Human mesenchymal stem cells (MSC) are important tools for several cell-based therapies. However, their
use in such therapies requires in vitro expansion during which MSCs quickly reach replicative senescence. Recent studies
on the other hand, have implicated telomerase in the cellular response to oxidative damage, suggesting that telomerase has
a telomere-length independent function that promotes survival. Here, we studied the DNA damage accumulation
and repair during in vitro expansion as well as after acute external oxidative exposure of control MSCs and MSCs that
overexpress the catalytic subunit of telomerase (hTERT MSCs). We showed that hTERT MSCs at high passages
have a significant lower percentage of DNA lesions as compared to control cells of the same passages. Additionally, less damage was accumulated due to external oxidative insult in the nuclei of hTERT overexpressing cells as compared to the
control cells. Moreover, we demonstrated that oxidative stress leads to diverse nucleus malformations, such as multillobular
nuclei or donut-shaped nuclei, in the control cells whereas hTERT MSCs showed significant resistance to the formation
of such defects. On the basis of these results, we propose that hTERT enhancement confers resistance to genomic damage due to the amelioration of the cell’s basic antioxidant machinery.
Human mesenchymal stem cells (MSC) are important tools for several cell-based therapies. However, their
use in such therapies requires in vitro expansion during which MSCs quickly reach replicative senescence. Recent studies
on the other hand, have implicated telomerase in the cellular response to oxidative damage, suggesting that telomerase has
a telomere-length independent function that promotes survival. Here, we studied the DNA damage accumulation
and repair during in vitro expansion as well as after acute external oxidative exposure of control MSCs and MSCs that
overexpress the catalytic subunit of telomerase (hTERT MSCs). We showed that hTERT MSCs at high passages
have a significant lower percentage of DNA lesions as compared to control cells of the same passages. Additionally, less damage was accumulated due to external oxidative insult in the nuclei of hTERT overexpressing cells as compared to the
control cells. Moreover, we demonstrated that oxidative stress leads to diverse nucleus malformations, such as multillobular
nuclei or donut-shaped nuclei, in the control cells whereas hTERT MSCs showed significant resistance to the formation
of such defects. On the basis of these results, we propose that hTERT enhancement confers resistance to genomic damage due to the amelioration of the cell’s basic antioxidant machinery.
Neuromics base presentation 2020 with Virus Transport MediaPete Shuster
Neuromics' is a leader in providing Biopharmas, Academic and Government with CFR compliant 2 and 3-D human primary cell assays, media and supplements for discovery. We also provide antibodies, proteins/growth factors, apoptosis kits and genetic engineering/manipulation tools. We now have FDA registered Virus Transport Media (VTM).
EUTOX CME ERA-EDTA 2016 Vienna
A short overview on unhealthy endothelium during CKD and the role of selected uremic toxins mainly indoles, but with chocolate and zebrafish inside.
Effect of stemregenin1 and sb431542 small molecules on ex vivo expansion of u...Liberty University (LU)
Cord blood Hematopoietic stem cells (HSCs) with several advantages including low chance of viral contamination and low rate of Graft versus host disease (GVHD) are appropriate candidate for vast medical applications such as transplantation. The main obstacle of cord blood HSCs is the low number cells. To improve ex-vivo expansion of umbilical cord HSCs we introduced a new culture system. Isolated HSCs were seeded in Three-dimensional(3D) on Polyethersulfone(PES) scaffolds and Twodimensional(2D) culture conditions and treated with SB431542 and Stemregenin1(SR1) small molecules. On the fifth and tenth days the expanded cells in different groups were investigated for expression of specific markers by flow cytometry, expression of some stemness genes by qRT-PCR and colony formation by methocult medium. SR1 molecule significantly increased expansion of CD34+ cells while SB431542 induced more CD34+/38+ cells. Also SB431542 treated cells showed higher colony formation capacity. SR1 increased the expression of c-Myc, HOXB4 and SALL4 while SB431542 seemed to inhibit HOXB4 expression and increase SALL4.Together all, this study introduced a new ex vivo culture setting for further medical application of HSCs. Our data showed simultaneous use of these two small molecules can provide appropriate outcome for HSCs transplantation includes both of engraftment and repopulation.
Neuromics base presentation 2020 with Virus Transport MediaPete Shuster
Neuromics' is a leader in providing Biopharmas, Academic and Government with CFR compliant 2 and 3-D human primary cell assays, media and supplements for discovery. We also provide antibodies, proteins/growth factors, apoptosis kits and genetic engineering/manipulation tools. We now have FDA registered Virus Transport Media (VTM).
EUTOX CME ERA-EDTA 2016 Vienna
A short overview on unhealthy endothelium during CKD and the role of selected uremic toxins mainly indoles, but with chocolate and zebrafish inside.
Effect of stemregenin1 and sb431542 small molecules on ex vivo expansion of u...Liberty University (LU)
Cord blood Hematopoietic stem cells (HSCs) with several advantages including low chance of viral contamination and low rate of Graft versus host disease (GVHD) are appropriate candidate for vast medical applications such as transplantation. The main obstacle of cord blood HSCs is the low number cells. To improve ex-vivo expansion of umbilical cord HSCs we introduced a new culture system. Isolated HSCs were seeded in Three-dimensional(3D) on Polyethersulfone(PES) scaffolds and Twodimensional(2D) culture conditions and treated with SB431542 and Stemregenin1(SR1) small molecules. On the fifth and tenth days the expanded cells in different groups were investigated for expression of specific markers by flow cytometry, expression of some stemness genes by qRT-PCR and colony formation by methocult medium. SR1 molecule significantly increased expansion of CD34+ cells while SB431542 induced more CD34+/38+ cells. Also SB431542 treated cells showed higher colony formation capacity. SR1 increased the expression of c-Myc, HOXB4 and SALL4 while SB431542 seemed to inhibit HOXB4 expression and increase SALL4.Together all, this study introduced a new ex vivo culture setting for further medical application of HSCs. Our data showed simultaneous use of these two small molecules can provide appropriate outcome for HSCs transplantation includes both of engraftment and repopulation.
Of all the body systems, the lymphatic system is perhaps the least familiar to most people. Yet without it, neither the circulatory system nor the immune system could function—circulation would shut down from fluid loss, and the body would be overrun by infection for lack of immunity.
Nephrotic syndrome in Sickle Cell Disease of Western Odisha, India: A case re...inventionjournals
Sickle cell disease causes a distinct pattern of glomerular dysfunction. Subjects with sickle cell disease (SCD) are known to develop many potential functional and structural renal abnormalities. Glomerular hypertension and hyper filtration are thought to play a major role in the development of glomerular disease in subjects with SCD. We reported 5 unusual cases of sickle cell disease presenting as nephrotic syndrome. KEYWORDS- Nephrotic syndrome, sickle cell disease
Nephrotic syndrome in Sickle Cell Disease of Western Odisha, India: A case re...inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Stem-cell therapy in medicine–how far we came and what we can expect?Apollo Hospitals
The name ‘stem-cell’ is making the news in recent times both for good and not. The current articles tries to give a snap shot of the scientific and clinical picture of stem-cells in medicine as of today and discuss what it have to offer in the to the mankind. The article discusses the characters and types of stem-cells, their current indication in therapeutics (both established and upcoming), as well as their use in research. It also gives a brief overview of the current laws guiding its use in clinical practice and the various cultural beliefs associated with the use of same.
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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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 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
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.
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
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
1. Editorial Slides
VP Watch, January 16, 2002, Volume 2, Issue 2
Part II - Animal Models of Heart Attack? Plaque
Rupture/Thrombosis
2. Part - I
Cell culture is a convenient way to ask
mechanistic questions, but it lacks complexity of a
real disease thus limiting the scope of testable
hypotheses. Human observations provide rich soil
for making hypotheses, but for obvious ethical
reasons our ability to test these hypotheses in
men is very limited. Animal models are essential
for testing mechanistic hypotheses in a controlled
manner.1
Ideal animal model is situated in the middle of this
range. 1
3. 1- Japanese
quail
2- Pigeon
3- Chicken
Reported Animal Models for
Atherosclerosis
4- Dog
5- Monkey
6- Pig
7- Rat
8- Rabbit
9- Mouse
4. Quail:
- Studies on Japanese quail have shown that the
RES birds were resistant to the disease and
developed little atherosclerosis on a diet
containing 1% cholesterol. The SUS birds were
sensitive and developed severe atherosclerosis in
8-9 wks on a diet containing only 0.5%
cholesterol. 14,15,16
5. Pigeon:
- Tesar and Kottke showed that two distinct types of
fatty streaks can be identified in white Carneau
pigeon and their biologic features can be defined
and related to their propensity for atherogenesis.6
6. Chicken:
- Wong discussed that chicken is a good animal
model for the study of atherosclerosis research
because it is able to develop spontaneous
atherosclerosis and capable of producing
atherosclerosis after cholesterol feeding with
elevated hypercholesterolemia. There is no
essential difference between vascular lesions
seen in chickens as a result of cholesterol diet and
that of atherosclerosis observed in man.2,3
7. Dog:
- Reducing platelet accumulation at sites of balloon
angioplasty may attenuate restenosis. Willerson,
et al. tested this hypothesis by inducing repetitive
platelet aggregation at coronary angioplasty sites
in cholesterol sensitive dogs and measured
subsequent neointima formation. 4,5
8. Monkey:
- Blaton and Peeters discussed that the
chimpanzee lipoproteins are useful models for
understanding the relationship between function
and structure of the plasma lipoproteins in health
and disease. Baboon and rhesus monkeys show
similar results, but more differences to the human
lipoproteins in health and disease were
observed.8,9
9. Swine:
- Massmann, and others showed relations between
spontaneous and induced arterial lesions in swine
and arteriosclerosis in humans. 7,21
10. Rat:
- Bennani-Kabchi et al. showed the potential of the
sand rat to develop atherosclerotic lesions at
different stages which opens the field to
therapeutic tests of new anti-atherogenic agents.
- More recently Herrera et al. demonstrated that
cholesteryl ester transfer protein can be
proatherogenic. The interaction of polygenic
hypertension and hyperlipidemia in the
pathogenesis of atherosclerosis in Tg [hCETP] DS
rats substantiates epidemiological observations in
humans.10,11
11. Rabbit:
- Hereditary Watanabe rabbit - Clubb et
al. evaluated temporal distribution of leukocytes,
macrophages, foam cells, vascular smooth
muscle cells, and subendothelial lipid in Watanabe
heritable hyperlipedimic (WHHL) rabbit aortas.19
- Cholesterol fed New Zealand rabbit -
Atherosclerotic plaques were produced in New
Zealand White rabbits by intermittent cholesterol
feeding.20
12. Rekhter, et al. have developed a rabbit
model in which an atherosclerotic
plaque can be ruptured at will after an
inflatable balloon becomes embedded
into the plaque. This model as well can
be used for induction of thrombi
associated with plaque rupture. 17
13. Mouse:
- The apoE-deficient mouse contains the entire
spectrum of lesions observed during
atherogenesis and is the first mouse model to
develop lesions similar to those in humans. 12,13
14. Part - II
The process of atherosclerotic plaque disruption has
been difficult to monitor because of the lack of an
animal model of plaque rupture. 23
More than 30 years ago, Constantinides and
Chakravarti triggered plaque rupture and thrombosis
in aorta of chlolesterol fed rabbits by intraperitoneal
injection of Russell's viper venom (RVV, a potent
procoagulant and endothelial toxin) followed by the
intravenous injection of histamine, a vasopressor. 25
The aortas of the rabbits were then accordingly
found to have disrupted atherosclerotic plaques with
overlying platelet-rich thrombi. 25
15. The advantage of Constantinides model is use of
a biological intervention for triggering localized
plaque thrombosis. However the non-physiological
use of a toxic and potent thrombogenic substance
(snake toxin) to induce plaque thrombosis can be
considered a major drawback. 24
Other disadvantages of the Constantinides model
are the low yield of triggering (only about one third
of the rabbits developed thrombosis) and the long
(8-month) preparatory period. 24
16. Abela, Muller and colleagues challenged the
limitations of Constantinides model by having the
rabbits undergo aortic balloon injury followed by 8
weeks of 1% cholesterol diet. 24
In addition, they wanted to determine whether
mechanical injury to the aorta early in the
preparatory phase could enhance the development
of vulnerable plaques, thereby increasing the yield
of disrupted plaques and shortening the preparatory
period. the rate of plaque disruption after
pharmacological triggering increased to 71%. 24
They found that the rate of plaque disruption after
pharmacological triggering increased up to 71%.24
17. Johnstone, Manning, and colleagues used the
modified Constantinides model and documented
plaque disruption by MRI that resemble those found
in human coronary arteries. 23
A major advantage of the use of a rabbit over other
animals is that the rabbit’s aorta is approximately the
same anatomic size as the human coronary artery. 23
18. As highlighted in this week of VP Watch,
Braun, Krieger, et al. showed that mice with
homozygous null mutations in the genes for
both the LDL and apoE receptors (SR-BI/apoE
double knockout mice) exhibit morphological
and functional defects with similarities to those
seen in human coronary heart disease.22
The SR-BI/apoE dKO mice are distinct
because they have extensive coronary artery
lesions with fibrin deposition and
spontaneously develop extensive MIs on a
standard chow diet at a very young age (5
weeks).22
19. The authors indicated that severe occlusive,
fibrin-containing coronary arterial lesions,
probable ischemia, multiple MIs, enlarged
hearts, and cardiac dysfunction in very young
('5 weeks old), low-fat/ low-cholesterol fed
SR-BI/apoE dKO mice provide a novel model
of CHD.22
Fibrin deposits were found in the core regions
of 8 of 10 lesions in 3 of 3 dKO mice.22
However, clear evidence for plaque rupture
was not found in these animals neither was
thin fibrous cap.22
20. Conclusion:
I. Comparing to the previous animal models of
atherosclerosis, double knockout LDL/apoE mice
seem to offer an improvement in studying the clinical
complications of atherosclerosis closer to human
ischemic heart disease.
II. However, it is unclear as to what degree the new
model simulates the pathophysiology and pathology
characteristic of human vulnerable atherosclerotic
plaques.
21. Questions:
1. Which one the following animal models more closely
resembles human coronary artery disease?
- Watanabe rabbits
- New Zealand cholesterol fed rabbits
- CETP/DS transgenic rat
- Apo-E deficient mice
- LDL deficient mice
- Double KO LDL/apoE mice
22. Questions:
2. Since clinical atherosclerosis is predominantly an
athero-thrombotic disease, besides the plaque
characteristics in these animals, the question is how
closely their blood factors and coagulation system
resembles of those in human?
3. Since transgenic animal models of atherosclerosis do
not live long, knowing the major role of age in the
natural history of human atherosclerosis and its
complications such as plaque rupture, can we find a
representative model of repeated plaque rupture in
these animals.
24. 1. Rekhter MD, Hicks GW, Brammer DW, Work CW, Kim JS, Gordon D, Keiser JA, Ryan MJ.
Animal model that mimics atherosclerotic plaque rupture. Circ Res. 1998 Oct 5;83(7):705-13.
2. Wong HY; The cockerel as an animal model for atherosclerosis research.
Adv Exp Med Biol. 1975;63:381-91.
3. Lucas A, Yue W, Jiang XY, Liu L, Yan W, Bauer J, Schneider W, Tulip J, Chagpar A, Dai E,
Perk M,Montague P, Garbutt M, Radosavljevic M. Development of an avian model for
restenosis. Atherosclerosis. 1996 Jan 5;119(1):17-41.
4. Folts JD, Crowell EB, Rowe GG. Platelet aggregation in partially obstructed vessels and its
elimination with aspirin. Circulation. 1976; 54: 365–370.
5. Anderson HV, McNatt J, Clubb FJ, Herman M, Maffrand JP, DeClerck F, Ahn C, Buja LM,
Willerson JT.; Platelet inhibition reduces cyclic flow variations and neointimal proliferation in
normal and hypercholesterolemic-atherosclerotic canine coronary arteries.; Circulation. 2001
Nov 6;104(19):2331-7.
6. Tesar GE, Kottke BA.; Location and sequence of atherosclerotic plaque formation in white
Carneau and show racer pigeons: reevaluation and redefinition.Arch Pathol Lab Med. 1978
Nov;102(11):581
7. Massmann J, Muller H, Weidenbach H, Wagner J, Krug H.; Relations between spontaneous
and induced arterial lesions in swine and arteriosclerosis in humans. Exp Pathol (Jena). 1977
Jul- Aug;14(1-2):89-99
8. Blaton V, Peeters H.; The nonhuman primates as models for studying human atherosclerosis:
studies on the chimpanzee, the baboon and the rhesus macacus.Adv Exp Med Biol.
1976;67(00):33-64.
9. Daum G, Pham J, Deou J.; Arsenite inhibits Ras-dependent activation of ERK but activates
ERK in the presence of oncogenic Ras in baboon vascular smooth muscle cells.; Mol Cell
Biochem. 2001 Jan;217(1-2):131-6.
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25. 10. Herrera VL, Makrides SC, Xie HX, Adari H, Krauss RM, Ryan US, Ruiz-Opazo N.;
Spontaneous combined hyperlipidemia, coronary heart disease and decreased survival in
Dahl salt-sensitive hypertensive rats transgenic for human cholesteryl ester transfer protein.;
Nat Med. 1999 Dec;5(12):1383-9.
11. Bennani-Kabchi N, Kehel L, el Bouayadi F, Fdhil H, Amarti A, Saidi A, Marquie G.; New model
of atherosclerosis in sand rats subjected to a high cholesterol diet and vitamin D2. Therapie.
1999 Sep-Oct;54(5):559-65.
12. Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. ApoE-deficient mice develop
lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb. 1994
Jan;14(1):133-40.
13. Saiura A, Sata M, Hirata Y, Nagai R, Makuuchi M.; Tranilast inhibits transplant-associated
coronary arteriosclerosis in a murine model of cardiac transplantation. Eur J Pharmacol. 2001
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