Induction of gp120-specific protective immune responses by genetic vaccination with linear polyethylenimine-plasmid complex

The induction of IFN-gamma-secreting CD8+ T cells and neutralizing antibodies to HIV-1 are both key requirements for prevention of viral transmission and clearance of pathogenic HIV. Although DNA vaccination has been shown to induce both humoral and cellular immune responses against HIV antigens, the magnitude of the immune responses has always been disappointing. In this report, we analyze the ability of polyethylenimine (PEI)-DNA complex expressing an HIV-glycoprotein 120 (gp120) antigen (PEI-pgp120) to induce systemic CD8+ T cell and humoral responses to the gp120 antigen. The administration of PEI-plasmid complex resulted in rapid elevation of serum levels of IL-12 and IFN-gamma. Furthermore, a single administration of PEI-pgp120 complex elicits a number of gp120-specific CD8+ T cells 20 times higher than that elicited by three intramuscular injections of naked DNA. Interestingly, we found that systemic vaccination with PEI-pgp120 induced protective immune responses against both systemic and mucosal challenges with a recombinant vaccinia virus expressing a gp120 antigen. The data also demonstrated that the depletion of macrophages with liposome-encapsulated clodronate completely abolished gp120-specific cellular response. Overall, our results showed that a single administration of PEI-pgp120 complexes, eliciting strong immune responses, is an effective vaccination approach to generate protection against systemic and mucosal viral infections.     

Needs and its relation to symptom dimensions in a sample of outpatients with schizophrenia

OBJECTIVE: To analyse the association between symptom dimensions in schizophrenia and number and type of met and unmet needs. METHOD: A sample of 231 outpatients randomly selected from a register that included all patients treated in 5 mental health care centres (MHCC) was evaluated. Assessment instruments included the Camberwell Assessment of Needs (CAN) questionnaire and the PANSS. RESULTS: Number of needs are related to overall severity of psychopathology. Patients with more symptoms have more total needs (p < 0.001) and unmet needs (p < 0.001). A multiple lineal regression model showed that the disorganized and excited dimensions of the PANSS are the most important components for explaining the variance of number of needs. Type of needs is related to subtypes of schizophrenia, specially with disorganized and excited symptoms. CONCLUSION: Psychosocial needs are related to schizophrenia subtypes. Patients with more needs are those with more disorganized and excitatory symptoms.     

Increased mitochondrial respiratory chain enzyme activities correlate with minor extent of liver damage in mice suffering from erythropoietic protoporphyria

Mitochondrial dysfunction might play a role in the pathogenesis of liver damage in erythropoietic protoporphyria (EPP). Changes in mitochondrial respiratory chain activities were evaluated in the Fech(m1pas)/Fech(m1pas) mouse model for EPP. Mice from different strains congenic for the same ferrochelatase germline mutation manifest variable degrees of hepatobiliary injury. Protoporphyric animals bred into the C57BL/6J background showed a higher degree of hepatomegaly and liver damage as well as higher protoporphyrin (PP) accumulation than those bred into the SJL/J and BALB/cJ backgrounds. Whereas mitochondrial respiratory chain activities remained unchanged in the liver of protoporphyric mice C57BL/6J, they were increased in protoporphyric mice from both SJL/J and BALB/cJ backgrounds, when compared to wild-type animals. Mitochondrial respiratory chain activities were increased in Hep G2 cell line after accumulation of PP following addition of aminolevulinic acid. As a direct effect of these elevated mitochondrial activities, in both hepatic cells from mutant mouse strains and Hep G2 cells, adenosine 5'-triphosphate (ATP) levels significantly increased as the intracellular PP concentration was reduced. These results indicate that PP modifies intracellular ATP requirements as well as hepatic mitochondrial respiratory chain enzymatic activities and further suggest that an increase of these activities may provide a certain degree of protection against liver damage in protoporphyric mice.     

Can a congenital dysfunctional bladder be diagnosed from a smile? The Ochoa syndrome updated

During the last 40 years over 100 patients have been reported with a dysfunctional lower urinary tract associated with a peculiar distortion of the facial expression. This most unusual disorder was initially considered a local observation. Time, however, has proven otherwise, since patients with this syndrome have now been reported from various countries throughout the world. This association of lower urinary tract and bowel dysfunction with an abnormal facial expression was named the urofacial (Ochoa) syndrome. Genetic studies have demonstrated that this condition is inherited as an autosomal recessive trait, and a potential gene has been mapped to chromosome 10q23-q24. There is also enough evidence to suggest that patients with this syndrome as well as those with subclinical neurological bladder, occult neuropathic bladder, non-neurogenic neurogenic bladder or Hinman syndrome, dysfunctional voiding, or dysfunctional elimination may be affected by the same congenital disorder of neurological origin.