Facile iterative synthesis of biphenyl dendrons with a functionalized focus.

An iterative procedure gives 1,3,5-phenyl-linked dendrons of up to the fourth generation and enables the formation of different generations of iridium(III) complex-cored dendrimers. The convergent synthesis uses N,N'-1,8-naphthyl-3,5-dibromophenylboronamide as the key building block. The iterative synthesis cycle involves deprotection of the boronamide-focused dendron to form a boronic acid and subsequent Suzuki coupling either with the N,N'-1,8-naphthyl-3,5-dibromophenylboronamide to give the next dendron generation or with an activated core to form a dendrimer.

Benefits of nifedipine GITS in stable coronary artery disease: Further analysis of the "ACTION" database.

Introduction: Retrospective analyses of specific subgroups of patients from the database of the ACTION study have evaluated the effectiveness of a nifedipine gastrointestinal therapeutic system (GITS) on clinical outcomes. These subgroups included those patients receiving: 1) full "optimal" therapy at baseline; 2) full "optimal" therapy at baseline but excluding renin angiotensin system (RAS)-blocking drugs; 3) treatment with nifedipine GITS who were not treated with RAS blockers versus those treated with RAS blockers but not nifedipine GITS.

Methods: Analyses were performed on an intention-to-treat basis.

Preferential benefits of nifedipine GITS in systolic hypertension and in combination with RAS blockade: further analysis of the 'ACTION' database in patients with angina.

A retrospective analysis of the database from A Coronary Disease Trial Investigating Outcome with Nifedipine (ACTION) evaluated the effectiveness of nifedipine gastrointestinal therapeutic system (GITS) (i) in combination with renin angiotensin system (RAS) blockers and (ii) in patients with isolated systolic hypertension (ISH). Analysed on an intention-to-treat basis, treatment groups were compared by the log-rank test without adjustment for covariates and hazard ratios with 95% CIs were obtained using Cox proportional hazards models. Of 7665 randomized patients, 1732 patients were receiving RAS blockade at baseline, the addition of nifedipine GITS significantly reduced any cardiovascular (CV) event (-20%; P<0.

Gaseous adsorption in melanins: hydrophilic biomacromolecules with high electrical conductivities.

The melanins are an important class of multifunctional biomacromolecules that possess a number of intriguing physical and chemical properties including electrical and photoconductivity. Unusually for a conducting organic material, eumelanin is hydrophilic and its electrical properties are strongly dependent on its hydration state. We have therefore measured adsorption isotherms for two polar adsorbates, water and ethanol, in the pressed powder pellets of synthetic eumelanin typically used in electrical studies.

Comparison of the efficacy of candesartan and losartan: a meta-analysis of trials in the treatment of hypertension.

Informed by the findings from prospective observational studies and randomized outcome trials, guidelines for the management of hypertension acknowledge that the benefit of treatment can be attributed largely to blood pressure (BP) reduction. Therefore, quantification of differential BP lowering of different agents within classes of anti-hypertensives is of practical importance. The objective of this analysis was to compare the efficacy of candesartan and losartan with respect to reduction in systolic and diastolic BP (SBP and DBP).

Solid-state dendrimer sensors: probing the diffusion of an explosive analogue using neutron reflectometry.

Determining how analytes are sequestered into thin films is important for solid-state sensors that detect the presence of the analyte by oxidative luminescence quenching. We show that thin (230 +/- 30 A) and thick (750 +/- 50 A) films of a first-generation dendrimer comprised of 2-ethylhexyloxy surface groups, biphenyl-based dendrons, and a 9,9,9',9'-tetra-n-propyl-2,2'-bifluorene core, can rapidly and reversibly detect p-nitrotoluene by oxidative luminescence quenching. For both the thin and thick films the photoluminescence (PL) is quenched by p-nitrotoluene by approximately 90% in 4 s, which is much faster than that reported for luminescent polymer films.

Potential concerns about generic substitution: bioequivalence versus therapeutic equivalence of different amlodipine salt forms.

Background And Scope: Whether generic drug products are truly therapeutically identical and interchangeable with their innovator counterparts is still a matter of debate. This review discusses the controversies related to the criteria for bioequivalence and therapeutic equivalence. These concerns are illustrated by using the calcium antagonist amlodipine besylate (innovator drug) versus amlodipine maleate (generic), indicated for the treatment of hypertension and angina pectoris, as an example.

Chemical and structural diversity in eumelanins: unexplored bio-optoelectronic materials.

Eumelanins, the characteristic black, insoluble, and heterogeneous biopolymers of human skin, hair, and eyes, have intrigued and challenged generations of chemists, physicists, and biologists because of their unique structural and optoelectronic properties. Recently, the methods of organic chemistry have been combined with advanced spectroscopic and imaging techniques, theoretical calculations, and methods of condensed-matter physics to gradually force these materials to reveal their secrets. Herein we review the latest advances in the field with a view to showing how the emerging knowledge is not only helping to explain eumelanin functionality, but may also be translated into effective strategies for exploiting their properties to create a new class of biologically inspired high-tech materials.

Clinical outcomes according to baseline blood pressure in patients with a low ejection fraction in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Program.

Objectives: This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (
Background: Hypotension is a predictor of poor prognosis in heart failure, yet many treatments shown to reduce morbidity and mortality lower blood pressure.

Laboratory simulation of volcano seismicity.

The physical processes generating seismicity within volcanic edifices are highly complex and not fully understood. We report results from a laboratory experiment in which basalt from Mount Etna volcano (Italy) was deformed and fractured. The experiment was monitored with an array of transducers around the sample to permit full-waveform capture, location, and analysis of microseismic events.

Seismogenic lavas and explosive eruption forecasting.

Volcanic dome-building episodes commonly exhibit acceleration in both effusive discharge rate and seismicity before explosive eruptions. This should enable the application of material failure forecasting methods to eruption forecasting. To date, such methods have been based exclusively on the seismicity of the country rock.

Synthesis and polymerization studies of organic-soluble eumelanins.

The isolation, structure determination and chemical characterization of eumelanins has been plagued by their very low solubility in organic solvents. To gain insights into the structure and reactivity of these unusual and important biologic macromolecules and to pave the way for their use in electronics, we have prepared soluble melanins via the synthesis of monomeric precursors containing lipophilic substituents. Two such monomers derived from 5,6-dihydroxyindole-2-carboxylic acid (DHICA) were prepared, namely the benzyl and octyl ester derivatives.

Solvochromic effects in model eumelanin compounds.

We have created an indolic compound which is ideally suited to the study of the relationship between structure and function in eumelanin formation. N-methyl-5-hydroxy-6-methoxyindole (MHMI) is stable in solid and liquid states, highly soluble in a variety of solvents and forms a dimer only through the 4-4' positions. The limited binding possibilities are due to functional groups strategically placed to inhibit chemical interactions through the 2 and 7 positions.

Effect of dimerization on vibrational spectra of eumelanin precursors.

We have synthesized a compound ideally suited to the study of structure-function relationships in eumelanin synthesis. N-methyl-5-hydroxy-6-methoxy-indole (MHMI) has key functional groups strategically placed on the indole framework to hinder binding in the 2, 5, 6 and 7 positions. Thus, the dimer bound exclusively in the 4-4' positions was isolated and characterized.

Time-resolved and steady-state fluorescence spectroscopy of eumelanin and indolic polymers.

Eumelanin plays a variety of important physiological roles in human skin. However, its structure and fundamental properties still remain poorly understood. Although the absorbance of eumelanin is broad and reveals little about its structure, a variety of techniques have revealed the presence of a disordered array of chromophores within the melanin compound.

Transition dipole strength of eumelanin.

We report the transition dipole strength of eumelanin (the principal human photoprotective pigment) in the ultraviolet and visible. We have used both theoretical (density functional) and experimental methods to show that eumelanin is not an unusually strong absorber amongst organic chromophores. This is somewhat surprising given its role as a photoprotectant, and suggests that the dark coloring in vivo (and in vitro) of the eumelanin pigment is a concentration effect.

A review of the evidence linking adult attachment theory and chronic pain: presenting a conceptual model.

It is now well established that pain is a multidimensional phenomenon, affected by a gamut of psychosocial and biological variables. According to diathesis-stress models of chronic pain, some individuals are more vulnerable to developing disability following acute pain because they possess particular psychosocial vulnerabilities which interact with physical pathology to impact negatively upon outcome. Attachment theory, a theory of social and personality development, has been proposed as a comprehensive developmental model of pain, implicating individual adult attachment pattern in the ontogenesis and maintenance of chronic pain.

Candesartan cilexetil--a review of effects on cardiovascular complications in hypertension and chronic heart failure.

Unlabelled: Therapeutic interventions that block the renin-angiotensin-aldosterone system (RAAS) have an important role in slowing the progression of cardiovascular risk actors to established cardiovascular diseases. In recent years, angiotensin receptor blockers (ARBs) have emerged as effective and well-tolerated alternatives to an angiotensin-converting enzyme inhibitor (ACEi) for RAAS blockade. The ARB candesartan was initially established as an effective once-daily antihypertensive treatment, providing 24-h blood pressure (BP) control with a trough:peak ratio close to 100%.

Towards structure-property-function relationships for eumelanin.

We discuss recent progress towards the establishment of important structure-property-function relationships in eumelanins-key functional bio-macromolecular systems responsible for photo-protection and immune response in humans, and implicated in the development of melanoma skin cancer. We focus on the link between eumelanin's secondary structure and optical properties such as broad band UV-visible absorption and strong non-radiative relaxation; both key features of the photo-protective function. We emphasise the insights gained through a holistic approach combining optical spectroscopy with first principles quantum chemical calculations, and advance the hypothesis that the robust functionality characteristic of eumelanin is related to extreme chemical and structural disorder at the secondary level.

The physical and chemical properties of eumelanin.

In this article, we review the current state of knowledge concerning the physical and chemical properties of the eumelanin pigment. We examine properties related to its photoprotective functionality, and draw the crucial link between fundamental molecular structure and observable macroscopic behaviour. Where necessary, we also briefly review certain aspects of the pheomelanin literature to draw relevant comparison.