Pharmacology of metformin - An update.

Despite being a successful diabetes type 2 drug for more than a half-century in Europe, the mode of action of metformin is still debated. It is the purpose of this review to inform the reader about most recent findings for metformin with respect to its antidiabetic activity as well as proposed benefits beyond glucose control in humans. Clinical evidence now suggests that most of metformin benefits originate from its actions in the gut, involving hormone signaling by glucagon-like peptide 1 and peptide YY.

Metformin and Aging: A Review.

Metformin is sometimes proposed to be an "anti-aging" drug, based on preclinical experiments with lower-order organisms and numerous retrospective data on beneficial health outcomes for type 2 diabetics. Large prospective, placebo-controlled trials are planned, in pilot stage or running, to find a new use (or indication) for an aging population. As one of the metformin trials has "frailty" as its endpoint, similar to a trial with a plant-derived senolytic, the latter class of novel anti-aging drugs is briefly discussed.

Torpor: The Rise and Fall of 3-Monoiodothyronamine from Brain to Gut-From Gut to Brain?

(T1AM), first isolated from rat brain, is reported to be an endogenous, rapidly acting metabolite of thyroxine. One of its numerous effects is the induction of a "torpor-like" state in experimental animals. A critical analysis of T1AM, to serve as an endogenous cryogen, is given.

On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.

Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity.

Largely reduced grid densities in a vibrational self-consistent field treatment do not significantly impact the resultingwavenumbers.

Especially for larger molecules relevant to life sciences, vibrational self-consistent field (VSCF) calculations can become unmanageably demanding even when only first and second order potential coupling terms are considered. This paper investigates to what extent the grid density of the VSCF's underlying potential energy surface can be reduced without sacrificing accuracy of the resulting wavenumbers. Including single-mode and pair contributions, a reduction to eight points per mode did not introduce a significant deviation but improved the computational efficiency by a factor of four.

Structure and dynamics of chromatographically relevant Fe(III)-chelates.

Immobilized metal ion affinity chromatography (IMAC) is an important chromatographic technique for biomolecules. In order to get a detailed understanding of the hydration of immobilized Fe(III), complexes of Fe(III) with methyl substituted iminodiacetate ([Fe(MSIDA)(H2O)3](+)) as well as with methyl substituted nitrilotriacetate ([Fe(MSNTA)(H2O)2]) were simulated in aqueous solutions with the quantum mechanical charge field molecular dynamics (QMCF MD) approach. The simulations were carried out at the Hartree-Fock (HF) level of theory, since cluster calculations at the HF, MP2, and B3LYP levels of theory showed that this method results in a good compromise between computational effort and accuracy.

A dissociative quantum mechanical/molecular mechanical molecular dynamics simulation and infrared experiments reveal characteristics of the strongly hydrolytic arsenic(III).

This work presents a hybrid ab initio quantum mechanical/molecular mechanical simulation at the RI-MP2 level of theory investigating the hydrolysis process of arsenic(III), ultimately leading to arsenous acid (H3AsO3). A newly implemented dissociative water model has been applied to treat the interactions in the classical region, which is capable of describing non-neutral water species such as hydroxide and oxonium ions. Three stages of hydrolysis have been observed during the simulation and besides profound dynamical considerations, detailed insights into structural changes and atomic partial charge shifts are presented.

The impact of highly correlated potential energy surfaces on the anharmonically corrected IR spectrum of acetonitrile.

This paper discusses the quality and feasibility of highly correlated ab initio techniques in a vibrational self-consistent field (VSCF) approach using acetonitrile as a model system. The topical renormalized coupled-cluster technique exploiting the similarity-transformed Hamiltonian's left eigenstates (i.e.

Reproducible quantification of ethanol in gasoline via a customized mobile near-infrared spectrometer.

This work describes the modification of an InGaAs diode array detector equipped miniaturized near-infrared (NIR) spectrometer enabling the reliable quantification of ethanol blended gasoline. A transflectance measurement cell is presented, utilizing a thermoelectric cooling (TEC) appliance ensuring thermostatic measurement conditions and a gold-coated spherical mirror as a reflector superior to conventional Spectralon(®). In total, four measurement modes (Spectralon(®) reflector, gold reflector and either reflectors with employed TEC) are discussed, enabling a straightforward comparison of the results.

Erbium(III) in aqueous solution: an ab initio molecular dynamics study.

Structural and dynamical properties of the erbium(III) ion in water have been obtained by means of ab initio quantum mechanical charge field molecular dynamics (QMCF-MD) simulations for the ground state and an excited state. The quality of the simulations has been monitored by recording UV/vis and Raman spectra of dilute solutions of ErCl3 and Er(NO3)3 in water and by comparison with EXAFS data from literature. Slight deviations between these data can be mainly attributed to relativistic effects, which are not sufficiently considered by the methodological framework.

Combined Ab Initio Computational and Infrared Spectroscopic Study of the cis- and trans-Bis(glycinato)copper(II) Complexes in Aqueous Environment.

The cis- and trans-bis(glycinato)copper(II) complexes in aqueous solution have been investigated by means of a combined theoretical and experimental approach. The conducted quantum mechanical charge field molecular dynamics (QMCF-MD) studies, being the first quantum mechanical simulations of organometallic complexes by this method, yielded accurate structural details of the investigated isomers as well as novel dynamic data, which has successfully been confirmed and extended by subsequent mid-infrared measurements. The spectroscopic results, critically assessed by adjacent multivariate data analysis, indicate an isomeric stability at ambient conditions, vanishing at elevated temperatures.

Computational study of the cerium(III) ion in aqueous environment.

This work comprises the first quantum chemical simulation study of the Ce ion in aqueous environment. The structural and dynamical properties have been investigated by means of the quantum mechanical charge field (QMCF) molecular dynamics (MD) approach and the results, where applicable, have been compared to experimental data. Besides conventional analytical tools, angular radial distribution functions have been employed to gain deeper insight into the structure of the hydrate.

Hydration of trivalent lanthanum revisited - An QMCF-MD approach.

The previously investigated La-hydrate has been re-evaluated by means of the quantum mechanical charge field (QMCF) molecular dynamics (MD) approach. Improved description of the hydration characteristics has been realised by including the full second hydration shell into the quantum mechanically treated region and by introducing the influence of the surrounding bulk via an electrostatic embedding technique. Analytical tools such as the ligand angular radial distribution analysis have been employed to gain deeper insight into the structural features of the hydrate.

A QMCF-MD investigation of the structure and dynamics of Ce4+ in aqueous solution.

A quantum-mechanical charge-field molecular dynamics simulation has been performed for a tetravalent Ce ion in aqueous solution. In this framework, the complete first and second hydration spheres are treated by ab initio quantum mechanics supplemented by an electrostatic embedding technique, making the construction of non-Coulombic solute-solvent potentials unnecessary. During the 10 ps of simulation time, the structural aspects of the solution were analyzed by various methods.