This document discusses research into using superparamagnetic iron oxide (SPIO) nanoparticles and MRI to non-invasively detect vulnerable plaque. In vitro studies showed macrophages uptake SPIO, reducing T2 relaxation time in a time- and concentration-dependent manner. SPIO were also found to be taken up by macrophages in atherosclerotic plaques of ApoE mice but not in normal aortas. MRI of ApoE mice showed negatively enhanced aortic walls after SPIO injection compared to control mice. Other studies have also used SPIO-enhanced MRI to image atherosclerotic plaques in rabbits. The research aims to develop an MRI method using SPIO to identify inflammation, leaky angiogenesis, and other features
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
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.
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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
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
13. Less angiogenesis (?)Extensive angiogenesis
Low modified cholesterolHigh modified cholesterol
High collagen contentLow collagen content
Small or no lipid poolLarge lipid pool
Thick fibrous capThin fibrous cap
Low-Risk Plaque,
Hard Plaque
Unstable Plaque, High-Risk
Plaque, Soft Plaque
Structural or Morphologic Classification
Vulnerable Plaque Stable Plaque
14. Not exposed but may
contain as much
Exposed proteoglycans
(versican and hyaluronan)
Intact endothelial lawyerEndothelial denudation
High collagen contentOverlaying thrombosis
No thrombosisDisrupted / fissured cap
Concentric (negative
remodeling)
Eccentric (positive
remodeling)
Small or large plaque
volume
Small or large plaque
volume
Structural or Morphologic Classification
Vulnerable Plaque Stable Plaque
Cont…
16. Minimum apoptosis
…
Excessive apoptosis
…
Low oxidative stressHigh oxidative stress
(excessive oxygen and nitrogen free
radical formation)
Normal or high pH with
minimum pH heterogeneity
Acidic with high pH
heterogeneity
Normal temperature with
minimal heterogeneity
Hot with increased
temperature heterogeneity
Low traffic (monocyte and T
cell recruitment)
High traffic (monocyte and T
cell recruitment)
Quiescent Plaque
Low-Risk Plaque
Active Plaques
Unstable Plaque
High-Risk Plaque
Functional or Physiologic Classification
Vulnerable Plaque Stable Plaque
17. Plaque characterization
by MRI has been
introduced by Toussaint
and others to study
structural properties of
atherosclerotic plaque.
MRI and Plaque Characterization:
19. Question!
Lets assume that we are in our
dreamland and non-invasive MR
imaging of coronary artery with
<100 micron resolution is easily
obtained, now the question is
whether we are able to accurately
detect all vulnerable plaques only
by studying their structural
properties or we need more?
20. Plaque Morphology
vs.
Plaque Activity
Why do we need to go beyond
morphological assessment of
plaques? Why do we need both?
The short answer is: because not all
plaques with similar morphology would
result in similar outcome.
21. Functional vs. Structural Imaging
Inactive and
non-inflamed
plaque
Active and
inflamed plaque
Different
Similar
IVUS OCT MRI
w/o CM
Structural:
Functional:
Thermography,
Spectroscopy, MRI w/ CM
23. We need MRI with vulnerable plaque
targeted contrast media that identifies:
1- Inflammation (macrophage infiltration),
2- Fissured/Permeable Cap,
3- Leaking Angiogenesis and
4- Intra-Plaque Hemorrhage
5- …
24. Willerson et al:
Study of fluorescent labeled
macrophage homing into
Apo E deficient mice
Circ 1998
25. SPIO
Super
Paramagnetic
Iron
Oxide
Colloidal coated nano-particles of iron oxide, e.g.
dextran coated SPIO
20-100 nanometer particle size
Phagocyted by, and accumulated in cells with
phagocytic activity
Shortening MR relaxation time, early T2 and late
T1 effect
26. USPIO
Ultra
Super
Paramagnetic
Iron
Oxide
Smaller particle size which yields a
longer circulation time, yet less
phagocytosis and more uptake by non-
immune cells
32. Cardiac Application
Monitoring rejection of transplanted
heart and lungs following rat
allograft and homograft
transplantation, w/wo cyclosporin
Ho et al, ISMRM 2000
33. Old literature!
Iron particles observed
immediately under the
endothelium 5 hours after the
administration, in artery, in a
rat with 7 days hypertension
33 years ago !!!
Gordon et al, 1968
Maamoun add Ref
34. Our Hypothesis:
Vulnerable atherosclerotic plaques
which have 1) active recruitment of
monocytes and T cells, 2)
extensive leaking angiogenesis 3)
fissured or permeable cap can be
detected by excessive uptake of
SPIO particles.
35. vasa vasorum
Over magnification is a major advantage of SPIO
Darkening property of SPIO in the white background of fat and
water of plaque is another advantage
36. Why negative enhancement?!!
Positive Contrast Negative ContrastV.S.
Gd-compounds SPIOs
+ -
Knowing that plaque has white background due to its fat and water
37. What we have done:
- In vitro study of SPIO uptake by
macrophages using fluorescent
labeled home-made SPIO
-In vitro study of SPIO uptake by
macrophages and its effect on T2
relaxation time
-In vitro study of effect of SPIO on
macrophage biology and super
oxide production
38. What we have done:
- In vivo study of bio distribution of
SPIO in Apo E deficient
atherosclerotic mice vs normal wild
type C57 black mice
In vivo MRI study of aortic wall in
Apo E deficient mice vs. wild type
normal mice 4.7 T -in collaboration
with Dr Quast’s lab UTMB
39. Invitro Study of
Macrophage SPIO Uptake
In a series of invitro studies we
have tested the rate of SPIO
uptake by human activated
monocytes in different conditions
regarding incubation time and
concentration of SPIO. All SPIO
were labeled by a fluorescent dye
(DCFA)
42. Double DAPI Staining with Fluorescence-labeled SPIO
Macrophages after 24hr Incubation
43.
44. SPIO and T2 Effect
Invitro study to show the effect
of macrophage SPIO uptake on
their T2 relaxation time
45. Protocol:
We used 8 flasks of CBM macrophages.
After preparing the cells, Feridex was
added with the proper concentration to
each labeled tube.
Incubation was done at 37 C.
For each time, pellet the tubes at 1000
rpm’s for 5 min.
Washed with 1X PBS for 5 min 3 times.
Resuspended in 2% paraformaldehyde, to
fix the cells.
49. Macrophage Uptake of Feridex After 20
Min Shown by T2 Reduction
0
10
20
30
40
50
60
70
80
90
50 100 250 500 control control
20 min
Concentration µl
53. 0
10
20
30
40
50
60
70
80
90
50 100 250 500 control control
20 min
60 min
6 hours
24 hours
Macrophage Uptake of Feridex with Time
and Concentration Shown by T2
Reduction
Concentration µl
54. 0
10
20
30
40
50
60
70
80
90
20 Min 60 Min 6 Hours 24 Hours
50
100
250
500
control
control
Macrophage Uptake of Feridex with
Concentration and Time Shown by T2
Reduction
µl
55. Study of production of
Reactive Oxygen Species
by SPIO Incubated
Macrophages
56. Since the production of
reactive oxygen species
(ROS) in the plaque might
have unfavorable effects on
the biology of the plaque,
we have planned to check if
the SPIO would excessively
produce ROS.
57. Facts
Any event of phagocytosis is immediately followed by
a transient release of super oxide due to the
assembly of the NADPH oxidase against the plasma
membrane. Subsequently the oxidase translocates
onto the phagosomes containing the SPIO to
produce intracellular ROS.
Thus an early extra cellular secretion of super oxide
is detectable (using luminol) soon after phagocytosis
and a later event of intracellular secretion is
measurable using DCFDA dye .
58. Method
· The suspension of SPIO (1.25-10 uL) was added to
macrophages (1x10*4/well in 96 well plates). Cells
were incubated for 1 h and washed to remove extra
cellular FDIO. For each dose three wells were tested.
Isoluminol substrate was added and super oxide
induced luminescence measured at 15, 30 and 45
min intervals using a luminometer.
59. Results
· SPIO was internalized by macrophages as
early as 15 min after addition.
· Uptake was followed by release of super oxide
for all four doses tested.
Super oxide was released by SPIO at all
doses tested (1.25-10 ul)
60. Dosage of SPIO: 1.25micL
0
500
1000
1500
2000
2500
3000
3500
15min 30min 45min NOSPIO
Sample1
Sample2
Sample3
ROS Production: Time VS SPIO Concentration
68. SPIO Accumulation in
Atherosclerotic Plaque
Atherosclerotic plaque
in aortic root
Normal aortic segment
Iron staining of Apo E K/O Aorta, 24 hour after SPIO injection
Iron
particles
69. ApoE Mouse 3 Days After
Injection
H&E Pearl’s
Aorta-2
Atherosclerotic plaque in thoracic aorta
70. Aortic Root after 5 days
Dense infiltration of iron particles as
shown by light blue in Pearl’s staining
83. MR Image of Abdominal Aorta After
SPIO Injection in Apo E and Control Mice
Apo E
deficient
mouse
C57B1
(control)
mouse
Before Injection After Injection (5 Days )
Dark (negatively enhanced) aortic wall, full of iron particles
Bright aortic lumen and wall without negative enhancement
and no significant number of iron particles in pathology
84. MRI Imaging of
Atherosclerosis using SPIO
Studies done recently by others:
1- Schmitz SA, Coupland SE, Gust R,
Winterhalter S, Wagner S, Kresse M,
Semmler W, Wolf KJ
Superparamagnetic iron oxide-enhanced
MRI of atherosclerotic plaques in
Watanabe hereditable hyperlipidemic
rabbits.
Invest Radiol. 2000 Aug;35(8):460-71.
85. Group I II III IV
USPIO 0 50µmol Fe/kg 50µmol 200µmol
Time - 8 hr 24 hr 48 hr
Schmitz et al J. Inv. Radiol. 2000
91. 2- Ruehm SG, Corot C, Vogt P, Kolb S,
Debatin JF.
Magnetic resonance imaging of atherosclerotic
plaque with ultrasmall superparamagnetic
particles of iron oxide in hyperlipidemic rabbits.
Circulation. 2001 Jan 23;103(3):415-22.
Studies done recently by others:
MRI Imaging of
Atherosclerosis using SPIO
92. A, Coronal MIP and (B) sagittal oblique and (C) coronal oblique
reformatted images of contrast-enhanced 3D MRA data set collected
after intravenous administration of Gd-DOTA displaying aorta of 7-
month-old hyperlipidemic rabbit. Aortic wall is smooth, without
evidence of luminal narrowing.
Reuhm et al,
Circulation
2001
93. A, Coronal MIP and (B) sagittal oblique and (C) coronal oblique
reformatted images of contrast-enhanced 3D MRA data sets of same
hyperlipidemic rabbit as depicted in Figure 1 obtained 5 days after
intravenous injection of USPIO agent Sinerem. Note susceptibility
effects originating within vessel wall and representing Fe uptake in
macrophages embedded in plaque.
Reuhm et al,
Circulation
2001
94. A, Intraluminal signal measured in single large ROI (9 mm2
) revealed significant
increase in SNR, with maximum reached at day 5 after contrast administration. These
changes reflect T2* effects, which decreased over time. B, SNR values based on 3
ROI measurements in aortic wall of each animal failed to reveal statistical difference
between precontrast and 5 days post-Sinerem image sets in normal control rabbits. In
hyperlipidemic animals, conversely, significant decrease in SNR corresponding to
select USPIO uptake in plaque formations containing MPS cells was evident.
Reuhm et al, Circulation 2001
95. Ex vivo imaging of contrast-filled aortic specimen of (A) hyperlipidemic rabbit 5 days
after administration of Sinerem, (B) normal control rabbit 5 days after administration of
Sinerem, and (C) hyperlipidemic rabbit that did not receive Sinerem. Marked
susceptibility artifacts are present in aortic wall of hyperlipidemic rabbit that had
received Sinerem (A). No such changes are visualized in other 2 rabbits (B, C).
Reuhm et al,
Circulation
2001
96. Cross-sectional histopathological sections with Prussian blue staining of aorta of same
hyperlipidemic rabbit as depicted in Figures 1 and 3, killed 5 days after administration
of USPIO agent Sinerem. Note thickening of intima with marked staining of Fe
particles embedded in atherosclerotic plaque formations.
Rheum et al,
Circulation
2001
97. Conclusion:
Non-invasive MRI study of
atherosclerotic plaques using SPIO
(pre and post injection
comparison) may be a likely
method for detection of vulnerable
plaques
Further studies particularly human
clinical trials are warranted
98. SPIO Clinical Trial:
- The first human clinical trial on
detection of carotid vulnerable plaque
using SPIO in patients undergoing
carotid endartherectomy
Baseline
SPIO
Injection
1hr post-
injection
5days
Scan
Surgery
99. Dr. Naghavi – The first
volunteer subject in his
Carotid MRI SPIO Study
100.
101.
102.
103.
104. Multi-Center Trial:
The second site of the study is
going to be Univ. of Washington
Seattle directed by Dr. Yuan.
The interim report of the trial will be
presented at AHA 2001 in
Anaheim
105. The Online Cardiovascular Research Community
www.VulnerablePlaque.org
All slides will be available on: