RESUMO
Immunotherapy has been proposed as a method to treat mucosal leishmaniasis for many years, but the approach has been hampered by poor definition and variability of antigens used, and results have been inconclusive. We report here a case of antimonial-refractory mucosal leishmaniasis in a 45 year old male who was treated with three single injections (one per month) with a cocktail of four Leishmania recombinant antigens selected after documented hypo-responsiveness of the patient to these antigens, plus 50 microg of GM-CSF as vaccine adjuvant. Three months after treatment, all lesions had resolved completely and the patient remains without relapse after two years. Side effects of the treatment included only moderate erythema and induration at the injection site after the second and third injections. We conclude that carefully selected microbial antigens and cytokine adjuvant can be successful as immunotherapy for patients with antimonial-refractory mucosal leishmaniasis.
Assuntos
Antígenos de Protozoários/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Imunoterapia , Úlcera da Perna/tratamento farmacológico , Leishmania/imunologia , Leishmaniose Mucocutânea/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Animais , Humanos , Leishmaniose Mucocutânea/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
The effects of conditioned media either from aggregates or from explants of embryonic chick retinae and of recombinant neurotrophins were tested upon the survival in vitro of ganglion cells in dissociated cell cultures from the retina of newborn rats. Ganglion cells were identified by the detection of retrogradely transported horseradish peroxidase injected bilaterally into the superior colliculus. Conditioned media increased significantly the survival of ganglion cells after 2 days in culture, at a wide range of plating densities, and had no effect upon adhesion of rat retinal cells. Media conditioned by cell ensembles from chick retinae from embryonic day 8 (E8) to E16 had neurotrophic effects. Release of neurotrophic activity peaked at E10 E12, irrespective of the numbers of cells or total concentration of protein in the conditioned media. The active molecules were non-dialyzable and were released either in the presence or in the absence of fetal calf serum. The neurotrophic activity was abolished by trypsinization, and recovered by salting-out with 25 75% ammonium sulfate. NT-4, BDNF and, to a lesser extent, NT-3, increased the survival of ganglion cells in our assay, while NGF had no effect. The data show that chick retinal cells release soluble trophic proteins according to a developmentally regulated pattern. These neurotrophic factors may be involved in local competitive interactions that help control naturally occurring neuron death among ganglion cells of the vertebrate retina.
Assuntos
Fatores de Crescimento Neural/metabolismo , Retina/crescimento & desenvolvimento , Retina/metabolismo , Animais , Animais Recém-Nascidos/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Meios de Cultivo Condicionados/farmacologia , Embrião de Mamíferos/fisiologia , Desenvolvimento Embrionário e Fetal , Técnicas In Vitro , Fatores de Crescimento Neural/farmacologia , Ratos , Ratos Endogâmicos , Proteínas Recombinantes , Retina/embriologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/fisiologiaRESUMO
Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retinal tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.
Assuntos
Apoptose/fisiologia , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Técnicas de Cultura , Degeneração Retiniana/metabolismo , Transdução de Sinais/fisiologia , Animais , Camundongos , RatosRESUMO
Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retianl tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.
Assuntos
Camundongos , Ratos , Animais , Apoptose/fisiologia , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Técnicas de Cultura , Técnicas In Vitro , Degeneração Retiniana/metabolismo , Transdução de Sinais/fisiologiaRESUMO
The authors analysed the visceral leishmaniasis (VL) aspects in the state of Maranhão, Brazil, from 1982 to 1993. The disease happens to occur predominantly in São Luís Island (MA) and during the epidemic period, town of São Luís was pointed out as the main endemic area. The greatest frequency of cases occurred in 1993, despite the use of insecticide and dogs control. There was predominance of age between 0- to 4-year-old population with 58.04% of cases. Neither the human disease nor the rainfall index had significant seasonal variation. However they were correlated moderately, with high number of cases after the period of great precipitation of rain. After this study, the data obtained will allow a better control of the disease, despite some factors such as: the urbanization, localization and dynamic of transmission in endemic areas in the Maranhão state.
Assuntos
Leishmania infantum , Leishmaniose Visceral/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Animais , Brasil/epidemiologia , Criança , Pré-Escolar , Surtos de Doenças/estatística & dados numéricos , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano , Distribuição por SexoRESUMO
The axon orientation and axo-dendritic polarities of ganglion cells were investigated in the retinae of developing and adult rats labeled with retrograde tracers. The cells were classified as either regular, if both parameters corresponded to those found among the majority of ganglion cells in the retina of adult rats, or irregular, if either axon orientation or axo-dentritic polarity, or both to follow the norm of adult retinae. The number of regular cells declined from 118,000 to the adult value of 63,000 during the first 5 days following birth, while the number of irregular cells remained stable at 90,000-100,000 during this period and declined thereafter to 46,000. These data suggest that the geometry of neurites within the retina affect the selective elimination of ganglion cells during postnatal development in rats
Assuntos
Animais , Ratos , Neurite (Inflamação) , Células Ganglionares da Retina/ultraestrutura , Retina/ultraestrutura , Microscopia de Fluorescência , Retina/crescimento & desenvolvimentoRESUMO
The axon orientation and axo-dendritic polarities of ganglion cells were investigated in the retinae of developing and adult rats labeled with retrograde tracers. The cells were classified as either regular, if both parameters corresponded to those found among the majority of ganglion cells in the retina of adult rats, or irregular, if either axon orientation or axo-dendritic polarity, or both, failed to follow the norm of adult retinae. The number of regular cells declined from 118,000 to the adult value of 63,000 during the first 5 days following birth, while the number of irregular cells remained stable at 90,000-100,000 during this period and declined thereafter to 46,000. These data suggest that the geometry of neurites within the retina affect the selective elimination of ganglion cells during postnatal development in rats.