The serum levels of resistin in rheumatoid arthritis patients

OBJECTIVE: Adipocyte-derived resistin is a circulating protein implicated in insulin resistance, but the role of human resistin is uncertain because it is produced largely by macrophages. The aim of this study was to analyze serum resistin concentrations in rheumatoid arthritis (RA) patients to determine the role of resistin in human inflammatory diseases. MATERIALS AND METHODS: Resistin concentrations were assessed by ELISA in serum samples from 42 patients with RA. Serum samples from 38 healthy subjects acted as controls. We also evaluated the circulating levels of tumor necrosis factor- alpha (TNF-alpha) and disease activity markers in RA patients. RESULTS: In RA patients, serum resistin levels were significantly higher than those in healthy subjects. Serum resistin levels in RA patients were correlated with the RA disease activity markers, CRP and ESR. Furthermore, resistin levels in RA patients were significantly correlated with circulating levels of TNF-alpha. CONCLUSION: Serum resistin levels were significantly increased in RA patients and correlated with inflammatory markers and TNF-alpha, suggesting that resistin may play a role in the rheumatoid inflammatory process.     

Free serum histidine levels in patients with rheumatoid arthritis and control subjects following an oral load of free L-histidine.

A dose of 3.7 g of free-L-histidine was administered by mouth to 26 patients with active rheumatoid arthritis and to 29 control subjects. The patients with rheumatoid arthritis had a statistically significant (p=10(-12)) lower pretreatment concentration of free histidine in serum (1.20 mg/100 ml, SE=0.04) than the control subjects (1.90 mg/100 ml, SE=0.06). However, there were no statistically significant differences between rheumatoid and control subjects with respect to the serum histidine concentrations 1 hr, 3 hr, and 4 hr after the ingestion of L-histidine. The changes in the serum histidine concentrations at 1 hr, 3 hr, and 4 hr (compared to the pretest values) were also not significantly different in the patients with rheumatoid arthritis relative to the control subjects. This study suggests that the subnormal free serum histidine concentration of rheumatoid arthritis is not associated with abnormal serum levels of free histidine following an oral load of free histidine.     

Kinetic investigations into the possible cause of low serum histidine in rheumatoid arthritis.

To investigate the cause of low serum histidine in rheumatoid arthritis (RA) single oral and intravenous doses of L-histidine were administered to patients with active RA, and to an equal number of age and sex matched control subjects. In the first study 13 patients and their controls received a 100 mg kg-1 dose of L-histidine as an aqueous slurry. Significant differences were seen in body weight, predose baseline serum histidine concentration, Cmax, t1/2, and area under curve, AUC0-infinity. In a second study six patients and six controls each received a 50 mg kg-1 dose of L-histidine both orally and intravenously on two separate occasions. The patients with RA had a lower baseline serum histidine concentration, a lower volume of distribution, and a shorter plasma half life than the controls, but these differences were not statistically significant. No difference was seen in bioavailability or clearance. Low serum histidine in RA is unlikely to be due to malabsorption from the gut, uptake by abnormal gut flora, or increased metabolism.     

Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a decrease of 1 mg/dl in mean minimum concentration.     

Gold serum levels in children with juvenile rheumatoid arthritis.

Serum gold levels were monitored in 66 children with juvenile rheumatoid arthritis, treated with different i.m. dosage schedules of sodium aurothiomalate (Myocrisin, Pharma Rhodia). The ages of the children varied from 1 to 15 years. Gold serum levels in children were related to the dose of Myocrisin calculated per kg of body weight or per square metre of body surface area. The results of our study indicate that in order to achieve a peak serum level at about 500--600 microgram/100 ml (25--30 micromol/l) with weekly injections, the dose of Myocrisin should be about 0.7 mg/kg, or 20 mg/m2. In order to avoid excessively high gold serum concentrations, the maximum single dose should not exceed 27 mg/m2 of body surface area.     

The effect of methotrexate versus other disease-modifying anti-rheumatic drugs on serum drug levels and clinical response in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors

Clinical Rheumatology - To investigate the effect of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with adalimumab or infliximab on maintaining serum drug and...     

The effect of vitamin D levels on the assessment of disease activity in rheumatoid arthritis

Disease activity in rheumatoid arthritis (RA) is assessed by a combination of objective and subjective tests, combined to produce a disease activity score in 28 joints (DAS28). There is some evidence that RA disease activity, as assessed by DAS28, can be influenced by vitamin D levels. It is difficult to know whether this is due to a true immunomodulatory effect of vitamin D or a more subjective effect of low vitamin D on pain perception. We addressed this issue by comparing vitamin D levels with disease activity, analysing each component of the DAS28 score separately. We measured 25-hydroxy vitamin D levels in 176 outpatients with RA at two different centres and recorded a DAS28 score using an ESR checked at the same time. We calculated DAS28 both with and without the patient’s rating of their symptoms on the visual analogue score (VAS) to assess the effect of VAS on DAS28. The vitamin D results were expressed as nanomole per litre with 50 nmol/l taken as the lower limit of normal. We calculated mean levels of vitamin D and undertook a multivariate regression analysis to assess correlations between vitamin D levels and DAS28 (and its individual components), corrected for centre, age and gender. The overall mean DAS28 score was 3.66 (SE?±?0.11) using all four criteria and 3.43 (SE?±?0.10) using just three criteria (omitting VAS). The mean vitamin D level was 39.42 nmol/l (SE?±?1.55). There was no significant correlation between vitamin D and DAS28 scores with or without the inclusion of VAS. However, there was a significant inverse relationship between vitamin D and VAS itself (coefficient?=?0.249, p?=?0.013). The mean DAS28 score was greater in vitamin D-deficient patients and this was explained by their higher VAS scores. Our data confirms that vitamin D deficiency is common in RA. This paper provides evidence that the VAS component, assessing patient perception of symptoms, is inversely related to vitamin D, with lower levels producing higher VAS values. Although there was no overall correlation between vitamin D levels and DAS28, patients may perceive themselves or be perceived by assessors as having responded less well to disease modification in the presence of vitamin D deficiency. This could have major implications for subsequent management, and clinicians need to be aware of the potential confounding effect of vitamin D deficiency in assessing RA disease activity using the full DAS28 tool.     

Serum histidine in rheumatoid arthritis: a family study

We have compared free serum histidine in patients with rheumatoid arthritis, their blood relatives, and their non-blood relatives. The hypohistidinaemia of rheumatoid arthritis is acquired with the disease and does not provide a biochemical marker of those at risk.     

Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis

Twenty-three children with destructive polyarticular juvenile rheumatoid arthritis (JRA) were treated for 0.5-4.3 years (median 1.6 years) with weekly doses of methotrexate (MTX) (0.11-0.6 mg/kg/week). Serum levels of MTX at 1 hour and at 24 hours after drug administration were obtained at each dosage level and every 3 months after a stable dosage was achieved. No patient had serum levels of MTX that were in the toxic range nor evidence of hematologic, skin, mucous membrane, gastrointestinal, or pulmonary abnormalities. Ten patients had transiently elevated serum transaminase levels. Arthritis symptoms improved in 21 of these JRA patients, and the improvement was significantly associated with a mean 1-hour serum MTX level of greater than or equal to 5.8 x 10(-7)M (P = 0.008) and a dosage of greater than or equal to 0.3 mg/kg/week (P = 0.004). The 1-hour serum level of MTX was correlated with the MTX dosage (r = 0.28, P = 0.005). Our observations suggest that with close monitoring, MTX can be used safely at dosages as high as 0.6 mg/kg/week, and improvement in the symptoms of JRA will become evident when the serum levels of MTX 1 hour after administration approach 6.0 x 10(-7)M.     

The relationship of serum leptin levels with disease activity in Egyptian patients with rheumatoid arthritis

Aim of the workTo investigate whether serum leptin levels are elevated in patients with rheumatoid arthritis (RA) and whether these levels correlate with disease activity.Patients and methodsA case-control study was made on 37 patients with RA and 34 healthy control subjects. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts, disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analog scale (VAS) of pain and serum leptin concentrations.ResultsPatients with RA had mild to moderate (DAS28 < 5.1) disease activity. The mean serum leptin in patients with RA (12.15 ± 11.48 ng/mL) was significantly higher (p < 0.001) than controls (3.99 ± 1.84 ng/mL). Serum leptin levels were significantly (p < 0.001) higher in female RA patients than in female controls. A nonsignificant difference (p = 0.41) was found between male patients with RA and male controls. Serum leptin levels were significantly (p < 0.001) higher in women than in men in both patients and controls. Serum leptin levels did not show correlation with age, disease duration, duration of morning stiffness, VAS, number of swollen and tender joints, DAS28, HAQ, ESR or CRP in patients with RA. Serum leptin levels were correlated positively with BMI in RA patients. The BMI was significantly higher (p < 0.001) in female than in male patients with RA.ConclusionAlthough leptin levels were higher in RA patients, there was no correlation with disease activity parameters, therefore, leptin levels cannot be used to reflect disease activity.