Niacin administration significantly reduces oxidative stress in patients with hypercholesterolemia and low levels of high-density lipoprotein cholesterol.

Oxidative stress has been implicated in the pathogenesis of cardiovascular disorders, including atherosclerosis. In pharmacological doses, niacin (vitamin B3) was proven to reduce total cholesterol, triglyceride, very-low-density lipoprotein, and low-density lipoprotein levels, and to increase high-density lipoprotein (HDL) levels. The aim of this study was to evaluate the effect of niacin treatment in patients with low levels of HDL cholesterol (HDL-C; <40 mg%) on their lipid profile and oxidative stress status. Seventeen patients with hypercholesterolemia and low HDL-C and 8 healthy control subjects were enrolled in the study. The patients were treated with niacin for 12 weeks. Lipid profile, oxidative stress and C-reactive protein (CRP) levels were determined at the time of enrollment, and 2 and 12 weeks after initiation of niacin treatment. Subjects with lower HDL-C levels exhibited higher oxidative stress compared with subjects with normal HDL-C levels. Niacin treatment in hypercholesterolemic patients caused a significant increase in HDL-C and apolipoprotein A1 levels, and a decrease in triglyceride levels. Niacin also significantly reduced oxidative stress, as measured by a significant decrease in the serum content of thiobarbituric acid reactive substances, lipid peroxides and paraoxonase activity, compared with the levels before treatment. Although serum CRP levels were not affected by niacin treatment, a correlation between CRP and HDL levels was obtained when computing the results. Niacin treatment in hypercholesterolemic patients with low HDL levels caused a significant decrease in their oxidative stress status. These results indicate an additional beneficial effect of niacin beyond its ability to affect the lipid profile.

RCT of montelukast as prophylaxis for upper respiratory tract infections in children.

BACKGROUND: Infections with viruses causing upper respiratory tract infection (URI) are associated with increased leukotriene levels in the upper airways. Montelukast, a selective leukotriene-receptor antagonist, is an effective treatment of asthma and allergic rhinitis. OBJECTIVE: To determine whether prophylactic treatment with montelukast reduces the incidence and severity of URI in children. METHODS: A randomized, double-blind, placebo-controlled study was performed in 3 primary care pediatric ambulatory clinics in Israel. Healthy children aged 1 to 5 years were randomly assigned in a 1:1 ratio to receive 12-week treatment with 4 mg oral montelukast or look-alike placebo. Patients were excluded if they had a previous history of reactive airway disease. A study coordinator contacted the parents by phone once a week to obtain information regarding the occurrence of acute respiratory episodes. The parents received a diary card to record any acute symptoms of URI. The primary outcome measure was the number of URI episodes. RESULTS: Three hundred children were recruited and randomly assigned into montelukast (n = 153) or placebo (n = 147) groups. One hundred thirty-one (85.6%) of the children treated with montelukast and 129 (87.7%) of the children treated with placebo completed 12 weeks of treatment. The number of weeks in which URI was reported was 30.4% in children treated with montelukast and 30.7% in children treated with placebo. There was no significant difference in any of the secondary variables between the groups. CONCLUSIONS: In preschool-aged children, 12-week treatment with montelukast, compared with placebo, did not reduce the incidence of URI.

Prophylactic etoricoxib is effective in preventing "first of Ramadan" headache: a placebo-controlled double-blind and randomized trial of prophylactic etoricoxib for ritual fasting headache.

BACKGROUND: Religious fasting is associated with headache. This has been documented as "Yom Kippur headache" and "first of Ramadan headache." Etoricoxib, a Cox-2 inhibitor with a 22-hour half-life, has been shown effective in preventing fasting headache when taken just prior to the 25-hour Yom Kippur fast. We hypothesized that etoricoxib would also be effective in preventing headache during Ramadan, despite the different characteristics of the fast. METHODS: We performed a double-blind randomized prospective crossover trial of etoricoxib 90mg vs placebo, taken just prior to the onset of fasting, during the first 2 weeks of Ramadan 2010. Healthy adults aged 18-65 years were enrolled. Demographics, headache history and a daily post-fast survey were collected. We compared incidence, time of onset, and intensity of headache on each day and side effects in control and treatment groups. RESULTS: We enrolled 222 patients and 189 completed the post-fast questionnaire (87%). Etoricoxib reduced the incidence of "first of Ramadan" headache by 54% (46% in placebo group [n=92] vs 21% [n=96] in etoricoxib group) (P<.0001, OR 3.19 [95% CI 1.68-6.06]). For days 1-6, the mean number of headache days for the placebo group was 1.60 (n=92) and for the treatment group the mean was 0.86 (n=99) headache days (P=.003). Median severity of headache in the treatment group was significantly lower. In the second week, there was no significant difference in incidence of headache between groups, and the incidence of headache in the placebo group dropped markedly over time. CONCLUSION: Etoricoxib 90mg taken prior to a 15-hour ritual fast decreases incidence of and attenuates headache during the first 5 days of the month of Ramadan.

Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and excessive fluid retention. The effects of early versus late treatment with low or high doses of oral everolimus, a mammalian target of rapamycin inhibitor, on proteinuria in NS have not been previously described. METHODS: The effects of early treatment (2 days prior to NS induction) versus late treatment (beginning 2 weeks following the establishment of NS) with a low (20 mg/L) or high (100 mg/L) dose of everolimus for 5-7 weeks on proteinuria and nephrin/podocin abundance were assessed in male adult SD rats with adriamycin-induced NS. RESULTS: Adriamycin caused a significant increase in daily and cumulative proteinuria throughout the experimental period. Early, and to a lesser extent late treatment, with a low dose of everolimus, significantly decreased both daily and cumulative proteinuria and improved renal function. The anti-proteinuric effects of low-dose everolimus were associated with restoration of the disruptive glomerular nephrin/podocin abundance. In contrast, administration of a high dose of everolimus resulted in a decrease in proteinuria in NS rats, subsequently to deterioration of renal function. CONCLUSIONS: Early, and to a lesser extent late treatment, with a low but not a high dose of everolimus is effective in reducing proteinuria in nephrotic rats. The mechanism may be via nephrin/podocin protection.

Prophylactic etoricoxib is effective in preventing Yom Kippur headache: a placebo-controlled double-blind and randomized trial of prophylaxis for ritual fasting headache.

BACKGROUND: Religious fasting is associated with headache. This has been documented as "Yom Kippur Headache" and "First-of-Ramadan Headache." Rofecoxib (Vioxx®), a cyclooxygenase-2 (Cox-2) inhibitor with a 17-hour half-life, has been shown to be effective in preventing fasting headache when taken just prior to the 25-hour Yom Kippur fast. Unfortunately for fasters rofecoxib is no longer available. We hypothesized that etoricoxib, another Cox-2 inhibitor with a longer half-life, would also be effective in preventing fasting headache. METHODS: We performed a double-blind randomized prospective trial of etoricoxib 120 mg vs placebo, taken just prior to the onset of fasting, Yom Kippur 2008. Healthy adults aged 18-65 years were enrolled from the community. Subjects completed a demographic data form and questions regarding headache history and a post-fast survey on headache during the fast. We compared incidence, time of onset and intensity of headache, general ease of fasting, and side effects in control and treatment groups. RESULTS: We enrolled 211 patients and 195 completed the post-fast questionnaire (92%). Of those subjects receiving etoricoxib (n=99), 36 or 36.4% vs 65 or 67.7% of the placebo group (n=96) developed any headache during the fast (P< .0001). Median severity of headache in the treatment group was significantly lower for the treatment group (3.0 vs 5.0 on a visual analog scale of 10; P= .024). Also, participants in the treatment group reported an easier fast than the placebo group, as compared with previous fasting experience (4.0 vs 3.5 on a scale of 1-5; P< .0001). CONCLUSION: Etoricoxib 120 mg taken prior to a 25-hour ritual fast decreases incidence of and attenuates fasting headache.