Genetic variants of the organic cation transporter 2 (protein, OCT2; gene, SLC22A2) were evaluated for their contribution to the variations in the pharmacokinetics of metformin, especially to its ...renal elimination. Genetic variants of SLC22A2 (c.596C>T, c.602C>T, and c.808G>T) showed significant differences in metformin pharmacokinetics when compared with the reference genotype, with higher peak plasma concentration (Cmax) and area under the curve (AUC) and lower renal clearance (Clrenal), thereby suggesting that a decrease in transport function associated with the SLC22A2 variants results in reduced Clrenal of metformin and consequently leads to increased plasma concentrations.
Clinical Pharmacology & Therapeutics (2008); 84, 5, 559–562 doi:10.1038/clpt.2008.61
Highlights • Alteration of mitochondrial proteins in the substantia nigra (SN) of db / db and high-fat diet mice. • Parkin is significantly decreased in the SN of diabetic models. • Insulin ...resistance disrupts Parkin–PARIS–PGC-1α pathway and increases the vulnerability to MPP+. • Metformin restores the level of parkin, PARIS, and PGC-1α. • Mild DA degeneration in chronic HFD is protected by metformin.
Strengthening behavior of composite containing discontinuous reinforcement is strongly related with load transfer at the reinforcement–matrix interface. We selected multi-walled carbon nanotube ...(MWCNT) and few-layer graphene (FLG) as a reinforcing agent. By varying a volume fraction of the reinforcement, aluminum (Al) matrix composites were produced by a powder metallurgy method. Uniform dispersion and uniaxial alignment of MWCNT and FLG in the Al matrix are evidenced by high-resolution transmission electron microscope analysis. Although the reinforcements have a similar molecular structure, FLG has a 12.8 times larger specific surface area per volume more than MWCNT due to geometric difference. Therefore an increment of a yield stress versus a reinforcement volume fraction for FLG shows 3.5 times higher than that of MWCNT Consequently, for both reinforcements, the composite strength proportionally increases with the specific surface area on the composite, and the composites containing 0.7vol% FLG exhibit 440MPa of tensile strength.
Biomedical applications of nisin Shin, J.M.; Gwak, J.W.; Kamarajan, P. ...
Journal of applied microbiology,
June 2016, Letnik:
120, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Summary
Nisin is a bacteriocin produced by a group of Gram‐positive bacteria that belongs to Lactococcus and Streptococcus species. Nisin is classified as a Type A (I) lantibiotic that is synthesized ...from mRNA and the translated peptide contains several unusual amino acids due to post‐translational modifications. Over the past few decades, nisin has been used widely as a food biopreservative. Since then, many natural and genetically modified variants of nisin have been identified and studied for their unique antimicrobial properties. Nisin is FDA approved and generally regarded as a safe peptide with recognized potential for clinical use. Over the past two decades the application of nisin has been extended to biomedical fields. Studies have reported that nisin can prevent the growth of drug‐resistant bacterial strains, such as methicillin‐resistant Staphylococcus aureus, Streptococcus pneumoniae, Enterococci and Clostridium difficile. Nisin has now been shown to have antimicrobial activity against both Gram‐positive and Gram‐negative disease‐associated pathogens. Nisin has been reported to have anti‐biofilm properties and can work synergistically in combination with conventional therapeutic drugs. In addition, like host‐defence peptides, nisin may activate the adaptive immune response and have an immunomodulatory role. Increasing evidence indicates that nisin can influence the growth of tumours and exhibit selective cytotoxicity towards cancer cells. Collectively, the application of nisin has advanced beyond its role as a food biopreservative. Thus, this review will describe and compare studies on nisin and provide insight into its future biomedical applications.
Abstract In 2016, MLOS (myasthenia gravis Lambert–Eaton overlap syndrome) was coined to represent an entity of overlap syndrome of myasthenia gravis and Lambert–Eaton myasthenic syndrome. Fifty‐five ...MLOS patients have been identified. Modification of the diagnostic criteria for MG by adding MuSK positive antibody testing is recommended. Two MuSK positive MLOS patients were identified by the new diagnostic criteria.
There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. Although repurposed drugs with favorable safety profiles could have ...significant benefit, widely available prevention or treatment options for COVID-19 have yet to be identified. Efforts to identify approved drugs with in vitro activity against SARS-CoV-2 resulted in identification of antiviral sigma-1 receptor ligands, including antihistamines in the histamine-1 receptor binding class. We identified antihistamine candidates for repurposing by mining electronic health records of usage in population of more than 219,000 subjects tested for SARS-CoV-2. Usage of diphenhydramine, hydroxyzine and azelastine was associated with reduced incidence of SARS-CoV-2 positivity in subjects greater than age 61. We found diphenhydramine, hydroxyzine and azelastine to exhibit direct antiviral activity against SARS-CoV-2 in vitro. Although mechanisms by which specific antihistamines exert antiviral effects is not clear, hydroxyzine, and possibly azelastine, bind Angiotensin Converting Enzyme-2 (ACE2) and the sigma-1 receptor as off-targets. Clinical studies are needed to measure the effectiveness of diphenhydramine, hydroxyzine and azelastine for disease prevention, for early intervention, or as adjuvant therapy for severe COVID-19.
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