Objective Alpha2-Heremans Schmid glycoprotein/Fetuin-A (AHSG) is a circulating negative acute-phase protein, which inhibits bimineralization. It is often considered as a potential mediator between ...chronic inflammation and cardiovascular diseases. The metabolism of AHSG in patients with rheumatoid arthritis (RA) is unknown. Methods Serum AHSG concentrations were measured in 102 patients with RA using a newly developed indirect enzyme-linked immunosorbent assay (ELISA). Results The serum AHSG levels in the RA patients were significantly lower than that in healthy volunteers (249.8 ± 84.1 vs 425.0 ± 93.0 μg/ml, P<0.0001). Serum C-reactive protein concentration and erythrocyte sedimentation rate were inversely correlated, while albumin, hemoglobin and total cholesterol were positively correlated with AHSG. Current serum AHSG levels did not affect the presence of aortic calcification, whereas cumulative glucocorticoid dosage was significantly related to aortic calcification (P=0.005). Conclusion Serum AHSG levels were significantly decreased in patients with RA. The levels reflected inflammatory and malnutritional conditions. Its role in the development of cardiovascular diseases or inflammatory bone resorption remain uncertain in RA patients.
Assessment of intracranial vessels includes transcranial Doppler (TCD). TCD performance requires intact temporal acoustic windows (TAW). Failure of TAW (TAWF) is present in 8–20% of people. There ...have been no reports on TAWF in rheumatoid arthritis (RA). Altogether, 62 female RA patients were included. Among them, 20 were MTX-treated and biologic-free, 20 received infliximab, and 22 tocilizumab. The controls included 60 non-RA women. TAWF, temporal bone thickness, and texture were determined by ultrasound and CT. BMD and T-scores of multiple bones were determined by DEXA. Several bone biomarkers were assessed by ELISA. In RA, 54.8% of the patients had TAWF on at least one side. Neither TAW could be identified in 34% of RA subjects. In contrast, only 20.0% of control subjects had TAWF on either or both sides (
p
< 0.001). In RA vs controls, 53.0 vs 2.9% of subjects exerted the trilayer, “sandwich-like” structure of TAW (
p
< 0.001). Finally, in RA vs controls, the mean temporal bone thickness values of the right TAW were 3.58 ± 1.43 vs 2.92 ± 1.22 mm (
p
= NS), while those of the left TAW were 4.16 ± 1.56 vs 2.90 ± 1.16 mm (
p
= 0.001). There was close association between TAWF, bone thickness, and texture (
p
< 0.05). These TAW parameters all correlated with age; however, TAW failure and texture also correlated with serum osteoprotegerin. TAW bone thickness inversely correlated with hip BMD (
p
< 0.05). TAWF, thicker, and heterogeneous temporal bones were associated with RA. These features have been associated with bone loss and OPG production. Bone loss seen in RA may result in OPG release and stimulation of bone formation around TAW.
We describe an optimized compound 12 to have desired activity against IKKβ, good stability to plasma and microsome, and excellent selectivity over other kinases. Display omitted
We have previously ...reported the identification of a rhodanine compound (1) with well-balanced inhibitory activity against IKKβ and collagen-induced TNFα activated cells. However, we need more optimized compounds because of its instability over plasma and microsome. As part of a program directed toward the optimization of IKKβ inhibitor, we modified a substituent of parent compound to a series of functional groups. Among substituted compounds, fluorine substituent (12) on the para position of phenyl ring restored the stability toward plasma and microsome while retaining inhibitory potency and selectivity against IKKβ over other kinases. Also, we have demonstrated that compound 12 is an ATP non-competitive inhibitor and safe enough to apply to animal experiment from an acute toxicity test.
Abstract The generation of gaseous mixtures containing nitric oxide (gNO) from different plasma sources has been widely used for various clinical applications. Concentrations of biologically active ...species generated in those discharges in addition to gNO were calculated for different gas temperatures. Synergistic actions of gNO with other plasma species are discussed. New therapeutic effects of gNO-containing plasmas achieved for the treatment of skin scars, rheumatoid arthritis, osteoarthritis and sport injuries are reported.
The reason for the increased lymphoma risk in patients with rheumatoid arthritis (RA) has remained unclear. Reports of lymphomas in patients treated with TNF-blockers have brought renewed interest in ...this issue. This review summarizes data on possible associations between RA and lymphomas, including different treatments and RA disease related risk factors.
Some recent studies reported increased lymphoma risks linked to RA disease activity. The hypothesis that disease-modifying drugs, and in particular methotrexate, would increase the lymphoma risk receives little support. Observation times for the TNF-blocking therapies are still short, but so far no clear increased risk for lymphoma has been observed. Presence of Epstein-Barr virus, as analyzed with EBER in situ hybridization, appears to be uncommon in RA related lymphomas. Hypothetically, an increased proliferative drive caused by self or non-self antigens may play a role in lymphoma development in RA patients, but this has to be further studied.
Rheumatologists need to be aware of the increased lymphoma risk in their RA patients. The reason for the increased lymphoma risk in RA patients is still unclear, but available studies rather support the hypothesis of a link between RA disease severity and the risk of lymphoma than increased risks associated with specific treatment regimens. To facilitate the future evaluation of lymphoma risks in connection with treatment, we suggest that patients treated with new drugs should be subject to structured surveillance. Collected information should include data about RA disease activity and severity.
Osteonecrosis of the jaw (ONJ) has been recently described after intravenous administration of amino-bisphosphonates and - less frequently - in association with the use of oral bisphosphonates. ...Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) may affect mandible bone (65%), maxilla bone (26%) and rarely (9%) both sites simultaneously. Although causality may never be proven, emerging experimental data have established a strong association between monthly intravenous bisphosphonate administration and ONJ. Current level of evidence does not fully support a cause and effect relationship between the use of oral BPs and ONJ. In this paper, we report a clinical case of BRONJ in a 73 years old woman affected by rheumatoid arthritis (RA) and periodontitis, after three years of treatment with alendronate 70 mg one a week, plus daily calcium and vitamin D. The patient developed a tooth abscess at the lower jaw, accompanied by increased inflammatory markers, that never returned to normal range despite antibiotic therapy, inducing deterioration of joint synovium. The worsening of joint status after the onset of ONJ was reflected by the progressive increase in the number of swollen (SJ) and tender (TJ) joints, by the deterioration of the score DAS 28 (which passed from 5.46 to 7.07), pain (with VAS increasing from 60 to 90), and by a progressively impaired quality of life, as reported using the HAQ score (from 1,25 to 2,5). The patient was switched to antifracture therapy with strontium ranelate and the osteonecrosis was successfully treated with antibiotics, surgical curettage and local ultrasounds.
Resumen: En nuestra permanente preocupación por el bienestar de nuestros pacientes, especialmente en rela ción con el riesgo de Infección por COVID 19; la Sociedad Chilena de Reumatología ha ...elaborado una serie de recomendaciones sobre el tratamiento farmacológico de nuestros pacientes y la preven ción de infección COVID-19. Sugerimos que, ante cualquier sospecha de infección, se comuniquen con su médico para establecer los pasos a seguir, que busquen y cumplan con los consejos ofrecidos por el Ministerio de Salud, Servicios de Salud o sus respectivos Hospitales y Centros de Salud, ya que contarán con la información más actualizada y adaptada a las circunstancias locales. Y para finalizar, reiteramos las medidas preventivas que el Minsal ha difundido sobre el distanciamiento social, lavado de manos, uso de mascarilla y protección facial.
Summary
Anti-TNF agents like infliximab, etanercept and adalimumab are efficacious in the treatment of ankylosing spondylitis (AS), psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Lack of ...efficacy, side effects and loss of efficacy over time may be reasons for switching to a second anti-TNF agent and sometimes switching to a third anti-TNF agent may be useful. Effects of switching may be different in patients with AS, PsA and RA. We analysed data of 301 patients with rheumatic diseases treated with anti-TNF agents. Forty-six patients had AS, 63 PsA and 192 RA. Totally 38% of these patients received more than one anti-TNF agent. Switching to a second anti-TNF agent was necessary in 115 (38%) of our patients, in detail in 11 of our AS patients, in 21 of PsA patients and in 83 of RA patients. Patient with PsA showed the best response rate to the second anti-TNF agent. Finally, 46 patients, 5 with SPA, 3 with PsA and 38 with RA received a third anti-TNF agent. We conclude that anti-TNF switching in AS and PsA is less frequent than in RA patients. Survival of anti-TNF agents in AS (
p
= 0.025) and also in PsA (n.s.,
p
= 0.215) seems to be better than in RA. Switching anti-TNF agents for loss of efficacy over time may have the best effect in patients with AS, PsA and predominantly in RA. Our data suggest that switching for lack of efficacy in RA patients cannot be recommended, but may be an alternative in patients with AS and PsA. Switching to a second anti-TNF agent for side effects may be reasonable, switching to a third anti-TNF agent again for side effects cannot be recommended.
Introducción: La Artritis Reumatoidea (AR) se caracteriza por la inflamación crónica de las articulaciones, lo que lleva a la destrucción del cartílago articular y del hueso. Aproximadamente el 75% ...de los pacientes con AR desarrolla erosiones articulares dentro de los dos primeros años de comienzo de los síntomas. La presencia de erosiones tempranas expresa enfermedad más agresiva y se asocia a un pronóstico más desfavorable. Se ha demostrado que el daño erosivo puede observarse en resonancia magnética (RM) aun antes de los 6 meses luego de iniciada la enfermedad, siendo esta técnica de mayor sensibilidad que la radiología convencional. La evaluación por RM utilizando el score de Outcome Measures in Rheumatology Clinical Trials (OMERACT) / Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) permite realizar una valoración semicuantitativa del edema óseo, la sinovitis y las erosiones. Objetivo: Evaluar las características del daño estructural por RM en pacientes con AR temprana (menos de un año de evolución) que no presentaron erosiones en radiografías de manos. Materiales y métodos: Se seleccionaron 10 pacientes con AR según criterios ACR 1987, que presentaban score radiológico de Sharp / van der Heijde igual a 0 (cero) para erosiones. A ellos se les realizó RM de ambas manos. Se utilizó el score de Sharp / van der Heijde para evaluar el pinzamiento articular y el score de OMERACT-RAMRIS para cuantificar las lesiones articulares detectadas por RM. Se comparó el score final obtenido por ambos métodos. Resultados: Se incluyeron 10 pacientes (9 mujeres y 1 varón) con score radiológico de Sharp / van der Heijde igual a cero para erosiones. La edad media fue de 45,8 años (rango 25 - 71). El tiempo medio de evolución de la AR a la obtención de las imágenes fue de 3,6 meses (rango 1 - 8). El score medio de pinzamiento radiológico fue de 52 (rango 36 - 83). El score medio OMERACT-RAMRIS fue de 24 (rango 4-55); todos los pacientes presentaron sinovitis y 7 (70 %), edema óseo. Apesar de no observarse erosiones en la radiografía, 7 pacientes (70 %) las mostraron en RM. La erosión representó el 26,25% del score total de RM. Conclusión: Tradicionalmente, el daño estructural de la AR se mide utilizando diferentes métodos de score radiológicos. Dado que la detección precoz de erosiones predice una enfermedad más agresiva, la RM debería ser considerada en pacientes con AR temprana para la evaluación del pronóstico. Sin embargo, es necesario evaluar a un mayor número de pacientes para certificar esta observación.Introduction: Rheumatoid Arthritis (RA) is characterized by chronic inflammation of the joints, leading to destruction of articular cartilage and bone. Approximately 75% of RA patients develop joint erosions within the first two years of onset of symptoms. The presence of early erosions reveals more aggressive disease and is associated with an unfavorable prognosis. It has been shown that erosion damage can be seen on magnetic resonance imaging (MRI) even before 6 months of the disease onset. This technique appears to be more sensitive than conventional radiology. MRI evaluation using the score of Outcome Measures in Rheumatology Clinical Trials (OMERACT) / Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) allows semiquantitative assessment of bone edema, synovitis and erosions. Objective: To evaluate the characteristics of structural damage by MRI in patients with early RA (less than one year of progression), with no erosions of hands on the X-ray. Materials and methods: We selected 10 patients with RA according to the ACR criteria 1987, whose score showed radiographic Sharp / van der Heijde equal to 0 (zero) for erosions. They underwent MRI of both hands. The Sharp / van der Heijde method was used to assess articular impingement, and the OMERACT-RAMRIS score to quantify joint lesions detected by MRI. The final scores obtained by both methods were compared. Results: Ten patients (9 females and 1 male) with radiographic score Sharp / van der Heijde zero for erosion were included. Mean age was 45.8 years (range 25-71). When the MRI was performed, the mean time of RA progression was 3.6 months (range 1 to 8). The average score was 52 radiological clamping (range 36 to 83). The OMERACT-RAMRIS half score was 24 (range 4- 55); all patients had synovitis, and 7 (70%) had bone edema. Although no erosions have been seen on radiographs, in 7 patients (70%) erosions were seen on the MRI. Erosions accounted for 26.25% of the total MRI score. Conclusion: Traditionally, the RA-related structural damage has been measured using different radiological score methods. Since early detection of erosions predicts a more aggressive disease, MRI should be considered in patients with early RA to evaluate their prognosis. However, a larger number of patients should be analyzed to confirm this observation.
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