Biomarkers provide objective measures of periodontal disease that can help with early diagnosis, predicting disease progression, and assessing response to treatment. Common biomarkers found in gingival crevicular fluid, saliva, and serum include enzymes, proteins, ions, hormones, bacteria, and inflammatory mediators. Specific biomarkers like alkaline phosphatase, interleukin-1β, C-reactive protein, matrix metalloproteinases, prostaglandin E2, and proinflammatory cytokines like tumor necrosis factor-α and interleukin-6 have been associated with periodontal disease severity and activity. However, no single biomarker can currently be used alone as most provide only limited diagnostic information.
Biomarker is an objective measure that has been evaluated and confirmed either as an indicator of physiologic health, a pathogenic process or a pharmacologic response to a therapeutic intervention. Biomarkers, whether produces by normal healthy individuals or by individuals affected by specific systemic diseases, are tell tale molecules that could be used to monitor health status, disease onset, treatment response and outcome.The biomarkers can help for the determination of present as well as future disease activity along with diagnosis and previous periodontal diseases.
”Contemporary Biomarkers In Periodontitis”- Guest lecture as a part of Dr NTRUHS Zonal CDE programme at Government Dental College and Hospital, Hyderabad, India on 281/1/2011, SIBAR Institute of Dental Sciences, Guntur, India on 29/12/12 and at Meghna Institute of Dental Sciences, Nizamabad, India on 31/7/2013.
Biomarker is an objective measure that has been evaluated and confirmed either as an indicator of physiologic health, a pathogenic process or a pharmacologic response to a therapeutic intervention. Biomarkers, whether produces by normal healthy individuals or by individuals affected by specific systemic diseases, are tell tale molecules that could be used to monitor health status, disease onset, treatment response and outcome.The biomarkers can help for the determination of present as well as future disease activity along with diagnosis and previous periodontal diseases.
”Contemporary Biomarkers In Periodontitis”- Guest lecture as a part of Dr NTRUHS Zonal CDE programme at Government Dental College and Hospital, Hyderabad, India on 281/1/2011, SIBAR Institute of Dental Sciences, Guntur, India on 29/12/12 and at Meghna Institute of Dental Sciences, Nizamabad, India on 31/7/2013.
The future of dentistry and periodontics lies in regeneration. The goals of periodontal therapy lies in not only the arrest of periodontal disease progression but also regeneration of the lost periodontal structures. This presentation provides a review of the current understanding of the regeneration of the periodontium and the procedures involved to restore the periodontal tissues around the teeth.
Porphyromonas gingivalis belongs to the phylum Bacteroidetes and is a nonmotile, Gram-negative, rod-shaped, anaerobic, pathogenic bacterium. It forms black colonies on blood agar.
It is found in the oral cavity, where it is implicated in certain forms of periodontal disease, as well as in the upper gastrointestinal tract, the respiratory tract, and the colon. It has also been isolated from women with bacterial vaginosis. Collagen degradation observed in chronic periodontal disease results in part from the collagenase enzymes of this species. It has been shown in an in vitro study that P. gingivalis can invade human gingival fibroblasts and can survive in them in the presence of considerable concentrations of antibiotics.P. gingivalis also invades gingival epithelial cells in high numbers, in which cases both bacteria and epithelial cells survive for extended periods of time. High levels of specific antibodies can be detected in patients harboring P. gingivalis. Dr Harshavardhan Patwal , explains the various enzymes enzyme peptidyl-arginine deiminase, which is involved in citrullination.[4] Patients with rheumatoid arthritis have an increased incidence of periodontal disease, and antibodies against the bacterium are significantly more common in these patients.
P. gingivalis is divided into K-serotypes based upon capsular antigenicity of the various types.
Bruxism and its effect on periodontiumRamya Ganesh
Bruxism/teeth grinding is a common habit seen among pediatric patients and in older patients with relation to improper occlusion. This habit can cause extreme damage to facial muscles and TMJ. Various treatment options are available including botox injections. Hence as a dentist it is our duty to restore patient's oral health in harmony with other oro facial structures.
A brief description of all topics to recent advances,SDD, host modulation and diabetes, host modulation in smokers, chemically modified tetracyclines, bisphosphonates
Local drug delivery is simple to use and may conceivably in the future be delivered by the patients themselves, hence can be used as an adjunct to mechanical plaque removal.
The future of dentistry and periodontics lies in regeneration. The goals of periodontal therapy lies in not only the arrest of periodontal disease progression but also regeneration of the lost periodontal structures. This presentation provides a review of the current understanding of the regeneration of the periodontium and the procedures involved to restore the periodontal tissues around the teeth.
Porphyromonas gingivalis belongs to the phylum Bacteroidetes and is a nonmotile, Gram-negative, rod-shaped, anaerobic, pathogenic bacterium. It forms black colonies on blood agar.
It is found in the oral cavity, where it is implicated in certain forms of periodontal disease, as well as in the upper gastrointestinal tract, the respiratory tract, and the colon. It has also been isolated from women with bacterial vaginosis. Collagen degradation observed in chronic periodontal disease results in part from the collagenase enzymes of this species. It has been shown in an in vitro study that P. gingivalis can invade human gingival fibroblasts and can survive in them in the presence of considerable concentrations of antibiotics.P. gingivalis also invades gingival epithelial cells in high numbers, in which cases both bacteria and epithelial cells survive for extended periods of time. High levels of specific antibodies can be detected in patients harboring P. gingivalis. Dr Harshavardhan Patwal , explains the various enzymes enzyme peptidyl-arginine deiminase, which is involved in citrullination.[4] Patients with rheumatoid arthritis have an increased incidence of periodontal disease, and antibodies against the bacterium are significantly more common in these patients.
P. gingivalis is divided into K-serotypes based upon capsular antigenicity of the various types.
Bruxism and its effect on periodontiumRamya Ganesh
Bruxism/teeth grinding is a common habit seen among pediatric patients and in older patients with relation to improper occlusion. This habit can cause extreme damage to facial muscles and TMJ. Various treatment options are available including botox injections. Hence as a dentist it is our duty to restore patient's oral health in harmony with other oro facial structures.
A brief description of all topics to recent advances,SDD, host modulation and diabetes, host modulation in smokers, chemically modified tetracyclines, bisphosphonates
Local drug delivery is simple to use and may conceivably in the future be delivered by the patients themselves, hence can be used as an adjunct to mechanical plaque removal.
This is a brief compilation of the how periodontal diseases come about. It explains the concept of the causative agent and all virulence factors used. it also outlines the host response to these irritating factors which has been known to be more responsible for the clinical outcome of periodontal diseases.
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
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
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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
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.
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.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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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
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.
2. • Periodontal Diagnosis
• Clinical diagnostic parameters
• probing depths, bleeding on probing, clinical attachment levels, plaque index, and radiographs assessing
alveolar bone level
• Require a 2- to 3-mm threshold change before a site can be identified as having experienced a significant
anatomic event. Goodson JM.
• Advances in oral and periodontal disease diagnostic research are moving toward methods whereby
periodontal risk can be identified and quantified by objective measures such as biomarkers
Chapple I. Periodontal diagnosis and treatment-where does the future lie? Periodontology 2000;
51:9-24
INTRODUCTION:
3. • Early recognition of the microbial challenge to the host
• To determine the presence of current disease activity, predict sites vulnerable for
future breakdown
• To assess the response to periodontal intervention
• Haffajee et al 1983
• Ultimately improve the clinical management of periodontal patients.
NEED FOR ADVANCED DIAGNOSTIC
INDICATORS
4. • Biomarkers -“cellular, biochemical, molecular, or genetic alterations by which a normal, abnormal, or
simply biologic process can be recognized or monitored”
NIH BIOMARKER DEFINITIONS WORKING GROUP, 1998
• Also described as measures of health & disease that define the underlying biological basis to a condition
presenting as a characteristic clinical phenotype & are potentially more objective than clinical indices.
Beck et al. 2000
• A substance that is measured objectively and evaluated as an indicator of normal biologic processes,
pathogenic processes, or pharmacologic responses to a therapeutic intervention
Biomarkers Definitions Working Group.2001
DEFINITION:
6. SOURCES
Khiste SV, Ranganath V, Nichani AS, Rajani V. Critical analysis of biomarkers in the current periodontal practice.
J Indian Soc Periodontol 2011;15:104-10
ORAL FLUIDS
Mucosal
Tramsudate
GCF Saliva
GaryC. Armitage 2004
7. GCF SALIVA SERUM
- More than 65 GCF
constituents have
been evaluated as
potential diagnostic
markers of
periodontal disease
progression
(Armitage et al
2004 )
- Non-invasive
collection
method
- Detection of
RNA in the
salivary fluid
Zimmermann
BG
- eg: Salih E et al.
- Inflammatory
mediators are
released into
circulation
- Not the preferred
source today due to
lack of definitive
evidence
- Mainly used for
genetic risk marker
identification
- More invasive than
GCF or saliva
9. Biomarkers Examples
Enzymes
Alkaline phosphatise, Amino peptidase, Trypsin, â galactosidase, â
â glucoronidase, Gelatinase, Esterase, Collagenase Kininase
Immunoglobulins Ig A, Ig G, Ig M,
Protein
Cystatin, Fibronectin, Lactoferrin, Vascular endothelial growth factors, Platelet
activating factors, Epidermal growth factors
Phenotypic marker Epithelial keratin
Host cell Leukocytes (PMN’S)
Ion Calcium
Hormones Cortisol
Bacteria Aa, Pg, Pi, C. rectus, T. denticola, B. forsythus , mycoplasma
Volatile Compounds
Hydrogen sulphide, Methyl mercaptan, Picolines, Pyridines.
Possible Salivary Biomarkers
10. • LPS-HOST DEFENSE
• MMP-1 & MMP-8,IL 1 &TNF-α
PROTEOMIC APPROACH
• IL-1 and TNFα, the anti-inflammatory cytokine IL-10
and the Fc gamma receptors
• Yoshie et al
• Reactive O2 species; 8-OHdG
GENOMIC APPROACH
• Bacteria present due to plaque, tongue, GCF, Pdl
pocket..
MICROBIAL APPROACH
DISCOVERY & AN OVERVIEW
11. Alkaline Phosphatase (ALP):
• Mixed saliva of adult periodontitis
patients revealed the highest enzyme
activities with ALP
• Associated with alveolar bone loss, a
key feature of periodontal disease.
Interleukin (IL) 1β:
• Proinflammatory cytokine
• Functions:
- Osteoclastic activity in periodontitis
• Influences:
- Immune cell recruitment
- Cell proliferation
- Tissue destruction
- Vascular smooth muscle cell contraction
INDIVIDUAL SALIVARY BIOMARKER
Acta Odontol Scand.2015 Jul;73(5):343-7
12. • Synthesised in Liver
• Systemic marker and indicator of acute phase of an inflammatory response.
• Circulating CRP reaches saliva via GCF or salivary glands.
• Christodoulides N et al reported that high levels CRP are associated with chronic
and aggressive periodontal diseases.
C-reactive protein (CRP) :
Journal of Indian Society of Periodontology. Jan-Feb 2013:17(1):36-41
13. 8-OHdG
• Most stable product of ROS
• Marker of mitochondrial DNA
damage caused by premature
oxidation in the gingival tissues of
periodontitis patients
{Canakci CF et al}
IL-17
• Proinflammatory cytokine produced by
T-helper 17 cells
• Stimulate various cell types to produce
other inflammatory cytokines and
chemokines
• Preserves immune homeostasis
• Supports immune responses (Th1) and
combines with receptor activator of
RANK and RANKL, resulting in
osteoclastic bone resorption
Yang et al
J Periodontol.2015
14. • Key enzyme in extracellular collagen matrix degradation,
• Origin: PMNs during acute stages of periodontal disease
• Significantly increased the risk of periodontal disease
• MMP-8 is not only an indicator of disease severity, but also disease activity.
• MMP-1 (interstitial collagenase) also appeared to be activated in periodontitis.
MATRIX METALLOPROTEINASES
15. • Possible markers for the progression of periodontitis fall into three general
categories:
1. Host-derived enzymes and their inhibitors
2. Tissue breakdown products
3. Inflammatory mediators and host response modifiers
GCF BIOMARKERS
17. Biomarker Type Function
Interferon alpha Cytokine Antiviral
Increased MHC Cl-I expression
Interferon gamma Cytokine Macrophage Activation,Th2
suppression
IgA Antibody Antigen Neutralization
IgG, IgG1,IgG2, G3,G4, IgM Antibody Antigen Neutralization
IL-1 ra (Receptor Antagonist) Cytokine Antagonist of IL-1
IL-1 Cytokine Regulates immune and
inflammatory reactions,
stimulates bone resorption
IL-4 Cytokine Antiinflammatory, macropge
inhibitor,Th2 differentiation
18. Pro inflammatory Cytokines
• Monocytes, macrophages, fibroblasts and endothelial cells respond to plaque
microorganisms by secreting chemokines and inflammatory cytokines ( TNF-α,
PGE2, IL-1β and IL-6)
(Beck et al 1998)
• Can be obtained from GCF and saliva (IL1, TNF-α)
19. TNF -α
• Origin: Mononuclear phagocyte.
• The main stimulus for release is the Lipopolysaccharide of bacterial cell walls.
• Functions:
Bone resorption
Inhibit bone collagen synthesis.
Induce collagenases
Stimulate osteoclast differentiation in the presence of M-CSF
• Act synergistically with cytokines and induces release of IL-1.
20. TNF – β (Lymphotoxin)
• 25 KD glycoprotein
• Activated T cells
• 28% homology to TNF-
• Functions:
CTL stimulation
Osteoclast activation of PMNLs and
Antiviral activity.
• 17 KD
• Origin: Stimulated macrophages
• (+) cytoxic T lymphocytes (CTL).
• ↑ in periodontitis
Gorska et al
• ↑ bone resorption and CT
degradation by (+) PGE2 and
Collagenase
Morimoto Y et al,2008
• Shapira et al 2001, Ejeil AL et al 2003
TNF - à
21. INTERLEUKINS
IL-1
Stimulate adhesion
molecule and
chemokine
expression
Enhance
Osteoclast
formation and
activity
Induce matrix
metalloproteinase
expression
Stimulate
production of
inflammatory
mediators(PGE
Stimulate apoptosis
of matrix producing
cells
Inflammation Bone loss
Connective
Tissue
Breakdown
Limit repair of
periodontium
Mechanism by which IL-1 could contribute to the net loss of periodontal tissues
22. IL-6
• Produced by various cells such as activated monocytes or macrophages, endothelial
cells, activated T-cells, and fibroblasts.
• Earlier Names: B- cells stimulatory factor II, interferon B2 and plasmacytoma growth
factor.
• Functions :
o B cells : Promote growth and facilitate maturation of the B cells causing immunoglobulin
secretion.
o Osteoclast formation and activity
o ↑ in sites of gingival inflammation and plays a role in bone resorption.
23. • On measuring the level of IL-1β, IL-2, IL-4, IL-6 and TNF- α in GCF by ELISA
assays :
• Results showed high individual variability of cytokine profiles, and no association
between cytokine concentrations and clinical parameters of periodontitis
Gorska et al
• Disease activity thought to be related to Th1-Th2 cytokine profile
• Th2 cytokines like IL4, IL5, IL6 associated with progressive disease
Seymour 2002
24. • Sakai et al 2006, Yucel et al 2008, Liu et al 1996, Homlund et al 2004,
Engebretson et al.2002, Ozmeric 1998, Toker et al 2008, Tsai et al 2007 reported
increased GCF and salivary levels of proinflammatory cytokines like IL 1, IL6, IL8
in periodontal disease.
• Th1 cytokines IFN γ, IL2 associated with progressive lesion
Berglundh 2003
• In the absence of evidence, there is no single inflammatory cytokine that can be
used as a marker as yet.
25. Biomarker Type Function
IL-6 Cytokine Regulator of t and B cell
Acute phase protein
IL-8 Cytokine Recruitment and activation of
neutrophils
IL-15 Cytokine Anti-apoptotic effect on cells
Lactoferrin Acute Phase Protein Antibacterial, creates Fe limiting
environment
TNF - alpha Cytokine Delays neutrophil apoptosis
Leukotriene B4 Proinflammatory mediator Stimultes chemotaxis, adhesion,
oxidative burst, degranulation
Prostaglandin E2 Immune Mediator Multiple pro inflammatory and
immunomodulatory effects
Pradeep AR, Manjunath SG et al. J Periodontol. 2007;78:2325-30.
Kim DM et al. J Periodontol. 2007 ;78:1620-6.
Goodson et al. in 1974
26. PGE2
• In untreated cases ,gcf levels not able to distinguish between progressive and non
progressive sites Offenbacher-94
• Reduction in GCF levels after nonsurgical therapy Sengupta 1990
• Attachment loss at one or more sites after 6 months had significantly higher mean GCF
PGE2 levels of 113 ng/ml at the baseline.
• Levels greater than 66 ng/ml were found to be predictive of further possible loss of
attachment and this level was used as a cut off value in a positive and negative
screening test.
27. • Membrane-derived lipid mediator formed from arachidonic acid.
• Source : PMNLs
• Tsai et al 1998, Back et al.2006, Pradeep et al 2007,Emingil 2001 reported difference
in levels in health,disease and post treatment.
• Evidence indicates that LTB4 is elevated in inflamed deeper periodontal tissues.
• Offenbacher et al. (1991)
• AR Pradeep et al
LtB4
29. Beta Glucuronidase
• Degradation of the connective tissue ground substance – glycoproteins, proteoglycans
• Marker for primary granule release from PMNL
• May be obtained from both saliva and GCF
• Also positively associated with spirochetes, P. gingivalis, P.intermedia and negatively
associated with cocci.
• Lamster et al 1988 showed that sites that showed the higher β -glucuronidase activity
at baseline and again at 3 months had the highest association with loss of attachment.
• Lamster et al 1988, Harper et al 1989, Wolff et al, 1997, Lamster and Novak 2002
30. Neutrophil elastase
• Serine endopeptidase found in primary granules
• Marker of intracrevicular PMN activity
• Degrades collagenous & non collagenous substrates, activates collagenases.
• Seen either adjacent to junctional epithelium or in granulation tissue at the
advancing front of the lesion.
• Anti bacterial activity
31. • Palcanis et al 1992 did a 6-month longitudinal study using a test kit system, and showed
significant differences of total elastase activity at baseline in progressive and non-
progressive sites assessed 2-6 months later.
• Eley and Cox 2006 did a longitudinal study for 2 years and found levels above critical
values for total elastase activity and enzyme concentration present at all Rapid
Attachment Loss sites, both at the time of attachment loss and 3 months previously
(predictive time).
33. • Eley & Cox (1996) compared the GCF contents of cathepsin B to probing
depths to determine the success of cathepsin B as a marker for active disease.
• 75 patients with moderate chronic periodontitis were tested; with a high degree of specificity and
sensitivity (99.8% and 100%, respectively)
• Cathepsin B was able to better identify active pocket destruction than other markers in GCF..
• Kunimatsu et al 1990, Eley & Cox (1996), Chen et al 1998 reported its ability to
distinguish Progressive & Non progressive disease and aid in Prognosis/Therapy
• Loos et al 2005
34. Matrix Metallo Proteinases
• Family of homologous zinc endopeptidases, that collectively cleave most if not all
constituents of ECM
• Key mediators of tissue destruction (Kinane et al 2000)
• Source: Macrophages, neutrophils, fibroblasts and keratinocyte
Gingival fibroblast-MMP8
Monocytes and macrophges:MMP9
Gingival fibroblast , epithelial cells:MMP2
35. MMP-9
• Degrades collagen extracellular
ground substance
• Teng et al : 2x ↑ in MMP-9 with
recurrent attachment loss
• Metronidazole : ↓ MMP-9
• Most prevalent MMP found in diseased
periodontal tissue and GCF
• Mancini and co-workers: 18x ↑ MMP-8 in
patients experiencing active periodontal
tissue breakdown
• ↑ in disease and ↓ by 60% during the 2-
month protocol of LDD
Golub et al
• ↑ in PISF from periimplantitis lesion
• Collagen –I & II breakdown
MMP-8 (Collagenase 2)
Matrix Metallo Proteinases
36. Aspartate Amino transferase (AST)
Source :Epithelial cells, gingival and PDL fibroblasts
Evidence of cell death within the periodontal tissues and, hence, possibly disease
activity.
• Chambers et al.1988, Chambers et al. (1991), Smith et al 1998, Persson et al 1992,
Oringer 2001 reported greater AST activity in periodontal disease
• Chair side Test
Pocketwatch
Perioguard
38. Pyridinoline cross links (ICTP) levels
• Class of collagen degradation molecules that include pyridinoline, deoxy pyridinoline,
N telopeptide and C telopeptide.
• 12 to 20 kd fragment of bone type I collagen released by digestion with trypsin or
bacterial collagenase
• Specific biomarkers for bone resorption
Eriksen et al
39. • Palys et al. related ICTP levels to the subgingival microflora of various disease states
on GCF.
• Levels differed significantly between health, gingivitis, and periodontitis subjects
• Related modestly to several clinical disease parameters.
• Strongly correlated with whole subject levels of several periodontal pathogens including T.
forsythensis, P. gingivalis, P. intermedia, and T. denticola.
• Golub et al.
• Elevated GCF ICTP levels at baseline, especially at shallow sites, were found to be
predictive for future attachment loss as early as 1 month after sampling.
40. Osteocalcin
• Most abundant non-collagenous protein of mineralized tissues.
• Source: osteoblasts. It is a small calcium-binding protein of bone.
• Function:
promotes hydroxyapatite binding and accumulation of bone.
chemotactically attracts osteoclast progenitor cells and blood monocytes.
41. • Kunimatsu et al 1993
GCF osteocalcin has positive correlation with clinical parameters in a cross-sectional
study of patients with periodontitis.
also reported that osteocalcin could not be detected in patients with gingivitis
• In contrast, Nakashima et al 1994
• GCF osteocalcin levels higher in both periodontitis and gingivitis patients.
• Contradicting results osteocalcin has a potential role as a bone specific marker of
bone turnover but not as a predictive indicator for periodontal disease.
42. OSTEONECTIN AND BONE PHOSPHOPROTEIN
(N-PROPEPTIDE)
• Imp in initial phase of mineralization.
• Bone phosphoprotein an amino propeptide extension of alpha 1 chains of type I
collagen, appears to be involved in the attachment of connective tissue cells to the
substratum.
Bowers et al 1989
• Both detected in GCF from CP pts.
• Total amount increases with PD
Bowers et al 1989
• They therefore may be associated with periodontal disease severity.
43. Osteopontin
• Found in bone matrix
• Highly concentrated at sites where osteoclasts are attached to the underlying
mineral surface
• Source: Both osteoblasts and osteoclasts,
• Function-
-it holds a dual function in bone maturation
44. • GCF OPN ≈ PD measures of periodontally healthy and diseased patients.
Kido et al 2001
• GCF OPN concentrations ≈ progression of disease; on nonsurgical pdl
treatment , levels were significantly reduced.
Sharma et al 2006
45. GAGs
• Most common GAG : nonsulfated hyaluronic acid, sulfated heparan sulfate,
chondroitin-4 sulfate and chondroitin-6 sulfate.
• chondroitin-4-sulfate : Most common GAG in periodontium but
distributions differ.
• Dermatan sulfate : rare in bone, cementum; common in pdl and gingiva.
probably reflecting a functional involvement of the molecule in the
mineralization process.
• Function: Proteoglycans bind most collagens as well as fibronectin. On
degradation of pdl tissues, GAGs are released GCF.
46. • Embery et al 1982 : The non-sulphated GAG, hyaluronic acid was present in all
samples, and was the only major GAG found in chronic gingivitis patients.
• Sulphated GAG, c-4-sulphate, in GCF from sites with
untreated advanced periodontitis,
JP
around teeth undergoing orthodontic movement,
teeth subject to occlusal trauma
• The presence of c-4-sulphate in GCF may be a sensitive method of indicating active
phases of destructive periodontal disease.
47. • Embery G et al 1982
• In contrast to periodontitis, GCF collected from sites of gingivitis usually contain
only the nonsulfated hyaluronic acid.
• Last & Embery 1987 suggested -- hyaluronic acid may be a marker of nonactive
sites; found that sites of ANUG recover their hyaluronic acid levels after antibacterial
treatments.
• Last et al 1991; Beck et al 1991 - Studies on the levels of C-4-S in GCF from sites
with endosseous dental implants, where forces on the supporting bone induced
changes in C4S quantity, lend support to the fact that C4S being a bone marker
48. Rankl and OPG
• Regulation of osteoclastogenesis in bone remodeling and inflammatory osteolysis.
• Lacey et al 1998 : In vivo treatment of mice with RANKL activates osteoclasts
bone loss
• Osteoprotegerin (OPG) : a secreted glycoprotein, is a decoy receptor for RANKL
• OPG binds to RANKL the cell-to-cell signaling between marrow stromal cells and
osteoclast precursors is inhibited osteoclasts are not formed
Simonet et al 1997; Yasuda et al 1998
49. • Thus, RANKL and decoy receptors OPG expressed by bone-associated cells play
important roles during osteoclast formation by balancing induction and inhibition
• GCF RANK-L increased in CP patients, supporting its role in the alveolar
bone loss developed in the disease.
Rolando Verna et al 2004
50. • RANKL levels : low in health and gingivitis groups; increased in CP.
• OPG : higher in health compared to gingivitis and periodontitis.
• There were no differences in RANKL and OPG levels between CP and GAP groups
Bostanci N et al 2007
51. • The development of rapid point-of-care (POC) chairside diagnostics has the
potential for the early detection of periodontal infection and progression to
identify incipient disease and reduce health care costs. However, validation of
effective diagnostics requires the identification and verification of biomarkers
correlated with disease progression (Ramseier CA et al., 2009).
Chairside kit
55. • OBESITY RELATED
• Chemerin - an adipokine ; CP & DM Pradeep et al,2015
• Leptin - The decreasing leptin level in GCF and gingival tissue was associated with a deteriorated
periodontal status, and smokers also showed reduced GCF leptin levels in recent studies
• SYSTEMIC DISEASE RELATED
• Progranulin – CP & type 2 DM. Pradeep et al 2013
Capsase 3 - GCF and the serum concentration of caspase-3 proportionally increases with the progression of
periodontal disease Pradeep et al 2014
• IL-29 - antiviral IL-29 level was highest in GCF of aggressive periodontitis patients while that of chronic
periodontitis lying in between. After non-surgical periodontal therapy, IL-29 levels increased both in chronic and
aggressive periodontitis patients a potential therapeutic agent in treating periodontitis.
Shivaprasad BM ,Pradeep AR 2013
RECENT BIOMARKERS
56. • Though several products show potential benefit; which gives a clue as to which tissue
components are at risk, most of the test kit, or biomarkers yield little or no additional
information, at high costing.
• It is also clear that no single marker has been able to fulfil all the criteria necessary for
assessment of the clinical state of the periodontium.
• Future research should be directed possibly at the production of "marker packages"
• As of now various efforts are on to develop an ideal test, but actual use as a chairside
diagnostic is still illusive. Therefore the development of a wide spectrum of markers is the
primary goal of periodontal research
CONCLUSION:
57. 1.Periodontology 2000 vol.39,50,51,70
2.Kolokythas A et al. Salivary biomarkers associated with bone deterioration in
patients with medication-related osteonecrosis of the jaws. J Oral Maxillofac
Surg : 2015.
3.Christodoulides N et-al. Lab-on-a-chip methods for point-of-care measurements
of salivary biomarkers of periodontitis. Ann. N.Y. Acad. Sci.2007: 1098: 411–428 .
4.Carranza’s CLINICAL PERIODONTOLOGY .11th Edition
5.Pradeep A.R et-al. Correlation of human S100A12 (EN-RAGE) and high-
sensitivity C-reactive protein as gingival crevicular fluid and serum markers of
inflammation in chronic periodontitis and type 2 diabetes. Inflamm. Res. (2014)
63:317–323.
6.Gingival crevicular fluid and plasma levels of neuropeptide Substance-P in
periodontal health, disease and after nonsurgical therapy. Pradeep AR, Raj
S, Aruna G, Chowdhry S. J Periodontal Res. 2009;44:232-7.
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