Cytotoxic Effects of Loperamide Hydrochloride on Canine Cancer Cells

Loperamide is a peripheral opiate agonist that can cause apoptosis and G2/M arrest in human cancer cell lines and may sensitize cells to chemotherapy. The objectives of this study were to investigate the effects of loperamide on viability, apoptosis and cell cycle kinetics in canine cancer cells and to establish whether the drug sensitizes cells to doxorubicin. Cell viability was assessed using Alamar Blue. Cell death and cell cycle were studied using flow cytometry with 7-Aminoactinomycin-D (7-AAD) and propidium iodide (PI), respectively. Loperamide decreased cell viability in a dose-dependent fashion and was most effective against canine osteosarcoma cells. In all cell lines, it induced a dose and time dependent apoptosis and resulted in accumulation in G0/G1. When co-incubated with doxorubicin, loperamide induced a synergistic cell kill in canine carcinoma cells. Investigation is warranted into the role of loperamide in the treatment of canine cancer.     

Cytochrome P4502E in vivo and in vitro in the dwarf goat: effects of enzyme induction and the applicability of chlorzoxazone as marker substrate

Cytochrome P4502E activities, inducibility and the applicability of chlorzoxazone as a marker substrate for this enzyme were investigated in female dwarf goats. Goats were treated with either isoniazid or β-naphthoflavone. Treatment with isoniazid resulted in a 1.4 fold increase of the chlorzoxazone hydroxylation rate in hepatic microsomes. Aniline- and p-nitrophenol hydroxylation rates were increased by roughly the same extent (1.6 and 1.25 fold resp.) and increased levels of cytochrome P4502E apoproteins were found by Western blotting. Treatment with the cytochrome P4501A inducer β-naphthoflavone resulted in a 2.5 fold induction of the in vitro chlorzoxazone hydroxylation rate, whereas the hydroxylation rates of aniline and p-nitrophenol were not induced. After treatment with isoniazid, chlorzoxazone plasma clearance was increased from 5.0 mL/min/kg to 11.0 mL/min/kg. Chlorzoxazone was almost completely excreted in the urine as conjugated hydroxy metabolites. These results do not support the hypothesis that cytochrome P4502E is of particular importance in goats, as has been suggested earlier. Furthermore, chlorzoxazone has limited value as a marker substrate for this enzyme, since cytochrome P4501A enzymes appear to play an important role in its biotransformation.     

Evaluation of the influence of different species and cultivars of lupin kernel meal on the extrusion process, pellet properties and viscosity parameters of salmonid feeds

This study examined the influence of different lupin species and cultivars and their inclusion levels on the physical properties of an extruded diet. Lupin kernel meals were included into a fish diet formulation at 0%, 10%, 20% and 30%. Soybean meal was also included in a series of diets on a similar basis as a reference. The diet mashes were extruded using a laboratory-scale APV19:45 twin-screw extruder. The pellets were examined for radial expansion, bulk density, vacuum oil uptakes, sink rate, shear and crush strengths. Inclusion of lupin kernel meal significantly increased bulk density, sink rate, shear and crush strength of the pellets. With the increase in lupin kernel meal inclusion level, a concomitant decline in vacuum oil uptake and radial expansion was also observed. An assessment of the diet mashes using a Rapid Visco Analyser showed that the inclusion of lupin kernel meals increased the rate and degree of gelatinization of the mash starch content compared with that with a similar inclusion level of soybean meal. The inclusion of lupin kernel meals in the diet mash also improved the water-holding capacity of the extrudate, which has important implications for the reduction in extruder wear.     

The Geography of a Mixed‐Race Society

The pattern and level of separation among ethnic groups continues to change, and there are certainly more mixed neighborhoods both in cities and suburbs than two decades ago. The immigration flows of the past decade have substantially altered the ethnic mix and neighborhood mixing. In addition, multi‐ethnic individuals themselves are altering the level of mixing among racial and ethnic groups. The research in this article shows that those who report themselves of more than one race have high levels of residential integration both in central cities and suburbs. These residential patterns can be interpreted as further evidence of tentative steps to a society in which race per se is less critical in residential patterning. The level of integration, for Asian mixed and black mixed is different and substantially higher than for those who report one race alone. The research in this article builds on previous aggregate studies of mixed‐race individuals to show substantial patterns of integration in California's metropolitan areas.     

Modification by domperidone of dopamine- and apomorphine - induced inhibition of extrinsic ruminal contractions in goats

Goat ruminal strips reacted with an increase in smooth muscle tone after exposure to apomorphine. This rise in tone could be blocked by domperidone, but not by naltrexone. In vivo , both dopamine and apomorphine caused inhibition of extrinsic ruminal contractions. These effects were completely prevented by domperidone pretreatment, whereas naltrexone was not an effective antagonist. These results suggest that apomorphine-induced inhibition of rumen motility is due to DA-receptor activation. The exact location of these DA-receptors remains to be determined.     

Loperamide: evidence for a centrally mediated opioid effect on rumen motility in conscious goats and sheep

Loperamide inhibited the frequency and amplitude of cyclical contractions of the rumen in conscious goats (100 micrograms/kg, i.v. and sheep (250 micrograms/kg, i.v.). In goats, the inhibitory effect of loperamide could be prevented by pretreatment with the opiate antagonist naltrexone (greater than or equal to 12.5 micrograms/kg, i.v.) but not by pretreatment with the dopaminergic antagonist domperidone (500 micrograms/kg, i.v.). Intracerebroventricular administration of 1 microgram/kg loperamide in goats significantly depressed ruminal contraction frequency, whereas intravenous administration of 10 micrograms/kg loperamide did not affect cyclical motility. Administered via the carotid artery, loperamide (4 micrograms/kg) depressed both frequency and amplitude of cyclical contractions of reticulum and rumen, whereas the same dose was ineffective via the coeliac artery. In vitro, loperamide (10 nM-100 microM) had no influence on spontaneous activity or tone of the reticular longitudinal muscle strips. It is concluded that loperamide inhibits cyclical ruminal contractions through a central opioid pathway.