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Disease Progression from Chronic Hepatitis C to Cirrhosis and Hepatocellular Carcinoma is Associated with Increasing DNA Promoter Methylation

  • Zekri, Abd El-Rahman Nabawy;Nassar, Auhood Abdel-Monem;El-Rouby, Mahmoud Nour El-Din;Shousha, Hend Ibrahim;Barakat, Ahmed Barakat;El-Desouky, Eman Desouky;Zayed, Naglaa Ali;Ahmed, Ola Sayed;Youssef, Amira Salah El-Din;Kaseb, Ahmed Omar;El-Aziz, Ashraf Omar Abd;Bahnassy, Abeer Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6721-6726
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    • 2013
  • Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

Use of Respiratory Motion Reduction Device (RRD) in Treatment of Hepatoma (간암의 방사선치료 시 호흡운동 감소장치(respiratory motion reduction device, RRD)의 유용성에 관한 연구)

  • Lee Suk;Seong Jinsil;Kim Yong Bae;Cho Kwang Hwan;Kim Joo Ho;Jang Sae Kyung;Kwon Soo Il;Chu Sung Sil;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.19 no.4
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    • pp.319-326
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    • 2001
  • Purpose : Planning target volume (PTV) for tumors in abdomen or thorax includes enough margin for breathing-related movement of tumor volumes during treatment. Depending on the location of the tumor, the magnitude of PTV margin extends from 10 mm to 30 mm, which increases substantial volume of the irradiated normal tissue hence, resulting in increase of normal tissue complication probability (NTCP). We developed a simple and handy method which can reduce PTV margins in patients with liver tumors, respiratory motion reduction device (RRD). Materials and methods : For 10 liver cancer patients, the data of internal organ motion were obtained by examining the diaphragm motion under fluoroscope. It was tested for both supine and prone position. A RRD was made using MeV-Green and Styrofoam panels and then applied to the patients. By analyzing the diaphragm movement from patients with RRD, the magnitude of PTV margin was determined and dose volume histogram (DVH) was computed using AcQ-Plan, a treatment planning software. Dose to normal tissue between patients with RRD and without RRD was analyzed by comparing the fraction of the normal liver receiving to $50\%$ of the isocenter dose. DVH and NTCP for normal liver and adjacent organs were also evaluated. Results : When patients breathed freely, average movement of diaphragm was $12{\pm}1.9\;mm$ in prone position in contrast to $16{\pm}1.9\;mm$ in supine position. In prone position, difference in diaphragm movement with and without RRD was $3{\pm}0.9\;mm$ and 12 mm, respectively, showing that PTV margins could be reduced to as much as 9 mm. With RRD, volume of the irradiated normal liver reduced up to $22.7\%$ in DVH analysis. Conclusion : Internal organ motion due to breathing can be reduced using RRD, which is simple and easy to use in clinical setting. It can reduce the organ motion-related PTV margin, thereby decrease volume of the irradiated normal tissue.

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Antioxidant Activities of Amaranth (Amaranthus spp. L.) Flower Extracts (아마란스 꽃 추출물의 항산화에 관한 연구)

  • Jo, Hyeon-Ju;Kim, Jeong Won;Yoon, Jin-A;Kim, Kyoung Im;Chung, Kang-Hyun;Song, Byeong Chun;An, Jeung Hee
    • The Korean Journal of Food And Nutrition
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    • v.27 no.2
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    • pp.175-182
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    • 2014
  • This study investigates the free radical-scavenging activities of Amaranth (Amaranthus spp. L.) red and purple flower extracts. The methanol and hot water extracts of flower are being evaluated for its total polyphenol and flavonoid contents, scavenging activities by the DPPH and ABTS analysis, SOD-like activity, and inhibition activities of superoxide radical on the HL-60 cells and nitric oxide of the RAW 264.7 cells. The PFM (purple flower extracted with MeOH) showed the highest total phenolic and flavonoid content, 606.95 mg GAE/100 g and 254.69 mg CE/100 g, respectively. Amongst the scavenging activities of the DPPH radicals, PFM($RC_{50}=155.06{\mu}g/m{\ell}$) is the highest of all the samples. The ABTS radical-scavenging activity is also highest for PFM (53.16%) at the $250{\mu}g/m{\ell}$ concentration. But, the SOD-like activity of the PFW (purple flower extracted with hot water) increases more than 3 folds of the PFM. In the leukemia HL-60 cell, the PFM shows strongly inhibited superoxide radical generations at a concentration of $200{\mu}g/m{\ell}$ at 72.34%, which increases with 1.79 folds more than the RFW (red flower extracted with hot water). The inhibition activity of nitric oxide in Raw 264.7 cells is the highest for PMF (46.90%) at a $250{\mu}g/m{\ell}$ concentration. In conclusion, PMF show the highest flavonoid contents and the most powerful free radical-scavenging activity. Our results suggest that the increase of antioxidant activities depend on flavonoid contents. Thus, Amaranth flower can be useful for natural antioxidant compounds.

Comparison of Inhalation Scan and Perfusion Scan for the Prediction of Postoperative Pulmonary Function (수술후 폐기능 변화의 예측에 대한 연무 흡입스캔과 관류스캔의 비교)

  • Cheon, Young-Kug;Kwak, Young-Im;Yun, Jong-Gil;Zo, Jae-Ill;Shim, Young-Mog;Lim, Sang-Moo;Hong, Sung-Woon;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.2
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    • pp.111-119
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    • 1994
  • Background: Because of the common etiologic factor, such as smoking, lung cancer and chronic obstructive pulmonary disease are often present in the same patient. The preoperative prediction of remaining pulmonary function after the resectional surgery is very important to prevent serious complication and postoperative respiratory failure. $^{99m}Tc$-MAA perfusion scan has been used for the prediction of postoperative pulmonary function, but it may be inaccurate in case of large V/Q mismatching. We compared $^{99m}Tc$-DTPA radioaerosol inhalation scan with $^{99m}Tc$-MAA perfusion scan in predicting postoperative lung function. Method: Preoperative inhalation scan and/or perfusion scan were performed and pulmonary function test were performed preoperatively and 2 month after operation. We predicted the postoperative pulmonary functions using the following equations. Postpneurnonectomy $FEV_1$=Preop $FEV_1x%$ of total function of lung to remain Postlobectomy $FEV_1$=Preop $FEV_1{\times}$(% of total 1-function of affected lung${\times}$$\frac{Number\;of\;segments\;to\;be\;resected}{Number\;of\;segments\;of\;affected\;lung})$ Results: 1) The inhalation scan showed good correlations between measured and predicted $FEV_1$, FVC and $FEF_{25-75%}$. (correlation coefficiency; 0.94, 0.91, 0.87 respectively). 2) The perfusion scan also showed good correlations between measured and predicted $FEV_1$, FVC and $FEF_{25-75%}$. (correlation coefficiency; 0.86, 0.72, 0.87 respectively). 3) Among three parameters, $FEV_1$ showed the best correlations in the prediction by lung scans. 4) Comparison between inhalation scan and perfusion scan in predicting pulmonary function did not show any significant differneces except FVC. Conclusion: The inhalation scan and perfusion scan are very useful in the prediction of postoperative lung function and don't make a difference in the prediction of pulmonary function a1though the former showed a better correlation in FVC.

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The Usefulness of Tc-99m MIBI SPECT in the Localization and the Assessment of Radiotherapy in Non-Small Cell Lung Cancer (비소세포 폐암의 국소화 및 방사선치료 판정에 있어 Tc-99m MIBI SPECT의 유용성)

  • Bom, Hee-Seung;Song, Ho-Chun;Kim, Ji-Yeul;Nam, Taek-Keum;Ahn, Sung-Ja;Chung, Woong-Ki;Nah, Byung-Sik
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.2
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    • pp.186-191
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    • 1994
  • Tc-99m MIBI, a lipophilic cation, was reported as a useful agent for localization of lung cancer. The effect of radiation therapy on the uptake of Tc-99m MIBI in lung cancer, however, was not well evaluated. The aim of the present study was to elucidate the usefulness of Tc-99m MIBI SPECT in the localization and the assessment of radiotherapy in non-small cell lung cancer. Twenty patients(19 males and 1 female, mean age 59, 16 squamous cell ca and 4 adenoca) were studied with Tc-99m MIBI SPECT before radiation therapy. Eleven patients(10 males and 1 female, mean age 59, 8 squamous cell ca and 3 adenoca) were repeated the study 1 month after the completion of radiation therapy(mean dose 6453cGy). All patients showed positive uptakes of Tc-99m MIBI in their tumors. One patient showed a hot uptake in atelectatic area. There was no difference of Tc-99m MIBI uptakes between squamous cell ca and adenoca either on planar or tomographic images. Tc-99m MIBI uptake ratios of squamous cell ca and adenoca were $1.50{\pm}0.16$ and $1.45{\pm}0.15$ on planar images, and $2.73{\pm}0.46$ and $2.54{\pm}0.37$ on tomographic images, respectively. The concordance between radiological change(chest x-ray and CT) and change of Tc-99m MIBI uptakes was 9/11 (81.8% ). In conclusion, Tc-99m MIBI SPECT was useful in the localization of tumor and the assessment of radiation therapy in non-small cell lung cancer.

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A Study on the Screening of the Novel Genes Associated with Lysosomal Trafficking and Mutation Detection in Fibroblasts of the Patients with Mucolipidosis type II and III (리소좀 교통 이상을 초래하는 뮤코지방증 2형과 3형 환자의 섬유아세포를 이용한 신규 유전자 탐색 및 돌연변이에 대한 연구)

  • Song, Seng Mi;Chang, Soo Hee;Paik, Kyung Hoon;Jin, Dong-Kyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.5 no.1
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    • pp.65-75
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    • 2005
  • Purpose: To understand genetic differences and similarities between mucolipidosis and control. Methods: Using the fibroblast of the mucolipidosis II and control, forward and reverse subtracted libraries were constructed. Among these clones, we investigated mutations in the GNPTA (MGC4170) gene, which codes for the ${\alpha}/{\beta}$ subunits of phosphotransferase, and in the GNPTAG gene, which codes for the ${\gamma}$ subunits in 5 Korean patients with mucolipidosis type II or IIIA. Result: Several differentially expressed cDNAs were cloned and their sequences were determined. Mutation analysis of the interested gene, GNPTA was performed and we identified 7 mutations in the GNPTA gene, but none in the GNPTAG gene. The mutations in type II patients included p.Q104X(c.310C>T), p.R1189X(c.3565C>T), p.S1058X(c.3173C>G), p.W894X(c.2681G>A) and p.H1158fsX15(c.3474_3475delTA), all of which are non-sense or frame shift mutations. However, a splicing site mutation, IVS13+1G>A (c.2715+1G>A) was detected along with a non-sense or a frame shift mutation (p.R1189X or p.E858fsX3(c.2574_2575delGA)) in two mucolipidosis type IIIA patients. Conclusion: This report shows that mutations in the GNPTA gene coding for the ${\alpha}{\beta}$subunits of phosphotransferase, and not mutations in the GNPTAG gene, account for most of mutations found in Korean patients with mucolipidosis type II or IIIA.

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Measurement of thermal expansion characteristic of root canal filling materials : Gutta-percha and Resilon (수 종의 근관충전재의 열팽창 특성 측정 : Gutta-percha와 Resilon)

  • Jeon, Kyung-A;Lee, In-Bog;Bae, Kwang-Shik;Lee, Woo-Cheol;Baek, Seung-Ho
    • Restorative Dentistry and Endodontics
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    • v.31 no.5
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    • pp.344-351
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    • 2006
  • The purpose of this study was to evaluate the thermal expansion characteristics of injectable ther-moplasticized gutta-perchas and a Resilon. The materials investigated are Obtura gutta-percha, Diadent gutta-percha, E&Q Gutta-percha Bar and Epiphany (Resilon). The temperature at the heating chamber orifice of an Obtura II syringe and the extruded gutta-percha from the tip of both 23- and 20-gauge needle was determined using a Digital thermometer. A cylindrical ceramic mold was fabricated for thermal expansion test, which was 27 mm long, with an internal bore diameter of 3 mm and an outer diameter of 10 mm. The mold was filled with each experimental material and barrel ends were closed with two ceramic plunger. The samples in ceramic molds were heated in a dilatometer over the temperature range from $25^{\circ}C$ to $75^{\circ}C$. From the change of specimen length as a function of temperature, the coefficients of thermal expansion were deter-mined. There was no statistical difference between four materials in the thermal expansion in the range from $35^{\circ}C$ to $55^{\circ}C$ (p > 0.05). However, Obtura Gutta-percha showed smaller thermal expansion than Diadent and Metadent ones from $35^{\circ}C$ to $75^{\circ}C$ (p < 0.05). The thermal expansion of Epiphany was similar to those of the other gutta-percha groups.

The Effect of the Pain on the TMJ and Masticatory Muscles to Tension-type Headache (측두하악관절과 저작근의 통증이 긴장성 두통에 미치는 영향)

  • Kim, Jin-Suk;Auh, Q-Schick;Lee, Jin-Yong;Hong, Jung-Pyo;Chun, Yang-Hyun
    • Journal of Oral Medicine and Pain
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    • v.31 no.4
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    • pp.327-335
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    • 2006
  • Generally, Tension-Type Headache(TTH) patients exhibit muscle pain, but can also have TMJ pain, which includes mouth opening limitation or joint sounds. The purpose of our study is to observe the clinical pain characteristics between TTH patients with muscle pain and TMJ pain. One hundred sixty-seven patients were diagnosed with TTH according to the questionnaires based on the International Headache Society's proposal on the diagnostic criteria of TTH. The patients were classified into three group; arthralgia group (18 patients), myalgia group (50 patients) and arthromyalgia group (99 patients). TTH patients with pericranial muscle pain were classified in the myalgia group. TTH patients with temporal region pain were classified in the arthralgia group. TTH patients with both types of pain were classified in the arthromyalgia group. The parameters in the diagnostic criteria such as quality, intensity, laterality of pain, and aggravation due to physical activities were compared among the three groups. 1. There were no significant differences in the quality of pain among the three groups. 2. There were no significant differences in the intensity of pain among the three groups. 3. There were no significant differences in the laterality of pain among the three groups. 4. A higher percentage of patients in the arthromyalgia group experienced headaches that were aggravated due to physical activity (p=0.03) compared to the other groups. The results of this study show that TTH patients with both arthralgia (TMJ pain) and myalgia (pericranial muscle pain) are more aggravated by physical activity than TTH patients with either one.

Semi-quantitative Procalcitonin Assay in Critically ill Patients with Respiratory infections (중환자 호흡 감염에서 반정량적 Procalcitonin 분석)

  • Kim, Ji-Youn;Kim, Cheol-Hong;Park, Sunghoon;Lee, Chang-Youl;Hwang, Yong Il;Choi, Jeong-Hee;Shin, Taerim;Park, Yong-Bum;Jang, Seung-Hun;Lee, Jae Young;Park, Sang Myeon;Kim, Dong-Gyu;Lee, Myung-Goo;Hyun, In-Gyu;Jung, Ki-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.3
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    • pp.205-211
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    • 2009
  • Background: Serum procalcitonin level has been considered prognostic during sepsis and septic shock. We investigated the significance of procalcitonin in critically ill patients with respiratory infections. Methods: The patients who had radiographically diagnosed diffuse lung infiltrations were enrolled on a prospective basis. Bronchoalveolar lavage (BAL) fluid for the purpose of quantitative cultures (${\geq}10^4$ cfu/mL) was obtained from all patients. Serum procalcitonin levels determined by PCT-Q kit were measured on BAL day and classified as follows; <0.5 ng/mL, 0.5~2.0 ng/mL, 2.0~10.0 ng/mL and >10.0 ng/mL. We analyzed the patient's characteristics according to outcome; favorable or unfavorable, defined as death. Results: Patients from the following categories were included: medical 17 (47.2%), surgical 9 (25%), and burned 10 (27.8%). APACHE II scores on admission to intensive care unit were 11.5${\pm}$6.89 and 11 (30.6%) had unfavorable outcomes. A procalcitonin level ${\geq}$0.5 ng/mL was in 17 (47.2%) of all. On univariate analysis, the frequencies of burn injury, mechanical ventilation, multiple organ failure, and a procalcitonin level ${\geq}$0.5 ng/mL were more often increased in patients with unfavorable outcomes than in those with favorable outcomes (p<.05). Also, a higher procalcitonin range and ventilator-associated pneumonia (VAP) were more closely associated with an unfavorable outcome (p<.05). However in multivariate analysis, a strong predictor of unfavorable outcome was burn injury (p<.05). A procalcitonin level ${\geq}$0.5 ng/mL was more sensitive in predicting VAP than unfavorable outcome. Conclusion: A higher procalcitonin level seems to be associated with VAP, but further study is required to know that procalcitonin would be a prognostic marker in critically ill patients with respiratory infections.

The Effects of Environment-Friendly Diets on the Growth Performance, Nutrient Digestibility, Fecal Excretion, Nitrogen Excretion and Emission Gases in Manure for Growing Pigs (환경친화적인 사료의 급여가 육성돈의 성장 능력, 영양소 소화율, 분 배설량, 분뇨내 질소배설량 및 악취 가스에 미치는 영향)

  • Yoo, J.S.;Cho, J.H.;Chen, Y.G.;Kim, H.J.;Wang, Q.;Hyun, Y.;Ko, T.G.;Park, C.S.;Kim, I.H.
    • Journal of Animal Science and Technology
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    • v.49 no.4
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    • pp.491-500
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    • 2007
  • Two experiments were used to determine the effects of environment-friendly diets on growth performance, fecal excretion, nitrogen excretion and emission gases in manure for growing pigs. In experiment 1, ninety six crossed pigs(Landrace×Yorkshire×Duroc) were allocated into four treatments. Treatments were AME(adequate ME diet, 3,265 kcal/kg), LME(lower ME diet, 3,100 kcal/kg), LME 0.05(lower ME diet+α- galactosidase & β-mannanase 0.05%) and LME 0.10(lower ME diet+α-galactosidase & β-mannanase 0.10%). Pigs fed AME diet had lower ADFI(Average Daily Feed Intake) than pigs fed other diets(p<0.05). DM(Dry Matter) digestibility in pigs fed AME and LME 0.10 diets had greater than pigs fed LME diet(p<0.05). Energy digestibility is higher in pigs fed AME and LME 0.10 diets than other treatments(p<0.05). In experiment 2, twenty four crossbred pigs(33.71 kg average BW) were used in a 14-d metabolism experiment. The pigs were housed in individual cages equipped with plastic bed flooring. Treatments were CP(Crude protein) 18% without Bacillus sp., CP 18% diet+Bacillus sp. 0.05%, CP 14% without Bacillus sp. and CP 14% diet+Bacillus sp. 0.05%. Nitrogen intake was higher for CP 18% diets than CP 14% diets(p<0.05). DM, N(Nitrogen) and energy digestibility were affected by probiotics(p<0.05). With the high CP in diets, Energy and N digestibility, urine N percent, urine N excretion and total N excretion were increased significantly compared to low CP in diets(p<0.05). Among the treatments, DM and N digestibilities, feces N excretion, N absorption were decreased significantly(p<0.05), however, feces excretion, feces N, urine N percent, urine N excretion and total N excretion were increased significantly(p<0.05) when pigs fed without probiotics diets compare to pigs fed with probiotics diets. DM and N digestibility, feces excretion, feces N excretion, urine N percent, urine N excretion, total N excretion, N absorption and N adsorption ratio were CP×probiotic interactions in p<0.05. Ammonia(p<0.01) and H2S(p<0.05) in manure were lower in CP 14% diets than CP 18% diets. Also, ammonia and H2S in manure were CP×probiotic interactions in p<0.05. In conclusion, low energy and reduction of CP dietary added enzyme and probiotics improved nutrient digestibility and reduced odors emission in manure for growing pigs.