Acute pericarditis in patients receiving coronavirus disease 2019 vaccines: a case series from the community.

BACKGROUND: International agencies reported that cases of pericarditis occur very rarely following the administration of coronavirus disease 2019 (COVID-19) vaccines. Herewith, we described a series of patients from the community diagnosed with acute pericarditis after vaccination. METHODS: We retrospectively included 28 patients (median age 51 years, 79% female) with or without a positive history of acute respiratory syndrome coronavirus 2 recovered infection who were diagnosed with acute pericarditis following the administration of COVID-19 vaccine. We excluded specific identifiable causes of pericarditis, including infectious, autoimmune, neoplastic and metabolic disease. Patients were referred for a complete cardiovascular evaluation. Transthoracic echocardiography (TTE) was performed and diagnosis of acute pericarditis was achieved according to current guidelines. RESULTS: There were 16 patients administered with Pfizer-BioNTech/Comirnaty vaccine, 8 with Moderna/Spikevax vaccine and 4 with Astra Zeneca/Vaxzevria vaccine. Nine patients had been previously diagnosed with COVID-19, while the others had no prior history of COVID-19. Eleven patients had no comorbidity while the others had between one and four comorbidities. Ten patients had a history of rheumatic or autoimmune diseases. Chest pain was present in 24 patients. Minor ECG abnormalities were detected in 10 patients, T-wave inversion in 6, and 7 patients had concave ST elevation. The majority of patients showed mild pericardial effusions at TTE. Only two patients exhibited large pericardial effusions. CONCLUSION: This case series shows a higher incidence of acute pericarditis in patients administered with COVID-19 vaccines than previously estimated, probably because of a more comprehensive assessment of clinical as well as echocardiographic parameters.

Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder mainly characterized by a hormonal and metabolic disbalance that leads to oligo/anovulation, hyperandrogenism and the formation of ovarian cysts. Despite the progress that has been reached in its diagnosis and management, little is known about the molecular mechanisms and signaling pathways underlying the pathogenic mechanisms. In this sense, recent research has suggested that the influence of multiple factors, including age, environment, lifestyle and the disease state environment can change the clinical presentation of PCOS via epigenetic modifications. Variants in the genes encoding for proteins involved in steroidogenesis and glucose homeostasis play a crucial role in the development of the disease. Other genes involved in inflammation and cell proliferation seem to undergo an epigenetic control. Moreover, lifestyle factors influence the PCOS course and prognosis, including diet and physical activity, which are fundamental in reducing oxidative stress, inflammation and in improving metabolic and hormonal parameters. In the present review, literature evidence on molecular and epigenetic mechanisms related to PCOS etiology will be discussed, with a particular attention on the positive influence of diet and physical activity as nonpharmacological ways of intervention in the management of the disease.

Energy cost and psychological impact of robotic-assisted gait training in people with spinal cord injury: effect of two different types of devices.

BACKGROUND: In the last years, there has been an intense technological development of robotic devices for gait rehabilitation in spinal cord injury (SCI) patients. The aim of the present study was to evaluate energy cost and psychological impact during a rehabilitation program with two different types of robotic rehabilitation systems (stationary system on a treadmill, Lokomat, and overground walking system, Ekso GT). METHODS: Fifteen SCI patients with different injury levels underwent robot-assisted gait training sessions, divided into 2 phases: in the first phase, all subjects completed 3 sessions both Lokomat and Ekso GT. Afterwards, participants were randomly assigned to Lokomat or the Ekso for 17 sessions. A questionnaire, investigating the subjective psychological impact (SPI) during gait training, was administered. The functional outcome measures were oxygen consumption (VO2), carbon dioxide production (VCO2), metabolic equivalent of task (MET), walking economy, and heart rate (HR). RESULTS: The metabolic responses (7.73 ± 1.02 mL/kg/min) and MET values (3.20 ± 1.01) during robotic overground walking resulted to be higher than those during robotic treadmill walking (3.91 ± 0.93 mL/kg/min and 1.58 ± 0.44; p < 0.01). Both devices showed high scores in emotion and satisfaction. Overground walking resulted in higher scores of fatigue, mental effort, and discomfort while walking with Lokomat showed a higher score in muscle relaxation. All patients showed improvements in walking economy due to a decrease in energy cost with increased speed and workload. CONCLUSIONS: Overground robotic-assisted gait training in rehabilitation program needs higher cognitive and cardiovascular efforts than robot-assisted gait training on a treadmill.

An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds.

Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation.

Current evidence and future perspectives on n-3 PUFAs.

The family of polyunsaturated fatty acids (PUFAs), which can be found in most lipid classes, includes n-3 PUFAs essential for mammals and whose deficiency is associated with multiple diseases. Because of their multiple physiological actions, n-3 PUFAs play a crucial role in normal human metabolism as well as maintenance of a healthy status, with clinical effects that are not limited to the cardiovascular system but also include maternal and offspring health, growth and development, immune system disorders, cancer, cognitive function and psychological status. Multiple health organisations and scientific societies recommend increasing food-derived n-3 PUFA intake and also suggest that patients with documented coronary heart disease receive a minimum of 1000 mg/day of eicosapentaenoic acid and docosahexaenoic acid. The preventive and therapeutic effects of n-3 PUFAs appear to be largely dependent on the dosages employed and the characteristics of selected patients. So, in the era of personalised medicine, the time has come to move from generic advice to increase n-3 PUFA intake to a more evidence-based approach characterised by tailored indications to n-3 PUFA dietary or supplement consumption. This approach will require evaluation on a case-to-case basis the potential usefulness of n-3 PUFAs, taking into consideration their 'pleiotropic effects', the optimal dose for any given indication in relation to international guidelines, potential interactions with background therapy, possible side effects, differences in genetics and dietary response to supplementation, and the cost:benefit ratio, which is likely to vary as a function of differences in the range of fish intake in the diet.

Sudden death and physical exercise: timely diagnosis of congenital anomalies of the coronary arteries with the new 320-slide multi-detector computed tomography.

Congenital abnormalities of the coronary arteries here described are an uncommon form of structural heart disease. Nevertheless, they deserve attention because may cause chest pain and, in some cases, sudden cardiac death even during exercise. Traditional angiography has limitations due to its projectional and invasive nature. The recent development of the 320-slide multi-detector computer tomography with low radiation exposure has the potential to modify the current diagnostic work-up, as it allows even in young people a timely identification of clinical significant coronary anomalies minimizing the risks related to radiation exposure.

Subcutaneous adipose tissue blood flow and vasomotion in morbidly obese patients: long term effect of gastric bypass surgery.

Since recent findings suggest a relationship between reduction in adipose tissue blood flow (ATBF) and metabolic or vascular complications in obese patients (Ob-pts), increase in ATBF may be considered as a further goal in the treatment of obesity, besides fat mass reduction. Therefore, this preliminary study aimed at assess subcutaneous ATBF and vasomotion in morbidly obese patients and whether sustained weight loss induced by Roux-en-Y gastric bypass (RYGB) affects the same parameters. Using laser-Doppler flowmetry (LDF) and spectral Fourier analysis, subcutaneous ATBF was measured and subcutaneous ATBF oscillations (ATBF-O) were analyzed - within three frequency intervals related to vasomotion - in 16 Ob-pts, before and about one year after RYGB, and in 10 lean, healthy control subjects (CS). Before RYGB, Ob-Pts showed an important reduction in subcutaneous ATBF compared to CS (4.8 ± 2.7 PU vs 79.9 ± 34.5 PU, respectively; p < 0.0001), as well as higher normalized power spectral density (N-PSD) values of subcutaneous ATBF-O, - related to vasomotion. One year after RYGB, sustained weight loss in Ob-pts was associated with a slight but significant increase in subcutaneous ATBF (10.0 ± 6.6 PU, p < 0.05) and with almost complete normalization in N-PSD values of ATBF-O, related to vasomotion, compared to before RYGB. The slight subcutaneous ATBF increase, we observed in Ob-pts after sustained weight loss, moves toward a desirable goal. This finding suggests verifying whether an even more sustained weight loss in Ob-pts could determine a greater increase in subcutaneous ATBF and/or, more importantly, it could also determine a significant increase in visceral ATBF.

High serum levels of CXCL11 in mixed cryoglobulinemia are associated with increased circulating levels of interferon-γ.

OBJECTIVE: No study has evaluated circulating chemokine C-X-C motif ligand (CXCL)11 in patients with "mixed cryoglobulinemia and chronic hepatitis C infection" (MC+HCV). We measured CXCL11, and correlated this measurement to the clinical phenotype. METHODS: Serum CXCL11, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were assayed in 97 MC+HCV patients and in 97 sex- and age-matched controls. RESULTS: MC+HCV patients showed significantly higher mean CXCL11 serum levels than controls (254 ± 295, 68 ± 16 pg/ml, respectively; p = 0.0002; ANOVA). CXCL11 was significantly increased in 36 cryoglobulinemic patients with compared to those without active vasculitis (303 ± 208 vs 179 ± 62 pg/ml, respectively; p < 0.001; ANOVA). IFN-γ levels were significantly higher in MC+HCV than in controls [6.1 (range 0.8-114.5), 1.4 (range 0.7-2.4) pg/ml, respectively; p < 0.05; Mann-Whitney U test]. Serum TNF-α mean levels were significantly higher in MC+HCV than in controls [13.4 (range 1.8-369), 1.1 (range 0.7-3.2) pg/ml, respectively; p < 0.0001; Mann-Whitney U test]. A multiple regression analysis considering CXCL11 as a dependent variable, and age, alanine aminotransferase, IFN-γ, and TNF-α as independent variables, showed in MC+HCV patients a significant association only with IFN-γ (p < 0.0001). CONCLUSION: Our study demonstrates markedly high serum levels of CXCL11 in patients with MC+HCV compared to healthy controls overall in the presence of active vasculitis. A strong relationship between circulating IFN-γ and CXCL11 was shown, strongly supporting the role of a T helper 1 immune response in the pathogenesis of MC+HCV.

Circulating chemokine (CXC motif) ligand (CXCL)9 is increased in aggressive chronic autoimmune thyroiditis, in association with CXCL10.

Chemokine (CXC motif) ligand (CXCL)9 (CXCL9) has been shown to be involved in autoimmune thyroid disorders, however no data are present about CXCL9 circulating levels in chronic autoimmune thyroiditis (AT) vs controls. Serum CXCL9 (and for comparison CXCL10) has been measured in patients with AT vs normal control and nontoxic multinodular goiter, and this parameter has been related to the clinical phenotype. For this study we selected 189 consecutive patients with newly diagnosed AT, 63 euthyroid controls, 30 patients with nontoxic multinodular goiter. The three groups were similar in gender distribution and age; 26% of AT patients had subclinical hypothyroidism. Serum CXCL9 was significantly higher in AT (148±110 pg/mL) than in controls (71±34 pg/mL) or patients with multinodular goiter (87±35 pg/mL) (p<0.0001). Among AT patients, CXCL9 levels were significantly higher in patients older than 50 years, those with a hypoechoic ultrasonographic pattern or with hypothyroidism. Also CXCL10 was confirmed to be associated with AT, overall in presence of hypothyroidism. In a multiple linear regression model of CXCL9 (ln[pg/mL]) vs age, thyroid volume, TSH, AbTg, AbTPO, hypoechoic pattern, the presence of hypervascularity, and CXCL10 (ln[pg/mL]), only TSH and CXCL10 (ln[pg/mL]) were significantly related to serum CXCL9 levels. We show that circulating CXCL9 is increased in patients with aggressive thyroiditis and hypothyroidism. A strong relation between circulating CXCL9 and CXCL10 has been first shown, underlining the importance of a T helper 1 immune attack in the initiation of AT.

Cardiovascular complications in patients with pheochromocytoma: a mini-review.

Phaeochromocytomas are rare neuroendocrine tumours secreting high levels of catecholamines, able to exert serious metabolic and cardiovascular effects. The serious and potentially lethal cardiovascular complications of these tumours are due to the potent effects of secreted catecholamines, especially noradrenaline, the main transmitter released from sympathetic nerve terminals. Hypertension, tachycardia, pallor, headache and anxiety, usually dominate the clinical presentation. Occasionally, patients with predominantly epinephrine-secreting tumours present hypotension or even shock. Other cardiovascular complications of pheochromocytoma include ischaemic heart disease, acute myocardial infarction, cardiac arrhythmias, heart failure due to toxic cardiomyopathy, or pulmonary edema. Catecholamines have been shown to influence the extracellular matrix with collagen deposition and subsequent fibrosis in the arterial wall and in the myocardium. These morphofunctional changes of the myocardium and of arterial wall can be emphasized by ultrasound imaging. Indeed, ultrasound imaging of the myocardium and arterial wall not only identifies wall thickness but also contains information on texture that may be revealed by acoustic tissue characterization. The latter can be quantified through videodensitometric analysis of echographic images or through ultrasonic integrated backscatter signal analysis. This paper reviews cardiovascular complications in patients with pheochromocytoma and utility of the new ultrasound technique as backscatter signal. It is useful for evaluating preclinical pathological morphofunctional changes of the myocardium and arterial wall, characterized by increased collagen content in pheochromocytoma patients. The recognition of early catecholamine-induced alterations in patients with pheochromocytoma, is important to prevent at least morbidity and mortality, before surgical treatment.

In vitro and in vivo study on the antioxidant activity of dexrazoxane.

OBJECTIVES: The iron chelator dexrazoxane has been shown to significantly reduce anthracycline-induced cardiac toxicity in several randomized controlled studies. Aim of the present study was to assess the in vitro and in vivo antioxidant effects of dexrazoxane. METHODS: The in vitro antioxidant activity of dexrazoxane as its total oxyradical scavenging capacity (TOSC) was assessed and compared to that of some classic antioxidants such as reduced glutathione (GSH), uric acid and trolox. The plasma antioxidant activity of 20 newly-diagnosed non-Hodgkin lymphoma (NHL) patients scheduled to receive anthracycline-containing chemotherapy (ProMECE-CytaBOM) was also evaluated. Results were expressed as TOSC units. RESULTS: Dexrazoxane exhibited an in vitro scavenging capacity towards hydroxyl radicals 320% higher than that of GSH (p<0.00001), 20% higher than that of uric acid (p<0.001), and 100% higher than that of trolox (p<0.001). In the clinical study, ProMECE-CytaBOM infusion significantly reduced plasma TOSC in NHL patients (p=0.0001). Dexrazoxane supplementation was able to restore plasma antioxidant activity in two hours from the end of the ProMECE-CytaBOM infusion. CONCLUSIONS: Dexrazoxane has in vitro antioxidant capacity. In vivo, it is able to reduce the epirubicin-induced free radical production. The intrinsic antioxidant effect of this compound could explain the reduction of the anthracyclines-induced toxicity in those patients treated with dexrazoxane supplementation.

High circulating levels of N-terminal pro-brain natriuretic peptide and interleukin 6 in patients with mixed cryoglobulinemia.

Many patients with mixed cryoglobulinemia and chronic HCV infection experience symptoms, such as dyspnea, which sometimes do not seem to indicate the involvement of the liver but rather the symptoms of heart failure. To our knowledge, there has been no other study evaluating the serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and Interleukin 6 (IL-6) in such patients. Serum NTproBNP and IL-6 were assayed in 54 patients with mixed cryoglobulinemia and chronic HCV infection, and in 54 sex- and age-matched controls. Cryoglobulinemic-patients showed significantly higher mean NTproBNP and IL-6 levels than the controls (P = 0.005). By defining a high NTproBNP level as a value higher than 125 pg/ml (the single cut-off point for patients under 75 years of age), 30% of patients with mixed cryoglobulinemia and chronic HCV infection and 7% of controls had high NTproBNP (chi-square; P < 0.003). With a cut-off point of 300 pg/ml (used to rule out heart failure in patients under 75 years of age), 5/49 patients with mixed cryoglobulinemia and chronic HCV infection and 0/54 controls had high NTproBNP (chi-square; P < 0.04). With a cut-off point of 900 pg/ml (used for including heart failure in patients aged between 50 and 75, such as the patients in this study) 3/51 of patients with mixed cryoglobulinemia and chronic HCV infection and 0/54 controls had high NTproBNP (chi-square; P = 0.07). The study revealed high levels of circulating NTproBNP and IL-6 in patients with mixed cryoglobulinemia and chronic HCV infection. The increase in NTproBNP could indicate the presence of a subclinical cardiac dysfunction.

High circulating N-terminal pro-brain natriuretic peptide and tumor necrosis factor-alpha in mixed cryoglobulinemia.

AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor alpha (TNF-alpha) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV). METHODS: Serum NTproBNP and TNF-alpha levels were assayed in 50 patients with MC+HCV, and in 50 sex- and age-matched controls. RESULTS: Cryoglobulinemic patients showed significantly higher mean NTproBNP and TNF-alpha levels than controls (P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a value higher than 125 pg/mL (the single cut-off point for outpatients under 75 years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (c2, P < 0.01). With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP (c2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in patients aged 50-75 years; such as the patients of our study), 6% of MC+HCV and 0 controls had high NTproBNP (c2, P = 0.08). CONCLUSION: The study demonstrates high levels of circulating NTproBNP and TNF-alpha in MC+HCV patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction.

High values of CXCL10 serum levels in mixed cryoglobulinemia associated with hepatitis C infection.

OBJECTIVES: No study has evaluated circulating CXCL10 in patients with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) chronic infection. The aim of this study is to measure inteferon-inducible protein 10 (CXCL10/IP-10), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) (Th1 cytokines) in a series of cryoglobulinemic patients and to correlate this parameter to the clinical phenotype. METHODS: Serum CXCL10, IFN-gamma, and TNF-alpha were assayed in 102 patients with hepatitis C-associated cryoglobulinemia (MC + HCV), in 102 sex- and age-matched patients with type C chronic hepatitis without cryoglobulinemia (HCV+), and in 102 sex- and age-matched controls. RESULTS: Cryoglobulinemic patients showed significantly higher mean CXCL10 serum levels than controls (P < 0.0001) or HCV+ patients (P < 0.0001) (397 +/- 132 pg/mL, 92 +/- 53 pg/mL, 280 +/- 149 pg/mL, respectively). Moreover, CXCL10 was significantly increased in 30 cryoglobulinemic patients with active vasculitis compared to those without it (460 +/- 104 pg/mL vs 369 +/- 139 pg/mL, respectively; P < 0.001). Both groups of MC + HCV patients with or without active vasculitis had serum CXCL10 significantly higher than HCV+ patients (P < 0.001, P= 0.02, respectively). IFN-gamma levels were not significantly different in MC + HCV than in HCV+ patients or controls. Serum TNF-alpha levels were significantly higher in MC + HCV than in HCV+ patients or controls (median [interquartile range]: 12.0 [9.8], 5.7 [5.4], 1.3 [2.1] pg/mL, respectively; P < 0.0001). CONCLUSIONS: The study demonstrates high CXCL10 and TNF-alpha serum levels in patients with hepatitis C-associated cryoglobulinemia. Moreover, in MC + HCV patients, increased CXCL10 levels were significantly associated with the presence of active vasculitis.

Normalization of catecholamine production following resection of phaeochromocytoma positively influences carotid vascular remodelling.

OBJECTIVE: To evaluate the influence of plasma catecholamines on the vascular structure in humans, the effects of catecholamine normalization on the carotid wall of patients with phaeochromocytoma (PHEO) were investigated. A prospective study in patients with PHEO before and after (first follow-up: 20.5+/-1.8 months, second follow-up: 31.5+/-2.2 months) successful surgery was conducted in the University Referral Center for Blood Pressure Diseases. Ten consecutive patients with PHEOs and ten age- and blood pressure-matched controls were investigated. Intima-media thickness (IMT) by two-dimensional conventional ultrasonography and corrected ultrasonic integrated backscatter signal (C-IBS) analysis of carotid arteries were investigated in basal conditions and after mass removal. RESULTS: In PHEOs, at variance with the expected reduction in metanephrines and catecholamines, no variation in body weight, blood pressure and lipid profile was observed after operation. IMT and C-IBS values in patients with PHEO were greater (at least P<0.01) than in controls. At long-term follow-up after surgery, a significant reduction in mean carotid IMT (P<0.0009) and C-IBS (P<0.009) values was observed. A significant correlation (r=0.54, P<0.03) was found between absolute reduction in C-IBS values and absolute decrement in urinary normetanephrine levels. CONCLUSIONS: Our study shows that normalization of catecholamine levels after the removal of PHEO improves carotid IMT and reduces carotid wall fibrosis even without influencing blood pressure and lipid profile. These findings confirm that high catecholamine tone in humans directly influences vascular remodelling of carotid arteries.

High values of CXCL10 serum levels in patients with hepatitis C associated mixed cryoglobulinemia in presence or absence of autoimmune thyroiditis.

The aim of this study was to evaluate CXCL10 serum levels in patients with hepatitis C virus chronic infection (HCV) associated mixed cyoglobulinemia (MC), in the presence or absence of autoimmune thyroiditis (AT). CXCL10 was assayed in 50 MC patients without AT, in 40 MC patients with AT (MC+AT), in 2 gender- and age-matched control groups [50 healthy controls (without HCV or AT; control); 40 controls with AT (without HCV and MC; control+AT)]. CXCL10 was significantly higher: (1) in control+AT than in control (p<0.001); (2) in MC patients than in control (p<0.001); (3) in MC+AT patients than in control (p<0.001), control+AT (p<0.001), or in MC (p=0.002). CXCL10 was significantly increased in MC+AT patients with thyroid hypoechogenicity (388+/-147 vs 302+/-112; p=0.03), or hypothyroidism (391+/-142 vs 307+/-118; p=0.04), compared to those without. By defining a high CXCL10 level as a value at least 2 SD above the mean value of the control (>167 pg/ml), 8% of control, 22% of control+AT, 47% of MC and 80% of MC+AT had high CXCL10 (p<0.0001). In conclusion, our study is the first to demonstrate high serum levels of CXCL10 in MC and that CXCL10 in MC+AT patients are significantly higher compared to MC patients.

Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells.

PURPOSE: To study whether telmisartan, an angiotensin II (AII) receptor blocker (ARB), modulates endothelial inflammation and oxidative cell damage induced by AII-independent stimuli in cultured human umbilical vein endothelial cell (HUVEC)s. METHODS: Endothelial inflammation, as reflected by increased VCAM-1 and ICAM-1 expression (ELISA), was induced by TNF-alpha, an inflammatory cytokine, and cell damage (COMET and MTT assay) by hydrogen peroxide, a reactive oxygen species. Losartan, another ARB, its active metabolites (EXP-3174, EXP-3179), dexamethasone, a synthetic steroid, and pyrrolidine dithiocarbamate (PDTC), an anti-oxidant, were the controls. The contribution of PPAR-gamma agonism was assessed through synthetic PPAR-gamma agonists and antagonists and the antagonism for AII-type 1 receptor-mediated stimuli by evaluating the interference against cell death induced by AII (MTT assay), a pro-apoptotic peptide that induces oxidative stress. The in vitro scavenging properties for oxyradicals were quantified by the TOSC assay. RESULTS: Telmisartan and PDTC reduced TNF-alpha-stimulated VCAM-1 in a concentration-dependent manner while losartan, EXP-3174, EXP-3179 and dexamethasone were ineffective. All compounds did not modify ICAM-1 expression. PPAR-gamma agonists or antagonists did not interfere with the effect of telmisartan. Both ARBs antagonized AII-induced cell death but only telmisartan reduced hydrogen peroxide-induced cell damage. Telmisartan scavenged selectively hydroxyl radicals without affecting peroxyl radicals and peroxynitrite. CONCLUSIONS: Telmisartan modulates pleiotropically TNF-alpha induced VCAM-1 expression and oxidative damage in vascular endothelium, possibly by acting as a hydroxyl radical scavenger. Those anti-inflammatory and antioxidant properties may contribute to the therapeutic effect, although the applicability of these data to the clinical situations has to be verified.

Preclinical cardiac involvement in phaeochromocytoma: a study with integrated backscatter.

OBJECTIVE: It is well known that vascular and cardiac structure may be influenced by circulating neurohormonal factors. Our aim was to study the myocardial wall texture by integrated backscatter (IBS) analysis in patients with phaeochromocytoma (PHEO). DESIGN: Fourteen patients with PHEO, 15 matched high-normal blood pressure (BP) subjects, 15 mild essential hypertensives and 15 normotensive controls underwent two-dimensional conventional ultrasonography and ultrasonic IBS of the myocardial wall. IBS analysis was performed at both interventricular septum and posterior wall levels. IBS values were expressed in decibels and corrected for the IBS values obtained within the pericardium (C-IBS). The systo-diastolic cyclical variations in IBS (CV-IBS), an index of myocardial contractile performance, were also evaluated. RESULTS: Patients with PHEO showed C-IBS values comparable to those of hypertensive patients, and significantly higher than those of high-normal BP subjects and controls at both septum and posterior wall levels (P < 0.001 for all). In PHEO patients, CV-IBS was lower than that of normotensive, high-normal BP subjects and hypertensive patients, at both septum and posterior wall levels (P < 0.001 for all). An inverse relationship was found in the PHEO group between 24-h urinary normetanephrine and CV-IBS of both septum (r(2) = -0.29, P < 0.05) and posterior wall (r(2) = -0.46, P < 0.05). CONCLUSIONS: Our results show that patients with PHEO have myocardial remodelling characterized by increased myocardial fibrosis, confirmed by an increase in the overall myocardial backscatter level measured. The observed decrease in the magnitude of CV-IBS suggests an impairment of myocardial contractile performance. These results may provide insights into the role of catecholamines in left ventricular (LV) structure and function in PHEO.

Carotid integrated backscatter analysis in patients with subclinical hypothyroidism.

OBJECTIVE: The aim of the present study was to determine whether integrated backscatter (IBS) analysis combined with conventional ultrasonography could differentiate the tissue characteristics of carotid artery intimal hyperplasia in patients with subclinical hypothyroidism (SH). METHODS: Forty-one patients with SH, as judged by elevated serum TSH levels and free thyroid hormones within the normal range, and 31 sex- and age-matched euthyroid volunteers underwent two-dimensional conventional ultrasonography and IBS analysis of the carotid wall. Carotid intima-media thickness (IMT) and corrected IBS (C-IBS), an index of arterial wall degeneration and fibrosis, were evaluated. RESULTS: Mean IMT as well C-IBS values were higher in SH than in controls (P < 0.0001 for both), whereas the carotid diameter was not significantly different between the two groups. The distribution of C-IBS values in each group showed that regions with higher C-IBS values were found more frequently in SH patients than in control subjects. The percentage of regions that could be considered as fibromatous (C-IBS value from -18 to -21 dB) was 28% in SH and 9% in euthyroid subjects (P < 0.0001). In the SH group, C-IBS values were significantly and positively associated with plasma TSH (r = 0.32, P < 0.05 and r = 0.59, P < 0.0001, respectively) and with both total cholesterol (r = 0.46, P = 0.01) and low density lipoprotein (LDL)-cholesterol (r = 0.55, P = 0.001). CONCLUSIONS: Carotid IMT in subclinically hypothyroid patients is higher than that in euthyroid controls. This is characterized by increased IBS values, which are related to the collagen content of the arterial wall. The severity of this remodelling process seems to be related to TSH and cholesterol levels.

Carotid vascular remodeling in patients with pheochromocytoma.

CONTEXT: The influence of catecholamines on vascular remodeling in humans was investigated. OBJECTIVE: The objective was to study the carotid vascular wall in patients with pheochromocytoma (PHEO). DESIGN AND SETTING: An observational study was conducted in a university referral center for blood pressure diseases. PATIENTS: Fourteen patients with PHEO, 15 matched high-normal essential hypertensives, 15 mild essential hypertensives, and 15 controls underwent two-dimensional conventional ultrasonography and ultrasonic tissue characterization of the carotid wall. MAIN OUTCOME MEASURES: Intimal media thickness (IMT), diameter, and corrected ultrasonic integrated backscatter signal (C-IBS) of carotid arteries were evaluated. RESULTS: IMT in PHEOs (0.844 +/- 0.18 mm, mean +/- sd) was greater than not only controls (0.596 +/- 0.09 mm, P < 0.0002) but also high-normal (0.710 +/- 0.17 mm, P < 0.03), and even mild (0.727 +/- 0.20 mm, P = 0.06) hypertensives. IMT in the latter was higher than in controls (P < 0.03), without difference in comparison with high-normal hypertensives. C-IBS values in PHEOs (-21.71 +/- 2.0 dB, mean +/- sd) were greater than in controls (-26.20 +/- 1.73 dB, P < 0.0001) but also than in high-normal (-23.84 +/- 1.16 dB, P < 0.002) and mild (-23.37 +/- 1.99 dB, P < 0.01) hypertensives. C-IBS values in controls were lower than in high-normal (P < 0.0005) and mild (P < 0.0001) hypertensives. Carotid diameter was not significantly different in the four groups. In PHEOs, C-IBS was associated with urinary noradrenaline (r = 0.640, P < 0.01) and normethanephrine (r = 0.737, P < 0.009). CONCLUSIONS: Carotid IMT of PHEOs is higher than in controls and matched groups of hypertensives with comparable or even higher blood pressure. This vascular rearrangement is characterized by increased IBS values due to collagen deposition and vascular fibrosis. Therefore, our data show that abnormal catecholamine levels take part per se in carotid wall remodeling of patients with PHEO.