M Mar 12 Mar 2013 - 11:01Il a été présenté lors de la dernière conférence de l'institut des maladies neuro vasculaires, j'aime bien :-)
Ils ont oublié le rétrovirus de Fred, c'est vrai!
Using systems analysis to investigate the root causes of multiple sclerosis, developing an integrated treatment strategy
Harald U. Sverdrup (1), Kristín Vala Ragnarsdóttir (2), Thomas Ragnar Wood (3), Ulrik Sverdrup (4)
1 Chemical Engineering, Lund University, Box 124, SE-221 00 Lund, Sweden
2 Earth Sciences, University of Iceland, 101 IS-Reykjavik, Iceland
3 Guy's and St Thomas' Hospital, Great Maze Pond, London SE1 9RT, Great Britain
4 Physics Engineering Programme, LTH, Lund University, SE-221 00 Lund, Sweden
Abstract We have been able to show that multiple sclerosis is a systemic illness with multiple interacting causes and mechanisms, by applying the methods of systems analysis to the problem. The results were obtained by synthesizing state-of-the-art research into a whole systemic picture. Some main components make up the illness system:
1. The root cause: Permeable blood-brain barrier (BBB) and transmission of provocative substances, antibodies and leucocytes into the brain, caused by:
a. Chronic cerebro-spinal vascular insufficiency (CCSVI), caused by valve malfunction, venous stenosis and venous blockage, causing reductions in blood flow through the brain and stagnant flow in capillaries, leading to microclotting and puncturing of the BBB
b. Venous inflammation, and stimulus of MMP by Interleukin 1b, leading to BBB permeability
c. Histamine overload, leading to BBB permeability
2. Triggers:
a. Antibodies to myelin and oligodendrocytes from
i. infections of certain bacteria and viruses;
ii. allergic attacks
iii. myelin and oligodendrocyte debris in the blood stream and the cerebro-spinal fluid
iv. Food particles leaking into the blood, most important are gluten and proteins from dairy products
3. Reinforcing loops:
a. Feedback system involving iron in the autocatalytic Fenton cycle and production of oxidants and free reactive radicals, prominently peroxynitrite, reinforcing the increased permeability of the BBB; keeping the BBB compromised
b. Immune response feedback loop involving immune system and myelin sheath breakdown, leading to brain side damages to the BBB, driven by oxidative denaturalization of the myelin surfaces.
c. Oxidant stresses, leading to scaring at damaged sites and impairment of the ability to repair myelin sheaths, making the physical damage permanent
The different causal mechanisms were linked together into one integrated model. Our analysis shows that multiple sclerosis has no single cause, it is a system of causes that in a feedback system produces multiple sclerosis as output. Qualitatively, the model is capable of describing the untreated progress of the illness as it has been observed in patients. Multiple sclerosis is contracted by a combination of several factors; an opening of the blood-brain-barrier under a prolonged period of time, provocative substances available in the blood to initiate a vicious cycle of oxidative stresses and an immune attack, set in three nested reinforcing loops. The conceptual model was used to investigate the dynamics of the illness and understand its initiation and subsequent illness progression. With the model we analyse how treatment and a cure for multiple sclerosis must be approached in a multi-disciplinary way in order to be successful. The conceptual model was further developed into a dynamic simulation model in the STELLA environment based on an interlinked differential equation system. The simulation model is capable of reconstructing the basic outline of the illness, the onset at 20-30 years of age, the transition to primary progressive at 45-55 years of age. This seems to confirm the validity of the fundamental features of our model.
Ils ont oublié le rétrovirus de Fred, c'est vrai!
Using systems analysis to investigate the root causes of multiple sclerosis, developing an integrated treatment strategy
Harald U. Sverdrup (1), Kristín Vala Ragnarsdóttir (2), Thomas Ragnar Wood (3), Ulrik Sverdrup (4)
1 Chemical Engineering, Lund University, Box 124, SE-221 00 Lund, Sweden
2 Earth Sciences, University of Iceland, 101 IS-Reykjavik, Iceland
3 Guy's and St Thomas' Hospital, Great Maze Pond, London SE1 9RT, Great Britain
4 Physics Engineering Programme, LTH, Lund University, SE-221 00 Lund, Sweden
Abstract We have been able to show that multiple sclerosis is a systemic illness with multiple interacting causes and mechanisms, by applying the methods of systems analysis to the problem. The results were obtained by synthesizing state-of-the-art research into a whole systemic picture. Some main components make up the illness system:
1. The root cause: Permeable blood-brain barrier (BBB) and transmission of provocative substances, antibodies and leucocytes into the brain, caused by:
a. Chronic cerebro-spinal vascular insufficiency (CCSVI), caused by valve malfunction, venous stenosis and venous blockage, causing reductions in blood flow through the brain and stagnant flow in capillaries, leading to microclotting and puncturing of the BBB
b. Venous inflammation, and stimulus of MMP by Interleukin 1b, leading to BBB permeability
c. Histamine overload, leading to BBB permeability
2. Triggers:
a. Antibodies to myelin and oligodendrocytes from
i. infections of certain bacteria and viruses;
ii. allergic attacks
iii. myelin and oligodendrocyte debris in the blood stream and the cerebro-spinal fluid
iv. Food particles leaking into the blood, most important are gluten and proteins from dairy products
3. Reinforcing loops:
a. Feedback system involving iron in the autocatalytic Fenton cycle and production of oxidants and free reactive radicals, prominently peroxynitrite, reinforcing the increased permeability of the BBB; keeping the BBB compromised
b. Immune response feedback loop involving immune system and myelin sheath breakdown, leading to brain side damages to the BBB, driven by oxidative denaturalization of the myelin surfaces.
c. Oxidant stresses, leading to scaring at damaged sites and impairment of the ability to repair myelin sheaths, making the physical damage permanent
The different causal mechanisms were linked together into one integrated model. Our analysis shows that multiple sclerosis has no single cause, it is a system of causes that in a feedback system produces multiple sclerosis as output. Qualitatively, the model is capable of describing the untreated progress of the illness as it has been observed in patients. Multiple sclerosis is contracted by a combination of several factors; an opening of the blood-brain-barrier under a prolonged period of time, provocative substances available in the blood to initiate a vicious cycle of oxidative stresses and an immune attack, set in three nested reinforcing loops. The conceptual model was used to investigate the dynamics of the illness and understand its initiation and subsequent illness progression. With the model we analyse how treatment and a cure for multiple sclerosis must be approached in a multi-disciplinary way in order to be successful. The conceptual model was further developed into a dynamic simulation model in the STELLA environment based on an interlinked differential equation system. The simulation model is capable of reconstructing the basic outline of the illness, the onset at 20-30 years of age, the transition to primary progressive at 45-55 years of age. This seems to confirm the validity of the fundamental features of our model.
Dernière édition par Fred1208 le Mar 12 Mar 2013 - 13:02, édité 1 fois (Raison : Edition pour plus de visibilité, balises inutiles supprimées)
