Significance of the angiotensin I/angiotensin II/angiotensin-(1-7) axis in the pathogenesis of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a multisystemic disease with an extensive microvasculopathy. Previously, disturbances in plasma levels of angiotensin II (Ang II) and its antagonistic angiotensin-(1-7) (Ang-(1-7)) were found in patients with SSc. Their significance in a pathogenesis of SSc stays unclear due to discrepancies of earlier studies. OBJECTIVES: To evaluate a significance of disturbances in production pathway of angiotensins in a development of SSc. METHODS: There were enrolled 27 patients with established SSc, 23 subjects with very early SSc and 23 healthy controls. The diagnosis of SSc was established in patients who met EULAR/ACR 2013 classification criteria. Very early SSc described patients with Raynaud's phenomenon having SSc-specific antinuclear antibodies and SSc-like abnormalities in nailfold videocapillaroscopy. Patients were submitted to evaluation of internal organ involvement and blood sampling to assay plasma levels of angiotensin I, angiotensin II and angiotensin-(1-7) with ELISA technique. RESULTS: Plasma level of angiotensin-(1-7) was significantly reduced in both SSc group (median = 47.2 pg/mL; P < 0.001) and ones with very early SSc (median = 102.7 pg/mL; P = 0.002) when compared to healthy controls (median = 176.1 pg/mL). A tendency to higher than in control group (median = 214 pg/mL) plasma level of angiotensin I was seen in SSc group (median = 392 pg/mL; P = 0.059). Differences in plasma level of angiotensin II were insignificant between all study groups. Those disturbances produced unfavourable angiotensin-(1-7)/angiotensin II (%) ratio in both groups of patients, which achieved statistical significance in subjects with established SSc (P < 0.001). Production pathway of angiotensins showed a dependence on a subtype of SSc, immune profile and a presence of interstitial lung disease. CONCLUSIONS: Production of angiotensin-(1-7) was significantly reduced in both SSc patients and those ones with very early SSc, although a significant imbalance between angiotensin II and angiotensin-(1-7) occurred only in subjects with established disease.

Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). METHODS: We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). RESULTS: Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3-12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06-9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05-6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3-25.5), skin involvement (OR = 4.4; 95% CI = 1.02-19.6), and age > 65 (OR = 6.3; 95% CI = 1.18-33.7). CONCLUSIONS: In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database.

OBJECTIVE: To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc). METHODS: This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs. RESULTS: We recruited 7286 patients with SSc; their mean age was 56 +/- 14 years, disease duration 10 +/- 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable. CONCLUSION: Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation.

Influence of short-time application of a low sodium diet on blood pressure in patients with hyperthyroidism or hypothyroidism during therapy.

Hyperthyroidism or hypothyroidism are commonly associated with altered blood pressure (BP). Restriction of sodium in the diet produces a decrease in BP in some individuals. It is also well known that hormones other than thyroid affect BP. The present study was designed to evaluate the influence of a low sodium diet on BP in patients with hyperthyroidism or hypothyroidism during therapy. The occurrence of salt-sensitive or salt-nonsensitive BP was compared with hormonal levels (plasma renin activity, aldosterone, atrial natriuretic peptide, and arginine vasopressin). Patients with hyperthyroidism (75 subjects) were investigated before the initiation of treatment, 2 weeks after the treatment, and after the attainment of euthyroid state. Patients with hypothyroidism (31 subjects) were studied before the treatment and in the euthyroid state. Control values were obtained from 37 healthy individuals. Blood pressure, changes of plasma volume, serum aldosterone, atrial natriuretic peptide, vasopressin levels, and plasma renin activity were measured in all investigated subjects after application of a normal sodium diet and after 3 days on a low sodium diet. Elevated systolic BP was found in patients with hyperthyroidism and hypothyroidism. Mean arterial BP was higher only in the untreated hypothyroid patients. The high incidence of salt-sensitive BP was found only in untreated hypothyroid patients. Also in hypothyroid patients the application of a low sodium diet led to a lower increase in plasma renin activity in subjects with salt-sensitive BP than in individuals with salt-resistant BP. Therefore, different mechanisms are responsible for BP elevation in patients with hyperthyroidism or hypothyroidism.

A decreased serum leptin level in patients with systemic sclerosis.

Serum leptin levels were determined in 31 women with systemic sclerosis and 24 age-matched healthy controls. Both groups were divided into premenopausal and postmenopausal subgroups. A decreased serum leptin was found in the patients with systemic sclerosis. The premenopausal patients and controls had higher serum leptin than those in the postmenopausal subgroups. Serum leptin correlated with body mass index in the patients with systemic sclerosis.

The systolic function of the left ventricle of the heart in patients with hyperthyroidism during therapy.

Hyperthyroidism is associated with enhanced systolic function. The present study was designed to evaluate systolic cardiac function in patients with hyperthyroidism during a short-term and a long-term pharmacotherapy. The diagnostic value of various indices of the left ventricle function was analysed. Fifty-one hyperthyroid patients were investigated before initiation of the treatment, after 14 days of therapy with thiamazol (mean dose 54 mg/24 hr), a short-term treatment and after attainment of normal thyroid function, a long-term treatment (mean period 9 months). Control values were obtained from 30 healthy individuals. All investigated subjects were aged 18-50 yr. The following indices were determined with ultrasonocardiographic method: preejection period (PEP), left ventricle ejection time (LVET), preejection period index (PEPI) and left ventricle ejection time index (LVETI), index PEP/LVET, left ventricle shortening fraction (LVSF), left ventricle ejection fraction (LVEF), mean velocity of the circumferential fiber shortening (mVcf), contractility index (CIx), stroke volume (SV), cardiac index (CI), output-pressure index (OPI) and end-systolic wall stress (ESWS). Additionally, total peripheral resistance index (TPRI) and double product (DP) were calculated. In patients with untreated hyperthyroidism, a significant shortening of PEP, PEPI, LVET and low PEP/LVET index and TPRI as well as increased LVSF, LVEF, mVcf, CIx, CI, OPI and DP were shown. There was no changes in LVETI, SV and ESWS. A short-term treatment resulted in changes in PEP, PEPI, LVET, mVcf, CI and OPI in direction of normal values. After a long-term treatment all altered indices were normal with an exception of OPI, CI and DP. It is concluded that enhanced systolic function of the heart in patients with hyperthyroidism becomes normal after pharmacological control of the thyroid gland. Some changes are seen after a short-term treatment with thiamazol. The indices which reverse early are PEP, PEPI, LVET, mVcf and CI. Changes in ejection function of the left ventricle in patients with hyperthyroidism are resulted from increased heart rate and were found to be related to total peripheral vascular resistance.

Changes of plasma arginine-vasopressin level in patients with hyperthyroidism during treatment.

BACKGROUND: Hyperthyroidism is associated with several kinds of changes in the circulatory system, including alterations in blood volume. Arginine-vasopressin (AVP) is known to be one of the major factors regulating plasma volume. The present study was designed to evaluate the plasma AVP level in patients with hyperthyroidism during treatment. MATERIAL AND METHODS: AVP was measured under basal conditions and after stimulation with a low-sodium diet and upright position. Seventy-four patients with hyperthyroidism and 37 controls were investigated. Measurements were taken before treatment, two weeks after pharmacological treatment, and after attaining euthyroid status. The following indices were determined: AVP, total and free thyroxin and triiodothyronine, thyrotropin, sodium, potassium, hematocrit, arterial blood pressure, cardiac index, and total peripheral resistance index. Plasma osmolality and changes in plasma volume were calculated indirectly. RESULTS: Plasma AVP was higher in patients with hyperthyroidism before treatment. After normalization of thyroid status, the AVP level was similar to that of the controls. The application of a low-sodium diet and upright position resulted in a greater decrease in plasma volume than the controls. AVP correlated with thyroxin level and plasma osmolality in patients with hyperthyroidism. CONCLUSION: Enhanced AVP level in patients with hyperthyroidism is suggested to be the result of alterations in plasma volume and is relatively independent of changes in plasma osmolality.

Serum matrix-degrading enzymes in rats intoxicated with selenium.

The effect of poisoning doses of selenium on serum matrix-degrading enzymes activity was investigated in rats intoxicated with selenium. Fifteen animals were receiving orally sodium selenite in a daily dose of 300 microg/kg body weight. Intoxication with selenium was carried out for 10 weeks. The present study revealed significant increase in activities of enzymes involved in the connective tissue matrix metabolism i.e. beta-glucuronidase, N-acetyl-beta-glucosaminidase, elastase and collagen peptidase. There was no change in the cathepsin activity. The relative enzyme activities calculated over protein level resulted in higher values than those found in direct measurements. Serum enzyme activity was increased most for elastase (about 31%) and N-acetyl-beta-glucosaminidase (about 33%) based on activity per gram of protein. The current data indicate that lysosomes are target organelles for selenium toxicity. Generalized increase in lysosomal enzymes activity contributes to the altered metabolism of the connective tissue in selenium-intoxicated animals. The mechanisms that lead to the increase of lysosomal enzymes activity in rats receiving poisoning doses of selenium could be related to biochemical disturbances caused by selenium toxicity.