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1.
Parasite ; 16(3): 215-21, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19839267

ABSTRACT

We studied the stress proteins induced in protozoa Leishmania donovani after treatment with edelfosine, miltefosine and ilmofosine. We studied the morphological and structural modifications caused in the promastigote forms of the parasite after treatment with the three alkyl-lysophospholipids (ALPs). A resistant strain of L. donovani to miltefosine was obtained and the morphological modifications were observed. The stress proteins induction was studied in promastigote forms and also in amastigote-like forms obtained in vitro. The proteins synthesized with the three alkyl-lysophospholipids were compared to those obtained by heat shock. The axenic amastigote forms synthesized a pattern of different proteins for those observed in the promastigote forms. The morphological alterations were observed under electronic microscopy. The membrane and mitochondria were the organs most affected by the three ALPs. We noted an apparition of vacuoles and vesicles in the treated promastigotes. In the resistant strain, we noted myelin bodies in the treated and untreated parasites.


Subject(s)
Antineoplastic Agents/pharmacology , Leishmania donovani/drug effects , Phospholipid Ethers/pharmacology , Animals , Autoradiography , Drug Resistance , Heat-Shock Proteins/drug effects , Heat-Shock Proteins/metabolism , Humans , Leishmania donovani/ultrastructure , Leishmaniasis, Visceral/epidemiology , Microscopy, Electron , Protozoan Proteins/drug effects , Protozoan Proteins/metabolism , World Health Organization
2.
Vet Parasitol ; 143(1): 42-9, 2007 Jan 19.
Article in English | MEDLINE | ID: mdl-16973283

ABSTRACT

Sheep from the areas of Fondouk-Jeddid, Bir Mchergua and El Fahs, located in the Northeast of Tunisia, were examined by ultrasonography between 2001 and 2004 in order to assess their infection with Echinococcus granulosus, the agent of hydatid disease, and to evaluate this method as an efficient aire for hydatid cysts. A total of 1039 sheep, aged between 1 and 14 years was examined. The highest prevalence was found in sheep aged more than 8 years. The least infected animals were aged between 1 and 2 years. All hydatid cysts detected by ultrasound were located in the liver. In all age-groups, the dead cysts were more numerous than viable cysts. Eighteen positive sheep were autopsied and a comparison between ultrasound and autopsy results was performed. The results showed a prevalence of about 40% for the three areas. Ultrasonography allowed the cysts, deep or superficial to localize in the central or left part in relation to the caudal vena cava of the animals. Consequently, all the cysts were not detected with this technique. This work shows that ultrasonography confirms the importance of ovine hydatid cyst in Tunisia and that its use as a mass screening approach for cystic echinococcosis in sheep could be helpful for the monitoring of this disease in a hydatid control program without great stress for the animals.


Subject(s)
Echinococcosis, Hepatic/veterinary , Echinococcus granulosus/isolation & purification , Sheep Diseases/diagnostic imaging , Age Factors , Animals , Echinococcosis, Hepatic/diagnostic imaging , Echinococcosis, Hepatic/epidemiology , Female , Male , Mass Screening/veterinary , Sentinel Surveillance/veterinary , Sheep , Sheep Diseases/epidemiology , Tunisia/epidemiology , Ultrasonography
3.
J Parasitol ; 92(5): 877-83, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17152926

ABSTRACT

To discover the mode of action of alkyl-lysophospholipids in Leishmania donovani, we studied the effects of edelfosine, miltefosine, and ilmofosine on intracellular pH, the parasite's cell cycle, and the induction of apoptosis. The effect of the alkyl-lysophospholipids was combined with that of inhibitors of some pumps and exchange regulators of intracellular pH (Na+/ H+; Cl-/CO- 3; and the Na+/K+ ATPase). The effect of the 3 alkyl-lysophospholipids on intracellular pH was indirect; the primary action occurred in the parasite's cell membrane. To determine intracellular pH, we used flow cytometry for the macrophages and axenic amastigotes and spectrofluorometry for the promastigote forms. Apoptosis and the cell cycle were studied by flow cytometry. Treatment of the extracellular promastigote form of L. donovani with the 3 alkyl-lysophospholipids induced death by apoptosis, whereas in the infected cell they caused necrosis rather than apoptosis. Miltefosine and ilmofosine at doses of 38 microM caused G2/M cell cycle inhibition in L. donovani promastigotes.


Subject(s)
Antiprotozoal Agents/pharmacology , Leishmania donovani/drug effects , Macrophages/parasitology , Phospholipid Ethers/pharmacology , Animals , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line , Cricetinae , Female , Humans , Hydrogen-Ion Concentration/drug effects , Leishmania donovani/cytology , Macrophages/chemistry , Macrophages/cytology , Macrophages/drug effects , Mice , Mice, Inbred BALB C , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/pharmacology
4.
Vet Res Commun ; 30(4): 379-91, 2006 May.
Article in English | MEDLINE | ID: mdl-16502106

ABSTRACT

An in vitro and in vivo study was conducted to show the effect of dipeptide methyl ester on the protoscolices of Echinococcus granulosus and in naturally infected sheep. Easily punctured cysts were located by ultrasonography. A PAIR and PAI method were performed by the injection of dipeptide methyl ester into these cysts at a final concentration of 110 mmol/L. Follow-up was conducted monthly by ultrasonography. After injection of the compound, the sheep were sacrificed at different times from 6 to 17 weeks. The size and the morphological aspect of treated cysts were noted. Samples were collected for histology and electron microscopy. In conclusion, these studies revealed significant and rapid detachment of the membrane of the treated cyst and alteration of the inner membrane in less than 5 min after injection of the drug, confirming the effect of the compound on the laminated layer of the parasite.


Subject(s)
Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Dipeptides/administration & dosage , Dipeptides/therapeutic use , Echinococcosis, Hepatic/veterinary , Sheep Diseases/therapy , Animals , Cysts/ultrastructure , Dose-Response Relationship, Drug , Echinococcosis, Hepatic/drug therapy , Echinococcosis, Hepatic/pathology , Echinococcosis, Hepatic/therapy , Echinococcus granulosus/drug effects , Injections, Intralesional/methods , Injections, Intralesional/veterinary , Sheep , Sheep Diseases/drug therapy
5.
Parasite ; 12(3): 251-8, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16218213

ABSTRACT

33 polycyclic derivatives have been studied and tested on Leishmania donovani and L. major promastigotes. Their antileishmanial activity was assessed in vitro and an assay of their cytotoxicity was realized on human myelomonocytic cell line. The reference molecules used in the assays were amphotericin B and pentamidine. Among the compounds tested, 29 possess an antileishmanial activity; 25 of those were more active against L. donovani than amphotericin B, and nine were as effective as amphotericin B against L. major. Many synthesized derivatives were more active against L. donovani than against L. major. The cytotoxicity studies have shown that among the thirty-three derivatives tested, 12 molecules have an IC50 towards THP-1 cells about equal than that reference drugs, the 21 other derivatives are much less toxic. A 3D QSAR study was undertaken and has permitted to predict activity against L. donovani and L. major and to highlight critical area to optimize activity against the two species.


Subject(s)
Amphotericin B/pharmacology , Antiprotozoal Agents/pharmacology , Leishmania/drug effects , Pentamidine/pharmacology , Polycyclic Compounds/pharmacology , Animals , Cell Line , Cell Survival/drug effects , Humans , Quantitative Structure-Activity Relationship
6.
Parasitol Res ; 96(2): 113-20, 2005 May.
Article in English | MEDLINE | ID: mdl-15824902

ABSTRACT

Here, we investigate in mice the immunogenicity of two antigens EgA31 and EgTrp which are expressed by the larval stage of Echinococcus granulosus. These recombinant proteins were used alone or as a mixture (EgA31-EgTrp) to immunize BALB/c mice. By flow cytometry, we have shown that the ratio CD4+/CD8+ of splenocytes were significantly higher in the antigen-immunized groups. The specific antibody in the sera and cytokine producing splenocytes was evaluated by enzyme-linked immunosorbent assay. EgA31, EgTrp or EgA31-EgTrp elicited high antibody titer of IgG and IgA. Among IgG isotypes, IgG1 was predominant for each antigen tested alone or combined. The production of IL-12, IFN-gamma, IL-10 and IL-6 cytokines was significantly higher in mice immunized with recombinant proteins. Our results suggest that, in BALB/c mice, a mixed Th1/Th2, response to EgA31, EgTrp and EgA31-EgTrp is obtained. The use of both antigens separately or in combination as candidate vaccine proteins is discussed.


Subject(s)
Antibodies, Helminth/blood , Antigens, Helminth/immunology , Echinococcus granulosus/immunology , T-Lymphocytes/immunology , Animals , Antigens, Helminth/administration & dosage , Antigens, Helminth/genetics , CD4-CD8 Ratio , Cytokines/metabolism , Echinococcosis/mortality , Echinococcosis/prevention & control , Echinococcus granulosus/genetics , Female , Flow Cytometry , Humans , Immunization , Immunoglobulin G/blood , Lymphocyte Activation , Mice , Mice, Inbred BALB C , Vaccines/administration & dosage , Vaccines/genetics , Vaccines/immunology
7.
Parasitol Res ; 92(6): 506-12, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15007640

ABSTRACT

With the aim of proposing an alternative model to animal experimentation, we investigated cytokine production in response to antigens in an in vitro system. This is a co-culture system of healthy human leukocytes and enterocyte-like Caco-2 cells. The antigens tested, EgA31, EgTrp, and FABP1, are candidates for vaccines in infections caused by Echinococcus spp. in the gut. All three have previously been described in the protoscolex stage and belong to protein families which confer protective immunity against several helminths. In this study, we evaluate the Th1/Th2 profile (Th1: IL-12, IFN-gamma; Th2: IL-6, IL-10) in response to protoscoleces, EgA31 and the mixture of EgA31, EgTrp and FABP1. No cytokine production was detected in response to protoscoleces. Neither IFN-gamma nor IL-6, but a significant IL-10 and IL-12 concentration was detected in response to both types of antigens. These findings suggest that EgA31 and the mixture EgA31/EgTrp/FABP1 generated an immunogenic response associated with a mixed Th1/Th2 cytokine.


Subject(s)
Antigens, Helminth/immunology , Carrier Proteins/immunology , Cytokines/metabolism , Echinococcus/immunology , Fish Proteins , Leukocytes/immunology , Animals , Caco-2 Cells , Cell Culture Techniques , Cell Line , Coculture Techniques , Fatty Acid-Binding Proteins , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-12/metabolism , Interleukin-6/metabolism
8.
J Helminthol ; 75(3): 251-7, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11551315

ABSTRACT

A protoscoleces/vesicles in vitro maintenance test with assessment of viability by eosin exclusion was used to evaluate the quantitative and qualitative activities of isoprinosine, its active component inosine and the dipeptide methylester L-Phe-Phe-OMe on isolated protoscoleces of Echinococcus multilocularis for 24 and 48 h. Isoprinosine and inosine showed dose- and time-dependent activity, the latter displaying a more rapid effect than the former. A high activity was shown with L-Phe-Phe-OMe, when compared to praziquantel. Ultrastructural alterations were much more striking with L-Phe-Phe-OMe, with an effect similar to that of praziquantel, whereas the chemotherapeutic activity of inosine and isoprinosine appeared to be directed against a metabolic target, with a lethal effect not immediately visible at the ultrastructural level. Thus, the previously reported in vivo activities of these drugs result largely from a direct effect on the parasite.


Subject(s)
Anthelmintics/pharmacology , Echinococcus/drug effects , Inosine Pranobex/pharmacology , Animals , Dipeptides/pharmacology , Dose-Response Relationship, Drug , Echinococcus/ultrastructure , Inosine/pharmacology , Microscopy, Phase-Contrast , Parasitology/methods , Praziquantel/pharmacology
9.
Scand J Immunol ; 52(6): 534-43, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11119257

ABSTRACT

Reactivation of cerebral toxoplasmosis occurs in approximately 30% of acquired immune deficiency syndrome (AIDS) patients who are seropositive for Toxoplasma gondii and a change in the levels of cytokines during this relapse is observed. Several cytokines are able to initiate meningeal inflammation and may play a role in the immunopathogenesis of the disease. The induction of a type 1 inflammatory cytokine response is a key event in the initiation of immunity to T. gondii. Interleukin (IL)-10 production in infected brain facilitates the persistence of parasites by down-regulating the intracerebral immune response. The in vivo and in vitro models are very numerous and this may explain the heterogeneity of the results. The role of gamma interferon is important because it is the principal mediator inducing a host resistance against T. gondii. Several cytokines stimulating or decreasing interferon (IFN)-gamma levels are reported. The particular case of AIDS patients whose humoral response is altered, is studied.


Subject(s)
AIDS-Related Opportunistic Infections/immunology , Cytokines/pharmacology , Toxoplasmosis, Cerebral/immunology , Animals , Humans , Interferon-gamma/pharmacology , Models, Immunological , Toxoplasma/drug effects
10.
Bioorg Med Chem Lett ; 10(9): 871-3, 2000 May 01.
Article in English | MEDLINE | ID: mdl-10853649

ABSTRACT

2-methylfuro[2,3-g]isoquinoline-4,7,9-trione (4) and 2-methylfuro[3,2-g]isoquinoline-4,6,9-trione (5) were prepared regiospecifically from 2-azadiene 9 and bromobenzofuran-4,7-diones 1 or 11. The activity of these two compounds and some other quinonic derivatives was evaluated in vitro against a virulent strain of Toxoplasma gondii. Compounds 4 and 7 were found to be as active as pyrimethamine.


Subject(s)
Antiprotozoal Agents/chemical synthesis , Furans/chemical synthesis , Quinolines/chemical synthesis , Toxoplasma/drug effects , Animals , Antiprotozoal Agents/pharmacology , Cell Line , Furans/pharmacology , Humans , Monocytes/drug effects , Monocytes/parasitology , Quinolines/pharmacology , Toxoplasma/growth & development
11.
Am J Trop Med Hyg ; 62(1): 73-6, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10761727

ABSTRACT

The effect of artesunate and its metabolite dihydroartemisinin against the cerebral cysts of Toxoplasma gondii was studied. In vitro experiments were performed with the THP-1 cell line and showed an inhibition of parasite growth of approximately 70% with 0.1-0.5 microg/ml of dihydroartemisinin for 96 hr. However, with artesunate, dihydroartemisinin, or a combination (50:50) of them, the number of tachyzoites decreased approximately 40-50% and they appeared motionless. Fifty-eight to 72 hr after washing of the tachyzoites and THP-1 cells in culture, parasitized cells reappeared. In vivo, the 50:50 artesunate-dihydroartemisinin combination produced a decrease in cerebral cysts of approximately 40% after only 5 days of treatment. However, transplantations into naive mice using brains of treated mice gave positive results.


Subject(s)
Antimalarials/therapeutic use , Artemisinins , Sesquiterpenes/therapeutic use , Toxoplasma/drug effects , Toxoplasmosis, Animal/drug therapy , Animals , Antimalarials/pharmacology , Artesunate , Brain/parasitology , Brain/pathology , Cell Line , Cell Survival/drug effects , Drug Combinations , Female , Histocytochemistry , Humans , Mice , Sesquiterpenes/pharmacology , Toxoplasmosis, Animal/pathology
12.
Parasite ; 7(1): 39-42, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10743646

ABSTRACT

In this study we investigated the effect of the antiretroviral molecule 2',3'-dideoxyinosine (Videx) against cerebral cysts in a murine model of toxoplasmic encephalitis caused by a wild cystic strain of Toxoplasma gondii. The role of the vehicle was also studied. Three doses were used: 50, 100 and 150 mg/kg of body weight/day. The doses of 50 and 150 mg/kg were prepared by dissolving pure 2',3'-dideoxyinosine powder in Maalox suspension before gavaging the mice; the dose of 100 mg/kg was prepared by grinding tablets of Videx that were suspended in water. A decrease in the number of cysts and a morphological modification of them were noted from day 15 with the lowest dose. The most important decrease could be observed with the dose of 100 mg/kg/d. After 30 days of treatment with this dose, 65% of the cysts were destroyed compared to controls. For the doses of 50 and 150 mg/kg/d prepared with Maalox, 36% and 51% of the cysts were destroyed respectively. So ddI has an effect on the cerebral cysts of T. gondii even at a low dose. The galenic formulation influences its action since the doses prepared with Maalox were less efficient than those prepared from ground tablets.


Subject(s)
Didanosine/administration & dosage , Didanosine/therapeutic use , Encephalitis/drug therapy , Toxoplasmosis, Cerebral/drug therapy , Animals , Antacids , Buffers , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Compounding/methods , Female , Mice , Toxoplasma
13.
Life Sci ; 65(17): 1733-8, 1999.
Article in English | MEDLINE | ID: mdl-10576552

ABSTRACT

The activities of purine salvage enzymes in tachyzoites from a cyst-forming strain of Toxoplasma gondii were determined using HPLC. Six enzymes were assayed both in vitro and in vivo: adenosine deaminase, guanine deaminase, purine nucleoside phosphorylase, xanthine oxidase, hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase. In vitro, the tachyzoites were cultured in the human myelomonocytic cell line THP-1, for 24 h to 96 h. Neither guanine deaminase nor hypoxanthine-guanine phosphoribosyltransferase activity was detected in 24 and 96 h cultures. In vivo, in controls and infected animals, the purine nucleoside phosphorylase and adenosine deaminase activities were the most important activities both in sera and cerebral tissue in comparison with the other activities. It was also noted that the infection modified the enzymatic activities of this purine salvage pathway, in particular, the guanine deaminase cerebral activity of infected mice was 20-fold lower than the value of controls. The treatment of mice with 2',3'-dideoxyinosine, a purine analog, at the dose of 100 mg.kg(-1).d for 30 days, induced an important increase of all enzymatic activities in the brains in comparison with control animals. These data suggest that one target of 2',3'-dideoxyinosine is the purine metabolism.


Subject(s)
Purines/metabolism , Toxoplasma/enzymology , Toxoplasmosis, Animal/parasitology , Amidohydrolases/blood , Amidohydrolases/metabolism , Animals , Antimetabolites/pharmacology , Cells, Cultured , Cerebral Cortex/enzymology , Cerebral Cortex/parasitology , Chromatography, High Pressure Liquid , Didanosine/pharmacology , Female , Glycosyltransferases/blood , Glycosyltransferases/metabolism , Humans , Mice , Pregnancy , Toxoplasmosis, Animal/blood , Toxoplasmosis, Animal/enzymology , Xanthine Oxidase/blood , Xanthine Oxidase/metabolism
14.
Article in English | MEDLINE | ID: mdl-9854810

ABSTRACT

The activities of the enzymes in Echinococcus multilocularis metacestodes involved in purine salvage were studied by HPLC. As in most parasites, this cestode relies entirely on salvage of preformed bases and nucleosides for its purine requirement. Therefore, these enzymes may be targets for drugs in the chemotherapeutic treatment of diseases caused by this parasite. The animals used in this study were gerbils (Meriones unguiculatus). Enzyme activities from sera and hepatic tissue in control and infected animals were similar with the exception of adenine phosphoribosyltransferase which showed an activity 4-fold greater in the serum from control than in serum from infected animals. In the parasite, adenine and hypoxanthine-guanine phosphoribosyltransferases and adenosine deaminase had the highest activities. Therefore, in E. multilocularis metacestodes, this pathway seems to be important for the parasite's metabolism.


Subject(s)
Echinococcus/metabolism , Purines/metabolism , Adenine Phosphoribosyltransferase/blood , Adenine Phosphoribosyltransferase/metabolism , Adenosine Deaminase/blood , Adenosine Deaminase/metabolism , Animals , Echinococcosis/drug therapy , Echinococcosis/enzymology , Echinococcosis/parasitology , Echinococcus/drug effects , Echinococcus/enzymology , Gerbillinae , Guanine Deaminase/blood , Guanine Deaminase/metabolism , Host-Parasite Interactions , Humans , Hypoxanthine Phosphoribosyltransferase/blood , Hypoxanthine Phosphoribosyltransferase/metabolism , Liver/enzymology , Purine-Nucleoside Phosphorylase/blood , Purine-Nucleoside Phosphorylase/metabolism , Xanthine Oxidase/blood , Xanthine Oxidase/metabolism
15.
J Parasitol ; 84(5): 1055-9, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9794657

ABSTRACT

The time-course of action of the antiviral agent 2',3'-dideoxyinosine (ddI) against Toxoplasma gondii tachyzoites in vitro and its effects at the ultrastructural level were investigated. The very short latency of effect and high efficacy of ddI were evidenced by the fact that the drugs' effects on parasite growth occurred 2 hr after addition to the culture medium, and that an IL90 value of 0.5 microg/ml was reached after 72 hr. Although without apparent effect on uninfected cells, ddI clearly acted on the intracellular parasites, which tended to disappear. Remaining tachyzoites were almost exclusively extracellularly located and often exhibited a clustering of mitochondria-like bodies and subsequent deep alterations of their plasma membranes. These results confirm previous findings and emphasize the potential usefulness of ddI in the management of cerebral toxoplasmosis, a major health problem in acquired immune deficiency syndrome patients.


Subject(s)
Antimetabolites/pharmacology , Didanosine/pharmacology , Toxoplasma/drug effects , Animals , Cell Line , Humans , Microscopy, Electron , Time Factors , Toxoplasma/ultrastructure
16.
Parasite ; 5(4): 359-64, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9879558

ABSTRACT

The action of phenylalanine derivatives against a cyst forming strain of Toxoplasma gondii was tested in vitro and in vivo in mice. These compounds were Phe-Phe-OMe (dipeptide methyl ester) 1 and its cyclized product, 3,6-dibenzyl-2,5-dioxopiperazine 2, Boc-L-Phe 3, L-Phe-OMe 4, Boc-L-Phe-L-Phe-OMe 5. After a 48 hr incubation in vitro, the compounds 3 and 5 induced a higher inhibition than the control molecule, pyrimethamine. In the in vivo studies, the compound 3 induced a 77% decrease in the number of cerebral cysts, comparable to pyrimethamine. Compounds 1, 5 and 4 induced a decrease of about 63% in the cyst number. A size reduction and an alteration of the wall of treated cysts were often noted. In a histological study, a reduction in cyst size without either inflammation or intervention of the nevroglial cells was observed. The present study provides evidence on the efficacy of phenylalanine derivatives and especially Boc-Phe 3, against T.gondii brain cysts in mice.


Subject(s)
Brain/parasitology , Phenylalanine/analogs & derivatives , Toxoplasma/drug effects , Toxoplasmosis, Animal/drug therapy , Animals , Cell Line , Female , Humans , Mice , Phenylalanine/pharmacology , Phenylalanine/therapeutic use
17.
Exp Parasitol ; 87(2): 142-9, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9326889

ABSTRACT

Echinococcus multilocularis metacestodes possess an alkaline phosphatase (EmAP) which has been extensively characterized at the biochemical level in previous studies. The apparent molecular weight of the enzyme monomer and its isoelectric point matched those originally described for the Em2 antigen, a reference antigen currently used for the immunodiagnosis of E. multilocularis infection. These observations raised questions about the molecular relationship between the two molecules. In order to investigate the relations between EmAP and the Em2 antigen, immunoblotting and ELISA were carried out using polyclonal and monoclonal antibodies directed against EmAP and the Em2 antigen, respectively. In addition, the localization of EmAP and the Em2 antigen was compared by immunofluorescence and immunogold electron microscopy in in vitro-generated E. multilocularis metacestodes. The results show that common epitopes between EmAP and Em2 exist, which are predominantly of a peptidic nature. Both antigens are localized in an acellular parasite structure, the laminated layer, with additional locations for the EmAP on the glycocalyx and in the central region of invaginated protoscoleces. These results suggest a putative functional relationship between the two antigens and that Em2 could originate from EmAP.


Subject(s)
Alkaline Phosphatase/analysis , Antigens, Helminth/analysis , Echinococcus/enzymology , Echinococcus/immunology , Alkaline Phosphatase/immunology , Animals , Antibodies, Monoclonal/immunology , Antigens, Helminth/immunology , Echinococcus/ultrastructure , Enzyme-Linked Immunosorbent Assay , Epitopes/immunology , Fluorescent Antibody Technique , Gerbillinae , Humans , Immunoblotting , Immunohistochemistry , Microscopy, Immunoelectron
18.
Antimicrob Agents Chemother ; 41(7): 1531-6, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9210679

ABSTRACT

The activity against Toxoplasma gondii of 2',3' dideoxyinosine (ddI), an anti-human immunodeficiency virus drug, was examined in an in vitro and in vivo study. Cell cultures infected with a strain known to cause chronic infections were used to show the dose-dependent effect of this drug compared with spiramycin and sulfadiazine. When a dose of 4 microg/ml was used, no infected THP-1 cells or parasites were found after 60 h of incubation. An electron-microscopic study confirmed that after 12 h at 1 microg/ml, the few parasites observed were severely altered. The treatment of chronically infected mice 3 months postinfection showed that a 30-day treatment with 2 mg of ddI/ml induced a significant reduction in the number of T. gondii cysts in the cerebral tissue. These cysts were not viable, as confirmed by immunofluorescence and reinfection experiments. These experiments suggest a possible role for ddI in the treatment of toxoplasmosis, and this possibility deserves further investigation.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiprotozoal Agents/therapeutic use , Cysts/parasitology , Didanosine/therapeutic use , Toxoplasma/drug effects , Toxoplasmosis, Animal/drug therapy , Animals , Cell Line , Drug Evaluation, Preclinical , Female , Humans , Mice
19.
Am J Trop Med Hyg ; 56(2): 226-30, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9080884

ABSTRACT

Three months after infection with Echinococcus multilocularis, Mongolian gerbils were given either the dipeptide methyl ester (Phe-Phe-OMe) or a combination of Phe-Phe-OMe plus albendazole to treat alveolar echinococcosis. Each drug was given orally at the daily dose of 50 mg/kg of body weight following various administration regimens. Histologic and ultrastructural studies of parasites recovered from infected gerbil tissues showed that the dipeptide methyl ester increases the effect of albendazole.


Subject(s)
Albendazole/pharmacology , Anthelmintics/pharmacology , Dipeptides/pharmacology , Echinococcosis, Hepatic/drug therapy , Echinococcus/drug effects , Serine Proteinase Inhibitors/pharmacology , Albendazole/therapeutic use , Albendazole/toxicity , Animals , Anthelmintics/therapeutic use , Anthelmintics/toxicity , Dipeptides/therapeutic use , Dipeptides/toxicity , Drug Combinations , Echinococcus/ultrastructure , Female , Gerbillinae , Male , Mice , Microscopy, Electron , Serine Proteinase Inhibitors/therapeutic use , Serine Proteinase Inhibitors/toxicity
20.
Exp Anim ; 46(1): 25-30, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9027468

ABSTRACT

Histochemical observations of alkaline phosphatase activity of Echinococcus multilocularis during the in vivo development in golden hamster, an alternative definitive host. The present work reports on the ability of protoscoleces from a European fox strain of E. multilocularis to differentiate and develop into the adult form in the small intestine of male golden hamsters treated with prednisolone. Detection of alkaline phosphatase activity on various stages of the developing worm was performed by histochemical methods. The enzyme activity was not demonstrable in the early stages of infection but occurred with strobilization. Age-related changes in the distribution of the enzyme activity took place during strobilization. Alkaline phosphatase activity was evident in the excretory ducts of 8 to 11 day old strobila and in the tegument of mature proglottis of 16 day old worms. This in vivo procedure with rodents as definitive hosts provides interesting preliminary results on the biology of the E. multilocularis adult. Further investigations on membrane-bound enzymes involved in physiological and nutritional processes are in progress.


Subject(s)
Alkaline Phosphatase/metabolism , Echinococcus/enzymology , Echinococcus/growth & development , Histocytochemistry , Mesocricetus/parasitology , Animals , Cricetinae , Echinococcosis/enzymology , Echinococcosis/parasitology , Echinococcosis/veterinary , Female , Foxes/parasitology , Intestine, Small/parasitology , Male , Prednisolone/pharmacology
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