RESUMO
The nervous system of flatworms is quite simple although there is increasing evidence indicating that it is chemically complex. Studies of the nervous system in these animals have only been performed in the larval stage or in the adult worms, which are easy to obtain in nature, while the description of the nervous system in developing stages of these organisms is missing. Mesocestoides corti is a parasitic platyhelminth whose larvae can be induced in vitro to develop to adult, sexually mature worms, opening the possibility of studying the nervous system of a flatworm in different stages of development. Here, we describe the presence, activity, location, and molecular forms of acetylcholinesterase (AChE) in different stages of development of M. corti, from the larvae to adult forms of this endoparasite, obtained in in vitro cultures after induction of the larval stage with trypsin. Our results point to AChE as a molecular marker of the nervous system in platyhelminthes. The change in molecular forms of this enzyme and the increase in its activity during development from larvae to adult worm may reflect the presence of a more complex nervous system, necessary to adjust and coordinate the movement of a much bigger structure. A relationship between the development of the reproductive apparatus in segmented and adult worms with a more complex nervous system in these stages is also apparent. Finally, our study opens the possibility of applying anti-AChE as more effective therapeutic strategies against cestode parasites.
Assuntos
Acetilcolinesterase/metabolismo , Estágios do Ciclo de Vida/fisiologia , Mesocestoides/crescimento & desenvolvimento , Mesocestoides/metabolismo , Acetilcolinesterase/química , Animais , Feminino , Estágios do Ciclo de Vida/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Tripsina/farmacologiaRESUMO
INTRODUCTION: Notwithstanding its substantial decline over the last two decades, acquired tetanus is still a serious health problem in most developing countries. Epidemiological transition is often cited as an explanation for this decline, the increase in vaccination coverage of children being the most obvious cause. Few studies have looked carefully at the current epidemiological patterns of acquired tetanus in developing countries. METHODOLOGY: A descriptive, retrospective (series of cases). An acute care 400 - bed university referral hospital situated in a densely populated and highly urbanized area in Southeastern Brazil (Campinas, SP). Patient records the data-base analysed were from the Epidemiological Surveillance Unit of the hospital. RESULTS: In the 57 month period from January 1989 to March 1996 fifty-three patients were admitted with a diagnosis of acquired tetanus. Fifty patients had clinical confirmation, 3 were otherwise diagnosed. Thirty-two (64%) were male and 18 (36%) female. Fourteen (28%) were from rural areas and 36 (72%) from urban. Mean age was 47.6 years, with a median of 49.5. Of the rural patients, 42.85% were under 30 years and 21.42% were over 50, mean age was 36.21 with a median of 34.5. Fewer urban patients were under 30 (13.88%) than over 50 (58.33%), mean age was 52.19 with a median of 54.5. Trismus was the most frequent (92.0%) clinical sign on admittance, followed by abdominal muscular rigidity (84.0%). Treatment measures were uniform and included tetanus immune globulin, antibiotics, surgical debridement of the wound when feasible, diazepan or curare depending on the intensity of spasms. In the second half of the study period, penicillin was replaced by metronidazol. Overall case fatality rate was 20%, in patients that had to receive curare, it was 60%. Hospitalization exceeded 21 days in 56% (28) of the cases, only 10% (5) had a hospital stay of less than 7 days. CONCLUSION: A high proportion of patients were from rural areas, despite an urbanization rate of more than 90%. In the Campinas region there are two different epidemiological patterns of acquired tetanus: a rural pattern, with a higher proportion of younger patients, determined by an inadequate immunization rate and an urban pattern, similar to that found in industrialized countries, with a higher proportion of older patients. RECOMMENDATIONS: There is an obvious need to immunize older individuals in urban areas and young adults in rural areas. The elimination of acquired tetanus will only be achieved with a wider and more intensive adult vaccination program.
Assuntos
Acidentes , Tétano/epidemiologia , Adolescente , Adulto , Idoso , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , População Rural , Tétano/diagnóstico , Tétano/prevenção & controle , Toxoide Tetânico/uso terapêutico , População UrbanaRESUMO
Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-beta peptide (Abeta) during its assembly into filaments, in agreement with its colocalization with the Abeta deposits of Alzheimer's brain. The association of the enzyme with nascent Abeta aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic activity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE-amyloid complexes is higher than that of the Abeta aggregates alone. Thus, in addition to its possible role as a heterogeneous nucleator during amyloid formation, AChE, by forming such stable complexes, may increase the neurotoxicity of Abeta fibrils and thus may determine the selective neuronal loss observed in Alzheimer's brain.
Assuntos
Acetilcolinesterase/química , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/química , Proteínas do Tecido Nervoso/química , Neurônios/patologia , Doença de Alzheimer/metabolismo , Animais , Morte Celular , Células Cultivadas , Embrião de Galinha , Estabilidade Enzimática , Modelos Logísticos , Células PC12 , Ratos , SolubilidadeRESUMO
Collagen-tailed asymmetric acetylcholinesterase (AChE) forms are believed to be anchored to the synaptic basal lamina via electrostatic interactions involving proteoglycans. However, it was recently found that in avian and rat muscles, high ionic strength or polyanionic buffers could not detach AChE from cell-surface clusters and that these buffers solubilized intracellular non-junctional asymmetric AChE rather than synaptic forms of the enzyme. In the present study, asymmetric AChE forms were specifically solubilized by ionic buffers from synaptic basal lamina-enriched fractions, largely devoid of intracellular material, obtained from the electric organ of Torpedo californica and the end plate regions of rat diaphragm muscle. Furthermore, foci of AChE activity were seen to diminish in size, number, and staining intensity when the rat synaptic basal lamina-enriched preparations were treated with the extraction buffers. In the case of Torpedo, almost all the AChE activity was removed from the pure basal lamina sheets. We therefore conclude that a major portion of extracellular collagen-tailed AChE is extractable from rat and Torpedo synaptic basal lamina by high ionic strength and heparin buffers, although some non-extractable AChE activity remains associated with the junctional regions.
Assuntos
Acetilcolinesterase/metabolismo , Membrana Basal/enzimologia , Heparina/farmacologia , Sais/farmacologia , Acetilcolinesterase/classificação , Animais , Membrana Basal/citologia , Membrana Basal/ultraestrutura , Centrifugação com Gradiente de Concentração , Diafragma/enzimologia , Órgão Elétrico/enzimologia , Histocitoquímica , Microscopia Eletrônica , Placa Motora/citologia , Placa Motora/enzimologia , Concentração Osmolar , Ratos , Solubilidade , Sinapses/enzimologia , TorpedoRESUMO
Progressive spastic paraparesis (PSP) is a demyelinating disease of the central nervous system. We studied the ability of the cerebrospinal fluid (CSF) of patients to induce alterations in rat peroneal nerves, and to modify the proteolytic activity of trypsin in vitro. Subperineurial injection of native or heated CSF of patients induced segmental demyelination and other cytological alterations 5-7 days later, in the infiltrated zone, while proximal and distal regions were normal. The CSF of normal subjects did not induce demyelination, but upon heating, it did so. Trypsin was strongly inhibited by the normal CSF but upon heating, its inhibitory activity was replaced by a strong potentiation. In contrast, native and heated CSF of patients potentiated trypsin. Our findings indicate that (1) the normal CSF contains a thermostable factor that potentiates trypsin whose function is overruled by thermolabile protease inhibitors; (2) the CSF of PSP patients has a reduced inhibitory activity and a conserved ability to potentiate trypsin; and (3) the CSF is endowed with a pathogenic power that correlates with an unchecked potentiating activity. We propose that the imbalance of a protease system may play a role in the pathogenesis of PSP lesions.
Assuntos
Doenças Desmielinizantes/etiologia , Paraparesia Espástica Tropical/líquido cefalorraquidiano , Animais , Líquido Cefalorraquidiano/fisiologia , Doenças Desmielinizantes/patologia , Temperatura Alta , Humanos , Injeções , Peptídeo Hidrolases/metabolismo , Nervo Fibular/patologia , Ratos , Valores de Referência , Tripsina/farmacologiaRESUMO
The biology of planktotrophic larvae of Concholepas concholepas is the main bottleneck towards developing biotechnologies to rear this muricid. Data concerning planktonic larvae development, diets and environmental signals triggering larval settlement and recruitment is scarce. We have begun the study of the molecular and cell biology of embryos, larvae and recruits having as a final goal, the development of appropriate biotechnologies to rear this gastropod. First, an inverse ratio between BuChE and AChE enzyme activities was established. This ratio may be a precise developmental marker for this species. Second, for the first time a phosphoinositide related regulatory pathway is reported in a muricid, opening a new approach to the biotechnological management of larvae. Third, the relation between sulfate in sea water and larval motility was studied. Concentrations below 125 microM sulfate decreases larval motility. The sulfate is incorporated in proteoglycans which participate in different developmental phenomena. Lastly, a genomic Concholepas concholepas DNA sequence, similar to that of a human growth hormone probe was detected. This is very interesting since growth factors are key molecules during development, growth and are involved in food conversion rates in fish and also, in a variety of marine invertebrates.