Tadalafil in Increasing Doses: The Influence on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts.

INTRODUCTION: This study aimed to assess the influence of different doses of tadalafil on coronary flow and oxidative stress in isolated rat hearts. METHODS: The hearts of male Wistar albino rats (n = 48) were retrogradely perfused according to the Langendorff technique at gradually increased constant perfusion pressure (CPP) (40-120 mm Hg). Coronary flow and oxidative stress markers: nitrite oxide (NO) outflow and superoxide anion production in coronary effluent were measured. The experiments were performed during control conditions and in the presence of tadalafil (10, 20, 50, and 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 µM). RESULTS: Tadalafil administration significantly increased coronary flow at all CPP values at all administered doses. Tadalafil led to an increase in the NO levels, but a statistically significant NO release increase was found only at the highest dose and highest CPP. Tadalafil did not significantly affect the release of O2-. After inhibiting the nitrite oxide synthase system by L-NAME, tadalafil-induced changes in cardiac flow and NO levels were reversed. L-NAME administration had no pronounced effect on the O2- release. CONCLUSION: Tadalafil causes changes in the heart vasculature in a dose-dependent manner. It does not lead to a significant increase in the production of superoxide anion radicals.

High-protein diet and omega-3 fatty acids improve redox status in olanzapine-treated rats.

The present study aimed to estimate the effects of high-protein diet (PD)-isolated whey protein and omega-3 fatty acids-docosahexaenoic and eicosapentaenoic acid on oxidative parameters of rats treated with Olanzapine (OLZ). Experiments were carried out on 8-week-old Wistar albino male rats (n = 64) weighing 200 ± 20 g. By dietary and pharmacological treatment, all animals were divided into 8 groups: 1. CTRL group; 2. CTRL + OLZ group; 3. CTRL + FA group; 4. CTRL + OLZ + FA group; 5. PD group; 6. PD + OLZ group; 7. PD + FA group; 8. PD + OLZ + FA group. After 6 weeks of pharmacological/diet treatment, all animals were sacrificed to collect blood samples and determine the biomarkers of oxidative stress. The following oxidative stress markers were measured spectrophotometrically: superoxide anion radical (O2-), hydrogen peroxide (H2O2), nitric oxide (NO-), index of lipid peroxidation measured as TBARS, reduced glutathione, catalase and superoxide dismutase. The study has shown that Olanzapine treatment was associated with increased release of pro-oxidants and diminished activity of anti-oxidant markers. Additional supplementation with PD and FA succeeded in abolishing the negative influence in most of the measured parameters. However, these beneficial impacts were stronger in the case of their separate application, which could be the practical and clinical importance of these results.

Garlic Derived Diallyl Trisulfide in Experimental Metabolic Syndrome: Metabolic Effects and Cardioprotective Role.

This study aimed to examine the effects of diallyl trisulfide (DATS), the most potent polysulfide derived from garlic, on metabolic syndrome and myocardial function in rats with metabolic syndrome (MetS). For that purpose, we used 36 male Wistar albino rats divided into control rats, rats with MetS and MetS rats treated with 40 mg/kg of DATS every second day for 3 weeks. In the first part, we studied the impact of DATS on MetS control and found that DATS significantly raised H2S, decreased homocysteine and glucose levels and enhanced lipid and antioxidative, while reducing prooxidative parameters. Additionally, this polysulfide improved cardiac function. In the second part, we investigated the impact of DATS on ex vivo induced ischemia/reperfusion (I/R) heart injury and found that DATS consumption significantly improved cardiodynamic parameters and prevented oxidative and histo-architectural variation in the heart. In addition, DATS significantly increased relative gene expression of eNOS, SOD-1 and -2, Bcl-2 and decreased relative gene expression of NF-κB, IL-17A, Bax, and caspases-3 and -9. Taken together, the data show that DATS can effectively mitigate MetS and have protective effects against ex vivo induced myocardial I/R injury in MetS rat.

Chronic effects of platinum(IV) complex and its diamine ligand on rat heart function: comparison with cisplatin.

The aim of the present study was to compare the cardiodynamic parameters in the isolated rat heart in animals chronically treated with cisplatin, platinum(IV) complex and its diamine ligand. Sixty Wistar albino rats (8 weeks old) were divided into five groups: three experimental and two control groups. Animals in all groups were treated with a dose of 4 mg/kg body weight once a week for 4 weeks with different substances; experimental groups received cisplatin, ligand and octahedral platinum(IV) complex, and control groups received saline and dimethyl sulfoxide. After sacrificing the animals, hearts were isolated and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of change of pressure in the left ventricle, systolic and diastolic left ventricular pressure, heart rate and coronary flow. The results showed statistically significant differences between all experimental groups in maximum and minimum rate of pressure development as well as in systolic pressure of the left ventricle, whereas cisplatin, ligand and the platinum(IV) complex had effects on heart contractility without significant influences on coronary circulation. The findings of the present study could be important for a better understanding of anticancer drug cardiac side effects. Our results indicate that compared to cisplatin as a "gold standard", novel platinum complexes and ligands do not possess fewer negative effects on the heart, indicating insufficient safety for their usage in terms of affecting cardiac function, a result that can be of great interest for further investigations.

The impact of aerobic and anaerobic training regimes on blood pressure in normotensive and hypertensive rats: focus on redox changes.

This study was aimed to assess the impact of aerobic and anaerobic type of exercise on blood pressure and redox status in normotensive and hypertensive rats. After 1 week of preconditioning feeding and 1 week of preconditioning running regimen, Wistar albino rats (n = 72; bw: 270 ± 50 g) were randomly assigned to three groups according to running protocol (high-intensity interval training (HIIT) or moderate-intensity training (MIT)): sedentary control, MIT, HIIT; spontaneous hypertensive sedentary control (SHR), SHR + MIT and SHR + HIIT. Blood pressure (BP) measurement was performed by a tail-cuff noninvasive method BP system. After 48 h of rest following the final training, the rats were fasted for 24 h and sacrificed under ketamine/xylazine anesthesia and blood samples were collected. The level of the next prooxidants were measured: superoxide anion radical (O2-); hydrogen peroxide (H2O2); nitrite level (NO2-) and index of lipid peroxidation (thiobarbituric acid reactive substances), and the activity of antioxidative enzymes: reduced glutathione (GSH) superoxide dismutase (SOD) and catalase (CAT) activity. After the last week of running, HIIT strongly affected SP, DP, and HR in SHR rats compared to other hypertensive rats, as well as after MIT in normotensive conditions. We have found that HIIT training protocol induced a higher increase of O2- and H2O2 as compared to MIT. Findings of the present study pointed out that contrary to normotensive conditions, in hypertensive conditions both training regimes reduced the BP levels, which was more prominent in case of HIIT. In addition, MIT seems to be connected with milder disturbance of pro-oxidant production and better antioxidant response.

The cardioprotective effects of diallyl trisulfide on diabetic rats with ex vivo induced ischemia/reperfusion injury.

Diallyl trisulfide (DATS) is distinguished as the most potent polysulfide isolated from garlic. The aim of our study was to investigate effects of oral administration of DATS on healthy and diabetic rats, with special attention on heart function. Rats were randomly divided into four groups: CTRL (healthy rats), DATS (healthy rats treated with DATS), DM (diabetic rats), DM + DATS (diabetic rats treated with DATS). DATS (40 mg/kg of body weight) was administered every other day for 3 weeks, at the end of which rats underwent echocardiography, glycemic measurement and redox status assessment. Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion, after which heart tissue was counterstain with hematoxylin and eosin and cardiac Troponin T staining (cTnT), while expression of Bax, B cell lymphoma 2 (Bcl-2), caspase-3, caspase-9 and superoxide dismutase-2 were examined in the left ventricle. DATS treatment significantly reduced blood glucose levels of diabetic rats, and improved cardiac function recovery, diminished oxidation status, attenuated cardiac remodeling and inhibited myocardial apoptosis in healthy and diabetic rats. DATS treatment causes promising cardioprotective effects on ex vivo-induced ischemia/reperfusion (I/R) injury in diabetic and healthy rat heart probably mediated by inhibited myocardial apoptosis. Moreover, appropriate DATS consumption may provide potential co-therapy or prevention of hyperglycemia and various cardiac complications in rats with DM.

Efficiency of atorvastatin and simvastatin in improving cardiac function during the different degrees of hyperhomocysteinemia.

The aim of this study was to assess the impact of atorvastatin and simvastatin on myocardial contractility during the different degrees of hyperhomocysteinemia (HHcy) in rats. Study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. Animals were exposed to pharmacology treatment with atorvastatin in dose of 3 mg/kg per day i.p. or simvastatin in dose of 5 mg/kg per day i.p. at the same time every day, according to equivalent therapeutic doses of these statins (10 mg atorvastatin = 20 mg simvastatin). After the dietary manipulation and pharmacological treatment and confirmation of HHcy, all animals were sacrificed, hearts were isolated, and cardiac function was tested according to the Langendorff technique. Size of recovery of maximum rate of left ventricular development (dp/dtmax), minimum rate of left ventricular development (dp/dtmin), systolic left ventricular development, diastolic left ventricular development, heart rate, and coronary flow at the 40, 60, 80, 100, and 120 cmH2O coronary perfusion pressure were measured in state of physiological condition (homocysteine less than 15 µmol/L), mild HHcy, and moderate HHcy. Atorvastatin treatment significantly attenuated homocysteine-induced impairment of myocyte contractility and dominantly decreased dp/dtmax, dp/dtmin, and heart rate and induced greater changes in systolic left ventricular development compared with simvastatin. Treatment with atorvastatin seems able to revert systolic abnormalities and improve contractility during the different degrees of HHcy.

Comparison of training and detraining on redox state of rats: gender specific differences.

Given the fact that oxidative stress response induced by training/detraining has still not been clarified and may be influenced by gender, the aim of our investigation was to compare the effects of swimming training and detraining on oxidative and antioxidative parameters in rats, with a special focus on sex differences. Wistar albino rats (n = 64) were divided into 4 groups: control, trained group, groups exposed to 2 and 4 weeks of detraining. Each group included two subgroups: males and females. After sacrificing, hearts were isolated and retrogradely perfused according to Langendorff technique. Levels of superoxide anion radical, hydrogen peroxide, nitrites and thiobarbituric acid reactive substances were measured in plasma and coronary venous effluent, while reduced glutathione, activities of superoxide dismutase and catalase were measured in erythrocytes. Our results indicate that swimming training doesn't promote oxidative damage, nor act protectively within the heart. However, 2 and 4 weeks of detraining led to a partial lost in exercise-induced adaptation. It seems that moderate-intensity physical exercise of sufficient duration leads to beneficial adaptations, which may be partially lost during detraining period. Positive antioxidative effects of training remained longer in males. Findings of present study may help in elucidation of training and detraining effects on modulation of redox homeostasis, especially from aspect of gender differences.

The perfusion of cisplatin and cisplatin structural analogues through the isolated rat heart: The effects on coronary flow and cardiodynamic parameters.

The therapeutic use of cisplatin for the treatment of solid tumours is associated with organ toxicity. Amongst those, the cardiotoxicity is an occasional but very serious and severe side effect. To prevent or reduce these negative effects, many cisplatin analogues have been synthesized and evaluated in terms of being a less toxic and more effective agent. In present study, we examined the effects of cisplatin and its three analogues in the isolated rat heart to determine whether changes in the structure of the platinum complexes (changing of carrier ligands - ethylenediamine; 1,2-diaminocyclohexane; 2,2':6',2''-terpyridine) can influence their cardiotoxic effects. The results of our research indicate that the introduction of aromatic rings in the structure of the platinum complexes has a negative influence on the heart function. Conversely, the other two examined complexes had less negative effects on heart function compared to cisplatin. Our findings may be of interest for a possible synthetic strategy of introducing a carrier ligand that will exert a less cardiotoxic effect.

The effects of zofenopril on cardiac function and pro-oxidative parameters in the streptozotocin-induced diabetic rat heart.

Diabetes mellitus is a chronic condition that continues to increase in both incidence and prevalence. Renin-Angiotensin-Aldosterone System is one of the main modulators of chronic hyperglycaemia and, thus, its influence on tissues. Hyperglycaemia-induced oxidative stress is an important factor in diabetic cardiomyopathy. The present study was carried out on 24 adult male Wistar albino rats (8-week-old and with body masses of 190 ± 10 g). We evaluated the influence of acute administration of zofenopril on ex vivo myocardial function from rats with streptozotocin-induced diabetes mellitus, with a special emphasis on cardiodynamic and oxidative stress parameters in diabetic rat hearts. Rats were divided randomly into two groups (12 animals per group): control non-diabetic animals (C) were healthy rats perfused with 1.5 µM of zofenopril, and STZ-treated diabetic animals (DM) were diabetic animals perfused with 1.5 µM of zofenopril 4 weeks after the induction of diabetes. Our results demonstrated that diabetic rats are characterized by a depressed cardiac performance and that oxidative markers are related to alterations in cardiac function in rats with 4 weeks of STZ-induced diabetes. Additionally, the use of zofenopril as a monotherapy slightly diminished cardiac damage induced by chronic hyperglycaemia. However, long-term follow-up intervention trials are necessary to fully demonstrate the benefit of zofenopril in this context. A challenge for future investigations will be to identify the effects of chronic administration or combination therapy with angiotensin-converting enzyme inhibitors in various models of diabetes.

Coronary flow and oxidative stress during local anaphylactic reaction in isolated mice heart: the role of nitric oxide (NO).

The aim of this study was to assess the role of nitric oxide (NO) in cardiac anaphylaxis regarding changes in coronary reactivity and oxidative status of the mice heart. The animals were divided into two groups: experimental group (CBA, iNOS(-/-) mice) and control group: wild-type mice (CBA/H). The hearts of male mice (n = 24; 6-8 weeks old, body mass 20-25 g, 12 in each experimental group) were excised and retrogradely perfused according to the Langendorff technique at a constant perfusion pressure (70 cm H2O). Cardiac anaphylaxis was elicited by injection of solution (1 mg/1 ml) of ovalbumin into the aortic cannula. For the next 10 min, in intervals of 2 min (0-2, 2-4, 4-6, 6-8, 8-10 min) coronary flow (CF) rates were measured and samples of coronary effluent were collected. Markers of oxidative stress including index of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), NO measured in the form of nitrites (NO2(-)), superoxide anion radical (O2(-)), and hydrogen peroxide (H2O2) in the coronary venous effluent were assessed spectrophotometrically. After the ovalbumin challenge, CF was significantly lower in the wild mice group. NO and H2O2 release were significantly higher in iNOS(-/-) mice group. TBARS and O2(-) values did not vary significantly between wild and iNOS(-/-) mice groups. Our results indicate that coronary vasoconstriction during cardiac anaphylaxis does not necessarily depend on inducible nitric oxide synthase (iNOS)/NO activity and that iNOS/NO pathway may not be an only influential mediator of redox changes in this model of cardiac anaphylaxis.

Acute effects of nandrolone decanoate on cardiodynamic parameters in isolated rat heart.

Despite worldwide use of anabolic steroids in last decades, there is still contradictory information about their acute influence on myocardium. The aim of this study was to examine the acute effects of nandrolone decanoate (ND) on cardiodynamics and coronary flow in isolated rat heart. The hearts of male Wistar albino rats (n = 48, 12 per group, age 8 weeks, body mass 180-200 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). After the control sets of experiments, the hearts in different groups were perfused with different doses of ND (1, 10, or 100 µmol/L separately). Using a sensor placed in the left ventricle, we registered maximum and minimum rate of pressure development in the left ventricle (dP/dtmax and dP/dtmin), systolic and diastolic left ventricular pressure (SLVP and DLVP), and heart rate (HR). Coronary flow (CF) was measured flowmetrically. The results clearly show the depression in cardiac function caused by higher doses of ND. The highest concentration of ND (100 µmol/L) induced the most deleterious impact on the myocardial function and perfusion of the heart (coronary circulation), which could be of clinical significance.

Biphasic response of cardiodynamic adaptations to swimming exercise in rats.

The aim of research was to assess exercise-induced changes in mechanics of hearts isolated from rats, as well as time-course of those changes. Wistar rats (n = 42) were divided into control, moderately trained (swimming 1 hour, 5 days a week for 9 or 12 weeks) and strenuously trained (swimming 2, 3 and 4 times a day for an hour in weeks 10, 11 and 12, respectively) groups. After sacrificing, hearts (weight: 1480.82 ± 145.38 mg) were isolated and perfused on a Langendorff apparatus. Coronary perfusion pressure (CPP) was gradually increased (from 40 to 120 cm H(2)O) in order to establish coronary autoregulation. Parameters of cardiac contractility were recorded: maximum and minimum rate of change of pressure in the left ventricle (dp/dt max and dp/dt min), systolic and diastolic left ventricular pressure (SLVP and DLVP), heart rate (HR) and coronary flow (CF). Nine weeks of moderate exercise induced slight depression of coronary function (decrease of dp/dt max, dp/dt min, SLVP and DLVP), while 3 additional weeks of moderate training improved hearts function, but not to the extent that the strenuous training program did. The results of our study add evidence about beneficial effects of regular moderate exercise on heart, and furthermore, show that exercising frequently, if the intensity stays within moderate range, may not have detrimental effects on cardiodynamics.

Effects of Different Therapeutic Approaches on Redox Balance in Psoriatic Patients.

Given that oxidative stress represents an important etiological factor in the pathogenesis of psoriasis, the aim of this study was to assess the effects of different therapeutic approaches, methotrexate, secukinumab, and ustekinumab on systemic oxidative stress biomarkers in psoriatic patients. This study involved 78 psoriatic patients, divided into the group treated with methotrexate (23 patients), secukinumab (28 patients), and ustekinumab (27 patients), and 15 healthy controls. Oxidative stress biomarkers (index of lipid peroxidation measured as TBARS, nitrites (NO2-), superoxide anion radical (O2-), and hydrogen peroxide (H2O2)) and antioxidative defense system (superoxide dismutase (SOD) activity, catalase (CAT) activity, and reduced glutathione (GSH)) were determined spectrophotometrically from the blood before the initiation of therapy in 16th, 28th, and 52nd week. O2- and SOD showed the most prominent changes comparing the psoriatic patients and healthy controls. CAT activity was significantly lower in psoriatic patients, and methotrexate induced a further decline in CAT activity. Ustekinumab induced a significant increase in GSH level after 52 weeks of treatment, while methotrexate reduced GSH. All applied therapeutic options induced a reduction in PASI, BSA, DLQI, and EARP. Biological drugs exert more pronounced antioxidant effects compared to methotrexate, which is most clearly observed in the values of O2- and SOD.

The effects of cyclooxygenase and nitric oxide synthase inhibition on oxidative stress in isolated rat heart.

Despite the widespread clinical use of cyclooxygenase (COX) inhibitors, dilemmas still exist about potential impact of these drugs on cardiovascular system. The present study was aimed to estimate the effects of different COX inhibitors (meloxicam, acetylsalicylic acid [ASA], and SC-560) on oxidative stress in isolated rat heart, with special focus on L-arginine/NO system. The hearts of male Wistar albino rats (total number n = 96, each group 12 rats, 8 weeks old, body mass 180-200 g) were retrogradely perfused according to the Langendorff technique at gradually increased perfusion pressure (40-120 cmH2O). After control experiments the hearts were perfused with the following drugs: 100 µmol/l ASA (Aspirin), alone or in combination with 30 µmol/l L-NAME, 0.3 µmol/l meloxicam (movalis) with or without 30 µmol/l L-NAME, 3 µmol/l meloxicam (alone or in combination with 30 µmol/l L-NAME), 30 µmol/l L-NAME, and administration of 0.25 µmol/l SC-560. In samples of coronary venous effluent the following oxidative stress markers were measured spectrophotometrically: index of lipid peroxidation (measured as thiobarbituric acid reactive substances [TBARS]), superoxide anion radical release (O2(-)), and hydrogen peroxide (H2O2). While ASA was found to have an adverse influence on redox balance in coronary circulation, and coronary perfusion, meloxicam and SC-560 do not negatively affect the intact model of the heart. Furthermore, all effects were modulated by NOS inhibition. It seems that interaction between COX and L-arginine/NO system truly exists in coronary circulation, and can be one of the possible causes for achieved effects. That means: those effects induced by different inhibitors of COX are modulated by subsequent inhibition of NOS.

Variations of Redox Balance in Different Stages of Childhood Immune Thrombocytopenic Purpura.

BACKGROUND: Few previous studies indicated the role of oxidative stress in the pathogenesis of childhood idiopathic thrombocytopenic purpura (ITP), but there are little data regarding changes in redox balance in different forms of the disease, and changes after therapeutic procedures. We aimed to investigate the values of pro-oxidants and antioxidative capacity in various forms of ITP before and after the applying therapy. MATERIALS AND METHODS: The research included 102 children, classified into the following groups: (1) newly diagnosed ITP (ndITP), (2) persistent ITP, (3) chronic ITP (chITP), and (4) control groups: (A) healthy control and (B) previously experienced ITP-healthy children who had been suffering from ITP earlier. During the clinical assessment, a blood sample was taken from the patients, from which the value of pro-oxidants (index of lipid peroxidation measured as TBARS, nitrites [NO2 -], as measurement of nitric oxide [NO] production, superoxide anion radical [O2 -], and hydrogen peroxide [H2O2]) and the capacity of antioxidant protection (activity of superoxide dismutase and catalase, and quantity of reduced glutathione) were determined spectrophotometrically. RESULTS: Our results demonstrated that values of pro-oxidants, especially reflected through the TBARS and O2 -, were the highest in the ndITP and exacerbated chITP groups. Also, the activity of the endogenous antioxidative defense system was the lowest in these groups. Intravenous immunoglobulin therapy in the ndITP group exerted the most prominent effect on the redox balance. CONCLUSION: It can be concluded that severity and exacerbation of the ITP are closely related to the redox status.

Comparison of blood pro/antioxidant levels before and after acute exercise in athletes and non-athletes.

The aims of our study were to assess the redox state of adolescent athletes and non-athletes both at rest and after acute exposure to physical load and to find relations between parameters of redox state and morphofunctional characteristics of subjects. 58 young handball players and 37 non-athletes were subjected to body composition analysis, measuring of maximal oxygen consumption and blood sampling immediately before and after a maximal progressive exercise test. At rest, athletes had significantly higher superoxide dismutase (SOD) and catalase (CAT) activity, higher levels of glutathione (GSH) and nitric oxide (NO) and lower levels of lipid peroxidation (TBARS) compared with non-athletes. A maximal exercise test induced statistically significant rise of superoxide anion radical (O2-), hydrogen peroxide (H2O2) and NO levels in non-athletes, while TBARS levels decreased. Athletes experienced the fall in NO levels and the fall in CAT activity. After exercise, athletes had significantly lower levels of O2- compared with non-athletes. Two way repeated measures ANOVA showed that the response of O2-, NO and TBARS to the exercise test was dependent on the sports engagement (training experience) of subjects. Significant correlations between morphofunctional and redox parameters were found. These results suggest that physical fitness affects redox homeostasis.

Carotid artery intima-media thickness and brachial artery flow-mediated vasodilatation in patients with rheumatoid arthritis.

BACKGROUND: Cardiovascular (CV) morbidity and mortality are increased in patients with rheumatoid arthritis (RA). Our study aim was to determine the relationship between carotid artery intima-media wall thickness (IMT) and flow-mediated endothelium-dependent vasodilatation (FMD) in a patients with RA, in context with clinical and laboratory measurements. PATIENTS AND METHODS: Fifty-two patients with RA and 30 matched healthy controls without clinically evident CV disease were studied. Brachial and carotid ultrasonography was performed to determine FMD and IMT, respectively. We also assayed immunological, inflammatory and metabolic laboratory markers. RESULTS: IMT was significantly higher in RA patients (1.00 ± 0.16 mm) patients than in controls (0.89 ± 0.13 mm) (P = 0.001). FMD was significantly lower in RA (9.16 ± 7.03) as compared to controls (12.60 ± 5.49) (p = 0.005). RA patients had significant positive correlations between erythrocyte sedimentation rate (ESR) (r=0.395 p = 0.021) and IMT and negative correlation between visual analog scale (VAS) (r= -0.311, p= 0.025) and IMT. RA patients who used low doses of corticosteroids have, statistically, significantly better FMD, than those who do not use corticosteroids. Linear regression analysis revealed that IMT was related to tender joint count (p = 0.008), VAS (p < 0.001), ESR (p = 0.048) and total cholesterol/high density lipoprotein cholesterol ratio (p = 0.039). CONCLUSIONS: In patients with RA, FMD was impaired and IMT was increased, indicating early endothelial dysfunction and accelerated atherosclerosis. Early treatment of disease may reduce the risk of atherosclerosis in RA.

Psoriasis between Autoimmunity and Oxidative Stress: Changes Induced by Different Therapeutic Approaches.

Psoriasis is defined as chronic, immune-mediated disease. Regardless of the development of new therapeutic approaches, the precise etiology of psoriasis remains unknown and speculative. The aim of this review was to systematize the results of previous research on the role of oxidative stress and aberrant immune response in the pathogenesis of psoriasis, as well as the impact of certain therapeutic modalities on the oxidative status in patients with psoriasis. Complex immune pathways of both the innate and adaptive immune systems appear to be major pathomechanisms in the development of psoriasis. Oxidative stress represents another important contributor to the pathophysiology of disease, and the redox imbalance in psoriasis has been reported in skin cells and, systemically, in plasma and blood cells, and more recently, also in saliva. Current immune model of psoriasis begins with activation of immune system in susceptible person by some environmental factor and loss of immune tolerance to psoriasis autoantigens. Increased production of IL-17 appears to be the most prominent role in psoriasis pathogenesis, while IL-23 is recognized as master regulator in psoriasis having a specific role in cross bridging the production of IL-17 by innate and acquired immunity. Other proinflammatory cytokines, including IFN-γ, TNF-α, IL-1ß, IL-6, IL-22, IL-26, IL-29, or IL-36, have also been reported to play important roles in the development of psoriasis. Oxidative stress can promote inflammation through several signaling pathways. The most noticeable and most powerful antioxidative effects exert various biologics compared to more convenient therapeutic modalities, such as methotrexate or phototherapy. The complex interaction of redox, immune, and inflammatory signaling pathways should be focused on further researches tackling the pathophysiology of psoriasis, while antioxidative supplementation could be the solution in some refractory cases of the disease.