Inherited human gp91phox deficiency is associated with impaired isoprostane formation and platelet dysfunction

Platelet isoprostane 8-ISO-prostaglandin F2α (8-iso-PGF2α), a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation

The role of antioxidants supplementation in clinical practice. focus on cardiovascular risk factors

Oxidative stress may be defined as an imbalance between reactive oxygen species (ROS) and the antioxidant system to counteract or detoxify these potentially damaging molecules. This phenomenon is a common feature of many human disorders, such as cardiovascular disease. Many of the risk factors, including smoking, hypertension, hypercholesterolemia, diabetes, and obesity, are associated with an increased risk of developing cardiovascular disease, involving an elevated oxidative stress burden (either due to enhanced ROS production or decreased antioxidant protec-tion). There are many therapeutic options to treat oxidative stress-associated cardiovascular dis-eases. Numerous studies have focused on the utility of antioxidant supplementation. However, whether antioxidant supplementation has any preventive and/or therapeutic value in cardiovascular pathology is still a matter of debate. In this review, we provide a detailed description of oxidative stress biomarkers in several cardiovascular risk factors. We also discuss the clinical implications of the supplementation with several classes of antioxidants, and their potential role for protecting against cardiovascular risk factors

Hereditary Deficiency of gp91(phox) Is Associated With Enhanced Arterial Dilatation Results of a Multicenter Study

Background-NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). Methods and Results-Twenty-five patients with hereditary deficiency of gp91(phox), the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91(phox), serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91(phox) expression was downregulated in X-CGD patients (1.0+/-0.8 mean fluorescence; P<0.001) and upregulated in obese patients (4.1+/-2.2 mean fluorescence; P=0.01) compared with healthy subjects (2.9+/-1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7+/-33.3 pg/mg creatinine; P = 0.04) and increased in obese patients (154.4+/-91 pg/mg creatinine; P<0.001) compared with healthy subjects (69.5+/-52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3+/-6.7 versus 24.8+/-9.8 U/L; P<0.001) and X-CGD patients (28.5+/-7.2 U/L; P<0.001). X-CGD patients had significantly higher FMD (14.7+/-5.9%) compared with healthy subjects (7.9+/-2.5%; P<0.001); obese patients had lower FMD (5.3+/-3.0%; P+/-0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0+/-10.8+/-mol/L; P<0.016) and lower in obese patients (9.3+/-11.0 mu mol/L; P<0.001) compared with healthy subjects (27.1+/-19.1 mu mol/L). Serum nitrite and nitrate levels significantly correlated with FMD (R-s = 0.403, P<0.001) and platelet gp91(phox) (R-s = -0.515, P<0.001). FMD inversely correlated with platelet gp91(phox) (R-s = -0.502, P<0.001) and isoprostanes (R-s = -0.513, P<0.001). Conclusion-This study provides the first evidence that, in humans, gp91(phox) is implicated in the modulation of arterial ton

Clinical Features of Patients with Cervical Artery Dissection and Fibromuscular Dysplasia

Background and Purpose: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. Methods: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD-). Results: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13-2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06-18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26-0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58-7.31] and 2.07 [95% CI, 1.06-4.03], respectively) in multivariable Cox proportional hazards analysis. Conclusions: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence

Le perniciose malariche. Esperienze personali

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CHLOROQUINE-RESISTANT FALCIPARUM-MALARIA FROM GUINEA

Authors describe the first case of chloroquine-resistant malaria due to Plasmodium falciparum in Guinea