Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n ؍ 182) or placebo (n ؍ 61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log 10 copies/mL in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log 10 reduction at week 34 and 2.02 log 10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P < 0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. Conclusion: A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B. (
A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission.
To elucidate the pathogenesis of hepatocellular carcinoma (HCC) and develop useful prognosis predictors, it is necessary to identify biologically relevant genomic alterations in HCC. In our study, we defined recurrently altered regions (RARs) common to many cases of HCCs, which may contain tumor-related genes, using whole-genome array-CGH and explored their associations with the clinicopathologic features. Gene set enrichment analysis was performed to investigate functional implication of RARs. On an average, 23.1% of the total probes were altered per case. Mean numbers of altered probes are significantly higher in high-grade, bigger and microvascular invasion (MVI) positive tumors. In total, 32 RARs (14 gains and 18 losses) were defined and 4 most frequent RARs are gains in 1q21.1-q32.1 (64.5%), 1q32.1-q44 (59.2%), 8q11.21-q24.3 (48.7%) and a loss in 17p13.3-p12 (51.3%). Through focusing on RARs, we identified genes and functional pathways likely to be involved in hepatocarcinogenesis. Among genes in the recurrently gained regions on 1q, expression of KIF14 and TPM3 was significantly increased, suggesting their oncogenic potential in HCC. Some RARs showed the significant associations with the clinical features. Especially, the recurrent loss in 9p24.2-p21.1 and gain in 8q11.21-q24.3 are associated with the high tumor grade and MVI, respectively. Functional analysis showed that cytokine receptor binding and defense response to virus pathways are significantly enriched in high grade-related RARs. Taken together, our results and the strategy of analysis will help to elucidate pathogenesis of HCC and to develop biomarkers for predicting behaviors of HCC.
To elucidate the efficacy of different soy protein sources on piglet's performance, a total of 280 weaned piglets (Duroc×Yorkshire×Landrace, 23±3 d of age, 5.86±0.45 kg initial BW) were allotted to 5 treatment diets comprising soybean meal (SBM), soy protein concentrate (SPC), Hamlet protein (HP300), fungal (Aspergillus oryzae) fermented soy protein (FSP-A), and fungal plus bacterial (A. oryzae+Bacillus subtilis) fermented soy protein (FSP-B), respectively. Experimental diets for feeding trial were formulated to contain each soy protein sources at 8% level to corn-whey powder basal diet. There were 14 pigs per pen and 4 pens per treatment. Experimental diets were fed from 0 to 14 d after weaning and then a common commercial diet was fed from 15 to 35 d. Also for ileal digestibility studies, 18 pigs were assigned to 6 dietary treatments as N-free, SBM, SPC, HP300, FSP-A and FSP-B with Tcanulation at distal ileum for 6 days. At 14 th d of experimental feeding, the ADG was significantly higher (p<0.05) in SPC fed diet as compared with others. Similar trend was noticed during the 15-35 d and overall study (0-35 d). All the processed soy protein sources tested in this experiment improved (p<0.05) growth than SBM during overall study. The nutrient digestibility of GE, DM, CP and Ca showed lower (p<0.05) values in SBM and FSP-A fed groups than SPC and FSP-B treatments. The apparent ileal digestibility of TEAA, non-TEAA and TAA showed lower (p<0.05) in SBM treatments compared with other soy protein sources. The true ileal digestibility of TEAA, non-TEAA and TAA were lower (p<0.05) in SBM fed group than SPC and HP300 treatments, and lower than FSP treatments though they didn't achieve significant difference (p>0.05). Villous height and crypt depth was not affected by dietary treatments. In conclusion, the growth and digestibility of nutrients in weaned pigs fed SPC was superior to others. Also FSP-A and FSP-B showed improved performance than those fed SBM.
Four experiments were conducted to determine the effects of dietary supplementation of corn distillers dried grain with solubles (DDGS) diets with mannanase on performance, apparent total tract digestibility (ATTD) of energy and nutrients, blood metabolites, and carcass characteristics of grower-finisher pigs. In Exp. 1, 96 grower pigs (initial BW, 57.6 kg), 6 pigs per pen and 4 pens per treatment, were fed corn-soybean meal-based diets containing 10% DDGS and 0, 200, 400, or 600 units (U) of mannanase/kg. The ADG and blood glucose increased (linear, P < 0.05) with increasing concentrations of dietary mannanase. Pigs fed diets containing increasing levels of mannanase had improved ATTD of DM and CP (quadratic, P < 0.05). In Exp. 2, 64 finisher pigs (initial BW, 92.7 kg) were allotted to 4 treatment groups with 4 pigs per pen and 4 pens per treatment. Pigs were fed corn-soybean meal-based diets containing 15% DDGS and 0, 200, 400, or 600 U of mannanase/kg. Linear increases (P < 0.05) in ADG, blood glucose, and ATTD of DM, GE, and CP were observed with increasing levels of dietary mannanase supplementation. In Exp. 3, 208 grower pigs (initial BW, 60.5 kg) were allotted to 4 treatment groups with 13 pigs per pen and 4 pens per treatment. Pigs were fed diets containing 0 or 10% DDGS and 0 or 400 U of mannanase/kg in a 2 x 2 factorial arrangement. An increase (P < 0.05) in ADG and blood glucose for pigs fed diets containing mannanase was observed. The ATTD of DM and CP (P < 0.05) was decreased with the inclusion of DDGS, whereas pigs fed the mannanase-supplemented diets had an increased (P < 0.05) ATTD of CP. In Exp. 4, 208 finisher pigs (initial BW, 86.5 kg), with 13 pigs per pen and 4 pens per treatment, were fed diets containing 0 or 15% DDGS and 0 or 400 U of mannanase/kg in a 2 x 2 factorial arrangement. The ADG and blood glucose increased (P < 0.05) when mannanase was included in the diets. The ATTD of DM (P < 0.05), GE (P < 0.10), and CP (P < 0.05) increased by the supplementation with mannanase in the diets of finisher pigs. The carcass characteristics and meat quality were not affected by the DDGS or mannanase inclusion. These results indicated that including 10 and 15% DDGS in conventional swine grower and finisher diets had no detrimental effects on growth performance or carcass characteristics. In addition, supplementation with 400 U of mannanase/kg to diets containing 10 and 15% DDGS fed to grower and finisher pigs may improve growth performance and the ATTD of CP.
The present study was conducted to evaluate and compare the effects of various animal and plant protein sources on piglet's performance, digestibility of amino acids and gut morphology in weaned pigs until 28 days after weaning. The plant protein sources used were soybean meal (SBM), fermented soy protein (FSP), rice protein concentrate (RPC); and animal protein sources tested were, whey protein concentrate (WPC) and fishmeal (FM). Iso-proteinous (21%) diets were formulated and lysine (1.55%) content was similar in all the diets. The level of each protein source added was 6% by replacing SBM to the same extent from the control diet containing 15% SBM. The ADG was higher (p<0.05) in the groups fed animal proteins as compared with plant proteins at all the levels of measurement, except during 15-28 days. The highest ADG was noted in WPC and FM fed diets and lowest in SBM fed diet. The feed intake was higher in animal protein fed groups than plant proteins at all phases, but the feed:gain ratio was not affected by protein sources except during overall (0 to 14 day) measurement which was improved (p<0.05) in animal protein fed diets compared to plant protein sources. The digestibilities of gross energy, dry matter and crude protein were higher in animal protein fed groups than for plant protein fed sources. The apparent ileal digestibilities of essential amino acids like Leu, Thr, and Met were significantly (p<0.05) higher in animal proteins fed animals as compared with plant protein fed animals. But the apparent fecal digestibilities of essential amino acids like Arg and Ile were significantly higher (p<0.05) in plant protein diets than animal protein sources. The villous structure studied by scanning electron microscope were prominent, straight finger-like, although shortened and densely located in FM fed group as compared with others. The lactic acid bacteria and C. perfringens counts were higher in caecal contents of pigs fed plant proteins than the animal proteins. Overall, it could be concluded that animal protein sources in the present study showed better effects on growth performance, nutrient digestibility and gut morphology than plant protein sources.
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