• Journal of Pharmaceutical Investigation
• /
• v.28 no.2
• /
• pp.73-80
• /
• 1998

In order to elucidate the effect of N-demethylation on the in vivo metabolite kinetics, especially hepatic first-pass effect of trimebutine(TMB), the N-demethylation of TMB to N-monodesmethyl trimebutine(N-TMB) was studied in rats. TMB(10 mg/kg) and N-TMB(10 mg/kg) were injected into the femoral and the portal vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of TMB and N-TMB determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the urinary and biliary excreated amounts of TMB and N-TMB were lower than 0.1% of the administered dose. According to the hepatic biotransformation model and metabolic pathways of TMB proposed, it was found that the fraction of systemic clearance of TMB which formed N-TMB in liver$(G_{mi})$ was 0.826, that of TMB which furnishes the available N-TMB to the systemic circulation$(F_{mi})$ was 0.083, and the absolute hepatic bioavailability of N-TMB formed trom TMB$(F_{mi.p})$ was 0.1. These results showed that TMB was suspected of the sequential hepatic first-pass metabolism and N-demethylated by 82.6%. Therefore, the residue would be hydrolyzed by the esterase in the liver. That is, the ability of N-demethylation of TMB was 4.75-fold larger than that of hydrolysis by the esterase in rats.

• Journal of Pharmaceutical Investigation
• /
• v.31 no.4
• /
• pp.209-216
• /
• 2001

The purpose of the present study was to investigate the hepatic uptake and biliary excretion of l-anilino-8-naphthalene sulfonate (ANS) in vivo. The plasma concentration and liver concentration of ANS were determined after its i.v. bolus administration at a dose of $30\;{\mu}mol/kg$ in rats. The hepatic uptake clearance $(CL_{uptake})$ of ANS was 0.1 ml/min/g liver. On the basis of the unbound concentration of ANS, the permeability-surface area product $(PS_{influx})$ was calculated to be l0.4 ml/min/g liver, being comparable of in vitro data. On the other hand, we determined the plasma concentration, liver concentration and biliary excretion rate of ANS at steady-state after its i. v. infusion $(0.2-1.6\;{\mu}mol/min/kg)$ in rats. The excretion clearance $(CL_{excretion})$ of ANS showed Michaelis-Menten kinetics with increasing the infusion rate. The permeability-surface area product $(PS_{excretion})$ based on the unbound concentration in the liver was calculated to be 0.0165 ml/min/g liver, which is negligible compared with the intrinsic clearance $(CL_{int}=3.3\;ml/min/g\;liver)$ by rat liver microsomes. The sequestration process of ANS, therefore, was considered to be mainly due to the metabolic process in the liver $(PS_{seq}{\risingdotseq}CL_{int})$. Furthermore, $PS_{efflux}$ value calculated from $PS_{influx}$ and $PS_{seq}$ was 4.4 ml/min/g liver, which was comparable of in vitro data. In conclusion, in vivo parameters such as $PS_{influx}$, $PS_{efflux}$ and $PS_{seq}$ in the present study showed good in vivo-in vitro relationship. Thus, the kinetic analysis method proposed in the present study would be useful to analyze the hepatic transport of drugs in vivo.

• Asian-Australasian Journal of Animal Sciences
• /
• v.33 no.8
• /
• pp.1323-1331
• /
• 2020

Objective: Three types of dietary fiber were fed to sows during gestation and lactation stages to monitor their physiological and metabolic adaptations during the pre-partum period and to determine how these effects may influence the lactation period and sow performance. Methods: Soon after breeding, 54 sows were selected and were fed with 20% supplementation as fed of wheat bran (WB), soya hulls (SH), or rice hulls (RH) in diets during gestation and lactation. Sows were weighed, backfat thickness was measured ultrasonically and jugular blood samples were collected from all sows. The litter size was equalized to 10, by fostering piglets from sows on the same treatment. Results: Sows gained 22.0, 21.8, and 25.5 kg of net maternal body weight during gestation (for WB, SH, and RH sows, respectively; p = 0.007). There was no treatment effect on the body weight change during lactation (p = 0.158), however RH sows consumed an average of 133.66 kg of feed, WB sows took 121.29 kg and SH sows took 126.77 kg during lactation (p<0.001). The SH litters gained an average of 59.34 kg of weight during lactation, while other litters gained 51.58 and 49.98 kg (for WB and RH litters, respectively; p<0.001). Exception for aspartate aminotransferase and alanine aminotransferase, measured serum biochemical values were broadly in agreement with earlier reports. Despite the use of additional vegetable oil to balance the energy level, RH sows still had lower concentrations of serum triglycerides in late gestation. Conclusion: Different types of fibrous ingredients in the gestation diet influenced most of the investigated reference values for sows. The values of serum biochemical parameters were generally not affected by fiber type during the lactation stage. The SH supplementation for sows is an effective approach to give heavier litters at birth and weaning and to increase voluntary feed intake in early lactation.

• Radiation Oncology Journal
• /
• v.36 no.2
• /
• pp.95-102
• /
• 2018

Purpose: To evaluate the prognostic value of $^{18}F$-fluorodeoxyglucose positron-emission tomography (FDG PET) with computed tomography (CT) before and during radiotherapy (RT) in patients with head and neck cancer. Methods: Twenty patients with primary head and neck squamous cell carcinoma were enrolled in this study, of whom 6 had oropharyngeal cancer, 10 had hypopharyngeal cancer, and 4 had laryngeal cancer. Fifteen patients received concurrent cisplatin and 2 received concurrent cetuximab chemotherapy. FDG PET/CT was performed before RT and in the 4th week of RT. The parameters of maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of the primary tumor were measured, and the prognostic significance of each was analyzed with the Cox proportional hazards model. Results: Higher TLG (>19.0) on FDG PET/CT during RT was a poor prognostic factor for overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.007). In the multivariate analysis, TLG during RT as a continuous variable was significantly associated with OS and PFS rate (p = 0.023 and p = 0.016, respectively). Tumor response worse than partial remission at 1 month after RT was another independent prognostic factor for PFS (p = 0.024). Conclusions: Higher TLG of the primary tumor on FDG PET/CT during RT was a poor prognostic factor for OS and PFS in patients with head and neck cancer.

• Journal of Periodontal and Implant Science
• /
• v.30 no.4
• /
• pp.747-757
• /
• 2000

Cyclosporin A(CsA) is an immunosuppressive agent widely used for preventing graft rejecting response in organ transplantation. The basic properties of CsA to osteoblast has not been well known yet. A better understanding of the mechanisms of CsA function on bone could provide valuable information regarding basic properties of bone remodeling, pharmacotherapeutic intervention in metabolic bone disease, and the consequences of immunosuppression in bone physiology. The purpose of this study was to investigate the effect of CsA on osteoblast by evaluating parameters of proliferation, collagen synthetic activity, alkaline phosphatase activity, and ALP mRNA expression in mouse calvarial cell. 1. CsA ($3{\mu}g/m{\ell}$) treated mouse calvarial cell showed statistically significant increase in cell proliferation.(P<0.05) 2. CsA($1,\; 3{\mu}g/m{\ell}$) treated MC3T3 cell line showed statistically significant increase in cell proliferation. 3. The amount of collagen of CsA($3{\mu}g/m{\ell}$) treated mouse calvarial cell was decreased statistically significantly. 4. Alkaline phosphatase activity was increased statistically significantly in CsA treated group($1{\mu}g/m{\ell}$). 5. mRNA expression of ALP was increased in CsA treated group These results suggest that CsA could affect bone remodeling by modulating proliferation & differentiation of osteoblast.

• Food Science and Preservation
• /
• v.16 no.5
• /
• pp.782-788
• /
• 2009

The genotoxicological safety of gamma-irradiated egg white and yolk was examined to ensure that required safety parameters were met, and in an effort to further apply gamma-irradiation for improvement of the hygienic qualities of eggs. Egg white and yolk were irradiated at 20 kGy, much higher than the legally approved dose (less than 5 kGy), and possible genotoxicity was evaluated using in vitro and in vivo tests. The SOS chromotest employing Escherichia coli PQ37, and a chromosomal aberration test in cultured Chinese hamster lung (CHL) cells, were performed in vitro with or without metabolic activation (S9). An in vivo micronucleus development test was conducted using mouse bone marrow cells. Negative results were obtained in the SOS chromotest. The incidence of chromosomal aberration in CHL cells and the frequency of micronuclear developmentin mouse bone marrow cells treated with irradiated samples were not significantly different from those of non-irradiated controls. Thus, it may be concluded that up to 20 kGy of gamma irradiation applied to egg white and yolk did not show any genotoxic effects under our experimental conditions.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.22 no.6
• /
• pp.724-733
• /
• 1993

In order to investigate the relationships of obesity in childhood to plasma lipid, blood pressure and blood glucose concentration, we selected 21 subjects for the moderate obese group(MO), 9 for mild obese group(MI), and 19 for the control group(C) among children aged 10~12. While the level of plasma triglyceride and VLDL-cholesterol of the MO group was much higher than that of group C, a significantly lower percentage of HDL-cholesterol was found in the MO compared to the percentage found in group C. Also the level of the total cholesterol and LDL-cholesterol of the MI group as well as the MO was much higher than that of C. The elevated total-cholesterol level of the Mi group was due to increased LDL-cholesterol and that of the MO was due to increases in both VLDL-cholesterol and LDL-cholesterol. As the result of these differences, the atherogenic index of the MO was significantly higher than that of C. The incidence of hypercholesterolemia( 200mg/dl) of the MI and MO was 60.0% and 77.8% respectively, All of the physical parameters and indexes except height were positively correlated with plasma lipid levels, systolic blood pressure, and blood glucose concentration. The analyses of the correlated with plasma lipid levels, systolic blood pressure, and blood glucose concentration. The analyses of the correlation indicated that central fat to peripheral fat ratio and waist to thigh girth ratio seemed to be closely associated to plasma lipid levels and atherogenic index. The MO had significantly higher systolic blood pressure than C and significantly higher blood glucose concentration was found in both MI and MO than in C. These results confirmed that obesity in childhood may be relevant to chronic metabolic diseases such as abnormal lipid metabolism, atherosclerosis, high blood pressure and diabetes mellitus.

• Journal of Chest Surgery
• /
• v.25 no.7
• /
• pp.693-701
• /
• 1992

Extracorporeal cardiopulmonary bypass[CPB] has been associated with a wide variety of hematologic derangements, including a transient deformation and hemolysis of red blood cells[RBCs], which is supposed to be due to mechanical trauma and/or metabolic alterations. Since membrane integrity is, in part, maintained by energy requiring process, inadequate function of erythrocyte glycolytic pathway, which is inevitalble during CPB, may cause depletion of high energy phosphate pool and result in hemolysis. The authors performed an investigation to assess whether administration of Fructose-l, 6-diphsphate [FDP], which has been known to enhance intracellular glycolytic activities, could counteract erythrocyte hemolytic events caused by CPB. Sixty pateints with cyanotic congenital heart diseases, who underwent open heart surgery under CPB longer than 60 minutes, were randomly divided into two groups depending on whether use of FDP[Group FDP] or not[Group Control]. The age, sex, CPB time, preoperative hemoglobin level, disease entities were all similar[Table 1], and membrane type oxygenators were used in all patients. In Group, FDP, a dose of 250mg/kg body weight of FDP was administered by intravenous dripping every 12 hours from the morning of the operation to postoperative 48 hours, To demonstrate the degree and pattern of hemolysis of erythrocyte, reticulocyte count, indirect /direct bilirubin, haptoglobin, plasma hemoglobin, lactate dehydrogenase were measured every 12 hours from the time of cessation of CPB to 48 hours and RBC morphologic study, osmotic fragility test were done every 24 hours. All parameters revealed less hemolytic in group FDP [Fig. 1~5], though the differences between two groups were not significant, except plasma hemoglobin, lactate dehydrogenase changes. A pattern of sequential changes of plasma hemoglobin, lactate deh-ydrogenase showed the highest level at the time of CPB stop and abrupt decrease in following 24 hours in both groups, and statistically significant differences were demonstrated in group FDP at least for the first 12 hours postoperatively[p<0.05]. The authors conclude that they can expect the benificial effect of FDP on the maintenance of membrane stability of RBC probably by energy enhancement during the shock status of CPB, but FDP could not completely prevent the damaging effect on RBC by cardiopulmonary bypass

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.19 no.2
• /
• pp.459-465
• /
• 2005

This study was conducted to investigate the application possibility of leaf and stem extract(LSE) extracted from mixture of leaf and stem of ginseng radix (Panax Ginseng C.A. Meyer). We conducted analysis of the ginsenoside content by HPLC. Also we investigate the effects of the LSE on the reduction of serum lipid and improvement of blood parameters in rats fed high fat diet 5 weeks. We examined by analyzing the serum total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride and atherogenic index and hematological datas and serum metabolic variables. Sprague-Dawley rat weigh $150\;g\;{\pm}\;15\;g$, were ramdomly assigned to 4 groups, basal diet only(BDG), high fat diet weithout LSE(FDCG), high fat diet and 10% LSE(FD10G), high fat diet and 20% LSE(FD20G). The result of this study were as follow. Hematological datas of 4 groups were same level, which were not significant. The activities of ALP, GOT and LDH level were significantly different. Total cholesterol, LDL-cholesterol, triglyceride contentrations in serum and atherogenic index were remarkably reduced in LSE supplemented groups as compared high fat control groups. These result imply that LSE could be used as possible for decrease of serum lipid concentration.

• Journal of Nutrition and Health
• /
• v.26 no.9
• /
• pp.1033-1048
• /
• 1993

This study was designed to describe the effect of the protein quality at different intake level of protein on the protein metabolism in the whole body of growing pigs with a simulation model. Varying to the protein level in feeds, four simulations were conducted. The feed protein level, represented as proportions of digestible protein to the metabolic energy (DP/ME, g/MJ), were 6-8, 11-13, 17-19, and 23-25 DP/ME, respectively. Two protein quality and six weeks of growth time were used at each simulation. The objective function for the simulations was protein deposition in the whole body, which was calculated from the experimental results. The parameters in the simulation were determined by the parameter estimation technique. The results obtained from the simulation were as follows: The protein synthesis and breakdown rates(g/day) in the whole body was increased with the increase of protein quality only at lower or required level of protein intake. They showed a parallel behavior in the course of growth, irrespective of quality and level of feed protein intake. The simulated protein deposition and protein synthesis showed a linear relationship between them at different protein quality and level. The affinity parameter showed a linear relationship between them at different protein quality and level. The affinity parameter showed that arginine, tryptophan and isoleucine were more efficient in the stimulation ofbody protein synthesis. Lysine and phenylalanine+tyrosine were less efficient. The oxidation parameter showed that histidine, pheyalanine+tyrosine were less efficient. The oxidation parameter showed that histidine, phenyalanine+tyrosine, and methionine+cystine were oxidized in larger magnitude than lysine and threonine. The oxidation parameter of most amino acids increased with the increase of protein intake beyond the requirement level, but not any more at highest protein intake level. Finally it was found that the improvement of feed protein quality at the lower or required level of protein intake increase protein deposition through a parallel increase of protein synthesis and breakdown.