ABSTRACT
Addiction and withdrawal are problems disturbing the health of the individual and also causes difficulties for society, raising the rates of divorce, unemployment and government spending on legal and medical systems. Opioids show an important pharmacological effect in the treatment of pain, with extremely addictive potential. Chronic opioid exposure is known to produce the complex behaviors of tolerance and dependence, a state exposed by opioid abstinence leading to withdrawal syndrome, as well as oxidative stress. Studies show that calcium mediated secondary messengers play a crucial role in the mechanism of addictive process and oxidative stress induced by chronic opioid usage. Calcium/calmodulin-dependent protein kinase II (CaMKII), is a major calcium regulated signal transducer that controls many neuronal systems and play important role in neuronal plasticity and can act as a key and direct promoting opioid tolerance and dependence and identifying such a direct mechanism may be useful for designing a pharmacology treatment for these conditions, recent studies, has been shown that calcium channels antagonist can be used in the treatment of withdrawal syndrome. Chronic opioid exposure associated with tolerance, dependence withdrawal syndrome and oxidative stress. Studies has shown that calcium mediated secondary messengers involved in the genesis of these conditions, better understanding of biological mechanisms underlie reduction in neuronal cell excitability could help in the identification of pharmacological targets for treatment.
ABSTRACT
Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals resident in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analysis of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studied analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable of neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successfull: while the Brazilian B clade B" variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.