Previous work in the rabbit has shown that there is a significant flux of plasma hyaluronic acid (HA) which is taken up and degraded mainly in the liver but also concentrated in the spleen. Purified 14C-labelled HA of high average molecular wt prepared by biosynthesis from D-[U-14C] glucose was injected i.v. in mice and its tissue distribution was determined by whole-body autoradiography during the next 24 h. As blood levels declined, radioactivity was concentrated in the liver and spleen as found in the rabbit, and also in bone marrow and lymph nodes. Distribution was uniform in liver tissue, concentrated and relatively persistent in the periphery of lymph nodes, and distinctly nodular within the spleen. Analysis of an aqueous liver extract taken 4 h after injection identified 14C in HA, in a macromolecular fraction resistant to fungal hyaluronidase, and in metabolites of low molecular wt. These findings confirm and extend observations based on tissue extraction in rabbits. The pattern of distribution through the body and the restricted localization within spleen and lymph nodes further suggest that HA is absorbed from plasma and tissue fluids by elements of the reticuloendothelial system.
The nephrotoxic mycotoxin ochratoxin A was studied in rainbow trout by whole‐body autoradiography and scintillation counting using 14C‐labelled toxin. After one single intravenous injection of 10 μCi/fish, corresponding to 160 ng toxin/g body weight, the tissue affinity was studied during an eight day period. As soon as 5 min. after injection the concentration of the radioactivity in the blood had dropped to one tenth of that in the kidney and the urinary bladder. The autoradiograms showed two patterns of blackening in the kidney, one diffuse in the pronephros and one very strong spotty blackening in the opistonephros. In addition to the kidney very high concentrations of radioactivity were also noticed in the bile and the pseudobranch. The muscular tissue of treated trouts contained almost no radioactivity during the whole experiment. Chemical analysis revealed that the radioactivity that could be extracted from the organs was mainly ochratoxin A.
To evaluate the effects of clenbuterol on cardio-respiratory parameters and blood lactate relation to exercise tolerance, experimental horses performed standardized exercise tests on a high-speed treadmill before and after administration of the drug. Clenbuterol was administered in feed to six healthy Standardbreds at a dose rate of 0.8 micrograms/kg b.wt twice daily for 5.5 days. Each horse was tested twice, without and with a respiratory mask, during two consecutive days. One week elapsed between the baseline tests without drug and the tests with clenbuterol treatment (each horse served as its own control). The results show an unchanged heart rate response to exercise 2 h after the last clenbuterol administration. The blood lactate response and the arterial oxygen tension during exercise did not differ before and after drug treatment. The oxygen uptake as well as pulmonary ventilation relative to the work load performed was essentially unaffected. The arterial pH during exercise was significantly increased (P less than 0.05) following clenbuterol treatment. Plasma levels of clenbuterol were maximal 2 h post-administration with values between 0.45 and 0.75 ng/ml. The plasma half-life of elimination was 10.4 h (+/- 2.25 SD). In conclusion, clenbuterol did not cause any major effects on the cardio-respiratory and blood lactate parameters studied in healthy horses performing submaximal exercise tolerance tests.
Beta2-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine. We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chambers. The affinities of these drugs to the beta2-adrenoceptors in homogenates of the same muscle tissue were also examined. These experiments were performed with radioligand binding studies using the very potent beta-adrenoceptor antagonist 125I-cyanopindolol. The three drugs were almost equipotent in relaxing the muscle strips. The EC50-values for salbutamol, terbutaline and clenbuterol were 5.6, 13.8 and 2.1 nM, respectively, and all three drugs relaxed the preparations completely. In the competitive binding study, however, the Kd-value of clenbuterol was much lower (24 nM) than that of salbutamol and terbutaline (1100 nM and 3900 nM, respectively). The amount of receptors bound at the EC50-value of clenbuterol was 8% compared to less than 1% for salbutamol and terbutaline. This indicates a lower intrinsic efficacy of clenbuterol than of the other two drugs. The beta-adrenoceptor density was 45 +/- 14.3 fmol/mg protein (mean +/- SD) and the Kd-value of 125I-cyanopindolol was 11.4 +/- 3.3 pM.
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