The document discusses various cardiac biomarkers used in the diagnosis of acute myocardial infarction (AMI) and heart failure. It provides details on commonly used biomarkers like Creatine Kinase MB (CK-MB), Myoglobin, Cardiac Troponins T and I, and B-type Natriuretic Peptide (BNP). It describes the time course of rise and fall of each biomarker, their tissue specificity, clinical applications and limitations. Evaluation of newer biomarkers like Ischemia Modified Albumin (IMA) and Heart Fatty Acid Binding Protein (H-FABP) is also covered along with their role in early diagnosis of AMI.
Lymphoma is a cancer of lymphocytes. The most common place for abnormal lymphocytes is in lymph nodes (glands) particularly
under the arms, in the neck and in the groin.
Lymphoma is solid tumors of the immune system arising from cells of lymphoid tissues; lymphocytes, histiocytes, and reticulum cells. It can happen anywhere in the immune system, but usually in lymph nodes, spleen, marrow, and tonsils. Location and the behavior of lymphomas separate them from leukemia.The malignancy starts and restricted to lymphoid tissues and progress to involve the BM and appears in PB, at this stage it may be named, “lymphosarcoma cell leukemia.
MI is one of the CVS complication leading to mortality whose diagnosis is mainly dependent on clinical presentation and other supportive investigation. clinical laboratory plays crucial role in its diagnosis, prognosis and monitoring therapy.
Antibody mediated rejection of solid organ allograftstashagarwal
Objectives:
Introduction of Antibody mediated rejection AMR
Role of C4d in transplant rejection
Donor specific antibodies DSA
Presentation of AMR in kidney, liver, lung and heart.
Lymphoma is a cancer of lymphocytes. The most common place for abnormal lymphocytes is in lymph nodes (glands) particularly
under the arms, in the neck and in the groin.
Lymphoma is solid tumors of the immune system arising from cells of lymphoid tissues; lymphocytes, histiocytes, and reticulum cells. It can happen anywhere in the immune system, but usually in lymph nodes, spleen, marrow, and tonsils. Location and the behavior of lymphomas separate them from leukemia.The malignancy starts and restricted to lymphoid tissues and progress to involve the BM and appears in PB, at this stage it may be named, “lymphosarcoma cell leukemia.
MI is one of the CVS complication leading to mortality whose diagnosis is mainly dependent on clinical presentation and other supportive investigation. clinical laboratory plays crucial role in its diagnosis, prognosis and monitoring therapy.
Antibody mediated rejection of solid organ allograftstashagarwal
Objectives:
Introduction of Antibody mediated rejection AMR
Role of C4d in transplant rejection
Donor specific antibodies DSA
Presentation of AMR in kidney, liver, lung and heart.
Bio-Markers of Heart Failure (Dr.LIKHIT T)Likhit T
A brief on bio-markers of Heart failure...First of all, I thank the Authors of all the books from which I picked the points to make this presentation.. This presentation includes classification of bio-markers and explanation according their importance.. Thank you
Lipid Profile test & Cardiac Markers for MBBS, Lab. Med. and Nursing.pptxRajendra Dev Bhatt
The lipid profile is a group of tests that have been shown to be good indicators of whether someone is likely to have a Coronary disease or heart attack or stroke caused by blockage of blood vessels or hardening of the arteries (atherosclerois).
cardiac bio markers are important diagnostic and prognostic tool in acute coronary syndrome. several new emerging bio markers are coming with more sensitivity and specificity.
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
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
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
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
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
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
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
2. Chairman
Dr. K.V.Venkteswaran, Professor, Dept. of
Veterinary Pharmacology and Toxicology, MVC,
Chennai
Members
Dr. S.Selvasubramanian, Professor, Dept. of
Veterinary Pharmacology and Toxicology, MVC,
Chennai
Dr.P.S.L.Sesh, Assistant Professor, Dept. o
VeterinaryBiochemistry, MVC, Chennai
3. “A biomarker is a substance used as an
indicator of a biologic state”.
Morrow and de lomos three criteria
for biomarkers
› Accurate repeated measurements at
reasonable cost
› Must provide additional information
› Should aid treatment
4. HEART FAILURE
Heart failure a major and growing health problem
appears to result not only from cardiac overload or
injury but also from complex interplay among
genetic, inflammatory and biological changes acting
on cardiac myocytes, the cardiac interstitium or
both.
ACUTE MYOCARDIAL INFARCTION
A sudden occlusion of a coronary artey by
thrombus or by embolisation causes an acute
myocardial infarction.
5. Cardiac biomarkers are protein molecules released
into the blood stream from damaged heart muscle
Since ECG…… inconclusive ….biomarkers !!!!!?????
myocardial injury
These biomarkers have a characteristic rise and fall
pattern
Dr. Jaikanth
6. High cardiac specificity
Pharmacokinetics of cardiac biomarker
Easy diagnosis
Marker should play a designed role in the treatment
and management of clinical subject
7. 1954 - SGOT (AST)
1955 - LDH
1960 - CPK
1972 - CPK isoforms by Electrophoresis
1975 - CK - MB by immunoinhibition
1975 - Myoglobin
1985 - CK - MB Mass immunoassay
1989 - Troponin T
1992 - Troponin I
8. Biomarkers of myocardial injury
› markers of myocardial necrosis
› markers of myocardial ischemia
Biomarkers of haemodynamic stress
Inflammatory and prognostic Biomarkers
9.
10. Markers of myocardial necrosis
› Creatine kinase – MB
› Myoglobin
› Cardiac troponins
• Markers of myocardial ischemia
Ischemia Modified Albumin (IMA)
Heart-type fatty acid binding protein (H-FABP)
Dr. Jaikanth
11.
12.
13. Zones of Ischemia Injury and Infarction with
Transmural and Subendocardial Infarction
14. Creatine kinase (CK/CPK) is an enzyme expressed in a
number of tissues.
Function: it catalyses the conversion of creatine to
phosphocreatine degrading ATP to ADP
The CK enzyme consists of two subunits, B (brain type) or
M (muscle type), Making three different isoenzymes: CK-MM,
CK-BB and CK-MB
CK-BB occurs mainly in tissues, rarely of any significance in the
bloodstream
Skeletal muscle expresses CK-MM (98%) and low levels of CK-
MB (1%)
The myocardium has CK-MM at 70% and CK-MB at ~30%
15. High specificity for cardiac tissue
Begins to rise 4-6 hours after onset of infarction
Peaks at about 12 hours
Returns to baseline at 24-36 hours
Can be used to indicate early re-infarction if level
normalizes and then increases again
16. CK-MB now measured via a highly sensitive monoclonal antibody
assay
Immunological Sandwich technique using two Abs for different
epitopes of CK –MB molecule
The first Ab is rendered immobile on a matrix (e.g. CrO2
particles)
The second Ab conjugate to an enzyme (β- galacto- sidase)
Separated bound sandwiches are reacted with their substrate
(e.g. Chlorophenol β- Red Galactopyranoside)
Liberated end product chlorophenol is measured
spectrophotometrically and is proportionate to CK-MB amount
(not the activity)
17.
18. The CK-MB isoforms may also be analyzed using high-
voltage electrophoresis
The ratio of MB2/MB1 is calculated
MB2 released from heart muscle and converted to MB1
A level of MB2 > or = 1 and a ratio of MB2/MB1 > 1.5
indicates myocardial injury
A result is positive if MB2 is elevated and the ratio is
more than 1.5
19. False positive (for MI) CK-MB elevation can be seen in:
› Significant skeletal muscle injury
› The MB fraction is determined to be expressed during the
process of muscle regeneration
› Cardiac injury for reason other than MI
Defibrillation
Blunt chest trauma
Cocaine abuse
The search for cardiac specificity continues…
20. Small-size heme protein found in all tissues mainly assists in
oxygen transport
It is released from all damaged tissues
Increases often occur more rapidly than TI and CK
Released from damaged tissue within 1 hour
Normal value: 17.4-105.7 ng/ml
Timing:
› Earliest Rise: 1-3 hrs
› Peak 6-9 hrs
› Return to normal: 12 hrs
22. Rapid monitor of success of thrombolytic
therapy
Negative predictor of MI
DRAWBACKS
Due to poor specificity, myoglobin levels do not
always predict myocardial injury
Not utilized often for AMI/cardiac damage
assessment because of its very rapid metabolism
23. Troponin is a complex of three regulatory proteins that is
integral to non-smooth muscle contraction in skeletal as well as
cardiac muscle
Troponin is attached to the tropomyosin sitting in the groove
between actin filaments in muscle tissue
Troponin has three subunits, TnC, TnT, and TnI
› Troponin-C has calcium binding ability and has no diagnostic
value
› Troponin-T binds the troponin tropomyosin complex,
› Troponin-I is an inhibitory protein
24.
25.
26.
27.
28. Less than 5% in cytosol
Troponin levels begin to rise 2-3 hours after onset of
myocardial injury
Elevations in Troponin-I and Troponin-T can persist for up
to 10 days after MI
Remember, CK-MB returns to baseline by 48 hours
Thus far, studies have failed to find a source of
Troponin-I outside the heart, but have found some
Troponin-T in skeletal muscle
32. Troponin T and I are not detected in healthy
individuals
Significant increase in Troponins reflects
myocardial necrosis
ACC/ESC has defined increase in Troponins as a
measurement above 99th percentile value of
reference group
To reduce false-positive outcomes, CV of 10% at
decision limit is recommended
33. • TropT (Roche Diagnostics, Germany)
• Trop I (Siemens Healthcare Diagnostics)
• Troponin T
› 99th percentile limits - 0.01 ng/mL
› assay ranges - 0.01-25 ng/mL
(Troponin I)
› 99th percentile limits -0.04 ng/mL
› assay range -0.04-40 ng/mL
• Reference limits based on the 99th percentile for a
healthy population are 0.01 ng/mL (Troponin T) and
0.04 ng/mL (Troponin I)
34. They used the concentration of 0.04 ng per mL as
the upper reference limit and established the diagnosis
of myocardial infarction if one value of more than 0.04
ng per mL was documented, combined with a rise or fall
in the value of 30% or more within 6 hours after
admission.
Patients with troponin rises benefit more from
Glycoprotein IIb IIIa inhibitors such as,
Abciximab
Eptifibatin
Clopidogrel
35. Most commonly used in dogs and cats
Clinical conditions
Congestive heart failure
Percardial disease
Doxorubicin toxicity
Gastric dilatation and volvulus etc,.
36. 120 animals were examined in emergency
with cardiac troponin assays,
First group= ctni less than .15ng/ml
Second group= ctni .15-1 ng/ml
Third group= ctni more than 1 ng/ml
Prognosis grave in second and third group
37.
38.
39. A novel marker of ischemia, is produced when circulating
serum albumin contacts ischemic heart tissues
IMA can be measured by the albumin cobalt binding (ACB)
assay that is based on IMA's inability to bind to cobalt
Mechanism- due to structural change in the amino terminal
end of albumin
IMA levels rise within 6 hours
remain elevated for 12 hours
40. Drawbacks
IMA levels raised in non- cardiac ischemia
Modification to n- terminal end may also be
induced by extracellular hypoxia, acidosis etc,
Conclusion
FDA in 2010 has approved a multimarker approach
for using the combination of ECG, the cTnI, and the
IMA levels achieving a sensitivity of 95% for ACS
41. Heart-type fatty acid binding protein (H-FABP)
H-FABP is a very stable abundant [138] low molecularweight
protein (14–15 kDa) in the cytoplasm of myocardial cells
Appearing as early as 90 min after symptom onset and peaking
within 6 h
Parameters of kinetic release make it an ideal candidate both for
early assessment or exclusion of AMI and for the measurement
of a recurrent infarction
42. A study by Puls et al
› the negative predictive value (NPV) of H-FABP was an impressive
100%
› its Positive predictive value was 41% which was greater than that
of both cTnT (29%) and NT-proBNP (19%).
The myoglobin/heart FABP ratio has been used to differentiate
between heart muscle and skeletal muscle injury
Cardiodetect
Dr. Jaikanth
43.
44.
45. The natriuretic peptides (NP) are a group of
structurally similar but genetically distinct
peptides.
NPs are identified as regulatory diuretic-natriuretic
substances responsible for salt and water
homeostasis
Lowers blood pressure.
46. The NP family includes
ANP : -atrial natriuretic peptide (28 a.a.)
N-terminal proANP (98 a.a.)
BNP : brain natriuretic peptide (32 a.a.)
N-terminal proBNP (76 a.a.)
CNP : C-type natriuretic peptide (22 and 53 a.a.)
47. Fig. Schematic representation of the ANP and BNP precursors with sequence
numbering defining low-molecular-mass forms, N-terminal forms and high-
molecular-mass precursors
48. ANP is released primarily in response to
atrial wall stretching and intravascular
volume expansion.
BNP is mainly secreted by the ventricles
CNP is found predominantly in the brain and
also synthesized by vascular endothelial cells
49. originally isolated from porcine brain
Subsequently also isolated from human heart
Circulating levels of BNP are raised in patients
with cardiovascular or renal disease
More important than ANP in heart failure
Greatest proportion of circulating BNP is
thought to come from the ventricles (left)
51. Three receptors for natriuretic peptides :
Natriuretic peptide receptor -A
Natriuretic peptide receptor -B
Natriuretic peptide receptor -C
NPR-A and NPR-B
NPR-A and NPR-B are particulate guanylyl cyclases that
catalyses the conversion of GTP to c-GMP
NPR-C
They lack the guanyl cyclase domain and may influence
the target cell function through inhibitory guanine
nucleotide (Gi) protein, and they likely also act as clearance
receptors for circulating peptides.
52. NPR-A and NPR-B
NPR- A is the most abundant type in
large blood vessels
NPR-B predominate in the brain
Both receptors are present in the
adrenal glands and the kidney
Affinity
for NPR-A : ANP > BNP > CNP
for NPR-B : CNP > BNP > ANP
54. ANP and BNP concentrations increase in
response to volume expansion and pressure
overload of the heart
ANP and BNP have been shown to be
physiological antagonists of the effects of
(1) angiotensin II on vascular tone
(2) aldosterone secretion
(3) renal-tubule sodium reabsorption
(4) vascular-cell growth
57. Clearance factors for natriuretic peptides
NPR-C and neutral endopeptidase
Endopeptidase
Neutral endopeptidase inactivates all
three natriuretic peptides
Present within renal tubular cells and
vascular cells
58. Conditions or factors commonly associated with B-type
natriuretic peptide or N-terminal-pro-B-type natriuretic
peptide
elevations
Age
Arrhythmias
Cardiomyopathy: hypertrophic, ischemic, or dilated
Congestive heart failure
Coronary artery disease
Gender
Hypertension
Left ventricular diastolic dysfunction
Pulmonary embolism
Renal failure
Right heart failure
Right ventricular overloading: fluid, or pressure overloading
Sepsis or septic shock
Sepsis-related myocardial dysfunction
59. Prospective study of 1586 patients presenting to the emergency
department with acute dyspnea
Outcomes of the study
The predictive value of BNP much superior to previous standards including
radiographic, clinical exam, or Framingham Criteria
Bnp cut point was fixed at 100pg/ml and it showed 90% sensitivity and 80%
specificity for diagnosing heart failure
Veterinary field
Chronic left ventricular systolic and diastolic dysfunction
Cardiac vs non- cardiac dyspnoea
Recent development of ELISA kits for canine and feline NTproBNPby
Guildhay Ltd (www. guildhay. Co.uk)
60. ANP and BNP infusion
Decrease renin and aldosterone
concentration
Increase urinary sodium and water
excretion
Neutralendopeptidase inhibitor
Nesiritide is a new drug that is a synthetic
BNP that vasodilates vessels and serves as
a potent diuretic agent
61. BNP for Rx of decompensated heart
failure Nesiritide (h-BNP)
32 amino acid sequence
Recombinant technology using E-co
D
R I
M
K
R
G
S S
S
S
G
L
G
F
C
C
S S
G
SGQVM
K V L R
R
H
KPS
NOTE: hBNP affects assay for BNP, but can still use proBNP or one of the proANP assays
65. CRP is an acute-phase protein produced by
the liver
Pentameric structure consisting of five 23-
kDa identical subunits
Plasma levels can increase rapidly to 10000x
levels
High-sensitivity CRP (hs-CRP) assays
66.
67. CRP previously known to be a marker of high
risk in cardiovascular disease
More recent data may implicate CRP as an
actual mediator of atherogenesis
Mechanism of CRP-mediated atherogenesis:
Once ligand-bound, CRP can:
› Activate the classical compliment pathway
› Stimulate phagocytosis
› Bind to immunoglobulin receptors
› Endothelial dysfunction via ↑ NO synthesis
› ↑LDL deposition in plaque by CRP-stimulated macrophages
68.
69.
70. Clinical Uses
› Screening for cardiovascular risk in otherwise
“healthy” individuals
› Predictive value of CRP levels for disease
severity in pre-existing Coronary artery
disease
Elevated levels predictive of
• Long-term risk of first MI
• Ischemic stroke
71. Limitations of CRP
Low specificity
No evidence that lowering CRP levels decreases CV risk
Industry and FDA staff guidelines 2005 had given clinical cut
off value as less than 1 mg/l as safe levels with hs-CRP
tests
CRP Risk for CVD
Less than 1.0 mg/L Low
1.0-2.9 mg/L Intermediate
Greater than 3.0 mg/L High
72. MPO is an enzyme that aids white blood cells
in destroying bacteria and viral particles
MPO catalyzes the conversion of hydrogen
peroxide and chloride ions (Cl-) into
hypochlorous acid
MPO is released in response to infection and
inflammation
EPIC Norfolk Study
Sugiyama Am J Pathology 2001
73. MPO leads to oxidized LDL cholesterol
› Oxidized LDL is phagocytosed by macrophages
producing foam cells
MPO leads to the consumption of nitric oxide
› Vasoconstriction and endothelial dysfunction
MPO can cause endothelial denuding and
superficial platelet aggregation
MPO indicates activated immune cells
› Activated immune cells and inflammation lead
to unstable plaque
Inflammatory plaque is inherently less stable
› Thin fibrous cap/fissured/denuded
74.
75. In august 2005, FDA approved the first
MPO assay, Cardio MPO tm developed by
Prognostix,inc.
The test is a sandwich enzyme immuno
assay
Normal plasma MPO levels are 51-
633pmol/ml
76. Progression of Biomarkers in ACS
ACS, acute coronary syndrome; UA, unstable angina; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment
elevation myocardial infarction
Adapted from: Apple Clinical Chemistry March 2005
STEMIUA/NSTEMISTABLE CAD PLAQUE RUPTURE
MPO
CRP
IL-6
MPO
ICAM
sCD40L
PAPP-A
MPO
D-dimer
IMA
FABP
TnI
TnT
Myoglobin
CKMB
Inflammation has been linked to the development of
vulnerable plaque and to plaque rupture
77. Intermediary amino acid formed by the
conversion of methionine to cysteine
Moderate hyperhomocysteinemia occurs in 5-
7% of the population
Recognized as an independent risk factor for
the development of atherosclerotic vascular
disease and venous thrombosis
Can result from genetic defects, drugs,
vitamin deficiencies
78. Homocysteine implicated directly in
vascular injury including:
› Intimal thickening
› Disruption of elastic lamina
› Smooth muscle hypertrophy
› Platelet aggregation
Vascular injury induced by leukocyte
recruitment, foam cell formation, and
inhibition of NO synthesis
Normal levels less than 6micro mol/l
79. Elevated levels appear to be an
independent risk factor, though less
important than the classic CV risk factors
Treatment includes supplementation with
folate, B6 and B12
80. Stefan Blankenberg, MD; Renate Schnabel, MD; Edith Lubos, MD, et al., Myeloperoxidase Early Indicator of Acute Coronary Syndrome and
Predictor of Future Cardiovascular Events 2005
81. Send the comments of this ppt to
jaipersie@gmail.com for further
enhancement of my presentations
Dr. Jaikanth
82.
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