Influence of hypertension, obesity and nicotine abuse on quantitative and qualitative changes in acute-phase proteins in patients with essential hypertension.

BACKGROUND: Hypertension is a powerful risk factor for cardiovascular disease and frequently occurs in conjunction with obesity. Accumulative evidence suggests a link between inflammation and hypertension. The aim of study was to evaluate whether blood pressure, obesity and smoking may influence acute-phase response. MATERIAL/METHODS: Ninety-two patients with essential hypertension and 75 healthy volunteers as a control group were studied. In all subjects assessment of hsCRP, alpha1-acid glycoprotein (AGP), alpha1-antichymotrypsin, transferrin, alpha1-antitrypsin, and C3 and C4 complement were performed. Evaluation of glycosylation profile and reactivity coefficient (RC) for AGP was done by means of affinity immunoelectrophoresis with concanavalin A as a ligand. RESULTS: When compared to the controls, hypertensive subjects presented significantly higher hsCRP concentrations and lower transferrin level. Hypertensive patients had elevated AGP-AC. The intensification of the inflammatory reaction was greater in the subgroup of hypertensive patients smoking cigarettes. In obese hypertensives, elevated serum C3 complement level was found. CONCLUSIONS: We conclude that arterial hypertension may evoke the acute-phase response in humans. Markers of acute-phase response are particularly strongly expressed in smokers. Serum C 3 complement, but not other APPs, is elevated in hypertension coexisting with obesity.

[Could serum DHEA and DHEAS levels be good risk predictors of metabolic syndrome and osteoporosis in the population of ageing men?]. / Czy stezenia dehydroepiandrosteronu oraz jego siarczanu w surowicy sa dobrymi wskaznikami zagrozenia wystapienia zespolu metabolicznego i osteoporozy u starzejacych sie mezczyzn?

UNLABELLED: The occurrence of metabolic syndrome (MS) and osteoporosis is essentials danger for public health. It seems that one of epidemiological factors of those diseases is age-depending adrenal androgens deficiency. AIM OF THE STUDY: was to evaluate relationships between DHEA/DHEAS serum levels and BMD along with frequency of MS in ageing Caucasian men. MATERIALS AND METHODS: In 271 randomly chosen men aged 40 to 80 years living in Lubuskie district (Poland) adrenal androgens, anthropometrical indices in addition to densitometry were estimated. RESULTS: DHEA/DHEAS serum levels showed positive correlation with BMD (r = 0.16 and r = 0.18, respectively, p < 0.001). Statistic essential dependencies between decreased adrenal androgens and coexistence of neoplastic diseases (p < 0.001), hypertension (p < 0.05), peripheral perfusion disturbances (p < 0.005) and dementia (p < 0.0001) were also observed. CONCLUSIONS: The evaluation of DHEA/DHEAS serum level is useful in estimation of general health status of ageing men, but does not identify participants suffering from metabolic syndrome.

Does low-dose and short-term glucocorticoids treatment increase the risk of osteoporosis in rheumatoid arthritis female patients?

Rheumatoid arthritis (RA) is frequently complicated by peri-articular and generalized osteoporosis due to increased bone resorption by activated osteoclasts. Pro-inflammatory cytokines, such as TNF-alpha, interleukin 1 (IL1), and interleukin 6 (IL6) are thought, among other factors, to be directly responsible for this extra-articular complication of RA. Glucocorticoids (GCS) commonly prescribed in RA due to their strong anti-inflammatory effect are also well known for causing secondary osteoporosis during a prolonged use. An influence of low-dose GCS therapy (8.7 mg per day) on a bone turnover in female RA patients with or without previous history of GCS treatment was investigated by measuring bone mineral content (BMC), bone mineral density (BMD), and various biochemical markers of inflammation and bone metabolism in comparison to results obtained from: (1) RA patients who have not been treated with GCS and (2) the control group of healthy individuals. Sixty-two female patients with established active RA and 178 healthy individuals from the control group have been investigated. The RA patients were divided into three groups: 21 treated with GCS before the trial--these patients have continued GCS therapy using low doses during the observation; 21 with low-dose GCS therapy launched at the beginning of the trial; and 20 left without GCS treatment. All patients have been assessed twice: at the beginning and after 12 months of observation. BMC and BMD have been measured in all patients in a distal part of forearm. Additionally, several different biochemical markers of osteoporosis and inflammation have been determined. We did not notice any increase in bone metabolism between RA patients receiving GCS therapy for the first time and those treated without GCS after 12 months of observation. Results of BMC, BMD osteocalcin level, total and bone alkaline phosphatase, carboxy-terminal collagen cross links, carboxy-terminal propeptides of type 1 collagen, deoxypyridynoline, and calcium/creatinine ratio were comparable in both groups at the end of the study. There was a significant decrease of the level of IL-6 in patients who had GCS therapy launched at the beginning of observation (p<0.01). However, levels of C-reactive protein (CRP) and alpha1-acid-glycoprotein (AGP) have not changed; the level of ESR dropped significantly (p<0.05) in this group. In contrast, in the group of patients with the previous history of prolonged GCS treatment receiving low doses of GCS during the trial, statistically significant increase of CRP and AGP could be observed (p<0.05) along with further significant worsening of the primary low BMD (p<0.05). Based on the obtained data, we came to the conclusion that anti-inflammatory effect of the low-dose GCS therapy in RA patients without previous history of their use may balance their direct negative effect on BMC and BMD. In this group of RA patients, benefits resulting from the 12-month GCS therapy prevail over adverse effects, even if calcium with vitamin D3 supplementation, biphosphonians, or estrogens have not been introduced. On the other hand, low-dose GCS therapy could have no benefit for RA patients with the previous history of their prolonged use, as a rise of markers of inflammation and bone turnover, resulting in the further bone loss, has been observed.

The effect of methylprednisolone pulse treatment on cytokine network in Graves ophthalmopathy.

The etiology of Graves ophthalmopathy (GO), representing the most common extrathyroidal manifestation of Graves disease, is multifactorial. Among multiple genetic, environmental, and endogenous factors, cytokines play a critical role in its etiopathogenesis. We studied an effect of glucocorticoid therapy on the serum IL-6, IL-4, and IL-13 levels in 18 GO patients. All the patients presented euthyroid GO with over 4 points according to the CAS classification (range 4-6; mean 4.94). The patients were treated with methylprednisolone (1 g every second day for three times) followed by 6 months oral prednisone (60 mg/day, with gradual reduction). The clinical examination (Clinical Activity Score and the GO severity by modified NOSPECS classification) and measurement of anti-TPO, anti-TG, anti-TSHR (TRAK), IL-6, IL-4, as well as IL-13 serum levels were performed before, after 2 weeks, and after 6 months of the glucocorticoid therapy. Significant serum IL-6 increases (p < 0.001) and moderate serum IL-4 and IL-13 increases (p < 0.05) were found in GO patients compared with healthy controls. After 2 weeks of the therapy, the serum IL-6 levels decreased in majority of the patients, however after 6-month observation, lower serum IL-6 levels were only in 8 patients who seemed to respond clinically to the therapy (mean value of the Clinical Activity Score decreased from 4.5 before the therapy initiation to 1.25 after 6 months of the glucocorticoid therapy). No changes in IL-4 and IL-13 serum levels during the therapy were observed. Statistical analysis revealed a good correlation between serum IL-6 level and the Clinical Activity Score (p < 0.01). Based on the obtained data, we conclude that IL-6 plays an important role in GO. It seems that IL-6 may serve as a useful factor in the inflammatory events of GO.

[Changes in certain biochemical markers of bone turnover in rheumatoid arthritis patients treated with short-term low dose glucocorticosteroids]. / Ocena zmian wybranych biochemicznych wskazników metabolizmu tkanki kostnej u chorych na reumatoidalne zapalenie stawów krótkotrwale leczonych glikokortykosteroidami.

Osteoporosis associated with rheumatoid arthritis (RA) is induced by chronic inflammation. Glucocorticosteriods (GCS) applied in the treatment of RA chronically reduce production of proinflammatory cytokines (IL-1, IL-6, and TNF) which are potent stimulators of bone resorption. On the other hand they directly reduce bone mass by inhibition of osteoblast. In order to assess bone turnover the following parameters have been measured: Alkaline phosphatase (AP), alkaline phosphatase-bone formation (AP-B), deoxypirydynoline (Dpd) and carboxyterminal telopeptides of type I collagen (CTx). Based on the obtained findings we conclude that: 1. Decrease in level of AP-B and CTx may suggest reduction of bone turnover, 2. Short-term low dose GCS therapy dramatically reduce inflammation which temporarily may reduce the loss of bone mass.

Cardiac valvular disease in patients with systemic lupus erythematosus. Relationship with anticardiolipin antibodies.

We performed two-dimensional and Doppler echocardiography in 52 patients with systemic lupus erythematosus and in 34 healthy controls. In 25 patients (48.1%) echocardiographic disturbances were found (25/52 vs 2/34, p<0.001). Valvular abnormalities were detected in 18 patients (34.6%) but in only two controls (18/52 vs 2/34, p<0.01). The mitral valve was involved in 12 patients (23.1%). The most frequent finding was mild (13.5%) and moderate (9.6%) regurgitation or valvular thickening (9.6%). The aortic valve was involved in six and the tricuspid valve in three patients (11.5% and 5.8%, respectively). Only one patient had echocardiographic non-infective verrucous vegetation affecting the tricuspid valve. We did not observe significant hemodynamic valve disease. Endocardial findings were related to disease duration (p<0.05) but not to disease activity. Twenty-eight SLE patients (53.8%) had increased anticardiolipin antibodies (aCL). Patients with aCL (particularly those with IgG class) were characterized by a high incidence of echocardiographic abnormalities (p<0.001), mainly valvular (mitral or aortic) regurgitation (p<0.05). We found a relationship between anticardiolipin antibodies and disease activity (p<0.05). In conclusion, we postulate a prominent role for anticardiolipin antibodies in the pathogenesis of heart valve disease in patients with SLE.

The effect of long-term glucocorticoids on bone metabolism in systemic lupus erythematosus patients: the prevalence of its anti-inflammatory action upon bone resorption.

The study was made to evaluate bone turnover in systemic lupus erythematosus (SLE) patients undergoing long-term glucocorticoid therapy. Thirty-eight female patients with established SLE were compared with a control group consisting from 160 age-matched healthy women. Serum concentrations of proinflammatory cytokines: interleukin-1alpha, interleukin-6, tumor necrosis factor-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) and some biochemical markers of osteoporosis (osteocalcin, total and bone alkaline phosphatase, procollagen type I carboxyterminal propeptide, carboxyterminal telopeptides of type I collagen--CTx) were measured. Additionally, morning urine excretions of deoxypyridinoline and calcium/creatinin ratios were determined. The forearm densitometry (DXA) was performed in all patients. Bone mineral content (BMC) and bone mineral density (BMD) in the SLE group was not significantly different from the controls, and no relationship was found between the glucocorticoid exposure and the BMC/BMD. However, biochemical markers of bone resorption--CTx and calcium/creatinin ratio--were significantly increased in the patient group. Our results suggest that BMD/BMC is preserved in glucocorticoid-treated SLE patients despite accelerated bone turnover.

Rheumatoid arthritis susceptibility genes: An overview.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes have been indicated so far in the pathogenesis of RA. Apart from human leukocyte antigen, large genome wide association studies have identified many loci involved in RA pathogenesis. These genes include protein tyrosine phosphatase, nonreceptor type 22, Peptidyl Arginine Deiminase type IV, signal transducer and activator of transcription 4, cytotoxic T-lymphocyte-associated protein 4, tumor necrosis factor-receptor associated factor 1/complement component 5, tumor necrosis factor and others. It is important to determine whether a combination of RA risk alleles are able to identify patients who will develop certain clinical outcomes, such myocardium infarction, severe infection or lymphoma, as well as to identify patients who will respond to biological medication therapy.

Influence of infliximab on cytokines network and markers of bone remodeling in rheumatoid arthritis patients.

PURPOSE: Our aim was to determine the effects of infliximab on bone mineral metabolism in rheumatoid arthritis (RA) patients and analyze the relationship between inflammatory markers of acute phase thought to play a major role in bone remodeling. MATERIALS AND METHODS: 36 patients with established RA were investigated. All patients underwent physical examination and blood and urinary analysis at baseline, 2 weeks, 14 weeks, 6 months and 12 months after the initiation of treatment. The serum levels of: tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor alpha receptor 1 (TNFR1), TNFR2, interleukin 6 (IL-6), IL-17, IL-23 and markers of bone remodeling such as osteocalcin (BGP), deoxypyridynoline (Dpd), and N-telopeptide of type I collagen (NTx) were measured by ELISA. RESULTS: The results showed significant decrease of all the above cytokines levels in RA patients in comparison with those after 2 weeks of treatment. After 6 months, the markers of bone formation and resorption decreased compared to baseline values. We found positive correlation between the levels of NTx and the levels of IL-6, IL-17 and TNFR1, and between the levels of Dpd and IL-6 and Dpd and TNFR2, whereas negative correlation between BGP and IL-23. After 12 months the positive association was found at the BGP level and IL-6 as well as Dpd and the level of IL-6. We also observed a positive relation between Dpd and TNF-alpha and negative between BGP and TNFR1. CONCLUSION: We suggest that infliximab treatment may limit the risk of osteoporosis in RA patients.

Assessment of selected serum inflammatory markers of acute phase response and their correlations with adrenal androgens and metabolic syndrome in a population of men over the age of 40.

INTRODUCTION: Inflammatory mechanisms and decreasing adrenal androgen production are involved in the pathogenesis of numerous age-related diseases. OBJECTIVES: The aim of our study was to assess selected negative (transferrin) and positive (alpha1-antichymotrypsin [alpha1-ACT], C-reactive protein [CRP]) acute phase proteins, and to investigate associations between these proteins and serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels, as well as anthropometrical and biochemical indices of metabolic syndrome (MS) in men over 40 years of age. PATIENTS AND METHODS: In 271 randomly selected men aged 40 to 80 years and living in the province of Lubuskie, Poland, transferrin, alpha1-ACT, CRP, and adrenal androgens were measured and features of metabolic syndrome were evaluated. RESULTS: Age is strongly correlated with acute phase proteins in men: positively for CRP and alpha1-ACT (r = 0.216, P <0.001 and r = 0.193, P <0.05, respectively) and negatively for transferrin (r = -0.268, P <0.0001). CRP revealed a negative correlation with DHEA (r = -0.248, P <0.05), although not with DHEA-S. There were no correlations between alpha1-ACT, transferrin, and adrenal androgens. As opposed to adrenal androgens, serum CRP and transferrin (but not alpha1-ACT) levels are associated with metabolic syndrome (MS) in men over 40 years of age (P <0.001). CONCLUSIONS: A prognostic test using systemic markers of general inflammation (especially CRP) may help (as opposed to DHEA and DHEA-S) identify men over 40 years of age who suffer from MS.

[Change in biomarkers of osteoporosis in rheumatoid arthritis patients treated with infliximab]. / Zmiany wskazników biochemicznych metabolizmu tkanki kostnej u chorych na reumatoidalne zapalenie stawów leczonych infliksymabem.

A study was made to evaluate bone turn-over in rheumatoid arthritis (RA) patients treated with infliximab. Twenty-two patients with established RA were included. In all patients, biochemical markers of osteoporosis: osteocalcin (BGP), alkaline phosphatase (bone isoenzyme), deoxypyridinoline (Dpd), acute phase proteins (CRP, AGP, ACT, AGP-RC), and interleukin 6 (IL-6) were determined before treatment, at week 30, and at week 46. Two markers (BGP, Dpd) were significantly decreased at both weeks 30 and 46. Moreover, a fall in serum levels of acute phase proteins and IL-6 was seen. The results suggest that anti-TNF treatment with infliximab not only decreases activity of inflammation but also may slow down bone turn-over. Further research is needed to assess its potential in reducing risk of osteoporosis in RA.