Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Evaluation of the antimicrobial activity of each component in Grossman’s sealer Avaliação da atividade antimicrobiana de cada um dos componentes do cimento de Grossman

The antimicrobial activity of Grossman’s sealer and its components was evaluated on 13 different strains using the double layer well-diffusion method. Results revealed that Grossman’s sealer presented antimicrobial activity against all the tested strains. Among the components of the cement, sodium tetraborate presented the greatest antimicrobial activity, both in type and diameter of the halo and ring of inhibition. Sealer powder, rosin, and eugenol presented similar activity, with no effect on P. aeruginosa and C. albicans. Among these, only eugenol had an effect on E. coli. Zinc oxide was only active against S. sobrinus and E. coli. Barium sulfate and bismuth subcarbonate did not show any antimicrobial effect.<br>Os autores estudaram a atividade antimicrobiana do cimento de Grossman e de seus componentes sobre 13 diferentes cepas pelo método de difusão de poço em camada dupla. Os resultados revelaram que o cimento de Grossman apresentou atividade antimicrobiana contra todas as cepas utilizadas. Dos componentes do cimento, o tetraborato de sódio foi o que apresentou maior atividade antimicrobiana, tanto por tipo como por tamanho do halo e aro de inibição. O pó do cimento, o breu e o eugenol apresentaram atividades semelhantes, sendo que eles não tiveram ação sobre P. aeruginosa e C. albicans e, dos três componentes, somente o eugenol teve ação sobre E coli. O óxido de zinco somente teve ação sobre S. sobrinus e E. coli. O sulfato de bário e o subcarbonato de bismuto não tiveram nenhuma ação antimicrobiana