Diclazuril Protects against Maternal Gastrointestinal Syndrome and Congenital Toxoplasmosis (original) (raw)
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Frontiers in microbiology, 2014
Toxoplasmosis is a major cause of foodborne disease, congenital complication, and morbidity. There is an urgent need for safe and effective therapies to encounter congenital and persisting toxoplasmosis. The hypothesis was: combination diclazuril plus atovaquone to exert a novel therapeutic synergy to prevent toxoplasmosis syndromes. Pregnant dams were treated with diclazuril and atovaquone monotherapy or combination therapy and infected i.p with Toxoplasma tachyzoites. Infected dams developed severe toxoplasmosis associated syndrome with increases in the abdominal adiposity surrounding uteri, gansterointestinal and other internal organs and excessive weight gain. Numerous organisms along with infiltration of inflammatory cells were detected scattered into adipose tissues. Combination therapy (p < 0.01) and to a lesser extent diclazuril (p < 0.05) protected dams from inflammatory fat and excess weight gains. This was consistent with pancreatitis development in infected dams (v...
Gastroenterology & Hepatology: Open Access, 2017
Diarrheal diseases are the second leading cause of death in children under 5 years of age. Their symptoms are caused by viruses, bacteria or parasites that reach the digestive tract. In Argentina the bacterial etiology is the most common. Its most common etiology is related to Shigella or enter hemorrhagic Escherichia coli producing Shiga toxin (Stx), which are responsible for endemoepidemic hemolytic uremic syndrome (HUS) in Argentina. Recent studies have analyzed and clarified some of the mechanisms involved in the therapeutic effects of bismuth hydroxide gel (BHG). The latest research focused on identifying its effects on the growth and pathogen city factors of various microorganisms responsible for gastrointestinal infections, including human Rotavirus Wa, E. coli and Shigella, as well as those strains that produce Stx and Campylobacter jejuni. The research identified the ability of BHG to block the spread of genes that encode Stx mediated by lambdoid phages and its inhibitory action on Stx in the human colon. It reports on advances in knowledge about the effect of BHG on enterotoxigenic E. coli in the bovine reservoir and its influence on limiting the potential contamination of meat and its derivatives. The reviewed research clarifies the mechanisms involved in the therapeutic action of BHG. It affected three events intervening in the process of bacterial adhesion and colonization: fimbriation, mobility and surface hydrophobicity. It inhibits the replication of the phage transmitting the Stx gene and the cytotoxic action of Stx2 in the human colon.
Effect of Propranolol Alone and in Combination with Pyrimethamine on Acute Murine Toxoplasmosis
Jundishapur Journal of Microbiology, 2015
Background: Toxoplasmosis is a public health problem worldwide. This complication principally affects immunodeficient patients and pregnant women. Toxoplasma gondii is an opportunistic parasite, causing severe illness among and death of high-risk individuals and treatment is becoming increasingly difficult owing to side effects and low efficacies of drugs. Objectives: In this study, we investigated the anti-Toxoplasma gondii efficacy of propranolol in vivo. Materials and Methods: This study was performed in two separate pre-treatment and post-treatment groups. In each group, 18 female Balb/c mice in six subgroups (n = 3) were used to assess the anti-Toxoplasma effect of propranolol at 2 and 3 mg/kg/day, pyrimethamine at 50 mg/kg/day, propranolol at 2 and 3 mg/kg/day plus pyrimethamine, and phosphate-buffered saline (PBS; as negative control). Treatment was performed 4, 24, and 48 hours before and after an intraperitoneal challenge of 1 × 10 3 tachyzoites of the virulent RH strain of T. gondii, in pre-treatment and post-treatment groups. Mice peritoneal exudates were collected on the seventh day after the challenge and parasite numbers were recorded as percent of growth inhibition and survival rate. Results: In the pre-treatment group, results showed that propranolol at 2 and 3 mg/kg combined with pyrimethamine was more effective in inhibiting growth of tachyzoites (86% and 98%, respectively) when compared with propranolol at 2 and 3 mg/kg (37% and 39%, respectively) and pyrimethamine (41%) alone. In the post-treatment group, all combined treatments significantly reduced parasite load. The growth inhibition of tachyzoites in mice receiving propranolol (2 and 3 mg/kg) was 75% and 51%, with the mean tachyzoites count being 1526 ± 171.4 and 2948 ± 1452.8, respectively, compared with pyrimethamine treatment outcome, which represents 99.9% growth inhibition. Conclusions: Our results demonstrated the promising prophylactic and therapeutic effects of propranolol against T. gondii infection. Propranolol also increases the efficacy of pyrimethamine in combination therapies.
Experimental Toxoplasmosis: Evaluation of the Hepatic Damage in Murines
Revista de Patologia Tropical, 2014
Toxoplasma gondii is the most common protozoan found in animals and humans and has been found in several of the host's organs, including the liver. This study aimed to evaluate hepatic injury in experimental toxoplasmosis caused by two strains of T. gondii (RH and Me-49 strains). Biochemical and histopathological analyses were performed. It was possible to detect significant increases in serum levels of AST, ALT and LDH in both infections. The histopathological analysis showed inflammatory infiltration in the Me-49 strain infection and hyperemia and vasodilation in the RH strain infection. The acute infection (RH strain) induced hepatic failure and the death of the host. The chronic infection (ME-49 strain) caused liver damage but not enough to kill the host. Therefore this study validates the importance of biochemical concentrations for the evaluation of the infection, showing the importance of rigorous clinical assessment of T. gondii infected individuals.
Pharmacological Research, 2003
The aim of this study was to investigate whether Toxocara canis infection in guinea pigs provokes changes in ileum responsiveness to histamine. Ileum segments from control and T. canis-infected groups were placed at isometric conditions and submitted to various doses of histamine. No changes were observed between controls and T. canis-infected groups at days 3, 6 and 12 after infection. However, at days 18 and 24 after infection, there was a significant increase in ileum responsiveness to histamine in T. canis-infected group. Pre-incubation of ileum segments with 1 mg ml −1 disodium cromoglycate (DSCG) prevented the increased responsiveness to histamine in T. canis-infected guinea pigs and did not affect ileum contractility in non-infected animals. These results indicate that T. canis-infected guinea pigs develop increased intestinal responsiveness to histamine and that DSCG prevents alterations in smooth-muscle contractility.
Antimicrobial Agents and Chemotherapy, 2016
Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 ؋ 10 3 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 ؋ 10 6 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P < 0.001). Propranolol in the pretreatment group showed higher anti-Toxoplasma activity than propranolol in posttreatment in brain tissues, displaying therapeutic efficiency on toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine.
Frontiers in cellular and infection microbiology, 2017
Classical treatment for congenital toxoplasmosis is based on combination of sulfadiazine and pyrimethamine plus folinic acid. Due to teratogenic effects and bone marrow suppression caused by pyrimethamine, the establishment of new therapeutic strategies is indispensable to minimize the side effects and improve the control of infection. Previous studies demonstrated that enrofloxacin and toltrazuril reduced the incidence of Neospora caninum and Toxoplasma gondii infection. The aim of the present study was to evaluate the efficacy of enrofloxacin and toltrazuril in the control of T. gondii infection in human trophoblast cells (BeWo line) and in human villous explants from the third trimester. BeWo cells and villous were treated with several concentrations of enrofloxacin, toltrazuril, sulfadiazine, pyrimethamine, or combination of sulfadiazine+pyrimethamine, and the cellular or tissue viability was verified. Next, BeWo cells were infected by T. gondii (2F1 clone or the ME49 strain), w...
Effect of albendazole in experimental toxocariasis of mice
Annals of Tropical Medicine & Parasitology, 1989
Fifty-five mice were each infected with 800 embryonated eggs of Toxocara canis. Beginning on the second day of the infection, one group received a single 9 mg dose ofalbendazole every 24 hours for an eightday period while a second group received 3 mg of albendazole every eight hours for the same period. On the tenth day of infection, mice in each treatment group and their corresponding controls were sacrificed, and the presence and motility ofT. canis larvae in the brain were determined. With both therapeutical procedures the administration of albendazole reduced the number of larvae which reach the brain. However, for the same total dose, the administration of the drug every eight hours yielded results which were significantly superior to those produced by administering a single dose every 24 hours, reducing both the number oflarvae in the brain and their motility.