AIM： To evaluate the efficacy of continuous regional arterial infusion therapy （CRAI） with gabexate mesilate and antibiotics for severe acute pancreatitis （SAP）. METHODS： We conducted a prospective study on pati...AIM： To evaluate the efficacy of continuous regional arterial infusion therapy （CRAI） with gabexate mesilate and antibiotics for severe acute pancreatitis （SAP）. METHODS： We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulfilled clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy （non-CRAI）. CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate （2400 mg/d） was continuously administered for 3 to 5 d. The clinical outcome including serum inflammation-related parameters were examined. RESULTS- The duration of abdominal pain in the CRAI group was 1.9 =1：0.26 d, whereas that in the non-CRAI group was 4.3 ±0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared significantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization significantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION： The present results suggest that CRAI using gabexate mesilate was effective against SAP.展开更多
AIM: To investigate the effi cacy and safety of rabepra-zole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. METHODS: Subjects comprised patients undergoi...AIM: To investigate the effi cacy and safety of rabepra-zole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. METHODS: Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal en-doscopy revealed an ulcerous lesion (open ulcer) with diameter ≥ 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classifi cation. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events.RESULTS: Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64).CONCLUSION: The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID ad-ministration was confi rmed.展开更多
AIM:To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B(CHB).METHODS:We retrospectively analyzed the clinical data of CHB patients treated with ...AIM:To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B(CHB).METHODS:We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d.The biochemical response,as assessed by serum alanine aminotransferase(ALT) activity,virologic response,as assessed by serum hepatitis B virus DNA(HBV DNA) titer,serologic response,as assessed by hepatitis B e antigen(HBeAg) status,and virologic breakthrough with genotypic mutations were assessed.RESULTS:Two-hundred and fifty-four patients [clevudine(n = 118) vs entecavir(n = 136)] were enrolled.In clevudine-treated patients,the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96(80.9% and 91.2% in the entecavir group,respectively),the mean titer changes in serum HBV DNA were-6.03 and-6.55 log 10 copies/mL(-6.35 and-6.86 log 10 copies/mL,respectively,in the entecavir group),and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1%(74.4% and 83.8%,respectively,in the entecavir group).These results were similar to those of entecavir-treated patients.The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine,which was similar to patients treated with entecavir(22.8% and 27.7%,respectively).The virologic breakthrough in the clevudine group occurred in 9(7.6%) patients at weeks 48 and 15(12.7%) patients at week 96,which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M.There was no virologic breakthrough in the entecavir group.CONCLUSION:In antiviral-naive CHB patients,longterm treatment outcomes of clevudine were not inferior to those of entecavir,except for virologic breakthrough.展开更多
Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective...Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective and better tolerated therapies are urgently needed. HCV is a positive, single-stranded RNA virus with a 9.6 kb genome that encodes ten viral proteins. Among them, the NS3 protease and the NS5B polymerase are essential for viral replication and have been the main focus of drug discovery efforts. Aided by structure-based drug design, potent and specific inhibitors of NS3 and NS5B have been identified, some of which are in late stage clinical trials and may significantly improve current HCV treatment. Inhibitors of other viral targets such as NS5A are also being pursued. However, HCV is an RNA virus characterized by high replication and mutation rates and consequently, resistance emerges quickly in patients treated with specific antivirals as monotherapy. A complementary approach is to target host factors such as cyclophilins that are also essential for viral replication and may present a higher genetic barrier to resistance. Combinations of these inhibitors of different mechanism are likely to become the essential components of future HCV therapies in order to maximize antiviral efficacy and prevent the emergence of resistance.展开更多
The purpose of this work was to explore the feasibility of ethosomes for improving the anti-arthritic efficacy of topically administered tetrandrine, a bisbenzylisoquinoline alkaloid. Ethosomes were prepared by using ...The purpose of this work was to explore the feasibility of ethosomes for improving the anti-arthritic efficacy of topically administered tetrandrine, a bisbenzylisoquinoline alkaloid. Ethosomes were prepared by using the transmembrane pH-gradient loading method and characterized by mean diameter, morphology and entrapment efficiency. The prepared tetrandrine-loaded ethosomes exhibited spherical shape with about 78 nm of average diameter and entrapment efficiency of （52.87±3.81）%, whereas the liposomes had bigger size （99 nm） and higher entrapment efficiency （98.80±0.01）%. In addition, ethosomes exhibited favorable and enhanced penetration behavior as compared with liposomes. More importantly, tetrandrine-loaded ethosomes had a significantly better anti-adjuvant arthritis efficacy in rats compared to liposomes formulation, but no significant difference in the anti-arthritic efficacy between tetrandrine-loaded ethosomes and commercial dexamethasone ointment was observed. These results suggest that ethosomes would be a promising nanocarrier for topical delivery of tetrandrine across skin.展开更多
基金Supported by Grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, No. 20590808The Research Committee of Intractable Diseases of the Pancreas, provided by the Ministry of Health, Labour, and Welfare Japan, No. 50253448
文摘AIM： To evaluate the efficacy of continuous regional arterial infusion therapy （CRAI） with gabexate mesilate and antibiotics for severe acute pancreatitis （SAP）. METHODS： We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulfilled clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy （non-CRAI）. CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate （2400 mg/d） was continuously administered for 3 to 5 d. The clinical outcome including serum inflammation-related parameters were examined. RESULTS- The duration of abdominal pain in the CRAI group was 1.9 =1：0.26 d, whereas that in the non-CRAI group was 4.3 ±0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared significantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization significantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION： The present results suggest that CRAI using gabexate mesilate was effective against SAP.
文摘AIM: To investigate the effi cacy and safety of rabepra-zole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. METHODS: Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal en-doscopy revealed an ulcerous lesion (open ulcer) with diameter ≥ 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classifi cation. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events.RESULTS: Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64).CONCLUSION: The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID ad-ministration was confi rmed.
文摘AIM:To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B(CHB).METHODS:We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d.The biochemical response,as assessed by serum alanine aminotransferase(ALT) activity,virologic response,as assessed by serum hepatitis B virus DNA(HBV DNA) titer,serologic response,as assessed by hepatitis B e antigen(HBeAg) status,and virologic breakthrough with genotypic mutations were assessed.RESULTS:Two-hundred and fifty-four patients [clevudine(n = 118) vs entecavir(n = 136)] were enrolled.In clevudine-treated patients,the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96(80.9% and 91.2% in the entecavir group,respectively),the mean titer changes in serum HBV DNA were-6.03 and-6.55 log 10 copies/mL(-6.35 and-6.86 log 10 copies/mL,respectively,in the entecavir group),and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1%(74.4% and 83.8%,respectively,in the entecavir group).These results were similar to those of entecavir-treated patients.The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine,which was similar to patients treated with entecavir(22.8% and 27.7%,respectively).The virologic breakthrough in the clevudine group occurred in 9(7.6%) patients at weeks 48 and 15(12.7%) patients at week 96,which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M.There was no virologic breakthrough in the entecavir group.CONCLUSION:In antiviral-naive CHB patients,longterm treatment outcomes of clevudine were not inferior to those of entecavir,except for virologic breakthrough.
文摘Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective and better tolerated therapies are urgently needed. HCV is a positive, single-stranded RNA virus with a 9.6 kb genome that encodes ten viral proteins. Among them, the NS3 protease and the NS5B polymerase are essential for viral replication and have been the main focus of drug discovery efforts. Aided by structure-based drug design, potent and specific inhibitors of NS3 and NS5B have been identified, some of which are in late stage clinical trials and may significantly improve current HCV treatment. Inhibitors of other viral targets such as NS5A are also being pursued. However, HCV is an RNA virus characterized by high replication and mutation rates and consequently, resistance emerges quickly in patients treated with specific antivirals as monotherapy. A complementary approach is to target host factors such as cyclophilins that are also essential for viral replication and may present a higher genetic barrier to resistance. Combinations of these inhibitors of different mechanism are likely to become the essential components of future HCV therapies in order to maximize antiviral efficacy and prevent the emergence of resistance.
基金National Natural Science Foundation of China (Grant No. 81172990)National Development of Significant New Drugs of China (New Preparation and New Technology,Grant No. 2009zx09310-001)+1 种基金National Key Science Research Program of China (973 Program, Grant No. 2009CB930300)Innovation Team of Ministry of Education (Grant No. BMU20110263)
文摘The purpose of this work was to explore the feasibility of ethosomes for improving the anti-arthritic efficacy of topically administered tetrandrine, a bisbenzylisoquinoline alkaloid. Ethosomes were prepared by using the transmembrane pH-gradient loading method and characterized by mean diameter, morphology and entrapment efficiency. The prepared tetrandrine-loaded ethosomes exhibited spherical shape with about 78 nm of average diameter and entrapment efficiency of （52.87±3.81）%, whereas the liposomes had bigger size （99 nm） and higher entrapment efficiency （98.80±0.01）%. In addition, ethosomes exhibited favorable and enhanced penetration behavior as compared with liposomes. More importantly, tetrandrine-loaded ethosomes had a significantly better anti-adjuvant arthritis efficacy in rats compared to liposomes formulation, but no significant difference in the anti-arthritic efficacy between tetrandrine-loaded ethosomes and commercial dexamethasone ointment was observed. These results suggest that ethosomes would be a promising nanocarrier for topical delivery of tetrandrine across skin.
