Single-dose Methotrexate Research Articles

Outcome of cesarean scar pregnancy treated with local methotrexate injection.

ABSTRACTLocal injection of methotrexate (MTX) has been widely used for caesarean scar pregnancy (CSP), but the optimal candidate remains undetermined. The aim of this study is to determine the risk factors associated with treatment failure among patients who received a single dose of local MTX.This is a retrospective cohort study. Clinical information was compared between treatment success vs. failure groups. Risk factors related to treatment failure were also investigated with multivariate analysis.Of 47 patients diagnosed with CSP, 30 received local MTX injection. The initial serum ß- human chorionic gonadotropin (hCG) level in the failure group was significantly higher than in the success group (p = 0.048), and the cut-off value was 47,000 mIU/ml. The rate of type 2 position of the gestational sac in the failure group was significantly higher than in the treatment success group (p = 0.031). A high initial serum ß-hCG level (≥ 47,000 mIU/ml) was identified as the independent risk factor for treatment failure (adjusted odds ratio = 21.9; 95% confidence interval = 1.3–383.1).Type 2 gestational sac position and a higher level of ß-hCG at diagnosis appear to be associated with poor outcomes after local injection of a single dose of MTX.

Ethanolic extract of Iris songarica rhizome attenuates methotrexate-induced liver and kidney damages in rats.

The long-term sequelae of methotrexate (MTX) remain the major cause of concern for both patients and therapists. Therefore, new approaches to decrease MTX side effects are needed. The study was carried out to evaluate the effects of Iris songarica Schrenk (IS) rhizome extract against MTX-induced hepatic and renal injuries in rats. Forty male Wistar rats were randomly divided into five groups (n=8) including control, MTX, IS50, IS150 and IS300. Control and MTX groups were only treated orally with saline; whereas, IS50, IS150 and IS300 groups were treated with IS extract at three different doses (50, 150, and 300 mg/kg, respectively). Besides, the MTX and experimental groups were received a single dose of MTX (20 mg/kg) intraperitoneally on day 4. On the ninth day, animals were sacrificed, blood transaminases, urea and creatinine were assessed and the concentration of malondialdehyde (MDA) and the activity of super-oxide dismutase (SOD) were determined in both liver and kidney tissues. Moreover, hepatic and renal damages were evaluated histopathologically. MTX by increasing oxidative stress (MDA) and decreasing antioxidant capacity (SOD) induced hepatic and renal damages as confirmed by biochemical and histological parameters analyses. However, treatment with IS caused significant improvements in hepatic and renal histological architectures and SOD activity (p<0.01) along with reducing liver enzymes, urea, creatinine and MDA (p<0.01). The results of the present study showed that IS extract through antioxidant and probably anti-inflammatory activities, could effectively limit MTX-induced hepatic and renal injuries in rats.

Caesarean scar pregnancy: descriptive paper of three different types of management on a series of clinical cases.

IntroductionA caesarean scar pregnancy is a complex iatrogenic pathology, which represents a consequence of a previous caesarean section. It increased in recent years due to parallel increase of cesarean sections.Material and methodsWe present a retrospective study on patients with caesarean scar pregnancy diagnosed in our department from June 2016 to June 2019. Stable women with an embryo (with or without cardiac activity) who accepted our experimental protocol were treated with single dose of methotrexate (50 mg administered locally intracavitary + 50 mg administered intramuscularly) and folinic acid (15 mg/day orally for 30 days). Clinically stable women with embryo (without cardiac activity) who decided to wait, were monitored by serial assays of b-hCG and clinical and ultrasonographic follow up. Women who were clinically unstable with embryo (without cardiac activity), were referred for urgent surgical treatment with dilation and curettage.ResultsCaesarean scar pregnancy was diagnosed in sixteen women. Among these women, seven were treated according to our experimental protocol with methotrexate and folinic acid and only one had profuse bleeding, which required a laparotomic hysterectomy. Four women were treated urgently with dilatation and curettage. Five women chose to wait: they were monitored and all spontaneously had a miscarriage.ConclusionsIn our preliminary study, we highlighted how our experimental protocol gave encouraging results in the first 10 weeks of caesarean scar pregnancy. However, caution is needed in patients with advanced gestational age, a gestational sac with large diameter, higher CRL and presence of embryonic cardiac activity.

Resolution of pembrolizumab-associated lichenoid dermatitis with a single dose of methotrexate

We present a 53-year-old woman with severe lichenoid dermatitis secondary to pembrolizumab therapy that was refractory to both topical and oral steroids. After almost three months without improvement, the rash was effectively combated with a single 15mg dose of methotrexate. We hope this case will help guide the management of the cutaneous adverse effects of anti-PD1 immunotherapy.

Effect of Single-Dose Methotrexate Treatment on Ovarian Reserve in Women with Ectopic Pregnancy Undergoing Infertility Treatment: A Single-Center Experience.

BackgroundThe aim of this study was evaluation of the impact of single-dose methotrexate (MTX) treatment on ovarian reserve in women with ectopic pregnancy (EP) undergoing infertility treatment in Iranian population.Materials and MethodsThis prospective cohort study was done between March 2015 and March 2017 in Tehran General Women Hospital, Tehran, Iran. We enrolled 20 patients with EP who conceived during infertility treatment and received a single-dose MTX (50 mg/m2) intramuscularly. Serum anti-Mullerian hormone (AMH), 17 beta-estra diol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) on transvaginal ultrasonography, were evaluated before and 8 weeks after administration of MTX.ResultsAMH did not significantly vary after the administration of MTX, compared to before treatment value (P=0.36). FSH, E2 and AFC changes were not statistically significant, while increment of LH was significant (P=0.02).ConclusionResults indicated that single-dose MTX treatment did not reduce ovarian reserve in women with EP. Further randomized controlled clinical trial studies with larger sample sizes, by using multiple dosages of MTX, and with long-term follow up are suggested to be done.

Which protocol is better for treatment of ectopic pregnancy by methotrexate? Single-dose or multiple-dose

Background:Ectopic pregnancy (EP) is the most common cause of death in the first trimester of pregnancy. Methotrexate (MTX) is an acceptable treatment in the cases with the lack of tube rupture or no important one, which has reduced surgical treatment. Despite numerous studies, there is still no consensus about medications. The present study is aimed to evaluate the single- and multiple-dose of MTX among these patients.Materials and Methods:This clinical trial study was done on 108 EP patients who were selected for the systemic MTX treatment and divided into two groups. For the single-dose group, MTX was administered once and β human chorionic gonadotropin (βHCG) levels were measured first and then on days 4 and 7. In the multi-dose group, 1 mg/kg MTX was injected on days 1, 3, 5, and 7. In both groups, MTX was prescribed following these days if βHCG was not reduced. In the two groups, βHCG levels were assessed after 1 week. The success rate of treatment and complications were followed up and recorded up to 6 weeks after treatment.Results:The success rate in the single-dose and multiple-dose MTX group was 47% and 51%. The MTX level in the single dose group decreased from 2532 ± 1154 mIU/mL to 1341 ± 553 mIU/mL and in the multiple dose group from 2671 ± 2685 mIU/mL to 1313 ± 605 mIU/mL (P < 0.05). Although a significant decrease was observed in each of the two groups over time, no significant difference was found between the two groups (P > 0.05).Conclusion:Single and multi-dose regimen did not show a significant difference in terms of the success of treatment. Therefore, given that the lower dose of the drug associated with lower the risk of complications, it is safe to choose the single-dose regimen.

Single dose of Methotrexate therapy followed by suction curettage for management of Cesarean Scar Pregnancy

Aim: To evaluate the efficacy and safety of single dose of of Systemic MTX 50 mg/m2 followed by D&amp;S in cases of Cesarean scar pregnancy (CSP). Objective: Implantation of the pregnancy in a cesarean scar is a rare condition named; Cesarean scar pregnancy (CSP). Maternal complications can be prevented with the early diagnosis and an appropriate management. It is a prospective clinical study to evaluate the efficacy and success rate of single dose use of methotrexate (MTX) followed by dilation and suction (D&amp;S) regimen in the management of women with cesarean scar pregnancy (CSP). Methods: 50mg of MTX in the form of a single dose Intramuscular injection then cervical dilatation and suction aspiration with a Karman cannula (D&amp;S) under guidance of ultrasound after 48 preceded by vaginal misoprostol 2 tablet (200 mg) 4 hours ago. Results: The mean gestational age at diagnosis was (8.5±1.6) and the mean gestational age of pregnancy was 8.5±1.6. The mean level of serum b-human chorionic gonadotrophin was (7424±2.560). 88.7% was the successive rate without complication or need of intervention, 2 (5.7%) patients needed intrauterine foley's catheter for 24 hours as a mechanical hemostasis. 2 (5.7 %) had laparotomy with wedge resection of the gestational sac lesion and successful repair of the uterine defect and one (2.8 %) underwent subtotal hysterectomy. Conclusion: Systemic single dose MTX injection followed by D&amp;S is an effective and harmless management for CSP. Nevertheless more studies are required to prove the efficiency, safety, and reproductive outcome of variant modalities in treatment of CSP.

Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats.

Liver injury is one of the adverse effects of methotrexate (MTX). Ferulic acid (FA) is an antioxidant phytochemical that confers hepatoprotective efficacy; however, its effect against MTX hepatotoxicity remains unexplored. This study investigated the role of FA in modulating oxidative stress, inflammation, Nrf2/HO-1 signaling, and PPARγ in MTX-administered rats. Following oral FA supplementation for 15days, rats received a single dose of MTX at day 16 and samples were collected at day 19. MTX provoked multiple histological manifestations, including degenerative changes, steatosis, inflammatory cells infiltration and hemorrhage, and altered serum transaminases, bilirubin, and albumin. Reactive oxygen species, lipid peroxidation, and nitric oxide were increased in the liver of rats that received MTX. FA prevented all histological alterations, ameliorated liver function markers, suppressed oxidative stress, and boosted antioxidants in MTX-induced rats. FA reduced serum TNF-α and IL-1β, and hepatic NF-κB p65, Bax, and caspase-3, whereas increased Bcl-2, Nrf2, NQO1, HO-1, and PPARγ. In conclusion, FA prevented MTX hepatotoxicity by activating Nrf2/HO-1 signaling and PPARγ, and attenuating oxidative stress, inflammation, and cell death.

Single Dose of Methotrexate Therapy Followed By Suction Curettage for Management of Cesarean Scar Pregnancy

Objective Implantation of the pregnancy in a cesarean scar is a rare condition named ; Cesarean scar pregnancy (CSP). Maternal complications can be prevented with the early diagnosis and an appropriate management .It is a Prospective clinical study to evaluate the efficacy and success rate of single dose use of methotrexate (MTX) followed by dilation and suction (D&amp;S) regimen in management of women with cesarean scar pregnancy (CSP) . Methods 50mg of MTX in the form of a single dose Intramuscular injection then cervical dilatation and suction aspiration with a Karman cannula(D&amp;S) under guidance of ultrasound after 48 preeceeded by vaginal misoprostol 2 tablet (200 mg) 4 hours ago. Results The mean gestational age at diagnosis was (8.5±1.6 ) and The mean level of serum b-human chorionic gonadotropin was (7424±2.560 ) and The mean gestational age of pregnancy was (8.5±1.6 ) .88.7% is the successive rate without complication need intervention, 2 (5.7%) patients needed intrauterine Foley's catheter for 24 hours as a mechanical hemostasis . 2 (5.7 %) had laparotomy with wedge resection of the gestational sac lesion and successful repair of the uterine defect and one (2.8 %)underwent subtotal hysterectomy. Conclusion: Systemic single dose MTX injection followed by D&amp;S is an effective and harmless management for CSP. Nevertheless more studies are required to prove the efficiency, safety, and reproductive outcome of variant modalities in treatment of CSP.

The effect of ultrasonography in predicting medical treatment success in ectopic pregnancy

Ectopic pregnancy(EP) treatment success in a single dose methotrexate(MTX) regimen is decided by more than 15% β chorionic gonadotropin reduction in the 4th and 7th days after administration of 50mg/m² of medication. In our study , it was aimed whether the EP mass size less than 40mm detected by ultrasonography and the adnexal side on which it was located had an effect on the success of medical treatment.&#x0D; 82 patients who treated with MTX included in the study were divided into two groups as those with a single dose of methotrexate success and those without (n:67 vs n:15). The groups were compared in terms of age, parity, size of adnexal mass detected on ultrasonography, and the side of ectopic pregnancy.&#x0D; The parity rates and the age of patients were similar in both groups(p = 0.615, p = 0.742). Although the average adnexal mass size was found to be higher in the patient group those single dose MTX treatment was not successful, there was no statistically significant difference(p = 0.098). Ectopic pregnancy was frequently observed on the right side in the group in which the medical treatment was successful(66 % vs 33%).&#x0D; The effect of ectopic pregnancy mass size on medical treatment prediction was investigated in cases with mass size less than 40mm. Ectopic pregnancy mass size, even if it is below 40 mm, may not indicate the medical treatment success.

Ameliorating Effect of Alpha-lipoic Acid on Methotrexate-induced Histological and Biochemical Changes in The Lung of Adult Albino Rat

Background: Owing to its antioxidant, anti-inflammatory and anti-fibrotic properties, alpha-lipoic acid (ALA) has been evaluated in a diversity of degenerative diseases and experimental toxicological studies.Aim of the Work: This study was performed to assess the ability of ALA to reverse the histological and biochemical alterations that take place in the rat lungs after exposure to methotrexate.Materials and Methods: This study was done using thirty-two male Wistar albino rats (180–220 g). The animals were divided into four equal groups. The control group: received distilled water by oral gavage for ten days and injected intraperitoneally (i.p.) with1 ml of physiologic saline (0.09% NaCl) solution on the fourth day. ALA group: received ALA (200 mg/kg once daily) dissolved in distilled water and given by oral gavage for ten days. Methotrexate (MTX) group: injected with a single dose of 20mg/kg MTX i.p. on the fourth day of the study. MTX+ALA group: received an oral dose of ALA (200 mg/kg) for ten days and a single dose of MTX (20mg /kg) i.p. on the fourth day. By the end of the experiment, all the animals were anaesthetized using phenobarbital 3%. Blood samples were collected to measure c-reactive protein (CRP). The lungs were dissected out and prepared for tissue homogenates, routine histological study and caspase-3 immunohistochemical evaluation.Results: In the MTX group, there were high levels of CPR, glutathione (GSH) and malondialdehyde (MDA) with reduction of superoxide dismutase (SOD) and catalase (CAT) activities. Lung sections revealed marked inflammatory cells infiltration, thickening of interalveolar septa, congested blood vessels, intrapulmonary hemorrhages, abundant collagen fibers and significant expression of caspase-3. In ALA+MTX group, there was an overt improvement in lung histoarchitecture. Additionally, SOD activity. CRP, MDA levels and caspase-3 expression were significantly less.Conclusion: Administration of ALA can work against oxidative damage in the lung induced by MTX.

Single Dose of Methotrexate Therapy Followed By Suction Curettage for Management of Cesarean Scar Pregnancy

Objective Implantation of the pregnancy in a cesarean scar is a rare condition named ; Cesarean scar pregnancy (CSP). Maternal complications can be prevented with the early diagnosis and an appropriate management .It is a Prospective clinical study to evaluate the efficacy and success rate of single dose use of methotrexate (MTX) followed by dilation and suction (D&amp;S) regimen in management of women with cesarean scar pregnancy (CSP) . Methods 50mg of MTX in the form of a single dose Intramuscular injection then cervical dilatation and suction aspiration with a Karman cannula(D&amp;S) under guidance of ultrasound after 48 preeceeded by vaginal misoprostol 2 tablet (200 mg) 4 hours ago. Results The mean gestational age at diagnosis was (8.5±1.6 ) and The mean level of serum b-human chorionic gonadotropin was (7424±2.560 ) and The mean gestational age of pregnancy was (8.5±1.6 ) .88.7% is the successive rate without complication need intervention, 2 (5.7%) patients needed intrauterine Foley's catheter for 24 hours as a mechanical hemostasis . 2 (5.7 %) had laparotomy with wedge resection of the gestational sac lesion and successful repair of the uterine defect and one (2.8 %)underwent subtotal hysterectomy. Conclusion: Systemic single dose MTX injection followed by D&amp;S is an effective and harmless management for CSP. Nevertheless more studies are required to prove the efficiency, safety, and reproductive outcome of variant modalities in treatment of CSP.

Ellagic acid reduces methotrexate-induced apoptosis and mitochondrial dysfunction via up-regulating Nrf2 expression and inhibiting the IĸBα/NFĸB in rats.

The clinical application of methotrexate (MTX), an efficacious cytotoxic drug, is restricted due to its associated liver toxicity. Ellagic acid (EA), a natural polyphenol, possesses hepatoprotective, antioxidant and anti-inflammatory properties. The present study seeks to address the hepatoprotective effects of Ellagic acid (EA) against MTX-mediated oxidative stress (OS) and widen our current knowledge of the underlying molecular mechanisms of MTX toxicity. Wistar rats were orally given EA (5mg/kg and 10mg/kg) for 10 successive days and at the end of the third day they were administered a single dose of MTX (20mg/kg i.p). After performing biochemical analysis, liver enzymes and malondialdehyde were significantly higher in the MTX group, indicating hepatic oxidative damage. MTX-induced OS was further confirmed with observation of events such as reactive oxygen species (ROS) overproduction, mitochondrial outer membrane potential decrease, mitochondrial swelling, cytochrome c release and caspase-3/9 increase, resulting in apoptosis. Furthermore, overexpression of pro-inflammatory factors such as nuclear factor kappa B (NF-ĸB) and interleukin 6 (IL-6) indicated the MTX-induced inflammation in MTX-treated group. Interestingly, EA was able to significantly prevent OS, mitochondrial dysfunction, apoptosis and inflammation induced by MTX. Also, EA-treated rats demonstrated significant upregulation of both nuclear factor erythroid 2-related factor 2 (Nrf2) and hemoxygenase-1 (HO-1), which were considerably downregulated in MTX-treated rats. EA protects rats against MTX-induced apoptosis and mitochondrial dysfunction via up-Regulating Nrf2 and HO-1 expression and inhibiting the NF-κB signaling pathway. Therefore, EA may protect patients against MTX-induced hepatotoxicity and encourage its clinical application. Graphical abstract Beneficial effect of Ellagic acid (EA) on Methotrexate (MTX)-induced liver injury: molecular mechanism.

1261 Risk Factors for Recurrent Ectopic Pregnancy Following Single-Dose Methotrexate Treatment

Study Objective We aimed to investigate the predisposing factors for recurrent ectopic pregnancy (REP) following single-dose methotrexate (MTX) treatment. Design A retrospective cohort study. Setting A tertiary medical center. Patients or Participants All patients diagnosed with a first EP and treated by intention of single-dose regimen of intramuscular MTX. Interventions Cases (REP) and controls (first-time only EP) were compared in order to identify risk factors for REP. Forward stepwise multivariate logistic regression analyses were subsequently carried out. Measurements and Main Results 272 women were included in the cohort of the study. Of those 22 (8.1%) had a REP. Women in the REP group had higher proportion of history of abortions (45.4% vs. 23.6%, p=0.02), higher rates of previous pelvic surgery and a history of both pelvic and uterine surgery (45.4% vs. 6.4%, 4.5% vs. 1.6%, respectively, p Conclusion Among women with EP, attention should be paid to women with previous pelvic surgery. Efforts should be made in order to achieve medical treatment success to prevent REP.

1225 Early Prediction of Methotrexate Treatment Success by 24‐Hour Pretreatment HCG Increment and Day 1-4 HCG Ratio

Study Objective Several studies have tried to identify early markers for treatment outcome after methotrexate (MTX) treatment for an ectopic pregnancy (EP) including pretreatment and day 4 hCG levels and corresponding ratio, and hCG increment during the initial 24 hours following treatment, with conflicting results. We aim to re‐evaluate the role the aforementioned markers in the earlier identification of treatment success in a large cohort of women. Design A retrospective cohort study. Setting A tertiary medical center during 2010-2018. Patients or Participants All women diagnosed with an EP and treated by intention of single-dose regimen of intramuscular MTX. Interventions A comparison of maternal and gestation characteristics was performed between treatment success and failure groups. Measurements and Main Results 292 women treated with single-dose intramuscular MTX for EP during were included in this study. Treatment success rate with a single dose of MTX of the overall cohort was 62.7% (183/292). Only two independent determinants were significantly associated with the treatment success: initial 24 hours hCG percentage of increment (adjusted odds ratio [OR]: 1.82; 95% confidence intervals [CI]: 1.26, 2.63; p Conclusion A low rise in hCG levels 24 hours prior to treatment with MTX, alongside a decline in hCG levels from day 1 to day 4 may predict success of medical treatment of EP.

Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats.

Acute kidney injury (AKI) is a serious complication of methotrexate (MTX). This study explored the protective effect of the isoflavone formononetin (FN) against MTX nephrotoxicity with an emphasis on oxidative stress, inflammation, and nuclear factor (erythroid-derived 2)-like 2/heme oxygenase 1 (Nrf2/HO-1) signaling. Rats received FN (10, 20, and 40 mg/kg) for 10 days and a single dose of MTX on day 7. MTX induced kidney injury was characterized by increased serum creatinine and urea, kidney injury molecule-1 (Kim-1), and several histological alterations. FN ameliorated kidney function and inhibited the renal tissue injury induced by MTX. Reactive oxygen species (ROS), lipid peroxidation (LPO), nitric oxide, and 8-Oxo-2′-deoxyguanosine were increased, whereas antioxidant defenses were diminished in the kidney of MTX-administered rats. In addition, MTX upregulated renal iNOS, COX-2, TNF-α, IL-1β, Bax, caspase-9, and caspase-3, and decreased Bcl-2, Nrf2, and HO-1. FN suppressed oxidative stress, LPO, DNA damage, iNOS, COX-2, proinflammatory cytokines, and apoptosis, and boosted Bcl-2, antioxidants, and Nrf2/HO-1 signaling in MTX-administered rats. In conclusion, FN prevents MTX-induced AKI by activating Nrf2/HO-1 signaling and attenuates oxidative damage and inflammation. Thus, FN may represent an effective adjuvant that can prevent MTX nephrotoxicity, pending further mechanistic studies.

Single dose Methotrexate injection, could be a safe and effective treatment for early cases of tubal ectopic pregnancy, with minimal maternal health hazards

first method is described as a conservative medical method in which we use a chemotherapeutic agent (Methotrexate) to eradicate the ectopic tubal conception, whereas the second method implies a conservative laparoscopic surgery in which overwhelming efforts are done in order to maintain a tube affected by ectopic pregnancy as healthy as possible following removal of the ectopic pregnancy mass. The fallopian tubes are assessed for patency and tubal lumen contour and pattern 3 months following successful treatment, in order to detect which method would lead to a high cure rate with the least tubal detrimental effect. Patients and Methods: In the current study, 58 patients diagnosed with tubal ectopic pregnancy were given Methotrexate as a first choice chemotherapeutic agent aiming to resolve the ectopic pregnancy, whereas 58 patients with the same condition gone directly through laparoscopic salpingostomy, with the aim of maintaining patent healthy tube finally after successful treatment. Results: The study revealed no significant difference for either treatment modalities in affecting the rate of bilateral tubal obstruction, or tubal patency with a recognized tubal defect with a p >0.05. On the other hand, cases with unilateral tubal obstruction involving the affected tube were remarkably increased in the methotrexate group (13 cases) out of 52 cases with successful treatment compared to 6 cases successfully treated by salpingostomy (6 cases) out of 52 cases successfully treated, with a p<0.05 . Conclusion: In conclusion, single dose methotrexate has proven to be a safe, effective and reasonably convenient treatment for most patients, shown during counseling to be so worry about surgery and its potential detrimental consequences on their future fertility. Yet, it should be obviously highlighted that such concepts and perspectives for keeping fertility can’t be taken as for granted and a guarantee for a healthy patent tube as it is quite obvious that even with successful elimination of the chorionic tissue in the tube, the affected tube might still be blocked and with a significant rate further exceeding the excepted rate with laparoscopic salpingostomy.

Effects of Infliximab against Methotrexate Toxicity in Splenic Tissue via the Regulation of CD3, CD68, and C200R in Rats

Methotrexate (MTX), which has been used in clinical practice for approximately 70 years, is still widely employed in the treatment of rheumatoid arthritis (RA), psoriasis, and cancer. Although MTX toxicity causes nephrotoxicity, hepatotoxicity, bone marrow suppression, pulmonary fibrosis, and gastrointestinal damage, previous studies have not addressed splenic toxicity. This is the first study to examine the effectiveness of infliximab (INF) against MTX-induced toxicity in splenic tissues via the regulation of CD3, CD68, and C200R. We investigated the effects of MTX on macrophages and T lymphocytes in the spleen at the molecular level and examined the protective potential of the tumor necrosis factor (TNF)-α antagonist INF against MTX toxicity. Three groups of rats were set up. Group 1 received saline solution only, group 2 a single dose of MTX (20 mg/kg), and group 3 INF (7 mg/kg) before administration of a single dose of MTX (20 mg/kg). All injections were given intraperitoneally. Spleen tissues were removed 5 days after MTX administration and evaluated for CD3, CD68, and CD200R using immunohistochemical staining. Finally, the mean numerical density of CD3+, CD68+, and CD200R+ cells was estimated by a histopathologist using StereoInvestigator 8. MTX increased the numerical densities of CD3+, CD68+, and CD200R+ cells (p < 0.05). We also observed that INF reduced the numerical densities of these cells following MTX administration (p < 0.05). INF may, therefore, be a promising candidate for the prevention of the deleterious effects on spleen tissue of MTX, used in the treatment of RA and cancer.

Risk factors for recurrent ectopic pregnancy following single-dose methotrexate treatment

Objective: Our study aimed to investigate the predisposing factors for recurrence of an ectopic pregnancy (EP) following single-dose methotrexate (MTX) treatment for a primary EP.Methods: This was a retrospective cohort study performed in a tertiary care medical centre including all patients diagnosed with primary EP and treated with a single-dose regimen of intramuscular MTX. EPs with future recurrence were compared with first time only EPs, to identify risk factors for recurrent EP. Forward stepwise multivariate logistic regression analyses were subsequently carried out.Results: The study included 272 women. Of those, 22 (8.1%) had a recurrent EP. Women in the recurrent EP group had a higher rate of abortions (45.5% vs 32.7%; p = 0.02), previous pelvic surgery (45.5% vs 6.5%; p < 0.001) and both pelvic and uterine surgery (4.5% vs 1.6%; p < 0.001). Conception by assisted reproductive technology (ART) was more common among the non-recurrent EP group (23.0% vs 4.5%; p = 0.04). Success of single-dose MTX treatment was lower in the recurrent EP group compared with the non-recurrent EP group (36.4% vs 65.7%; p = 0.006). A history of pelvic surgery was independently associated with recurrent EP (adjusted odds ratio [OR] 17.6; 95% confidence interval [CI] 4.9, 63.2; p = 0.001). Treatment success of single-dose MTX was independently protective for recurrent EP (adjusted OR 0.25; 95% CI 0.08, 0.76; p = 0.02).Conclusions: Among women with an EP, attention should be paid to those with previous pelvic surgery. Efforts should be made to achieve medical treatment success to prevent recurrent EP.

Hesperidin Alleviates Methotrexate-Induced Memory Deficits via Hippocampal Neurogenesis in Adult Rats.

Methotrexate (MTX), a folic acid antagonist, is widely used in cancer treatment. However, treatment with MTX reduces hippocampal neurogenesis, leading to memory deficits. Hesperidin (Hsd) is a flavonoid glycoside that promotes anti-inflammation, acts as an antioxidant, and has neuroprotective properties. Consumption of Hsd enhances learning and memory. In the present study, we investigated the protective effects of Hsd against MTX-induced impairments of memory and neurogenesis; male Sprague Dawley rats were administered with a single dose of MTX (75 mg/kg) by intravenous (i.v.) injection on days 8 and 15 or Hsd (100 mg/kg) by oral gavage for 21 days. Memory was tested using novel object location (NOL) and novel object recognition (NOR) tasks. Immunofluorescence staining of Ki-67, bromodeoxyuridine (BrdU), and doublecortin (DCX) was performed to assess cell proliferation, survival, and immature neurons. The data showed that Hsd and MTX did not disable locomotor ability. The MTX animals exhibited memory deficits in both memory tests. There were significant decreases in the numbers of cell proliferation, survival, and immature neurons in the MTX animals. However, co-administration with MTX and Hsd alleviated memory loss and neurogenesis decline. These results revealed that Hsd could protect against MTX side effects in the animals in this study.