RESUMEN
WHAT IS KNOWN AND OBJECTIVE: Therapeutic success is characterized by undetectable viral load, immune reconstitution confirmed by CD4+ T-cell count and no clinical manifestations of disease. High treatment adherence is a major determinant of therapeutic success that needs prevention of viral replication, allowing immune reconstitution. Adherence to treatment <95% has been associated with both immune and viral failure. The objective of this study was to evaluate factors associated with therapeutic success in adult patients on highly active antiretroviral therapy (HAART) in a specialized centre for HIV-AIDS in southern Brazil, being defined therapeutic success as achieving and maintaining undetectable viral load, stable immune status (CD4+ T lymphocyte count ≥200 cells/mm(3) ) and adherence to HAART ≥ 95%. METHODS: We conducted a historical cohort study nested in the PC-HIV randomized clinical trial of PC-HIV. We included adults who were on HAART at Pelotas HIV/AIDS Assistance Service between June 2006 and July 2007 and for whom information on treatment adherence, viral load and CD4+ cell count was available. Pregnant women were excluded. We obtained clinical data from medical records and socio-demographic information in an interview. Therapeutic success was defined as achieving and maintaining undetectable viral load, stable immune status (CD4+ T lymphocyte count ≥200 cells/mm(3) ) and adherence to HAART ≥95%. RESULTS AND DISCUSSION: We included 136 patients (60% male) in the cohort study. Mean age was 40 ± 10 years, and median treatment duration was 59 months (IQR 25-93). Family income varied from 0 to 8 times the minimum wage (IQR 1·0-2·3). Therapeutic success was achieved by 90% (122 patients), and it was associated with previously undetectable viral load (PR = 1·30; 95% CI = 1·13-1·49) and treatment adherence prior to study entry (PR = 1·34; 95% CI = 1·07-1·69), independently of sex, age and previous immune status. WHAT IS NOW AND CONCLUSION: When undetectable viral load, CD4+ cell count ≥200 cells/mm(3) and treatment adherence above 95% are included in the definition of therapeutic success, the rate was elevated (90%) and the factors associated were previous history of adherence to HAART and previous undetectable viral load.
Asunto(s)
Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Brasil , Linfocitos T CD4-Positivos , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Factores Socioeconómicos , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
Transplantation of autologous bone marrow mononuclear cells (BMMCs) has been proven safe in animal and human studies. However, there are very few studies in stroke patients. In this study, intra-arterial autologous BMMCs were infused in patients with moderate to severe acute middle cerebral artery infarcts. The subjects of this study included 20 patients with early or late spontaneous recanalization but with persistent deficits, in whom treatment could be initiated between 3 and 7 days after stroke onset. Mononuclear cells were isolated from bone marrow aspirates and infused at the proximal middle cerebral artery of the affected hemisphere. Safety analysis (primary endpoint) during the 6-month follow-up assessed death, any serious clinical events, neurological worsening with ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) scores, seizures, epileptogenic activity on electroencephalogram, and neuroimaging complications including new ischemic, hemorrhagic, or neoplastic lesions. Satisfactory clinical improvement (secondary endpoint) at 90 days was defined according to the pretreatment NIHSS scores as follows: modified Rankin Scale score of 0 in patients with NIHSS <8, modified Rankin Scale scores of 0-1 in patients with NIHSS 8-14, or modified Rankin Scale scores 0-2 in patients with NIHSS >14. Good clinical outcome was defined as mRS ≤2 at 90 days. Serial clinical, laboratory, electroencephalogram, and imaging evaluations showed no procedure-related adverse events. Satisfactory clinical improvement occurred in 6/20 (30%) patients at 90 days. Eight patients (40%) showed a good clinical outcome. Infusion of intra-arterial autologous BMMCs appears to be safe in patients with moderate to severe acute middle cerebral artery strokes. No cases of intrahospital mortality were seen in this pilot trial. Larger prospective randomized trials are warranted to assess the efficacy of this treatment approach.
Asunto(s)
Trasplante de Médula Ósea/métodos , Infarto de la Arteria Cerebral Media/cirugía , Enfermedad Aguda , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
According to Khan et al. [Khan, A. U., Kovacic, D., Kolbanovskiy, A., Desai, M., Frenkel, K. & Geacintov, N. E. (2000) Proc. Natl. Acad. Sci. USA 97, 2984-2989], peroxynitrite (ONOO(-)) decomposes after protonation to singlet oxygen ((1)Delta(g)O(2)) and singlet oxonitrate (nitroxyl, (1)NO(-)) in high yield. They claimed to have observed nitrosyl hemoglobin from the reaction of NO(-) with methemoglobin; however, contamination with hydrogen peroxide gave rise to ferryl hemoglobin, the spectrum of which was mistakenly assigned to nitrosyl hemoglobin. We have carried out UV-visible and EPR experiments with methemoglobin and hydrogen peroxide-free peroxynitrite and find that no NO(-) is formed. With this peroxynitrite preparation, no light emission from singlet oxygen at 1270 nm is observed, nor is singlet oxygen chemically trapped; however, singlet oxygen was trapped when hydrogen peroxide was also present, as previously described [Di Mascio, P., Bechara, E. J. H., Medeiros, M. H. G., Briviba, K. & Sies, H. (1994) FEBS Lett. 355, 287-289]. Quantum mechanical and thermodynamic calculations show that formation of the postulated intermediate, a cyclic form of peroxynitrous acid (trioxazetidine), and the products (1)NO(-) and (1)Delta(g)O(2) requires Gibbs energies of ca. +415 kJ .mol(-1) and ca. +180 kJ.mol(-1), respectively. Our results show that the results of Khan et al. are best explained by interference from contaminating hydrogen peroxide left from the synthesis of peroxynitrite.
Asunto(s)
Nitratos/química , Óxidos de Nitrógeno/química , Oxígeno , Cromatografía Líquida de Alta Presión , Espectrometría de Masas , Oxígeno SingleteRESUMEN
The proliferative T cell responses to poly(GluLysTyr) (GLT) and poly(GLULysPhe) (GLPhe) are restricted by the E alpha E beta class II MHC molecule (E) in most responded strains. Some nonresponder strains that carry responder E beta, but cannot express cell surface E molecules, can complement with other nonresponder strains that provide the missing E alpha chain needed for the expression of E molecules and for responsiveness to GLT and GLPhe. Here another type of complementation is described between two E-nonexpressor haplotypes, H-2f and H-2s, which result in E-nonexpressor F1 hybrids, which are responders to GLT. The restriction element involved in this response is an Af/As hybrid molecule. The data support the hypothesis that conformational determinants resulting from the free association of alpha and beta chains in heterozygotes can increase the immune potential of the individual.
Asunto(s)
Antígenos de Histocompatibilidad Clase II/inmunología , Péptidos/inmunología , Linfocitos T/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Reacciones Cruzadas , Prueba de Complementación Genética , Antígenos H-2/inmunología , Antígenos de Histocompatibilidad Clase II/genética , Activación de Linfocitos , Ratones , Ratones Endogámicos/inmunología , Polímeros , Conformación Proteica , Multimerización de ProteínaRESUMEN
The immunogenicity of the four sequential polymers of alpha-L-amino acids referred to below was studied in inbred strains of mice. The responses were linked to the H-2 haplotype, and the Ir genes controlling the responses were mapped to the IA region. The responses were restricted to two haplotypes as follows: (Ala-Tyr-Glu-Gly)n and (Ala-Glu-Tyr-Gly)n - H-2k; (Glu-Ala-Tyr-Gly)n - H-2b; (Glu-Tyr-Ala-Gly)n - H-2k and b. The absence of reciprocal crossreactions among all of these polymers, plus the sequential polymers (Tyr-Ala-Glu-Gly)n and (Tyr-Glu-Ala-Gly)n at both the antibody and T-cell levels, indicated that each of these six polymers was indeed structurally unique.
Asunto(s)
Antígenos de Histocompatibilidad Clase II/genética , Complejo Mayor de Histocompatibilidad , Ratones Endogámicos/inmunología , Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/genética , Secuencia de Aminoácidos , Animales , Formación de Anticuerpos , Ligamiento Genético , Haplotipos , Antígenos de Histocompatibilidad Clase II/inmunología , Ratones , Ratones Endogámicos/genética , Datos de Secuencia Molecular , Receptores de Antígenos de Linfocitos T/aislamiento & purificación , Linfocitos T/inmunologíaRESUMEN
The murine immune response patterns to (Phe-Glu-Ala-Gly)n and (Phe-Ala-Glu-Gly)n differ from those of the tyrosine analogues (Tyr-Glu-Ala-Gly)n and (Tyr-Ala-Glu-Gly)n. (Phe-Glu-Ala-Gly)n was not immunogenetic in inbred, congenic or recombinant strains of mice. (Phe-Ala-Glu-Gly)n was immunogenic only in mice having f alleles in the IA subregion of the H-2 complex. Reciprocal in vitro cross reactions were noted with T cells from mice of H-2f that respond to either (Phe-Ala-Glu-Gly)n or (Tyr-Ala-Glu-Gly)n. T cells from mice of H-2b, which are responders to (Tyr-Glu-Ala-Gly)n, could not be stimulated with the nonimmunogenic (Phe-Glu-Ala-Gly)n. These results support other studies showing that for any polymer to elicit cross T-cell proliferative responses it must be (a) structurally related to the homologous polymer and (b) immunogenic in the mouse strain whose T cells are being challenged in vitro. Explanations are offered for these statements.