Prognostic Value of Ceramide Dynamics in Patients with Acute Coronary Syndrome.

A dynamic study of ceramide concentrations and their association with recurrent event risk could enhance our understanding of cardiovascular complications. To assess the prognostic value of ceramide concentrations (Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), Cer(d18:1/24:0)) and their dynamics in combination with standard clinical and laboratory parameters and therapeutic interventions in ACS patients. Among 110 ACS patients, triple blood sampling was performed for targeted lipidomic analysis using high-performance liquid chromatography-tandem mass spectrometry.

Light green leaf sectors of variegated Dracaena fragrans plants show similar rates of oxygenic photosynthesis tо that of normal, dark green leaf sectors.

Adaptation and functional significance of chlorophyll deficit in the light green leaf sectors of variegated plants are little known. Efficiency of photosystem II for dark and light adapted states (F/F and ΔF/F') and fluorescence decrease rates (R) of light green leaf sectors of Dracaena fragrans L. were studied by methods of PAM-fluorometry and video registration.

Genetic heterogeneity of familial hypercholesterolaemia in two populations from two different countries.

Background: Familial hypercholesterolemia (FH) is a genetically determined monogenic disorder of predominantly autosomal dominant inheritance. A number of studies on differences in the genetic profile of patients with FH have demonstrated the importance of a more substantive evaluation of genetic features. The aim of this study was to evaluate the genetic profile of patients with clinical FH among Italian and Russian patients.

Chlorophyll fluorometry in evaluating photosynthetic performance: key limitations, possibilities, perspectives and alternatives.

Non-destructive methods for the assessment of photosynthetic parameters of plants are widely applied to evaluate rapidly the photosynthetic performance, plant health, and shifts in plant productivity induced by environmental and cultivation conditions. Most of these methods are based on measurements of chlorophyll fluorescence kinetics, particularly on pulse modulation (PAM) fluorometry. In this paper, fluorescence methods are critically discussed in regard to some their possibilities and limitations inherent to vascular plants and microalgae.

Chlorophyll fluorescence kinetics and oxygen evolution in Chlorella vulgaris cells: Blue vs. red light.

Oxygen evolution and chlorophyll fluorescence kinetics in cells of the Chlorella vulgaris strain (Europolytest, Russia) were studied under low, moderate and high photosynthetic photon flux densities (PPFD 40, 130 and 350 μmol photons m s) of the red and blue actinic light. A novel method of a pulse amplitude modulated (PAM) Fourier chlorophyll fluorometry was applied to obtain photoinduction curves simultaneously for the red and blue measuring light for one sample. It was found that the red light did not induce oxygen evolution at low and moderate PPFD, whereas at high PPFD it caused a declining oxygen release.

Combination therapy with nifedipine GITS 60 mg: subanalysis of a prospective, 12-week observational study (AdADOSE).

Background: AdADOSE was a 12-week, international, observational study conducted in the Middle East and Russia where patients received nifedipine gastrointestinal therapeutic system (GITS) at a daily dose of 30, 60, or 90 mg as part of an antihypertensive combination therapy. This subgroup analysis of the AdADOSE study assesses the efficacy and tolerability of nifedipine GITS combination therapy when used specifically at the 60-mg strength.

Methods: Patients with hypertension who received a daily nifedipine GITS dose of 60 mg, either at constant dose (n = 686) or up-titrated from 30 mg (n = 392), were analyzed.

Effectiveness of combination therapy with nifedipine GITS: a prospective, 12-week observational study (AdADOSE).

Background: Observational studies can provide important information on the efficacy and safety of antihypertensive agents in the real-life clinical setting. AdADOSE was a large observational study to assess the effectiveness of nifedipine GITS in combination with other antihypertensive agent(s). The study was also the first to examine the role of combination therapy with nifedipine GITS in the Middle East, Pakistan and Russia, regions that are associated with particularly high cardiovascular risk.

2'-deoxy-4'-azido nucleoside analogs are highly potent inhibitors of hepatitis C virus replication despite the lack of 2'-alpha-hydroxyl groups.

RNA polymerases effectively discriminate against deoxyribonucleotides and specifically recognize ribonucleotide substrates most likely through direct hydrogen bonding interaction with the 2'-alpha-hydroxy moieties of ribonucleosides. Therefore, ribonucleoside analogs as inhibitors of viral RNA polymerases have mostly been designed to retain hydrogen bonding potential at this site for optimal inhibitory potency. Here, two novel nucleoside triphosphate analogs are described, which are efficiently incorporated into nascent RNA by the RNA-dependent RNA polymerase NS5B of hepatitis C virus (HCV), causing chain termination, despite the lack of alpha-hydroxy moieties.

Hydrophilically enhanced 3-carboranyl thymidine analogues (3CTAs) for boron neutron capture therapy (BNCT) of cancer.

Five novel 3-carboranyl thymidine analogues (3CTAs) were designed and synthesized for boron neutron capture therapy (BNCT) of cancer. Phosphorylation of all five 3CTAs was catalyzed by recombinant human thymidine kinase (hTK1) using adenosine triphosphate (ATP) as the phosphate donor. The obtained phosphorylation rates ranged from 4% to 64.

Fluorescence energy transfer studies of human deoxycytidine kinase: role of cysteine 185 in the conformational changes that occur upon substrate binding.

Human deoxycytidine kinase (dCK) phosphorylates both pyrimidine and purine deoxynucleosides, including numerous nucleoside analogue prodrugs. Energy transfer studies of transfer between Trp residues of dCK and the fluorescent probe N-(1-pyrene)maleimide (PM), which specifically labels Cys residues in proteins, were performed. Two of the six Cys residues in dCK were labeled, yielding a protein that was functionally active.

Human deoxycytidine kinase as a deoxyribonucleoside phosphorylase.

Human deoxycytidine kinase (dCK) is a key enzyme in the 5'-phosphorylation of purine and pyrimidine deoxynucleosides with deoxycytidine as the most efficient substrate. The ability of dCK to degrade 2'-deoxyribonucleosides to free nucleobases and 2-deoxy-alpha-d-ribofuranose-1-phosphate was demonstrated by 1H-31P correlation spectroscopy and by isotope enzyme kinetic methods. The reaction depended on inorganic phosphate, and dCK showed maximum cleavage activity between pH 7 and pH 8.

Hydrodynamic and spectroscopic studies of substrate binding to human recombinant deoxycytidine kinase.

Deoxycytidine kinase (dCK), a cytosolic enzyme with broad substrate specificity, plays a key role in the activation of therapeutic nucleoside analogues by their 5'-phosphorylation. The structure of human dCK is still not known and the current work was undertaken to determine its oligomeric and secondary structure. Biophysical studies were conducted with purified recombinant human dCK.

Identification of residues involved in the substrate specificity of human and murine dCK.

Deoxycytidine kinase (dCK) is a salvage pathway enzyme that can phosphorylate both pyrimidine and purine deoxynucleosides, including important antiviral and cytostatic agents. Earlier studies showed that there are differences in kinetic properties between human and murine dCK, which may explain differences in toxic effects of nucleoside analogs. To determine if certain substitutions in amino acid sequences between human and mouse dCK give these differences in substrate specificity the 14 mutants and hybrid forms of human dCK were studied.