BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alan...BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.展开更多
Metabolic rewiring underlies the effector functions of macrophages1-3,but the mechanisms involved remain incompletely defined.Here,using unbiased metabolomics and stable isotope-assisted tracing,we show that an inflam...Metabolic rewiring underlies the effector functions of macrophages1-3,but the mechanisms involved remain incompletely defined.Here,using unbiased metabolomics and stable isotope-assisted tracing,we show that an inflammatory aspartate argininosuccinate shunt is induced following lipopolysaccharide stimulation.The shunt,supported by increased argininosuccinate synthase(ASS1)expression,also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination.Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase(FH)further increases intracellular fumarate levels.展开更多
Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarat...Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.展开更多
To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, t...To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTSHistological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSIONDMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.展开更多
A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electroc...A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electrochemical properties are investigated exercising the cyclic voltammetry and square wave voltammetry (SWV). Enhanced peak current associated with bisoprolol fumarate oxidation at EPPGE is due to its better electron transfer property. Quantification of bisoprolol fumarate was carried out at pH 7.2 at both the pyrolytic graphite electrodes. Well-defined peak has been observed at ~ 792 and 954 mV at EPPGE and BPPGE respectively for bisoprolol fumarate oxidation. The detection limit is found to be 2.8 × 10–7 M and 7.3 × 10–7 M for EPPGE and BPPGE respectively. A comparison of common quantification parameters for bisoprolol at carbon nanotube modified glassy carbon electrode and bare BPPGE and EPPGE has been made and it is observed that carbon naotube modified glassy carbon exhibits sensitivity and detection limit close to that observed at bare basal plane pyrolytic graphite electrode. The method developed is applicable for determination of bisoprolol fumarate in pharmaceutical preparations and real samples.展开更多
Biallelic inactivation of fumarate hydratase (FH) causes type 2 papillary renal cell carcinoma (PRCC2), uterine fibroids, and cutaneous leimyomas, a condition known as hereditary leiomyomatosis and renal cell cancer (...Biallelic inactivation of fumarate hydratase (FH) causes type 2 papillary renal cell carcinoma (PRCC2), uterine fibroids, and cutaneous leimyomas, a condition known as hereditary leiomyomatosis and renal cell cancer (HLRCC). The most direct effect of FH inactivation is intracellular fumarate accumulation. A majority of studies on FH inactivation over the past decade have focused on the theory that intracellular fumarate stabilizes hypoxia-inducible factor 1α (HIF1A) through competitive inhibition of HIF prolyl hydroxylases. Recently, a competing theory that intracellular fumarate activates nuclear factor (erythroid-derived 2)-like 2 (NRF2) through post-translational modification of its negative regulator. Kelch-like ECH-associated protein 1 (KEAP1) has emerged from a computational modeling study and mouse model studies. This review dissects the origin of these two governing theories and highlights the presence of chromatin-structure-regulated targets of transcription factors, which we refer to as "cryptic targets" of transcription factors. One such cryptic target is heme oxygenase I (HMOX1), the expression of which is known to be modulated by the gene product of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1).展开更多
Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats wer...Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats were given the intraperitoneal injection of L-arginine for 5times(250 mg/100 kg,twice per time,each interval of 1 h) for building of CP model.Rats were divided into control group,CP group,DMF group and CP+DMF group.Rats in CP+DMF group were given the oral intragastric administration of DMF(25 mg/kg),while rats in control group and CP group were given the equal volume of normal saline.The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed(IPGTT,2 g/kg).The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets.Meanwhile,the histology of non-endocrine tissues and levels of myeloperoxidase(MPO) and malondialdchyde(MDA) were detected.Results:Compared with control group,the weight of rats in CP group was significantly reduced at week 2,4 and 6;the blood glucose significantly increased,AUC increased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration increased,levels of MDA and MPO increased,the islet equivalent and islet activity decreased at 0.30,60,120 and 180 min.Compared with CP group,the weight of rats in CP+DMF group significantly increased at week 2,4 and 6;the blood glucose significantly decreased.AUC decreased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration decreased,levels of MDA and MPO decreased,the islet equivalent and islet activity increased at 0,30.60,120 and 180 min.Conclusions:DMF treatment can improve CP induced by L-argininc and islet function in rats.展开更多
[ Objective] The study aimed to discuss the effects of ferrous fumarate on growth performance, blood biochemical parameters and content of trace element of Oncorhynchus mykiss. [ Method ] Juvenile rainbow trout with a...[ Objective] The study aimed to discuss the effects of ferrous fumarate on growth performance, blood biochemical parameters and content of trace element of Oncorhynchus mykiss. [ Method ] Juvenile rainbow trout with an initial weight of (89.2 ±0.2) g were fed with the basal fodder supplemented with different levels of ferrous fumarate (0, 20, 40, 80,160 and 480 mg/kg iron) for 60 d, and the six groups were named DO, D20, D40, D80, D160 and D480, wherein DO was as the control group, actually containing 62.60, 79.50, 99.60, 139.30, 215.20 and 538.40 mg/kg iron respectively. [ Result] The growth performance of juvenile rainbow trout was not affected by different dietary iron levels obviously ( P 〉 0.05). With the increase of dietary iron level, hemoglobin (Hb) content and number of red blood cells(RBC) rose firstly and then leveled off. No significance was found in hematocrit (Hct) among the six groups (P 〉0.05). Iron content in the whole body, vertebrae and muscle increased significantly with the improvement of dietary iron level( P 〈0.05), and iron concentration in the liver increased firstly and then leveled off in groups from D40 to D480. No significant difference in zinc content of the whole body was found among the six groups ( P〉0.05), while zinc content in the vertebrae and muscle in control group was significantly higher than that of other groups ( P〈0.05), and zinc concentration in the liver in groups DO and 1320 was significantly higher than that of other groups ( P 〈0.05). Copper content in the whole body increased significantly with the increase of dietary iron level (P 〈 0.05 ), while no significant difference was observed in the vertebrae ( P 〉0.05), and copper concentration in the muscle in control group was significantly lower than that of other groups ( P 〈0.05). Serum lysozyme (LZM) activity of group DO was significantly lower than that of other groups ( P 〈 0.05) except for group D480 ( P 〉 0.05). Catalase (CAT) activity of serum enhanced significantly ( P 〈 0.05) from DO to EH0 and then decreased obviously (P 〈0.05). [ Conclusion] Based on hemoglobin and iron content in the liver, the broken-line model analysis showed that the dietary iron level provided by ferrous fumarate for juvenile rainbow trout was estimated to be 99.8 and 100.4 mg/kg respectively in the experiment.展开更多
Symmetric, diesters of cis- or trans- bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylate were prepared by aqueous Diels-Alder reaction of cyclopentadiene with symmetric diester of fumarate or maleate.
[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcita...[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcitation=277 nm andλemission=596 nm,with the increase of CCu2+,the fluorescence signal intensity of bisoprolol fumarate weakened,and the difference between the fluorescence intensity of bisoprolol fumarate itself and the fluorescence intensity of the test solution after the quencher Cu2+was added(ΔF)and Cbisoprolol fumarate showed a good linear relationship.[Results]In the range of 15.39-76.93μg/mL,ΔF=146.7 Cbisoprolol fumarate+482.1,r=0.9988,and the detection limit is 0.1391μg/mL.[Conclusions]The fluorescence quenching method has been applied to the determination of actual samples with a recovery rate of 99.9%and an RSD of 2.7%.The results are satisfactory.展开更多
Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective ...Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm<sup>-1</sup> (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.展开更多
Objective:To evaluate the protective effect and mechanism of clemastine fumarate(CLE)on acute lung injury(ALI)in intestinal ischemia-reperfusion(I/R)mice.Methods:Twenty-four SPF Balb/c mice were randomly divided into ...Objective:To evaluate the protective effect and mechanism of clemastine fumarate(CLE)on acute lung injury(ALI)in intestinal ischemia-reperfusion(I/R)mice.Methods:Twenty-four SPF Balb/c mice were randomly divided into sham operation group(sham group),ischemia-reperfusion group(I/R group),and clemastine fumarate pretreatment group(I/R+C group).In the I/R group,an intestinal ischemia-reperfusion model was established(ischemia for 40 minutes,reperfusion for 2 hours).In the I/R+C group,CLE 5 mg/kg was intraperitoneally injected before the operation.Lung tissue morphology was observed and scored by HE staining;and the ratios of wet weight to dry weight(W/D)were recorded.the levels of MDA,SOD,GSH-px,NF-κB and TNF-αin lung tissue of each group were determined by ELISA;Western blot method was used to determine the expression of TLR4 protein in lung tissue.Results:Compared with the Sham group,the I/R group had significantly higher lung tissue injury score and wet/dry ratio(P<0.05),increased lung tissue MDA level(P<0.05),decreased SOD and GSH-px levels(P<0.05),and increased NF-κB and TNF-αlevels,the expression of TLR4 protein in lung tissue increased(P<0.05);compared with the I/R group,the lung tissue injury score and wet/dry ratio of the I/R+C group decreased(P<0.05),the level of MDA in lung tissue decreased(P<0.05),the levels of SOD and GSH-px increased(P<0.05),and the levels of NF-κB and TNF-毩decreased(P<0.05),the expression of TLR4 protein in lung tissue decreased(P<0.05).Conclusion:Clemastine fumarate can alleviate acute lung injury after intestinal ischemia-reperfusion in mice,and the mechanism may be related to the inhibition of oxidative stress and inflammatory response in lung tissue.展开更多
Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and me...Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and methods: A descriptive single-center retrospective study, on chronic viral hepatitis B mono-infected, followed in the hepatogastroenterology department of the University Hospital of Yopougon and treated with tenofovir from February 2012 to February 2015. The studied parameters were demographic, clinical, biochemical, serological, virological, abdominal ultrasound. Liver fibrosis was assessed either by liver biopsy or non-invasive tests. Results: 110 patients were treated with tenofovir disoproxil fumarate with a mean age of 40.4 years and a male predominance. Clinical examination revealed jaundice in 9% of cases, hepatomegaly in 7.3% of cases, splenomegaly in 9.1% of cases and ascites in 15.5% of cases. The AST averaged 77.3 IU/l, the ALT 76.8 IU/l, prothrombin rate at 76.6% , albumin level at 32.3 g/l, total bilirubin at 29.9 g/l, alpha fetoprotein rate at 15.3 ng/ml. HBe antigen was negative in 76.2% of cases. The average rate of DNA at baseline was 7.4 log10 IU/l. 27.5% was cirrhotic. The average time of starting treatment was 23.7 months. Conclusion: TDF is the first-line treatment for chronic hepatitis B in our country, because it is a well-tolerated, potent therapy with a high threshold for resistance development. Our study population had an average age of 40.4 years. Virological profile was dominated by HBe antigen negative patients and high viral load of HVB DNA. One third of patients were at the stage of cirrhosis. This treatment must be delivered free of charge in all the country hospitals, which is going to improve significantly the natural evolution of the disease and to decrease the incidence of the HCC.展开更多
文摘BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.
文摘Metabolic rewiring underlies the effector functions of macrophages1-3,but the mechanisms involved remain incompletely defined.Here,using unbiased metabolomics and stable isotope-assisted tracing,we show that an inflammatory aspartate argininosuccinate shunt is induced following lipopolysaccharide stimulation.The shunt,supported by increased argininosuccinate synthase(ASS1)expression,also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination.Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase(FH)further increases intracellular fumarate levels.
文摘Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.
文摘To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTSHistological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSIONDMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.
文摘A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electrochemical properties are investigated exercising the cyclic voltammetry and square wave voltammetry (SWV). Enhanced peak current associated with bisoprolol fumarate oxidation at EPPGE is due to its better electron transfer property. Quantification of bisoprolol fumarate was carried out at pH 7.2 at both the pyrolytic graphite electrodes. Well-defined peak has been observed at ~ 792 and 954 mV at EPPGE and BPPGE respectively for bisoprolol fumarate oxidation. The detection limit is found to be 2.8 × 10–7 M and 7.3 × 10–7 M for EPPGE and BPPGE respectively. A comparison of common quantification parameters for bisoprolol at carbon nanotube modified glassy carbon electrode and bare BPPGE and EPPGE has been made and it is observed that carbon naotube modified glassy carbon exhibits sensitivity and detection limit close to that observed at bare basal plane pyrolytic graphite electrode. The method developed is applicable for determination of bisoprolol fumarate in pharmaceutical preparations and real samples.
文摘Biallelic inactivation of fumarate hydratase (FH) causes type 2 papillary renal cell carcinoma (PRCC2), uterine fibroids, and cutaneous leimyomas, a condition known as hereditary leiomyomatosis and renal cell cancer (HLRCC). The most direct effect of FH inactivation is intracellular fumarate accumulation. A majority of studies on FH inactivation over the past decade have focused on the theory that intracellular fumarate stabilizes hypoxia-inducible factor 1α (HIF1A) through competitive inhibition of HIF prolyl hydroxylases. Recently, a competing theory that intracellular fumarate activates nuclear factor (erythroid-derived 2)-like 2 (NRF2) through post-translational modification of its negative regulator. Kelch-like ECH-associated protein 1 (KEAP1) has emerged from a computational modeling study and mouse model studies. This review dissects the origin of these two governing theories and highlights the presence of chromatin-structure-regulated targets of transcription factors, which we refer to as "cryptic targets" of transcription factors. One such cryptic target is heme oxygenase I (HMOX1), the expression of which is known to be modulated by the gene product of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1).
基金supported by the College Science Technology Research Project of Hebei Province(Grant No:ZD20131002)
文摘Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats were given the intraperitoneal injection of L-arginine for 5times(250 mg/100 kg,twice per time,each interval of 1 h) for building of CP model.Rats were divided into control group,CP group,DMF group and CP+DMF group.Rats in CP+DMF group were given the oral intragastric administration of DMF(25 mg/kg),while rats in control group and CP group were given the equal volume of normal saline.The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed(IPGTT,2 g/kg).The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets.Meanwhile,the histology of non-endocrine tissues and levels of myeloperoxidase(MPO) and malondialdchyde(MDA) were detected.Results:Compared with control group,the weight of rats in CP group was significantly reduced at week 2,4 and 6;the blood glucose significantly increased,AUC increased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration increased,levels of MDA and MPO increased,the islet equivalent and islet activity decreased at 0.30,60,120 and 180 min.Compared with CP group,the weight of rats in CP+DMF group significantly increased at week 2,4 and 6;the blood glucose significantly decreased.AUC decreased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration decreased,levels of MDA and MPO decreased,the islet equivalent and islet activity increased at 0,30.60,120 and 180 min.Conclusions:DMF treatment can improve CP induced by L-argininc and islet function in rats.
基金funded by Technical System of Modern Agricultural Industry (nycytx-50 )Agriculture Transfer Fund of Ministry of Science and Technology (03EFN213700155)+1 种基金Scientific and Technological Development Plan Project of Shandong Province (2010-2013)Taishan Scholar Post Fund about Aquatic Animal Nutrient and Feed of Shandong Province(HY201004)
文摘[ Objective] The study aimed to discuss the effects of ferrous fumarate on growth performance, blood biochemical parameters and content of trace element of Oncorhynchus mykiss. [ Method ] Juvenile rainbow trout with an initial weight of (89.2 ±0.2) g were fed with the basal fodder supplemented with different levels of ferrous fumarate (0, 20, 40, 80,160 and 480 mg/kg iron) for 60 d, and the six groups were named DO, D20, D40, D80, D160 and D480, wherein DO was as the control group, actually containing 62.60, 79.50, 99.60, 139.30, 215.20 and 538.40 mg/kg iron respectively. [ Result] The growth performance of juvenile rainbow trout was not affected by different dietary iron levels obviously ( P 〉 0.05). With the increase of dietary iron level, hemoglobin (Hb) content and number of red blood cells(RBC) rose firstly and then leveled off. No significance was found in hematocrit (Hct) among the six groups (P 〉0.05). Iron content in the whole body, vertebrae and muscle increased significantly with the improvement of dietary iron level( P 〈0.05), and iron concentration in the liver increased firstly and then leveled off in groups from D40 to D480. No significant difference in zinc content of the whole body was found among the six groups ( P〉0.05), while zinc content in the vertebrae and muscle in control group was significantly higher than that of other groups ( P〈0.05), and zinc concentration in the liver in groups DO and 1320 was significantly higher than that of other groups ( P 〈0.05). Copper content in the whole body increased significantly with the increase of dietary iron level (P 〈 0.05 ), while no significant difference was observed in the vertebrae ( P 〉0.05), and copper concentration in the muscle in control group was significantly lower than that of other groups ( P 〈0.05). Serum lysozyme (LZM) activity of group DO was significantly lower than that of other groups ( P 〈 0.05) except for group D480 ( P 〉 0.05). Catalase (CAT) activity of serum enhanced significantly ( P 〈 0.05) from DO to EH0 and then decreased obviously (P 〈0.05). [ Conclusion] Based on hemoglobin and iron content in the liver, the broken-line model analysis showed that the dietary iron level provided by ferrous fumarate for juvenile rainbow trout was estimated to be 99.8 and 100.4 mg/kg respectively in the experiment.
文摘Symmetric, diesters of cis- or trans- bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylate were prepared by aqueous Diels-Alder reaction of cyclopentadiene with symmetric diester of fumarate or maleate.
基金Project for Improving Basic Research Ability of Middle Aged and Young Teachers in Colleges and Universities of Guangxi in 2017(2017KY0284)Project of Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine(GXZYKF2019-7)+2 种基金Program of Key Laboratory for Extraction and Purification and Quality Analysis of TCM in 2017(J1700208)Project of Guangxi University of Chinese Medicine(YB14004)Collaborative Innovation Center of Zhuang and Yao Ethnic Medicine([2013]No.20).
文摘[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcitation=277 nm andλemission=596 nm,with the increase of CCu2+,the fluorescence signal intensity of bisoprolol fumarate weakened,and the difference between the fluorescence intensity of bisoprolol fumarate itself and the fluorescence intensity of the test solution after the quencher Cu2+was added(ΔF)and Cbisoprolol fumarate showed a good linear relationship.[Results]In the range of 15.39-76.93μg/mL,ΔF=146.7 Cbisoprolol fumarate+482.1,r=0.9988,and the detection limit is 0.1391μg/mL.[Conclusions]The fluorescence quenching method has been applied to the determination of actual samples with a recovery rate of 99.9%and an RSD of 2.7%.The results are satisfactory.
文摘Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm<sup>-1</sup> (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.
基金This study was supported by Natural Science Foundation of Gansu Province(No.20JR10RA727)。
文摘Objective:To evaluate the protective effect and mechanism of clemastine fumarate(CLE)on acute lung injury(ALI)in intestinal ischemia-reperfusion(I/R)mice.Methods:Twenty-four SPF Balb/c mice were randomly divided into sham operation group(sham group),ischemia-reperfusion group(I/R group),and clemastine fumarate pretreatment group(I/R+C group).In the I/R group,an intestinal ischemia-reperfusion model was established(ischemia for 40 minutes,reperfusion for 2 hours).In the I/R+C group,CLE 5 mg/kg was intraperitoneally injected before the operation.Lung tissue morphology was observed and scored by HE staining;and the ratios of wet weight to dry weight(W/D)were recorded.the levels of MDA,SOD,GSH-px,NF-κB and TNF-αin lung tissue of each group were determined by ELISA;Western blot method was used to determine the expression of TLR4 protein in lung tissue.Results:Compared with the Sham group,the I/R group had significantly higher lung tissue injury score and wet/dry ratio(P<0.05),increased lung tissue MDA level(P<0.05),decreased SOD and GSH-px levels(P<0.05),and increased NF-κB and TNF-αlevels,the expression of TLR4 protein in lung tissue increased(P<0.05);compared with the I/R group,the lung tissue injury score and wet/dry ratio of the I/R+C group decreased(P<0.05),the level of MDA in lung tissue decreased(P<0.05),the levels of SOD and GSH-px increased(P<0.05),and the levels of NF-κB and TNF-毩decreased(P<0.05),the expression of TLR4 protein in lung tissue decreased(P<0.05).Conclusion:Clemastine fumarate can alleviate acute lung injury after intestinal ischemia-reperfusion in mice,and the mechanism may be related to the inhibition of oxidative stress and inflammatory response in lung tissue.
文摘Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and methods: A descriptive single-center retrospective study, on chronic viral hepatitis B mono-infected, followed in the hepatogastroenterology department of the University Hospital of Yopougon and treated with tenofovir from February 2012 to February 2015. The studied parameters were demographic, clinical, biochemical, serological, virological, abdominal ultrasound. Liver fibrosis was assessed either by liver biopsy or non-invasive tests. Results: 110 patients were treated with tenofovir disoproxil fumarate with a mean age of 40.4 years and a male predominance. Clinical examination revealed jaundice in 9% of cases, hepatomegaly in 7.3% of cases, splenomegaly in 9.1% of cases and ascites in 15.5% of cases. The AST averaged 77.3 IU/l, the ALT 76.8 IU/l, prothrombin rate at 76.6% , albumin level at 32.3 g/l, total bilirubin at 29.9 g/l, alpha fetoprotein rate at 15.3 ng/ml. HBe antigen was negative in 76.2% of cases. The average rate of DNA at baseline was 7.4 log10 IU/l. 27.5% was cirrhotic. The average time of starting treatment was 23.7 months. Conclusion: TDF is the first-line treatment for chronic hepatitis B in our country, because it is a well-tolerated, potent therapy with a high threshold for resistance development. Our study population had an average age of 40.4 years. Virological profile was dominated by HBe antigen negative patients and high viral load of HVB DNA. One third of patients were at the stage of cirrhosis. This treatment must be delivered free of charge in all the country hospitals, which is going to improve significantly the natural evolution of the disease and to decrease the incidence of the HCC.