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1.
Parasit Vectors ; 17(1): 336, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39127700

ABSTRACT

BACKGROUND: Giardiasis, caused by the protozoan parasite Giardia intestinalis, often presents a treatment challenge, particularly in terms of resistance to metronidazole. Despite extensive research, markers for metronidazole resistance have not yet been identified. METHODS: This study analysed 28 clinical samples of G. intestinalis from sub-assemblage AII, characterised by varying responses to metronidazole treatment. We focussed on copy number variation (CNV) of the multi-copy flavohemoprotein gene, analysed using digital polymerase chain reaction (dPCR) and next generation sequencing (NGS). Additionally, chromosomal ploidy was tested in 18 of these samples. Flavohemoprotein CNV was also assessed in 17 samples from other sub-assemblages. RESULTS: Analyses revealed variable CNVs of the flavohemoprotein gene among the isolates, with no correlation to clinical metronidazole resistance. Discrepancies in CNVs detected from NGS data were attributed to biases linked to the whole genome amplification. However, dPCR helped to clarify these discrepancies by providing more consistent CNV data. Significant differences in flavohemoprotein CNVs were observed across different G. intestinalis sub-assemblages. Notably, Giardia exhibits a propensity for aneuploidy, contributing to genomic variability within and between sub-assemblages. CONCLUSIONS: The complexity of the clinical metronidazole resistance in Giardia is influenced by multiple genetic factors, including CNVs and aneuploidy. No significant differences in the CNV of the flavohemoprotein gene between isolates from metronidazole-resistant and metronidazole-sensitive cases of giardiasis were found, underscoring the need for further research to identify reliable genetic markers for resistance. We demonstrate that dPCR and NGS are robust methods for analysing CNVs and provide cross-validating results, highlighting their utility in the genetic analyses of this parasite.


Subject(s)
Antiprotozoal Agents , DNA Copy Number Variations , Drug Resistance , Giardia lamblia , Giardiasis , Metronidazole , Giardia lamblia/genetics , Giardia lamblia/drug effects , Metronidazole/pharmacology , Drug Resistance/genetics , Humans , Giardiasis/parasitology , Giardiasis/drug therapy , Antiprotozoal Agents/pharmacology , High-Throughput Nucleotide Sequencing , Protozoan Proteins/genetics
2.
J Water Health ; 22(6): 1102-1110, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38935460

ABSTRACT

Ferrate (Fe(VI): HFeO4- /FeO42-), a potent oxidant, has been investigated as an alternative chemical disinfectant in water treatment due to its reduced production of disinfection by-products. In this study, we assessed the disinfecting ability of potassium ferrate against a variety of microorganisms, including waterborne pathogens, under varying pH and water temperature conditions. We presented CT values, a metric of ferrate concentrations (C) and contact time (T), to quantify microbial inactivation rates. Among the tested microorganisms, human adenovirus was the least resistant to ferrate, followed by waterborne bacteria such as Escherichia coli and Vibrio cholerae, and finally, the protozoan parasite Giardia duodenalis. We further investigated the impact of two pH values (7 and 8) and two temperatures (5 and 25 °C) on microbial inactivation rates, observing that inactivation rates increased with lower pH and higher temperature. In addition to showcasing ferrate's capacity to effectively inactivate a range of the tested microorganisms, we offer a ferrate CT table to facilitate the comparison of the effectiveness of various disinfection methods.


Subject(s)
Disinfectants , Giardia lamblia , Temperature , Hydrogen-Ion Concentration , Disinfectants/pharmacology , Giardia lamblia/drug effects , Adenoviruses, Human/drug effects , Potassium Compounds/pharmacology , Potassium Compounds/chemistry , Water Microbiology , Disinfection/methods , Water Purification/methods , Iron Compounds/pharmacology , Iron Compounds/chemistry , Humans , Escherichia coli/drug effects
3.
Int J Mol Sci ; 25(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38892424

ABSTRACT

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.


Subject(s)
Antiprotozoal Agents , Giardia lamblia , Giardiasis , Molecular Docking Simulation , United States Food and Drug Administration , Giardiasis/drug therapy , Giardia lamblia/drug effects , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , United States , Humans , Protozoan Proteins/chemistry , Protozoan Proteins/metabolism , Protozoan Proteins/antagonists & inhibitors , Molecular Dynamics Simulation
4.
Exp Parasitol ; 262: 108773, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723845

ABSTRACT

Giardiasis is a prevalent parasitic diarrheal disease caused by Giardia lamblia, affecting people worldwide. Recently, the availability of several drugs for its treatment has highlighted issues such as multidrug resistance, limited effectiveness and undesirable side effects. Therefore, it is necessary to develop alternative new drugs and treatment strategies that can enhance therapeutic outcomes and effectively treat giardiasis. Natural compounds show promise in the search for more potent anti-giardial agents. Our investigation focused on the effect of Andrographolide (ADG), an active compound of the Andrographis paniculata plant, on Giardia lamblia, assessing trophozoite growth, morphological changes, cell cycle arrest, DNA damage and inhibition of gene expression associated with pathogenic factors. ADG demonstrated anti-Giardia activity almost equivalent to the reference drug metronidazole, with an IC50 value of 4.99 µM after 24 h of incubation. In cytotoxicity assessments and morphological examinations, it showed significant alterations in trophozoite shape and size and effectively hindered the adhesion of trophozoites. It also caused excessive ROS generation, DNA damage, cell cycle arrest and inhibited the gene expression related to pathogenesis. Our findings have revealed the anti-giardial efficacy of ADG, suggesting its potential as an agent against Giardia infections. This could offer a natural and low-risk treatment option for giardiasis, reducing the risk of side effects and drug resistance.


Subject(s)
Antiprotozoal Agents , Cell Cycle Checkpoints , DNA Damage , Diterpenes , Giardia lamblia , Inhibitory Concentration 50 , Reactive Oxygen Species , Trophozoites , Diterpenes/pharmacology , Giardia lamblia/drug effects , Giardia lamblia/growth & development , Giardia lamblia/genetics , Trophozoites/drug effects , Trophozoites/growth & development , Cell Cycle Checkpoints/drug effects , Reactive Oxygen Species/metabolism , DNA Damage/drug effects , Antiprotozoal Agents/pharmacology , Humans , Animals , Gene Expression/drug effects , Metronidazole/pharmacology
5.
Talanta ; 274: 126000, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38608630

ABSTRACT

Luminescent ß-diketonate-europium(III) complexes have been found a wide range of applications in time-gated luminescence (TGL) bioassays, but their poor water solubility is a main problem that limits their effective uses. In this work we propose a simple and general strategy to enhance the water solubility of luminescent ß-diketonate-europium(III) complexes that permits facile synthesis and purification. By introducing the fluorinated carboxylic acid group into the structures of ß-diketone ligands, two highly water-soluble and luminescent Eu3+ complexes, PBBHD-Eu3+ and CPBBHD-Eu3+, were designed and synthesized. An excellent solubility exceeding 20 mg/mL for PBBHD-Eu3+ was found in a pure aqueous buffer, while it also displayed strong and long-lived luminescence (quantum yield φ = 26%, lifetime τ = 0.49 ms). After the carboxyl groups of PBBHD-Eu3+ were activated, the PBBHD-Eu3+-labeled streptavidin-bovine serum albumin (SA-BSA) conjugate was prepared, and successfully used for the immunoassay of human α-fetoprotein (AFP) and the imaging of an environmental pathogen Giardia lamblia under TGL mode, which demonstrated the practicability of PBBHD-Eu3+ for highly sensitive TGL bioassays. The carboxyl groups of PBBHD can also be easily derivatized with other reactive chemical groups, which enables PBBHD-Eu3+ to meet diverse requirements of biolabeling technique, to provide new opportunities for developing functional europium(III) complex biolabels serving for TGL bioassays.


Subject(s)
Europium , Solubility , Water , Europium/chemistry , Water/chemistry , Humans , Luminescent Measurements/methods , Serum Albumin, Bovine/chemistry , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Giardia lamblia/drug effects , Luminescence , Animals , Biological Assay/methods , Luminescent Agents/chemistry , Luminescent Agents/chemical synthesis , Streptavidin/chemistry , Time Factors , Cattle , Keto Acids/chemistry
6.
Acta Trop ; 255: 107201, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38604329

ABSTRACT

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.


Subject(s)
Antiprotozoal Agents , Giardia lamblia , Giardiasis , Oxidative Stress , Animals , Giardia lamblia/drug effects , Oxidative Stress/drug effects , Mice , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Giardiasis/drug therapy , Giardiasis/parasitology , Inflammation/drug therapy , Metronidazole/pharmacology , Cell Survival/drug effects , Disease Models, Animal , Cell Membrane Permeability/drug effects , Female , Trophozoites/drug effects , Mice, Inbred BALB C , Inhibitory Concentration 50 , Cytokines/metabolism
7.
Int J Parasitol Drugs Drug Resist ; 25: 100543, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38685159

ABSTRACT

Functional gene and protein characterizations in parasitic protists are often limited by their genetic tractability. Despite the development of CRISPR-Cas9-derived or inspired approaches for a handful of protist parasites, the overall genetic tractability of these organisms remains limited. The intestinal parasite Giardia lamblia is one such species, with the added challenge of a paucity of reliable selection markers. To address this limitation, we tested the feasibility of using Nourseothricin as an effective selection agent in Giardia. Here, we report that axenically-grown WB Giardia cells are sensitive to Nourseothricin and that engineering expression of the streptothricin acetyltransferase (SAT-1) gene from Streptomyces rochei in transgenic parasites confers resistance to this antibiotic. Furthermore, we determine that SAT-1-expressing parasites are cross-resistant neither to Neomycin nor Puromycin, which are widely used to select for transgenic parasites. Consequently, we show that Nourseothricin can be used in sequential combination with both Neomycin and Puromycin to select for dual transfection events. This work increases the number of reliable selection agents and markers for Giardia genetic manipulation, expanding the limited molecular toolbox for this species of global medical importance.


Subject(s)
Giardia lamblia , Streptothricins , Giardia lamblia/genetics , Giardia lamblia/drug effects , Streptothricins/pharmacology , Acetyltransferases/genetics , Drug Resistance/genetics , Streptomyces/genetics , Streptomyces/drug effects , Antiprotozoal Agents/pharmacology , Organisms, Genetically Modified , CRISPR-Cas Systems
8.
Acta Parasitol ; 69(1): 1073-1077, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38499920

ABSTRACT

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.


Subject(s)
Antiprotozoal Agents , Drug Resistance , Genetic Variation , Giardia lamblia , Giardiasis , Metronidazole , Nitroreductases , Polymerase Chain Reaction , Metronidazole/pharmacology , Giardia lamblia/genetics , Giardia lamblia/drug effects , Giardiasis/parasitology , Giardiasis/drug therapy , Humans , Drug Resistance/genetics , Antiprotozoal Agents/pharmacology , Nitroreductases/genetics , Nitroreductases/metabolism , Iran , Feces/parasitology , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Thioredoxin-Disulfide Reductase/genetics , Thioredoxin-Disulfide Reductase/metabolism , Molecular Docking Simulation , DNA, Protozoan/genetics
9.
Mem. Inst. Oswaldo Cruz ; 115: e200127, 2020. graf
Article in English | LILACS, Sec. Est. Saúde SP | ID: biblio-1135244

ABSTRACT

BACKGROUND Kaempferol (KPF) is a flavonoid with antiparasitic activity including experimental giardiasis which mechanism of action is unknown. OBJECTIVE To analyse the cytotoxic effects of KPF on Giardia duodenalis trophozoites and to identify a likely parasite target of this compound. METHODS We used inhibitory concentrations of KPF (IC25, IC50 and IC100) and albendazole (ABZ) as reference drug. The ultrastructure of the trophozoites was analysed by transmission electron microscopy (TEM) whilst apoptosis/necrosis, production of reactive oxygen species (ROS) and cell cycle progression were assessed by flow cytometry (FCM) and confocal laser microscopy (CLM). Ligand-protein docking analyses were carried out using KPF structure from a drug library and crystal structure of a G. duodenalis aldose reductase (GdAldRed) homolog. RESULTS KPF provoked appearance of perinuclear and periplasmic spaces devoid of cytosolic content and multilamellar structures. KPF induced proapoptotic death associated with partial arrest in the S phase without ROS production. Bioinformatics approaches predicted that GdAldRed is a viable KPF target (ΔG = -7.09 kCal/mol), exhibiting 92% structural identity and a similar coupling pattern as its human homolog. CONCLUSIONS KPF exerted a proapoptotic effect on G. duodenalis trophozoites involving partial interruption of DNA synthesis without oxidative stress or structure damage to chromatin and cytoskeletal structures. GdAldRed is a likely target underlying its antigiardial activity.


Subject(s)
Humans , Animals , Giardiasis , Giardia lamblia/drug effects , Kaempferols , Computational Biology , Trophozoites
10.
Mem. Inst. Oswaldo Cruz ; 115: e200303, 2020. tab, graf
Article in English | LILACS, Sec. Est. Saúde SP | ID: biblio-1135270

ABSTRACT

Giardiasis is an infectious disease caused by Giardia duodenalis. The pro-drug metronidazole (MTZ) is the first-line treatment for giardiasis. Parasite's proteins as pyruvate:ferredoxin oxidoreductase (PFOR), ferredoxin (Fd), nitroreductase-1 (NR-1) and thioredoxin reductase (TrxR) participate in MTZ activation. Here, we showed Giardia trophozoites long-term exposed to MTZ presented higher IC50 than controls, showing the drug influenced the parasite survival. That reduction in MTZ's susceptibility does not seem to be related to mutations in the genes pfor, fd, nr-1 or trxr. It points that different mechanism as alterations in other metabolic pathways can account for Giardia resistance to MTZ therapy.


Subject(s)
Drug Resistance/genetics , Prodrugs , Giardia lamblia/drug effects , Giardia lamblia/genetics , Metronidazole/pharmacology , Antiprotozoal Agents/pharmacology , Activation, Metabolic , Nucleotides
11.
Mem. Inst. Oswaldo Cruz ; 115: e190348, 2020. tab, graf
Article in English | LILACS | ID: biblio-1091246

ABSTRACT

BACKGROUND It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB strain than metronidazole and albendazole and similar to nitazoxanide. OBJETIVES To evaluate the in vitro activity of CMC-20 against G. intestinalis strains with different susceptibility/resistance to albendazole and nitazoxanide and evaluate its effect on the distribution of parasite cytoskeletal proteins and its in vivo giardicidal activity. METHODS CMC-20 activity was tested against two isolates from patients with chronic and acute giardiasis, an experimentally induced albendazole resistant strain and a nitazoxanide resistant clinical isolate. CMC-20 effect on the distribution of parasite cytoskeletal proteins was analysed by indirect immunofluorescence and its activity was evaluated in a murine model of giardiasis. FINDINGS CMC-20 showed broad activity against susceptible and resistant strains to albendazole and nitaxozanide. It affected the parasite microtubule reservoir and triggered the parasite encystation. In this process, alpha-7.2 giardin co-localised with CWP-1 protein. CMC-20 reduced the infection time and cyst load in feces of G. muris infected mice similar to albendazole. MAIN CONCLUSIONS The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis.


Subject(s)
Humans , Animals , Mice , Thiazoles/pharmacology , Albendazole/pharmacology , Giardia lamblia/drug effects , Cytoskeletal Proteins/drug effects , Antiprotozoal Agents/pharmacology , Thiazoles/chemistry , Time Factors , Albendazole/chemistry , Fluorescent Antibody Technique, Indirect , Parasitic Sensitivity Tests , Antiprotozoal Agents/chemistry
12.
Mem. Inst. Oswaldo Cruz ; 115: e190348, 2020. tab, graf
Article in English | LILACS | ID: biblio-1056773

ABSTRACT

BACKGROUND It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB strain than metronidazole and albendazole and similar to nitazoxanide. OBJETIVES To evaluate the in vitro activity of CMC-20 against G. intestinalis strains with different susceptibility/resistance to albendazole and nitazoxanide and evaluate its effect on the distribution of parasite cytoskeletal proteins and its in vivo giardicidal activity. METHODS CMC-20 activity was tested against two isolates from patients with chronic and acute giardiasis, an experimentally induced albendazole resistant strain and a nitazoxanide resistant clinical isolate. CMC-20 effect on the distribution of parasite cytoskeletal proteins was analysed by indirect immunofluorescence and its activity was evaluated in a murine model of giardiasis. FINDINGS CMC-20 showed broad activity against susceptible and resistant strains to albendazole and nitaxozanide. It affected the parasite microtubule reservoir and triggered the parasite encystation. In this process, alpha-7.2 giardin co-localised with CWP-1 protein. CMC-20 reduced the infection time and cyst load in feces of G. muris infected mice similar to albendazole. MAIN CONCLUSIONS The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis.


Subject(s)
Humans , Animals , Mice , Thiazoles/pharmacology , Albendazole/pharmacology , Giardia lamblia/drug effects , Cytoskeletal Proteins/drug effects , Antiprotozoal Agents/pharmacology , Thiazoles/chemistry , Time Factors , Albendazole/chemistry , Fluorescent Antibody Technique, Indirect , Parasitic Sensitivity Tests , Antiprotozoal Agents/chemistry
13.
Medisan ; 22(3)mar. 2018. tab
Article in Spanish | LILACS | ID: biblio-894698

ABSTRACT

Se realizó un ensayo clínico en fase IV para evaluar la efectividad del Oleozón® aplicado por vía oral en niños y adolescentes con giardiasis, atendidos en la interconsulta de Pediatría del Policlínico Universitario Julián Grimau García de Santiago de Cuba, desde enero hasta diciembre del 2015. El universo estuvo constituido por 116 pacientes (con igual número de casos y controles) en las edades de 1 a 18 años, infectados por Giardia lamblia, quienes presentaban dolor abdominal, vómito y anorexia como síntomas fundamentales. En la serie se obtuvo que el mayor número de los pacientes del grupo experimental, cuyo esquema terapéutico incluía el Oleozón®, resolvió el dolor abdominal y mejoró su estado general al disminuir el resto de los síntomas. Pudo concluirse que el Oleozón® resultó efectivo en el tratamiento contra la giardiasis, pues las muestras de heces fecales dieron negativo en todos los casos; además, no se produjeron reacciones adversas y su costo es bajo, lo que conlleva un impacto económico, social y medioambiental


A clinical assay in phase IV was carried out to evaluate the effectiveness of oral Oleozón® used in children and adolescents with giardiasis, assisted in the Pediatrics specialty consultation from Julián Grimau García University Polyclinic in Santiago de Cuba, from January to December, 2015. The universe was constituted by 116 patients (with the same number of cases and controls) and aged 1 to 18 years, infected by Giardia lamblia who presented abdominal pain, vomit and anorexy as fundamental symptoms. In the series it was obtained that the highest number in the patients of the experimental group whose therapeutic schedule included Oleozón® , solved the abdominal pain and it improved their general state when decreasing the rest of the symptoms. It could be concluded that the Oleozón® was effective in the treatment against giardiasis, because the samples of faeces were negative in all cases; besides, it produced no adverse reactions and its cost is low, what bears an economic, social and environmental impact


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Giardiasis/drug therapy , Evaluation of the Efficacy-Effectiveness of Interventions , Sunflower Oil/therapeutic use , Giardia lamblia/drug effects , Clinical Trial, Phase IV
14.
Mem. Inst. Oswaldo Cruz ; 109(8): 1078-1080, 12/2014. tab, graf
Article in English | LILACS | ID: lil-732594

ABSTRACT

Giardia duodenalis (syn. lamblia; syn. intestinalis) susceptibility testing is not routinely performed because the classical culture methods are very time-consuming and laborious. We developed a novel flow cytometry (FC) assay to evaluate the susceptibility of G. duodenalis trophozoites to metronidazole (MTZ). Different concentrations of MTZ were added to cultures of trophozoites (10 5 /mL) and the cultures were incubated for different periods. The 50% inhibitory concentration was calculated and propidium iodide (PI) was used to quantify the number of dead cells. After treatment, PI-positive trophozoites increased with increasing drug concentration and exposure time. An excellent correlation was found between FC and the classical method. A novel, accurate and reliable method is now available to evaluate G. duodenalis viability. .


Subject(s)
Antiprotozoal Agents/pharmacology , Giardia lamblia/drug effects , Metronidazole/pharmacology , Microbial Viability/drug effects , Flow Cytometry , Giardia lamblia/physiology , Parasitic Sensitivity Tests , Propidium
15.
Rev. gastroenterol. Méx ; 64(3): 122-6, jul.-sept. 1999. tab
Article in Spanish | LILACS | ID: lil-276250

ABSTRACT

Objetivo: comparar la eficacia y seguridad de mebendazol contra nitazoxanida en el tratamiento de Giardia lamblia en niñosLa giardiasis es una protozoosis intestinal de distribución mundial que afecta con mayor frecuencia a la población infantil. En México se ha encontrado una frecuencia de tres a 60 por ciento. Se han utilizado diferentes fármacos para su tratamiento, pero la experiencia con mebendazol y nitazoxanida es escasa..Método: estudio experimental tipo ensayo clínico. Se incluyeron niños de cuatro a doce años de edad, que tuvieran un estudio de heces positivo para quistes de Giardia lamblia. Los niños se dividieron en dos grupos: A, se les administró mebendazol 100 mg cada 12 h, por tres días. B, recibieron nitazoxanida 100 mg cada 12 h, por tres días. Se les realizaron estudios de heces de control a los tres, cinco y siete días posterior al tratamiento. Al final del tratamiento se les preguntó a los padres si los niños habían presentado reacciones secundarias durante la administración del medicamento. Para el análisis estadístico se utilizó la t de Student's y chi cuadradaResultados: se estudiaron 82 niños, 41 (50 por ciento) para cada grupo. En el grupo A, los estudios de heces de una control fueron negativos en 33 para dar una eficacia de 80.4 por ciento; en el B, fueron negativos en 32 para dar una eficacia de 78.0 por ciento, sin ser estadísticamente significativo con una p = 0.8. Las reacciones secundarias fueron encontradas en 9 (22 por ciento) niños del grupo A, y 16 (39 por ciento) en el grupo B, no hubo diferencia estadísticamente significativa con una p = 0.09, sin embargo, el dolor abdominal fue encontrado con mayor frecuencia en los niños que se les administró nitazoxanida..Conclusiones: podemos concluir que tanto el mebendazol como la nitazoxanida tienen buena eficacia contra la infección por Giardia lamblia, sin embargo, las reacciones secundarias por nitazoxanida son más frecuentes que con mebendazol


Subject(s)
Humans , Female , Male , Anthelmintics/adverse effects , Anthelmintics/therapeutic use , Giardia lamblia/drug effects , Mebendazole/adverse effects , Mebendazole/therapeutic use , Feces/parasitology
16.
Rev. mex. pueric. ped ; 6(27): 25-9, ene.-feb. 1998. tab, ilus
Article in Spanish | LILACS | ID: lil-240960

ABSTRACT

Se realizó un estudio in vitro para conocer el efecto farmacológico de prazicuantel sobre los trofozoítos de Giardia intestinalis cepa P-1. Después de cultivarlos axénicamente, con cinco diferentes concentraciones de prazicuantel (de 0.32 hasta 1.62 nM/mL) durante 24 h a 37ºC, la viabilidad y la CI50 evaluada por la captación de colorante fluorogénico con citometría de flujo mostró un desplazamiento logarítmico de 10º a 10 a la tercera lo que correspondió a una concentración de 1.28 nM/mL. La incorporación de H3 metil-timidina como parámetro de crecimiento celular a 50 por ciento alcanzó 1.20 nM/mL de prazicuantel y el efecto citotóxico calculado por la capacidad de lisar células CHO (células de ovario de hámster chino) marcados con Cr51 se observó para la CI50 en una concentración de 1.05 nM/mL. Con estos tres parámetros se puede inferir qué viabilidad a 50 por ciento se observó a concentraciones más altas de prazicuantel comparadas con la capacidad para dividirse, así como el efecto citolítico, en donde la concentraciones más altas de prazicuantel comparadas con la capacidad para dividirse, así como el efecto citolítico, en donde la concentración de prazicuantel fue la más baja a lo que se atribuye la cualidad de apagar radicales libres, sin embargo, esto no fue proporcional al incrementar la concentración suponiéndose una importante capacidad detoxificante en Giardia. Se concluye que prazicuantel desarrolló actividad farmacológica en protozoarios, lo que le hace susceptible de emplearse contra la giardiasis


Subject(s)
Cricetinae , Praziquantel/analysis , Praziquantel/pharmacokinetics , Thymidine/pharmacokinetics , Cell Survival/drug effects , Cricetulus , Giardia lamblia/cytology , Giardia lamblia/drug effects , In Vitro Techniques
17.
Braz. j. med. biol. res ; 30(1): 93-9, Jan. 1997. graf
Article in English | LILACS | ID: lil-187340

ABSTRACT

Giardia lamblia trophozoites were incubated for 2 h with activated murine macrophages, nitric oxide (NO) donors or a superoxide anion generator (20 mU/ml xanthine oxidase plus 1 mM xanthine). Activated macrophages were cytotoxic to Giardia trophozoites (~60 per cent dead trophozoites). This effect was inhibited (>90 per cent) by an NO synthase inhibitor (200 muM) and unaffected by superoxide dismutase (SOD, 300 U/ml). Giardia trophozoites were killed by the NO donors S-nitroso-acetyl-penicillamine(SNAP)and sodium nitroprusside (SNP) in a dose-dependent manner (LD50 300 and 50 muM, respectively). A dual NO-superoxide anion donor, 3-morpholino-sydnonimine hydrochloride (SIN-1), did not have a killing effect in concentration up to 1 mM. However, when SOD (300 U/ml) was added simultaneously with SIN-1 to Giardia, a significant trophozoite-killing effect was observed (~35 per cent dead trophozoites at 1 mM). The mixture of SNAP or SNP with superoxide anion, which yields peroxynitrite, abolished the trophozoite killing induced by NO donors. Authentic peroxynitrite only killed trophozoites at very high concentrations (3 mM). These results indicate that NO accounts for Giardia trophozoite killing and this effect is not mediated by peroxynitrite.


Subject(s)
Mice , Giardia lamblia/drug effects , Giardiasis/drug therapy , Macrophages/metabolism , Nitric Oxide/therapeutic use , Nitroprusside/pharmacology , Penicillamine/pharmacology , Superoxides/therapeutic use , Cell Culture Techniques , Mice, Inbred C57BL , Penicillamine/analogs & derivatives
18.
Rev. mex. pediatr ; 62(3): 94-5, mayo-jun. 1995. tab
Article in Spanish | LILACS | ID: lil-151933

ABSTRACT

Se informa de los resultados del tratamiento son secnidazol de 100 niños entre uno y 12 años. El medicamento se dio a razón de 30 mg/Kg/día, por tres días. El resultado del tratamiento se valoró 10 días después en 95 niños; en ocho la G. lamblia aún estaba presente en las heces por lo que se estimó una efectividad de 84 por ciento. La manifestación indeseable al medicamento que se presentó con mayor frecuencia (36.8 por ciento) fue el ®mal sabor¼


Subject(s)
Adolescent , Humans , Male , Female , Giardia lamblia/drug effects , Giardia lamblia/pathogenicity , Feces/parasitology , Metronidazole/administration & dosage , Metronidazole/analogs & derivatives , Metronidazole/adverse effects
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