Plain language review: the safety of relugolix combination therapy for advanced prostate cancer.

What Is This Summary About?: Advanced prostate cancer is a cancer that began in the prostate (a part of the male body) and has spread to other parts of the body. This is a review of two clinical research studies of patients with advanced prostate cancer who were treated with relugolix combination therapy. Relugolix is a medicine taken by mouth that lowers a male sex , called testosterone.

Engineering of 3D printed personalized polypills for the treatment of the metabolic syndrome.

Metabolic syndrome is a collection of abnormalities, including at least three of the following insulin resistance, hypertension, dyslipidemia, type 2 diabetes, obesity, inflammation, and non-alcoholic fatty liver disease. 3D printed solid dosage forms have emerged as a promising tool enabling the fabrication of personalized medicines and offering solutions that cannot be achieved by industrial mass production. Most attempts found in the literature to manufacture polypills for this syndrome contain just two drugs.

Oxidation-reduction and photophysical properties of isomeric forms of Safranin.

Safranine O is widely used in the bioenergetics community as an indicator dye to determine membrane potentials and as an electron transfer mediator in potentiometric titrations. Here we show that two different commercial preparations of Safranine O contain less than sixty percent by weight of the title compound, with the rest primarily consisting of two closely related safranine isomers. All three major isomer components were isolated using reverse phase HPLC and their structures determined using mass spectrometry and two-dimensional NMR.

Fluoride binding to characteristic heme-pocket centers: Insights into ligand stability.

The studies on the L. pectinata hemoglobins (HbI, HbII, and HbIII) are essential because of their biological roles in hydrogen sulfide transport and metabolism. Variation in the pH could also play a role in the transport of hydrogen sulfide by HbI and oxygen by HbII and HbIII, respectively.

3D printed spherical mini-tablets: Geometry versus composition effects in controlling dissolution from personalised solid dosage forms.

Oral dosage forms are by far the most common prescription and over-the-counter pharmaceutical dosage forms used worldwide. However, many patients suffer from adverse effects caused by their use of "one-size fits all" mass produced commercially available solid dosage forms, whereby they do not receive dedicated medication or dosage adjusted to their specific needs. The development of 3D printing paves the way for personalised medicine.

Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms.

Although not readily accessible yet to many community and hospital pharmacists, fuse deposition modelling (FDM) is a 3D printing technique that can be used to create a 3D pharmaceutical dosage form by employing drug loaded filaments extruded via a nozzle, melted and deposited layer by layer. FDM requires printable filaments, which are commonly manufactured by hot melt extrusion, and identifying a suitable extrudable drug-excipient mixture can sometimes be challenging. We propose here the use of passive diffusion as an accessible loading method for filaments that can be printed using FDM technology to allow for the fabrication of oral personalised medicines in clinical settings.

Partial Nephrectomy versus Thermal Ablation for Clinical Stage T1 Renal Masses: Systematic Review and Meta-Analysis of More than 3,900 Patients.

Purpose: A systematic review and meta-analysis of clinical trials was undertaken to compare percutaneous thermal ablation versus partial nephrectomy (PN) for stage T1 renal tumors.

Materials And Methods: A comprehensive search of major databases was conducted from October 2000 to July 2016. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed.

Designing Light-Activated Charge-Separating Proteins with a Naphthoquinone Amino Acid.

The first principles design of manmade redox-protein maquettes is used to clarify the physical/chemical engineering supporting the mechanisms of natural enzymes with a view to recapitulate and surpass natural performance. Herein, we use intein-based protein semisynthesis to pair a synthetic naphthoquinone amino acid (Naq) with histidine-ligated photoactive metal-tetrapyrrole cofactors, creating a 100 μs photochemical charge separation unit akin to photosynthetic reaction centers. By using propargyl groups to protect the redox-active para-quinone during synthesis and assembly while permitting selective activation, we gain the ability to employ the quinone amino acid redox cofactor with the full set of natural amino acids in protein design.

Evaluation of heme peripheral group interactions in extremely low-dielectric constant media and their contributions to the heme reduction potential.

In this study, we measured the contributions of the ionization of the heme propionates to the reduction potentials of heme b and heme a (bis)N-methylimidazole complexes in various low-dielectric constant conditions. Additionally, we measured the effects of H-bond to the heme a formyl group on the reduction potential of the heme. The performed electrochemical measurements show that ionization of the heme propionates lead to the largest redox change in dichloromethane with no electrolyte.

Electrochemical determination of heme-linked pKa values and the importance of using fluoride binding in heme proteins.

The ultraviolet-visible (UV-vis) spectroelectrochemical measurements of heme proteins in the presence of a heme-bound fluoride ion can be used as a probe for heme-linked ionizations of acid-base groups in the heme pocket. A detailed study of the pH dependence of the midpoint potential of skeletal horse myoglobin (Mb) with a heme-bound fluoride ion (Mb-F) reveals how protonation of the distal histidine (H64) changes the redox properties of the protein with a determined pKa of 5.3.

A three-dimensional printed cell for rapid, low-volume spectroelectrochemistry.

We have used three-dimensional (3D) printing technology to create an inexpensive spectroelectrochemical cell insert that fits inside a standard cuvette and can be used with any transmission spectrometer. The cell positions the working, counter, and reference electrodes and has an interior volume of approximately 200 μl while simultaneously providing a full 1-cm path length for spectroscopic measurements. This method reduces the time required to perform a potentiometric titration on a molecule compared with standard chemical titration methods and achieves complete electrolysis of protein samples within minutes.

Manipulating Reduction Potentials in an Artificial Safranin Cofactor.

Safranines hold great promise as artificial flavin-like electron transfer cofactors with tunable properties. We report the design and chemical synthesis of the p-methoxy derivative of safranine O using a new synthetic route based on the Ulmann condensation. Spectroelectrochemical comparison of the purified parent safranine and this derivative demonstrates that the modification increases its two-electron reduction potential by 125 mV, or 5.

Ventricular fibrillation conduction through an isthmus of preserved myocardium between radiofrequency lesions.

Background: Selective local acceleration of myocardial activation during ventricular fibrillation (VF) contributes information on the interactions between neighboring zones during the arrhythmia. This study analyzes these interactions, centering the observations on an isthmus of myocardium between two radiofrequency (RF) lesions.

Methods: In nine isolated rabbit hearts, a gap of preserved myocardium was established between two RF lesions in the anterolateral left ventricle (LV) wall.

Electrochemical and structural coupling of the naphthoquinone amino acid.

As a prelude to engineering artificial energy conversion proteins emulating biology, we examine the inclusion of a synthetic naphthoquinone amino acid in a characterized host-guest protein and determine the effects of its quinone and hydroquinone forms on the helix-coil distribution.

Reversible proton coupled electron transfer in a peptide-incorporated naphthoquinone amino acid.

The synthesis of a naphthoquinone amino acid and its electrochemical characterization in a peptide is presented.

Hydrogen bond-free flavin redox properties: managing flavins in extreme aprotic solvents.

We report a simple, single step reaction that transforms riboflavin, which is insoluble in benzene, to tetraphenylacetyl riboflavin (TPARF), which is soluble in this solvent to over 250 mM. Electrochemical analysis of TPARF both alone and in complexes with two benzene-soluble flavin receptors: dibenzylamidopyridine (DBAP) and monobenzylamidopyridine (MBAP), prove that this model system behaves similarly to other previously studied flavin model systems which were soluble only in more polar solvents such as dichloromethane. Binding titrations in both benzene and dichloromethane show that the association constants of TPARF with its ligands are over an order of magnitude higher in benzene than dichloromethane, a consequence of the fact that benzene does not compete for H-bonds, but dichloromethane does.

[Changes in the spectral characteristics of ventricular fibrillation in lesions produced by radiofrequency ablation. An experimental study].

Introduction And Objectives: Although electro- physiological databases contain information about changes in the time domain in lesions produced by radiofrequency ablation, very few data on changes in the frequency domain are available. The aim of this study was to investigate changes in the spectral characteristics of ventricular fibrillation in zones with radiofrequency lesions.

Methods: Recordings of ventricular fibrillation were obtained in 11 isolated perfused rabbit heart preparations using a multiple epicardial electrode located on the left ventricular free wall.

A Flavin Analogue with Improved Solubility in Organic Solvents.

We report the synthesis and initial electrochemical characterization of a benzene-soluble flavin analogue: N(10)-2,2-dibenzylethyl-7,8-dimethylisoalloxazine (DBF, 1). This analogue, which has an unmodified flavin headgroup, is intended for use in the spectroscopic examination of the electronic effects of flavin hydrogen bonding in simple model systems in aprotic, non-hydrogen bonding solvents. With future spectroscopic studies in mind, we have developed a synthetic route which allows the incorporation of isotopic labels using inexpensive starting materials.

Selective myocardial isolation and ventricular fibrillation.

Background: Few experimental studies have analyzed the effects of selective radiofrequency (RF) lesions upon ventricular fibrillation (VF). The RF-induced isolation of selected zones would make it possible to determine whether these zones are essential for existence of the arrhythmia.

Methods: In 31 Langendorff-perfused rabbit hearts, the characteristics and inducibility of VF were analyzed before and after the induction of RF lesions comprising: (1) the posterior zone of the septum and of the walls of both ventricles (n = 10); (2) the anterior zone of the septum and of the walls of both ventricles (n = 11); and (3) the midseptal zone (n = 10).

Nativelike structure in designed four alpha-helix bundles driven by buried polar interactions.

We show that a single internal polar interaction per helix is sufficient to engender structural specificity in that helix in helical bundle proteins. Furthermore, we use histidine-binding cofactors of different shapes which bind directly into the core, demonstrating that this structural specificity is not the result of a prescribed complimentary, "knobs in holes" core packing. We show that we can switch structural specificity of individual helices on and off by ligating cofactors, singly and in pairs, which bind either one or two histidine ligands.

Hydrogen-bonding conformations of tyrosine B10 tailor the hemeprotein reactivity of ferryl species.

Ferryl compounds [Fe(IV)=O] in living organisms play an essential role in the radical catalytic cycle and degradation processes of hemeproteins. We studied the reactions between H2O2 and hemoglobin II (HbII) (GlnE7, TyrB10, PheCD1, PheE11), recombinant hemoglobin I (HbI) (GlnE7, PheB10, PheCD1, PheE11), and the HbI PheB10Tyr mutant of L. pectinata.

Potential role of heme oxygenase-1 in the progression of rat adjuvant arthritis.

Rat adjuvant arthritis is an experimental model widely used to evaluate etiopathogenetic mechanisms in chronic inflammation. We have examined the participation of heme oxygenase-1 (HO-1) in this experimental arthritis. In this study, an increased nitric oxide (NO) production in the paw preceded the upregulation of HO-1, whereas selective inhibition of inducible NO synthase (iNOS) after the onset of arthritis decreased HO-1 expression, suggesting that the induction of this enzyme may depend on NO produced by iNOS.

Evidence for nonhydrogen bonded compound II in cyclic reaction of hemoglobin I from Lucina pectinata with hydrogen peroxide.

Studies that elucidate the behavior of the hemoglobins (Hbs) and myoglobins upon reaction with hydrogen peroxide are essential to the development of oxygen carrier substitutes. Stopped-flow kinetics and resonance Raman data show that the reaction between hydrogen peroxide and oxygenated and deoxygenated ferric Hb I (oxy- and deoxy-HbI) from Lucina pectinata produce compound I and compound II ferryl species. The rate constants ratio (k23/k41) between the formation of compound II from compound I (k23) and the oxidation of the ferrous HbI (k41, i.