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1.
Int J Pharm ; 663: 124586, 2024 Sep 30.
Article de Anglais | MEDLINE | ID: mdl-39147249

RÉSUMÉ

This study demonstrates the application of Langmuir and Langmuir-Blodgett films as biomimetic drug reservoirs and delivery systems to investigate the effect of an anthelmintic on cancer cell culture. The repurposing of benzimidazole anthelmintics for cancer therapy due to their microtubule-inhibiting properties has gained attention, showing promising anticancer effects and tumor-suppressive properties. Although widely used in medicine, the low aqueous solubility of benzimidazole compounds poses challenges for studying their effects on cancer cells, requiring incorporation into various formulations. Our study demonstrates that incorporating albendazole into stable Palmitic Acid Langmuir monolayers, forming Langmuir-Blodgett films, significantly affects the proliferation of liver carcinoma cells. This report presents the initial findings of the effect of an antitumoral drug on cancer cell culture using a simple and repeatable methodology.


Sujet(s)
Albendazole , Antinéoplasiques , Prolifération cellulaire , Systèmes de délivrance de médicaments , Albendazole/composition chimique , Albendazole/administration et posologie , Albendazole/pharmacologie , Humains , Systèmes de délivrance de médicaments/méthodes , Antinéoplasiques/composition chimique , Antinéoplasiques/administration et posologie , Antinéoplasiques/pharmacologie , Prolifération cellulaire/effets des médicaments et des substances chimiques , Cellules HepG2 , Lignée cellulaire tumorale , Anthelminthiques/composition chimique , Anthelminthiques/administration et posologie , Anthelminthiques/pharmacologie , Solubilité , Propriétés de surface
2.
BMC Infect Dis ; 24(1): 737, 2024 Jul 25.
Article de Anglais | MEDLINE | ID: mdl-39060987

RÉSUMÉ

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.


Sujet(s)
Albendazole , Anthelminthiques , Échinococcose , Praziquantel , Humains , Albendazole/usage thérapeutique , Albendazole/administration et posologie , Praziquantel/usage thérapeutique , Praziquantel/administration et posologie , Échinococcose/traitement médicamenteux , Échinococcose/chirurgie , Mâle , Femelle , Uruguay , Adulte , Adulte d'âge moyen , Études de suivi , Anthelminthiques/usage thérapeutique , Anthelminthiques/administration et posologie , Jeune adulte , Résultat thérapeutique , Adolescent , Sujet âgé , Association de médicaments
3.
Am J Trop Med Hyg ; 111(1): 80-88, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38806041

RÉSUMÉ

In countries where soil-transmitted helminth (STH) infections are endemic, deworming programs are recommended to reduce morbidity; however, increasing levels of resistance to benzimidazoles are of concern. In an observational study in Peru, we studied the clinical efficacy of 400 mg of albendazole 20 days after treatment among children aged 2-11 years. Of 426 participants who provided samples, 52.3% were infected with a STH, 144 (33.8%) were positive for Ascaris (41.8% light, 50.8% moderate, and 7.4% heavy infections), 147 (34.5%) were positive for Trichuris (75.2% light, 22.5% moderate, and 2.3% heavy infections), and 1.1% were positive for hookworm species (100% light infections). Additional stool samples were examined at 20, 90, and 130 days after the initial treatment. At 20 days post-administration of albendazole, the cure rate (CR) of Ascaris infection was 80.1% (95% CI: 73.5-86.7), and the egg reduction rate (ERR) was 70.8% (95% CI: 57.8-88.7); the CR for Trichuris infection was 27.1% (95% CI: 20.0-34.3), and the ERR was 29.8% (95% CI: -1.40 to 57.5). Among participants with persistent or recurrent infections with Trichuris, the combined therapy of albendazole (400 mg) and ivermectin at 600 µg/dose increased overall CR for Trichuris infection to 75.2% (95% CI: 67.3-83.2%) with an ERR of 84.2% (95% CI: 61.3-93.8%). Albendazole administration alone for the control of STH was associated with high rates of treatment failure, especially for Trichuris. Combined single doses of albendazole and ivermectin was observed to have improved efficacy.


Sujet(s)
Albendazole , Anthelminthiques , Helminthiase , Ivermectine , Sol , Humains , Albendazole/usage thérapeutique , Albendazole/administration et posologie , Pérou/épidémiologie , Enfant d'âge préscolaire , Enfant , Ivermectine/usage thérapeutique , Ivermectine/administration et posologie , Mâle , Femelle , Sol/parasitologie , Helminthiase/traitement médicamenteux , Helminthiase/épidémiologie , Anthelminthiques/usage thérapeutique , Anthelminthiques/administration et posologie , Fèces/parasitologie , Association de médicaments , Animaux , Résultat thérapeutique , Trichocéphalose/traitement médicamenteux , Trichocéphalose/épidémiologie , Ascaridiose/traitement médicamenteux , Ascaridiose/épidémiologie , Trichuris/effets des médicaments et des substances chimiques
4.
Int J Parasitol Drugs Drug Resist ; 24: 100527, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38447333

RÉSUMÉ

Haemonchus contortus and Trichostrongylus colubriformis are the most important gastrointestinal nematodes causing serious losses in sheep production of tropical and subtropical regions. Prophylaxis of gastrointestinal nematode infections is based on anthelmintics use, but their frequent administration selects multiple-resistant parasites. To evaluate how the situation has changed over the last decades, the anthelmintic resistance status of gastrointestinal nematodes in sheep flocks was assessed in the current study and compared to previous surveys. In each one of the 15 flocks evaluated, animals (n ≥ 7) were allocated into at least five groups and treated as follows: 1) untreated control; 2) albendazole; 3) levamisole; 4) ivermectin; and 5) monepantel. If more animals were available, two additional groups were included: 6) closantel, and 7) moxidectin. The faecal egg count reduction test (FECRT) was carried out to evaluate the pre- and post-treatment using the SHINY tool. Haemonchus spp. was the most prevalent nematode from faecal cultures. The mean efficacy of albendazole was 40%. Only in two farms, levamisole presented a relatively high percentage of reduction in the FECRT about 90%, while ivermectin and moxidectin presented the worst mean efficacy of 34% and 21% among all farms, respectively. Like other anthelmintics, closantel demonstrated low efficacy (63%) across all farms evaluated. Monepantel presented an overall mean efficacy of 79%, but it was the only anthelmintic that presented efficacy ≥95%, in five farms. The results revealed that gastrointestinal nematodes with multiple anthelmintic resistance were prevalent in all 15 sheep herds. The research suggests that nematodes are becoming more and more resistant to various anthelmintic compounds, which has made the problem worse. This circumstance highlights the necessity to put into practice sustainable and long-lasting methods to prevent gastrointestinal nematode infections in sheep husbandry.


Sujet(s)
Amino-acétonitrile/analogues et dérivés , Anthelminthiques , Haemonchus , Macrolides , Nematoda , Nématodoses , Salicylanilides , Maladies des ovins , Animaux , Ovis , Lévamisole/pharmacologie , Lévamisole/usage thérapeutique , Ivermectine/usage thérapeutique , Albendazole/usage thérapeutique , Brésil/épidémiologie , Anthelminthiques/pharmacologie , Anthelminthiques/usage thérapeutique , Nématodoses/traitement médicamenteux , Nématodoses/épidémiologie , Nématodoses/médecine vétérinaire , Fèces/parasitologie , Maladies des ovins/traitement médicamenteux , Maladies des ovins/épidémiologie , Maladies des ovins/parasitologie , Numération des oeufs de parasites/médecine vétérinaire , Résistance aux substances
5.
Sci Rep ; 14(1): 6271, 2024 03 15.
Article de Anglais | MEDLINE | ID: mdl-38491091

RÉSUMÉ

Soil-transmitted-helminth (STH) infections continue to be a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA). Coverage and compliance assessment is critical to understanding the true effectiveness of albendazole (ABZ) in those MDA programs. The aims of this work were to characterize the pattern of albendazole and metabolites excretion in human saliva, and to develop a saliva-based biomarker (HPLC drug/metabolite detection) useful to accurately estimate the coverage/compliance in MDA campaigns. The study subjects were 12 healthy volunteers treated with a single oral dose of ABZ (400 mg). Saliva and blood (dried blood spot, DBS) samples were taken previously and between 2 and 72 h post-treatment. The samples were analyzed by HPLC with UV detection, C18 reversed-phase column. ABZ sulphoxide was the main analyte recovered up to 72 h p.t. in blood and saliva. The concentration profiles measured in the blood (DBS samples) were higher (P < 0.05) than those in saliva, however, this ABZ-metabolite was recovered longer in saliva. The in vivo measurement of drugs/metabolites in saliva samples from ABZ-treated volunteers offers strong scientific evidence to support the use of saliva as a valid biological sample for assessing compliance in MDA programs.


Sujet(s)
Albendazole , Anthelminthiques , Humains , Albendazole/usage thérapeutique , Salive/métabolisme , Administration massive de médicament , Observance par le patient
6.
Rev Soc Bras Med Trop ; 57: e008012024, 2024.
Article de Anglais | MEDLINE | ID: mdl-38451691

RÉSUMÉ

We report a case of eosinophilic meningitis associated with the ingestion of raw fish (Cichla sp.) from the Brazilian Amazon, likely caused by Gnathostoma. A 36-year-old male visited Juruena river on a fishing trip. After 50 days, the patient presented with an intense frontal headache. A cerebrospinal fluid examination revealed 63% eosinophilia. Another individual who ingested raw fish developed linear dermatitis on the abdominal wall. Anti-Gnathostoma serum antibodies were detected, and the patient made a full recovery after treatment with corticosteroids and albendazole. To date, autochthonous Gnathostoma spp. infections in Latin American countries have only caused linear panniculitis. This report raises awareness of gnathostomiasis-causing meningitis.


Sujet(s)
Gnathostomose , Méningite , Animaux , Mâle , Humains , Adulte , Gnathostomose/diagnostic , Gnathostomose/traitement médicamenteux , Brésil , Méningite/diagnostic , Méningite/traitement médicamenteux , Albendazole/usage thérapeutique , Consommation alimentaire
7.
Brain Pathol ; 34(5): e13237, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38212958

RÉSUMÉ

Despite being a leading cause of acquired seizures in endemic regions, the pathological mechanisms of neurocysticercosis are still poorly understood. This study aims to investigate the impact of anthelmintic treatment on neuropathological features in a rat model of neurocysticercosis. Rats were intracranially infected with Taenia solium oncospheres and treated with albendazole + praziquantel (ABZ), oxfendazole + praziquantel (OXF), or untreated placebo (UT) for 7 days. Following the last dose of treatment, brain tissues were evaluated at 24 h and 2 months. We performed neuropathological assessment for cyst damage, perilesional brain inflammation, presence of axonal spheroids, and spongy changes. Both treatments showed comparable efficacy in cyst damage and inflammation. The presence of spongy change correlated with spheroids counts and were not affected by anthelmintic treatment. Compared to white matter, gray matter showed greater spongy change (91.7% vs. 21.4%, p < 0.0001), higher spheroids count (45.2 vs. 0.2, p = 0.0001), and increased inflammation (72.0% vs. 21.4%, p = 0.003). In this rat model, anthelmintic treatment destroyed brain parasitic cysts at the cost of local inflammation similar to what is described in human neurocysticercosis. Axonal spheroids and spongy changes as markers of damage were topographically correlated, and not affected by anthelmintic treatment.


Sujet(s)
Anthelminthiques , Encéphale , Neurocysticercose , Taenia solium , Animaux , Neurocysticercose/traitement médicamenteux , Neurocysticercose/anatomopathologie , Rats , Anthelminthiques/usage thérapeutique , Encéphale/anatomopathologie , Encéphale/parasitologie , Albendazole/usage thérapeutique , Albendazole/pharmacologie , Praziquantel/usage thérapeutique , Modèles animaux de maladie humaine , Mâle , Femelle , Benzimidazoles
8.
Braz. j. biol ; 84: e250723, 2024. tab
Article de Anglais | LILACS, VETINDEX | ID: biblio-1355902

RÉSUMÉ

Abstract This study assessed the anthelminthic feed additive albendazole effect on the main indicators of the quality of sheep meat obtained from infected and deworming animals. A total of 20 heads of Akzhaik meat and wool sheep (i.e. 2 years of age, of different sex) were used in a 20-day experiment and 2 groups of 10 heads were formed (n = 4). The sheep were fed with the basic diet (i.e. control, group CON), without adding anything, and the second group was fed the basic diet orally with the addition of a dose of 1.2 g / head (an experimental group). At the end of the experiment, a control slaughter was carried out from each group in order to study the biochemical composition of meat and its quality. The anthelmintic feed additive albendazole did not have a significant effect on the indicators (organoleptic and physicochemical) of meat quality (P> 0.04). However, the ratio of fat and ash in the meat of the control group has differences in indicators and is reduced by 24.81% and 0.03%, respectively. The drug had a significant effect on the biological value of meat in the experimental group, where there is a higher content of essential amino acids (P = 0.06), nonessential (P = 0.05) concentrations in comparison with the CON groups. The results obtained show that the meat of the experimental groups of sheep, when using the anthelminthic feed additive albendazole, did not have a significant effect on organoleptic parameters, but significantly positively influenced the metabolism, live weight gain and biological value of meat.


Resumo Este estudo avaliou o efeito do aditivo anti-helmíntico albendazol sobre os principais indicadores de qualidade da carne ovina obtida de animais infectados e desparasitados. Um total de 20 cabeças de carne Akzhaik e ovelhas de lã (ou seja, 2 anos de idade, de sexo diferente) foi usado em um experimento de 20 dias e dois grupos de 10 cabeças foram formados (n = 4). As ovelhas foram alimentadas com dieta básica (ou seja, controle, grupo CON), sem adicionar nada, e o segundo grupo foi alimentado com dieta básica por via oral com a adição de uma dose de 1,2 g / cabeça (um grupo experimental). Ao final do experimento, foi realizado um abate controle de cada grupo para estudar a composição bioquímica da carne e sua qualidade. O aditivo anti-helmíntico albendazol não teve efeito significativo sobre os indicadores (organolépticos e físico-químicos) de qualidade da carne (P > 0,04). No entanto, a proporção de gordura e cinzas na carne do grupo de controle tem diferenças nos indicadores e é reduzida em 24,81% e 0,03%, respectivamente. A droga teve efeito significativo sobre o valor biológico da carne no grupo experimental, onde há maior teor de aminoácidos essenciais (P = 0,06), concentrações não essenciais (P = 0,05) em comparação com os grupos CON. Os resultados obtidos mostram que a carne dos grupos experimentais de ovinos, ao utilizar o aditivo anti-helmíntico albendazol, não teve efeito significativo nos parâmetros organolépticos, mas influenciou positivamente de forma significativa no metabolismo, ganho de peso vivo e valor biológico da carne.


Sujet(s)
Animaux , Aliment pour animaux/analyse , Anthelminthiques , Ovis , Albendazole , Régime alimentaire/médecine vétérinaire , Viande/analyse
9.
Rev Paul Pediatr ; 42: e2023077, 2023.
Article de Anglais | MEDLINE | ID: mdl-38126440

RÉSUMÉ

OBJECTIVE: To describe the first known case of human Bertiellosis in Paraná (Brazil). CASE DESCRIPTION: A 6-year-old male residing in the Brazilian state of Paraná was suffering from intermittent nonspecific abdominal pain and abdominal distension, associated with expulsion of live tapeworms in his feces for 7 months. He had a history of interaction with monkeys on an island. His first feces analysis was inconclusive, with an initial hypothesis of an atypical Taenia. However, after additional research, the parasitologist identified pregnant proglottids of Bertiella sp. The patient was initially treated with an unknown dosage of albendazole and nitazoxanide, as it was believed he had been infected with Taenia sp. Since the symptoms persisted, praziquantel 10 mg/kg was prescribed without further proglottids elimination. COMMENTS: Human Bertiellosis is a rare zoonosis, with less than one hundred cases reported. However, it is a cause of chronic abdominal pain and should be kept as a differential diagnosis, especially in cases reporting recurrent tapeworm expulsion in feces and refractory treatment with albendazole.


Sujet(s)
Cestoda , Infections à cestodes , Mâle , Enfant , Animaux , Humains , Brésil , Albendazole/usage thérapeutique , Infections à cestodes/diagnostic , Douleur abdominale/étiologie
10.
J Parasitol ; 109(6): 537-542, 2023 11 01.
Article de Anglais | MEDLINE | ID: mdl-37944597

RÉSUMÉ

Intestinal parasites continue to be a public health problem in low- and middle-income countries. Broad use of anthelmintics during deworming programs is still necessary in many regions. However, description of the usage of these medications in general medical practice has been limited. The objective of this study was to determine the use of anthelmintic drugs and their indications in a group of Colombian patients. This was a descriptive study from a drug-dispensing database, identifying patients with prescriptions for anthelmintic drugs. A total of 381 cases were randomly selected, and their medical records were reviewed, analyzing sociodemographic, clinical, and pharmacological variables (indication of use). The lack of diagnosis registration or clinical manifestations of parasites was determined as a prescription without indication. In total, 50.9% (n = 194) of patients were female, and 67.4% of all patients were under 18 yr of age. The diagnosis of helminthiases was clearly stated in 114 (29.9%) patients, and only 4.2% (n = 16) of these had microbiological confirmation. The most commonly used anthelmintic drug was albendazole (70.4% of all prescriptions). The use of anthelmintics was not indicated in 266 cases (69.8%). Nutritional supplements or vitamin prescriptions were associated with using anthelmintics without indication (odds ratio: 2.25; 95% confidence interval: 1.26-4.03). A high proportion of patients lacked symptoms or diagnoses in their clinical records that supported the use of anthelmintic drugs.


Sujet(s)
Anthelminthiques , Helminthiase , Adolescent , Adulte , Enfant , Femelle , Humains , Mâle , Albendazole/usage thérapeutique , Anthelminthiques/usage thérapeutique , Colombie/épidémiologie , Études transversales , Helminthiase/traitement médicamenteux , Helminthiase/épidémiologie
11.
Vet Parasitol Reg Stud Reports ; 45: 100927, 2023 10.
Article de Anglais | MEDLINE | ID: mdl-37783530

RÉSUMÉ

In the fall of 2022, decreased triclabendazole (TCBZ) efficacy against F. hepatica was suspected in a sheep farm located in the Santa Cruz province, Argentinian Patagonia. Since TCBZ-resistance in F. hepatica has never been reported in this province, this study aimed to confirm potential TCBZ-resistance in F. hepatica and to evaluate the efficacy of closantel (CLO) and nitroxinil (NTX), through faecal egg count reduction test (FECRT), and the efficacy of albendazole (ABZ) through the in vitro egg hatch test (EHT) in sheep. Sixty-eight (68) animals were selected from a herd of eighty (80) female Merino naturally infected with F. hepatica based on eggs per gram of F. hepatica (EPGFh) counts and assigned into four (4) groups (n = 17 per group): Group Control, animals did not receive anthelmintic treatment; Group TCBZ, animals were orally treated with TCBZ (12 mg/kg); Group CLO, animals were orally treated with CLO (10 mg/kg); and Group NTX, animals were subcutaneously treated with NTX (10 mg/kg). The fluke egg output was monitored on days 0 and 21 post-treatment. For the EHT, liver fluke eggs were isolated from faecal samples (approx. 50 g) collected from animals of the control group. TCBZ efficacy against liver fluke was 53.4%, confirming the presence of TCBZ-resistant isolates on the farm. CLO and NTX were highly effective (100%) for the treatment of F. hepatica on this farm. The EHT was carried out in two different laboratories, in which was observed an ABZ efficacy of 95.8 (Bariloche) and 96.5% (Tandil). These results indicate the ABZ susceptibility of this F. hepatica isolate and the inter-laboratory precision of the test.


Sujet(s)
Fasciola hepatica , Fasciolase , Maladies des ovins , Femelle , Ovis , Animaux , Triclabendazole/usage thérapeutique , Fasciolase/traitement médicamenteux , Fasciolase/médecine vétérinaire , Benzimidazoles/pharmacologie , Benzimidazoles/usage thérapeutique , Résistance aux substances , Maladies des ovins/traitement médicamenteux , Albendazole/pharmacologie , Albendazole/usage thérapeutique , Nitroxinil , Ovis aries
12.
Int J Mol Sci ; 24(19)2023 Oct 06.
Article de Anglais | MEDLINE | ID: mdl-37834396

RÉSUMÉ

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.


Sujet(s)
Antiprotozoaires , Giardia lamblia , Giardiase , Animaux , Souris , Albendazole/composition chimique , Giardiase/traitement médicamenteux , Giardiase/parasitologie , Antiprotozoaires/pharmacologie , Antiprotozoaires/usage thérapeutique , Tubuline , Simulation de docking moléculaire , Solubilité
13.
AAPS PharmSciTech ; 24(6): 158, 2023 Jul 27.
Article de Anglais | MEDLINE | ID: mdl-37498473

RÉSUMÉ

Albendazole is a broad-spectrum anthelmintic drug used for parasitic infections. In addition, due to its mechanism of action, it has been studied as an anticancer agent. However, poor and highly variable bioavailability are limiting factors for its use in systemic illnesses. The present study aimed to develop two parenteral formulations of albendazole and to compare its pharmacokinetic profile with the conventional oral administration. Parenteral formulations were developed using two different approaches: a phosphonooxymethylated prodrug and cosolvents. For the albendazole prodrug, once synthetized, its solubility and hydrolysis with alkaline phosphatase were evaluated. A factorial design of experiments was used for the cosolvent formulation. Stability and hemolytic activity were assessed. A pharmacokinetic study was performed on New Zealand rabbits. Both formulations were administered intravenously, and the prodrug was also administered intramuscularly. Results were compared with those obtained after the oral administration of albendazole. A 20,000-fold and 6000-fold increase in albendazole solubility was found with the prodrug and cosolvent formulations, respectively. Both parenteral formulations displayed higher albendazole plasma concentrations for the first 2 h compared with oral administration, even when the oral dose was doubled. The absolute bioavailability of oral albendazole was 15.5% while for the intramuscular administration of the prodrug was 102.6%. Both parenteral formulations showed a significant decrease in the formation of albendazole sulfoxide (ANOVA p<0.05) and allowed greater exposure to albendazole. Albendazole cosolvent parenteral formulation could be a promising option in systemic illnesses considering its ease of preparation and superb pharmacokinetic performance.


Sujet(s)
Anthelminthiques , Antinéoplasiques , Promédicaments , Animaux , Lapins , Albendazole , Promédicaments/pharmacocinétique , Biodisponibilité , Administration par voie orale
14.
Infect Immun ; 91(7): e0051722, 2023 07 18.
Article de Anglais | MEDLINE | ID: mdl-37341599

RÉSUMÉ

Parasitic diseases are a major public health problem worldwide. Plant-derived products appear to be ideal candidates from a biotechnological perspective, being sustainable and environmentally friendly. The antiparasitic properties of Carica papaya have been attributed to some of its components, including papain and other compounds that are concentrated in the latex and seeds. This study demonstrated in vitro a high and insignificantly different cysticidal activity of soluble extract that was obtained after the disruption of nontransformed wild-type (WT) cells as well as transformed papaya calluses (PC-9, PC-12, and PC-23) and papaya cell suspensions (CS-9, CS-12, and CS-23). In vivo, cell suspensions of CS-WT and CS-23 that had been previously lyophilized were tested with respect to their cysticidal effects, compared with those of three commercial antiparasitic drugs. CS-WT and CS-23 together reduced the number of cysticerci, the number of buds, and the percentage of calcified cysticerci in a similar extent to albendazole and niclosamide, whereas ivermectin was less effective. Mice were then orally immunized with CS-23 that expressed the anti-cysticercal KETc7 antigen (10 µg/mouse), CS-WT (10 mg/mouse), or both together to evaluate their preventive properties. CS-23 and CS-WT significantly reduced the expected parasite and increased the percentage of calcified cysticerci as well as recovery, being more effective when employed together. The results reported in this study support the feasibility of the development of an anti-cysticercosis vaccine from cells of C. papaya in in vitro cultures, as they are a source of an anthelmintic, natural, and reproducible product.


Sujet(s)
Carica , Souris , Animaux , Suspensions , Albendazole , Extraits de plantes/pharmacologie , Graines
15.
Exp Parasitol ; 251: 108568, 2023 Aug.
Article de Anglais | MEDLINE | ID: mdl-37327965

RÉSUMÉ

Neurocysticercosis (NCC) is a public health issue in endemic regions and is considered the main preventable cause of neurologic disease. It is caused by the presence of Taenia solium cysticercus in the central nervous system. The current treatment is performed with anthelminthic drugs - albendazole (ABZ) or praziquantel - associated with anti-inflammatory and corticosteroids in order to prevent the negative effects of the inflammatory reaction to the parasite's death. Ivermectin (IVM) is an anthelminthic drug that has been shown to present an anti-inflammatory effect. The aim of this study was to was to evaluate the histopathologic aspects of experimental NCC after in vivo treatment with a combination of ABZ-IVM. Balb/c mice were intracranially inoculated with T. crassiceps cysticerci and after 30 days of infection were treated with a single dose of NaCl 0.9% (control group), ABZ monotherapy (40 mg/kg), IVM monotherapy (0.2 mg/kg) or a combination of ABZ-IVM. 24h after the treatment the animals were euthanized and the brain was removed for histopathologic analysis. The IVM monotherapy and ABZ-IVM combination showed more degenerated cysticerci, less inflammatory infiltration, meningitis and hyperemia than the other groups. Therefore, it is possible to recommend the combination of albendazole and ivermectin as alternative chemotherapy for NCC due to its antiparasitic and anti-inflammatory effects, with potential to decrease the negative effects of the inflammatory burst when the parasite is killed within the CNS.


Sujet(s)
Anthelminthiques , Neurocysticercose , Animaux , Souris , Albendazole/pharmacologie , Albendazole/usage thérapeutique , Neurocysticercose/traitement médicamenteux , Ivermectine/pharmacologie , Ivermectine/usage thérapeutique , Anthelminthiques/pharmacologie , Cysticercus , Inflammation/traitement médicamenteux , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/usage thérapeutique
16.
Vet Parasitol ; 318: 109929, 2023 Jun.
Article de Anglais | MEDLINE | ID: mdl-37080069

RÉSUMÉ

Citrus fruits are consumed all over the world and their by-products are used for animal feed and essential oils production. This study aimed to evaluate the in vitro and in vivo activity of Citrus aurantium var. Dulcis essential oil (CaEO) combined with ABZ against benzimidazole resistant Haemonchus contortus. In vitro egg hatching assays (EHA) were performed using CaEO and ABZ to estimate the effective concentration to achieve 50% egg death (EC50) values and calculate the test essential oil and drug combinations using a simplex-centroid mixture design. These concentrations were used for a second round of EHAs. Sixteen sheep were randomly allocated into two groups and treated with ABZ and the combination of CaEO and ABZ, and faecal egg count reduction tests were performed. In the first round of EHA, CaEO and ABZ showed EC50 values of 0.57 and 0.0048 mg mL-1, respectively. The H. contortus strain used in the study was shown to be highly benzimidazole resistant, with only 1.5% of parasites having susceptible ß-tubulin SNP genotypes. The ABZ reduced the shedding of nematode eggs by 78%, however, its combination with CaEO reduced faecal egg counts by only 9%. The present study is important to highlight the interferences of natural products in anthelmintic metabolism and consequently in drug efficacy.


Sujet(s)
Anthelminthiques , Citrus , Infections à Haemonchus , Haemonchus , Nematoda , Huile essentielle , Maladies des ovins , Animaux , Ovis , Albendazole/pharmacologie , Albendazole/usage thérapeutique , Huile essentielle/pharmacologie , Huile essentielle/usage thérapeutique , Anthelminthiques/pharmacologie , Anthelminthiques/usage thérapeutique , Benzimidazoles/pharmacologie , Fèces/parasitologie , Maladies des ovins/traitement médicamenteux , Maladies des ovins/parasitologie , Numération des oeufs de parasites/médecine vétérinaire , Résistance aux substances , Infections à Haemonchus/traitement médicamenteux , Infections à Haemonchus/médecine vétérinaire , Infections à Haemonchus/parasitologie
17.
Rev. chil. infectol ; Rev. chil. infectol;40(2): 174-177, abr. 2023. ilus
Article de Espagnol | LILACS | ID: biblio-1441407

RÉSUMÉ

La hidatidosis o equinococosis quística es una zoonosis parasitaria endémica causada por el estadio larvario del cestode Echinococcus granulosus. El hígado y el pulmón son los órganos con afección más frecuente. Su ubicación subcutánea es una entidad rara, poco descrita, y por ende un reto diagnóstico. Describimos el caso de una mujer, de 18 años de edad, procedente de un área endémica, que presentó un quiste hidatídico primario supraclavicular.


Hydatid disease or cystic echinococcosis is an endemic parasitic zoonosis caused by the larval stage of the cestode Echinococcus granulosus, the liver and lung being the most frequently affected organs. Its subcutaneous location is a rare entity, little described, and therefore a diagnostic challenge. We describe the case of an 18-year-old woman from an endemic area who presented with a primary supraclavicular hydatid cyst.


Sujet(s)
Humains , Femelle , Adolescent , Échinococcose/chirurgie , Échinococcose/diagnostic , Échinococcose/traitement médicamenteux , Albendazole/usage thérapeutique , Cytoponction , Echinococcus granulosus , Antihelminthiques anticestodes/usage thérapeutique
20.
Arch. argent. pediatr ; 121(1): e202102500, feb. 2023. ilus
Article de Anglais, Espagnol | LILACS, BINACIS | ID: biblio-1413458

RÉSUMÉ

La hidatidosis pancreática representa el 0,2-0,6 % de los casos, siendo la población pediátrica la de mayor riesgo. Las lesiones suelen localizarse en cabeza del páncreas (50-58 %); la localización en cuerpo y cola del páncreas se encuentra en el 24-34 % y el 19 %, respectivamente. Dada la posibilidad de complicaciones, suele realizarse tratamiento quirúrgico. Se sugiriere indicar albendazol antes y después del acto quirúrgico por los riesgos de ruptura y diseminación de los protoescólices. Se presenta el caso de una niña de 5 años de edad con dolor abdominal progresivo y lesión quística en páncreas compatible con hidatidosis en la ultrasonografía. En la tomografía computada se observa compresión de la vía biliar. La hemoaglutinación indirecta fue negativa. Presentó elevación de la bilirrubina total, con franco predominio de bilirrubina directa, y aumento de enzimas hepáticas. Se realizó laparotomía exploradora, colecistectomía y destechamiento del quiste. Evolucionó favorablemente, continuó con albendazol durante 3 meses luego de la cirugía.


Pancreatic echinococcosis accounts for 0.2­0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of the pancreas (50­58%); and in the body and tail in 24­34% and 19% of cases, respectively. Given the potential complications, surgery is usually performed. Albendazole is recommended before and after the surgery due to the risks for rupture and dissemination of protoscolices. Here we describe the case of a 5-year-old girl with progressive abdominal pain and cystic lesion in the pancreas compatible with echinococcosis in the ultrasound. The computed tomography showed bile duct compression. Indirect hemagglutination was negative. She had elevated total bilirubin, with a clear predominance of direct bilirubin, and high liver enzymes. Exploratory laparotomy, cholecystectomy, and unroofing of the cyst were performed. The patient had a favorable course and continued with albendazole for 3 months after the surgery.


Sujet(s)
Humains , Femelle , Enfant d'âge préscolaire , Maladies du pancréas/chirurgie , Maladies du pancréas/complications , Maladies du pancréas/diagnostic , Échinococcose/chirurgie , Échinococcose/complications , Échinococcose/diagnostic , Pancréas , Albendazole/usage thérapeutique , Abdomen
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