Treatment with Enterococcus faecalis CECT7121 Is Not Effective as Therapy in Mice with an Established Allergy Status

In allergies, an unbalanced immune response towards a T helper (Th) 2 profile with high levels of Immunoglobulin (Ig) E is produced. We have demonstrated that the pre-administration of Enterococcus faecalis CECT7121 prevents the development of allergy in ovalbumin-immunized mice. In this work, we evaluated whether this bacterium can also revert an established allergic status. Mice were immunized with ovalbumin (OVA) and after that, were inoculated with an E. faecalis CECT7121 suspension. In immunized animals, serum specific immune response, proliferative activity of memory splenocytes, and levels of Th2 cytokines were assessed. The in vivo active cutaneous anaphylaxis test was also performed. The treatment with E. faecalis CECT7121 only increased anti-OVA IgG2a levels. No differences were observed in other specific immunological parameters. Probiotic-treatment did not prove to have any desensitizing effect on mice. These results, together with those recently published, can be concluded that this bacterium would not be appropriate for the treatment of allergic symptoms.Facultad de Ciencias Médicas (FCM

Treatment with Enterococcus faecalis CECT7121 Is Not Effective as Therapy in Mice with an Established Allergy Status

In allergies, an unbalanced immune response towards a T helper (Th) 2 profile with high levels of Immunoglobulin (Ig) E is produced. We have demonstrated that the pre-administration of Enterococcus faecalis CECT7121 prevents the development of allergy in ovalbumin-immunized mice. In this work, we evaluated whether this bacterium can also revert an established allergic status. Mice were immunized with ovalbumin (OVA) and after that, were inoculated with an E. faecalis CECT7121 suspension. In immunized animals, serum specific immune response, proliferative activity of memory splenocytes, and levels of Th2 cytokines were assessed. The in vivo active cutaneous anaphylaxis test was also performed. The treatment with E. faecalis CECT7121 only increased anti-OVA IgG2a levels. No differences were observed in other specific immunological parameters. Probiotic-treatment did not prove to have any desensitizing effect on mice. These results, together with those recently published, can be concluded that this bacterium would not be appropriate for the treatment of allergic symptoms.Facultad de Ciencias Médicas (FCM

The NRG1 exon 11 missense variant is not associated with autism in the Central Valley of Costa Rica

<p>Abstract</p> <p>Background</p> <p>We are conducting a genetic study of autism in the isolated population of the Central Valley of Costa Rica (CVCR). A novel Neuregulin 1 (NRG1) missense variant (exon 11 G>T) was recently associated with psychosis and schizophrenia (SCZ) in the same population isolate.</p> <p>Methods</p> <p>We genotyped the NRG1 exon 11 missense variant in 146 cases with autism, or autism spectrum disorder, with CVCR ancestry, and both parents when available (N = 267 parents) from 143 independent families. Additional microsatellites were genotyped to examine haplotypes bearing the exon 11 variant.</p> <p>Results</p> <p>The NRG1 exon 11 G>T variant was found in 4/146 cases including one de novo occurrence. The frequency of the variant in case chromosomes was 0.014 and 0.045 in the parental non-transmitted chromosomes. At least 6 haplotypes extending 0.229 Mb were associated with the T allele. Three independent individuals, with no personal or family history of psychiatric disorder, shared at least a 1 megabase haplotype 5' to the T allele.</p> <p>Conclusion</p> <p>The NRG1 exon 11 missense variant is not associated with autism in the CVCR.</p

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.