The renal handling and tissue distribution of pyrazinamide were studied after administration of single dose intravenous injection for 15 min or constant infusion in New Zealand White rabbits. Peak pyrazinamide serum concentration ranged from 57.3 to $105.0{\mu}g/ml$ ($mean{\pm}SD;83.0{\pm}17.8$). The mean half-life of the a phase was $0.143{\pm}0.047$ hr while the ${\beta}$ phase ranged from 1.66 to 3.25 hr($mean{\pm}SD;2.38{\pm}0.57$). The mean steady-state volume of distribution in non-compartmental model was $0.935{\pm}0.362\;L/kg$ Excretion ratio of pyrazinamide was dramatically reduced from 1.02 to 0.30 when unbound serum pyrazinamide concentration was increased from 6.04 to $60.9\;{\mu}g/ml$. The urine flow dependency of renal clearance of pyrazinamide was demonstrated in steady-state serum concentration. The tissue/serum concentration ratio of pyrazinamide was highest in kidney and lowest in skeletal muscle among the tissues examined. The results suggested that a large fraction of pyrazinamide filtered by glomerulus and secreted by renal tubule was reabsorbed and this tubular reabsorption of pyrazinamide might be greatly influenced by urine flow.
The purpose of this study was to investigate the effect of H$_2$O fraction of Dioscorea japonica Thunb(DJT) with selenium(Se) treatment on blood glucose and lipid metabolism in streptozotocin(STZ)-induced diabetic rats. Male Sprague-Dawley rats(180-220g) weighing were divided into five groups, that is one normal group and four diabetic experimental groups : the STZ-control group, the DJT group, the DJT-Se group and the Se group. Diabetes mellitus was induced in the male rats by injection of STZ into the tail vein at a dose of 45mg/kg B.W. The H,0 fraction of DJT(500mg/kg) given orally were administered for 14 days. The Se treated group were fed a AIN-76 recommendation diet mixed with Na$_2$SeO$_3$(2mg/kg diet), which was prepared fresh daily. The body weight and food intake was monitored daily and plasma levels of glucose, insulin, hematocrit and protein were determined. The plasma concentrations of cholesterol, HDL-cholesterol, triglyceride and fire fatty acid were measured. The activities of aminotrans ferase were analysed. The body weight gain was shown to be significantly higher in the normal group than all diabetic groups. The blood glucose levels of the DIT-Se group was significantly lower compared to those of the experimental groups. The administration of H$_2$O fraction of DJT and selenium showed an increase in plasma protein concentrations. The plasma cholesterol levels of all STZ-groups were not significantly different and HDL-cholesterol levels were increased in the diabetic experimental groups fed on H$_2$O fraction of DJT or Se supplementation. Plasma triglyceride levels were lower in the DJT-Se and Se group than in the STZ-control group. free fatty acid levels were not significantly differ among STZ-control groups. STZ treatment increased aminotransferase activity and that of DJT group was highest. In conclusion, the data from the present experiments indicate that the treatment of the H$_2$O fraction of DJT with selenium showed a synergistic effect and the two can have an influence on hyperg1ycemia and lipid metabolites when administered together. (Korean J Nutrition 31(9) : 1377-1384, 1998)
We investigated the effect of dietary mulberry leaf powder (MP) on loperamide-induced constipation in rats. Male Sprague-Dawley rats were given MP in their diets at a concentration of 0% 5% and 10% for 33 days. Rats were divided into 4 groups: normal diet group (NOR), normal diet and loperamide treated group (MPL0), 5% MP and loperamide treated group (MPL5), and 10% MP and loperamide treated group (MPL10). Constipation was induced by subcutaneous injection of loperamide (1.5 mg/kg body weight/day) for the final 5 days of the experiment Supplemental MP had no effect on the food efficiency ratio, but it reduced body weight gain and food intake in a concentration dependent manner. Administration of loperamide decreased food intake. MP had a concentration-dependent effect on decreasing total cholesterol, LDL-cholesterol, and triglycerides and on increasing HDL-cholesterol. Loperamide had no significant effect on serum lipid profiles. Loperamide decreased the number and wet weight of fecal pellets and fecal water content MP increased the number and wet weight of fecal pellets and fecal water content in a dose-dependent manner. In addition, MP increased gut transit time and transit speed, and the guts of mts treated with MP plus loperamide were longer than those of mts treated with loperamide alone. These results indicate that MP is an effective treatment for constipation.
Background: The pathogenesis of silicosis has been focused on the interaction between alveolar macrophages and silica particle. Although fibrosis in silicosis has been studied extensively, the mechanism is still not fully understood. There is increasing evidence that monokines and arachidonic acid metabolites macrophage are involved in pathogenesis of silicosis. Recently, it was reported that prostaglandin E2 produced from macrophage counteracts the stimulatory effects of other monokines on fibroblast proliferation or collagen production. Until now, it was remained uncertain by which mechanism silica particle may activate alveolar macrophage to an enhanced release of prostaglandin E2. Methods: In order to investigate the relationship between the activity of alveolar macrophage and the production of $PGE_2$ from activated alveolar macrophage, the authors measured hydrogen peroxide and $PGE_2$ from alveolar macrophages activated by silica in vitro and from alveolar macrophages in the silicotic nodules from rat. Experimental silicosis was induced by intratracheal infusion of silica($SiO_2$) suspended in saline(50 mg/ml) in Sprague-Dawley rats. Results: produced by 1) The silicotic nodules with fibrosis were seen from the sections of rat lung at 60 days after intratracheal injection with 50 mg aqueous suspension of silica(Fig. 1). 2) In vitro, silica caused the dose dependent increase of hydrogen peroxide(p<0.05, Fig. 2A) and $PGE_2$(p>0.05, Fig. 2B) release from alveolar macrophages. Alveolar macrophages from rat with silicotic nodules released more hydrogen peroxide and $PGE_2$ than those of control group(p<0.05, Fig. 3). Conclusion: These results suggest that silica particle could activate macrophage directly and enhanced the release of $PGE_2$ and hydrogen peroxide from the alveolar macrophage.
The Journal of the Korean Society for Microbiology
/
v.16
no.1
/
pp.49-55
/
1981
Recent studies have demonstrated that histamine could have a modulatory influence on the immune response in vitro and in vivo. However, the effect of histamine on immune response in mice has not been extensivley analyzed. In the present study the regulatory effects of cimetidine, a histamine-2-receptor antagonist(H2 blocker) and histamine on the immune response to sheep red blood cells(SRBC) were evaluated in mice. Mice pretreated with daily intraperitoneal injection of varying concentrations of cimetidine for 14 days were immunized intraperitoneally with various concentrations of SRBC($10^6,\;10^7,\;and\;10^8$ cells) and challenged 4 days post immunization. The cellular immune response was determined by measuring the footpad swelling reaction. Footpad swelling reaction of each mouse was measured at 3hr(Arthus) reaction) and 24 or 48 hr(delayed reactions) after challenge. The humoral immune response was determined by measuring hemagglutinins to SRBC. Histamine in varying concentrations($10^{-1},\;10^{-3}\;and\;10^{-5}M$(was added in SRBC suspension at the time of antigen challenge into footpad, and 24-hr delayed type hypersensitivity(DTH) was measured. Cimetidine in varying concentrations(10, 50, 250, 1250 and 6250${\mu}g$) enhanced 24-hr DTH and this enhancement of DTH was more pronounced at 250${\mu}g$ of cimetidine. However, there were no significant differences between the cimetidine-pretreated groups and controls in Arthus reaction and hemagglutinin titers. Histamine suppressed the DTH in the dose-dependent fashion. This suppression was more pronounced at lower concentration of immunizing antigen($10^7\;and\;10^6$ SRBC). However, histamine did not diminish the DTH at higher concentration of antigen($10^8$ SRBC). These results present the evidences which strongly suggest that cimetidine enhances the cell-mediated immune response but not significantlly influences the humoral immune response and that exogenous and endogenous histamine is involved in the modulation of cellular immune response as well as immediate hypersensitivity.
Kim, Seon-Gu;Kim, Chang-Guhn;Lee, Kang-Mo;Kim, Hye-Won;Min Byung-Cheol;Choi, See-Sung;Lee, Jong-Deuk;Yang, David J.;Kim, E. Edmund;Lee, Hyun-Chul;Won Jong-Jin
The Korean Journal of Nuclear Medicine
/
v.32
no.4
/
pp.374-381
/
1998
Purpose: I-131 labeled (2'-deoxy-2'-iodo-${\beta}$-D-arabinofuranosyl) adenine (IAD) may be involved in DNA synthesis during active proliferation of tumor cells. We conducted this study to find out the biodistribution of IAD and it's feasibility for scintigraphic tumor imaging. Materials and Methods: Tosyl acetyl-adenosine was dissolved in acetonitrile, and I-131-NaI was added and heated to synthesize IAD. Female Fisher 344 rats innoculated with breast tumor cells were injected with 0.27 MBq of IAD. Rats were sacrificed at 0.5, 1, 2, 4, 24h and the % of injected dose per gram of tissue (%ID/g) was determined. For scintigraphy, rats bearing breast cancer were administered with 1.11 MBq of IAD and imaging was performed after 2 and 24h. Then, rat body was fixed and microtomized slice was placed on radiographic film for autoradiography. Results: %ID/g of tumor was 0.74 (0.5h),0.73 (1h), 0.55 (2h), 0.38 (4h), and 0.05 (24h), respectively. At 1h after injection, %ID/g of tumor was higher than that of heart (0.34), liver (0.42), spleen (0.47), kidney (0.69), muscle (0.14), bone (0.33) and intestine (0.51). However, %ID/g of tumor was lower than blood (1.06), lung (0.77), and thyroid (177.71). At 4h, %ID/g of tumor in comparison with other tissue did not change. Tumor contrast expressed by tumor to blood ratio was 0.69 and tumor to muscle ratio was 5.11 at 1h. However, these ratios did not improve through 24h. On autoradiogram and scintigraphy at 2 and 24 hour, the tumor was well visualized. Conclusion: This results suggest that IAD may have a potential for tumor scintigraphy. However, further work is needed to improve localization in tumor tissue.
The purpose or this study was to investigate the effect or H $_2$O fraction or Dioscorea japonica Thunb(DJT) and selenium(Se) on the lipid peroxidation in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats weighing 180∼220g were divided into 5 groups: One normal rat group and 4 diabetic rat groups(the STZ-Control group, the DJT group, the DJT-Se group and the Se group). Diabetes was induced in the male rats by injection of STZ into tail vein at a dose of 45 mg/kg. The H$_2$O-fraction of DJT(500 mg/kg) was administered orally for 14 days. The supplementation was achieved with the AIN-76 recommendation diet by adding 2 mg/kg diet of selenium as Na$_2$SeO$_3$ which was prepared freshly everyday. The levels of glycogen in liver and muscle and protein in kidney, liver and muscle were measured. The liver concentrations of cholesterol and triglyceride were analyzed. Also, the malondialdehyde(MDA) levels in kidney, liver and lung were determined. The glycogen levels of liver and muscle in diabetic groups were not significantly different from the normal group. The protein concentrations of kidney, liver and muscle were not significantly different either, but the level of muscle protein was higher than STZ-Control group. The levels of liver cholesterol were significantly different between normal and STZ-Control groups and decreased in all diabetic experimental groups fed on H$_2$O-fraction of DJT and Se supplementation compared with the STZ-Control group. The levels of liver triglyceride were higher in the DJT-Se group than the STZ-Control group. The concentrations of MDA in lung decreased greatly by the administration of Se among all and the concentration of liver MDA was significantly reduced and that of DJT-Se group was the lowest. In conclusion, the results indicated that the administration of H$_2$O-fraction of DJT with selenium supplementation has a synergistic antioxidative effect by influencing on lipid metabolites and peroxidation especially in liver.
Yang Jung-hoon;Kang Han-sem;Bae Jae-sung;Song Chang-hyun;Kim Jung-eun;Jin Hee-kyung;Jang Kwang-ho
Journal of Veterinary Clinics
/
v.22
no.2
/
pp.94-99
/
2005
This prospective study aimed to assess the efficacy of dexamethasone to prevent xylazine induced emesis in dogs. The antiemetic effect of graded, single high-dose intravenous dexamethasone against xylazine hydrochloride was studied. Clinically healthy mixed breed dogs that weighed $ 4.64\pm1.25kg$ were used in this study. Food and water were given 3 hours before the experiment. Venous blood specimens were collected from all experimental animals for hema-tological and blood chemical test pre- and post-experiment. Twenty-eight experimental animals were randomly divided into 4 groups; the group treated with 0.2ml/kg of normal saline (Control group), the groups treated with 1mg/kg (D1 group), 2mg/kg (D2 group) and 4 mg/kg of dexamethasone (D4 group). Three doses of the dexamethasone or normal saline was administered intravenousely to each group and after 5 minutes, xylazine (2.2 mg/kg) was administered intramuscularly. The time until onset of the first emetic episode and rate of emesis were investigated. At the same time, the extent of sedation was scored subjectively 5, 15, 30 and 60 minutes after injection of xylazine hydrochloride using Visual Sedation Score. The time until onset of the first emetic episode was $203.25\pm11.35$ sec in Control group, $187.33\pm48.0l$ sec in D1 group and 218.33± 13.58 sec in D2 group. The rate of xylazine induced emesis were $57\%$ in Control group and $43\%$ in D1 and D2 group respectively. On the other hand, any emetic episodes were not observed in 04 group. At extent of sedation score, all experimental animals especially including the animals in D1 group were highly sedated at 15 minutes after administration of xylazine hydrochloride. Hematological and blood chemical values showed normal ranges pre- and post-experiment. We concluded that prior treatment with 4 mg/kg of dexamethasone hardly caused xylazine-induced emesis without disturbing the sedative effect of xylazine in dogs.
The purpose of this study was to examine the effect of Allium hookeri (AH) root on hepatic antioxidative enzyme contents in streptozotocin (STZ)-induced rats. Diabetes mellitus was induced in male Sprague-Dawley rats through injection of STZ dissolved in citrate buffer into tail veins at a dose of 45 mg/kg body weight. Sprague-Dawley rats were fed an AIN-93 recommended diet, and the experimental groups were fed a modified diet containing 5% and 10% of AH root powder for 4 weeks. The experimental groups were divided into four groups: a normal control (N-control), STZ-control, STZ-AH 5%, and STZ-AH 10% supplemented groups. The STZ-AH 5% group showed a significant increase in liver glycogen compared to the STZ-control group. Muscle glycogen and liver protein contents significantly increased in the AH-supplemented groups compared to the STZ-control group. The liver malondialdehyde content of the AH-supplemented group was significantly lower than that of the STZ-control group. Xanthine oxidase content was significantly reduced in all experimental groups. Glutathione-S-transferase content was significantly elevated in the AH-treated groups compared to the STZ-control group. Superoxide dismutase content was not significantly different among the experimental groups. Catalase content was significantly higher in the STZ-AH 10% group compared to the STZ-control group. These results show that supplementation with AH root may be useful for diabetic therapy and damage from oxidative stress.
Journal of the Korean Society of Food Science and Nutrition
/
v.39
no.10
/
pp.1446-1451
/
2010
Silk sericin protein was hydrolyzed by seven proteolytic enzymes to examine the effectiveness of the hydrolysates to bind iron. The amino acid nitrogen contents of hydrolysates by Flavourzyme were higher than the others enzymes, and its iron binding capacity showed dose-dependent increase. The bioavailability of iron binding peptide from sericin hydolysates was investigated in iron-deficient rats. Three-week-old male rats were fed iron-deficient diet for three weeks. Rats were divided into four groups (DD: no treated group on iron deficient diet, DD+HI: heme-iron treated group, DD+OI: sericin-Fe, and DD+II: inorganic iron ($FeSO_4$) treated group, and then iron supplemented by injection for one week. After oral administration for one week, the iron contents of serum and liver were significantly higher in DD+OI ($4.2\;{\mu}g/mL$ and $80.1\;{\mu}g/mL$) and DD+HI ($3.2\;{\mu}g/mL$ and $70.6\;{\mu}g/mL$) than DD ($2.0\;{\mu}g/mL$ and $47.9\;{\mu}g/mL$). Hemoglobin content of treated groups was significantly higher than DD, but the significant difference among groups was not shown. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels did not show any significant difference among all groups. Binding iron to peptide from sericin hydolysates seems to improve its bioavailability and to hasten the cure of iron deficiency in experimental rat.
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