Thermodynamic properties of the binding of alpha-, omega-amino acids to the isolated kringle 4 region of human plasminogen as determined by high sensitivity titration calorimetry.
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The binding of alpha-, omega-amino acids, which are important effectors of human plasminogen activation, to the isolated kringle 4 (K4) peptide region of this protein has been investigated by high sensitivity titration calorimetry. The titration curve of the heat changes accompanying binding of the widely employed ligand, epsilon-aminocaproic acid (EACA), to K4 were deconvoluted to yield the following binding characteristics: n = 0.87 +/- 0.08 mol/mol; Ka = 3.82 +/- 0.37 x 10(4) M-1; delta H = -4.50 +/- 0.22 kcal/mol; delta S = 6.01 +/- 0.7 entropy units; and delta G = 6.29 +/- 0.06 kcal/mol. Here, both delta H and delta S provide the driving force of the interaction, with both hydrogen bonds and hydrophobic interactions, the latter which may result from an induced conformational change in K4 upon ligand binding, as well as possible alterations in peptide-bound water structure, providing the stabilizing forces for complex formation. The thermodynamic binding parameters were not greatly influenced by pH between the values of 5.5 and 8.2, suggesting that titratable groups on K4 in this pH region did not influence the binding. Investigations of the binding properties of structural analogues of EACA to K4 demonstrated that definable steric requirements existed for a maximal interaction, with spacing between the functional groups on EACA, as well as a hydrophobic region of this molecule, being important. This rapid and reliable method for measuring all thermodynamic parameters of formation of this complex at a given temperature can now be employed to investigate this important interaction with a wide variety of kringles and modified kringles to provide a more complete understanding of the necessary factors for this binding to occur. (+info)
Effect of gamma aminobutyric acid on the carbon dioxide rebreathing response of normal subjects: a study using vigabatrin.
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Animal studies suggest that gamma aminobutyric acid (GABA) may be an important neurotransmitter in the control of respiration. Vigabatrin, a new drug for the treatment of epilepsy, is thought to exert its effect by increasing GABA concentrations in the brain. To assess the effect of increased GABA concentrations in the brain on human respiration we measured the ventilatory response to carbon dioxide in seven normal subjects after they had taken vigabatrin or placebo for three days in a double blind crossover study. There was no change in either the slope or the intercept of the curve of the ventilatory response to carbon dioxide after vigabatrin by comparison with placebo. This study suggests that GABA does not have an important role in the control of respiration in normal individuals. (+info)
Conditions for the formation of dilysyl-dipyrrolones A and B, and novel yellow dipyrrolone derivatives formed from xylose and amino acids in the presence of lysine.
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Foods derived from plants contain pentose in addition to hexose. It is well known that pentose contributes more to browning by the Maillard reaction than hexose does. We have recently found novel yellow compounds formed from xylose and lysine under weakly acidic conditions, named dilysyldipyrrolones (dilysyl-DPLs) A and B. We indicate in this study that dilysyl-DPLs were specifically formed under weakly acidic conditions from pentose, but not hexose. Moreover, we found novel DPL derivatives which were formed from xylose and such amino acids as alanine, arginine, aspartic acid, glutamic acid, isoleucine, leucine, phenylalanine, serine, and valine in the presence of lysine. (+info)
Increased arginase activity contributes to airway remodelling in chronic allergic asthma.
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Pharmacokinetics of the individual enantiomers of vigabatrin (gamma-vinyl GABA) in epileptic children.
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1. The pharmacokinetics of the enantiomers of vigabatrin were investigated after oral administration of a single 50 mg kg-1 dose of the racemate to two groups of six epileptic children (I: 5 months-2 years, II: 4-14 years). 2. The mean (+/- s.d.) values of maximum plasma concentration and area under the plasma concentration-time curve of the R(-) enantiomer were significantly higher than those of S(+) vigabatrin in both groups: R(-) Cmax: 21 +/- 6.6 (I)-41.3 +/- 13.9 (II) vs S(+) Cmax: 13.9 +/- 4.5 (I)-23.8 +/- 12.2 (II) mg l-1; R(-) AUC: 106 +/- 28.5 (I)-147 +/- 34 (II) vs S(+) AUC: 90.9 +/- 27.9 (I)-117 +/- 26 (II) mg l-1 h. In group I, the half-life of the R(-) isomer was significantly shorter than that of the S(+) isomer; in group II, the half-lives were comparable. 3. For the R(-) enantiomer the area under the curve, and the elimination half-life increased linearly with age. 4. During chronic administration (50 mg kg-1 vigabatrin racemate twice a day for 4 days), the morning trough plasma drug concentrations did not increase. (+info)
Comparative analysis of antifibrinolytic medications in pediatric heart surgery.
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Evaluation of vigabatrin as an add-on drug in the management of severe epilepsy.
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The effects of the addition of Vigabatrin, a new anti-epileptic drug, to the therapy of 128 patients with severe medically refractory epilepsy is reported. Forty two (33%) of patients experienced side effects, which were predominantly neurotropic. In 28 (22%), the drug was withdrawn because of these side effects. The commonest side effects were drowsiness and behavioural change. The remaining 100 patients were followed for a mean of 30 weeks (range 12-75). Forty one of these patients showed a marked improvement in seizure frequency (a 50% or more reduction when compared with the pre-trial period), and nine (7%) were rendered seizure free. Apparent tolerance to the effects of the drug were noted in five patients. An exacerbation of seizures may occur if the drug is withdrawn too quickly. Vigabatrin appears to be a promising new anti-epileptic drug. (+info)