Agonists at dopamine D2 and D3 receptors are important therapeutic agents in the treatment of Parkinson's disease. Compared with the use of agonists, allosteric potentiators offer potential advantages such as temporal, regional, and phasic potentiation of natural signaling, and that of receptor subtype selectivity. We report the identification of a stereoselective interaction of a benzothiazol racemic compound that acts as a positive allosteric modulator (PAM) of the rat and human dopamine D2 and D3 receptors. The R isomer did not directly stimulate the dopamine D2 receptor but potentiated the effects of dopamine. In contrast the S isomer attenuated the effects of the PAM and the effects of dopamine. In radioligand binding studies, these compounds do not compete for binding of orthosteric ligands, but indeed the R isomer increased the number of high-affinity sites for [ 3 H]-dopamine without affecting K d . We went on to identify a more potent PAM for use in native receptor systems. This compound potentiated the effects of D2/D3 signaling in vitro in electrophysiologic studies on dissociated striatal neurons and in vivo on the effects of L-dopa in the 6OHDA (6-hydroxydopamine) contralateral turning model. These PAMs
Idarubicin is an anthracycline antibiotic extensively used in acute leukemia. In the present study we investigated whether vitamin E and catechin can reduce the toxic effects of idarubicin. Vitamin E (200 IU kg -1 week -1 ), catechin (200 mg kg -1 week -1 ), idarubicin (5 mg kg -1 week -1 ), idarubicin + vitamin E (200 IU kg -1 week -1 ), and idarubicin + catechin (200 mg kg -1 week -1 ) combinations were given to male Sprague-Dawley rats weighing 210 to 230 g (N = 6/group). Idarubicintreated animals exhibited a decrease in body and heart weight, a decrease in myocardial contractility, and changes in ECG parameters (P<0.01). Catechin + idarubicin-and vitamin E + idarubicin-treated groups exhibited similar alterations, but changes were attenuated in comparison to those in cardiac muscle of idarubicin-treated rats (P<0.05). Superoxide dismutase and catalase activity was reduced in the idarubicin-treated group (P<0.05). Glutathione peroxidase levels were decreased in the idarubicin-treated group (P<0.05) and reached maximum concentrations in the catechin-and catechin + idarubicintreated groups compared to control (P<0.01). Malondialdehyde activity was decreased in the catechin + idarubicin-treated groups compared to control and increased in the other groups, reaching maximum concentrations in the vitamin E-treated group (P<0.01). In electron microscopy studies, swelling of the mitochondria and dilatation of the sarcoplasmic reticulum of myocytes were observed in the idarubicintreated groups. In groups that were given idarubicin + vitamin E and idarubicin + catechin, the only morphological change was a weak dilatation of the sarcoplasmic reticulum. We conclude that catechin and vitamin E significantly reduce idarubicin-induced cardiotoxicity in rats.
Canine pyometra is a dioestrus period disease in which systemic inflammatory response syndrome (SIRS) is a common outcome due to the response of the body to the bacterial infection. The purpose of this study was i) to differentiate canine pyometra and cystic endometrial hyperplasia (CEH)/mucometra by measuring serum C-reactive protein (CRP) and prostaglandin F2α metabolite (PGFM) concentrations in blood and ii) to compare serum concentrations of CRP and PGFM in bitches with a pathological uterus (pyometra or CEH/mucometra) to concentrations in bitches with a healthy uterus. Mean CRP concentrations were found significantly higher (p < 0.001) in dogs with pyometra compared to those with CEH/mucometra or healthy uterus. However, no statistical difference could be detected between the groups for mean PGFM concentrations. Mean white blood cell count (WBC), alkaline phosphatase (ALP) and total protein concentrations were found significantly higher (p < 0.001) in dogs with pyometra. Escherichia coli was the most frequently isolated microorganism from dogs with pyometra (64.3%). Edwardsiella spp. was detected in a single case of pyometra for the first time. In conclusion, our results demonstrate that serum CRP concentrations were increased in dogs with pyometra and thus we conclude that serum CRP concentration but not PGFM might be useful as a marker to differentiate a case of CEH/mucometra from pyometra in female dogs. To the authors' knowledge, this is the first report in which Edwardsiella spp. has been isolated in the canine uterus.
The study evaluated the effect of essential oils from lavender (Lavandula stoaches) (LEO), on growth performance, carcass quality and antioxidant status of broilers. Three nutritionally adequate diets were composed with the addition of LEO at 0, 24, and 48 mg/kg of feed. The diets were fed as mash in the starter (d 0-21) and grower (d 22-39) phases. A total of 405 day-old chicks (Ross-308) were allocated to the three dietary treatments, each with three replicate pens with 45 birds per pen. After the first 21-day feeding period, the bodyweight of chicks fed 24 mg/kg LEO was higher (P <0.01) than the 48 mg/kg LEO treatment, but only slightly higher than that of the untreated group. Diets with 24 and 48 mg/kg of LEO tended to increase final bodyweight of birds at 39 days old. No differences were observed for feed intake (FI), feed conversion ratio (FCR) and mortality among treatments. Feeding chickens on a diet with added LEO significantly reduced the relative weight of liver (P <0.01) compared with the control (CNT) group. Percentage of spleen weight of birds fed 24 mg/kg LEO was lower (P <0.05) than for those who received 48 mg/kg LEO. However, it was similar to that of the CNT. Birds fed diets supplemented with 24 and 48 mg/kg LEO had breast meat with higher brightness (L* value) and higher concentration of superoxide dismutase (SOD) compared with birds that did not receive LEO. Based on the data, it can be concluded that LEO could be used as a growth promoter in broiler nutrition with potential improvements in breast meat quality. ______________________________________________________________________________________
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