Taurine mitigates cognitive impairment induced by chronic co-exposure of male Wistar rats to chlorpyrifos and lead acetate.

Organophosphate pesticides and heavy metals are ubiquitous environmental pollutants and neurotoxicants. We investigated the effects of taurine (an antioxidant; TA) on oxidative stress and cognition in male Wistar rats co-treated with chlorpyrifos (an organophosphate pesticide; CPF) and lead acetate (heavy metal; LA). The Wistar rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil respectively. The remaining three groups were administered with taurine (TA), 50 mg/kg body weight, CPF+LA group [CPF (4.25 mg/kg, 1/20 LD50] and LA (233.25 mg/kg, 1/20 LD50) and TA+CPF+LA group [TA (50 mg/kg), CPF (4.25 mg/kg) and LA (233.25 mg/kg)]. The xenobiotics were administered once daily by oral gavage for 16 weeks. The results showed reductions in the activities of brain antioxidant enzymes and acetylcholinesterase, increased lipoperoxidation and histopathological alterations of the cerebral cortex in the CPF+LA group. However, TA mitigated perturbations in the activities of the antioxidant enzymes and acetylcholinesterase, counteracted oxidative stress and brain lipoperoxidation and attenuated neuronal degeneration induced by joint CPF and LA-induced neurotoxicity. The results suggested that TA is neuroprotective following chronic co-exposure of rats to CPF and LA.

Pharmacokinetics of diminazene in plasma and lymph of goats.

OBJECTIVE: To characterize the pharmacokinetics of diminazene in plasma and pseudo-afferent lymph of East Africa X Galla goats. DESIGN: The efferent prescapular lymphatic duct of 3 goats was cannulated 8 weeks after surgical removal of the lymph node. Thereafter, 3.5 mg of diminazene base/ kg of body weight was administered to these goats and to 3 noncannulated goats. PROCEDURE: Using high-performance liquid chromatography, concentration of diminazene was determined in plasma and lymph collected up to 96 hours after treatment. RESULTS: Maximal concentrations of diminazene in plasma of noncannulated goats (median [range], 4.30 [4.28 to 5.01] micrograms/ml), plasma of cannulated goats (3.94 [2.94 to 4.06] micrograms/ml), and lymph (1.06¿0.73 to 1.86] micrograms/ml) were significantly different (P < 0.05); values in lymph were considerably lower than those in plasma from noncannulated and cannulated animals. Time to reach maximal concentration did not differ significantly between lymph and plasma of noncannulated and cannulated goats. Over the first 24 hours after drug administration, concentration of diminazene in plasma of noncannulated goats was generally higher than that in lymph, but thereafter was similar. Apparent volume of distribution of diminazene in the plasma of noncannulated (2.57 [1.93 to 2.60] L/kg) and cannulated (2.30 [1.04 to 2.40] L/kg goats did not differ significantly. Penetration ratio of diminazene into lymph, compared with plasma, of cannulated goats was 1.69:1. CONCLUSIONS: Disposition of diminazene in goats is characterized by higher concentration in plasma than in lymph. However, the drug persists longer in lymph than in plasma. CLINICAL RELEVANCE: The longer persistence of diminazene in lymph than in plasma may account for the enhanced therapeutic efficacy of diminazene in the early stage, compared with later stages, of a tsetse fly-transmitted trypanosome infection.

Pharmacokinetics of diminazene in female Boran (Bos indicus) cattle.

The disposition kinetics and bioavailability of diminazene in five healthy heifers were determined after single intravenous (i.v.) and intramuscular (i.m.) administration of the drug in sequence with a wash-out period between administrations of 6 weeks. Intact diminazene in plasma, whole blood and urine samples was analysed using high-performance liquid chromatography. Nonlinear regression analysis of the i.v. and i.m. data indicated that, for either route, the plasma disappearance curves of diminazene were best described by triexponential equations. The i.v. bolus was followed by rapid and biphasic distribution with half-life values of 0.04 h and 0.58 h, Vd(ss) was 1.91 +/- 0.42 l/kg, elimination half-life was 31.7 h while Cl averaged 1.74 +/- 0.40 ml/min/kg. Within 30 min of the i.v. dose, the erythrocyte/plasma partition ratio of diminazene was 0.30 +/- 0.15. Diminazene was rapidly absorbed following i.m. administration; t1/2ka was 0.60 h. Cmax, 4.68 +/- 1.12 micrograms/ml, was attained in 10-15 min and systemic availability was 102.42 +/- 7.25%. The half-life of the terminal disappearance phase was 145.48 h. About 8.26% of the i.m. dose was excreted intact in the urine within the first 24 h of treatment. In vitro, diminazene was bound to bovine plasma albumin to the extent of 38.01-91.10%.

Comparative pharmacokinetics of diminazene in noninfected Boran (Bos indicus) cattle and Boran cattle infected with Trypanosoma congolense.

The pharmacokinetics of diminazene in five female Boran (Bos indicus) cattle before and then during acute and chronic phases of experimental infections with Trypanosoma congolense were investigated. A 7.0% (wt/vol) solution of diminazene aceturate (Berenil) was used in all three phases of the study and administered as a single intramuscular dose of 3.5 mg of diminazene base per kg of body weight. There were no significant differences between the values of pharmacokinetic parameters for the noninfected cattle and the values for cattle with a chronic T. congolense infection. However, the maximum concentration of the drug in plasma during the acute phase of infection (8.25 +/- 1.72 micrograms/ml) was significantly (P < 0.01) greater than that during chronic infection (5.04 +/- 0.26 micrograms/ml) and that in the noninfected state (4.76 +/- 0.76 micrograms/ml). Similarly, the time to maximum concentration of the drug in plasma when diminazene was administered during the acute phase of infection (18.00 +/- 6.71 min) was significantly (P < 0.02) shorter than that for noninfected cattle (36.00 +/- 8.22 min) and that during chronic infection (33.75 +/- 7.50 min). The volume of distribution at steady state during acute infection (1.01 +/- 0.31 liter/kg) was significantly (P < 0.01) smaller than that in the noninfected state (1.37 +/- 0.17 liter/kg) and that in chronic infection (1.51 +/- 0.24 liter/kg). Eight hours after the drug had been administered, the concentration-time data profiles for each of the three study phases were very similar. Mean concentrations of diminazene in plasma 48 h after administration of the drug were 0.43 +/- 0.07 microgram/ml in noninfected cattle, 0.43 +/- 0.11 microgram/ml during the acute phase of trypanosome infection, and 0.44 +/- 0.09 microgram/ml during the chronic phase of the infection. Results of the present study indicate that the area under the concentration-time curve for diminazene in trypanosome-infected cattle did not differ significantly for noninfected cattle. It, therefore, appears that the total amount of diminazene attained and maintained in the plasma of cattle is not significantly altered during infection with T. congolense.

Response of Trypanosoma congolense in goats to single and double treatment with diminazene aceturate.

Diminazene aceturate is one of a limited number of compounds currently marketed for treatment of trypanosomiasis in cattle, sheep and goats. The pharmacokinetics of the compound in goats suggest that double treatment with diminazene aceturate might enhance the compound's therapeutic activity. A study was therefore conducted in goats using two clones of Trypanosoma congolense, IL 3274 and IL 1180, which were previously shown to be resistant and sensitive, respectively, to single treatment with diminazene aceturate. The results indicated that, as compared to single treatment, double treatment with diminazene aceturate at a dose of 7.2 mg kg-1 bodyweight, at either eight or 24 hour intervals, did not greatly enhance the therapeutic activity of the drug. Furthermore, treatment with the same drug dose eliminated infections with T congolense IL 3274 when treatment was administered 24 hours after infected Glossina morsitans centralis had fed, but failed to do so if treatment was delayed until after goats were detected to be parasitaemic. This suggests that failure of T congolense IL 3274 to respond to treatment with diminazene may not be due to drug resistance per se.

Acute toxicity of crude extracts of Aspergillus quadrilineatus isolated from acha (Digitaria exilis Stapf).

In a survey of fungi and mycotoxin conterminating acha (Digitaria exilis Stapf) in Plateau State of Nigeria, 96 fungal isolates were made. Screening of the fungi isolates for their mycotoxin-producing potentials showed that Aspergillus quadrilineatus (Thom and Raper) produced some of the most toxic mycotoxins. Two extracts of the Aspergillus quadrilineatus (the petroleum ether soluble extracts [PER] and the petroleum ether defatted crude extract [PEDCR]) were tested for acute toxicity in mice, chicks and cattle. The ip LD50 of PER in mice was 1148 mg/kg, and the oral LD50 of PEDCR was 566 mg/kg in mice and 556 mg/kg in chicks. The ip LD50 of PEDCR in mice was 21 mg/kg. The toxic signs of PER and PEDCR in mice and chicks included tachypnea, tachycardia, anorexia, somnolence, diarrhea, coma and death. The main postmortem findings were congestion of heart, liver, kidney and lungs and sloughing of the wall of stomach and hemorrhagic enteritis. The histopathologic findings in dead animals included edema and mild degeneration of the myocardium and necrosis of kidney tubular epithelial cells, hepatocytes and bronchioles. The only clinical observation in 1 calf orally dosed with a culture of Aspergillus quadrilineatus of maize was transient whole body tremors which occurred 1 h after dosing, tachycardia and profuse salivation. No significant histopathologic changes were found in the organs of the sacrificed calf.

The lead content of plants and animals as indicators of environmental contamination.

Lead content of tissues from some edible plants, pigeons and a vulture, and from human and cattle blood were determined to gain insight into the extent of environmental lead contamination in Zaria and Kaduna environs of Kaduna state of Nigeria. The results suggest that environmental lead contamination in these areas was insignificant when compared to values from developed countries like US. However, there is need for more work of this nature on a regional basis to ascertain the true picture of total environmental lead pollution in Nigeria.

The mycoflora and some mycotoxins found in acha (Digitaria exilis Stapf) in Plateau State, Nigeria.

Mouldy acha (Digitaria exilis) samples were collected at three different periods of the year from some local government areas of Plateau State and were screened for their mycoflora and for seven mycotoxins. Phoma sorghina was the most common contaminant during the cold dry harmattan period (November-February) and during the humid and wet period (June-October). This was followed by Fusarium moniliforme and then by Aspergillus spp. During the hot and dry period (March-May), Aspergillus spp. were the most prevalent fungi, followed by Fusarium spp. and Phoma sorghina in that order. Zearalenone was the most prevalent mycotoxin in mouldy acha samples collected during the cold and dry period, while aflatoxins were the most prevalent in samples collected during the hot and dry period. Zearalenone was only detected in one of the samples collected during the hot, humid and wet period.

Field observations on adult zebu bulls immunised against anaplasmosis by infection and treatment plus integrated tick control.

Fourteen adult zebu bulls which were negative for Anaplasma marginale infection both serologically and on blood smear examinations were infected with a virulent Nigerian isolate of A. marginale. Forty days following the immunising infection when clinical reactions were established groups of seven animals were treated with either two doses of imidocarb dipropionate (2 X 5 mg/kg given intramuscularly 14 days apart) or a single intramuscular dose of long-acting oxytetracycline (5 mg/kg). Following clinical recovery, two weeks after the first treatment the immunised animals and seven susceptible controls were then introduced into a tick-infested area and held there for 15 months with regular tick control. There were significant differences between the mean weight gains of surviving animals in the oxytetracycline group and the controls and surviving animals in the imidocarb group and control cattle. The protective effect of tick control alone was inferior to that of integrated tick control plus anaplasmosis control by either method of immunisation. Losses occurred in all groups due mainly to the effects of other tick-borne diseases, babesiosis and heartwater.

The mycoflora and some mycotoxins found in maize (Zea mays) in the Plateau State of Nigeria.

Mouldy maize samples were collected at three periods of the year (Dry harmattan period, November-February; hot and dry period, March-May; and hot humid and wet period, June-September) from local government areas of Plateau State of Nigeria. They were screened for their mycoflora, aflatoxins, ochratoxin A and zearalenone contents. Fusarium spp were the commonest fungi found in maize during the dry harmattan and hot and dry periods and Neurospora spp were the commonest fungi found during the hot, humid and wet period. The highest level of aflatoxin was found in samples from Langtang (B1 = 960, B2 = 544 micrograms/kg) and the highest level of zearalenone was found in samples from Jos and Langtang areas (17,500 micrograms/kg). The highest level of ochratoxin was found in the field samples from the Jos area (150 micrograms/kg).

Pharmacokinetics of diminazene in sheep.

The pharmacokinetic behavior of diminazene in plasma after administration of 2 mg/kg i.v. and 3.5 mg/kg i.m. was studied in four healthy Dala x Ryggja rams. Following i.v. injection, the data were satisfactorily described by a tri-exponential equation; the apparent volume of distribution at the steady-state was 0.56 +/- 0.04 L/Kg (mean +/- SD; n = 4); total body clearance averaged 1.1 +/- 0.09 ml/kg/min and elimination half-life was 9.30 +/- 1.40 hr. After intramuscular administration peak plasma levels of 6.30-7.57 micrograms/ml were reached in 20 to 45 min and the mean absorption time averaged 5.83 +/- 1.61 hr. Systemic availability relative to the intravenous dose was 95.10 +/- 23.21% and mean residence time averaged 14.16 +/- 1.55 hr. The partition of diminazene between erythrocytes and plasma averaged 0.64 +/- 0.10; plasma protein binding was high (65-85%) and concentration-dependent. Based on the experimental data obtained, an initial i.m. dose of 2.5 mg/kg followed by 2 mg/kg 24 hr later should be safe and effective in cases of babesiosis and trypanosomiasis sensitive to diminazene. A preslaughter withdrawal period of 14-26 days was estimated.

Seasonal variations in rectal temperature of Yankasa sheep.

From measurements of rectal temperature (Tre) at 06:00h (06:00Tre) and at 14:00h (14:00Tre), meteorological stress was determined in six Yankasa ewes in terms of per cent rise of 14:00Tre over 06:00Tre reference values during the harmattan and hot-dry seasons. Absolute and mean Tre values were significantly higher (P less than 0.05) during the harmattan than the hot-dry season. In both seasons, mean 14:00Tre was significantly higher (P less than 0.01) than 06:00Tre. The mean diurnal difference between 14:00Tre and 06:00Tre, i.e. delta Tre was about 1 degrees C during the harmattan but ranged between 0.5 and 0.7 degrees C during the hot-dry season. All animals were observed to shiver during harmattan nights.

Effect of season on estrous cycle of Yankasa sheep.

An investigation was conducted to establish the effects of harmattan and hot-dry season on estrous cycle length, onset, and duration of estrus in Yankasa sheep indigenous to the Nigerian guinea savanna zone. Mean cycle lengths were 16.8 +/- 0.58 and 16.4 +/- 0.53 days during harmattan and hot-dry seasons, respectively; short cycles, 5-13 days, and long cycles, 21 to 30 days, were observed during both seasons. During the harmattan season, 57.1% of estrus began at night while 70% started at night during the hot-dry season. The duration of normal estrus observed during the harmattan, 33.6 +/- 5.87h, significantly decreased (P0.05) during the hot-dry season (24.0 +/- 5.45h). It is suggested that twice daily observation at 12-hour intervals will suffice to detect estrus in this breed of sheep.

Urinary delta-aminolevulinic acid (ALA) excretion in humans and cattle as an index of exposure to lead.

Disposable ion-exchange chromatographic columns were used to determine delta-aminolevulinic acid (ALA) concentrations in 11 bovine and 184 human urine samples. The mean urinary ALA concentrations in persons working as battery charges, autopainters, automechanics, and urban first-grade pupils were 11.61 +/- 14.23, 6.51 +/- 3.31, 6.48 +/- 3.36, and 5.71 +/- 2.91 micrograms/ml respectively. These values were higher than those found in urine from gasoline station attendants, university students and laboratory assistants, rural adult farmers, and rural first-grade pupils, which were 4.90 +/- 1.95, 4.93 +/- 1.76, 4.40 +/- 1.79 and 4.51 +/- 2.65 micrograms/ml respectively. In cattle (Holstein Friesian/White Fulani cross) the mean urinary ALA concentration was 1.84 +/- 0.04 micron/ml. The data indicates that persons working around automobile, lead batteries and leaded gasoline had elevated ALA concentrations in urine. Rural humans and cattle did not have significant elevations of urinary ALA.

Absorption, distribution, and excretion of imidocarb dipropionate in sheep.

Spectrophotometric and thin-layer chromatographic methods for determination of imidocarb in biological specimens are described. Following intravenous injection of imidocarb (2.0 mg/kg) into 3 sheep, plasma concentrations, initially averaging 10.8 microgram/ml, decreased to an average of 1.9 microgram/ml within 1 hour and then to less than 1 microgram/ml within the next 4 hours. When imidocarb (4.5 mg/kg) was injected intramuscularly (IM) into 7 sheep, peak plasma concentrations averaging 7.9 microgram/ml were achieved within 4 hours and then rapidly decreased to 4.6 microgram/ml within the next 2 hours. Plasma values then decayed very slowly by first-order kinetics and trace amounts were still present 4 weeks after treatment. Imidocarb was bound to plasma proteins and the apparent volume of distribution was estimated to be slightly higher than the total body water. The concentrations of the drug in the plasma and in the erythrocytes were approximately equal. Detectable amounts were present in all examined tissues 4 weeks after IM administration Twenty-four hours after IM administration, the highest concentrations were in kidney, liver, and brain. The 14C-labeled imidocarb could be detected in all regions of the central nervous system examined, in the hypophysis, and in the pineal body. Metabolic or biotransformation products were not detected by the methods used. Of the administered IM dose, 11 to 17% was excreted in the urine within 24 hours; thereafter, the excretion rate was low, and detectable amounts were still present in the urine for 4 weeks. Renal clearance of imidocarb was less than glomerular filtration rate, indicating net tubular reabsorption. The relatively high concentration of imidocarb in the bile suggests that the bile is an important route of excretion. High concentrations were also found in the mild of lactating ewes, but the drug could not be detected in the plasma of lambs fed milk from these ewes.

Urinary excretion of protein by adult Yankasa rams.

Total urine was collected from 12 adult Yankasa rams for 13 days. The rams excreted a mean urine volume of 508-0 +/- 201-6 ml each day. The total solids concentration excreted in the urine averaged 9-0 +/- 5-2 g/100g of urine. All the 178 urine samples contained protein. The urinary total protein concentration varied from 0-6 to 2-8 mg/dl. The total protein excreted was 7-0 + 2-6 mg/day of which the globulin content was 3-3 +/- 1-2 mg; mucoprotein, 2-0 +/- 0-7 mg; albumin, 1-7 + 0.6 mg; and A/G ratio, 0-52 +/- 0.06. Electrophoretic analysis of the urinary proteins showed three components which were comparable on a mobility basis with the serum proteins, namely albumin, combined alpha- and beta-globulin, and gamma-globulin. The largest fraction of the urine protein was gamma-globulin. Protein excretion in the urine of adult Yankasa rams was much lower than that reported in sheep bred for temperate climates, a trait that would have survival value in their hot, dry, semi-arid environment.