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Biomedical subjects

A V Semenov

Publications and source records attributed to A V Semenov.

At least 19 recordsLinked to original sources
PubMed2005

Monomeric and multimeric blockers of selectins: comparison of in vitro and in vivo activity.

The potency of the oligosaccharides SiaLe(x), SiaLe(a), HSO(3)Le(x), and HSO(3)Le(a), their conjugates with polyacrylamide (PAA, 40 kD), and other monomeric and polymeric selectin inhibitors has been compared with that of the polysaccharide fucoidan. The following assay systems were used: 1) a 96-well assay based either on the use of recombinant E-, P-, and L-selectins or an analogous assay with natural P-selectin isolated from human platelets; 2) a platelet-based P-selectin cell assay; and 3) a rat model of peritoneal inflammation. IC(50) values for the neoglycoconjugate SiaLe(a)-PAA were 6, 40, and 85 microM for recombinant E-, P-, and L-selectins, respectively; all monomeric inhibitors were about two orders of magnitude weaker. PAA-conjugates, containing as a ligand tyrosine-O-sulfate (sTyr) in addition to one of the sialylated oligosaccharides, were the most potent synthetic blockers in vitro. Compared with fucoidan, the most potent known P- and L-selectin blocker, the bi-ligand glycoconjugate HSO(3)Le(a)-PAA-sTyr displayed similar inhibitory activity in vitro towards L-selectin and about ten times lower activity towards P-selectin. All of the tested synthetic polymers displayed a similar ability to inhibit neutrophil extravasation in the peritonitis model (in vivo) at 10 mg/kg. The data provide evidence that monomeric SiaLe(x) is considerably more effective as a selectin blocker in vivo than in vitro, whereas the opposite is true for fucoidan and the bi-ligand neoglycoconjugate HSO(3)Le(a)-PAA-sTyr.

Acrylic Resins↗
PubMed2004

[Age dymamics of stable chromosome aberration frequency in humans with natural and pathological senescence].

The age dynamics of stable chromosome aberration (SCA) frequency was analysed by fluorescent in situ hybridization (FISH) in human blood lymphocytes derived from donors, irradiated by low doses of ionizing radiation (Chernobyl clean-up workers, nuclear weapon testers, etc.) and patients with hereditary premature aging--Werner's syndrome and Hutchinson-Gilford's syndrome. It was found that the level of SCA was age-dependent and increased in irradiated persons. So, the SCA level may be really an index of a so-called "radiation senescence", and may show a real biological age of irradiated persons. The patients with Werner's syndrome demonstrate increased SCA level in blood lymphocytes, corresponding to the premature aging of the organisms. But in the case of another form of premature aging--Hutchinson--Gilford's syndrome-- no rise of SCA level was found. Some possible reasons of such results are discussed.

Adolescent↗
PubMed2002

Safety, inhibition of platelet aggregation and pharmacokinetics of Fab'2 fragments of the anti-glycoprotein IIb-IIIa monoclonal antibody FRaMon in high-risk coronary angioplasty.

The purpose of the study was to evaluate safety, effects on platelet aggregation and pharmacokinetics of F(ab')(2) fragments of anti-glycoprotein (GP) IIb-IIIa murine monoclonal antibody FRaMon (F(ab')(2) FRaMon) upon its intravenous administration in patients undergoing high-risk coronary angioplasty. Patients were treated before angioplasty with F(ab')(2) FRaMon at 0.2 mg/kg (n = 17) and 0.25 mg/kg (n = 12) bolus or with abciximab at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min (n = 29). F(ab')(2) FRaMon at both doses decreased platelet aggregation induced by 20 microM ADP to <10, <20, <40 and <70% of the predrug level at 1, 12, 24 and 72 h after injection, respectively. No significant differences were observed between F(ab')(2) FRaMon and abciximab antiaggregatory effects. In none of the patients did F(ab')(2) FRaMon cause allergic reactions, major bleedings or deep thrombocytopenia. Antibodies against F(ab')(2) FRaMon were detected in one patient. Free F(ab')(2) FRaMon was cleared from plasma within 12 h, while platelet-bound preparation occupied >95, 70-80 and 40-50% of GP IIb-IIIa at 1 and 12-24 h and 3 days after injection, respectively. Thrombotic complications within the first month after angioplasty in groups treated with F(ab')(2) FRaMon and abciximab were observed in one and two patients, respectively. The data obtained have shown that F(ab')(2) FRaMon at bolus administration to patients undergoing coronary angioplasty caused no serious side effects and at comparative dosage inhibited platelet aggregation with the same efficacy as abciximab at bolus + infusion administration.

Abciximab↗
PubMed2002

[Genoprotective human blood activity and its mechanisms].

Anticlastogenic properties of plasma and proteins (albumin and gamma-globulin) of the human blood were studied using seeds of Crepis capillaris (chromosome aberration assay). Antimutagen p-amino-benzoic acid was used as a comparative reagent. Anticlastogenic activity dependent of processing conditions of the biosubstrate used; for the pre-processing and combined processing anticlastogenic effect was higher than for post-processing, the processing properties of the blood being higher than those of the blood proteins. Anticlastogenic potential of biosubstrates did not depend on mutation inductor. Complex-formimg properties of plasma and blood albumen have been revealed using spectrop-hotometry through the substantial spectral displacement--relative to the expected spectrum--for the mixture of biosubstrata and mutagens. Using chemoluminescence, all plasma, albumin and gamma-globulin concentrations have been shown to enhance generation of hydroxyl radical of the Fenton reagent, especially for albumin in 1.0 g/l concentration. The general trend for all experiments was that the said substances diminished the stimulating effect as their concentrations grew. Peroxidation of yolk lipoproteids showed that only high concentrations of blood's plasma and albumen have antioxidizing properties. gamma-Globulin did not reveal any ability to inhibit lipid peroxidation of yolk lipoproteids. Complex-forming mechanisms of blood's albumen and antioxidizing property of human plasma and proteins have been proved to form the blood's anticlastogenic potential.

Albumins↗
PubMed2002

[Activity of blood platelets and functional state of endothelium in patients with unstable angina with favorable and unfavorable outcome (prospective study)].

Functional activity of platelets (aggregation and plasma levels of soluble P-selectin) and functional state of endothelium (antiaggregatory activity of vessel wall - AAVW, cuff occasion test, and plasma content of von Willebrand factor) were assessed in patients with unstable (n=41) and stable (n=19) angina and healthy donors (n=20). According to results of follow up for 1 year patients with unstable angina (UA) were divided into 2 groups - with (n=21) and without (n=20) events (coronary death, nonfatal myocardial infarction). In patients with UA and events parameters of spontaneous and ADP-induced platelet aggregation, contents of P-selectin and von Willebrand factor were higher while AAVW lower than in UA patients without events, patients with stable angina and healthy subjects. Correlations between AAVW and platelet aggregation, between AAVW and level of von Willebrand factor were negative in patients with UA, and positive in patients with stable angina and healthy subjects. These results of correlation analysis were interpreted as a reflection of impairment of antithrombotic endothelial function in patients with UA.

Angina Pectoris↗
PubMed2002

[Pharmacodynamics, safety, and clinical effects of a novel glycoprotein IIb/IIIa antagonist framon during high risk coronary angioplasty].

Preparation framon [F(ab')2 fragments of the anti-glycoprotein (GP) IIb/IIIa monoclonal antibody (FRaMon)] blocks fibrinogen binding to GP IIb/IIIa and platelet aggregation. Dynamics of platelet aggregation inhibition, safety, and clinical effects of framon were studied in high-risk coronary angioplasty. Twenty seven patients underwent angioplasty with framon, 29 - with abciximab and 28 - with no GP IIb/IIIa antagonists. Framon at 0.2 mg/kg (n=16) and 0.25 mg/kg (n=11) bolus administration inhibited platelet aggregation induced by 20 mcM ADP by more than 90%, 80%, 60% and 30% in comparison with the predrug level 1, 12, 24 and 72 h after injection, respectively. Almost the same dynamics of aggregation inhibition was observed upon abciximab administration at 0.25 mg/kg bolus + 0.125 mcg/kg/min infusion for 12 h. No signs of individual intolerance and side effects including allergic reactions and bleedings were detected in patients treated with framon. Slight decrease of platelet count (15-20%) was observed on the first day after framon administration. Antibodies against framon were detected in 1 out of 22 tested patients. Free (nonbound to platelets) framon was completely removed from the circulation 12 h after injection. The number of endpoints (death, myocardial infarction and indications for repeat revascularization) within 1 year after angioplasty was approximately the same in the groups with framon and abciximab - 7 of 25 (28%) and 7 of 28 (25%), respectively, and more than 1.5 fold higher in the group without GP IIb/IIIa blockers - 12 of 27 (44,4%).

Angioplasty, Balloon, Coronary↗
PubMed2002

[Chlamydia infections in children with acquired cicatricial laryngeal and tracheal stenosis].

The examination for Chlamydial infection was carried out in 49 children aged from 1 year 10 months to 15 years (mean age 9 years 6 months +/- 3 years 8 months) with laryngotracheal cicatricial stenosis (CS) provoked by long nasotracheal intubation. Antibodies to C. pneumoniae in diagnostically significant titers were detected in 13 of 49 children (26.5%), to C. trachomatis--in 1 patient who had both infections. All the infected patients except the latter carried tracheal canules or were decanulated. Age of the patients with Chlamydial infection at the time of examination and development of CS was significantly older than of non-infected children. No significant difference was found between these patients by duration of the intubation and of the disease. Consideration of the fact that 12 of 13 children with C. pneumoniae infection carried tracheocanules suggests that the infection may be secondary.

Adolescent↗
PubMed2001

Evidence of ehrlichiosis agents found in ticks (Acari: Ixodidae) collected from migratory birds.

Two Ehrlichia pathogens were found in immature Ixodes ricinus (L.) ticks collected from migratory passerine birds in the Curonian Spit area of the Baltic Region of Russia (Kaliningrad enclave). During the spring and fall of 2000, 1,606 passerine birds (eight species) were collected; 6.8% of them (110/1,606) were infested by ticks, and 51.8% (57/110) of tick clusters contained various human pathogenic microorganisms. Human monocytic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE) agents were found in 14% (8/57) of cases. Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto were found in 92.9% (53/57) of the ticks. In five out of eight cases, infection of both Ehrlichia and Borrelia were obtained. In one case, a single nymph contained HME, B. afzelii, and B. garinii. Borrelia burgdorferi s.s. and B. afzelii were found together in one pool of four nymphs and one larva. All agents were identified using polymerase chain reaction and species-specific primers. In 8.8% of the ticks collected from birds in the fall and 22% in the spring, pathogens were isolated from attached co-feeding nymphs and larvae. These data demonstrate that Ehrlichia exchange could occur between co-feeding ticks on animals without systemic infection.

Animals↗
PubMed2000

[Soluble P-selectin - a marker of platelet activation and vessel wall injury: increase of soluble P-selectin in plasma of patients with myocardial infarction, massive atherosclerosis and primary pulmonary hypertension].

AIM: A comparative analysis of the content of the soluble form of cell adhesion protein P-selectin in the blood plasma of patients with acute myocardial infarction (AMI), massive atherosclerosis (MA) and primary pulmonary hypertension (PPH), investigation of the relationship between plasma content of P-selectin and known markers of platelets and endothelial cells activation, preliminary assessment of the prognostic value of P-selectin determination. MATERIALS AND METHODS: This study included 16 patients with AMI, 20 patients with MA, 21 patients with PPH and 18 healthy donors. The follow-up was 1-5 years. End-points in the group of patients with AMI were recurrent acute coronary syndrome and coronary artery by-pass operation, in the group with MA--thrombotic complications (acute coronary syndrome, ischemic stroke) and in the group with PPH--death. P-selectin was measured by ELISA and platelet factor 4 (PF4), thromboxane B2 (TXB2), endothelin-I and stable prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by means of commercial ELISA kits. RESULTS: Mean level of P-selectin in blood plasma of patients with AMI (1 day) (361 +/- 18 ng/ml), MA (410 +/- 31 ng/ml) and PPH (627 +/- 83 ng/ml) was increased in comparison with the group of healthy donors (269 +/- 12 ng/ml) (everywhere p < 0.001). In AMI, P-selectin was increased on day 1 only, on days 2, 3 and 10-14 of the disease the level of P-selectin was significantly lower than on day 1 and did not differ from the control level in the group of donors. In patients with MA a significant correlation was detected between plasma content of P-selectin and platelet activation marker PF4 (r = 0.606, P = 0.007) and in patients with PPH between the content of P-selectin and another platelet activation marker TXB2 (r = 0.622, p = 0.013). However, no correlation was found in PPH patients between the content of P-selectin and markers of endothelial activation and/or damage (endothelin-1 and 6-keto-PGF1 alpha). Difference in the concentration of P-selectin in patients with or without end-points during the follow-up period was detected in patients with AMI (353 +/- 14 ng/ml and 451 +/- 24 ng/ml, p = 0.009) and PPH (477 +/- 58 ng/ml and 927 +/- 184 ng/ml, p = 0.017) but not with MA (426 +/- 37 ng/ml and 361 +/- 24 ng/ml, p = 0.295). CONCLUSION: The level of P-selectin in plasma was increased in patients with acute thrombosis (AMI, 1 day) as well as in patients without clinical signs of thrombosis but with a massive injury of the vasculature (MA and PPH). The increase of P-selectin was, presumably, caused by its secretion from activated platelets since its concentration in plasma correlated with platelet concentration but not endothelial activation markers. Preliminary data indicate that blood plasma soluble P-selectin may be considered as a potential prognostic marker in AMI and PPH.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Production of soluble P-selectin by platelets and endothelial cells.

The distribution of a soluble form of a cell adhesion molecule, P-selectin, in human platelets and cultivated endothelial cells has been studied by enzyme-linked immunosorbent assay (ELISA). The concentration of soluble P-selectin in the blood plasma of healthy donors and patients with abnormal platelet count has also been determined. P-selectin was measured in the Triton X-100 lysate of platelets and endothelial cells (total P-selectin), in the 100,000g supernatant obtained after sedimentation of the membrane fraction from the homogenate of sonicated platelets and endothelial cells (intracellular soluble P-selectin), in the supernatant of activated and nonactivated platelets, and in the culture medium of endothelial cells. A soluble form of P-selectin which did not coprecipitate with the membrane fraction was detected in platelets and accounted for approximately 10% of the total P-selectin. Platelet activation by thrombin, ADP, or a thromboxane A2 analog resulted in the secretion of 30-50% of the intracellular soluble P-selectin. Measurements of P-selectin in endothelial cell culture revealed that endothelium from aorta contained about twofold more P-selectin than endothelium from umbilical vein. Intracellular soluble P-selectin was identified in both types of endothelial cells. In endothelial cells from the umbilical vein this form made up approximately 10% of the total P-selectin. Soluble P-selectin was also detected in the medium of cultivated endothelial cells, where its content correlated with the total cellular P-selectin. Concentration of P-selectin in blood plasma strongly correlated with the platelet count in the blood of healthy donors and patients with thrombocytosis and thrombocytopenia. These data indicate that platelets serve as one of the main source of plasma P-selectin. However, the presence of P-selectin in the plasma of patients with severe thrombocytopenia suggests that endothelium can also be involved in plasma P-selectin production. Thus, in vitro experiments as well as measurements of plasma P-selectin have shown that both platelets and endothelial cells can produce a soluble form of the protein. Platelet-derived soluble P-selectin and plasma P-selectin were shown to react with antibodies against the cytoplasmic domain of P-selectin. These data prove that at least part of soluble P-selectin is produced by synthesis employing special mRNA which lacks the sequence encoding the transmembrane domain, but not by the proteolytic shedding of the extracellular portion of membrane P-selectin.

Antibodies↗
PubMed1997

Fucoidan inhibits leukocyte recruitment in a model peritoneal inflammation in rat and blocks interaction of P-selectin with its carbohydrate ligand.

Neutrophil recruitment into systemic inflammatory sites in vivo is thought to be initiated by selectin-mediated endothelial adherence. The effect of fucoidan (natural sulfated polymer of L-fucose) on the selectin dependent PMN migration into rat peritoneum following the induction of inflammation by peptone injection was studied. Peritonitis was characterized by an increase in the total cell number (from 45.3 x 10(6) to 91.6 x 10(6)/rat), and by highly elevated PMN content (from 0.2% to 58%) in the rat peritoneal cavity 3 h after peptone injection. Intravenous administration of fucoidan was found to reduce, in a dose-dependent manner, neutrophil migration into peritoneum. Fucoidan in a dose as low as 0.8 mg per rat caused 96.8% reduction of neutrophil extravasation. The inhibitory effect of fucoidan was also dependent on the time intervals between the peptone and fucoidan injections. The maximal inhibitory effect of fucoidan was observed within the first 15 min after the induction of peritonitis and it was maintained at a level of 80% during 1.5 h. Administration of fucoidan 2.5 h after peptone injection had practically no effect on PMN extravasation. Since P-selectin is known to play a key role at the earlier stages of PMN extravasation, it was suggested that the inhibitory effect of fucoidan was mostly due to its interaction with P-selectin. The in vitro experiments demonstrated the high affinity of fucoidan for both isolated P-selectin and P-selectin in plasma membranes of activated platelets.

Animals↗
PubMed1997

[The nephron microanatomy of the kidney in the lamprey Lampetra fluviatilis L. before and after metamorphosis].

Isolated nephrons from premetamorphic lamprey larvae and adult animals were obtained using microdissection and kidney collagenase treatment methods. Significant differences in the architectonics of kidney tubules were found in larvae as compared with adults. The position of larval kidney was cranial while that in adult lampreys was caudal. The absence of nephron loop was noted in larval kidney. Distal and proximal tubules were shifted one from another in mediolateral direction. Distal tubule was significantly larger than proximal one. Mesonephric duct was located laterally near the glomus. Kidney tubules morphogenesis and nephron population number increase was observed at premetamorphic stage of larval kidney development.

Animals↗
PubMed1991

[Treatment of pulmonary thromboembolism with small doses of streptokinase combined with heparin, nitroglycerin, and prednisolone].

The efficiency of method worked out by the authors for pulmonary thromboembolism management surpasses the existing routine schemes of treatment by standard doses of streptokinase. The opportune application of this method gives positive results in considerable percentage of cases, i.e. in massive and submassive thromboembolism with acute or recidivating course.

Adult↗