Treatment of multiple sclerosis with recombinant interferon alfa-2b (pilot study)

Multiple Sclerosis (MS) is an inflammatory-demyelinating disease of the Central Nervous System (CNS). It is characterized in the acute period by the presence of an inflammatory cellular infiltrate with breakdown of the blood-brain barrier. Although remyelination can occur at any time, glial proliferation determines scarring.

Only symptomatic treatments are available with the use of steroids, especially high doses of methylprednisolone that shorten the duration and intensity of relapses. However, to date, there is no effective treatment to modify the course of the disease in the chronic progressive form, while in the exacerbation-remission (ER) form it has recently been shown that interferons (IFN) can change the natural history of this clinical form.

IFNs are biological response modifiers with antiproliferative, antiviral and immunomodulatory actions. It has been shown that IFN gamma or type II plays a pathogenic role in the development of MS, while this action is counteracted by type I IFNs, alpha and beta, which share the same receptor on the cell membrane and certain structural homology.

Type I IFNs have been shown to reverse many of the CNS immune alterations that occur in MS:.

Numerous clinical trials have been conducted with IFN in MS. Two preparations of recombinant IFN beta (the one produced in bacteria and the glycosylated one, produced in mammalian cells), have been shown to be effective in reducing the frequency of relapses in exacerbation-remission MS (ER-MS), as well as in reducing the progression of neurological disability and lesions observed by nuclear magnetic resonance (MRI) images.

These results derive from a study in nine patients with characteristic lesions of the disease using magnetic resonance imaging and oligoclonal bands (IgG bands) in the cerebrospinal fluid without presenting alterations in the motor and sensory conduction speeds of the four extremities.

Cytogenetic evaluation with G-banding techniques

In this technique, metaphase chromosomes (about 450 bands) are analyzed using trypsin and giemsa as dyes. In this way we can observe the chromosomes with light bands and dark bands, with which the different pairs of chromosomes can be differentiated. Through banding, chromosomal anomalies are detected: Numerical (trisomies, monosomies...); structural (deletions, duplications, translocations...). This is a routine technique in genetic evaluation that allows the diagnosis to be made in 4-34.1% of children with maturational delay/mental retardation. It is a simple and economical technique, although it has the drawback that it does not detect very small anomalous structural segments.

Cytogenetic evaluation with G-banding and high resolution techniques

Analyze chromosomes in prometaphase (equal to or greater than 600 bands). These studies are useful for detecting deletions and duplications that may go unnoticed with the previous technique. The authors agree that in children with a greater number of dysmorphisms and more significant mental retardation, chromosomal anomalies are more frequently found.

Subtelomeric FISH

The use of the analysis method in subtelomeric regions for the etiological investigation of mental retardation is associated with the discovery that in these regions there is a high concentration of functioning genes that, through arrangements, produce clinical anomalies. The technique consists of the use of multiprobe FISH (multiple FISH technique) for these regions. Very variable percentages of detection of subtelomeric pathologies are described in children with moderate-gave mental retardation: 6.5-7.4% and 0.5-10.3% in individuals with mild mental retardation.

Comparative genomic hybridization (CGH) or microarray

This recent technique allows, through the use of DNA microchips (microarrays), the simultaneous exploration of multiple areas of the genome or chromosomes. To compare specific areas of DNA from two different genomes: from the patient and from a known control (control).

This technique, which detects anomalies with a resolution of approximately 1Mb, diagnoses imbalances in 14-20% of idiopathic mental retardations.

Screening techniques

It is an automated epfluorescent microscopy system for image acquisition and subsequent analysis. Using biochemical markers, especially alpha-fetoprotein (AFP), beta-chorionic gonadotropin (b-hCG), Associated Plasma Protein A (PAPP-A) and unconjugated estriol (UE), it allows non-invasive <<screening>> of chromosomal abnormalities in patients younger than 35-38 years.

Using neuroimaging techniques, attempts are made to find brain alterations that are characteristic of schizophrenia. Among them we can highlight magnetic resonance imaging and positron emission tomography (PET) and single photon emission tomography (SPECT).

There are also other groups of diseases associated with the nervous system that have not been treated and numerous fields of research for the development of new techniques applied to neuroscience: Techniques in Genomics and Proteomics; Cellular therapy; Preimplantation Genetic Diagnosis (PGD)&action=edit&redlink=1 "Preimplantation Genetic Diagnosis (PGD) (not yet written)");Magnetoencephalography Techniques"); etc.

These techniques are producing encouraging results in diseases such as those mentioned and other disorders such as: the rehabilitation of brain injuries (Fregni & Pascual-Leone, 2007), epilepsy, pain, sleep disorders, depression, obsessive-compulsive disorder and attention deficit and hyperactivity disorder (Butnik, 2005), etc. In addition, virtual reality is being applied to the psychological treatment of post-traumatic stress disorders, anxiety and phobias. This consists of introducing the patient into a virtual environment to gradually and repeatedly expose him to the object that causes fear (insects, heights, open spaces, crowds, etc.), so that the patient ends up becoming desensitized to the situations that induced extreme anxiety reactions.

In the workplace, neuroergonomics stands out (Parasuraman & Rizzo, 2007). Neuroergonomics aims to improve human-machine interaction through the application of knowledge about the brain. Virtual reality is also used in neuroergonomics, for example, to safely study how workers would behave in computer-simulated dangerous situations (a fire or explosion in a factory), and to train workers in complex tasks such as piloting airplanes and telesurgery. Another application consists of designing devices to monitor the psychophysiological activity of the worker (muscle and brain activity, heart rate, sweating, breathing and blinking frequency, etc.) to avoid states of drowsiness, fatigue, distractions or negative emotions during the execution of dangerous tasks.

Neuroscience in architecture

General background.

Being neuroscience, the science that deals with the nervous system, cognitive neuroscience has emerged as support for the complex study of man, making a synthesis between cognitive psychology, neuroscience and computer science. “The objective of neuroscience is to understand the mind: how we perceive, move, think and remember” (SUTIL & PERAN, 2012).

Establishing a balance with our mind and the physical space we inhabit improves human well-being and facilitates cognitive functions, favoring the design of spaces for healing, education and creativity, it is necessary to accept the historical and embodied essence of human existence, experience, cognition and memory.

Scientific basis.

Neuroscience and environmental psychology studies have developed discoveries between architecture and the study of the brain, pioneered by neuroscientist Fred H. Gage of the Salk Institute for Biological Studies, La Jolla, California, who in 1998, together with Peter Eriksson of Sahlgrenska University Hospital, Gothenburg, Sweden, announced the discovery that the human brain is capable of producing new nerve cells (neurons) in adulthood and that this is facilitated by an environment rich in stimuli.

Based on this, the Academy of Neurosciences for Architecture (ANFA [1]), founded in 2003 in San Diego, trusts that brain science is capable of generating architectural development and its mission is to promote the advances discovered in the lines of neuroscience to bring closer understanding of the human stimuli caused by the constructed building.

Relationship with architecture.

The architectural context gives the human experience a unique structure and meaning through photogrammatic projections and specific horizons for the perception and understanding of our own existential situation. (Pallasma, 2013).

Recent insights into the complexities of the study of the human brain and nervous systems emphasize the innate multisensory nature of our existential architectural experiences.

The work of architecture has become a partner in the development of knowledge and behavior, the purpose of which is to increase the capabilities of being at the service of society.

Architecture being a social discipline, it is important to know what function it has with respect to other disciplines, particularly with neurosciences. The task of architecture extends beyond its materiality, functionality and dimensions and even beyond aesthetics, into the mental and existential sphere of living.

Antonio Damasio, a neurologist who studies the neurobiological bases of human life, says that "The brain can act directly on the object itself that it is perceiving. It can do so by modifying the state of the object, or by altering its transmission of signals."

The perception of architectural space as favorable or unfavorable in emotions or behaviors is influenced by individual experiences and thinking, as well as by design pickpockets in the space.

Researchers.

Some researchers comment that: “It involves considering how each aspect of an architectural environment could influence certain brain processes, such as those related to stress, emotion, and memory,” Eve Edelstein), Ph.D., professor, neurologist, and architect.

John Zeisel"), delves into the field of neuroscience to describe the impact of buildings and spaces on our lives. It is about “knowing ourselves from the inside, to be able to conceive buildings and spaces in line with our well-being, not only physical, but also mental.”

Neuroscience is associated with psychophysics, which studies behavior and reactions to different spaces, in a pragmatic, stimulus-response way, also with environmental psychology, biophilic design and many others.

"We certainly have similar remains in our mental constitution, of our biological and cultural historicity; one aspect of such deeply hidden memory was pointed out by Sigmund Freud and Carl G Jung, namely, of archetypes. Jung defined archetypes dynamically as certain tendencies of distinct images to evoke certain types of associations and feelings." (Pallasma, 2013).

Research.

Meredith Bnasiak, associate research architect ANFA (Academy of Neuroscience for Architecture), teaching at the University of Colorado in a graduate seminar on “Design with the Brain in Mind,” which examines the connections between cognitive science and our environment.

As part of his research with Dr. Layne Kalbfleisch, cognitive neuroscientist and director of KIDLAB at the Krasnow Institute, George Mason University, they conducted an examination of scale effects on cognition in children and the aging population, and the role of visual stimuli in problem solving.

Eve Edelstein, Ph.D. in neurophysiology, working with Professor Eduardo Macagno and the California Institute of Telecommunications and Information Technologies (Calit2), the team has developed synchronous systems to explore the human body and brain for response to design while immersed in full-scale, three-dimensional projections of a building within a virtual reality “CAVE.”

With a research grant from HMC Architects, they created innovative software that allows architects to immediately experiment and evaluate design changes in which multiple design hypotheses can be tested. The team developed remote EEG systems to track navigation and visual attention, tracking how a person reacts to cues to find specific paths and architectural features.

REFERENCES.

DAMASIO, A. (2006). In search of Spinza. Neurobiology of emotion and feelings. Barcelona: (Spanish translation by Joandomenec) Editorial Crítica.

ERIKSSON, S. P., PERFILIEVA, E., BJORK-ERIKSSON, T., ALBORON, A.-M., NORDBORG, C., PETERSON, D., and others. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine.

SUTIL, L., & PERAN, J. L. (2012). Neuroarchitecture and consumer behavior: a design model proposal. King Juan Carlos University, Barcelona.

BELL, P., GREENE, T. C., FISHER, J. D., & BAUM, A. (2001). Environmental Psychology. Fifth edition.

Pallasmaa, Juhani, Mallgrave, Harry, and Arbib, Michael. Architecture and Neuroscience – a Tapio Wirkkala – Rut Bryk Design Reader. Espoo, Finland: Tapio Wirkkala Rut Bryk Foundation, 2013.

http://www.anfarch.org/.

Treatment of multiple sclerosis with recombinant interferon alfa-2b (pilot study)

Multiple Sclerosis (MS) is an inflammatory-demyelinating disease of the Central Nervous System (CNS). It is characterized in the acute period by the presence of an inflammatory cellular infiltrate with breakdown of the blood-brain barrier. Although remyelination can occur at any time, glial proliferation determines scarring.

Only symptomatic treatments are available with the use of steroids, especially high doses of methylprednisolone that shorten the duration and intensity of relapses. However, to date, there is no effective treatment to modify the course of the disease in the chronic progressive form, while in the exacerbation-remission (ER) form it has recently been shown that interferons (IFN) can change the natural history of this clinical form.

IFNs are biological response modifiers with antiproliferative, antiviral and immunomodulatory actions. It has been shown that IFN gamma or type II plays a pathogenic role in the development of MS, while this action is counteracted by type I IFNs, alpha and beta, which share the same receptor on the cell membrane and certain structural homology.

Type I IFNs have been shown to reverse many of the CNS immune alterations that occur in MS:.

Numerous clinical trials have been conducted with IFN in MS. Two preparations of recombinant IFN beta (the one produced in bacteria and the glycosylated one, produced in mammalian cells), have been shown to be effective in reducing the frequency of relapses in exacerbation-remission MS (ER-MS), as well as in reducing the progression of neurological disability and lesions observed by nuclear magnetic resonance (MRI) images.

These results derive from a study in nine patients with characteristic lesions of the disease using magnetic resonance imaging and oligoclonal bands (IgG bands) in the cerebrospinal fluid without presenting alterations in the motor and sensory conduction speeds of the four extremities.

Cytogenetic evaluation with G-banding techniques

In this technique, metaphase chromosomes (about 450 bands) are analyzed using trypsin and giemsa as dyes. In this way we can observe the chromosomes with light bands and dark bands, with which the different pairs of chromosomes can be differentiated. Through banding, chromosomal anomalies are detected: Numerical (trisomies, monosomies...); structural (deletions, duplications, translocations...). This is a routine technique in genetic evaluation that allows the diagnosis to be made in 4-34.1% of children with maturational delay/mental retardation. It is a simple and economical technique, although it has the drawback that it does not detect very small anomalous structural segments.

Cytogenetic evaluation with G-banding and high resolution techniques

Analyze chromosomes in prometaphase (equal to or greater than 600 bands). These studies are useful for detecting deletions and duplications that may go unnoticed with the previous technique. The authors agree that in children with a greater number of dysmorphisms and more significant mental retardation, chromosomal anomalies are more frequently found.

Subtelomeric FISH

The use of the analysis method in subtelomeric regions for the etiological investigation of mental retardation is associated with the discovery that in these regions there is a high concentration of functioning genes that, through arrangements, produce clinical anomalies. The technique consists of the use of multiprobe FISH (multiple FISH technique) for these regions. Very variable percentages of detection of subtelomeric pathologies are described in children with moderate-gave mental retardation: 6.5-7.4% and 0.5-10.3% in individuals with mild mental retardation.

Comparative genomic hybridization (CGH) or microarray

This recent technique allows, through the use of DNA microchips (microarrays), the simultaneous exploration of multiple areas of the genome or chromosomes. To compare specific areas of DNA from two different genomes: from the patient and from a known control (control).

This technique, which detects anomalies with a resolution of approximately 1Mb, diagnoses imbalances in 14-20% of idiopathic mental retardations.

Screening techniques

It is an automated epfluorescent microscopy system for image acquisition and subsequent analysis. Using biochemical markers, especially alpha-fetoprotein (AFP), beta-chorionic gonadotropin (b-hCG), Associated Plasma Protein A (PAPP-A) and unconjugated estriol (UE), it allows non-invasive <<screening>> of chromosomal abnormalities in patients younger than 35-38 years.

Using neuroimaging techniques, attempts are made to find brain alterations that are characteristic of schizophrenia. Among them we can highlight magnetic resonance imaging and positron emission tomography (PET) and single photon emission tomography (SPECT).

There are also other groups of diseases associated with the nervous system that have not been treated and numerous fields of research for the development of new techniques applied to neuroscience: Techniques in Genomics and Proteomics; Cellular therapy; Preimplantation Genetic Diagnosis (PGD)&action=edit&redlink=1 "Preimplantation Genetic Diagnosis (PGD) (not yet written)");Magnetoencephalography Techniques"); etc.

These techniques are producing encouraging results in diseases such as those mentioned and other disorders such as: the rehabilitation of brain injuries (Fregni & Pascual-Leone, 2007), epilepsy, pain, sleep disorders, depression, obsessive-compulsive disorder and attention deficit and hyperactivity disorder (Butnik, 2005), etc. In addition, virtual reality is being applied to the psychological treatment of post-traumatic stress disorders, anxiety and phobias. This consists of introducing the patient into a virtual environment to gradually and repeatedly expose him to the object that causes fear (insects, heights, open spaces, crowds, etc.), so that the patient ends up becoming desensitized to the situations that induced extreme anxiety reactions.

In the workplace, neuroergonomics stands out (Parasuraman & Rizzo, 2007). Neuroergonomics aims to improve human-machine interaction through the application of knowledge about the brain. Virtual reality is also used in neuroergonomics, for example, to safely study how workers would behave in computer-simulated dangerous situations (a fire or explosion in a factory), and to train workers in complex tasks such as piloting airplanes and telesurgery. Another application consists of designing devices to monitor the psychophysiological activity of the worker (muscle and brain activity, heart rate, sweating, breathing and blinking frequency, etc.) to avoid states of drowsiness, fatigue, distractions or negative emotions during the execution of dangerous tasks.

Neuroscience in architecture

General background.

Being neuroscience, the science that deals with the nervous system, cognitive neuroscience has emerged as support for the complex study of man, making a synthesis between cognitive psychology, neuroscience and computer science. “The objective of neuroscience is to understand the mind: how we perceive, move, think and remember” (SUTIL & PERAN, 2012).

Establishing a balance with our mind and the physical space we inhabit improves human well-being and facilitates cognitive functions, favoring the design of spaces for healing, education and creativity, it is necessary to accept the historical and embodied essence of human existence, experience, cognition and memory.

Scientific basis.

Neuroscience and environmental psychology studies have developed discoveries between architecture and the study of the brain, pioneered by neuroscientist Fred H. Gage of the Salk Institute for Biological Studies, La Jolla, California, who in 1998, together with Peter Eriksson of Sahlgrenska University Hospital, Gothenburg, Sweden, announced the discovery that the human brain is capable of producing new nerve cells (neurons) in adulthood and that this is facilitated by an environment rich in stimuli.

Based on this, the Academy of Neurosciences for Architecture (ANFA [1]), founded in 2003 in San Diego, trusts that brain science is capable of generating architectural development and its mission is to promote the advances discovered in the lines of neuroscience to bring closer understanding of the human stimuli caused by the constructed building.

Relationship with architecture.

The architectural context gives the human experience a unique structure and meaning through photogrammatic projections and specific horizons for the perception and understanding of our own existential situation. (Pallasma, 2013).

Recent insights into the complexities of the study of the human brain and nervous systems emphasize the innate multisensory nature of our existential architectural experiences.

The work of architecture has become a partner in the development of knowledge and behavior, the purpose of which is to increase the capabilities of being at the service of society.

Architecture being a social discipline, it is important to know what function it has with respect to other disciplines, particularly with neurosciences. The task of architecture extends beyond its materiality, functionality and dimensions and even beyond aesthetics, into the mental and existential sphere of living.

Antonio Damasio, a neurologist who studies the neurobiological bases of human life, says that "The brain can act directly on the object itself that it is perceiving. It can do so by modifying the state of the object, or by altering its transmission of signals."

The perception of architectural space as favorable or unfavorable in emotions or behaviors is influenced by individual experiences and thinking, as well as by design pickpockets in the space.

Researchers.

Some researchers comment that: “It involves considering how each aspect of an architectural environment could influence certain brain processes, such as those related to stress, emotion, and memory,” Eve Edelstein), Ph.D., professor, neurologist, and architect.

John Zeisel"), delves into the field of neuroscience to describe the impact of buildings and spaces on our lives. It is about “knowing ourselves from the inside, to be able to conceive buildings and spaces in line with our well-being, not only physical, but also mental.”

Neuroscience is associated with psychophysics, which studies behavior and reactions to different spaces, in a pragmatic, stimulus-response way, also with environmental psychology, biophilic design and many others.

"We certainly have similar remains in our mental constitution, of our biological and cultural historicity; one aspect of such deeply hidden memory was pointed out by Sigmund Freud and Carl G Jung, namely, of archetypes. Jung defined archetypes dynamically as certain tendencies of distinct images to evoke certain types of associations and feelings." (Pallasma, 2013).

Research.

Meredith Bnasiak, associate research architect ANFA (Academy of Neuroscience for Architecture), teaching at the University of Colorado in a graduate seminar on “Design with the Brain in Mind,” which examines the connections between cognitive science and our environment.

As part of his research with Dr. Layne Kalbfleisch, cognitive neuroscientist and director of KIDLAB at the Krasnow Institute, George Mason University, they conducted an examination of scale effects on cognition in children and the aging population, and the role of visual stimuli in problem solving.

Eve Edelstein, Ph.D. in neurophysiology, working with Professor Eduardo Macagno and the California Institute of Telecommunications and Information Technologies (Calit2), the team has developed synchronous systems to explore the human body and brain for response to design while immersed in full-scale, three-dimensional projections of a building within a virtual reality “CAVE.”

With a research grant from HMC Architects, they created innovative software that allows architects to immediately experiment and evaluate design changes in which multiple design hypotheses can be tested. The team developed remote EEG systems to track navigation and visual attention, tracking how a person reacts to cues to find specific paths and architectural features.

REFERENCES.

DAMASIO, A. (2006). In search of Spinza. Neurobiology of emotion and feelings. Barcelona: (Spanish translation by Joandomenec) Editorial Crítica.

ERIKSSON, S. P., PERFILIEVA, E., BJORK-ERIKSSON, T., ALBORON, A.-M., NORDBORG, C., PETERSON, D., and others. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine.

SUTIL, L., & PERAN, J. L. (2012). Neuroarchitecture and consumer behavior: a design model proposal. King Juan Carlos University, Barcelona.

BELL, P., GREENE, T. C., FISHER, J. D., & BAUM, A. (2001). Environmental Psychology. Fifth edition.

Pallasmaa, Juhani, Mallgrave, Harry, and Arbib, Michael. Architecture and Neuroscience – a Tapio Wirkkala – Rut Bryk Design Reader. Espoo, Finland: Tapio Wirkkala Rut Bryk Foundation, 2013.

http://www.anfarch.org/.