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L V Kuznetsova

Publications and source records attributed to L V Kuznetsova.

At least 19 recordsLinked to original sources
PubMed2006

Metabolism of new-generation taxanes in human, pig, minipig and rat liver microsomes.

The novel taxanes SB-T-1102, SB-T-1214 and SB-T-1216 are up to 1000-fold more cytotoxic for resistant tumour cells than clinically used paclitaxel and docetaxel, and the current study has examined the metabolism of these new taxanes in human, rat, pig and minipig liver microsomes. Metabolites were characterized by high-performance liquid chromatography (HPLC)/tandem mass spectrometry (MS/MS) analysis. Metabolic pathways derived from their structures were confirmed by investigating subsequent metabolism of purified metabolites. SB-T-1102, SB-T-1214 and SB-T-1216 were metabolized to 14, 10 and 11 products, respectively. In contrast to docetaxel, side-chain hydroxylation did not occur at their tert-butyl group, but on the isobutyl (SB-T-1102) or isobutenyl (SB-T-1214 and SB-T-1216) chains. Species differences in their metabolism were observed. For example, human and untreated rat microsomes hydroxylated SB-T-1216 preferentially at the side-chain, whereas pig and minipig microsomes preferentially metabolized more at the taxane core. The increased formation of secondary and tertiary metabolites in rat microsomes with high expression of CYP3A1/2 compared with uninduced rats confirmed the role of CYP3A in taxane metabolism. All major products were formed by human cDNA-expressed CYP3A4 and none by CYP1A2, 1B1, 2A6, 2C9 and 2E1, indicating the principal role of CYP3A orthologues in SB-T metabolism. The knowledge of metabolic pathways of the examined agents and of their rates of formation is important due to possible metabolic inactivation of these three novel drugs with a great potential for the therapy of taxane-resistant tumours. The relatively slow metabolism of SB-T-1102 could be favourable for its antitumour efficiency in vivo.

Adolescent↗
PubMed2005

Systemic administration of antibodies to glutamate increases seizure threshold for pentylenetetrazole.

We studied the effect of single intraperitoneal treatment with antibodies to glutamate on pentylenetetrazole-induced acute generalized epileptiform activity in C57Bl/6 mice. The antiepileptic effect was observed 1.5 and 24 h after administration of antibodies to glutamate in doses of 10, 25, and 50 mg/kg. This treatment increased the thresholds of clonic seizures and tonic phase of seizures with lethal outcome.

Animals↗
PubMed2003

Elevation of corazol-induced seizure threshold after active immunization of mice of various genetic strains with glutamate-bovine serum albumin conjugate.

We studied the effect of active immunization with glutamate-bovine serum albumin conjugate on acute generalized epileptiform activity evoked by single administration of corazol. Antibodies to glutamate produced an antiepileptic effect and elevated the threshold for clonic seizures and tonic phase of lethal seizures. In BALB/c mice this effect was more pronounced than in C57BL/6 mice.

Animals↗
PubMed2003

[Effect of insertional mutation in the cspA gene encoding the major cold-shock protein on radiation resistance of Escherichia coli].

Plasmid pCspA::Km carrying a cloned mutant allele of the cspA gene for the major Escherichia coli cold-shock protein CspA with an insertion of the kanamycin resistance gene cassette from transposon Tn903 into the core region of the coding sequence causes a 2.3-fold increase in radioresistance of wild-type E. coli cells (cspA+). The radioprotective effect of this plasmid is abolished or drastically reduced in mutants recA13 and rpoH15 defective in RecA protein and in induction of the heat-shock protein regulon, respectively. Plasmid pCspA::Km causes a 1.3-fold elevation in the resistance to gamma-irradiation of E. coli mutants with an intermediate level of radioresistance (Gamr445 and KS0160) but slightly diminishes resistance of a highly radiation-resistant Gamr445 mutant. In the chromosome of E. coli with normal DNA repair systems, the cspA::Km mutation in the homozygous state enhances resistance to the lethal effect of gamma-rays and UV light 2.9 and 1.4 times, respectively. These data suggest that the system of cold-shock proteins can modulate resistance of E. coli cells to the lethal effect of gamma-rays and UV light.

Amino Acid Sequence↗
PubMed2001

Polyquinanes by [4 + 4] cycloaddition-transannular cyclization.

[reaction: see text] Photocycloaddition of 2-pyridones yields a rigid polycyclic product containing a 1,5-cyclooctadiene. The cis isomer, with the alkenes in close proximity, undergoes a transannular reaction when treated with chlorine to give a polyquinane product. The chlorination reaction involves migration of an amide nitrogen and forms a single isomer, generating eight stereogenic centers in two steps.

Alkenes↗
PubMed2000

Successful hepatic grafting after partial portal vein ligation in the rat: complete reversal of hemodynamic abnormalities.

BACKGROUND: Partial portal vein ligation (PPVL) is an established approach in the study of prehepatic portal hypertension in animals. The effect of orthotopic liver transplants (OLT) on hemodynamics in PPVL animals has not been investigated to date. The aim of this study was to develop a model of OLT in PPVL rats and to investigate its hemodynamic consequences. METHODS: Three groups of male Lewis rats were investigated (1) control animals (n=7), (2) PPVL (n=9), and (3) PPVL/OLT (n=16). Three weeks after PPVL, 9 animals were taken for hemodynamic measurements. OLT was performed in the remaining 16 PPVL rats (PPVL/OLT), and, 4 weeks later, hemodynamic measurements were made. Blood biochemical analysis was performed at different time points in all 3 groups. RESULTS: The PPVL animals presented with hyperdynamic systemic circulation, extensive collateral vascularization in the hilar region, and portal-systemic shunting (portal systemic shunting; 35.3+/-5.5%). In the PPVL/OLT group, 15 rats survived for 4 weeks (survival: 93.8%, 15 of 16). Of these PPVL/OLT rats, 3 died during the blood sampling protocol. In 3 PPVL/OLT rats, abnormal liver function and histology were found and deranged systemic and hepatic hemodynamics persisted after OLT. In the remaining 9 PPVL/OLT rats, systemic and hepatic hemodynamics had returned to normal at 4 weeks and portal systemic shunting was markedly reduced (2.5+/-0.9%). Liver function was in the normal range. CONCLUSIONS: (1) The possibility of performing OLT in PPVL rats with a high rate of survival has been confirmed. (2) In the majority of cases, complete reversal of hemodynamic abnormalities in the PPVL animals occurs after OLT (3). PPVL/OLT represents a new and important model in OLT research.

Animals↗
PubMed1999

[A mutant allele gam18, participating in the RecF repair path in Escherichia coli K-12].

Plasmid pGam18 carrying one of the cloned mutant loci, responsible for enhanced radiation resistance in the strain Escherichia coli Gamr444, was shown to increase resistance to the lethal effect of gamma-rays with a dose modification factor DMF = 2. Enhanced resistance was observed in wild-type cells and in the mutant recBC sbcB, but not recFBC sbcA. This indicates the involvement of a product of the gam18 locus in the RecF pathway of recombinational repair. The protective effect of plasmid pGam18 against radiation was completely abolished by mutations in the most RecF pathway genes (recF, recJ, recR, recO, recQ, recN, and ruvB). However, three mutations in the uvrD gene, which encodes DNA helicase II and belongs to the RecF pathway, can be partially complemented by plasmid pGam18. These data suggest that the mutant allele gam18 affects the DNA helicase II activity at the presynaptic stage of the RecF pathway-mediated repair of DNA double-stranded breaks induced by gamma-irradiation.

Alleles↗
PubMed1998

Dissociation between volume blood flow and laser-Doppler signal from rat muscle during changes in vascular tone.

Although the laser-Doppler flowmetry (LDF) signal from skeletal muscle has been shown to provide a good measure of blood flow under some conditions, its behavior during administration of vasoactive substances has never been addressed. The aims of this study were to compare 1) changes in LDF signal with those in total muscle blood flow measured with radioactive microspheres after ganglionic blockade (chlorisondamine) and during administration of angiotensin II (ANG II), phenylephrine (PE), and isoproterenol (Iso) and 2) changes in vascular resistance estimated by the two techniques. The LDF signal from the biceps femoris muscle was investigated in anesthetized male Wistar rats. Ganglionic blockade led to a significant (P < 0.05) fall in mean arterial pressure (MAP) [medians (lower, upper quartiles): 78 (72, 83) vs. 127 (114, 138) mmHg under basal conditions], muscle blood flow (MBF, microsphere technique; 61%), and the LDF signal (29%). Muscle vascular resistance (MVR = MAP/MBF) was increased (64%, P < 0.05), but vascular resistance estimated as MAP/LDF signal (MVRLDF) was unchanged. During ANG II and PE infusions, MAP rose (P < 0.05) to 178 (155, 194) and 127 (124, 142) mmHg, respectively; MBF did not change compared with the preinfusion (postganglionic blockade) level and remained significantly (P < 0.05) lower than baseline, whereas the LDF signal increased up to a level not different from baseline. MVR rose and was significantly (P < 0.05) higher than baseline, whereas MVRLDF did not differ significantly from baseline. During Iso infusion, MAP fell [58 (56, 60) vs. 94 (92, 102) mmHg, P < 0.05], the LDF signal was reduced (49%, P < 0.05) despite a large increase in MBF (139%, P < 0.05), and MVR fell (74%, P < 0.05), whereas MVRLDF did not change vs. preinfusion level. Our results suggest that 1) changes in the LDF signal from muscle may not correlate with changes in total muscle blood flow measured by the microsphere technique during infusion of vasoactive substances and 2) the use of LDF data for estimation of MVR during changes in vascular tone in rat skeletal muscle is probably not appropriate.

Adrenergic beta-Agonists↗
PubMed1998

[Use of personal dosimetry in the determination of average concentrations of methylmethacrylate in the air].

This article describes a method that uses sampling by diffusion dosimetry to determine mean shift concentrations of methylmethacrylate in the air of workplace. Silochrome S-80 with PMS-100 liquid phase worked as an adsorbent of methylmethacrylate vapors. Thermodesorption or elution with subsequent gas chromatography were used for extraction of the chemical from the adsorbent. The method successfully passed occupational trials in evaluation of air pollution with methylmethacrylate.

Air Pollutants, Occupational↗
PubMed1995

Effect of orthotopic transplantation of liver on systemic and splanchnic hemodynamics in conscious rat.

The long-term cardiovascular effects of orthotopic liver transplantation (OLT) were studied in conscious Lewis rats with a radioactive microsphere technique. Three months after OLT with an all-suture technique for graft revascularization (s-OLT), all hemodynamic parameters were similar to control. OLT with "cuffs" fitted to the portal vein and infrahepatic inferior vena cava (c-OLT) led to prominent hemodynamic disturbances including 1) hyperkinetic circulation with increased cardiac index (CI; 22%; P < 0.05) and decreased mean arterial pressure (15%; P < 0.05) and total peripheral resistance (TPR; 28%; P < 0.05); 2) a slight increase in portal pressure (11.8 +/- 0.9 vs. 9.3 +/- 1.7 mmHg in control) and marked portal-systemic shunting (51 +/- 11 vs. 0.05 +/- 0.04% in control; P < 0.05); 3) increased hepatic arterial blood flow (0.49 +/- 0.06 vs. 0.27 +/- 0.04 ml.min-1.g liver wt-1; P < 0.05); 4) splanchnic vasodilation with vascular resistance significantly (P < 0.05) lower in the liver, stomach, and large intestine; and 5) increased blood flow and decreased vascular resistance in the kidneys and heart. Ganglionic blockade with chlorisondamine (5 mg/kg body wt iv) indicated that the increase in CI seen in the c-OLT rats was probably sympathetically mediated, whereas the increase in renal blood flow was a reflection of the increase in CI. After ganglionic blocker administration, TPR and regional vascular resistances decreased to approximately the same extent in the control and c-OLT groups, indicating that vascular sympathetic tone was unchanged in the c-OLT rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Mutagenic effect of oxidizing agents on the thermally-induced prophage lambda cI857: effect of a system of oxidative stress].

The lethal and mutagenic effects of hydrogen peroxide H2O (2-20 mM), cumene hydroperoxide (0.2-2.0 mM), and potassium permanganate KMnO4 (0.25-1.0 mM) on the heat-inducible lambda cI857 prophage were studied under conditions of heat-induction immediately after the mutagenic treatment of lysogenic cells of Escherichia coli oxyR+ or oxyR delta 3. Within the range of the doses used, these agents decreased prophage survival by 3-5 orders of magnitude and increased mutation frequency by up to 0.2% under the action of hydrogen peroxide and cumene hydroperoxide, and up to 1.5% in the case of KMnO4 (in oxyR+ cells). In the absence of the inducible OxyR system of oxidative stress, both lethal and mutagenic effects of H2O were enhanced. The oxyR delta 3 mutation increased lethal and mutagenic effects of cumene hydroperoxide and KMnO4 only at the highest concentrations used. Apparently, the OxyR system does not repair lesions induced by oxidative agents, but only prevents their formation.

Bacteriophage lambda↗
PubMed1995

Regression of bile duct damage and bile duct proliferation in the non-rearterialized transplanted rat liver is associated with spontaneous graft rearterialization.

The aim of this study was to investigate the long-term consequences of non-rearterialization of the graft in rat liver transplantation. Liver transplantation with (AOLT) and without graft rearterialization (NOLT) was performed in anesthetized male Lewis rats. Quantitative morphometry and semiquantitative histopathology of the liver were performed at various times after operation. Volume fractions of tissue components were determined. The number of arteries and bile ducts per portal tract were measured in histological sections from both groups. Hepatic blood flow was measured using the radioactive microsphere technique in rats after NOLT (6 months). AOLT livers had a preserved lobular architecture at all time points and unaltered volume fractions. In addition, AOLT livers maintained approximately one artery and one bile duct per portal tract after transplantation. NOLT livers showed bile duct damage at 3 days, cellular infiltration and ductular proliferation at 1 week, increased ductular proliferation at 4 weeks, and fibrosis at 6 months. The volume fractions for nonhepatocyte parenchyma (3 days, 19.14 +/- 1.29; 1 week, 20.44 +/- 1.76; 4 weeks, 15.46 +/- 3.14), bile ducts/ductules (1 week, 4.88 +/- 1.07; 4 weeks, 7.20 +/- 2.42), and connective tissue (4 weeks, 4.02 +/- 1.66; 6 months, 14.94 +/- 0.63) were significantly increased. Hepatocyte volume fraction was significantly decreased at all time points. A total of 1.58 +/- 0.08 arteries/portal tract were found in NOLT livers after 4 weeks, rising to 2.44 +/- 0.10 arteries/portal tract after 6 months. At 6 months, hepatic arterial blood flow (0.69 mL/min/g) was significantly higher (P < .02) than control (0.25 mL/min/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Mutant alleles for radioresistance form the Escherichia coli strain Gam(r)444): cloning and preliminary characteristics].

Mutant alleles Gamr, which are able to increase the resistance to radiation of Escherichia coli wild-type cells, were cloned from the hyperradioresistant mutant Gamr444 on a plasmid mini-Mu vector MudII4042. The influence of recombinant plasmids on the sensitivity of wild-type and mutant (recA and htpR) cells to gamma-irradiation was studied. It was shown that the enhanced resistance of the Gamr444 strain to radiation was caused by mutations of two different classes, dominant and recessive. The cloned recessive mutation gamr12 increases resistance to radiation only after homogenization, that is, radiation-induced transfer from the plasmid to the chromosome, and it imposes constitutive expression of the heat-shock promoter htpG. Dominant mutant gamr alleles are active in the trans-position. A mutation-insertion into a chromosomal gene impaired by one of the dominant mutations, gamr18, was constructed. The insertion causes drastic cell radiosensitization on the recB sbcB background and probably disturbs the RecF pathway of recombination and repair. Dominant plasmids of the second type lead to the RecA-independent inhibition of DNA postirradiation degradation. The radioprotective action of recessive and dominant gamr mutations is additive.

Alleles↗
PubMed1993

[Cardiac output and its distribution in waking rats with acute streptozotocin diabetes].

Cardiac output and its regional distribution were studied in conscious rats with acute 24-hour streptozotocin (STZ)-induced diabetes using the labeled microsphere technique. Rats were made diabetic with a single intravenous injection of STZ (60 mg/kg). One day post-STZ all rats were divided into two groups in accordance with the results of urine analysis: rats with ketonuria (n = 6) and rats without ketonuria (n = 7). All the experimental animals had similar blood glucose concentration 24 hours after STZ-injection: 408 +/- 15 and 421 +/- 16 mg/100 ml in rats with and without ketonuria, respectively. All STZ-treated rats showed significant alterations in the systemic hemodynamics one day post-STZ. They included a slight hypotension, a decrease in the total peripheral resistance (TPR) and an increase in the cardiac index (CI) and stroke volume (SV) compared to pre-injection level. Rats with ketonuria showed more prominent decrease in TPR (57 +/- 6 vs. 38 +/- 4% in rats without ketonuria, p < 0.05) and more prominent increase in CI (102 +/- 18 vs. 41 +/- 8% in rats without ketonuria, p < 0.05) and SV (105 +/- 19 vs. 32 +/- 10% in rats without ketonuria, p < 0.05). In both experimental groups the blood flow was significantly increased in the small intestine, heart, brain and kidneys compared to preinjection level. Additionally, rats with ketonuria had increased blood flow in the skin and skeletal muscle (by 0.076 +/- 0.019 and 0.056 +/- 0.020 ml/min/g, respectively, p < 0.05).

Animals↗