RESUMO
BACKGROUND & OBJECTIVE: Lymphatic filariasis is a disabling disease that continues to cripple population in tropical countries. Currently available antifilarial drugs are not able to control the disease. Therefore, a better antifilarial is urgently required for proper management of the disease. We undertook this study to assess the antifilarial activity of Caesalpinia bonducella-seed kernel against rodent filarial parasite in experimental model. METHODS: Microfilaraemic cotton rats and Mastomys coucha harbouring Litomosoides sigmodontis and Brugia malayi respectively, were treated with crude extract or fractions of the seed kernel C. bonducella through oral route for 5 consecutive days. Microfilaricidal, macrofilaricidal and female worm sterilizing efficacy was assessed. RESULTS: Crude extract showed gradual fall in microfilariae (mf) count in L. sigmodontis-cotton rat model from day 8 post-treatment attaining more than 95 per cent fall by the end of observation period. It also exhibited 96 per cent macrofilaricidal and 100 per cent female sterilizing efficacy. The butanol fraction F018 caused 73.7 per cent reduction in mf count and 82.5 per cent mortality in adult worms with 100 per cent female sterilization. The aqueous fraction F019 exerted more than 90 per cent microfilaricidal activity and 100 per cent worm sterilization. Two chromatographic fractions, F024 and F025 of hexane soluble fraction exhibited 64 and 95 per cent macrofilaricidal activity, respectively. Both the fractions caused gradual fall in microfilaraemia and 100 per cent worm sterilization. In B. malayi-M. coucha model F025 showed gradual reduction in microfilaraemia and caused 80 per cent sterilization of female parasites INTERPRETATION & CONCLUSION: In conclusion, C. bonducella- seed kernel extract and fractions showed microfilaricidal, macrofilaricidal and female-sterilizing efficacy against L. sigmodontis and microfilaricidal and female-sterilizing efficacy against B. malayi in animal models, indicating the potential of this plant in providing a lead for new antifilarial drug development.
Assuntos
Brugia Malayi/efeitos dos fármacos , Caesalpinia , Filariose Linfática/tratamento farmacológico , Filarioidea/efeitos dos fármacos , Preparações de Plantas/farmacologia , Animais , Modelos Animais de Doenças , Fitoterapia/métodos , Sementes , SigmodontinaeRESUMO
The role of vitamin A was evaluated for its chemotherapeutic and chemoprophylactic action against Acanthocheilonema viteae infection in Mastomys coucha. Vitamin A was administered for 10 days, five days before infection and five days post infection. On day 0 experimental animals as well as controls were infected with L3, the infective stage. Establishment of the worms revealed significantly less percentage of worm recovery over untreated controls. Cell-mediated response was found to be the cause of this reduction in worm recovery, whereas humoral response was not significant as IgG, IgA and IgM titres were low.
Assuntos
Anti-Helmínticos/isolamento & purificação , Filariose/prevenção & controle , Mansonella/fisiologia , Murinae/parasitologia , Vitamina A/uso terapêutico , Animais , Movimento Celular/efeitos dos fármacos , Feminino , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Mansonella/isolamento & purificação , ÚteroRESUMO
Microfilariae can be transmitted by blood transfusion and they may be circulated in the recipient's blood but they do not develop into adult worms. Mortality associated with transfusion associated filarial infection is not documented but it may give rise to morbidity in transfusion recipients in terms of allergic reaction. The present study was carried out to investigate the association of post transfusion reactions and filarial infections in an endemic area. About 11,752 transfusion recipients were followed up and in 15 months period, 47 (0.4%) post transfusion reactions (PTR) were reported. Routine investigations for post transfusion reaction were carried out in all 47 patients and their respective blood donor. Moreover, blood culture, microfilaria detection by concentration technique, filarial antibody and antigen detection (both by ELISA) were done in all subjects. Out of 47 patients showing post transfusion reaction, 29 (61.7%) patients developed allergic reaction. Eighteen (38.3%) patients having allergic reaction did not have previous history of blood transfusion and 14 (29.8%) of them received transfusion from blood donors who was either positive for microfilaria, filarial antigen or antibody. Microfilaremia was demonstrated in 4 (8.5%) patients and 5 (10.6%) blood donors. Microfilaria was concurrently present in 2 patients and their respective donors. Filarial antibody was detected in 27 (56.5%) patients and 26 (55.3%) blood donors but microfilaria was detected in 3 (6.4%) and 4 (8.5%) subjects, respectively. Antigen detection test correlated with microfileraemic state of subjects. The result shows that transfusion associated filarial infection may be a probable cause for transfusion-associated morbidity in endemic areas. In 14 (29.8%) patients having allergic reactions, the probable cause was transfusion-associated filarial infection. Filarial antigen detection test was found to be more useful in detecting infections. Blood donors with active history of filarial infection should be deferred from donating blood. Filarial antigen detection test may be employed as screening test for blood donors, if possible.
Assuntos
Filariose/transmissão , Reação Transfusional , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/sangue , Filariose/parasitologia , Humanos , Microfilárias/imunologiaRESUMO
A well known glucose antimetabolite, 2-deoxy glucose (2DG) widely used in chemotherapy of cancer along with radiation, was evaluated as an antifilarial agent by nuclear magnetic resonance. The uptake and metabolism of 2DG in the experimental filarial infection Acanthocheilonema viteae was studied by in vivo multinuclear NMR. An unusually long retention time of 2DG6P within these parasites was observed on continuous 31P NMR monitoring, along with a decrease in ATP levels. These results led to therapeutic investigation in A. viteae infected host Mastomys coucha. 2DG showed a remarkable adulticidal activity (73.6%) with 50% sterilization of surviving female worms at a dose of 250 mg/kg x 5, p.o. NMR observations and activity profile substantiate the findings of one another, directed towards the hitting of bioenergetic machinery of A. viteae by macrofilaricidal agent (2DG).
Assuntos
Desoxiglucose/farmacologia , Dipetalonema/efeitos dos fármacos , Dipetalonema/metabolismo , Filaricidas/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Camundongos/parasitologia , Administração Oral , Animais , Antimetabólitos/administração & dosagem , Antimetabólitos/farmacocinética , Desoxiglucose/farmacocinética , Infecções por Dipetalonema/tratamento farmacológico , Infecções por Dipetalonema/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Metabolismo Energético/efeitos dos fármacos , Filaricidas/farmacocinética , Interações Hospedeiro-Parasita , Lactatos/metabolismo , Resultado do TratamentoRESUMO
Six synthetic 2H-1-benzopyran-2-one (cournarin) derivatives (CDRI compounds # 1, 2, 3, 4, 5 and 6) were evaluated for filaricidal activity against Litomosoides carinii and Acanthocheilonema viteae infections in cotton rats (Sigmodon hispidus) and Mastomys coucha respectively. Significant effects on macrofilariae (>80% death/sterilisation) were detected with compounds #2, 3 and 6 against L. carinii and/or A. viteae. Thus detection of filaricidal activity in benzopyrones, which are so far known for anti-inflammatory activity, provides a new lead for development of better filaricidal agents for combating filariasis.
Assuntos
Anticoagulantes/farmacologia , Cumarínicos/farmacologia , Infecções por Dipetalonema/tratamento farmacológico , Dipetalonema/efeitos dos fármacos , Filariose/tratamento farmacológico , Filarioidea/efeitos dos fármacos , Administração Oral , Animais , Anticoagulantes/administração & dosagem , Cumarínicos/administração & dosagem , Infecções por Dipetalonema/sangue , Feminino , Filariose/sangue , Humanos , Injeções Intravenosas/veterinária , Masculino , Microfilárias , CarrapatosRESUMO
The syntheses of 7-chloro-4-(substituted amino) quinolines (2-22) and their antifilarial activities are delineated. Some of the screened compounds have shown promising filarial response and sterilization effect on female Acanthocheilonema viteae in rodents.
Assuntos
Aminoquinolinas/química , Aminoquinolinas/farmacologia , Dipetalonema/efeitos dos fármacos , Filaricidas/farmacologia , Aminoquinolinas/uso terapêutico , Animais , Química Farmacêutica , Infecções por Dipetalonema/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Feminino , Filaricidas/química , Filaricidas/uso terapêutico , Estrutura Molecular , MuridaeRESUMO
Quinolones have been discovered in our laboratory as a new class of antifilarial agents. This has led to the design, synthesis, and antifilarial evaluation of a number of N-substituted quinol-4(1H)-one-3-carboxamide derivatives 4-6. The macrofilaricidal activity of the target compounds was initially evaluated in vivo against Acanthoeilonema viteae by oral administration of 200 mg/kg x 5 days. Among all the synthesized compounds, 13 displayed activity, with the most potent compound (4a) exhibiting 100% macrofilaricidal and 90% microfilaricidal activities. Compound 4e elicited significant macrofilaricidal (80%) response while compound 5c showed 100% sterilization of female worms. Finally, the two most potent macrofilaricidal compounds, namely 4a and 4e, have been screened for their potency against DNA topoisomerase II, and it has been observed that both have the capability to interfere with this enzyme at 10 micromol/mL concentration. The structure-activity relationship (SAR) associated with position-3 and aryl ring substituents is discussed.
Assuntos
Filariose/tratamento farmacológico , Filaricidas/farmacologia , Quinolonas/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Filaricidas/química , Filaricidas/uso terapêutico , Masculino , Muridae , Quinolonas/química , Quinolonas/uso terapêuticoRESUMO
Several secondary amines exhibit promising macrofilaricidal response in vivo through oral route of administration against Acanthocheilonema viteae in which N-hexylcyclohexylamine (1) shows 100% macrofilaricidal activity while a tertiary amine such as 9 elicits predominantly microfilaricidal (93%) response.
Assuntos
Aminas/uso terapêutico , Filaricidas/uso terapêutico , Animais , Antinematódeos/química , Antinematódeos/uso terapêutico , Cicloexilaminas/uso terapêutico , Dipetalonema/efeitos dos fármacos , Desenho de Fármacos , Feminino , Filariose/tratamento farmacológico , Filaricidas/química , Masculino , Muridae/parasitologia , Relação Estrutura-AtividadeRESUMO
Metabolite mapping of human filarial parasite, Brugia malayi was carried out in vitro as well as in situ in host Mastomys coucha by 31P nuclear magnetic resonance (NMR) spectroscopy. Detection of parasites by visualizing contrast spots due to pathologic changes was observed by 1H magnetic resonance imaging (MRI). Major metabolites of adult B. malayi observed by 31P-NMR spectroscopy were of sugar phosphates (SP), phosphomonoesters (PME), glycerophosphoryl-ethanolamine (GPE), -choline (GPC), phosphoenolpyruvate (PEP), inorganic phosphate (Pi), nucleoside diphosphosugar and nucleotides-mono, -di and -tri phosphates. PEP and GPC were present in high concentration; PEP being the major energy reservoir and GPC the major phospholipid in this species of filaria. The 31P NMR spectra of testis of mastomys, showed seven major peaks of SP, PME, phosphocreatine (PCr), phosphodiesters (PDE), Pi, and nucleotides di- and tri-phosphates. The 31P-NMR spectra of testis of B. malayi infected animal also consisted of seven major peaks with significant decrease in the SP and PME peak showing changes in the carbohydrate and lipid metabolism of filaria infected testis. Thus, in vivo 31P MRS provided a non-invasive assessment of tissue bioenergetics and phospholipid metabolism.
Assuntos
Brugia Malayi/metabolismo , Filariose/metabolismo , Espectroscopia de Ressonância Magnética , Fosfolipídeos/metabolismo , Fosfatos Açúcares/metabolismo , Doenças Testiculares/metabolismo , Testículo/metabolismo , Animais , Brugia Malayi/anatomia & histologia , Brugia Malayi/isolamento & purificação , Feminino , Filariose/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Ratos , Doenças Testiculares/diagnóstico , Doenças Testiculares/parasitologia , Testículo/patologiaRESUMO
To investigate the cell-mediated immune (CMI) responses of the host during the development of acute filarial disease manifestations, we studied the sequential changes in CD4+ and CD8+ T-cell subsets, leukocyte migration inhibition (LMI) response to Brugia malayi adult worm antigen, and concanavalin-A (ConA) and filarial antigen-induced lymphocyte transformation (LT) in the Indian leaf monkey (Presbytis entellus)-B. malayi model. Filarial infection was established in monkeys by subcutaneous inoculations of infective larvae (L3) (700-1,250 L3/monkey) in multiple doses, and the infected monkeys were categorized as symptomatic (Sym) and asymptomatic (Asym) depending on whether or not acute clinical manifestations were shown by them. In Sym monkeys, LMI response to homologous adult parasite antigen was significantly suppressed as compared to Asym monkeys. In Asym monkeys, LMI response varied among the animals; 2 showed an increase throughout the study period and 2 showed suppression at different time points. When compared with Asym monkeys, CD8+ T cells in Sym monkeys showed a trend of significant increase after day 180 postinoculation (PI). CD4+ T cells remained within the normal range till day 300 (PI), after which they showed a marginal increase. ConA-stimulated LT was suppressed in Asym monkeys from day 60 PI. Antigen-stimulated LT was unresponsive in both Asym and Sym animals. Thus, the host's LT response to ConA is suppressed in Asym animals, and alteration in CD8+ T-cell number and LMI response in Sym monkeys may be involved in the development of the acute disease manifestations in this model.
Assuntos
Brugia Malayi/imunologia , Cercopithecidae/parasitologia , Filariose/imunologia , Doença Aguda , Animais , Antígenos de Helmintos/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Inibição de Migração Celular , Modelos Animais de Doenças , Edema/imunologia , Edema/parasitologia , Imunidade Celular , Leucócitos Mononucleares/imunologia , Estudos Longitudinais , Ativação Linfocitária , Masculino , Parasitemia/imunologia , Parasitemia/parasitologiaRESUMO
Humoral immune responses of the Indian leaf monkey (Presbytis entellus) experimentally infected with Brugia malayi and exhibiting disease manifestations were studied. Microfilaraemia, filaria-specific IgG and circulating immune complexes (CICs) were determined in the monkeys at different time-points after inoculation of B. malayi 3rd-stage larvae. Sera were analysed for recognition pattern of adult parasite antigen molecules by immunoblotting. More than 60% of the infected monkeys developed episodic or persistent limb oedema with or without fever and with low or no microfilaraemia. While both CIC and filaria specific IgG levels were comparable in animals showing no disease symptoms (asymptomatics) and some animals showing symptoms (symptomatics), IgG levels peaked during pre-patent stage in symptomatics and during latent stage in asymptomatic animals. However, some of the symptomatic animals showed a low level of filaria-specific IgG as compared to asymptomatic and other symptomatic animals. The immunoblot analysis showed non-reactivity of 17 and 55 kDa antigens with sera of symptomatic animals. The results thus suggest that humoral immune responses as measured in the present study do not precede the development of the manifestations. However, 2 non-reactive antigen molecules identified by symptomatic sera need further study to establish their possible involvement, if any, in the development of acute disease manifestations in this model.
Assuntos
Anticorpos Anti-Helmínticos/sangue , Brugia Malayi/imunologia , Cercopithecidae/parasitologia , Filariose/veterinária , Doenças dos Macacos/imunologia , Animais , Especificidade de Anticorpos , Complexo Antígeno-Anticorpo/sangue , Antígenos de Helmintos/imunologia , Portador Sadio , Edema , Filariose Linfática/imunologia , Filariose Linfática/veterinária , Ensaio de Imunoadsorção Enzimática , Filariose/imunologia , Masculino , Hidrocele TesticularRESUMO
Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines) identified in our laboratory as potential pharmacophore for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for high order of adulticidal activity. This has led to syntheses and macrofilaricidal evaluations of a number of 1-aryl-9H-pyrido[3,4-b]indole-3-carboxylate derivatives (3-7). The macrofilarical activity was initially evaluated in vivo against Acanthoeilonema viteae. Amongst all the synthesized compounds, only twelve compounds namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i and 7h have exhibited either > 90% micro- or macrofilaricidal activity or sterilization of female worms. These compounds have also been screened against Litomosoides carinii and of these only 3f and 5a have also been found to be active. Finally these two compounds have been evaluated against Brugia malayi. The structure activity relationship (SAR) associated with position-1 and 3 substituents in beta-carbolines have been discussed. It has been observed that the presence of carbomethoxy at position-3 and an aryl substituent at position- in beta-carbolines effectively enhance antifilarial activity particularly against A. viteae. Amongst the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate (4c) has shown highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxyla te (3a) has shown highest microfilaricidal action against A. viteae at 50 mg/ kg x 5 days (i.p.). Another derivative of this compound namely 1-(4-chlorophenyl)-3-hydroxymethyl-9H-pyrido[3,4-b]indole (5a) exhibited highest activity against L. carinii at 30 mg/kg x 5 days (i.p.) and against B. malayi at 50 mg/kg x 5 days (i.p.) or at 200 mg/kg x 5 days (p.o.).
Assuntos
Carbolinas/síntese química , Filariose/tratamento farmacológico , Filaricidas/síntese química , Animais , Brugia Malayi/efeitos dos fármacos , Carbolinas/farmacologia , Dipetalonema/efeitos dos fármacos , Infecções por Dipetalonema/tratamento farmacológico , Modelos Animais de Doenças , Filaricidas/uso terapêutico , Filarioidea/efeitos dos fármacos , Chumbo/química , Chumbo/uso terapêutico , Masculino , Ratos , Relação Estrutura-AtividadeRESUMO
Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines), identified in our laboratory as potential pharmacophores for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for the high order of adulticidal activity. This has led to syntheses and macrofilaricidal evaluations of a number of 1-aryl-9H-pyrido[3,4-b]indole-3-carboxylate derivatives (3-7). The macrofilaricidal activity was initially evaluated in vivo against Acanthoeilonema viteae. Among all the synthesized compounds, only 12 compounds, namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i, and 7h, have exhibited either >90% micro- or macrofilaricidal activity or sterlization of female worms. These compounds have also been screened against Litomosoides carinii, and of these only 3f and 5a have also been found to be active. Finally these two compounds have been evaluated against Brugia malayi. The structure-activity relationship (SAR) associated with position 1 and 3 substituents in beta-carbolines has been discussed. It has been observed that the presence of a carbomethoxy at position 3 and an aryl substituent at position 1 in beta-carbolines effectively enhances antifilarial activity particularly against A. viteae. Among the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate (4c) has shown the highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3, 4-b]indole-3-carboxylate (3a) has shown the highest microfilaricidal action against A. viteae at 50 mg/kg x 5 days (ip). Another derivative of this compound, namely 1-(4-chlorophenyl)-3-(hydroxymethyl)-9H-pyrido[3,4-b]indole (5a), exhibited the highest activity against L. carinii at 30 mg/kg x 5 days (ip) and against B. malayiat 50 mg/kg x 5 days (ip) or at 200 mg/kg x 5 days (po).
Assuntos
Filaricidas/síntese química , Indóis/síntese química , Animais , Brugia Malayi , Infecções por Dipetalonema/tratamento farmacológico , Feminino , Filariose/tratamento farmacológico , Filaricidas/química , Filaricidas/farmacologia , Filarioidea , Indóis/química , Indóis/farmacologia , Masculino , Muridae , Sigmodontinae , Relação Estrutura-AtividadeRESUMO
Investigations on various aspects of human filariasis using target filarial parasite, Brugia malayi is jeopardised to a great extent due to its prolonged incubation period and poor harvest from the existing experimental animal models. To obviate these difficulties it was decided to establish B. malayi infection in immunosuppressed Mastomys coucha. Cortisone, a well-known immunosuppressant, was used at 10-mg/kg dose level subcutaneously in two courses each of 5 days duration. The first course was administered 1 week before and the second, 1 week after infective exposure. Mastomys were exposed either with 100 or 200 L3 each. Untreated age-matched animals were also exposed simultaneously. The minimum prepatent period was observed to be 90.7 days in immunosuppressed animals exposed to 200 L3. The course of microfilaraemia in immunosuppressed and control animals was identical up to 180 days of observation period. However, the adult worm recovery from the former group of mastomys was higher. It is surmised that exposure with B. malayi L3 in immunosuppressed mastomys would be of great advantage in getting larger harvests of adult worms of B. malayi.
Assuntos
Brugia Malayi/crescimento & desenvolvimento , Filariose/parasitologia , Terapia de Imunossupressão , Muridae/parasitologia , Animais , Cortisona/administração & dosagem , Modelos Animais de Doenças , Larva/fisiologia , Masculino , Parasitemia/parasitologiaRESUMO
Evaluation of antifilarial activity of new potential agents in vivo is extremely time consuming and uneconomic. In the present study effort has been made to develop an in vitro screening method using Acanthocheilonema viteae, a subcutaneously dwelling rodent filariid with anaerobic metabolic characteristics like human filariids, W. Bancrofti/Brugia malayi as test parasite. Motility test and tetrazolium (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT) based colorimetric assay were used as parameters in in vitro assay. Results showed that 92.3% of compounds (in vivo active) could be picked up in the in vitro assay when both adults and microfilarae (mf) were used simultaneously. Mf and adult stages separately detected, respectively, 84.6 and 69.2% of in vivo active compounds. The adults and mf separately and both the life stages together exhibited, respectively, 80.0, 50.0 and 80.0% false positive results in the in vitro test with in vivo inactive compounds. It is felt that mf stage when used in in vitro test using motility and MTT assays as parameters would be useful in primary screening of new potential filaricides.
Assuntos
Dipetalonema/efeitos dos fármacos , Filaricidas/farmacologia , Animais , Colorimetria , Corantes/química , Dipetalonema/crescimento & desenvolvimento , Dipetalonema/fisiologia , Infecções por Dipetalonema/tratamento farmacológico , Infecções por Dipetalonema/parasitologia , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Masculino , Microfilárias/efeitos dos fármacos , Microfilárias/fisiologia , Movimento/efeitos dos fármacos , Muridae , Oxirredução , Valor Preditivo dos Testes , Sais de Tetrazólio/química , Tiazóis/químicaRESUMO
Investigations on various aspects of human filariasis using target filarial parasite, Brugia malayi is jeopardised to a great extent due to its prolonged incubation period and poor harvest from the existing experimental animal models. To obviate these difficulties it was contemplated to establish B. malayi infection in immunosuppressed Mastomys coucha. Cortisone, a well known immunosuppressant, was used at 10 mg/kg dose level subcutaneously in two courses each of 5 days duration. The first course was administered 1 week before and the second, a week after infective exposure. Mastomys were exposed either with 100 or 200 infective larvae (L3) each. Untreated age-matched animals were also exposed simultaneously. The minimum prepatent period was observed to be 90.7 days in immunosuppressed animals exposed to 200 L3. The course of microfilaraemia in immunosuppressed and control animals was identical up to 180 days of observation period. However, the adult worm recovery from the former group of Mastomys was higher. It is surmised that exposure with B. malayi L3 in immunosuppressed Mastomys would be of great advantage in getting larger harvests of adult worms of B. malayi.
Assuntos
Brugia Malayi/fisiologia , Modelos Animais de Doenças , Filariose/parasitologia , Terapia de Imunossupressão , Muridae/parasitologia , Animais , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/análogos & derivados , Imunossupressores/administração & dosagem , Masculino , Muridae/imunologia , ParasitemiaRESUMO
OBJECTIVE: To determine mitogenic and antigen-specific cellular immune responses of two species of rodents, viz. Meriones unguiculatus and Mastomys coucha to assess the usefulness of the A. viteae/Mastomys model for cellular immune studies in experimental filariasis. METHODS: Lymphocyte blast transformation test (LTT) using spleen cells of normal and A. viteae infected animals. RESULTS: The proliferative response of gerbils was much higher than that of Mastomys to both ConA and filarial antigens. Cells of both species of rodents did not respond to microfilarial (mf) antigen, however, their mitogenic response differed during infection. Some degree of nonspecific suppression was observed in gerbils during prepatent and patent stages of infection, while Mastomys revealed highest proliferation during patent microfilaraemia. Mastomys cells did not respond to adult or mf antigen, while adult-specific proliferation was detected in the case of gerbils. CONCLUSION: The A. viteae/gerbil model shows more similarity to human filarial infection regarding cellular immune response. Markedly low responsiveness of a high percentage of Mastomys and wide variations in the cellular response to nonspecific mitogen limit the usefulness of Mastomys coucha in immunological studies, especially cellular immunity.
Assuntos
Infecções por Dipetalonema/imunologia , Modelos Animais de Doenças , Gerbillinae/imunologia , Muridae/imunologia , Animais , Antígenos de Helmintos/imunologia , Dipetalonema/imunologia , Humanos , Tolerância Imunológica , Imunidade Celular , Ativação Linfocitária , Masculino , Microfilárias/imunologiaRESUMO
Successful experimental transmission of the human lymphatic dwelling nocturnal periodic strain of Wuchereria bancrofti has been achieved from man to Indian leaf monkey (Presbytis entellus) through a susceptible strain of Aedes aegypti. The prepatent period varied between 195 and 240 days. Microfilaria (mf) levels were in general low and the peak count was attained at 1800 hr. Of the adult worms 5-12.5% were recovered from male langur while females revealed poor (2.54%) recovery. This host--parasite model thus makes available the target parasite material in substantial quantity to work on chemotherapeutic and immunological investigations.
Assuntos
Cercopithecidae/parasitologia , Modelos Animais de Doenças , Filariose Linfática/transmissão , Periodicidade , Wuchereria bancrofti/fisiologia , Animais , Filariose Linfática/parasitologia , Feminino , Humanos , Linfonodos/parasitologia , Masculino , Microfilárias/fisiologiaRESUMO
CDRI Compound 92/138, a synthetic analogue of aplysinopsin, was evaluated in experimental filarial infections, Litomosoides carinii in cotton rats (Sigmodon hispidus) and Acanthocheilonema viteae in Mastomys coucha. The compound killed 63.8 and 90% of adult L. carinii and A. viteae at doses of 30 and 50 mg/kg (i.p.) respectively given for 5 days. By the oral route, at 100 mg/kg for 5 days the compound caused 50.9 and 57% mortality of adult L. carinii and A. viteae, respectively. At 200 mg/kg administered orally on days 0, 10 and 25 post-infection, it reduced establishment of adult A. viteae by 68.5%. We also found 43.7 and 37.8% effect in vivo respectively on L3 and L4 stages of A. viteae at a single dose of 250 mg/kg, p.o. The compound was active in vitro at 100 micrograms/ml concentration and caused a significant decline in MTT reduction and 14C-glucose uptake by adult filariids. Thus synthetic marine aplysinopsin could provide a new pharmacophore for the development of antifilarial agents.
Assuntos
Filariose/tratamento farmacológico , Filaricidas/uso terapêutico , Imidazóis/uso terapêutico , Indóis/uso terapêutico , Animais , Infecções por Dipetalonema/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Filaricidas/farmacologia , Filarioidea/efeitos dos fármacos , Imidazóis/farmacologia , Indóis/farmacologia , Masculino , Muridae , SigmodontinaeRESUMO
The quick and easy method of tetrazolium based colorimetric assay with MTT [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] was used to test the viability of the adult parasites of a rodent filariid Acanthocheilonema viteae in vitro. The ideal conditions required for antifilarial screening were determined by correlating the MTT reduction ability of worms with their size and age in the vertebrate host, also the duration of incubation and temperature of the in vitro culture. It was observed that the worms collected from the host after 90 days of L3 (infective larvae) exposure were not suitable for in vitro screen as they could not reduce MTT to that extent as the worms of early infection. Healthy and full grown worms and also those incubated at 37 degrees C for 16 hr or more caused maximum MTT reduction. Thus, it is recommended to select healthy adult filariids of proper age and size (male > 3.5 cm; female > 7.0 cm). The incubation temperature of the in vitro culture system needs to be adjusted to 37 degrees C and parasites might be exposed to drugs upto 24 hr without much alteration in MTT reduction of untreated controls.