This document discusses advanced glycation end products (AGEs), which are compounds formed when sugars bind to proteins or lipids. AGEs accumulate in tissues over time and can promote oxidative stress and inflammation. The document notes that AGEs can enter the body through diet, as many cooking methods promote AGE formation, and through smoking. It explores the mechanisms by which AGEs may contribute to diseases like diabetes through depletion of antioxidant defenses. The document also discusses evidence that a low-AGE diet can help reduce circulating AGE levels and markers of oxidative stress and inflammation.
Aging is the progressive accumulation of damage to an organism over time leading to disease and death. Aging research has been very intensive in the last years aiming at characterizing the Pathophysiology of aging and finding possibilities to fight age-related diseases. Various theories of aging have been proposed. In the last years advanced glycation end products (AGEs) have received particular attention in this context. AGEs are formed in high amounts in diabetes but also in the physiological organism during aging. Higher levels of diabetic complications are due to poor glycemic control. The incidence and prevalence of diabetes mellitus is rising. About 50% of people with diabetes mellitus are unaware of their condition. Pharmacotherapy and Therapeutic lifestyle change (Diet, Regular exercises, Sunshine, Vitamin D and Calcium normal levels) should be the cornerstone of diabetes management.
Aging is the progressive accumulation of damage to an organism over time leading to disease and death. Aging research has been very intensive in the last years aiming at characterizing the Pathophysiology of aging and finding possibilities to fight age-related diseases. Various theories of aging have been proposed. In the last years advanced glycation end products (AGEs) have received particular attention in this context. AGEs are formed in high amounts in diabetes but also in the physiological organism during aging. Higher levels of diabetic complications are due to poor glycemic control. The incidence and prevalence of diabetes mellitus is rising. About 50% of people with diabetes mellitus are unaware of their condition. Pharmacotherapy and Therapeutic lifestyle change (Diet, Regular exercises, Sunshine, Vitamin D and Calcium normal levels) should be the cornerstone of diabetes management.
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporters are present in all phyla.
GLP-1 is an incretin (hormone that increases insulin secretion in response to a meal), which is a 30-amino acid peptide secreted in response to the oral ingestion of nutrients by intestinal L cells.
GLP-1 receptors (GLP-1R) are located in islet cells, central nervous system, and other organs. GLP-1 is metabolized by the enzyme dipeptidyl peptidase-4 (DPP-4).
Incretin effect is a phenomenon whereby a glucose load delivered orally produces a much greater insulin secretion than the same glucose load administered intravenously.
This presentation is an overview of the entire GLP-1 system, followed by an introduction to leveraging its therapeutic potential using GLP-1 analogues (Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide) and DPP-4 inhibitors (Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Trelagliptin, Omarigliptin).
Shashikiran Umakanth delivered this talk at Manipal on 30th November, 2015
Keratinized tissue, also known as keratinized mucosa, refers to the band of tissue surrounding your teeth at the point where they meet the gums. The word "keratinized" is used to describe cells that produce large amounts of a protein called keratin, making them strong and better at forming barriers. Local irritation interferes with keratinization, and healthy gingiva is more keratinized than diseased, irritated gingiva. Nonepithelial cells are also present in the oral gingival epithelium. These include melanocytes, and Langerhans cells in the stratum spinosum. In the oral cavity, keratinized mucosa is found in the gingiva and palate mucosa, whereas the non-keratinized mucosa is found in the buccal mucosa.
pathology and Complications of type 2 diabetes mellitusAiswarya Thomas
explains in detail abou various complications of diabetes mellitus and its pathophysiology. Described about the peripheral, microvascular, macrovascular comlpication
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporters are present in all phyla.
GLP-1 is an incretin (hormone that increases insulin secretion in response to a meal), which is a 30-amino acid peptide secreted in response to the oral ingestion of nutrients by intestinal L cells.
GLP-1 receptors (GLP-1R) are located in islet cells, central nervous system, and other organs. GLP-1 is metabolized by the enzyme dipeptidyl peptidase-4 (DPP-4).
Incretin effect is a phenomenon whereby a glucose load delivered orally produces a much greater insulin secretion than the same glucose load administered intravenously.
This presentation is an overview of the entire GLP-1 system, followed by an introduction to leveraging its therapeutic potential using GLP-1 analogues (Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide) and DPP-4 inhibitors (Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Trelagliptin, Omarigliptin).
Shashikiran Umakanth delivered this talk at Manipal on 30th November, 2015
Keratinized tissue, also known as keratinized mucosa, refers to the band of tissue surrounding your teeth at the point where they meet the gums. The word "keratinized" is used to describe cells that produce large amounts of a protein called keratin, making them strong and better at forming barriers. Local irritation interferes with keratinization, and healthy gingiva is more keratinized than diseased, irritated gingiva. Nonepithelial cells are also present in the oral gingival epithelium. These include melanocytes, and Langerhans cells in the stratum spinosum. In the oral cavity, keratinized mucosa is found in the gingiva and palate mucosa, whereas the non-keratinized mucosa is found in the buccal mucosa.
pathology and Complications of type 2 diabetes mellitusAiswarya Thomas
explains in detail abou various complications of diabetes mellitus and its pathophysiology. Described about the peripheral, microvascular, macrovascular comlpication
Microvascular complications of diabetes pathophysiologyMWIZERWA JEAN-LUC
it is presented by a MEDICAL STUDENT AT UNIVERSITY OF RWANDA
topic is about pathophysiology mechanisms of glypcerglycemia in causing microvascular complications. it will help medical student to know deep in cascade how high concentration ogf glucose is converted into other substances to affect blood vessels.
Resveratrol, Caloric Restriction and Longevity in Human Mitochondrial Dysfunc...Ayetenew Abita Desa
Caloric restriction and the phytoalexin resveratrol found to increase longevity and decrease aging. This is the summary I have made after extensive review. everybody is invited to comment on it.
Type 2 diabetes mellitus (T2DM) is a complex, heterogeneous group of metabolic disorders characterized by insulin resistance
and failure of pancreatic β-cell leading to chronic hyperglycemia. Hyperglycemia causes dysfunctions in multiple organs or tissues, which not only decrease life quality and expectancy, but are also becoming a problem regarding the financial burden for healthcare systems. Therefore, the continually increasing of diabetes worldwide, understanding the pathophysiology, the main risk factors, and the underlying molecular mechanisms may establish a basis for prevention and therapy. In this regard, research was performed revealing further evidence of formation of advanced glycation end products (AGEs), which are a complex and heterogeneous group of modified proteins and/or lipids with damaging potential, is one contributing factor. However, it has been reported that AGEs increase the level of reactive oxygen species formation and impair antioxidant systems, on the other hand the formation of some AGEs is induced per se under oxidative conditions. However, the role of AGEs in the pathogenesis of T2DM and diabetic complications if they are causal or simply an effect is only partly understood. This review will highlight the mechanisms involvement of AGEs in the development and progression of T2DM and the role of AGEs in the development of diabetic complications.
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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
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
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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.
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.
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
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.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
8. gs
What are AGE
AGE and diet
AGE mediated injury - mechanism
AGE are they diabetogenic?
AGE and diabetes
AGE- therapeutic implication
9. gs
AGEs can be introduced into the circulation even in
the absence of diabetes, together with nutrients
processed by common methods such as dry heat or
during tobacco smoking .
Food processing - dry heat, ionization, or
irradiation accelerates the generation of new AGEs
whether done at industrial or commercial levels
Heat and dehydration are also common in home
cooking.
Though intended to improve safety, digestibility,
and transportability of foods - heat and
dehydration amplify the formation of AGEs.
For the food industry, AGEs in food are highly
desirable because of the profound effect of AGEs on
food flavor and, hence, on food consumption
11. gs
Human and animal studies
demonstrated that about 10 % of
AGEs contained in a meal can be
absorbed into the circulation, of
which two-thirds remain in the body
for 72 hours
they stay long enough to promote
OS, more AGEs, and potentially more
tissue injury.
12. gs
A high- or low-AGE diet is defined on
whether the estimated dietary AGE
intake is greater or lower than 15,000
AGE kU/day
This happens to be the median
dietary AGE intake in our cohort of
healthy community dwellers .
This is largely attributed to the fact
that most favored methods of food
preparation promote AGE formation.
13. gs
What are AGE
AGE and diet
AGE mediated injury - mechanism
AGE are they diabetogenic?
AGE and diabetes
AGE- therapeutic implication
14. gs
Steady-state AGE levels reflect
- glycemia and also
- balance of oral intake
- endogenous formation
- catabolism of AGEs
AGE catabolism is dependent on
- tissue anti-oxidant reserves
- macromolecular turnover
- receptor-mediated AGE degradation
15. gs
AGEs induce native AGER1.
Prolonged supply of external
AGEs depletes AGER1.
The ensuing surplus OS
promotes inflammation via RAGE
16. gs
Chronically elevated
AGEs,via high OS
cause SIRT1
depletion.
Decreased SIRT1
levels promote NF-κB
p65 hyper-acetylation
and enhanced
transcription of
inflammatory genes,
such as TNFα, which
contributes to insulin
resistance.
17. gs
AGER1and SIRT1 and other defense
mechanisms, is suppressed in chronic
diabetes.
both AGER1 and SIRT1 are restored after
lowering the external oxidant burden by
AGE restriction.
19. gs
What are AGE
AGE and diet
AGE mediated injury - mechanism
AGE are they diabetogenic?
AGE and diabetes
AGE- therapeutic implication
20. gs
On a chronic basis,consumption of
high AGE foods can cause a strain
upon, and eventually a depletion of
native anti-oxidant defenses, setting
the stage for disease, ie, diabetes.
23. gs
primary adipocytes from trans-generational
mice exposed for life to specific AGEs were
compared to a low diet mouse
by the fifth generation MG-fed mice developed
insulin resistance as early as 16–18 months of
age instead of 24– 26 months of age seen in
the regular chow-fed controls.
The AGE-restricted cohort did not develop
these changes until beyond the age of 36
months or a time interval corresponding to
approximately 20 human years.
24. gs
These findings show that
prolonged exposure to an oxidant force
that normally does not exist in nature over the
span of several generations
can deplete innate immune defenses,
misfiring inflammatory responses or
fostering metabolic defects namely insulin
action
AGE-mediated β-cell toxicity is through the
inhibition of cytochrome-c oxidase and reduced
ATP production and impairing insulin secretion
25. gs
High AGE levels in T2D patients had been
attributed to endogenous sources, namely
hyperglycemia and OS
nondiabetic persons too could have “diabetic”
levels of serum AGEs and OS if they consumed
a diet with a high AGE content .
Serum AGEs correlated with dietary AGE
intake, as well as with established markers of
OS and inflammation, such as hsCRP and TNFα
independent of age or diabetes
26. gs
What are AGE
AGE and diet
AGE mediated injury - mechanism
AGE are they diabetogenic?
AGE and diabetes
AGE- therapeutic implication
29. gs
Serum AGEs were shown to correlate with
fasting insulin, HOMA-IR and BMI and after a 4-
month treatment with an AGE-restricted diet, a
significant reduction in plasma insulin and
leptin were associated with a marked rise in
adiponectin consistent with improved insulin
sensitivity.
significant increase in AGER1 and SIRT1 levels
tied to reduced mononuclear cell NF-κB activity
and decreased TNFα levels - consistent with
suppressed inflammation
30. gs
These findings were independent of any
changes in standard medical therapy, they
support the postulate that the externally
derived proinflammatory AGEs are an
important culprit
these abnormalities can be effectively and
economically modulated by a modest decrease
(~50 %) of the amount of AGEs in the diet,
without changes in nutrient or calories.
32. gs
What are AGE
AGE and diet
AGE mediated injury - mechanism
AGE are they diabetogenic?
AGE and diabetes
AGE- therapeutic implication
33. gs
Cigarette smoking
The processing or curing of tobacco involves
AGE formation since the plant leaves are heat-
dried in the presence of reducing sugars, added
for purposes such as taste and smell.
Subsequent combustion can lead to the
inhalation of AGE derivatives and transferred
into the circulation
chronic cigarette smokers compared with their
peers had higher
AGE levels in the arterial wall samples or
ocular lenses
Levels of serum AGEs
Serum LDL-apolipoprotein-B
34. gs
a low AGE intake can be easily achieved by using
lower heat,
higher humidity
instead of roasting, grilling or frying, use
stewing, poaching
avoiding highly processed pre-packaged and
fast foods
Patients with diabetes have found such a program
to be easily incorporated into their personal and
family life.
Various inhibitors of post-Amadori glycation
intermediates (glyoxal, methylglyoxal, 3-
deoxyglucosone) are described including
aminoguanidine , pyridoxamine, benfotiamine
35. gs
use of antioxidants as anti-AGE agents like
vitamin E
N-acetylcysteine
taurine
alpha lipoic acid
penicillamine
showed disappointing results
Bot all these previous trials did not consider the
large exogenous oxidant surplus entering the
gastrointestinal tract and likely neutralizing them,
their failure may not be surprising.
More studies with new agents and expanded range
of dosages will be needed to definitively establish
their effectiveness
36. gs
sevelamer carbonate, an oral nonabsorbable negatively
charged polymer, known clinically for its phosphate-
binding capacity can bind AGEs in a pH-dependent
manner and sequester AGEs in the gut.
After 2 months, sevelamer carbonate, but not CaCO3,
another phosphate-binder that does not bind AGEs,
effectively lowered circulating AGEs, as well as markers
of OS and inflammation in diabetic subjects with chronic
kidney disease
the agent restored AGER1 and SIRT-1 to normal levels
This strategy, confirming the importance of reducing
absorption of oral AGEs, provides critical support to
AGE-restriction and may offer an important adjunct
treatment strategy.
37. gs
What are AGE
AGE and diet
AGE mediated injury - mechanism
AGE are they diabetogenic?
AGE and diabetes
AGE- therapeutic implication
41. gs
Degradation products of AGE-proteins resulting
from the action of AGER1 and other receptor
give rise to AGE-peptides, which normally filter
across the glomerular membrane.
After filtration they undergo variable degrees of
tubular reabsorption or further catabolism by
the proximal tubule, and excretion in the urine.
an inverse correlation exist between serum
AGE levels and renal function estimated by
glomerular filtration rate
42. gs
The protective effects of AGER1 may
stem from its long extracellular tail
with high-affinity AGE-binding domain
These domains competitively interfere
with other AGE cell surface
interactions leading to ROS
43. gs
RAGE promote and perpetuate cell
activation and tissue injury via increased
OS .
The balance between these 2 receptors
may be critical in the maintenance of
oxidant homeostasis or progression to
diabetes
AGER1 disrupts RAGE signaling and
promotes the expression and
functions of SIRT1
SIRT1 is a regulator of inflammation
and the metabolic actions of insulin.
45. gs
In self-declared normal controls from our
population a significant association with HOMA,
an indicator of IR, was noted suggesting that
the standard western diet could serve as a
constant source of oxidants
Other studies reported lowered levels of serum
AGEs in diabetic patients after 2 months on a
low-AGE diet .
a low AGE diet program can be highly effective
in reducing chronic OS and inflammation so
the modern food environment can act as a
significant source of AGEs, which are capable of
altering native defenses and of disturbing
antioxidant balance in humans.