CARDIOTOXICITY: AN UNUSUAL CASE OF METHOTREXATE OVERDOSE

The methotrexate (MTX) is an antimetabolite, whose dosages vary according to indication. It is used in the treatment of tumoral pathologies, as acute lymphoblastic leukaemias and, in rheumatology, in the rheumatoid polyarthritis (RP) and other chronic inflammatory rheumatisms The methotrexate belongs to the group of antifolates: it inhibits purine and pyrimidine synthesis, which accounts for its efficacy in the therapy of cancer as well as for some of its toxicities. Relative or absolute overdoses in low-dose methotrexate treatments for non-oncological diseases are regularly reported, either in isolated cases or in small series. The bone marrow toxicity with thrombocytopenia and leuconeutropenia is most often the first sign of general involvement. The cardiotoxicity of methotrexate is very rare, in this article we report the observation of pancytopenia associated with cardiotoxicity in a woman treated for RA, for whom the etiological investigation revealed inadvertent methotrexate intoxication by mistake of dosage.

New Molecular Targets in the Therapy of Arthrosis Patients

Introduction: Arthrosis represents the progressive degeneration of the joint cartilage, accompanied by the narrowing of the articular space and inflammation, which affects 70% of the population after the age of 60. Research purpose: This paper reviews the opportunity of using proinflammatory cytokine inhibitors as a means of stopping the progress of arthrosis. Material and method: As a result to a research into various clinical trial registers (Arthritis Clinical Trials, Clinical Research and Drug Information) and on specialized e-platforms, 5 randomized, multicentric double-blind clinical studies have been identified, which monitored the efficiency of various biological molecules in the treatment of arthrosis (etanercept, adalimumab, litikizumab, fasinumab and tanezumab). Results: The current pharmacological interventions consist mainly in the prescription of analgesics (acetaminophen, opioid analgesics), non-steroidal and chondroprotective anti-inflammatories. The proinflammatory cytokine inhibitors are already widely used in the inflammatory joint diseases, such as the rheumatoid polyarthritis. Their introduction into the treatment of arthrosis blocks the disease’s etiopathogenic mechanisms. Discussions: Arthrosis physiopathology involves a series of systemic, biological, biochemical factors, molecular and enzymatic processes that generate minimum inflammation. IL-1b and TNF-α are two major cytokines produced by the synovial cells and chondrocytes, which are involved in the destruction of the cartilage matrix by stimulating the production of proteolytic enzymes (MMP and aggrecanase). Conclusions: The utilisation of proinflammatory cytokine inhibitors in arthrosis represents a therapeutic option that requires studies in order to establish whether the introduction of proinflammatory cytokine inhibitors in arthrosis therapy might slow down the disease’s etiopathogenic mechanisms.

The Impact of Proinflammatory Cytokynes of Rheumatoid Polyarthritis on the Generalized Loss of Bone Mass

There is a bidirectional interaction between most immune cells and osteoblasts, osteoclasts and their precursor cells. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK/osteoprotegerin (OPG) system plays an essential role in the formation of osteoblasts, but it also has implications in osteoclast biology and implicitly on the diseases characterized by bone loss. Proinflammatory cytokines existing at synovial level function as direct or indirect stimulators of osteoclast differentiation, but also of its survival or activity, although some cytokines may also play an antiosteocastogenic role. The fate of bone destruction is determined by the balance between osteoclastogenic and antiosteoclastogenic mediators. Our study has shown that the early initiation of the therapy with anti-TNF and anti-IL6 biological agents, in patients with rheumatoid arthritis, inhibits bone destruction, regardless of the anti-inflammatory activity in patients with rheumatoid arthritis.

HOW MANY REVISION ARTHROPLASTIES DO WE UNDERTAKE PRIOR TO ARTHRODESIS? (CASE REPORT OF A PATIENT WITH RHEUMATOID KNEE ARTHRITIS)

The authors present a clinical case of a female patient with seropositive rheumatoid polyarthritis mainly affecting the knee joints. The patient underwent a primary total bilateral knee replacement. Surgical site infection required multiple revisions including replacement of extensive bone defects of AORI type 3 by structural femur and tibia allografts as well as allografting of extensor mechanism. Repeated attempts to eliminate infection, to gain support ability of extremities and joints motion were not successful. Long-term staged surgical treatment resulted in removal of prostheses and bilateral knee arthrodesis to restore support function of the extremities.

Hydroxychloroquine (HCQ) induces inhibition of Col-II and COMP expression in the chondrocytes

<p>Osteoarthritis (OA) is the disease of joints which results in articular cartilage degradation and remodeling of bones accompanied by joint pain and stiffness. Chloroquine (CQ) analogs like hydroxychloroquine have been used for the treatment of systemic lupus rheumatoid polyarthritis and erythematosus. The present study was aimed to investigate the effect of hydroxychloroquine (HCQ) on the level of collagen type II (Col-II) and oligo­meric matrix protein COMP expression in chondrocytes of knee osteoarthritis. The rate of growth in cartilage cells was analyzed using MTT assay where as the Col-2 and COMP expression levels were detected by RT-PCR and western blotting analyses. For the determination of MMP-13 expression, ELISA test was used. The results revealed a no significant change in the rate of cartilage cell proliferation in HCQ treated compared to the untreated cells. HCQ treatment exhibited concentration and time-dependent effect on the inhibition of Col-2 and COMP expression in chondrocytes. However, its treatment caused a significant enhancement in the expression levels of MMP-13 compared to the untreated cells. Therefore, HCQ promotes expression of MMP-13 and reduces Col-2 and COMP expression levels in the chondrocytes without any significant change in the growth of the cells.</p><p> </p>

Clinical case of rheumatoid arthritis with antiphospholipid antibody syndrome

The article presents a clinical case of development of secondary antiphospholipid syndrome (APS) with early active rheumatoid polyarthritis, complication in the form of acute deep vein thrombosis of forearm on the left and chronic left vein thrombosis of the lower extremity. Patient treatment with methotrexate has developed an infectious complication and resulting in the need to go to therapy of leflunomide. This therapy have positive effect. In a survey of the patient revealed a rare form of adrenal pheochromocytoma confirmed by computed tomography and measurements of plasma normetanephrine, but not accompanied an increase of blood pressure. This article discusses the modern classification of APS, pathogenesis, clinical and laboratory diagnostic criteria, methods of therapy as rheumatoid arthritis, and APS.