In order to evaluate the mode of action of ginseng saponin. metabolic changes in the plasma of normal and aloxan-intoxicated rats were compared Normal groups were administered only ginseng saponin 0, 5, 50mg/kg for 16 days, but alloxan-intoxicated groups were administered alloxan 25mg/kg for 3 days in addition to ginseng saponin. (1) No significant change in the concentration of glucose, cholesterol, and triglyceride (TG) was observed in normal rats but great inhibitory effect, except elevation of TG, was observed in alloxan-intoxicated rats. However, blood urea nitrogen was elevated in both normal and alloxan- intoxicated rats by administration of ginseng saponin 50mg/kg, and it was considered to be due to the impaired kidney function caused by overdose toxicity. (2) In normal rats, COT and ALP actIn,its were not changed by administration of ginseng saponin but GPT activity was decreased significantly. In alloxan-intoxicated rats, ginseng saponin exerted inhibitory action on the elevation of COT, CPT and ALP activity. But administration of ginseng saponin Smghg was much more effective than administration of 50mg/kg. (3) There fore, we concluded that ginseng saponin has the adaptogenic activity showing little effect on normal metabolism but great preventive action on alloxan-intoxicated rats.
Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.
Journal of The Korean Society of Grassland and Forage Science
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v.26
no.4
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pp.239-248
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2006
This study was conducted not only to investigate effects of different supplementation levels of Acanthopanax senticosus leaves on feed intakes, nutrient digestibility, nitrogen retention, and blood metabolites in Korean black goats but also to obtain basic data for nutritive value of Acanthopanax senticosus leaves and production of high quality functional animal products. Twelve Korean black goats were allotted to treatments in four groups of three goats per treatment and then they were housed in individual metabolism cages with completely random arrangements for 21 days. Four treatments were separated into controls and three different supplementation levels of Acanthopanax senticosus such as 10, 20 and 30%, respectively. For the chemical composition of experimental diets, crude protein (CP) contents of controls were 13.39% and those of supplementation treatments were lowered with increasing levels of Acanthopanax senticosus. Control groups tended to have higher acid detergent fiber (ADF) and neutral detergent fiber (NDF) contents as compared to supplementation groups, but non-fibrous carbohydrate (NFC) contents tended to be higher far supplementation groups than those for controls. Feed intakes had no significant difference among treatments, but digestible dry matter amounts were significantly higher for 20 and 30% supplementation groups than those for other treatments. Dry matter intakes per metabolic body weight and their ratio per body weight were highest in 20% group, but those of 40% groups were lowest (p<0.05). Crude protein, ADF and NDF digestibilities were significantly higher in Acanthopanax senticosus supplementation groups in comparison to controls (p<0.05), and in particular, they were increased with increasing supplementation levels of tranthopanax senticosus. Nitrogen retention was significantly higher for 20 and 30% treatments than those fur controls (p<0.05). Plasma urea nitrogen concentration was significantly lower for 30% supplementation group than those fur controls (p<0.05). Furthermore, plasma triglyceride concentration was significantly lower for Acanthopanax senticosus groups than those for controls (p<0.05). The results showed that supplemental level of 20% Acanthopnnax senticosus leaves to Korean black goats improved nutrient digestibility, nitrogen retention, and plasma urea nitrogen and triglyceride concentrations. Consequently, it might contribute to more efficient production of Korean black goats.
Background:It has been suggested that the cyclooxygenase metabolites play an important role in changes of early hemodynamic parameters in the endotoxin-induced acute lung injury. But there have been many debates about their role in the late increase of alveolar-capillary permeability, and it is not known whether they act directly or indirectly through oxygen free radicals which have been known to be produced during the metabolic process of cyclooxygenase pathway. So we performed this study to identify the pathogenetic role of cyclooxygenase metabolites in the endotoxin-induced acute lung injury in domestic pigs. Method: We infused endotoxin into 8 domestic pigs; endotoxin only (n=3), and pretreatment with indomethacin (n=5). We observed the sequential changes in hemodynamic parameters, the concentration of plasma oxidized glutathione (GSSG) in pulmonary arterial and venous blood, and albumin content in bronchoalveolar lavage fluid (BALF). Results: 1) While cardiac output decreased, mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference increased over phase 1 (0-2hr) and phase 2 (2-4.5hr) by endotoxin, indomethacin attenuated the decrease in cardiac output during phase 1 and increase in mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference during both phases. 2) The increase in plasma GSSG content during phase 2 was not attenuated by indomethacin. 3) The content of BALF albumin was significantly lower in indomethacin groups than that of endotoxin group. Conclusion: These results suggest that it is likely that cyclooxygenase metabolites have an effect on endotoxin-induced acute lung injury during both phases probably through direct action.
Purpose: Telmisartan, an angiotensin receptor blocker has been known to be a potent blocker of both CYP2J2 and P-glycoprotein (P-gp) in vitro. This study aims to investigate the drug-drug interactions between telmisartan and ebastine, a CYP2J2 and P-gp substrate in rats. Method: Ebastine (10 mg/kg) was orally given in the presence and absence of telmisartan (4 mg/kg, p.o.). Heparinized blood was serially taken and the plasma concentrations of ebastine and its three metabolites (hydroxyebastine, carebastine and desalkylebastine) were determined using LC-MS/MS, and their pharmacokinetic parameters were compared. Results: Peak concentrations ($C_{max}$) and AUC of ebastine were significantly (p<0.05) increased in the presence of telmisartan by 2.1 and 1.9 times, respectively. While $C_{max}$ of hydroxyebastine was significantly increased by 1.9 times, the half-life of hydroxyebasteine was decreased significantly with telmisartan (p<0.05). There was no change in the pharmacokinetic parameters of carebastine, the active metabolite of ebastine, and desalkylebastine was not detected in plasma. The systemic exposure of ebastine was significantly augmented by telmisartan, indicating that telmisartan may enhance the absorption of ebastine by blocking P-gp. Conclusion: Although telmisartan may also partially contribute to inhibit the biotransformation to hydroxyebastine, the inhibitory action seemed to be overridden by the enhancement of absorption, because the generation of hydroxyebastine was not diminished. In spite of such interactions between telmisartan and ebastine, no clinical consequence could be expected due to no significant change of the active metabolite, carebastine.
This study was conducted to determine the rumen fermentation dynamics of lupin flakes and elucidate the effects of lupin flake supplementation on the growth performance, blood metabolites, and carcass characteristics of Hanwoo steers. In vitro and in situ trials of lupin grains and lupin flakes were conducted using three Hanwoo cows with rumen fistulas. The feeding trial included 40 early-fattening Hanwoo steers randomly divided into four groups: control, T1, T2, and T3. Their formula feed contained 0%, 3%, 6%, and 9% lupin flakes, respectively. In vitro rumen pH and ammonia concentrations were lower in the lupin flake group than in the lupin grain group after 6 and 24 h of incubation, respectively (p < 0.05). Concentrations of propionate, butyrate, and total volatile fatty acids were higher in the lupin flake group than in the lupin grain group after 12 h of incubation (p < 0.05), as was the crude protein disappearance rate at 9 and 12 h of rumen fermentation (p < 0.05). Supplementation with lupin flakes did not affect the average daily gain. Compared to that in the control group, dry matter intake was lower in the lupin flake-supplemented groups (p < 0.05); the feed conversion ratio was lower in T2 and T3 (p < 0.05); and plasma total protein concentration in 29-month-old steers was lower in T1 and T3 (p < 0.05). Plasma triglyceride concentration was lower in the lupin flake-supplemented groups than in the control group (p < 0.05). The incidence rate of yield grade A was higher in T1 and T2 than in the control group; the incidence rate of meat quality 1+ grade or higher was highest in T2. The carcass auction price was higher in T2 than in the other groups. Overall, compared to whole lupin grains, lupin flakes seem to more substantially affect rumen ammonia concentrations and crude protein disappearance rate. Additionally, we suggest that supplementation with 6% lupin flake formula feed exerts positive effects on the feed conversion ratio, yield grade, and quality grade of Hanwoo steers.
Cho, Hyun Min;Macelline, Shemil Priyan;Wickramasuriya, Samiru Sudharaka;Shin, Taeg Kyun;Kim, Eunjoo;Son, Hong Cheol;Heo, Jung Min
Animal Bioscience
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v.35
no.3
/
pp.434-443
/
2022
Objective: The study was conducted to investigate the impact of boron supplementation on nutrient digestibility, inflammatory responses, blood metabolites and diarrhea index, and their relevance to growth performance in weaned pigs housed in good and poor sanitary environments for 14 days after weaning. Methods: A total of 108 male pigs (Duroc×[Yorkshire×Landrace]) weaned at 21 days of age were used in a randomized complete block design with 2×3 factorial arrangement. Pigs were assigned to three boron treatments (0, 5, and 10 mg/kg) under two environments (good and poor sanitary) to give six replicates per treatment (3 pigs per replicate). On 0, 7, and 14 days, one pig per replicate was euthanized to collect, ileum tissue samples, and rectal fecal samples. Results: Boron supplementation quadratically influenced (p<0.001) feed intake and weight gain in pigs housed in good sanitary conditions from 1 to 14 days post-weaning where pigs offered 5 mg/kg boron optimized weight gain and feed intake. There is a quadratic interaction (p = 0.019) on feed intake for 1 to 14 days post-weaning where 5 mg/kg boron increased feed intake in good sanitary conditions. Pigs housed in the poor sanitary environment decreased (p<0.001) villus height and crypt depth in ileum at days 7 and 14. On day 7 and 14, crude protein digestibility was quadratically influenced (p<0.05) by boron supplementation. Boron supplementation linearly increased (p<0.05) plasma calcium and cholesterol levels whilst linearly (p = 0.005) reducing plasma triglyceride concentrations. Diarrhea index was quadratically influenced (p<0.05) by boron supplementations regardless of sanitary conditions where 5 mg/kg boron inclusion achieved the lowest diarrhea index. Conclusion: Pigs offered 5 mg/kg of boron increased weight gain which may be deduced by improved dry matter, crude protein, and energy digestibility regardless of the sanitary conditions.
Khummuang, Saichit;Lee, Hyo Gun;Joo, Sang Seok;Park, Jeong-Woong;Choi, Jae-Young;Oh, Jin Hyeog;Kim, Kyoung Hwan;Youn, Hyun-Hee;Kim, Myunghoo;Cho, Byung-Wook
Asian-Australasian Journal of Animal Sciences
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v.33
no.3
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pp.424-435
/
2020
Objective: The study was conducted to investigate variations in the immunophysiological responses to exercise-induced stress in Jeju and Thoroughbred horses. Methods: Blood samples were collected from the jugular veins of adult Jeju (n = 5) and Thoroughbred (n = 5) horses before and after 30 min of exercise. The hematological, biochemical, and immunological profiles of the blood samples were analyzed. Blood smears were stained and observed under a microscope. The concentration of cell-free (cf) DNA in the plasma was determined using real time polymerase chain reaction (PCR). Peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells were separated using Polymorphprep, and the expression of various stress-related and chemokine receptor genes was measured using reverse transcriptase (RT) and real-time PCR. Results: After exercise, Jeju and Thoroughbred horses displayed stress responses with significantly increased rectal temperatures, cortisol levels, and muscle catabolism-associated metabolites. Red blood cell indices were significantly higher in Thoroughbred horses than in Jeju horses after exercise. In addition, exercise-induced stress triggered the formation of neutrophil extracellular traps (NETs) and reduced platelet counts in Jeju horses but not in Thoroughbred horses. Heat shock protein 72 and heat shock protein family A (Hsp70) member 6 expression is rapidly modulated in response to exercise-induced stress in the PBMCs of Jeju horses. The expression of CXC chemokine receptor 4 in PBMCs was higher in Thoroughbred horses than in Jeju horses after exercise. Conclusion: In summary, the different immunophysiological responses of Jeju and Thoroughbred horses explain the differences in the physiological and anatomical properties of the two breeds. The physiology of Thoroughbred horses makes them suitable for racing as they are less sensitive to exercise-induced stress compared to that of Jeju horses. This study provides a basis for investigating the link between exercise-induced stresses and the physiological alteration of horses. Hence, our findings show that some of assessed parameters could be used to determine the endurance performance of horses.
An experiment was conducted to determine the effects of two levels of rumen undegradable protein (RUP) without or with whole or extruded flaxseed on milk yield, milk component, milk fatty acids (FAs) profile and plasma metabolites in transition ewes. Three weeks before and after lambing, seventy-two Baluchi ewes were used in a completely randomized design with a 3 × 2 factorial arrangement of treatments. The treatments contained 1) no flaxseed + 20% RUP (no flaxseed, low RUP [NFLR]); 2) no flaxseed + 40% RUP (no flaxseed, high RUP [NFHR]); 3) 10% whole flaxseed + 20% RUP (whole flaxseed, low RUP [WFLR]); 4) 10% whole flaxseed + 40% RUP (whole flaxseed, high RUP [WFHR]); 5) 10% extruded flaxseed + 20% RUP (extruded flaxseed, low RUP [EFLR]), and 6) 10% extruded flaxseed + 40% RUP (extruded flaxseed, high RUP [EFHR]). Ewes fed 10% extruded flaxseed exhibited higher (p < 0.001) dry matter intake (DMI) and colostrum yield (p < 0.1) compared to other treatments. Two types of flaxseed and RUP levels had no significant effect on milk yield, but milk fat and protein contents decreased and increased in diets containing 40% RUP, respectively. Ewes fed extruded flaxseed produced milk with lower concentrations of saturated fatty acids (SFA) and higher α-linolenic and linoleic acids and also polyunsaturated fatty acids (PUFA) compared to other groups (p < 0.05). During post-lambing, the ewes fed diets containing flaxseed exhibited higher concentration of serum non-esterified FAs (NEFA) compared to diets without flaxseed (p < 0.01). The concentration of serum β-hydroxybutyric acid (BHBA) decreased in the diets containing flaxseed types at pre-lambing, but increased in diets containing extruded flaxseed at post-lambing (p < 0.01). The serum glucose concentration of ewes (pre and post-lambing) which consumed diets containing extruded flaxseed or 40% RUP increased, but blood urea concentration was elevated following supplementation of diet with whole flaxseed or 40% RUP (p < 0.001). In conclusion, utilization of 10% extruded flaxseed in the diets of transition ewes had positive effects on animal performance with favorable changes in milk FAs profile. However, there is no considerable advantage to supply more than 20% RUP level in the diet of transition dairy sheep.
Objective: Reducing roughage feeding without negatively affecting rumen health is of interest in ruminant nutrition. We investigated the effects of roughage sources and concentrate types on growth performance, ruminal fermentation, and blood metabolite levels in growing cattle. Methods: In this 24-week trial, 24 Hanwoo cattle ($224{\pm}24.7kg$) were fed similar nitrous and energy levels of total mixed ration formulated using two kinds of roughage (timothy hay and ryegrass straw) and two types of concentrate mixes (high starch [HS] and high fiber [HF]). The treatments were arranged in a $2{\times}2$ factorial, consisting of 32% timothy-68% HS, 24% timothy-76% HF, 24% ryegrass-76% HS, and 17% ryegrass-83% HF. Daily feed intakes were measured. Every four weeks, blood were sampled, and body weight was measured before morning feeding. Every eight weeks, rumen fluid was collected using a stomach tube over five consecutive days. Results: The mean dry matter intake (7.33 kg) and average daily gain (1,033 g) did not differ among treatments. However, significant interactions between roughage source and concentrate type were observed for the rumen and blood parameters (p<0.05). Total volatile fatty acid concentration was highest (p<0.05) in timothy-HF-fed calves. With ryegrass as the roughage source, decreasing the roughage inclusion rate increased the molar proportion of propionate and decreased the acetate-to-propionate ratio; the opposite was observed with timothy as the roughage source. Similarly, the effects of concentrate types on plasma total protein, alanine transaminase, Ca, inorganic P, total cholesterol, triglycerides, and creatinine concentrations differed with roughage source (p<0.05). Conclusion: Decreasing the dietary roughage inclusion rate by replacing forage neutral detergent fiber with that from non-roughage fiber source might be a feasible feeding practice in growing cattle. A combination of low-quality roughage with a high fiber concentrate might be economically beneficial.
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