Abstract: The effect of morphine, Tinct. opii, loperamide, pethidine and atropine on intestinal transit and the faecal and urinary excretion of water and electrolytes was studied in ponies. The rate of passage of a particulate marker was slowed by morphine, hastened then slowed by loperamide and Tinct. opii, and hastened by atropine. The liquid marker was slowed by Tinct. opii and hastened then slowed by the other drugs. Only loperamide decreased the faecal sodium excretion. This drug also decreased faecal water and weight; it appeared worthy of clinical trial in diarrhoea. Tinct. opii decreased by morphine, pethidine and atropine increased faecal water.

Abstract: 1,4,5,6-Tetrahydronicotinamide adenine dinucleotide (H2NADH) has been investigated as a reduced coenzyme analog in the reaction between trans-4-N,N-dimethylaminocinnamaldehyde (I) (lambdamax 398 nm, epsilonmax 3.15 X 10-4 M-minus 1 cm-minus 1) and the horse liver alcohol dehydrogenase-NADH complex. These equilibrium binding and temperature-jump kinetic studies establish the following. (i) Substitution of H2NADH for NADH limits reaction to the reversible formation of a new chromophoric species, lambdamax 468 nm, epsilonmax 5.8 x 10-4 M-minus 1 cm-minus 1. This chromophore is demonstrated to be structurally analogous to the transient intermediate formed during the reaction of I with the enzyme-NADH complex [Dunn, M. F., and Hutchison, J. S. (1973), Biochemistry 12, 4882]. (ii) The process of intermediate formation with the enzyme-NADH complex is independent of pH over the range 6.13-10.54. Although studies were limited to the pH range 5.98-8.72, a similar pH independence appears to hold for the H2NADH system. (iii) Within the ternary complex, I is bound within van der Waal's contact distance of the coenzyme nicotinamide ring. (iv) Formation of the transient intermediate does not involve covalent modification of coenzyme. Based on these findings, we conclude that zinc ion has a Lewis acid function in facilitating the chemical activation of the aldehyde carbonyl for reduction, and that reduced coenzyme plays a noncovalent effector role in this substrate activating step.

Abstract: BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.

Abstract: Nosocomial infections are a serious threat to optimum patient care. In addition, nosocomial infections can have far-reaching consequences for the hospital personnel and the financial aspects of the hospital. Nosocomial infections with Salmonella spp have been described among hospitalized equine populations more frequently than any other agent. Salmonella spp associated with hospitalized equids often possess more antimicrobial resistance determinants than do Salmonella spp isolated from healthy horses in the general population. There is little evidence to suggest that resistant salmonellae are more virulent than nonresistant forms. MDR forms of Salmonella complicate the selection of appropriate antimicrobials when they are indicated, however. Furthermore, the use of some antimicrobials may apply selection pressure toward enhanced ability of MDR Salmonella to colonize equine patients. Further research should help to elucidate the risky uses of antimicrobials in the hospital setting and define the role of disinfectants and treatments such as NSAIDs in the ecology of MDR forms of nosocomial infections, including Salmonella. In the meantime, thoughtful selection of when and how to use antimicrobials in equine patients, together with deliberate selection of which antimicrobials to use based on monitoring data and other factors, such as safety and spectrum, is advised.