On uniform regularity and strong regularity.

We investigate uniform versions of (metric) regularity and strong (metric) regularity on compact subsets of Banach spaces, in particular, along continuous paths. These two properties turn out to play a key role in analyzing path-following schemes for tracking a solution trajectory of a parametric generalized equation or, more generally, of a differential generalized equation (DGE). The latter model allows us to describe in a unified way several problems in control and optimization such as differential variational inequalities and control systems with state constraints. We study two inexact path-following methods for DGEs having the order of the grid error O ( h ) and O ( h 2 ) , respectively. We provide numerical experiments, comparing the schemes derived, for simple problems arising in physics. Finally, we study metric regularity of mappings associated with a particular case of the DGE arising in control theory. We establish the relationship between the pointwise version of this property and its counterpart in function spaces.

Photocatalytic esterification under Mitsunobu reaction conditions mediated by flavin and visible light.

The usefulness of flavin-based aerial photooxidation in esterification under Mitsunobu reaction conditions was demonstrated, providing aerial dialkyl azodicarboxylate recycling/generation from the corresponding dialkyl hydrazine dicarboxylate. Simultaneously, activation of triphenylphosphine (Ph3P) by photoinduced electron transfer from flavin allows azo-reagent-free esterification. An optimized system with 3-methylriboflavin tetraacetate (10%), oxygen (terminal oxidant), visible light (450 nm), Ph3P, and dialkyl hydrazine dicarboxylate (10%) has been shown to provide efficient and stereoselective coupling of various alcohols and acids to esters with retention of configuration.

Metabolic disorders in patients with chronic kidney failure.

This review article summarizes the problems of metabolic disorders and nutrition imbalances that often occur in chronic kidney failure (CKF) or following regular dialysis treatment. In this survey, we cover the pathogenesis of these disorders, their clinical consequences, and their association with the most severe complications of chronic kidney failure and dialysis treatment. These complications are primarily atherosclerosis, malnutrition, anemia, hyperparathyroidism, and other serious problems that markedly and negatively affect prognosis and the quality of life of uremic patients. Risk factors for cardiovascular disease are discussed in-depth because cardiovascular disease is the leading cause of death in patients with chronic kidney failure. It is important to pay attention to the development of these complications because early diagnosis and therapy can improve the prognosis for these patients and reduce treatment costs.

Influence of endothelin-1 gene polymorphisms on the progression of autosomal dominant polycystic kidney disease.

BACKGROUND/AIM: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability cannot be fully explained by the genetic heterogeneity of the disease. Endothelin-1 (ET-1) has been suggested to be a major promoting factor in renal diseases. The role of the ET-1 gene locus (EDN1) in the renal function in the general nondiabetic population was evaluated. We examined the influence of three single-nucleotide polymorphisms of the ET-1 gene (EDN1)--K198N, 3A/4A, and T-1370G--on the progression of ADPKD towards end-stage renal disease (ESRD). METHODS: Two hundred and five ADPKD patients (113 males and 92 females) who had reached ESRD were analyzed. The patients were divided into three groups: (1) 48 patients (23 males and 25 females) with ESRD later than 63 years of age (slow progressors), (2) 74 patients (41 males and 33 females) with ESRD before 45 years of age (rapid progressors), and (3) 83 patients (49 males and 34 females) with ESRD between 45 and 63 years old. DNA samples from collected blood were genotyped for three single-nucleotide polymorphisms of EDN1: K198N, 3A/4A, and T-1370G. Haplotype analysis was also done in 200 healthy individuals. We compared the frequencies of the different genotypes between the groups of slow and rapid progressors and the ages at the time of ESRD regarding the EDN1 genotypes. RESULTS: The EDN1 genotype distribution showed no differences among the groups of slow progressors, rapid progressors, the ADPKD group with ESRD between 45 and 63 years old, and the control group. Comparing the ages of ESRD of all patients, we did not find significant differences with regard to the different genotypes. Furthermore, we compared the combinations of the different haplotypes and the ages at the time of ESRD. We found no differences in ages at the time of ESRD in patients with different haplotypes in the endothelin promoter (T-1370G) in combination with 3A/4A or K198N polymorphisms. Comparing the ages at the time of ESRD in patients with different 3A/4A and K198N haplotypes, we found a significantly lower age at the time of ESRD (47.1 +/- 8.7 years) in the carriers of the 4A allele in combination with the 198N allele (4A/4A, 3A/4A + 198KN,NN) than in the carriers of the 4A allele homozygous for the K198 allele (52.9 +/- 10.9 years; 4A/4A, 3A/4A + 198KK; t test: p < 0.01) and in the carriers of the 198N allele homozygous for the 3A allele (53 +/- 11.2 years; 3A/3A + 198KN,NN; t test: p < 0.05). CONCLUSIONS: We excluded an effect of K198N, 3A/4A, and T-1370G polymorphisms of EDN1 on the progression of ADPKD. However, a deleterious effect of the combination of 4A and 198N alleles of EDN1 was observed in APKDK individuals.

[Asymmetric dimethylarginine--a novel cardiovascular risk factor]. / Asymetrický dimetylarginin--nový rizikový faktor kardiovaskulárních onemocnení.

Understanding metabolism of nitric oxide (NO), signal molecule releasing from endothelial cells and influencing vascular tone, belongs to the most remarkable knowledge of last ten years. NO increases vascular tone, inhibits adhesion of monocytes and leukocytes to the vascular endothelium and reduces atherogenic process. Low NO level is one of pathogenic factors starting cardiovascular diseases. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of enzyme NO synthase, enzyme catalyzing NO production from arginine. This article gives a brief overview of contemporary state of the relation between ADMA and cardiovascular diseases. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilatation. In several prospective studies, ADMA evolved as a marker of cardiovascular risk. In the first chapters is described state of the art of biosynthesis, degradation and excretion of ADMA in connection with endothelial dysfunction, coronary artery disease, chronic heart failure, cardiovascular risk in haemodialysis patients, diabetes mellitus, hypertension, lipid metabolism disorders and intensive care unit treatment. Next chapters shortly summarize methods of ADMA detection and their applications. In conclusion clinical relevance of measurement of ADMA levels as a marker of endothelial dysfunction is discussed. Future research tasks of ADMA lead to prospective studies with different types of patients and also healthy population. Moreover ADMA is becoming a goal for pharmacotherapeutic intervention to improve endothelium-dependent vascular function in subjects with high ADMA levels.

Inhibition of copper amine oxidases by pyridine-derived aldoximes and ketoximes.

The reactions of pea diamine oxidase (PSAO) and 2-phenylethylamine oxidase from Arthrobacter globiformis (AGAO) with pyridine-derived oximes were studied. Pyridine carbaldoximes and alkyl pyridyl ketoximes act as strong non-competitive inhibitors of the enzymes. The inhibition constants K(i) of these compounds vary between 10(-4) and 10(-5) M, for AGAO and some of the studied oximes were found even micromolar K(i) values. The presence of pyridine moiety in the studied compounds has remarkable influence on the inhibition potency. Elementary oximes lacking the heterocyclic ring, i.e., aliphatic (acetone oxime), alicyclic (cyclohexanone oxime) and aromatic (benzaldoxime), are considerably weaker non-competitive inhibitors (K(i) similar to 10(-3) or 10(-2) M). The position of the pyridine ring substitution by -C(R)=NOH group does not play a significant role for the inhibition potency of the studied oxime compounds. If the pyridine nitrogen is quaternised (in hydroxyiminomethyl-1-methylpyridinium iodides), the compound looses its inhibitory properties. Extended length of alkyl substituents on the ketoxime group of alkyl pyridyl ketoximes increases the K(i) value. The enzyme-bound copper represents one of possible target sites for pyridine-derived oxime inhibitors. The addition of an alkyl pyridyl ketoxime or a pyridine carbaldoxime to a native PSAO sample perturbs the absorption spectrum of the enzyme (by an absorption increase in the region 300-400 nm) that is not observed in the spectrum of reacted PSAO apoenzyme. However, an additional formation of hydrogen bonds with amino acid side-chains at the active site should be considered, namely for 3- and 4-substituted pyridine derivatives.