• Title/Summary/Keyword: P450 2C19

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Anti-inflammatory Effects in LPS-treated RAW 264.7 Cells and the Influences on Drug Metabolizing Enzyme Activities by the Traditional Herbal Formulas, Yongdamsagan-Tang and Paljung-san

  • Ha, Hyekyung;Jin, Seong Eun;Seo, Chang-Seob;Shin, Hyeun-kyoo
    • The Journal of Korean Medicine
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    • v.42 no.4
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    • pp.10-24
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    • 2021
  • Objectives: Yongdamsagan-tang (YST) and Paljung-san (PJS) in traditional medicine and finasteride in modern medicine are used to treat benign prostatic hyperplasia (BPH). In recent, the use of combination herbal remedies with conventional drugs has been increasing. Therefore, we investigated the anti-inflammatory effects of these drugs to treat BPH and the influence of herbal formulas on finasteride metabolism. Methods: The inhibitory effects of the herbal formulas and finasteride on the production of inflammatory mediators and cytokines were determined in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Additionally, the influence of herbal formulas on activities of human drug metabolizing enzymes (DMEs) was assessed using human microsomal enzymes. Results: We observed that YST, PJS and finasteride inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2) and interleukin-6 (IL-6) in RAW 264.7 cells. The half maximal inhibitory concentration (IC50) of YST on PGE2 production was calculated to be below 25 ㎍/mL. YST inhibited the activity of uridine diphosphate-glucuronosyltransterase (UGT) 1A4 with an IC50 value of 49.35 ㎍/mL. The activities of cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP3A4, and UGT1A1 were inhibited by PJS (IC50 < 100 ㎍/mL, each). Although PJS and YST inhibited the activities of CYP3A4 and UGT1A4, respectively, these formulas may not influence the metabolism of finasteride because the IC50 values of herbal formulas on DMEs are too high to affect metabolism. Conclusions: Our results suggest that the combination of finasteride and YST or PJS might not influence their drug metabolism and that the drugs may have synergistic effects against BPH.

Culture Conditions for Hydrogen Production of Enterobacter cloacae YJ-1 (수소생산을 위한 Enterobacter cloacae YJ-1의 배양조건)

  • Lee Ki-Seok;Kang Chang-Min;Chung Seon-Yong
    • KSBB Journal
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    • v.19 no.6 s.89
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    • pp.446-450
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    • 2004
  • We investigated the effective culture conditions of anaerobic bacteria, Enterobacter cloacae YJ-1 on hydrogen production. It was cultured with 60 mL of working volume at $35^{\circ}C$, 120 rpm for 40 h. With culture time, hydrogen production and cell growth increased, but residual glucose and pH decreased. When the $2\%$ of glucose was used as single carbon source, hydrogen production was 975.1 mL/L. To enhance hydrogen productivity, mixed carbon sources of glucose and sucrose were added. The maximum hydrogen production was earned at the mixing ratio of 25:75, and it was 1319.5 mL/L. When we added 50 mM of phosphate to protect the pH drop in culture broth, hydrogen production increased 1.3 times more than that of initial concentration. The organic nitrogen sources were more effective than inorganic nitrogen for hydrogen production. Among organic nitrogen, yeast extract was the most effective and its hydrogen production was 1691.3 mL/L. Among 9 of mineral sources, Ferric citrate and $NaMoO_4$ were especially effective, and their productions were 1782.3 mL/L and 1784.8 mL/L, respectively.

A Case of Late-onset Episodic Myopathic Form with Intermittent Rhabdomyolysis of Very-long-chain acyl-coenzyme A Dehydrogenase (VLCAD) Deficiency Diagnosed by Multigene Panel Sequencing (유전자패널 시퀀싱으로 진단된 성인형 very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) 결핍증 증례)

  • Sohn, Young Bae;Ahn, Sunhyun;Jang, Ja-Hyun;Lee, Sae-Mi
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.19 no.1
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    • pp.20-25
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    • 2019
  • Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (OMIM#201475) is an autosomal recessively inherited metabolic disorder of mitochondrial long-chain fatty acid oxidation. The clinical features of VLCAD deficiency is classified by three clinical forms according to the severity. Here, we report a case of later-onset episodic myopathic form of VLCAD deficiency whose diagnosis was confirmed by plasma acylcarnitine analysis and" multigene panel multigene panel sequencing. A 34-year old female patient visited genetics clinic for genetic evaluation for history of recurrent myopathy with intermittent rhabdomyolysis. She suffered first episode of rhabdomyolysis with acute renal failure requiring hemodialysis at twelve years old. After then, she suffered several times of recurrent rhabdomyolysis provoked by prolonged exercise or fasting. Physical and neurologic exam was normal. Serum AST/ALT and creatinine kinase (CK) levels were mildly elevated. However, according to her previous medical records, her AST/ALT, CK were highly elevated when she had rhabdomyolysis. In suspicion of fatty acid oxidation disorder, multigene panel sequencing and plasma acylcarnitine analysis were performed in non-fasting, asymptomatic condition for the differential diagnosis. Plasma acylcarnitine analysis revealed elevated levels of C14:1 ($1.453{\mu}mol/L$; reference, 0.044-0.285), and C14:2 ($0.323{\mu}mol/L$; 0.032-0.301) and upper normal level of C14 ($0.841{\mu}mol/L$; 0.065 -0.920). Two heterozygous mutation in ACADVL were detected by multigene panel sequencing and confirmed by Sanger sequencing: c.[1202G>A(;) 1349G>A] (p.[(Ser 401Asn)(;)(Arg450His)]). Diagnosis of VLCAD deficiency was confirmed and frequent meal with low-fat diet was educated for preventing acute metabolic derangement. Fatty acid oxidation disorders have diagnostic challenges due to their intermittent clinical and laboratorial presentations, especially in milder late-onset forms. We suggest that multigene panel sequencing could be a useful diagnostic tool for the genetically and clinically heterogeneous fatty acid oxidation disorders.

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The Effect of Au Addition on the Hardening Mechanism in Ag-20wt% Pd-20wt% Cu (Ag-20wt% Pd-20wt% Cu 3원합금(元合金) 및 Au첨가합금(添加合金)의 시효경화특성(時效硬化特性))

  • Park, M.H.;Bae, B.J.;Lee, H.S.;Lee, K.D.
    • Journal of Technologic Dentistry
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    • v.19 no.1
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    • pp.21-35
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    • 1997
  • The Ag-Pd-Cu alloys containing a small amount of Au is commonly used for dental purposes, because this alloy is cheaper than Au-base alloys for clinical use. However, the most important characteristic of this alloy is age-hardenability, which is not exhibited by other Ag-base dental alloys. The specimens used were Ag-20Pd-20Cu ternary alloy and Au addition alloy. These alloys were melted and casted by induction electic furace and centrifugal casting machine in Ar atmoshpere. These specimens were solution treated for 2hr at $800^{\circ}C$ and were then quenched into iced water, and aged at $350{\sim}550^{\circ}C$ Age-hardening characteristics of the small Au-containing Ag-pPd-Cu dental alloys were investigated by means of hardness testing, X-ray diffraction and electron microscope observations, electrical resistance, differential scanning calorimetric, emergy dispersed spectra and electron probe microanalysis. Principal results are as follows : Hardening occured in two stages, I. e., stage I in low temperature and stage II in high temperature regions, during continuous aging. The case of hardening in stage I was due to the formation of the Llo type face centered tetragonal PdCu-ordered phase in the grain interior and hardening in stage I was affedted by the Cu concentration. In stage II, decomposition of the $\alpha$ solid solution to a PdCu ordered phase(L1o type) and an Agrich ${\alpha}2$ phase occurred and a discontiunous precipitation occurred at the grain boundary. Form the electron microscope study, it was concluded that the cause of age-hardening in this alloy is the precipitation of the PdCu ordered phase, which has AuCu I type face-centered tetragonal structure. Precipitation procedure was ${\alpha}\to{\alpha}+{\alpha}2+PdCu\to{\alpha}1+{\alpha}2+PdCu$ at Pd/Cu = 1 Ag-Pd-Cu alloy is more effective dental alloy as ageing treatment and is suitable to isothermal ageing at $450^{\circ}C$.

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Effects of Applying Cattle Manure on Carrying Capacity of Organic Livestock per Unit Area of Summer Forage Crops (우분뇨 시용이 하계사료작물의 단위면적당 유기가축 사육능력에 미치는 영향)

  • Jo, Ik-Hwan
    • Korean Journal of Organic Agriculture
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    • v.19 no.2
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    • pp.185-198
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    • 2011
  • This study was carried out to select a proper forage crop, and to estimate the proper level of application of cattle manure and carrying capacity of organic livestock per unit area. Corns and forage sorghum hybrids were cultivated with different types of livestock manures and different amount of them to produce organic forage. For both corns and forage sorghum hybrids, no fertilizer plots had significantly (p<0.05) lower annual dry matter (DM), crude protein (CP) and total digestible nutrients (TDN) yields than those of other plots, whereas the N-P-K (nitrogen-phosphorous-kalium) plots ranked the highest yields, followed by 150% cattle manure plots and 100% cattle manure plots. DM, CP and TDN yields of in cattle manure plots were significantly (p<0.05) higher than those of no fertilizer and P-K (phosphorous-kalium) plots. The yields of in cattle slurry plots tended to be a little higher than those of in composted cattle manure plots. Assuming that corn and forage sorghum hybrids produced from this trial were fed at 70% level to 450kg of Hanwoo heifer for 400g of average daily gain, the carrying capacity (head/year/ha) of livestock ranked the highest in 150% cattle slurry plots (mean 6.0 heads), followed by 100% cattle slurry plots (mean 5.3 heads), 150% composted cattle manure plots (mean 4.7 heads), 100% composted cattle manure plots (mean 4.4 heads), and no fertilizer plots (mean 2.8 heads) in corns (or the cultivation of corns). Meanwhile, in the case of forage sorghum hybrids, 150% cattle slurry plots (mean 6.4 heads) ranked the highest carrying capacity, followed by 150% composted cattle manure plots (mean 4.8 heads), 100% cattle slurry plots (mean 4.4 heads), 100% composted cattle manure plots (mean 4.1 heads), and no fertilizer plots (mean 2.8 heads). The results indicated that the application of livestock manure to cultivated soil could enhance not only DM and TDN yields, but also the carrying capacity of organic livestock as compared with the effect of chemical fertilizers. In conclusion, the production of organic forage with reutilized livestock manure will facilitate the reduction of environmental pollution and the production of environmentally friendly agricultural products by resource circulating system.

Comparison of Growth, Milk Yield and Draughtability of Murrah-Philippine Crossbred and Philippine Native Buffaloes

  • Salas, R.C.D.;van der Lende, T.;Udo, H.M.J.;Mamuad, F.V.;Garillo, E.P.;Cruz, L.C.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.5
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    • pp.580-586
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    • 2000
  • Data collected between 1981 and 1991 at the Philippine Carabao Center at Central Luzon State University (PCC-CLSU) were used for the comparison of growth, milk yield and draughtability of Murrah-Philippine crossbred and Philippine native buffaloes. Body weights and body measurements were available at 3-month intervals from birth to 36 months of age for a total of 34 $Murrah{\times}Philippine$ native buffalo F1 crossbreds (CBB; 21 cows, 13 bulls) and 32 Philippine native buffaloes (PNB; 16 cows, 16 bulls). Lactation records were available for 14 CBB and 19 PNB cows. Data for draughtability under wet and dry ploughing conditions were available for 4 CBB and 4 PNB steers. The results indicate that crossbreds grow faster (0-9 months of age: cows $442{\pm}19$ vs. $301{\pm}21g/day$, bulls $305{\pm}23$ vs. $296{\pm}21g/day$; 9-36 months of age: cows $227{\pm}10$ vs. $147{\pm}12g/day$, bulls $282{\pm}13$ vs. $138{\pm}12g/day$), mature earlier and produce more milk (1st lactation: $1139{\pm}153$ vs. $450{\pm}112kg$; 2nd lactation: $1115{\pm}132$ vs. $488{\pm}136kg$) than native buffaloes, but have a poorer draughtability (wet ploughing; force as % of body weight $8.8{\pm}0.2$ vs. $12.2{\pm}0.6$; dry ploughing: cut depth $10.98{\pm}0.25$ vs. $11.92{\pm}0.13cm$, velocity $0.50{\pm}0.03$ vs. $0.60{\pm}0.02m/sec$, force as % of body weight $9.0{\pm}0.6$ vs. $11.3{\pm}0.7$). The correlation coefficients between body weight and body measurements at birth and at 3-month intervals indicate that heart girth has a relatively high correlation with body weight, especially in crossbreds. It is concluded that in Philippine smallholder farming systems in which meat and milk production are secondary to draught power, the native buffalo is preferable from the point of view of input needed to maintain the number of animals kept for a required draught force.

Effects of FK224, a $NK_1$ and $NK_2$ Receptor Antagonist, on Plasma Extravasation of Neurogenic Inflammation in Rat Airways (미주 신경의 전기적 자극으로 유발된 백서의 기도내 혈장 유출에 대한 FK224의 효과)

  • Shim, Jae-Jeong;Lee, Sang-Yeub;Lee, Sang-Hwa;Park, Sang-Myun;Seo, Jeong-Kyung;Cho, Jae-Yun;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.744-751
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    • 1995
  • Background: Asthma is an inflammatory disease because there are many inflammatory changes in the asthmatic airways. Axon reflex mechanisms may be involved in the pathogenesis of asthma. Sensory neuropeptides are involved in this inflammation, which is defined as neurogenic inflammation. Substance p, neurokinin A, and neurokinin B may be main neuropeptides of neurogenic inflammation in airways. These tachykinins act on neurokinin receptors. Three types of neurokinin receptors, such as $NK_1$, $NK_2$, and $NK_3$, are currently recognized, at which substance p, neurokinin A, and neurokinin B may be the most relevant natural agonist of neurogenic inflammation in airways. The receptor subtypes present in several tissues have been characterized on the basis of differential sensitivity to substance p, neurokinin A, and neurokinin B. Plasma extravasation and vasodilation are induced by substance p more potently than by neurokinin A, indicating NK1 receptors on endothelial cells mediate the response. But airway contraction is induced by neurokinin A more potently than by substance P, indicating the $NK_2$ receptors in airway smooth muscles. These receptors are used to evaluate the pathogenesis of brochial asthma. FK224 was identified from the fermentation products of Streptomyces violaceoniger. FK224 is a dual antagonist of both $NK_1$ and $NK_2$ receptors. Purpose: For a study of pathogenesis of bronchial asthma, the effect of FK224 on plasma extravasation induced by vagal NANC electrical stimulation was evaluated in rat airway. Method: Male Sprague-Dawley rats weighing 180~450gm were anesthetized by i.p. injection of urethane. Plasma extravasation was induced by electrical stimulation of cervical vagus NANC nerves with 5Hz, 1mA, and 5V for 2 minutes(NANC2 group) and for sham operation without nerve stimulation(control group). To evaluate the effect of FK224 on plasma extravasation in neurogenic inflammation, FK224(1mg/kg, Fujisawa Pharmaceutical Co., dissolved in dimethylsulphoxide; DMSO, Sigma Co.) was injected 1 min before nerve stimulation(FK224 group). To assess plasma exudation, Evans blue dye(20mg/kg, dissolved in saline) was used as a plasma marker and was injected before nerve stimulation. After removal of intravascular dye, the evans blue dye in the tissue was extracted in formamide($37^{\circ}C$, 24h) and quantified spectrophotometrically by measuring dye absorbance at 629nm wavelength. Tissue dye content was expressed as ng of dye per mg of wet weight tissue. The amount of plasma extravasation was measured on the part of airways in each groups. Results: 1) Vagus nerve(NANC) stimulation significantly increased plasma leakage in trachea, main bronchus, and peripheral bronchus compared with control group, $14.1{\pm}1.6$ to $49.7{\pm}2.5$, $17.5{\pm}2.0$ to $38.7{\pm}2.8$, and $12.7{\pm}2.2$ to $19.1{\pm}1.6ng$ of dye per mg of tissue(mean ${\pm}$ SE), respectively(p<0.05). But there was not significantly changed in lung parenchyma(p>0.05) 2) FK224 had significant inhibitory effect upon vagal nerve stimulation-induced airway plasma leakage in any airway tissues of rat,such as trachea, main bronchus, and peripheral bronchus compared with vagus nerve stimulation group, 49%, 58%, and 70%, respectively(p<0.05). Inhibitory effect of FK224 on airway plasma leakage in neurogenic inflammation was revealed the more significant in peripheral bronchus, but no significant in lung parenchyma. Conclusion: These results suggest that FK224 is a selective NK receptor antagonist which effectively inhibits airway plasma leakage induced by the endogenous neurotransmitters relased by neurogenic inflammation in rat airway. Tachykinin receptor antagonists may be useful in the treatment of brochial asthma.

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Effect of Feeding Organic Acid Mixture and Yeast Culture on Performance and Egg Quality of Laying Hens (유기산제와 효모배양물의 급여가 산란계의 생산성 및 계란품질에 미치는 영향)

  • 류경선;박재홍;박강희
    • Korean Journal of Poultry Science
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    • v.29 no.2
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    • pp.109-116
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    • 2002
  • The objective of this study was to investigate the effect of feeding organic acid mixture and yeast culture on the Performance and e99 quality of laying hens fur sixteen weeks. Four hundred and fifty 19-wk-old ISA Brown layers were alloted to five treatments with five replications of each. The supplemental levels of organic acid mixture(OAM) and yeast culture(YC) in the experimental diets were 0(control), OAM 0.1, 0.2%, and YC 0.1, 0.2%, respectively. Corn -Soy basal diet containing 16.0% CP and ME 2,770 kca1/kg ME. Eggs were collected and weighed every day. Eg3 Production, fred intake and fled conversion were recorded in every four weeks. Fatty acid composition of e99 Yolk, e99she11 breaking strength, thickness and Haugh unit were measured a(her every eight weeks. Egg Production and daily egg mass of birds fed 0.2% OAM and 0.1% YC tended to be higher than those of the other treatment groups. Egg weight was the highest in hens fed with 0.2% OAM treatment, but was not significantly different. Feed conversion of hens in all OAM and YC treatments was lower than those of control, but was not statistically different. Eggshell breaking strength of hens on OAM treatments tended to be higher than those of YC treatment and control. Haugh units of the birds fed OAM was significantly higher than controls (P<0.05). 599 yolk color score of OAM treatment was higher than those of YC treatments and control, but the difference was not significant. At 27-wk-old, arachidonnic acid content in eggs from the birds fed 0.1% OAM diet was significantly higher(P<0.05) than controls. The results of this experiment indicated that dietary organic acid mixture and yeast culture tended to improve the egg Production and internal egg quality.

Quality Characteristic of Glasswort (Salicornia herbacea L.) Fermented by Bacillus subtilis (Bacillus subtilis를 이용하여 발효시킨 퉁퉁마디(Salicornia herbacea L.)의 품질 특성)

  • Park, In-Bae;Park, Jeong-Wook;Lee, Young-Jae;Shin, Gung-Won;Kim, Hae-Seop;Jo, Yeong-Cheol
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.7
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    • pp.902-908
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    • 2009
  • In this study, we investigated the quality of glasswort (Salicornia herbacea L.) fermented by Bacillus subtilis at $37^{\circ}C$ for 48 hours. We determined the changes in temperature, the contents of moisture, crude protein, crude fat, crude ash, carbohydrate, solid content, pH, Brix, salinity, free amino acid, Hunter's color value, electron donating ability (EDA) activities and angiotensin converting enzyme (ACE) inhibition. The contents of crude protein, crude fat, crude ash and carbohydrate after fermentation to mixing ratio of glasswort were $10.45{\sim}30.18%$, $11.69{\sim}19.26%$, $17.65{\sim}25.56%$ and $21.01{\sim}59.10%$ (dry basis), respectively. The solid content, pH, sugar and salinity of fermented glasswort were $39.56{\sim}52.25%$, $6.01{\sim}6.71$, $1.2{\sim}1.7$ Brix and $0.3{\sim}0.6%$, respectively. Total amino acid level of the fermented glasswort was $447.57{\sim}668.89\;mg$/100 g, and was the highest in glasswort mixed with rice bran at a ratio of 1 (w) : 1 (w). Moreover, aspartic acid, asparagine, glutamic acid, alanine, valine, $\beta$-aminoisobutyric acid, lysine and arginine were the main free amino acids. EDA activities and ACE inhibition after fermentation were $46.66{\pm}1.21{\sim}50.87{\pm}1.84%$ and $96.77{\pm}1.23{\sim}97.56{\pm}1.23%$, respectively.

Effect of Feeding Multiple Probiotics on Performance and Fecal Noxious Gas Emission in Broiler Chicks (혼합 생균제의 급여가 육계의 생산성 및 계분의 유해가스 발생에 미치는 영향)

  • Yoon C.;Na C. S.;Park J. H.;Han S. K.;Nam Y. M.;Kwon J. T.
    • Korean Journal of Poultry Science
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    • v.31 no.4
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    • pp.229-235
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    • 2004
  • A study was conducted to examine the effect of dietary supplementation of multiple probiotics (EM) on growth performance, blood cholesterol, intestinal micro flora, and fecal gas emission in broiler chicks. A total of 450 one day old male broiler chicks (Ross $\times$ Ross) were divided into six treatments with five replications in each treatment for five weeks. Treatments were factorially designed with two levels of diet containing probiotics (DW; 0, $0.2\%$) and three levels of drinking water containing probiotics (DW; 0, 0.01, $0.1\%$). Basal diets contained $21.5\%$ CP and 3,100 kcal/kg ME for starting and $19\%$ CP and 3,100 kcal/kg ME for finishing period. Weight gain, feed intake, and feed conversions of birds fed with probiotics were not significantly different between Ds. Total cholesterol and triglyceride levels were significantly lower (P<0.05) in birds fed with DW $0.01\%$ or $0.1\%$ compared with no probiotics group, but there was no significant difference between D treatments. The number of E. coli, Salmonella and Lactobacillus in the ileum and cecum of the birds fed multiple probiotics were not significantly different from those of no probiotic groups. There were no significant differences in the $CO_2$ gas emissions of fecal between birds fed with Ds or among birds fed with DW. However, $NH_3$ gas emissions of DW $0.1\%$ were significantly lower (P<0.05) than DW $0\%$. In the results of this study, supplementation of probiotics tended to decrease the serum cholesterol and triglyceride compared to those of control groups and reduction of fecal $NH_3$ gas emission.