BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current ...BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current use of MTX among French gastroenterologists.METHODS An online questionnaire was distributed between March and August 2023 to 116 French gastroenterologists managing CD.A total of 87 respondents completed the survey and were included in the analysis.RESULTS Respondents reported a mean annual caseload of 140 CD patients(median:50).Overall,71%prescribed MTX,predominantly in injectable form(92%),either as monotherapy or in combination with biologics or cyclosporin.MTX was prescribed for mild-to-moderate CD by 64%of respondents,and for severe CD by 58%,often in combination with an anti-tumor necrosis factor agent(89%and 94%,respectively).Injectable MTX was favored(84%)in specific clinical scenarios:Patients with articular manifestations(77%),Epstein-Barr virus-negative status(65%),or aged over 65 years(58%).Among the 29%of non-prescribers,the primary reason cited was lack of familiarity with MTX use(60%).Both prescribers and non-prescribers expressed the need for clearer guidelines and real-world data to support MTX use.CONCLUSION Regardless of prescribing habits,most respondents had a favorable opinion of MTX and recognized its good longterm safety profile.French learned societies and medical associations should provide consensus guidelines on MTX use,supported by validated real-world safety and effectiveness data.展开更多
Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis ...Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis and advanced liver fibrosis has been described in psoriasis.The influence of MetS and its compounds,patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 gene polymorphisms and the cumulative dose of methotrexate(MTX)in the progression of steatotic disease are still under debate.A suitable new classification for psoriasis-related liver disease,under the umbrella of steatotic liver disease(SLD),might be evaluated due to the potential impact of MTX on liver steatosis.Considering the interplay between the MetS,steatosis and MTX,a new definition for this complex disease might be discussed since it is not entirely addressed under the umbrella of SLD and metabolic-dysfunction associated SLD.Hence,shortly,a discussion could be raised on the feasible term“Met-Drug SLD”,metabolic and drug-induced SLD,which comprises both metabolic dysfunction and drug-related SLD.This review aims to report the best evidence to accurately classify liver disease in psoriasis,considering the new definition of SLD,allowing appropriate management once it is carefully defined.展开更多
This study aimed to establish a highly accurate method for quantifying methotrexate(MTX)concentrations in serum using an ultra-high performance liquid chromatography-tandem mass spectrometry system(UPLC-MS/MS)and to c...This study aimed to establish a highly accurate method for quantifying methotrexate(MTX)concentrations in serum using an ultra-high performance liquid chromatography-tandem mass spectrometry system(UPLC-MS/MS)and to compare its performance with the chemiluminescence microparticle immunoassay(CMIA).A total of 211 serum samples from pediatric patients with intracranial tumors undergoing high-dose MTX treatment were analyzed using both techniques.Correlation and agreement analyses were performed to assess the level of concordance between these methods.The results demonstrated a significant correlation(P<0.05)between the two methods,with correlation coefficients of 0.9913 and 0.9893,respectively.However,a statistical difference was noted in MTX serum concentrations at lower levels(0.04-1.5μmol/L),while no significant difference was observed at higher concentrations(1.5-400μmol/L).Specifically,in the 0.04-1.5μmol/L range(107 cases),Bland-Altman analysis indicated a bias of 0.018 between the two methods.Given the observed discrepancies,particularly at lower concentrations,it is advised that the UPLC-MS/MS method should not be used interchangeably with the CMIA assay for therapeutic drug monitoring in patients receiving high-dose MTX treatment.展开更多
In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients....In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.展开更多
Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to eva...Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.展开更多
OBJECTIVE: To systematically evaluate the curative clinical efficacy and safety of sinomenine(SIN) in treatment of rheumatoid arthritis(RA) in comparison to methotrexate(MTX).METHODS: We searched the China National Kn...OBJECTIVE: To systematically evaluate the curative clinical efficacy and safety of sinomenine(SIN) in treatment of rheumatoid arthritis(RA) in comparison to methotrexate(MTX).METHODS: We searched the China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, Pubmed and Cochrane Library electronically up to August 31,2015, without language limitation. Only randomized controlled trials(RCTs) were included. Software Review Manager 5.3 was used for Meta-analysis.RESULTS: A total of 16 eligible studies within 1500RA patients were included. The meta-analysis indicated that on basis of MTX, SIN was more effective in total effective rate(P < 0.000 01). Besides, SIN alone versus MTX also showed advantages in RA therapy(P = 0.04) Taken together, adverse events occurred less frequently in combination of SIN and MTX than MTX alone(P < 0.0001), especially in digestive system(P < 0.000 01),while occurred more in dermato mucosal system with SIN treatment versus MTX(P = 0.02), and were similar for both remedies in nervous system(P = 0.12) and hematological system(P = 0.25).CONCLUTION: Compared to MTX, SIN had better clinical efficacy and relatively fewer adverse events in treatment of RA, especially when it was used together with MTX. Due to the poor methodological quality, well-designed, multiple-center RCTs are still required to further confirm the findings.展开更多
Methotrexate(MTX)is a folate antagonist drug used for several diseases,such as cancers,various malignancies,rheumatoid arthritis(RA)and inflammatory bowel disease.Due to its structural features,including the presence ...Methotrexate(MTX)is a folate antagonist drug used for several diseases,such as cancers,various malignancies,rheumatoid arthritis(RA)and inflammatory bowel disease.Due to its structural features,including the presence of two carboxylic acid groups and its low native fluorescence,there are some challenges to develop analytical methods for its determination.MTX is metabolized to 7-hydroxymethotrexate(7-OH-MTX),2,4-diamino-N10-methylpteroic acid(DAMPA),and the active MTX polyglutamates(MTXPGs)in the liver,intestine,and red blood cells(RBCs),respectively.Additionally,the drug has a narrow therapeutic range;hence,its therapeutic drug monitoring(TDM)is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity.Due to environmental toxicity of MTX;its sensitive,fast and low cost determination in workplace environments is of great interest.A large number of methodologies including high performance liquid chromatography equipped with UVevisible,fluorescence,or electrochemical detection,liquid chromatography-mass spectroscopy,capillary electrophoresis,UVevisible spectrophotometry,and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical,biological,and environmental samples.This paper will attempt to review several published methodologies and the instrumental conditions,which have been applied to measure MTX and its metabolites within the last decade.展开更多
Methylprednisolone is a commonly used drug for the treatment of spinal cord injury, but high doses of methylprednisolone can increase the incidence of infectious diseases. Methotrexate has anti-inflammatory activity a...Methylprednisolone is a commonly used drug for the treatment of spinal cord injury, but high doses of methylprednisolone can increase the incidence of infectious diseases. Methotrexate has anti-inflammatory activity and immunosuppressive effects, and can reduce in- flammation after spinal cord injury. To analyze gene expression changes and the molecular mechanism of methotrexate combined with methylprednisolone in the treatment of spinal cord injury, a rat model of spinal cord contusion was prepared using the PinPointTM preci- sion cortical impactor technique. Rats were injected with methylprednisolone 30 mg/kg 30 minutes after injury, and then subcutaneously injected with 0.3 mg/kg methotrexate 1 day after injury, once a day, for 2 weeks. TreadScan gait analysis found that at 4 and 8 weeks after injury, methotrexate combined with methylprednisolone significantly improved hind limb swing time, stride time, minimum longitudinal deviation, instant speed, footprint area and regularity index. Solexa high-throughput sequencing was used to analyze differential gene ex- pression. Compared with methylprednisolone alone, differential expression of 316 genes was detected in injured spinal cord treated with methotrexate and methylprednisolone. The 275 up-regulated genes were mainly related to nerve recovery, anti-oxidative, anti-inflammatory and anti-apoptotic functions, while 41 down-regulated genes were mainly related to proinflammatory and pro-apoptotic functions. These results indicate that methotrexate combined with methylprednisolone exhibited better effects on inhibiting the activity of inflammatory cytokines and enhancing antioxidant and anti-apoptotic effects and thereby produced stronger neuroprotective effects than methotrexate alone. The 316 differentially expressed genes play an important role in the above processes.展开更多
Methotrexate(MTX)is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world.The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing c...Methotrexate(MTX)is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world.The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing concern due to its potential to induce water pollution.In the present study,the degradation of MTX in aqueous medium was investigated by UV-activated peroxymonosulfate(PMS).A significant improvement in degradation rate by increasing UV intensity and PMS concentration while the decrease in degradation efficiency with the increase of solution p H and initial concentration of MTX was observed.The proposed UV/PMS process could achieve more than 90%MTX degradation in 30 min with a good mineralization degree(65%).A pseudofirst order kinetic model was employed and successfully predicted the degradation of MTX.The effect of other operational parameters such as the initial concentration of the targeted compound,dosage of oxidant(PMS),solution p H and UV intensity on the degradation rate were investigated.At the last,the main transform intermediates were identified using LC–MS and possible degradation pathways were proposed.The results show that UV/PMS can be used as an efficient technology to treat pharmaceuticals such as methotrexate containing water and wastewater.展开更多
Methotrexate is the first line drug treatment for anumber of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than ...Methotrexate is the first line drug treatment for anumber of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than many alternatives. Use in rheumatoid arthritis infers a significant morbidity and mortality benefit. Methotrexate is generally well tolerated but can cause symptomatic adverse events. Multiple serious adverse events have been attributed to methotrexate, based largely on older reports using high or daily doses, and subsequent case reports and circumstantial evidence. The risk with modern dosing regimens: Lower doses, weekly schedules, and concomitant folic acid is less clear. Clarification and dissemination of the actual risk is crucial so appropriate judgements can be made for patients who may benefit from this treatment. Methotrexate has been associated with a range of liver related adverse events ranging from asymptomatic transaminase elevations to fibrosis and fatal hepatic necrosis. Concern over potential liver toxicity has resulted in treatment avoidance, cessation, or recommendations for investigations which may be costly, invasive and unwarranted. Modern laboratory monitoring of liver blood tests may also influence the risk of more serious complications. The majority of present day studies report an approximate doubling of the relative risk of elevated transaminases in methotrexate treated patients but no increased risk of symptomatic or severe liver related adverse events. In this article we will review the evidence around methotrexate and liver related adverse events.展开更多
OBJECTIVE: To investigate the effect of Sanhuangyilong decoction plus methotrexate(MTX) on Interferon gamma(IFN-γ) and tumor necrosis factor alpha(TNF-α) in the serum and synovial fluid of rheumatoid arthritis(RA) p...OBJECTIVE: To investigate the effect of Sanhuangyilong decoction plus methotrexate(MTX) on Interferon gamma(IFN-γ) and tumor necrosis factor alpha(TNF-α) in the serum and synovial fluid of rheumatoid arthritis(RA) patients with damp-heat-obstruction symptom pattern, Sanhuangyilong decoction and the role of TNF-α and IFN-γ in the development of RA.METHODS: RA inpatients with damp-heat-obstruction symptom pattern(partly with knee joint effusion) were selected as the research subjects. Before the treatment, healthy subjects and osteoarthritis(OA) patients with knee joint effusion were assigned to the serum control group and the synovial fluid control group, respectively; during the treatment, RA patients with damp-heat-obstruction symptom pattern were divided into two groups:one is combined group that was administered Sanhuangyilong decoction plus MTX; the other group was MTX group that received MTX only. The expression levels of TNF-α and IFN-γ in the serum and synovial fluid were measured with enzyme-linked immunosorbent assay(ELISA) before and after the treatment, and the peripheral blood levels of erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) and disease activity score in 28 joints(DAS28)were determined.RESULTS: Before treatment, the serum levels of TNF-α and IFN-γ in the RA patients with dampheat-obstruction symptom pattern were higher than those in healthy control group(P < 0.05).The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those in the serum of the RA patients(P < 0.05). The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those of the sy-novial fluid of the osteoarthritis patients(P < 0.05).The expression of TNF-α and IFN-γ in the serum and synovial fluid of the RA patients had no correlation with the inflammatory activity index ESR, CRP,or DAS28(P > 0.05). After 2 weeks of treatment, the expression level of TNF-α and IFN-γ in the combined group had increased, although the difference was not statistically significant(P > 0.05); in contrast, ESR, CRP, and DAS28 decreased, and the difference was statistically significant(P < 0.01). After 4 weeks of therapy, TNF-alpha and IFN-γ, ESR,CRP, and DAS28 in the combined group decreased compared with the before-treatment levels(P <0.01). After 2 w of treatment, the differences in the TNF-α and IFN-γ expression levels in the combined group were not statistically significant(P > 0.05)compared with that in the MTX group, although there were statistically significant differences in the ESR, CRP, and DAS28(P < 0.05). After 4 weeks of treatment, differences in TNF-α, IFN-γ, ESR, CRP, and DAS28 in the combined group compared with MTX group were statistically significant(P < 0.01).CONCLUSION: TNF-α and IFN-γ might be involved in the development of RA. The RA patients with damp-heat-obstruction symptom pattern show better benefits from the treatment of Sanhuangyilong decoction plus MTX, and the treatment is superior to that of using MTX only.展开更多
Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bo...Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn's disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.展开更多
AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.
Objective: To compare the degree of ameliorative effects of Melatonin(MEL), Ursodeoxycholic acid(UDCA) and Balanites aegyptiaca(BA) against hepatotoxicity induced by MTX for one month. Methods: Eighty adult male rats(...Objective: To compare the degree of ameliorative effects of Melatonin(MEL), Ursodeoxycholic acid(UDCA) and Balanites aegyptiaca(BA) against hepatotoxicity induced by MTX for one month. Methods: Eighty adult male rats(Sprague Dawely) weighing(190±10g), were randomly divided into eight equal groups: Control, MTX, MEL, BA, UDCA, MTX+MEL, MTX+BA, MTX+UDCA. Liver function biomarker enzymes, liver tissue oxidative stress parameters, together with total antioxidant capacity and tumor necrosis factor(TNF-α) were determined. Histopathological and immunohistochemistry examinations for TNF-α were also done. Results: MTX showed significant increase in alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), gamma glutamyl transferase(GGT), total and direct bilirubin, as well as TNF-α levels, oxidized glutathione(GSSG), malodialdehyde(MDA) and nitric oxide(NO). whereas, total protein, albumin, total antioxidant capacity, reduced glutathione(GSH), glutathione peroxidase(GPx), glutathione reductase(GR), glutathione S-transferase(GST), superoxide dismutase(SOD) and catalase(CAT) levels were significantly decreased in MTX treated group. These alterations were improved by MEL and BA treatment, whereas no improvement was noticed in UDCA treatment. Conclusions: BA may be as promising as MEL in the hepatoprotection against MTX toxicity through their antioxidant and radical scavenging activities. In addition, it is not recommended to co-administer UDCA with MTX as it enhanced inflammation and damage to the liver.展开更多
AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology. METHODS: Pati...AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology. METHODS: Patients with psoriasis treated with MTX referred to the Department of Gastroenterology, Tan Tock Seng Hospital for liver biopsy were identified and retrospectively studied. Patient case notes and electronic records were retrieved from the hospital database and relevant data collated. Histological changes of liver biopsies were staged according to Roengik score. The factors assessed were age, gender, ethnicity, cumulative dose of MTX, presence of comorbid conditions such as diabetes, hypertension, hyperlipidemia, and ethanol use. We also assessed the histological change in those with multiple liver biopsies. Statistical analysis was performed using Stata V.9.2. RESULTS: There were altogether 59 patients (median age 50 years old, range 22-81 years old, male, 88%) with 98 biopsies liver biopsies; 6 normal [median cumulative dose (MCD), 2285 mg]; 62 gradeⅠ (MCD 2885 mg), 23 grade Ⅱ (MCD 1800 mg) and 7 grade Ⅲ (MCD 1500 mg). There was no grade Ⅳ or cirrhosis. The prevalence of liver fibrosis (grade Ⅲ) was 12%. Of the factors assessed, diabetes (P=0.001) and hypertension (P=0.003) were significant for fibrosis on univariate analysis but not on multivariate analysis. Of the 26 patients who had more than one biopsy (median 2, range 2-6), 57.7% (n=15) were stable, 34.6% (n=9) had progression and 7.7% (n=2) had regression of histological grades. On univariate analysis, nonChinese ethnicity (P=0.031), diabetes (P=0.018), and hyperlipidemia (P=0.011) were predictive of progression of grades, but these were not significant on multivariate analysis. CONCLUSION: Liver fibrosis in Asian psoriatic population on MTX is comparable to the West. Cumulative dose was not associated with liver fibrosis. Metabolic syndrome is important factors.展开更多
We report the case of a cervical pregnancy successfully treated with intramuscular injection of methotrexate(MTX) and intramniotic administration of potassium chloride. A 41-year-old woman was admitted to our Departme...We report the case of a cervical pregnancy successfully treated with intramuscular injection of methotrexate(MTX) and intramniotic administration of potassium chloride. A 41-year-old woman was admitted to our Department with the suspicion of ectopic pregnancy. Transvaginal ultrasound revealed empty endometrialcavity, gestational sac within the cervical canal and embryonic echo measuring crown rump length 1.5 mm. Serum beta human chorionic gonadotropine(β-HCG) was measured 28590 IU/L. No cardiac activity was detected. The diagnosis of a cervical pregnancy was made. Patient was treated with intramuscular administration of methotrexate(50 mg/m2) in combination with ultrasoundguided intramniotic injection of KCl(2 meq/mL). Gradual decrease of β-HCG levels as well as ultrasound observation of collapsed gestational sac was observed. No curettage was necessitated. Patient was discharged on day 10 th and was set in follow-up on a weekly basis. β-HCG values were measured < 10 IU/L on 56 th day after MTX administration. Intramuscular administration of MTX may be effective in treatment of cervical pregnancy without additional interventional measures.展开更多
We described clinical process of two cases of intraocular lymphoma in aspects of early diagnosis by fine needle aspiration（FNA） and biopsy and treatment by intravitreal methotrexate（MTX）.Two patients were suspecte...We described clinical process of two cases of intraocular lymphoma in aspects of early diagnosis by fine needle aspiration（FNA） and biopsy and treatment by intravitreal methotrexate（MTX）.Two patients were suspected to have primary intraocular lymphoma（PIOL） with geographic yellow-white infiltrates and vitreous opacity.FNA confirmed malignant intraocular lymphoma in one patient and failed in the other patient due to complication of vitreous hemorrhage.Subsequent vitreous biopsy confirmed malignant intraocular lymphoma in the other patient.Both patients were treated by intravitreal methotrexate.In case 1 the tumor had complete remission and follow-up of 12 months had not found any signs of recurrence.In case 2 the patient died of brain metastasis 22 months after the ocular biopsy.Our findings demonstrate that although cytological examination of vitrectomy specimens remains the gold standard in diagnosis of PIOL,examination of FNA and biopsy increases the reliability of early diagnosing or excluding a PIOL.Individualized intravitreal methotrexate can be used to effectively treat PIOL.More effective integrated program treating primary central nervous system lymphoma/PIOL is worthy of looking forward to.展开更多
Over one half the patients with rheumatoid arthritis （RA） are being treated with methotrexate （MTX）. Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic bioma...Over one half the patients with rheumatoid arthritis （RA） are being treated with methotrexate （MTX）. Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis （CIA） and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M 1H-nuclear magnetic resonance （1H-NMR） for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats （n=20） was different from that from the non-responsive rats （n=11）. Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis （PLS-DA） （R2=0.812, Q2=0.604）. In targeted profiling, 13 endogenous metabolites （uric acid, taurine, histidine, methionine, glycine, etc.） were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that 1H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.展开更多
A 27-year-old patient was diagnosed by hysteroscopy with uterine diverticulum in pregnancy and admitted to the hospital. Under the guidance of hysteroscopy combined with methotrexate, the scraping of the uterus was do...A 27-year-old patient was diagnosed by hysteroscopy with uterine diverticulum in pregnancy and admitted to the hospital. Under the guidance of hysteroscopy combined with methotrexate, the scraping of the uterus was done and operation successfully completed. The management of this case showed that hysteroscopy was a kind of valuable approach to the diagnosis and treatment of uterine diverticulum and curettage of the uterus under hysteroscope combined with drug was a safe, effective and conservative treatment.展开更多
Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced ...Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate （40 mg/kg） intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase （1 day post-injection）, while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the eady （1 day post-injection） and late phases （7-14 days post-injection）. Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase （7-14 days post-injection）. Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.展开更多
文摘BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current use of MTX among French gastroenterologists.METHODS An online questionnaire was distributed between March and August 2023 to 116 French gastroenterologists managing CD.A total of 87 respondents completed the survey and were included in the analysis.RESULTS Respondents reported a mean annual caseload of 140 CD patients(median:50).Overall,71%prescribed MTX,predominantly in injectable form(92%),either as monotherapy or in combination with biologics or cyclosporin.MTX was prescribed for mild-to-moderate CD by 64%of respondents,and for severe CD by 58%,often in combination with an anti-tumor necrosis factor agent(89%and 94%,respectively).Injectable MTX was favored(84%)in specific clinical scenarios:Patients with articular manifestations(77%),Epstein-Barr virus-negative status(65%),or aged over 65 years(58%).Among the 29%of non-prescribers,the primary reason cited was lack of familiarity with MTX use(60%).Both prescribers and non-prescribers expressed the need for clearer guidelines and real-world data to support MTX use.CONCLUSION Regardless of prescribing habits,most respondents had a favorable opinion of MTX and recognized its good longterm safety profile.French learned societies and medical associations should provide consensus guidelines on MTX use,supported by validated real-world safety and effectiveness data.
文摘Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis and advanced liver fibrosis has been described in psoriasis.The influence of MetS and its compounds,patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 gene polymorphisms and the cumulative dose of methotrexate(MTX)in the progression of steatotic disease are still under debate.A suitable new classification for psoriasis-related liver disease,under the umbrella of steatotic liver disease(SLD),might be evaluated due to the potential impact of MTX on liver steatosis.Considering the interplay between the MetS,steatosis and MTX,a new definition for this complex disease might be discussed since it is not entirely addressed under the umbrella of SLD and metabolic-dysfunction associated SLD.Hence,shortly,a discussion could be raised on the feasible term“Met-Drug SLD”,metabolic and drug-induced SLD,which comprises both metabolic dysfunction and drug-related SLD.This review aims to report the best evidence to accurately classify liver disease in psoriasis,considering the new definition of SLD,allowing appropriate management once it is carefully defined.
基金The Science and Technology Fund of Beijing Shijitan Hospital(Grant No.2022-C06)the National Key Research and Development Program of China(Grant No.2020YFF01014606).
文摘This study aimed to establish a highly accurate method for quantifying methotrexate(MTX)concentrations in serum using an ultra-high performance liquid chromatography-tandem mass spectrometry system(UPLC-MS/MS)and to compare its performance with the chemiluminescence microparticle immunoassay(CMIA).A total of 211 serum samples from pediatric patients with intracranial tumors undergoing high-dose MTX treatment were analyzed using both techniques.Correlation and agreement analyses were performed to assess the level of concordance between these methods.The results demonstrated a significant correlation(P<0.05)between the two methods,with correlation coefficients of 0.9913 and 0.9893,respectively.However,a statistical difference was noted in MTX serum concentrations at lower levels(0.04-1.5μmol/L),while no significant difference was observed at higher concentrations(1.5-400μmol/L).Specifically,in the 0.04-1.5μmol/L range(107 cases),Bland-Altman analysis indicated a bias of 0.018 between the two methods.Given the observed discrepancies,particularly at lower concentrations,it is advised that the UPLC-MS/MS method should not be used interchangeably with the CMIA assay for therapeutic drug monitoring in patients receiving high-dose MTX treatment.
文摘In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.
基金supported by the National Natural Science Foundation of China(No.81700147 and No.82070172).
文摘Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.
基金Supported by National Natural Science Foundation of China(Based on VIP to Investigate the Mechanism of Lung-Intestines Combined Therapeutic Method in Treating Sjogren's Syndrome No.81473607)State Administration of Traditional Chinese Medicine Key Discipline Open Project(Bi-Syndrome of Traditional Chinese Medicine Science,No.BBXK2013101)
文摘OBJECTIVE: To systematically evaluate the curative clinical efficacy and safety of sinomenine(SIN) in treatment of rheumatoid arthritis(RA) in comparison to methotrexate(MTX).METHODS: We searched the China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, Pubmed and Cochrane Library electronically up to August 31,2015, without language limitation. Only randomized controlled trials(RCTs) were included. Software Review Manager 5.3 was used for Meta-analysis.RESULTS: A total of 16 eligible studies within 1500RA patients were included. The meta-analysis indicated that on basis of MTX, SIN was more effective in total effective rate(P < 0.000 01). Besides, SIN alone versus MTX also showed advantages in RA therapy(P = 0.04) Taken together, adverse events occurred less frequently in combination of SIN and MTX than MTX alone(P < 0.0001), especially in digestive system(P < 0.000 01),while occurred more in dermato mucosal system with SIN treatment versus MTX(P = 0.02), and were similar for both remedies in nervous system(P = 0.12) and hematological system(P = 0.25).CONCLUTION: Compared to MTX, SIN had better clinical efficacy and relatively fewer adverse events in treatment of RA, especially when it was used together with MTX. Due to the poor methodological quality, well-designed, multiple-center RCTs are still required to further confirm the findings.
基金support of the Vice-Chancellor for Research,Shiraz University of Medical Sciences,Iran(project No.97-01-36-18308)
文摘Methotrexate(MTX)is a folate antagonist drug used for several diseases,such as cancers,various malignancies,rheumatoid arthritis(RA)and inflammatory bowel disease.Due to its structural features,including the presence of two carboxylic acid groups and its low native fluorescence,there are some challenges to develop analytical methods for its determination.MTX is metabolized to 7-hydroxymethotrexate(7-OH-MTX),2,4-diamino-N10-methylpteroic acid(DAMPA),and the active MTX polyglutamates(MTXPGs)in the liver,intestine,and red blood cells(RBCs),respectively.Additionally,the drug has a narrow therapeutic range;hence,its therapeutic drug monitoring(TDM)is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity.Due to environmental toxicity of MTX;its sensitive,fast and low cost determination in workplace environments is of great interest.A large number of methodologies including high performance liquid chromatography equipped with UVevisible,fluorescence,or electrochemical detection,liquid chromatography-mass spectroscopy,capillary electrophoresis,UVevisible spectrophotometry,and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical,biological,and environmental samples.This paper will attempt to review several published methodologies and the instrumental conditions,which have been applied to measure MTX and its metabolites within the last decade.
基金supported by the National Natural Science Foundation of China,No.30960448the Natural Science Foundation of Jiangxi Province,No.20142BAB205023the Ph.D.Start-up Fund of Natural Science Foundation of Jiangxi Science&Technology Normal University in China,No.3000990122
文摘Methylprednisolone is a commonly used drug for the treatment of spinal cord injury, but high doses of methylprednisolone can increase the incidence of infectious diseases. Methotrexate has anti-inflammatory activity and immunosuppressive effects, and can reduce in- flammation after spinal cord injury. To analyze gene expression changes and the molecular mechanism of methotrexate combined with methylprednisolone in the treatment of spinal cord injury, a rat model of spinal cord contusion was prepared using the PinPointTM preci- sion cortical impactor technique. Rats were injected with methylprednisolone 30 mg/kg 30 minutes after injury, and then subcutaneously injected with 0.3 mg/kg methotrexate 1 day after injury, once a day, for 2 weeks. TreadScan gait analysis found that at 4 and 8 weeks after injury, methotrexate combined with methylprednisolone significantly improved hind limb swing time, stride time, minimum longitudinal deviation, instant speed, footprint area and regularity index. Solexa high-throughput sequencing was used to analyze differential gene ex- pression. Compared with methylprednisolone alone, differential expression of 316 genes was detected in injured spinal cord treated with methotrexate and methylprednisolone. The 275 up-regulated genes were mainly related to nerve recovery, anti-oxidative, anti-inflammatory and anti-apoptotic functions, while 41 down-regulated genes were mainly related to proinflammatory and pro-apoptotic functions. These results indicate that methotrexate combined with methylprednisolone exhibited better effects on inhibiting the activity of inflammatory cytokines and enhancing antioxidant and anti-apoptotic effects and thereby produced stronger neuroprotective effects than methotrexate alone. The 316 differentially expressed genes play an important role in the above processes.
基金the financial support of research grants from the Hong Kong Polytechnic University(Q67H)and Higher Education Commission(HEC),Pakistan for the financial support during IRSIP。
文摘Methotrexate(MTX)is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world.The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing concern due to its potential to induce water pollution.In the present study,the degradation of MTX in aqueous medium was investigated by UV-activated peroxymonosulfate(PMS).A significant improvement in degradation rate by increasing UV intensity and PMS concentration while the decrease in degradation efficiency with the increase of solution p H and initial concentration of MTX was observed.The proposed UV/PMS process could achieve more than 90%MTX degradation in 30 min with a good mineralization degree(65%).A pseudofirst order kinetic model was employed and successfully predicted the degradation of MTX.The effect of other operational parameters such as the initial concentration of the targeted compound,dosage of oxidant(PMS),solution p H and UV intensity on the degradation rate were investigated.At the last,the main transform intermediates were identified using LC–MS and possible degradation pathways were proposed.The results show that UV/PMS can be used as an efficient technology to treat pharmaceuticals such as methotrexate containing water and wastewater.
文摘Methotrexate is the first line drug treatment for anumber of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than many alternatives. Use in rheumatoid arthritis infers a significant morbidity and mortality benefit. Methotrexate is generally well tolerated but can cause symptomatic adverse events. Multiple serious adverse events have been attributed to methotrexate, based largely on older reports using high or daily doses, and subsequent case reports and circumstantial evidence. The risk with modern dosing regimens: Lower doses, weekly schedules, and concomitant folic acid is less clear. Clarification and dissemination of the actual risk is crucial so appropriate judgements can be made for patients who may benefit from this treatment. Methotrexate has been associated with a range of liver related adverse events ranging from asymptomatic transaminase elevations to fibrosis and fatal hepatic necrosis. Concern over potential liver toxicity has resulted in treatment avoidance, cessation, or recommendations for investigations which may be costly, invasive and unwarranted. Modern laboratory monitoring of liver blood tests may also influence the risk of more serious complications. The majority of present day studies report an approximate doubling of the relative risk of elevated transaminases in methotrexate treated patients but no increased risk of symptomatic or severe liver related adverse events. In this article we will review the evidence around methotrexate and liver related adverse events.
基金Supported by National Natural Science Foundation Project of China(Investigation of the Influence of Functional Polymorphisms in ANAPC4 on Susceptibility to Rheumatoid Arthritis,No.81072455)the Army Medical Research "Twelfth Five Year Plan" Key Project(High Humidity Environment Factors Damage the Establishment of Appropriate Technology Platform and Study Comprehensive Medical Service Safeguard Measures,No.BWS11J06)the Sichuan Provincial Health Department(Study the Regulatory Mechanism of the Cells in Rheumatoid Arthritis Treated with Sanhuangyilong Decoction and its Component united with Methotrexate,No.120573)
文摘OBJECTIVE: To investigate the effect of Sanhuangyilong decoction plus methotrexate(MTX) on Interferon gamma(IFN-γ) and tumor necrosis factor alpha(TNF-α) in the serum and synovial fluid of rheumatoid arthritis(RA) patients with damp-heat-obstruction symptom pattern, Sanhuangyilong decoction and the role of TNF-α and IFN-γ in the development of RA.METHODS: RA inpatients with damp-heat-obstruction symptom pattern(partly with knee joint effusion) were selected as the research subjects. Before the treatment, healthy subjects and osteoarthritis(OA) patients with knee joint effusion were assigned to the serum control group and the synovial fluid control group, respectively; during the treatment, RA patients with damp-heat-obstruction symptom pattern were divided into two groups:one is combined group that was administered Sanhuangyilong decoction plus MTX; the other group was MTX group that received MTX only. The expression levels of TNF-α and IFN-γ in the serum and synovial fluid were measured with enzyme-linked immunosorbent assay(ELISA) before and after the treatment, and the peripheral blood levels of erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) and disease activity score in 28 joints(DAS28)were determined.RESULTS: Before treatment, the serum levels of TNF-α and IFN-γ in the RA patients with dampheat-obstruction symptom pattern were higher than those in healthy control group(P < 0.05).The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those in the serum of the RA patients(P < 0.05). The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those of the sy-novial fluid of the osteoarthritis patients(P < 0.05).The expression of TNF-α and IFN-γ in the serum and synovial fluid of the RA patients had no correlation with the inflammatory activity index ESR, CRP,or DAS28(P > 0.05). After 2 weeks of treatment, the expression level of TNF-α and IFN-γ in the combined group had increased, although the difference was not statistically significant(P > 0.05); in contrast, ESR, CRP, and DAS28 decreased, and the difference was statistically significant(P < 0.01). After 4 weeks of therapy, TNF-alpha and IFN-γ, ESR,CRP, and DAS28 in the combined group decreased compared with the before-treatment levels(P <0.01). After 2 w of treatment, the differences in the TNF-α and IFN-γ expression levels in the combined group were not statistically significant(P > 0.05)compared with that in the MTX group, although there were statistically significant differences in the ESR, CRP, and DAS28(P < 0.05). After 4 weeks of treatment, differences in TNF-α, IFN-γ, ESR, CRP, and DAS28 in the combined group compared with MTX group were statistically significant(P < 0.01).CONCLUSION: TNF-α and IFN-γ might be involved in the development of RA. The RA patients with damp-heat-obstruction symptom pattern show better benefits from the treatment of Sanhuangyilong decoction plus MTX, and the treatment is superior to that of using MTX only.
文摘Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn's disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.
文摘AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.
文摘Objective: To compare the degree of ameliorative effects of Melatonin(MEL), Ursodeoxycholic acid(UDCA) and Balanites aegyptiaca(BA) against hepatotoxicity induced by MTX for one month. Methods: Eighty adult male rats(Sprague Dawely) weighing(190±10g), were randomly divided into eight equal groups: Control, MTX, MEL, BA, UDCA, MTX+MEL, MTX+BA, MTX+UDCA. Liver function biomarker enzymes, liver tissue oxidative stress parameters, together with total antioxidant capacity and tumor necrosis factor(TNF-α) were determined. Histopathological and immunohistochemistry examinations for TNF-α were also done. Results: MTX showed significant increase in alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), gamma glutamyl transferase(GGT), total and direct bilirubin, as well as TNF-α levels, oxidized glutathione(GSSG), malodialdehyde(MDA) and nitric oxide(NO). whereas, total protein, albumin, total antioxidant capacity, reduced glutathione(GSH), glutathione peroxidase(GPx), glutathione reductase(GR), glutathione S-transferase(GST), superoxide dismutase(SOD) and catalase(CAT) levels were significantly decreased in MTX treated group. These alterations were improved by MEL and BA treatment, whereas no improvement was noticed in UDCA treatment. Conclusions: BA may be as promising as MEL in the hepatoprotection against MTX toxicity through their antioxidant and radical scavenging activities. In addition, it is not recommended to co-administer UDCA with MTX as it enhanced inflammation and damage to the liver.
文摘AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology. METHODS: Patients with psoriasis treated with MTX referred to the Department of Gastroenterology, Tan Tock Seng Hospital for liver biopsy were identified and retrospectively studied. Patient case notes and electronic records were retrieved from the hospital database and relevant data collated. Histological changes of liver biopsies were staged according to Roengik score. The factors assessed were age, gender, ethnicity, cumulative dose of MTX, presence of comorbid conditions such as diabetes, hypertension, hyperlipidemia, and ethanol use. We also assessed the histological change in those with multiple liver biopsies. Statistical analysis was performed using Stata V.9.2. RESULTS: There were altogether 59 patients (median age 50 years old, range 22-81 years old, male, 88%) with 98 biopsies liver biopsies; 6 normal [median cumulative dose (MCD), 2285 mg]; 62 gradeⅠ (MCD 2885 mg), 23 grade Ⅱ (MCD 1800 mg) and 7 grade Ⅲ (MCD 1500 mg). There was no grade Ⅳ or cirrhosis. The prevalence of liver fibrosis (grade Ⅲ) was 12%. Of the factors assessed, diabetes (P=0.001) and hypertension (P=0.003) were significant for fibrosis on univariate analysis but not on multivariate analysis. Of the 26 patients who had more than one biopsy (median 2, range 2-6), 57.7% (n=15) were stable, 34.6% (n=9) had progression and 7.7% (n=2) had regression of histological grades. On univariate analysis, nonChinese ethnicity (P=0.031), diabetes (P=0.018), and hyperlipidemia (P=0.011) were predictive of progression of grades, but these were not significant on multivariate analysis. CONCLUSION: Liver fibrosis in Asian psoriatic population on MTX is comparable to the West. Cumulative dose was not associated with liver fibrosis. Metabolic syndrome is important factors.
文摘We report the case of a cervical pregnancy successfully treated with intramuscular injection of methotrexate(MTX) and intramniotic administration of potassium chloride. A 41-year-old woman was admitted to our Department with the suspicion of ectopic pregnancy. Transvaginal ultrasound revealed empty endometrialcavity, gestational sac within the cervical canal and embryonic echo measuring crown rump length 1.5 mm. Serum beta human chorionic gonadotropine(β-HCG) was measured 28590 IU/L. No cardiac activity was detected. The diagnosis of a cervical pregnancy was made. Patient was treated with intramuscular administration of methotrexate(50 mg/m2) in combination with ultrasoundguided intramniotic injection of KCl(2 meq/mL). Gradual decrease of β-HCG levels as well as ultrasound observation of collapsed gestational sac was observed. No curettage was necessitated. Patient was discharged on day 10 th and was set in follow-up on a weekly basis. β-HCG values were measured < 10 IU/L on 56 th day after MTX administration. Intramuscular administration of MTX may be effective in treatment of cervical pregnancy without additional interventional measures.
文摘We described clinical process of two cases of intraocular lymphoma in aspects of early diagnosis by fine needle aspiration（FNA） and biopsy and treatment by intravitreal methotrexate（MTX）.Two patients were suspected to have primary intraocular lymphoma（PIOL） with geographic yellow-white infiltrates and vitreous opacity.FNA confirmed malignant intraocular lymphoma in one patient and failed in the other patient due to complication of vitreous hemorrhage.Subsequent vitreous biopsy confirmed malignant intraocular lymphoma in the other patient.Both patients were treated by intravitreal methotrexate.In case 1 the tumor had complete remission and follow-up of 12 months had not found any signs of recurrence.In case 2 the patient died of brain metastasis 22 months after the ocular biopsy.Our findings demonstrate that although cytological examination of vitrectomy specimens remains the gold standard in diagnosis of PIOL,examination of FNA and biopsy increases the reliability of early diagnosing or excluding a PIOL.Individualized intravitreal methotrexate can be used to effectively treat PIOL.More effective integrated program treating primary central nervous system lymphoma/PIOL is worthy of looking forward to.
文摘Over one half the patients with rheumatoid arthritis （RA） are being treated with methotrexate （MTX）. Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis （CIA） and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M 1H-nuclear magnetic resonance （1H-NMR） for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats （n=20） was different from that from the non-responsive rats （n=11）. Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis （PLS-DA） （R2=0.812, Q2=0.604）. In targeted profiling, 13 endogenous metabolites （uric acid, taurine, histidine, methionine, glycine, etc.） were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that 1H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
文摘A 27-year-old patient was diagnosed by hysteroscopy with uterine diverticulum in pregnancy and admitted to the hospital. Under the guidance of hysteroscopy combined with methotrexate, the scraping of the uterus was done and operation successfully completed. The management of this case showed that hysteroscopy was a kind of valuable approach to the diagnosis and treatment of uterine diverticulum and curettage of the uterus under hysteroscope combined with drug was a safe, effective and conservative treatment.
基金supported by the National Research Foundation of Korea Grant funded by the Korean Government(No. NRF-2010-0015393)supported by Animal Medical Institute of Chonnam Na-tional University
文摘Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate （40 mg/kg） intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase （1 day post-injection）, while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the eady （1 day post-injection） and late phases （7-14 days post-injection）. Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase （7-14 days post-injection）. Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.
