Determination of inherent dissolution performance of drug substances

The dissolution behavior of novel active pharmaceutical ingredients (API) is a crucial parameter in drug formulation since it frequently affects the drug release. Generally, a distinction is made between surface-reaction- and diffusion-controlled drug release. Therefore, dissolution studies such as the intrinsic dissolution test defined in the pharmacopeia have been performed for many years. In order to overcome the disadvantages of the common intrinsic dissolution test, a new experimental setup was developed within this study. Specifically, a flow channel was designed and tested for measuring the mass transfer from a flat, solid surface dissolving into a fluid flowing over the surface with well-defined flow conditions. A mathematical model was developed that distinguishes between surface-reaction- and diffusion-limited drug release based on experimental data. Three different drugs—benzocaine, theophylline and griseofulvin—were used to investigate the mass flux during dissolution due to surface reaction, diffusion and convection kinetics. This new technique shows potential to be a valuable tool for the identification of formulation strategies

Remote and reversible inhibition of neurons and circuits by small molecule induced potassium channel stabilization

Manipulating the function of neurons and circuits that translate electrical and chemical signals into behavior represents a major challenges in neuroscience. In addition to optogenetic methods using light-activatable channels, pharmacogenetic methods with ligand induced modulation of cell signaling and excitability have been developed. However, they are largely based on ectopic expression of exogenous or chimera proteins. Now, we describe the remote and reversible expression of a Kir2.1 type potassium channel using the chemogenetic technique of small molecule induced protein stabilization. Based on shield1-mediated shedding of a destabilizing domain fused to a protein of interest and inhibition of protein degradation, this principle has been adopted for biomedicine, but not in neuroscience so far. Here, we apply this chemogenetic approach in brain research for the first time in order to control a potassium channel in a remote and reversible manner. We could show that shield1-mediated ectopic Kir2.1 stabilization induces neuronal silencing in vitro and in vivo in the mouse brain. We also validated this novel pharmacogenetic method in different neurobehavioral paradigms. The DD-Kir2.1 may complement the existing portfolio of pharmaco- and optogenetic techniques for specific neuron manipulation, but it may also provide an example for future applications of this principle in neuroscience research

Exercise therapy in Type 2 diabetes

Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity

Voltammetric Detection of Damage to DNA by Arsenic Compounds at a DNA Biosensor

DNA biosensor can serve as a powerfull tool for simple in vitro tests of chemicaltoxicity. In this paper, damage to DNA attached to the surface of screen-printed carbonelectrode by arsenic compounds in solution is described. Using the Co(III) complex with1,10-phenanthroline, [Co(phen)3]3+ , as an electrochemical DNA marker and the Ru(II)complex with bipyridyne, [Ru(bipy)3]2+ , as a DNA oxidation catalyst, the portion of originaldsDNA which survives an incubation of the biosensor in the cleavage medium was evaluated.The model cleavage mixture was composed of an arsenic compound at 10-3 mol/Lconcentration corresponding to real contaminated water, 2x10-4 mol/L Fe(II) or Cu(II) ions asthe redox catalyst, and 1.5x10-2 mol/L hydrogen peroxide. DNA damage by arsenite,dimethylarsinic acid as the metabolic product of inorganic arsenic and widely used herbicide,as well as phenylarsonic acid and p-arsanilic acid as the representatives of feed additives wasfound in difference to arsenate

Voltammetric detection of damage to DNA by arsenic compounds at a DNA biosensor

Abstract: DNA biosensor can serve as a powerfull tool for simple in vitro tests of chemical toxicity. In this paper, damage to DNA attached to the surface of screen-printed carbon electrode by arsenic compounds in solution is described. Using the Co(III) complex with 1,10-phenanthroline, [Co(phen)3] 3+, as an electrochemical DNA marker and the Ru(II) complex with bipyridyne, [Ru(bipy)3] 2+, as a DNA oxidation catalyst, the portion of original dsDNA which survives an incubation of the biosensor in the cleavage medium was evaluated. The model cleavage mixture was composed of an arsenic compound at 10-3 mol/L concentration corresponding to real contaminated water, 2x10-4 mol/L Fe(II) or Cu(II) ions as the redox catalyst, and 1.5x10-2 mol/L hydrogen peroxide. DNA damage by arsenite, dimethylarsinic acid as the metabolic product of inorganic arsenic and widely used herbicide, as well as phenylarsonic acid and p-arsanilic acid as the representatives of feed additives was found in difference to arsenate

Detection of Antioxidative Activity of Plant Extracts at the DNA-Modified Screen-Printed Electrode

A simple procedure for the voltammetric detection of antioxidative activity of plant extracts based on the protection from DNA damage at the electrode surface is reported. A disposable electrochemical DNA biosensor fabricated as a carbon-based screen-printed electrode modified by a surface layer of the calf thymus double stranded (ds) DNA was used as a working electrode in combination with a silver/silver chloride reference electrode and a separate platinum auxiliary electrode. The [Co(phen)3]3+ ion served as the dsDNA redox marker and the [Fe(EDTA)]- complex with hydrogen peroxide under the electrochemical reduction of the iron atom were used as the DNA cleavage mixture. A remarkable antioxidative activity of phenolic antioxidants such as rosmarinic and caffeic acids as standards and the extracts of lemon balm, oregano, thyme and agrimony was found which is quite in agreement with an antiradical activity determined spectrophotometrically using 2,2’-diphenyl-1-picrylhydrazyl (DPPH) radical