miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis

Neutrophil extracellular traps (NET) induce a procoagulant response linking inflammation and thrombosis. Low levels of miR-146a, a brake of inflammatory response, are involved in higher risk of cardiovascular events, but the mechanisms explaining how miR-146a exerts its function remain largely undefined. The aim of this study was to explore the impact of miR-146a deficiency in NETosis both in sterile and non-sterile models in vivo, and to investigate the underlying mechanism. Two models of inflammation were used: (i) Ldlr^-/- mice transplanted with bone marrow from miR-146a^-/- or wild-type mice were fed a high-fat diet, generating an atherosclerosis model; and (ii) an acute inflammation model was generated by injecting lipopolysaccharide (1 mg/kg) into miR-146a^-/- and wildtype mice. miR-146a deficiency increased NETosis in both models. Accordingly, miR-146a^-/- mice showed significantly reduced carotid occlusion time and elevated levels of NET in thrombi following FeCl3-induced thrombosis. Infusion of DNAse I abolished arterial thrombosis in both WT and miR-146a^-/- mice. Interestingly, miR-146a-deficient mice have aged, hyperreactive and pro-inflammatory neutrophils in their circulation which are more prone to form NET independently of the stimulus. Furthermore, we demonstrated that patients with community-acquired pneumonia with reduced miR-146a levels associated with the T variant of the functional rs2431697 had an increased risk of cardiovascular events due, in part, to an increased generation of NET.     

Performance of transcatheter pacing system use in relation to patients’ age

Journal of Interventional Cardiac Electrophysiology - Advanced non-fluoroscopic mapping systems for radiofrequency ablation (RFA) have shown to be an effective treatment of atrial fibrillation....     

Primary aortic sarcoma with widespread vascular embolic metastases

Intimal sarcoma of the aorta is a rare and aggressive mesenchymal neoplasm with a propensity to metastasize and to embolize distant arteries. The diagnosis is most commonly made by autopsy or after surgery for an aortic aneurysm. Surgery is the treatment of choice in patients who do not have metastatic disease. The prognosis is generally poor, with death resulting in most patients within a few months from diagnosis. We describe a rare case of intimal sarcoma of the aorta that showed simultaneous involvement of the thoracic and abdominal aorta and also widespread embolic metastases to the main large vessels of the brain, heart, liver, kidneys, and spleen.     

Peripheral arterial disease in HIV patients older than 50 years of age

Our objective was to analyze the prevalence of peripheral arterial disease (PAD) in HIV patients at risk and to compare them with the general population. All HIV patients older than 50 years who attended our unit from October 2005-July 2006 and all persons attending for an annual medical checkup at an employees' insurance association during the same period were invited to participate in the study. Of the latter (n = 407), a person of the same sex and age (+/-5 years) was included for each HIV patient. PAD was assessed by the ankle-brachial index (ABI) in all subjects, and all completed the Edinburgh questionnaire. Ninety-nine HIV patients and 99 persons from the general population of the same age and sex were included in the study. The HIV patients had a greater prevalence of dyslipidemia, diabetes, and PAD, which was symptomatic in five of them and in one subject from the general population. Patients with HIV infection older than 50 had a high prevalence of PAD, and as it was asymptomatic in half the cases, an ABI may be performed in this population to actively look for PAD. Control of cardiovascular risk factors and the use of such drugs as platelet antiaggregation agents should therefore be optimized in this population.     

Metastatic ocular melanoma to the left ventricle inducing near-syncope attacks in an 84-year-old woman

Cardiac tumors may represent mechanical causes for syncope by limiting left ventricular filling and/or by obstructing the left ventricular outflow tract. Malignant melanoma is known to metastasize to the myocardium or pericardium, but there are only a very limited number of reports describing endocardial involvement by the tumor. We describe herein an 84-year-old woman who presented with daily near-syncope episodes, 9 years after treatment for a choroidal melanoma. The echocardiography and the pathologic examination revealed a metastatic melanoma. This is the first reported case of an ocular melanoma metastasizing to the heart and presenting as a left ventricular intracavitary pedunculated mass.     

Does melatonin induce apoptosis in MCF‐7 human breast cancer cells in vitro?

Melatonin inhibits proliferation of the estrogen-responsive MCF-7 human breast cancer cells. The objective of this work was to assess whether melatonin not only regulates MCF-7 cell proliferation but also induces apoptosis. In this experiment we used 1,25-dihydroxycholecalciferol (D3) as a positive control because it inhibits MCF-7 cell proliferation and induces apoptosis. MCF-7 cells were cultured with either I nM melatonin, 100 nM D3 or its diluent to determine their effects on cell proliferation, cell viability, cell-cycle phase distribution, population of apoptotic cells, and expression of p53, p21WAF1, bcl-2, bcl-X(L) and bax proteins. After 24 or 48 hr of incubation, both melatonin and D3-treatment significantly decreased the number of viable cells in relation to the controls, although no differences in cell viability were observed between the treatments. The incidence of apoptosis, measured as the population of cells falling in the sub-G1 region of the DNA histogram, or by the TUNEL reaction, was similar in melatonin-treated and control cells whereas, as expected, apoptosis was higher among cells treated with D3 than in controls. The expression of p53 and p21WAF1 proteins significantly increased after 24 or 48 hr of incubation with either melatonin or D3. No significant changes in bcl-2, bcl-XL and bax mRNAs were detected after treatment with melatonin whereas in D3-treated cells, a significant drop in bcl-XL was observed. These data support the hypothesis that melatonin reduces MCF-7 cell proliferation by modulating cell-cycle length through the control of the p53-p21 pathway, but without clearly inducing apoptosis.     

Increased IGF-I : IGFBP-3 ratio in patients with hepatocellular carcinoma

BACKGROUND: The development of hepatocellular carcinoma in liver cirrhosis is associated with altered synthesis and secretion of several growth factors. AIM: The aim of this prospective study was to investigate the potential implication of IGF-I and its major binding protein (IGFBP-3) in the development of hepatocellular carcinoma. PATIENTS AND METHODS: IGF-I and IGFBP-3 were measured in 150 healthy subjects, 40 patients with liver cirrhosis and 63 with liver cirrhosis and untreated hepatocellular carcinoma. The ratio between IGF-I and IGFBP-3 was also calculated. RESULTS: Serum IGF-I (70 +/- 10 and 65 +/- 7 vs. 185 +/- 6.4 microg/l, P < 0.001) and IGFBP-3 levels (1225 +/- 113 and 984 +/- 67 vs. 3017 +/ -80 microg/l, P < 0.001) were lower in patients with liver cirrhosis, without or with hepatocellular carcinoma, than in controls. Age was negatively correlated with IGF-I levels in patients with liver cirrhosis (r = -0.6; P = 0.0002) as well as in controls (r = -0.8, P < 0.0001), but not in patients with hepatocellular carcinoma (r = -0.2; P = 0.2). Additionally, in patients with liver cirrhosis (r = -0.54; P = 0.0003) and more weakly in those with hepatocellular carcinoma (r = -0.24; P = 0.04) IGF-I levels were negatively correlated with liver failure measured according with Child class. Despite patients with class C hepatocellular carcinoma being older than those in the same functional class with cirrhosis (64 +/- 2 vs. 57 +/- 12 years, P < 0.01), they had a significantly increased IGF-I : IGFBP-3 ratio (0.18 +/- 0.05 vs. 0.41 +/- 0.09, P = 0.04), due mostly to increased IGF-I levels (27.1 +/- 5.6 vs. 42 +/- 6.2 microg/l) as IGFBP-3 levels were similar to patients with cirrhosis (734 +/- 81 vs. 679 +/- 83 microg/l). CONCLUSIONS: Hepatocellular carcinoma is associated with a higher IGF-I : IGFBP-3 ratio than that found in patients with liver cirrhosis and a similar degree of liver failure.