Biophysical Semeiotics: Towards the Unified Pathogenetic Theory.
(by Sergio Stagnaro)
Biophysical Semeiotics: Towards the Unified Pathogenetic Theory. 1
Introduction Article. 1
Clinical observation and Unified Pathogenetic Theory. 2
Biologic-molecular data supporting the Unified Pathogenetic Theory. 3
Biophysic-semeiotical constitutions and Unified Pathogenetic Theory. 5
In 70s, the discover of Congenital Acidosic Enzyme-Metabolic Histangiopathy-, found out to be conditio sine qua non of most serious and common human diseases, suggested me the possible and foreseeable existence of a Unified Pathogenetic Theory, as source of the onset of these pathologies. Indeed, in three decades, on the base of biophysical-semeiotic clinical data I gathered bed-side, I proved that “all” (“all”, easily questionable, is rich of information since it is also easy to falsify) diabetic, hypertensive, dyslipidaemic, oncologic, glaucomatous, osteoporotic, lithiasic, etc. patients, had and/or have ICAEM-, corroborating my theory on the existence of a common pathogenic mecchanism. 7
Dott.Sergio Stagnaro 9
An unrestrainable natural instinct seems to lead the human being along the path of the plotinian return from the problematic and manifold determinate, to the indeterminate, necessary to the unit.
In 70s, after the discovery of a peculiar functional mitochondrial cytopathology, subsequently described as Congenital Acidosic Enzyme-Metabolic Histangiopathy- (ICAEM-) (1-3, 5), a ten-years-long clinical observation allowed me to prove that this mitochondrial cytopathy represents the conditio sine qua non of the most frequent, disabling or mortal human pathologies, such as diabetes mellitous, arterial hypertension, gout, osteoporosis, glaucoma, lithiasis, arteriosclerosis and cancer.
In “Das Wesen der Wissenschaft” Jasper states that the whole knowledge is implicit in the method; the clinical method of diagnosis and research that then it was available was the auscultatory-percussion reflex-diagnostic, originated from the re-evaluation of the obsolete auscultatory percussion (4); at the beginning of 90s that allowed me to found Biophysical Semeiotics (see web HONCode 233736, www.semeioticabiofisica.it Bibliography).
Then, towards the end of the last century, it was inevitable that I carefully researched on the obvious possible existence of different biophysical-semeiotic constitutions, arisen on the common base of ICAEM-; my research was able to justify the onset of the most frequent and serious human pathologies, fostered by particular environmental conditions. In fact, nowadays all authors agree that phenotype is the result of the influence of the environmental risk factors on genotype (5).
At the beginning of the third millennium, the detailled description of the several constitutions, followed by their proper characterisation according to the biophysical-semeiotics (5, 6) (see cited web site in: Costituzioni Semeiotico-Biofisiche; Single Patient Based Medicine), essentially and definitively contributed to the formulation of the Unified Pathogenetic Theory.
The aim of this introductive paper is to show the rational and scientific bases on which the theory is founded; the following articles will provide a wide description of the theoretical and practical aspects of it with detailed reference to the most serious human diseases, today considered like real epidemics.
Clinical observation and Unified Pathogenetic Theory.
At the end of the last century physicists believed that they were going to find out a way to the creation enabling them to solve the mathematical secret of the universe: a discovery leading to the “theory of the whole” (7). So, with this cosmic Rosetta stone, at last they would have been able to read the book of the Nature comprehensively and from the time point of view, acquiring a an omni-comprehensive view of the laws of nature, from which the inevitability of reality originates, within and without us.
Likewise already in the past doctors thought that few were the causes of the then-known diseases, they implied a common pathogenetic base. Later on, considering the essential role of the psycho-physical constitution, doctors, like Andrea Cesalpino, underlined the importance of the necessity of a deep knowledge of the patient, together with pathogenetic process common to several diseases, in order to be able to cure him; they were rightly persuaded that only ill people existed, not illnesses.
In this connection, it is proper to quote a great master of the 20th century, Luigi Condorelli: “Not less important it is the concept – for the first time precisely stated [by Andrea Cesalpino] – of the necessity of the knowledge of the exact pathological conditions and constitutional characteristics of the patient, and the action mechanism of medication, to come to an effective therapy. The medication could be either good or bad according to the conditions of the patient. We cure the patient not the disease”; he also warned “Cesalpino’s definition of «Medical Matter» is still topical; indeed it should be revaluated to admonish those hasty doctors of today, who think the therapeutic prescription just in terms of a list of medicines, whose composition and action they merely know; those hasty doctors who neglect to provide a rational diet and the not-less-important rules of hygiene to prevent diseases” (9).
Also during the last century a similar pathogenetic interpretation was shared by great minds; they maintained that human diseases develop from an intoxication of the body, due to genetic and environmental factors, able to compromise the detoxicating function together with that of physiological emunctories. For these reasons they prescribed precise dietetic therapies, whose function was firstly aimed to restore the physiological function of kidneys, liver, stomach and intestine (8).
In an article of 1926, referring to the use of “dietetic” therapy he developed, Arnaldi C. stated, “Human body keeps accumulating pervading poisons both for heredity reasons and diurnal exercise. Unlike the action of purgatives, affecting only the intestine, the Arnaldiana care affects the main cause, the only, the atony of the intestine but also of apparats, and restore the balance once upset, detoxicating human body in general” (10).
In a similar situation of unitary interpretation of pathogenesis of the most frequent and serious human diseases, I was inevitably directed by the discover of several biophysical-semeiotic constitutions, which opened new and effective possibilities in primary prevention (6) (see cited web).
Indeed, the careful analysis of a large number of very old clinical observations should have advised us to consider human diseases like an event made possible because of the congenital conditions of biological systems. And in rare and exceptional cases this is what actually happens.
Since at least thirty years the biophysical-semeiotic clinical observation has allowed me to demonstrate that all the most disabling or mortal diseases are built on the Congenital Acidosic Enzyme-Metabolic Histangiopathy- (1-3, 5) (see cited web above), It represents the common base of all the described constitutions: diabetic, dyslipidemic, arteriosclerotical, hypertensional, osteoporotic, lithiasic, reumatic, glaucomatous, and oncological, i.e., Oncological Terrain (5, 6).
In other words, “all” the patients affected by the above disorders, which I personally took care of during the years, resulted carriers of ICAEM-, whose intensity was of course different from patient to patient, from biological system to biological system, and from part to part of the same biological system, depending on the underlying pathology (even in the same tissue).
It follows that a common pathogenesis of all the most serious and common human diseases must by necessity exist; in the second half of the last century, in several congresses I showed this idea in a slide through a schematic tree, now artistically elaborated by a painter friend: roots and trunk symbolize the ICAEM-, the several branches are different diseases (see cited web: Physician’s Corner).
To a careful observation, in the same patient we can frequently recognize more pathologies together, whose common origin (ICAEM-) can be individuated and proved by a clinical tool, Biophysical Semeiotics (5, 11, 12, 13). For example in a patient with arterial hypertension it is possible to diagnose an alteration of glucidic and lipidic metabolisms (14, 15), while the subject with varicose veins or histangiopathic hypotonic phlebopathy (16, 17) is affected by lipidic dysmetabolism, obesity, cholecyst and renal lithiasis, with a higher frequency than randomly.
We could go on with many more examples but the conclusion would still be that a genetic factor, common to all the most serious human diseases, must by necessity exist, represented by a particular functional mitochondrial cytopathology, ICAEM-, as a 47-years-long clinical experience proves.
Biologic-molecular data supporting the Unified Pathogenetic Theory.
From the 90s of the last century on the interest of researchers was more and more turned to the deepening of the knowledge of metabolic syndrome and the true nature of its relation to other diseases, especially cardiovascular pathology and glucose and lipid metabolism abnormalities (18-22).
In some of my previous articles I proved that base of metabolic syndrome is always ICAEM-, which can show a “variant” form, conditio sine qua non of calcium deposit in the tissues and chole- and renal lithiasis (5, 11, 12).
To corroborate the theory we are here discussing it is interesting to point out the fact that the association of different metabolic alterations in a single patient can be understood “unified”, also at a biologic-molecolar level. For this reason we are going to provide a single example, reminding that on the base of ICAEM- at first we have the several constitutions, then the Pre-Metabolic Syndrome (see web www.semeioticabiofisica.it/microangiologia), subsequently the metabolic one, and in the end the different pathologies.
As a matter of fact in the pathogenesis of metabolic syndrome, the metabolism of skeletal muscle has a key role, to a point that this biological system has soon arisen as critical target in the battle against obesity (22, 23), type 2 diabetes (24), dyslipidaemia (25, 26) and metabolic syndrome (25).
In fact it has been proved that nuclear receptors (NRs), e.g. LXR, PPARs alfa, beta o delta and gamma, and their numerous sub-types (25, 27, 28) are responsible for the increase of the cellular absorption of glucose stimulated by insulin, the reduction of triglycerides, increasing lipidic catabolism, expenditure of energy, discard of cholesterol and plasmatic levels of HDL cholesterol.
Also recently two researches about the action of delta PPAR in the cell (23) and muscular tissue (25), proved that NR causes the genic expression, which takes part in the releasing of cholesterol and expenditure of energy. In addition the activation of delta PPAR take part in the increasing of the insulin sensitivity and the opposition to obesity (29).
Fortunately, today doctor can evaluate at the bed-side PPARs activity, adenopectine, leptine as well as insulin sensitivity with the aid of biophysical-semeiotics in a quick, easy, and reliable way (See in above cited web site: Practical Applications, 4 articles).
From the above remarks, it is evident that just the knowledge of the relation between ROR-alfa, and glico-lipidic metabolism of skeletal muscle, including lipidic and cholesterolic homeostasis, makes easy to understand that we can formulate a Unified Pathogenetic Theory, based on ICAEM- and its subsequent “variations” of a single pathogenetic mechanism. (For further information: Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory SRL., Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm - in press-)
Biophysic-semeiotical constitutions and Unified Pathogenetic Theory.
To better understand the key role of biophysical-semeiotic constitutions, which are often coexisting in the same person, in the Unified Pathogenetic Theory, it is necessary to reflect on the present possibility of gathering biophysical-semeiotic bed-side data, rich in biological and biological-molecular information of different apparata, organs and tissues of our subject, such as to allow the description of a well-defined constitutional types.
Of course in some cases this kind of data can be observed only this way, not just with the use of the traditional physical semeiotics unable to transfer biologic-molecular events to the clinical dimension, which is the most original and fertile part of Biophysical Semeiotics.
Surely what I am here saying will meet skeptisism of many once again, corroborating the statement “great minds have always met the opposition of poor minds” (1), unfortunately increasing in number.
As a matter of fact first of all it is well known that the genome carries all the necessary information for the development and conservation of the individual: a mutation, an alteration of the fine and variegated DNA processes, an obstacle or a stimulus to the action of certain genes can lead to cancer or other pathologies, or favour their onset in particular environmental situations (6).
“Clinicians”, who are now very few and whom I proudly belong to, are directly interested nor to the study neither to the understanding of biologic-molecular events, that are the base of the above-cited processes and others, neither to the update of the daily discover of mutated genes thought to be cause of different pathologies.
However as “clinician”, I can rightly assume that to a whatever biological-molecular event, genetically determined, it follows a series of other events expressed in a different biological dimension, e.g., at a microvascular-tissue level; I am supported by the observation of a 47-years-long experience, according to which parenchyma and respective microvessels are closely correlated, both on a functional level and a structural one, following the concept of Angiobiopathy, which completes the tischendorfian one of Angiobiotopy (5, 6, 22).
In short, to make clear this concept without misunderstandings it is useful to provide an analogy, which not only represents a “form” of Thought but also one of his “structures”: for vocation or election we “clinicians” don’t worry about “analysing the composition of water from the top of the mountains before flowing down into a river-bed, but we prefer to analyse it from the first bank-sides, patiently following it in its slow growing into a proper river, accompanying it to the complete maturity in a valley, and in the end observing its full characteristics close to see” (6).
For these reasons, as written in Introduzione alla Semeiotica Biofisica (5), Krogh was right: “today the study of microvessels eventually shows its original essential and favourable repercussion on the investigation of all tissues and biological systems, and of course the macro- and micro-circulatory system, in physiological and pathological conditions”.
Many years ago, my attention turned to the interesting relations between parenchyma and respective microvessels with regard to the central nervous system (32-36), clinically proving the perfect “symmetry”, in an healthy subject, between the two biological subsystems: if, for example, the subject “thinks” of moving (or also actually moves) a finger of his hand or foot, it immediately appears (though temporarily) the type I microcirculatory associated activation (See web site www.semeioticabiofisica.it/microangiologia.it) in local, related neurological centre. So it was right to state that clinically it was possible to reliably evaluate congenital alterations in the several biological systems through the investigation of the related microvascular-tissue units.
Starting-point – Anfangspunkt – of this reasoning is the “intuition” that, through half-known biologic-molecular events (opening of DNA helix, synthesis of mRNA, protein synthesis, etc.), the genome controls the formation and conservation of many parenchymas, but at the same time inevitably and in a direct or /and indirect way it carries on a decisive action on the structure and function of related microvessels, respecting the principle expressed by Sherington, with reference to the brain (32-36), about the existing anatomo-funzionale correlation between tissue and respectivemicrovessels.
According to the original “intuition” (starting and metaphysical point of any scientific discover of great importance), information carried by genoma are sent both to parenchyma and respective microvessels, obviously including vasa vasorum:
Once accepted this “intuition” of ours, even if provisionally or as theory “Zero”, here it comes another and fundamental question:
“How does the genoma affect development and conservation of microvascular-tissuesub-systems of the several biological systems?” It is well known that a healthy subject the genetic information provides the necessary instructions for formation, mending and maintenance of single microvessels subsystems, which nowadays we can eventually study, evaluate basically and through stress tests, and also know bed-side through the original Biophysical Semeiotics (5, 6).
Accordingly, the “map” is not the “territory”, however the map allows a better knowledge of it, giving useful information to forecast, as a healthy microvascular-tissue system has a known-to-us structure able to carry on a precise and very articulated functional activity; this structure is widely illustrated from the clinical point of view, in “static” and dynamic ways, in the web site and cited articles.
Also in a healthy subject, for example during tests of simulation (stress tests, as cited above), the major request of energy from the parenchyma, whatever its origin, at once causes the activation of fine mechanisms, which are the base of Functional Microcirculatory Reserve (FMR), aimed to satisfy the requests of the tissues of matter-energy-information, e.g. in the case they have suddenly increased by the type I microcirculatory associated activation.
It is interesting to stress the fact that these congenital alterations of structure and function of the microvascular-tissue units are identical in the different constitutions, but they differ for tissue localization.
Once again, after the intuition it is necessary to logically think in order to formulate empirical statements, and then foresee that possibly changed information of the genoma, caused by mutations or other modifications (polymorphysms, catalytic genes, promoters, etc.) must necessarily display themselves into two directions, like biologic-molecular pathogenic events, whether at a parenchymal level or at a microvascular-tissueone, as explained in the pattern above.
In accordance with logic-deductive thought, further to what we said above, it is not possible to accept the presence of a “healthy” microvascular-tissuesystem associated to a parenchyma which is at the moment only “potentially” ill, as far as the microvessel alteration might be restricted to an area and not systematic.
In other words, I think that wrong genetic information, whatever the origin, must be inevitably responsible both on the parenchyma and respective microvessels, independently of quality and seriousness of changed information, “also” according to the above tischendorfian idea of Angiobiotopy, which states that microvascular-tissuesub-system is structurally and functionally related to the parenchymal system, as for instance in a tissue full of fibroblasts the microvessel function-structure proves: plenty of emoderivative structures and poverty of nutritional capillaries.
In the spirit of personal philosophy, critical-dialectical-analectic realism (5), after the “metaphysical” starting point, turning to every train of thought, in scientific discover it is necessary to go on in a strictly logic-deductive way, on a logic base founded on the principle of non-contradiction and internal and external coherence, which represents the necessary condition of reality, without the pretence of corresponding to reality.
Once again, starting from “intuitive, axiomatic and apodictic” premises, temporary accepted as truths, proceeding with logic-deductive order, eventually I came to an “empirical” statement, liable of falsification or provisional corroboration through the comparison with clinical reality: biophysical-semeiotic constitutions do exist and are based on a functional mitochondrial cytopathy, almost always passed on via maternal way, ICAEM-. From these constitutions, through stages of Pre-Metabolic Syndrome, classical and “variant” (www.semeioticabiofisica.it/microangiologia.it), and metabolic, classical e variant as well, it is possible to arrive at the most common and serious human pathologies: diabetes, dyslipidaemia, obesity, hypertension, glaucoma, osteoporosis (37), cancer (5, 6).
In 70s, the discover of Congenital Acidosic Enzyme-Metabolic Histangiopathy-, found out to be conditio sine qua non of most serious and common human diseases, suggested me the possible and foreseeable existence of a Unified Pathogenetic Theory, as source of the onset of these pathologies. Indeed, in three decades, on the base of biophysical-semeiotic clinical data I gathered bed-side, I proved that “all” (“all”, easily questionable, is rich of information since it is also easy to falsify) diabetic, hypertensive, dyslipidaemic, oncologic, glaucomatous, osteoporotic, lithiasic, etc. patients, had and/or have ICAEM-, corroborating my theory on the existence of a common pathogenic mecchanism.
In 90s, the discover and further description of the several biophysical-semeiotic constitutions had a key-role in the definition of Unified Pathogenetical Theory, inspiring the investigation of the evolution of ICAEM-, in its several constitutions (White Zone), to the onset of several diseases (Black Zone), going through the pre-metabolic, classical e variant, which represents the Grey Zone. It is a matter of analysing the alteration caused by environmental factors of risk on mitochondrions which have an anomalous redox function, genetically straight from almost exclusively maternal origin, whose seriousness varies from subject to subject and in the same person from tissue to tissue, and from area to area of that tissue.
Ignoring the existence of mitochondria and consequently the fundamental importance of physiologic cellular respiration and red-ox processes, ATP production, Q cycle, glicidic-lipidic-proteic metabolism, the obstacle to the onset of cancers (= “mitochondrial” activity, and then mit-DNA, which unfortunately is still today ignored even by oncologists around the world), wise doctors of the past ordered diets able to improve the mitochondrial activities opposing, more or less effectively, damages due to organismic economy.
So, if this theory, object of the introductory article, is supported by biophisical-semeiotic data, its practical repercussions (on primary prevention and therapies for the most serious and common human diseases) will be of relevant value, as I can state on the base of my personal 47-year-long clinical experience.
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Specialist in Blood, Gastrointestinal, and Metabolic Diseases