• Asian-Australasian Journal of Animal Sciences
• /
• v.31 no.4
• /
• pp.595-606
• /
• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• Journal of Pharmaceutical Investigation
• /
• v.36 no.1
• /
• pp.67-73
• /
• 2006

Lornoxicam is a nonsteroidal anti-inflammatory drug that decreases prostaglandin synthesis by inhibiting cyclooxygenase. It has analgesic, antipyretic and antiinflammatory effects. The purpose of the present study was to evaluate the bioequivalence of two lornoxicam tablets, $Xefo^{\circledR}$ (Hyundai Pharmaceutical Ind. Co., Ltd.) and Lornocam (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of lornoxicam from the two lornoxicam formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $24.39{\pm}1.95$ years in age and $68.63{\pm}7.25$ kg in body weight, were divided into two groups and a randomized $2\;{\time}\;2$ cross-over study was employed. After a single tablet containing 4 mg as lornoxicam was orally administered, blood samples were taken at predetermined time intervals and the concentrations of lornoxicam in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t,\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Xefo^{\circledR},$ were -1.56%, 2.16% and -17.12% for $AUC_t,\;C_{max}\;and\;T_{max},$ respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log\;0.90{\sim}log\;1.05$ and $log\; 0.88{\sim}log\;1.17$ for $AUC_t\;and\;C_{max},$ respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Lornocam tablet was bioequivalent to $Xefo^{\circledR}$ tablet.

• Korean Journal of Organic Agriculture
• /
• v.22 no.2
• /
• pp.281-291
• /
• 2014

This study was conducted to examined the effect of dietary supplementation of yellow loess on the growth performance and blood component profiles in pigs. A total of one hundred fifty three pigs (60 one weeks old piglets and 93 adult pigs). Piglets were randomly divided into 3 groups which were control, control + 0.5% yellow loess, control + 1% yellow loess. We measured body weight and weight gain among treatment group. Indeed, we obtained hematological data with WBC, RBC, Hb, Hct, MCV, MCH, MCHC, RDW, and PLT in all loess supplemented group compared to the control. Adults were divided into 2 group (control and control + 1% yellow loess) and serum albumin levels in 1% yellow loess supplemented group was significantly higher than the control group (p<0.01). Amount of crude fat in feces was significantly reduced in yellow loess supplemented group (p<0.001), but no differences were observed at crude protein and crude ash in both groups. In carcass weight and back fat thickness, no significant differences were observed between control and yellow loess supplemented groups. The carcass grade was improved by the dietary supplementation of yellow loess compared to the pig fed control. As a results, dietary yellow loess improves nutrient absorption and carcass grade.

• Journal of Oriental Neuropsychiatry
• /
• v.18 no.2
• /
• pp.57-74
• /
• 2007

Objective : The purpose of this study was to investigate the anti-obesity and anti-hyperlipidemic Effects of Taeyeumjowee-tang and its modified prescription on the animal model of obesity and hyperlipidemia induced high-fat diet. Method : 1) The extracts of Taeyeumjowee-tang (TJT) and its modified prescription, Taeyeumjoweetang gagam-bang (TJGB) were evaluated for its inhibitory effects on obesity. 2) The body weight and feed weight were determined in the pre-treated and post-treated mice and the lipid profiles in the serum were analyzed in order to evaluate the anti-hyperlipidemia action of the extracts. 3) The effect of each extract was investigated for the influences on monoamine oxidase activity and HMG-CoA reductase activity. Results 1. TJT and TJGB extracts dose-dependently reduced the body weight and feed intake in normal mice. The effect of TJGB extract was better than that of TJT extract. 2. TJGB extract diminished the body weight increase and reduced the feed intake in the pre-treatment or post-treatment of the extract 3. TJGB extract decreased the amount of total cholesterol slightly and triglyceride potently after the pre-treatment or post-treatment, but HDL cholesterol exhibited no remarkable change compared with control. 4. TJGB extract weakly potentiated the monoamine oxidase activity, but its effect was better than that of TJT extract. 5. TJGB extract weakly inhibited the HMG-CoA reductase activity, but its effect was better than that of TJT extract. Conclusion : Taeyeumjowee-tang and its modified prescription can clinically be useful as anti-obesity drug and also for the improvement of hyperlipidemia.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.30 no.2
• /
• pp.88-94
• /
• 2016

The study was carried out to examine the anti-obesity effects of 40% ethanol extract from green tea seed (GS) and quantitative determination of caffeine as its major compound. The specificity was satisfied with retention time and UV spectrum by analysis of caffeine using HPLC and comparison with standard compound. It showed a high linearity in the calibration curve with a coefficient of correlation (R²) of 0.9974. The amount of caffeine in GS was about 4.649 mg/g (0.465%) in the three times analysis, and relative standard deviation (RSD) was less than 0.452% by the validated method. The anti-obesity effects of GS were evaluated by using Oil Red O staining in 3T3-L1 adipocytes and body weight, visceral fat and lipid profiles in high fat diet (HFD)-induced C57BL/6 obese mice. Our results indicated that treatment with GS dose-dependently decreased lipid accumulation contents (p<0.001). Moreover, after oral administration for 30 days feeding with HFD-induced obses mice, GS (100 and 300 mg/kg/day) produced a significant decrease in serum total cholesterol (TC), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and visceral fat. Thus, the result of this study indicate that the GS may be a useful resource for the management of obesity.

• Childhood Kidney Diseases
• /
• v.7 no.1
• /
• pp.9-15
• /
• 2003

Purpose : Several studies have suggested that hyperlipidemia might be a causative factor contributing to the progression of initial glomerular injury through the development of glomerulosclerosis. We examined the potential beneficial effect of atorvastatin - which blocks the rate limiting step of cholesterol synthesis by inhibiting HMG-CoA reductase - in PAN-induced nephrosis. Materials and Methods : Glomerulosclerosis was induced in Sprague-Dawley male rats by repeated administration of PAN. Sprague-Dawley male rats were divided into 3 groups : group I(control), group II(PAN 20 mg/kg, subcutaneous injection), group III(PAN 20 mg/kg subcutaneous injection and atorvastatin 50 mg/kg/day per oral). On the 11th week, upon sacrifice of the experimental animals, blood sampling, 24-hr urine collection and nephrectomy were performed. Results : Group III had significantly lower BUN and higher serum albumin($30.9{\pm}17.2\;vs.\;17.3{\pm}2.5\;mg/dL;\;2.3{\pm}0.1\;vs.\;2.5{\pm}0.2\;g/dL$, P<0.05) compared with group II. In the lipid profiles, group III was associated with a reduction in total cholesterol and LDL($291{\pm}173\;vs.\;167{\pm}72\;mg/dL:\;57{\pm}53\;vs.\;27{\pm}12\;mg/dL$, P>0.05) compared with group II. Atorvastatin administration lowered the glomerular sclerosing index significantly(26.2% vs. 13.3%, P<0.05). Conclusion : Puromycin-induced glomerulosclerosis could be ameliorated by the reduction of hyperlipidemia with atorvastatin. This suggests that hyperlipidemia contributes to the pathogenesis of glomerulosclerosis.

• Toxicological Research
• /
• v.8 no.2
• /
• pp.217-233
• /
• 1992

This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.

• Toxicological Research
• /
• v.8 no.2
• /
• pp.235-253
• /
• 1992

A subacute toxicity study of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) was carried out to obtain information on its toxicological profiles, and to determine the maximum tolerated dose in beagle dogs. Four groups of beagle dogs (2M and 2F per group, 0,0.5,1.0,2.0mg/kg/day)were given 15 i.v. injections of SKI 2053R. In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group was treated with cisplatin(0.7mg/kg/day)according to the same treatment schedule. The dosing schedule was divided into 3 courses of 5 consecutive days with 23-day dose-free intervals between each course. After completion of the treatments, remaining dogs were necropsied under established guidelines. Three of four dogs in the high dose group and one of four dogs in the middle dose group treated with SKI 2053R died of hypovolemic shock secondary to hemorrhagic and ulcerative enterocolitis. No toxicity-related mortality occurred in the low dose group of SKI 2053R. No survivor was observed in the group of cisplatin. Clinical signs including vomiting, diarrhea, anorexia and loss body weight were apparent in dogs given either cisplatin or high and middle doses of SKI 2053R. Severe thrombocytopenia and leukocytopenia were observed in the high dose group of SKI 2053R and cisplatin-treatment group, while toxicities as bone marrow suppression were reversible. The significant elevation of serum ALP values in group of SKI 2053R(2.0 mg/kg/day and 1.0mg/kg/day) and cisplatin(0.7mg/kg/day)was observed. Slight proteinuria waa observed in high and middle dose level groups of SKI 2053R. In histopathological examinations, pathological alterations of liver, kidney and spleen were noted dose-dependantly in dogs treated with SKI 2053R, and there was no overt sign of toxicity in low dose group of SKI 2053R. Compared to SKI 2053R, more severe durg-related toxicities occurred in dogs treated with cisplatin. It waw estimated that maximum tolerated dose of SKI 2053R in this treatment schedule was 0.5~0.7mg/kg/day. In conclusion, overall toxic potential of SKI 2053R was approximately 3 times lower than that of cisplatin with respect of lethality.

• Korean Journal of Veterinary Research
• /
• v.34 no.2
• /
• pp.259-266
• /
• 1994

The study was carried out to determine the pharmacokinetic parameters after intravenous(iv) and intramuscular(im) administration (10mg/kr) in healthy rabbits. The results obtained through the experiments were summarized as follows: 1. Bioassay (Bacillus cereus 11778) was evaluated very useful for the determination of oxytetracycline(OTC) in the rabbit serum and tissues, with the detection limit of $0.125{\mu}g/ml$. 2. The pharmacokinetic profiles of OTC (10mg/kg, iv) in rabbits were best described with a two compartment open model $(C=29.5e^{-4,3t}{\pm}3.6^{-0.2t})$, whereas that of OTC (10mg/kg, im) showed a one compartment curve fitting. 3. Following iv administration, a rapid distribution phase was predominant [$t_{\frac{1}{2}}({\alpha}):1.43{\pm}0.98hr$ (♂), $0.5{\pm}0.1hr$(♀)], and then more slow elimination phase ensued [$t_{\frac{1}{2}}({\beta}):4.52{\pm}0.76hr$(♂), $7.32{\pm}2.52hr$(♀)]. Other computer generated pharmacokinetic values were as follows:C1 [$67.76{\pm}18.59ml/kg/h$(♂), $76.03{\pm}22.98ml/kg/h$ (♀)] Vd [$257.74{\pm}180.47ml/kg$ (♂), $92.33{\pm}23.62$ (♀)] AUC [$25.6{\pm}4.44mgh/L$ (♂), $39.6{\pm}12.13mgh/l$ (♀)]. There were no statistical significance between both sexes for all the parameters at the confidence level of 95%. 4. After im administaration, the absorption from the injection sites was very rapid [ Ka:$0.18{\pm}0.03h^{-1}$ (♂), $0.24{\pm}0.02h^{-1}$ (♀)] followed by a monoexponential elimination fashion. The time to peak blood level (Tmax) were calculated $1.64{\pm}0.15hr$ and $1.34{\pm}0.24hr$, in the male and female, respectively. The peak levels (Cmax) at the corresponding time were $1.69{\pm}0.23{\mu}g/ml$ (♂) and $2.08{\pm}0.16{\mu}g/ml$ (♀), with no statistical differences (p>0.05).

• Journal of Pharmaceutical Investigation
• /
• v.25 no.3
• /
• pp.249-264
• /
• 1995

Although liposome has many advantages as a pharmaceutical dosage form, its application in the industrial field has been limited because of some problems such as preparation method, reproducibility, scale-up, stability and sterilization etc. Liposomes prepared by microemulsification method had defined size, narrow size distribution, reproducibility and high entrapment efficiency. For enhancing the stability, the dry form of liposome was recommended. These types of liposome are proliposome and freeze-dried liposome. The liposome must have some properties for preparing of freeze-dried liposome; small size $(50{\sim}200\;nm)$, narrow size distribution and cryoprotectant. In this experiment, the liposomes containing 5-Fluorouracil(5-FU) and its prodrug(pentyl-5-FU-1-acetate; PFA, hexyl-5-FU-1-acetate; HFA) were made with soybean phosphatidylcholine, cholesterol, stearylamine(SA) and dicetyl phosphate(DCP) employing hydration method or microemulsification method using $Microfluidizer^{TM}$. Both or liposome types were MLV and MEL. After preparation, freeze drying and rehydration were performed. In the process of freezing, trehalose(Tr) was added as a cryoprotectant. Their evaluation methods were as follows; entrapment efficiency, mean particle size and size distribution, dissolution test, retain of entrapment efficiency and turbidity after freeze-drying. The results are summarized as belows. The entrapment efficiency of 5-FU was dependent on total lipid concentration and cholesterol content but that of PFA and HFA was decreased when cholesterol was added. When DCP and SA were added, entrapment efficiency was decreased. As the partition coefficient of drug was increased, entrapment efficiency was increased. Under the same condition, entrapment efficiency of MEL is similar to that of MLV. The mean particle size and size distribution of MEL were smaller than those of MLV. Dissolution rates of drug from both liposome types were comparatively similar. Dissolution rates of drugs with serum and liver homogenate were faster than without these material. After preparation of liposome, free drug was removed efficiency by Dowex 50W-X4. When liposome was freeze-dried and then rehydrated in the presence of Tr, characteristics of liposome were maintained well in MEL than MLV. Tr Was used successfully as a cryoprotectant in the process of freeze drying and the optimal ratio of Tr:Lipid was 4:1(g/g).