Free radicals are molecules with unpaired electrons that are highly reactive. They are produced through normal cellular metabolism and environmental exposures. Reactive oxygen species (ROS) include superoxide, hydrogen peroxide, and hydroxyl radicals. Lipid peroxidation occurs in three phases - initiation, propagation, and termination. ROS can damage lipids, proteins, carbohydrates, and nucleic acids. This contributes to diseases like cancer, cardiovascular disease, diabetes, and neurological disorders. Antioxidants help prevent and limit oxidative damage from free radicals. Enzymatic antioxidants like superoxide dismutase, catalase, and glutathione peroxidase neutralize ROS.
A free radical is a molecule or molecular fragment that contains one or more unpaired electrons in its outermost orbital.
Free radical is generally represented by superscript dot.
lutathione (GSH) is an antioxidant in plants, animals, fungi, and some bacteria and archaea.Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It also plays a role in the hepatic biotransformation and detoxification process; it acts as a hydrophilic molecule that is added to other lipophilic toxins or wastes prior to entering biliary excretion.
Free radicals in human diseases and the roleMohammed Sakr
Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Free radicals are a main cause of cardiovascular diseases, cancer, aging and immune defense disorders. Foods like berries and carrot protect us against free radicals.
A free radical is a molecule or molecular fragment that contains one or more unpaired electrons in its outermost orbital.
Free radical is generally represented by superscript dot.
lutathione (GSH) is an antioxidant in plants, animals, fungi, and some bacteria and archaea.Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It also plays a role in the hepatic biotransformation and detoxification process; it acts as a hydrophilic molecule that is added to other lipophilic toxins or wastes prior to entering biliary excretion.
Free radicals in human diseases and the roleMohammed Sakr
Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Free radicals are a main cause of cardiovascular diseases, cancer, aging and immune defense disorders. Foods like berries and carrot protect us against free radicals.
De novo synthesis of fatty acids (Biosynthesis of fatty acids)Ashok Katta
Synthesis of fatty acids in the body. Detailed pathway for de novo synthesis of fatty acids in the body including its energetic and regulation. also cover Multienzyme complex
Protein which are major component of our diet have amino acid as their precursor and also act as important energy source. Any imbalance in the metabolism of these amino acid cause disorders
Estimated amimo acids contribute 5-15% of energy during prolonged exercise
Because energy demands are so high during exercise, a small percentage is still substantial
Amino acids are essential to integrity of skeletal muscle, their use for energy is of concern
free radicals and antioxidants , effect of free radicals , phases , free radicals in cancer, diabeties and neurodegenerative disease including pathology of each disease.
De novo synthesis of fatty acids (Biosynthesis of fatty acids)Ashok Katta
Synthesis of fatty acids in the body. Detailed pathway for de novo synthesis of fatty acids in the body including its energetic and regulation. also cover Multienzyme complex
Protein which are major component of our diet have amino acid as their precursor and also act as important energy source. Any imbalance in the metabolism of these amino acid cause disorders
Estimated amimo acids contribute 5-15% of energy during prolonged exercise
Because energy demands are so high during exercise, a small percentage is still substantial
Amino acids are essential to integrity of skeletal muscle, their use for energy is of concern
free radicals and antioxidants , effect of free radicals , phases , free radicals in cancer, diabeties and neurodegenerative disease including pathology of each disease.
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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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
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
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists
FREE RADICALS & ANTIOXIDANTS
1.
2. A free radical is a molecule or molecular
fragment that contains one or more unpaired
electrons in its outer orbital.
Represented by a superscript dot, (R•).
Oxidation reactions ensure that molecular
oxygen is completely reduced to water.
The products of partial reduction of oxygen
are highly reactive, called Reactive oxygen
species or ROS
4. H2O2 & singlet oxygen are not free radicals
Because of their extreme reactivity, they are
included in the group of ROS.
Characteristics of ROS:
Extreme reactivity.
Short life span.
Generation of new ROS by chain reaction.
Damage to various tissues.
5. Cellular Metabolism
Leakage of electrons from ETC
Production of H2O2 or O2 by xanthine oxidase & NADPH oxidase.
Due to membrane lipid peroxidation
Peroxisomal generation-oxidation of O2 & H2O2
During prostaglandin synthesis
Production of nitric oxide from arginine
During phagocytosis
In the oxidation of heme to bile pigments
Auto-oxidation (e.g. metal ions, Fe2+, Cu2+ glutathione, ascorbic acid)
6. Environmental effects
Result of drug metabolism. Cytochrome P450 related reactions.
Due to damage caused by ionizing radiations on tissues (X-rays)
Photolysis of O2 by light
Photoexcitation of organic molecules
Cigarette smoke
Alcohol promotes lipid peroxidation.
7.
8. Lipid peroxidation of occurs in 3 stages-
initiation, propagation & termination
Initiation phase:
This step involves the removal of hydrogen
atom (H) from polyunsaturated fatty acids
(LH), caused by hydroxyl radical.
LH + OH- L- + H2O
9. Propagation phase:
Under aerobic conditions, the fatty acid
radical (L-) takes up oxygen to form peroxy
radical (LOO-).
The latter, in turn, can remove H-atom from
another PUFA (LH) to form lipid
hydroperoxide (LOOH).
LH + OH- L- + H2O
LOO- + LH LOOH + L-
10. The hydroperoxides are capable of further
stimulating lipid peroxidation as they can
form alkoxy (LO-) & peroxyl (LOO-) radicals.
2LOOH LO- + LO2- + H2O
LOOH LO- + LOO- + aldehydes
Termination:
Lipid peroxidation proceeds as a chain
reaction until the PUFA gets oxidized.
11. The products of lipid peroxidation are unstable e.g.
carbonyls, esters, alkanes, alkenes, 2-alkenal ,2 ,4-
alkadienal, MDA.
Malondialdehyde (-CHO-CH2-CHO-) is a marker for
the assessment of lipid peroxidation.
MDA & other aldehydes react with thiobarbituric
acid & produce red-coloured products -
thiobarbituric acid reactive substances (TBARS)
which can be measured colorimetrically.
12. During the course of phagocytosis,
inflammatory cells, particularly the
macrophages produce superoxide, by NADPH
oxidase.
This O2 radical gets converted to H2O2 & then
to hypochlorous acid (HCIO).
Superoxide radical along with hypochlorous
ions brings about bactericidal action.
13. The beneficial affects of the free radicals
generated by the body.
A large amount of O2 is consumed by
macrophages during their bactericidal
function, a phenomenon referred to as
respiratory burst.
14. Proteins: Free radicals cause oxidation of
sulfhydryl groups & modification of certain
amino acids (e.g. methionine, cysteine,
histidine, tryptophan).
ROS may damage proteins by
fragmentation, cross-linking & aggregation.
Lipids: PUFA are susceptible to damage by
free radicals.
15. Carbohydrates:
Oxidation of monosaccharides (e .g. glucose)
can produce H2O2 & oxoaldehyde.
Glycation increases the susceptibility of
proteins to the attack by free radicals. E.g. DM.
Nucleic acids:
Free radicals may cause DNA strand breaks,
fragmentation of bases & deoxyribose.
16. Chronic Inflammation
Chronic inflammatory diseases such as
rheumatoid arthritis are self-perpetuated by
the free radicals released by neutrophils.
ROS induced tissue damage appears to be
involved in pathogenesis of chronic
ulcerative colitis, chronic glomerulonephritis,
17. Cardiovascular diseases (CHD):
Oxidized low density lipoproteins (LDL),
formed by the action of free radicals,
promote atherosclerosis & CHD.
Cancer:
Free radicals can damage DNA & cause
mutagenicity and cytotoxicity & play a key
role in carcinogenesis.
18. Respiratory diseases:
Direct exposure of lungs to 100% oxygen for a
long period is known to destroy endothelium
& cause lung edema.
This is mediated by free radicals.
ROS are also responsible for adult
respiratory distress syndrome (ARDS), a
disorder characterized by pulmonary edema.
19. Diabetes:
Destruction of islets of pancreas due to the
accumulation of free radicals is one of the
causes for the pathogenesis of IDDM.
Cataract:
Increased exposure to oxidative stress
contributes to cataract formation.
Male infertility: Free radicals reduce sperm
motility & viability & male infertility.
20. Aging process:
Reactive oxygen metabolites (ROM) play a
pivotal role in the degenerative brain
disorders such as Parkinsonism, Alzheimer's
dementia and multiple sclerosis.
Cumulative effects of free radical injury
cause gradual deterioration in aging
process.
21. Antioxidants in relation to lipid peroxidation:
Preventive antioxidants that will block the
initial production of free radicals e.g.
catalase, glutathione peroxidase.
Chain breaking antioxidants that inhibit the
propagative phase of lipid peroxidation e.g.
Superoxide dismutase, vitamin E, uric acid.
22. According to location:
Plasma antioxidants: e.g. β-carotene,
ascorbic acid, bilirubin, uric acid,
ceruloplasmin, transferrin.
Cell membrane antioxidants: e.g. α-
tocopherol.
Intracellular antioxidants: e.g. SOD,
catalase, glutathione peroxidase.
23. According to nature & action:
Enzymatic antioxidants:
E.g. SOD, catalase, glutathione peroxidase &
glutathione reductase.
Non-enzymatic antioxidants:
Nutrient: carotenoids, α-tocopherol, selenium &
vitamin C.
Metabolic: glutathione, ceruloplasmin, albumin,
bilirubin, transferrin, ferritin, uric acid.
24. Superoxide dismutase:
It converts superoxide (O2) to hydrogen
peroxide & O2.
This is the first line of defense to protect cells
from the injurious effects of superoxide
Catalase:
H2O2 is metabolised by catalase.
25. Glutathione peroxidase:
It detoxifies H2O2 to H2O, while reduced
glutathione (G-SH) is converted to oxidized
glutathione (GS-SG).
The reduced glutathione can be regenerated
by glutathione reductase utilizing NADPH.
HMP shunt is the major source of NADPH.
26. Textbook of Biochemistry - U Satyanarayana
Textbook of Biochemistry - DM Vasudevan