Relationship between mixed exposure to phenyl hydroxides, polycyclic aromatic hydrocarbons, and phthalates and the risk of arthritis.

BACKGROUND: To determine the relationship between mixed exposure to three types of endocrine-disrupting chemicals (EDCs), namely phenyl hydroxides, polycyclic aromatic hydrocarbons (PAHs), and phthalates (PAEs), and risk of arthritis. METHODS: Participants were selected from National Health and Nutrition Examination Survey (NHANES). The relationships between the urinary concentrations of phenyl hydroxides, PAHs, and PAEs and the risk of arthritis were analyzed by generalized linear regression model. The mixed exposure to these EDCs and the risk of arthritis was analyzed by weighted quantile sums (WQSs) and Bayesian kernel machine regression (BKMR) model. RESULTS: Our analysis showed that participants with urinary benzophenone-3 and methylparaben concentrations in the highest quartile (Q4) had an increased risk of arthritis compared with those in Q1. For each one-unit increase in the natural logarithm-converted urinary concentrations of 1-hydroxynapthalene and 2-hydroxynapthalene, the risk of arthritis increased by 5% and 8%, respectively. Chemical mixing index coefficients were significantly associated with risk of arthritis in both WQS positive- and negative-constraint models. In the BKMR model, there was a significant positive correlation between mixed exposure and the risk of arthritis. CONCLUSION: Mixed exposure to phenyl hydroxides, PAHs, and PAEs increased the risk of arthritis, with exposure to PAHs being the key factor.

Increased prevalence of JC polyomavirus viruria was associated with arthritis/arthralgia in patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this paper is to investigate the prevalence of reactivation of the human polyomavirus John Cunningham virus (JCV) in patients with systemic lupus erythematosus (SLE) and its associated clinical manifestations. METHODS: Sixty-one patients with SLE and 22 controls were enrolled. Urine JCV viral load was quantified by real-time polymerase chain reaction (PCR). Length variants of the VP1 gene were analyzed using capillary electrophoresis. RESULTS: The prevalence of JCV viruria (63.9% vs. 18.2%, p < 0.001) and urine JCV viral load (2.92 ± 2.76 vs. 0.81 ± 1.85 copies/ml by log10 scale, p < 0.001) were significantly higher in patients with SLE compared with controls. JCV viruria (+) SLE patients had a higher occurrence of arthritis/arthralgia compared with JCV viruria (-) SLE patients (64.1% vs. 22.7%, p = 0.003). In SLE patients, the urine JCV viral load was significantly associated with the occurrence of arthritis/arthralgia. SLE patients with urine JCV viral load >10,000 copies/ml exhibited a 12.75-fold (95% confidence interval 2.88-56.40) risk in clinical arthritis/arthralgia, 18.90-fold (95% confidence interval 2.10-170.39) risk in persistent arthritis, and significantly greater number of length variants in the VP1 gene of JCV compared with JCV viruria (-) SLE patients. CONCLUSION: Reactivation of JCV in the urinary tract of SLE patients was very common. Both JCV viruria and urine JCV viral load were associated with the occurrence of arthritis/arthralgia in patients with SLE. High urine JCV viral load also was associated with the genetic variant in the VP1 gene.

Urinary heavy metals and associated medical conditions in the US adult population.

Health effects of heavy metals have been widely investigated, but further evaluation is required to comprehensively delineate their toxicity. Using data from the 2007-2008 National Health and Nutrition Examination Survey, a multivariate logistic regression analysis was performed on 1,857 adults to examine the relationship between urinary heavy metals and various medical conditions. Cardiovascular diseases were correlated to cadmium (OR: 4.94, 95% CI: 1.48-16.56) and lead (OR: 5.32, 95% CI: 1.08-26.21). Asthma was related to tungsten (OR: 1.72, 95% CI: 1.15-2.59) and uranium (OR: 1.52, 95% CI: 1.01-2.28). Hepatotoxicity was associated with molybdenum (OR: 3.09, 95% CI: 1.24-7.73) and uranium (OR: 4.79, 95% CI: 1.74-13.19). Surprising inverse relationships occurred for excessive weight with lead (OR: 0.72, 95% CI: 0.52-0.98), reduced visual acuity with cobalt (OR: 0.65, 95% CI: 0.44-0.95) and cesium (OR: 0.52, 95% CI: 0.35-0.77). This study supports some previous evidence of potential relationships and provides insights for future research.

Prediction of response of collagen-induced arthritis rats to methotrexate: an (1)H-NMR-based urine metabolomic analysis.

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.

Antihypertensive effect of the combination of fosinopril and HCTZ is resistant to interference by nonsteroidal antiinflammatory drugs.

Nonsteroidal antiinflammatory drugs (NSAID) are frequently reported to interfere with the blood pressure lowering actions of various antihypertensive medications. We studied 17 women with arthritis and hypertension who were receiving fosinopril and HCTZ, and administered sequentially in random order ibuprofen, sulindac, and nabumetone for 1 month each, with an intervening 2-week washout period between each treatment period. During the washout period, subjects received acetaminophen. Blood pressure at the end of 2 weeks of acetaminophen was compared with blood pressure after 1 month of treatment with each of the NSAID. Mean blood pressure was unchanged before and after all NSAID: 108 +/- 7 v 107 +/- 9 for nabumetone, 108 +/-9 v 108 +/- 9 for sulindac, and 108 +/- 8 v 107 +/- 9 for ibuprofen. The 24-h urinary sodium excretion was not significantly different. We conclude that the three NSAID did not neutralize the antihypertensive effect of the combination of fosinopril and HCTZ, and hence the blood pressure lowering action of the combination may not be prostaglandin dependent.

Compared effects of isoxicam and indomethacin on the urinary excretion of prostaglandins in degenerative articular diseases.

The effects of a 7 day-treatment with isoxicam (200 mg/24 h) on the urinary excretion of prostaglandins (PG) were compared to those of indomethacin (150 mg/24 h) in a double-blind randomized study conducted in 18 patients with degenerative arthritic disease and normal renal function. Indomethacin decreased the urinary excretion of PGF2 alpha by about 70% and 6-keto-PGF1 alpha and thromboxane (Tx)B2, the stable break-down products of prostacyclin and TxA2 respectively, by about 40%. Isoxicam effects on urinary PG did not significantly differ from those of indomethacin. During both treatments, urinary gamma-glutamyl transferase and N- acetyl-glucosaminidase remained stable and none of the changes in the urinary excretion of PGs could be related to either plasma or urinary drug concentrations. In conclusion, chronic administration of isoxicam inhibited the renal PG biosynthesis to a similar extent than indomethacin which suggests that non steroidal anti-inflammatory drugs of the oxicam group ought also be used cautiously in patients with renal impairment.

Effect of nonsteroidal anti-inflammatory drugs on the renal excretion of uric acid.

The effect of 9 nonsteroidal anti-inflammatory drugs on the renal excretion of uric acid was studied in patients with normal renal function. Diflunisal, Azapropazone and Indomethacin caused an increase and Piroxicam a decrease in the uric acid excretion. Other drugs studied had no significant influence.

Renal affection in patients with ankylosing spondylitis and psoriatic arthritis.

In a retrospective study of 148 patients with well-defined ankylosing spondylitis (AS), psoriatic arthritis (PSA) or reactive arthritis (ReA) an 11% prevalence of idiopathic hematuria, proteinuria, or cylinduria was found in the former two groups. None of the patients with ReA had unexplained pathological urinary findings. Such findings were associated with raised ESR and presence of peripheral arthritis in AS and with the duration of disease in PSA. No patient lacking sacroiliitis showed pathological urinary findings. We believe that such findings may reflect nephropathy associated with AS and PSA.

Interference by nonsteroidal anti-inflammatory drugs in EMIT and TDx assays for drugs of abuse.

Fourteen nonsteroidal anti-inflammatory drugs were evaluated for interference in EMIT and TDx assays for drugs of abuse. Only tolmetin demonstrated significant interferences in the EMIT assay. Urine samples that contained high concentrations of tolmetin (1800 mg/L) had characteristic high molar absorptivity at the wavelength used in EMIT assays (340 nm). Consequently, EMIT analysis of samples resulted in instrument error alarms on a Hitachi 704 instrument and depressed milliabsorbance values (delta A) relative to calibrators. Similar results were obtained with urine samples collected from an arthritic patient after the administration of 200 and 400 mg of tolmetin. When tolmetin samples were mixed with drugs of abuse, depressed delta A values were noted in all assays. Samples containing opiates and cannabinoids tested negative, and instrument error alarms were produced with samples that contained amphetamines. A gas chromatographic-mass spectrometric (GC-MS) assay for benzoylecgonine in the presence of tolmetin was successful, and no interferences were noted. Similar interferences by tolmetin were not observed in TDx assays, probably because of the different wavelength (525 nm) used in this assay. However, a potential for false-positive results in the TDx benzodiazepine assay was noted for urine samples containing high concentrations of fenoprofen, flurbiprofen, indomethacin, ketoprofen, and tolmetin. Generally, it was concluded that the presence of tolmetin in urine samples could lead to the production of unacceptable results by the EMIT assay for drugs of abuse. However, TDx and GC-MS assays were useful alternatives for the analysis of urine samples suspected of containing tolmetin.

Effect of bioflavonoids on the urinary excretion of hydroxyproline, hydroxylysyl glycosides and hexosamine in adjuvant arthritis.

The effects of (+)--Catechin (AC) and 0--(beta hydroxyethyl) rutosides (HR) on the urinary collagen metabolites were studied up to 49 days in rats with adjuvant-induced arthritis. The elevated levels of urinary total, non-dialysable and dialysable hydroxyproline, hydroxylysyl glycosides and total hexosamine in the arthritic animals were found to be slightly decreased in the acute phase and significantly decreased in the chronic phase of the disease due to the administration of bioflavonoids. Of the two bioflavonoids tests, CA was found to afford more protective action than HR.

Urinary excretion of hydroxyproline and hydroxylysyl glycosides in adjuvant-induced arthritis.

The effect of adjuvant-induced arthritis on the urinary excretion of hydroxyproline and hydroxylysyl glycosides (glc-gal-hyl and gal-hyl) was investigated in male Sprague-Dawley rats up to 70 days after the injection of Freund's complete adjuvant. In comparison with control animals the total urinary hydroxyproline is significantly increased in the arthritic rats at one day after injection, returns to normal level at one week and is further significantly increased between the 2nd to 7th week. The excretion of total glycosides in urine parallels the excretion of total hydroxyproline. However, the low ratio of glc-gal-hyl/gal-hyl provides circumstantial evidence in favour of the hypothesis of bone collagen degradation in the acute stage of adjuvant-induced arthritis in rats (between 2 and 3 weeks), while high absolute values but normal ratios of glc-gal-hyl/gal-hyl suggest degradation of both bone and skin collagen in equal amounts between the 4th and 7th week. No significant differences are found between control and arthritic groups in the later part of the experiment.

Long-term tolerability study of Voltaren.

Clinical and laboratory examinations were conducted in order to assess the long-term tolerability of Voltaren, a new anti-inflammatory and analgesic agent. Pre-treatment, repeated on-treatment and after-treatment investigations of haemoglobin, erythrocyte count, total and differential leucocyte count, platelet count, SGOT, SGPT, alkaline phosphatase, total serum proteins and urinary protein and sugar were conducted in 13 patients. The period of treatment with Voltaren was 110 to 559 days. In all these tests, there were no unwanted effects attributable to long-term treatment with Voltaren. Our study would indicate that Voltaren is a safe drug which has no effect on the organs of haemopoiesis, nor on hepatic or renal function, even in long-term therapy. Therefore, Voltaren can be used as an anti-inflammatory and analgesic agent not only in short-term therapy but also in the long-term treatment of chronic diseases.

[The effect of indomethacin and dexamethasone on the excretion of epinephrine, levarterenol and dopamine in the urine of rats with adjuvant arthritis]. / Einfluss von Indometacin bzw. Dexamethason auf die Ausscheidung von Epinephrin, Levarterenol und Dopamin im Urin von Ratten mit Adjuvansarthritis.

The repeated application of indometacine or dexamethasone on rats with adjuvant arthritis results in a most cases significant inhibition of the arthritis in the primary and secondary phase as well as in a normalisation of the increased urinary excretion of epinephrine and norepinephrine of untreated arthritis rats. The dopamine excretion of adjuvant arthritis rats was also higher then the prepared rats. We suppose, that the results show the regulative endogenous excretion of epinephrine and norepinephrine in inflammatory processes. Consequently these drugs have essentially antiinflammatory activities. The inhibition of the inflammation is than connected with the normalisation of the excretion of catecholamines.

[Fluorometric determination of levarterenol, epinephrine and dopamine in the urine of rats with carrageenan edema and adjuvant arthritis]. / Fluorimetrische Bestimmung von Levarterenol, Epinephrin und Dopamin im Urin von Ratten mit Carrageeninödem und Adjuvansarthritis.

After adsorption-chromatographic separation (using aluminium oxide) and chemical conversion to the corresponding trihydroxyindole derivatives, epinephrine, levarterenol and dopamine were determined fluorometrically in urine from rats. In case of carrageenin oedema, as well as during the secondary phase of adjuvant arthritis, the excretion of epinephrine and levarterenol was increased as compared to that in control animals. This difference was statistically significant. These findings can possibly be connected with an inhibitory activity of the catecholamines in inflammatory processes; as to dopamine, it seems to be of minor importance.

A case report of spontaneous polyarthritis in cynomolgus monkeys.

Veterinary x-ray photography and examinations of synovial fluid, blood and urine were conducted on a Cynomolgus Monkey from China (5 years old) which exhibited macroscopically visible systemic joint swelling after the quarantine period. The presence of inflammatory cells in the synovial fluid obtained by arthrocentesis, high counts of neutrophils, monocytes and large unstained cells and the elevated serum CRP level suggested that the lesions in this animal were due to polyarthritis.