Analogs of squalene and oxidosqualene inhibit oxidosqualene cyclase of <Emphasis Type="Italic">Trypanosoma cruzi</Emphasis> expressed in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

Recently, a number of inhibitors of the enzyme oxidosqualene cyclase (OSC; EC 5.4.99.7), a key enzyme in sterol biosynthesis, were shown to inhibit in mammalian cells the multiplication of Trypanosoma cruzi, the parasite agent of Chagas’ disease. The gene coding for the OSC of T. cruzi has been cloned and expressed in Saccharomyces cerevisiae. The expression in yeast cells could be a safe and easy model for studying the activity and the selectivity of the potential inhibitors of T. cruzi OSC. Using a homogenate of S. cerevisiae cells expressing T. cruzi OSC, we have tested 19 inhibitors: aza, methylidene, vinyl sulfide, and conjugated vinyl sulfide derivatives of oxidosqualene and squalene, selected as representative of different classes of substrate analog inhibitors of OSC. The IC₅₀ values of inhibition (the compound concentration at which the enzyme is inhibited by 50%) are compared with the values obtained using OSC of pig liver and S. cerevisiae. Many inhibitors of pig liver and S. cerevisiae OSC show comparable IC₅₀ for T. cruzi OSC, but some phenylthiovinyl derivatives are 10–100 times more effective on the T. cruzi enzyme than on the pig or S. cerevisiae enzymes. The expression of proteins of pathogenic organisms in yeast seems very promising for preliminary screening of compounds that have potential therapeutic activity.     

Lung Microbiome in Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases

Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host–microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.     

Electro‐Drawn Drug‐Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection

Hypodermic needle injection is still the most common method of drug delivery despite its numerous limitations and drawbacks, such as pain, one‐shot administration, and risk of infection. Seeking a viable, safe, and pain‐free alternative to the over 16 billion injections per year has therefore become a top priority for our modern technological society. Here, a system that uses a pyroelectric cartridge in lieu of the syringe piston as a potential solution is discussed. Upon stimulation, the cartridge electro‐draws, at room temperature, an array of drug‐encapsulated, biodegradable polymer microneedles, able to deliver into hypodermic tissue both hydrophobic and hydrophilic bioactive agents, according to a predefined chrono‐programme. This mould‐free and contact‐free method permits the fabrication of biodegradable polymer microneedles into a ready‐to‐use configuration. In fact, they are formed on a flexible substrate/holder by drawing them directly from drop reservoirs, using a controlled electro‐hydrodynamic force. Tests of insertion are performed and discussed in order to demonstrate the possibility to prepare microneedles with suitable geometric and mechanical properties using this method.     

Detection and quantification of lanthanide complexes in cell lysates by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Gadolinium (III) complexes are under intense scrutiny as contrast agents for magnetic resonance imaging. Although currently used mainly as extracellular agents, there is a growing interest to exploit their contrast enhancing ability in the intracellular environment. To ascertain the preservation of their chemical integrity upon the intracellular entrapment, it is necessary to have a method for their dosage in the cell lysates. Herein, a mass spectrometric method for detection and quantification of gadolinium complexes in cell lysates is reported. The detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was carried out by using a non-acidic matrix (2,4,6-trihydroxyacetophenone), which does not allow any leakage of gadolinium from the complex. Quantification has been possible by using as an internal standard an ytterbium complex with the same ligand of the analyte. Ytterbium was chosen because, among the lanthanides, it is the one with the isotopic distribution pattern the most similar to that of gadolinium. Sensitivity was enough to detect low micromolar quantities of a cationic complex and high micromolar quantities of a neutral complex in cell lysates of rat hepatoma cells. In the case of anionic complexes, sensitivity was too low for quantitative analysis. To the best of our knowledge, this is the first report concerning the quantification of metal complexes by MALDI-TOF-MS.     

Fetal growth restriction: adaptations and consequences

A range of pathophysiological factors can result in a perturbation or restriction of fetal growth, and the cardiovascular, neuroendocrine and metabolic adaptations of the fetus to these stimuli will depend on their nature, timing and intensity. The critical importance of these physiological adaptations for both immediate survival and long-term health outcomes has provided an impetus for experimental studies of the nature and consequences of specific fetal adaptations to a poor intrauterine environment. This review summarizes data from recent studies that have focused on the responses of the fetal cardiovascular, sympathoadrenal, hypothalamo-pituitary-adrenal and renin-angiotensin systems to experimental restriction of placental function in the sheep and discusses the consequences of these adaptations for fetal, neonatal and adult health.     

Long-term results from metacarpophalangeal arthroplasty

The authors have been using Swanson's prostheses for MP joint replacement in rheumatoid arthritis since 1968. After thirteen years of experience, they present an analysis of these prostheses from a clinical and radiological point of view. 88 joints replacements in 20 patients are reviewed. These operations were performed between 1968 and 1976. The average follow-up is nine years. The authors compare their results with those obtained in a previous study made in 1975. They show that a replacement arthroplasty with a Swanson type prosthesis, imparts considerable benefits to the patient in the form of complete disappearance of pain, improvement in function, and a more normal looking hand, in spite of radiologic deterioration.     

Separation and analysis of phospholipids in different foods with a light-scattering detector

A method for the separation of phospholipids (PL) from total lipids by solid-phase extraction (SPE) with reversephase C₈ cartridges is described. The method was validated with a standard mixture of PL and applied to natural food matrixes, such as egg, chicken meat, salami, and ripened cheese. The recovery of PL ranged between 93 and 99.7% and was evaluated by an organic phosphorus spectrophotometric determination. The egg powder PL fraction obtained by SPE contained about 20% (w/w) nonpolar PL material when 100–150 mg of lipids were loaded onto the cartridge. Higher percentages of nonphospholipid components (30–43%) were obtained when the amount of lipids loaded was below or above the 100–150 mg range. The purified PL fractions were analyzed by high-performance liquid chromatography (HPLC) with an evaporative light-scattering detector. Good HPLC performance was observed even with low-purity SPE fractions (43% nonphospholipid material).     

Experimental study and mathematical model on remediation of Cd spiked kaolinite by electrokinetics

An experimental study on electrokinetic removal of cadmium from kaolinitic clays is presented in this work, which is aimed to investigate the effect of surface reactions on the electrokinetic process. Enhanced electrokinetic tests were performed in which the pH of the compartments was controlled. Cadmium spiked kaolin was adopted in the experimental runs. On the basis of the experimental results, a numerical model was formulated to simulate the cadmium (Cd) transport under an electric field by combining a one-dimensional diffusion-advection model with a geochemical model: the combined model describes the contaminant transport driven by chemical and electrical gradients, as well as the effect of the surface reactions. The geochemical model utilized parameters derived from the literature, and it was validated by experimental data obtained by sorption and titration experiments. Electrokinetic tests were utilized to validate the results of the proposed model. A good prediction of the behaviour of the soil/cadmium ions system under electrical field was obtained: the differences between experimental and model predicted profiles for the species considered were less than 5% in all the examined conditions.     

Perfluorooctanesulfonate and related fluorinated hydrocarbons in marine mammals,fishes, and birds from coasts of the Baltic and the Mediterranean Seas

Perfluorooctanesulfonate (PFOS; C8F17SO3-), perfluorooctanesulfonamide (FOSA; C8F17SO2NH2), perfluorohexanesulfonate (PFHxS; C6F13SO3-), and perfluorooctanoate (PFOA; C7F15CO2-) were detected in 175 samples of liver and blood of bluefin tuna (Thunnus thynnus), swordfish (Xiphias gladius), common cormorants (Phalacrocorax carbo), bottlenose dolphins (Tursiops truncatus), striped dolphins (Stenella coeruleoalba), common dolphins (Delphinus delphi), fin whales (Balenoptera physalus), and long-finned pilot whales (Globicephala melas) from the Italian coast of the Mediterranean Sea and in livers of ringed seals (Phoca hispida), gray seals (Halichoerus grypus), white-tailed sea eagles (Haliaeetus albicilla), and Atlantic salmon (Salmo salar) from coastal areas of the Baltic Sea. PFOS was detected in all of the wildlife species analyzed. Concentrations of PFOS in blood decreased in order of bottlenose dolphins > bluefin tuna > swordfish. Mean PFOS concentrations (61 ng/ g, wet wt) in cormorant livers collected from Sardinia Island in the Mediterranean Sea were less than the concentrations of PFOA (95 ng/g, wetwt). PFOS concentrations in cormorant livers were significantly correlated with those of PFOA. FOSA was found in 14 of 19 livers or blood samples of marine mammals from the Mediterranean Sea. The highest concentration of 878 ng FOSA/g, wet wt, was found in the liver of a common dolphin. Livers of ringed and gray seals from the Bothnian Bay in the Baltic Sea contained PFOS concentrations ranging from 130 to 1,100 ng/g, wet wt. No relationships between PFOS concentrations and ages of ringed or gray seals were observed. Concentrations of PFOS in livers of seals were 5.5-fold greater than those in corresponding blood. A significant positive correlation existed between the PFOS concentrations in liver and blood, which indicates that blood can be used for nonlethal monitoring of PFOS. Trend analysis of PFOS concentrations in livers of white-tailed sea eagles collected from eastern Germany and Poland since 1979 indicated an increase in concentrations during the 1990s. Livers of Atlantic salmons did not contain quantifiable concentrations of any of the fluorochemicals monitored. PFOS is a widespread contaminant in wildlife from the Baltic and the Mediterranean Seas, while FOSA and PFOA were detected only in certain locations indicating their sporadic spatial distribution.