A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine,...A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated.The conventional plasma sample preparation method of nucleoside analogues is solidphase extraction(SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation(LLOQ)of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.展开更多
Objective:To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019(COVID-19)in intensive care unit(ICU).Methods:This double-blind clinical trial was carried out...Objective:To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019(COVID-19)in intensive care unit(ICU).Methods:This double-blind clinical trial was carried out in 2022-2023.64 Patients with COVID-19 were selected from Amiralmomenin and Khansari hospitals in Arak,Iran.They were randomly assigned to the control and the L-carnitine treatment group via block randomization.Venous blood gases,disease severity,and levels of D-dimer,lactate dehydrogenase,ferritin,and C-reactive protein were daily assessed during the seven days of the intervention,and the length of ICU stay,the need for endotracheal intubation,and mortality rate were documented.Results:There were significant differences in length of ICU stay,the need for endotracheal intubation,and levels of D-dimer,lactate dehydrogenase,ferritin,APACHE栻score,and C-reactive protein between the two groups(P<0.05).However,the groups did not significantly differ in mortality rate and venous blood gas indexes(P>0.05).Conclusions:L-carnitine can improve outcomes of patients with COVID-19.Therefore,it can be used as an adjuvant therapy for these patients.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)dominates the landscape of modern hepatology.Affecting 25%of the general population,there is critical unmet need to identify broadly available,safe and cost-effective...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)dominates the landscape of modern hepatology.Affecting 25%of the general population,there is critical unmet need to identify broadly available,safe and cost-effective treatments.Cumulative evidence in animal and human models suggests that intrahepatic and skeletal muscle fatty acid oxidation is impaired in NAFLD,such that lipid accretion is not matched by efficient utilisation.L-carnitine is a crucial mediator of fatty acid metabolism in vivo,promoting mitochondrial lipidβ-oxidation and enhancing tissue metabolic flexibility.These physiological properties have generated research interest in L-carnitine as a potentially effective adjunctive therapy in NAFLD.AIM To systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry,liver fat and insulin sensitivity in NAFLD.METHODS Search strategies,eligibility criteria and analytic methods were specified a priori(PROSPERO reference:CRD42018107063).Ovid MEDLINE,Ovid EMBASE,PubMed,Web of Science and the Cochrane Library were searched from their inception until April 2019.Outcome measures included serum concentrations of alanine and aspartate aminotransferase(ALT and AST),liver fat and insulin sensitivity assessed by the homeostasis model of insulin resistance(HOMA-IR).A random effects meta-analysis was performed for,ALT,AST and HOMA-IR measures separately.Between-study heterogeneity was measured using I2 statistics.RESULTS Five eligible randomised trials were included in the qualitative and quantitative synthesis(n=338).All of the 5 included trials assessed the effect of L-carnitine on serum ALT,identified from Italy,South Korea and Iran.Weighted mean difference(WMD)for ALT between L-carnitine and control groups after intervention was-25.34 IU/L[95%CI:-41.74-(-8.94);P=0.002].WMD for AST between L-carnitine and control groups was-13.68 IU/L(95%CI:-28.26-0.89;P=0.066).In three studies(n=204),HOMA-IR was evaluated.WMD for HOMA-IR between L-carnitine and control groups was-0.74 units[95%CI:-1.02-(-0.46);P<0.001].Two studies using validated outcome measures reported a significant reduction in liver fat in L-carnitine vs control groups post-intervention(P<0.001).CONCLUSION Pooled results indicate that L-carnitine supplementation attenuates ALT,liver fat and insulin resistance in NAFLD cohorts,confirming a beneficial effect of Lcarnitine for a highly prevalent condition with a growing economic burden.展开更多
[Objective] The aim was to study the effects of L-carnitine on population growth of Nannochloropsis oculata and Tetrahymena sp..[Method] When the concentration of L-carnitine was 0,50,100 and 1 000 mg/L,population den...[Objective] The aim was to study the effects of L-carnitine on population growth of Nannochloropsis oculata and Tetrahymena sp..[Method] When the concentration of L-carnitine was 0,50,100 and 1 000 mg/L,population densities of Nannochloropsis oculata and Tetrahymena were determined respectively.[Result] Adding high-dose L-carnitine had a significant inhibition effect on the population growth of Nannochloropsis oculata （P0.05）.Adding L-carnitine had a significant proliferation promoting effect on the population growth of Tetrahymena （P0.05）.[Conclusion] The research provides theoretical basis for the application of L-carnitine as feed additive in aquaculture.展开更多
To investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury in rat heart,all harvested isolated hearts were perfused on Langendorff apparatus with oxygenized K-H solution for 20 min. ...To investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury in rat heart,all harvested isolated hearts were perfused on Langendorff apparatus with oxygenized K-H solution for 20 min. The hearts were then exposed to ischemia for 30 min. Following the ischemia the hearts were re-perfused with K-H solution for 120 min to serve as the control group A. Either 5 or 10 mmol/L of L-carnitine was added into the K-H solution for 20 min at the beginning of reperfusion to generate group B and group C, respectively. The derivatives of the intraventricular pressure curve （DP/DT）, left ventricular developed pressure （LVDP）, and coronary flux were monitored during the entire experiment. The levels of ATP, hepatin, malondialdehyde （MDA）, and superoxide dismutase （SOD） in tissue, and lactic dehydrogenase （LDH）, creatine phosphate kinase （CPK）, malondialdehyde （MDA）, and superoxide dismutase （SOD） concentration in the coronary efflux were all measured. Compared with the control group, the treatment with L-carnitine resulted in better results, i. e. , higher DP/DTmax and LVDP. At the same time, ventricular fibrillation was reduced, and the levels of ATP, hepatin and SOD were all elevated. However, the concentrations of MDA, CPK and LDH were all reduced. In conclusion, L-carnitine has a protective effect on ischemia-reperfusion injury, which is partly due to its prevention of energy loss and its antioxidant activity.展开更多
AIM：To evaluate the efficacy of L-carnitine on alleviating anemia,thrombocytopenia and leukopenia,and minimizing dose reductions in patients with chronic hepatitis C virus（HCV）in treatment with Interferonα（IFN-α...AIM：To evaluate the efficacy of L-carnitine on alleviating anemia,thrombocytopenia and leukopenia,and minimizing dose reductions in patients with chronic hepatitis C virus（HCV）in treatment with Interferonα（IFN-α）plus ribavirin.METHODS：Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two groups.group A（n=35）received Peg-IFN-α2b plus ribavirin plus L-carnitine,and group B（n=34）received Peg-IFN-αand ribavirin for 12 mo.All patients underwent laboratory investigations including：red cell count,he-moglobin,white cell count,platelets,bilirubin,alanineaminotransferase（ALT）,aspartate aminotransferase（AST）,and viremia.RESULTS：After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8（IU/L;P0.001）,ALT 137.vs 112.3（IU/L;P 0.001）,viremia 4.04 vs 2.36（106 copies/mL;P 0.001）,Hb 1 vs 3.5（g/dL;P0.05）,red blood cells 0.3 vs 1.1（1012/L;P0.001）,white blood cells 1.5 vs 3（10/L;P0.001）and platelets 86 vs 85（×10/L;P0.001）.The end treatment responders were 18 vs 12（60%vs 44%）and the non responders were 12 vs 15（40%vs 50%）[odds ratio（OR）1.65,5%CI =0.65-5.37,P0.05.In group A compared to group B there was a significant improvement of sustained vi-rological response in 15 vs 7 patients（50%vs25%）,while the relapsers were 3 vs 5（10%vs 18%）（OR 3.57,5%CI=0.65-1.3,P0.001）.CONCLUSION：L-carnitine supplementations modulate erythropoiesis,leucopoiesis and thrombocytopoiesis,and may be useful in patients treated for HCV.L-carni-tine treatment offers the possibility of achieving a sus-tained virological response while preventing overtreat-ment.展开更多
L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with th...L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with the amine function of the target molecule L-carnitine. The imprinted polymers were used as stationary phases in high-performance liquid chromatography (HPLC). It was shown that L-carnitine imprinted polymer exhibited a higher affinity to its template molecule, while the non-imprinted polymer had no affinity to the compounds tested. Racemic carnitine hydrochloride was efficiently resolved on the L-carnitine imprinted polymer, and the separation factor is 1.9.展开更多
基金the financial support from the National Natural Science Foundation of China (No. 81173009)Technology Bureau in Shenyang (No. ZCJJ2013402)+2 种基金the financial support from Project for New Century Excellent Talents of Ministry of Education (No.NCET-12-1015)Specific Science Foundation of Shenyang Pharmaceutical University (No. ZCJJ2014409)National Undergraduate Training Program for Innovation and Entrepreneurship (2016)
文摘A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated.The conventional plasma sample preparation method of nucleoside analogues is solidphase extraction(SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation(LLOQ)of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.
文摘Objective:To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019(COVID-19)in intensive care unit(ICU).Methods:This double-blind clinical trial was carried out in 2022-2023.64 Patients with COVID-19 were selected from Amiralmomenin and Khansari hospitals in Arak,Iran.They were randomly assigned to the control and the L-carnitine treatment group via block randomization.Venous blood gases,disease severity,and levels of D-dimer,lactate dehydrogenase,ferritin,and C-reactive protein were daily assessed during the seven days of the intervention,and the length of ICU stay,the need for endotracheal intubation,and mortality rate were documented.Results:There were significant differences in length of ICU stay,the need for endotracheal intubation,and levels of D-dimer,lactate dehydrogenase,ferritin,APACHE栻score,and C-reactive protein between the two groups(P<0.05).However,the groups did not significantly differ in mortality rate and venous blood gas indexes(P>0.05).Conclusions:L-carnitine can improve outcomes of patients with COVID-19.Therefore,it can be used as an adjuvant therapy for these patients.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)dominates the landscape of modern hepatology.Affecting 25%of the general population,there is critical unmet need to identify broadly available,safe and cost-effective treatments.Cumulative evidence in animal and human models suggests that intrahepatic and skeletal muscle fatty acid oxidation is impaired in NAFLD,such that lipid accretion is not matched by efficient utilisation.L-carnitine is a crucial mediator of fatty acid metabolism in vivo,promoting mitochondrial lipidβ-oxidation and enhancing tissue metabolic flexibility.These physiological properties have generated research interest in L-carnitine as a potentially effective adjunctive therapy in NAFLD.AIM To systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry,liver fat and insulin sensitivity in NAFLD.METHODS Search strategies,eligibility criteria and analytic methods were specified a priori(PROSPERO reference:CRD42018107063).Ovid MEDLINE,Ovid EMBASE,PubMed,Web of Science and the Cochrane Library were searched from their inception until April 2019.Outcome measures included serum concentrations of alanine and aspartate aminotransferase(ALT and AST),liver fat and insulin sensitivity assessed by the homeostasis model of insulin resistance(HOMA-IR).A random effects meta-analysis was performed for,ALT,AST and HOMA-IR measures separately.Between-study heterogeneity was measured using I2 statistics.RESULTS Five eligible randomised trials were included in the qualitative and quantitative synthesis(n=338).All of the 5 included trials assessed the effect of L-carnitine on serum ALT,identified from Italy,South Korea and Iran.Weighted mean difference(WMD)for ALT between L-carnitine and control groups after intervention was-25.34 IU/L[95%CI:-41.74-(-8.94);P=0.002].WMD for AST between L-carnitine and control groups was-13.68 IU/L(95%CI:-28.26-0.89;P=0.066).In three studies(n=204),HOMA-IR was evaluated.WMD for HOMA-IR between L-carnitine and control groups was-0.74 units[95%CI:-1.02-(-0.46);P<0.001].Two studies using validated outcome measures reported a significant reduction in liver fat in L-carnitine vs control groups post-intervention(P<0.001).CONCLUSION Pooled results indicate that L-carnitine supplementation attenuates ALT,liver fat and insulin resistance in NAFLD cohorts,confirming a beneficial effect of Lcarnitine for a highly prevalent condition with a growing economic burden.
基金Supported by National Natural Science Foundation of China(30671621)~~
文摘[Objective] The aim was to study the effects of L-carnitine on population growth of Nannochloropsis oculata and Tetrahymena sp..[Method] When the concentration of L-carnitine was 0,50,100 and 1 000 mg/L,population densities of Nannochloropsis oculata and Tetrahymena were determined respectively.[Result] Adding high-dose L-carnitine had a significant inhibition effect on the population growth of Nannochloropsis oculata （P0.05）.Adding L-carnitine had a significant proliferation promoting effect on the population growth of Tetrahymena （P0.05）.[Conclusion] The research provides theoretical basis for the application of L-carnitine as feed additive in aquaculture.
文摘To investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury in rat heart,all harvested isolated hearts were perfused on Langendorff apparatus with oxygenized K-H solution for 20 min. The hearts were then exposed to ischemia for 30 min. Following the ischemia the hearts were re-perfused with K-H solution for 120 min to serve as the control group A. Either 5 or 10 mmol/L of L-carnitine was added into the K-H solution for 20 min at the beginning of reperfusion to generate group B and group C, respectively. The derivatives of the intraventricular pressure curve （DP/DT）, left ventricular developed pressure （LVDP）, and coronary flux were monitored during the entire experiment. The levels of ATP, hepatin, malondialdehyde （MDA）, and superoxide dismutase （SOD） in tissue, and lactic dehydrogenase （LDH）, creatine phosphate kinase （CPK）, malondialdehyde （MDA）, and superoxide dismutase （SOD） concentration in the coronary efflux were all measured. Compared with the control group, the treatment with L-carnitine resulted in better results, i. e. , higher DP/DTmax and LVDP. At the same time, ventricular fibrillation was reduced, and the levels of ATP, hepatin and SOD were all elevated. However, the concentrations of MDA, CPK and LDH were all reduced. In conclusion, L-carnitine has a protective effect on ischemia-reperfusion injury, which is partly due to its prevention of energy loss and its antioxidant activity.
基金Supported by Ministero dell’Università e Ricerca Scientifica e Tecnologica
文摘AIM：To evaluate the efficacy of L-carnitine on alleviating anemia,thrombocytopenia and leukopenia,and minimizing dose reductions in patients with chronic hepatitis C virus（HCV）in treatment with Interferonα（IFN-α）plus ribavirin.METHODS：Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two groups.group A（n=35）received Peg-IFN-α2b plus ribavirin plus L-carnitine,and group B（n=34）received Peg-IFN-αand ribavirin for 12 mo.All patients underwent laboratory investigations including：red cell count,he-moglobin,white cell count,platelets,bilirubin,alanineaminotransferase（ALT）,aspartate aminotransferase（AST）,and viremia.RESULTS：After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8（IU/L;P0.001）,ALT 137.vs 112.3（IU/L;P 0.001）,viremia 4.04 vs 2.36（106 copies/mL;P 0.001）,Hb 1 vs 3.5（g/dL;P0.05）,red blood cells 0.3 vs 1.1（1012/L;P0.001）,white blood cells 1.5 vs 3（10/L;P0.001）and platelets 86 vs 85（×10/L;P0.001）.The end treatment responders were 18 vs 12（60%vs 44%）and the non responders were 12 vs 15（40%vs 50%）[odds ratio（OR）1.65,5%CI =0.65-5.37,P0.05.In group A compared to group B there was a significant improvement of sustained vi-rological response in 15 vs 7 patients（50%vs25%）,while the relapsers were 3 vs 5（10%vs 18%）（OR 3.57,5%CI=0.65-1.3,P0.001）.CONCLUSION：L-carnitine supplementations modulate erythropoiesis,leucopoiesis and thrombocytopoiesis,and may be useful in patients treated for HCV.L-carni-tine treatment offers the possibility of achieving a sus-tained virological response while preventing overtreat-ment.
基金Research supported by The Analysis & Test Fund of Zhejiang Province.
文摘L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with the amine function of the target molecule L-carnitine. The imprinted polymers were used as stationary phases in high-performance liquid chromatography (HPLC). It was shown that L-carnitine imprinted polymer exhibited a higher affinity to its template molecule, while the non-imprinted polymer had no affinity to the compounds tested. Racemic carnitine hydrochloride was efficiently resolved on the L-carnitine imprinted polymer, and the separation factor is 1.9.
