The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Jennifer Keiser - One of the best experts on this subject based on the ideXlab platform.
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assessment of tegumental damage to schistosoma mansoni and s haematobium after in vitro exposure to ferrocenyl ruthenocenyl and benzyl derivatives of Oxamniquine using scanning electron microscopy
Parasites & Vectors, 2018Co-Authors: Valentin Buchter, Jeannine Hess, Gilles Gasser, Jennifer KeiserAbstract:Schistosomiasis is one of the most harmful parasitic diseases worldwide, praziquantel being the only drug in widespread use to treat it. We recently demonstrated that ferrocenyl, ruthenocenyl and benzyl derivatives of Oxamniquine (Fc-OXA, Rc-OXA and Bn-OXA) are promising antischistosomal drug candidates. In this study we assessed the tegumental damage of these three derivatives of Oxamniquine using scanning electron microscopy. Adult Schistosoma mansoni and S. haematobium were exposed to a concentration of 100 μM of each drug and incubated for 4–120 h, according to their onset of action and activity. While on S. mansoni the fastest acting compound was Fc-OXA, which revealed high activity after 4 h of incubation, on S. haematobium, Rc-OXA revealed the quickest onset, being lethal on all males within 24 h. In both species studied, the three derivatives showed the same patterns of tegumental damage consisting of blebs, sloughing and tegument rupturing all over the body. Additionally, on S. mansoni distinct patterns of tegumental damage were observed for each of the compounds: tissue ruptures in the gynaecophoric canal for Fc-OXA, loss of spines for Rc-OXA and oral sucker rupture for Bn-OXA. Our study confirmed that Fc-OXA, Rc-OXA and Bn-OXA are promising broad spectrum antischistosomal drug candidates. All derivatives show fast in vitro activity against S. mansoni and S. haematobium while validating the previous finding that the parent drug Oxamniquine is less active in vitro under the conditions described. This work sets the base for further studies on the identification of a lead Oxamniquine derivative, with the aim of identifying a molecule with the potential to become a new drug for human use.
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Assessment of tegumental damage to Schistosoma mansoni and S. haematobium after in vitro exposure to ferrocenyl, ruthenocenyl and benzyl derivatives of Oxamniquine using scanning electron microscopy
BMC, 2018Co-Authors: Valentin Buchter, Jeannine Hess, Gilles Gasser, Jennifer KeiserAbstract:Abstract Background Schistosomiasis is one of the most harmful parasitic diseases worldwide, praziquantel being the only drug in widespread use to treat it. We recently demonstrated that ferrocenyl, ruthenocenyl and benzyl derivatives of Oxamniquine (Fc-OXA, Rc-OXA and Bn-OXA) are promising antischistosomal drug candidates. Methods In this study we assessed the tegumental damage of these three derivatives of Oxamniquine using scanning electron microscopy. Adult Schistosoma mansoni and S. haematobium were exposed to a concentration of 100 μM of each drug and incubated for 4–120 h, according to their onset of action and activity. Results While on S. mansoni the fastest acting compound was Fc-OXA, which revealed high activity after 4 h of incubation, on S. haematobium, Rc-OXA revealed the quickest onset, being lethal on all males within 24 h. In both species studied, the three derivatives showed the same patterns of tegumental damage consisting of blebs, sloughing and tegument rupturing all over the body. Additionally, on S. mansoni distinct patterns of tegumental damage were observed for each of the compounds: tissue ruptures in the gynaecophoric canal for Fc-OXA, loss of spines for Rc-OXA and oral sucker rupture for Bn-OXA. Conclusions Our study confirmed that Fc-OXA, Rc-OXA and Bn-OXA are promising broad spectrum antischistosomal drug candidates. All derivatives show fast in vitro activity against S. mansoni and S. haematobium while validating the previous finding that the parent drug Oxamniquine is less active in vitro under the conditions described. This work sets the base for further studies on the identification of a lead Oxamniquine derivative, with the aim of identifying a molecule with the potential to become a new drug for human use
Valentin Buchter - One of the best experts on this subject based on the ideXlab platform.
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assessment of tegumental damage to schistosoma mansoni and s haematobium after in vitro exposure to ferrocenyl ruthenocenyl and benzyl derivatives of Oxamniquine using scanning electron microscopy
Parasites & Vectors, 2018Co-Authors: Valentin Buchter, Jeannine Hess, Gilles Gasser, Jennifer KeiserAbstract:Schistosomiasis is one of the most harmful parasitic diseases worldwide, praziquantel being the only drug in widespread use to treat it. We recently demonstrated that ferrocenyl, ruthenocenyl and benzyl derivatives of Oxamniquine (Fc-OXA, Rc-OXA and Bn-OXA) are promising antischistosomal drug candidates. In this study we assessed the tegumental damage of these three derivatives of Oxamniquine using scanning electron microscopy. Adult Schistosoma mansoni and S. haematobium were exposed to a concentration of 100 μM of each drug and incubated for 4–120 h, according to their onset of action and activity. While on S. mansoni the fastest acting compound was Fc-OXA, which revealed high activity after 4 h of incubation, on S. haematobium, Rc-OXA revealed the quickest onset, being lethal on all males within 24 h. In both species studied, the three derivatives showed the same patterns of tegumental damage consisting of blebs, sloughing and tegument rupturing all over the body. Additionally, on S. mansoni distinct patterns of tegumental damage were observed for each of the compounds: tissue ruptures in the gynaecophoric canal for Fc-OXA, loss of spines for Rc-OXA and oral sucker rupture for Bn-OXA. Our study confirmed that Fc-OXA, Rc-OXA and Bn-OXA are promising broad spectrum antischistosomal drug candidates. All derivatives show fast in vitro activity against S. mansoni and S. haematobium while validating the previous finding that the parent drug Oxamniquine is less active in vitro under the conditions described. This work sets the base for further studies on the identification of a lead Oxamniquine derivative, with the aim of identifying a molecule with the potential to become a new drug for human use.
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Assessment of tegumental damage to Schistosoma mansoni and S. haematobium after in vitro exposure to ferrocenyl, ruthenocenyl and benzyl derivatives of Oxamniquine using scanning electron microscopy
BMC, 2018Co-Authors: Valentin Buchter, Jeannine Hess, Gilles Gasser, Jennifer KeiserAbstract:Abstract Background Schistosomiasis is one of the most harmful parasitic diseases worldwide, praziquantel being the only drug in widespread use to treat it. We recently demonstrated that ferrocenyl, ruthenocenyl and benzyl derivatives of Oxamniquine (Fc-OXA, Rc-OXA and Bn-OXA) are promising antischistosomal drug candidates. Methods In this study we assessed the tegumental damage of these three derivatives of Oxamniquine using scanning electron microscopy. Adult Schistosoma mansoni and S. haematobium were exposed to a concentration of 100 μM of each drug and incubated for 4–120 h, according to their onset of action and activity. Results While on S. mansoni the fastest acting compound was Fc-OXA, which revealed high activity after 4 h of incubation, on S. haematobium, Rc-OXA revealed the quickest onset, being lethal on all males within 24 h. In both species studied, the three derivatives showed the same patterns of tegumental damage consisting of blebs, sloughing and tegument rupturing all over the body. Additionally, on S. mansoni distinct patterns of tegumental damage were observed for each of the compounds: tissue ruptures in the gynaecophoric canal for Fc-OXA, loss of spines for Rc-OXA and oral sucker rupture for Bn-OXA. Conclusions Our study confirmed that Fc-OXA, Rc-OXA and Bn-OXA are promising broad spectrum antischistosomal drug candidates. All derivatives show fast in vitro activity against S. mansoni and S. haematobium while validating the previous finding that the parent drug Oxamniquine is less active in vitro under the conditions described. This work sets the base for further studies on the identification of a lead Oxamniquine derivative, with the aim of identifying a molecule with the potential to become a new drug for human use
Jurg Utzinger - One of the best experts on this subject based on the ideXlab platform.
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drugs for treating schistosoma mansoni infection
Cochrane Database of Systematic Reviews, 2013Co-Authors: Anthony Dansoappiah, Piero Olliaro, Sarah Donegan, David A Sinclair, Jurg UtzingerAbstract:Schistosoma mansoni is a parasitic infection common in the tropics and sub-tropics. Chronic and advanced disease includes abdominal pain, diarrhoea, blood in the stool, liver cirrhosis, portal hypertension, and premature death. OBJECTIVES: To evaluate the effects of antischistosomal drugs, used alone or in combination, for treating S. mansoni infection. SEARCH METHODS: We searched MEDLINE, EMBASE and LILACS from inception to October 2012, with no language restrictions. We also searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2012) and mRCT. The reference lists of articles were reviewed and experts were contacted for unpublished studies. SELECTION CRITERIA: Randomized controlled trials of antischistosomal drugs, used alone or in combination, versus placebo, different antischistosomal drugs, or different doses of the same antischistosomal drug for treating S. mansoni infection. DATA COLLECTION AND ANALYSIS: One author extracted data and assessed eligibility and risk of bias in the included studies, which were independently checked by a second author. We combined dichotomous outcomes using risk ratio (RR) and continuous data weighted mean difference (WMD); we presented both with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: Fifty-two trials enrolling 10,269 participants were included. The evidence was of moderate or low quality due to the trial methods and small numbers of included participants.Praziquantel: Compared to placebo, praziquantel 40 mg/kg probably reduces parasitological treatment failure at one month post-treatment (RR 3.13, 95% CI 1.03 to 9.53, two trials, 414 participants, moderate quality evidence). Compared to this standard dose, lower doses may be inferior (30 mg/kg: RR 1.52, 95% CI 1.15 to 2.01, three trials, 521 participants, low quality evidence; 20 mg/kg: RR 2.23, 95% CI 1.64 to 3.02, two trials, 341 participants, low quality evidence); and higher doses, up to 60 mg/kg, do not appear to show any advantage (four trials, 783 participants, moderate quality evidence).The absolute parasitological cure rate at one month with praziquantel 40 mg/kg varied substantially across studies, ranging from 52% in Senegal in 1993 to 92% in Brazil in 2006/2007. Oxamniquine: Compared to placebo, Oxamniquine 40 mg/kg probably reduces parasitological treatment failure at three months (RR 8.74, 95% CI 3.74 to 20.43, two trials, 82 participants, moderate quality evidence). Lower doses than 40 mg/kg may be inferior at one month (30 mg/kg: RR 1.78, 95% CI 1.15 to 2.75, four trials, 268 participants, low quality evidence; 20 mg/kg: RR 3.78, 95% CI 2.05 to 6.99, two trials, 190 participants, low quality evidence), and higher doses, such as 60 mg/kg, do not show a consistent benefit (four trials, 317 participants, low quality evidence).These trials are now over 20 years old and only limited information was provided on the study designs and methods. Praziquantel versus Oxamniquine: Only one small study directly compared praziquantel 40 mg/kg with Oxamniquine 40 mg/kg and we are uncertain which treatment is more effective in reducing parasitological failure (one trial, 33 participants, very low quality evidence). A further 10 trials compared Oxamniquine at 20, 30 and 60 mg/kg with praziquantel 40 mg/kg and did not show any marked differences in failure rate or percent egg reduction.Combination treatments: We are uncertain whether combining praziquantel with artesunate reduces failures compared to praziquantel alone at one month (one trial, 75 participants, very low quality evidence). Two trials also compared combinations of praziquantel and Oxamniquine in different doses, but did not find statistically significant differences in failure (two trials, 87 participants). Other outcomes and analyses: In trials reporting clinical improvement evaluating lower doses (20 mg/kg and 30 mg/kg) against the standard 40 mg/kg both praziquantel or Oxamniquine, no dose effect was demonstrable in resolving abdominal pain, diarrhoea, blood in stool, hepatomegaly, and splenomegaly (follow up at one, three, six, 12, and 24 months; three trials, 655 participants).Adverse events were not well-reported but were mostly described as minor and transient.In an additional analysis of treatment failure in the treatment arm of individual studies stratified by age, failure rates with 40 mg/kg of both praziquantel and Oxamniquine were higher in children.
Mc Chung - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and biological activity of 6-formyl-Oxamniquine derivative
Brasil, 2015Co-Authors: Ae ,de Almeida, De Souza Alr, Sm Allegretti, Tf Frezza, Mc Pinto, Ag Ferreira, Mc ChungAbstract:Schistosomiasis, an important disease in Brazil, is caused by a trematode of the genus Schistosoma, reaching millions of person in one of the most endemic region of this disease in the whole globe. The main goal of this work was to syntetize the 6-formyl-Oxamniquine derivative and evaluate its biological activity. The 6-formyl-Oxamniquine derivative was obtained by the oxidation of Oxamniquine with MnO2, applying the CH2Cl2 as solvent at room temperature for 24 hours. The obtaintion of 6-formyl-Oxamniquine derivative compound was confirmed by IT spectroscopy and C-13 NMR and H-1 NMR, presenting similar activity when compared to the commercial Oxamniquine (Mansil (R)).44474975
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Synthesis and thermal study of the prodrug of Oxamniquine
Journal of Thermal Analysis and Calorimetry, 2006Co-Authors: A E Almeida, Ag Ferreira, M S Crespi, Z A Andrade, Mc ChungAbstract:Oxamniquine polymeric prodrug with potential antischistosomal activity was prepared using dextran T-70 as a carrier, which was analysed by 1HNMR, 13C NMR and IR spectroscopy. The formation of the Oxamniquine salt was confirmed by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC) which showed a different thermal behaviour when compared to the physical mixture.
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Synthesis and thermal study of the prodrug of Oxamniquine
Journal of Thermal Analysis and Calorimetry, 2006Co-Authors: A E Almeida, Ag Ferreira, M S Crespi, Z A Andrade, Mc ChungAbstract:Oxamniquine polymeric prodrug with potential antischistosomal activity was prepared using dextran T-70 as a carrier, which was analysed by ^1HNMR, ^13C NMR and IR spectroscopy. The formation of the Oxamniquine salt was confirmed by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC) which showed a different thermal behaviour when compared to the physical mixture.
Padraic G. Fallon - One of the best experts on this subject based on the ideXlab platform.
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EFFECT OF PRAZIQUANTEL AND Oxamniquine TREATMENT ON HUMAN ISOTYPE RESPONSES TO SCHISTOSOMA MANSONI: ELEVATED IGE TO ADULT WORM
Parasite immunology, 1997Co-Authors: M. Webster, Padraic G. Fallon, Anthony J. C. Fulford, Anthony E. Butterworth, John H. Ouma, Gachuhi Kimani, David W. DunneAbstract:Pre- and post-treatment antibody isotype responses to Schistosoma mansoni adult worm and soluble egg antigens were compared in a study population previously used to show that IgE against adult worm correlates negatively with intensity of reinfection following chemotherapeutic cure. IgG subclass responses to adult worm were lower after treatment whereas IgM and IgE were higher. The increase in IgE to adult worm was observed with different preparations of adult worm, including the worm tegument, and with both praziquantel and Oxamniquine therapy. No significant difference was observed between pre- and post-treatment isotype responses to egg antigens following either praziquantel or Oxamniquine therapy.
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Temporal differences in praziquantel- and Oxamniquine-induced tegumental damage to adult Schistosoma mansoni: implications for drug-antibody synergy.
Parasitology, 1996Co-Authors: Padraic G. Fallon, R.e. Fookes, G. A. WhartonAbstract:A temporal study of the effects on the tegument of Schistosoma mansoni adult worm following in vivo praziquantel and Oxamniquine treatment was performed. Drug-induced damage to the tegument, exposure of surface antigens and attachment of host antibody occurred rapidly, within 1 h, following praziquantel treatment. Oxamniquine-treated worms required 4-8 days for these effects to be apparent. The 2 drugs differed in the degree and sites of damage on the worm surface. The administration of 2 different polyspecific rabbit sera with drug significantly increased the efficacy of praziquantel when administered with the drug, but not when given 6-9 days after drug treatment. In contrast, only 1 serum was synergistic with Oxamniquine when administered with drug and both sera were synergistic when given 6-9 days after drug treatment. The effect of immune killing of drug-treated worms is discussed.
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Efficacy of treatment of murine Schistosoma mansoni infections with praziquantel and Oxamniquine correlates with infection intensity: role of host antibody.
Parasitology, 1995Co-Authors: Padraic G. Fallon, J. V. Hamilton, Michael J. DoenhoffAbstract:The reduction in worm burden obtained by treatment of Schistosoma mansoni with praziquantel and Oxamniquine was greater in mice with heavy infections than in relatively lightly infected animals. The reduction in worm burden achieved by each drug correlated with the size of the pre-treatment worm burden (r 2 = 0·82 and 0·81 for praziquantel and Oxamniquine, respectively). Intensity of infection did not affect the degree of tegumental damage and drug-induced antigen exposure on worms recovered soon after treatment with praziquantel. However, praziquantel-treated worms from mice with heavy infections had significantly more murine antibody attached to the treated-worm surface than worms from praziquantel-treated lightly infected mice. Heavily infected mice had greater levels of circulating anti-worm antibodies than lighter infected mice. The correlation between infection intensity and cure rates achieved by praziquantel and Oxamniquine may thus be a reflection of the higher litres of relevant antibody in heavily infected mice mediating death of drug-treated worms.
