• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.87-93
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• 1997

DA-5018, a new capsaicin derivative, showed potent analgesic effect comparable to that of morphine in various experimental acute pain models. in this study, whether the analgesic mechanism of DA-5018 is related to opiate receptors or prostanoids was investigated. The affinity of DA-5018 for opiate receptor was determined by receptor binding assay. The Ki values of DA-5018 for nonspecific and specific $\mu$, $textsc{k}$, $\delta$-opiate receptor was 299$\pm$8.88, 735$\pm$215, 2930$\pm$ 163, 1550$\pm$813 nM, respectively and DA-5018 exhibited lower affinity than morphine. DA-5018 (10-"~3$\times$10-′M) inhibited electrically-evoked contractions of the guinea ply ileum and rat vas deferens, and these inhibition was not antagonized by naloxone(10 nM), an opiate receptor antagonist. Antagonism of analgesic effect of 7A-5018 by naloxone was examined by tail pinch test. Analgesic action of DA-5018(0.1 ~2 mg/kg, 5.c.) was not antagonized by naloxone(1 mg/rg, i.p.). These results indicate that pharmacological action of DA-5018 is not related with opiate receptor. Cyclooxygenase and 5-lipoxygenase activities in rat peritoneal neutrophil treated with A23187 and arachidonic acid were measured by radioimmunoassay. DA-5018 stimulated the cyclooxygenase activity and the concentration show-ing the two fold increase of activity was 124$\mu$M. DA-5018 slightly inhibited 5-lipoxygenase activity and these results together indicate that analgesic action of 3A-5018 is not mediated through inhibition of cyclooxy genase or lipoxygenase. These results suggest that the analgesic effect of DA-5018 is not due to blocking opiate receptor or to inhibiting the synthesis of prostanoids in the arachidonic acid metabolism pathway.

• Korean Journal of Veterinary Research
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• v.42 no.3
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• pp.335-349
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• 2002

The immune response against Salmonella gallinarum infection was investigated in immunosuppresed chickens. Newly hatched chickens were treated with cyclophosphamide at the first and second day after birth and were challenged intraperitoneally with S gallinarum ($1{\times}10^7CFU/m{\ell}$) on day 6. Group 1, Immunosuppresed and Challenged group, was treated with cyclophaiphamide and challenged with S gallinarum; group 2, Immunosuppressed group, was only treated with cyclophsphamide; group 3, Challenged group, was only challenged with S gallinarum; group 4, Control group. In each group, the localization of lymphocytes of the lymphoid organs and intestine was immunohistochemically compared using a variety of monoclonal antiboies ($CD4^+$, $CD8^+$, and B lymphocyte). Also, S gallinarum were assessed by Maccallum-Goodpasture stain and immunohistochemical analysis in the paraffin-embedded intestinal tissues. In S gallinarum challenged chickens, $CD4^+$ and $CD8^+$ lymphocytes of the intestinal organs such as duodenum, jejunum, ileum and colon were increased. However, in cyclophophamide treated chickens, $CD4^+$ and $CD8^+$ lymphocytes and especially B lymphocytes of the lymphoid organs such as thymus, spleen, and bursa of Fabricius were dramatically decreased. These results suggest that cyclophsophamide is an immunosuppressive agent that especially causes depletion of B lymphocytes, suppress humoral immunity and eventually suppresses avian immune responses. Its protection against S gallinarum infection is mainly dependent on both cell-mediated mechanism and the humoral immune response.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.9
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• pp.1282-1287
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• 2011

The objective of this study was to assess the effect of xylanase on net energy for production, performance, nutrient digestion and gut microflora of broilers fed corn/soy-based diet. Eighty-four day-old male broiler chicks were allocated to two groups receiving two treatments, respectively. Each treatment had six replicate cages with seven broilers per cage. The diets were based on corn and soybean. The treatments were: i) basal diet reduced in apparent metabolizable energy (-0.63 MJ/kg compared to commercial diet specifications); ii) basal diet supplemented xylanase at 4,000 u/kg feed. The experiment used the auto-control, open circuit respiration calorimetry apparatus to examine the heat production and net energy for production. The results revealed that xylanase supplementation did not affect growth performance and diet AME value, but increased $NE_p$ value by 18.2% (p<0.05) and decreased daily heat production per $kg^{0.75}$ by 31.7% (p<0.05). There was no effect (p>0.05) of xylanase supplementation on the ileal digestibility of N and hemicelluloses, but the ileum digestibility of energy was increased by 2% by xylanase supplementation (p<0.05). Xylanase supplementation increased (p<0.05) the count of lactobacillus and bifidobacterial in the caecum.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2006.11a
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• pp.66-68
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• 2006

This experiment was conducted to study the effects of medicinal plant extract on performance in broiler chickens. A total of eight hundred forty, 1-d-old broiler chicks(Ross) were randomly allocated to 7 treatments with 4 replicates of 30 birds per replicate. The treatments were negative control (NC, diets without antibiotics), positive control (PC, diets with-containing antibiotics), Schisandrae fructus (T1), Scutellariae radix (T2), Camellia sinensis (T3), Artemisia capillaris (T4) and mixed medicinal plants (T5) extracts added to drinking water. The final body weight, body weight gain and feed conversion rate were significantly improved in all treatments compared to NC (P<0.05). No significant differences were observed in the relative weights of liver, spleen, pancreas, bursa of Fabricius and intestinal tract among the groups. The relative lengths of duodenum, jejunum and ileum were significantly decreased in PC compared with other groups (P<0.05). No significant differences were observed in the cecal microflora. The contents of triacylglycerol (TG), blood urea nitrogen (BUN), glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) in blood serum were not significantly influenced. The concentration of cholesterol in blood serum was significantly decreased in all treated groups as compared to those of the control (P<0.05). There was no difference in the components of leukocytes and erythrocytes among the groups.

• Journal of Ginseng Research
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• v.14 no.2
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• pp.178-186
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponine intracerebrally or intrathecally. The development of morphine tolerance and dependence, and the abrupt expression of naloxone inducted abstinence syndrom were also inhibited by ginsenoside Rb1, Rb2, Rg1 and Re. These results suggest that ginsenoside Rbl, Hbs, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence sindrome. In addition, further research on the minor components of Pnnnxkinsenl should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain in level of monoamines at the variolls time intervals and at the various day intervals, respectively. The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum ($\mu$-receptor) and mouse vats deferens ($\delta$-receptor) were not mediated through opioid receptors. The antagonism of a $\chi$ receptor agonist, U-50, 488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, but mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine 6-dehydrogenase which catalyzed the production of morphinone from morphine, and increased hepatic glutathione contents for the detoxication of morphinone. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• Korean Journal of Poultry Science
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• v.21 no.2
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• pp.83-92
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• 1994

In order to study performance enhancing effects of supplementary antibiotics (avoparcin, nosiheptide and enramycin), two feeding trials were conducted. In Experiment 1, 1, 040 male Arbor Acres were reared in floor pens for 6 wk. Chicks were assigned to one of the following four treatments: Basal diet(B), B+avoparcin 10 ppm, B+nosiheptide 2.5 ppm and B+enramycin 5 ppm. Each treatment had five replications of 52 chicks each. In Experiment 2, two antibiotics (avoparcin and enramycin) were compared in $2{\times}2$ (antibiotics$\times$sex) factorial design. One thousand broiler chicks were reared in floor pens for 6 wk. Each of the 4 treatments had five replications of 50 chicks each. The results of Experiment 1 showed that antibiotic treatments (enramycin, avoparcin and nosiheptide) significantly(P <0.05) improved weight gain. Feed/gain ratio of avoparcin treatment and enramycin treatment tended to he lower than the control but they were not statistically significant. Dressing percentages were high in avoparcin and enramycin treatments compared to the control and nosiheptide treatment. The number of E. coli and Cl. perfringens in ileum and cecal contents were decreased by antibiotic treatments. Moisture contents in excreta of the birds were not significantly affected by the treatments. Leg abnormality and mortality were not significaniy different among treatments. In Experiment 2, weight gain was significantly (P<0.01) different between sexes, but not between antibiotic treatments. Significant effects of antibiotics (P<0.01), sex (P<0.01) and interaction (P<0.05) were shown in feed in take. Feed/gain ratio of avoparcin treatment was significantly (P<0.01) lower than that of enramycin treatment. leg abnormality and mortality were not significantly different among treatments but those in male broiler tended to be higher than in female broilers. It was concluded that nonsystemic antibiotics supplemented to the broiler diets suppress undesirable microorganisms and improve broiler performace in general and avoparcin was most effective in improving feed/gain ratio.

• Biomolecules & Therapeutics
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• v.11 no.1
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• pp.41-50
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• 2003

General pharmacological properties of DA-8159, a new pyrazolopyrimidinone derivative were examined in laboratory animals to investigate its safety profile. The oral administration of DA-8159 (1, 5 or 30 mg/kg) in mice and rats had no effect on general behaviors and central nervous system of the animals in test systems, such as hexobarbital-induced sleeping time, motor coordination, normal body temperature, writhing syndromes induced by 0.75% acetic acid solution, chemo-shock produced by pentetrazole solution and rotar rod test. Anesthetized cats treated intravenously with DA-8159 (0.1, 0.3, 1, 3 or 10 mg/kg) showed transient and mild decrease in blood pressure. However, heart rate, respiration rate and tidal volume were not changed by intravenous DA-8159. In the isolated organs including ileum, heart (sinus rate of atria and contractility of papillary muscle), trachea of guinea pigs and phrenic nerve of rats, DA-8159 ($10^{-8}$ ∼$10^{-5}$ mg/L) did not elicit any effect or inhibitory action on the chemically or electrically stimulated contraction. DA-8159 did not influence gastric secretion, pH and total acid output in rats and intestinal propulsion in mice. The administration of DA-8159 in rats had no effect on the platelet aggregation induced by ADP in rabbit plasma, urinary volume and electrolyte ion ($Na^{+}$, $K^{+}$, $Cl^{-}$) excretion in rats. Prothrombin time (PT) of the rats showed a mild but significant increase after administration of DA-8159. Activated partial thromboplastin time (APTT), however, was not affected by DA-8159. These results indicate that DA-8159 does not exert any of serious pharmacological effects.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.114-121
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• 2004

This study was undertaken to evaluate the general pharmacological properties of CJ-11828, an amlodipine adipate, in experimental animals and in vitro system. CJ-11828 had no effects on general behavior, motor coordination, writhing syndromes, pentetrazol-induced chemoshock and electric shock in mice at dose levels of 3,10, anti 30 mg/kg, po. But there were decrease of body temperature, prolongation of sleeping time, and inhibition of intestinal activity in mice treated with CJ-11828 at doses of 10 and 30 mg/kg, po. CJ-11828 decreased the blood pressure in coscuous fog at the dose level of 2mg/kg, po, but it was expected as a result of pharmacological activity of CJ-11828. Any effect on respiratory system was not observed in conscious rat at doses of 3,10, and 30 mg/kg, po. The slight decrease in spontaneous motor activity was observed in mice treated with CJ-11828 at high dose, 30 mg/kg. In vitro experiments, CJ-11828 had no effect on agonists-induced contraction of isolated guinea pig ileum at 0.1, 1, and 10 ${\mu}$M. Based on these results, it was concluded that CJ-11828 had no pharmacological effect ill these studies even up to the 36-fold anticipated clinical dose, 3 mg/kg.

• Toxicological Research
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• v.26 no.3
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• pp.223-232
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• 2010

Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR), and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial). Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.26-31
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• 2005

The present study examined effects of a water-soluble fraction from mulberry leaves (ML water fraction) on the circulatory and autonomic nervous systems, which were compared with those of acetylcholine (ACh) used as a reference drug in order to elucidate its mechanism of action. Intravenous administration of ACh or a ML water fraction produced temporary depressor and tachycardiac responses in a dose-dependent manner in unrestrained, conscious Sprague-Dawley rats. The systemic hemodynamic effects of ACh and a ML water fraction were almost completely blocked by pretreatment with atropine, a muscarinic antagonist. The depressor responses to ACh and a ML water fraction were slightly enhanced and prolonged by pretreatment with neostigmine, an anticholinesterase, whereas the tachycardiac responses were remarkably blocked by pretreatment with pentolinium, a ganglionic blocking agent. In vitro experiments using the ileum isolated from rats showed that ACh and a ML water fraction increased ileal contractility in a dose-dependent manner. The increases in ileal contractility were also completely abolished in the presence of atropine. Finally, the specific binding of [$^3H$]quinuclidinyl benzilate, a muscarinic antagonist, to rat cortical synaptic membranes was inhibited by a ML water fraction in a concentration-dependent manner with an IC$_{50}$ value of 9.5 mg/ml. The results suggest that the effects of a ML water fraction are mediated through direct stimulation of muscarinic cholinergic receptors by unknown cholinomimetic substance(s) contained in that fraction.