The effectiveness of ziprasidone in treating impaired quality of life in schizophrenia: a 12-month, open-label, flexible-dose, naturalistic observational study of patients undergoing usual care

OBJECTIVE: Health related quality of life (HRQL) has become an important outcome measure in the treatment of psychiatric disorders. This long-term observational study examined ziprasidone-induced improvement in satisfaction with HRQL in schizophrenia patients treated under real-world conditions. METHOD: Seventy schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dose (40-160 mg/d), large-scale, naturalistic trial. Outcome measures were taken at baseline, 6, and 12 months, and included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), severity of symptoms, distress, and side effects. RESULTS: Thirty-two patients fully completed the study protocol. Patients reported poorer general HRQL compared with healthy subjects. At the end of the study, significant improvement in general activity, and satisfaction with life was observed. The effect sizes for these changes were moderate (0.55, and 0.72, respectively). After Bonferroni correction for multiple comparisons improvement in satisfaction with general activity remained significant. No significant changes were noted in other Q-LES-Q dimensions. Improvement in general activity was associated with a reduction in the severity of symptoms and emotional distress, but was unrelated to the ziprasidone daily dose, side effect scores, and concomitantly prescribed antidepressants, anxiolytics, mood stabilizers, or antiparkinson drugs. CONCLUSION: This study indicates that ziprasidone treatment resulted in the improvement of the satisfaction with general activity that tended to increase over time, from month 6 onwards. This effect was associated with reduction in the severity of clinical symptoms, and emotional distress.     

Protection against mouse and avian influenza A strains via vaccination with a combination of conserved proteins NP, M1 and NS1

Background Experimental data accumulated over more than a decade indicate that cross‐strain protection against influenza may be achieved by immunization with conserved influenza proteins. At the same time, the efficacy of immunization schemes designed along these lines and involving internal influenza proteins, mostly NP and M1, has not been sufficient. Objective To test the immunogenicity and protective efficacy of DNA vaccination with a combination of NP, M1 and NS1 genes of influenza virus. Methods The immunogenicity and protective efficacy of DNA vaccination with NP, M1 and NS1 was tested in mice and chickens. Mice were challenged with mouse‐adapted viral strains H3N2 and H5N2 and chicken challenged with avian H5N3 virus. Results In these settings, wild‐type NS1 did not impede the cellular and humoral response to NP/M1 immunization in vivo. Moreover, addition of NS1‐encoding plasmid to the NP/M1 immunization protocol resulted in a significantly increased protective efficacy in vivo. Conclusions The addition of NS1 to an influenza immunization regimen based on conserved proteins bears promise. It is feasible that upon further genetic modification of these and additional conserved influenza proteins, providing for their higher safety, expression and immunogenicity, a recombinant vaccine based on several structural and non‐structural proteins or their epitopes will offer broad anti‐influenza protection in a wide range of species.     

Stabilization of neurotoxic Alzheimer amyloid-β oligomers by protein engineering

Soluble oligomeric aggregates of the amyloid-β peptide (Aβ) have been implicated in the pathogenesis of Alzheimer’s disease (AD). Although the conformation adopted by Aβ within these aggregates is not known, a β-hairpin conformation is known to be accessible to monomeric Aβ. Here we show that this β-hairpin is a building block of toxic Aβ oligomers by engineering a double-cysteine mutant (called Aβcc) in which the β-hairpin is stabilized by an intramolecular disulfide bond. Aβ₄₀cc and Aβ₄₂cc both spontaneously form stable oligomeric species with distinct molecular weights and secondary-structure content, but both are unable to convert into amyloid fibrils. Biochemical and biophysical experiments and assays with conformation-specific antibodies used to detect Aβ aggregates in vivo indicate that the wild-type oligomer structure is preserved and stabilized in Aβcc oligomers. Stable oligomers are expected to become highly toxic and, accordingly, we find that β-sheet-containing Aβ₄₂cc oligomers or protofibrillar species formed by these oligomers are 50 times more potent inducers of neuronal apoptosis than amyloid fibrils or samples of monomeric wild-type Aβ₄₂, in which toxic aggregates are only transiently formed. The possibility of obtaining completely stable and physiologically relevant neurotoxic Aβ oligomer preparations will facilitate studies of their structure and role in the pathogenesis of AD. For example, here we show how kinetic partitioning into different aggregation pathways can explain why Aβ₄₂ is more toxic than the shorter Aβ₄₀, and why certain inherited mutations are linked to protofibril formation and early-onset AD.     

Comparative studies of local antibody and cellular immune responses to influenza infection and vaccination with live attenuated reassortant influenza vaccine (LAIV) utilizing a mouse nasal-associated lymphoid tissue (NALT) separation method

The first and most significant barrier against influenza infection is the mucosal-associated lymphoid tissue of the upper airways and rodent nasopharyngeal-associated lymphoid tissue (NALT) is considered equivalent to the lymphoid tissue of human Valdryer's ring. This study is the first attempt to analyze and compare local and systemic cellular and antibody immune responses in NALT and spleen in a mouse model of experimental influenza infection and intranasal vaccination with LAIV (live attenuated reassortant influenza vaccine). It was shown that the vaccine strain completely inherited the ability to induce high-grade local antibody responses (secretory IgA + IgG + IgM), local cellular lymphoproliferative activity, CD4⁺, CD8⁺ and CD19⁺ lymphocyte and cytokine production responses from the virulent parental strain but it had less capacity to stimulate production of serum IgG, accumulation of CD8⁺ cells and IFN-γ production in the spleen. Primary non-complicated influenza infection and primary vaccination were accompanied by a short-term (24 h) increase in the levels of lymphocyte apoptosis in both NALT and spleen. However, experimental data indicated that vaccination with LAIV and uncomplicated forms of influenza infection did not influence immune system apoptosis following a secondary immune response.