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Biomedical subjects

A V Smirnov

Publications and source records attributed to A V Smirnov.

At least 19 recordsLinked to original sources

Photophysics of hypericin and hypocrellin A in complex with subcellular components: interactions with human serum albumin.

Time-resolved fluorescence and absorption measurements are performed on hypericin complexed with human serum albumin, HSA (1:4, 1:1 and approximately 5:1 hypericin: HSA complexes). Detailed comparisons with hypocrellin A/HSA complexes (1:4 and 1:1) are made. Our results are consistent with the conclusions of previous studies indicating that hypericin binds to HSA by means of a specific hydrogen-bonded interaction between its carbonyl oxygen and the N1-H of the tryptophan residue in the IIA subdomain of HSA. (They also indicate that some hypericin binds nonspecifically to the surface of the protein.) A single-exponential rotational diffusion time of 31 ns is measured for hypericin bound to HSA, indicating that it is very rigidly held. Energy transfer from the tryptophan residue of HSA to hypericin is very efficient and is characterized by a critical distance of 94 A, from which we estimate a time constant for energy transfer of approximately 3 x 10(-15) s. Although it is tightly bound to HSA, hypericin is still capable of executing excited-state intramolecular proton (or hydrogen atom) transfer in the approximately 5:1 complex, albeit to a lesser extent than when it is free in solution. It appears that the proton transfer process is completely impeded in the 1:1 complex. The implications of these results for hypericin (and hypocrellin A) are discussed in terms of the mechanism of intramolecular excited-state proton transfer, the mode of binding to HSA and the light-induced antiviral and antitumor activity.

Anthracenes

Role of the ADP/ATP and aspartate/glutamate antiporters in the uncoupling effect of fatty acids, lauryl sulfate, and 2, 4-dinitrophenol in liver mitochondria.

Study of the uncoupling effect of various saturated fatty acids (from caprylic to palmitic) revealed that the glutamate recoupling effect was more pronounced in the case of short chain fatty acids, whereas recoupling of mitochondria by carboxyatractylate was more effective in the case of long chain fatty acids. The overall recoupling effect, however, did not depend on the fatty acid chain length. Besides carboxyatractylate, glutamate and aspartate also exhibited a recoupling effect under uncoupling by lauryl sulfate. The uncoupling effect of lauryl sulfate was markedly weaker in the presence of DNP or laurate (but not FCCP) which were added in concentrations causing twofold increase in mitochondrial respiration. In the presence of lauryl sulfate the uncoupling action of laurate and DNP was insensitive to carboxyatractylate and glutamate. With laurate and DNP as uncouplers increasing the pH from 7.0 to 7.8 potentiated the recoupling effect of carboxyatractylate and attenuated the recoupling effect of glutamate. In the case of uncoupling by lauryl sulfate similar changes in the recoupling effect of carboxyatractylate and glutamate were observed only in the presence of 10 microM tetraphenylphosphonium. Thus, when uncoupling is induced by fatty acids, DNP, and lauryl sulfate, the ADP/ATP and aspartate/glutamate antiporters function as two parallel and independent pathways for mitochondrial membrane potential dissipation. We suggest that the role of the ADP/ATP antiporter in uncoupling includes proton capture from the intermembrane space with subsequent protonation of uncoupler anions, their transport as neutral molecules on the internal side, and deprotonation followed by proton release into the matrix and transfer of the uncoupler anion in the reverse direction. During uncoupling the aspartate/glutamate antiporter cyclically carries the uncoupler anion with simultaneous proton transfer from the intermembrane space into the matrix.

2,4-Dinitrophenol

Fluorescence properties of recombinant tropomyosin containing tryptophan, 5-hydroxytryptophan and 7-azatryptophan.

Tropomyosin mutants containing either tryptophan (122W), 5-hydroxytryptophan (5OH122W) or 7-azatryptophan (7N122W) have been expressed in Escherichia coli and their fluorescence properties studied. The fluorescent amino acids were located at position 122 of the tropomyosin primary sequence, corresponding to a solvent-exposed position c of the coiled-coil heptapeptide repeat. The emission spectrum of the probe in each mutant is blue-shifted slightly with respect to that of the probe in water. The fluorescence anisotropy decays are single exponential, with a time constant of 2-3 ns while the fluorescence lifetimes of the probes incorporated into the proteins, in water, are nonexponential. Because tryptophan in water has an intrinsic nonexponential fluorescence decay, it is not surprising that the fluorescence decay of 122W is well described by a triple exponential. The fluorescence decays in water of the nonnatural amino acids 5-hydroxytryptophan and 7-azatryptophan (when emission is collected from the entire band) are single exponential. Incorporation into tropomyosin induces triple-exponential fluorescence decay in 5-hydroxytryptophan and double-exponential fluorescence decay in 7-azatryptophan. The range of lifetimes observed for 5-hydroxyindole and 5-hydroxytryptophan at high pH and in the nonaqueous solvents were used as a base with which to interpret the lifetimes observed for the 5OH122W and indicate that the chromophore exists in several solvent environments in both its protonated and unprotonated forms in 5OH122W.

5-Hydroxytryptophan

[A new approach to the therapy of pyoderma in servicemen: the use of the actoprotector bemitil].

At 51 men at the age from 20 till 30, sick with pyodermatitis, the clinical-immunological aspects and efficiency of-actoprotector, capable to support motor activity and human performance in the extreme environments. Bemitil has appeared more effective in comparison with conventional therapy: by general and combined application the parameters of immunity have been normalized statistically authentically, and at outside application-the places of damage were cleared faster, disappeared painfulness, hyperemia, edema, terms of staying in the hospital were reduced. The clinical recovery was in 86.3 +/- 4.8% of the patients, while effectiveness from conventional means was 62.1 +/- 6.8%.

Adjuvants, Immunologic

Involvement of aspartate/glutamate antiporter in fatty acid-induced uncoupling of liver mitochondria.

Effects of aspartate, glutamate and an inhibitor of the aspartate/glutamate antiporter, diethylpyrocarbonate (DEPC), on uncoupling of the energy transduction processes in rat liver mitochondria have been investigated. It is found that both the antiporter substrates and the antiporter inhibitor operate as recouplers when uncoupling is caused by free fatty acids (FFA). Recoupling consists in (1) partial inhibition of the FFA-stimulated respiration and (2) some increase in the membrane potential. Half-maximal effects are observed at concentrations of glutamate and aspartate close the K(m) values of the antiporter. Recouplings by glutamate (aspartate) and DEPC are not additive. On the other hand, recoupling by any of these compounds and carboxyatractylate or ADP appears to be additive. Uncoupling by dinitrophenol is less sensitive to the recouplers whereas that by FCCP is not sensitive at all. It is concluded that uncoupling by FFA in rat liver mitochondria is mediated not only by the ATP/ADP antiporter but also by the aspartate/glutamate antiporter.

Amino Acid Transport Systems, Acidic

[Involvement of the temporomandibular joints in Bechterew's disease].

Temporomandibular joints are involved in Bechterew's diseases in 59.6% of cases, more often in the peripheral form of the disease. Involvement at the debut of the disease was observed in 33.3%, including monoarthritis in 28.6%. The incidence of these lesions correlated with involvement of the hip, knee, and ankle joints. Unstable symmetrical arthritides with early rigidity predominate in the clinical picture. Extraarticular symptoms, such as defiguration, tenosynovitis, are typical. X-ray examination reveals pseudodilatation of the joint fissure, periarticular osteosclerosis, ossification of the ligaments, early ankylosis without predestruction. Erosive changes of the temporomandibular joint are not typical. Scintigraphy with pertechnephore is an informative method for ruling out other diseases of the temporomandibular joint.

Cephalometry

[The use of rumalon in gonarthrosis].

An open prospective study in 100 industrial workers suffering from gonarthrosis has been performed 80 patients were treated with rumalon, 30 ml injections, twice/year, for 3 years in combination with ibuprofen film tabs, max daily dose (when required) 1800 mg. 20 patients have received ibuprofen only, the same dose. The control group was matched by sex, age, profession and duration of service. Significant differences for functional index of Lequesne between the two groups were detected after 1.5 years of the treatment (p < 0.05). An increase in the range of movements in knee joints in rumalon group was detected in comparison with the control group (p < 0.04). The improvement of joint function was achieved in 87% of the rumalon group patients while in the control group half of the patients got aggravation. The analysis of x-ray data has revealed no significant differences between the two groups. Rumalon is an effective agent against pain syndrome in gonarthrosis patients, preserves and improves joint function. Rumalon should be administered for long-term periods.

Absenteeism

[The clinical x-ray variants of the osteolytic forms of rheumatoid arthritis of the temporomandibular joint].

Patients with grave forms of generalized rheumatoid arthritis characterized by high activity and fulminant course are liable to develop osteolytic variants of destructive processes. Clinical and x-ray variants of osteolysis are as follows: surface (50%), partial (38%), and complete (22%). X-ray examination showed pseudodilatation of the articular fissure and blurred and destroyed articular surfaces. Osteolysis eventuates in the development of a false joint or fibrous ankylosis.

Adult

[The use of the antihypoxants olifen and amtizol for treating patients with chronic stage-IIB circulatory failure].

To compare efficacy of conventional therapy, antihypoxants olifen and amthizol (groups 1, 2 and 3, respectively) 49 patients with congestive heart failure stage IIb according to the Vasilenko-Strazhesko classification were treated. In hospital the pre-hospital scheme of treatment was not changed except the following positions: group 1 patients received strophanthin instead of oral digoxin, group 2 and 3 patients received adjuvant olifen and amthizol, respectively. Stabilization of the condition occurred in 10 days, on the average, in each group. In the 1st group good results were obtained due to stroke volume increase, in the 2nd and 3d due to the ability of olifen and amthizol to prevent tissue hypoxia.

Antioxidants

[The effect of p-chloromercuribenzoate on regulation of oxidative phosphorylation by ADP and ATP and stimulation of liver mitochondrial respiration by palmitate].

The effect of p-chloromercuribenzoate (pCMB) on oxidative phosphorylation and palmitate-stimulated respiration of liver mitochondria has been studied. pCMB (1 microM) does not affect oxidative phosphorylation but reduces the inhibiting effect of ATP on this process. Used at the same concentration, pCMB eliminates the inhibiting effect of ADP and ATP on mitochondrial respiration in the presence of 10 and 20 microM palmitate. pCMB has no effect on inhibition of oxidative phosphorylation by carboxyatractyloside or on palmitate-stimulated respiration of mitochondria. It is concluded that the SH-groups of mitochondria localized in the hydrophilic region outside the inner mitochondrial membrane participate in regulation of oxidative phosphorylation by ATP and in regulation of palmitate-stimulated respiration by ADP + ATP.

Adenosine Diphosphate

Synthesis and spectral characterization of 5'-phosphopyridoxyl-D,L-7-azatryptophan, a photophysical probe of protein structure and dynamics.

We report the first isolation of a unique adduct of pyridoxal 5'-phosphate, 5'-phosphopyridoxyl-D,L-7-azatryptophan, and suggest a new and easier route for synthesis and purification of 5'-phosphopyridoxyl-L-(or -D-)tryptophan. The absorbance and emission spectra of the 7-azatryptophan adduct are distinctly different than those of pyridoxal 5'-phosphate or the tryptophan adduct. We propose that 5'-phosphopyridoxyl-D,L-7-azatryptophan has great potential as an intrinsic probe in optical studies of protein dynamics.

Indicators and Reagents