Effects of growth hormone-releasing factor and(or) thyrotropin-releasing hormone on growth, feed efficiency, carcass characteristics, and blood hormones and metabolites in beef heifers

The objective of this study was to determine the effect of long-term administration of a growth hormone (GH)-releasing factor analog (GRFa) and(or) thyrotropin-releasing hormone (TRH) on growth, feed efficiency, carcass characteristics, and blood hormones and metabolites in beef heifers. Crossbred heifers (n = 48; 345.9 +/- 2.8 kg) were divided into four equal groups: control (vehicle), 1 microgram of GRFa (human GRF 1-29 analog).kg BW-1.d-1, 1 microgram of TRH.kg BW-1.d-1, or GRFa + TRH. Daily s.c. injections continued for 86 d. Blood samples were collected from half of the heifers after injection on d 1, 36, and 78. On d 89, all heifers were slaughtered. Treatments did not affect (P > .05) ADG but GRFa + TRH decreased (P < .05) ADFI relative to all other treatments. Feed conversion efficiency tended (P < .10) to be improved in the groups given GRFa alone or TRH alone. Treatment with GRFa and(or) TRH did not affect carcass weight, dressing percentage, conformation score, backfat thickness, or weights of liver, kidneys, pituitary, and ovaries. The GRFa + TRH treatment reduced (P < .05) fat score and increased (P < .05) longissimus muscle area relative to other treatments. The GRFa treatments reduced (P < .05) the weight and fat percentage of the mammary gland and increased (P < .05) heart weight. Treatment with TRH alone failed to stimulate GH on d 1, 36, and 78. Treatment with GRFa alone increased (P < .05) GH above controls on d 36, whereas GRFa + TRH increased (P < .05) GH on d 1, 36, and 78. Treatment with GRFa alone increased (P < .05) IGF-I only on d 1, whereas GRFa + TRH was without effect on all days. Across sampling days, treatments had little effect on blood concentrations of insulin, triiodothyronine, nonesterified fatty acids, urea nitrogen, and glucose. The GRFa alone and GRFa + TRH decreased (P < .05) and TRH alone increased (P < .05) thyroxine concentrations. In conclusion, with the dose and administration regimen used, GRFa and(or) TRH yielded small but positive improvements in animal performance.     

Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes

The NADPH-dependent metabolism of ifosphamide catalyzed by rat liver microsomes was investigated in order to identify individual P450 enzymes that activate this anti-cancer drug and to ascertain their relationship to the P450 enzymes that activate the isomeric drug cyclophosphamide. Pretreatment of rats with phenobarbital or clofibrate increased by up to 8-fold the activation of both ifosphamide and cyclophosphamide catalyzed by isolated liver microsomes. Studies using P450 form-selective inhibitory antibodies demonstrated that constitutively expressed P450s belonging to subfamily 2C (forms 2C11/2C6) make significant contributions to the activation of both oxazaphosphorines in uninduced male rat liver microsomes, while the phenobarbital-inducible P450 2B1 was shown to be a major catalyst of these activations in phenobarbital-induced microsomes. Pretreatment of rats with dexamethasone increased liver microsomal activation of ifosphamide approximately 6-fold without a corresponding effect on cyclophosphamide activation rates. Ifosphamide activation catalyzed by dexamethasone-induced liver microsomes was minimally inhibited by anti-P450 2B or anti-P450 2C antibodies, but was selectively inhibited by anti-P450 3A antibodies. Selective inhibition of liver microsomal ifosphamide activation was also effected by the macrolide antibiotic triacetyloleandomycin, an inhibitor of several dexamethasone-inducible 3A P450s. These studies establish that a dexamethasone-inducible family 3A P450 can make an important contribution to rat liver microsomal ifosphamide activation, and suggest that dexamethasone pretreatment might provide a useful approach for modulation of ifosphamide metabolism in order to improve its therapeutic efficacy in cancer patients.     

Two mechanisms for the recapture of extracellular GM2 activator protein: evidence for a major secretory form of the protein

The GM2 activator protein is a small monomeric protein containing a single site for Asn-linked glycosylation. Its only proven in vivo function is to act as a substrate specific cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A. However, we and others have shown it can act as a general glycolipid transporter at neutral pH in vitro. Any other possible in vivo functions would require that some of the newly synthesized activator molecules not be targeted to the lysosome. The lysosomal targeting mechanism for the activator has not been conclusively identified. While earlier reports suggested that it is likely through the mannose-6-phosphate receptor, another more recent report demonstrated that deficient human cells could recapture nonglycosylated, bacterially produced activator, suggesting its use of an alternate targeting pathway. Here, we demonstrate that the mannose-6-phosphate pathway is likely the major intracellular, biosynthetic route to the lysosome, as well as a high affinity recapture pathway for the endocytosis of activator protein from extracellular fluids. Additionally, we show that there exists a second lower affinity recapture pathway that requires its native protein structure, is carbohydrate independent, and likely does not involve its ability to bind glycosphingolipids in the plasma membrane. Finally, we document that the pool of newly synthesized precursor activator protein contains a majority of molecules with a complex-type oligosaccharide, which cannot contain a functional mannose-6-phosphate targeting signal. These molecules makeup the secreted forms of the protein in normal human fibroblasts.     

Work-site smoking policies: their population impact in Washington State

This article presents data from a population-based, random-digit dialing telephone survey of 1228 employed adults in Washington State, conducted 1989 through 1990. Eighty-one percent of men and 91% of women reported work-site smoking restrictions. Employees in work sites with no-smoking policies were less likely to be current smokers; men in work sites with policies restricting smoking smoked fewer cigarettes on both workdays and nonworkdays. Forty-eight percent of male and 53% of female smokers reported reduced smoking as a result of work-site policy. Work-site smoking policies, intended to protect against smoke exposure, may also reduce employee smoking.     

Comparison of Etest to broth microdilution method for testing Streptococcus pneumoniae susceptibility to levofloxacin and three macrolides

When the Etest was compared to broth microdilution for susceptibility testing of Streptococcus pneumoniae, levofloxacin, erythromycin, and penicillin results correlated for both methods; azithromycin and clarithromycin showed discrepancies of > or = 2 dilutions for 95.8% and 31.5% of the isolates, respectively. Levofloxacin was active against 141 of 142 isolates (< or = 2.0 micrograms/ml), making it a potentially useful new fluoroquinolone.     

Ocular toxocariasis

Toxocara canis is a preventable cause of intraocular inflammation and visual loss ... caused by the larvae of toxocara canis usually occurring in children and young adults following accidental ingestion of the larvae from infected dogs. Treatment of ocular toxocariasis can include a combination of cryopexy and photocoagulation, with vitrectomy surgery utilized in the more serious cases.