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 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 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
Objective:To determine the effect of Ancylostoma caninum(A.caninum)and trypanosome parasites on the immune response to vaccination in dogs in endemic environments.Methods:Sixteen dogs for the experiment were grouped i...Objective:To determine the effect of Ancylostoma caninum(A.caninum)and trypanosome parasites on the immune response to vaccination in dogs in endemic environments.Methods:Sixteen dogs for the experiment were grouped into 4 of 4 members each.Group I was the uninfected control one,and GPII was infected with A.caninum;GPIII was infected with A.caninum/Trypanosoma congolense(T.congolense),and GPIV was infected with Trypanosoma brucei(T.brucei)/A.caninum.The dogs were first vaccinated with antirabies vaccine before infecting GPII,GPIII and GPIV with A.caninum which were done 4 weeks after vaccination.By 2-week post-vaccination,trypanosome parasites were superimposed on both GPIII and GPIV.A secondary vaccination was given to GPI,GPII,GPIII,and GPIV by Week 12 of the experiment(4 weeks post treatment).Results:The prepatent period was(3.00±1.40)days,in the conjunct infection of T.brucei/A.caninum.It was(9.00±1.10)days,in conjunct T.congolense/A.caninum.The prepatent period of A.caninum was(14.0±2.0)days in the single A.caninum group and(13.0±1.0)days in the conjunct trypanosome/A.caninum.At the 1st week after vaccination,the antibody titer in all the vaccinated groups(GPI,GPII,GPIII,and GPIV)significantly increased(P<0.05)and peaked at the 3rd week after vaccination.Following infections,there were marked significant decreases(P<0.05)in the antibody production against rabies in GPII,GPIII and GPIV.The significant decrease(P<0.05)in antibody titer was highest in the conjunct groups(GPIII and GPIV)compared to the single infection(GPII).Treatment with diminazene aceturate and mebendazole did not significantly improve antibody response in the dogs.A secondary vaccination administered at the 12th week after the primary vaccination significantly increased(P<0.05)the antibody titer with a peak at the 3rd week after the secondary vaccination.Conclusions:It was therefore concluded that A.caninum,T.brucei and T.congolense induced immunosuppression in antirabies vaccination in dogs.展开更多
The present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as a potential drug against Leishmania donovani. Amphotericin B was used as a positive control drug. In vi...The present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as a potential drug against Leishmania donovani. Amphotericin B was used as a positive control drug. In vitro activity involved incubation of various drug concentrations with promastigotes or vero cells in culture before determination of parasite growth inhibition or cell death while in vivo evaluations involved infection of various mice groups with virulent L. donovani parasites and treatment with test drug compounds following disease establishment. Weight changes in experimental mice were also evaluated before infection and throughout the experiment. The results indicated that the diminazene-chloroquine combination was at least nine times more efficacious than individual drugs in killing promastigotes in culture. The diminazene-chloroquine combination was safer （Ld50=0.03±0.04） than Amphotericin B （Ld50=0.02±0.01）. Body weight in infected mice increased significantly （P=0.0007） from day 7 to day 37 following infection （P=0.026）. However, body weight remained comparable in all mice groups during treatment （P=0.16）. The diminazene-chloroquine combination significantly reduced splenic parasite numbers as compared to individual drug therapies （P=0.0001） although Amphotericin B was still more efficacious than any other treatment （P=0.0001）. Amongst the test compounds, the diminazene-chloroquine combination showed the lowest level of IgG antibody responses with results indicating significant negative correlation between antileishmanial antibody responses and protection against disease. These findings demonstrate the positive advantage and the potential use of a combined therapy of diminazene-chloroquine over the constituent drugs. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.展开更多
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.
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 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.
基金Supported by the Tertiary Education Trust Fund(TETFUND)(Grant No.MOUAU/ETF/DO/40/VOL.1/59).
文摘Objective:To determine the effect of Ancylostoma caninum(A.caninum)and trypanosome parasites on the immune response to vaccination in dogs in endemic environments.Methods:Sixteen dogs for the experiment were grouped into 4 of 4 members each.Group I was the uninfected control one,and GPII was infected with A.caninum;GPIII was infected with A.caninum/Trypanosoma congolense(T.congolense),and GPIV was infected with Trypanosoma brucei(T.brucei)/A.caninum.The dogs were first vaccinated with antirabies vaccine before infecting GPII,GPIII and GPIV with A.caninum which were done 4 weeks after vaccination.By 2-week post-vaccination,trypanosome parasites were superimposed on both GPIII and GPIV.A secondary vaccination was given to GPI,GPII,GPIII,and GPIV by Week 12 of the experiment(4 weeks post treatment).Results:The prepatent period was(3.00±1.40)days,in the conjunct infection of T.brucei/A.caninum.It was(9.00±1.10)days,in conjunct T.congolense/A.caninum.The prepatent period of A.caninum was(14.0±2.0)days in the single A.caninum group and(13.0±1.0)days in the conjunct trypanosome/A.caninum.At the 1st week after vaccination,the antibody titer in all the vaccinated groups(GPI,GPII,GPIII,and GPIV)significantly increased(P<0.05)and peaked at the 3rd week after vaccination.Following infections,there were marked significant decreases(P<0.05)in the antibody production against rabies in GPII,GPIII and GPIV.The significant decrease(P<0.05)in antibody titer was highest in the conjunct groups(GPIII and GPIV)compared to the single infection(GPII).Treatment with diminazene aceturate and mebendazole did not significantly improve antibody response in the dogs.A secondary vaccination administered at the 12th week after the primary vaccination significantly increased(P<0.05)the antibody titer with a peak at the 3rd week after the secondary vaccination.Conclusions:It was therefore concluded that A.caninum,T.brucei and T.congolense induced immunosuppression in antirabies vaccination in dogs.
基金supported by the National Natural Science Foundation of China(No.81372029)the National Students’Innovation and Entrepreneurship Training Program of China(No.201510081007)+2 种基金the Postgraduate Innovation Funding Program of Hebei ProvinceChina(No.CXZZBS2017127)the Graduate Student Innovation Fund of North China University of Science and Technology(No.2017B10)
基金partly supported by BPM Bulk Medicine and Pharmaceuticals Production,TROPMED GMbH,Neuhofer Welche 48,D-19370 Parchtm,Germany,courtesy of Dr Alain J.Bourdichon
文摘The present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as a potential drug against Leishmania donovani. Amphotericin B was used as a positive control drug. In vitro activity involved incubation of various drug concentrations with promastigotes or vero cells in culture before determination of parasite growth inhibition or cell death while in vivo evaluations involved infection of various mice groups with virulent L. donovani parasites and treatment with test drug compounds following disease establishment. Weight changes in experimental mice were also evaluated before infection and throughout the experiment. The results indicated that the diminazene-chloroquine combination was at least nine times more efficacious than individual drugs in killing promastigotes in culture. The diminazene-chloroquine combination was safer （Ld50=0.03±0.04） than Amphotericin B （Ld50=0.02±0.01）. Body weight in infected mice increased significantly （P=0.0007） from day 7 to day 37 following infection （P=0.026）. However, body weight remained comparable in all mice groups during treatment （P=0.16）. The diminazene-chloroquine combination significantly reduced splenic parasite numbers as compared to individual drug therapies （P=0.0001） although Amphotericin B was still more efficacious than any other treatment （P=0.0001）. Amongst the test compounds, the diminazene-chloroquine combination showed the lowest level of IgG antibody responses with results indicating significant negative correlation between antileishmanial antibody responses and protection against disease. These findings demonstrate the positive advantage and the potential use of a combined therapy of diminazene-chloroquine over the constituent drugs. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.
