The Elevated Interferon Gamma Production is an Important Immunological Marker in HAM/TSP Pathogenesis

Human T-lymphotropic virus type 1 (HTLV-1) is the agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may Occur in > 5% of patients during their lifetime. HTLV-1-infection causes disturbances in the immune system, and the viral load may also play an important role in the pathogenesis of HAM/TSP. Some cytokines are involved in the pathogenesis of this disorder. We have determined IL-2, IL-4, IL-10, IL-12 p70, IFN-gamma and TNF-alpha production among HTLV-1-infected subjects from our HTLV-out Clinic in Institute of Infectious `Emilio Ribas` in Sao Paulo city, Brazil. PBMC obtained from healthy controls (n = 32), asymptomatic HTLV-1 carriers (n = 68) and HAM/TSP patients (n = 44) were grown in the absence and in the presence of phytohaemagglutinin (PHA), and the supernatants` fluids were measured for cytokines production. IL-2 levels were increased in the a-symptomatic HTLV-1 carriers, and IFN-gamma was increased in both groups of patients (asymptomatic HTLV-1 carriers and more significantly among HAM/TSP patients). IL-4, IL-10, TNF-alpha and IL-12 p70 levels were not significantly increased on both groups of patients, as compared with controls. The major finding Of this Study is that IFN-gamma was an important cytokine for the HAM/TSP pathogenesis. Therefore, immune modulation of IFN-gamma may be critical to treat of HAM/TSP patients.

Conservation of hepatitis C virus nonstructural protein 3 amino acid sequence in viral isolates during liver transplantation

As a consequence of selective pressure exerted by the immune response during hepatitis C virus (HCV) infection, a high rate of nucleotide mutations in the viral genome is observed which leads to the emergence of viral escape mutants. The aim of this study was to evaluate the evolution of the amino acid (aa) sequence of the HCV nonstructural protein 3 (NS3) in viral isolates after liver transplantation. Six patients with HCV-induced liver disease undergoing liver transplantation (LT) were followed up for sequence analysis. Hepatitis C recurrence was observed in all patients after LT. The rate of synonymous (dS) nucleotide substitutions was much higher than that of nonsynonymous (dN) ones in the NS3 encoding region. The high values of the dS/dN ratios suggest no sustained adaptive evolution selection pressure and, therefore, absence of specific NS3 viral populations. Clinical genotype assignments were supported by phylogenetic analysis. Serial samples from each patient showed lower mean nucleotide genetic distance when compared with samples of the same HCV genotype and subtype. The NS3 samples studied had an N-terminal aa sequence with several differences as compared with reference ones, mainly in genotype 1b-infected patients. After LT, as compared with the sequences before, a few reverted aa substitutions and several established aa substitutions were observed at the N-terminal of NS3. Sites described to be involved in important functions of NS3, notably those of the catalytic triad and zinc binding, remained unaltered in terms of aa sequence. Rare or frequent aa substitutions occurred indiscriminately in different positions. Several cytotoxic T lymphocyte epitopes described for HCV were present in our 1b samples. Nevertheless, the deduced secondary structure of the NS3 protease showed a few alterations in samples from genotype 3a patients, but none were seen in 1b cases. Our data, obtained from patients under important selective pressure during LT, show that the NS3 protease remains well conserved, mainly in HCV 3a patients. It reinforces its potential use as an antigenic candidate for further studies aiming at the development of a protective immune response.

Contributions of Non-consumptive Wildlife Tourism to Conservation

Wildlife tourism has the potential to contribute to conservation through a variety of mechanisms. This chapter presents a preliminary assessment of the extent to which this potential is currently being realised, comparing tourism based on viewing of animals in captive settings (with a focus on federated zoos) with that in free-ranging situations (wildlife watching). The key mechanisms involved are: direct wildlife management and research; use of income derived from wildlife tourism to fund conservation; education of visitors to behave in a more conservation-friendly manner; political lobbying in support of conservation; and provision of a socio-economic incentive for conservation. All of these occur in at least some zoos and wildlife-watching situations, and collectively the contribution of non-consumptive wildlife tourism to conservation is significant, though impossible to quantify. The key strengths of the zoo sector in this regard are its inputs into captive breeding and its potential to educate large numbers of people. in contrast, wildlife watching provides significant socio-economic incentives for conservation of natural habitats. There seem to be significant opportunities for expanding the role of non-consumptive wildlife tourism in conservation.

Corticosteroid therapy in TSP/HAM patients: The results from a 10 years open cohort

Background: The use of corticosteroids for treating tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) has yielded controversial results. We report the use of corticosteroids for the treatment of TSP/HAM in an open cohort. Methods: The clinical efficacy of long-term, high dose of corticosteroid therapy was studied in thirty-nine TSP/HAM patients. Disability and motor dysfunction was evaluated based on the Disability Status Scale (DSS), Osame`s Motor Disability Scales (OMDS), and Incapacity Status Scale (ISS), before and after treatment. Treatment included use of methyl-predmisolone, 1 g/day for three days, every 3-4 months. The primary end-point was a change in the scores of the neurological scales from baseline until the fifth visit after therapy. Results: After a mean follow-up of 2.2 years and an average of four pulses per patient, we noted a significant neurological improvement, reaching 24.5% according to the ISS score. No statistically significant differences in scores according to the OMDS and DSS scales were noted. Conclusion: We observed neurological improvement with the use of corticosteroids, with physical therapy and anti spastic-drugs as adjunctive treatment. However, randomized clinical trials should be done to assess the use of corticosteroids and other potentially useful immune-based therapies for TSP/HAM treatment. (C) 2008 Elsevier B.V. All rights reserved.