Yeast-Derived Nucleotides Enhance Fibroblast Migration and Proliferation and Provide Clinical Benefits in Atopic Dermatitis.

Nucleotides, glycosaminoglycans, and omega-3 essential fatty acids (O3s) could be used for improving skin health, although their modes of action, alone or in combination, are not yet fully understood. To gain some insight into these mechanisms, we performed two in vitro tests and one in vivo pilot trial. The effects on human dermal fibroblast proliferation and migration were evaluated with the following compounds and combinations: 0.156 mg/mL O3s, 0.0017 mg/mL hyaluronic acid (HA), 0.0004 mg/mL dermatan sulfate (DS), 0.0818 mg/mL nucleotides, and [O3s + HA + DS] and [O3s + HA + DS + nucleotides] at the same concentrations. In both in vitro assays, adding nucleotides to [O3s + HA + DS] provided significant improvements. The resulting combination [O3s + HA + DS + nucleotides] was then tested in vivo in dogs with atopic dermatitis by oral administration of a supplement providing a daily amount of 40 mg/kg nucleotides, 0.9 mg/kg HA, 0.18 mg/kg DS, 53.4 mg/kg EPA, and 7.6 mg/kg DHA. After 30 days, the pruritus visual analog scale (pVAS) score was significantly reduced, and no adverse effects were observed. In conclusion, the combination of nucleotides plus glycosaminoglycans and O3s could serve as a useful therapeutic alternative in skin health applications.

The Influence of Rheumatoid Arthritis and Osteoarthritis on the Occurrence of Arterial Hypertension: An 8-Year Prospective Clinical Observational Cohort Study.

Rheumatoid arthritis (RA) increases the risk of cardiovascular mortality and morbidity, including a 50-60% increased risk of cardiovascular disease (CVD). Arterial hypertension (HT) is considered the major contributing risk factor for CVD development in RA patients. In this investigation, we compared the incidence and prevalence of HT between RA and osteoarthritis (OA) and the influence of HT on CVD development in CVD-naive patients in both groups. This was a prospective clinical cohort investigation with an 8-year follow-up period. A total of 201 participants, 124 with RA (investigation group) and 77 with OA (control group), without diagnosed CVD or symptomatic heart failure were included. After selection according to inclusion and exclusion criteria, both groups underwent initial and final visits, and the investigation group underwent annual visits to assess disease activity. Case report forms were completed for each visit. The obtained data were analyzed by a statistician. No difference in the incidence or prevalence of HT was found between the investigation and control groups. No difference in the prevalence of HT was reported between the study groups and age-standardized data from the general population. The investigation group had a higher incidence of CVD than the control group. RA participants with long-term remission had a marginally lower HT prevalence. Although previous studies reported a higher HT prevalence in RA than in OA and the general population, our findings did not support this. The RA group had a higher incidence of CVD, but it is possible that optimal disease control with long-term remission could reduce HT incidence and prevalence while also having beneficial effects on other cardiovascular risk factors (CV) and, consequently, CVD occurrence.

Role of Inflammatory Cytokines in Rheumatoid Arthritis and Development of Atherosclerosis: A Review.

Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis and its clinical manifestations, focusing on the inflammatory mechanisms leading to arterial wall damage, rapid atherosclerotic plaque formation, and thrombosis. Furthermore, the effect of medications used to treat rheumatoid arthritis on the cardiovascular system was studied. The effect of chronic inflammation and medication on traditional cardiovascular risk factors is not the main subject of this review. We observed that uncontrolled chronic inflammation and some medications directly impact all the stages of atherosclerosis. In conclusion, reducing inflammation and maintaining long-term remission in rheumatoid arthritis may prevent early atherosclerosis. We believe that this review will encourage a better interdisciplinary approach to the management of these patients and further research in this field.

Role of galectin-3 in diagnosis and severity assessment of epicardial artery lesions in patients with suspected coronary artery disease.

BACKGROUND: This study aimed to investigate the possible role of serum galectin-3 (Gal-3) levels in the diagnosis and assessment of significant epicardial artery lesions in patients with suspected coronary artery disease (CAD). METHODS: This was a single-center cross sectional cohort study including 168 subjects with suspected CAD and indications for coronary angiography divided into three groups: percutaneous coronary intervention (PCI) group (N 64), coronary artery bypass graft surgery (CABG) group (N 57), and group with no coronary stenosis (N 47). Gal-3 levels were measured and the syntax score (Ss) was calculated. RESULTS: The mean value of Gal-3 in the PCI and CABG group was 19.98 ng/ml, while in the control group, it was 9.51 ng/ml (p < 0.001). The highest value of Gal-3 was found in the group of subjects with three-vessel disease (p < 0.001). When subgroups were analyzed by Gal-3 levels (< 17.8 ng/ml low, 18.8-25.9 ng/ml intermediate, > 25 ng/ml high risk) there was a significant difference between at least two Gal-3 groups for the arithmetic mean of Syntax score (p < 0.001). The syntax I's arithmetic mean at low and intermediate-risk Gal-3 levels was significantly lower than at high-risk Gal-3 levels (p < 0.001). CONCLUSION: Gal-3 could be used as an additional tool for diagnosis and severity assessment of atherosclerotic disease in patients with suspected CAD. Furthermore, it could help identify high-risk subjects in patients with stable CAD.

Coronary Tortuosity Index vs. Angle Measurement Method for the Quantification of the Tortuosity of Coronary Arteries in Non-Obstructive Coronary Disease.

Coronary tortuosity has been recognized as a potential pathophysiological mechanism in the development of non-obstructive coronary artery disease (CAD). The aim of this study was to examine the role of two coronary tortuosity measurement methods in the detection of clinically significant coronary tortuosity. The study included 160 patients with angina symptoms and myocardial ischemia detected by cardiac stress tests in chronic settings and those diagnosed with acute coronary syndrome. After coronary angiography, tortuosity of coronary arteries was assessed by two methods, including measurement of tortuosity angles and calculating of tortuosity index. Significantly more tortuous coronary arteries were detected in the group with non-obstructive CAD (p < 0.01 for all three arteries), with significantly higher tortuosity index (TI) for all three coronary arteries in this group of patients, compared to patients with obstructive CAD. The highest TI for LCX was found in patients with lateral ischemia (p < 0.001) and for LAD in patients with anterior ischemia (p < 0.001). When measured by the angle method, the only association was found between LCX tortuosity and lateral ischemia (OR 4.9, p = 0.046). In conclusion, coronary tortuosity represents a pathophysiological mechanism for myocardial ischemia in non-obstructive CAD. The coronary tortuosity index could be a reliable and widely applicable tool for the quantification of coronary tortuosity.

From Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) to Chronic Coronary Syndrome: Clinical Diagnostic Use of Laser Doppler Flowmetry in Coronary Microvascular Dysfunction.

BACKGROUND MINOCA is defined as myocardial infarction with non-obstructive coronary changes, or the absence of atherosclerotic coronary plaques (less than 50%). The long-term prognosis of these patients is as poor as for those with obstructive coronary disease. Possibilities for treatment follow-up and improvement are still lacking. This case report provides a retrospective analysis of a case of MINOCA that transformed into chronic coronary syndrome (CCS). CASE REPORT A 40-year-old patient had acute coronary syndrome without atherosclerotic changes in the great epicardial coronary arteries, but with slow coronary flow in the left anterior descending coronary artery in 2011 and 2014. Two-dimensional transthoracic echocardiography showed no echocardiographic impairment of myocardial contractility. The comorbidities were visceral obesity, dyslipidemia, and smoking history. After the addition of a calcium channel blocker and trimetazidine to standard therapy, there were no anginal symptoms. In 2019, during a regular health check-up, contrast echocardiography showed a slow rinse of contrast in the apical and medial/distal anterolateral segment with reduced longitudinal strain in the same myocardial segments. Laser Doppler flowmetry (LDF) showed impaired microcirculatory function in the skin microcirculation. CONCLUSIONS This case report highlights: 1) use of the non-invasive, inexpensive, and easy-to-use LDF technique for microcirculatory dysfunction confirmation; 2) follow-up of MINOCA to CCS transition; 3) visceral obesity as a risk factor for MINOCA and CCS; and 4) the role of trimetazidine in CCS.

Coronary microvascular dysfunction in diabetes mellitus.

The significance, mechanisms and consequences of coronary microvascular dysfunction associated with diabetes mellitus are topics into which we have insufficient insight at this time. It is widely recognized that endothelial dysfunction that is caused by diabetes in various vascular beds contributes to a wide range of complications and exerts unfavorable effects on microcirculatory regulation. The coronary microcirculation is precisely regulated through a number of interconnected physiological processes with the purpose of matching local blood flow to myocardial metabolic demands. Dysregulation of this network might contribute to varying degrees of pathological consequences. This review discusses the most important findings regarding coronary microvascular dysfunction in diabetes from pre-clinical and clinical perspectives.

Prognostic value of galectin-3 in patients with heart failure.

Galectins are a family of soluble ß-galactoside-binding lectins that have important role in inflammation, immunity, and cancer. Galectin-3 as a part of this lectin family plays a very important role in development of heart failure. According to recent papers, galectin-3 plasma level correlates with heart failure outcome, primarily with rehospitalisation and death from heart failure. This paper summarizes the most recent advances in galectin-3 research, with the accent on the role of galectin-3 in pathophysiology of myocardial remodelling and heart failure development--with preserved and reduced ejection fraction, and some implication on development of new disease modifying drugs.

Therapeutic dilemmas in the treatment of acute coronary syndrome as manifestation of essential thrombocythaemia.

Essential thrombocythemia (ET), a chronic myeloproliferative disease, is characterized by an increased number of platelets and risk of vascular thrombosis. A case of a patient treated for ET who had acute myocardial infarction (MI) and reinfarction within a month is presented. A 55-year-old male patient was hospitalized because of subacute inferolateral non-ST-segment-elevation MI, without risk factors for cardiovascular diseases. The patient has been treated for ET for the past 8 years, received anagrelide for the past two years. The first coronary-angiography did not detect significant stenosis of epicardial vessels; the patient was discharged in stable condition with anagrelide therapy. Two weeks later, the patient had an acute anterolateral ST-segment-elevation MI. Primary percutaneous coronary intervention showed thrombus in the distal part of the left anterior descending coronary artery. Percutaneous transluminal coronary angioplasty was performed and eptifibatide was administered after the procedure. There was no residual stenosis, prescribed therapy included clopidogrel and low-molecular-weight heparin. Anagrelide therapy was replaced with hydroxyurea (HU) and acetylsalicylic acid (ASA). It is necessary to treat ET in line with the standard treatment protocol for coronary diseases. In the treatment of high-risk hematology patients anagrelide proved to be a worse option than the combination of HU and ASA. .

Overweight - early stage of "adipokines related cardiovascular diseases": leptin and adiponectin relation to anthropometric parametars.

AIM: Adipose tissue possess endocrine functions that include synthesis of various adipocytokines, which affect the metabolism of lipids and glucoses, development of atherosclerotic processes, and are involved in the development of hypertension and cardiovascular diseases. Body fat distribution is a significant risk factor for the development of obesity related diseases. Leptin and adiponectin are adipokines whose concentrations vary with the level of obesity. The aim of this research is to determine the relation of the changes in leptin and adiponectin concentrations in overweight persons with anthropometric parameters of the subjects. METHODS: The study included 40 adult, hypertensive subjects - divided into two groups according to sex, with the body mass index 25-30 kg/m², with regular glycemia and renal function. All subjects underwent biochemical (serum lipid, glucose and creatinine level) and anthropometric measurements. Leptin concentration was determined by radioimmunoassay, while adiponectin concentration was determined by enzyme immunoassay. RESULTS: Both leptin and adiponectin concentrations significantly correlated with the waist circumference in both groups of subjects. In male subjects, leptin concentration correlated positively with the body mass index and the hip circumference, while adiponectin concentration correlated negatively with the hip circumference. CONCLUSION: Being overweight is a condition marked by pathologically altered values of leptin concentration (increased level) and adiponectin (decreased level), that are changing as the obesity level and the waist circumference increase. It can be concluded that abdominal obesity and higher body mass index increase the risk for the development of overweight-obesity-related diseases.

Low adiponectin serum level--reduced protective effect on the left ventricular wall thickness.

Adiponectin, secreted by fat tissue, is down - regulated in obesity and may be involved in obesity-related disorders. It has anti-inflammatory, antiatherosclerotic and antidiabetic effect. Obesity is a strong predictor for hypertension and cardiovascular diseases. Recent studies showed that adiponectin level has important role in metabolic disorders, arterial hypertension and ischemic heart disease but its effect on left ventricular hypertrophy (LVH) has not been fully clarified. The aim of this research is to determine whether the protective effect of adiponectin against development of left ventricular hypertrophy is decreased in hypertensive overweight patients. The study included 61 adult, overweight hypertensive patients, with body mass index in range 25-30 kg/m2. Patients had regular morning glucose serum values and regular creatinine level. They were divided into four groups, according to sex and the presence of LVH. There were 16 female and 15 male hypertensive patients with LVH and 15 female and 15 male hypertensive patients without LVH, who were a control group. Glucose profile, lipidogram, creatinine clearance and anthropometric measures were determined in all patients. Cardiovascular measurements were taken applying two-dimensional ultrasound. Adiponectin serum level was measured using enzyme immunoassay (ELISA). Results showed that adiponectin serum level was significantly lower in hypertensive, overweight females and males with LVH than in the control groups without LVH. Adiponectin serum level did not correlate significant with intraventricular or with posterior wall thickness of left ventricle. Hypoadiponectinemia presents part of neurohumoral, non-haemodynamic system who contributes to obesity-related hypertension and left ventricular hypertrophy development. Low adiponectin level together with others adipokines, cytokines and chemokines secreted by fat tissue could contribute to pathophysiologic changes of the myocardium via unknown molecular mechanisms yet.

Clinical characteristics of patients with spondyloarthritides and HLA-B27 positive antigen.

The aim of this study was to present our experiences in diagnosing spondyloarthritides (SpA), and to list the most common clinical features of HLA-B27 positive patients. The study included 65 HLA-B27 positive patients with confirmed diagnosis of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) who were analyzed between 2009 and 2010 in Clinic of Internal Medicine in Osijek. The diagnosis of seronegative spondyloarthritides was based on the ASAS (Assessment in AS Working Group) classification criteria for axial and then supplemented with ASAS criteria for peripheral SpA and was confirmed by radiological techniques. For diagnosing the ankylosing spondylitis (AS), there have been applied the modified New York criteria. Radiological criteria for definite sacroiliitis according to the modified New York criteria is bilateral sacroiliitis, grade 2-4 (> or = 2) or unilateral sacroiliitis, grade 3-4. For diagnosing the psoriatic arthritis (PsA), there were used CASPAR diagnostic criteria. Other features of SpA are defined within the existing classification criteria. HLA-B27 antigen was determined by direct immune-fluorescence technique using flow cytometer. The average age of patients was 50.34 years, of whom 27 female (41.53%), 38 male (58.46%). Duration of illness was 15.79 years on average. With 75.38% of patients, there had been determined the diagnosis of AS; 24.62% of patients had the diagnosis of PsA. The most common clinical characteristics that patients had were: inflammatory back pain (pain Inflammation along the lumbosacral spine), peripheral arthritis, intermittent pain in the gluteus, sacroiliitis, enthesitis, uveitis, dactilitis.

[Arthritis in paraneoplastic syndrome--a way to early cancer diagnosis? A case report]. / Artritis u sklopu paraneoplasticnog sindroma- -put do rane dijagnoze neoplazme? Prikaz bolesnika.

Paraneoplastic syndrome is defined by clinical, radiological, and biological features associated with malignant disease without direct tumor invasion. The aim of our study was to present clinical and laboratory features of six cases ofparaneoplastic arthritis, witch can help to establish early cancer diagnosis, and help to distinguish paraneoplastic arthritis from other rheumatic diseases. According to our case analysis, pareneoplastic arthritis has occurred in both sex equally, all patients were older than 45 years, in most of cases it occurred within 14 months before cancer diagnosis, usually in early stage of cancer. Clinical features of paraneoplastic arthritis were: symmetric poliarthritis, usually were affected small hand joints and knees, predominant acute onset, and rheumatic nodes weren't present. Laboratory tests showed: high inflammatory markers (C-reactive protein, and erythrocyte sedimentation level), negative rheumatoid factor, and negative anti-citrullinated protein antibody. X-ray scan did not show signs of joint destruction. Long term remission ofparaneoplastic arthritis was achieved by treatment of cancer.

[Diagnostic and therapeutic approach to pregnant women suspect on antiphospholipid syndrome]. / Dijagnosticko-terapijski pristup trudnicama suspektnim na antifosfolipidni sindrom.

Antiphospholipid syndrome includes the presence of antiphospholipid antibodies, vascular thrombosis and reproductive function disturbances. The aim was to show our diagnostic and therapeutic experiences. 62 women were included in study, 32 with primary antiphospholipd syndrome (PAPS), and 30 with secondary antiphospholipid syndrome (SAPS). 36 were pregnant and studied prospectively throughout pregnancy and six weeks after the delivery. Lupus-anticoagulant (LA) was positive in 23 patients with PAPS (71.9%), and in 10 patients with SAPS (33.3%). In SAPS group anticardiolipin antibodies (aCL) was positive in 8 patients (26.6%) compared to PAPS group with 3 aCL positive patients (9.4%). Antibeta2glycoprotein1 (antibeta2GP1) was positive in 3 patients with PAPS. Complications in previous pregnancies were in 25 cases (69.4%) spontaneous abortion, in 7 cases (19.4%) preeclampsia with intrauterine growth restriction (IUGR) in 3 patients. In 4 cases the complication was fetal death in utero. Average pregnancy lasted 37.06+/-0.707 weeks. Therapy with low dose aspirin and low-molecular-weight heparin was successful in 97.2%.

Hyperleptinemia--non-haemodynamic risk factor for the left ventricular hypertrophy development in hypertensive overweight females.

Obesity is directly and strongly associated with hypertension and left ventricular hypertrophy (LVH). Development of LVH is multifactorial, caused both by haemodynamic and non-haemodynamic factors. Hypertension is the main haemodynamic factor. Humoral mechanisms, as a non-haemodynamic factor for LVH development, have not been completely explained. The aim of this study is to determine whether hyperleptinemia can be one of humoral--non-haemodynamic factor inducing LVH together with haemodynamic factors in overweight females. The study was done on thirty six adult, overweight female patients, body mass index in range 25-30 kg/m2. Patients are nondiabetic with regular renal function. Twenty one female patients were hypertensive with left ventricular hypertrophy. Control group included fifteen hypertensive female patients without left ventricular hypertrophy. In all patients was determined glucose profile and creatinine clearance, cholesterol, triglycerides, LDL, HDL. Weight, high, circumference of the waist and hips was taken. Cardiovascular determination was done applying two-dimensional ultrasound. Serum leptin level was measured using radioimmunoassay method (RIA). Results showed that serum leptin level was significantly higher in hypertensive, overweight females with LVH. This suggests that non-haemodynamic factors, such as hyperleptinemia, participate in left ventricular hypertrophy development together with haemodynamic factors in adult hypertonic, overweight females.

Vascular thrombosis associated with antiphospholipide syndrome.

The aim of this study was to present our diagnostic and therapeutic experience with antiphospholipide syndrome (APS) and vascular thrombosis. Ninety-nine patients with positive antiphospholipide antibodies (aPL) and vascular thrombosis were included in the study: forty patients, according to clinical classification criteria, had primary antiphospholipide syndrome (PAPS), and fifty-nine patients had secondary antiphospholipide syndrome (SAPS). In PAPS group, 82.5% of the patients were LA-positive, 37.5% of the patients were IgG aCL-positive, 27.5% of the patients were IgM aCL-positive, and 15% of the patients were IgG antibeta2GPI-positive. In SAPS group, 61% of the patients were LA-positive, 50.8% of the patients were IgG aCL-positive, and 47.5% of the patients were IgM aCL-positive. Administered therapy was low molecular weight heparin (LMWH) throughout 7 days, followed by warfarin with prothrombin time maintained between 2.0 and 3.0 INR.

Giant cell arteritis: how to diagnose?--a case report.

We present a case of 77 years old male with suspected giant cell arteritis. With anamnesis, physical examination, immunological tests, Colour Doppler ultrasonography of superficial temporal artery and finally with patohistological analysis of temporal artery biopsy, we came to right diagnosis.

Antibody profile of pregnant women with antiphospholipid syndrome and pregnancy outcome after treatment with low dose aspirin and low-weight-molecular heparin.

The aim of the research was to show our diagnostic and therapeutic experience with antiphospholipid syndrome (APS) in pregnant women. 36 pregnant women suspect on APS were included in the study: 32 with primary antiphospholipd syndrome (PAPS) and 4 with secondary antiphospholipid syndrome (SAPS). All pregnant women received low-molecular-weight-heparin (LMWH) and low dose aspirin (LDA) therapy. Control group represented 26 women with SAPS and previous bad reproductive anamnesis. Average pregnancy lasted 37.06 +/- 0.707 weeks. LMWH and LDA therapy was successful in 97.22%. Lupus anticoagulant (LA) was found to be more frequent in PAPS group (71.87%). Anticardiolipin antibodies (aCL) were found to be more frequent in SAPS (26.66%). For three patients (3.37%), PAPS was diagnosed due to a fact that they had positive antibeta2-glycoproteinl (antibeta-GP1). To make APS diagnosis, it is of great importance to search for all antiphospholipid antibodies. LMWH and low dose of acetylsalicylic acid should be the first choice therapy.

Anti-citrullinated antibodies, radiological joint damages and their correlations with disease activity score (DAS28).

Determination of anti-citrullinated peptides (anti-CCP) specificity as a predictor of joint erosive changes, correlation between their serum level and radiological damages as well as disease activity score (DAS28). A trial has been conducted on a 211 patient sample fulfilling ACR criteria for rheumatoid arthritis (RA). There was assigned anti-CCP serum level, disease activity score by the formula for DAS28(3)-CRP and assessed radiological changes degree after Steinbrocker score. In 132 patient (62.559%) the serum anti-CCP concentration was positive for RA. Specificity of the test was 100% and sensitivity 65% (Z = 0.731, p = 0.465). There is a medium intensity correlation between variables representing anti-CCP and Steinbrocker score. Pearson's coefficient was 0.479 and Spearman's rank correlation coefficient was 0.614, i.e. statistically significant (p = 0.000). There is no statistically significant correlation between variables representing anti-CCP and DAS28(3)-CRP Anti-CCP are good RA predictor and their concentration correlate with radiological damages degree.