What a week! We think we are getting there, we are arranging a meeting with Vicki Farmer to discuss the cellular biology, once we apply this info further, we will meet with a periodontist. IT NEEDS TO BE REFERENCED - don't worry
Inflammation denotes the body’s response to cellular injury by a variety of harmful stimuli including trauma, tissue necrosis and infection. The purpose of inflammation is to confine and neutralize the damaging agent, initiate repair of the tissues and restore them to original function. Acute and chronic inflammation are terms used to divide the phases of inflammation, however, they are not independent of each other and occur on a continuum.
Acute inflammation refers to the initial, non specific response triggered in the surrounding tissues of the harmful stimuli. Chemical mediator’s prostaglandins, leukotriene B4, serotonin, histamine and heparin are released causing vascular dilation, vascular permeability and neutrophil activation and migration. Neutrophils phagocytose bacteria and tissue debris; opsonisation (whereby complement and immunoglobulin alter the microorganism) enhances the efficacy of phagocytosis. Soft tissue destruction occurs due to the necessary release of collagenase. (Refer to Figure1). Clinically acute inflammation is observed as the cardinal signs- calor, dolor, rubor, tumour and impaired function (Bhatavadekar & Williams 2009; Lang et al 2009; Ohlrich et al 2009; Paquette & Williams 2000: Wolf & Hassel 2006) Depending on the severity, acute inflammation can occur within minutes, and usually lasts only for days. Acute inflammation can resolve or heal by repair; however, it may also progress to chronic inflammation, commonly acute and chronic inflammation responses coexist. Failure to restore the tissues to health can be a result of a dysregulated inflammatory response.
Concepts of inflammation have evolved and our understanding of the inflammatory response has become more sophisticated. Traditionally it was understood that resolution of inflammation was a passive process whereby a gradual “burning out” of neutrophil migration occurred; therapeutics for non responders to conventional therapy were therefore targeted at inhibiting the inflammatory response. New evidence postulates resolution is an active process determined in the acute phase of inflammation (REF REF REF).
According to this emerging evidence, after entering the tissues, PMN’s promote the switch from pro-inflammatory mediators; prostaglandins and leukotrines to anti-inflammatory mediators; lipoxins (and others unknown). Anti-inflammatory mediators initiate the terminal sequence or “breaking signals” for neutrophil recruitment, thus ceasing activation and migration and allowing apoptosis. However, for tissue resolution to occur, the toxins released must be removed. It is now understood that pro – resolution molecules promote macrophage clearance of apoptotic cells at the inflamed sites, and stimulation of anti-microbial activities of mucosal epithelial cells, promoting healing of the lesion. Lipoxins, derived from arachidonic acid, and Resolvin E1, Resolvin D1 and Protectin D1, derived from Omega- 3 fatty acids, constitute the known endogenous pro-resolution anti-inflammatory molecules. Inadequate resolution of acute inflammation and failure for the host to restore tissue homeostasis results in neutrophil-mediated tissue destruction (Van Dyke), not the initial inflammation itself.
Literature suggests inflammatory diseases of the body, inclusive of periodontal diseases, are a result of hyperfunctional neutrophils which release elevated levels of prostaglandins and leukotrines at the injured site which is thought to amplify inflammation. Haemostasis cannot be achieved as there is an imbalance in the levels of pro-inflammatory and anti-inflammatory mediators, thus leading to a chronic inflammatory lesion. It follows that if “the development of periodontitis only occurs in areas of long standing gingivitis” (Lang et al) failure to resolve inflammation inevitability becomes a risk factor for periodontal disease.
Thursday, June 24, 2010
Wednesday, June 23, 2010
Reflection from Sophie
Ok guys.. I think I am getting the drift of what you are wanting to achieve.
1. You want to create a user friendly version of the pathogenisis of periodontitis which includes both the acute and chronic inflammation stages and repair, resolution and regeneration.
2. From this, you want to highlight the advances in host repsonse modulating therapies for the treatment and managemetn of periodontitis as compared to conventional approaches such as calculus removal and treatment with antimcirobial agents. Perhaps you want to look at the limited success that these conventional approaches have had.
3. Finally, a focus on the new directions for the role of the dental hygienist in response to the use of imune modulating therapies for the treatment and management of perio.
Am I correct?
if so, lets break up your research into these 3 categories and work on each of these as phase 1, phase 2 and finally phase 3.
What do you think?
1. You want to create a user friendly version of the pathogenisis of periodontitis which includes both the acute and chronic inflammation stages and repair, resolution and regeneration.
2. From this, you want to highlight the advances in host repsonse modulating therapies for the treatment and managemetn of periodontitis as compared to conventional approaches such as calculus removal and treatment with antimcirobial agents. Perhaps you want to look at the limited success that these conventional approaches have had.
3. Finally, a focus on the new directions for the role of the dental hygienist in response to the use of imune modulating therapies for the treatment and management of perio.
Am I correct?
if so, lets break up your research into these 3 categories and work on each of these as phase 1, phase 2 and finally phase 3.
What do you think?
Monday, June 21, 2010
Resolution of Inflammation - Neutrophil action
Paraphased from Article: Van-Dyke TE & Serhan CN 2003 Resolution of inflammation: A New Padagrim for the Pathogenisis of Periodontal Diseases J Dent Res 82(2) 82-90
It is understood that Neutrophils are a part of the first line of defence and protect the host from infection by phagocytosis.
Evidence now suggests that periodontitis is the result of hyperfunctional neutrophil action, these cells release toxins from the cell in large amounts (which are responisible for tissue destruction) due to excess activity. Neutrophils are not deficient or hypofunctional in periodontitis.
Inflammation, a multicellular response (similar to atherosclerosis and thrombosis) is controlled by cell to cell interactions. The cell to cell interactions that occur during the inflammatory process can provoke “transcellular biosynthetic routes” that lead to either the anti-inflammatory or proinflammatory process. In regular functioning neutrophils the anti-inflammatory process produces breaking signals (lipoxins and others unknown) which stop the inflammatory process and restore haemostasis. However, the exaggerated signals produced by hyperfunctional neutrophils (such as leukotrines and prostaglandins) advances the inflammatory process thus leading to a chronic lesion.
Further to this, Lang et al states “the development of periodontitis only occurs in areas of long standing gingivitis”
Paraphased from Article: Van-Dyke TE & Serhan CN 2003 Resolution of inflammation: A New Padagrim for the Pathogenisis of Periodontal Diseases J Dent Res 82(2) 82-90
It is understood that Neutrophils are a part of the first line of defence and protect the host from infection by phagocytosis.
Evidence now suggests that periodontitis is the result of hyperfunctional neutrophil action, these cells release toxins from the cell in large amounts (which are responisible for tissue destruction) due to excess activity. Neutrophils are not deficient or hypofunctional in periodontitis.
Inflammation, a multicellular response (similar to atherosclerosis and thrombosis) is controlled by cell to cell interactions. The cell to cell interactions that occur during the inflammatory process can provoke “transcellular biosynthetic routes” that lead to either the anti-inflammatory or proinflammatory process. In regular functioning neutrophils the anti-inflammatory process produces breaking signals (lipoxins and others unknown) which stop the inflammatory process and restore haemostasis. However, the exaggerated signals produced by hyperfunctional neutrophils (such as leukotrines and prostaglandins) advances the inflammatory process thus leading to a chronic lesion.
Further to this, Lang et al states “the development of periodontitis only occurs in areas of long standing gingivitis”
Our initial literature review
Here is a copy of our initial literature review... we have definately come along way since this!
Introduction
Chronic periodontitis is global pandemic, exhibiting a complex disease pathogenesis which remains incompletely understood (Alpdogan & Van Dyke 2005; Bhatavadekar & Williams 2009; Paquette & Williams 2000; Van-Dyke 2008; Van-Dyke & Serhan 2003). An increased understanding of cell biology and a better interpretation of the behaviour of periodontal tissues has demanded a greater understanding of disease pathogenesis by dental hygienists (Wolf & Hassel 2006). Furthermore, a dental hygienist currently assumes more responsibility of his/her patients, as the interrelationships between oral and general health are become evident.
Traditional treatment strategies (calculus removal) complement the understanding that primary mediators of periodontal destruction are plaque bacteria (Paquette & Williams 2000, Wolf & Hassel 2006). However, whilst gram negative microorganisms remain the primary etiologic determinant of the disease, emerging evidence places stronger emphasis on the host inflammatory response in the pathogenesis of periodontal destruction, thus highlighting one’s inflammatory response as a risk factor for periodontal disease (Paquette & Williams 2000; Alpdogan & Van Dyke 2005; Bhatavadekar & Williams 2009). Furthermore, literature now suggests new treatment strategies should incorporate modulation of the host inflammatory response to achieve complete healing of the condition (Alpdogan & Van Dyke 2005; Bhatavadekar & Williams 2009; Paquette & Williams 2000; Van-Dyke 2008; Van-Dyke & Serhan 2003; Wolf & Hassel 2006) This paper will present a learning contract for an Oral Health Elective responsive to the dental hygienists responsibility in emerging therapeutic developments regarding pro-resolution, anti-inflammatory agents.
Background
Bachelor of Oral Health students currently recognise periodontitis as inflammation and loss of periodontal attachment; however, a lack in the depth of understanding of the inflammatory response is apparent. Literature and teaching staff alike, acknowledge the many inconsistencies of periodontal disease, which challenges students to evaluate the information provided. Thus, a literature review has been performed to gain a higher level of knowledge. A broad search of the PubMed database was conducted from 1990 – 2010, using “periodontitis AND inflammation*[tiab]” and “periodontitis AND new treatment*[tiab]”. Relevant and recent papers published in English were reviewed, with the understanding that further searches will be conducted during the course of the Oral Health Elective.
Literature Review
It has been well recognised throughout literature, that predominance of gram negative flora and its by-products in the periodontium triggers a reactive inflammatory response in the host, classically described in terms of cardinal signs- calor, dolor, rubor, tumour and impaired function (Bhatavadekar & Williams 2009; Lang et al 2009; Ohlrich et al 2009; Paquette & Williams 2000: Wolf & Hassel 2006). The cause-and-effect of specific periodontopathogens, however, remains unclear. It is suggested that failure of the host to resolve persistent acute inflammation essentially leads to chronic inflammation. Chronic inflammation is characterized by a shift in the type of cells which are present at the site of inflammation; macrophages are the dominate cells in these injured tissue (Bhatavadekar & Williams 2009, Ling et al 2009; Schwab et al 2007; Van Dyke 2008; Wolf & Hassel 2006). Whilst, macrophages are defensive against periodontopathogens, the toxins released during this defense mechanism are injurious to the host. Thus, tissue destruction occurs during periodontal disease due to the host response rather than the initial inflammation. (Bhatavadekar & Williams 2009, Ling et al 2009; Schwab et al 2007; Van Dyke 2008; Wolf & Hassel 2006). This potentially exhibits a genetic, negative phenotype and predisposition. It logically follows that modulation of host response through blocking the inflammatory cascade may prevent disease progression, particularly for high-risk individuals non-responsive to conventional treatment, thus the notion of anti-inflammatory therapy (Van Dyke 2007).
Undesirable effects, including an unfavourable removal of protective benefits of inflammation and concomitant increase in infections questions the feasibility of such an approach (Bhatavadekar & Williams 2009, Serhan et al 2007). However, an increased understanding of resolution pathways has led to interest in proresolving lipid mediators which contribute to homeostasis (Van Dyke 2008). It is now evident that resolution of inflammation is an active, rather than passive process, whereby activation of proresolving molecules, including Resolvin E1 and Protectin D1 is required to eliminate inflammatory leukocytes and therefore prevent pathology (Bhatavadekar & Williams 2009; Schwab et al 2007; Serhan et al 2007; Van Dyke 2008). Van Dyke (2008) speculates that by introducing pharmacologic proresolving agents, resolution of inflammation would cause elimination of pathogenic bacteria in turn. This concept of control of inflammation confers new implications for pharmacological approaches for disease management; by targeting proresolution rather than inflammation alone; benefits of the inflammation may be harnessed in conjunction with a timely return to homeostasis (Bhatavadekar & Williams 2009; Van Dyke 2008). Although more research is required, animal models have shown effective resolution and healing obtained from Lipoxins and Resolvin E1 (Hasturk et al 2007; Romano 2006).
Whilst the suggested novel approaches of therapeutic modulation of host response of periodontal disease appear promising, their correct indications for use are unclear due a current lack of evidence (Bhatavadekar & Williams 2009). Thus, greater importance must be placed on a student’s understanding of the complete periodontal disease process, so that if/or when therapeutics are initiated into periodontal treatment they can be administered effectively.
ADD INS (just now thought of):
-Hygienists: epidemiological perspective, increase removal of calculus has not decreased prevalence of severe periodontitis (REFERENCE). – role of education as an adjunct to therapy must not be undermined.
-education in clinical setting is not effective- anticipatory guidance.
-upstream health promotion, common risk factor approach required.
Introduction
Chronic periodontitis is global pandemic, exhibiting a complex disease pathogenesis which remains incompletely understood (Alpdogan & Van Dyke 2005; Bhatavadekar & Williams 2009; Paquette & Williams 2000; Van-Dyke 2008; Van-Dyke & Serhan 2003). An increased understanding of cell biology and a better interpretation of the behaviour of periodontal tissues has demanded a greater understanding of disease pathogenesis by dental hygienists (Wolf & Hassel 2006). Furthermore, a dental hygienist currently assumes more responsibility of his/her patients, as the interrelationships between oral and general health are become evident.
Traditional treatment strategies (calculus removal) complement the understanding that primary mediators of periodontal destruction are plaque bacteria (Paquette & Williams 2000, Wolf & Hassel 2006). However, whilst gram negative microorganisms remain the primary etiologic determinant of the disease, emerging evidence places stronger emphasis on the host inflammatory response in the pathogenesis of periodontal destruction, thus highlighting one’s inflammatory response as a risk factor for periodontal disease (Paquette & Williams 2000; Alpdogan & Van Dyke 2005; Bhatavadekar & Williams 2009). Furthermore, literature now suggests new treatment strategies should incorporate modulation of the host inflammatory response to achieve complete healing of the condition (Alpdogan & Van Dyke 2005; Bhatavadekar & Williams 2009; Paquette & Williams 2000; Van-Dyke 2008; Van-Dyke & Serhan 2003; Wolf & Hassel 2006) This paper will present a learning contract for an Oral Health Elective responsive to the dental hygienists responsibility in emerging therapeutic developments regarding pro-resolution, anti-inflammatory agents.
Background
Bachelor of Oral Health students currently recognise periodontitis as inflammation and loss of periodontal attachment; however, a lack in the depth of understanding of the inflammatory response is apparent. Literature and teaching staff alike, acknowledge the many inconsistencies of periodontal disease, which challenges students to evaluate the information provided. Thus, a literature review has been performed to gain a higher level of knowledge. A broad search of the PubMed database was conducted from 1990 – 2010, using “periodontitis AND inflammation*[tiab]” and “periodontitis AND new treatment*[tiab]”. Relevant and recent papers published in English were reviewed, with the understanding that further searches will be conducted during the course of the Oral Health Elective.
Literature Review
It has been well recognised throughout literature, that predominance of gram negative flora and its by-products in the periodontium triggers a reactive inflammatory response in the host, classically described in terms of cardinal signs- calor, dolor, rubor, tumour and impaired function (Bhatavadekar & Williams 2009; Lang et al 2009; Ohlrich et al 2009; Paquette & Williams 2000: Wolf & Hassel 2006). The cause-and-effect of specific periodontopathogens, however, remains unclear. It is suggested that failure of the host to resolve persistent acute inflammation essentially leads to chronic inflammation. Chronic inflammation is characterized by a shift in the type of cells which are present at the site of inflammation; macrophages are the dominate cells in these injured tissue (Bhatavadekar & Williams 2009, Ling et al 2009; Schwab et al 2007; Van Dyke 2008; Wolf & Hassel 2006). Whilst, macrophages are defensive against periodontopathogens, the toxins released during this defense mechanism are injurious to the host. Thus, tissue destruction occurs during periodontal disease due to the host response rather than the initial inflammation. (Bhatavadekar & Williams 2009, Ling et al 2009; Schwab et al 2007; Van Dyke 2008; Wolf & Hassel 2006). This potentially exhibits a genetic, negative phenotype and predisposition. It logically follows that modulation of host response through blocking the inflammatory cascade may prevent disease progression, particularly for high-risk individuals non-responsive to conventional treatment, thus the notion of anti-inflammatory therapy (Van Dyke 2007).
Undesirable effects, including an unfavourable removal of protective benefits of inflammation and concomitant increase in infections questions the feasibility of such an approach (Bhatavadekar & Williams 2009, Serhan et al 2007). However, an increased understanding of resolution pathways has led to interest in proresolving lipid mediators which contribute to homeostasis (Van Dyke 2008). It is now evident that resolution of inflammation is an active, rather than passive process, whereby activation of proresolving molecules, including Resolvin E1 and Protectin D1 is required to eliminate inflammatory leukocytes and therefore prevent pathology (Bhatavadekar & Williams 2009; Schwab et al 2007; Serhan et al 2007; Van Dyke 2008). Van Dyke (2008) speculates that by introducing pharmacologic proresolving agents, resolution of inflammation would cause elimination of pathogenic bacteria in turn. This concept of control of inflammation confers new implications for pharmacological approaches for disease management; by targeting proresolution rather than inflammation alone; benefits of the inflammation may be harnessed in conjunction with a timely return to homeostasis (Bhatavadekar & Williams 2009; Van Dyke 2008). Although more research is required, animal models have shown effective resolution and healing obtained from Lipoxins and Resolvin E1 (Hasturk et al 2007; Romano 2006).
Whilst the suggested novel approaches of therapeutic modulation of host response of periodontal disease appear promising, their correct indications for use are unclear due a current lack of evidence (Bhatavadekar & Williams 2009). Thus, greater importance must be placed on a student’s understanding of the complete periodontal disease process, so that if/or when therapeutics are initiated into periodontal treatment they can be administered effectively.
ADD INS (just now thought of):
-Hygienists: epidemiological perspective, increase removal of calculus has not decreased prevalence of severe periodontitis (REFERENCE). – role of education as an adjunct to therapy must not be undermined.
-education in clinical setting is not effective- anticipatory guidance.
-upstream health promotion, common risk factor approach required.
The "Inflammatory response"
Hi Sophie!
So we are looking at defining what the :inflammatory response" is in reference to the periodontium.
We took another lok at Wolf and Hassell yesterday, and according to page 41, "Host response- Mechansims and Participants," the following were listed as "inflammatory cells":
-PMNs, which include neutrophils, eosinophilic granulocytes, basophilic granulocytes AND
-thromocytes
We decided to revise these cells, and Leticia is about to blog what we found on an internet search.
I guess now our problem lies in this -
THE INFLAMMATORY PROCESS itself. WE understand inflammation is an INNATE response, with an initial ACUTE stage, and later CHRONIC stage if left unresolved. In the ACUTE stage, the cells above are the "major players," but in the chronic stage, it seems that macrophages and acquired immune response becomes involved (T cells, B cells), and this is where we have to remove ourselves. regardless, we would like to form a flow chart of both acute and chronic stage of inflammation. We had access to one last year, but are unable to access it now, as it seems that human biology content has been blocked from second year (we tried the pencil thing). We also felt that we did not completely understand inflammation last year anyway.
So we are looking at defining what the :inflammatory response" is in reference to the periodontium.
We took another lok at Wolf and Hassell yesterday, and according to page 41, "Host response- Mechansims and Participants," the following were listed as "inflammatory cells":
-PMNs, which include neutrophils, eosinophilic granulocytes, basophilic granulocytes AND
-thromocytes
We decided to revise these cells, and Leticia is about to blog what we found on an internet search.
I guess now our problem lies in this -
THE INFLAMMATORY PROCESS itself. WE understand inflammation is an INNATE response, with an initial ACUTE stage, and later CHRONIC stage if left unresolved. In the ACUTE stage, the cells above are the "major players," but in the chronic stage, it seems that macrophages and acquired immune response becomes involved (T cells, B cells), and this is where we have to remove ourselves. regardless, we would like to form a flow chart of both acute and chronic stage of inflammation. We had access to one last year, but are unable to access it now, as it seems that human biology content has been blocked from second year (we tried the pencil thing). We also felt that we did not completely understand inflammation last year anyway.
Inflammatory cells
PMN – polymorphonuclear granulocyte
· White blood cells with nuclei of varied forms, characterized by the presence of granules in their cytoplasm
· Granulocytes or PMN are released from the bone marrow by the regulatory complement proteins.
Neutrophils
· A PMN granular leukocyte
· They are the circulating white blood cells essential for phagocytosis and proteolysis
· Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, constituting 50% to 60% of the total circulating white blood cells.
· Live approximately five days
· Once neutrophils have received the appropriate signals, it takes them about thirty minutes to leave the blood and reach the site of an infection
· Rapidly engulf invaders coated with antibodies and complement, and damaged cells or cellular debris.
Neutrophils do not return to the blood; they turn into pus cells and die
Eosinophilic granulocytes
· They are antigen presenting cells, they regulate other immune cell functions
PMN – polymorphonuclear granulocyte
· White blood cells with nuclei of varied forms, characterized by the presence of granules in their cytoplasm
· Granulocytes or PMN are released from the bone marrow by the regulatory complement proteins.
Neutrophils
· A PMN granular leukocyte
· They are the circulating white blood cells essential for phagocytosis and proteolysis
· Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, constituting 50% to 60% of the total circulating white blood cells.
· Live approximately five days
· Once neutrophils have received the appropriate signals, it takes them about thirty minutes to leave the blood and reach the site of an infection
· Rapidly engulf invaders coated with antibodies and complement, and damaged cells or cellular debris.
Neutrophils do not return to the blood; they turn into pus cells and die
Eosinophilic granulocytes
· They are antigen presenting cells, they regulate other immune cell functions
· Kill parasites (e.g. enteric nematodes) because their granules contain a unique, toxic basic protein and cationic protein receptors that bind to IgE
· These cells also have a limited ability to participate in phagocytosis
· Involved in the destruction of tumor cells
· Promote the repair of damaged tissue
· A chemical called interleukin - 5 interacts with eosinophils and causes them to grow and differentiate
Basophilic granulocytes, mast cells
Basophils are one of the least abundant cells in bone marrow & blood
When an infection occurs mature basophils will be released from the bone marrow and travel to the site of infection
When basophils are injured they will release histamine; this contributes to the inflamm response that helps fight invading organisms.
Histamine causes dilation and increased permeability of capillaries close to the basophil.
Injured basophils and other leukocytes will release another substance called prostoglandins that contributes to an increased blood flow to the site of infection. Both of these mechanisms allow blood clotting elements to be delivered to the infected area (this begins the recovery process and blocks the travel of microbes to other parts of the body)
Increased permeability of the blood also allows for more phagocyte migration to the site of infection so that they can consume microbes
Thrombocytes
In mammals thrombocytes = Platelets, key role in blood clotting
Platelets - are small, irregularly-shaped anuclear cell fragments
Average lifespan of a platelet is normally just 5 to 9 days
Platelets play a fundamental role in hemostasis and are a natural source of growth factors
If the number of platelets is too low, excessive bleeding can occur
If the number of platelets is too high, blood clots can form = thrombosis
Platelets release a multitude of growth factors including platelet-derived growth factor (PDGF), & TGF beta, which stimulates the deposition of extracellular matrix.
Both of these growth factors have been shown to play a significant role in the repair and regeneration of connective tissue.
The problems with Perio Path
Hey Elvina and Leticia
Start this blog by letting me know what your issues are with pathogenesis...
Start this blog by letting me know what your issues are with pathogenesis...
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