Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy...Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.展开更多
Hiccups commonly occur in patients undergoing chemotherapy for lung cancer and may diminish their motivation for treatment. Therefore, it is important to characterize the hiccups and their risk factors. We examined th...Hiccups commonly occur in patients undergoing chemotherapy for lung cancer and may diminish their motivation for treatment. Therefore, it is important to characterize the hiccups and their risk factors. We examined the medical records of 120 patients with lung cancer during their initial chemotherapy and extracted data on the patients’ profiles and the onset, duration, and severity of their hiccup episodes. We found the incidence of hiccups to be 19.2% among the patients. Hiccups appeared within 3 days of beginning the chemotherapy and disappeared within 4 days. Hiccups hindered sleep in two patients. The characteristics of the hiccups episodes in our study were not different from those of previous studies. We also investigated distinctive features of the patients who developed hiccups. The occurrence of hiccups was associated with gender, age, and the treatment with platinum agents. Antiemetic agents, dexamethasone and neurokinin-1 receptor antagonists, also showed significant effects on hiccup episodes. Although the dose-responsive effect of dexamethasone on hiccups was insignificant and the effects of two neurokinin-1 receptor antagonists, aprepitant and fosaprepitant, on hiccups appeared identical. From these results, we suggest that a high incidence of hiccups may be anticipated with a prophylactic use of antiemetic agents, dexamethasone and neurokinin-1 receptor antagonists.展开更多
AIM: To study the influence of inducers of drug metabolism enzyme, β-naphthoflavone (BNF) and dexamethasone (DEX), on the stereoselective metabolism of propafenone in the rat hepatic microsomes.METHODS: Phase I meta...AIM: To study the influence of inducers of drug metabolism enzyme, β-naphthoflavone (BNF) and dexamethasone (DEX), on the stereoselective metabolism of propafenone in the rat hepatic microsomes.METHODS: Phase I metabolism of propafenone was studied using the microsomes induced by BNF and DEX and the non-induced microsome was used as the control. The enzymatic kinetics parameters of propafenone enantiomers were calculated by regress analysis of Eadie-Hofstee Plots.Propafenone enantiomer concentrations were assayed by a chiral HPLC.RESULTS: The metabolite of propafenone, N-desalkylpropafenone, was found after incubstion of propafenone with the rat hepatic microsomes induced by BNF and DEX. In these two groups, the stereoselectivity favoring R ( - ) isomer was observed in metabolism st Iow substrate concentrations of racemic propafenone, but lost the stereoselectivity st high substrate concentrations.However; in control group, no stereeselectivity was observed. The enzyme kinetic parameters were: ① Km.Control group: R( - ) 83 ± 6, S( + ) 94 ± 7; BNF group: R (-)105 ± 6, S( + )128 ± 14; DEX group: R( - ) 86± 11, S( + ) 118 ± 16; ② vmax. Control group: R( - ) 0.75 ± 0.16, S( + ) 0.72±0.07; BNF group: R( - )1.04± 0.15, S( + )1.07±14; DEX group: R( - ) 0.93 ± 0.06, S( + ) 1.04 ± 0.09; (③)Clint. Control group: R( - ) 8.9± 1.1, S( + ) 7.6±0.7; BNFgroup: R( - )9.9±0.9, S( + )8.3±0.7; DEX group: R( - )10.9± 0.8, S( + ) 8.9 ± 0.9. The enantiomeric differences in Km and Clint were both significant, but not in Vmax, in BNF and DEX group. Whereas enantiomeric differences in three parameters were all insignificant in control group.Furthermore, Km and Umax were both significantly less than those in BNF or DEX group. In the rat liver microsorne induced by DEX, nimodipine (NDP) decreased the stereoselectivity in propafenone metabolism at Iow substrate concentration. The inhibition of NDP on the metabolism of propafenone was stereo.selective with R ( - )-isomer being impaired more than S ( + )-isomer. The inhibition constant (Ki) of S ( + )- and R ( - )-propafenone, calculated from Dixon plots, was 15.4 and 8.6 mg.L-1, respectively.CONCLUSION: CYP1A subfamily (induced by BNF) and CYP3A4(induced by DEX) have pronounced contribution to propafenone N-deselkylation which exhibited stereoselectivity depending on substrate concentration. The molecular base for this phenomenon is the stereoselectivity in affinity of subetrate to the enzyme activity centers instead of at the catalyzing sites.展开更多
Diabetes mellitus(DM)is an independent risk factor for admission to intensive care unit and death in patients with coronavirus disease 2019(COVID-19).On the other hand,medications used in the management of COVID-19 ar...Diabetes mellitus(DM)is an independent risk factor for admission to intensive care unit and death in patients with coronavirus disease 2019(COVID-19).On the other hand,medications used in the management of COVID-19 are potentially associated with increases in blood glucose levels and a higher incidence of infections.Accordingly,care of patients with DM and acute COVID-19 requires careful consideration of both diseases.Hyperglycemia and hypoglycemia are associated with adverse outcomes and therefore frequent measurement of blood glucose levels and a basal-bolus insulin regimen are required in most patients.Regarding the management of COVID-19,dexamethasone increases blood glucose levels and might also increase the risk for infections.On the other hand,limited data suggest that antiviral and immunomodulatory agents used in COVID-19 are not strongly associated with higher incidence of infections in this population.As knowledge evolves in this field,optimization of the management of both DM and COVID-19 will hopefully improve the outcome of these patients。展开更多
AIM To study the effects of aminoguanidine(AG) and two L-arginine analogues Nω-nitro-L-arginine methyl ester (L-NAME) and Nω-nitro-L-arginine (L-NNA) on nitric oxide (NO) productioninduced by cytokines (TNF-α, IL-1...AIM To study the effects of aminoguanidine(AG) and two L-arginine analogues Nω-nitro-L-arginine methyl ester (L-NAME) and Nω-nitro-L-arginine (L-NNA) on nitric oxide (NO) productioninduced by cytokines (TNF-α, IL-11β, and IFN-γ)and bacterial lipopolysaccharide (LPS) mixture(CM) in the cultured rat hepatocytes, andexamine their mechanisms action.METHODS Rat hepatocytes were incubatedwith AG, L-NAME, L-NNA, Actinomycin D (ActD)and dexamethasene in a medium containing CM(LPS plus TNF-α, IL-1β, and IFN-γ) for 24 h. NOproduction in the cultured supernatant wasmeasured with the Griese reaction. IntracellularcGMP level was detected with radioimmunoasey.RESULTS NO production was markedlyblocked by AG and L-NAME in a dose-dependentmanner under inflammatory stimuli conditiontriggered by CM in vitro. The rate of themaximum inhibitory effects of L-NAME (38.9%)was less potent than that obtained with AG(53.7%, P<0.05). There was no significantdifference between the inhibitory effects of AGand two L-arginine analogues on intracellularcGMP accumulation in rat cultured hepatocytes.Non-specific NOS expression inhibitordexamethasone ( DEX ) and iNOS mRNAtranscriptional inhibitor ActD also significantlyinhibited CM-induced NO production. AG(0.1mmol.L-1) and ActD (0.2ng@Lt) wereequipotent in decreasing NO production inducedby inflammatory stimuli in vitro, and botheffects were more potent than that induced bynon-selectivity NOS activity inhibitor L-NAME(0. 1 mmol@ L- 1) under similar stimuli conditions(P＜O.O1).CONCLUSION AG is a potent selectiveinhibitor of inducible isoform of NOS, and themechanism of action may be not onlycompetitive inhibition in the substrate level, butalso the gene expression level in rathepatocytes .展开更多
From April 1992 to April 1998, 104 cases of chemotherapy-induced leukopenia were treated by injection into Zusanli (ST 36) with a mixture consisting of dexamethasone, 654-2, ATP and inosine. The therapeutic results we...From April 1992 to April 1998, 104 cases of chemotherapy-induced leukopenia were treated by injection into Zusanli (ST 36) with a mixture consisting of dexamethasone, 654-2, ATP and inosine. The therapeutic results were satisfactory as reported in the following.
Clinical Data
In this series, all the 127 cases were definitely diagnosed by pathological examination. Of them, 93 were male and 34 female, ranging in age from 12 to 75 years. 38 cases were carcinoma of esophagus, 22 carcinoma of cardia of stomach, 21 cancer of lung, 11 hepatic carcinoma, 8 lymphoma, 8 mammary cancer, 7 carcinoma of colon, and 12 other kinds of the tumors. Leukocyte count was below 4.0×109/L in all the patients after being treated by chemotherapy.展开更多
基金supported by the Technology Fund of Zhangzhou City in China,No.Z2010086
文摘Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.
文摘Hiccups commonly occur in patients undergoing chemotherapy for lung cancer and may diminish their motivation for treatment. Therefore, it is important to characterize the hiccups and their risk factors. We examined the medical records of 120 patients with lung cancer during their initial chemotherapy and extracted data on the patients’ profiles and the onset, duration, and severity of their hiccup episodes. We found the incidence of hiccups to be 19.2% among the patients. Hiccups appeared within 3 days of beginning the chemotherapy and disappeared within 4 days. Hiccups hindered sleep in two patients. The characteristics of the hiccups episodes in our study were not different from those of previous studies. We also investigated distinctive features of the patients who developed hiccups. The occurrence of hiccups was associated with gender, age, and the treatment with platinum agents. Antiemetic agents, dexamethasone and neurokinin-1 receptor antagonists, also showed significant effects on hiccup episodes. Although the dose-responsive effect of dexamethasone on hiccups was insignificant and the effects of two neurokinin-1 receptor antagonists, aprepitant and fosaprepitant, on hiccups appeared identical. From these results, we suggest that a high incidence of hiccups may be anticipated with a prophylactic use of antiemetic agents, dexamethasone and neurokinin-1 receptor antagonists.
基金Supported by the National Natural Science Foundation of China(No.39370805,N039770868)Zhejiang Natural Science Foundation(No.RC97016)of Zhejiang Province
文摘AIM: To study the influence of inducers of drug metabolism enzyme, β-naphthoflavone (BNF) and dexamethasone (DEX), on the stereoselective metabolism of propafenone in the rat hepatic microsomes.METHODS: Phase I metabolism of propafenone was studied using the microsomes induced by BNF and DEX and the non-induced microsome was used as the control. The enzymatic kinetics parameters of propafenone enantiomers were calculated by regress analysis of Eadie-Hofstee Plots.Propafenone enantiomer concentrations were assayed by a chiral HPLC.RESULTS: The metabolite of propafenone, N-desalkylpropafenone, was found after incubstion of propafenone with the rat hepatic microsomes induced by BNF and DEX. In these two groups, the stereoselectivity favoring R ( - ) isomer was observed in metabolism st Iow substrate concentrations of racemic propafenone, but lost the stereoselectivity st high substrate concentrations.However; in control group, no stereeselectivity was observed. The enzyme kinetic parameters were: ① Km.Control group: R( - ) 83 ± 6, S( + ) 94 ± 7; BNF group: R (-)105 ± 6, S( + )128 ± 14; DEX group: R( - ) 86± 11, S( + ) 118 ± 16; ② vmax. Control group: R( - ) 0.75 ± 0.16, S( + ) 0.72±0.07; BNF group: R( - )1.04± 0.15, S( + )1.07±14; DEX group: R( - ) 0.93 ± 0.06, S( + ) 1.04 ± 0.09; (③)Clint. Control group: R( - ) 8.9± 1.1, S( + ) 7.6±0.7; BNFgroup: R( - )9.9±0.9, S( + )8.3±0.7; DEX group: R( - )10.9± 0.8, S( + ) 8.9 ± 0.9. The enantiomeric differences in Km and Clint were both significant, but not in Vmax, in BNF and DEX group. Whereas enantiomeric differences in three parameters were all insignificant in control group.Furthermore, Km and Umax were both significantly less than those in BNF or DEX group. In the rat liver microsorne induced by DEX, nimodipine (NDP) decreased the stereoselectivity in propafenone metabolism at Iow substrate concentration. The inhibition of NDP on the metabolism of propafenone was stereo.selective with R ( - )-isomer being impaired more than S ( + )-isomer. The inhibition constant (Ki) of S ( + )- and R ( - )-propafenone, calculated from Dixon plots, was 15.4 and 8.6 mg.L-1, respectively.CONCLUSION: CYP1A subfamily (induced by BNF) and CYP3A4(induced by DEX) have pronounced contribution to propafenone N-deselkylation which exhibited stereoselectivity depending on substrate concentration. The molecular base for this phenomenon is the stereoselectivity in affinity of subetrate to the enzyme activity centers instead of at the catalyzing sites.
文摘Diabetes mellitus(DM)is an independent risk factor for admission to intensive care unit and death in patients with coronavirus disease 2019(COVID-19).On the other hand,medications used in the management of COVID-19 are potentially associated with increases in blood glucose levels and a higher incidence of infections.Accordingly,care of patients with DM and acute COVID-19 requires careful consideration of both diseases.Hyperglycemia and hypoglycemia are associated with adverse outcomes and therefore frequent measurement of blood glucose levels and a basal-bolus insulin regimen are required in most patients.Regarding the management of COVID-19,dexamethasone increases blood glucose levels and might also increase the risk for infections.On the other hand,limited data suggest that antiviral and immunomodulatory agents used in COVID-19 are not strongly associated with higher incidence of infections in this population.As knowledge evolves in this field,optimization of the management of both DM and COVID-19 will hopefully improve the outcome of these patients。
基金Project supported by the National Natural Science Foundation of China,No.39770861.and JANSSEN Science Research Foundation.
文摘AIM To study the effects of aminoguanidine(AG) and two L-arginine analogues Nω-nitro-L-arginine methyl ester (L-NAME) and Nω-nitro-L-arginine (L-NNA) on nitric oxide (NO) productioninduced by cytokines (TNF-α, IL-11β, and IFN-γ)and bacterial lipopolysaccharide (LPS) mixture(CM) in the cultured rat hepatocytes, andexamine their mechanisms action.METHODS Rat hepatocytes were incubatedwith AG, L-NAME, L-NNA, Actinomycin D (ActD)and dexamethasene in a medium containing CM(LPS plus TNF-α, IL-1β, and IFN-γ) for 24 h. NOproduction in the cultured supernatant wasmeasured with the Griese reaction. IntracellularcGMP level was detected with radioimmunoasey.RESULTS NO production was markedlyblocked by AG and L-NAME in a dose-dependentmanner under inflammatory stimuli conditiontriggered by CM in vitro. The rate of themaximum inhibitory effects of L-NAME (38.9%)was less potent than that obtained with AG(53.7%, P<0.05). There was no significantdifference between the inhibitory effects of AGand two L-arginine analogues on intracellularcGMP accumulation in rat cultured hepatocytes.Non-specific NOS expression inhibitordexamethasone ( DEX ) and iNOS mRNAtranscriptional inhibitor ActD also significantlyinhibited CM-induced NO production. AG(0.1mmol.L-1) and ActD (0.2ng@Lt) wereequipotent in decreasing NO production inducedby inflammatory stimuli in vitro, and botheffects were more potent than that induced bynon-selectivity NOS activity inhibitor L-NAME(0. 1 mmol@ L- 1) under similar stimuli conditions(P＜O.O1).CONCLUSION AG is a potent selectiveinhibitor of inducible isoform of NOS, and themechanism of action may be not onlycompetitive inhibition in the substrate level, butalso the gene expression level in rathepatocytes .
文摘From April 1992 to April 1998, 104 cases of chemotherapy-induced leukopenia were treated by injection into Zusanli (ST 36) with a mixture consisting of dexamethasone, 654-2, ATP and inosine. The therapeutic results were satisfactory as reported in the following.
Clinical Data
In this series, all the 127 cases were definitely diagnosed by pathological examination. Of them, 93 were male and 34 female, ranging in age from 12 to 75 years. 38 cases were carcinoma of esophagus, 22 carcinoma of cardia of stomach, 21 cancer of lung, 11 hepatic carcinoma, 8 lymphoma, 8 mammary cancer, 7 carcinoma of colon, and 12 other kinds of the tumors. Leukocyte count was below 4.0×109/L in all the patients after being treated by chemotherapy.
