A large potentiation effect of serum on the in vitro potency of tulathromycin against Mannheimia haemolytica and Pasteurella multocida.

The antimicrobial properties of tulathromycin were investigated for M. haemolytica and P. multocida. Three in vitro indices of antimicrobial activity, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves, were established for six isolates of each organism. Each index was measured in two growth media: Mueller-Hinton broth (MHB) and calf serum. It was shown that MICs and MBCs were markedly lower in serum than in MHB. MHB:serum ratios for MIC were 47:1 (M. haemolytica) and 53:1 (P. multocida). For both serum and MHB, adjustment of pH led to greater potency at alkaline compared to acid pH. Tulathromycin MIC was influenced by size of inoculum count, being 4.0- to 7.7-fold greater for high compared to low initial counts. It was concluded that for the purpose of determining dosages for therapeutic use, pharmacodynamic data for tulathromycin should be derived in biological fluids such as serum. It is hypothesized that in vitro measurement of MIC in broth, conducted according to internationally recommended standards, may be misleading as a basis for estimating the in vivo potency of tulathromycin.

Global and right ventricular end-diastolic volumes correlate better with preload after correction for ejection fraction.

BACKGROUND: Volumetric monitoring with right ventricular end-diastolic volume indexed (RVEDVi) and global end-diastolic volume indexed (GEDVi) is increasingly being suggested as a superior preload indicator compared with the filling pressures central venous pressure (CVP) or the pulmonary capillary wedge pressure (PCWP). However, static monitoring of these volumetric parameters has not consistently been shown to be able to predict changes in cardiac index (CI). The aim of this study was to evaluate whether a correction of RVEDVi and GEDVi with a measure of the individual contractile reserve, assessed by right ventricular ejection fraction (RVEF) and global ejection fraction, improves the ability of RVEDVi and GEDVi to monitor changes in preload over time in critically ill patients. METHODS: Hemodynamic measurements, both by pulmonary artery and by transcardiopulmonary thermodilution, were performed in 11 mechanically ventilated medical ICU patients. Correction of volumes was achieved by normalization to EF deviation from normal EF values in an exponential fashion. Data before and after fluid administration were obtained in eight patients, while data before and after diuretics were obtained in seven patients. RESULTS: No correlation was found between the change in cardiac filling pressures (DeltaCVP, DeltaPCWP) and DeltaCI (R(2) 0.01 and 0.00, respectively). Further, no correlation was found between DeltaRVEDVi or DeltaGEDVi and DeltaCI (R(2) 0.10 and 0.13, respectively). In contrast, a significant correlation was found between DeltaRVEDVi corrected to RVEF (DeltacRVEDVi) and DeltaCI (R(2) 0.64), as well as between DeltacGEDVi and DeltaCI (R(2) 0.59). An increase in the net fluid balance with +844 + or - 495 ml/m(2) resulted in a significant increase in CI of 0.5 + or - 0.3 l/min/m(2); however, only DeltacRVEDVi (R(2) 0.58) and DeltacGEDVi (R(2) 0.36) correlated significantly with DeltaCI. Administration of diuretics resulting in a net fluid balance of -942 + or - 658 ml/m(2) caused a significant decrease in CI with 0.7 + or - 0.5 l/min/m(2); however, only DeltacRVEDVi (R(2) 0.80) and DeltacGEDVi (R(2) 0.61) correlated significantly with DeltaCI. CONCLUSION: Correction of volumetric preload parameters by measures of ejection fraction improved the ability of these parameters to assess changes in preload over time in this heterogeneous group of critically ill patients.

Methods and normal values for echocardiography in adult dairy cattle.

OBJECTIVE: The objective of the study was to report normal ultrasonographic appearance and intra-cardiac dimensions in two dairy breeds and to calculate cardiac output (CO) using echocardiography. BACKGROUND: Intra-cardiac dimensions, time indices and CO estimation have not previously been reported in adult cattle. ANIMALS, MATERIALS AND METHODS: Echocardiograms were obtained from healthy adult dairy cows (10 Jersey (J) and 12 Holstein Friesians (HF)) in the body weight range of 400 to 700 kg. Standard echocardiographic images were obtained from the left and right hemithoraces. Velocity time integrals were obtained in order to calculate CO using pulsed wave Doppler of aortic flow in the J cows. Measurements obtained included pulmonary artery and aortic diameters, left and right ventricular diameters (and calculated fractional shortening and left ventricular ejection fraction), left atrial size and time indices assessing valve function. RESULTS: HF cows had significantly (p<0.05) larger pulmonary artery and aortic diameters, larger left atrial diameters and left ventricular internal diameters during diastole, but these were not different when corrected for body weight. Left and right ventricular dimensions, adjusted for body weight, were significantly larger (p=0.02 and p=0.035 respectively) in J cows when compared to HF cows. No differences were noted in the time indices between the two groups. No significant differences were noted in intra-operator variability and the only significant difference in inter-operator variability was in measurement of the pulmonary artery (p=0.03; ICC=0.63). CONCLUSIONS: It is possible to obtain repeatable, reliable echocardiograms in order that meaningful intra-cardiac dimensions can be obtained in adult dairy cattle.

Ontogeny of biphasic locomotor effects of quinpirole.

The effects of the dopamine D2/D3 receptor agonist quinpirole (LY171555) on locomotor activity were tested on rats of 10, 15, 20, 30, and 60 days of age. In two separate experiments, doses of 0 (vehicle), 0.02, 0.2, or 2.0 mg/kg quinpirole were injected SC into rats at each age, and their effects measured either for 2 h at 15-min intervals, or 30 min at 5-min intervals. At 10, 15, and 20 days of age, quinpirole significantly increased distance travelled in a dose-dependent manner. At 30 and 60 days of age, quinpirole significantly decreased distance travelled early in the session and increased it later. These results suggest that a dopamine autoreceptor begins to function between 20 and 30 days of age. Concomitant with the appearance of quinpirole-induced locomotor suppression early in the session, the amount of quinpirole-induced activation late in the session declined.

Biphasic effects of dopamine agonist N-0434 on locomotor behaviors in rats.

The effects of a dopamine agonist, (+/-)-2-(N-penylethyl-N-propyl)amino-5- hydroxytetralin (N-0434) (SC doses of 0.00, 0.01, 0.1, and 1.0 mg/kg) were tested in rats for 120 min in an activity monitor. The durations in seconds of horizontal locomotor time, rearing time, stereotypy time, and margin time (thigmotaxis) were measured during 12 10-min time blocks. N-0434 (0.1 and 1.0 mg/kg) resulted in biphasic effects (initial inhibition followed by potentiation) of linear locomotor time and an attenuation of thigmotaxis. The 0.1- and 1.0-mg/kg doses initially suppressed rearing time but had mixed potentiation effects. The 0.01- to 1.0-mg/kg doses suppressed stereotypy time. The differential behavioral profiles were discussed in reference to the functions of dopamine receptors.

Locomotor activity following intra-accumbens microinjections of dopamine D1 agonist SK&F 38393 in rats.

The present study examined the effects of the dopamine D1 receptor subtypes agonist SK&F 38393 on locomotor activities after bilateral microinjection (0.00, 0.01, 0.1, 1.0, 10.0 micrograms) into the nucleus accumbens (Acb). The dose of 0.1 microgram elicited the highest response rate across measures of locomotion, rearing and stereotypy behavior. On the other hand, the largest dose of 10.0 micrograms was associated with significant increase in center time behaviors. The data were supportive of the hypothesis that dose-related locomotor activities elicited by microinjections of SK&F 38393 into the Acb are independently mediated by D1 receptors.

Effects of dopamine D1 antagonists SCH23390 and SK&F83566 on locomotor activities in rats.

The effects of the dopamine D1 antagonists R-(+)-7-chloro-8-hydroxy-3-methyl-1phenyl-2,3,4,5-tetrahydro-1-H-3 -benzazapine (SCH23390) and (+-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1- H-3-benzazapine (SK&F83566) were tested for 2 h on linear locomotor, rearing, stereotypy, and margin times in an open field. Each of the antagonists attenuated the duration of linear locomotion, rearing, and stereotypy times in a dose- and time-dependent manner. The effectiveness of the antagonists was relatively brief and SCH23390 was more effective than SK&F83566 on each behavior. The two antagonists had differential effects on margin time.

Differential effects of dopamine D2 agonist quinpirole upon the dorsal immobility response in rats.

The effects of various dose levels of systemically injected quinpirole upon the dorsal immobility response (DIR) over a time course was investigated in male rats. A low dose of quinpirole (0.01 mg/kg) significantly attenuated the duration of the DIR following the 10-min interval, whereas the highest dose (1.0 mg/kg) had a biphasic effect so that at the 10-min interval the duration of the DIR was significantly potentiated and at the 60-min interval the duration of the DIR was significantly attenuated. The intermediate dose (0.1 mg/kg) had intermediate behavioral effects. The data support the growing evidence that quinpirole has differential effects upon behavior over time as a function of the dose levels. The present data were discussed in reference to presynaptic and postsynaptic dopamine D2 receptor theory.

Effects of cholinergic agonists on the dorsal immobility response.

The effects of pilocarpine, arecoline, and physostigmine on the dorsal immobility response in ovariectomized female rats were tested. The effect of pretreatment with the cholinergic antagonist scopolamine was also tested. Pilocarpine, arecoline, and physostigmine all significantly decreased the duration of the dorsal immobility response in a dose-dependent way. Scopolamine significantly blocked the effect of pilocarpine. Thus, cholinergic agonists attenuate the dorsal immobility response via their effect on cholinergic systems in the central nervous system.

Effect of bombesin and gastrin-releasing peptide on canine sphincter of Oddi.

This study reports the effects of bombesin and gastrin-releasing peptide (GRP) on the canine sphincter of Oddi using a method that allows repeated cannulation of the biliary sphincter in the unanesthetized animal through a Thomas cannula placed opposite the biliary papilla. Immediately after intravenous administration of bombesin or GRP, phasic sphincter contractions disappeared, basal sphincter pressures fell, and common bile duct pressures rose. Because bombesin releases cholecystokinin (CCK) and CCK resulted in a similar pattern to that of bombesin, the bombesin effect on the sphincter of Oddi may have been secondary to CCK's effect on the sphincter. To test if the bombesin effect on the sphincter of Oddi was due to the release of CCK, we blocked CCK release by administration of somatostatin, having first established that somatostatin blocked endogenous CCK release in our animal model by use of an intraduodenal infusion of lipid. Exogenous administration of bombesin failed to alter sphincter of Oddi or common bile duct pressures in dogs treated with somatostatin. Somatostatin did not, however, block CCK's effect on gallbladder contraction, since exogenous administration of CCK after somatostatin injection resulted in the pressure changes in the biliary tree typical of CCK-induced gallbladder contraction. Thus bombesin administration appears to result in sphincter relaxation and gallbladder contraction by the release of endogenous CCK rather than by a direct effect. The increase in common bile duct pressures was due to gallbladder contraction, since this rise in pressure was abolished by cholecystectomy. The peptide effect on sphincter contraction and basal sphincter pressure were unaffected by cholecystectomy.

The effect of lactulose on psychomotor performance tests in alcoholic cirrhotics without overt hepatic encephalopathy.

Thirty-two alcoholic cirrhotics without clinical evidence of encephalopathy were randomized to lactulose or sucrose treatment in order to evaluate the effects of chronic lactulose therapy on five psychomotor performance tests. Statistically significant improvement was seen in three of the five tests in the lactulose-treated group, while no significant improvement in any test was noted in the sucrose group. However, because of the limited extent of improvement in the lactulose treated group, problems with medication intolerance, and lack of improvement in complex psychosocial behavior, the impact of chronic lactulose therapy on mental function in cirrhotics without overt encephalopathy appears to be limited.