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1.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38892424

RESUMO

Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.


Assuntos
Antiprotozoários , Giardia lamblia , Giardíase , Simulação de Acoplamento Molecular , United States Food and Drug Administration , Giardíase/tratamento farmacológico , Giardia lamblia/efeitos dos fármacos , Antiprotozoários/farmacologia , Antiprotozoários/química , Estados Unidos , Humanos , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/antagonistas & inibidores , Simulação de Dinâmica Molecular
2.
J Infect Dev Ctries ; 18(5): 839-842, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38865402

RESUMO

INTRODUCTION: Iron deficiency anaemia (IDA), the most prevalent type of anaemia, is recognised as a significant global health concern that affects individuals of all ages. CASE PRESENTATION: Herein, we present a case involving an adult male coinfected with Helicobacter pylori and Giardia duodenalis, which precipitated severe IDA. RESULTS: A 24-year-old male presented with symptoms including fatigue, dizziness, headache, abdominal pain, and diarrhoea persisting for four weeks. Thorough blood tests, including complete blood counts, blood film, and iron studies, conclusively established the presence of severe IDA. Furthermore, his faecal sample was collected and subjected to analysis of common bacterial and parasitic gastrointestinal infections. Examination of upper and lower gastrointestinal pathogens indicated that the severe IDA was most likely a result of coinfection with H. pylori and G. duodenalis. The patient received treatment involving antibiotics and iron replacement therapy, which resulted in an improvement in both his symptoms and laboratory results. CONCLUSIONS: The present report provides crucial insights into the synergistic effect of concurrent H. pylori and G. duodenalis infections, highlighting their potential to induce severe IDA in infected patients.


Assuntos
Anemia Ferropriva , Coinfecção , Giardia lamblia , Giardíase , Infecções por Helicobacter , Helicobacter pylori , Humanos , Masculino , Anemia Ferropriva/complicações , Giardíase/complicações , Giardíase/tratamento farmacológico , Adulto Jovem , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Coinfecção/microbiologia , Coinfecção/parasitologia , Giardia lamblia/isolamento & purificação , Antibacterianos/uso terapêutico , Fezes/parasitologia , Fezes/microbiologia
3.
Acta Trop ; 255: 107201, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38604329

RESUMO

Reportedly, synthetic drugs such as metronidazole, furazolidone, tinidazole, and quinacrine are used for the treatment of giardiasis but are associated with adverse effects. In this study, we aimed to investigate the in vitro and in vivo effects of eucalyptol (ECT, 1,8 cineole) alone and in combination with metronidazole (MNZ) on Giardia lamblia. The effects of ECT on cell viability, plasma membrane permeability, and gene expression levels of adenylate cyclase (AK) and extracellular signal kinases 1 and 2 (ERK1 and ERK2) in trophozoites of G. lamblia were assessed. In vivo, the effects of ECT alone and in combination with MNZ were assessed on mice infected with G. lamblia. In addition, the gene expression of inflammatory genes (e.g., TNF-α, IL-1ß, and IL-10) and antioxidant genes (catalase (CAT), superoxide dismutase 1 (SOD1), glutathione peroxidase 2 (GPX2)) was determined by real-time PCR. The IC50 values of ECT, MNZ, and ECT+MNZ on trophozoites were 30.2 µg/mL, 21.6 µg/mL, and 8.5 µg/mL, respectively. The estimated Fractional inhibitory concentration index (FICI) values for ECT and MNZ were 0.28 and 0.39, respectively. The application of ECT on G. lamblia trophozoites resulted in a dose-dependent increase in plasma membrane permeability, particularly at concentrations of ½ IC50 and IC50 (P < 0.05). The treatment of infected mice with various doses of ECT, mainly in combination with MNZ for 7 days, resulted in a significant decrease (P < 0.001) in the average number and viability of cysts. ECT, especially when combined with MNZ, caused a significant (P < 0.001) reduction in the expression of TNF-α and IL-6 genes, and an increase (P < 0.05) in the expression of IL-10 genes. ECT alone and mainly in combination with MNZ leads to a significant (P < 0.001) increase in the gene expression of CAT, SOD, and GPX genes. These findings demonstrate that the use of ECT in these doses, even for 14 days, does not have any toxic effects on the function of vital liver and kidney tissues. The study findings confirmed the promising effects of ECT against G. lamblia infection both in vitro and in vivo. Considering the possible mechanisms, ECT increases plasma membrane permeability and reduces the expression levels of infectivity-related genes. In addition, ECT suppresses inflammation and oxidative stress, controlling giardiasis in mice. More studies are needed to clarify these findings.


Assuntos
Antiprotozoários , Giardia lamblia , Giardíase , Estresse Oxidativo , Animais , Giardia lamblia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Inflamação/tratamento farmacológico , Metronidazol/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Permeabilidade da Membrana Celular/efeitos dos fármacos , Feminino , Trofozoítos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Concentração Inibidora 50 , Citocinas/metabolismo
4.
Acta Parasitol ; 69(1): 1073-1077, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38499920

RESUMO

PURPOSE: Investigating the genetic variation in thioredoxin reductase (TrxR) and nitroreductase (NR) genes in both treatment-resistant and -sensitive Giardia duodenalis isolates can provide valuable information in identifying potential markers of resistance to metronidazole. The rapid increase in metronidazole treatment failures suggests the presence of genetic resistance mechanisms. By analyzing these genes, researchers can gain insights into the efficacy of metronidazole against G. duodenalis and potentially develop alternative treatment strategies. In this regard, four G. duodenalis isolates (two clinically sensitive and two clinically resistant to metronidazole) were collected from various hospitals of Shiraz, southwestern Iran. METHODS: Parasitological methods including sucrose flotation and microscopy were employed for the primary confirmation of G. duodenalis cysts in stool samples. Microscopy-positive samples were approved by SSU-PCR amplification of the parasite DNA. All four positive G. duodenalis specimens at SSU-PCR were afterward analyzed utilizing designed primers based on important metronidazole metabolism genes including TrxR, NR1, and NR2. RESULTS: Unlike TrxR gene, the results of NR1 and NR2 genes showed that there are non-synonymous variations between sequences of treatment-sensitive and -resistant samples compared to reference sequences. Furthermore, the outcomes of molecular docking revealed that there is an interaction between the protein sequence and spatial shape of treatment-resistant samples and metronidazole in the position of serine amino acid based on the NR1 gene. CONCLUSION: This issue can be one of the possible factors involved in the resistance of Giardia parasites to metronidazole. To reach more accurate results, a large sample size along with simulation and advanced molecular dynamics investigations are needed.


Assuntos
Antiprotozoários , Resistência a Medicamentos , Variação Genética , Giardia lamblia , Giardíase , Metronidazol , Nitrorredutases , Reação em Cadeia da Polimerase , Metronidazol/farmacologia , Giardia lamblia/genética , Giardia lamblia/efeitos dos fármacos , Giardíase/parasitologia , Giardíase/tratamento farmacológico , Humanos , Resistência a Medicamentos/genética , Antiprotozoários/farmacologia , Nitrorredutases/genética , Nitrorredutases/metabolismo , Irã (Geográfico) , Fezes/parasitologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Tiorredoxina Dissulfeto Redutase/genética , Tiorredoxina Dissulfeto Redutase/metabolismo , Simulação de Acoplamento Molecular , DNA de Protozoário/genética
5.
Antimicrob Agents Chemother ; 68(1): e0073123, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38063401

RESUMO

The intestinal parasites Giardia lamblia and Entamoeba histolytica are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of E. histolytica to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and antiamebic activities of the rediscovered nitroimidazole compound, fexinidazole, and its sulfone and sulfoxide metabolites. Fexinidazole is equally active against E. histolytica and G. lamblia trophozoites, and both metabolites were 3- to 18-fold more active than the parent drug. Fexinidazole and its metabolites were also active against a metronidazole-resistant strain of G. lamblia. G. lamblia and E. histolytica cell extracts exhibited decreased residual nitroreductase activity when metabolites were used as substrates, indicating nitroreductase may be central to the mechanism of action of fexinidazole. In a cell invasion model, fexinidazole and its metabolites significantly reduced the invasiveness of E. histolytica trophozoites through basement membrane matrix. A q.d. oral dose of fexinidazole and its metabolites at 10 mg/kg for 3 days reduced G. lamblia infection significantly in mice compared to control. The newly discovered antigiardial and antiamebic activities of fexinidazole, combined with its FDA-approval and inclusion in the WHO Model List of Essential Medicines for the treatment of human African trypanosomiasis, offer decreased risk and a shortened development timeline toward clinical use of fexinidazole for treatment of giardiasis or amebiasis.


Assuntos
Amebíase , Entamoeba histolytica , Giardia lamblia , Giardíase , Nitroimidazóis , Camundongos , Animais , Humanos , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Nitroimidazóis/farmacologia , Nitrorredutases
6.
Artigo em Alemão | MEDLINE | ID: mdl-38056479

RESUMO

Giardia duodenalis is a facultative pathogenic intestinal parasite. Giardiosis in dogs and cats may appear with or without clinical signs. Typical signs include diarrhea with or without vomiting. The prevalence in young animals is high and may amount to up to 50%. There are 8 different genotypes (A - H), which are called assemblages. Assemblages C and D are most common in dogs and assemblage F most frequent in cats. However, animals may also be infected with the zoonotically effective assemblages A and B or exhibit mixed infections. The immunofluorescence test (IFA), the enzyme-linked immunosorbent assay (ELISA) and fecal centrifugation using zinc sulphate solution are currently recommended as diagnostic methods. Polymerase chain reaction (PCR) may be used to determine the corresponding assemblage. Approved treatments for giardiosis include fenbendazole and metronidazole. In addition, undertaking specific hygiene measures is warranted. Only animals showing clinical signs or those living in the same household with high-risk patients (e. g. immunosuppressed humans) are recommended to receive medication. The aim of treatment is clinical improvement of the diseased dogs and cats. Frequently, complete elimination of Giardia is not attained.


Assuntos
Doenças do Gato , Doenças do Cão , Giardia lamblia , Giardíase , Animais , Gatos , Cães , Humanos , Doenças do Gato/diagnóstico , Doenças do Gato/tratamento farmacológico , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Giardíase/diagnóstico , Giardíase/tratamento farmacológico , Giardíase/veterinária , Giardia lamblia/genética , Reação em Cadeia da Polimerase/veterinária , Fezes/parasitologia
7.
Int J Mol Sci ; 24(19)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37834396

RESUMO

Parasitic diseases, including giardiasis caused by Giardia lamblia (G. lamblia), present a considerable global health burden. The limited effectiveness and adverse effects of current treatment options underscore the necessity for novel therapeutic compounds. In this study, we employed a rational design strategy to synthesize retroalbendazole (RetroABZ), aiming to address the limitations associated with albendazole, a commonly used drug for giardiasis treatment. RetroABZ exhibited enhanced in vitro activity against G. lamblia trophozoites, demonstrating nanomolar potency (IC50 = 83 nM), outperforming albendazole (189 nM). Moreover, our in vivo murine model of giardiasis displayed a strong correlation, supporting the efficacy of RetroABZ, which exhibited an eleven-fold increase in potency compared to albendazole, with median effective dose (ED50) values of 5 µg/kg and 55 µg/kg, respectively. A notable finding was RetroABZ's significantly improved water solubility (245.74 µg/mL), representing a 23-fold increase compared to albendazole, thereby offering potential opportunities for developing derivatives that effectively target invasive parasites. The molecular docking study revealed that RetroABZ displays an interaction profile with tubulin similar to albendazole, forming hydrogen bonds with Glu198 and Cys236 of the ß-tubulin. Additionally, molecular dynamics studies demonstrated that RetroABZ has a greater number of hydrophobic interactions with the binding site in the ß-tubulin, due to the orientation of the propylthio substituent. Consequently, RetroABZ exhibited a higher affinity compared to albendazole. Overall, our findings underscore RetroABZ's potential as a promising therapeutic candidate not only for giardiasis but also for other parasitic diseases.


Assuntos
Antiprotozoários , Giardia lamblia , Giardíase , Animais , Camundongos , Albendazol/química , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Tubulina (Proteína) , Simulação de Acoplamento Molecular , Solubilidade
8.
Artigo em Inglês | MEDLINE | ID: mdl-37776606

RESUMO

Giardia duodenalis is the causative agent of the neglected diarrhoeal disease giardiasis. While often self-limiting, giardiasis is ubiquitous and impacts hundreds of millions of people annually. It is also a common gastro-intestinal disease of domestic pets, wildlife, and livestock animals. However, despite this impact, there is no vaccine for Giardia currently available. In addition, treatment relies on chemotherapies that are associated with increasing failure rates. To identify new treatment options for giardiasis we recently screened the Compounds Australia Scaffold Library for new chemotypes with selective anti-Giardia activity, identifying three compounds with sub-µM activity and promising selectivity. Here we extended these studies by examining the anti-Giardia activity of series CL9569 compounds. This compound series was of interest given the promising activity (IC50 1.2 µM) and selectivity demonstrated by representative compound, SN00798525 (1). Data from this work has identified an additional three thieno [3,2-b]pyrrole 5-carboxamides with anti-Giardia activity, including 2 which displayed potent cytocidal (IC50 ≤ 10 nM) and selective activity against multiple Giardia strains, including representatives from both human-infecting assemblages and metronidazole resistant parasites. Preclinical studies in mice also demonstrated that 2 is well-tolerated, does not impact the normal gut microbiota and can reduce Giardia parasite burden in these animals.


Assuntos
Giardia lamblia , Giardíase , Parasitos , Humanos , Animais , Camundongos , Giardíase/tratamento farmacológico , Giardíase/veterinária , Giardíase/parasitologia , Giardia , Metronidazol/uso terapêutico , Fezes/parasitologia
9.
Acta Trop ; 248: 107026, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37722447

RESUMO

Giardia lamblia is a globally distributed protozoan parasite that causes intestinal disease. Recently, there is an increase in refractory cases of giardiasis to chemotherapeutic agents, and drugs available cause side effects that may limit its use or cause therapeutic non-compliance. Therefore, search for alternative and less harmful drugs to treat giardiasis is an important task. In this sense, resveratrol (RSV) is a polyphenol with a wide range of pharmacological effects such as antimicrobial, anticarcinogenic and antioxidant. The aim of this study was to evaluate the effects of RSV on Giardia lamblia trophozoites in vitro and in silico, focusing on tubulin affectation, a major protein of the Giardia cytoskeleton which participates in relevant processes for cell survival. In vitro determinations showed that RSV inhibits parasite growth and adherence, causes morphological changes, and induces apoptosis-like cell death through tubulin alterations demonstrated by immunolocalization and Western blot assays. Bioinformatic analysis by molecular docking suggested that RSV binds to Giardia tubulin interface heterodimer, sharing binding residues to those reported with depolymerization inhibitors. These findings suggest that RSV affects microtubular dynamics and make it an interesting compound to study for its safety and antigiardiasic potential.


Assuntos
Giardia lamblia , Giardíase , Animais , Humanos , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/farmacologia , Tubulina (Proteína)/uso terapêutico , Resveratrol/farmacologia , Trofozoítos , Simulação de Acoplamento Molecular
10.
Infect Disord Drug Targets ; 23(7): 82-85, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448372

RESUMO

INTRODUCTION: Giardia lamblia is a neglected parasitic infection that typically affects the developing nations of the world. It is a microscopic intestinal parasite that is known to cause stomach cramps, bloating, nausea and bouts of diarrhoea. CASE PRESENTATION: Here, we are presenting the case of a 1.5 years-old-baby with an immunocompromised condition who got infected by Giardia lamblia. The baby with fibrosarcoma was receiving treatment in our tertiary care centre, and later developed abdominal and minor systemic complaints. Stool samples were collected, which showed trophozoites and cysts of Giardia. DISCUSSION: To the best of our knowledge, this is the first case of Giardia lamblia infection in a paediatric patient with fibrosarcoma. The patient improved after taking metronidazole for ten days. CONCLUSION: It is critical to keep a watch out for this neglected parasite, and suggested samples, particularly stool samples, must be sent for investigation in order to diagnose and manage these cases properly.


Assuntos
Fibrossarcoma , Giardia lamblia , Giardíase , Criança , Lactente , Humanos , Giardíase/complicações , Giardíase/diagnóstico , Giardíase/tratamento farmacológico , Metronidazol/uso terapêutico , Diarreia , Fibrossarcoma/diagnóstico , Fibrossarcoma/tratamento farmacológico
11.
Parasitol Res ; 122(9): 1961-1971, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37400534

RESUMO

Giardia duodenalis is a protozoan intestinal parasite that causes a significant number of infections worldwide each year, particularly in low-income and developing countries. Despite the availability of treatments for this parasitic infection, treatment failures are alarmingly common. As a result, new therapeutic strategies are urgently needed to effectively combat this disease. On the other hand, within the eukaryotic nucleus, the nucleolus stands out as the most prominent structure. It plays a crucial role in coordinating ribosome biogenesis and is involved in vital processes such as maintaining genome stability, regulating cell cycle progression, controlling cell senescence, and responding to stress. Given its significance, the nucleolus presents itself as a valuable target for selectively inducing cell death in undesirable cells, making it a potential avenue for anti-Giardia treatments. Despite its potential importance, the Giardia nucleolus remains poorly studied and often overlooked. In light of this, the objective of this study is to provide a detailed molecular description of the structure and function of the Giardia nucleolus, with a primary focus on its involvement in ribosomal biogenesis. Likewise, it discusses the targeting of the Giardia nucleolus as a therapeutic strategy, its feasibility, and the challenges involved.


Assuntos
Nucléolo Celular , Giardia , Ribossomos , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , Giardia/citologia , Giardia/genética , RNA Ribossômico/genética , DNA Ribossômico/genética , DNA de Protozoário/genética , RNA de Protozoário/genética , Transcrição Gênica , Regulação da Expressão Gênica , Processamento Pós-Transcricional do RNA/genética , Ribossomos/genética , Ribossomos/metabolismo , Giardíase/tratamento farmacológico , Antiparasitários/uso terapêutico , Desenvolvimento de Medicamentos/tendências
12.
Int J Mol Sci ; 24(14)2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37511272

RESUMO

Giardiasis, which is caused by Giardia lamblia infection, is a relevant cause of morbidity and mortality worldwide. Because no vaccines are currently available to treat giardiasis, chemotherapeutic drugs are the main options for controlling infection. Evidence has shown that the nitro drug nitazoxanide (NTZ) is a commonly prescribed treatment for giardiasis; however, the mechanisms underlying NTZ's antigiardial activity are not well-understood. Herein, we identified the glucose-6-phosphate::6-phosphogluconate dehydrogenase (GlG6PD::6PGL) fused enzyme as a nitazoxanide target, as NTZ behaves as a GlG6PD::6PGL catalytic inhibitor. Furthermore, fluorescence assays suggest alterations in the stability of GlG6PD::6PGL protein, whereas the results indicate a loss of catalytic activity due to conformational and folding changes. Molecular docking and dynamic simulation studies suggest a model of NTZ binding on the active site of the G6PD domain and near the structural NADP+ binding site. The findings of this study provide a novel mechanistic basis and strategy for the antigiardial activity of the NTZ drug.


Assuntos
Giardia lamblia , Giardíase , Humanos , Giardíase/tratamento farmacológico , Simulação de Acoplamento Molecular , Tiazóis/farmacologia , Tiazóis/uso terapêutico
13.
Res Vet Sci ; 159: 252-256, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37182304

RESUMO

Giardia duodenalis is a protozoan parasite that infects many mammals, including dogs and cats. This waterborne and foodborne zoonosis is a major problem in one health. Treatment can be challenging because of long regimens and drug resistance. The objective of this study was to evaluate the efficacy of single-dose nitazoxanide (NTZ) for dogs naturally infected by Giardia duodenalis. Although widely used in humans, pharmacological safety is incipient, since the approval of the safe use of nitaxozanide for dogs is not a consensus in the world. Fifty dogs diagnosed with G. duodenalis by zinc sulfate flotation technique (Faust method) and cysts detection by light microscopy. Half of the animals received a dose of 50 mg/kg of NTZ and the other half received 3 doses of 50 mg/kg of fenbendazole (FBZ), both orally. One week after treatment, new fecal exams were done to prove the effectiveness. Of the animals treated with NTZ, 84% were negative for the protozoan, while 76% of the animals treated with FBZ were negative, no significant difference was identified. Side effects such as vomiting and hyporexia were manageable in NTZ treatment and no changes in laboratory tests showed hepatic or renal impairment. We conclude that the use of NTZ in a single dose of 50 mg/kg is effective for canine giardiasis, constituting an option to be considered for dogs with relapses, poor response to conventional drugs and to facilitate administration regimens.


Assuntos
Doenças do Gato , Doenças do Cão , Giardia lamblia , Giardíase , Humanos , Animais , Cães , Gatos , Doenças do Gato/diagnóstico , Doenças do Cão/diagnóstico , Giardíase/tratamento farmacológico , Giardíase/veterinária , Fezes/parasitologia , Mamíferos
14.
Expert Opin Ther Pat ; 33(3): 211-245, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37099697

RESUMO

INTRODUCTION: Toxoplasma gondii, Trichomonas vaginalis, and Giardia intestinalis are the causative agents of toxoplasmosis, trichomoniasis, and giardiasis, three important infections threatening human health and affecting millions of people worldwide. Although drugs and treatment are available to fight these protozoan parasites, side effects and increasing drug resistance require continuous efforts for the development of novel effective drugs. AREAS COVERED: The patents search was carried out in September/October 2022 with four official scientific databases (Espacenet, Scifinder, Reaxys, Google Patents). Treatments for toxoplasmosis, trichomoniasis, and giardiasis (2015-2022) have been grouped according to their chemotypes. In particular, novel chemical entities have been reported and investigated for their structure-activity relationship, when accessible. On the other hand, drug repurposing, extensively exploited to obtain novel antiprotozoal treatment, has been in-depth described. Finally, natural metabolites and extracts have also been reported. EXPERT OPINION: T. gondii, T. vaginalis, and G. intestinalis are protozoan infections usually controlled by immune system in immunocompetent patients; however, they could represent a threatening health for immunocompromised people. The needs of novel effective drugs, endowed with new mechanisms of actions, arises from the increasing drug resistance affecting antibiotic as well as antiprotozoal therapies. In this review different therapeutic approaches to treat protozoan infections have been reported.


Assuntos
Antiprotozoários , Giardíase , Toxoplasma , Toxoplasmose , Tricomoníase , Trichomonas vaginalis , Humanos , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Trichomonas vaginalis/metabolismo , Patentes como Assunto , Antiprotozoários/farmacologia , Tricomoníase/tratamento farmacológico , Toxoplasmose/tratamento farmacológico
16.
Acta Trop ; 237: 106748, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36368413

RESUMO

Giardiasis is an intestinal protozoal disease caused by Giardia lamblia (G. lamblia) which is a major worldwide health problem due to development of resistance to commonly used drugs. Therefore, it is necessary to identify an effective drug for giardiasis. This study aimed to assess the therapeutic role of L-citrulline against giardiasis in experimental animals. 40 male Swiss Albino weaned rats were used in this study, divided into four groups. Group I: normal control; group II: infected un-treated; group III: infected and treated with L-citrulline and Group IV: infected and treated with metronidazole. The efficacy was evaluated by counting Giardia trophozoites in the intestinal mucosa and cysts in the stool of infected rats. Histopathological analyses, immunohistochemistry expression of inducible nitric oxide synthase (iNOS) in the small intestine tissues were performed. Along with, serum IL6, the intestinal arginase enzyme level and giardial flavohemoglobin (flavoHb) expression were measured. L-citrulline administration reduced the mean number of G. lamblia cysts and trophozoites, serum IL-6, and intestinal arginase enzyme levels. Furthermore, the intestinal brush border was restored, with a reduction in the inflammatory infiltrate and an increase in iNOS activity. Moreover, there was a significant decrease in flavoHb gene expression in both the L-citrulline and metronidazole treated groups. Thus L-citrulline is effective in NO production therefore it has a therapeutic potential in controlling giardiasis.


Assuntos
Cistos , Giardia lamblia , Giardíase , Masculino , Camundongos , Ratos , Animais , Giardíase/tratamento farmacológico , Citrulina/farmacologia , Citrulina/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Arginase , Giardia , Trofozoítos , Arginina/farmacologia , Imunidade
17.
BMJ Case Rep ; 15(11)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323453

RESUMO

A woman in her 40s presented with malaise, nausea, reduced appetite, abdominal distention, loose stools and weight loss. Symptoms had started 6 months earlier and worsened in the last 2 weeks. CT enterography showed hypotonic dilated small bowel loops in absence of any mechanical obstruction. Endoscopic examinations including capsule endoscopy did not reveal any obstructing lesion, but a delayed small bowel transit time of the capsule. Duodenal histology revealed Marsh 3a villous atrophy. Secondary causes of intestinal pseudo-obstruction and villous atrophy were investigated. Giardia lamblia trophozoites were found in the stools and in the duodenal biopsies. The patient's symptoms quickly resolved after metronidazole treatment with complete normalisation of duodenal histology.


Assuntos
Giardia lamblia , Giardíase , Pseudo-Obstrução Intestinal , Feminino , Humanos , Giardíase/complicações , Giardíase/diagnóstico , Giardíase/tratamento farmacológico , Duodeno/patologia , Pseudo-Obstrução Intestinal/diagnóstico por imagem , Pseudo-Obstrução Intestinal/etiologia , Atrofia/patologia
18.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36430836

RESUMO

Treatments to combat giardiasis have been reported to have several drawbacks, partly due to the drug resistance and toxicity of current antiparasitic agents. These constraints have prompted many researchers to investigate new drugs that act against protozoan parasites. Enzyme inhibition is an important means of regulating pathogen metabolism and has recently been identified as a significant alternative target in the search for new treatments. Glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase (G6PD::6PGL) is a bifunctional enzyme involved in the pentose phosphate pathway (PPP) in Giardia lamblia (G. lamblia). The G. lamblia enzyme is unusual since, unlike the human enzyme, it is a fused enzyme. Here, we show, through inhibition assays, that an in-house chemical library of 120 compounds and four target compounds, named CNZ-7, CNZ-8, CMC-1, and FLP-2, are potent inhibitors of the G. lamblia G6PD::6PGL fused enzyme. With a constant (k2) of 2.3, 3.2, and 2.8 M−1 s−1, respectively, they provoke alterations in the secondary and tertiary protein structure and global stability. As a novel approach, target compounds show antigiardial activity, with IC50 values of 8.7, 15.2, 15.3, and 24.1 µM in trophozoites from G. lamblia. Moreover, these compounds show selectivity against G. lamblia, since, through counter-screening in Caco-2 and HT29 human cells, they were found to have low toxicity. This finding positions these compounds as a potential and attractive starting point for new antigiardial drugs.


Assuntos
Giardia lamblia , Giardíase , Animais , Humanos , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Trofozoítos/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Células CACO-2
19.
J Med Life ; 15(10): 1278-1282, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36420289

RESUMO

Recently, many cases of mixed invasion by Giardia and ascarids have been registered. Gastrointestinal lesions in patients are often accompanied by dysbiotic changes. The aim was to study the effect of probiotics containing Saccharomyces bouvardias CNCM I-745 in the complex therapy of patients with giardiasis, ascariasis, and mixed invasion. 90 patients with giardiasis, ascariasis and mixed invasion were divided into 3 groups, depending on the type of invasion. Each group was divided into two subgroups, depending on the treatment (basic treatment and treatment with probiotics). When studying the state of the intestinal microbiota, the following changes were detected in all patients before treatment. The content of Bifidobacterium spp., Lactobacillus spp., Enterococcus spp. and the total content of E. coli was reduced. At the same time, there was an increase in the content of Peptostreptococcus spp., Bacteroides spp., E. coli with low enzymatic properties, hemolytic E. coli, opportunistic Enterobacteriaceae spp., Candida spp. and Staphylococcus spp. Under the influence of treatment, the subgroup with probiotics addition to the basic treatment, was more effective for all types of invasions. The use of probiotics containing Saccharomyces bouvardias CNCM I-745 in the complex therapy of patients with mixed invasion of giardiasis and ascariasis increased treatment efficiency following a significant improvement in intestinal microbiota.


Assuntos
Ascaríase , Microbioma Gastrointestinal , Giardíase , Probióticos , Humanos , Giardíase/tratamento farmacológico , Escherichia coli , Probióticos/uso terapêutico
20.
J Infect Dev Ctries ; 16(11): 1781-1783, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36449653

RESUMO

INTRODUCTION: Giardia intestinalis causes diarrhea and malabsorption, especially in developed countries. Although it primarily affects the gastrointestinal system, on rare occasions it causes allergic symptoms such as itching, urticaria, and eczema. Here we describe the case of a 19-year-old man with no past medical history who presented to our hospital with an atypical urticarial rash. DIAGNOSIS: The only abnormal result in laboratory findings of stool parasitology was G. intestinalis. The patient was diagnosed with urticaria due to giardiasis. INTERVENTION AND OUTCOMES: The patient was prescribed Bilastine tablet 20 mg 1 × 1 and referred to the Infectious Diseases Department for treatment. Co-Trimoxazole 400 mg/80 mg tablets 2 × 1 and Metronidazole 500 mg tablets 3 × 1 were prescribed. The urticaria had disappeared at the follow-up visit. The patient confirmed that urticarial symptoms did not recur. CONCLUSIONS: Despite their rarity, Giardia and other parasite infections can cause allergic symptoms. Parasitic factors should be considered in patients, especially those living in the communal areas, who present with treatment-resistant urticaria.


Assuntos
Giardia lamblia , Giardíase , Urticária , Masculino , Humanos , Adulto Jovem , Adulto , Giardíase/complicações , Giardíase/diagnóstico , Giardíase/tratamento farmacológico , Urticária/diagnóstico , Urticária/etiologia , Diarreia , Prurido
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