Ç̲ÑÒ (Contents)
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C. (P.) | |
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2-7 | |
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ÎÃËßÄÈ (REVIEWS) |
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ÌÎËÅÊÓËßÐÍÛÅ ÌÈØÅÍÈ ÍÅÔÐÎÒÎÊÑÈ×ÅÑÊÎÃÎ ÄÅÉÑÒÂÈß ÏÎËÈÌÈÊÑÈÍÎÂ
Ëèñíÿê Þ. Â.
The rapid spread of multidrug-resistant gram-negative bacterial strains has necessitated the search for the more efficient antimicrobial agents and prompted a renewed interest in polymyxins which have been invaluable for the therapy of serious nosocomial pathogens but withdrawn due to their nephrotoxicity. Polymyxins are nonribosomal cyclic lipopeptides isolated from Paenibacillus polymyxa. Several distinct groups of polymyxins have been structurally identified, each group is characterized by the unique amino acid sequence and the chemical structure of the fatty acyl group. But, only two polymyxins, polymyxin B and colistin (polymyxin E), have been clinically used. The revival of polymyxins into clinical practice has stimulated further thorough investigations of their toxicity. During the last decade, the toxicity of polymyxin B and colistin has been thoroughly studied (taking into account the chemical purity, homogeneity, dosing regimens and other factors) and appeared to be not as high as reported earlier. Nevertheless, it still may substantially complicate therapy and even result in its stoppage. Thus, the development of less toxic polymyxin derivatives remains to be a topical problem. Understanding of molecular mechanism(s) of polymyxin’s toxicity based on detailed knowledge of the peculiarities of their intermolecular interactions with the targets of their toxic action is a prerequisite of a purposeful search for such polymyxin-based compounds. Nephrotoxic effect of polymyxins is determined by their accumulation in the epithelial cells of the kidney proximal tubules. The main factor of the accumulation of these antibiotics considered to be their interaction with megalin, the giant receptor of cell surface, which is the most abundant in the apical membrane of renal proximal tubules. Megalin is a representative of the low-density lipoprotein receptor (LDL-receptor) family which contains several structurally homologous receptors. Megalin is the largest member of the family; molecular weight of rat megalin is about 600 êDà. Its amino acid sequence involves about 4660 amino acid residues and is identical to one of human megalin by approximately 77%. All members of this receptor family have a modular structure, in particular, they contain clusters of two or more cysteine-rich complement-type repeats (CR modules) which are the binding sites of the most ligands of LDL-receptors. Each of CR domains consists of approximately 40 amino acid residues. The binding site of the cationic ligands on the LDL-receptors shown to contain a common structure motif, so called DXDXD motif, which consists of three negatively charged aspartic acid residues coordinated by Ñà2+ ion and a hydrophobic residue. As a rule, the cationic part of a ligand is represented by lysine residue. The binding occurs mainly due to electrostatic interactions between positively charged lysine residue and negatively charged residues of aspartic acid. The binding is enhanced by hydrophobic interactions between aromatic residue of CR module and aliphatic region of lysine. Structural data on megalin are rather limited now: there is known a structure of CR12 domain of rat megalin and a structure of CR10 domain of human megalin (as well as its complexes with gentamicin) both solved by NMR in solution. Polymyxin binding site on the megalin is not yet determined experimentally, there are absent as well any structural models at atomic level for polymyxin interaction with megalin. However, based on an analysis of available data on the structure of ligand-target complexes for the members of LDL-receptors family, there are reasons to suppose that polymyxin’s molecular fragment which binds to megalin is represented by cationic residues of di-amino-butanoic acid (an analogue of lysine), and the structural DXDXD motifs of CR domains of megalin compose binding sites for polymyxin as well. In the review, the available data on the structure and three-dimensional organization of megalin and other members of LDL-receptors family are represented; the peculiarities of their ligand-target intermolecular interactions are considered. It is concluded that the weakening of polymyxins binding with megalin may be an effective preventive measure against polymyxin-induced nephrotoxicity. Key words: polymyxins, megalin, nephrotoxicity, molecular target,
LDL-receptors. |
8-24 | |
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Á²ÎÔ²ÇÈ×ÍÀ ÕÀÐÀÊÒÅÐÈÑÒÈÊÀ
ÂÏËÈÂÓ ÅËÅÊÒÐÎÌÀÃͲÒÍÈÕ ÒÀ ÓËÜÒÐÀÇÂÓÊÎÂÈÕ ÕÂÈËÜ ÍÀ Á²ÎÎÁ'ªÊÒÈ
BIOPHYSICAL CHARACTERIZATION
OF THE IMPACT OF ELECTROMAGNETIC AND ULTRASONIC WAVES ON BIOLOGICAL OBJECTS In recent years the physical mechanisms of action of
electromagnetic fields on biological objects are actively studied. Extensive
research about the effect of weak electromagnetic waves on biological objects
were launched in the second half of the 60-ies of XX century. It has been
suggested that the millimeter waves to biological objects are natural and are
used by cells to control basic physiological functions. This review is
summarizes the data of foreign and domestic literature related to influence
of electromagnetic and ultrasonic waves on biological objects. The concepts
of sound waves and electromagnetic field are sanctified. Several hypotheses
and points of view of mechanisms of action of microwave radiation on
biological objects were discussed in details. One of the hypotheses suggests
that the acoustic vibrations of extremely power range can stimulate the cell
plasma membrane. Other hypothesis of the mechanism of influence weak signals
on biological systems are associated with the discovery of the phenomenon of
stochastic resonance. It is assumed that the initiation of acoustic-electrical
waves in the lipid-protein membrane of the cell activates the transport of
water, ions and various substances through it. The data about the effect of
electromagnetic millimeter waves on photosynthetic organisms have been
summarized by several scientists. They established that exposure in the
microwave range is realized on the membrane level and is connected with the
change of oscillation spectrum. Peculiarities of influence of ultrasonic
waves on microorganisms and cell membranes have been analysed. Scientists
have discovered that detonation of dichloride nitrogen takes place under the
influence of ultrasonic waves. Dichloride nitrogen causes breakdown of
protein particles. Cavitation effect is one of bactericide action of
ultrasonic waves. The mechanism of action of ultrasonic waves in the
literature is explained by two theories: cavitation-mechanical,
cavitation-electrochemical. According to the first theory of ultrasonic waves
propagating in a dense environment, causing it to alternating compression and
decompression. Cavitation-electrochemical theory explains the ionization
liquid vapor and the presence in it gases in the formation of cavitation
bubble. Àn electric discharge occurs at break bubbles. The electrical
discharge accompanied by a sharp rise in temperature and in the formation of
cavitation bubble electric high voltage charge. Then the vapor of the liquid
and high molecular weight compounds in the cavitation chamber are split into
hydrogen and hydroxyl groups with formation of active oxygen, hydrogen peroxide,
nitrous acid and nitric acid, resulting in inactivation of enzymes and
proteins coagulate. All this causes the death of microbial cells. As well
ultrasonic vibrations can be used to initiate chemical reactions, the
commission of a number of new methods of synthesis and accelerate the slow
reactions in organic systems. One of the actions of the ultrasonic waves on
microorganisms is a change of concentration various substances in the
cytoplasm due to a change of the equilibrium concentration of substances
inside and outside the cell. It was found that the effects can be different.
On the one hand, researchers observed an increase in the agglutination and
the loss or total loss of virulent bacteria. On the other hand there was
opposite effect - increasing the number of viable cells. Application of
ultrasound in medical microbiology is theoretically proved in this article.
Ultrasonic techniques in microbiology used not only as an effect on
biological objects and the ability to change the physico-chemical characteristics
of substrates for culturing microorganisms. Application of such techniques is
important for controlling the composition of artificial culture medium, in
particular the concentration and the activation of molecular oxygen by
ultrasonic degassing culture medium.
Key words: electromagnetic
waves, ultrasonic waves, biological objects |
25-36 | |
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ÄÎÑßÃÍÅÍÍß ÎÑÒÀÍÍ²Õ ÐÎÊ²Â Ó ÏÎØÓÊÓ
ÏÎÒÅÍÖ²ÉÍÈÕ ÀÍÒÈÊÎÍÂÓËÜÑÀÍҲ ÑÅÐÅÄ ÏÎÕ²ÄÍÈÕ ÀÇÀÃÅÒÅÐÎÖÈÊ˲Â
Introduction.
Epilepsy is one of the most common diseases of the nervous system that
affects all aspects of life. This fact stimulates an in-depth analysis of the
problem of epilepsy from medical and social points of view. The social
significance is determined by the prevalence of epilepsy, the possibility of
personality and psyche changes in 1/3 patients, and complex social, legal and
economic issues associated with the disease. Thus, it is vital to constantly
improve the anticonvulsant drug therapy in order to find the most
pharmacologically active and safe anticonvulsants. In addition, one of the
priority areas of the pharmaceutical industry in Ukraine is the import substitution,
which in turn requires the introduction of production that is not only
generic drugs, but also original ones. Analyzing the published data we found
that five-membered di(three) aza-heterocycles is quite promising matrix based
on which the search of these anticonvulsants can be done. In this paper is
introduced the structures of the synthesized in recent years 1,2,3-triazoles
derivatives, 1,2,4-triazoles, 1,3,4-oxadiazoles and 1,3,4-thiadiazole that
possess an anticonvulsant effect with bringing of specific models of a
convulsive state. Analyzed and summarized published data regarding the
qualitative and quantitative relation "structure-activity” (SAR and QSAR
analysis) in the series of anticonvulsants that are now widely used -
benzodiazepine, barbiturates and hydantoin, and a number of new compounds
that are under preclinical trials. Introduced the correlation dependencies in
the form of regression equations that connect anticonvulsant effect with
structural characteristics of anticonvulsants that are expressed by means of
molecular descriptors of different types. These descriptors consistently
affect the amount of anticonvulsant activity, in particular, dipole moment,
molecular weight, Gammet’s constant, Taft’s steric parameter of substituents
in certain atoms, atomic charges, electron density, and lower energy of free
molecular orbital. Also, there is demonstrated an important role of a
lipophilicity for manifestation of anticonvulsant activity and are given
equations of its correlation with retention time, determined by HPLC. There
was proved an availability for further study of anticonvulsants’ activity
based on derivatives of 1,2,3-triazoles, 1,2,4-triazoles, 1,3,4-oxadiazoles
and 1,3,4-thiadiazole and common areas of chemical modification have been
identified in order to search for perspective anticonvulsants. Promising
methods included an introduction to the structure of benzylamine residue
(substituted and unsubstituted), carboxamide group, ester groups, free amino
and carboxyl groups, sulfonyl groups, aromatic rings and heterocyclic
π-redundant heterocyclic systems. In paper there was outlined a
question, which is not resolved yet of the described in the literature SAR
and QSAR models that are built only for narrow homogeneous samples of compounds
that usually belong to the same chemical class. At the same time, the
creation of reliable model for various sample compounds that allow using one
correlation equation to predict the anticonvulsant properties of compounds of
not only homologous, but different chemical structure has not been resolved.
In addition, methodological rules for constructing such models are not
explicitly formulated. However, in most scientific papers are used either
pre-selected descriptors by the authors, or an automatic descriptor selection
from a sufficiently large number of them (usually with descriptors
implemented in a particular program). Conclusion. A detailed study of
the prospective structures in the series of the five-membered derivatives of
di(three) aza-heterocycles and summarizing the progress of recent years in
SAR and QSAR analysis will further allow to choose the most promising ways of
modification in order to improve the search efficiency of new
anticonvulsants.
Keywords: epilepsy, anticonvulsant agent, SAR, QSAR.
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37-45 | |
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ÅÊÑÏÅÐÈÌÅÍÒÀËÜͲ ÐÎÁÎÒÈ Experimental papers
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THE STUDY OF THE ANTI-NEURAMINIDASE AND
INTERFERON INDUCING ACTIVITY OF ALTABOR SUBSTANCE Influenza is acute respiratory disease of viral
etiology characterized by the phenomena of general intoxication and
respiratory tract lesions. Hemagglutinin and neuraminidase, surface antigen
of influenza virus are the factors of aggression. Hemagglutinin is a
polypeptide, a surface protein of the viral envelope, due to it the virus
attaches to the surface of the host cell. Neuraminidase is an enzyme, a
glycoproteid complex that determines the enzymatic activity and is
responsible for the ability of a viral virion to penetrate the host cell and
leave it after propagation. In other words, neuraminidase helps viral
particles to penetrate the secretions of the mucous membranes to achieve
epithelial cells of the respiratory tract by virions. In addition, the
properties of hemagglutinin determine the intensity of intoxication in
disease, and neuraminidase exhibits a marked immunosuppressive effect.
Therefore, for prevention and treatment of influenza diseases it is advisable
to use two schemes, which would affect two elements of the infectious
process, namely the use of drugs that would affect influenza virus destroying
it, and medicines for strengthening the body's defences by stimulating the
interferon inducing activity. Thus, the search for drugs that would have a
combined scheme of action is appropriate and promising. The aim of the work
was to study the anti-influenza activity of Altabor substance obtained
from the collective fruit of black alder (Alnus glutinosa) and grey
alder (Alnus incana) in order to determine its effect on the virion of
influenza virus concerning its destruction and on a human in relation to
increase of the body defences. The research of the antiviral activity of
Altabor substance was conducted by studying its effects on isolated
neuraminidase and different strains of the influenza virus. The effect of the
drug on interferon production was also studied. The antineuraminidase activity of Altabor
substance was studied on the example of inhibition of neuraminidases of
different types of influenza viruses (A/Hong Kong/68/H3N2/,
A/Victoria/75/H3N2, A/Khabarovsk/H1N1/) and neuraminidase isolated from
Astrobacter ureafaciens 1 unit Calbiochem, Hoest in the concentrations of 105
and 51.5 γ/ml/min with Altabor solution in the concentration of 1 mg/ml.
The interferon inducing activity of Altabor was studied in the culture of
human leukocytes. The solution of the drug in different doses was added to 3
mln of human leukocytes and cultured at 37î Ñ for 24 hours. After that the supernatant was
collected, and the pH value was adjusted to 2.0, left at 4
îÑ
for 48-72 h, then the pH of the liquid was
restored to 7.3, and the level of interferon was determined. Thus, based on
the results it can be concluded that Altabor substance in the dose of 1 mg/ml
completely inhibited 1/6 enzyme units or 51.5 γ/ml/min of neuraminidase
(Astrobacter ureafaciens 1 unit Calbiochem, Hoest), and there is 84.2 and
85.0 % reduction in the activity of neuraminidase of A/Hong Kong/68/H3N2/,
A/Victoria/75/H3N2, A/Khabarovsk/H1N1/ influenza viruses. These data show
that Altabor dose-dependently stimulates the production of interferon in
human leukocytes indicating the activity of the drug and its prospects as an
interferon inducer. The results of the studies conducted on the antiviral
activity of Altabor substance have shown that this substance effectively
inhibits the reproduction of influenza viruses. The mechanism of the
anti-influenza action of Altabor is due to inhibition of the neuramidase
activity of influenza viruses with simultaneous induction of interferon by
human cells.
Key words: altabor, antiviral activity, influenza, neuraminidase, interferon inducing activity.
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46-48 | |
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ÕÀÐÀÊÒÅÐÈÑÒÈÊÀ
ÖÈÒÎʲÍÎÂÎÃÎ ÎÁ̲ÍÓ Ó ÕÂÎÐÈÕ ÍÀ ÃÎÑÒв ²ÐÓÑͲ ÌÅͲÍòÒÈ
FEATURE CYTOKINE
METABOLISM IN PATIENTS WITH ACUTE VIRAL MENINGITIS Introduction. The urgency of the
problem of viral meningitis etiology is due to the high frequency of severe
forms of the disease, significant levels of mortality, spread spectrum
etiopatogenia, the difficulty of differential diagnosis. The leading role in
the pathogenesis of CNS is given to pathological processes that occur in
Sabar mi area, i.e. the blood-brain barrier and causes changes intrathecal
homeostasis. The height of the inflammatory syndrome and release of
anti-inflammatory cytokines (CK), as well as alternative Pro-inflammatory
patients of acute viral meningitis (AVM) associated with the penetration into
CSF infectious pathogen or molecular patterns, which act as trigger cells of
the immune response. Material and methods. 26 patients were
examined with a diagnosis of GUM who was admitted on an emergency basis in
regional clinical infectious diseases hospital, Kharkov. The age of patients
ranged from 17 to 65 years, and was dominated by persons younger than 40
years (the average age of women was 37 years, and 25 for men). The majority
of patients with GUM was identified enterovirus and herpesvirus etiology of
the disease: in 9 patients were diagnosed with enteroviral meningitis, and 12
patients herpesviruses meningitis (HSV-1/2–7, VZV–1, EBV–1, CMV–2, HHV-6–1).
The diagnosis was verified on the basis of clinical and lquiroga, serological
and molecular genetic studies. The research material was cerebrospinal fluid
(CSF) of patients GUM which was received in early disease and in the recovery
period. The concentration of GC (IL– 1, 2, 4, 6, 10 and TNF-α) in CSF
were determined by ELISA method. The control group consisted of 11
individuals with intact CSF. The results are statistically processed on a
computer using standard computer programs (Excel and Statistica 6. Results and discussion.
In the acute period of the disease, patients AVM GC content that were
studied, were significantly higher compared with the control group:
TNF-α – 8.7-fold (p <0.05), IL-1 – 6.7-fold (p <0.05), IL-2 – 10.4
times (p <0.05), IL-4 – 3.5 times (p <0.05), IL-6 – 2.3 times (p
<0.05) and IL-10 – 4.4-fold (p <0.05). Regarding the concentration of
GC in the period of convalescence: NEF-α was higher than the control
value 5.8-fold (p <0.05), IL-1 – 3.7 times (p <0.05), IL-2 – 6.2 times
(p<0.05), IL-4 2.7 times (p <0.05), IL-6 2.2 – fold (p <0.05), IL-10
– 2.7 times (p <0.05). In connection with monodirectional changes in
cytokines exchange in the form of increased levels of both inflammatory and
anti-inflammatory cytokines, to assess the nature of compensatory mechanisms
between inflammatory and anti-inflammatory was used normalized indicator –
t-test. The degree of activity of inflammatory CK in the acute period of the
disease was only 15% higher in comparison with indicators of the Central
Committee of anti-inflammatory. This indicates a balance of both classes of
the Central Committee and on the functioning of cytokine exchange in the
direction normocapnic. To understand the compensatory capacity of cytokine
exchange in the period of convalescence was also assessed the balance between
inflammatory and anti-inflammatory activity of the Central Committee of the
inflammatory activity of the Central Committee slightly (15.9%) was higher
than the rates of inflammatory CK. So, inflammatory and anti-inflammatory CK
in CSF of patients GUM in the period of convalescence also balanced, and
their functions are normocapnic. Conclusion. Patients with AVM in the dynamics of the
disease, the increase in the levels of proinflammatory (IL-1, IL-2, IL-6,
TNF-α) and antiinflammatory (IL-4, IL-10) cytokines compared with
control, and also pathogenetic balance (normocapnia) cytokines. The increase
in the GA concentration in the acute phase GUM evidence of both the existence
of laws neurontina processes and peculiarities, caused by the pathogen, and
an increase in the stage of convalescence – preservation of intrathecal
inflammation. Research in CSF in the CNS allows not only to clarify the
pathogenesis of the disease, but in the long term to make a differential diagnosis
between serous and purulent nature of inflammation of the meninges, to
predict the severity of disease.
Key words: acute viral meningitis,
cerebrospinal fluid, cytokines. |
49-52 | |
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Ê˲ͲÊÎ-ÅϲÄÅ̲ÎËÎò×ÍÅ
ÎÁ¥ÐÓÍÒÓÂÀÍÍß ÊÎÌÁ²ÍÎÂÀÍί ÑÒÐÀÒÅò¯ ÑÊÐÈͲÍÃÓ ÇÀÕÂÎÐÞÂÀÍÜ ØÈÉÊÈ ÌÀÒÊÈ ÑÅÐÅÄ
ƲÍÎÊ ÓÊÐÀ¯ÍÈ
CLINICAL AND
EPIDEMIOLOGICAL BACKGROUND OF COMBINED STRATEGY FOR CERVICAL SCREENING OF
WOMEN IN UKRAINE
Key words: diagnostic screening strategy,
cervical cancer, utility function, HPV testing, cytological smear.
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53-58 | |
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ÌÅÒÎÄÈ ÑÓ×ÀÑÍί IJÀÃÍÎÑÒÈÊÈ ÁÀÁÅDzÎÇÀ. ÊÐÈÒÅв¯ ßÊÎÑÒ². ÏÅÐÅÂÀÃÈ ÒÀ
ÍÅÄÎ˲ÊÈ (Ïîâ³äîìëåííÿ ïåðøå)
METHODS OF THE BABESIOSIS MODERN DIAGNOSTICS. QUALITY CRYTERIUM.
ADVANTAGES AND LIMITATIONS (First report) Introduction. Babesia spp. is a tick-transmitted
protozoan parasite, one of the causative agents of piroplasmosis
(babesiosis). The disease is characterized by sings of malaise, inappetence,
fever, hemolytic anemia and hemoglobinuria. The parasite has a wide
distribution and occurs on all continents, except Australia. The life cycle
of the parasite in animals organism (equine hosts, cattle, raveling dogs,
cats) comprises two intracellular stages: sporozoites innoculated by infected
ticks develop into schizonts within lymphocytes where they maltiply and
subsequently transform into microzoites, which then invide erythrocytes.
Purpose and tests was to study the retrospective analysis of scientific
reports about classic and modern microscopic and culture technique of blood
smear staining. Materials and methods
The objects of this investigations are the retrospective analysis of
Ukrainian, European and pan American scientific papers (reports) about using
classic and modern microscopic and culture technique of blood smear
staining. Results of the study. As the
result of the study (theoretic and patent literature analysis) it was
revealed that the used microscopic (by Romanovsky, Write, Papengaim, Nocht)
and culture technique of blood smear staining in healthy domestic dogs and
those ill with Babesia infection had certain advantages. This method is
simple, undemanding, short-term and not labour-consuming; these features make
it promising for use in field conditions of expeditions, etc. The method is
reasonable for its pricing; the ingredients are actively used in research
practice by Ukrainian scientists and widely represented on the domestic
market. The presence of stains, which contrast by their wide colour spectrum,
facilitates the integral awareness of the morphological plot of changes in
studied tissues. From the technical viewpoint there are typical appeals of
clear visualization in the structural differentiation of nuclei, cytoplasmic
components and membrane. In conditions of analysis of blood preparations
(smears), which belonged to control animals, the expressiveness and
saturation of staining of blood cells, well-outlined borders of each of them
and absence of any grey and blur in their contours were striking.
Erythrocytes were bright braun, characterized by a round shape and presence
of clarification in their centre (discocytes). Single sajes were well
discerned; determination of their quantity was not a problem. The cytoplasm
of leukocytes was notable for its gray and the nuclei for their violet-red
tints. The colour of the granules was saturated, up to blue. The
intracellular components were visualized, their differentiation was obvious.
In case of observation of affected cells the qualitative properties of the
stains remained unchanged. Erythrocytes were red-grey, with a well-outlined
border and evident changes of the superficial architectonics (echino-,
dacryo-, stomato-. ovalo- and microspherocytes). Poikilocytosis was rather
strongly pronounced in 60 % of preparations, anisocytosis in 25 %. The
phenomenon of formation of “coin columns” was more widespread than in
controls. The intracellular inclusions were lilac and red-violet. The
character of colour of the leukocyte population did not change. Some cases
demonstrated numerous aggregations of thrombocytes in the immediate proximity
to erythrocytes. These blood platelets were crimson, their granules (with
different shape and size according to the degree of thrombocyte maturity)
were notable for their dark blue tint. The revealed phenomena were attributed
to pronounced adsorptive properties of the above stains against a background
of absorptive ability of blood cells (connective-tissue ones according to typology)
and the result of summation of the wide colour spectrum. Through diffusion of
chemical components of the used stains facilitated long-term preservation of
the preparations within the established period of observation as well as
qualitative representation of major elements of cell structures and
intracellular inclusions. Conclusions:
investigations of the scientific reports about the declared technique
(microscopic and culture) of staining of blood smears from domestic dogs and
cattie have been proved that is a qualitative, economically sound and
technically available method of rapid diagnosis of haemoparasitic diseases
like babesiosis.
Kaywords: retrospective analysis scientific
reports, classic and modern microscopic methods, culture technique, blood
smears staining, domestic dogs, cattie, babesiosis. |
59-65 | |
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ÈÑÑËÅÄÎÂÀÍÈÅ
ÏÐÎÒÈÂÎÌÈÊÐÎÁÍÎÉ ÀÊÒÈÂÍÎÑÒÈ ËÅ×ÅÁÍÎ-ÊÎÑÌÅÒÈ×ÅÑÊÈÕ ÑÐÅÄÑÒ ÄËß ÏÐÈÌÅÍÅÍÈß Â
ÑÒÎÌÀÒÎËÎÃÈÈ
STUDY OF ANTIMICROBIAL
ACTIVITY OF MEDICAL-COSMETIC PRODUCTS USED IN DENTISTRY |
66-71 | |
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²ÑÒÎÐ²ß ÌÅÄÈÖÈÍÈ (HISTORY OF MEDICINE) |
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ÊÝÐÈ ÌÓËËÈÑ –
ßÐÊÎÅ ÈÌß Â ÈÑÒÎÐÈÈ ÍÀÓÊÈ KARY MULLIS -
BRIGHT NAME IN THE HISTORY OF SCIENCE |
72-74 | |
| ÍÀÓ×ÍÛÅ ÈÄÅÈ ÌÅ×ÍÈÊÎÂÀ È
ÑÎÂÐÅÌÅÍÍÎÑÒÜ Ïîïîâ Í. Í. , Êîëîòîâà Ò. Þ. MECHNIKOFF’S SCIENTIFIC IDEAS AND MODERNITY Popov N.N , Kolotova T. Yu. On
May 15, 2015, we celebrated the 170th anniversary of the Ilya
Metchnikoff, the author of the hypothesis about parenchymella, the
father of cellular immunology and inflammation theory, founder of
gerontology, aging and longevity science. He was at the vanguard of the
probiotics use in elderly therapy. In his work “Essays about the Origin
of Species” Metchnikoff critically reviewed the history of evolution
ideas development. He rejected the idea that the struggle for existence
occurs primarily among member of the same species and is the starting
place of the new species development and complexity. There is still
dispute about the mechanisms of speciation about whether evolution is
punctuated rather than smoothly gradual about the role of natural
selection in the new species creation and generation of life
complexity. Metchnikoff devoted many years to studying the comparative
development of the embryonic layers of lower animals. He proved that in
their development the lower animals follow a plan similar to that of
the higher animals. Ilya Ilyich demonstrated that cnidarians gastrulate
by introgression of cells which move from the blastula wall into the
interior blastocoel and formed parenchymella or phagocytella. Also he
assumed that invagination arose as a secondary mechanism of
gastrulation. In the paper we discussed the contemporary views about
parenchymella and multicellular animal origin. Metchnikoff is rightly
famous for his theories of phagocytosis and inflammation. He proposed
that macrophages evolved first to regulate development, and that these
function are the stage for their evolution into the cells of innate
immunity, He revealed of phagocytic cells functions in clearing
infections and inflammation. He described of phagocytosis as an active
process and its role in host defence, across a wide range of organisms
digestion. It is very importantly that cells and microorganisms were
taken up by an active process, involving living, and not only dead
organisms. He demonstrated killing by leukocytic enzymes (‘cytase’).
The humoral theory claimed that the phagocytes caused the spread of
disease in the body and thus would harm the host, rather than defend
it, against bacterial invasion. Metchnikoff devoted much of his
scientific work to the development and defense of the role of
phagocytosis in inflammation. He observed diapedesis through vessel
walls, aggregation of leukocytes at sites of inflammation. Phagocytosis
not only destructs of infectious microbes including bacteria,
spirochaetes and yeasts, but uptake of host cells, e.g. erythrocytes,
from diverse species as well. More broadly phagocytes are the cells
which preserving the integrity and defining the identity of the
organism. In the article we summarized the new data and concepts about
the development and functions of phagocytes in innate immunity,
inflammation, oncogenesis and tissues repair. Metchnikoff believed that
the disabilities of old age are the work of phagocytes transformed from
defenders against infection into destroyers of tissues by autotoxins
derived from putrefactive bacteria residing in the colon. According to
his concept, senile degeneration of the nervous system, for example, is
the work of macrophages induced by autotoxins cause them to atrophy.
Such degenerative changes, he believed were nearly always premature and
potentially prevented by procedures directed against the putrefactive
bacteria. Metchnikoff hypothesized that diminishing the number of
putrefactive bacteria in the gut with probiotics could prolong life.
Until recently it was generally assumed that phagocytic removal of
neurons occurs only after neuronal death. But now it has been
convincingly proved that stressed but viable neurons reversibly exposed
the “eat-me” signal leading to their phagocytosis by microglia; this
neuronal loss was prevented in the absence of microglia. As a result
these data breathe life into the Metchnikoff ageing theory.
Keywords: evolution, natural selection, parallel evolution, complexity, parenchymella, phagocytella, gastrula, phagocytes, inflammation, innate immunity, M1 macrophage, M2 macrophage, probiotics, ageing theory |
5-98 | |
Ê 120-ëåòèþ ñî äíÿ ðîæäåíèÿ
ÂËÀÄÈÌÈÐÀ ÀËÅÊÑÀÍÄÐÎÂÈ×À
ÁÅËÎÓÑÎÂÀ (ïàìÿòè ó÷èòåëÿ ïîñâÿùàåòñÿ) |
99-100 |
|
| Äîïîâíåííÿ (Supplementation) | ||
|
ÒÅÇÈ ÄÎÏβÄÅÉ Ì²ÆÍÀÐÎÄÍί ÍÀÓÊÎÂÎ-ÏÐÀÊÒÈ×Íί
ÊÎÍÔÅÐÅÍÖ²¯ «ÀÊÒÓÀËÜͲ ÏÈÒÀÍÍß ÁÎÐÎÒÜÁÈ Ç ²ÍÔÅÊÖ²ÉÍÈÌÈ ÇÀÕÂÎÐÞÂÀÍÍßÌÈ»,
ïðèñâÿ÷åíà 170-é ð³÷íèö³ ç äíÿ íàðîäæåííÿ ². ².
Ìå÷íèêîâà |
1-139 | |