Arterial and venous involvement in Behçet’s syndrome: a narrative review

Behçet syndrome (BS) is a unique type of vasculitis that affects veins and arteries of all sizes, leading to recurrent vascular events, mostly venous thrombosis. The prevalence of venous thromboembolism in BS patients ranges between 15 and 40%. Thrombosis is usually an early manifestation leading to diagnosis of BS in up to 40% of patients. BS is per se a model of inflammation-induced thrombosis. The primary autoimmune response activates lymphocytes that in turn produce a cytokine cascade that activates neutrophils, which modify the secondary structure of fibrinogen making it less susceptible to plasmin-induced lysis. This leads to endothelial dysfunction, platelet activation and overexpression of tissue factor leading to inflammatory thrombi, usually attached to the wall. The pathogenesis of thrombosis is especially relevant to direct the specific treatment, that is based on immunosuppression rather than anticoagulation. Superficial vein thrombosis (SVT) and deep vein thrombosis (DVT) are the most common form of thrombosis in BS, but thrombosis in atypical sites (cava vein, suprahepatic veins, intracardiac thrombus) and arterial involvement can also occur. We assessed the latest update of the European League Against Rheumatism recommendations for the management of BS. Vascular Behçet treatment is usually based of immunosuppressants, and the role of anticoagulation remains controversial. The use of interventional and surgical procedures should be carefully evaluated, due to the risk of triggering a vascular pathergy phenomenon.

     

Atypical antioxidant activity of non-phenolic amino-coumarins

Coumarin compounds have been described as anti-inflammatories, and chemotherapeutic agents as well as antioxidants. However, the origin of the antioxidant activity of non phenolic coumarins remains obscure. In the present report, we demonstrate that non-phenolic 7-dialkyl-aminocoumarins may also have significant antioxidant properties against free radicals derived from 2,2′-azobis(2-amidinopropane) dihydrochloride under aerobic conditions. This atypical behaviour is due to the presence of traces of very reactive hydroxycinnamic acid-type compounds. Changing functional groups at the C-3 and C-4 positions shifts the reactivity of the compounds from peroxyl to alkoxyl free radicals. Kinetic and theoretical studies based on Density Functional Theory support the formation of reactive hydroxycinnamic acid and directly link the antioxidant behaviour of the compounds to hydrogen atom transfer.

Relevant antioxidant properties of non-phenolic 7-dialkyl-aminocoumarins against free radicals derived from 2,2′-azobis(2-amidinopropane) dihydrochloride under aerobic conditions have been experimentally and theoretically demonstrated.     

Comparison of sodium nitroprusside and adenosine for fractional flow reserve assessment: a systematic review and meta-analysis

Background: Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed.

Methods: Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: ‘fractional flow reserve’ AND ‘nitroprusside’. Data were summarized using weighted mean differences for paired data.

Results: Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) ?0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02–0.30, P < 0.0001).

Conclusions: NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.     

Intraparental Inconsistency: The Influence of Parenting Behaviors on Aggression and Depression in Children

The authors examined several different predictive and mediation models of longitudinal parental inconsistency over a 3‐year time span. They hypothesized that parental behavior (communication/affection, kindness, and positive control) mediated the relationship between parental inconsistency (mother or father) and two emotional problems in children: (a) aggression and (b) depression. Data were obtained from a 3‐wave study (2007, 2008, and 2009) of 523 Spanish families with children ranging from 9–15 years of age at the beginning of Wave 1 (41.3% boys). Structural equation models revealed that multiple dimensions of parenting (mother or father) fully or partially mediated the relationship between longitudinal parental inconsistency and the child's adjustment. Communication/affection and kindness are the main processes through which parental inconsistency affects a child's aggression and depression. These results represent an important contribution to the improvement of parenting models of relationships between parental inconsistency and child adjustment.     

Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

Purpose

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m²) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II‐infused rats

Angiotensin II (Ang II) and aldosterone contribute to hypertension, oxidative stress and cardiovascular damage, but the contributions of aldosterone during Ang II‐dependent hypertension are not well defined because of the difficulty to assess each independently. To test the hypothesis that during Ang II infusion, oxidative and nitrosative damage is mediated through both the mineralocorticoid receptor (MR) and angiotensin type 1 receptor (AT1), five groups of Sprague–Dawley rats were studied: (i) control; (ii) Ang II infused (80 ng/min × 28 days); (iii) Ang II + AT1 receptor blocker (ARB; 10 mg losartan/kg per day × 21 days); (iv) Ang II + mineralocorticoid receptor (MR) antagonist (Epl; 100 mg eplerenone/day × 21 days); and (v) Ang II + ARB + Epl (Combo; × 21 days). Both ARB and combination treatments completely alleviated the Ang II‐induced hypertension, whereas eplerenone treatment only prolonged the onset of the hypertension. Eplerenone treatment exacerbated the Ang II‐mediated increase in plasma and heart aldosterone 2.3‐ and 1.8‐fold, respectively, while ARB treatment reduced both. Chronic MR blockade was sufficient to ameliorate the AT1‐mediated increase in oxidative damage. All treatments normalized protein oxidation (nitrotyrosine) levels; however, only ARB and Combo treatments completely reduced lipid peroxidation (4‐hydroxynonenal) to control levels. Collectively, these data suggest that receptor signalling, and not the elevated arterial blood pressure, is the principal culprit in the oxidative stress‐associated cardiovascular damage in Ang II‐dependent hypertension.