The Role of Antioxidant Systems in the Response of Escherichia colito Heat Shock

Shifting the temperature from 30 to 45°C in an aerobic Escherichia coliculture inhibited the expression of the antioxidant genes katG, katE, sodA, and gor.The expression was evaluated by measuring -galactosidase activity in E. colistrains that contained fusions of the antioxidant gene promoters with the lacZoperon. Heat shock inhibited catalase and glutathione reductase, lowered the intracellular level of glutathione, and increased its extracellular level. It also suppressed the growth of mutants deficient in the katG-encoded catalase HPI, whereas the sensitivity of the wild-type andsodA sodBmutant cells to heat shock was almost the same. In the E. coliculture adapted to growth at 42°C, the content of both intracellular and extracellular glutathione was two times higher than in the culture grown at 30°C. The temperature-adapted cells grown aerobically at 42°C showed an increased ability to express the fused katG–lacZgenes.     

P-(alkyl)-nucleoside 5'-hydrogenphosphonates as depot forms of antiviral nucleotide analogues

P-(Alkyl)esters of AZT 5'-hydrogenphosphonate were synthesized and their stabilities in the phosphate buffer and human serum were evaluated. The esters bearing residues of primary and secondary alcohols were degraded to give AZT, whereas those containing tertiary alkyl groups yielded AZT 5'-hydrogenphosphonate. The corresponding derivatives of d2A and d4T showed the same properties.     

A photoreactive analogue of 2'3'-dideoxyuridine 5'-triphosphate: preparation and use for photoaffinity modification of human replication protein A

A new reagent for photoaffinity modification of biopolymers, 5-[E-N-(2-nitro-5-azidobenzoyl)-3-amino-1-propen-1-yl]-2',3'-dideoxyuridine 5'-triphosphate (NAB-ddUTP), was synthesized. Like a similar derivative of 2'-deoxyuridine 5'-triphosphate (NAB-dUTP), it was shown to be able to effectively substitute for dTTP in the synthesis of DNA catalyzed by eukaryotic DNA polymerase beta and to terminate DNA synthesis. A 5'-32P-labeled primer with a photoreactive group at the 3'-terminus was derived from NAB-ddUTP and used for photoaffinity labeling of the human replication protein A (RPA). The covalent attachment of RPA p32 and p70 subunits to the labeled primers was demonstrated. NAB-ddUTP is a promising tool for studying the interaction of proteins of the replicative complex with NA in cellular extracts and living cells during the termination of DNA synthesis.     

The synthesis of imidodiphosphoric acid derivatives as potential substrates in the pyrophosphorolysis reaction

The preparation conditions for dichlorophosphinylphosphorimidic trichloride were optimized. It was used in the synthesis of esters of imidodiphosphoric acid. The interaction of the trichloride with amines resulted in the corresponding amidodiphosphates rather than in the expected amides of imidodiphosphoric acid.     

Association of polymorphic markers I/D of gene ACE and A1166C of gene AT2R1 with ischemic chronic heart failure in the Russian and Tatar populations of Bashkortostan Republic

Polymerase chain reaction was used to study the association of polymorphic markers I/D of the angiotensin-converting enzyme gene (ACE) and A1166C of the angiotensin II type 1 receptor gene (AT2R1) with chronic heart failure (CHF) in Russian and Tatar patients that had had myocardial infarction. In Russian patients aged 50 years or younger that had had macrofocal myocardial infarction, the CC genotype of the A1166C polymorphic marker of gene AT2R1 was associated with an increased risk of CHF (OR = 11.36). Genotype DD and allele D of the I/D polymorphic marker of gene ACE were associated with a more severe CHF (functional class III–IV) in Russian patients (OR = 3.50 and 2.06). In Tatar patients, polymorphic markers I/D of gene ACE and A1166C of gene AT2R1 were not associated with CHF.     

Association of polymorphic markers I/D of gene ACE and A1166C of gene AT2R1 with ischemic chronic heart failure in the Russian and Tatar populations of Bashkortostan Republic

Polymerase chain reaction was used to study the association of polymorphic markers I/D of the angiotensin-converting enzyme gene (ACE) and A1166C of the angiotensin II type 1 receptor gene (AT2R1) with chronic heart failure (CHF) in Russian and Tatar patients that had had myocardial infarction. In Russian patients aged 50 years or younger that had had macrofocal myocardial infarction, the CC genotype of the A1166C polymorphic marker of gene AT2R1 was associated with an increased risk of CHF (OR = 11.36). Genotype DD and allele D of the I/D polymorphic marker of gene ACE were associated with a more severe CHF (functional class III-IV) in Russian patients (OR = 3.50 and 2.06). In Tatar patients, polymorphic markers I/D of gene ACE and A1166C of gene AT2R1 were not associated with CHF.     

Phosphoramidate derivatives of acyclovir: Synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro

The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM. It also inhibited replication of wild-type HSV-1 (9.7 μM) as well as an acyclovir-resistant strain (25 μM). None of the synthesised compounds showed any cytotoxicity.     

Enterosorption as an approach to the elimination of chronic endotoxin aggression

Examination of 25 patients with chronic inflammatory diseases (in remission) has shown that enterosorption can considerably decrease the total concentration of bacterial lipopolysaccharide in the systemic blood flow.