Different Doses Of Methotrexate Research Articles

Assessment of the Effects of Two Different Doses of Methotrexate in Rat Ovarian Tissue: A Histological Study

Objective: The use of methotrexate (MTH), a drug commonly prescribed to treat rheumatoid arthritis, cancer, and certain autoimmune diseases, has been linked to early ovarian failure and infertility in women when used in varying amounts and durations. In this study, the possible effects of MTH exposure at different doses on rat ovary were investigated histologically and immunohistochemically. Materials and Methods: A total of 21 female rats, Wistar albino, were utilized in the investigation. The control group (n = 7) was not subjected to any treatment. The 10 mg/kg MTH group (n = 7) and the 20 mg/kg MTH group (n = 7) were given intraperitoneal injections of 10 mg/kg and 20 mg/kg methotrexate, respectively. Five days after injection, the ovarian tissues were taken out of the anesthetized rats and subjected to routine histological tissue processing. The histological evaluation was performed with hematoxylin and eosin (H & E) and Masson's trichrome (MT) on paraffin block sections. Additionally, immunohistochemical staining was performed to determine AMH immunoreactivity. Results: In both MTH groups, histopathological changes were observed, particularly in the 20 mg/kg group, and these included the presence of areas of edema as well as dilated or congested blood vessels. Furthermore, the 20 mg/kg MTH group exhibited increased fibrotic tissue in the ovarian medulla. The number of follicles and AMH immunoreactivity were observed to be reduced in the MTH groups, with the reduction reaching a statistically significant level in the 20 mg/kg MTH group ovary. In terms of AMH immunoreactivity, it is demonstrated that there is no statistical significance between the control and 10 mg/kg MTH groups. Conclusion: The dose of MTH should be considered carefully, as increasing the dose may lead to deterioration of ovarian histopathology and a reduction in the reserve of the ovary.

TNF-α and TNF-R-1 level in pregnancy with ecotopic pregnancy

The aim of our work was to study the relationship of tumor necrotic factor and receptor 1 to tumor necrotic factor in physiological uterine pregnancy in the first trimester and in pregnant women with ectopic pregnancy who received different doses of cytostatic methotrexate for its treatment.Methods and materialsWe analyzed the results of special research methods and examined 30 pregnant women with advanced uterine pregnancy in the first trimester and 40 pregnant women with advanced ectopic pregnancy treated with methotrexate, depending on the dose of methotrexate patients were divided into 2 groups of 20 women. The first group (M1) received 75-100 mg (based on kg of weight) of methotrexate intramuscularly, and the second group (M2) received methotrexate at a dose of 75-100 mg twice after 7 days.Research resultsIn healthy pregnant women with physiological pregnancy for 3-4 weeks, the level of TNF-α in blood neutrophils was within 2.02 ± 0.16 ng / ml and in pregnant women with ectopic pregnancy - 2.64 ± 0.19 ng / ml. In the M1 group, TNF-α level was slightly higher (5.49 ± 0.24 ng / ml, p <0.01) than in the group of women with ectopic pregnancy before treatment (2.64 ± 0.19) ng / ml, whereas in the methotrexate (M2) reintroduction group this indicator increased almost 4 times (10.30 ± 0.26 ng / ml) and in the M1 group almost 2.3 times (5.49 ± 0.24) ng / ml). The number of activated TNF-R1 neutrophils in the M1 group was (11.16 ± 0.30) ng / ml, versus (16.26 ± 0.43) ng / ml in the M2 group (p <0.05).ConclusionsNeutrophil blood cells are sensitive cells of the body to study the assessment of the depth of action of cytostatic at the body level as a whole.Indicators of tumor necrotic factor and receptor 1 tumor necrotic factor can be used as a marker of activity of cytotoxic action of different doses of methotrexate for the treatment of progressing ectopic pregnancy.

Effect of methotrexate on regulation for the number of regulatory T cells and expression of Foxp3 in psoriasis

To explore the role of methotrexate (MTX) in regulating the number of regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3. Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8-week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in mice every day. The morphological changes of lesion in mice were evaluated by the psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was randomly divided into a control group and an MTX group. The MTX group was treated with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this experiment. The morphological changes of lesion in mice were evaluated by PASI and HE staining. We tested the number of Treg and the expression level of Foxp3 mRNA in splenic lymphocytes. Results: 1) The number of Treg and the expression level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical psoriasis-like skin lesions, such as red scaly skin plaque were found after topical application of IMQ. Both the number of Treg in the splenic lymphocytes of mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3) Different doses of MTX for mice showed the ability to improve skin lesion, increase the number of Treg in the spleen of mice and Foxp3 mRNA level in psoriatic dermatitis of mice (P<0.05). Conclusion: MTX is able to regulate the number of Treg and Foxp3 mRNA expression in psoriasis.

Similar Improvements in Patient-Reported Outcomes Among Rheumatoid Arthritis Patients Treated with Two Different Doses of Methotrexate in Combination with Adalimumab: Results From the MUSICA Trial.

In patients with rheumatoid arthritis (RA), combination treatment with methotrexate (MTX) and adalimumab is more effective than MTX monotherapy. From the patients' perspective, the impact of reduced MTX doses upon initiating adalimumab is not known. The objective was to evaluate the effects of low and high MTX doses in combination with adalimumab initiation on patient-reported outcomes (PROs), in MTX-inadequate responders (MTX-IR) with moderate-to-severe RA. MUSICA was a randomized, double-blind, controlled trial evaluating the efficacy of 7.5 or 20mg/week MTX, in combination with adalimumab for 24weeks in MTX-IR RA patients receiving prior MTX ≥ 15mg/week for ≥ 12weeks. PROs were recorded at each visit, including physical function, health-related quality-of-life, work productivity, quality-of-sleep, satisfaction with treatment medication, sexual impairment due to RA, patient global assessment of disease activity (PGA), and patient pain. Last observation carried forward was used to account for missing values. At baseline, patients in both MTX dosage groups had similar demographics, disease characteristics, and PRO scores. Overall, initiation of adalimumab led to significant improvements from baseline in the PROs assessed for both MTX dosage groups. Improvements in presenteeism from baseline were strongly correlated with corresponding improvements in SF-36 (vitality), pain, and physical function. Physical and mental well-being had a good correlation with improvement in sleep. Overall, improvements in disease activity from baseline were correlated with improvements in several PROs. The addition of adalimumab to MTX in MTX-IR patients with moderate-to-severe RA led to improvements in physical function, quality-of-life, work productivity, quality of sleep, satisfaction with treatment medication, and sexual impairment due to RA, regardless of the concomitant MTX dosage. AbbVie. Clinicaltrials.gov identifier, NCT01185288.

Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab

BackgroundTreatment of rheumatoid arthritis (RA) with a combination of methotrexate (MTX)+adalimumab (ADA) is more effective than ADA monotherapy. We assessed the toxicity of different doses of MTX and treatment efficacy...

Anti-ulcerative, Anti-oxidative, and Anti-inflammatory Effects of Rosuvastatin and Isosorbide Dinitrate on Cysteamine-Induced Chronic Duodenal Ulcer in Rats

Background: Methotrexate (MXT) is the corner stone in treatment of rheumatoid arthritis. Although methotrexate is usually administrated in low weakly dose in patients with rheumatoid arthritis discontinuation rates are as high as 16% due to adverse effects. Hepatotoxicity is the most common side effect after long term course of methotrexate. Aim of the study: This work aimed to investigate the potential effect of sitagliptin alone and in combination with different doses of methotrexate on rheumatoid arthritis (RA) induced experimentally in rats. Moreover, we investigated the benefits of sitaglipitn co-administration with methotrexate not only on RA progression, but also on organs commonly injured on using methotrexate alone as a disease-modifying anti-rheumatic drug such as the liver. Methods: 42 male adult Sprague Dawley rats divided into seven equal groups: Normal control group, None treated Freund,s adjuvant induced rheumatoid arthritis,High dose MXT treated rheumatoid arthritis (1 mg/kg/3 days i.p.) over 4 weeks,Sitagliptin treated rheumatoid arthritis (10 mg/kg/day p.o) for 4 weeks, high dose MXT+ sitagliptin treated arthritis, 1/2 dose MXT+ sitagliptin treated arthritis, 1/4 dose MXT+ sitagliptin treated arthritis. Serological parameters namely, cyclic citrullinated peptide antibodies (Anti-CCP), matrix metalloproteinase-3(MMP-3), cartilage oligometric matrix protein (COMP) and TNF-α level were measured. Liver tissue and hind paw joint were subjected to histopathological examination. Results: Best degree of improvement was obtained with high dose MXT+ sitagliptin. It is significantly better than that of either drug alone. Half dose of MXT /sitagliptin combination was proved to be equally effective to the full dose of methotrexate alone regarding all tested parameters. Conclusion: concomitant administration of sitagliptin augmented immunosuppressive effect and ameliorated hepatotoxicity of methotrexate in Freund,s adjuvant model of rheumatoid arthritis.

An Analysis of Micronuclei and DNA Damage Induced by Methotrexate Treatment of Male Albino Mice

Background: Methotrexate is an antineoplastic, antipsoriatic and antirheumatic agent belongs to the group of antimetabolites and inhibits folic acid metabolism. Materials and methods: To investigate its possible effect, sixty male mice were randomly assigned to one of four groups (one control and three treated groups with different doses of methotrexate). Mice of groups 1, 2 and 3 were intraperitoneally injected with 2.5, 5 and 10 mg /kg b.wt. methotrexate respectively. All the control and treated animals were sacrificed at 24, 48 and 72 hour by cervical dislocation post treatment. Results:Micronucleus assay results showed that methotrexate treatment induced genotoxicity in bone marrow cells, the number of micronucleated polychromatic erythrocytes (MNPCEs) and the ratio of polychromatic erythrocytes / normochromatic erythrocytes was gradually increased significantly (P < 0.001) by increasing dose and time of treatment in methotrexate treated groups in comparison with the control group. An analysis of randomly amplified polymorphism DNA-polymerase chain reaction (RAPD-PCR) showed different ranges of DNA modifications in the treated groups after 24, 48 and 72 hour of treatment in comparison with the control group. Results of this study indicate that methotrexate treatment induced cytotoxic and genotoxic effect on bone marrow cells and DNA content of male albino mice even after a low dose and single treatment. Conclusion: Therefore, the therapeutic uses of methotrexate should be restricted to a very narrow range border.

Genotoxic Effect of Methotrexate on Bone Marrow Chromosomes and DNA of Male Albino Mice (Mus Musculus)

Aim of the work-Methotrexate (MTX), a structural analogue of folic acid, is an antineoplastic and antirheumatic agent which is used in a variety of clinical schedules and combination therapy regimens in man. Material and methods- Sixty mice of nearly the same age were randomly categorized into four groups (one control and three treated groups with different doses of methotrexate). Mice of the treated groups 1, 2 and 3 were intraperitoneally injected with a single dose of methotrexate (2.5, 5 or 10 mg/kg b. wt. respectively) at the first day of the experiment. All the control and the treated animals were sacrificed after 24, 48 or 72 hour by cervical dislocation post treatment. Results-Methotrexate treatment induced structural and numerical chromosomal aberrations in male mice bone marrow cells which were significantly increased (P< 0.001) by dose and time. Structural aberrations were chromosomal gap, fragment, break, centromeric attenuation, deletion, centric fusion, ring formation, end to end association and beaded chromosomes. Numerical aberration was polyploidy. Also, methotrexate treatment decreased the mitotic index in bone marrow cells of all the treated mice in comparison with the control group by increasing dose and time of treatment. Comet assay results indicated that treatment with methotrexate significantly increased (P< 0.001) DNA damage in the blood leukocytes in dose and time dependent manner. Conclusion- It can be concluded that methotrexate induced genetic damage on the chromosomes and DNA content of male albino mice even after single treatment with low doses.

Safety and efficacy of adalimumab in combination with different doses of methotrexate in patients with psoriatic arthritis: Subanalysis of ADEPT

Safety and efficacy of adalimumab in combination with different doses of methotrexate in patients with psoriatic arthritis: Subanalysis of ADEPT

Effect of methotrexate and vitamin A on NOR expression in seminiferous tubules of Wistar rats

Abstract Introduction: The histopathology and expression of nucleolar organizing regions (NORs), of seminiferous tubules was studied after the administration of methotrexate (MTX) and vitamin A (VA). Objective of the study was to test if the NOR count increases or decreases with different doses of MTX. Material and Methods: Male Wistar rats aged 4 months, maintained in our institution were used in the present study. The rats were divided into following groups, group I - control (saline treated), group II - animals treated with 8 mg of MTX, group III - animals treated with 10 mg of MTX, group IV - animals treated with 12 mg of MTX, group V - animals treated with VA (5000 IU), Group VI - animals treated with VA (5000 IU) and MTX (12 mg). Results: The animals treated with MTX showed significant decrease in the diameter of seminiferous tubules and increase in interstitial space. The spermatogenesis was not complete in some tubules. When MTX was given with VA, the damage done by MTX was decreased. There was an overall numerical decrease in the total NOR count from the control to 12 mg dose MTX. The total count included small, medium and large sized NORs. Conclusion: Higher the dose of MTX, lesser the NOR count and lesser the irregularity of NORs. However VA co-administration reduces the damage produced by MTX. We believe that indings of the present study might be useful in understanding the long term effect of MTX and its adverse effects.

Histopathological effects of Methotrexate in mice livers

Background:Methotrexate is a folic acid antagonists that inhibits dihydrofolate reductase, resulting in a block in the synthesis of thymidine and inhibition of DNA synthesis. Methotrexate has been used for the treatment of malignancy, rheumatic disorders, and psoriasis and termination of intrauterine pregnancy. Recently, methotrexate has become a standard treatment for ectopic pregnancy. However, the use of methotrexate is limited due to high incidence of serious dose-dependent toxicity of methotrexate, including hepatotoxicity, renal damage, bone marrow suppression and gastrointestinal mucosal inflammation . Objective:Evaluate the effect of the treatment with multiple doses of methotrexate in the livers of mice. Materials &Methods: A total of (70) white mice at the ages of (4-8 weeks) and body weight of about (25+2 gm) were used in the study. Mice were divided into seven groups where each group received multiple doses of (0.05mg/Kg) of methotrexate during an interval of six weeks where the animals of each group had injected with a single dose of(0.05mg/Kg) of methotrexate at the beginning of each week and then, they were killed and autopsied after five days. On the other hand, the control group had received (0.1ml) of normal saline. Liver slide sections were examined by light microscope and photographed. Then, images were assessed histopathologically and comparisons were made between mice groups received different doses of methotrexate. Results: Results showed that, a single dose of (0.05mg/kg) of methotrexate produced no liver tissue histopathological effects on the liver of the treated mice. While, six weeks of methotrexate treatment produced significant changes in the liver of the treated mice including lymphocyte infiltration, necrosis, liver tissue fatty degeneration and congestion and dalitation of the hepatic vein. Conclusions: It was concluded that, a single dose of (0.05mg/Kg) of methotrexate had no effect on mice liver histology. While, multiple doses of methotrexate were associated with significant side effects included a hallmark of cellular infiltration and lesions of necrotic hepatocytes with congestion and dalitation of hepatic vein. Thus, the administration of multiple doses of methotrexate for the treatment of various medical conditions should be considered carefully to avoid liver damage of the patient especially in the case of ectopic pregnancy.

AB0401 The Efficacy of Some Biologicals after Optimal MTX Therapy Failure in RA Patients

BackgroundEULAR Task Force strongly discourage the use of bDMARDSs before trying a csDMARDs, particularly MTX. Maximisation of treatment effects includes reaching an optimal MTX dose within a few weeks and...

O33. Efficacy, Pharmacokinetics and Safety of Different Doses of Methotrexate in Combination with Adalimumab: Results from the Concerto Trial

O33. Efficacy, Pharmacokinetics and Safety of Different Doses of Methotrexate in Combination with Adalimumab: Results from the Concerto Trial

Effect of Methotrexate and Vitamin A on NOR Expression in the Lining Epithelium of Gastric Mucosa in Male Wistar Rats

Background and objective: The histopathology and expression of nucleolar organising regions (NORs) of gastric mucosa were studied after the administration of methotrexate (MTX) and vitamin A (VA). The objective was to test whether the argyrophylic nucleolar organiser region (AgNOR) count increases or decreases with different doses of MTX. The literatures on AgNORs suggest that there may be a possible association between AgNOR counts and disease transformation. MTX is one of the commonest drugs used in several diseases. It is interesting to hypothesise the numbers, shape and the distribution of AgNORs after the administration of MTX. Methods: Male Wistar rats aged 4 months, maintained in our institution, were used in the present study. The rats were divided into following groups, group I - control (saline treated), group II - animals treated with 8 mg of MTX, group III - animals treated with 10 mg of MTX, group IV - animals treated with 12 mg of MTX, group V - animals treated with VA (5,000 IU), group VI - animals treated with VA (5,000 IU) and MTX (12 mg). Results: It was observed that MTX treatment showed abrupted or incomplete surface epithelium in the gastric mucosa. The gastric pits were short and epithelium showed lightly stained nuclei and cytoplasm. When MTX was given along with VA, the VA minimised the severity of damage caused by MTX. The frequency of large-size NOR was reduced after treatment with MTX. However, the medium and small-size NOR count were increased. When treated with MTX and VA, NOR frequency increased and reached almost the level of the control group. Conclusion: The present study observed that large-sized NOR decreases numerically while medium and small sized NORs increases with the administration of MTX. We believe that the NOR fusion was affected by the MTX drug. Higher the dose of MTX, lesser the NOR count and lesser the irregularity of NORs. However, VA co-administration reduces the damage produced by MTX. We believe that findings of the present study might be useful in understanding the long-term effect of MTX and its adverse effects.

OP0067 Efficacy, Pharmacokinetics, and Safety of Different Doses of Methotrexate in Combination with Adalimumab: Results from the Concerto Trial

BackgroundAnti-TNF plus methotrexate (MTX) is more effective than either as monotherapy. Thus far, no controlled data are available on the benefit:risk of different doses of MTX in combination with anti-TNF.ObjectivesTo...

Methotrexate for ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterized by sacroiliitis and spondylitis. Methotrexate (MTX), a widely used disease-modifying antirheumatic drug (DMARD), is effective for rheumatoid arthritis (RA), and so might work for AS. This is an update of a Cochrane review first published in 2004, and previously updated in 2006. To evaluate the benefits and harms of MTX for treating AS. We searched CENTRAL (The Cochrane Library Issue 6, 2012), MEDLINE (2005 to June 25, 2012), EMBASE (2005 to June 25, 2012), Ovid MEDLINE Scopus, World Health Organization International Clinical Trials Registry Platform and the reference sections of retrieved articles. Trials published in any language were acceptable. Randomized controlled trials (RCTs) and quasi-randomized controlled trials (qRCTs) examining the benefits and harms of MTX versus placebo, other medication, or no medication for treatment of AS. Two review authors independently extracted data and assessed risk of bias. We resolved any disagreements through discussions with a third review author. In the absence of significant heterogeneity, we combined results for continuous data using mean difference or standardized mean difference values. We calculated the risk ratio for dichotomous data. We identified three RCTs (no additional new studies), which included 116 participants. Of these three trials, one was a 12-month trial that compared naproxen plus MTX with naproxen alone. Also, there were two 24-week trials that compared different doses of MTX with placebo. We included the outcomes of response, physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs, and patient and physician global assessment. We judged only one trial to be at low risk of bias. Across these three trials, we did not identify any statistically significant differences favoring MTX treatment over no MTX treatment apart from one exception. The response rate in one trial showed a statistically significant absolute benefit of 36% and a number to treat for benefit (NNT) of three in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was based on a composite index that included assessments of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. We did not identify any outcome that showed a statistically significant difference between the MTX treated and no MTX treatment groups when endpoint results were compared. Furthermore, no serious side effects were reported in any of the included trials. There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality RCTs of larger sample sizes are needed to clarify the effect(s) of MTX on AS.

Influence of the antifolate drug Methotrexate on the development of murine neural tube defects and genomic instability

Impaired folate metabolism is considered a risk factor for neural tube defects (NTDs). However, the relationship between folate deficiency and the risk of NTDs remains unclear, because experimentally induced dietary folate deficiency is insufficient to cause NTDs in non-mutant mice. Methotrexate (MTX) is a specific folate antagonist that competitively inhibits dihydrofolate reductase (DHFR) activity. The objective of this study was to develop a folate dysmetabolism murine model, and study the development of NTDs and its mechanism. Pregnant mice were injected with different doses of MTX [0, 0.5, 1.0, 3.0, 4.5 and 6.0 mg kg(-1) body weight (b/w) intraperitoneally (i.p.)] on gestational day 7.5 and sacrificed on gestational day 11.5. DHFR activity in embryonic tissues was detected, and folate concentrations were analyzed using LC/MS/MS. Copy number variations (CNVs) in neural tube tissues were detected using array comparative genomic hybridization (aCGH). A dose of MTX 4.5 mg kg(-1) b/w, resulted in the highest incidence of NTDs (31.4%) compared with the other groups, and DHFR activities, 5-MeTHF and 5-FoTHF concentrations in embryonic tissues decreased significantly after MTX injection. Furthermore, we found three high-confidence CNVs on chromosome X using aCGH, which was confirmed by RT-PCR and MassARRAY. These results indicate that MTX could cause a folate-associated dysmetabolism, which is similar to that of dietary folate deficiency in mice. The presence of CNVs in neural tube tissues was associated with the development of NTDs.

Effects of intrathecal methotrexate on mechanical allodynia in rats with tibial bone cancer pain

Objective To investigate effects of intrathecal methotrexate on mechanical allodynia in rats with tibial bone cancer pain.Methods Forty-eight female SD rats weighing 150-180 g were randomly divided into 6 groups ( n =8 each):group Ⅰ sham operation + artificial cerebrospinal fluid(SA group),group Ⅱ sham operation + methotrexate 200 μg(SM group),group Ⅲ bone cancer pain + artificial cerebrospinal fluid(CA group),group Ⅳ-Ⅵ bone cancer pain + different doses of methotrexate (CM1-3 groups).The model of tibial bone cancer pain was induced by injecting Walker-256 cell into the tibial marrow cavity.CA and CM1-3 groups were intrathecal injected artificial cerebrospinal fluid,methotrexate 50,100 and 200 μg.SA and SM200 groups were intrathecal injected artificial cerebrospinal fluid and methotrexate 200 μg.The mechanical withdrawl threshold (MWT) was measured at day 1 before Walker-256 injection (baseline),7 day after injection (T0 ) and 2,4,8,24 hour and 1,3,5,7 days after intrathecal injection ( T1-8 ).Results Compered with the baseline,MWT was decrease in CA and CM1-s groups.Competed with To,MWT was decreased at T5-8 in CA group,MWT was increased at T3-5 in CM1 group,at T2-6 in CM2 group and at T2-7 in CM3 groups.MWT was decrease in CA and CM1-3 groups as compered with SA group; MWT was increased at T4-7 in CM1 group and at T3-7 in CM2 and CM3 groups.Conclusion Intrathecal injection of methotrexate can reduce tibial bone cancer pain in rats. Key words: Bone neoplasms; Pain; Methotrexate; Injections,spinal

A retrospective study to compare two methotrexate-based regimens for primary central nervous system lymphoma

A retrospective analysis to compare the treatment outcomes of two regimens with different doses of methotrexate (MTX). Seventy-two patients, newly diagnosed with primary central nervous system lymphoma between 1995 and 2006, were included. All patients were treated with one of the two different MTX regimens depending on when the diagnosis was made. Thirty-six patients diagnosed between 1995 and 2002 were treated with 1 g/m2 of intravenous MTX (HD-MTX 1 g/m2, cohort 1). The other 36 patients, diagnosed between 2003 and 2006, received 3.5 g/m2 of intravenous MTX (HD-MTX 3.5 g/m2, cohort 2). The median age was 47 years (range, 17–78 years) and 42 patients (58.3%) were male. The median overall survival (OS) and progression-free survival (PFS) of all patients was 90.3 and 52.9 months, respectively. Although OS and PFS was not statistically different between the two cohorts, cohort 2 achieved higher complete response/unconfirmed complete response rates than cohort 1 at an evaluation conducted between completion of intravenous MTX therapy and the initiation of radiotherapy (52.8% vs. 16.7%, respectively; p = 0.005). Furthermore, there were no deaths within 6 months of MTX therapy for the cohort 2, whereas there were eight deaths by 6-months for cohort 1 (p = 0.003). Even though cohort 2 failed to show superior survival outcomes compared with cohort 1 after sequential brain radiotherapy and intravenous cytarabine, the higher early CR/CRu rate of cohort 2 compared with cohort 1 might indicate that a high dose of MTX is desirable.

Changes of biochemical parameters in rat intestinal mucosa induced by methotrexate and effects of enteral administration of glutamine

BACKGROUND: Rapidly proliferating crypt cells of the intestinal epithelium, the precursors of the mature enterocytes, are extremely sensitive to the effects of cytostatic agents. We investigated the effects of the methotrexate on rat intestinal mucosa in order to get the information on biochemical indicators of intestinal damage. METHODS: Biochemical parameters were investigated in isolated intestinal mucosa of Sprague-Dawley rats, previously treated with methotrexate by intraperitoneal administration. Glutamine was dissolved in water and administered orally. RESULTS: The activity of glutaminase and alkaline phosphatase showed the enzymatic response to different doses of methotrexate. The activity of both enzymes was significantly lower in the mucosa of treated animals, compared to control group. CONCLUSION: Minimal mucosal damage and regeneration time is dose dependent and influenced by the dosage schedule of antitumor therapy.