.

1. POSTER ABSTRACT DUBAI 2020 DEMENTIA
“2nd International Conference on Dementia & Alzheimer’sDisease”which is going to be held in the month of 8 -10thApril, 2020 in
Dubai,UAE
Title : THE TURING MACHINE THEORY FOR SOME SPINAL CORD AND BRAIN CONDITION , A TOXICOLOGICAL – ANTIDOTIC
DEPURATIVE NEW APPROACH.
Authors
1) Mauro luisetto , applied pharmacologist , Europeanspecialist lab. Medicine, IMA academ. Branch General Toxicology Italy 29121
maurolu65@gmail.com
2) Behzad Nili Ahmadabadi, Pharm D/PhD innovativePharmaceutical product development specialist, USA
3) Ahmed Yesvi Rafa, Founder and President YugenResearch org. ,Independent Researcher, Bangladesh
4) Ghulam Rasool Mashori, professor of pharmacology , Department of Medical & Health Sciences for Woman, Peoples University of
Medical and Health Sciences for Women, Pakistan
5) Farhan Ahmad KhanProfessor & Head Department of Pharmacology Government Medical College andHospital Shahdol, M.P., India.
Keywords: SPINALCORD, BRAIN , DEGENERATIVE DISEASE, TRAUMA , IMMUNE DISEASE ,NEUROTOXICITY PATHOLOGY ,
TOXICOLOGY,PHARMACOLOGY , DEPURATIVE METHODS ,INFORMATICS , ALGORYTMS
Abstract
Aim of this research and review work is to produce a general theory related an new depurative strategy to be verified for reduce or delay some
spinal cord and brain degenerativeand inflammatory- chronic disease or acute traumatic condition .It is used and informatics approach in
order to set adequately the problem and the process .Scopeof this project is to submit to the researcher a new therapeutic strategy ( under a
depurative- toxicological-pharmacological ) in this complex kind of disease. A TURING machine THEORY say us a method to TRASLATEthe
need of a strategy in a practical hypotesys Of work . A global- conceptual map can help in this field.
Introduction
This poster abstract start from a recent publication related some neurodegenerative condition : The turing machine theory for some
spinal cord and brain condition, A toxicological – antidotic depurative approach. J Neurosci Neurol Disord. 2019; 3: 102-134.
https://doi.org.10.29328/journal.jnnd.1001023
But Before to start this work is crucial to verify what happenin other field like botany :

2. IN ARTICLE Amiotrophyc Lateral Sclerosis and Endogenous -Exogenous Toxicological Movens:New model to verify other Pharmacological
Strategies 2018 is reported that :
“This work start from some question related neuro-degenerative disease and related other science : in article Brain and immune system: KURU
disease a toxicological process was written observing also the different degenerative brain -disease, with accumulation we can verify if exist an
immune systems role.(AD, PD, Lewy Body Dementia, Pick disease and other CNS amyloidosis) NEURO-DEGENERATIVE PROTEIN RELATED
DISEASE (tau-patie), with brain accumulation andinterferencewith many cognitive functions.
Are there similarity in some neuro-degenerative pathology like Tua-patie, alfa – sincucleino-paty and CJD, prions disease? Andrelated to other
progressive dementias suchas AD and PD, ALS ? (catabolic- cumulated immunetoxic mediated
process ?) Is universally know that in example some plants producesalckaloids as bioproducts in their metabolism not having excretor
apparatus as other animal organism.
Can we consider waste of immune systems some accumulationsubstanties’ in some brain- Pathology?(Materials that cannot leave from central
nervous system:a global catabolic- afinalistic process?) Observing this scientific - literature we can say that some neurologic disease canpresent
common aspect:Accumulationof some metabolic- catabolic toxic substantia and relatedto the progression of disease and involved with immune
system activation.”
And also some question can be usefull to the scope of this research :
Why in example different regionof brain ( and different function ) are involved in the different neuro-degenerative- inflammatory pathology ?
In example DA - cortical – cognitive , PD in basal nuclei – movement, ALS often spinal cord involvement – progressive paralisys ?
Why in dementia are more involved cortical neuron (andhippocampus ) vs spinal ? there is a gradient ( top-bottom ) ?
The selective sensibility of the various type of neurons or other factors can influencethe process?
Other question : in many neuro-degenerative diseasethere is an increase of some catabolic-metabolic products that can produceor are related to
the neuro-degeneration( DA, PD et other ) .
And is involved also a kind of “waste system “ of SNC?
BEE is a natural barrier that protect SNC from toxic substantia, but this barrier is also efficacy in reverse sense : from inside SCN to outside ?
And the role played by cephalo- rachidan liquid ? like a blood and lymphatic role played in other organ.
A brain omeostatic fluid .( in brais is absent a lymphatic structure organized) .BEE contribute to physiology of the cephalo rachidion fluid
composition .
Why the space between brain cells may increase during sleep, allowing the brain to flush out toxins that build up during waking h ours.?
It depend by position ? or due by different brain activation level?
And what imply human evolution as bipedal position? In brain wastingsystem efficacy ?
Related evolutionof vertebrates : cortex is a more recent structure than spinal cord , mesencefalus andrombencephaus so is possible to say that
the washing central nervous system present a different efficacy in kinetics of the “washing activity” form catabolites?
There is a reason why in DA are involved more cortex andhippocampus thanspinal cord? In a sort of gradient different from top to bottom ?
And this can be related to physiology of wasting brain system?

3. In DA cognitive problems are more than other spinal damages effect.
BBB present the same barrier properties also from inside of SNC and outside like form external to internal ?
normal brain function requires a large amount energy, to supply enough oxygenand remove adequate amounts of wastes for respiration, large
ne2rks of capillaries must be constructedin the brain for molecular exchange.
A high prevalence of capillaries allows for quick diffusion of reactants andproducts of respiration, and increases the possibility that other contents
in the blood may diffuse across the capillary wall.
The BBB evolved to allow for a higher rate of selectivity for what may pass through to the brain tissueto help preserve andprotect the brain from
possible detrimental molecules or organisms in the blood.
Scope of this article is to verify some relevant condition involvingthe “ SNC washing system” that can be useful in some neuro-degenerativeor
inflammatory ( but also acute trauma) pathology .
Some image can efficacy provide exampleof this argument useful to the discussion:
Figure n 1 imanging normav vs AD and Picks disease
Figure n 2 dementia LEWY BODYES , histology

4. Figure n 3 MR findings in Dementia
Figure n 4 Alzheimer disease stages
Figure n 5 regions and neurons vulnerability in neuro-degenerativepathology

5. figure n 6 : Pathology of CNS degenerations
figure n 7 LCR flux
Figure n 8 dementia
CSF CSF is a fluid and is in SNC whit different function like to reduce the brain weight , to make possible brain perfusion at kostant pressure,
but also a Lhympatic like function .
it is under proper dynamic movement related heart activity : during systolic from lateral ventricules to 3-4 ventricules, thes intrarachidea space
and in medullar channel.

6. During diastolic phases : opposite direction
In Magendie forame and Luschka direction is always from firts compartment (intracranic)to theone extracranic (2 nd meningeal compartement
;the same for 3 th meningeal compartement .
Every organ present its wasting system to collect products of catabolism or other substantiaso is interesting to observe brain and spinal cord “
wasting system “:
Bee is a natural barrier the protect SNC from toxic subtstantia but this barrier is also a barrier to the flux in reverse WAY ? ( from CNS
to the out brain environment ?)
After this first referencereported : Observing other science like informatics and the translation of information by algorytm is possible to have
new powerful tools to better treat the neuro-degenerative disease we have see. :
Turing machine ( 1936) is a mathematical- model of computation that defines an abstract machine, that manipulates symbols on a strip of tape
according to a table of definite rules.
Algorithm: simulating that algorithm's logic can be constructed.
by A. Turing.
A Turing machine is an example of a CPU that controls all data manipulationdone by a computer, with the canonical machineusing sequential
memory to store data.
it is a machine capable of enumerating somearbitrary subset of valid strings of an alphabet; these strings are part of a recursively enumerableset.
A Turing machine has a tape of infinitelength on which it can perform read andwrite operations.
In project named ULTRA A. ( in second world war) A. Turing make possible to translate with an algoritm the secret messages produced with
ENIGMA.
Figure n 9 : ENIGMA machine (word War second secret way of communication used by Germany )
INPUT ----------------OUTPUT
In some medical condition to reduce thetoxicity os some metabolic product are used specific procedure
( depurative ) in order to reduce toxic level ( in example in blood ) .
But can we think to apply this general concept to other not classic situationlike some spinal cord neuro -degenerative condition like some ALS
forms involving SOD disfunctions or brain conditions like DA and other ?
TOXIC MICRO-ENVIRONMENT---------DETOXICANT PROCEDURE
NORMAL VELOCITYOF DISEASE PROGRESSION-------------- DELAY

7. METHODS: MEDICAL DEVICES, DEPURATIVE PROCEDURE, PERSISTANCE OF ACTIONS, LEVEL OF EFFICACY.
PRINCIPLES: the procedure must efficacy remove the toxic catabolic methabolic- pathological substantia
( using or not a pharmacological - or other phisic prcess that increase the efficacy in remove process ) .
COSNTRAINTS : NO ADDED TOXICITY OR DAMAGE TO THE TISSUE
FIGURE N 10 ) dyalisis scheme
Figure n. 11 ) peritoneal dialisy
Emoperfusion,emofiltration plasmaferesys ,
Figure n 12 ) ferrous rust

8. Forced diuresys , urine alcalinization : in some in poisoning
Also other antidothes use : COMPLEXANT agents for some heavy metal poison, Cyanide binder and other
In all this procedure a toxic substantiais removed from a body part with low damage for the organism .
Material and methods
Whit an observational approach somerelevant literature ( in our opinion)is analyzed in order to produce a global hypothesis of work to be
submitted to the researcher. ( reported in references )
All literature comes from biomedical databases ( like PUBMED ) .
After this review process a practical experimental project hypotesys ( in vitro ) is provided .
Experimental project hypotesys : in vitro
In order to verify the efficacy and safety of a SPINAL CORD neuro tissue ( or LCR ) dialitic like - depurative procedure is possible to
Hypotize a in vitro model ( animal model ?) whit a spine cord to be submitted to the procedure , using different kind of solutionor other ( lime
MD) to depurateform toxic substanties responsible of progression of some neuro-degenerative disease.
The procedure must be observed in Different time of exposition andin different level of action to find the really best condition .
( since also after acute trauma) . The right window of time to have the best result must be evalued .
The same must be verified the better direction that can provide useful effect ( SPINAL CORD top- bottom or bottom – top) andif a
pharmacological or a non- pharmacological system ( MD or other physic process) can providebetter results.
The affinity of innovative pharmacological molecule must be evalued to choose the 1 with high link with the toxic substantia ( amiloids, proteins,
amminoacids , FREE oxygen radicals and other) , with the best profile for an efficacy tissue celaracence.
Other parameter must be take in consideration like : lipophilic- idorfilic profile of toxic substantia, molecular weight, molecular conformation , links
profile , electrical charge, Idrogenbinds, and other useful to have an efficacy extraction.
Safety of the proceduce must be evalued ( histology, electric conduction and other possible) .
Discussion and conclusion
Form literature reported in references is possible to verifay that:
A)"reducedCSF turnover may be a contributing factor to the buildup of toxic metabolites andproteins that cause neuro -degenerativedisorders."
And that "reducedCSF turnover may be a contributing factor to the buildup of toxic metabolites andproteins that causeneuro -degenerative
disorders." https://news.psu.edu/story/579374/2019/07/01/research/sense-smell-pollution-and-neurological-disease-connection-explored
UNIVERSITY PARK, Pa
B)”a team of neuroscientists at the University of Rochester Medical Center has identifieda fascinatingfast-track cleansing system in the brain
called the glymphatic system” •Is reported in the article DETOXING FOR BRAIN HEALTH – NEWRESEARCH FINDINGS:CranioSacral Therapy
Improves Glymphatic Cleansingof Brain Tissue Carolyn Simon:

9. C) “In most of the body, a ne2rk of vessels carry lymph, a fluid that removes excess plasma, dead blood cells, debris and other waste. But the
brain is different. Insteadof lymph, the brain is bathed in cerebro-spinal fluid” and “ To see how waste is carried by CSFin a living mouse, they
injected the mice with radioactive molecules that could be traced using laser-scanningtechnology.
The molecules' journey beganafter being injectedinto the subarachnoid space, a cavity between membranes covering the brain and spinal cord.
The researchers observed that, like a river, CSFcarried these molecules rapidly alongspecific channels. Glial cells along the outside of arteries
form these channels, creating a flume for CSFthat follows the brain's blood vessels. In addition, the researchers foundthat these glial cells mediate
the channel's activity, assisting theflow of fluid through the channel.
From channels alongside arteries, the tracer-bearing fluid then passes throughbrain tissues. At the other end of tissues, it flows into similar
channels along veins. The fluid follows theseveins theneither returns to the subarachnoid space, enters the bloodstream or eventually drains into
the body's lymphatic system”. “the researchers injected proteins called amyloid betainto mice's brains. In Alzheimer's, this protein—present in all
healthy brains—can accumulateand clump, developinginto cell-damaging plaque. Theresearchers compared mice with a normal glymphatic
system to those with a disabled gene that prevented glial cells from assisting in the fluid flow. They found that in the normal mice, the protein
rapidly cleared from the brain along thesechannels, but amyloid removal diminished in the gene-alteredanimals”. FROM ARTICLE
https://www.scientificamerican.com/article/brain-cleaning-discovery/
D) .” Each day, the adult brain eliminates a quarter of an ounceof worn-out proteins that must be replacedwith newly made 1s, a figure that
translates into the replacement of half a pound of detritus a month andthree pounds, the brain's own weight, over the courseof a year.To survive,
the brain must have some way of flushing out debris” and “Experiments thatwe conducted inmice showed thatduring sleep, the glymphatic
system did indeed remove beta-amyloid fromthebrain with remarkable efficiency:its clearanceratemorethandoubledwith sleep” according
Maiken Nedergaardet al
E) “The primary traumatic mechanical injury to the spinal cord causes death of a number of neurons .
These events are then exacerbatedby a variety of secondary mechanisms including vascular changes, ischemia, vasospasms, hemorrhage and
thrombosis, neuro-transmitter (especially glutamate) accumulation, generationof free radicals and nitric oxide (NO), calcium overload, compromised
energy metabolism and inflammatory factors “. Accordingarticle J. Pineal Res. 2010; 49:201–209 Melatoninplus exercise-basedneuro-
rehabilitativetherapy for spinal cord injury
F) “current research suggests that an impaired clearance in late onset AD plays a critical role in the process of amyoid formationand the
pathogensis of the disease.
Many pathways are currently being investigated,among them Peri-vascular drainage,receptor-mediated celluptake,bloodBrain barrier(BBB)
transport,and local proteolytic degradation,
All undoubtedly contributors to brain Ab clearance in Conjunction with the bulk flow of ISF into the CSF through theChoroid plexus
epithelium,which Remarkably shares many of The receptors involved inBBB clearance as well as the recently described paths for CSF recycling
through the ISF”. According FARRON et al
G)” it is known that Alzheimer’s disease primarily affects parts of the brain that play a role in memory, whereas PD predominantly affects parts of
the brain that are involved in body movement.The reasons that other brain regions remain unaffectedin these diseases are un known” . Jckson
H)” Reduction of the CSF turnover rate during ageing leads to accumulation of catabolites in the brain and CSF that are also observed in certain
neuro-degenerative diseases” Sakkaa

10. i)“Extracellular Aβ deposits can be removedfrom the brain by various clearancesystems, most importantly, transport across the blood–brain
barrier.” Tarasoff
l) “Increasing evidences suggest a link between neuro-inflammation andneuronal dysfunction in AD, orchestrated by the progressive activationof
microglial cells and astrocytes with the consequent overproductionof proinflammatory molecules.” AHMAD
m) “The present study shows that treatment with detox gel in AD mice can be effective as a therapeutic methodfor lowering Aβ levels in the
APPSWE mice(Tg2546). The highaffinity sequestering ability combined with the lack of immunogenicity and capacity to improve
memory parameters make it an interesting drugcandidate for the treatment of AD. Thus our detox gel therapy might becomea welcome non-
immune based therapy with a future in human clinical settings.”
and “ Quantitative analysis of Aβ-42 in brain Aβ in brain was extracted by methods described in experimental methods section. Aβ-42
levels were measured in brain extracts by an ELISA usinga commercial antibody. The 2step extraction methodthat we employedyields total Aβ.
The results show that there is a reduction in the level of total Aβ-42 by 30% in the group of mice that received the detox gel
when comparedto the untreated group with a statistical significance (p < 0.001)” .Int J Pept Res Ther. 2012 June 1; 18(2): 99–106.
doi:10.1007/s10989-011-9283-7.
novel Detox Gel Depot sequesters β-Amyloid Peptides in a mouse model of Alzheimer’s Disease Ranjini K. Sundaram et al
and related the Brain's Drain:Neuro-scientists Discover Cranial Cleansing System
The time of BBB evolution is unknown, but through ancient fish BBB studies Bundgaard and Abbott (2008) : invertebrates are descendants of a
common ancestor that hadevolved a glial cell based BBB before differentiation and six separate convergent evolutions of the endothelial.
They support this assumption by observations made on ancient species that still exist today (lung fish, hagfish, lamprey ) and their tendency to
retain glial cell based BBBs. evidence that this was the first type of BBB, by pointingout that many mammals for a primitive glial cell BBB in the
womb before the more complex endothelial cell BBB is formed, and many vertebrates andinvertebrates that form a endothelial BBB retain sections
of BBB made up of more permeable glial cells (Abbott 2005).
The reason for its presence is normal brain- function requires a large amount energy( to supply enough oxygen and remove adequateamounts of
wastes for respiration), large ne2rks of capillaries must be constructed in the brain for molecular exchange.
A high prevalence of capillaries not only allows for quick diffusion of reactants andproducts of respiration, increases thepossibility that other
contents in the blood may diffuseacross the capillary wall. The BBB evolved to allow for a higher rate of selectivity for wh at may pass through to
the brain tissue to help preserve /protect the brain from possible detrimental molecules or organisms in the blood.
Related the BRAIN EFFLUX status ( physiology, BEEbarrier et other factors ) and SNC clearance
Is clearly that some depurative procedure are currently applied to some poisoning or disease ( in example in severe or terminal renal failure )
But if this procedure present various level of efficacy this kind of approachis not currently applied in other
Pathology like some neuro-degenerative spinal cord disease.( ALS involved with SOD mutation ) but also in some spinal cord traumatic condition
with accumulationof amino acid after ischemia .
An informatics approachhelp in adeguately set the problem to increaseefficacy but reducing the
Risk of damage for an delicate structure.

11. The algoritm: need to detox the micro-environment and related detoxicant strategy ( OR modifying the mebabolic catabolic status) imply a not
toxicity of the procedure versus the complex and weakness tissueas the spinal cord.
The process must set the way of subministration , the mechanism of action, the safety andall over involved in a practical experience.
The question is way related blood purification with dialitic procedure is possible to reduce the toxcic urea conc. And noncan be used in other
tissue ? ( dialitic procedure to be consider as a separating procedure of toxic from tissue in every way possible : phisic – chemical-
pharmaocolgical, MABS , medical deviceor other strategy )
Depurative procedure : example
In use ? usefull Difficult procedure Do be developed? Danger
emodialisys yes yes medium Already in use accepted
Perit1al dialisys yes yes medium Already in use accepted
Emoperfusion yes yes yes Already in use accepted
Plasma exchange yes yes Medium Already in use accepted
Iperbarich therapy yes yes Medium Already in use accepted
ECMO
ExtraCorporeal
Membrane
Oxygenatio
Yes yes medium Already in use accepted
Antidotic therapy yes yes No- little-medium Already in use accepted
Spinal cord – brain
depurativestrategy
no It could be Very difficult Yes :
Hypotesys to be
verified
To be verified on
field
( in vitro model –
other model )
Other
In emodialisys : form ancient dal greck αἷμα, àima, "blood ", e διάλυσις, diàlysis, "separation, ", derivate form διαλύω, dialỳō, "distinguish ") is a
phisic therapy that replace some renal function in uremic patient in IRA .
the procedure replace4 renal function:removeof toxic substantia ,electrolitic and acido – bases re balances,liquidremove ( in anuric pz ) .
The procedure imply that blood pass trought a filter and solution ( with a semipermeabile membrane ) by witch pass only the toxic subtantia.
Related a new procedure to think depurate Brain or spinal cord tissue Possible Mechanism of action must be evaluated .
Immnunological links : mabs
Differential solubility ( idrophilic- lipophilic balance) .
Molecular weight ( differential )
Dimension – diameter of particles

12. Differential in electrical charge
Chemical : _ complexant agent
Enzymatic – remove
Facilitator of excretions : chemical groups to be linked to increase clearance
Increase factor that improve catabolism or clearance of toxic substantia
Free radicals blockers strategy .
Flogosys control ( sustained local action )
Temperature level : low level make more permeability of BEE
gamma-frequency oscillations ? IN VITRO MODEL
clearance of the system ( brain waste flux) status: kinetics
Transport at the neuro-vascular unit across the glial barrier and BBB: depends on the solubility, molecular weight and diameter of the protein.
Other
related the bibliography reported in this article a new depurative strategy to treat some spinal cord and brain neuro-degenerative –inflamatory
pathology in example ALS SOD mutation and AD. related can be hypotized procedure similar to a dyalitic LIKE process or other depurative
strategy ( in spinal cord place or LCR ).
“The wastes of brain metabolism, peroxidation products and glycosylated proteins,accumulate with age -relateddecreased CSF turnover.
Reduction of the CSF turnover rate during ageing leads to accumulation of catabolites in the brain and CSF that are also obse rved
incertain neuro-degenerative diseases.” L. Sakkaab et al
Observing the TURING machine theory is possible to verify that a conceptual map make possible to translate from a languageto other that seem
not related ( word War second and ENIGMA machine : secret way of communication ) .
The same is possible to think that a algoritm – machine can traducesome NEED in RESPONSE :
In example in some neuro-degenerative or inflammatory brain or spinal cord diseasea process that can DEPURATE
Form some toxic metabolites or immune-products can delay the progression of some severe disease.
Is possible to introduce the hypotesis that a pharmacological, antidotic ,or medical devices or other physic strategy can help in this setting
providing a sustained action duringin time or to restore the normal flux of brain wasting system?
In an animal model maoue “The results show that there is a reduction in the level of total Aβ-42 by 30% in the group of mice that received the
detox gel when compared to the untreated group with a statistical significance (p < 0.001)”
Scope of this research work is not to produce details of the procedure but that this strategy can be followed.
Can a machine better of humans verify all strategy to be used to depurate nobletissue like central nervous system consideredso
mysterious by the collective meaning?

13. A Computational- machine with artificial intelligence can help in choosing the better strategy respecting physiology of this
Delicate structure ,providing the right information about affinity of a new product to the toxic substantia and relatedto the kinetics of the elimination
process.
clarifications :
this poster abstract is produced under a toxicological- pharmacological andpharmaceutical point of view ,without any therapeutic or diagnostic
intent only to producenew research hypotesys to be submittedto the researcher
ethical consideration
this work is produced under the light of actual ethical rules , is an experimental hypotesys of work to be submitted to the researcher for future
development .
conflict of interests: NO
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