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Diminazene Aceturate (Berenil) Modulates the Host Cellular and Inflammatory Responses to Trypanosoma congolense Infection  [PDF]
Shiby Kuriakose,Helen M. Muleme,Chukwunonso Onyilagha,Rani Singh,Ping Jia,Jude E. Uzonna
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048696
Abstract: Trypanosoma congolense are extracellular and intravascular blood parasites that cause debilitating acute or chronic disease in cattle and other domestic animals. Diminazene aceturate (Berenil) has been widely used as a chemotherapeutic agent for trypanosomiasis in livestock since 1955. As in livestock, treatment of infected highly susceptible BALB/c mice with Berenil leads to rapid control of parasitemia and survival from an otherwise lethal infection. The molecular and biochemical mechanisms of action of Berenil are still not very well defined and its effect on the host immune system has remained relatively unstudied. Here, we investigated whether Berenil has, in addition to its trypanolytic effect, a modulatory effect on the host immune response to Trypanosoma congolense.
Protective efficacy of isometamidium chloride and diminazene aceturate against natural Trypanosoma brucei, Trypanosoma congolense and Trypanosoma vivax infections in cattle under a suppressed tsetse population in Uganda  [cached]
J.W. Magona,J.S.P. Mayende,R. Okiria,N.M. Okuna
Onderstepoort Journal of Veterinary Research , 2010, DOI: 10.4102/ojvr.v71i3.265
Abstract: The protective efficacy of isometamidium chloride (ISMM) and diminazene aceturate (DIM) against Trypanosoma brucei, Trypanosoma congolense and Trypanosoma vivax infections in cattle under a suppressed tsetse population was assessed in southeast Uganda. A total of 66 and 57 trypanosome-infected cattle were treated with ISMM and DIM, respectively together with 177 trypanosomefree animals not treated were followed for 12 months, checked every 4 weeks. There was no statistical difference in the mean time to infection with any trypanosome species in animals treated with ISMM or DIM. However, the mean time to trypanosome infection was significantly longer for treated animals than controls. The mean time to infection with each of the three trypanosome species differed significantly, with the average time to T. vivax infection the lowest, followed by T. congolense and then T. brucei. The protective efficacy of DIM was as good as that of ISMM; implying curative treatments against trypanosomosis are sufficient for combination with tsetse control. Isometamidium chloride or DIM had the highest impact on T. brucei and T. congolense infections in cattle.
Effects of DMSO on Diminazene Efficacy in Experimental Murine T. brucei Infection
K.I. Eghianruwa,S.M. Anika
International Journal of Animal and Veterinary Advances , 2012,
Abstract: This study evaluated the influence of dimethyl sulfoxide (DMSO) daily supplementation on diminazene treatment of trypanosomosis. Four groups of Trypanosoma brucei brucei infected rats received 7.0 mg/kg diminazene aceturate on day 7 post infection. Three of the four groups received different doses of DMSO (0.5, 1.0 and 2.0 g/kg, respectively) in addition to diminazene treatment. The changes in hematological parameters and the weights of liver, spleen and heart caused by T. brucei infection were monitored and used to assess the efficacy of treatment. The prepatent period of infection was four days. Infection caused significant increases in WBC count, spleen and liver weights but it caused decreases in PCV, HB and RBC by day 7 post infection (PI7). By PI14, spleen weight and WBC counts were reduced from the PI7 level without treatment. Diminazene/DMSO combination did not reduce liver weight or increased hematological parameters more significantly than diminazene treatment alone. Increase in the dose of DMSO caused increases in liver weight. Diminazene/DMSO combination reduced spleen weight more significantly than diminazene treatment alone. Diminazene/DMSO combination delayed re-emergence of parasites beyond PT21 at which time parasites were detected in the blood of rats treated only with diminazene. The limited advantages of diminazene/DMSO combination over diminazene alone as well as the possible liver toxicity of DMSO at high doses would not make DMSO supplementation a viable addition to trypanosomosis chemotherapy.
The effects of diminazene aceturate on systemic blood pressure in clinically healthy adult dogs  [cached]
K.E. Joubert,F. Kettner,R.G. Lobetti,D.M. Miller
Journal of the South African Veterinary Association , 2012, DOI: 10.4102/jsava.v74i3.513
Abstract: Diminazene aceturate is a commonly used antibabesial agent. It has been postulated that diminazine may induce a decrease in blood pressure and exacerbate the hypotension presented in dogs with babesiosis. This study was undertaken to assess the effect of diminazine aceturate on the blood pressure of healthy dogs. Six healthy German shepherd dogs between 18 and 24 months of age with a mean weight of 30.4 ± 2.75 kg were used. Blood pressure was directly measured at the following time intervals: –5, 0, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 90 and 120 minutes after treatment with diminazine aceturate (4.2 mg/kg) intramuscularly. No statistical difference (P > 0.05) was found in blood pressure between any of the time intervals. An increase in heart rate was seen 5 minutes after the administration of diminazine aceturate but no change in blood pressure was evident. This study concluded that diminazene aceturate in its current formulation with antipyrine does not alter blood pressure in healthy adult dogs.
The pharmacokinetics of diminazene aceturate after intramuscular administration in healthy dogs  [cached]
D.M. Miller,G.E. Swan,R.G. Lobetti,L.S. Jacobson
Journal of the South African Veterinary Association , 2012, DOI: 10.4102/jsava.v76i3.416
Abstract: The pharmacokinetics of diminazene aceturate following intramuscular (i.m.) administration at 4.2 mg/kg was evaluated in 8 healthy German Shepherd dogs. Blood samples were collected at 19 intervals over a period of 21 days. Diminazene plasma concentrations were measured using a validated HPLC method with UV detection and a sensitivity of 25 ng/m . The in vitro and in vivo binding of diminazene to blood elements was additionally determined. Diminazene pharmacokinetics showed a large inter-individual variation after i.m. administration. It had a short absorption half-life (K01-HL of 0.11 + 0.18 h), resulting in a Cmax of 1849 + 268.7 ng/m at Tmax of 0.37 h and a mean overall elimination half-life (T1/2 ) of 5.31 + 3.89 h. A terminal half-life of 27.5 + 25.0 h was measured. At 1 h after i.m. injection, 75% of the diminazene in whole blood was in the plasma fraction. The results of this study indicate that diminazene is rapidly distributed and sequestered into the liver, followed by a slower terminal phase during which diminazene is both redistributed to the peripheral tissues and/or renally excreted. It is recommended that diminazene administered i.m. at 4.2 mg/kg should not be repeated within a 21-day period.
The effect of diminazene aceturate on cholinesterase activity in dogs with canine babesiosis  [cached]
R.J. Milner,F. Reyers,J.H. Taylor,J.S. Van den Berg
Journal of the South African Veterinary Association , 2012, DOI: 10.4102/jsava.v68i4.890
Abstract: A clinical trial was designed to evaluate the effects of diminazene aceturate and its stabiliser antipyrine on serum pseudocholinesterase (PChE) and red blood cell acetylcholinesterase (RBC AChE) in dogs with babesiosis. The trial was conducted on naturally occurring, uncomplicated cases of babesiosis (n = 20) that were randomly allocated to groups receiving a standard therapeutic dose of diminazene aceturate with antipyrine stabiliser (n = 10) or antipyrine alone (n = 10). Blood was drawn immediately before and every 15 minutes for 1 hour after treatment. Plasma PChE showed a 4 % decrease between 0 and 60 min within the treatment group (p < 0.05). No statistically significant differences were found between the treatment and control groups at any of the time intervals for PChE. There was an increase in RBC AChE activity at 15 min in the treatment group (p < 0.05). No significant differences were found between the treatment and control groups at any time interval for RBC AChE. In view of the difference in PChE, samples from additional, new cases (n = 10) of canine babesiosis were collected to identify the affect of the drug over 12 hours. No significant depression was identified over this time interval. The results suggests that the underlying mechanism in producing side-effects, when they do occur, is unlikely to be through cholinesterase depression.
Efficacy of Diminazene Aceturate with and without Levamisole or Dimethyl Sulfoxide in Reducing Organ Weight and Parasitemia in T. congolense Infected Rats
Eghianruwa, K.I.,Anika, S.M.
International Journal of Animal and Veterinary Advances , 2012,
Abstract: The efficacies of diminazene aceturate alone and in separate combinations with levamisole and Dimethyl Sulfoxide (DMSO) in the treatment of T. congolense infection in rats were assessed on day 7 post infection and days 7 and 14 post treatment using changes in the weights and histology of the liver, spleen, heart and brain as well as parasitemia as parameters. Infected rats were treated with 7.0 mg/kg diminazene aceturate on day 7 post infection following which DMSO (0.5, 1.0 and 2.0 g/kg, respectively) and levamisole (10, 20 and 40 mg/kg, respectively) were administered as daily supplements to different groups of rats. Trypanosoma congolense only caused significant increase in spleen weight. There were no histopathological lesions in any organ. Infection had no effect on heart weight. Liver and spleen weights were lower in the diminazene group by day 7 Post Treatment (PT), but this situation was reversed by day 14 PT. Increase in the dose of DMSO caused increased liver weight. Diminazene/DMSO combination was more effective at 14 days PT in reducing spleen weight than treatment with diminazene alone. On the contrary, diminazene/levamisole combination was less effective than diminazene alone in reducing spleen weight. Parasites disappeared after diminazene treatment but reappeared only in the diminazene and levamisole groups by day 14 PT. Early relapse and high virulence of the Basa strainof T. congolense used may be responsible for the ineffectiveness of the three treatment protocols.
The susceptibility of Trypanosoma congolense isolated in Zambézia Province, Mozambique, to isometamidium chloride, diminazene aceturate and homidium chloride  [cached]
S. Jamal,I. Sigauque,C. Macuamule,L. Neves
Onderstepoort Journal of Veterinary Research , 2010, DOI: 10.4102/ojvr.v72i4.190
Abstract: Resistance to trypanocidal drugs has been detected in various African countries and is a serious impediment to the control of livestock trypanosomosis. To determine whether drug resistant trypanosome strains are present in the Zambézia Province of Mozambique a study was initiated. To assess the effect of the farming system and the drug-use regimen on the development of drug resistance, trypanosome isolates were collected from cattle from subsistence and commercial livestock production systems. The susceptibility of seven isolates against isometamidium chloride, diminazene aceturate and homidium chloride was tested in mice using a multiple-dose test. In four of the seven isolates high levels of drug resistance to diminazene aceturate and isometamidium chloride were detected. In most cases the observed levels of drug resistance correlated with the drug-use practices in the particular livestock production system.
Trypanocidal efficacy of diminazene in diabetic rats  [PDF]
U. S. Chigozie,A. B. Maduka,J. G. Ifeanyi
Iraqi Journal of Veterinary Sciences , 2012,
Abstract: The experiment was conducted to investigate the impact of hyperglycaemia on the trypanocidal efficacy of diminazene aceturate. Groups of alloxan-induced diabetic rats infected with T. brucei and T. congolense were treated with diminazene aceturate, and trypanocidal effects compared with normal non-diabetic controls. Results showed that the prepatent period was shorter in the diabetic (11.25±1.65 days) than non-diabetic-T. congolense (15.0±1.73 days), and also variations in responses to the trypanocidal therapy between the diabetic and non-diabetic groups were detected. Parasite clearance time did not differ significantly between the diabetic and non-diabetic (43.2±8.89 versus 52.8±8.89 hours in T. brucei and 33.6±5.9 versus 36.0±6.93 hours in T. congolense, respectively). The relapse intervals were shorter in the diabetic than non-diabetic (16 days versus 23 days in T. brucei, and 7 days versus 14 days in T. congolense, respectively). Proportion of relapses was greater in the diabetic- (100%) than non-diabetic-T. congolense (66.7%). We also find parasite species-related differences in susceptibility to the trypanocide, with a higher apparent cure rate in the T. brucei than T. congolense group. We conclude from the results of this study that the chemotherapeutic effectiveness of diminazene aceturate may be diminished in patients with diabetes mellitus. Further study is needed to validate this hypothesis.
The effects of single and combined chemotherapy of DL - α -Difluoromethyornithine and diminazene aceturate in experimental Trypanosoma brucei gambiense infection in mice
AW Mbaya, MM Aliyu, B Gamba
Nigerian Veterinary Journal , 2008,
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