The specific binding of 3H-labeled gamma-aminobutyric acid ([3H]GABA) to synaptic plasma membranes from rat brains was inhibited by various quinolonecarboxylic derivatives (quinolones), and these inhibitions were concentration dependent. [3H]muscimol GABAA sites also inhibited. These inhibitory potencies differed widely among the quinolones examined. Dixon plots showed that a newly developed difluorinated quinolone, NY-198 [1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-...

The characteristics of the transport cefixime, a new p.o. cephalosporin, antibiotic, were studied by using brush-border membrane vesicles from rat small intestine. initial rate uptake cefixime was not affected presence an inward gradient either Na+ or other monovalent cations. With intravesicular pHi 7.5, optimal occurred at extravesicular pHo 5.0, with about 6-fold acceleration compared that in absence proton (pHi = 7.5). A protonophore, carbonyl-cyanide-4-trifluoromethoxy-phenylhydrazone,...

The transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors through the blood-brain barrier was studied in vitro by using primary cultures bovine brain capillary endothelial cells (BCEC). uptake HMG-CoA with lactone form, [14C]lovastatin and [14C]simvastatin, slightly decreased to 65% control (37 degrees C) at low temperature (4 not affected pretreatment BCEC metabolic (2,4-dinitrophenol rotenone). [14C]Simvastatin acid (the ring-opened form) taken up a...

The kinetics and mechanism of the transport monocarboxylic acids (MCAs) were studied by using primary cultured bovine brain capillary endothelial cells. Concentration-dependent uptake acetic acid was observed, kinetic parameters estimated as follows: Michaelis constant, Kt, 3.41 +/- 1.87 mM, maximum rate, Jmax, 144.7 55.7 nmol/mg protein/min nonsaturable first-order rate Kd, 6.66 1.98 microliters/mg protein/min. At medium pH below 7.0, [3H]acetic increased markedly with decreasing pH,...

Nerve cell death accounts for various neurodegenerative disorders, in which altered immunity to the integrated central nervous system (CNS) might have destructive consequences. This undesirable immune response often affects progressive diseases such as Alzheimer's disease, Parkinson's schizophrenia and/or amyotrophic lateral sclerosis (ALS). It has been shown that commensal gut microbiota could influence brain several machineries of function. In other words, disorders may be connected...

Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder of fatty acid oxidation caused by defective cellular transport. The disease characterized metabolic derangement simulating Reye's syndrome, hypoglcaemia, progressive cardiomyopathy and skeletal myopathy. Recently, it was shown that SCD mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5). We report two novel mutations, W283R V446F, which are both missense affected infant. In vitro expression...

The blood-brain barrier (BBB) permeability of mepyramine was measured by the carotid injection technique to elucidate transport mechanism an H1-antagonist in central nervous system. Mepyramine found enter brain saturable and carrier-mediated transport. vivo kinetic parameters were estimated as follows: maximum uptake rate (Jmax) 7.12 +/- 1.37 mumol/min/g brain, Michaelis constant (Kt) 4.40 2.00 mM, nonsaturable first order (Kd) 0.28 0.02 ml/min/g brain. not inhibited either nutrients or...

Comparative physiological pharmacokinetic analysis has been carried out to elucidate the different tissue distribution characteristics among eight pyridonecarboxylic acids including newly developed NY-198. The urinary and fecal recoveries of NY-198 were 76.3 +/- 1.3% 21.0 0.1% dose (mean SE, N = 3), respectively, after iv administration [14C]NY-198 as a 20 mg/kg dose. Model-independent moment serum concentration-time profile gave volume at steady state per body weight (Vdss/BW) 1150 ml/kg....

The binding and internalization of a novel adrenocorticotropic hormone (ACTH) analog having potent neuromodulating effect, ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), by isolated bovine brain capillaries, were examined. Metabolism [5-125I-His]ebiratide occurred during 30-min incubation with capillaries at 37 degrees C. In the presence 20 mM EDTA, added to inhibit this metabolism, medium, after 30 min incubation, contained 82.3 +/- 0.5% unchanged ebiratide. total acid-resistant...

The transport mechanisms of beta-lactam antibiotics in the rat kidney and liver were studied with an vivo tissue-sampling single-injection technique using [3H]benzylpenicillin [( 3H]PCG) as a substrate. Concentration-dependent uptake [3H]PCG was observed kidney, kinetic parameters estimated follows: maximum rate (Jmax) 6.88 mumol/min/g MIchaelis constant (Kt) 1.39 mM nonsaturable first-order (kd) 0.414 ml/min/g kidney. inhibited by organic anions but not cations. Several also reduced...

Excess L-tryptophan (L-Trp) in the diet decreases fetal body weight. However, relationship between L-Trp concentration and its effects on maternal, placental, growth are not well-understood. We investigated of excess intake growth. Female mice were fed a 20% casein (control diet) or control plus 2% 5% during gestation. Pup weights did differ (L-Trp intake: 0.04 g/kg weight (BW)/day) groups 3.3 BW/day), but significantly lower group 7.0 BW/day) than groups. These results show that less BW/day...

SLC19A3 deficiency, also called thiamine metabolism dysfunction syndrome-2 (THMD2; OMIM 607483), is an autosomal recessive neurodegenerative disorder caused by mutations in SLC19A3, the gene encoding transporter 2. To investigate molecular mechanisms of neurodegeneration deficiency and whether administration high-dose prevents neurodegeneration, we generated homozygous Slc19a3 E314Q knock-in (KI) mice harboring mutation corresponding to human E320Q, which associated with severe form THMD2....

Staphylococcal enterotoxin A (SEA) is a toxin protein, and the most common cause of staphylococcal food poisoning. Polyphenols, such as catechins, are known to interact with proteins. In this study, we investigated binding catechins SEA using SPR (Biacore), Fourier transform infrared spectroscopy (FT-IR), isothermal titration calorimetry (ITC), protein-ligand docking. We found that (−)-epigallocatechin gallate (EGCG) could strongly bind SEA. According thermodynamic parameters, negative ΔG...

Excessive reactive oxygen species (ROS) may cause oxidative stress which is involved in aging and the pathogenesis of various human diseases. Whereas unregulated levels ROS be harmful, regulated basal level are even necessary to support cellular functions as a second messenger for homeostasis under physiological conditions. Therefore, redox medicine could develop new therapeutic concept health-benefits. Here, we introduce involvement on crossroads stemness, senescence, carcinogenesis stem...