Горюшкин Игорь Иванович: другие произведения.

Mechanisms alcoholism in aspect of a regulationary-structural relation (pathogenesis, diagnostics, treatment), Moscow, Russian

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  • Аннотация:
    = I.I. Goriushkin
       ( Science-research laboratory problems of narcology Russian State University of medicine, Moscow)
      It's monograph, the summary.
      Part 1-4. Principles of mechanisms of alcoholic and narcotic addiction (regulationary-structural aspect)
      (Горюшкин И.И. Механизмы алкоголизма:
    регуляционно-структурные отношения: патогенез, диагностика, лечение; научная монография, М.: Спутник+, 2008. -с.3-151.)
      This book is devoted to
    modern molecular biochemical aspects of a problem of alcoholism. The hypothesis about "elementary narcomania (toxicomania) unit" on the basis of the facts available in the literature in the book had formulated.
      = Keywords: alcoholism,
    abstinence abusing, narcotic, regulation, toxicomania, toxicomanogenesis, toxicomania, medicinal dependence, drug addictions, hypothesis, inertial system, functional limited, elemental unity of toxicomanogenesis, elemental unity of narcomanogenesis, gamma-glutamyltransferase, GGT, aspartate aminotransferase, AST, alanine aminotransferase, ALT, alcohol, carbohydrate, diagnostic, fat, pathogenesis, carbohydrate, metabolism name=Keywords
      =


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Горюшкин Игорь, Обложка книги, фотомантаж,  Механизмы алкоголизма, научная монография. Список цитированной литературый, фото дизайн и редактирование Игоря Горюшкина, Москва, 2018 г.

RESULTS
   OF
SCIENTIFIC RESEARCH


            - If among these truths, which are pushing and pressing each other, there is something, then how we shall distinguish and shall confirm it, if not by means of a science?!    / G. Gegel
       ====================


  This elementary unit represent of itself a regulationary-structural system which consist of: element of structure (a ferment either a receptor, or component of a membrane, etc.), and element of regulation (a gene, system of hormonal synthesis, etc.) and also transport element (blood, etc.), - that opportunity of considering it is as a "elementary addictive unit" of organism, i.e. the most simple model, allowing to explain of itself principles of origin and development of narcotic dependence (narcomanogenesis).
  It turns out that in a basis of molecular mechanisms a formation the drug of dependence (narcomania) lay (it is necessary and enough) four general-metabolic the phenomena: physical and chemical interaction, functional limitary, inertia of processes regulation, and psychic ability to project.
  This has allowed to prove and offer some new approaches to understanding pathogenesis of alcoholism, to its biochemical diagnostics, to its pathogenesis of treatment and it an opportunity of preventive measures.
  The book has 152 pages, 9 fig., table - 2, bibliog. - 208, subject index.
  Part 1. Principles of mechanisms of alcoholic and narcotic addiction (regulationary-structural aspect)
  Part 2. Pathogenesis of alcoholism (gamma-glutamyltransferase and aspartate aminotransferase and an alanine aminotransferase)
  Part 3. Objectivization of diagnostics of an alcoholism (gamma-glutamyltransferase and aspartate aminotransferase and an alanine aminotransferase)
  Part 4. That there is a pathogenetic treatment of an alcoholism (limiting components "find out themselves")

  Keywords:   abstinence abusing, adaptation, addiction, alanine aminotransferase, alcohol, alcoholism, aspartate aminotransferase, biochemical diagnostics, carbohydrate, diagnostic, drug dependence, drug addictions, elemental unity of narcomanogenesis, elemental unity of toxicomanogenesis, elementary addictive unit, euphoria, fatty liver, functional limited, gamma-glutamyltransferase, hypothesis, inertia, inertial system, limiting, limiting, medicinal dependence, mental, metabolism, molecular mechanisms, narcomania, narcomanogenesis, narcotic dependence, narcotics, objectivization of diagnostics, pathogenesis of alcoholism, pathogenetic treatment, psychic, readaptation, regulation, social, system analysis, system, therapeutic, toxicomania, toxicomanogenesis, transferases, treatment.




 Part 1.  Principles of mechanisms of alcoholic and narcotic addiction (regulationary-structural aspect)

  [ Принципы механизмов алкогольной и наркотической зависимости (регуляционно-структурный аспект) ]


- The sum and substance:

   Deductions (Part 1)

   1._ The highest nervous system of the person in the presence of narcotic substances appears "switched off", that is why and - not capable to adequate participation in elimination of the metabolic disbalance caused by presence in an organism of narcotics;

   2._ Endogenous functional (or metabolic) insufficiency of an organism can quite serve as that favorable background for which - the use of narcotic substances becomes more preferable;

   3._ Teenagers (namely, what name "difficult"), as well as a "morbid" part of the population of a society, of course, require the help; but not substitutes of type of alcohol, tobacco, narcotics or ideological abstraction, and - in social adaptation (anticipating, preventive and, the main thing, socially oriented), as well as - in possibility of the intellectual development (education, culture);

   4._ The structural-regulationary system which has aggregated in: (ferment, either a receptor, or component of a membrane, etc.) and regulationary components (a gene, system of hormonal synthesis, etc.), and also transport (blood, etc.), it is possible to consider as "elementary addictive unit" organism, i.e. - the most simple model, allowing to explain principles of occurrence and development of narcotic dependence (narcomanogenesis);

   5._ Features of functioning of this, "elementary addictive unit", are that, that in principle can explain molecular mechanisms of occurrence of such clinical phenomena of narcomanogenesis, toxicomanogenesis or drug addiction - as: euphoria, tolerance, an inclination, an abstinent syndrome (addiction) and a polynarcotism;

   6._ The basic biological reason of narcomanias, toxicomanias and drugs addiction (and, was probably, and other addictions, including behavioural) is - feature of processes of regulation existing in biological systems, namely, their inertiaful;

   7._ Dependence (alcoholic, narcotic, or any another) forms, first of all, at that level of the biochemical or neurophysiological organisation of an organism, where its is regulationary-functional relations with substances (or factors), causing dependence, develop most inertially;

   8._ For formation of an inclination to narcotic substance (or addictions) it is important, that the mental projection (euphoria, a condition of comfort and well-being), resulting the use of a narcotic - answered also it, the person, to psychological preferences and personal valuable orientations;

   9._ General inertiaful of interactions of an organism with narcotic substance can develop not obligatoryly of one, but also from several factors making it, of processes;

   10._ Interaction of narcotic substance with inertial component of biological system can remain and "not noted" until then - while this inertial system will not receive the intermediary (or the projection) at level of mentality (at level of behaviour of all organism);

   11._ - Participation of nervous system in formation of "elementary addictive unit", in principle, is important for clinical implications of narcomanogenesis, but not obligatoryly - for formation narcotic or drug addiction, as such;

   12._ Any uninertial system (separate component, sequence of components or more difficult biological organization), basically, shouldn't be capable to formation "in itself" neither toxicomanias, nor drug addiction, - and in an overall picture of narcomanogenesis will play a passive, "buffer" role;

   13._ Only directional influences and, first of all, on regulatory components and processes - towards reduction of their inertiaful - can provide efficiency of a readaptation of biological systems to their existence "without narcotics";

   14._ Search of ways of maintenance of a condition of the reduced inertiaful (during the moments of presence of a narcotic in an organism), - is one of probable paths to achievement as conditions of steady remission, and - "abilities to live with narcotics" without occurrence of dependence on them;

   15._ If, all told above to summarise, it is possible to assert, that - at the heart of mechanisms of formation of addiction (any, including narcotic) four biological phenomena (or the factor) lay all only:
    1) physics-chemical interaction (in our case - "narcotic interaction", i.e. ability of narcotic psychotropic substance to cause the answer at level of metabolic, physiologic or physical processes of an organism);
    2) a functional limited, i.e. - the most important role in formation of addiction - limiting stages of sequence of processes;
    3) a mental capability of project on, i.e. the immediate or mediated participation of narcotic, psychotropic substance in functioning of "emotionally-motivational apparatus" brain; and, at last,
    4) regulatory inertiaful, i.e. slow enough character of processes as adaptations, and readaptatia (bad reversibility);

   16._ As to two other factors: physics-chemical interaction and a mental capability of project on, - that intervention (controlling), in principle, can be organised already and "now", through preventive actions, - for example, strong-willed (the psychotherapy, socially oriented advertising, etc.) or organizational (restriction of access to narcotic substances, toughening of the control, etc.);

   17._ As a whole, for an exception of the possibility of occurrence of a narcomania, toxicomania or other dependences in biological system, basically, there is enough organization of corresponding effective measures in relation to one, any of four numbered requirements (or factors) narcomanogenesis (toxicomanogenesis).

The bases of these statements can be seen here:
I.I. Goriushkin "Molecular mechanisms of drug addictions, toxicomanias (regulationary-structural relations)", 1986
//  Zh Nevrol Psikhiatr Im SS Korsakova 1986;86(2):258-64. Russian





 Part 2.  Pathogenesis of an alcoholism (gamma-glutamyltransferase and aspartate aminotransferase and an alanine aminotransferase)

   [ Патогенез алкоголизма: гамма-глутамилтрасфераза, аспартатаминотрансфераза и аланинаминотрансфераза ]


- The sum and substance:

   Deductions (Part 2)

   ;1._ For an alcoholism, its 1st, an incipient state, characteristicly primary increase in blood serum of activity gamma-glutamyltransferase (GGT), with its yield for limits of borders of normal, at remaining within high bounds of normal activity aspartate aminotransferase (AST), alanine aminotransferase (ALT);

   2._ For 2nd, centre stage, an alcoholism characteristicly further increase in blood serum of activity of a GGT, and also - increase (with a yield for limits of borders of normal) and AST, at - normal of activity of the ALT remaining within high bounds;

   3._ While for 3rd, final stage of an alcoholism, increase for limits of borders of normal of activity of all three ferments is characteristic: both a GGT, and AST, and the ALT (though, it is fair it far not in all cases);

   4._ An alcoholism as procedural disease, differs sequence of involving of ferment systems in pathogenesis that finds the reflexion in initial, or primary, increase in blood of activity of a GGT, then - AST and, at last, the ALT;

   5._ Complex of ferment indexes: GGT, AST and ALT, - can be used with a view of objectivization of the clinical diagnosis of disease of the person an alcoholism;

   6._ And, for rising of objectivity and reliability of the diagnostic inference positioned on the basis of a complex of yielded ferments, repeated blood samplings are necessary for the analysis;

   7._ At the same time, it is necessary to mean, that 3rd stage of an alcoholism (on A.A.Portnov's classification) on character of changes of activity of the above-stated transferases of blood - nosologicaly do not represent homogeneous group;

   8._ The reason of increase of a GGT at abusing of the person alcohol (the beginning of an alcoholism, its 1st stage) are metabolic processes, namely, the adaptaion-regulatorial answer of an organism to the use of alcohol;

   9._ The hyperenzymatic of a GGT and AST (in 2 stages of an alcoholism) is also - result of intensifying of the general-metabolic adaptable-regulationary answer of an organism on proceeding use (and abusing) alcohol;

   10._ It, rising of activity of a GGT at an alcoholism (1я and 2я stages), are result of "necessity" of maintenance in an organism of conditions of "normal" passing of an exchange of alcohol (in the conditions of abusing it) - by maintenance in an organism more high speed of an exchange of a coenzyme A;

   11._ As abusing alcohol is often accompanied by deficiency of alimentary components, including, and proteins, and consequently, and deficiency of irreplaceable amino acids, which participating and in processes of an exchange of alcohol and lipids (such, for example, as cysteine or methionine);

   12._ The event at an alcoholism accumulation of fat in a liver, instead of in faty depots, is caused mainly by a condition of protein deficiency in an organism abusing alcohol and, consequently, enrichment of a ration abusing-complete protein - should promote prevention of processes and faty, and, following for it, a fibrous degeneration of a liver (cirrhosis);

   13._ Consequently, the adequate alimentary and therapeutic measures referred on elimination of protein deficiency and optimization of carbohydrate and faty exchanges at abusing alcohol, - should promote prevention of processes of a faty degeneration of a liver;

   14._ The mechanism of primary increase at an alcoholism of AST, instead of the ALT, - consists as in substrate activate of AST, and - substrate, but - limitation of the ALT;

   15._ And, for primary increase at an alcoholism of AST, instead of ALTs (in 2nd its stage) are responsible as processes of domination of fat metabolism (initiated by the use of alcohol), and, accompanying them, molecular braking mechanisms of carbohydrate metabolism.

   16._ In a condition of an alcoholic abstinence the organism of the patient urgently requires the enlarged quantities of a pyruvate (or alcohol!?) - for elimination of deficiency in acetyl-KoA and oxaloacetate, and also - for normalization of functioning of a cycle of tricarboxylic acids and, bound to it, processes of breath;

   17._ Thus, a carbohydrate foodstuff - natural, (instead of refined, type: sugar, pure glucose, etc.), as well as adequate pharmacological influences (thiamin, riboflavin, nicotinic acid, folic and ascorbic acids, etc.), referred on normalization of carbohydrate metabolism in an alcoholic abstinence, in principle, - should provide and the most pathogenetic and, consequently, "softer" replacement of alcohol; as well as, was probably, further and 'nonalcoholic existence'.




 Part 3.  Objectivization of diagnostics of an alcoholism (gamma-glutamyltransferase and aspartate aminotransferase and an alanine aminotransferase)

   [ Объективизация диагностики алкоголизма: гамма-глутамилтрасфераза, аспартатаминотрансфераза и аланинаминотрансфераза ]


- The sum and substance:

   Deductions (Part 3)

   1._ The purpose of use of laboratory biochemical methods in clinic of an alcoholism is - rising of efficiency of medical-diagnostic process that is reached by means of definition in blood serum of level of activity of transferases: gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT);

   2._ If cases get to group of "practically healthy" persons of "household drunkenness', or the beginning of disease by an alcoholism, or conditions of remission of an alcoholism, - that use of biochemical parameters and 'such normal' (for the purpose of specification of the diagnosis an alcoholism) can turn out unproductive;

   3._ The fact of fluctuation (that increases, decreases) ferment indexes of blood serum: the GGT, AST, the ALT, - found out during repeated researches of the patient, carries in itself also acknowledgement of the diagnosis an alcoholism;

   4._ It is important to understand always, that enzymatic laboratory indexes, as well as results of any other clinical research, of course, have real value only in a complex with symptoms.




 Part 4.  That there is a pathogenetic treatment of an alcoholism: limiting components "find out themselves"

   [ Что есть патогенетическая терапия алкоголизма, лимитирующие звенья себя обнаруживают ]


- The sum and substance:

   Deductions (Part 4)

   1._ Alcoholism, on advantage - disease intoxicationful and hepathologic (instead of purely narcological, or mental);

   2._ An inclination (to alcohol, to a narcotic or to an opposite sex) biologically - only the vital attribute referring an organism on realization actual for it, at present, of the vital necessity;

   3._ For a society the necessity for narcotic substances is socially unacceptable necessity; to be exact, excessive necessity, therefore as moderated is unacceptable: whether it be drunkenness or, for example, a tobacco smoking, - while, as is known, does not meet serious counteraction;

   4._ If the purpose of treatment of an alcoholism - to help the patient to recover, pathogenetic therapy is necessary;

   5._ An integral part of pathogenetic treatment of the alcoholic is - its social adaptation (i.e. reprogramming of its "consciousness") if I will, of course, be retried, as the purpose to have - to help the patient to recover;

   6._ Without knowledge of pathogenesis of diseases to turn to it (medicine), even by means of statistical calculations of "evidence-based medicine", - to system of scientific knowledge, nothing will help; today (and not only in the theory, but also in practice), - systems approach, systems analysis is necessary for medicine;

   8._ Correct use of mathematical methods (statistics) in medicine demands also ability to mathematical, abstract thinking and derivation; without same, use of statistics - and "the eaten away egg is not worthy";

   9._ If, a problem of an alcoholism to consider it is system, becomes obvious, that limiting processes in biological systems "and find out themselves";

   10._ And, consequently, increases of levels of activity of transferases: gamma-glutamyltransferase (GGT) and aspartate aminotransferase (AST) in blood serum of alcoholics also are that other, as limiting components of alcoholic pathogenesis finding out;

   11._ And, therefore, pathogenetic therapy of an alcoholism should be accompanied (first of all, or including) by normalization of levels of activity of these transferases;

   12._ And, consequently, only the adequate measures referred on normalization of activity of these transferases, can turn out sufficient and for "treatment" from an alcoholism;

   13._ Measurement in blood of alcoholics, along with a GGT and AST, - also an alanine aminotransferase (ALT), - it is necessary to consider as additional "agent" of the control over efficiency and pathogenestic of made treatment (i.e. - the control over change of "parameters of a biochemical condition" the patient);

   14._ Without the social equipment on abstention from abusing alcohol and on the healthy way of life, which else and a society were approved and encouraged, - no "purely pathogenetic treatment is able help the decision of a problem of an alcoholism;

   15._ If depression of level of transferases i n blood does not occur, fault to it can be, as we already noted, only two reasons: continuation (secret) use of alcohol or inadequate medical influence;

   16._ Thus, the biochemical estimation of a condition of the patient (with use of transferases) can help and in objectivization of the diagnosis of an alcoholism, and in specification of a stage of this disease and makes therapy of this disease of more effective - because the estimation of "biochemical state parameters" patient - is always concrete and is always individual.




  [ Copyright No  Горюшкин И.И., 2008 ( июнь ) ]
  (Март, 2018 г., Москва)


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  Keywords: abstinence abusing, adaptation, addiction, alanine aminotransferase, alcohol, alcoholism, aspartate aminotransferase, biochemical diagnostics, carbohydrate, diagnostic, drug dependence, drug addictions, elemental unity of narcomanogenesis, elemental unity of toxicomanogenesis, elementary addictive unit, euphoria, fatty liver, functional limited, gamma-glutamyltransferase, hypothesis, inertia, inertial system, limiting, limiting, medicinal dependence, mental, metabolism, molecular mechanisms, narcomania, narcomanogenesis, narcotic dependence, narcotics, objectivization of diagnostics, pathogenesis of alcoholism, pathogenetic treatment, psychic, readaptation, regulation, social, system analysis, system, therapeutic, toxicomania, toxicomanogenesis, transferases, treatment name=Keywords



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