• MeSH
• Bone Marrow Cells radiation effects   MeSH
• Rats MeSH
• Oxygen MeSH
• Radiation Effects MeSH
• Cell Survival MeSH
• Check Tag
• Rats MeSH

• MeSH
• Wound Healing * MeSH
• Humans MeSH
• Platelet-Rich Plasma MeSH
• Prospective Studies MeSH
• Plasma Skin Regeneration * MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Meeting Abstract MeSH

There are numerous studies supporting the contribution of oxidative stress to the pathogenesis of epilepsy. Prolonged oxidative stress is associated with the overexpression of ATP-binding cassette transporters, which results in antiepileptic drugs resistance. During our studies, three 1,2,4-triazole-3-thione derivatives were evaluated for the antioxidant activity and anticonvulsant effect in the 6 Hz model of pharmacoresistant epilepsy. The investigated compounds exhibited 2-3 times more potent anticonvulsant activity than valproic acid in 6 Hz test in mice, which is well-established preclinical model of pharmacoresistant epilepsy. The antioxidant/ROS scavenging activity was confirmed in both single-electron transfer-based methods (DPPH and CUPRAC) and during flow cytometric analysis of total ROS activity in U-87 MG cells. Based on the enzymatic studies on human carbonic anhydrases (CAs), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), one can assume that the herein investigated drug candidates will not impair the cognitive processes mediated by CAs and will have minimal off-target cholinergic effects.

• MeSH
• Acetylcholinesterase metabolism   MeSH
• Anticonvulsants chemical synthesis   chemistry   pharmacology   MeSH
• Antioxidants chemical synthesis   chemistry   pharmacology   MeSH
• Biphenyl Compounds antagonists & inhibitors   MeSH
• Butyrylcholinesterase metabolism   MeSH
• Cholinesterase Inhibitors chemical synthesis   chemistry   pharmacology   MeSH
• Epilepsy drug therapy   metabolism   MeSH
• Carbonic Anhydrase Inhibitors chemical synthesis   chemistry   pharmacology   MeSH
• Carbonic Anhydrases metabolism   MeSH
• Humans MeSH
• Models, Molecular MeSH
• Molecular Structure MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Oxidative Stress drug effects   MeSH
• Picrates antagonists & inhibitors   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Triazoles chemical synthesis   chemistry   pharmacology   MeSH
• Cell Survival drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The Escherichia coli protein WrbA, an FMN-dependent NAD(P)H:quinone oxidoreductase, was crystallized under new conditions in the presence of FAD or the native cofactor FMN. Slow-growing deep yellow crystals formed with FAD display the tetragonal bipyramidal shape typical for WrbA and diffract to 1.2 Å resolution, the highest yet reported. Faster-growing deep yellow crystals formed with FMN display an atypical shape, but diffract to only ∼1.6 Å resolution and are not analysed further here. The 1.2 Å resolution structure detailed here revealed only FMN in the active site and no electron density that can accommodate the missing parts of FAD. The very high resolution supports the modelling of the FMN isoalloxazine with a small but distinct propeller twist, apparently the first experimental observation of this predicted conformation, which appears to be enforced by the protein through a network of hydrogen bonds. Comparison of the electron density of the twisted isoalloxazine ring with the results of QM/MM simulations is compatible with the oxidized redox state. The very high resolution also supports the unique refinement of Met10 as the sulfoxide, confirmed by mass spectrometry. Bond lengths, intramolecular distances, and the pattern of hydrogen-bond donors and acceptors suggest the cofactor may interact with Met10. Slow incorporation of FMN, which is present as a trace contaminant in stocks of FAD, into growing crystals may be responsible for the near-atomic resolution, but a direct effect of the conformation of FMN and/or Met10 sulfoxide cannot be ruled out.

• MeSH
• X-Ray Diffraction MeSH
• Flavin-Adenine Dinucleotide chemistry   metabolism   MeSH
• Flavin Mononucleotide chemistry   metabolism   MeSH
• Crystallization MeSH
• Crystallography, X-Ray MeSH
• NAD(P)H Dehydrogenase (Quinone) chemistry   metabolism   MeSH
• Oxidation-Reduction MeSH
• Escherichia coli Proteins chemistry   metabolism   MeSH
• Repressor Proteins chemistry   metabolism   MeSH
• Protein Binding MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

In order to learn more about the molecular basis for the inhibition of DNA replication produced by antitumor platinum drugs, we investigated DNA polymerization using DNA templates site-specifically modified with the 1,2-GG intrastrand cross-link of dinuclear bifunctional [{trans-PtCl(NH(3))(2)}(2){l-spermidine-N1,N8}](3+)(BBR3571) or conventional mononuclear cisplatin. These cross-links which have the same nature, but differ in the size and character of the conformational alteration induced in double-helical DNA, were analyzed for bypass ability with reverse transcriptase of human immunodeficiency virus type 1 and Klenow fragment of DNA polymerase I deficient in exonuclease activity. We found that the 1,2-GG intrastrand CL of BBR3571 inhibited DNA translesion synthesis markedly more than the same adduct of cisplatin. This result was explained by a larger size of the cross-link of BBR3571 and by a flexibility induced in DNA by this cross-link which can make the productive binding of this adduct at the polymerase site more difficult.

• MeSH
• Cisplatin chemistry   MeSH
• DNA chemistry   MeSH
• Financing, Organized MeSH
• Nucleic Acid Conformation MeSH
• Oligonucleotides chemistry   MeSH
• Organoplatinum Compounds chemistry   MeSH
• DNA Damage MeSH
• Antineoplastic Agents chemistry   MeSH
• Cross-Linking Reagents MeSH
• Publication type
• Comparative Study MeSH

Besides its classical function as an orchestrator of calcium and phosphorus homeostasis, vitamin D also affects insulin secretion and tissue efficiency. A number of studies have consistently reported the inverse relationship between vitamin D deficiency and type 2 diabetes. Activation of certain metabolic pathways and down-stream transcription factors may protect from glucolipotoxicity and their targeted activation -e.g. by vitamin D - might explain the detrimental role of vitamin D deficiency in diabetes. The aim of the study was to quantify gene and protein expression of selected enzymes involved in the protection from glucolipotoxicity, specifically glyoxalase 1 (GLO1), and other enzymes with antioxidant activity - hemoxygenase (HMOX), thiamin pyrophosphokinase (TPK1) and transketolase (TKT), under normo- and hyperglycemic conditions and upon addition of vitamin D in peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The results of our study indicate that the active form of vitamin D regulates gene expression of enzymes opposing the harmful effect of glucolipotoxicity whose activities appear to be suppressed by hyperglycemia. However, we were unable to confirm this effect on protein expression. While we cannot speculate on the effect of vitamin D on diabetes itself our results support its role in the protection against existing glucolipotoxicity therefore possibly translating into the prevention of development of diabetic complications.

• MeSH
• Human Umbilical Vein Endothelial Cells drug effects   enzymology   MeSH
• Homeostasis drug effects   MeSH
• Insulin secretion   MeSH
• Cells, Cultured MeSH
• Lactoylglutathione Lyase genetics   metabolism   MeSH
• Leukocytes, Mononuclear drug effects   enzymology   MeSH
• Humans MeSH
• Gene Expression Regulation MeSH
• Thiamin Pyrophosphokinase genetics   metabolism   MeSH
• Transketolase genetics   metabolism   MeSH
• Vitamin D pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Antipsychotic Agents pharmacology   chemistry   MeSH
• Humans MeSH
• Piperazines pharmacology   chemistry   MeSH
• Check Tag
• Humans MeSH

Chemická látka 1,4-butandiol je řazena mezi průmyslová rozpouštědla, využívá se též jako základ pro výrobu plastických hmot, elastomerů a fólií. Ve 20. století byla tato substance v České republice často zneužívána pro své prosexuální a relaxační účinky jako rekreační droga, jako anabolikum a prostředek ke zvýšení tělesné výkonnosti. Článek prezentuje kazuistiku, která popisuje dlouhodobé pravidelné zneužívání této látky a shrnuje její vliv na lidský organismus.

The chemical substance 1,4 butanediol belongs among industrial solvents. It is also used as a base in production of plastic and elastomer substances and films. The substance was used for its prosexual and calming effect as a "recreational drug" and also as an anabolic agent and a substance to enhance physical performance. The case-report describes long-term and regular use of this substance and its impact to a human organism.

• Keywords
• tekutá extáze, tekuté mýdlo, GHB,
• MeSH
• Substance Withdrawal Syndrome MeSH
• Butylene Glycols * pharmacokinetics   poisoning   adverse effects   MeSH
• Delirium chemically induced   MeSH
• Hydroxybutyrates poisoning   adverse effects   MeSH
• Cognitive Dysfunction chemically induced   MeSH
• Middle Aged MeSH
• Humans MeSH
• Designer Drugs MeSH
• Sodium Oxybate analysis   metabolism   MeSH
• Sleep Wake Disorders chemically induced   MeSH
• Substance-Related Disorders * diagnosis   therapy   MeSH
• Dietary Supplements MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Antidotes pharmacology   MeSH
• Animal Experimentation MeSH
• GABA Antagonists MeSH
• GABA Agents administration & dosage   poisoning   MeSH
• Humans MeSH
• Morpholines MeSH
• Mice MeSH
• Drug Overdose mortality   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH

• MeSH
• Amines chemical synthesis   MeSH
• Anesthetics, Local chemical synthesis   MeSH
• Anticonvulsants chemical synthesis   MeSH
• Hypotonic Solutions chemical synthesis   MeSH
• Parasympatholytics chemical synthesis   MeSH