Deep venous thrombosis: epidemiologic, diagnostic and therapeutic aspects

Deep vein thrombosis (DVT) has a high social and economic cost disease being its prevalence in the general population elevated and producing possibly fatal (pulmonary embolism) or disabling (post-thrombotic syndrome) complications. Thus, it appears of great importance to know the epidemiological and clinical characteristics of DVT in order to perform the best diagnosis, therapy and prophylaxis. The study population is composed by 146 patients (84 males and 62 females, mean age 60.9 +/- 15.3 years, range 19.92 years), arrived in our Vascular Echography Laboratory with the clinical suspect of DVT confirmed by means of echo color Doppler. The most frequent clinical signs were skin hyperthermia in 118 patients (80.8%) and edema in 116 patients (79.5%), while the most common symptom was pain, 89 patients (61.0%). Eleven patients (7.5%) were asymptomatic. The echo criteria utilized were direct thrombus visualization, vessel diameter higher than the contralateral, reduced or absent vessel wall ability to be compressed, reduced or absent color Doppler venous flow, lack or reduction of respiratory flow modulation, visualization of collateral circulation. DVT was located in 131 patients (89.7%) in inferior limbs (proximal in 122 patients, isolated distal in 9 patients), in 14 patients (9.6%) in superior limbs and in 3 patients (2.1%) in the internal jugular vein. In 130 patients a risk factor or a predisposing condition was identified: secondary DVT; in 16 patients the DVT was considered idiopathic. The most frequent risk factors were: previous surgery 28.1%, immobilization 19.9% trauma 17.1%, tumors 9.6%. A hypercoagulation was detected in 4 patients: antithrombin III deficit in 2, post-splenectomy thrombocytosis in 1 and antiphospholipid antibodies syndrome in the last one. The Pisa territory epidemiologic data showed a male 0.51 and female 0.38/1000 subject/year DVT incidence, with significantly higher values in older than 45-54 males and 55-64 females. One hundred and thirty one patients were treated with 5-11 day heparin infusion and thereafter with warfarin at least for 6 months, 1 year or indefinitely depending on thromboembolic risk. Six patients with distal DVT and 9 patients with hemorrhagic risk were treated with subcutaneous calcic or low weight heparin. In 1 patient with a mobile thrombus judged as at very high risk of embolization, a caval filter was positioned. Anticoagulant therapy complications were: 2 minor bleedings, 1 alopecia, 1 thrombocytopenia. Two patients died for neoplastic complications. Fifty-seven patients completed a 6-month follow-up and were submitted to a control each study that evidenced: total recanalization in 15 (26.3%), partial recanalization in 25 (43.9%) and no recanalization in 17 patients (29.8%). In 6 patients there was a DVT relapse and in 9 pulmonary embolization: almost all these patients were in the partial recanalization group.     

Experimental proof of Doppler bandwidth invariance

A line flow of scatterers crossing the sound field produced by a focused circular transducer at uniform velocity originates a quasi-triangular Doppler spectrum. It is known that the spectrum shape and width depend on the line flow to beam axis angle, as well as on the transducer geometry. It has recently been theoretically predicted that this spectrum width is independent of the flow line location in the sound field. Experimental verification of the new theorem, based on the use of a thread phantom operated at various orientations, ranges, and offsets, with respect to the ultrasound transducer, is presented. The tests were made with a computerized pulsed Doppler system designed to perform optimal real-time spectral analysis of data obtained in this application. The prototype system and the experimental procedure adopted for demonstrating in vitro the invariance of the Doppler spectral bandwidth are described.     

Beneficial and Sexually Dimorphic Response to Combined HDAC Inhibitor Valproate and AMPK/SIRT1 Pathway Activator Resveratrol in the Treatment of ALS Mice

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder. There is no cure and current treatments fail to slow the progression of the disease. Epigenetic modulation in the acetylation state of NF-kB RelA and the histone 3 (H3) protein, involved in the development of neurodegeneration, is a drugable target for the class-I histone deacetylases (HDAC) inhibitors, entinostat or valproate, and the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator, resveratrol. In this study, we demonstrated that the combination of valproate and resveratrol can restore the normal acetylation state of RelA in the SOD1(G93A) murine model of ALS, in order to obtain the neuroprotective form of NF-kB. We also investigated the sexually dimorphic development of the disease, as well as the sex-sensibility to the treatment administered. We showed that the combined drugs, which rescued AMPK activation, RelA and the histone 3 acetylation state, reduced the motor deficit and the disease pathology associated with motor neuron loss and microglial reactivity, Brain-Derived Neurotrophic Factor (BDNF) and B-cell lymphoma-extra large (Bcl-xL) level decline. Specifically, vehicle-administered males showed earlier onset and slower progression of the disease when compared to females. The treatment, administered at 50 days of life, postponed the time of onset in the male by 22 days, but not in a significant way in females. Nevertheless, in females, the drugs significantly reduced symptom severity of the later phase of the disease and prolonged the mice’s survival. Only minor beneficial effects were produced in the latter stage in males. Overall, this study shows a beneficial and sexually dimorphic response to valproate and resveratrol treatment in ALS mice.     

Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates

The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens.     

Influence of phytosterol and phytostanol food supplementation on plasma liposoluble vitamins and provitamin A carotenoid levels in humans: An updated review of the evidence

Phytosterols and phytostanols (PAP) compete with cholesterol absorption in the intestine, resulting in a 5–15%-reduction in plasma total and LDL cholesterol. An important issue is the PAP potential to reduce the plasma concentrations of fat-soluble vitamins and provitamin A carotenoids. Here, an update of the scientific evidence is reviewed to evaluate plant PAP-enriched foods impact on plasma fat-soluble vitamins and carotenoid levels, and to discuss potential implications in terms of cardiovascular risk. Based on 49 human interventional and 3 bioavailability studies, results showed that regular consumption, particularly over the long term, of foods fortified with PAP as recommended in labeling does not significantly impact plasma vitamins A, D, and K concentration. A 10% significant median reduction was observed for α-tocopherol. Concerning carotenoids, while 13 studies did not demonstrate statistically significant plasma β-carotene reduction, 20 studies showed significant reductions, with median effect size of ?24%. This decline can be mitigated or offset by increased fruits and vegetables consumption. Furthermore, higher cardiovascular risk was observed for differences in plasma β-carotene concentration of the same magnitude as the estimated average decrease by PAP consumption. These results are supported by the only study of β-carotene bioavailability showing decrease in absorption by phytosterols daily intake.     

Controlling reaction selectivity in the oxidation of methanol at Cu(110) surfaces

When deuterated methanol (CD₃OH) and dioxygen mixtures are coadsorbed at Cu(110) surfaces at room temperature and above, the main reaction product can be switched between formaldehyde and formate by changing the mixture composition. For oxygen-rich mixtures formaldehyde is the major product but when methanol is in 5 : 1 excess only formate is produced. It is proposed that the reaction mechanism is controlled by the microscopic structure of the surface: when the reactants are adsorbed sequentially, separate islands of oxygen and methoxy develop which inhibit further oxidation but when reactants are coadsorbed a homogeneous mixture of adsorbates is produced creating a facile pathway to formate. This revised version was published online in July 2006 with corrections to the Cover Date.     

Comment on ``Comments on controlling reaction selectivity in the oxidation of methanol at Cu(110) surfaces'

No abstract available. This revised version was published online in July 2006 with corrections to the Cover Date.     

The Trigger System of the MAGIC Telescope

The MAGIC telescope aims at the detection of very low energy gamma rays (E>30 GeV) through the atmospheric emission of Cherenkov light. The high background rate originating from the night sky background, muons, hadronic showers and bright stars sets a serious challenge to this goal. Application of topological selection cuts at trigger level can have a big impact on background reduction allowing the telescope to operate at lower thresholds and reducing the minimum detectable energy. The trigger of the MAGIC telescope is a two-level system following a pipeline philosophy, similar to those adopted in high energy physics experiments. Operative since October 2002, the trigger system has been a key point in the commissioning of the MAGIC telescope that is now taking data. The trigger hardware is described in detail     

Optimisation of cake fat quantity and composition using response surface methodology

The influence of fat quantity and composition on the characteristics of a chemically leavened baked product was investigated, applying a central composite design combined with response surface methodology. Fats were blends of palm oil and palm olein with different slip melting points (from 36.3 to 11.3 °C, in dependence of increasing olein content). Fat content (from 5.3% to 30.7% on batter) and percentage of olein in the fat blend (from 42.7% to 92.2%) were varied. The increase of fat quantity enhanced cake softness, while lowering the volume; higher olein contents also decreased cake firmness. An optimised formulation containing 19.7% fat with 92% olein in the fat blend and showing good structural properties, comparable to those of a 18% butter reference cake, was identified. The optimised and the butter cake showed specific volume of 2.25 and 2.23 cm³ g^?1, respectively, and load at 25% strain of 7.68 and 5.63 N. These results demonstrated the possibility to replace butter with a liquid vegetable fat blend, thus increasing unsaturated fat content and reducing total cholesterol in the product.