The polytetrafluoroethylene-covered stent: a device with multiple potential advantages

The polytetrafluoroethylene (PTFE)-covered stent has emerged in the past year as a device with multiple potential advantages. Its structure (a sandwich composed of a layer of PTFE membrane between two stents) makes this the ideal tool for treating coronary ruptures, and for excluding coronary aneurysms. Furthermore, this device may be useful in the treatment of aortocoronary vein graft stenosis. In the present review, the authors summarize experiences with covered stents, and focus attention on available data on the implantation of PTFE-covered stents in human beings to treat coronary ruptures, aneurysms and aortocoronary vein graft stenosis.     

Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase

Understanding the regulation of Akt has been of major interest for elucidating the control of normal cellular physiology as well as malignant transformation. The paradigm for activation of Akt involves phosphatidylinositol 3-kinase-dependent membrane localization followed by activating phosphorylation of Thr-308 and Ser-473. Many of the activating signals for Akt involve the stimulation of receptor and non-receptor tyrosine kinases, and the most potent activator known is the tyrosine phosphatase inhibitor pervanadate, highlighting a possible role for tyrosine phosphorylation in the regulation of the enzyme. In this study we show that activation of Akt by pervanadate or serum is associated with tyrosine phosphorylation of Akt. In addition, in SKOV3 ovarian carcinoma cells that exhibit high basal levels of Akt activity, Akt was tyrosine-phosphorylated in the basal state, and this phosphorylation was further enhanced by both pervanadate and insulin-like growth factor-1. We have used NH(2)-terminal sequencing and phosphate release analysis to directly identify Tyr-474 as the site of tyrosine phosphorylation. Substitution of Tyr-474 with phenylalanine abolished tyrosine phosphorylation of Akt and resulted in up to 55% inhibition of Akt activation, indicating phosphorylation at Tyr-474 is required for full activation of the kinase. Our data identifies a novel regulatory mechanism for this pleiotropic enzyme that may be applicable to the AGC family of protein kinases given the conserved nature of the COOH-terminal hydrophobic motif containing Tyr-474.     

The combined use of oral and topical lipophilic antioxidants increases their levels both in sebum and stratum corneum

The concentration of Vitamin E (vit E) and ubiquinone (CoQ10), which together with squalene (SQ), play a key role against external oxidative insult, has been shown to decrease significantly during ageing. The aim of the present study is to inquire the effect of the combined use of topical bio-cosmetics containing natural active principles (including sebum-like lipid fractions, sebum and epidermal lipophilic and hydrophilic antioxidants), and oral antioxidant supplements on the antioxidant content of sebum and stratum corneum. We therefore treated the face and the back of 50 female volunteers aged 21-40, daily for two months, with a base cream containing 0.05% ubiquinone, 0.1% vit E, and 1% squalene. In addition 50 mg of CoQ10 + 50 mg of d-RRR-alpha-tocopheryl acetate + 50 microg of selenium were administered orally to half of the volunteers (Group A). Group B was represented by 25 volunteers who were treated only topically. Every 15 days during treatment the levels of CoQ10, vit E and SQ were verified in sebum, stratum corneum, and plasma. The daily topical application of the cream led to a significant increase, that peaked after 60 days, of the levels of CoQ10, d-RRR-alpha-tocopherol and SQ in the sebum (Group B), without significantly affecting the stratum corneum or plasma concentrations of the redox couple CoQ10H2/CoQ10 and vit E. The concomitant oral admistration of antioxidants produced in Group A a significant increase of the levels of CoQ10H2/CoQ10 and vit E both in plasma and stratum corneum after 15 and 30 days treatment respectively, compared to Group B. However the sebum levels of lipophilic antioxidants and SQ did not show a significant increase. After the treatments, the levels of CoQ10H2/CoQ10, vit E and SQ went back to basal levels within 6-8 days in sebum, 12-16 days in the stratum corneum, and 3-6 days in plasma. Therefore topical application of the antioxidants was able to increase their level in sebum, while the concomitant oral administration also affected the levels of vit E and CoQ10 in the stratum corneum.     

Blood Metals Concentration in Type 1 and Type 2 Diabetics

Mechanisms for the onset of diabetes and the development of diabetic complications remain under extensive investigations. One of these mechanisms is abnormal homeostasis of metals, as either deficiency or excess of metals, can contribute to certain diabetic outcomes. Therefore, this paper will report the blood levels of chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), mercury (Hg), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in subjects with type 1 diabetes (n?=?192, mean age 48.8 years, mean disease duration 20.6 years), type 2 diabetes (n?=?68, mean age 68.4 years, mean disease duration 10.2 years), and in control subjects (n?=?59, mean age 57.2 years), and discuss the results indicating their possible role in diabetes. The metal concentrations were measured by sector field inductively coupled plasma mass spectrometry after microwave-induced acid digestion of blood samples. The accuracy was checked using a blood-based certified reference material, and recoveries of all elements were in the range of 92–101 % of certified values. Type 1 diabetes was found to be associated with Cr (p?=?0.02), Mn (p?<?0.001), Ni (p?<?0.001), Pb (p?=?0.02), and Zn (p?<?0.001) deficiency, and type 2 diabetes with Cr (p?=?0.014), Mn (p?<?0.001), and Ni (p?<?0.001) deficiency. These deficiencies were appreciated also subdividing the understudied patients for gender and age groups. Furthermore, in type 1 diabetes, there was a positive correlation between Pb and age (p?<?0.001, ρ?=?0.400) and Pb and BMI (p?<?0.001, ρ?=?0.309), while a negative correlation between Fe and age (p?=?0.002, ρ?=??0.218). In type 2 diabetes, there was a negative correlation between Fe and age (p?=?0.017, ρ?=??0.294) and Fe and BMI (p?=?0.026, ρ?=??0.301). Thus, these elements may play a role in both forms of diabetes and combined mineral supplementations could have beneficial effects.     

Occurrence of Lepidopterism caused by the moth Hylesia nigricans (Berg) (Lepidoptera: Saturniidae) in Rio Grande do Sul State, Brazil

Lepidopterism by Hylesia nigricans (Berg) moth is recorded for the first time in southern Brazil. Preventive strategies of control are proposed based on information on the biology and ecology of this moth.     

The synthetic peptide RPRAATF allows specific assay of Akt activity in cell lysates

The Akt protein kinase is a critical signaling molecule in a range of cellular processes. A key to identifying the role of this pleiotropic kinase in any particular process is the ability to quantitate its activity. In this study we show that the synthetic peptide RPRAATF is a specific substrate for the kinase in crude cell extracts, thus enabling rapid, convenient, and sensitive assay of Akt activity. Peptide kinase activity was confined to a single peak upon sequential ion-exchange chromatography of whole-cell extracts of Balb/c 3T3 fibroblasts. This activity was stimulated by both platelet-derived growth factor and pervanadate, phosphatidyl inositol 3-kinase dependent, and inhibited by specific immunodepletion with anti-Akt antisera. Furthermore, direct assays of crude extracts from a range of cell types using this peptide were consistent with the results obtained using specific immunoprecipitation assays.     

Involvement of potassium channels in the antidepressant-like effect of venlafaxine in mice

AimsStudies have shown that the acute administration of venlafaxine elicits an antidepressant-like effect in the mouse forced swim test (FST) by a mechanism dependent on the l-arginine–nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway. Because it has been reported that NO activates different types of potassium (K⁺) channels in the brain, this study investigated the involvement of K⁺ channels in the antidepressant-like effect of venlafaxine in the mouse FST.Main methodsMale adult Swiss mice were pretreated with different K⁺ channel inhibitors or openers 15 min before venlafaxine administration. After 30 min, the open-field test (OFT) and FST were carried out.Key findingsIntracerebroventricular (i.c.v.) pretreatment of mice with subeffective doses of tetraethylammonium (TEA, a non-specific inhibitor of K⁺ channels, 25 pg/site), glibenclamide (an ATP-sensitive K⁺ channel inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K⁺ channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K⁺ channel inhibitor, 10 pg/site) was able to potentiate the action of a subeffective dose of venlafaxine (2 mg/kg, i.p.). Moreover, the reduction in the immobility time elicited by an effective dose of venlafaxine (8 mg/kg, i.p.) in the FST was prevented by the pretreatment of mice with the K⁺ channel openers cromakalim (10 µg/site, i.c.v.) and minoxidil (10 µg/site, i.c.v.). The drugs used in this study did not produce any change in locomotor activity.SignificanceThe results demonstrate that the neuromodulatory effects of venlafaxine, via the inhibition of K⁺ channels, are possibly involved in its anti-immobility activity in the mouse FST.     

D1 and D2 Inhibitions of the Soleus H-Reflex Are Differentially Modulated during Plantarflexion Force and Position Tasks

Presynaptic inhibition (PSI) has been shown to modulate several neuronal pathways of functional relevance by selectively gating the connections between sensory inputs and spinal motoneurons, thereby regulating the contribution of the stretch reflex circuitry to the ongoing motor activity. In this study, we investigated whether a differential regulation of Ia afferent inflow by PSI may be associated with the performance of two types of plantarflexion sensoriomotor tasks. The subjects (in a seated position) controlled either: 1) the force level exerted by the foot against a rigid restraint (force task, FT); or 2) the angular position of the ankle when sustaining inertial loads (position task, PT) that required the same level of muscle activation observed in FT. Subjects were instructed to maintain their force/position at target levels set at ~10% of maximum isometric voluntary contraction for FT and 90° for PT, while visual feedback of the corresponding force/position signals were provided. Unconditioned H-reflexes (i.e. control reflexes) and H-reflexes conditioned by electrical pulses applied to the common peroneal nerve with conditioning-to-test intervals of 21 ms and 100 ms (corresponding to D1 and D2 inhibitions, respectively) were evoked in a random fashion. A significant main effect for the type of the motor task (FT vs PT) (p = 0.005, η² _p = 0.603) indicated that PTs were undertaken with lower levels of Ia PSI converging onto the soleus motoneuron pool. Additionally, a significant interaction between the type of inhibition (D1 vs D2) and the type of motor task (FT vs PT) (p = 0.038, η² _p = 0.395) indicated that D1 inhibition was associated with a significant reduction in PSI levels from TF to TP (p = 0.001, η² _p = 0.731), whereas no significant difference between the tasks was observed for D2 inhibition (p = 0.078, η² _p = 0.305). These results suggest that D1 and D2 inhibitions of the soleus H-reflex are differentially modulated during the performance of plantarflexion FT and PT. The reduced level of ongoing PSI during PT suggests that, in comparison to FT, there is a larger reliance on inputs from muscle spindles primary afferents when the neuromuscular system is required to maintain position-controlled plantarflexion contractions.     

Effect of Oxidation on the Structure of Human Low- and High-Density Lipoproteins

This work presents a controlled study of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) structural changes due to in vitro oxidation with copper ions. The changes were studied by small-angle x-ray scattering (SAXS) and dynamic light scattering (DLS) techniques in the case of LDL and by SAXS, DLS, and Z-scan (ZS) techniques in the case of HDL. SAXS data were analyzed with a to our knowledge new deconvolution method. This method provides the electron density profile of the samples directly from the intensity scattering of the monomers. Results show that LDL particles oxidized for 18 h show significant structural changes when compared to nonoxidized particles. Changes were observed in the electrical density profile, in size polydispersity, and in the degree of flexibility of the APO-B protein on the particle. HDL optical results obtained with the ZS technique showed a decrease of the amplitude of the nonlinear optical signal as a function of oxidation time. In contrast to LDL results reported in the literature, the HDL ZS signal does not lead to a complete loss of nonlinear optical signal after 18 h of copper oxidation. Also, the SAXS results did not indicate significant structural changes due to oxidation of HDL particles, and DLS results showed that a small number of oligomers formed in the sample oxidized for 18 h. All experimental results for the HDL samples indicate that this lipoprotein is more resistant to the oxidation process than are LDL particles.     

Curcumin derivatives as new ligands of Aβ peptides

Curcumin derivatives with high chemical stability, improved solubility and carrying a functionalized appendage for the linkage to other entities, have been synthesized in a straightforward manner. All compounds retained Curcumin ability to bind Aβ peptide oligomers without inducing their aggregation. Moreover all Curcumin derivatives were able to stain very efficiently Aβ deposits.