Biodegradable hollow microfibres to produce bioactive scaffolds

Biodegradable hollow microfibres containing particles loaded with specific active agents can be potentially employed to produce a special kind of substrate for tissue engineering, able to function as a scaffold and at the same time to act as a drug‐releasing system. Biodegradable hollow microfibres based on poly(lactic acid) were produced by a dry–wet spinning procedure. Drug‐loaded microparticles were prepared by a simple oil‐in‐water emulsion and entrapped inside the fibres. The morphology of both fibres and particles was investigated by scanning electron microscopy. The mechanical and thermal properties of the fibres were investigated by tensile tests and differential scanning calorimetry. In vitro tests were performed to evaluate the release of the drug from the fibres loaded with the particles Copyright © 2004 Society of Chemical Industry     

Adaptive control of siso plants with unmodelled dynamics

In this paper we pursue a twofold aim. First we want to simplify the complexity of the classical Monopoli's scheme, the so-called ‘Augmented error signal control scheme’. Then we also wish to cope with the realistic situation in which the presence of unmodelled dynamics has to be taken into account. This latter problem has been faced in the literature by suitably modifying the adaptation mechanism in order to avoid undesired phenomena as well as to obtain an attractive stability region for the state trajectories starting from any point in a predefined initial condition set. In our case the necessity of introducing any sort of modification in the adaptation mechanism is completely avoided, but we still obtain asymptotic stability of the output error signal.     

Efficacy and pharmacokinetics of gallopamil in patients with coronary artery disease

We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coronary artery disease or to detect residual ischaemia after myocardial infarction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patients with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil treatment. At the end of the run-in period patients underwent two different exercise tests, the first 2 hours and the second 7 hours after placebo administration. During active treatment all patients underwent two different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy. On the same days in eight of the patients we evaluated gallopamil pharmacokinetic changes. Our data revealed a rapid increase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour after oral administration on both the 1st and 28th day of observation. Moreover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with gallopamil. Our clinical data showed an improvement in exercise results during gallopamil therapy related to increased concentration of the drug.     

A statistical analysis of the received signal from blood duringlaminar flow

In order to determine the limiting velocity resolution that can be achieved using ultrasound, and to provide a model which can be generalized for the analysis of disturbed flow, a theoretical and experimental evaluation of the statistics of the received signal from laminar flow following the transmission of a train of short pulses is presented. The authors derive the autocorrelation function and determine the length of the correlated signal for various flow rates, comparing experimental measurements to theoretical predictions. High resolution experimental RF M-mode images are used to verify the theoretical model. Using a fluid with a density, viscosity, volume concentration, particle size, and speed of sound which is similar to that of blood, the authors show that the signal remains correlated for a long interval under many conditions of clinical interest. Including a comparison with experimental data, the effect of the lateral transit time through the sample volume and the axial velocity spread within the sample volume on the correlation of the received signal is evaluated. When a significant range of velocity components is present within the sample volume, this range is the limiting factor in the length of the correlated signal interval. Therefore, the use of a wideband signal, which reduces the sample volume size, produces a returned signal that may be correlated for a larger number of pulses, or for a longer time     

Higher Order Sliding Mode Controllers With Optimal Reaching

Higher order sliding mode (HOSM) control design is considered for systems with a known permanent relative degree. In this paper, we introduce the robust Fuller's problem that is a robust generalization of the Fuller's problem, a standard optimal control problem for a chain of integrators with bounded control. By solving the robust Fuller's problem it is possible to obtain feedback laws that are HOSM algorithms of generic order and, in addition, provide optimal finite-time reaching of the sliding manifold. A common difficulty in the use of existing HOSM algorithms is the tuning of design parameters: our methodology proves useful for the tuning of HOSM controller parameters in order to assure desired performances and prevent instabilities. The convergence and stability properties of the proposed family of controllers are theoretically analyzed. Simulation evidence demonstrates their effectiveness.     

State-of-the-Art on Wound Vitality Evaluation: A Systematic Review

The vitality demonstration refers to determining if an injury has been caused ante- or post-mortem, while wound age means to evaluate how long a subject has survived after the infliction of an injury. Histology alone is not enough to prove the vitality of a lesion. Recently, immunohistochemistry, biochemistry, and molecular biology have been introduced in the field of lesions vitality and age demonstration. The study was conducted according to the preferred reporting items for systematic review (PRISMA) protocol. The search terms were “wound”, “lesion”, “vitality”, “evaluation”, “immunohistochemistry”, “proteins”, “electrolytes”, “mRNAs”, and “miRNAs” in the title, abstract, and keywords. This evaluation left 137 scientific papers. This review aimed to collect all the knowledge on vital wound demonstration and provide a temporal distribution of the methods currently available, in order to determine the age of lesions, thus helping forensic pathologists in finding a way through the tangled jungle of wound vitality evaluation.     

Energy Deposition around Swift Carbon-Ion Tracks in Liquid Water

Energetic carbon ions are promising projectiles used for cancer radiotherapy. A thorough knowledge of how the energy of these ions is deposited in biological media (mainly composed of liquid water) is required. This can be attained by means of detailed computer simulations, both macroscopically (relevant for appropriately delivering the dose) and at the nanoscale (important for determining the inflicted radiobiological damage). The energy lost per unit path length (i.e., the so-called stopping power) of carbon ions is here theoretically calculated within the dielectric formalism from the excitation spectrum of liquid water obtained from two complementary approaches (one relying on an optical-data model and the other exclusively on ab initio calculations). In addition, the energy carried at the nanometre scale by the generated secondary electrons around the ion’s path is simulated by means of a detailed Monte Carlo code. For this purpose, we use the ion and electron cross sections calculated by means of state-of-the art approaches suited to take into account the condensed-phase nature of the liquid water target. As a result of these simulations, the radial dose around the ion’s path is obtained, as well as the distributions of clustered events in nanometric volumes similar to the dimensions of DNA convolutions, contributing to the biological damage for carbon ions in a wide energy range, covering from the plateau to the maximum of the Bragg peak.     

Iron Mobilization from Ferritin in Yeast Cell Lysate and Physiological Implications

Most in vitro iron mobilization studies from ferritin have been performed in aqueous buffered solutions using a variety of reducing substances. The kinetics of iron mobilization from ferritin in a medium that resembles the complex milieu of cells could dramatically differ from those in aqueous solutions, and to our knowledge, no such studies have been performed. Here, we have studied the kinetics of iron release from ferritin in fresh yeast cell lysates and examined the effect of cellular metabolites on this process. Our results show that iron release from ferritin in buffer is extremely slow compared to cell lysate under identical experimental conditions, suggesting that certain cellular metabolites present in yeast cell lysate facilitate the reductive release of ferric iron from the ferritin core. Using filtration membranes with different molecular weight cut-offs (3, 10, 30, 50, and 100 kDa), we demonstrate that a cellular component >50 kDa is implicated in the reductive release of iron. When the cell lysate was washed three times with buffer, or when NADPH was omitted from the solution, a dramatic decrease in iron mobilization rates was observed. The addition of physiological concentrations of free flavins, such as FMN, FAD, and riboflavin showed about a two-fold increase in the amount of released iron. Notably, all iron release kinetics occurred while the solution oxygen level was still high. Altogether, our results indicate that in addition to ferritin proteolysis, there exists an auxiliary iron reductive mechanism that involves long-range electron transfer reactions facilitated by the ferritin shell. The physiological implications of such iron reductive mechanisms are discussed.     

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η⁶-arene)Ru(N,N′)L][PF₆]₂ containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λ_max = 418 nm) compared with C1 and C2 (λ_max = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC₅₀ = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).