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Biomedical subjects

Marietta Charakida

Publications and source records attributed to Marietta Charakida.

12 recordsLinked to original sources

Statins in heart failure. Beyond the lipid lowering effect.

Statins, the most widely prescribed medications in patients with hyperlipidemia and coronary heart disease, have a number of pleiotropic actions beyond cholesterol lowering. They improve endothelial function, they have antioxidant and anti-inflammatory effects, they regulate neovascularization and have immunomodulatory activities. Experimental evidence suggests that statins may be beneficial in heart failure as they can inhibit myocardial hypertrophy, reduce cardiomyocyte loss by apoptosis, reduce oxidative stress and restore neurohormonal imbalance. Furthermore small randomised clinical trials showed that short term statin administration may improve key pathophysiological aspects of this syndrome. Finally retrospective analyses of large statin trials imply a long term profit on clinical outcome in this group of patients. These results however need to be reviewed with caution as certain studies have demonstrated that low serum cholesterol is associated with worse prognosis in HF and that ubiquinone levels, a micronutrient with antioxidant actions, reduces significantly following statin administration. Large prospective randomised controlled trials are needed to confirm the beneficial effect of statins on cardiovascular outcome in HF patients and further elucidate the contributing mechanisms. Finally the statin dose and the interaction with co-administered drugs need to be studied.

Endothelium, Vascular↗

Non-invasive assessment of endothelial function: which technique?

OBJECTIVES: The purpose of this study was to compare 3 non-invasive techniques for assessment of endothelial function in adults and children and evaluate their utility in acute inflammation. BACKGROUND: Endothelial dysfunction is a key early event in pre-clinical atherosclerosis. Flow-mediated dilation (FMD), although the established technique, is expensive and technically demanding. Measurements of vascular responses to inhaled salbutamol by pulse wave analysis (PWA) or pulse contour analysis (PCA) are potential alternatives. METHODS: Sixteen adults (mean age 28 years, range 18 to 39) and 16 children (mean age 13 years, range 7 to 17) underwent concurrent vascular function testing on 2 occasions with ultrasound, PWA, and PCA. Eighteen men were also studied before and after typhoid vaccination. RESULTS: Reproducibility of FMD was high in adults and children (coefficient of variation [CV] = 7.1 and 6.3, respectively). Salbutamol responses were more variable with PWA (adults CV = 11.5, children CV = 17.1) and PCA particularly in children (adults CV = 18.2, children CV = 36.3). Flow-mediated dilation (p < 0.001) and PWA with salbutamol (p = 0.03) responses fell after typhoid vaccination, and PCA (p = 0.7) was unchanged. CONCLUSIONS: Vascular dysfunction during acute inflammation can be measured by FMD and by PWA with salbutamol. Flow-mediated dilation is less variable than PWA. Variability of PCA makes this technique currently unsuited to serial measures of endothelial function in children. Flow-mediated dilation remains the most reproducible method.

Adolescent↗

Differences in inflammatory and thrombotic markers between unstable angina and acute myocardial infarction.

BACKGROUND: Unstable coronary syndromes are characterised by increased inflammatory process and endothelial activation. However, the underlying mechanisms of the acute coronary syndromes are still obscure. We evaluated the differences of inflammatory and thrombotic markers, at the acute phase of unstable angina (UA) and acute myocardial infarction (AMI). METHODS: The population of the study consisted of 216 subjects: 136 patients with UA, 57 patients with AMI and 23 healthy controls. Blood samples were taken by their admission to the hospital. Inflammatory and thrombotic markers were measured by ELISA. RESULTS: Patients with UA had significantly higher levels of interleukin-6 (IL-6), soluble vascular cells adhesion molecule (sVCAM-1) and von Willebrand factor (vWF) (p<0.05 vs controls), and lower levels of antithrombin III (ATIII) (p<0.01 vs controls) and protein C (PrtC) (p<0.05 vs controls). Similarly, patients with AMI had higher levels of IL-6, sVCAM-1, vWF and tissue plasminogen activator (tPA) (p<0.01 vs controls) and lower levels of ATIII (p<0.01 vs controls) and prtC (p<005 vs controls). Patients with AMI had significantly higher levels of vWF, tPA and sVCAM-1 compared to UA patients (p<0.05). CONCLUSIONS: Patients with unstable coronary syndromes had increased levels of IL-6, sVCAM-1 and vWF as well as decreased levels of ATIII and PrtC by their admission. However, patients with AMI had higher levels of all the endothelium-derived inflammatory (e.g. sVCAM-1) of thrombotic/fibrinolytic (e.g. tPA and vWF) markers, compared to those with UA. These findings imply that patients with myocardial infarction show further increase of endothelium-derived inflammatory and thrombotic markers compared to patients with unstable angina, in response to a similar proinflammatory stimuli.

Angina, Unstable↗

Early atherosclerosis in childhood: diagnostic approaches and therapeutic strategies.

The long preclinical phase of atherosclerosis involves the interaction of genetic and environmental factors that modulate the progression of disease from early life. Injury to the endothelium is a critical step in atherosclerotic process. Conventional and novel risk factors for coronary artery disease operate from early in life. Noninvasive methods, using mostly ultrasound techniques, have enabled the assessment of early functional and structural arterial disease progression even from the first decade of life. These measures have been shown to be good surrogate markers for atherosclerotic disease progression and future clinical cardiovascular events. Lifestyle and dietary modifications as well as pharmacological interventions have beneficial effects in prevention and restoration of the early arterial changes.

Adolescent↗

Early structural and functional changes of the vasculature in HIV-infected children: impact of disease and antiretroviral therapy.

BACKGROUND: Premature cardiovascular disease is increasingly recognized in HIV-infected patients, but the mechanisms involved are unclear. The purpose of this study was to determine the impact of HIV infection and antiretroviral therapy (ART) on markers of early vascular disease in children. METHODS AND RESULTS: We studied 83 HIV-infected children (56 had taken ART, of whom 31 received a regimen containing protease inhibitors [PIs]; 27 were never treated) and a control group of 59 healthy children. Carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) were measured. IMT was significantly greater in HIV-infected children compared with the control subjects (P<0.001). Among the HIV-infected children, age and treatment were significantly associated with increased IMT. Children exposed to PIs had greater IMT compared with both non-PI-treated children and untreated children (P=0.02). FMD was also significantly reduced in the HIV-infected children compared with control subjects (P=0.02). Pairwise comparisons of different treatment exposure groups revealed that FMD was impaired by a mean of 3.6% (95% CI, 1.8 to 5.3; P<0.001) for children exposed to PIs compared with untreated children and by a mean of 1.8% (95% CI, 0.01 to 3.5; P=0.05) compared with non-PI-treated children. HIV-infected children had lipid abnormalities, but they did not account for the observed differences in either FMD or IMT. CONCLUSIONS: HIV infection in childhood is associated with adverse structural and functional vascular changes that are most pronounced in children exposed to PI therapy. Longitudinal studies are required to differentiate the relative impact of HIV disease and ART and to assess the potential for prevention.

Adolescent↗

Inflammation and endothelial dysfunction as therapeutic targets in patients with heart failure.

Evidence suggests that vascular endothelium plays key role in the regulation of vascular tone, in the process of inflammation and in the thrombotic mechanisms. Recent studies indicate that it is an important component of the pathophysiological mechanisms of heart failure. Heart failure may induce endothelial dysfunction by different mechanisms, such as reduced synthesis and release of nitric oxide (NO), increased degradation of NO or by increased production of endothelin-1. In addition, endothelial dysfunction has been associated with the progression of heart failure. Alterations in neurotransmitters, hormones and also in physiological stimuli are present in heart failure and affect the vascular endothelium. Treatments with beneficial effects on endothelial dysfunction may also improve prognosis in patients with heart failure.

Animals↗

Endothelial dysfunction in childhood infection.

BACKGROUND: Atherosclerosis begins in early life, and endothelial dysfunction is recognized as a key initiating event in the development of atherosclerosis. Although infection has been implicated in endothelial dysfunction and atherogenesis, the impact of acute common childhood infections on the vascular endothelium is unknown. METHODS AND RESULTS: We studied 600 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. The children were divided into 3 groups: those with current acute infection (AI; n=135; 73 boys and 62 girls); a convalescent group with infection in the past 2 weeks (n=166; 78 boys and 88 girls), and a healthy control group (n=299; 131 boys and 168 girls). Endothelial function was determined in all subjects by high-resolution ultrasound to measure brachial artery flow-mediated dilation (FMD) and was expressed as the percentage change in diameter from baseline after reactive hyperemia. FMD was repeated in 40 children in the AI group and 50 in the control group after a mean interval of 1 year. FMD was lower in both the AI group (6.3+/-2.7%, mean+/-SD) and the convalescent group (8.1+/-3.1%) than in the control group (9.7+/-2.5%; P<0.001 for both). The observed differences in FMD remained after adjustment for potential confounding variables. At the repeat visit, FMD was unchanged in controls (P=0.85) but improved in the AI group (P<0.001). CONCLUSIONS: Acute infection in childhood is associated with impaired endothelium-dependent vasodilation. These findings support a potential role for previously unsuspected extrinsic inflammatory stimuli in the pathogenesis of early atherosclerosis.

Arteriosclerosis↗

Phototherapy in the treatment of acne vulgaris: what is its role?

Acne vulgaris is a common dermatosis affecting 80% of the population. To date, different treatments have been used to manage this condition. Antibacterials and retinoids are currently the mainstay of treatment for acne, but their success rate varies. Phototherapy is emerging as an alternative option to treat acne vulgaris. Studies examining the role of different wavelengths and methods of light treatment have shown that phototherapy with visible light, specifically blue light, has a marked effect on inflammatory acne lesions and seems sufficient for the treatment of acne. In addition, the combination of blue-red light radiation seems to be superior to blue light alone, with minimal adverse effects. Photodynamic therapy has also been used, even in nodular and cystic acne, and had excellent therapeutic outcomes, although with significant adverse effects. Recently, low energy pulsed dye laser therapy has been used, and seems to be a promising alternative that would allow the simultaneous treatment of active acne and acne scarring. Further studies are needed to clarify the role of phototherapy as a monotherapy or an adjuvant treatment in the current management of acne vulgaris.

Acne Vulgaris↗

The impact of platelet glycoprotein IIIa and Ia polymorphisms in cardiovascular thrombotic disease.

Platelet adhesion and aggregation play key roles in initiating coronary thrombosis and acute coronary syndromes. During the last decade platelet glycoprotein Ia and IIIa polymorphisms have been studied intensely in order to clarify their contribution to the thrombotic process and moreover their role in acute coronary syndromes. Studies examining these polymorphisms have been inconclusive and often controversial. Polymorphisms in the glycoprotein Ia seem to increase the risk for acute coronary events in younger persons and especially in the presence of other risk factors. The correlation of the Leu33Pro allele of platelet glycoprotein IIIa regarding platelet thrombogenicity is strong but it does not seem to alter the thrombotic risk of the general population. In conclusion, further studies need to elucidate their impact and the potential association with acute thrombotic events.

Adult↗