Analysis and pharmacokinetics of cimaterol in growing Holstein steers.

Pharmacokinetic parameters for the beta 2-adrenergic agonist, cimaterol (CIM), were determined in growing Holstein steers. Compartmental analysis was used after measurement of CIM in body fluids by affinity chromatography and HPLC using UV detection. Recoveries from spiked plasma and urine standards were 70 +/- 1.2% and 68 +/- 1.1%, respectively. The minimum detection level in plasma was 1 ng/mL and the average CV was 5.1% for concentrations that ranged from 1 to 30 ng/mL. Four steers (276 +/- 24 kg) received 15 mg of CIM by bolus intravenous injection. Plasma CIM levels declined in a biphasic manner with half-lives of 2.5 min for the distribution phase and 54 min for the elimination phase. A two-compartment open model was used to describe the disappearance of CIM and the following pharmacokinetic parameters were obtained: central compartment volume (Vc) = .76 L/kg, apparent volume of distribution (Vd) = 4.1 L/kg, and transfer rate constants from the central to peripheral compartment (k12) = .177/min, from the peripheral to central compartment (k21) = .054/min and elimination from the central compartment (kel) = .074/min. After 8 h, total urinary CIM accounted for only 18.3% of the administered dose. Results suggest that circulating concentrations of CIM in growing steers are influenced by its accumulation in an unidentified peripheral pool and its conversion into unknown metabolite(s) before elimination.     

Eastern equine encephalitis in a flock of emus (Dromaius novaehollandiae).

Eastern equine encephalitis (EEE) was diagnosed in a flock of emus in southeastern Louisiana. The outbreak involved juvenile and adult breeders ranging in age from 20 to 36 months, with an attack rate of 76% and a case fatality rate of 87%. The diagnosis was confirmed by isolation and characterization of the viral agent, and by detection of EEE antibody in two recovered emus. High mortality was preceded by marked depression, hemorrhagic diarrhea, and emesis of blood-stained ingesta. On postmortem examination, hemorrhagic enteritis and multiple petechia of viscera were observed. Microscopic changes included severe necrosis of hepatocytes, intestinal mucosa, and necrotizing vasculitis of the spleen and lamina propria of the intestine. No nervous system lesions were observed. This outbreak occurred concurrently with EEE in horses and was attributed to unseasonably heavy rainfall with an abundance of arthropod vectors and proximity to free-living reservoir host species.     

Toxic peripheral neuropathy with demyelination in Sprague-Dawley rats given CGS 21595--a 5-lipoxygenase inhibitor.

Male and female Sprague-Dawley rats were given CGS 21595, a pro-drug that is almost immediately metabolized to CGS 19213, a naphthoquinone that acts as a 5-lipoxygenase inhibitor. The compound was administered by gavage to five groups of Sprague-Dawley rats (group Nos. 1, 5, n = 30; group Nos. 2-4, n = 20) at daily doses of 0, 50, 150, 500, or 1,000 mg/kg for 13 weeks. Rats in the higher dose groups had a reduced weight gain, but significant neurologic signs were not observed. A peripheral neuropathy consisting predominantly of myelin destruction in the spinal nerve roots and sciatic nerves in male rats treated with greater than or equal to 150 mg/kg CGS 21595 and in female rats treated with greater than or equal to 50 mg/kg CGS 21595 for 13 weeks. This lesion was not fully reversible after a recovery period of 4 weeks. Lesions consisted of ballooning of myelin sheaths, infiltration by macrophages, demyelination, and occasional areas of remyelination. Axons were generally preserved, and the brain and spinal cord were not affected. Male and female rats in all treatment groups had cytoplasmic hyaline droplets in the proximal renal tubules. This change was reversible after 4 weeks and was not associated with any other adverse effects on the kidney.     

Manipulated Mouse Embryos as Bioassay System for Water Quality Control

Mouse pronuclear stage embryos with intact slit zona pellucida (manipulated) were cultured in vitro until the hatched blastocyst stage in simplex optimized medium with higher K⁺ concentration (KSOM) prepared with three different water types: tap, deionized reverse osmosis (D‐O) water and Milli‐Q system (M‐Q) water. The culture media were supplemented with or without protein and ethylenediaminetetraacetic acid (EDTA, disodium salt). The rates of hatched blastocysts were significantly affected (p < 0.01) by micromanipulation, protein supplement and water source. The water source has no influence (p > 0.05) on development in EDTA‐supplemented protein‐free culture media, whereas in EDTA‐ and protein‐free culture media, the water quality significantly (p < 0.001) affected the rates of development, with higher rates in media prepared with M‐Q water. The micromanipulated embryos showed higher sensitivity to the water quality (p < 0.01). It worth mentioning that the rates of hatched blastocysts in protein‐free culture media were very low (0–7.5%). Furthermore, the three different water types were analysed by measuring the electrical conductivity, inorganic ions, total organic carbon and endotoxins to evaluate the purity. M‐Q water showed the lowest levels of inorganic ion, total organic carbon and endotoxin concentrations. We concluded that manipulated mouse embryos are good system to evaluate the quality of water used in biological system.     

Norsalsolinol uptake into secretory vesicles via vesicular monoamine transporter and its secretion by membrane depolarization or purinoceptor stimulation in PC12 cells.

The intracellular dynamics of norsalsolinol, a neurotoxin candidate causing parkinsonism-like symptoms, in PC12 cells was studied. We found that dopamine and norsalsolinol are co-localized to secretory granule layer by sucrose density gradient in norsalsolinol-treated PC12 cells. The norsalsolinol was actively taken up into isolated secretory vesicle fraction from PC12 cells with a Km value of 41.5+/-6.8 microM. The uptake of 10 microM of norsalsolinol was sensitive to reserpine (1 microM), an inhibitor of vesicular dopamine transporter, and dopamine, an endogenous substrate, but insensitive to GBR-12909, an inhibitor of dopamine transporter on plasma membrane. In norsalsolinol-treated PC12 cells, exposure to high K+ or ATP resulted in simultaneous release of norsalsolinol and dopamine. Time course of a release of dopamine and that of norsalsolinol evoked by 50 mM KCl or 100 microM ATP corresponded to each other. These releases were dependent on the concentrations of secretagogues. These data suggest that norsalsolinol is taken up with dopamine into secretory vesicle via vesicular catecholamine transporter.     

The Effect of Exogenous Hormone Treatment on Spermiation in Rhynchocypris oxycephalus (Sauvage and Dabry)

For the evaluation of hormonal control of spermiation in fish, a method to quanify the spermiation response of mature Rhynchocypris oxycephalus (Sauvage and Dabry) to hormonal therapy is described. Spermatocrit was determined after 7 min centrifugation at 18,000 ± g and sperm density was estimated by a standard hemocytomer method. Sperm density can be predicted from spermatocrit since their relationship is linear as described by the regression equation, Y = 3.68X - 27.18 ( R ² = 0.82, N = 50). where Y is spermatocrit and × is sperm density. Milt production by mature R. oxycephalus was highest at 24 h after injection of 1,000 IU human chorionic gonadotropin (HCG) and 50 μg luteinizing hormone-releasing hormone analogue (LHRHa) per kg body weight. Increased milt production coincided with low spermatocrit and sperm density levels. These results demonstrate that spermiation in mature R. oxycephalus can be reliably evaluated by a spermatocrit method and that HCG and LHRHa are effective in stimulating of spermiation in this species.     

Disappearance of acetic acid from the bovine reticulorumen at basal and elevated concentrations of acetic acid.

Disappearance of acetic acid was quantified to determine whether removal of this acid from the reticulorumen is altered when ruminal acetic acid concentrations are elevated. Ruminally fistulated beef steers (n = 3 per experiment; BW = 320 +/- 9 kg) were fed eight times daily a 46% corn-based concentrate:54% mixed hay diet to meet maintenance energy requirements (3.5 kg of DM/d). In situ production of acetic acid, determined by pulsed-continuous infusion of [1-14C]acetic acid, was 530 mmol/h (CV = 12%). Disappearance from the reticulorumen (i.e., presumed absorption) was 460 mmol/h (CV = 2%) or 87% (CV = 2%) of ruminal production. Variation is described within an operational steady state. Acetic acid concentrations were increased by continuous infusion of unlabeled acetic acid into the reticulorumen. Ruminal disappearance (mmol/h) increased when this simulated production was elevated up to and exceeding in situ rates reported previously (530 to 2,700 mmol/h). These data suggest that two-thirds to three-fourths of ruminal acetate production disappeared across the reticuloruminal wall when concentration was elevated; the complement exited from the rumen with the liquid phase. The reticulorumen has an additional capacity to remove acetic acid; however, it does so with an apparent reduced efficiency at higher production rates. Liquid out-flow may affect the efficiency of reticuloruminal disappearance. Sites distal to the rumen become quantitatively important when ruminal acetic acid concentrations are increased.     

Morphological study on the stomach of the lesser mouse deer (Tragulus javanicus) with special reference to the internal surface.

The stomach of the lesser mouse deer (Tragulus javanicus) was observed macroscopically. It consisted of only three compartments, rumen, reticulum and abomasum without omasum. The rumen was S-shaped with large ventral and caudoventral blind sacs and the reticulum was larger than the abomasum. Internally, the rumen was covered with numerous ruminal papillae even on the pillars and the ruminoreticular fold. These papillae were leaf- or tongue-like shaped and varied in size and density. The reticulum had honey-combed crests and the secondary crests were found rarely. The lips of the reticular groove were prominent and more developed in the aboral part than in the oral one. A sac-like transition zone, which had more prominent mucosal folds than had the floor of the reticular groove, was observed between the caudal end of the reticular groove and the abomasum. Mucosal folds of the abomasum were spiral, low but rather thick. These findings were discussed in view of comparison with other ruminants and of possible functional implications.