 also prevents lipoprotein lipid peroxidation in experimental models. OBJECTIVE: To investigate the effects of D-003 on lipid profile and lipid peroxidation in healthy human volunteers. PARTICIPANTS: Forty-six healthy volunteers (24 women, 22 men). METHODS: This double-blind, randomised, placebo-controlled study investigated the effects of D-003 at 5 and 10 mg/day on the susceptibility of LDL to lipid peroxidation induced by copper ions in healthy volunteers. Forty-six individuals were randomised (1 : 2) to placebo or D-003 at 5 or 10 mg/day, the tablets being taken once a day with the evening meal for 8 weeks. Laboratory determinations and physical examination were performed at baseline and after 4 and 8 weeks of therapy, and compliance and adverse experience assessments were performed at weeks 4 and 8. RESULTS: All groups were well matched at baseline. At study completion, D-003 at 5 and 10 mg/day significantly (p < 0.001) lowered LDL-C, the primary response variable, by 20.8% and 28.8%, respectively. In addition, D-003 at 5 and 10 mg/day reduced (p < 0.001) TC (12.7% and 17.5%, respectively), LDL-C/ HDL-C (25.9% and 36.3%, respectively) and TC/HDL-C (18.6% and 26.3%, respectively), while significantly (p < 0.01) increasing HDL-C (7.7% and 12.4%, respectively). Triglycerides were significantly (p < 0.05) reduced (8.8% and 13.1%, respectively) with respect to baseline, but not versus placebo. Responses assessed at 4 weeks showed significant reductions of LDL-C, TC and atherogenic ratios with both doses of D-003, whereas HDL-C was significantly increased. Triglycerides, however, remained unchanged. No significant changes in any lipid profile variable occurred in the placebo group. D-003 at 5 and 10 mg/day significantly (p < 0.05) increased lag time (18.3% and 32.0%, respectively) and decreased maximum rate of diene propagation (V(max)) [12.7% and 19.1%, respectively] of copper-induced LDL peroxidation. D-003 5 and 10 mg/day attenuated the reduction of the reactivity against 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) by 19.9% and 32.0%, respectively. The treatment was well tolerated. Three subjects (one from each group) discontinued the study. Only one, treated with D-003 5 mg/day, discontinued because of an adverse event (gastritis). CONCLUSIONS: D-003 at 5 and 10 mg/day demonstrated dose-dependent cholesterol-lowering effects in healthy volunteers characterised by reductions in LDL-C, TC and atherogenic ratios, and increases in HDL-C. Effects on triglycerides were modest and uncertain. As expected from experimental studies, D-003 inhibited the susceptibility of LDL to lipid peroxidation assessed by three indicators lag time V(max) and reactivity versus TNBS. Further studies investigating the effect of larger doses and treatment duration must be conducted to confirm the reproducibility of the present results in different study populations.