Methotrexate (MTX) is a cytotoxic immunosuppressant that is widely used in the treatment of tumours, rheumatoid arthritis and psoriasis. This study aims to evaluate the effects of whey proteins on MTX-induced liver and kidney damage by focusing on oxidant–antioxidant systems and eating habits. The study was conducted in four groups of thirty Sprague–Dawley rats (control, control + whey protein concentrate (WPC), MTX, MTX + WPC). A single dose of 20 mg/kg MTX was administered intraperitoneally to the MTX groups. Control and MTX groups were given 2 g/kg WPC by oral gavage every day for 10 d. At the end of day 10, blood samples were drawn and liver and kidney tissues were removed. MTX administration increased the lipid peroxidation level and decreased glutathione level, superoxide dismutase and glutathione-S-transferase activities in the liver and kidney. Administration of WPC significantly reduced the damage caused by MTX in the liver and kidney. While a decrease in serum urea level and an increase in serum creatinine level were detected in the MTX group, WPC administration reversed these results up to control group levels. Administration of WPC to the MTX group significantly reversed the histopathological damage scores of the liver and kidney. WPC administration ameliorated the MTX-induced oxidative damage in the liver and kidney tissues due to its antioxidant properties. Liver and kidney damage can be prevented by using whey proteins as a nutraceutical in MTX therapy. In conclusion, whey proteins demonstrated a protective effect against MTX-induced liver and kidney damage.

This article describes the development, implementation, and evaluation of a complex methotrexate ethics case used in teaching a Pharmacy Law and Ethics course. Qualitative analysis of student reflective writings provided useful insight into the students’ experience and comfort level with the final ethics case in the course. These data demonstrate a greater student appreciation of different perspectives, the potential for conflict in communicating about such cases, and the importance of patient autonomy. Faculty lessons learned are also described, facilitating adoption of this methotrexate ethics case by other healthcare profession educators.

Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTX-induced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

Growing evidence suggests that n-3 PUFA and their specific lipid mediators can reduce the activity of inflammatory processes. In the present study, we evaluated the effects of oral n-3 PUFA supplementation on intestinal structural changes, enterocyte proliferation and apoptosis during methotrexate (MTX)-induced intestinal damage in the rat. A total of thirty-two male rats were divided into four experimental groups: control (CONTR) rats; CONTR-n-3 PUFA rats treated with oral administration of n-3 PUFA at a dose of 300 μg/kg once per d 72 h before and 72 h following vehicle injection; MTX rats treated with a single dose of MTX; MTX-n-3 PUFA rats treated with oral n-3 PUFA following the injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis determined 72 h following MTX injection. Real-time PCR was used to determine B-cell lymphoma 2 (Bcl2)-associated X protein (Bax) and Bcl2 mRNA expression. Western blotting was used to determine phosphorylated extracellular signal-related kinase, β-catenin, Bax and Bcl2 protein levels. MTX-n-3 PUFA rats demonstrated a greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in the jejunum and ileum and crypt depth in the ileum, compared with MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-n-3 PUFA rats (v. MTX) was accompanied by decreased Bax mRNA and protein expression and increased Bcl2 mRNA levels. Thus, the treatment with oral n-3 PUFA prevented mucosal injury and improved intestinal recovery following MTX-injury in rats.

We report a case of B-cell lymphoma with the larynx as the primary site of presentation in a rheumatoid arthritis patient previously treated with methotrexate. Primary non-Hodgkin’s lymphoma (NHL) of the larynx is rare. There may be an increased risk of lymphoma in patients with rheumatoid arthritis, with an even higher risk in those patients treated with methotrexate. The diagnostic and treatment options are discussed.

A 67-year-old woman with rheumatoid arthritis was hospitalized because of dysphagia and severe nodulosis. Over a two-year period the patient had been treated with methotrexate. A computed tomography (CT) scan of the neck showed a 2 × 2 cm large tumour behind the top left lateral thyroid cartilage. A biopsy taken during direct laryngoscopy showed it was a rheumatic nodule. Treatment with colchicine reduced the patient's dysphagia. As methotrexate is used increasingly in the treatment of rheumatoid arthritis and as this particular drug causes rheumatic nodules in five to 10 per cent of the patients, it must be foreseen that the incidence of nodules in the upper airways will increase.

Primary malignant lymphoma is an uncommon disease of the central nervous system (CNS). Immunocompromised patients are at high risk of development of malignant lymphoma. We describe a case of primary CNS lymphoma presenting as a solitary cerebellopontine angle lesion. The patient had undergone extirpation of rectal cancer four years previously. Malignant lymphoma presenting as a cerebellopontine angle mass is extremely rare, with only 10 such cases (seven were primary, and the others secondary) previously reported.