You can gain ideas on toxico-kinetics from this presentation. Different aspects regarding bio-concentration and bioaccumulation. In addition, demerits of different toxic chemicals from food industries are discussed with examples.
ESTROUS CYCLE: Reproductive cycle of female, generally defined as period from one estrus to the next.
Two phases:
Follicular Phase
Luteal phase
TYPES OF ESTROUS CYCLE
INTRODUCTION
Toxicology is the science of the poisons. It also studies the nature, effects, detection, assessment and treatment of their effects on biological material.
Toxicology is a multidisciplinary science. The ultimate objective of the combined research is to determine how an organism is affected by exposure to an agent.
This includes an understanding of:
How the agent moves and interact with living cells and tissues of the organism;
What parts of the organism are affected by its presence and health outcomes of this exposure.
Evaluation of the toxicity of substances whose biological effects may not have been well characterized.
The influence of chemical toxicity is mainly
determined by the dosage, duration of exposure,
route of exposure, species, age, sex, and environment.
The goal of toxicology is to contribute to the
general knowledge and harmful actions of
chemical substances.
2. to study their mechanisms of action,
3. and to estimate their possible risks to humans
HISTORY
Dioscorides, a Greek physician in the court of the Roman emperor Nero, made the first attempt to classify plants according to their toxic and therapeutic effect. Poisonous plants and animals were recognized and their extracts used for hunting or in warfare.
In 1500 BC people used hemlock, opium, arrow poisons, and certain metals to poison enemies or for state executions.
Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493–1541) (also referred to as Paracelsus, a Roman physician from the first century) is considered "the father" of toxicology.
He stated that "All things are poisonous and nothing is without poison; only the dose makes a thing not poisonous.“
Mathieu Orfila (1813) is considered the modern father of toxicology.
In 1850, Jean Stas became the first person to successfully isolate plant poisons from human tissue.
Hippolyte Visart de Bocarmé used nicotine to kill his brother-in-law. He extracted nicotine from tobacco leaves.
The 20th and 21st Centuries have marked by great advancements in the level of understanding of toxicology. DNA and various biochemicals that maintain body functions have been discovered. Our level of knowledge of toxic effects on organs and cells has expanded to the molecular level.
You can gain ideas on toxico-kinetics from this presentation. Different aspects regarding bio-concentration and bioaccumulation. In addition, demerits of different toxic chemicals from food industries are discussed with examples.
ESTROUS CYCLE: Reproductive cycle of female, generally defined as period from one estrus to the next.
Two phases:
Follicular Phase
Luteal phase
TYPES OF ESTROUS CYCLE
INTRODUCTION
Toxicology is the science of the poisons. It also studies the nature, effects, detection, assessment and treatment of their effects on biological material.
Toxicology is a multidisciplinary science. The ultimate objective of the combined research is to determine how an organism is affected by exposure to an agent.
This includes an understanding of:
How the agent moves and interact with living cells and tissues of the organism;
What parts of the organism are affected by its presence and health outcomes of this exposure.
Evaluation of the toxicity of substances whose biological effects may not have been well characterized.
The influence of chemical toxicity is mainly
determined by the dosage, duration of exposure,
route of exposure, species, age, sex, and environment.
The goal of toxicology is to contribute to the
general knowledge and harmful actions of
chemical substances.
2. to study their mechanisms of action,
3. and to estimate their possible risks to humans
HISTORY
Dioscorides, a Greek physician in the court of the Roman emperor Nero, made the first attempt to classify plants according to their toxic and therapeutic effect. Poisonous plants and animals were recognized and their extracts used for hunting or in warfare.
In 1500 BC people used hemlock, opium, arrow poisons, and certain metals to poison enemies or for state executions.
Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493–1541) (also referred to as Paracelsus, a Roman physician from the first century) is considered "the father" of toxicology.
He stated that "All things are poisonous and nothing is without poison; only the dose makes a thing not poisonous.“
Mathieu Orfila (1813) is considered the modern father of toxicology.
In 1850, Jean Stas became the first person to successfully isolate plant poisons from human tissue.
Hippolyte Visart de Bocarmé used nicotine to kill his brother-in-law. He extracted nicotine from tobacco leaves.
The 20th and 21st Centuries have marked by great advancements in the level of understanding of toxicology. DNA and various biochemicals that maintain body functions have been discovered. Our level of knowledge of toxic effects on organs and cells has expanded to the molecular level.
A brief introduction about Pharmacology of free radicals, generation of free radicals, Antioxidants, Free radicals causing disorders such as cancer diabetes, neuro degenerative disorders such as Parkisonism's Disease
External agents like carcinogens, pollutants, ionizing radiations produce oxidative stress in living cells generating reactive oxygen
species [ROS]. Cells have built in defense against these reactive species and keep a balance between generated ROS and their
neutralization by endogenous antioxidants [AO]. In addition, many antioxidants present in our diets react with the ROS and make
them inactive. The maintenance of balance is a continuous process inside cells to keep them functioning normally. When
generation of ROS exceeds the level of endogenous and externally added AOs , cells are driven to pathogenic state leading to
diseases. A variety of dietary AOs are available from various sources of fruits and vegetables. This paper aims to review the
molecular mechanisms of oxidative stress, generation and reactions of ROS with vital molecules such as DNA, Protein and
membrane and involvement of ROS in the induction of cancer and other diseases. An attempt is made to suggest ways to reduce
cancer incidence risks , need to modify dietary foods by consuming vegetables, fruits for chemo prevention. An example has been
given to emphasize the role of curcumin as an antioxidant in the mechanism of chemoprevention.
Keywords: Oxidative stress, Carcinogens, ROS, Antioxidants, Chemoprevention.
Molecular Mechanisms of Radiation Damage. Dmitri Popov
Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005).
Conclusion: Specific antibodies – possible antagonists of Toll like receptors and can inhibit massive activation of lysosomal hydrolytic enzymes and prevent radiation toxicity after high doses of Radiation.
Protection of humans during long space flight. using cannabis to reduce biol...Dmitri Popov
Protection of humans during long space flight. using cannabis to reduce biological consequences of high doses of radiation, treat stress, anxiety, and depression Associated with Long-term Space Flight to Mars.
ANTIOXIDANTS AND POTASSIUM FERROCYANIDE, APROPHYLACTIC AND THERAPEUTIC MIXTU...Dmitri Popov
ANTIOXIDANTS AND POTASSIUM FERROCYANIDE, APROPHYLACTIC AND THERAPEUTIC MIXTURE COMPRISING THIS COMPOUND AND THE USE THEREOF FOR DECORPORATION OF RADIOCESIUM IN SUBJECTS AFFECTED BY NUCLEAR RADIATION
Implications for Immunotherapy of Acute Radiation Syndromes. Part 2.Dmitri Popov
Research Proposal: Implications for Immunotherapy of Acute Radiation Syndromes. Part 2.
Dmitri Popov
Full-text available · Research Proposal · Feb 2017
File name: Implications for Immunotherapy of ARS. Part 2.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
1. Dmitri Popov. PhD, Radiobiology. MD (Russia)
Advanced Medical Technology and Systems Inc.
Canada.
2. Radiation Toxicity: Lipid’s Radiation
Toxins.
Exposure to radiation induces generation of
reactive oxygen species (ROS) especially hydroxyl
radical
(·OH) and peroxyl radical (ROO·), which are
capable of inducing lipid peroxidation.
B. Lakshmi et al. CURRENT SCIENCE, VOL. 88, NO.
3, 10 FEBRUARY 2005
3. Radiation Toxicity: Lipid’s Radiation
Toxins.
Exposure of a cell to radiation can both directly and indirectly
alter molecules within the cell to affect cell viability. Radiation
energy absorbed by tissues and fluids is dissipated by the
radiolysis of water molecules and biomolecules. These reactions
result in redox-reactive products such as hydroxyl radical (HO*),
hydrogen peroxide (H2O2), hydrated electron (e-aq), and an
array of biomolecule-derived carbon-, oxygen-, sulfur-, and
nitrogen-centered radicals (i.e., RC*, RO*, RS*, and RN*) that
can in turn lead to the formation of organic peroxides and
superoxide anion radicals ( O2*- ) in the presence of molecular
oxygen. Jay A, LaVerne JA. OH Radicals and Oxidizing Products
in the Gamma Radiolysis of Water. Radiation Research. 2000;
153:196-200.
4. Radiation Toxicity: Lipid’s Radiation
Toxins.
While the strongly electrophilic HO* has the capacity
to damage molecules like polypeptides, amino acids,
and polyunsaturated fatty acids (PUFAs) directly, the
alterations caused by peroxide and superoxide radicals
are usually produced indirectly via Fenton-type
reactions. Juliann G. Kiang, Risaku Fukumoto and
Nikolai V. Gorbunov. http://dx.doi.org/10.5772/48189
5. Radiation Toxicity: Lipid’s Radiation Toxins.
Lipid A is a lipid component of an endotoxin held
responsible for toxicity of Gram-negative bacteria. It is
the innermost of the three regions of
the lipopolysaccharide(LPS, also called endotoxin)
molecule, and its hydrophobic nature allows it to
anchor the LPS to the outer membrane. While its toxic
effects can be damaging, the sensing of lipid A by the
human immune system may also be critical for the
onset of immune responses to Gram-negative
infection, and for the subsequent successful fight
against the infection.
http://en.wikipedia.org/wiki/Lipid_A.
8. Radiation Toxicity: Lipid’s Radiation Toxins. Infections and Radiation share
similar mechanisms of protease activation, transcription of pro-inflammatory
proteins, development of apoptosis or necrosis.
12. Radiation Toxicity: Lipid’s Radiotoxins.
Many of the immune activating abilities of LPS can be
attributed to the lipid A unit. It is a very potent
stimulant of the immune system, activating cells (for
example, monocytes or macrophages) at picogram per
milliliter quantities.
When present in the body at high concentrations
during a Gram-negative bacterial infection, it may
cause shock and death by an "out of control" excessive
immune reaction.
http://en.wikipedia.org/wiki/Lipid_A.
13. Radiation Toxicity: Lipid’s Radiation Toxins.
Lipid A consists of two glucosamine (carbohydrate/sugar)
units with attached acyl chains ("fatty acids”), and
normally containing one phosphate group on each .
carbohydrate
The optimal immune activating lipid A structure is
believed to contain 6 acyl chains. Four acyl chains
attached directly to the glucosamine sugars are beta
hydroxy acyl chains usually between 10 and 16 carbons in
length. Two additional acyl chains are often attached to the
beta hydroxy group. E. coli lipid A, as an example, typically
has four C14 hydroxy acyl chains attached to the sugars and
one C14 and one C12 attached to the beta hydroxy groups.
14. Radiation Toxicity: Lipid’s Radiation Toxins.
Lipid A with a reduced number of acyl chains (for
example; four) can serve as an inhibitor of immune
activation induced by Gram-negative bacteria, and
synthetic versions of these inhibitors are in clinical
trials for the prevention of harmful effects caused
by Gram-negative bacterial infections.
On the other hand, modified versions of lipid A can be
used as components of vaccines (adjuvants) to
improve their effect
15. Radiation Toxicity: Lipid’s Radiation Toxins.
Lipid A (and LPS) has been demonstrated to activate
cells via Toll-like receptor 4 (TLR4), MD2 and CD14on
the cell surface (Poltorak, Beutler et al., Blood Cells
Mol Dis 1998)(Beutler, Poltorak, J Endotoxin Res
2000)(Park et al., Nature 2009). Consequently, lipid
A analogs like eritoran can act as TLR4 antagonists.
They are being developed as drugs for the treatment of
excessive inflammatory responses to infections with
Gram-negative bacteria.
16. Radiation Toxicity: Lipid’s Radiation
Toxins.
Clinical symptoms induced by Bacterial
Superantigene:
Central Nervous System involvement
Peripheral nervous system
Confusion, Irritability, Lethargy
Cardio-Vascular System involvement
Systolic Blood Pressure :< 90 mmHg
Tachycardia >100 beats/min,
Hypotension, Hyperventilation, Loss of
Sympathetic responsiveness .
27. Radiation Toxicity: Lipid’s
Radiation Toxins.
Comparative analysis of clinical symptoms induced by
radiation and/or Radiation
Toxins – (SRD group 1-4)- induced ARS and those
produced by Toxic Shock Syndrome
induced by Bacterial Superantigene
28. Radiation Toxicity: Lipid’s Radiation
Toxins.
Biochim Biophys Acta. 1987 Oct 16;903(3):519-24.
Radioprotective effects of lipid A, liposomes, and
liposomes containing lipid A in mice.
Richardson EC1, Alving CR.
29. Radiation Toxicity: Lipid’s Radiation
Toxins.
“Lipid A from Gram-negative bacterial
lipopolysaccharide (endotoxin) was incorporated into
liposomal membranes and examined as a prophylactic
radioprotectant compound in lethally irradiated mice.
Splenic hematopoietic activity, resulting in increased
numbers of spleen cell colonies, was induced both by
lipid A alone or more strongly by liposomal lipid A.
Increased survival of lethally irradiated animals was
induced to a slight extent by liposomes alone, to a
greater extent by lipid A, and at the highest level by
liposomes containing lipid A.”
30. Radiation Toxicity: Lipid’s Radiation
Toxins.
“Under conditions where 100% of untreated or saline-
treated animals died of acute radiation syndrome after
20 days, more than 90% of the animals pretreated with
liposomal lipid A were still alive 30 days after
irradiation. We conclude that lipid A had substantial
radioprotectant activity by itself, and the activity was
enhanced by incorporation into liposomes. Liposomes
alone also exhibited mild radioprotectant effects.”