Treatment of ankylosing spondylitis with TNFα inhibitors does not affect serum levels of tryptophan metabolites.

The imbalance between the kynurenine and serotonin pathways can have serious consequences, e.g., depression. One of the factors leading to the imbalance between the pathways of tryptophan metabolism is inflammation. The aim of our study was to assess the impact of treatment with tumor necrosis factor-alpha (TNFα)-inhibitors on tryptophan metabolism in patients with ankylosing spondylitis (AS). Forty patients with AS (twenty-eight males, twelve females; mean age 40 ± 11 years), qualified to receive anti-TNF-α treatment, were prospectively assessed. As a control group, 20 healthy volunteers (7 males and 13 females, mean age 38 ± 5 years) were recruited from the general population. Patients underwent full clinical and biochemical assessment before and after 6 months of therapy. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The presence of depressive disorders was assessed with Beck's Depression Inventory (BDI) scale. Serum concentrations of tryptophan, serotonin, kynurenine, and quinolinic acid were measured. The predominance of the kynurenine pathway in AS patients (compared to the control group) was demonstrated (p < 0.001). Surprisingly, no significant changes in serum levels of tryptophan and its metabolites in AS patients after treatment were found, despite clinical improvement. Moreover, the components of tryptophan metabolism did not correlate significantly with the clinical activity of AS, depression nor laboratory inflammatory markers. Probably some other factors influence the pathways of tryptophan metabolism in patients with ankylosing spondylitis.

Salivary Cytokine Profile as a Possible Predictor of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by neurodevelopmental disorders and alterations in immune function and cytokine levels. The aim of this study is to determine the salivary levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES), and Eotaxin in children with ASD and in healthy controlsto assess their predictive potential. We explored correlations between the cytokine levels and the neurodevelopmental disorders related to ASD. The study comprised 19 children with ASD and 19 typically developing (TD) ones. We analyzed salivary levels of IL-1ß, IL-6, IL-8, TNFα, MCP-1, RANTES, and eotaxin on Luminex with custom-designed 7-plex kits. The level of RANTES in ASD children was significantly lower than those of TD. In TDs, the salivary levels of IL-1ß, MCP-1, and TNFα correlated positively with age. In ASD, the cytokine levels did not correlate with age. There were statistically significant differences between the RANTES level and aggression and gait disturbances, between IL-8 level and fixations/stimulations, and between IL-1ß level and no active speech. The levels of the cytokine detected can manifest both systemic and local changes related to ASD. The cytokine pattern cannot be used as a sole ASD predictor, but the salivary levels may be helpful in categorizing the ASD subtype.

The relationship between periodontal status and rheumatoid arthritis - systematic review.

There have been numerous publications investigating the relationship between periodontitis (PD) and rheumatoid arthritis (RA) so far. This publication presents the common risk factors for the development of PD and RA. The major impact of the pathological bacterial factor and cigarette smoking with chronic inflammation playing the key role in both diseases has been confirmed by numerous studies in various populations over the years. More research focuses nowadays also on the role of improper diet and obesity. Pathophysiological pathways, such as increased concentration of proinflammatory cytokines, indirectly affecting the cardiovascular complications and coagulation disorders, which has an impact on function disorders of tissue metalloproteinase inhibitors and the plasminogen activation system, were also researched. This systematic review of current literature has shown numerous discrepancies in previous analyses and the need for further detailed research on the relationship between periodontal status and RA.

A case of bizarre posttransplant anti-glomerular basement membrane disease.

The non-collagenous (NC1) domain of α3 and α5 chains of type IV collagen are eminent targets of abnormal immune response in anti-glomerular basement membrane (anti-GBM) disease, which can be diagnosed by the presence of strong linear IgG staining along GBM detected by direct immunofluorescence. The presence of linear GBM fixation in renal allograft is a rare finding. We observed a 33-year-old male with de novo renal failure in a kidney transplant. An examination of a kidney biopsy specimen revealed, in light microscopy, mild mesangial hypercellularity together with mild focal interstitial fibrosis and sparse inflammatory infiltrate. In immunofluorescence microscopy strong linear IgG staining along the capillary walls was seen. Serum anti-GBM antibodies were negative and no mutation in exons coding NC1 domains of α3 and α5 chains of type IV collagen were detected. We described a rare case of a patient with atypical anti-GBM disease in renal allograft, caused probably by the same process which affected the native kidneys.

Seasonal differences in rhythmicity of salivary cortisol in healthy adults.

The existence of seasonal changes in secretion of stress hormones and inflammatory mediators by humans is not certain. Here, we aimed to determine whether concentrations of cortisol and IL-6 displayed seasonal rhythmicity. The study was performed in Poznan, Poland (52°N, 16°E) in 7 healthy female volunteers (age 22.6 ± 0.8 yr). Samples of whole mixed unstimulated saliva were collected in winter (February) and summer (June) at 2-h intervals over a 24-h period and analyzed for cortisol and IL-6 by immunoassays. During each season, the subjects answered questionnaires related to their sleeping habits, food intake, physical activity, and perceived seasonality. It turned out that salivary concentrations of cortisol followed a daily rhythm both in winter and summer, as determined by a cosine analysis. However, compared with the winter season, a midline-estimating statistic of rhythm in the summer was significantly higher. Moreover, the rhythm acrophase occurred ~4 h later in the summer than in the winter, whereas the amplitudes did not differ. These fluctuations did not correspond to sleeping habits, food and fluid intake, physical exercise, and the self-assessed chronotype. However, the individuals with higher scores on the seasonal affective disorder scale showed a tendency toward lower relative cortisol amplitude in the summer. In contrast to cortisol, salivary IL-6 concentration did not display daily rhythmicity, and its concentrations did not differ significantly between the seasons. In conclusion, in the summer, cortisol level in saliva is elevated, and its circadian pattern of secretion is shifted. The causes for these alterations do not seem to be related to lifestyle and thus remain to be established.

The intensity of joint pain in relation to changes in serum TNFα during therapy with anti-TNFα inhibitors.

INTRODUCTION: Tumor necrosis factor-alpha (TNFα) inhibitors have significantly improved the outcomes of treatment for rheumatoid arthritis (RA). In the present study, we aimed to determine whether serum levels of TNFα during therapy with TNFα inhibitors do really reflect the disease activity and correspond to the intensity of pain experienced. MATERIALS AND METHODS: Thirty RA patients were examined before and after 12 weeks of routine therapy with TNFα inhibitors. Serum levels of TNFα were measured with a high-sensitivity immunoassay and related to patients' clinical and biochemical status. Disease activity was assessed by the modified disease activity score (DAS28). RESULTS: A median relative change in TNFα was 13%. The patients were stratified according to whether the relative change in serum TNFα after therapy was above or below this median value. The patients from both subgroups did not differ in baseline characteristics and response to therapy. However, the patients in whom serum TNFα increased after therapy above the median value had more tender joints after treatment than patients from the other group. Consequently, the number of tender joints after the treatment correlated with absolute TNFα concentrations at this time (r = 0.37; p = 0.049) and the magnitude of changes in serum TNFα correlated with a change in the number of tender joints (r = - 0.48; p = 0.008). CONCLUSIONS: Circulating TNFα levels did not decrease in RA patients treated with TNFα inhibitors, despite clinical and biochemical improvement. It is possible, that circulating TNFα is responsible for the persistence of joint pain in this group of patients.

Diagnostic value of salivary CRP and IL-6 in patients undergoing anti-TNF-alpha therapy for rheumatic disease.

INTRODUCTION: Saliva has been increasingly used as a diagnostic medium for disease detection and monitoring. The aim of this observational, prospective, pilot study was to investigate whether salivary concentrations of CRP and IL-6 correlate with those in serum and with the clinical course of a rheumatic disease. MATERIALS AND METHODS: Nineteen patients with rheumatic disease newly scheduled for anti-TNFα therapy were included. Patients received anti-TNFα treatment (adalimumab, certolizumab, golimumab or infliximab) as per standard protocols. CRP and IL-6 were measured with high-sensitivity immunoassays before and after 12 weeks of therapy, according to standard regimens. The data were analyzed with nonparametric statistics. RESULTS: Concentrations of CRP in saliva correlated significantly with those in serum (R = 0.62; p < 0.0001) and decreased markedly after successful response to treatment. In patients with a limited response to treatment salivary CRP levels increased. In contrast to CRP, the salivary concentrations of IL-6 did not change significantly over the course of therapy and they did not correlate with serum IL-6 concentrations. Salivary levels of neither CRP nor IL-6 corresponded to parameters of oral health and hygiene. CONCLUSIONS: Salivary CRP but not IL-6 could be of potential use for monitoring the rheumatic disease activity.

Bilateral primary pigmented nodular adrenal disease as a component of Carney syndrome - case report.

We report a case of a 20-year-old patient with Cushing's syndrome as a component of Carney syndrome. Carney syndrome is an autosomal dominant disease with co-existing bilateral pigmented nodular adrenal disease, heart and skin myxoma, skin pigmentation, breast fibroadenoma, testicular and ovarian tumours, thyroid tumours, and pituitary adenomas. (Endokrynol Pol 2017; 68 (1): 70-72).

The importance of residual renal function in peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) patients with preserved residual diuresis have a lower risk of death and complications. Here we analyzed associations between residual diuresis and presence of fluid overload and biomarkers of cardiac strain and nutrition in PD patients. METHODS: Among 44 PD patients placed into three subgroups, depending on volume of residual diuresis (group A ≤ 500; group B 600-1900; and group C ≥ 2000 mL/day), we examined: overhydration (OH) assessed by bioimpedance analysis (BIA; yielding OH index OHBIA) and by clinical criteria (edema and hypertension); nutritional status (by subjective global assessment, SGA); metabolic status (electrolytes, serum lipid profile, CRP, and albumin); biomarkers of fluid overload and cardiac strain (N-terminal probrain natriuretic peptide, NT-proBNP, and troponin T, TnT); and, echocardiography and chest X-ray. RESULTS: With increasing residual diuresis in group A, B and C, fewer patients had signs of overhydration defined as OHBIA > 1.1 L (75.0, 42.9 and 33.3 %) or peripheral edema (25.0, 21.4 and 0 %) and NT-proBNP (15199 ± 16150 vs. 5930 ± 9256 vs. 2600 ± 3907 pg/mL; p < 0.05) and TnT (0.15 ± 0.17 vs. 0.07 ± 0.09 vs. 0.04 ± 0.03 ng/mL; p < 0.05) were significantly lower. Significant differences were found also in ejection fraction, SGA, and total cholesterol, albumin and hemoglobin levels whereas blood pressures and serum CRP did not differ significantly. CONCLUSION: Signs of OH and cardiac strain are common in PD patients, even in those with diuresis of 1000-2000 mL/day and with no clinical signs or symptoms, suggesting that even moderate decrease in residual renal function in PD patients associate with OH and other complications.

Preliminary observations on the association between serum IL-6 and hydration status and cardiovascular risk in patients treated with peritoneal dialysis.

INTRODUCTION: Systemic inflammation, as defined by elevated blood IL-6, is a strong independent predictor of peritoneal dialysis (PD) patient survival. The present study has aimed to determine whether there exists a particular "phenotype" associated with high systemic IL-6 that characterizes PD patients in terms of their fluid status and cardiac parameters. METHODS: Fifty-seven prevalent PD patients were classified according to serum concentrations of IL-6. The degree of overhydration was assessed by bioimpedance analysis (BIA). Echocardiography and serum concentrations of NT-proBNP and troponin T were used to assess cardiovascular risk. RESULTS: Patients with high serum IL-6 were older, more often diabetic, treated with PD for longer, and significantly more overhydrated. There was a significant correlation between serum IL-6, hydration status (r=0.38; p=0.002) and serum albumin (r=-0.35; p=0.009). Multivariate regression analysis confirmed a strong association of overhydration, hypoalbuminemia, and systemic IL-6 concentration. Patients with high IL-6 had significantly increased levels of both NT-proBNP (r=0.36; p=0.006) and TnT (r=0.50; p<0.001) in the absence of abnormalities in echocardiography. CONCLUSIONS: High systemic IL-6 identifies PD patients with increased cardiovascular risk that is significantly related to overhydration. Thus, the measurement of serum IL-6 may contribute to the more accurate assessment of cardiovascular status in patients undergoing PD.

Patterns of glomerular disease based on 4-year kidney biopsy material analyzed by light microscopy and immunofluorescence: a retrospective single-center analysis in Poland.

The aim of this study was to assess the epidemiology of different patterns of chronic glomerular diseases based on clinical, histopathological and immunofluorescent findings of glomerulonephritis patients hospitalized in the Department of Nephrology, Transplantology and Internal Diseases in Poznan between January 2009 and December 2012. We retrospectively studied 418 patients who had been subjected to renal biopsies. Data on serum creatinine concentration, 24 h proteinuria, arterial hypertension, diabetes mellitus, and histological and immunofluorescent findings were collected. The patients' mean age was 42 ±15. The male sex prevailed (53.1%). Immunoglobulin A nephropathy was the most common finding (18.9%), followed by focal segmental glomerulosclerosis (16.3%), membranous glomerulonephritis (10.1%), lupus nephritis (8.4%), extracapillary glomerulonephritis (3.3%) and membranoproliferative glomerulonephritis (2.6%). In 69 (16.5%) patients the biopsy was non-informative or non-diagnostic. Patients with membranous nephropathy presented the highest frequency of nephrotic syndrome (71.4%), followed by membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Combined analysis of the clinical, histopathological and immunofluorescent findings in glomerulonephritis patients based on a single center's data can provide important epidemiological findings.