Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris

OBJECTIVES: This study was designed to evaluate whether the addition of transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy improves the natural history of unstable angina pectoris. BACKGROUND: Transdermal nitroglycerin is widely used to treat angina pectoris, but the development of tolerance is a major problem that may reduce its clinical efficacy. It has been suggested that the addition of N-acetylcysteine to nitroglycerin reverses the development of tolerance, potentiates the hemodynamic response to nitroglycerin and may improve in-hospital prognosis in unstable angina. METHODS: We assessed the efficacy of adding transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy in a randomized, double-blind, placebo-controlled trial involving 200 patients with unstable angina who were followed up for 4 months. RESULTS: Outcome events--death, myocardial infarction or refractory angina requiring revascularization--occurred in 31% of patients receiving nitroglycerin, 42% of those receiving N-acetylcysteine, 13% of those receiving nitroglycerin plus N-acetylcysteine and 39% of those receiving placebo (p = 0.0052). Kaplan-Meier curves showed a higher probability (p < 0.01) of no failure of medical treatment in the group receiving both nitroglycerin and N-acetylcysteine than in those receiving placebo, N-acetylcysteine or nitroglycerin alone. The combination of nitroglycerin and N-acetylcysteine was associated with a high incidence of side effects (35%), mainly intolerable headache, which was almost twice as frequent as in patients receiving nitroglycerin alone. CONCLUSIONS: The combination of nitroglycerin and N-acetylcysteine, associated with conventional medical therapy in the long-term treatment of patients with unstable angina, reduces the occurrence of outcome events. However, the high incidence of side effects limits the clinical applicability of this therapeutic strategy at least at the dosage used in the present study.     

Red mud and fly ash for remediation of mine sites contaminated with As, Cd, Cu, Pb and Zn

The paper presents the results of a laboratory investigation conducted for assessing the feasibility of immobilising the heavy metals (As, Cd, Cu, Pb and Zn) contained in a disused mine tailings dam. Samples of tailings were mixed with relatively small proportions of bauxite red mud and power station fly ash. The sorption capacity of these two materials, already determined for Cd, Cu, Pb and Zn, has been determined here for arsenic by means of batch experiments on purposely prepared solutions. The results of this preliminary investigation show that sorption capacity is strongly influenced by pH. While the red mud performs better at low pH, the ability of fly ash to adsorb As increases with increasing pH. Tests carried out in leach columns containing tailings alone and tailings mixed with 15% by weight neutralized red mud or fly ash demonstrate the heavy metal sorption potential of the two materials, the red mud proving to be the more effective.     

High performance automotive chassis design: a topology optimization based approach

Automotive chassis design in view of car weight reduction is a challenging task due to the many performance targets that must be satisfied, in particular in terms of vehicle safety. In this paper a methodology for automotive chassis design in involving optimization techniques is presented. In particular, topology, topometry and size optimizations are coupled with fem analyses and adopted in cascade for reaching an optimum chassis configuration. The methodology is applied to the design process of a rear-central engine high performance vehicle chassis. The objective of the optimization process is the chassis weight reduction, yet in fulfilment of structural performance constraints as required by Ferrari standards. The results demonstrate the general applicability of the methodology presented for obtaining the general trusses layout and thicknesses distribution of the structure. The numerical model at this stage shows a significant weight reduction when compared to the chassis of the Ferrari F458 Italia.     

A tomato stem cell extract, containing antioxidant compounds and metal chelating factors, protects skin cells from heavy metal-induced damages

Heavy metals can cause several genotoxic effects on cells, including oxidative stress, DNA sequence breakage and protein modification. Among the body organs, skin is certainly the most exposed to heavy metal stress and thus the most damaged by the toxic effects that these chemicals cause. Moreover, heavy metals, in particular nickel, can induce the over-expression of collagenases (enzymes responsible for collagen degradation), leading to weakening of the skin extracellular matrix. Plants have evolved sophisticated mechanisms to protect their cells from heavy metal toxicity, including the synthesis of metal chelating proteins and peptides, such as metallothioneins and phytochelatins (PC), which capture the metals and prevent the damages on the cellular structures. To protect human skin cells from heavy metal toxicity, we developed a new cosmetic active ingredient from Lycopersicon esculentum (tomato) cultured stem cells. This product, besides its high content of antioxidant compounds, contained PC, effective in the protection of skin cells towards heavy metal toxicity. We have demonstrated that this new product preserves nuclear DNA integrity from heavy metal damages, by inducing genes responsible for DNA repair and protection, and neutralizes the effect of heavy metals on collagen degradation, by inhibiting collagenase expression and inducing the synthesis of new collagen.     

Changes in plasmin-plasminogen-plasminogen activator system in milk from Italian Friesian herds

Changes in plasmin, plasminogen and plasminogen activator (PA) throughout the lactation were investigated in individual milk samples obtained from 32 Friesian cows from four commercial herds located in Northern Italy. Herds were chosen to represent four different, yet typical for Italy, diets. Increased levels of plasmin and PA (P < 0.05) were observed with advancing lactation. Plasminogen peaked during the fifth month of lactation. The increased levels of plasmin during the fifth month of lactation are partly due to increased plasminogen, which reflects increased permeability of mammary epithelium. However, the ratio of plasminogen to plasmin decreased with advancing lactation, suggesting accelerated conversion of plasminogen to plasmin. Major differences were observed between herds with respect to plasmin levels. These differences probably reflect differences in diets and management practices. This could be very important for Northern Italy where most of the milk produced is used for cheese manufacture. Plasmin, PA and somatic cell counts (SCC) were negatively correlated with casein/protein with coefficients of −0.38, −0.43 and −0.40, respectively. A significant correlation existed between PA and SCC (r = 0.50). PA was positively correlated with plasmin (r = 0.49).     

Short communication: isolation of Prototheca species strains from environmental sources in dairy herds

Composite milk samples from 548 cows, and samples from feces, feed, bedding, water, liners (before and after milking), and the postdipping product were aseptically collected from 2 Italian dairy herds from February to November of 2006. Prototheca zopfii was isolated from 11.9% of milk samples, 15% of feces, and 33.3% of bedding samples. No viable cells of P. zopfii were observed in water before washing procedures, whereas 25 to 28.6% of samples from water used for washing both refrigeration tanks and milking equipment were contaminated with this yeast-like microalga. Analogously, the presence of P. zopfii was detected only on swabs collected from the liners after milking. Interestingly, in 1 of the 2 herds, water from the drinking trough was contaminated by viable cells of both P. zopfii and the related environmental species Prototheca stagnora. No viable cells were observed in cow feed. On the basis of the results presented herein, P. zopfii seemed to be widespread throughout the environments of dairy herds where outbreaks of bovine mastitis had occurred.     

Mechanism of lustre formation in scheelite-based glazes

This work elucidates the mechanism responsible for the lustre effect of scheelite-based glazes for single-firing wall tiles. The surface decoration is obtained with a thin film composed of a Si–Ca–Zn–Al–K–B frit and 10 wt% WO₃ on zircon-engobed substrates for single-firing wall tiles (maximum temperature of 1130 °C for 50 min). The observed lustre effect is sub-adamantine and pearlescent. It is sub-adamantine because scheelite nanocrystals at the surface, with a relatively high refractive index (n = 1.93), cause considerable reflection of light. The lustre is also weakly pearlescent because the nano-crystals oriented with the (004) plane parallel to the surface give interference with the underlying glassy layer (n ≈ 1.5), where randomly dispersed scheelite crystals occur. This model apparently applies to the glazes decorated with ceria, although the latter exhibits iridescence due to the high refractive index of ceria (n = 2.05) which yields stronger interference effect with the underlying glassy substrate.     

Clinical utility of prothrombin fragment 1+2, thrombin antithrombin III complexes and D-dimer measurements in the diagnosis of deep vein thrombosis following total hip replacement

BACKGROUND: Measurements of prothrombin fragment 1+2 (F1+2), thrombin antithrombin III complexes (TAT) and D-dimer plasma levels have been proposed as non-invasive screening tests to exclude postoperative deep venous thrombosis (DVT). We investigated the diagnostic efficacy of these coagulation activation markers to rule out postoperative DVT in patients undergoing hip surgery under antithrombotic prophylaxis. METHODS: In this substudy of a randomized double-blind thrombosis prophylaxis trial comparing three doses of desirudin (10, 15 or 20 mg b.i.d.) with unfractionated heparin (5000 IU t.i.d.) we used ELISA procedures to measure F1+2, TAT and D-dimer in 159 patients undergoing total hip replacement at baseline (day 0) and on postoperative days 1, 3 and 6. Bilateral venography was performed in all cases 8-11 days after surgery. RESULTS: For the F1+2 assay sensitivity ranged from 73 to 83% in the three postoperative days investigated, and negative predictive value (NPV) from 68 to 74%. For TAT and D-dimer sensitivity ranged from 71 to 73% and from 71 to 83% and NPV from 61 to 65% and from 61 to 74% respectively. INTERPRETATION: In terms of sensitivity and NPV F1+2 and D-dimer are equivalent and are superior to TAT. However, their accuracy is too low to rule out the presence of DVT after hip surgery under antithrombotic prophylaxis.     

Short communication: Comparing real-time PCR and bacteriological cultures for Streptococcus agalactiae and Staphylococcus aureus in bulk-tank milk samples

For more than 30 yr, a control plan for Streptococcus agalactiae and Staphylococcus aureus has been carried out in more than 1,500 dairy herds of the province of Brescia (northern Italy). From 2010 to 2011, the apparent prevalence of Strep. agalactiae has been relatively stable around 10%, but the apparent prevalence of Staph. aureus has been greater than 40% with an increasing trend. The aim of this paper was to estimate and compare the diagnostic accuracy of 3 assays for the detection of Strep. agalactiae and Staph. aureus in bulk-tank milk samples (BTMS) in field conditions. The assays were a qualitative and a quantitative bacteriological culture (BC) for each pathogen and a homemade multiplex real-time PCR (rt-PCR). Because a gold standard was not available, the sensitivities (Se) and specificities (Sp) were evaluated using a Bayesian latent class approach. In 2012 we collected one BTMS from 165 dairy herds that were found positive for Strep. agalactiae in the previous 2-yr campaigns of eradication plan. In most cases, BTMS collected in these herds were positive for Staph. aureus as well, confirming the wide spread of this pathogen. At the same time we also collected composite milk samples from all the 8,624 lactating cows to evaluate the within-herd prevalence of Strep. agalactiae. Streptococcus agalactiae samples were cultured using a selective medium Tallium Kristalviolette Tossin, whereas for Staph. aureus, we used Baird Parker modified medium with added Rabbit Plasma Fibrinogen ISO-Formulation. In parallel, BTMS were tested using the rt-PCR. Regarding Strep. agalactiae, the posterior median of Se and Sp of the 2 BC was similar [qualitative BC: Se = 98%, posterior credible interval (95%PCI): 94–100%, and Sp = 99%, 95%PCI: 96–100%; quantitative BC: Se = 99%, 95%PCI: 96–100%, and Sp = 99%, 95%PCI: 95–100%] and higher than those of the rt-PCR (at 40 cycle threshold, Se = 92%, 95%PCI: 85–97%; Sp = 94%, 95%PCI: 88–98%). Also in case of Staph. aureus, the posterior medians of BC were generally higher than those of rt-PCR. In fact, although the Se of BC was slightly lower (rt-PCR at 40 cycle threshold, median Se = 99%, 95%PCI: 97–100%, and qualitative BC, median Se = 94%, 95%PCI: 87–99%), the Sp was much higher (rt-PCR at 40 cycle threshold, median Sp = 67%, 95%PCI: 38–97%; qualitative BC, median Sp = 95%; 95%PCI: 76–100%). Our study confirms that BC and rt-PCR are reliable diagnostic tools to detect Strep. agalactiae and Staph. aureus, and rt-PCR results should be confirmed by BC carried out on BTMS and possibly on composite milk samples.