Wound healing is a highly dynamic process and involves complex interactions of extracellular matrix molecules, soluble mediators, various resident cells, and infiltrating leukocyte subtypes.
inflammation and wound repair, Inflammation in physiological wound
repair: cell lineages, functions, and mediators, Inflammation directs the quality of tissue repair, Excess inflammation associated with impaired wound healing, Chronic inflammation associated with malignant progression in chronic wounds
Wound healing is a highly dynamic process and involves complex interactions of extracellular matrix molecules, soluble mediators, various resident cells, and infiltrating leukocyte subtypes.
The immediate goal in repair is to achieve tissue integrity and homeostasis
physiology of wound healing / dental implant courses by Indian dental academy Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
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inflammation and wound repair, Inflammation in physiological wound
repair: cell lineages, functions, and mediators, Inflammation directs the quality of tissue repair, Excess inflammation associated with impaired wound healing, Chronic inflammation associated with malignant progression in chronic wounds
Wound healing is a highly dynamic process and involves complex interactions of extracellular matrix molecules, soluble mediators, various resident cells, and infiltrating leukocyte subtypes.
The immediate goal in repair is to achieve tissue integrity and homeostasis
physiology of wound healing / dental implant courses by Indian dental academy Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The main effector cells of innate immunity are macrophages, neutrophils, dendritic cells, and natural killer (NK) cells .
Phagocytosis, release of inflammatory mediators, activation of complement system proteins, as well as synthesis of acute phase proteins, cytokines and chemokines are the main mechanisms in innate immunity
Immune system and its functions
The main effector cells of innate immunity are macrophages, neutrophils, dendritic cells, and natural killer (NK) cells .
Phagocytosis begins with adhesion of the phagocyte surface receptors to the pathogen, which then is internalized into vesicles called phagosomes.
Inside the phagocyte, the phagosome fuses to lysosomes, whose contents are released with consequent digestion and pathogen elimination.
Changes in the oxidase’s gene system components present in phagolysosome membrane lead to disability in respiratory burst and generation of reactive oxygen species (ROS).
Phagocytosis begins with adhesion of the phagocyte surface receptors to the pathogen, which then is internalized into vesicles called phagosomes.
Inside the phagocyte, the phagosome fuses to lysosomes, whose contents are released with consequent digestion and pathogen elimination.
Changes in the oxidase’s gene system components present in phagolysosome membrane lead to disability in respiratory burst and generation of reactive oxygen species (ROS).
Inflammatory gingival hyperplasia is an inflammatory restraint to local irritant correlating with the gingiva; the irritant could be microbial like plaque and calculus.
Clinically present as deep red or bluish, considerably friable and fine with smooth glossy surface and commonly bleed easily [1].
These conditions are presented with the epithelial to mesenchymal transition (EMT), where the basal lamina show disruptions and epithelial cells migrate into connective tissue and change their phenotypes to fibroblast-like cells [12].
Many evidences that CSCs also play a central role in the pathogenesis and progression of carcinomas of the head and neck (HNSCC), including OSCC,have been found.
Early tissue culture studies showed that only a subpopulation of OSCC cells can form expanding tumor colonies, suggesting that human OSCC may contain some form of stem cells and it was subsequently shown that only a small subpopulation of the cells in OSCC corresponds to tumor-initiating cells.
These finding are in accordance with CSCs concept (17,34) that the tumor mass is a mixture of (a) CSCs dividing themselves to feed the tumor's growth, b) transient amplifying cells that divide themselves a few times before maturing into (c) differentiated tumor cells that do not contribute to tumor growth (4).
The isolation of CSCs from oral cancers has mainly been performed with the CD44 marker that was initially used to isolate breast cancer CSCs.
The main effector cells of innate immunity are macrophages, neutrophils, dendritic cells, and natural killer (NK) cells .
Phagocytosis, release of inflammatory mediators, activation of complement system proteins, as well as synthesis of acute phase proteins, cytokines and chemokines are the main mechanisms in innate immunity
Immune system and its functions
The main effector cells of innate immunity are macrophages, neutrophils, dendritic cells, and natural killer (NK) cells .
Phagocytosis begins with adhesion of the phagocyte surface receptors to the pathogen, which then is internalized into vesicles called phagosomes.
Inside the phagocyte, the phagosome fuses to lysosomes, whose contents are released with consequent digestion and pathogen elimination.
Changes in the oxidase’s gene system components present in phagolysosome membrane lead to disability in respiratory burst and generation of reactive oxygen species (ROS).
Phagocytosis begins with adhesion of the phagocyte surface receptors to the pathogen, which then is internalized into vesicles called phagosomes.
Inside the phagocyte, the phagosome fuses to lysosomes, whose contents are released with consequent digestion and pathogen elimination.
Changes in the oxidase’s gene system components present in phagolysosome membrane lead to disability in respiratory burst and generation of reactive oxygen species (ROS).
Inflammatory gingival hyperplasia is an inflammatory restraint to local irritant correlating with the gingiva; the irritant could be microbial like plaque and calculus.
Clinically present as deep red or bluish, considerably friable and fine with smooth glossy surface and commonly bleed easily [1].
These conditions are presented with the epithelial to mesenchymal transition (EMT), where the basal lamina show disruptions and epithelial cells migrate into connective tissue and change their phenotypes to fibroblast-like cells [12].
Many evidences that CSCs also play a central role in the pathogenesis and progression of carcinomas of the head and neck (HNSCC), including OSCC,have been found.
Early tissue culture studies showed that only a subpopulation of OSCC cells can form expanding tumor colonies, suggesting that human OSCC may contain some form of stem cells and it was subsequently shown that only a small subpopulation of the cells in OSCC corresponds to tumor-initiating cells.
These finding are in accordance with CSCs concept (17,34) that the tumor mass is a mixture of (a) CSCs dividing themselves to feed the tumor's growth, b) transient amplifying cells that divide themselves a few times before maturing into (c) differentiated tumor cells that do not contribute to tumor growth (4).
The isolation of CSCs from oral cancers has mainly been performed with the CD44 marker that was initially used to isolate breast cancer CSCs.
Many evidences that CSCs also play a central role in the pathogenesis and progression of carcinomas of the head and neck (HNSCC), including OSCC,have been found.
Early tissue culture studies showed that only a subpopulation of OSCC cells can form expanding tumor colonies, suggesting that human OSCC may contain some form of stem cells and it was subsequently shown that only a small subpopulation of the cells in OSCC corresponds to tumor-initiating cells.
These finding are in accordance with CSCs concept (17,34) that the tumor mass is a mixture of (a) CSCs dividing themselves to feed the tumor's growth, b) transient amplifying cells that divide themselves a few times before maturing into (c) differentiated tumor cells that do not contribute to tumor growth (4).
The isolation of CSCs from oral cancers has mainly been performed with the CD44 marker that was initially used to isolate breast cancer CSCs.
Clinical Description
Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia representing a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities), to mild CCD, to isolated dental anomalies without other skeletal features [Golan et al 2000]. Most individuals are diagnosed because they have classic features. CCD spectrum disorder affects most prominently those bones derived from intramembranous ossification, such as the cranium and the clavicles, although bones formed through endochondral ossification can also be affected. Cooper et al [2001] recorded the natural history of 90 probands and 56 first- and second-degree relatives; findings highlight the clinical variability of this condition within affected members of the same family who harbor the same pathogenic variant. Roberts et al [2013] reviewed their experience with more than 100 affected individuals in South Africa.
Classic CCD. The most prominent clinical findings in individuals with classic CCD are listed in Suggestive Findings and include: abnormally large, wide-open fontanelles at birth that may remain open throughout life; clavicular hypoplasia resulting in narrow, sloping shoulders that can be opposed at the midline; and abnormal dentition
Further medical problems identified in individuals with CCD spectrum disorder include short stature, skeletal/orthopedic findings, dental complications, ENT complications, endocrine findings, and mild developmental delay.
Molecular Pathogenesis
RUNX2 encodes runt-related transcription factor 2 (RUNX2), a transcription factor involved in osteoblast differentiation and skeletal morphogenesis. RUNX2 is essential for osteoblast differentiation during intramembranous ossification as well as chondrocyte maturation during endochondral ossification [Zheng et al 2005]. RUNX2 contains an N-terminal stretch of consecutive polyglutamine and polyalanine repeats known as the Q/A domain, a runt domain, and a C-terminal proline/serine/threonine-rich (PST) activation domain. The runt domain is a 128-amino-acid polypeptide motif originally described in the Drosophila runt gene that has the unique ability to independently mediate DNA binding and protein heterodimerization [Zhou et al 1999].
The majority of RUNX2 pathogenic variants in individuals with classic CCD affect the runt domain and most are predicted to abolish DNA binding [Lee et al 1997, Mundlos et al 1997, Otto et al 2002]. Pathogenic missense variants cluster at arginine 225 (p.Arg225) of RUNX2, a critical residue for RUNX2 function. In vitro studies have shown that pathogenic missense variants at p.Arg225 interfere with nuclear accumulation of RUNX2.
Hypomorphic RUNX2 alleles with partial loss of protein function, c.90dupC and c.598A>G, are associated with mild CCD, isolated dental anomalies, and significant intrafamilial variability.
Mechanism of disease causation. Loss of function
RUNX2-sp
Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia representing a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities), to mild CCD, to isolated dental anomalies without other skeletal features [Golan et al 2000]. Most individuals are diagnosed because they have classic features. CCD spectrum disorder affects most prominently those bones derived from intramembranous ossification, such as the cranium and the clavicles, although bones formed through endochondral ossification can also be affected. Cooper et al [2001] recorded the natural history of 90 probands and 56 first- and second-degree relatives; findings highlight the clinical variability of this condition within affected members of the same family who harbor the same pathogenic variant. Roberts et al [2013] reviewed their experience with more than 100 affected individuals in South Africa.
PV is caused by autoantibodies that target cadherins, specifically desmogleins, though there may be some role for desmocollin; thus, this is a type 2 hypersensitivity reaction.[24][25] Acantholysis, or the loss of keratinocyte–keratinocyte adhesion, is interrupted by circulating IgG autoantibodies to intercellular adhesion molecules.[26][27] Acantholysis is seen as a result of the autoantibodies destroying the intracellular connections, leading to bullae that can easily rupture (known clinically as the Nikolsky sign).
A “super-compensation hypothesis” recently submitted by Sinha et al. proposes that additional factors may also play a role in PV.[28] Multiple mechanisms for antibody-induced acantholysis have been suggested, including the induction of signal transduction and the inhibition of adhesive molecule function through steric hindrance, which can trigger cell separation.[29] The pathogenesis of PV has been described in more detail by Hammers et al.[30]
In patients with PV, autoantibodies against desmoglein 1 (Dsg 1) and desmoglein 3 (Dsg 3) is the purported cause.[31] Desmogleins are transmembrane glycoproteins that are an integral part of desmosomes which, in part, are required for cell–cell adhesion via interaction with intermediate filaments. The most common targets of desmoglein for IgG antibodies are the extracellular cadherin domains, which can result in the loss of desmosome-adhesive properties. These signaling pathways trigger endocytosis, depletion, and direct inhibition of Dsg 3 interactions.[32] It is generally believed that the amino portion of the cadherin proteins is most implicated in the pathogenesis of acantholysis leading to PV.[33]
Many animal models have shown that enzymatic inactivation of Dsg 1 and gene deletion of Dsg 3 results in pathology similar to PV.[34][35] This phenomenon was observed to be dose-dependent and suggests that reducing the circulating levels of IgG against Dsg 1 and Dsg 3 can improve patient outcomes.[36] In patients with primarily cutaneous disease, Dsg 1 likely plays a role more superficially, whereas Dsg 3 is more likely to be found in deeper cutaneous structures and mucous membranes.[37][38] The implication is that Dsg 3 can compensate for the absence of Dsg 1 in mucosal structures (thus demonstrating PV in cutaneous lesions only). In contrast, Dsg 1 without Dsg 3 is insufficient to manage mucous membranes or cutaneous lesions alone, implying that Dsg 1 is in lower proportion in mucous membranes.
The binding of antibodies to desmogleins has been confirmed by epitope mapping and is presumed to disrupt desmoglein binding by affecting steric hindrance.[39] Another theory for the pathophysiology of PV is the desmoglein nonassembly depletion hypothesis. This theory suggests that autoantibodies not only bind desmoglein but that they also bind each other, leading to crosslinking and the inability of desmosomes to maintain cell–cell adhesion.[40][41]
PV is caused by autoantibodies that target cadherins, specifically desmogleins, though there may be some role for desmocollin; thus, this is a type 2 hypersensitivity reaction.[24][25] Acantholysis, or the loss of keratinocyte–keratinocyte adhesion, is interrupted by circulating IgG autoantibodies to intercellular adhesion molecules.[26][27] Acantholysis is seen as a result of the autoantibodies destroying the intracellular connections, leading to bullae that can easily rupture (known clinically as the Nikolsky sign).
A “super-compensation hypothesis” recently submitted by Sinha et al. proposes that additional factors may also play a role in PV.[28] Multiple mechanisms for antibody-induced acantholysis have been suggested, including the induction of signal transduction and the inhibition of adhesive molecule function through steric hindrance, which can trigger cell separation.[29] The pathogenesis of PV has been described in more detail by Hammers et al.[30]
In patients with PV, autoantibodies against desmoglein 1 (Dsg 1) and desmoglein 3 (Dsg 3) is the purported cause.[31] Desmogleins are transmembrane glycoproteins that are an integral part of desmosomes which, in part, are required for cell–cell adhesion via interaction with intermediate filaments. The most common targets of desmoglein for IgG antibodies are the extracellular cadherin domains, which can result in the loss of desmosome-adhesive properties. These signaling pathways trigger endocytosis, depletion, and direct inhibition of Dsg 3 interactions.[32] It is generally believed that the amino portion of the cadherin proteins is most implicated in the pathogenesis of acantholysis leading to PV.[33]
Many animal models have shown that enzymatic inactivation of Dsg 1 and gene deletion of Dsg 3 results in pathology similar to PV.[34][35] This phenomenon was observed to be dose-dependent and suggests that reducing the circulating levels of IgG against Dsg 1 and Dsg 3 can improve patient outcomes.[36] In patients with primarily cutaneous disease, Dsg 1 likely plays a role more superficially, whereas Dsg 3 is more likely to be found in deeper cutaneous structures and mucous membranes.[37][38] The implication is that Dsg 3 can compensate for the absence of Dsg 1 in mucosal structures (thus demonstrating PV in cutaneous lesions only). In contrast, Dsg 1 without Dsg 3 is insufficient to manage mucous membranes or cutaneous lesions alone, implying that Dsg 1 is in lower proportion in mucous membranes.
The binding of antibodies to desmogleins has been confirmed by epitope mapping and is presumed to disrupt desmoglein binding by affecting steric hindrance.[39] Another theory for the pathophysiology of PV is the desmoglein nonassembly depletion hypothesis. This theory suggests that autoantibodies not only bind desmoglein but that they also bind each other, leading to crosslinking and the inability of desmosomes to maintain cell–cell adhesion.[40][41]
The primary function of platelets is their role in hemostasis. Briefly, under normal physiological conditions, platelets will adhere to and begin to spread over the surface of subendothelial cells exposed by damage to the vascular endothelium.(1) Adhesion is dependent on the platelet membrane glycoprotein lb complex. The von Willebrand factor (vWF) is required for both adhesion and spreading.
The primary function of platelets is their role in hemostasis. Briefly, under normal physiological conditions, platelets will adhere to and begin to spread over the surface of subendothelial cells exposed by damage to the vascular endothelium.(1) Adhesion is dependent on the platelet membrane glycoprotein lb complex. The von Willebrand factor (vWF) is required for both adhesion and spreading.
Platelets have many functions, including phagocytosis of viruses, latex, immune complexes and iron; maintenance of vascular integrity
by filling gaps that form in the endothelium and by directly supporting endothelial cells; synthesis and release of vWF in humans and some animal species, and fibronectin;
participating in surface adhesion andactivation processess (Caen and Rosa, 1995; Clemetson, 1995; Nurden, 1995);
production and release of potent smooth muscle and endothelial cell proliferating factor( s); and retraction of clots, a process that stabilizes the initial hemostatic plug and activates clot lysis.
Platelets have many functions, including phagocytosis of viruses, latex, immune complexes and iron; maintenance of vascular integrity
by filling gaps that form in the endothelium and by directly supporting endothelial cells; synthesis and release of vWF in humans and some animal species, and fibronectin;
participating in surface adhesion andactivation processess (Caen and Rosa, 1995; Clemetson, 1995; Nurden, 1995);
production and release of potent smooth muscle and endothelial cell proliferating factor( s); and retraction of clots, a process that stabilizes the initial hemostatic plug and activates clot lysis.
Tooth development proceeds with reciprocal inductive interactions between stomadeum ectoderm and underlying ectomesenchymal cells in a strictly controlled temporal and spatial order.
Well studied at the molecular biologic level, over 300 genes and 100 growth and differentiation factors are implicated in the control of cellular differentiation and crosstalk in dental development that result in structures containing combination of mineralized tissues (enamel, dentine, cementum), soft connective tissues (dental pulp, periodontal ligament), blood vessels, nerves and lymphatics.
Tooth development proceeds with reciprocal inductive interactions between stomadeum ectoderm and underlying ectomesenchymal cells in a strictly controlled temporal and spatial order.
Well studied at the molecular biologic level, over 300 genes and 100 growth and differentiation factors are implicated in the control of cellular differentiation and crosstalk in dental development that result in structures containing combination of mineralized tissues (enamel, dentine, cementum), soft connective tissues (dental pulp, periodontal ligament), blood vessels, nerves and lymphatics
Diagnostic polymerase chain reaction (PCR) is an extremely powerful, rapid method for diagnosis of microbial infections and genetic diseases, as well as for detecting microorganisms in environmental and food samples.
However, the usefulness of diagnostic PCR is limited, in part, by the presence of inhibitory substances in complex biological samples, which reduce or even block the amplification capacity of PCR in comparison with pure solutions of nucleic acids .
In general, diagnostic PCR may be divided into four steps: (1) sampling, (2) sample preparation, (3) nucleic acid amplification, and (4) detection of PCR products
Diagnostic polymerase chain reaction (PCR) is an extremely powerful, rapid method for diagnosis of microbial infections and genetic diseases, as well as for detecting microorganisms in environmental and food samples.
However, the usefulness of diagnostic PCR is limited, in part, by the presence of inhibitory substances in complex biological samples, which reduce or even block the amplification capacity of PCR in comparison with pure solutions of nucleic acids .
In general, diagnostic PCR may be divided into four steps: (1) sampling, (2) sample preparation, (3) nucleic acid amplification, and (4) detection of PCR products
The etiology of a disease refers to the causative trigger(s), whereas pathogenesis refers to the mechanism(s) by which the disease progresses.
In other words, while the microbial biofilm developing on the tooth surface constitutes a necessary etiological factor, its mere presence is insufficient for the initiation of the disease.
Further risk factors, such as host genetics, lifestyle, stress, and systemic conditions, that dictate the immunopathogenesis are crucial for the transition from a healthy to a diseased state.
The etiology of a disease refers to the causative trigger(s), whereas pathogenesis refers to the mechanism(s) by which the disease progresses.
In other words, while the microbial biofilm developing on the tooth surface constitutes a necessary etiological factor, its mere presence is insufficient for the initiation of the disease.
Further risk factors, such as host genetics, lifestyle, stress, and systemic conditions, that dictate the immunopathogenesis are crucial for the transition from a healthy to a diseased state.
Nano-composite scaffolds based on electrospun nanofibers have gained great attention due to their ability to emulate natural extracellular matrix (ECM) that affects cell survival, attachment and reorganization.
Promoted protein absorption, cellular reactions, activation of specific gene expression and intracellular signaling, and high surface area to volume ratio are also important properties of nanofibrous scaffolds.
Moreover, several bioactive components, such as bioceramics and functional polymers can be easily blended into nanofibrous matrixes to regulate the physical-chemical-biological properties and regeneration abilities.
Simultaneously, functional growth factors, proteins and drugs are also incorporated to regulate cellular reactions and even modify the local inflammatory microenvironment, which benefit periodontal regeneration and functional restoration
Nano-composite scaffolds based on electrospun nanofibers have gained great attention due to their ability to emulate natural extracellular matrix (ECM) that affects cell survival, attachment and reorganization.
Promoted protein absorption, cellular reactions, activation of specific gene expression and intracellular signaling, and high surface area to volume ratio are also important properties of nanofibrous scaffolds.
Moreover, several bioactive components, such as bioceramics and functional polymers can be easily blended into nanofibrous matrixes to regulate the physical-chemical-biological properties and regeneration abilities.
Simultaneously, functional growth factors, proteins and drugs are also incorporated to regulate cellular reactions and even modify the local inflammatory microenvironment, which benefit periodontal regeneration and functional restoration
Immunologically mediated mucocutaneous diseases constitute a large group of oral mucosal disorders and are triggered by cellular or humoral responses directed against epithelial or connective tissues in a chronic, recurrent pattern.
The treatment of these disorders should be directed not only toward relief from symptoms but also toward treating the underlying immune dysregulation, preventing recurrences, and preserving organ integrity and function
More from Romissaa ali Esmail/ faculty of dentistry/Al-Azhar university (20)
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
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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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
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
inflammation.pdf
1. B Y
R O M I S S A A A L Y
A S S I S T A N T L E C T U R E R O F O R A L
M E D I C I N E , P E R I O D O N T O L O G Y , D I A G N O S I S
A N D D E N T A L R A D I O L O G Y ( A L - A Z H A R
U N I V E R S I T Y )
From Inflammation to Wound
Repair
2. Wound healing is a highly dynamic process and
involves complex interactions of extracellular matrix
molecules, soluble mediators, various resident cells, and
infiltrating leukocyte subtypes.
The immediate goal in repair is to achieve tissue integrity and
homeostasis (Martin 1997; Singer and Clark, 1999).
3. To achieve this goal, the healing process involves
three phases that overlap in time and space:
inflammation, tissue formation, and tissue remodeling.
During the inflammatory phase, platelet
aggregation is followed by infiltration of leukocytes
into the
wound site.
4. In tissue formation, epithelialization and newly
formed granulation tissue, consisting of
endothelial cells, macrophages and fibroblasts, begin
to cover and fill the wound area to restore tissue
integrity.
5. Synthesis, remodeling, and deposition of structural
extracellular matrix molecules, are indispensable for
initiating repair and progression into the healing state.
6. During the past decade numerous factors have been
identified that are engaged in a complex reciprocal dialogue
between epidermal and dermal cells to facilitate
wound repair (Werner and Grose, 2003).
7. The sensitive balance between stimulating and
inhibitory mediators during diverse stages of
repair is crucial to achieving tissue homeostasis
following injury.
8.
9. They are not only effector cells combating invading
pathogens but are also involved in tissue degradation and
tissue formation.
11. Tissue injury causes the immediate onset of acute
inflammation. It has long been considered that the
inflammatory response is instrumental to supplying
growth factor and cytokine signals that orchestrate the
cell and tissue movements necessary for repair (Simpson
and Ross, 1972)
12. In various experimental animal models and human skin
wounds, it has been demonstrated that the inflammatory
response during normal healing is characterized by
spatially and temporally changing patterns of
various leukocyte subsets (Martin 1997; Singer and
Clark, 1999).
13. PMNs: Immediately after injury extravasated blood
constituents form a hemostatic plug.
Platelets and polymorphonuclear leukocytes (neutrophils,
PMN) entrapped and aggregated in the blood clot release a wide
variety of factors that amplify the aggregation response, initiate
a coagulation cascade, and/or act as chemoattractants for cells
involved in the inflammatory phase
(Szpaderska et al., 2003).
14. Within a few hours post-injury the bulk of neutrophils in the
wound transmigrate across the endothelial cell wall of
blood capillaries, which have been activated by
proinflammatory cytokines IL-1b, tumor necrosis
factor-a (TNF-a), and IFN-g at the wound site, leading to
expression of various classes of adhesion molecules essential for
leukocyte adhesion and diapedesis
15. Adhesion molecules which are crucial for neutrophil
diapedesis include endothelial P- and E-selectins as well as
the ICAM- 1, -2.
These adhesins interact with integrins present at
the cells surface of neutrophils including CD11a/CD18
(LFA-1), CD11b/CD18 (MAC-1), CD11c/CD18 (gp150, 95), and
CD11d/CD18
(Kulidjian et al., 1999).
16. Chemokines and their receptors are most likely
crucial mediators for neutrophil recruitment during
repair (Gillitzer and Goebeler 2001; Esche et al.,
2005).
17. In addition, bacterial products, such as
lipopolysaccharides and formyl-methionyl peptides, which
accumulate in the bacterially infected wound, can
accelerate the directed neutrophil locomotion.
Recruited neutrophils begin the debridement of
devitalized tissue and phagocytosis of infectious agents.
18. To perform this task, neutrophils release a large
variety of highly active antimicrobial
substances (reactive oxygen species (ROS), cationic
peptides, eicosanoids) and proteases (elastase,
cathepsin G, proteinase 3, urokinase-type
plasminogen activator)
(Weiss 1989)
19. Recent in vitro studies demonstrated that neutrophils
isolated from sites of repair can modulate the
phenotype and cytokine profile expression of
macrophages, thereby regulating the innate immune
response during healing
(Daley et al., 2005).
20. In addition, a recent report shows that closure of
excisional wounds in CD18-depleted mice was
significantly delayed, most likely due to impaired
myofibroblast differentiation and reduced wound
contraction
(Peters et al., 2005).
21. CD18-deficient wounds, which are devoid of
neutrophils, the lack of apoptotic neutrophils at
the wound site deprives macrophages of their main
stimulus to secrete transforming growth factor-b1 (TGF-
b1), a key mediator involved in myofibroblast
differentiation.
22.
23. Macrophage infiltration into the wound site is
highly regulated by gradients of different chemotactic
factors, including growth factors,
proinflammatory cytokines, and chemokines
macrophage inflammatory protein 1a, MCP-1, RANTES)
(Werner and Grose 2003).
24. Major sources of these chemoattractants at the wound site
include platelets trapped in the fibrin clot at the wound
surface, hyperproliferative keratinocytes at the wound edge,
fibroblasts, and leukocytes subsets themselves.
As monocytes extravasate from the blood vessel they become
activated and differentiate into mature tissue macrophages.
25. There is evidence that the activation process is directed by
mediators present in the microenvironment, and
this pathway would be crucial for the proper adaptation of
macrophage function to the specific metabolic requirements
of the wound site
(Gordon, 2003)
26. Numerous cell surface receptors have been described
through which macrophages sense and respond to their
microenvironment, including Toll-like receptors,
complement receptors, and Fc receptors
(Gordon 2003; Karin et al., 2006).
27. Beside their immunological functions as antigen-presenting
cells and phagocytes during wound repair, macrophages are
thought to play an integral role in a successful outcome of the
healing response
28. through the synthesis of numerous potent growth factors,
such as TGF-b, TGF-a, basic fibroblast growth factor, platelet-
derived growth factor, and vascular endothelial growth factor,
which promote cell proliferation and the synthesis of
extracellular matrix molecules by resident skin cells.
(DiPietro and Polverini, 1993)
29.
30.
31. Mast cells are considered to be involved in tissue repair.
Following injury residential mast cells degranulate within
hours and thus may become less apparent. Mast cell levels
return to normal around 48 hours post-injury, and
then increase in number as tissue repair proceeds
(Trautmann et al.,2000).
32. Egozi et al. (2003) reported that mast cell-deficient mice
(WBB6F1/Jkit w/KitWV) showed a decreased number
of neutrophils at the wound site, whereas macrophage and T-
cell infiltration was normal.
In these studies, mast cell deficiency had no significant
effect on epithelialization, collagen synthesis, or angiogenesis.
These results suggest that mast cells modulate the
recruitment of neutrophils into the site of injury.
33. However, in normal uncomplicated conditions mast cells are
unlikely to exert functions that are rate limiting for repair in
mice.
Recently, both studies have been challenged by a report
describing a significant impact of mast cell deficiency on
vascular permeability, PMN influx, and ultimately
wound closure rate
(Weller et al., 2006).
34.
35. Fig. Mast cells are recruited to the site of injury by macrophage
and keratinocyte-derived MCP-1. MCs in return release
mediators mainly histamine, VEGF, IL-6, and IL-8 that
contribute to the increase of endothelial permeability and
vasodilation and facilitate migration of inflammatory cells such
as monocyte and neutrophil to the site of injury. Monocytes
transform into macrophages and play a key role in wound
healing. Neutrophils in humans are recruited by IL-8 to injury
sites where they release IL-1α and TNF-α and activate fibroblasts
and keratinocytes to facilitate wound healing
36. ƒ
Fig. Cellular and molecular interactions in
wound site. Keratinocytes by secreting SCF
recruit MCs to the site. MCs then recruit
other inflammatory cells including
neutrophils and monocytes. Proliferation
of fibroblast and differentiation to
myofibroblast are essential to produce
ECM, collagen, and α-SMA to restore
damaged barriers. MCs by releasing
mediators facilitate angiogenesis for the
purpose of nourishing infiltrated and
recently proliferated cells in the wound site
37. T cells.
Chemokines are crucial mediators for lymphocyte
chemotaxis and function (Baggiolini 1998; Luster et al., 1998;
Rossi and Zlotnik, 2000).
Lymphocyte accumulation is associated with the initial
appearance of MCP-1 4 days after injury by the chemokines
IFNg- inducible protein-10 and monokine induced by IFN-g.
38. Macrophages appear to be a major source for these
cytokines.
IFN-g is a major inducer of inducible protein-10
and monokine induced by IFN-g, which could reflect a
major shift in cytokine expression profile from
proinflammatory mediators to IFN-g.
39. IFN-g gene deficiency leads to an accelerated
healing response, most likely mediated by enhanced
TGF-b1
levels at the wound site, consequent augmented TGF-b1-
mediated signaling pathway and accelerated collagen
deposition
(Ishida et al., 2004).
40. The number of neutrophils, macrophages, and T cells were
significantly reduced at the wound site of IFN-g-deficient
mice, most likely due to the lack of endothelial activation.
These data may support a role for T cells in tissue remodeling.
41. It is likely that Th1- and Th2-cell subsets differentially
regulate the wound microenvironment by secreting
distinct cytokine profiles
(Azouz et al., 2004; Park and Barbul 2004).
42. Along these lines Th1 cells are characterized by the release
of IFN-g, IL- 2, and TNF-a, whereas Th2 cells classically
release IL-4, -5, and -10.
The expression pattern of both cytokine profiles has been
associated with diverse processes of tissue remodeling.
45. Such mechanisms might include: downregulation of
chemokine expression by anti-inflammatory
cytokines
such as IL-10 (Sato et al., 1999) or TGF-b1 (Ashcroft et al.,
1999a, 1999b; Werner et al., 2000),
or upregulation of anti-inflammatory molecules like IL-1
receptor antagonist or soluble TNF receptor; resolution of the
inflammatory response mediated by the cell surface
46. Interestingly, recent in vitro data suggested that matrix
metalloproteinases (MMPs) can downregulate
inflammation via cleavage of chemokines, which then act
as antagonists
(McQuibban et al., 2000, 2002)
49. Scar formation is the physiological and inevitable end
point of mammalian wound repair and there is substantial
evidence that inflammation is an essential prerequisite for
scarring.
50. There is considerable quantitative and qualitative variation in
scarring potential between species and even among various body
sites and organs.
In the human pathological conditions and genetic disorders
can lead to excessive scarring such as in hypertrophic scars or
keloids, which might become severe health problems.
51. Thus, a better understanding in cellular and molecular
mechanisms in inflammatory processes controlling
scarring will serve as a significant milestone in
the studies of tissue repair.
The implications for therapeutic applications in wound
management and in diseases where scarring is the basic
pathogenic mechanism would be significant.
52. Although there are numerous intrinsic and extrinsic
differences between the fetus and adult that may influence
tissue repair, the hallmark of fetal repair is the lack of
a typical inflammatory response
(Bullard et al., 2003; Reed et al., 2004).
53. example indicating that inflammation plays a major role in the
etiology of scarring is evident from studies investigating the
influence of reproductive hormones on this process.
These studies demonstrated that reduced systemic
estrogen levels in ovariectomized mice results in a
markedly impaired rate of healing associated with
excessive inflammation and scarring
55. Wound healing disorders in the clinic present as hypertrophic
scars or as nonhealing chronic wounds (ulcers), the latter
presenting the most prevalent wound healing problems in
man.
56. Most chronic wounds are associated with a small number of
well defined, clinical entities, in particular venous insufficiency,
diabetes mellitus, pressure necrosis, and vasculitis
(Singer and Clark, 1999; Eming et al., 2002, 2006; Scharffetter-
Kochanek et al., 2003).
57. Indeed, there is compelling evidence that the
unrestrained protease activity is one of the major
underlying pathomechanisms of non-healing wounds
(Palolathi et al., 1993; Harris et al., 1995; Saarialho-Kere,
1998; Barrick et al., 1999)
58. In addition to cells in the wound site, such as activated
keratinocytes at the wound edge, fibroblasts, and
endothelial cells, all of which increase their expression of
different protease classes, invading neutrophils and
macrophages are considered to be the major
source of numerous proteases.
59. The expression and the activity of various MMP classes,
including collagenases (MMP-1, MMP-8), gelatinases
(MMP-2, MMP-9), stromelysins (MMP-3, MMP-10, and
MMP-11), as well as the membrane type MMP (MT1-
MMP) have been shown to be highly upregulated in
chronic venous stasisulcers
(Saarialho-Kere, 1998; Norgauer et al., 2002).
60. The chronic wound is a highly prooxidant microenvironment
( Kochanek, 2005).
Leukocytes, especially neutrophils are a rich source
of various ROS (superoxide anion, hydroxyl radicals, singlet
oxygen, hydrogen peroxide), which are released into the
wound environment
(Weiss, 1989).
61. Endothelial cells and fibroblasts, in particular senescent
fibroblasts, which are prominent in chronic wounds, are
also potential sources for ROS
(Campisi, 1996; Mendez et al., 1998).
64. It has long been known that chronic wounds are at risk
for neoplastic progression (Baldursson et al., 1993,
1995, 1999).
The risk of squamous cell carcinoma (SCC) is
markedly increased, suggesting that keratinocytes
are especially vulnerable to malignant transformation.
Very little is known about the molecular inducers of
tumorgenesis in chronic wounds.
65. The tumor cell microenvironment, in particular the tumor
stroma, appears to play an important role in the control
of neoplastic progression through dynamic reciprocity
between tumor cells and their surrounding tissue
(Bissell andRadisky, 2001; Mueller and Fusenig,2004).
66. The inflammatory response within the tumor stroma,
which is closely linked to fibroplasia and angiogenesis,
has been considered to play a critical role in
carcinogenesis
(Balkwill and Mantovani, 2001)
67. Two proposed mechanisms relate the increased
inflammatory response within the stroma to cancerogenesis:
first, the highly vascularized and growth factor rich
tumor stroma provides an environment rich in nutrients
that supports tumor growth;
second, the tumor stroma might directly stimulate malignant
transformation.
68. For example, so-called carcinoma-associated fibroblasts
mediate oncogenic signals (directly or indirectly) that
stimulate the progression of a non-tumorigenic cell
population to a tumorigenic one
(Phillips et al., 2001; Tlsty, 2001).
69. Expression of structural molecules, generating the
adhesion complex are regulated by dermal mediators
and it is possible that the tumor–- stroma interactions
mediated by collagen VII might be relevant for tumor
development in chronic wounds.