The document provides an introduction to the integrative medical approach of Endobiogeny. It discusses how Endobiogeny aims to evaluate the human organism as a whole system and in its individual units of function through both quantitative and qualitative assessments. This includes using the Biology of Functions to quantify functional abilities and determine pathogenic tendencies. It also gives examples of how this approach could be applied to cardiovascular disease and interpreting laboratory results.
Introduction to the Biology of Functions and its application to CancerKamyar Hedayat
This document provides an overview of Biology of Functions (BoF) and its application to cancer assessment and treatment. It discusses some of the shortcomings of traditional cancer research and screening/prevention methods. BoF quantifies the functional abilities of the organism through indices defined by mathematical relationships between blood analysis data. It provides a dynamic, integrated assessment of cancer risk and progression based on endocrine, metabolic, immunological and other functional factors. A case study is then presented of a child with glioblastoma multiforme treated using an individualized approach based on BoF assessments over time.
Endobiogeny is a global systems approach to biology and medicine developed by the American Society of Endobiogenic Medicine and Integrative Physiology. It views the human body as a complex system and focuses on the relationships between parts rather than individual parts. Key aspects of endobiogeny include the theory of terrain, use of biomarkers interpreted through a systems lens, and treatment including herbal medicine, diet, and lifestyle changes. Endobiogeny is taught internationally and areas of research include cancer, autoimmune disorders, and neuropsychiatric conditions.
How Molecular Structure Influences Potency of a Therapeutic BiologicMerck Life Sciences
This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
Product characterization is key to successful biological drug development. Comprehensive characterization of new therapeutic monoclonal antibodies requires a deep understanding of their structural and functional critical quality attributes (CQAs) which may impact product potency, stability and safety. Various analytical approaches can be used to characterize the effects of changes during the process of generating a biological drug.
This webinar will review some of the approaches to N-glycan profiling of monoclonal antibodies using Mass Spectrometry (MS), including Hydrogen Deuterium Exchange (HDX-MS) analytics. Using the Humira monoclonal antibody, the effect of glycosylation on the Fc-region mediated effector function was assessed with binding and CDC and ADCC activity assays. This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
In this webinar you will learn:
- HDX-MS - when and why to use
- Glycosylation effects assessment by activity assays
This document discusses a new treatment option called SGN-35 for patients with relapsed lymphoma. SGN-35 is an antibody-drug conjugate that delivers the toxic agent MMAE to CD30-positive lymphoma cells. It has shown promising response rates of 34-57% for Hodgkin's lymphoma and ALCL in clinical trials. SGN-35 works by binding to CD30 on lymphoma cells and releasing MMAE intracellularly to induce apoptosis. It has fewer side effects than standard chemotherapy and may provide an alternative treatment for patients who are not cured with initial therapy.
ROLE OF FREE RADICAL IN NEURODEGENERATIVE DISEASE
Oxidative stress in AD??
Oxidative stress occurs when there is an imbalance between t he production and quenching of free radicals from oxygen species. These reactive oxygen species (ROS) play a role in many chronic diseases including mitochondrial diseases, neurodegenerative diseases, renal disease, arteriosclerosis, diabetes , cancer.
The process of aging is also associated with increased oxidative stress. Through pathological redox reactions ROS can denature biomolecules such as proteins, lipids and nucleic acids. This can initiate tissue damage via apoptosis and necrosis.
Oxidative stress plays a central role in the pathogenesis of AD leading to neuronal dysfunction and cell death.
Peripheral markers of oxidative stress are elevated in AD indicating that the damage is not brain-limited.
The increased level of oxidative stress in the AD brain is reflected by
increased protein and DNA oxidation,
Decreased level of cytochrome C oxidase and advanced glycosylation end products.
enhanced lipid peroxidation,
Lipid peroxidation can weaken cell membranes causes ion imbalance and impair metabolism.
Oxidative stress can influence DNA methylation which regulates gene expression.
Internalized beta-amyloid may play a role in this process.
Mitochondrial dysfunction, which is associated with an accumulation of ROS, appears to play a role in the early events of AD pathology.
Epigenetics is the study of mechanisms that control which genes are switched on or off. It involves epigenetic mechanisms like methylation and histone modification that manipulate the genome without changing the DNA sequence. Experiments show that exposures like chemicals, smoking, diet, and stress during pregnancy can cause epigenetic changes that affect gene expression and traits in subsequent generations. A study in Sweden found that poor harvests and malnutrition during pregnancy were associated with higher risk of cardiovascular disease in offspring, and periods of feast after famine extended this risk to grandchildren through epigenetic inheritance. Understanding epigenetics is important for studying evolution and treating diseases like cancer, genetic disorders, immunity and neuropsychiatric conditions.
Introduction to the Biology of Functions and its application to CancerKamyar Hedayat
This document provides an overview of Biology of Functions (BoF) and its application to cancer assessment and treatment. It discusses some of the shortcomings of traditional cancer research and screening/prevention methods. BoF quantifies the functional abilities of the organism through indices defined by mathematical relationships between blood analysis data. It provides a dynamic, integrated assessment of cancer risk and progression based on endocrine, metabolic, immunological and other functional factors. A case study is then presented of a child with glioblastoma multiforme treated using an individualized approach based on BoF assessments over time.
Endobiogeny is a global systems approach to biology and medicine developed by the American Society of Endobiogenic Medicine and Integrative Physiology. It views the human body as a complex system and focuses on the relationships between parts rather than individual parts. Key aspects of endobiogeny include the theory of terrain, use of biomarkers interpreted through a systems lens, and treatment including herbal medicine, diet, and lifestyle changes. Endobiogeny is taught internationally and areas of research include cancer, autoimmune disorders, and neuropsychiatric conditions.
How Molecular Structure Influences Potency of a Therapeutic BiologicMerck Life Sciences
This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
Product characterization is key to successful biological drug development. Comprehensive characterization of new therapeutic monoclonal antibodies requires a deep understanding of their structural and functional critical quality attributes (CQAs) which may impact product potency, stability and safety. Various analytical approaches can be used to characterize the effects of changes during the process of generating a biological drug.
This webinar will review some of the approaches to N-glycan profiling of monoclonal antibodies using Mass Spectrometry (MS), including Hydrogen Deuterium Exchange (HDX-MS) analytics. Using the Humira monoclonal antibody, the effect of glycosylation on the Fc-region mediated effector function was assessed with binding and CDC and ADCC activity assays. This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
In this webinar you will learn:
- HDX-MS - when and why to use
- Glycosylation effects assessment by activity assays
This document discusses a new treatment option called SGN-35 for patients with relapsed lymphoma. SGN-35 is an antibody-drug conjugate that delivers the toxic agent MMAE to CD30-positive lymphoma cells. It has shown promising response rates of 34-57% for Hodgkin's lymphoma and ALCL in clinical trials. SGN-35 works by binding to CD30 on lymphoma cells and releasing MMAE intracellularly to induce apoptosis. It has fewer side effects than standard chemotherapy and may provide an alternative treatment for patients who are not cured with initial therapy.
ROLE OF FREE RADICAL IN NEURODEGENERATIVE DISEASE
Oxidative stress in AD??
Oxidative stress occurs when there is an imbalance between t he production and quenching of free radicals from oxygen species. These reactive oxygen species (ROS) play a role in many chronic diseases including mitochondrial diseases, neurodegenerative diseases, renal disease, arteriosclerosis, diabetes , cancer.
The process of aging is also associated with increased oxidative stress. Through pathological redox reactions ROS can denature biomolecules such as proteins, lipids and nucleic acids. This can initiate tissue damage via apoptosis and necrosis.
Oxidative stress plays a central role in the pathogenesis of AD leading to neuronal dysfunction and cell death.
Peripheral markers of oxidative stress are elevated in AD indicating that the damage is not brain-limited.
The increased level of oxidative stress in the AD brain is reflected by
increased protein and DNA oxidation,
Decreased level of cytochrome C oxidase and advanced glycosylation end products.
enhanced lipid peroxidation,
Lipid peroxidation can weaken cell membranes causes ion imbalance and impair metabolism.
Oxidative stress can influence DNA methylation which regulates gene expression.
Internalized beta-amyloid may play a role in this process.
Mitochondrial dysfunction, which is associated with an accumulation of ROS, appears to play a role in the early events of AD pathology.
Epigenetics is the study of mechanisms that control which genes are switched on or off. It involves epigenetic mechanisms like methylation and histone modification that manipulate the genome without changing the DNA sequence. Experiments show that exposures like chemicals, smoking, diet, and stress during pregnancy can cause epigenetic changes that affect gene expression and traits in subsequent generations. A study in Sweden found that poor harvests and malnutrition during pregnancy were associated with higher risk of cardiovascular disease in offspring, and periods of feast after famine extended this risk to grandchildren through epigenetic inheritance. Understanding epigenetics is important for studying evolution and treating diseases like cancer, genetic disorders, immunity and neuropsychiatric conditions.
This document discusses biomarkers in diabetes, including:
1. Biomarkers can help improve understanding of disease processes, predict disease severity and complications, and monitor treatment efficacy.
2. Liver enzymes like ALT and GGT, inflammatory markers like CRP and IL-6, and adipokines like adiponectin have been implicated in diabetes pathogenesis.
3. Simple risk scores combining basic measures like HbA1c and lipids can effectively predict diabetes, though more research is still needed on novel biomarkers.
The cell cycle and molecular basis of cancer can be summarized as follows:
The cell cycle is tightly regulated by cyclins, cyclin-dependent kinases (CDKs), and their inhibitors to ensure proper cell division and growth. Defects in cell cycle regulation can lead to uncontrolled cell growth and cancer. Cancer develops through the accumulation of genetic mutations in oncogenes and tumor suppressor genes, which disrupt the normal cell cycle checkpoints and allow cells to proliferate uncontrollably. Key cellular capabilities acquired during cancer progression include self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.
This document summarizes the achievements and work of an expert in regenerative medicine. In three sentences:
The expert has received national and international awards for outstanding work in regenerative medicine. They have treated over 2,000 patients using cellular medicine and have published extensively in the field. The expert focuses on stem cells and their role in tissue regeneration, and has represented their country at international conferences on shifting medicine from a traditional to cellular model.
This document discusses biosimilars, which are biologic products that are highly similar to approved biologic reference products. It provides background on biosimilars, including their development process, advantages, limitations, and future outlook. The development process involves producing a cell line containing the gene for the desired protein, growing cells to produce the protein, purifying the protein, and preparing it for patient use. Biosimilars offer cost savings over biologics but have concerns around immunogenicity and long-term effects when switching between products. The global biosimilar market is expected to grow significantly as biologic patents expire and more companies develop biosimilar versions of treatments.
Developmental Origins of Obesity: The Role of Epigeneticszferraro
This presentation will:
- Review the concept of ‘fetal programming’
- Demonstrate that early life nutritional events may serve as molecular memory of individual in utero experiences
- Show how changes persist following multiple rounds of cell division
- Highlight extrinsic (recapitulation) & Intrinsic (genetic) mechanisms that strongly suggest Intergenerational transmission of traits via epigenetics in humans
- Look at how to best move forward as a scientific and clinical community
This document discusses the biology of healthy aging and longevity. It covers several topics:
1) Molecular mechanisms of aging including genome integrity, telomeres, epigenetics, protein stability, and pathways like mTOR, IIS, AMPK, and sirtuins that modify aging.
2) Biological models like yeast, worms, flies and mice that are used to study aging mechanisms.
3) Calorie restriction which increases longevity across species by reversing signs of aging.
4) Maintaining genome, telomere and epigenome integrity is important for healthy aging and preventing diseases.
5) Environmental factors and nutrition influence aging through epigenetic changes.
Recent research suggests that a variety of lifestyle - especially dietary - changes influencing the integrity of gastrointestinal function may be driving at least some portion of the increased prevalence of illnesses of civilization, including neuropsychiatric problems, such as autism, attention-deficit-hyperactivity disorder, major depression, obsessive-compulsive disorder and Alzheimer disease. One area of interest involves the relationship between the gut's microbiome (as well as the related functional integrity of the gastrointestinal tract) and mental health.
This document discusses the concepts of psychopharmacogenomics and provides examples of its applications. It begins by defining key terms like pharmacogenomics, pharmacogenetics, and psychopharmacogenomics. It then discusses the role of single nucleotide polymorphisms (SNPs) and cytochrome P450 enzymes in drug metabolism and response variability. The document provides examples of how genetic polymorphisms can impact drug dosage requirements and adverse reactions for medications metabolized by CYP2C9 and CYP2D6. Finally, it summarizes findings from pharmacogenomic studies on antidepressants, mood stabilizers, and antipsychotics in relation to specific genes.
Oracle JSON treatment evolution - from 12.1 to 18 AOUG-2018Alexander Tokarev
The presentation was prepared for Austria Oracle User group 30 years. It tells us a lot of challenges which Oracle developers face with implementing high-load json processing pipelines.
In this SlideShare, we'll be diving into Epigenetics and the unexplored approaches in therapeutics. Epigenetics refers to external modifications to DNA that turn genes ‘on’ or ‘off.’ These modifications do not change the DNA sequence itself, but instead, they alter the physical structure of DNA, which affects how our cells ‘read’ genes. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic therapy offers a potential way to influence those pathways directly.
The Journal of Biomarkers in Drug Development (JBDD) promotes rigorous research that makes a significant contribution in advancing knowledge for Biomarkers in Drug Development. JBDD includes all major themes pertaining to Biomarkers used in Drug Development.
Epigenetics refers to modifications that occur on top of genes in response to environmental factors like diet and stress. These modifications involve chemical tags that can turn genes on or off without altering the underlying genetic code. Studies show these epigenetic tags can be inherited from parents and influence stress response and tolerance in offspring. The environment can thus change our genes across generations through epigenetic mechanisms.
DOSTARLIMAB - A potential cure for Cancer. A programmed death-1 (PD-1) inhibitor called DOSTARLIMAB has been licensed for the treatment of certain tumors that have advanced during or after prior therapy and do not have any promising alternative choices. Dostarlimab has also demonstrated encouraging outcomes in the treatment of breast cancer, melanoma, head and neck cancer, endometrial cancer, and ovarian cancer. Dostarlimab, a monoclonal antibody against the programmed cell death protein (PD-1) that has been shown to completely (100%) cure patients with colorectal cancer, has enchanted the medical community in this period of rapid advancement. Also, none of the study participants experienced any significant negative effects, according to the findings of clinical trials. • Dostarlimab slows the growth of tumors and boosts the immune system's ability to combat cancer cells.
Epigenetics refers to modifications to DNA that change gene expression without altering the DNA sequence. These modifications, such as methylation, can be inherited and influence traits in offspring. Experiments show that environmental factors like chemical exposure, diet, and stress experienced by parents or grandparents can cause epigenetic changes leading to disease in subsequent generations, despite those generations not directly experiencing the original stressor. Further research on epigenetics may lead to new treatments for diseases and insights into disorders that differ between identical twins.
Cancer is characterized by uncontrolled cell growth and spread. At the cellular level, cancer cells proliferate excessively, grow in an uncoordinated manner, and infiltrate surrounding tissues. This uncontrolled growth is caused by genetic disorders that affect genes regulating cell growth. Cancer cells lose control over growth and multiplication and do not self-destruct like normal cells. They crowd out healthy cells. Genetic changes can activate oncogenes or inactivate tumor suppressor genes, disrupting the normal balance between cell proliferation and cell death. A variety of genetic, environmental, and viral factors can cause these genetic changes and contribute to cancer development.
Stem cells are unspecialized cells that can renew themselves and differentiate into specialized cell types. There are two main types: pluripotent stem cells like embryonic stem cells which can become any cell type, and adult or multipotent stem cells which can only become certain related cell types. Stem cells have properties of self-renewal and differentiation that make them useful for research, drug development, and cell therapies.
RAADfest 2019 Bill Faloon's Senolytics Slidesmaximuspeto
Senolytics are compounds that selectively destroy senescent cells and reduce signs of aging. Studies show that removing senescent cells in mice through senolytic drugs extends healthy lifespan, improves organ function, and delays age-related diseases. The first human trial of a senolytic drug combination showed improvements in physical function and markers of aging. Further research is exploring the potential benefits of senolytics for treating age-related conditions like diabetes, Alzheimer's, and cancer.
Humanized antibodies are antibodies made from non-human species whose protein sequences have been modified to increase their similarity to human antibodies. There are several technologies used to produce humanized antibodies including grafting complementarity determining regions from mouse antibodies onto human frameworks, using transgenic mice with human immunoglobulin genes, and phage display to select antibodies from human libraries. Humanized antibodies have the advantage of reducing immunogenicity while maintaining therapeutic value compared to murine or chimeric antibodies.
The document discusses the complex bidirectional communication between the gut and brain, known as the gut-brain axis. It outlines several key players in this communication: (1) the gut microbiome, which contains trillions of microbes that can influence brain development and mental health; (2) neuroactive substances like serotonin that are produced by microbes and can affect the brain; and (3) microbial metabolites like short-chain fatty acids and tryptophan derivatives that can modulate neuronal and immune function. The vagus nerve, gut hormones, and immune signals transmitted via the microbiome all help facilitate dialogue between the gut and brain. Disruptions to this gut-brain axis are implicated in several neurological and psychiatric disorders.
This document provides an introduction to the integrative medical approach of Endobiogeny. It discusses the objectives and components of Endobiogeny, which include a detailed patient history, physical exam, classical labs/imaging, and Biology of Functions assessment to evaluate the qualitative and quantitative state of the human organism. Endobiogeny aims to understand disease and health through an integrated analysis of physiological and endocrine relationships and functions. The document provides examples of how Endobiogeny analyzes clinical conditions like Polycystic Ovarian Syndrome through this integrative lens.
INTRODUCTION TO PAnnnnnnnnnnnnnnnnnnnn THOLOGY.pptxSubi Babu
This document provides an introduction and overview of pathology. It defines pathology as the scientific study of changes in structure and function of the body caused by disease. Key points covered include:
- Etiology (causes) of disease which can be genetic or environmental factors.
- Pathogenesis which describes the mechanism of how diseases develop.
- Morphology which refers to gross and microscopic changes seen in tissues and cells.
- Clinical significance relating to how morphological changes impact organ function and present clinically.
- Different areas of pathology study such as general pathology, clinical pathology, and importance of pathology for understanding disease and patient care.
This document discusses biomarkers in diabetes, including:
1. Biomarkers can help improve understanding of disease processes, predict disease severity and complications, and monitor treatment efficacy.
2. Liver enzymes like ALT and GGT, inflammatory markers like CRP and IL-6, and adipokines like adiponectin have been implicated in diabetes pathogenesis.
3. Simple risk scores combining basic measures like HbA1c and lipids can effectively predict diabetes, though more research is still needed on novel biomarkers.
The cell cycle and molecular basis of cancer can be summarized as follows:
The cell cycle is tightly regulated by cyclins, cyclin-dependent kinases (CDKs), and their inhibitors to ensure proper cell division and growth. Defects in cell cycle regulation can lead to uncontrolled cell growth and cancer. Cancer develops through the accumulation of genetic mutations in oncogenes and tumor suppressor genes, which disrupt the normal cell cycle checkpoints and allow cells to proliferate uncontrollably. Key cellular capabilities acquired during cancer progression include self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.
This document summarizes the achievements and work of an expert in regenerative medicine. In three sentences:
The expert has received national and international awards for outstanding work in regenerative medicine. They have treated over 2,000 patients using cellular medicine and have published extensively in the field. The expert focuses on stem cells and their role in tissue regeneration, and has represented their country at international conferences on shifting medicine from a traditional to cellular model.
This document discusses biosimilars, which are biologic products that are highly similar to approved biologic reference products. It provides background on biosimilars, including their development process, advantages, limitations, and future outlook. The development process involves producing a cell line containing the gene for the desired protein, growing cells to produce the protein, purifying the protein, and preparing it for patient use. Biosimilars offer cost savings over biologics but have concerns around immunogenicity and long-term effects when switching between products. The global biosimilar market is expected to grow significantly as biologic patents expire and more companies develop biosimilar versions of treatments.
Developmental Origins of Obesity: The Role of Epigeneticszferraro
This presentation will:
- Review the concept of ‘fetal programming’
- Demonstrate that early life nutritional events may serve as molecular memory of individual in utero experiences
- Show how changes persist following multiple rounds of cell division
- Highlight extrinsic (recapitulation) & Intrinsic (genetic) mechanisms that strongly suggest Intergenerational transmission of traits via epigenetics in humans
- Look at how to best move forward as a scientific and clinical community
This document discusses the biology of healthy aging and longevity. It covers several topics:
1) Molecular mechanisms of aging including genome integrity, telomeres, epigenetics, protein stability, and pathways like mTOR, IIS, AMPK, and sirtuins that modify aging.
2) Biological models like yeast, worms, flies and mice that are used to study aging mechanisms.
3) Calorie restriction which increases longevity across species by reversing signs of aging.
4) Maintaining genome, telomere and epigenome integrity is important for healthy aging and preventing diseases.
5) Environmental factors and nutrition influence aging through epigenetic changes.
Recent research suggests that a variety of lifestyle - especially dietary - changes influencing the integrity of gastrointestinal function may be driving at least some portion of the increased prevalence of illnesses of civilization, including neuropsychiatric problems, such as autism, attention-deficit-hyperactivity disorder, major depression, obsessive-compulsive disorder and Alzheimer disease. One area of interest involves the relationship between the gut's microbiome (as well as the related functional integrity of the gastrointestinal tract) and mental health.
This document discusses the concepts of psychopharmacogenomics and provides examples of its applications. It begins by defining key terms like pharmacogenomics, pharmacogenetics, and psychopharmacogenomics. It then discusses the role of single nucleotide polymorphisms (SNPs) and cytochrome P450 enzymes in drug metabolism and response variability. The document provides examples of how genetic polymorphisms can impact drug dosage requirements and adverse reactions for medications metabolized by CYP2C9 and CYP2D6. Finally, it summarizes findings from pharmacogenomic studies on antidepressants, mood stabilizers, and antipsychotics in relation to specific genes.
Oracle JSON treatment evolution - from 12.1 to 18 AOUG-2018Alexander Tokarev
The presentation was prepared for Austria Oracle User group 30 years. It tells us a lot of challenges which Oracle developers face with implementing high-load json processing pipelines.
In this SlideShare, we'll be diving into Epigenetics and the unexplored approaches in therapeutics. Epigenetics refers to external modifications to DNA that turn genes ‘on’ or ‘off.’ These modifications do not change the DNA sequence itself, but instead, they alter the physical structure of DNA, which affects how our cells ‘read’ genes. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic therapy offers a potential way to influence those pathways directly.
The Journal of Biomarkers in Drug Development (JBDD) promotes rigorous research that makes a significant contribution in advancing knowledge for Biomarkers in Drug Development. JBDD includes all major themes pertaining to Biomarkers used in Drug Development.
Epigenetics refers to modifications that occur on top of genes in response to environmental factors like diet and stress. These modifications involve chemical tags that can turn genes on or off without altering the underlying genetic code. Studies show these epigenetic tags can be inherited from parents and influence stress response and tolerance in offspring. The environment can thus change our genes across generations through epigenetic mechanisms.
DOSTARLIMAB - A potential cure for Cancer. A programmed death-1 (PD-1) inhibitor called DOSTARLIMAB has been licensed for the treatment of certain tumors that have advanced during or after prior therapy and do not have any promising alternative choices. Dostarlimab has also demonstrated encouraging outcomes in the treatment of breast cancer, melanoma, head and neck cancer, endometrial cancer, and ovarian cancer. Dostarlimab, a monoclonal antibody against the programmed cell death protein (PD-1) that has been shown to completely (100%) cure patients with colorectal cancer, has enchanted the medical community in this period of rapid advancement. Also, none of the study participants experienced any significant negative effects, according to the findings of clinical trials. • Dostarlimab slows the growth of tumors and boosts the immune system's ability to combat cancer cells.
Epigenetics refers to modifications to DNA that change gene expression without altering the DNA sequence. These modifications, such as methylation, can be inherited and influence traits in offspring. Experiments show that environmental factors like chemical exposure, diet, and stress experienced by parents or grandparents can cause epigenetic changes leading to disease in subsequent generations, despite those generations not directly experiencing the original stressor. Further research on epigenetics may lead to new treatments for diseases and insights into disorders that differ between identical twins.
Cancer is characterized by uncontrolled cell growth and spread. At the cellular level, cancer cells proliferate excessively, grow in an uncoordinated manner, and infiltrate surrounding tissues. This uncontrolled growth is caused by genetic disorders that affect genes regulating cell growth. Cancer cells lose control over growth and multiplication and do not self-destruct like normal cells. They crowd out healthy cells. Genetic changes can activate oncogenes or inactivate tumor suppressor genes, disrupting the normal balance between cell proliferation and cell death. A variety of genetic, environmental, and viral factors can cause these genetic changes and contribute to cancer development.
Stem cells are unspecialized cells that can renew themselves and differentiate into specialized cell types. There are two main types: pluripotent stem cells like embryonic stem cells which can become any cell type, and adult or multipotent stem cells which can only become certain related cell types. Stem cells have properties of self-renewal and differentiation that make them useful for research, drug development, and cell therapies.
RAADfest 2019 Bill Faloon's Senolytics Slidesmaximuspeto
Senolytics are compounds that selectively destroy senescent cells and reduce signs of aging. Studies show that removing senescent cells in mice through senolytic drugs extends healthy lifespan, improves organ function, and delays age-related diseases. The first human trial of a senolytic drug combination showed improvements in physical function and markers of aging. Further research is exploring the potential benefits of senolytics for treating age-related conditions like diabetes, Alzheimer's, and cancer.
Humanized antibodies are antibodies made from non-human species whose protein sequences have been modified to increase their similarity to human antibodies. There are several technologies used to produce humanized antibodies including grafting complementarity determining regions from mouse antibodies onto human frameworks, using transgenic mice with human immunoglobulin genes, and phage display to select antibodies from human libraries. Humanized antibodies have the advantage of reducing immunogenicity while maintaining therapeutic value compared to murine or chimeric antibodies.
The document discusses the complex bidirectional communication between the gut and brain, known as the gut-brain axis. It outlines several key players in this communication: (1) the gut microbiome, which contains trillions of microbes that can influence brain development and mental health; (2) neuroactive substances like serotonin that are produced by microbes and can affect the brain; and (3) microbial metabolites like short-chain fatty acids and tryptophan derivatives that can modulate neuronal and immune function. The vagus nerve, gut hormones, and immune signals transmitted via the microbiome all help facilitate dialogue between the gut and brain. Disruptions to this gut-brain axis are implicated in several neurological and psychiatric disorders.
This document provides an introduction to the integrative medical approach of Endobiogeny. It discusses the objectives and components of Endobiogeny, which include a detailed patient history, physical exam, classical labs/imaging, and Biology of Functions assessment to evaluate the qualitative and quantitative state of the human organism. Endobiogeny aims to understand disease and health through an integrated analysis of physiological and endocrine relationships and functions. The document provides examples of how Endobiogeny analyzes clinical conditions like Polycystic Ovarian Syndrome through this integrative lens.
INTRODUCTION TO PAnnnnnnnnnnnnnnnnnnnn THOLOGY.pptxSubi Babu
This document provides an introduction and overview of pathology. It defines pathology as the scientific study of changes in structure and function of the body caused by disease. Key points covered include:
- Etiology (causes) of disease which can be genetic or environmental factors.
- Pathogenesis which describes the mechanism of how diseases develop.
- Morphology which refers to gross and microscopic changes seen in tissues and cells.
- Clinical significance relating to how morphological changes impact organ function and present clinically.
- Different areas of pathology study such as general pathology, clinical pathology, and importance of pathology for understanding disease and patient care.
Lec 1 INTRODUCTION TO PHYSIOLOGY and its branches.pptxayeshavirk45
Introduction of physiology and discussion of various branches of physiology. Here you'll find definitions of physiology, difference between clinical and applied physiology, definition of neurophysiology, nutrient physiology, cellular physiology cardiovascular physiology, pathophysiology and importance of physiology. Here you'll find why understanding of physiology is important for healthcare professionals and medical students
This document provides an introduction to physiology by discussing what physiology is, its importance for medical students, and how it relates to other biological sciences. It defines physiology as the scientific study of normal function in living systems. Key points made include:
- Physiology is a branch of biology that focuses on functions and mechanisms in living systems.
- Understanding physiology provides the foundation for medicine and improves comprehension of pathology.
- Physiology is closely related to and informs fields like anatomy, biochemistry, molecular biology, genetics, and ecology.
- The document outlines the major human body systems and cellular organization of tissues before discussing cellular physiology and structure.
Pathophysiology is the study of the functional changes and clinical manifestations of disease. It examines four aspects of disease: 1) etiology or cause, 2) pathogenesis or the mechanism by which the cause produces symptoms, 3) morphologic or structural changes in cells and tissues, and 4) functional derangements and resulting signs and symptoms. Pathophysiology aims to understand how and why internal dysfunctions occur in the body as a result of causes such as genetics, infection, nutrition or chemicals and lead to clinical manifestations of disease that can be observed.
This field combines biology as well as chemistry to study the chemical structure of a living organism
Biochemistry is a basic science which deals with chemical nature and chemical behaviour of living matter and with the reactions and processes they undergo.
“The branch of science dealing with the study of all the life processes such as control and coordination within a living organism is called Biochemistry”
This document provides an introduction to the field of pathology. It defines pathology as the scientific study of disease and notes its two main branches: general pathology, which examines basic cellular reactions to stimuli, and systemic pathology, which examines organ-specific responses. It describes the main subdivisions or specialties within pathology and explains key aspects of disease processes, including etiology, pathogenesis, morphologic changes, and clinical manifestations. Finally, it outlines the components and design of the pathology course.
LECTURE Homeostasis maintenance of internal environment 1.pptibrahimtucker2023
Physiology is the study of normal life phenomena exhibited by living organisms. The goal is to explain the physical and chemical factors responsible for life. Homeostasis refers to maintaining relatively constant internal conditions despite external changes. The human body achieves this through integration of organ systems and three main regulatory mechanisms - chemical/hormonal, nervous, and autoregulation. Feedback control systems use negative feedback to prevent deviations from becoming too large, while positive feedback amplifies changes. Together these maintain homeostasis and allow the body to adapt to its environment.
Biochemistry is the study of chemical processes within living organisms. It focuses on understanding the biochemical basis of cellular processes. The main types of biomolecules studied in biochemistry are carbohydrates, lipids, proteins, and nucleic acids. Biochemistry is used to study biological processes at the molecular level in order to understand functions like metabolism and gene expression. It also helps elucidate disease mechanisms and develop new medical treatments. Biochemistry is important for medicine as it aids in physiology, pathology, diagnosis, and pharmacology.
This document provides an introduction to anatomy and physiology. It defines anatomy as the study of the structure of the body and physiology as the study of function in living organisms. The importance of anatomy and physiology is explained as understanding how the body responds to stimuli, maintains stable internal conditions, and is organized from the chemical to organism level. Key concepts covered include homeostasis, negative feedback mechanisms, anatomical position and directional terms, and structural levels from cells to organ systems.
1.1 Basic principles of Cell injury.pptxMUNEZEROEvase
This document provides an overview of basic principles of cell injury and adaptation. It defines key terms like homeostasis, feedback systems, and causes of cellular injury. The main mechanisms of cellular injury include damage to the cell membrane, mitochondria, ribosomes, and nucleus. Cells can adapt to injury through processes like atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia, which refer to changes in cell size and number. The document also discusses examples of homeostasis maintenance through negative and positive feedback systems.
This document discusses the different types of toxicology. It begins with an introduction to toxicology, defining terms like toxin, toxicant, and toxicity. It then describes the major types of toxicology as mechanistic toxicology, regulatory toxicology, and descriptive toxicology. Mechanistic toxicology examines toxicity at the molecular level. Regulatory toxicology supports rulemaking and product approval. Descriptive toxicology focuses on toxicity testing in animals to evaluate hazards. The document provides examples and explanations of each type.
Pathophysiology and Psychodynamics of Disease CausationChestha Arora
This document discusses pathophysiology and psychodynamics of disease causation. It begins with an introduction and outline. Then, it discusses various theories of disease causation from old theories like humoral theory to current biopsychosocial model. It also discusses pathogenesis of disease, concepts like iceberg phenomenon, and pathophysiological changes including alterations in fluid, electrolytes, immune response, and acid-base balance. It examines concepts like hypersensitivity, autoimmunity, and immunodeficiencies as they relate to immune system alterations.
At the end of the class the students will be able to,
Explain the basic concept of pathology
Describe the Cellular & tissue changes.
Describe the Infiltration and regeneration
Elaborate the inflammation and infection
This document discusses methodological considerations for biosocial research. It outlines why researchers combine biological and social data, including using biomarkers as objective health measures and understanding pathways between social factors and health. It also discusses issues like self-report bias, missing data, biological sample quality, and the need for theoretical frameworks and interdisciplinary teams to properly analyze relationships between genetic, phenotypic, social, and outcome data.
Reflection Paper Addiction and Theories Ksir, C., Hart, C.,.docxaryan532920
Reflection Paper: Addiction and Theories
Ksir, C., Hart, C., Ray,O. Drugs, Society and Human Behavior, Twelfth Edition. McGraw Hill Publisher
Read Chapter 2 of the text, note the definitions and the major theories about how drug use leads to drug abuse/addiction.
What is your favorite theory(s) of Addiction?
Why do people become addicted to alcohol, tobacco and other drugs (ATOD)?
Write a definition of addiction/dependency:
Nature of addiction/dependency – etiology: what happens to a person who is addicted/dependent on ATOD (See also chapter 1 “Drug Dependence” and “Stages of Drug Dependence”; Chapter 2 “The vicious Cycle of Drug Addiction)
Bio-Psycho-Social Model: write your favorite explanations of why someone might become addicted to AOD, based on specific theories in each of the following categories
Biological causes/factors of addiction/dependency
Psychological causes/factors of addiction/dependency
Social causes/factors of addiction/dependency
The Biopsychosocial Approach
The biopsychosocial approach was developed at Rochester decades ago by Drs. George Engel and John Romano. While traditional biomedical models of clinical medicine focus on pathophysiology and other biological approaches to disease, the biopsychosocial approach in our training programs emphasize the importance of understanding human health and illness in their fullest contexts. The biopsychosocial approach systematically considers biological, psychological, and social factors and their complex interactions in understanding health, illness, and health care delivery.
Biosphere
Society/ Nation
Culture/Subculture
Community
Family
Individual
Nervous System
Organs
Tissues
Cells
Molecules
• Biological, psychological, and social factors exist along a continuum of natural systems, as depicted in the list here.
• Systematic consideration of psychological and social factors requires application of relevant social sciences, just as consideration of biological factors requires application of relevant natural sciences. Therefore, both the natural and social sciences are ‘basic’ to medical practice. In other words, psychological and social factors are not merely epiphenomena: they can be understood in scientific ways at their own levels as well as in regard to their biological correlates.
• Humanistic qualities are highly valued complements to the biopsychosocial approach, which involves the application of the scientific method to diverse biological, psychological, and social phenomena as related to human health.
• While the biomedical approach takes the reductionistic view that all phenomena are best understood at the lowest level of natural systems (e.g., cellular or molecular), the biopsychosocial approach recognizes that different clinical scenarios may be most usefully understood scientifically at several levels of the natural systems continuum.
To apply the biopsychosocial approach to clinical practice, the clinician should:
• Recognize that relatio ...
This document provides an overview of toxicology and its types. It discusses the history and basic definitions of toxicology. It describes the importance of dose and outlines the major purposes and routes of exposure in toxicology. It then summarizes the general types of toxicology, including analytical, applied, clinical, veterinary, forensic, environmental, and industrial toxicology. Finally, it discusses the major areas of specialization in toxicology, including mechanistic, regulatory, and descriptive toxicology.
2. OBJECTIVES
• Introduce Endobiogeny and its component elements:
• Detailed history
• Detailed physical exam
• Classical labs and imaging studies
• Biology of Functions
• Integrative assessment, then…
• Therapeutic strategy
• Example: application of concepts of Endobiogeny to
cardiovascular disease
• Discuss opportunities to learn the Endobiogenic method
3. Introduction
An introduction to the Endobiogenic concept
A brief review of the history of medicine and its
schools of thought
4. Endobiogeny
• The integrative study of the functional mechanisms of
regulation of the organism in its basic structure during
homeostasis as well as its functional response to
internal and external stressors:
• As a whole system
• In its individual units of function
• core metabolism
• cell, tissue and organ
• in and of themselves and in relationship to each other
• Endobiogeny evaluates the qualitative and quantitative
state of the human organism and its internal milieu.
5. Example:
Quantitative assessment
• Consider a car factory to be like the ovaries. Does the
number of cars (amount of estrogen) produced tell you how
efficiently the factory (ovaries) is functioning or how well the
cars produced drive?
• A quantitative assessment of productivity tells you how many
cars are being produced (serum estrogen levels), but not how
well those cars drive (endocrine and metabolic activity of
estrogen).
• For example, if the output of cars meets demand, but the
gear shifter is faulty (altered estrogen-receptor binding), each
car carries fewer people than its normal capacity due to
decreased torque. In this case, more cars will be needed to
carry people.
• “Normal” factory output for this company (body) is insufficient
to meet demand
6. Example:
Qualitative assessment
• But what about a qualitative assessment? There may be supply
issues—not enough steel available. The factory cannot produce
cars without steel (cholesterol as a precursor to estrogen
production)
• Perhaps there are not enough workers on the assembly line
(Follicle stimulating hormone) and the workers present are over-
worked and will soon decline in productivity (pituitary stress).
• Perhaps there are ample supplies and workers, but the manager
is inefficient (hypothalamus) in managing the factory, not
regulating supply and demand issues.
• Perhaps the manager is efficient, but the workers do not always
follow his directives (altered thresholds of responsiveness).
• Thus, it is clear that both a quantitative and qualitative
assessment of physiological and endocrine activity is necessary
to properly understand disease and health.
7. Endocrine management
• Thus, Endobiogeny views the endocrine system as
the manager of the body, the controller of anabolism
and catabolism—which is what life itself is at every
level from the cell to the structure of the universe:
• destruction and reconstruction
• expansion and contraction
• growth and apoptosis
• birth and death
8. Philosophy
• Endobiogeny integrates the rational and empirical
schools of medicine with philosophy to create a
single coherent system of medicine:
• TheEndobiogenic approach begins with the
ontology (reason for existence) of structures and
physiology
• This leads to a logical approach to understanding
structural weaknesses in the organism as well as
determining the true cause of disease
• Endobiogenic approach treats the person, not the
disease; treats global system rather than
9. Integration of data
• Endobiogeny integrates:
• History
• Physical Exam
• Laboratory data and Imaging studies
• To reach a conclusion regarding the current, dynamic
physiological state of the individual in order to
formulate a treatment strategy which addresses:
• the identified imbalances individually
• as well as in their relationship to other imbalances
10. Treatment Options
• Endobiogenic treatments consist of various therapeutic
elements based on their safety and efficacy with no
prejudice to the school of thought from which the
treatment originates:
• Phytotherapeutic elements
• Homeopathic elements
• Pharmaceuticals elements: reasoned usage based on
severity of symptoms, of degree or lack of compensatory
physiology.
• Physical manipulations: craniosacral, myofascial, etc.
• Nutrition
• Oligoelement supplementation
• Stress modification, hydrotherapy, acupuncture, etc.
11. Individualized medicine
• Endobiogeny is individualized medicine based on:
• The patient’s symptomization of illness within the
context of the global functioning of the organism
• The physician’s determination of the signs of
physiological and endocrine dysfunction
• The physician’s objective assessment of endocrine
relationships
• The particular physical, physiological, psychological
and emotional realities of the individual.
12. Conclusion
• Endobiogenic treatment is determined by the totality of
the person:
• Static and dynamic aspects of the patient’s constitution
• Etiology, ontology, and integration of symptoms
• Adaptive and maladaptive aspects of physiology
14. Founders of
Endobiogeny
• Endobiogenie is the work of two
French medical doctors, Christian
Duraffourd, MD and Jean Claude
Lapraz, MD
• Drs. Duraffourd and Lapraz early in
their medical careers called into
question the predominant allopathic
concepts of disease as well as the
reliance on single-receptor synthetic
medications
• Since 1973, their work has focused on
the synthesis of modern
physiology, empirical medicine and
clinical phytotherapy
Dr. Duraffourd
Dr. Lapraz
15. Development of
Concepts
• The 1970s saw the establishment of the French Society for
Phytotherapy and Aromatherapy (SFPA) and the concerted
effort of a group of physicians to go beyond the reductionist
concepts of allopathic medicine
• 1980’s: Drs. Duraffourd and Lapraz spent over 7 years
treating cancer patients in an in-patient oncology ward,
which established the importance ofqualitative relationship
of hormones to one another as the basis of health and
illness
• 1990s: International teachings and publication of major
works in clinical phytotherapy and their neuro-endocrine
impact on the body
17. Laboratory studies
• Classical lab data is based on binary considerations:
• disease vs. no disease
• normal vs. abnormal value
• However, the human body works across a spectrum of
function.
• Pathophysiological disruption with elevated serum
enzymes or deranged blood elements is a late finding in
the disease process
• Long before this stage, patients experience a functional
dysfunction with sub-optimal activity, but normal labs
• Thus, it is self-evident that binary considerations cannot
be applied with any real assurance of its functional
relevance to a system as complex as the human body.
18. Laboratory studies
• Biological systems are complex, multi-tiered, dynamic
interrelated and integrated systems
Yeast Protein Interaction Network
Bader and Hogue (2002) Nature
Integrated, inter-related system
19. Integrated systems
• Objective quantitative data (laboratory values) are
required to assess the organism
• However, one must be able to provide functional
descriptions of quantitative and qualitative activity both
within a particular unit of activity, from one unit to
another, as well as within the system as a whole
• Only then can a truly dynamic and individualized
assessment of the patient occur
20. Laboratory studies
• The endocrine system, as the manager of the
metabolic activity of the body, is the ideal object of
evaluation.
• Serum levels of hormones reflect neither the
degree of stimulation needed nor the metabolic
costs incurred in producing a particular hormone.1-3
1) Raison CL, Miller AH. When not enough is too much: the role of insufficient
glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J
Psychiatry. Sep 2003;160(9):1554-1565
2) Chiam K, Tilley WD, Butler LM, Bianco-Miotto T. The dynamic and static
modification of the epigenome by hormones: A role in the developmental origin of
hormone related cancers. Biochem Biophys Acta. Apr 2009;1795(2):104-109.
3) Gerhard I, Waibel S, Daniel V, Runnebaum B. Impact of heavy metals on
hormonal and immunological factors in women with repeated miscarriages. Hum
Reprod Update. May-Jun 1998;4(3):301-309.
21. Laboratory studies
• Serum levels of hormones only reflect quantitative organ
output, not functional activity, which can be affected by:
• Hormone receptor binding (affected by over- or under-
expression of other hormones)1
• Intracellular messenger activity1
• Epigenetic changes2
• Heavy metal toxicity3, etc.
1) Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid
signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. Sep
2003;160(9):1554-1565
2) Chiam K, Tilley WD, Butler LM, Bianco-Miotto T. The dynamic and static modification of the
epigenome by hormones: A role in the developmental origin of hormone related cancers.
BiochemBiophysActa. Apr 2009;1795(2):104-109.
3) Gerhard I, Waibel S, Daniel V, Runnebaum B. Impact of heavy metals on hormonal and
immunological factors in women with repeated miscarriages. Hum Reprod Update. May-Jun
1998;4(3):301-309
22. Laboratory studies
• The ideal system of measurement of biological processes
thus should examine the metabolic products of hormonal
management of cellular activity
• Thus, the ideal laboratory system must
• Reflect the complex, integrated and dynamic nature of
biological systems
• Describe the functionality of the system in its
• Qualitative function
• Quantitative function
• Individual unit, relative to other units and as a whole
• Assess the organism at the metabolic and interstitial level
23. Biology of functions
• The Biology of Functions (BoF) quantifies functional
abilities of the organism, before and after theeffects of
adaptation to stressors. Because functionality is
dynamic, a dynamic, integrated and evolutionary
methodology must be used instead of static lab values
• BoF is based on a number of specific indices defined by
mathematical relations between commonly used blood
analysis data
• The algorithms that permit the calculation of these
indices are based on the physiological relations that
exist between the direct or indirect products of
hormonal activity: cells, hormones or enzymes
(eosinophils, TSH and LDH, for example).
24. Biology of Functions
• These relations allow one to visualize the
functioning of the organism at every level:
maintenance of homeostasis, adaptation, recovery
after aggression, immunity, etc.
• Each function is quantified by an index, specified
by a level of activity. The index expresses the
actual activity of that function, both in and of itself
and in relation to the metabolic and tissue needs of
the organism.
• The whole set of indices gives an evolutionary
assessment of an individual body’s functionality,
system by system, organ by organ.
25. Biology of functions
• SUMMARY: Biology of Functions:
• Allows one to determine:
• Pathogenic tendencies of the organism (i.e. cell
dysplasia—”pre-cancer”, fatty streaks—early
atheromatous plaque development, amyloid
plaques—degenerative neurological disease),
• The stage of development and severity of that
pathology
• Can be used as a tool to track
• the natural development of pathology
• To derive a rational therapeutic treatment
• To evaluate the efficacy of the treatment over time
26. Example:
Adaptation Index
• According to Dr. Duraffourd, an intra-pituitaryphysiologic
linkage exists in the stimulation of FSH by ACTH
• The Adaptation Index evaluates the relative activityof
ACTH relative to FSH in order to determine the degree
of efficiency of catabolism (cortisol) vs. thedegree of
efficiency of anabolism (estrogen) in response to stress
• The Adaptation Index examines thisactivityat the
metaboliclevel by examining the products of hormonal
activity (cortisol and estrogen in thisexample) as an
assessment of hormonal activity
• It iscalculated as the ratio of eosinophils to monocytes
27. Adaptation Index: Proofs
• Eosinophils are inverselyrelated to the
efficiency of ACTH activity in its adaptive
response to stress1
• ACTH stimulates cortisol activity
• Cortisol stimulates eosinophil apoptosis
• Cortisol resistance occurs during chronic
stimulation of the adrenal gland, or during
severe cases of acute illness3
1) Giembycz MA, Lindsay MA. Pharmacology of the eosinophil. Pharmacol Rev. Jun
1999;51(2):213-340.
2) Beishuizen A, Vermes I, Hylkema BS, Haanen C. Relative eosinophilia and
functional adrenal insufficiency in critically ill patients. Lancet. May 15
1999;353(9165):1675-1676.)
3) Miller GE, Cohen S, Ritchey AK. Chronic psychological stress and the regulation
of pro-inflammatory cytokines: a glucocorticoid-resistance model. Health Psychol.
Nov 2002;21(6):531-541.
28. Adaptation Index: Proofs
• Cortisol resistance has two effects:
• Elevated ACTH activity to stimulate more cortisol
production
• Loss of tonic inhibition of eosinophils, resulting in
eosinophilia1
• Eosinophilia is correlated with severity of critical
illness2
1) Giembycz MA, Lindsay MA. Pharmacology of the eosinophil. Pharmacol Rev. Jun
1999;51(2):213-340.
2) Beishuizen A, Vermes I, Hylkema BS, Haanen C. Relative eosinophilia and functional adrenal
insufficiency in critically ill patients. Lancet. May 15 1999;353(9165):1675-1676.)
29. Adaptation Index: Proofs
• Monocytes are inversely related to the efficiency of
FSH activity during adaptation to stress1
• Mechanism:
• FSH levels are proportional to estrogen
• Estrogen suppresses monocyte production2
• Monocytosis during stress indicates ineffective FSH
activity (even if serum levels are elevated) and is
correlated with increased mortality3, which is
reflected as a LOW Adaptation index
1) Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J
Leukoc Biol. Mar 2007;81(3):584-592.
2) Harkonen PL, Vaananen HK. Monocyte-macrophage system as a target for estrogen and selective
estrogen receptor modulators. Ann N Y Acad Sci. Nov 2006;1089:218-227)
3) Fingerle G, Pforte A, Passlick B, Blumenstein M, Strobel M, Ziegler-Heitbrock HW. The novel subset of
CD14+/CD16+ blood monocytes is expanded in sepsis patients. Blood. Nov 15 1993;82(10):3170-
3176.
31. Uniqueness of
Vasculature
• Vascular system unique system in body:
• Ubiquitous throughout the body
• Controlled by chemo-, baro-, hormonal, CNS factors
• Endocrine and paracrine system itself
• Means of transmission of information and nutrition
• Subjects global system to local phenomenon
• Participates in initiating and responding to local
events
• Contains a homunculus of itself: vasovasorum
32. Vascular Disease:
Atheromas
• When treating atheromatous lesions one must
distinguish between:
• Ontology: the true reason for the dysadaptation
• Etiology: mechanisms of response to the dysadaptation
• Primary: Endocrine, Neurovegetative (NV)
• Secondary: Paracrine, autocrine, adaptive elements,
pathophysiological
• Finality: the end result of the dysadaptation
33. Limitations of Etiology-based
treatments
• Cardiologists classically have focused on the mechanisms
of plaque formation rather than the reason for plaque
formation:
• Neuro-Vascular: Alpha-, beta-sympathetic activity
• Energetic elements: Cholesterol, HDL, LDL, TG, Glucose
• Lipids are a necessary but not sufficient factor for atheromatous
disease
• Hyperlipidemia ≠ Dyslipidemia
• Pathophysiological mediators: Inflammation, Free
radicals, Nitric Oxide, homocysteine, etc.
• Thus, we have failed to identify the fundamental
factors that allows atheromas to form in one patient
and not another, all screening factors being
equal, such as age, BMI, cholesterol and blood
34. Limitations of Etiology-based
treatments
• Treating local phenomena globally with beta-blockers
and statins have lead to reduction in CV events, but at
a global cost, such as increased risk of stroke and
loss of libido, muscle wasting, respectively.
• The entire body is subjected to suppression of factors
which are still adaptive and beneficial for the global
organism, but not for a particular part of the body
• The failure to identify and treat the true causes of CV
plaques results in anomalies such as “low risk”
patients having fatal MI’s and “high risk” patients living
long, healthy lives
35. Endobiogenic approach
• True cause of atheromatous plaques is dysadaptive
endocrine response to local needs for increased nutrition:
• Internal or external aggressors (viruses, emotional
stressors, tobacco smoke, heavy metals)
• Times of restructuring of the body (menopause, andropause)
• If the response to anabolic requirements is badly managed
by the body, or the demand is prolonged or the body is not
able to return to its previous homeostatic thresholds of
endocrine response, a dysmetabolic response ensues
• This is the true ontology of disease because endocrine
system manages all metabolic activity of the body
36. Etiology of Atheromas
• Local tissue or organ demand for anabolic adaptation demands
increased nutrient delivery:
• CATABOLIC: ACTH Cortisol: liberates glucose by
glycogenolysis for generation of ATP; TSH Thyroid: liberates
lipids for energy and cell wall building
• ANABOLIC: ProlactinInsulin: increases nutrient penetration
into cells; FSH/LH Estrogen and Testosterone: anabolic
steroid for protein incorporation and utilization in the cell
• Histamine: capillary leakextravasation of nutrients into extra-
cellular matrix
• Aldosterone: improve electrolyte presentation to cells, increase
circulating blood volume
• HTN: post-capillary increased duration of nutrient presentation
37. Etiology of Atheromas
Vasculature as transportation medium for these
factors carries them from local area of need, creating
systemic inflammation
Vasculature has greatest exposure to these
mediators, thus endothelium becomes damaged by
these mediators
Now that catabolic and anabolic activities are dysregu-
lated, with increased glucose, lipids and
inflammation, vasculature itself undergoes hyper-
anabolic repair of damaged endothelium and media
smooth muscle proliferation and atheromatous
plaques
38. Endobiogenic approach
• Endocrine factors have been well described since as early as
1950’s, but neither their relationship to each other nor their
ontological significance has been clearly elucidated by classical
medicine
• Two primary indices in the biology of functions describe the
relationship between these elements and assist the clinician in
evaluating the true cause of disease and the optimal treatment
option
• Thrombogenic index: describes the risk of lumenal narrowing from
atheromatous plaques, and by extension, the thrombogenic
potential
• Thrombotic index: describes the actual risk of developing thrombo-
embolic phenomenon from atheromas or due to altered blood
rheology. The thrombotic index contains the thrombotic index
39. Biology of functions (BoF):
Thrombogenic Index
Proportional to [labs] (related BoF index) :
• Acute stress [LDH] (Thyroid index)1
• Elevated ACTH (Adaptation index)2,3
• Relative Eosinophilia [eosinophil %] (Adaptation index)4-
6
• Cortisol [salivary cortisol] (Anabolism index)7
1) Karacalioglu O et al. Baseline serum levels of cardiac biomarkers in patients with stable coronary artery
disease. Biomarkers. Sep-Oct 2007;12(5):533-540.
2) Bloom B, Pierce FT, Jr. Relationship of ACTH and cortisone to serum lipoproteins and atherosclerosis in
humans. Metabolism. Mar 1952;1(2):155-162.
3) Letizia C, Barilla F, Cerci S, et al. beta-Endorphin and propiomelanocortin-correlates peptides response in
suspected and confirmed ischemic heart disease during exercise. Acta Cardiol. 1996;51(1):27-36.
4) Siddiqui S et al. Factors predicting outcome in a cohort of patients with atherosclerotic renal artery disease
diagnosed by magnetic resonance angiography. Am J Kidney Dis. Dec 2005;46(6):1065-1073.
5) Emanuele E et al. Association of plasma eotaxin levels with the presence and extent of angiographic
coronary artery disease. Atherosclerosis. May 2006;186(1):140-145.
6) Atkinson JB et al. Association of eosinophils with cardiac rupture. Hum Pathol. Jun 1985;16(6):562-568.
7) Dekker MJ et al. Salivary cortisol is related to atherosclerosis of carotid arteries. J Clin Endocrinol Metab.
Oct 2008;93(10):3741-3747.
40. Biology of functions (BoF):
Thrombogenic Index
Proportional to [labs] (related BoF index) :
• Gonadal Androgens [free Testosterone] (Androgenic)1
• Insulin (Anabolism index)9
• Sub-clinical hypothyroidism [TSH] (Bone remodeling
index)10-13
1) Dogramaci AC, Balci DD, Balci A, et al. Is androgenetic alopecia a risk for atherosclerosis? J Eur Acad
Dermatol Venereol. Feb 23 2009.
2) de Rooij S, Dekker J, Kozakova M, et al. Fasting insulin has a stronger association with an adverse cardio-
metabolic risk profile than insulin resistance: The RISC study. Eur J Endocrinol. May 13 2009
3) Stamatelopoulos KS, Kyrkou K, Chrysochoou E, et al. Arterial Stiffness but Not Intima-Media Thickness Is
Increased in Euthyroid Patients with Hashimoto's Thyroiditis: The Effect of Menopausal Status. Thyroid. Apr 6
2009.
4) Sidorenko BA, Begliarov MI, Titov VN, Masenko VP, Parkhimovich RM. [Blood thyroid hormones in ischemic
heart disease (a comparison with coronary angiographic data, severity of stenocardia and blood lipid level)].
Kardiologiia. Dec 1981;21(12):96-101.
41. Biology of functions (BoF):
Thrombogenic Index
Inversely proportional to [labs] (related BoF index) :
• Estrogen [Estradiol, free] (Estrogen index; Bone
Remodeling index)1
• Adrenal Androgens [DHEAS] (Androgenic index)2-4
1) Gopalakrishnan P, Ragland MM, Tak T. Gender differences in coronary artery
disease: review of diagnostic challenges and current treatment. Postgrad Med.
Mar 2009;121(2):60-68.
2) Ii M, Hoshiga M, Negoro N, et al. Adrenal androgen dehydroepiandrosterone
sulfate inhibits vascular remodeling following arterial injury. Atherosclerosis. Feb
27 2009.
3) Savastano S, Valentino R, Belfiore A, et al. Early carotid atherosclerosis in
normotensive severe obese premenopausal women with low DHEA(S). J
Endocrinol Invest. Mar 2003;26(3):236-243.
4) Altman R, Motton DD, Kota RS, Rutledge JC. Inhibition of vascular inflammation
by dehydroepiandrosterone sulfate in human aortic endothelial cells: roles of
PPARalpha and NF-kappaB. VasculPharmacol. Feb-Mar 2008;48(2-3):76-84.
42. Biology of functions (BoF):
Thrombogenic Index
The biology of function allows you to evaluate the risk
of lumenal narrowing from atheromas both from the
gestalt of risk factors
Allows the physician to indentify the risk factors
particular to the patient.
Allows the physician to assess risk on physiological
data rather than generalized risk factors based on
epidemiological data
44. Other Indices: Physiological
Thrombogenic index: Examines the risk of thrombo-
embolic phenomenon. Factors in all the risk factors
associated with atherogenesis as well as the role of
histamine1
Tx: Reduce histamine with Plantain, Vitamin C, or Lavender
Ischemia index: relates degree of tissue congestion relative
to rate of metabolism
Tx: Correct sick euthyroid: iodine, wolfberry, stone steed
Pro-amyloid: examines the degree of cellular nutritional
and oxygen deficiency, indirectly examining the degree of
mitochondrial strain and oxidative phosphorylation
Tx: CoQ10, L-Carnitine (if triglycerides), Creatine (if CPK)
1) Tanimoto A, Sasaguri Y, Ohtsu H. Histamine network in atherosclerosis. Trends Cardiovasc Med.
Nov 2006;16(8):280-284.
45. Other Indices:
Psychological
betaMSH/alpha MSH: characterizes the degree of
intrapsychic activity originating from Dopamine vs.
Norepinephrine
Adaptogenic: characterizes the degree of internal dialogue
Thyroid relaunching, corrected: characterizes the degree of
endocrine dysfunction originating from emotional issues
Interleukin-1: characterizes the impact of emotional and
endocrine factors on immune activity, immune regulation
and cellular proliferation (intimal thickening is a carcinoid
type of dedifferentiation of the smooth muscle)1
1) Argaman M, Gidron Y, Ariad S. Interleukin-1 may link helplessness-hopelessness with cancer
progression: a proposed model. Int J Behav Med. 2005;12(3):161-170.
47. Conclusions
• Endobiogeny is the study of the internal milieu of the organism
• Within itself
• In its relationship with its environment, stressors, etc.
• From the standpoint of the endocrine system as the manager of
human life
• In order to create a rational, individualized treatment
plan
48. Conclusions
• It combines in an integrative understanding:
• a philosophical consideration of the ontology of structures and
functions of the body,
• a rational approach to understanding physiology
• an empirical assessment of history and symptoms
• utilization of a dynamic, integrative and integrated metabolic
assessment of endocrine management of the organism called
the “Biology of Functions”
• an integrated assessment of all clinical data to obtain a precise
understanding of maladaptive physiology
49. Conclusions
• The Biology of Functions is an algorithmic assessment of the
qualitative and quantitative relationships of hormones in terms of
metabolic activity from nuclear, cellular, tissue, organ and
system-wide perspectives
• The Biology of Functions allows for an objective, longitudinal
assessment of the effects of therapy over time
• Endobiogeny relies on phytotherapy, oligotherapy, and diet as
well as lifestyle modification as its preferred methods of
ameliorating physiological imbalances
• It reserves the use of synthetic drugs for urgent cases, or when
the body is not able to establish an equilibrium by the effects of
functional regulation
50. Resources
• To learn more about Endobiogeny:
• Web:
• General information:
• www.eimcenter.org
• www.fullspectrumhealthmd.com
• Biology of Functions demonstration:
• http://extranet.endobiogenics.com/en/
• Seminars:
• Call: 858-455-9726
51. Practitioners
For more information contact Endobiogenic
practitioners
United States:
• Kamyar M. Hedayat, MD,
• Expertise: Critical care
physiology, neurodegenerative
disorders, pediatrics
• Contact: kmhedayat@aromamd.net
• Web: www.fullspectrumhealthmd.com
52. Practitioners
Continental Europe
• Jean Claude Lapraz, MD, co-developer of
Endobiogeny
• Expertise: Cancer, all areas
• Contact: jc.lapraz@orange.fr
• Patrice Pauly, PhD
• Expertise: Biology of Functions, systems analysis
• Contact: patricepauly@yahoo.fr
53. REFERENCES
SLIDE 22
1) Raison CL, Miller AH. When not enough is too much: the role of
insufficient glucocorticoid signaling in the pathophysiology of stress-
related disorders. Am J Psychiatry. Sep 2003;160(9):1554-1565
2) Chiam K, Tilley WD, Butler LM, Bianco-Miotto T. The dynamic and static
modification of the epigenome by hormones: A role in the developmental
origin of hormone related cancers. Biochem Biophys Acta. Apr
2009;1795(2):104-109.
3) Gerhard I, Waibel S, Daniel V, Runnebaum B. Impact of heavy metals on
hormonal and immunological factors in women with repeated
miscarriages. Hum Reprod Update. May-Jun 1998;4(3):301-309
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