Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid.

Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine), its use should be restricted to outbreaks of meningococcal disease.

Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine), its use should be restricted to outbreaks of meningococcal disease.

Long-term exposure to nonylphenol affects insulin signaling in the liver of adult male rats.

In the present study, we sought to investigate the long-term effects of nonylphenol (NP) on insulin signaling and glucose metabolism in liver. Furthermore, reactive oxygen species (ROS) in liver was evaluated as it is known to induce insulin resistance. Rats were administered NP by oral gavage at the doses of 15, 150 and 1500 µg/ kg body weight per day for 45 days. Hydrogen peroxide (H(2)O(2)) generation and lipid peroxidation were increased, and the activities of antioxidant enzymes were decreased in the liver of NP-treated rats. NP increased the plasma glucose and insulin levels and altered the enzymes of carbohydrate metabolism. Decrease in the protein levels of insulin signaling molecules insulin receptor (IR), IR substrate (IRS)-1, IRS-2 and phosphatidylinositol-3-kinase were observed with parallel increase in H(2)O(2) levels in the liver of NP-treated rats. These results suggest that NP downregulates insulin signaling in liver, which could be due to ROS production and oxidative damage.

Effects of corticosterone and 2,3,7,8-tetrachloro- dibenzo-p-dioxin on epididymal antioxidant system in adult rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, causes epididymal toxicity by inducing oxidative stress. Glucocorticoids have been found to influence TCDD action in vitro and in vivo. The present experiments were set up to analyze the effects of TCDD on rat epididymal antioxidant system under the influence of increased corticosterone level. Adult male Wistar/NIN rats (70-80 days old) numbering 24 (six per group) were used in the study. Corticosterone (3 mg/kg body weight per day) or TCDD (100 ng/kg body weight per day) were administered or coadministered to rats for 15 days. Treatment with corticosterone or TCDD decreased the levels of serum testosterone significantly. In caput, corpus, and cauda fractions, administration of corticosterone or TCDD increased the levels of lipid peroxidation and hydrogen peroxide and decreased the activities of superoxide dismutase and catalase significantly. Coadministration of corticosterone and TCDD to rats decreased the levels of serum testosterone significantly as compared with rats treated with TCDD alone. In caput, corpus, and cauda fractions, the levels of lipid peroxidation and hydrogen peroxide were increased and activities of superoxide dismutase and catalase were decreased significantly as compared with rats treated with TCDD alone. Stress, characterized by increased glucocorticoid levels and activity, may enhance TCDD-induced epididymal toxicity.

Differential capacities of outer membrane proteins from Neisseria meningitidis B to prime the murine immune system after vaccination.

Understanding the specificity of antibody response to Neisseria meningitidis serogroup B (Men B) is a key requirement for the development of an effective vaccine. This study was designed to investigate the antigen specificity of murine IgG1 and IgG2b antibodies induced by different primary immunization schedules and the booster dose with the Cuban Men B vaccine. Immunoblotting analyses were performed using outer membrane vesicles (OMV) from the vaccine strain (B:4,7:P1.19,15). IgG subclasses binding to PorA, PorB and RmpM were determined by digital scanning of the immunoreactive bands. Bactericidal antibody response after vaccination was also evaluated. The results indicated that IgG2b anti-PorA was the main antibody response induced by two doses of the vaccine. A primary series of three doses was found important for increasing IgG2b as well as IgG1 to PorB and RmpM. The fourth dose favoured the recognition of RmpM as detected by the increase of specific IgG1 and IgG2b. IgG subclasses anti-PorA did not change significantly if animals received two, three or four doses of the vaccine during the primary immunization or after the booster dose for all vaccine groups. The booster response to PorB and RmpM of groups BC2 and BC3 showed a significant increase in IgG2b levels compared with the primary response. However, the recall and the primary response of group BC4 were similar, suggesting a saturated dose-effect response after four doses of vaccine. The same was seen for bactericidal antibody response when human complement source was used in the assay.

Effect of piperine on the epididymis of adult male rats.

AIM: To study the effect of piperine on the epididymal antioxidant system of adult male rats. METHODS: Adult male rats were orally administered piperine at doses of 1 mg/kg, 10 mg/kg and 100 mg/kg body weight each day for 30 consecutive days. Twenty-four hours after the last treatment, the rats were weighed and killed with ether and the epididymis was dissected from the bodies. Sperm collected from the cauda region of the epididymis was used for the assessment of its count, motility and viability. Caput, corpus and cauda regions of the epididymis were separated and homogenized separately to obtain 10 % homogenates. The supernatants were used for the assays of sialic acid, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, lipid peroxidation and hydrogen peroxide generation. RESULTS: Body weight of the piperine-treated rats remained unchanged. The weights of the caput, corpus and cauda regions of the epididymis significantly decreased at dose of 100 mg/kg. Epididymal sperm count and motility decreased at 10 mg/kg and 100 mg/kg, and sperm viability decreased significantly at 100 mg/kg. Sialic acid levels in the epididymis decreased significantly at 100 mg/kg while significant decrease in the cauda region alone was observed at 10 mg/kg. A significant decline in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, along with an increase in hydrogen peroxide generation and lipid peroxidation were observed at 10 mg/kg and 100 mg/kg. CONCLUSION: Piperine caused a decrease in the activity of antioxidant enzymes and sialic acid levels in the epididymis and thereby increased reactive oxygen species levels that could damage the epididymal environment and sperm function.