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1.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892261

RESUMO

Flatworms are known for their remarkable regenerative ability, one which depends on totipotent cells known as germinative cells in cestodes. Depletion of germinative cells with hydroxyurea (HU) affects the regeneration of the parasite. Here, we studied the reduction and recovery of germinative cells in T. crassiceps cysticerci after HU treatment (25 mM and 40 mM of HU for 6 days) through in vitro assays. Viability and morphological changes were evaluated. The recovery of cysticerci's mobility and morphology was evaluated at 3 and 6 days, after 6 days of treatment. The number of proliferative cells was evaluated using EdU. Our results show morphological changes in the size, shape, and number of evaginated cysticerci at the 40 mM dose. The mobility of cysticerci was lower after 6 days of HU treatment at both concentrations. On days 3 and 6 of recovery after 25 mM of HU treatment, a partial recovery of the proliferative cells was observed. Proteomic and Gene Ontology analyses identified modifications in protein groups related to DNA binding, DNA damage, glycolytic enzymes, cytoskeleton, skeletal muscle, and RNA binding.


Assuntos
Proliferação de Células , Hidroxiureia , Taenia , Hidroxiureia/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Taenia/efeitos dos fármacos , Taenia/genética , Taenia/crescimento & desenvolvimento , Taenia/metabolismo , Proteômica/métodos , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genética , Proteoma/metabolismo , Cysticercus/efeitos dos fármacos , Cysticercus/metabolismo
2.
Acta Trop ; 221: 106027, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216560

RESUMO

Cysticercosis is the presence of Taenia solium larval stage in tissues such as central nervous system, skin, muscles and eye globe. The current treatment is based on albendazole and praziquantel which already present resistance reports. Therefore, the search for alternative treatments is paramount. The aim of this study was to determine the effect of flubendazole and nitazoxanide on cytoskeleton proteins from Taenia crassiceps cysticerci, an experimental model for cysticercosis. Cysticerci were cultured in RPMI supplemented medium containing nitazoxanide and/or flubendazole. 24 h after the exposure the cysticerci were processed for scanning and transmission electron microscopy and for protein analysis of the cytoskeleton. The proteins were detected through 1D electrophoresis and identified through Western Blot. Nitazoxanide exposure increased tubulin and actin quantifications in T. crassiceps cysticerci. While flubendazole alone and the drugs combinations induced an increase in α-tubulin and actin and decreased ß-tubulin quantifications in the parasite. Morphological changes such as swelling and rupture of vesicle, stiff membrane, decrease in movements were observed when the cysticerci were incubated with the different compounds. In conclusion the drugs induced significative impact in the parasite`s cytoskeleton and may be considered as alternative treatments for cysticercosis.


Assuntos
Citoesqueleto/efeitos dos fármacos , Mebendazol/análogos & derivados , Nitrocompostos/farmacologia , Taenia , Tiazóis/farmacologia , Animais , Cisticercose , Cysticercus/efeitos dos fármacos , Feminino , Mebendazol/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Taenia/efeitos dos fármacos
3.
BMC Infect Dis ; 20(1): 220, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171260

RESUMO

BACKGROUND: The management of disseminated cysticercosis is unclear and largely considered hazardous. The role of albendazole remains controversial in such patients. METHODS: A tertiary care, University hospital-based prospective intervention study was conducted from December 2015 to December 2017. Patients with disseminated cysticercosis, defined as the presence of multiple viable neurocysticerci (≥ 3) in the brain along with involvement of an additional extra site, were included in the study. Patients with cysticercal encephalitis were excluded. A detailed evaluation, including ophthalmoscopy, ocular B scans, ultrasound abdomen, and X-rays were done. Albendazole was administered at a dose of 15 mg/kg/day in 3 cycles of 28 days each. All patients were also given adjuvant corticosteroids and anti-epileptic drugs. Clinical and radiological follow up was carried out at a difference of 3 months between each treatment cycle. For radiological quantification, lesions were counted at 10 pre-specified levels. Statistical analysis was done to estimate the difference in seizure frequency and lesion load. RESULTS: Twenty-nine patients (21 with > 20 lesions; 8 with ≤ 20 lesions) were given albendazole as per the protocol. There was a significant reduction in the occurrence of seizures (P < 0.001) and headache (P < 0.001). A significant reduction in lesion load from baseline to third follow-up was seen in the estimations done at different levels (P < 0.001). No patient developed serious side-effect warranting cessation of therapy. CONCLUSION: Cyclical use of albendazole appears efficacious in treating disseminated cysticercosis. The method of quantification described may be used in future studies for objective assessment. TRIAL REGISTRATION: ISRCTN11630542; 28th September 2019; Retrospectively registered.


Assuntos
Albendazol/administração & dosagem , Albendazol/uso terapêutico , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Cysticercus/efeitos dos fármacos , Neurocisticercose/tratamento farmacológico , Carga Parasitária , Adolescente , Corticosteroides/uso terapêutico , Adulto , Animais , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Quimioterapia Combinada , Feminino , Seguimentos , Cefaleia , Humanos , Masculino , Pessoa de Meia-Idade , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/parasitologia , Estudos Prospectivos , Radiografia , Convulsões , Resultado do Tratamento , Adulto Jovem
4.
Acta Trop ; 202: 105254, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31689380

RESUMO

The benzimidazole derivative, 6-chloro-5-(2,3-dichlorophenoxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB15), has a similar mode of action and efficacy as albendazole, a commonly used anthelminthic drugs. The aim of this study was to evaluate its influence on the tricarboxylic acid cycle in Taenia crassiceps cysticerci. The parasites were cultured in supplemented RPMI medium containing albendazole sulfoxide (ABZSO) or RCB15, for 24 h. Then, frozen in liquid nitrogen for organic metabolites extraction. Samples were analyzed by high performance liquid chromatography and organic acids of the tricarboxylic acid cycle were detected. It was possible to observe changes in the concentrations of all acids involved in this metabolic pathway, with the exception of α-ketoglutarate, which was not detected in the control group neither in most of the treated groups. It indicates that the parasite presented a partial inhibition of the tricarboxylic acid cycle. The significant increase in the concentration of citrate, oxaloacetate and succinate in the RCB15 treated groups may indicate an activation of the fumarate reductase pathway, leading to metabolic distress. Therefore RCB15 may be considered an alternative for the treatment of tissue parasitic diseases, since it induced changes in the main metabolic pathway of the parasite.


Assuntos
Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Ciclo do Ácido Cítrico/efeitos dos fármacos , Cysticercus/efeitos dos fármacos , Taenia/efeitos dos fármacos , Animais , Cysticercus/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Taenia/metabolismo
5.
Exp Parasitol ; 208: 107792, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707003

RESUMO

Nitazoxanide (NTZ) is a broad-spectrum drug used in intestinal infections, but still poorly explored in the treatment of parasitic tissular infections. This study aimed to evaluate the in vitro responses of the energetic metabolism of T. crassiceps cysticerci induced by NTZ. The organic acids of the tricarboxylic acid cycle, products derived from fatty acids oxidation and protein catabolism were analyzed. These acids were quantified after 24 h of in vitro exposure to different NTZ concentrations. A positive control group was performed with albendazole sulfoxide (ABZSO). The significant alterations in citrate, fumarate and malate concentrations showed the NTZ influence in the tricarboxylic acid (TCA) cycle. The non-detection of acetate confirmed that the main mode of action of NTZ is effective against T. crassiceps cysticerci. The statistical differences in fumarate, urea and beta-hydroxybutyrate concentrations showed the NTZ effect on protein catabolism and fatty acid oxidation. Therefore, the main energetic pathways such as the TCA cycle, protein catabolism and fatty acids oxidation were altered after in vitro NTZ exposure. In conclusion, NTZ induced a significant metabolic stress in the parasite indicating that it may be used as an alternative therapeutic choice for cysticercosis treatment. The use of metabolic approaches to establish comparisons between anti parasitic drugs mode of actions is proposed.


Assuntos
Antiparasitários/farmacologia , Taenia/efeitos dos fármacos , Tiazóis/farmacologia , Albendazol/análogos & derivados , Albendazol/farmacologia , Análise de Variância , Animais , Anti-Helmínticos/farmacologia , Citratos/metabolismo , Ciclo do Ácido Cítrico/efeitos dos fármacos , Meios de Cultura/química , Cysticercus/efeitos dos fármacos , Cysticercus/metabolismo , Metabolismo Energético/efeitos dos fármacos , Fumaratos/metabolismo , Ácidos Cetoglutáricos/metabolismo , Malatos/metabolismo , Neurocisticercose/tratamento farmacológico , Nitrocompostos , Ácido Oxaloacético/metabolismo , Ácido Succínico/metabolismo , Taenia/metabolismo
6.
Parasitology ; 146(12): 1578-1582, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31303189

RESUMO

Benzimidazole derivatives such as albendazole (ABZ) and mebendazole are important molecules used in helminthic treatment. Neurocysticercosis is the main cause of acquired epilepsy throughout the world and is currently treated with ABZ. New molecules have been studied in order to aid in the treatment of this neglected tropical disease, among them RCB15 and RCB20. The aim of this study was to evaluate the metabolic impact of RCB15 and RCB20 on Taenia crassiceps cysticerci intracranially inoculated in Balb/c mice. Thirty days after the inoculation the mice were treated with 50 mg kg-1 of RCB15, RCB20, ABZ or NaCl 0.9%. The euthanasia and cysticerci removal were performed 24 h after the treatment. The cysticerci were analysed through high performance liquid chromatography. After the treatments, there was an impairment in the main energetic pathways such as glycolytic pathway, homolactic fermentation or in mitochondrion energy production detected through the decrease in pyruvate, lactate, oxaloacetate, malate and fumarate concentrations. This induced the parasite to resort to alternative energetic pathways such as proteins catabolism, propionate fermentation and fatty acids oxidation. Therefore, benzimidazole derivatives are a promising alternative to ABZ use as they also reach the brain tissue and induce a metabolic stress in the cysticerci.


Assuntos
Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Cysticercus/efeitos dos fármacos , Neurocisticercose/tratamento farmacológico , Animais , Cysticercus/fisiologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Camundongos , Camundongos Endogâmicos BALB C
7.
J Helminthol ; 93(5): 539-547, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30149822

RESUMO

Androgens have been shown to exert a cysticidal effect upon Taenia crassiceps, an experimental model of cysticercosis. To further inquire into this matter, the Taenia crassiceps model was used to evaluate the expression of several proteins after testosterone (T4) and dihydrotestosterone (DHT) in vitro treatment. Under 2-D proteomic maps, parasite extracts were resolved into approximately 130 proteins distributed in a molecular weight range of 10-250 kDa and isoelectrical point range of 3-10. The resultant proteomic pattern was analysed, and significant changes were observed in response to T4 and DHT. Based on our experience with electrophoretic patterns and proteomic maps of cytoskeletal proteins, alteration in the expression of isoforms of actin, tubulin and paramyosin and of other proteins was assessed. Considering that androgens may exert their biological activity in taeniids through the non-specific progesterone receptor membrane component (PGRMC), we harnessed bioinformatics to propose the identity of androgen-regulated proteins and establish their hypothetical physiological role in the parasites. These analyses yield a possible explanation of how androgens exert their cysticidal effects through changes in the expression of proteins involved in cytoskeletal rearrangement, dynamic vesicular traffic and transduction of intracellular signals.


Assuntos
Androgênios/farmacologia , Morte Celular , Proteoma , Taenia/efeitos dos fármacos , Taenia/fisiologia , Actinas/genética , Animais , Biologia Computacional , Cisticercose/patologia , Cysticercus/efeitos dos fármacos , Cysticercus/fisiologia , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/genética , Di-Hidrotestosterona/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Receptores de Progesterona/genética , Testosterona/farmacologia , Tropomiosina/genética , Tubulina (Proteína)/genética
8.
Acta Trop ; 190: 361-364, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30553893

RESUMO

Neurocysticercosis is the most frequent helminthiasis of the central nervous system and is caused by the presence of Taenia solium cysticerci. Nitazoxanide (NTZ) is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antiprotozoal activity due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme which is essential to anaerobic energy metabolism. The aim of this work was to determine the effect of NTZ on the energetic metabolism of Taenia crassiceps cysticerci intracranially inoculated BALB /c mice. The infected animals were treated with a single oral dose of NTZ 30 days after the inoculation. Analysis of the organic acids was performed through high performance liquid chromatography. Glucose was detected only in the treated groups, alongside with a significant decrease in lactate, pyruvate and oxaloacetate concentrations which indicate an increase in gluconeogenesis. The non-detection of alpha-ketoglutarate indicated the use of the fumarate reductase pathway in all groups. It was possible to confirm the drugs mode of action due to the non-detection of acetate in the treated groups. There was an increase in the fatty acids oxidation. Therefore it was possible to observe that NTZ induces gluconeogenesis as well as the increase of alternative energetic pathways such as fatty acids oxidation in T. crassiceps cysticerci.


Assuntos
Anti-Helmínticos/farmacologia , Cysticercus/metabolismo , Gluconeogênese/efeitos dos fármacos , Neurocisticercose/metabolismo , Taenia/metabolismo , Tiazóis/farmacologia , Administração Oral , Animais , Anti-Helmínticos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Cysticercus/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/metabolismo , Glucose/metabolismo , Ácido Láctico/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Neurocisticercose/tratamento farmacológico , Nitrocompostos , Ácido Oxaloacético/metabolismo , Oxirredução , Ácido Pirúvico/metabolismo , Taenia/efeitos dos fármacos , Tiazóis/uso terapêutico
9.
Drug Deliv Transl Res ; 8(5): 1265-1273, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30117119

RESUMO

Neurocysticercosis is the most common parasitic infection of the nervous system and currently represents a serious public health issue in many regions of Latin America, Asia, and Africa. To date, praziquantel is one of the chosen drugs for the treatment of neurocysticercosis. Its mechanism of action is based on the inhibition of different biochemical pathways within the parasite which contribute to its death. Thus, the aim of this work was to analyze, for the first time, whether the nanoformulations of praziquantel would modify the energetic pathway of Taenia crassiceps cysticerci, after an intracranial inoculation in BALB/c mice. Praziquantel nanosuspensions were formulated with polyvinyl alcohol, poloxamer 188, and poloxamer 407, as stabilizers. These formulations exhibited particle size in a range of 74-285 nm and zeta potential values in a range of - 8.1/- 13.2 depending on the type of stabilizer. Physical stability study at both 4 ± 2 and 25 ± 2 °C indicated that praziquantel (PZQ) nanoparticles were stable in terms of solubility and particle size after 120-day storage. In vivo studies demonstrated that those nanosystems were able to produce significant modifications on the concentrations of oxaloacetate, citrate, pyruvate, alpha-ketoglutarate, malate, succinate, lactate, beta-hydroxybutyrate, fumarate, and propionate involved in the metabolism of Taenia crassiceps cysticerci. Therefore, these nanoformulations may be considered as a promising tool to deliver praziquantel to the brain for the effective management of neurocysticercosis.


Assuntos
Anti-Helmínticos/administração & dosagem , Metaboloma/efeitos dos fármacos , Neurocisticercose/tratamento farmacológico , Praziquantel/administração & dosagem , Animais , Anti-Helmínticos/química , Anti-Helmínticos/uso terapêutico , Cysticercus/efeitos dos fármacos , Cysticercus/fisiologia , Modelos Animais de Doenças , Estabilidade de Medicamentos , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/química , Neurocisticercose/metabolismo , Tamanho da Partícula , Praziquantel/química , Praziquantel/uso terapêutico
10.
Acta Trop ; 176: 288-292, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28865900

RESUMO

The emergence of resistance to albendazole has encouraged the search for effective alternatives for cysticercosis and other parasitosis treatment. RCB15 is a benzimidazole derivative that may be used against such diseases. The aim of this study was to determine the in vitro effect of RCB15 on the alternative energetic pathways of Taenia crassiceps cysticerci. The cysticerci were in vitro exposed to albendazole sulphoxide (ABZSO) or RCB15 at different concentrations during 24h. The cysticerci extract and the culture medium were analyzed through spectrophotometry and high performance liquid chromatography as to detect glucose, urea, creatinine and organic acids of the energetic metabolism. The drugs did not influence the protein catabolism. Fatty acids oxidation was enhanced through significantly higher acetate concentrations in the groups treated with RCB15 and ABZSO. Beta-hydroxybutyrate concentrations were decreased which indicates the use of fatty acids towards acetyl-CoA synthesis. There was a decrease in glucose uptake and pyruvate concentrations. The absence of lactate indicates the use of pyruvate in gluconeogenesis. Therefore it is possible to conclude that RCB15 enhanced the alternative energetic pathways of cysticerci in vitro exposed to different concentration, with emphasis on the fatty acids catabolism.


Assuntos
Anticestoides/farmacologia , Benzimidazóis/farmacologia , Cysticercus/efeitos dos fármacos , Albendazol/análogos & derivados , Albendazol/farmacologia , Animais , Relação Dose-Resposta a Droga , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Glicólise , Ácido Láctico/metabolismo , Oxirredução/efeitos dos fármacos , Ácido Pirúvico/metabolismo
11.
Exp Parasitol ; 172: 12-17, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27884580

RESUMO

Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic benzimidazoles due to a differentiated site of action with similar outcome.


Assuntos
Albendazol/análogos & derivados , Anticestoides/farmacologia , Benzimidazóis/farmacologia , Ciclo do Ácido Cítrico/efeitos dos fármacos , Cysticercus/efeitos dos fármacos , Cysticercus/metabolismo , Metabolismo Energético/efeitos dos fármacos , Albendazol/farmacologia , Animais , Glucose/metabolismo , Glicólise/efeitos dos fármacos
12.
Acta Trop ; 161: 100-5, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27269203

RESUMO

The aim of this work was to develop nanosuspensions of praziquantel (PZQ) and to evaluate their influence on the energetic metabolism of cysticerci inoculated in BALB/c mice. We analyzed metabolic alterations of glycolytic pathways and the tricarboxylic acid cycle in the parasite. The nanosuspensions were prepared by precipitation and polyvinyl alcohol (PVA), poloxamer 188 (P188) and poloxamer 407 (P407) were used as stabilizers. Nanosuspension prepared with PVA had a particle size of 100nm, while P188- and P407-based nanosuspensions had particle sizes of 74nm and 285nm, respectively. The zeta potential was -8.1, -8.6, and -13.2 for the formulations stabilized with PVA, P188 and P407, respectively. Treatments of T. crassiceps cysticerci-infected mice resulted in an increase in glycolysis organic acids, and enhanced the partial reversion of the tricarboxylic acid cycle, the urea cycle and the production of ketonic bodies in the parasites when compared to the groups treated with conventional PZQ. These data suggest that PZQ nanosuspensions greatly modified the energetic metabolism of cysticerci in vivo. Moreover, the remarkable metabolic alterations produced by the stabilizers indicate that further studies on nanoformulations are required to find potentially suitable nanomedicines.


Assuntos
Cisticercose/tratamento farmacológico , Cisticercose/fisiopatologia , Cysticercus/efeitos dos fármacos , Cysticercus/metabolismo , Praziquantel/uso terapêutico , Taenia/efeitos dos fármacos , Taenia/metabolismo , Animais , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas
13.
PLoS Negl Trop Dis ; 10(2): e0004418, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26849048

RESUMO

BACKGROUND: Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. METHODS AND PRINCIPAL FINDINGS: PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10-0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24-7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. CONCLUSIONS: Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available.


Assuntos
Corticosteroides/uso terapêutico , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Cysticercus/efeitos dos fármacos , Granuloma/tratamento farmacológico , Adolescente , Animais , Criança , Cysticercus/crescimento & desenvolvimento , Quimioterapia Combinada , Feminino , Granuloma/parasitologia , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
14.
Parasitology ; 143(4): 488-93, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26707797

RESUMO

Biochemical studies of benzimidazole derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, ß-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in ß-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.


Assuntos
Albendazol/análogos & derivados , Anticestoides/farmacologia , Benzimidazóis/farmacologia , Cysticercus/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Ácido 3-Hidroxibutírico/metabolismo , Acetoacetatos/metabolismo , Albendazol/farmacologia , Animais , Creatinina/análise , Meios de Cultura/química , Cysticercus/metabolismo , Fumaratos/análise , Camundongos , Propionatos/metabolismo , Proteínas/análise , Taenia/efeitos dos fármacos , Taenia/metabolismo , Ureia/análise
15.
J Helminthol ; 90(1): 113-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25120032

RESUMO

An acute outbreak of Taenia hydatigena cysticercosis, causing mortality in 5 of 21 (23.8%) female lambs, is reported. Gross post-mortem examinations and histology showed Cysticercus tenuicollis as the cause of death. Biochemical parameters in infected lambs confirmed severe hepatitis. Praziquantel, given once at 15 mg/kg body weight (bw), was administered and a dramatic improvement in the clinical condition and biochemical parameters was observed up to 30 days following treatment.


Assuntos
Anti-Helmínticos/administração & dosagem , Cisticercose/veterinária , Praziquantel/administração & dosagem , Doenças dos Ovinos/tratamento farmacológico , Taenia/efeitos dos fármacos , Doença Aguda/terapia , Animais , Cisticercose/tratamento farmacológico , Cisticercose/parasitologia , Cysticercus/efeitos dos fármacos , Cysticercus/crescimento & desenvolvimento , Cysticercus/fisiologia , Feminino , Fígado/parasitologia , Ovinos , Doenças dos Ovinos/parasitologia , Taenia/crescimento & desenvolvimento , Taenia/fisiologia
16.
Int J Parasitol ; 45(12): 749-59, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26336013

RESUMO

Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antiparasitários/administração & dosagem , Encéfalo/patologia , Cisticercose/veterinária , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/patologia , Taenia solium/efeitos dos fármacos , Albendazol/administração & dosagem , Animais , Encéfalo/diagnóstico por imagem , Cisticercose/tratamento farmacológico , Cisticercose/patologia , Cysticercus/efeitos dos fármacos , Cysticercus/imunologia , Citocinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Imageamento por Ressonância Magnética , Reação em Cadeia da Polimerase , Prednisolona/administração & dosagem , Radiografia , Suínos , Taenia solium/imunologia , Resultado do Tratamento
17.
Exp Parasitol ; 156: 79-86, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26072200

RESUMO

In the search of new alternatives for neurocysticercosis treatment, the cysticidal activity of organic extracts of Teloxys graveolens was evaluated. The in vitro activity of hexane, ethyl acetate and methanol extracts against Taenia crassiceps cysts was tested and the selectivity index relative to human fibroblasts was determined. Subsequently, the in vivo efficacy of the methanolic extract at doses of 200 and 500 mg/kg in the murine cysticercosis model was evaluated. The ultrastructural effects in vitro and in vivo of the methanolic extract were also investigated using scanning electron microscopy. Additionally, a bioassay-guided fractionation for the isolation of the cysticidal components was performed. Our in vitro findings revealed that all extracts exhibited good cysticidal activity with EC50 values from 44.8 to 67.1 µg/mL. Although the ethyl acetate and methanolic extracts displayed low cytotoxicity, the methanolic extract was the most selective. The methanolic extract also showed in vivo efficacy which was similar to that obtained with ABZ. Significant alterations were found on the germinal layer of the cysts, with a high accumulation of granules of glycogen and vacuoles. The bioguided fractionation of methanolic extract led to the isolation of three flavonoids: chrysin, pinocembrin and pinostrobin; among them, pinocembrin was the compound that displayed cysticidal activity. This is the first study which reveals that T. graveolens could be a potential source for cysticidal and non-toxic compounds.


Assuntos
Amaranthaceae/química , Cisticercose/tratamento farmacológico , Cysticercus/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Bioensaio , Cysticercus/ultraestrutura , Feminino , Fibroblastos/efeitos dos fármacos , Flavanonas/química , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Gengiva/citologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade
18.
Mol Biochem Parasitol ; 201(1): 16-25, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26024834

RESUMO

Previously, we have studied the effect of the gold-compound auranofin (AF) on both thioredoxin-glutathione reductasa (TGR) activity and viability of Taenia crassiceps cysticerci. It was demonstrated that micromolar concentrations of AF were high enough to fully inhibit TGR and kill the parasites. In this work, the dynamics of changes in the glutathione pool of T. crassiceps cysticerci following the addition of AF, was analyzed. A dose-dependent decrease in the internal glutathione concentration, concomitant with an increase in ROS production was observed. These changes were simultaneous with the formation of glutathione-protein complexes and the export of glutathione disulfide (GSSG) to the culture medium. Incubation of cysticerci in the presence of both AF and N-acetyl cysteine (NAC) prevents all the above changes, maintaining cysticerci viability. By contrast, the presence of both AF and buthionine sulfoximine (BSO) resulted in a potentiation of the effects of the gold compound, jeopardizing cysticerci viability. These results suggest the lethal effect of AF on T. crassiceps cysticerci, observed at micromolar concentrations, can be explained as a consequence of major changes in the glutathione status, which results in a significant increase in the oxidative stress of the parasites.


Assuntos
Auranofina/toxicidade , Glutationa/análise , Oxidantes/toxicidade , Estresse Oxidativo , Taenia/química , Taenia/efeitos dos fármacos , Acetilcisteína/metabolismo , Animais , Antioxidantes/metabolismo , Butionina Sulfoximina/metabolismo , Cysticercus/química , Cysticercus/efeitos dos fármacos , Cysticercus/fisiologia , Espécies Reativas de Oxigênio/análise , Análise de Sobrevida , Taenia/fisiologia
19.
Artigo em Chinês | MEDLINE | ID: mdl-26930940

RESUMO

OBJECTIVE: To explore the clinical application value of diagnostic therapy of praziquantel for suspected cerebral cysticercosis. METHODS: The suspected cerebral cysticercosis patients were collected and treated with the diagnostic therapy [praziquantel, 50 mg/(kg · d)], and followed up for 1-2 years. RESULTS: Totally 94 suspected cerebral cysticercosis patients were collected. After the diagnostic therapy, 78 (82.98%) cases were confirmed as cerebral cysticercosis, 13 (13.83%) were diagnosed as other diseases, and 3 (3.19%) were not definitely diagnosed. CONCLUSION: The diagnostic therapy for suspected cerebral cysticercosis can reduce or avoid the missed diagnosis and misdiagnosis in some atypical cerebral cysticercosis patients.


Assuntos
Cysticercus/efeitos dos fármacos , Neurocisticercose/diagnóstico , Neurocisticercose/tratamento farmacológico , Praziquantel/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Anti-Helmínticos/uso terapêutico , Criança , Pré-Escolar , Cysticercus/fisiologia , Esquema de Medicação , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurocisticercose/parasitologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
20.
Exp Parasitol ; 149: 1-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25500213

RESUMO

In the search of new alternatives for neurocysticercosis treatment, Taenia crassiceps ORF strain cysticerci have been used instead of T. solium for in vitro studies. Up to date, the main criteria for the use of the murine cysticercosis model for drug efficacy evaluation have not been assessed. The aim of the present study was to evaluate the influence of two of the main variables related to the in vivo efficacy: the length of drug treatment and the starting time of treatment after experimental infection, using albendazole (ABZ) and praziquantel (PZQ) as test drugs. Additionally, the relationship between the number of cysts and the parasite weight was assessed. For the study, female BALB/c mice were experimentally infected with T. crassiceps cysts. Three different post-infection periods (10, 20 and 30 days) and three different lengths of treatment with ABZ or PZQ (10, 20 and 30 days) were selected. The efficacy of each treatment was evaluated by comparison with a control group. Our results show that for in vivo efficacy studies, the best time to start the drug treatment is 10 days post-infection and that a minimum of 20 days of treatment is required when ABZ or PZQ are used as positive control. Moreover, in this model the parasite weight can be used as a rapid tool to measure the in vivo drug activity.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Cisticercose/tratamento farmacológico , Praziquantel/uso terapêutico , Albendazol/administração & dosagem , Animais , Anti-Helmínticos/administração & dosagem , Cisticercose/parasitologia , Cysticercus/efeitos dos fármacos , Modelos Animais de Doenças , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Praziquantel/administração & dosagem , Fatores de Tempo
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