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Biomedical subjects

N V Ermakov

Publications and source records attributed to N V Ermakov.

At least 19 recordsLinked to original sources

[Kinetics of immunoglobulin G transport through the multi-layer epithelial-hematic barrier of the respiratory tract].

A new class of drugs is now utilized for in vivo diagnoses and therapy of many widespread diseases. In these pharmacological and diagnostic preparations the active substance is conjugated with a vector which transports the drug to specific biological targets. Monoclonal antibodies are the most commonly used vectors: estimation of their permeability through multilayer and unilayer biomembranes is an important step in the analysis of efficiency of vector drugs. Experiments with Sprague-Dawley rats (mature females weighing 500 to 160 g) have demonstrated the ability of immunoglobulins G to penetrate through the respiratory epithelial-hematic barrier. Using solid phase ELISA, it was found that 5-25% of the total amount of mouse antiinsulin immunoglobulins G1 injected into the trachea under hexenal anesthesia can penetrate into the blood plasma. Accumulation of antibodies in the blood begins 4 hours and ceases 32 hours after the drug application in a dose of 400 micrograms. The kinetics of transmembrane transport is described by an S-like saturation function: C(t) = Cmax/(1+e-(at-b]. Penetration of monoclonal antibodies into the blood is accompanied by their distribution in the organs and tissues as well as by their clearance from the blood plasma. The clearance of monoclonal antibodies is characterized by a 24 hour half-life and is described by an exponential equation: C(t) = C0 x exp-kt. An algorithm for the interaction of these processes which should be taken into account during measurements of the transport of monoclonal antibodies and their complexes through biomembranes is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Study of the affinity characteristics of monoclonal antibodies by solid-phase immunoenzyme analysis].

An approach is proposed for measuring the binding constant (Kb) for monoclonal antibodies (MA) interacting with an immobilized antigen in indirect ELISA. This approach allows the measurement of optical density (A405) in the peroxidase reaction initiated by the conjugate at different concentrations (C0) of antibodies. Using the Scatchard plots, the dependence of A405/C0 = f (A405) for the whole range of MA concentrations was examined, and the tangential of the slope (tg alpha = Kb) of the linear portion of the antigen molecule was calculated. Analysis of MA affinity parameters by using this approach may find wide use in immunodiagnostic studies aimed at measuring antigen and antibody concentrations in biological fluids as well as for estimating the efficiency of vector drugs in which the diagnostic or therapeutic component is conjugated with the vector (MA or F(ab) fragment) responsible for the drug transport to target cells. The method proposed was used for testing mouse (BALB/C) monoclonal antibodies (IgG1) to pig insulin produced by various hybridomas as well as for estimating the effect on MA of pH, temperature and hydrophobization. The minimal detectable concentration (method sensitivity) was found to depend on Kb.

Animals↗

A new hemoglobin variant: Hb Dagestan alpha 60(E9) Lys leads to Glu.

An electrophoretically I-like hemoglobin variant was detected during a survey for abnormal hemoglobins in Dagestan (USSR). Neither clinical nor hematological abnormalities were seen in the carrier for this mutant hemoglobin. Structural studies demonstrated a previously undescribed substitution of alpha 60 (E9) Lys leads to Glu.

Adult↗

[Primary structure of abnormal E-like hemoglobin].

An E-like abnormal hemoglobin was detected in a hematological patient and one of the members of her family. The composition of blood hemolyzates was characterized using acetate cellulose electrophoresis. The abnormal beta-chain was isolated by ion-exchange chromatography of total globin on CM-cellulose. Using peptide mapping of the abnormal beta-chain trypsin hydrolysates, it was shown that the amino acid substitution occurs in peptide beta T3. The amino acid analysis and determination of the abnormal fragment C-terminal amino acid allowed to establish the locus and type of this substitution. The first case of hemoglobin E(alpha 2 beta 2 26Glu leads to Lys) identification on the territory of the USSR is reported.

Amino Acid Sequence↗

[Determination of a primary structure of abnormal D-like hemoglobin isolated from a blood donor].

Abnormal hemoglobin with contents 40% was isolated from the blood of a donor. It was purified, its chains were separated, and the defect was found to locate at beta-chain. Abnormal betaT13 peptide was found under the separation of tryptic hydrolysate. Data on its amino acid composition, electrophoretic mobility as well as attempts to determine its N-terminal amino acid and N-terminal sequence made possible to identify the location and the character of the amino acid substitution in the abnormal hemoglobin. The first case of the presence of hemoglobin D Penjab alpha2beta2(121Glu leads to Gln) among the Russian population is described.

Amino Acid Sequence↗

[Toxic lesions of the organ of vision caused by chloroquine derivatives].

An analysis of complications resulting from a long-term administration of chloroquinine derivatives is presented in the paper. The efficacy of chloroquinine derivatives for patients with rheumatological and dermatological pathologies was demonstrated. However, the remote results showed, after the administration of the above preparations, highly serious complications in different organs and primarily in the organ of vision. As for our practice, complications of various severity degrees were found in 6 patients with rheumatoid arthritis, who received the preparations in question, such complications were classified as highly severe in 1 patient. Taking into consideration that the chloroquinine derivatives have been widely used, while many doctors are not aware of the complications caused by them. We found it advisable to compile a literature survey and to enlarge it with our own observations. Eventually, we concluded that the pathogenesis of disorders in visual functions could be explained by a toxic effect produced by the chloroquinine derivatives not only on the retina but also on the optic nerve and chiasm. Our opinion is that a thorough and differentiated approach is needed to patients with the mentioned pathologies while using the chloroquinine derivatives for treatment.

Adult↗

[2. Diagnostic resources and clinical indications].

Preliminary investigations, dedicated to the diagnostic application of three-dimension ultrasonic angioreconstruction, confirmed the feasibility of using the above method in ophthalmologic practice in cases of suspected intraocular and orbital neoplasms. 32 patients (37 eyes) with various pathologies of the eye and orbital cavity, including choroidal melanoma, facial angiomatosis, retinal detachment, chronic uveitis etc.) were examined. The results are indicative of that the three-dimension ultrasonic angioreconstruction makes it possible to detect the latent vascular neoplasms, which cannot be defined by the standard visual and ultrasonic examinations, and the dislocation of structural elements of the eyeball tunics. Besides, it provides for evaluating their special localization and their interrelations with the neighboring anatomic elements.

Adolescent↗

[Derivatives of 4-phenylpiperidine as substrates of rat brain monoamine oxidase].

A rate of utilization of 4-phenyl piperidine and its 12 derivatives by brain monoamine oxidase (MAO) was studied as compared with typical neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The enzyme was isolated from P2 synaptosomal fraction of brain corpus striatum of Sprague-Dawley rats. 10 drugs were oxidized in the MAO-catalyzed reaction with the rate close or similar to the MPTP oxidation while 6 of them exhibited the neurotoxic effect. Analysis of MAO inhibition, using 1 microM of chlorgyline and/or deprenyl, enabled to evaluate the contribution of MAO-A and MAO-B forms to utilization of 1 mM content of the substances studied. MAO-B was shown to oxidize preferably the drugs radicals of which were substituted at 3rd position of the piperidine ring, while MAO-A preferred the derivatives with radical substitution at 4th position. The rate of substrate oxidation was decreased distinctly after introduction of complete substituents into the 3rd and 4th positions of the nitrogenous heterocycle; at the same time, presence of cyclic fluorine-containing structures increased the rate of utilization, similar to that of MPTP oxidation. Derivatives of 4-phenyl piperidine, which contained in a number of drugs, were oxidized in the MAO-catalyzed reactions and might exhibit direct- or side-neurotoxic effects.

Animals↗

[Kinetic characteristics of monoamine oxidase in brain regions of animals with varying degrees of sensitivity to 1-methyl, 4-phenyl, 1,2,3,6- tetrahydropyridine].

Kinetic parameters of monoamine oxidase (MAO) were studied in synaptosomal fraction P2 of brain compartments obtained from mice, rats, rabbits, cats, dogs, guinea pigs, macaque rhesus, green and javanese macaques using I-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a substrate. Rates of MAO-catalyzed reactions were also studied in animals sensitive to the dopaminergic neurotoxin. At low concentrations of MPTR (about 1-5 mM) the rate of MAO reaction corresponded to the index Vmax/Km. Among the animals studied the highest values of the index were found in guinea pigs and macaque rhesus, the lowest values -- in rabbits. Value of the Vmax/Km index correlated with neurosensitivity to MPTP in neuromelanin-positive and neuromelanin-negative animal groups. The biochemical index for estimation of MAO-catalyzed reactions rates may be used in evaluation of brain compartments neurosensitivity to the dopaminergic neurotoxin and its derivatives.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗