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1.
PLoS Pathog ; 20(8): e1012479, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39178325

RESUMO

Alveolar echinococcosis (AE) is a highly lethal helminth infection. Current chemotherapeutic strategies for AE primarily involve the use of benzimidazoles (BZs) such as mebendazole (MDZ) and albendazole (ABZ), which exhibit limited efficacy. In a previous study, the vaccine of recombinant Echinococcus granulosus P29 (rEgP29) showed significant immunoprotection against E. granulosus in both mice and sheep. In the current study, we utilized hybridoma technology to generate five monoclonal antibodies (mAbs) against P29, among which 4G10F4 mAb exhibited the highest antigen-specific binding capacity. This mAb was selected for further investigation of anti-AE therapy, both in vivo and in vitro. In vitro, 4G10F4 inhibited a noteworthy inhibition of E. multilocularis protoscoleces and primary cells viability through complement-dependent cytotoxicity (CDC) mechanism. In vivo, two experiments were conducted. In the first experiment, mice were intraperitoneally injected with Em protoscoleces, and subsequently treated with 4G10F4 mAb (2.5/5/10 mg/kg) at 12 weeks postinfection once per week for 8 times via tail vein injection. Mice that were treated with 4G10F4 mAb only in dosage of 5mg/kg exhibited a significant lower mean parasite burden (0.89±0.97 g) compared to isotype mAb treated control mice (2.21±1.30 g). In the second experiment, mice were infected through hepatic portal vein and treated with 4G10F4 mAb (5mg/kg) at one week after surgery once per week for 8 times. The numbers of hepatic metacestode lesions of the 4G10F4 treatment group were significantly lower in comparison to the isotype control group. Pathological analysis revealed severe disruption of the inner structure of the metacestode in both experiments, particularly affecting the germinal and laminated layers, resulting in the transformation into infertile vesicles after treatment with 4G10F4. In addition, the safety of 4G10F4 for AE treatment was confirmed through assessment of mouse weight and evaluation of liver and kidney function. This study presents antigen-specific monoclonal antibody immunotherapy as a promising therapeutic approach against E. multilocularis induced AE.


Assuntos
Anticorpos Monoclonais , Equinococose , Animais , Equinococose/tratamento farmacológico , Equinococose/imunologia , Anticorpos Monoclonais/farmacologia , Camundongos , Proteínas de Helminto/imunologia , Proteínas de Helminto/farmacologia , Camundongos Endogâmicos BALB C , Echinococcus multilocularis/imunologia , Echinococcus multilocularis/efeitos dos fármacos , Feminino , Echinococcus granulosus/imunologia , Ovinos , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia
2.
Antimicrob Agents Chemother ; 68(3): e0120223, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38349157

RESUMO

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. There is an urgent need to develop new drug targets and drug molecules to treat CE. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a serine/threonine protein kinase consisting of α, ß, and γ subunits, plays a key role in the regulation of energy metabolism. However, the role of AMPK in regulating glucose metabolism in E. granulosus s.l. and its effects on parasite viability is unknown. In this study, we found that targeted knockdown of EgAMPKα or a small-molecule AMPK inhibitor inhibited the viability of E. granulosus sensu stricto (s.s.) and disrupted the ultrastructure. The results of in vivo experiments showed that the AMPK inhibitor had a significant therapeutic effect on E. granulosus s.s.-infected mice and resulted in the loss of cellular structures of the germinal layer. In addition, the inhibition of the EgAMPK/EgGLUT1 pathway limited glucose uptake and glucose metabolism functions in E. granulosus s.s.. Overall, our results suggest that EgAMPK can be a potential drug target for CE and that inhibition of EgAMPK activation is an effective strategy for the treatment of disease.


Assuntos
Equinococose , Echinococcus granulosus , Parasitos , Animais , Camundongos , Proteínas Quinases Ativadas por AMP , Equinococose/tratamento farmacológico , Equinococose/parasitologia , Zoonoses/parasitologia , Glucose , Genótipo
3.
Antimicrob Agents Chemother ; 68(10): e0094124, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39264188

RESUMO

Metformin, a safe biguanide derivative with antiproliferative properties, has shown antiparasitic efficacy against the Echinococcus larval stage. Hence, we assessed the efficacy of a dose of 250 mg kg-1 day-1 in experimental models of advanced CE, at 6 and 12 months post-infection with oral and intraperitoneal administration, respectively. At this high dose, metformin reached intracystic concentrations between 0.7 and 1.7 mM and triggered Eg-TOR inhibition through AMPK activation by AMP-independent and -dependent mechanisms, which are dependent on drug dose. Cystic metformin uptake was controlled by increased expression of organic cation transporters in the presence of the drug. In both experimental models, metformin reduced the weight of parasite cysts, altered the ultrastructural integrity of their germinal layers, and reduced the intracystic availability of glucose, limiting the cellular carbon and energy charge and the proliferative capacity of metacestodes. This glucose depletion in the parasite was associated with a slight increase in cystic uptake of 2-deoxiglucose and the transcriptional induction of GLUT genes in metacestodes. In this context, drastic glycogen consumption led to increased lactate production and altered intermediary metabolism in treated metacestodes. Specifically, the fraction of reducing soluble sugars decreased twofold, and the levels of non-reducing soluble sugars, such as sucrose and trehalose, were modified in both cystic fluid and germinal cells. Taken together, our findings highlight the relevance of metformin as a promising candidate for CE treatment and warrant further research to improve the therapeutic conditions of this chronic zoonosis in humans.


Assuntos
Equinococose , Metformina , Metformina/farmacologia , Animais , Equinococose/tratamento farmacológico , Equinococose/parasitologia , Camundongos , Carbono , Glucose/metabolismo , Echinococcus granulosus/efeitos dos fármacos , Echinococcus granulosus/metabolismo , Feminino , Larva/efeitos dos fármacos
4.
BMC Infect Dis ; 24(1): 737, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39060987

RESUMO

BACKGROUND: Cystic echinococcosis (CE) is a chronic disease considered a neglected one. Cystic echinococcosis is endemic in Uruguay and the region. Surgery, using various technical approaches, has the potential to safely remove the cyst(s) and lead to a complete cure in a high number of patients with simple forms of CE. However, surgery may be impractical in patients with multiple cysts in several organs, high surgical risk, or in patients with previous multiple surgeries. In these cases, the pharmacological treatment with the benzimidazolic drug Albendazole (ABZ) alone or combined with Praziquantel (PZQ), has been promising as the best choice to achieve improvement or cure. METHODS: In this study, we analyze the results obtained on the anti-parasitic treatment of 43 patients diagnosed with CE between the years 2003 and 2020. Patients were treated before and/or after surgery with ABZ or the combination ABZ/PZQ. The standardize protocol of the anti-parasitic drug treatment before surgery was 7 days, 15 days or 1 month depending on the urgency and availability of the surgical procedure. All cases that involved confirmed locations on lungs underwent immediate surgery with minimal pre-treatment when possible. After surgery, the standardize protocol of anti-parasitic drug treatment consisted of six cycles of 30 days each and resting intervals of 15 days in between. ABZ was used in all cases, administered orally, twice daily, at a total dosage of 15 mg/kg/day, with food high in fat content for improved absorption. The follow up was carried out according to WHO-IWGE guidelines for 5 years. RESULTS: Of the 43 patients fourteen were ≤ 15 years of age and had a differentiated pre-surgical treatment. From the ≥ 16 years of age, 36 completed the treatments and the 5 years follow up. Four patients changed geographical locations, without a forwarding contact, after the post-surgery treatment. No patient died during the study. Of the 36 patients that completed the study, 32 were treated only with ABZ; 93.75% achieved treatment success as determined by improvement or cure, and 6.25% treatment failure determined by no change or worsening. The last four patients received the ABZ/PZQ combination therapy and achieved 100% treatment success. CONCLUSION: The pharmacological treatment resulted in a good option not only as palliative but also as potentially curative. The main relevance of its use was in cases with previous multiple surgeries or surgeries with potential life-threatening complications due to the number and location of cysts and concurrent comorbidities. A follow-up of at least 5 years would be recommended to assure remission and control of the transmission. More randomized trials are needed to provide clear clinical evidence of different pharmacological treatments for CE.


Assuntos
Albendazol , Anti-Helmínticos , Equinococose , Praziquantel , Humanos , Albendazol/uso terapêutico , Albendazol/administração & dosagem , Praziquantel/uso terapêutico , Praziquantel/administração & dosagem , Equinococose/tratamento farmacológico , Equinococose/cirurgia , Masculino , Feminino , Uruguai , Adulto , Pessoa de Meia-Idade , Seguimentos , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/administração & dosagem , Adulto Jovem , Resultado do Tratamento , Adolescente , Idoso , Quimioterapia Combinada
5.
BMC Infect Dis ; 24(1): 980, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285332

RESUMO

BACKGROUND: Cystic echinococcosis (CE) is prevalent in livestock farming regions around the world. However, it remains relatively rare compared to other infectious diseases. CE typically affects the liver, lungs, brain, and kidneys. Spinal and pleural wall involvement is exceedingly rare. We report a unique case of intradural and pleural wall CE in a young male, successfully treated with surgery and postoperative medication. CASE PRESENTATION: A 19-year-old Tibetan male from the Qinghai-Tibet Plateau was diagnosed with intradural and pleural wall CE through imaging, serology, and surgical pathology. According to the Dew/Braithwaite & Lees (BL) classification, his condition was an exceptionally rare form of spinal echinococcosis, compounded by an even rarer pleural wall involvement. Prompt surgical intervention and postoperative medication resulted in significant improvement in spinal cord compression symptoms. CONCLUSIONS: This case highlights the diagnostic and therapeutic challenges of rare CE locations. MRI proved superior to CT in diagnosing bony cystic echinococcosis. Early surgical intervention combined with medication facilitates spinal cord function recovery, providing valuable insights for managing similar cases.


Assuntos
Equinococose , Humanos , Masculino , Equinococose/cirurgia , Equinococose/diagnóstico por imagem , Equinococose/diagnóstico , Equinococose/tratamento farmacológico , Adulto Jovem , Imageamento por Ressonância Magnética , Pleura/patologia , Pleura/diagnóstico por imagem , Pleura/cirurgia , Tomografia Computadorizada por Raios X , Tibet , Compressão da Medula Espinal/cirurgia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/parasitologia
6.
BMC Infect Dis ; 24(1): 778, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097707

RESUMO

BACKGROUND: Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. METHODS: Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. RESULTS: Drug NPs are characterized by uniform particle size, stability, high drug loading, and - 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. CONCLUSION: ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.


Assuntos
Albendazol , Atovaquona , Equinococose , Echinococcus granulosus , Metabolismo Energético , Nanopartículas , Animais , Albendazol/farmacologia , Albendazol/química , Albendazol/administração & dosagem , Camundongos , Metabolismo Energético/efeitos dos fármacos , Echinococcus granulosus/efeitos dos fármacos , Nanopartículas/química , Equinococose/tratamento farmacológico , Equinococose/parasitologia , Atovaquona/farmacologia , Anti-Helmínticos/farmacologia , Anti-Helmínticos/administração & dosagem , Humanos , Tamanho da Partícula , Modelos Animais de Doenças , Feminino
7.
Exp Parasitol ; 265: 108811, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39111383

RESUMO

Alveolar echinococcosis (AE) is a severe disease caused by the infection with the larval stage of Echinococcus multilocularis, the metacestode. As there is no actual curative drug therapy, recommendations to manage AE patients are based on radical surgery and prophylactic administration of albendazole or mebendazole during 2 years to prevent relapses. There is an urgent need for new therapeutic strategies for the management of AE, as the drugs in use are only parasitostatic, and can induce toxicity. This study aimed at developing a drug delivery system for mefloquine, an antiparasitic compound which is highly active against E. multilocularis in vitro and in experimentally infected mice. We formulated mefloquine-loaded PLGA-PEG-COOH (poly-(lactic-co-glycolic acid)) nanoparticles that exhibit stable physical properties and mefloquine content. These nanoparticles crossed the outer acellular laminated layer of metacestodes in vitro and delivered their content to the inner germinal layer within less than 5 min. The in vitro anti-echinococcal activity of mefloquine was not altered during the formulation process. However, toxicity against hepatocytes was not reduced when compared to free mefloquine. Altogether, this study shows that mefloquine-loaded PLGA-PEG-COOH nanoparticles are promising candidates for drug delivery during AE treatment. However, strategies for direct parasite-specific targeting of these particles should be developed.


Assuntos
Echinococcus multilocularis , Mefloquina , Nanopartículas , Polietilenoglicóis , Animais , Mefloquina/farmacologia , Mefloquina/administração & dosagem , Echinococcus multilocularis/efeitos dos fármacos , Camundongos , Polietilenoglicóis/química , Nanopartículas/química , Equinococose/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Feminino , Camundongos Endogâmicos BALB C , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Anti-Helmínticos/farmacologia , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/química , Humanos , Poliglactina 910
8.
Z Gastroenterol ; 62(4): 500-507, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37729942

RESUMO

Cystic echinococcosis (CE) is a worldwide helminthic zoonosis causing serious disease in humans. The WHO Informal Working Group on Echinococcosis recommends a stage-specific treatment approach of hepatic CE that facilitates the decision on what therapy option is most appropriate. Percutaneous aspiration, instillation of a scolicide, e.g., ethanol or hypertonic saline, and subsequent re-aspiration (PAIR) have been advocated for treating medium-size unilocular WHO-stage CE1 cysts. PAIR can pose a risk of toxic cholangitis because of spillage of ethanol in the case of a cysto-biliary fistula or of life-threatening hypernatriaemia when hypertonic saline is used. The purpose of our study is to develop an alternative, safe, minimally invasive method to treat CE1 cysts, avoiding the use of toxic topic scolicides.We opt for percutaneous drainage (PD) in four patients: the intrahepatic drainage catheter is placed under CT-fluoroscopy, intracystic fluid is aspirated, and the viability of intracystic echinococcal protoscolices is assessed microscopically. Oral praziquantel (PZQ) is added to albendazole (ABZ) instead of using topical scolicidals.Protoscolices degenerate within 5 to 10 days after PZQ co-medication at a cumulative dosage of 250 to 335 mg/kg, and the cysts collapse. The cysts degenerate, and no sign of spillage nor relapse is observed in the follow-up time of up to 24 months post-intervention.In conclusion, PD combined with oral PZQ under ABZ coverage is preferable to PAIR in patients with unilocular echinococcal cysts.


Assuntos
Cistos , Equinococose Hepática , Equinococose , Humanos , Albendazol/uso terapêutico , Praziquantel/uso terapêutico , Recidiva Local de Neoplasia , Equinococose/tratamento farmacológico , Drenagem , Equinococose Hepática/diagnóstico , Equinococose Hepática/tratamento farmacológico , Cistos/tratamento farmacológico , Etanol , Fígado
9.
J Helminthol ; 98: e40, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738533

RESUMO

In the past decade, interest has significantly increased regarding the medicinal and nutritional benefits of pomegranate (Punica granatum) peel. This study examined the effects of using pomegranate peel extract (PGE) alone and in combination with albendazole (ABZ) on ultrastructural and immunological changes in cystic echinococcosis in laboratory-infected mice. Results revealed that the smallest hydatid cyst size and weight (0.48 ± 0.47mm, 0.17 ± 0.18 gm) with the highest drug efficacy (56.2%) was detected in the PGE + ABZ group, which also exhibited marked histopathological improvement. Ultrastructural changes recorded by transmission electron microscopy including fragmentation of the nucleus, glycogen depletion, and multiple lysosomes in vacuolated cytoplasm were more often observed in PGE + ABZ group. IFN-γ levels were significantly increased in the group treated with ABZ, with a notable reduction following PGE treatment, whether administered alone or in combination with ABZ. Thus, PGE enhanced the therapeutic efficiency of ABZ, with improvement in histopathological and ultrastructural changes.


Assuntos
Albendazol , Equinococose , Extratos Vegetais , Punica granatum , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Punica granatum/química , Camundongos , Equinococose/tratamento farmacológico , Equinococose/parasitologia , Albendazol/farmacologia , Albendazol/administração & dosagem , Anti-Helmínticos/farmacologia , Anti-Helmínticos/administração & dosagem , Modelos Animais de Doenças , Microscopia Eletrônica de Transmissão , Interferon gama/sangue , Feminino , Masculino
10.
J Pak Med Assoc ; 74(10 (Supple-8)): S390-S393, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39434347

RESUMO

OBJECTIVE: To determine the anti-protocolises effect of aqueous and alcoholic zingiber extract. METHODS: The present experimental study was conducted from 01, July 2021 to 15. December, 2021 at the College of Education for Pure Sciences, Iraq, and comprised 25mg/mL, 50mg/mL, 100mg/mL and 200mg/mL concentrations of both aqueous and alcoholic extracts of zingiber officinale that were prepared and used in vitro on hydatid cyst protocolises with 10min, 20min, 30min, 40min, 50min and 60min exposure times. The data was analysed using statistical package for the social sciences (SPSS) version 10 by using ANOVA and t- test to determine the differences between groups. RESULTS: The concentration of 200mg/ml was more efficient against the protocolises for aqueous extract, while the alcoholic extract was effective at both 100mg/ml and 200mg/ml concentrations. There was a positive relationship of the degree of killing with both exposure time and concentration. CONCLUSIONS: Zingiber officinale could be a potential bioactive natural product and its active constituents could be isolated and used as anti-protoscolex without any side effects.


Assuntos
Equinococose , Extratos Vegetais , Zingiber officinale , Zingiber officinale/química , Extratos Vegetais/farmacologia , Equinococose/tratamento farmacológico , Animais , Humanos , Fatores de Tempo , Echinococcus granulosus/efeitos dos fármacos , Etanol
11.
Tidsskr Nor Laegeforen ; 144(10)2024 Sep 10.
Artigo em Inglês, Nor | MEDLINE | ID: mdl-39254012

RESUMO

Alveolar echinococcosis is a much-feared parasitic zoonosis caused by the larval stage of Echinococcus multilocularis. Mainland Norway is free from infection, but alveolar echinococcosis is, on rare occasions, imported from endemic regions. Those infected develop slow-growing, multicystic tumours that are clinically and radiologically reminiscent of malignant disease. The disease mainly attacks the liver. Treatment often consists of extensive surgical resection in combination with prolonged use of albendazole. In this clinical review article we summarise the life cycle, clinical findings, diagnosis, treatment and epidemiology of alveolar echinococcosis, and provide examples of the disease course with two patient case reports.


Assuntos
Albendazol , Equinococose Hepática , Equinococose , Echinococcus multilocularis , Humanos , Echinococcus multilocularis/isolamento & purificação , Equinococose Hepática/diagnóstico por imagem , Albendazol/uso terapêutico , Animais , Equinococose/diagnóstico , Equinococose/tratamento farmacológico , Equinococose/diagnóstico por imagem , Noruega , Masculino , Tomografia Computadorizada por Raios X , Adulto , Feminino , Pessoa de Meia-Idade , Anti-Helmínticos/uso terapêutico , Estágios do Ciclo de Vida
12.
Infect Immun ; 91(7): e0047022, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37310215

RESUMO

Cystic echinococcosis (CE) is a disease caused by the infection of Echinococcus granulosus. We sought to investigate the effects of dihydroartemisinin (DHA) against CE under in vitro and in vivo conditions. Protoscoleces (PSCs) from E. granulosus were divided into control, DMSO, ABZ, DHA-L, DHA-M, and DHA-H groups. PSC viability after DHA treatment was determined based on the eosin dye exclusion test, alkaline phosphatase content detection, and ultrastructure observation. DNA oxidative damage inducer hydrogen peroxide (H2O2), reactive oxygen species (ROS) scavenger mannitol, and the DNA damage repair inhibitor velparib were used to explore the anti-CE mechanism of DHA. The anti-CE effects and CE-induced liver injury and oxidative stress of DHA at different doses (50, 100, and 200 mg/kg) were assessed in CE mice. DHA showed antiparasitic effects on CE in both in vivo and in vitro experiments. DHA could elevate the ROS level and induce oxidative DNA damage in PSCs, thereby destroying hydatid cysts. DHA could inhibit the growth of cysts in a dose-dependent manner and reduce the content of biochemical parameters associated with liver injury in CE mice. It also significantly reversed oxidative stress in CE mice, which was characterized as the decreased tumor necrosis factor alpha and H2O2 content, as well as the increase of the ratio of glutathione/oxidized glutathione and total superoxide dismutase content. DHA showed antiparasitic effects. DNA damages induced by oxidative stress played important roles in this process.


Assuntos
Equinococose , Echinococcus granulosus , Animais , Camundongos , Peróxido de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Equinococose/tratamento farmacológico , Equinococose/parasitologia , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico
13.
Antimicrob Agents Chemother ; 67(6): e0009823, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37140388

RESUMO

Spinal cystic echinococcosis, a severely neglected, rare disease, is characterized by high morbidity, disability, and mortality in prevalent regions. Due to the high-risk nature of surgical treatment and the ineffectiveness of conventional drugs, there is an unmet need for novel safe and effective drugs for the treatment of this disease. In this study, we examined the therapeutic effects of α-mangostin for spinal cystic echinococcosis, and explored its potential pharmacological mechanism. The repurposed drug exhibited a potent in vitro protoscolicidal effect and significantly inhibited the evolution of larval encystation. Moreover, it demonstrated a remarkable anti-spinal cystic echinococcosis effect in gerbil models. Mechanistically, we found that α-mangostin intervention led to intracellular depolarization of mitochondrial membrane potential and reactive oxygen species generation. In addition, we observed elevated expression of autophagic proteins, aggregation of autophagic lysosomes, activated autophagic flux, and disrupted larval microstructure in protoscoleces. Further metabolite profiling showed that glutamine was imperative for autophagic activation and anti-echinococcal effects mediated by α-mangostin. These results suggest that α-mangostin is a potentially valuable therapeutic option against spinal cystic echinococcosis through its effect on glutamine metabolism.


Assuntos
Equinococose , Xantonas , Humanos , Glutamina/uso terapêutico , Equinococose/tratamento farmacológico , Xantonas/farmacologia , Proteínas
14.
Curr Opin Infect Dis ; 36(5): 303-307, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37593991

RESUMO

PURPOSE OF REVIEW: Cystic echinococcosis is a neglected zoonosis for which humans are dead end hosts. It is not only widely distributed in sheep rearing areas of low-income and middle-income countries but also has a significant presence in wealthy countries, for example, in Europe. It results in considerable morbidity, and its current management is far from optimal. Medical management is with a benzimidazole, with the addition of praziquantel under some circumstances. RECENT FINDINGS: Interest in mebendazole as an anticancer drug has stimulated research into new drug formulations to improve bioavailability and possibly reduce inter-individual variability in in-vivo drug levels, which may help its activity against cystic echinococcosis. Further evidence to support administration of albendazole with a fatty meal has been provided. GlaxoSmithKilne (GSK) has agreed to extend its albendazole donation programme to include echinococcosis. The search for new drugs has focussed on natural products, such as essential oils and on repurposing of existing drugs licensed for human use against other conditions. SUMMARY: The medical treatment of cystic echinococcosis remains sorely neglected, with no new drugs for almost 40 years. We need a better understanding of how to use the drugs we do have, whilst seeking new ones. Drug repurposing may be the best pathway.


Assuntos
Albendazol , Equinococose , Humanos , Animais , Ovinos , Albendazol/uso terapêutico , Equinococose/tratamento farmacológico , Zoonoses , Europa (Continente) , Mebendazol
15.
Exp Parasitol ; 246: 108456, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36610471

RESUMO

Echinococcosis is a zoonotic disease caused by larval stages of the Echinococcus genus (metastasis). In this study, salicylate-coated Zinc oxide nanoparticles (SA-ZnO-NPs) were fabricated and characterized by SEM, FTIR and XRD analytical techniques. After that, different doses of SA-ZnO-NPs, SA and ZnO-NPs were taken to assess scolicidal potency. Scanning electron microscopy (SEM) micrographs were also used to evaluate the morphological deformities of treated protoscoleces. Furthermore, Caspase-3&7 inductions were examined in protoscoleces cysts treated with all formulations. Based on SEM and DLS analyses, the size of SA-ZnO-NPs was between 30 and 40 nm, with a spherical shape. The FTIR spectrum verified the presence of SA functional groups on the ZnO coating. At 20 min, SA-ZnO-NPs at 2000 µg/ml exhibited the greatest activity on protoscolices with 100% mortality, followed by ZnO-NPs at 1500 µg/ml at 10 min and SA alone at 2000 µg/ml at 30 min. The activation of Caspase-3&7 apoptotic enzyme was determined for 2000 µg/ml of SA-ZnO-NPs, ZnO-NPs and SA to be 16.4, 31.4, and 35.7%, respectively. The SEM image revealed apoptogenic alterations and the induction of tegument surface wrinkles, as well as abnormalities in rostellum protoscolices. According to the current study, SA-ZnO-NPs have a high mortality rate against hydatid cyst protoscolices. As a result, further studies on the qualitative assessment of these nanoformulations in vivo and preclinical animal trials seem to be required. Furthermore, the adoption of nano-drugs potentially offers alternative therapeutic approaches to combat hydatid cysts.


Assuntos
Equinococose , Echinococcus granulosus , Echinococcus , Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Animais , Caspase 3 , Zinco , Óxido de Zinco/farmacologia , Nanopartículas Metálicas/uso terapêutico , Salicilatos/farmacologia , Salicilatos/uso terapêutico , Equinococose/tratamento farmacológico
16.
Exp Parasitol ; 244: 108430, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36435216

RESUMO

Cystic echinococcosis is a worldwide zoonotic disease caused by Echinococcus granulosus sensu lato (s.l.), which produces serious health and economic problems. For human treatment, chemotherapy with albendazole (ABZ), a derivative of benzimidazoles, is widely used. However, due to its low efficacy and the lack of alternatives to ABZ, novel compounds are urgently needed. Aromatic plants exhibit powerful pharmacological activities, are accessible, have a relatively low cost, and have generally mild toxicities, making them an effective choice to traditional therapies. In particular, the pharmaceutical properties of aromatic plants are partially attributed to essential oils (EOs). The aim of the present study was to assess the in vitro and in vivo effects of the combined carvacrol and thymol against E. granulosus sensu stricto (s.s.). The greatest protoscolicidal effect was observed with the 9:1 and 5:5 (carvacrol:thymol) combinations which caused a marked decrease in viability after 6 days post-incubation, agreeing with the ultrastructural changes obtained. Permeation of the cysts and loss of turgidity was observed with the incubation with the different combinations of carvacrol:thymol. In the clinical efficacy study, the combination of thymol (40 mg/kg) and carvacrol (40 mg/kg) caused a tendency to diminish the weight of the cysts in comparison with the control group. On the other hand, the treatment of infected mice with ABZ, thymol or carvacrol, caused a significant decrease in the weight of the cysts. In conclusion, we here demonstrated the efficacy of different concentrations of combined carvacrol and thymol against E. granulosus s.s. protoscoleces and murine cysts, where short periods of treatment were sufficient to achieve a pharmacological effect. Moreover, we observed a reduction in the weight of the cysts in experimentally infected mice after treatment with carvacrol and thymol. The strategy used has an advantage over synthetic drugs because natural compounds are generally safe and non-toxic. Moreover, the combination of two drugs with different modes of action would cause a reduction in the doses and treatment times. Based on the promising results obtained in vitro, in the future, different doses of the combined drugs will be assayed in vivo to determine the potential of these compounds for the treatment of cystic echinococcosis.


Assuntos
Cistos , Equinococose , Echinococcus granulosus , Camundongos , Animais , Humanos , Albendazol/farmacologia , Timol/farmacologia , Equinococose/tratamento farmacológico , Cistos/tratamento farmacológico
17.
Exp Parasitol ; 251: 108553, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37230322

RESUMO

BACKGROUND: Cystic echinococcosis (CE) is one of the most widespread and important global helminth zoonoses. Treatment relies mainly on surgery and, or percutaneous interventions. However, spillage of live protoscoleces (PSCs) leading to recurrence is a problem during surgery. So, the application of protoscolicidal agents before surgery is required. This study aimed to investigate the activity and safety of hydroalcoholic extracts of E. microtheca against PSCs of Echinococcus granulosus sensu stricto (s.s.) both in vitro and also ex vivo, which is a simulation to Puncture, Aspiration, Injection, and Re-aspiration (PAIR) method. METHODS: Considering the effects of heat on the protoscolicidal effecacy of Eucalyptus leaves, hydroalcoholic extraction was performed by both soxhlet extraction at 80 °C and percolation at room temperature. The protoscolicidal action of hydroalcoholic extracts was assessed by in vitro and ex vivo assessments. Infected sheep livers were collected from the slaughterhouse. Then, the genotype of hydatid cysts (HCs) was confirmed by sequencing and, isolates were limited to E. granulosus s.s. In the next step, ultrastructural changes of Eucalyptus-exposed PSCs were studied by scanning electron microscopy (SEM). Finally, a cytotoxicity test was conducted by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the safety of E. microtheca. RESULTS: The prepared extracts by soxhlet extraction and percolation were, successfully exerted strong protoscolicidal effects in both in vitro and ex vivo tests. The results of in vitro assessment indicated that hydroalcoholic extract of E. microtheca prepared by percolation at room temperature (EMP) and hydroalcoholic extract of E. microtheca prepared by soxhlet extraction at 80 °C (EMS) killed all PSCs (100%) at concentrations of 10 and 12.5 mg/mL, respectively. Also, EMP showed 99% protoscolicidal action after 20 min in an ex vivo setting compared to EMS. SEM micrographs confirmed potent protoscolicidal and destructive effects of E. microtheca against PSCs. The cytotoxicity of EMP was tested on the HeLa cell line using MTT assay. The value of 50% cytotoxic concentration (CC50) was calculated at 46.5 µg/mL after 24h. CONCLUSION: Both hydroalcoholic extracts showed potent protoscolicidal activity and, especially EMP produced remarkable protoscolicidal effects compared to the control group.


Assuntos
Equinococose , Echinococcus granulosus , Eucalyptus , Humanos , Animais , Ovinos , Microscopia Eletrônica de Varredura , Células HeLa , Equinococose/tratamento farmacológico , Equinococose/veterinária , Extratos Vegetais/farmacologia
18.
Exp Parasitol ; 246: 108463, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36649915

RESUMO

Herbal preparations have good medicinal value for potential use as therapeutic agents in cystic echinococcosis. The efficiency of crocin in the case of cystic echinococcosis was investigated, and compared with that of albendazole, one of the few licensed anti-echinococcosis drugs that served as a positive control. Five months after infecting BALB/C mice with E. granulosus sensu lato the experimental group was divided into 7 subgroups containing 10 animals each: 1- Crocin 80 (80 mg/kg), 2- Crocin 40 (40 mg/kg), 3- Crocin 10 (10 mg/kg), 4- Albendazole (200 mg/kg), 5- Crocin 10 (10 mg/kg) +Albendazole (100 mg/kg), 6- Crocin 20 (20 mg/kg) +Albendazole (50 mg/kg), 7- the control (infected and untreated). After two weeks of daily treatment, significant reductions of cysts' weights, sizes, and total numbers concerning the control group were achieved by treatment with crocin 80, crocin 40, crocin 10, crocin 10 + ABZ100, crocin 20+ ABZ50 and ABZ200 (p < 0.05). Moreover, there was no difference concentrations of crocin and those treated with albendazole,. The concentration of bilirubin was higher in the control group than all treated groups with crocin, significantly. However, the ALT activity showeda significant decrease in the crocin 10 group, compared to the crocin 80, crocin 40, crocin 10 + ABZ100, crocin 20 + ABZ50, control groups (p < 0.05). Based on our results, the administration of crocin used at 10 mg/kg concentrations seems a hopeful applicant for the treatment of cystic echinococcosis.


Assuntos
Equinococose , Echinococcus granulosus , Echinococcus , Animais , Camundongos , Albendazol/farmacologia , Albendazol/uso terapêutico , Camundongos Endogâmicos BALB C , Equinococose/tratamento farmacológico , Equinococose/veterinária
19.
BMC Pediatr ; 23(1): 170, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-37046243

RESUMO

BACKGROUND: Necrotizing pneumonia is rare in children and is one of the most serious complications of a lung infection caused by antibiotic failure. We present a 12-year-old leukopenic child with a long-lasting lung infection, presenting as having a lung hydatid cyst, but diagnosing with necrotizing pneumonia in the right bilobed lung. Failure to medical treatment and ongoing leukopenia justified surgical intervention with positive results. CASE PRESENTATION: The patient was referred to our teaching hospital's pediatric surgery department. He had previously been diagnosed with intestinal tuberculosis (TB) and received anti-TB treatment. On referral to our hospital, the patient was suffering from restlessness, frequent coughing, fever, vomiting, and diarrhea. Following the completion of the clinical work-up, a blood test revealed leukopenia (white blood cell count of 2100/microliter), a normal platelet count, and a lesion in the right lung. Computerized tomography scanning (CT-Scan) image reported a lung hydatid cyst. In the pediatrics ward, a broad-spectrum antibiotics regimen with triple-antibiotic therapy (linezolid, vancomycin, and metronidazole) was instituted and continued for a week with no response, but worsening of the condition. In the pediatric surgery ward, our decision for surgical intervention was due to the failure of medical treatment because of a pulmonary lesion. Our team performed right lung upper lobe anterior segment wedge resection due to necrotizing pneumonia and followed the patient 45 days post-operation with a reasonable result. CONCLUSION: Living in remote rural areas with low resources and inaccessibility to proper and specialized diagnostic and treatment centers will all contribute to an improper diagnosis and treatment of lung infection. In total, all of these will increase the morbidity and mortality due to lung necrosis in the pediatric population, regardless of their age. In low-resource facilities, high-risk patients can benefit from surgical intervention to control the ongoing infection process.


Assuntos
Equinococose , Leucopenia , Pneumonia Necrosante , Pneumonia , Masculino , Criança , Humanos , Pneumonia Necrosante/diagnóstico , Pneumonia Necrosante/cirurgia , Pneumonia Necrosante/tratamento farmacológico , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Pulmão/patologia , Pneumonia/diagnóstico , Pneumonia/etiologia , Pneumonia/tratamento farmacológico , Antibacterianos/uso terapêutico , Equinococose/tratamento farmacológico , Equinococose/patologia
20.
Parasitol Res ; 123(1): 40, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38095718

RESUMO

Echinococcal disease (hydatid disease (HD) is an endemic parasitosis caused by Echinococcus granulosus in the larval stage, and it is typically due to the production of unilocular cystic lesions, usually involving the liver for the majority of patients and the lungs in 25%, but also any other organs can be potentially involved in developing echinococcal disease. We report a case of extrahepatic, retroperitoneal echinococcal disease, caused by Echinococcus granulosus. The patient underwent a surgical removal of the abdominal mass, revealed by abdominal ultrasound and computerized tomography scanning, and in the founded clinical and radiological suspicion of echinococcal disease, multiple bioptical samples were sent for microbiological analysis and albendazole therapy was started; Echinococcus granulosus protoscolices were found on the bioptical sample, and the diagnosis was successfully confirmed. According to the current parasitology literature on echinococcal disease, extrahepatic localization, although rare, can be found, and it should be considered in the differential diagnosis of an abdominal mass when epidemiological risk factors and anamnestic data are present, regardless of the usual site of the disease.


Assuntos
Equinococose , Echinococcus granulosus , Echinococcus , Animais , Humanos , Equinococose/diagnóstico , Equinococose/tratamento farmacológico , Equinococose/cirurgia , Albendazol/uso terapêutico , Fatores de Risco
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