Susceptibility of Mycobacterium avium sbsp paratuberculosis to monensin sodium or tilmicosin phosphate in vitro and resulting infectivity in a murine model.

This study was designed to determine the susceptibility in vitro and infectivity of 1 field isolate of Mycobacterium avium sbsp paratuberculosis after exposure to monensin sodium and tilmicosin phosphate. Minimum inhibitory concentrations (0.39 microg monensin sodium/mL; 1.60 microg tilmicosin phosphate/mL) were determined in quintuplicate. Organisms were then incubated with 3 different concentrations of each medication for 3 different lengths of time, then washed and resuspended in sterile physiologic saline and injected intraperitoneally into mice that were genetically susceptible to infection. Mice were euthanatized 50 d later and the number of hepatic granulomas was used as the indicator of infectivity. Neither time of incubation nor concentration of medication had any effect on the infectivity of the organisms. Monensin sodium significantly reduced the number of hepatic granulomas in genetically susceptible mice while tilmicosin phosphate did not. Antimycobacterial activity of monensin sodium suggests that the role of monensin in the control of bovine paratuberculosis should be evaluated further.

Effect of monensin sodium on histological lesions of naturally occurring bovine paratuberculosis.

Of 19 adult cows naturally infected with paratuberculosis, 13 were treated with monensin sodium and six remained untreated. At the beginning of the study, the severity of the histological lesions was assessed from biopsy samples of ileum, liver, mesenteric lymph node and rectal mucosa. From the data acquired it was possible to assign the animals so that the lesions in the two groups were similar (P=0. 8323). Monensin was administered in the feed, which contained 147.5 mg/kg, and each treated cow received 450 mg of monensin daily for 120 days. At the end of this period all cows were killed and histopathological findings in the ileum, liver, mesenteric lymph node and rectal mucosa were compared with the initial findings. A scoring system showed that monensin had a beneficial effect in the ileum (P=0.077), liver (P=0.0322) and rectal mucosa (P=0.0578), but under the conditions of the experiment no such effect could be demonstrated in mesenteric lymph node (P=0.3599). There appeared to be an overall effect on all tissues taken together (P=0.1335). The effect of monensin may have been due to both a halting and a reversal of the pathological process. In all but one of the six untreated cows, the lesions worsened during the course of the experiment.

Pharmacokinetics of a recombinant bovine growth hormone and pituitary bovine growth hormone in lactating dairy cows.

The disposition of pituitary-derived bovine growth hormone (pbST) and of a recombinant bovine growth hormone (rbST) produced by Lilly (somidobove, USAN) were compared after an intravenous bolus administration (36.69 micrograms/kg for pbST and 35 micrograms/kg for rbST) to eight lactating cows in a crossover study. It was shown that dose-dependent parameters (volume of distribution, clearance) were significantly different between the two test articles. The steady mean state volume of distribution (.10 +/- .018 vs .12 +/- .015 L/kg) and clearance (.119 +/- .012 vs .143 +/- .011 L.kg-1.h-1) were lower for the pbST than for the somidobove. In contrast, the mean (+/- SD) residence times were not different for the two test articles (50.0 +/- 8.6 vs 46.9 +/- 5.9 min for pbST and somidobove, respectively). The origin of the difference is unclear, but it cannot be explained by the slight difference between the administered dose of the two test articles (< 5%) because the actual dose rate was used to calculate all dose-dependent parameters.

Prophylactic effect of monensin sodium against experimentally induced paratuberculosis in mice.

Monensin sodium (0, 15, or 30 mg/kg of complete feed) was fed ad libitum for 1 week to female mice (strain C57BL6/J) that were genetically susceptible to infection with Mycobacterium paratuberculosis. Ten mice in each of the 3 groups were inoculated intraperitoneally with M paratuberculosis (10(9) organisms). Sterile saline solution was injected intraperitoneally into 10 other mice in each group. Rations were continued for 50 days, then mice were euthanatized, and body weight, splenic weight, and hepatic weight for each mouse were recorded. Ratios of body weight to splenic weight and of body weight to hepatic weight were calculated for each mouse. Hepatic granulomas in 50 light microscopic fields were counted, and presence of acid-fast organisms in those granulomas was recorded. Infected mice given monensin had higher body weight and fewer hepatic granulomas than did mice not given monensin. Although hepatic granulomas were fewer in these mice, they contained acid-fast organisms. Effects of 15 mg of monensin and those of 30 mg of monensin/kg of complete feed were not different.

Amino acid and monoamine inhibition of sacral parasympathetic preganglionic neurons.

Parasympathetic preganglionic discharges recorded from pelvic nerves in spinal cats were evoked by single-pulse stimulation of sacral afferent fibers of descending excitatory pathways in the thoracic spinal cord. Evoked responses were analyzed on-line by signal averaging. Discharges evoked by either pathway were increased in size by 2-10 times by coadministration of both picrotoxin and strychnine, but not by either drug alone. The combination also markedly enhanced evoked increases in bladder pressure. Strychnine was also effective with bicuculline and in cats depleted of central GABA stores by semicarbazide. The monoamine precursors, 5-HTP and L-dopa, only depressed evoked discharges in both untreated and convulsant-treated animals; this depression was enhanced by tricyclic antidepressants. The results indicate that sacral parasympathetic preganglionic neurons are controlled by an unusual type of strong, local tonic inhibition which is mediated by both GABA and glycine. Both amino acid transmitters must be blocked to unmask this inhibition. Interruption of supraspinal control of this local inhibition may account in part for loss of bladder function following spinal injuries. The 5-HT and NE bulbospinal pathways that terminate near the preganglionic neurons also appear to be inhibitory. Enhancement of this inhibitory monoaminergic transmission by tricyclic antidepressants may contribute to the efficacy of these drugs in treating nocturnal enuresis.

Barbiturate-induced transmitter release at a frog neuromuscular junction.

1. The influence of barbiturates on neuromuscular transmission at end-plates of frog sartorius muscles was investigated electrophysiologically on preparations bathed in Ringer solution containing a low concentration of calcium and a high concentration of magnesium.2. Effects of a convulsant barbiturate, 5-(2-cyclohexylideneëthyl)-5-ethyl barbituric acid (CHEB), were compared with those of phenobarbitone.3. CHEB and phenobarbitone increased the mean quantum content of the end-plate potentials and decreased the mean amplitude of the miniature end-plate potentials.4. Both barbiturates enhanced the duration of the nerve-terminal action potential and had little or no effect on the effective resistance of the skeletal muscle membrane.