Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo.Methods:Bioinformatic analysis was performed using atom pair fingerprints.An i...Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo.Methods:Bioinformatic analysis was performed using atom pair fingerprints.An in vitro combination test was performed against Babesia bovis and Theileria equi.Moreover,the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay.Results:Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights.The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi.In addition,5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment.The combination therapy also normalized the hematological parameters of infected mice.Conclusions:An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice,suggesting it might be a new paradigm for the treatment of babesiosis.展开更多
Objective:To investigate the effect of diminazene aceturale(DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei.Methods:Thirty adul...Objective:To investigate the effect of diminazene aceturale(DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei.Methods:Thirty adult male albino rats,randomly assigned into 6 groups(A—F) of 5rats each were used.They were either infected with 1×10~a trypanosomes intraperitoneally(groups A-E) or uninfected(group F).The different groups were treated respectively as follows:group A-with 3.5 mg/kg DA;group B-3.5 mg/kg DA and 7.5 mg/kg levamisole;group C-3.S mg/kg DA and 100 mg/kg vitamin C;and group D-3.S mg/kg DA and 7.S mg/kg levamisole and 100 mg/kg vitamin C.Croup E was left untreated.Parameters assessed include:rectal temperature,body weight changes,packed cell volume(PCV),Haemoglobin concentration(Hb),total leucocyte count(TLC) differential leucocyte count(DLC),parasitaemia,clinical signs and survivability.Results:Average pre-patent period of 5 days was recorded.Parasites in the blood were cleared in all treated groups(A-D) within 48 hours post treatment(PT).Untreated rats in group E died between25 and 32 days post infection(PI).Relapse was not recorded in all the treated groups(A-D).The initial reduction in PCV,Hb,TLC and increases in rectal temperature following infection were reversed by the treatments.The rats that received drug combinations(groups B,C and D)showed faster and higher recovery rates than the uninfected control and group A.Conclusions:Levamisole and/or Vitamin C combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei.展开更多
Objective:To investigate the effects of comparatively high doses of diminazene aceturate on the reproductive performance of female rats in the early stage of pregnancy.Methods:After oestrus synchronisation and success...Objective:To investigate the effects of comparatively high doses of diminazene aceturate on the reproductive performance of female rats in the early stage of pregnancy.Methods:After oestrus synchronisation and successful mating,20 pregnant female rats were randomly divided into four groups(A-D).Group A rats served as the control and were given single intraperitoneal injection of 0.5 mL sterile water(vehicle only) while groups B.C and D rats were given single intraperitoneal doses of 7,14 and 21 mg/kg body weight diminazene aceturate respectively,on day 7 of pregnancy.The gestation length,litter size and weight at birth,and areas of foetal resorption in the uterus were determined post partum.The post-implantation survival index(%) and the gestation index(group%) were also evaluated for rats in all the groups.Results:There was a graded increase in the number of observed resorbed foetuses as the dose of diminazene aceturate was increased,although only groups C(14 mg/kg) and D(21 mg/kg) revealed a significant decrease(P<0.01,ANOVA) in the post implantation survival index of rat embryos.There was also a significant decrease(P<0.05) in the litter weights of rats in groups C and D.Conclusions: Although the pregnant rats showed no overt signs of systemic toxicity even at the highest dose of 21 mg/kg body weight diminazene aceturate in this study,it was concluded that the use of high doses of diminazene aceturate in an effort to combat resistant trypanosomes could have adverse reproductive effects on female animals in the early period of pregnancy.展开更多
Objective:To determine the effect of Trypanosoma brucei(T.brucei)on blood sugar level of infected rats.Methods:The experiment was done with 42 albino rats grouped into 3 groups of 14 members each.Group A was uninfecte...Objective:To determine the effect of Trypanosoma brucei(T.brucei)on blood sugar level of infected rats.Methods:The experiment was done with 42 albino rats grouped into 3 groups of 14 members each.Group A was uninfected(control group),Group B was infected with T.brucei and treated with diminazene aceturate,and Group C was infected with T.brucei and treated with imidocarb dipropionate.Blood samples were collected from the media canthus of the experimental rats on Days 0,1,2,3,4,5,6,7,8,9,10 for the assessment of change in blood sugar levels.The blood sugar levels were determined with a glucometer(Accu-chek active serial No.GN:10023338).Results:By 4 to 5 days post infection,there was a significant increase(P<0.05)in the blood sugar of Group B and Group C.By Day 6 post infection(Day 2 post treatment),no significant difference(P>0.05)was observed in the groups when compared with the control group till Day 12 of the experiment.Conclusions:T.brucei caused a significant increase in blood sugar of infected rats.展开更多
基金supported by Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia through the project number:ISP23-73.
文摘Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo.Methods:Bioinformatic analysis was performed using atom pair fingerprints.An in vitro combination test was performed against Babesia bovis and Theileria equi.Moreover,the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay.Results:Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights.The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi.In addition,5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment.The combination therapy also normalized the hematological parameters of infected mice.Conclusions:An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice,suggesting it might be a new paradigm for the treatment of babesiosis.
文摘Objective:To investigate the effect of diminazene aceturale(DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei.Methods:Thirty adult male albino rats,randomly assigned into 6 groups(A—F) of 5rats each were used.They were either infected with 1×10~a trypanosomes intraperitoneally(groups A-E) or uninfected(group F).The different groups were treated respectively as follows:group A-with 3.5 mg/kg DA;group B-3.5 mg/kg DA and 7.5 mg/kg levamisole;group C-3.S mg/kg DA and 100 mg/kg vitamin C;and group D-3.S mg/kg DA and 7.S mg/kg levamisole and 100 mg/kg vitamin C.Croup E was left untreated.Parameters assessed include:rectal temperature,body weight changes,packed cell volume(PCV),Haemoglobin concentration(Hb),total leucocyte count(TLC) differential leucocyte count(DLC),parasitaemia,clinical signs and survivability.Results:Average pre-patent period of 5 days was recorded.Parasites in the blood were cleared in all treated groups(A-D) within 48 hours post treatment(PT).Untreated rats in group E died between25 and 32 days post infection(PI).Relapse was not recorded in all the treated groups(A-D).The initial reduction in PCV,Hb,TLC and increases in rectal temperature following infection were reversed by the treatments.The rats that received drug combinations(groups B,C and D)showed faster and higher recovery rates than the uninfected control and group A.Conclusions:Levamisole and/or Vitamin C combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei.
文摘Objective:To investigate the effects of comparatively high doses of diminazene aceturate on the reproductive performance of female rats in the early stage of pregnancy.Methods:After oestrus synchronisation and successful mating,20 pregnant female rats were randomly divided into four groups(A-D).Group A rats served as the control and were given single intraperitoneal injection of 0.5 mL sterile water(vehicle only) while groups B.C and D rats were given single intraperitoneal doses of 7,14 and 21 mg/kg body weight diminazene aceturate respectively,on day 7 of pregnancy.The gestation length,litter size and weight at birth,and areas of foetal resorption in the uterus were determined post partum.The post-implantation survival index(%) and the gestation index(group%) were also evaluated for rats in all the groups.Results:There was a graded increase in the number of observed resorbed foetuses as the dose of diminazene aceturate was increased,although only groups C(14 mg/kg) and D(21 mg/kg) revealed a significant decrease(P<0.01,ANOVA) in the post implantation survival index of rat embryos.There was also a significant decrease(P<0.05) in the litter weights of rats in groups C and D.Conclusions: Although the pregnant rats showed no overt signs of systemic toxicity even at the highest dose of 21 mg/kg body weight diminazene aceturate in this study,it was concluded that the use of high doses of diminazene aceturate in an effort to combat resistant trypanosomes could have adverse reproductive effects on female animals in the early period of pregnancy.
文摘Objective:To determine the effect of Trypanosoma brucei(T.brucei)on blood sugar level of infected rats.Methods:The experiment was done with 42 albino rats grouped into 3 groups of 14 members each.Group A was uninfected(control group),Group B was infected with T.brucei and treated with diminazene aceturate,and Group C was infected with T.brucei and treated with imidocarb dipropionate.Blood samples were collected from the media canthus of the experimental rats on Days 0,1,2,3,4,5,6,7,8,9,10 for the assessment of change in blood sugar levels.The blood sugar levels were determined with a glucometer(Accu-chek active serial No.GN:10023338).Results:By 4 to 5 days post infection,there was a significant increase(P<0.05)in the blood sugar of Group B and Group C.By Day 6 post infection(Day 2 post treatment),no significant difference(P>0.05)was observed in the groups when compared with the control group till Day 12 of the experiment.Conclusions:T.brucei caused a significant increase in blood sugar of infected rats.