Metabolism of isometamidium in hepatocytes isolated from control and inducer-treated rats

Little is known about the metabolism and mechanism of action of the trypanocide, isometamidium (ISM), the major drug used for prophylaxis of trypanosomiasis. We have investigated its metabolism and distribution in isolated rat hepatocytes using liquid chromatography-mass spectrometry and confocal laser scanning microscopy (CLSM). Two putative metabolites were formed, which were proposed to be a mono-acetyl derivative and an oxidized metabolite (SII). This is the first demonstration of the hepatic metabolism of ISM, as previous in vivo studies were hampered by dose-limiting toxicity and insensitive analytical methods. The intrinsic fluorescence of the drug enabled its intracellular uptake to be followed by CLSM. It is taken up rapidly into the nucleolus, nuclear membrane and endoplasmic reticulum within 5 min, and retained in the nucleus for at least 24 h. Persistent binding of ISM to cellular macromolecules may contribute to its prophylactic effect in vivo. Pretreatment of rats with 3-methylcholanthrene, phenobarbitone (PB) or the widely used pyrethroid pesticide, deltamethrin, resulted in an increase in metabolism of ISM to the proposed SII after 1 h incubation with hepatocytes. 3-methylcholanthrene was the most potent inducer, causing a maximal 19.5-fold induction of SII formation after exposure of hepatocytes to ISM for 1 h compared with formation by control hepatocytes. In comparison, at the 1 h timepoint deltamethrin pre-treatment caused a 10.2-fold induction, and PB only 8.2 fold.     

Thyroid hormones modulate the hypothalamo–hypophyseal–gonadal axis in teleosts: Molecular insights

Reproduction in fishes is influenced by thyroid hormones at various levels of gonadal cell differentiation and steroidogenesis. Thyroid hormones have recently also emerged as an important modulator of season- and photoperiod-dependent variations in the reproductive cycle with a possible effect on the hypothalamo–hypophyseal axis and pineal interactions. This review describes the current status of thyroid hormone research in relation to reproduction, with special emphasis on contributions to this field by Indian researchers including our laboratory. Evidence is provided for the multifocal action of thyroid hormones at various levels of the hypothalamo–hypophyseal–gonadal axis affecting reproduction. The underlying physiological and molecular mechanisms pertaining to thyroid hormone modulation of reproduction, such as gonadotropin-releasing hormone (GnRH) synthesis and release, androgen and gonadotropin receptor expression, gonadotropin (GTH) expression, and tissue sensitivity to GTHs are highlighted with relevant discussions of the current technical limitations, applications, and future perspectives of research in this field.     

Ovine ceroid-lipofuscinosis is a proteolipid proteinosis

The pathogenesis of the ceroid-lipofuscinoses, inherited storage diseases of children, was studied in an ovine model. This was shown to have clinical and pathological features most in common with the late infantile and juvenile human forms of the disease. The ability to study sequential changes allowed the retinal lesions to be described as a dystrophy of photoreceptor outer segments which preceded loss of the photoreceptor cells. An early decrease in amplitude of the c-wave electroretinograph was attributed to a decrease in the transpigment epithelial component. The decreased a- and b-wave amplitudes were attributed to the changes in and loss of, photoreceptor cells. The chemical components of isolated storage cytosomes were analyzed and shown to consist mostly of protein. Sequence analysis of the dominantly stored protein showed that it was identical to the DCCD reactive proteolipid or subunit c of mitochondrial adenosine triphosphate synthase and that it comprised approximately 50% of storage material. Based on the adage that the dominantly stored species should reflect the underlying biochemical anomaly, it was concluded that it was of pathogenic significance. This highly hydrophobic protein tends to extract with lipids in chloroform/methanol and is thus known as a proteolipid. Some of the remainder of the stored proteins also had this characteristic. It was concluded that ovine ceroid-lipofuscinosis was a proteinosis, more specifically a proteolipid proteinosis and as such it forms the prototype of a new class of storage diseases. Recognition of the nature of the dominantly stored chemical species has helped understanding of a variety of chemical and physical characteristics attributed to the whole pigment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathophysiology of the periparturient egg rise in sheep: the role of prolactin

The involvement of prolactin in the periparturient rise in the faecal nematode egg count in sheep was investigated. Ostertagia circumcincta larvae (5000 third stage larvae three times weekly) were administered to adult immune ewes from three weeks before parturition to three weeks afterwards. Ten ewes were injected twice daily with 2-bromo-alpha-ergocryptine (bromocriptine), an antagonist of prolactin secretion, for two weeks starting two days after lambing while 10 ewes remained untreated. Bromocriptine treatment was initiated approximately two weeks pre partum in three other ewes. Plasma pepsinogen concentrations rose significantly by one week after the start of O circumcincta larval challenge in all the ewes but faecal egg counts remained negative until approximately one week post partum. Plasma prolactin concentration was reduced to a very low level in all bromocriptine treated ewes but this did not alter the dynamics of the periparturient rise in faecal egg counts. Neither cell-mediated nor humoral immunity of the ewes, as assessed by their sensitivity to BCG inoculation and by antibody titre raised against horse red blood cells, respectively, were impaired during the rise in faecal egg count, nor were these parameters altered by manipulation of plasma prolactin concentration. Lamb growth rate was not retarded by low plasma prolactin concentration in the bromocriptine treated ewes. These results are not consistent with the generally held hypothesis that elevated plasma prolactin concentration is directly associated with the periparturient rise.     

A 6-year survey of pathological conditions of slaughtered animals at Zango abattoir in Zaria,Kaduna State,Nigeria

A 6-year retrospective study (2000–2005) of animals slaughtered at the Zango abattoir in Zaria, Kaduna State, Nigeria was carried out to determine disease conditions encountered in slaughtered animals. Records kept at the abattoir were analysed. A total of 69,307 cattle, 3,820 goats and 1,763 sheep were slaughtered for the period under study. Of the 69,307 cattle slaughtered for the period, 22,459 (32.41%) were males and 46,848 (67.59%) were females, while 1,763 sheep were slaughtered comprising of 506 (28.70%) males and 1,257 (71.30%) females, and 3,820 goats made up of 1,212 (31.73%) males and 2,608 (68.27%) were females. The major disease and/or pathological conditions were helminthosis (fascioliasis, haemonchosis and paramphistomosis) 16.20%, Streptothricosis 4.15%, Pericarditis 2.20%, liver cirrhosis 2.08%, abscesses 1.04%, pneumonia 0.14%, nephritis 0.05% and Contagious Bovine Pleuropneumonia, Tuberculosis and Nocardiosis 0.01% each. Out of the 15,075 infected organs, 13,314 (88.38%) were partially salvaged while 1,751 (11.6%) whole organs were condemned. A total of 1,239 pregnant cows, 221 pregnant ewes and 637 pregnant does were slaughtered, representing a foetal wastage of 2.65% for cattle, 17.58% for sheep and 24.43% for goats. The result of this study apart from serving as an indicator of field disease condition also demonstrates cases of serious losses in production due to slaughter of pregnant animals especially for sheep and goats.     

Altered pharmacokinetics of enrofloxacin in experimental models of hepatic and renal impairment

We investigated the effects of hepatic and renal impairment on the pharmacokinetics of enrofloxacin in Sprague-Dawley rats. Experimental hepatic and renal failure were induced by carbon tetrachloride (CCL₄) and 5/6 nephrectomy, respectively. After intravenous dosing of enrofloxacin (10 mg/kg), plasma concentrations of enrofloxacin were measured using liquid chromatograph/mass spectrometry. There was no significant effect of hepatic impairment on enrofloxacin pharmacokinetics. However, renal impairment markedly prolonged elimination half life (t_1/2λz) of enrofloxacin (P < 0.05), comparing with respective control. Total body clearance (Cl_b) and volume of distribution at steady state (V_ss) were significantly decreased (P < 0.05) by renal impairment. In conclusion, these results suggested that renal impairment could affect the pharmacokinetics of enrofloxacin.     

Evaluation of the Rice pelvimeter for measuring pelvic area in double muscled Belgian Blue cows

The accuracy of the Rice pelvimeter for measuring pelvic area of double muscled Belgian Blue (BB) cattle was investigated by comparing measurements in the live animal with these obtained from the same animal after slaughter. Pelvic measurements from 466 BB-cows aged 2–10 years old and of an excellent carcass qualification (S and E in the SEUROP classification) were measured with the pelvimeter approximately 12 h prior to, and by graded ruler within 2 h after, slaughter. The mean difference of measurements between living and dead cattle were − 0.2 cm for pelvic width (95% limits of agreement − 2.5–2.1 cm), and 1.2 cm for pelvic height (95% limits of agreement − 1.8–4.1 cm). The correlation coefficient between all pelvic measurements was between 0.46 and 0.59 (p < 0.001). The age of the animals influenced only pelvic height whilst carcass weight influenced all the components of the pelvic area. There was a significant correlation between the pelvimetric measurements of the birth canal in living cattle obtained using a Rice pelvimeter compared to actual measurements obtained from the carcass. The Rice pelvimeter is a suitable tool for assessing accurate pelvic skeletal conformation and to select animals in this breed with a larger birth canal and hence less dystocia problems.     

Comparison between Haemophilus parasuis infection in colostrums-deprived and sow-reared piglets

The aim of this study was to compare the development of Glasser's disease in sow-reared and colostrum-deprived piglets. Ninety piglets from a commercial pig farm in Spain were used. The farm was positive for Haemophilus parasuis. Fifty-two pigs were sow-reared (SR) and 38 were colostrum-deprived (CD) piglets. The animals were intratracheally inoculated with H. parasuis serovar 5 and sacrificed at 1, 2 and 3 days post-infection. To assess the development of disease, antibody titers, clinical signs, pathological lesions, microbiological isolation and PCR amplification were compared between the groups. Inoculation of SR pigs did not cause clinical signs or lesions of Glasser's disease. In SR pigs, H. parasuis isolation and specific PCR amplification from tissues showed a very low number of positive samples. In contrast, in CD pigs, inoculation resulted in the typical signs and lesions of Glasser's disease. Positive microbiological isolation and specific PCR products were obtained from the majority of the tissues tested, and no antibodies against H. parasuis were detected. The experimental infection using CD pigs describes a successful method to study this microorganism and confirms the important role that maternal antibodies play in protection against clinical signs and disease.