RESUMEN
The potential therapeutic value of Moringa oleifera extract (MOE), due to its anti-inflammatory and anti-oxidant effects, has been reported previously. In this study, Hymenolepis nana antigen (HNA) in combination with MOE was used in immunization against H. nana infection. Adult worm and egg counts were taken, while histological changes in the intestine were observed. Mucosal mast (MMCs) and goblet cells (GCs) were stained with specific stains, while serum and intestinal IgA were assayed using enzyme-linked immunosorbent assay (ELISA). Reduced glutathione (GSH) and lipid peroxidation (thiobarbituric acid reactive substances, TBARS) were assayed. Real-time polymerase chain reaction (PCR) was used for detection of mRNA expression in ileum tissue. The results demonstrated an improvement in the architecture of intestinal villi, decreased inducible nitric oxide synthase (iNOs) and TBARS, and increased GSH in HNA, MOE and MOE + HNA groups. In the same groups, an increase in GCs, mucin 2 (MUC2), interleukins (IL)-4, -5 and -9, and stem cell factor (SCF) versus a decrease in both interferon-gamma (IFN-γ) and transforming growth factor (TGF-ß) expression appeared. HNA and MOE + HNA increased serum and intestinal IgA, respectively. MOE decreased MMCs and achieved the highest reductions in both adult worms and eggs. In conclusion, MOE could achieve protection against H. nana infections through decreased TGF-ß, IFN-γ and MMC counts versus increased GC counts, T-helper cell type 2 (Th2) cytokines and IgA level.
Asunto(s)
Himenolepiasis/tratamiento farmacológico , Hymenolepis/efectos de los fármacos , Intestinos/efectos de los fármacos , Intestinos/inmunología , Moringa oleifera/química , Extractos Vegetales/uso terapéutico , Animales , Antihelmínticos/administración & dosificación , Antihelmínticos/química , Antihelmínticos/uso terapéutico , Citocinas/efectos de los fármacos , Citocinas/inmunología , Glutatión/análisis , Himenolepiasis/inmunología , Himenolepiasis/parasitología , Inmunoglobulina A/análisis , Inmunoglobulina A/inmunología , Interferón gamma/efectos de los fármacos , Interferón gamma/genética , Interferón gamma/inmunología , Intestinos/parasitología , Peroxidación de Lípido , Ratones , Óxido Nítrico Sintasa/efectos de los fármacos , Óxido Nítrico Sintasa/genética , Recuento de Huevos de Parásitos , Extractos Vegetales/administración & dosificación , Células Th2/efectos de los fármacos , Células Th2/inmunologíaRESUMEN
Little is known about the efficacy of cysteine proteinases (CP) as anthelmintics for cestode infections in vivo. Hymenolepis microstoma is a natural parasite of house mice, and provides a convenient model system for the assessment of novel drugs for anthelmintic activity against cestodes. The experiments described in this paper indicate that treatment of H. microstoma infections in mice with the supernatant of papaya latex (PLS), containing active cysteine proteinases, is only minimally efficacious. The statistically significant effects seen on worm burden and biomass showed little evidence of dose dependency, were temporary and the role of cysteine proteinases as the active principles in PLS was not confirmed by specific inhibition with E-64. Worm fecundity was not affected by treatment at the doses used. We conclude also that this in vivo host-parasite system is not sensitive enough to be used reliably for the detection of cestocidal activity of compounds being screened as potential, novel anthelmintics.
Asunto(s)
Antihelmínticos/administración & dosificación , Carica/química , Proteasas de Cisteína/administración & dosificación , Himenolepiasis/tratamiento farmacológico , Hymenolepis/efectos de los fármacos , Látex/química , Animales , Humanos , Himenolepiasis/parasitología , Hymenolepis/fisiología , Leucina/administración & dosificación , Leucina/análogos & derivados , Masculino , Ratones , Ratones Endogámicos C3HAsunto(s)
Bromo/administración & dosificación , Himenolepiasis/parasitología , Salicilanilidas/síntesis química , Animales , Bromo/química , Humanos , Himenolepiasis/tratamiento farmacológico , Hymenolepis/efectos de los fármacos , Hymenolepis/patogenicidad , Ratones , Salicilanilidas/administración & dosificación , Salicilanilidas/químicaAsunto(s)
Bromo/administración & dosificación , Himenolepiasis/parasitología , Salicilanilidas/administración & dosificación , Salicilanilidas/síntesis química , Animales , Bromo/química , Humanos , Himenolepiasis/tratamiento farmacológico , Hymenolepis/efectos de los fármacos , Hymenolepis/patogenicidad , Ratones , Salicilanilidas/químicaAsunto(s)
Anilidas/farmacología , Anticestodos/farmacología , Benzamidas/farmacología , Himenolepiasis/tratamiento farmacológico , Hymenolepis/efectos de los fármacos , Sulfonamidas/farmacología , Anilidas/síntesis química , Animales , Anticestodos/síntesis química , Benzamidas/síntesis química , Relación Dosis-Respuesta a Droga , Himenolepiasis/parasitología , Hymenolepis/crecimiento & desarrollo , Ratones , Niclosamida/farmacología , Recuento de Huevos de Parásitos , Sulfonamidas/síntesis químicaAsunto(s)
Anticestodos/farmacología , Benzamidas/farmacología , Himenolepiasis/tratamiento farmacológico , Hymenolepis/efectos de los fármacos , Administración Oral , Animales , Anticestodos/síntesis química , Benzamidas/síntesis química , Relación Dosis-Respuesta a Droga , Himenolepiasis/parasitología , Hymenolepis/crecimiento & desarrollo , Inyecciones Intraperitoneales , Dosificación Letal Mediana , Ratones , Niclosamida/farmacología , Recuento de Huevos de Parásitos , Relación Estructura-ActividadAsunto(s)
Compuestos de Anilina/toxicidad , Antihelmínticos/toxicidad , Clorobenzoatos/toxicidad , Himenolepiasis/tratamiento farmacológico , Hymenolepis/efectos de los fármacos , Salicilatos/toxicidad , Compuestos de Anilina/síntesis química , Animales , Antihelmínticos/síntesis química , Clorobenzoatos/síntesis química , Relación Dosis-Respuesta a Droga , Himenolepiasis/mortalidad , Himenolepiasis/parasitología , Hymenolepis/crecimiento & desarrollo , Dosificación Letal Mediana , Ratones , Niclosamida/toxicidad , Salicilatos/síntesis química , Relación Estructura-ActividadAsunto(s)
Antihelmínticos/administración & dosificación , Antihelmínticos/síntesis química , Himenolepiasis/tratamiento farmacológico , Hymenolepis/efectos de los fármacos , Salicilanilidas/administración & dosificación , Salicilanilidas/síntesis química , Administración Oral , Animales , Animales no Consanguíneos , Antihelmínticos/toxicidad , Cromatografía de Gases , Relación Dosis-Respuesta a Droga , Himenolepiasis/mortalidad , Himenolepiasis/parasitología , Hymenolepis/fisiología , Inyecciones Intraperitoneales , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Recuento de Huevos de Parásitos , Salicilanilidas/toxicidad , Tasa de SupervivenciaRESUMEN
The manner in which the flatworm, Hymenolepis diminuta (Cestoda), regulates the transport of glucose and Na+ across the brush border was examined. While the presence of an unstirred region in the brush border may favor the reabsorption of leaked glucose, some leaked glucose was lost to the ambient medium. This loss was markedly enhanced by preloading the worms with glucose and by removing Na+ from the incubation medium. Since glucose and Na+ influxes are coupled, glucose leakage stimulated the influx of 22Na+. However, this 22Na+ influx was balanced by a simultaneous increased 22Na+ efflux. The presence of phlorizin inhibited both unidirectional fluxes of 22Na+ indicating that efflux of 22Na+ occurred by countertransport; countertransport of [14C] glucose appeared to be negligible. A model has been proposed in which the transport of glucose and compensating transfers of Na+ across the membrane occur via the same carrier.
Asunto(s)
Cestodos/metabolismo , Glucosa/metabolismo , Hymenolepis/metabolismo , Sodio/metabolismo , Animales , Unión Competitiva , Transporte Biológico , Transporte Biológico Activo , Desoxiglucosa/farmacología , Glucosa/farmacología , Hymenolepis/efectos de los fármacos , Cinética , Larva , Modelos Biológicos , Ouabaína/farmacología , Florizina/farmacologíaRESUMEN
The 31P NMR spectrum of the adult tapeworm, Hymenolepis diminuta, at 37 degrees C during perfusion with physiological saline was composed of 10 peaks. Based on chemical shifts and analysis of worm extracts, the phosphorus components included glucose-6-phosphate, fructose-6-phosphate, phosphorylcholine, glycerophosphoryl choline and -ethanolamine, nucleotide monophosphate-diphosphate and -triphosphate, nicotinamide adenine dinucleotide and uridine diphosphate glucose. The mean level of nucleotide triphosphate was 0.86 nmol (mg fresh weight)-1 and the nucleotide triphosphate/-diphosphate ratio 3.9. Based on the nucleotide triphosphate level, worms were viable for at least 3 h and the intracellular pH was maintained constant at approximately 6.7. Short-term exposure to mebendazole perfused at 11 or 27 microM solubilized in physiological saline containing 0.5% Tween 80 or 0.1% dimethyl sulphoxide had little effect on the nucleotide triphosphate level. Some cytological changes, however, were evident following perfusion of mebendazole. In contrast, exposure to 2,4-dinitrophenol caused a rapid decline in nucleotide triphosphate level. It was concluded that mebendazole does not exert its primary effect on oxidative phosphorylation.
Asunto(s)
Hymenolepis/efectos de los fármacos , Mebendazol/farmacología , Nucleótidos/metabolismo , Animales , Hymenolepis/metabolismo , Hymenolepis/ultraestructura , Espectroscopía de Resonancia Magnética , Microscopía Electrónica , Nucleótidos/análisis , FosforilaciónRESUMEN
Glucose uptake by Hymenolepis diminuta was linear for up to 60 min following in vitro incubation in 10 mM glucose. Following the addition of 1 mM 5-HT, with a 95% O2/5% CO2, gas phase, glucose uptake by H. diminuta was significantly (P less than 0.001) enhanced, remaining linear and parallel to that of control groups between 15 and 60 min incubation. Under air, the rates of glucose uptake were higher, but were only significantly increased by 5-HT during the first 30 min of incubation. In further experiments, in the absence of glucose in the incubation media worm glycogen reserves decreased by over 50% after 60 min. With the addition of 1 mM 5-HT, the reduction in glycogen content was significantly (P less than 0.025) greater, exceeding 65% after 60min. When glucose was added to the incubation media, worm glycogen reserves were not significantly depleted irrespective of the presence or absence of 5-HT. Incubations under a 95% O2/5% CO2 gas phase did not significantly influence glycogen content compared to corresponding groups incubated in air. The results suggest that 5-HT stimulates glycolysis in H. diminuta through increased glucose uptake by the worm or by a reduction in glycogen reserves in the absence of external glucose.
Asunto(s)
Glucosa/metabolismo , Glucógeno/metabolismo , Hymenolepis/metabolismo , Serotonina/farmacología , Animales , Hymenolepis/efectos de los fármacos , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
Incubation of Hymenolepis diminuta with the calmodulin antagonist trifluoperazine causes lesions in the brush border of the cestode. Exposure to a phenothiazine of lower lipophilicity, trifluoperazine sulphoxide, had little effect. Characterisation of isolated brush border revealed two forms of Ca2+-ATPase which exhibited maximum activity at pH 5.5 and 7.5. Both forms were Ca2+-dependent but only the latter was influenced by calmodulin and trifluoperazine. It is suggested that the Ca2+-ATPase present in the tapeworm brush border may be the site of trifluoperazine toxicity.
Asunto(s)
ATPasas Transportadoras de Calcio/metabolismo , Hymenolepis/efectos de los fármacos , Trifluoperazina/farmacología , Animales , Calmodulina/farmacología , Concentración de Iones de Hidrógeno , Hymenolepis/enzimología , Hymenolepis/ultraestructura , Microscopía Electrónica de Rastreo , Microvellosidades/efectos de los fármacos , Microvellosidades/enzimología , Microvellosidades/ultraestructura , Trifluoperazina/análogos & derivadosRESUMEN
Praziquantel (PZ) at concentrations down to 5 x 10(-8) M induced a rapid contraction of Hymenolepis diminuta musculature. This effect was accompanied by a strong inhibition of 45Ca2+ incorporation which showed some dependence on Ca2+ concentration. Ca2+ efflux experiments showed that PZ markedly stimulated the release of Ca2+ from tapeworms preloaded with 45Ca2+, with the effluxed Ca2+ being derived from a small fast pool and a larger slow pool. This stimulatory effect appeared., like PZ-induced muscle contraction, to be independent of external Ca2+. By carrying out 45Ca2+ exchange experiments under near equilibrium conditions and atomic absorption spectroscopy it could be demonstrated that PZ resulted in a net excretion of endogenous Ca2+. In PZ-induced contracted worms adenylate nucleotide levels and the adenylate energy charge were not significantly different from those of untreated control worms. Also, PZ had no effect on Ca2+-stimulated ATPase activity of the tapeworm's tegumental brush border. Nor did the drug alter the activities of Ca2+-ATPases in whole homogenates of worms or mitochondria, microsomal or soluble fractions. Although the mechanism of PZ-induced changes in Ca2+ transport was not elucidated, it is suggested that the sustained release of endogenous Ca2+ may affect the sequence of excitation-contraction coupling and that such interference may cause the observed massive contraction of the tapeworm's musculature.
Asunto(s)
Calcio/metabolismo , Hymenolepis/efectos de los fármacos , Isoquinolinas/farmacología , Praziquantel/farmacología , Nucleótidos de Adenina/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , ATPasas Transportadoras de Calcio/metabolismo , Hymenolepis/metabolismo , Cinética , Microvellosidades/enzimología , Mitocondrias/enzimología , Contracción Muscular/efectos de los fármacosRESUMEN
The direct effects of the inflammatory mediators, histamine (HI) and serotonin (SE), on the glucose metabolism of Hymenolepis diminuta in vitro were studied by analyzing the excretory products from culture media, containing D-1-13C-glucose and various concentrations of HI and/or SE, by 1H-nuclear magnetic resonance (n.m.r.) spectroscopy. The results revealed that HI markedly accelerated the glycolysis process by increasing the amount of lactate production. The increased glycolytic activity was reflected in a concentration-dependent increase in glucose uptake. Excretion of acetate was also stimulated by HI. A low concentration of SE significantly increased succinate, acetate and lactate excretions, whereas a high concentration had little effect on lactate production and significantly decreased succinate and acetate excretions. A combination of HI and SE treatment at a low concentration had no significant effect, but at a high concentration showed an additive effect, with an increase in lactate production, a decrease in succinate production and an increase in glucose uptake. Thus this work confirms that HI and SE directly influence, albeit differently, energy metabolism of the tapeworm H. diminuta.
Asunto(s)
Glucosa/metabolismo , Histamina/farmacología , Hymenolepis/efectos de los fármacos , Serotonina/farmacología , Animales , Hymenolepis/metabolismo , Espectroscopía de Resonancia MagnéticaRESUMEN
The effect of cyclosporin A, which is known to act both as immunosuppressant and as an antiparasitic drug in many host-parasite systems, was examined in a mouse-Hymenolepis nana system. When BDF1 mice were injected s.c. with cyclosporin A (100 mg kg-1 day-1) every 48 h from 11 days p.i. with eggs, expulsion of the adult worms from the intestines of mice was prevented completely until at least 30 days p.i. Worm burden, dry weight and the number of gravid proglottids were not significantly reduced. By contrast, in untreated mice most of the worms were eliminated by 19 days p.i. The drug also completely abolished acquired resistance to a challenge infection with eggs when mice were injected s.c. with cyclosporin A (100 mg kg-1 day-1) around the time of challenge infection (Days -2, -1, 0, 1 and 2 relative to challenge). Such immunosuppressive effects of cyclosporin A on worm expulsion and protective immunity to reinfection were similar to those of another immunosuppressant, cyclophosphamide. As for the antiparasitic action of cyclosporin A against H. nana, a smaller number of cysticercoids developed from eggs in mice given cyclosporin A (100 mg kg-1 day-1) for 5 days beginning 1 day before infection, than in untreated controls.
Asunto(s)
Anticestodos/farmacología , Ciclosporina/farmacología , Himenolepiasis/inmunología , Himenolepiasis/parasitología , Hymenolepis/efectos de los fármacos , Inmunosupresores/farmacología , Animales , Anticestodos/administración & dosificación , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacología , Ciclosporina/administración & dosificación , Interacciones Huésped-Parásitos , Himenolepiasis/tratamiento farmacológico , Hymenolepis/crecimiento & desarrollo , Inmunidad Activa/efectos de los fármacos , Terapia de Inmunosupresión , Inmunosupresores/administración & dosificación , Estadios del Ciclo de Vida , Masculino , Ratones , Recuento de Huevos de Parásitos , Factores de TiempoRESUMEN
14C-praziquantel penetrates the cyst wall of Cysticercus fasciolaris and kills the cysticercus within the cyst, although the uptake of praziquantel by the encysted larva was slower than by an isolated one. This fact is in good agreement with earlier in vitro chemotherapeutic studies. Scanning and transmission electron microscopic studies have shown that praziquantel causes a marked destruction of the tegument along the whole pseudostrobila and the scolex of C. fasciolaris. The type of tegumental damage is identical to that produced in adult tapeworms and trematodes.
Asunto(s)
Cisticercosis/tratamiento farmacológico , Isoquinolinas/uso terapéutico , Praziquantel/uso terapéutico , Animales , Hymenolepis/efectos de los fármacos , Ratones , Microscopía Electrónica de Rastreo , Praziquantel/metabolismo , Ratas , Schistosoma/efectos de los fármacos , Taenia/efectos de los fármacos , Taenia/ultraestructuraRESUMEN
The release of exogenously-supplied [3H]serotonin and of endogenous serotonin from H. diminuta tissue slices was studied using high [K+] depolarization. The release of [3H]serotonin was not calcium-dependent or magnesium-antagonized. While high-magnesium antagonism of endogenous serotonin release was inconclusive, this release was calcium-dependent. These findings suggest that, while exogenous serotonin is not taken into and released from nervous tissue, endogenous serotonin appears to be released from nervous tissue in a neurotransmitter-like manner.
Asunto(s)
Hymenolepis/metabolismo , Serotonina/metabolismo , Animales , Calcio/fisiología , Hymenolepis/efectos de los fármacos , Hymenolepis/fisiología , Técnicas In Vitro , Potasio/farmacología , Serotonina/farmacocinéticaRESUMEN
The glycocalyx of Hymenolepis diminuta (Cestoda, Cyclophyllidea) was isolated using 0.02 M EDTA or 3 M KCl. It was shown in the electron micrographs that 0.02 M EDTA did not damage the tapeworm plasma membrane, eliminating glycocylax only, in contrast to 3 M KCl which disrupted tegument up to the basal membrane. The protein analysis of extracts and the supernatant of homogenate of the whole tapeworm strobila by polyacrylamide gel electrophoresis (PAGE) and dodecyl sulphate-polyacrylamide gel electrophoresis (SDS) electrophoresis revealed that the substance extracted with 3 M KCl was more abundant in protein fractions than the two remaining ones. The substance extracted with 0.02 EDTA, collecting the tapeworm glycocalyx possessed the smallest amount of protein fractions, however, some of them were more abundant.
Asunto(s)
Ácido Edético/farmacología , Hymenolepis/efectos de los fármacos , Cloruro de Potasio/farmacología , Proteínas/análisis , Animales , Membrana Celular/efectos de los fármacos , Electroforesis en Gel de Poliacrilamida , Hymenolepis/análisis , Hymenolepis/ultraestructura , Masculino , Ratas , Ratas EndogámicasRESUMEN
A method is described for isolation of gram quantities of the components of the streptothricin complex S15-1 utilizing CM Sephadex column chromatography eluted with 10% acetic acid as an eluant followed by gradient elution with 10% acetic acid containing 0.02 N approximately 0.03 N HCI. Streptothricins F and E, as well as an unidentified component C1, have been isolated and their comparative biological activities determined. Streptothricins F and E were comparable in taeniacidal activity in mice infected with Hymenolepis nana ia feeding either one at 0.05% in the diet removed 92 approximately 100% of the adult tapeworms. The unidentified component C1 was inactive at the levels tested. In contrast, component C1 was the most active in antimicrobial activity against Bacillus subtilis and in inhibiting the urease activity of proteus mirabilis. In the former test, the ratios of activity were; 1:7:30 for F:E:C1 and in the latter; 1:2:4 for F:E:C1.