Background: Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. Several patients develop side effects, which may lead to...Background: Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. Several patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX-induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX. Objectives: To assess the efficacy of folinic acid in comparison to folic acid for reducing the side effects of MTX in JIA patients. Material and methods: In this prospective observational study, newly diagnosed cases of JIA who would be getting MTX were included by purposive sampling. Data were collected using a predesigned questionnaire. Among 40 patients, 20 received folinic acid (Group A), and 20 received folic acid (Group B). Disease activity levels were assessed by JADAS-27 (Juvenile Arthritis Disease Activity Score). Contents from the MISS (MTX Intolerance severity score) questionnaire were used to assess the side effects. All patients were evaluated at baseline, 6th, and 12th weeks. Results: There were significant differences in the frequency of MTX-related adverse events between folinic acid (Group A) and folic acid (Group B). Group A patients only had nausea (10% and 15% in the 6th & 12th week respectively) and vomiting (5% at both follow-ups). On the other hand, in addition to nausea (70% and 95% in the 6th & 12th week) and vomiting (20% and 90% in the 6th & 12th week), folic acid group patients had restlessness, crying, and irritability. Self-discontinuation of MTX was present in the folic acid group (5% & 10% in the 6th & 12th week). Improvement of disease activity was more in the folinic acid group. Conclusion: The folinic acid group had significantly fewer side effects. Improvement of disease activity was more and compliance was also better among them. Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. A number of patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX.展开更多
Fatty acid composition of four Sargassum species from Qingdao and Shidao,Shandong Provincewas investigated.16:0(palmitic acid)was the major saturated fatty acid.C<sub>18</sub> and C<sub>20</sub&...Fatty acid composition of four Sargassum species from Qingdao and Shidao,Shandong Provincewas investigated.16:0(palmitic acid)was the major saturated fatty acid.C<sub>18</sub> and C<sub>20</sub>were the mainpolyunsaturated fatty acids(PUFAs).Arachidonic acid and eicosapentaenoic acid predominated amongpolyenoic acids in all the algal species examined.except for Sargassum sp.which had low concentrationof eicosapentaenoic acid.展开更多
The feeding trial was conducted to determine the effects of flaxseed on layer's performance and egg quality, and the effects of the dietary ratio of ω-6 fatty acid to ω-3 fatty acid on fatty acid deposition in yolk...The feeding trial was conducted to determine the effects of flaxseed on layer's performance and egg quality, and the effects of the dietary ratio of ω-6 fatty acid to ω-3 fatty acid on fatty acid deposition in yolk using flaxseed as resource of ω-3 fatty acid and sunflower seed as resource of ω-6 fatty acid. 192 20-wk-old Newroman commercial hens were randomly divided into 4 treatment groups with 6 replicates containing 8 birds. The rations corresponding with the four treatments were formulated with 4% flaxseed + 9% sunflower seed, 8% flaxseed + 18% sunflower seed, 15% flaxseed, and soybean meal, respectively. Sunflower seed was unshelled and flaxseed was whole. Ratios of ω-6 fatty acid to ω-3 fatty acid in 4 dietary treatments were 5.67, 5.21, 1.07, and 11.83, respectively. It can be concluded that long-term feeding 15% flaxseed had no significant (P〉 0.05) influence on egg production, egg weight, eggshell quality, yolk weight, and percentage of yolk weight. Dietary ratio of ω-6 fatty acid to ω-3 fatty acid had impact on the 0-3 fatty acid levels in yolk, nevertheless yolk fatty acid profiles were different from those of dietary fatty acid compositions.展开更多
A surfactant modified zeolite( SMZ), i. e. , a zeolite modified by using hexadecyl trimethyl ammonium bromide (HDTMA) was used to remove fulvic acids(FA) from aqueous solution. The effects of the relevant parame...A surfactant modified zeolite( SMZ), i. e. , a zeolite modified by using hexadecyl trimethyl ammonium bromide (HDTMA) was used to remove fulvic acids(FA) from aqueous solution. The effects of the relevant parameters, such as the loading level of HDTMA, the contact time, the initial FA concentration, the pH, and the types of the metal carious and organics were examined. The results show that SMZ with an HDTMA loading-level of 120% of the external cation exchange capacity(ECEC) of zeolite exhibits the best performance. Although the removal of fulvic acids by SMZ occurs rapidly within the first 30 min of the contact time, a contact time of at least 4 h is required to attain the adsorption equilibrium. The removal capacity of FA by SMZ decreases with the increase of the initial FA concentration. The pH has an effect on the FA removal efficiency because it can influence the characteristics of the FA molecules. The removal of FA is considerably enhanced by Ca^2+ or Mg^2+ ions and is adversely affected by phenol or pentachlorophenol(PCP). Under the optimum conditions, 98% of FA could be removed by SMZ. Furthermore, the desorption of FA and the regeneration of SMZ were studied. The results show that a 30% ethanol solution is sufficient for the regeneration of SMZ.展开更多
Objective: To determine fatty acid synthase (FAS) expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods: FAS expression was determined by immunohistoche...Objective: To determine fatty acid synthase (FAS) expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods: FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction (RT-PCR) and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma (MM patients) and peripheral blood mononuclear cells (PBMCs) obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations (5 to 320 μg/ml) for 24 h, and metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Apoptosis was evaluated by dual Annexin V/Pl (propidium iodide) labeling and flow cytometry (FCM) in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results: By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^+/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^+/Pl^+ cells. Conclusion: Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.展开更多
Mouse blastocysts were exposed to doses of 0, 1 and 10 μmol/L retinoic acid (RA) for 24 h and the cytotoxic effect of RA on the mouse blastocysts in vitro was observed. FITC-labeled terminal deoxynucleotidyl transf...Mouse blastocysts were exposed to doses of 0, 1 and 10 μmol/L retinoic acid (RA) for 24 h and the cytotoxic effect of RA on the mouse blastocysts in vitro was observed. FITC-labeled terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL-FITC) assay was employed to stain apoptotic cells and immunohistochemical S-P staining method was used to detect the expression of Fas protein in mouse blastocysts in vitro. The results showed that RA could induce apoptosis and increase the expression of Fas proteins of trophectoderm (TE) and inner cell mass (ICM) cells in blastocysts. Compared with the findings for the control blastocysts, exposure to RA (10 μmol/L) resulted in a more significant apoptosis and higher expression level of Fas proteins (P〈0.01). It was concluded that RA could induce apoptosis, which may result in a significant reduction in the average number of total cells and the trophectoderm/inner cell mass in blastocysts and an increased expression of Fas protein, suggesting that RA had a cytotoxic effect on the growth and development of early embryos in mice.展开更多
Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid...Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid profiles in aestivated and non-aestivated A.japonicus using multivariate analyses(PERMANOVA,MDS,ANOSIM,and SIMPER).The results indicate that the fatty acid profiles of aestivated and non-aestivated sea cucumbers differed significantly.The FAs that were produced by bacteria and brown kelp contributed the most to the differences in the fatty acid composition of aestivated and nonaestivated sea cucumbers.Aestivated sea cucumbers may synthesize FAs from heterotrophic bacteria during early aestivation,and long chain FAs such as eicosapentaenoic(EPA) and docosahexaenoic acid(DHA) that produced from intestinal degradation,are digested during deep aestivation.Specific changes in the fatty acid composition of A.japonicus during aestivation needs more detailed study in the future.展开更多
AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). M...AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). METHODS: Thirty-one patients with hystologically- confirmed, inoperable HCC, received combination chemotherapy with PLD 25 mg/mq on d 1, 5FU 1200 mg/mq in 48 h continuous infusion, and oral FA 30 mg on d 1 and 2 every 3 wk until disease progression or intolerable toxicity. RESULTS: The median age was 65 years (range 41-82) and 28 patients were hepatitis C virus seropositive (90%). The majority of patients were Child-Pugh Class B (55%). Two patients showed a partial response (PR), and 16 had stable disease (SD). With a median follow-up of 14 mo, the median time to progression of all evaluable patients was 4 mo (95% CI 1.7-7). Median overall survival was 9 mo (95% CI 3-24 mo). After 1 year, 9 of 18 PR/SD patients were alive. Chemotherapy was well tolerated. CONCLUSION: PLD/FU/FA combination seems capable of achieving durable stabilization of HCC. The manageable toxicity supports a role for combination with other anticancer agents.展开更多
文摘Background: Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. Several patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX-induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX. Objectives: To assess the efficacy of folinic acid in comparison to folic acid for reducing the side effects of MTX in JIA patients. Material and methods: In this prospective observational study, newly diagnosed cases of JIA who would be getting MTX were included by purposive sampling. Data were collected using a predesigned questionnaire. Among 40 patients, 20 received folinic acid (Group A), and 20 received folic acid (Group B). Disease activity levels were assessed by JADAS-27 (Juvenile Arthritis Disease Activity Score). Contents from the MISS (MTX Intolerance severity score) questionnaire were used to assess the side effects. All patients were evaluated at baseline, 6th, and 12th weeks. Results: There were significant differences in the frequency of MTX-related adverse events between folinic acid (Group A) and folic acid (Group B). Group A patients only had nausea (10% and 15% in the 6th & 12th week respectively) and vomiting (5% at both follow-ups). On the other hand, in addition to nausea (70% and 95% in the 6th & 12th week) and vomiting (20% and 90% in the 6th & 12th week), folic acid group patients had restlessness, crying, and irritability. Self-discontinuation of MTX was present in the folic acid group (5% & 10% in the 6th & 12th week). Improvement of disease activity was more in the folinic acid group. Conclusion: The folinic acid group had significantly fewer side effects. Improvement of disease activity was more and compliance was also better among them. Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. A number of patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX.
文摘Fatty acid composition of four Sargassum species from Qingdao and Shidao,Shandong Provincewas investigated.16:0(palmitic acid)was the major saturated fatty acid.C<sub>18</sub> and C<sub>20</sub>were the mainpolyunsaturated fatty acids(PUFAs).Arachidonic acid and eicosapentaenoic acid predominated amongpolyenoic acids in all the algal species examined.except for Sargassum sp.which had low concentrationof eicosapentaenoic acid.
基金supported by the Heilongjiang Province Government Foundation,China(HL-98)
文摘The feeding trial was conducted to determine the effects of flaxseed on layer's performance and egg quality, and the effects of the dietary ratio of ω-6 fatty acid to ω-3 fatty acid on fatty acid deposition in yolk using flaxseed as resource of ω-3 fatty acid and sunflower seed as resource of ω-6 fatty acid. 192 20-wk-old Newroman commercial hens were randomly divided into 4 treatment groups with 6 replicates containing 8 birds. The rations corresponding with the four treatments were formulated with 4% flaxseed + 9% sunflower seed, 8% flaxseed + 18% sunflower seed, 15% flaxseed, and soybean meal, respectively. Sunflower seed was unshelled and flaxseed was whole. Ratios of ω-6 fatty acid to ω-3 fatty acid in 4 dietary treatments were 5.67, 5.21, 1.07, and 11.83, respectively. It can be concluded that long-term feeding 15% flaxseed had no significant (P〉 0.05) influence on egg production, egg weight, eggshell quality, yolk weight, and percentage of yolk weight. Dietary ratio of ω-6 fatty acid to ω-3 fatty acid had impact on the 0-3 fatty acid levels in yolk, nevertheless yolk fatty acid profiles were different from those of dietary fatty acid compositions.
基金Supported by the National High-tech and Development of Program of China(No. 2003AA601060).
文摘A surfactant modified zeolite( SMZ), i. e. , a zeolite modified by using hexadecyl trimethyl ammonium bromide (HDTMA) was used to remove fulvic acids(FA) from aqueous solution. The effects of the relevant parameters, such as the loading level of HDTMA, the contact time, the initial FA concentration, the pH, and the types of the metal carious and organics were examined. The results show that SMZ with an HDTMA loading-level of 120% of the external cation exchange capacity(ECEC) of zeolite exhibits the best performance. Although the removal of fulvic acids by SMZ occurs rapidly within the first 30 min of the contact time, a contact time of at least 4 h is required to attain the adsorption equilibrium. The removal capacity of FA by SMZ decreases with the increase of the initial FA concentration. The pH has an effect on the FA removal efficiency because it can influence the characteristics of the FA molecules. The removal of FA is considerably enhanced by Ca^2+ or Mg^2+ ions and is adversely affected by phenol or pentachlorophenol(PCP). Under the optimum conditions, 98% of FA could be removed by SMZ. Furthermore, the desorption of FA and the regeneration of SMZ were studied. The results show that a 30% ethanol solution is sufficient for the regeneration of SMZ.
基金Project supported by the Medicine and Health Research Fund of Zhejiang Province(No.2007B091)the Office of Education of Zhejiang Province,China(No.20070104)
文摘Objective: To determine fatty acid synthase (FAS) expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods: FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction (RT-PCR) and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma (MM patients) and peripheral blood mononuclear cells (PBMCs) obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations (5 to 320 μg/ml) for 24 h, and metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Apoptosis was evaluated by dual Annexin V/Pl (propidium iodide) labeling and flow cytometry (FCM) in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results: By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^+/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^+/Pl^+ cells. Conclusion: Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.
文摘Mouse blastocysts were exposed to doses of 0, 1 and 10 μmol/L retinoic acid (RA) for 24 h and the cytotoxic effect of RA on the mouse blastocysts in vitro was observed. FITC-labeled terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL-FITC) assay was employed to stain apoptotic cells and immunohistochemical S-P staining method was used to detect the expression of Fas protein in mouse blastocysts in vitro. The results showed that RA could induce apoptosis and increase the expression of Fas proteins of trophectoderm (TE) and inner cell mass (ICM) cells in blastocysts. Compared with the findings for the control blastocysts, exposure to RA (10 μmol/L) resulted in a more significant apoptosis and higher expression level of Fas proteins (P〈0.01). It was concluded that RA could induce apoptosis, which may result in a significant reduction in the average number of total cells and the trophectoderm/inner cell mass in blastocysts and an increased expression of Fas protein, suggesting that RA had a cytotoxic effect on the growth and development of early embryos in mice.
基金Supported by the National Marine Public Welfare Research Project(No.201305043)the National Natural Science Foundation of China(No.41106134)the National Key Technology R&D Program of China(Nos.2011BAD13B02,2010BAC68B01)
文摘Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid profiles in aestivated and non-aestivated A.japonicus using multivariate analyses(PERMANOVA,MDS,ANOSIM,and SIMPER).The results indicate that the fatty acid profiles of aestivated and non-aestivated sea cucumbers differed significantly.The FAs that were produced by bacteria and brown kelp contributed the most to the differences in the fatty acid composition of aestivated and nonaestivated sea cucumbers.Aestivated sea cucumbers may synthesize FAs from heterotrophic bacteria during early aestivation,and long chain FAs such as eicosapentaenoic(EPA) and docosahexaenoic acid(DHA) that produced from intestinal degradation,are digested during deep aestivation.Specific changes in the fatty acid composition of A.japonicus during aestivation needs more detailed study in the future.
文摘AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). METHODS: Thirty-one patients with hystologically- confirmed, inoperable HCC, received combination chemotherapy with PLD 25 mg/mq on d 1, 5FU 1200 mg/mq in 48 h continuous infusion, and oral FA 30 mg on d 1 and 2 every 3 wk until disease progression or intolerable toxicity. RESULTS: The median age was 65 years (range 41-82) and 28 patients were hepatitis C virus seropositive (90%). The majority of patients were Child-Pugh Class B (55%). Two patients showed a partial response (PR), and 16 had stable disease (SD). With a median follow-up of 14 mo, the median time to progression of all evaluable patients was 4 mo (95% CI 1.7-7). Median overall survival was 9 mo (95% CI 3-24 mo). After 1 year, 9 of 18 PR/SD patients were alive. Chemotherapy was well tolerated. CONCLUSION: PLD/FU/FA combination seems capable of achieving durable stabilization of HCC. The manageable toxicity supports a role for combination with other anticancer agents.