Paludisme grave : pourquoi doit-on développer des modèles in vitro sur le terrain ? - Conférence de la 8e édition du Cours international « Atelier Paludisme » - RAZAKANDRAINIBE Romy - Madagascar - romy@pasteur.mg
Stem Cells in A New Era of Cell based Therapies - Creative BiolabsCreative-Biolabs
A stem cell can replicate itself or differentiate into cells that carry out the specific functions of the body. The application of stem cells in regenerative medicine and disease therapeutics is one of the most exciting advances in medical science today. In cell-based therapies, stem cells may play two roles. The first role is as drug-delivery vehicles. The second role is as therapeutic agents themselves. Stem cells also offer opportunities for scientific advances that go far beyond cell-based therapies. Creative Biolabs is dedicated to facilitate the research of stem cells in both basic science and therapeutics development. Please contact us if you are interested in our services or products.
Gene Olinger, USAMRIID, Fort Detrick USA, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Protective Immune Reponses to Ebola Virus
Sanja Selak of Intercell AG, Vienna, Austria, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Intercell develops vaccines for the prevention and treatment of infectious diseases
ProImmune Antigen Characterization Summit Paul Mossamandacturner
Paul Moss, School of Cancer Sciences, Birmingham UK, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Cytomegalovirus and Cancer-specific Immunity
K562 cells were established the first human immortalized myelogenous leukemia line. This cell line is derived from a 53-year-old female chronic myelogenous leukemia patient in blast crisis. They can be used as a highly sensitive target for the in vitro natural killer assay. Recently, studies have shown the K562 blasts are multipotential, hematopoietic malignant cells that spontaneously differentiate into recognizable progenitors of the granulocyte, erythrocyte and monocytic series.
This slide is about the basics of mRNA-based therapy. The content includes: definition of mRNA, timeline of mRNA therapeutics, action mechanism and development strategies of mRNA drugs, therapeutic mRNA applications, and the related services provided by Creative Biolabs.
Stem Cells in A New Era of Cell based Therapies - Creative BiolabsCreative-Biolabs
A stem cell can replicate itself or differentiate into cells that carry out the specific functions of the body. The application of stem cells in regenerative medicine and disease therapeutics is one of the most exciting advances in medical science today. In cell-based therapies, stem cells may play two roles. The first role is as drug-delivery vehicles. The second role is as therapeutic agents themselves. Stem cells also offer opportunities for scientific advances that go far beyond cell-based therapies. Creative Biolabs is dedicated to facilitate the research of stem cells in both basic science and therapeutics development. Please contact us if you are interested in our services or products.
Gene Olinger, USAMRIID, Fort Detrick USA, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Protective Immune Reponses to Ebola Virus
Sanja Selak of Intercell AG, Vienna, Austria, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Intercell develops vaccines for the prevention and treatment of infectious diseases
ProImmune Antigen Characterization Summit Paul Mossamandacturner
Paul Moss, School of Cancer Sciences, Birmingham UK, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Cytomegalovirus and Cancer-specific Immunity
K562 cells were established the first human immortalized myelogenous leukemia line. This cell line is derived from a 53-year-old female chronic myelogenous leukemia patient in blast crisis. They can be used as a highly sensitive target for the in vitro natural killer assay. Recently, studies have shown the K562 blasts are multipotential, hematopoietic malignant cells that spontaneously differentiate into recognizable progenitors of the granulocyte, erythrocyte and monocytic series.
This slide is about the basics of mRNA-based therapy. The content includes: definition of mRNA, timeline of mRNA therapeutics, action mechanism and development strategies of mRNA drugs, therapeutic mRNA applications, and the related services provided by Creative Biolabs.
Monoclonal antibodies are been developed an produced from some identical parental immune cells. they can be developed to target and identify specific cells and antigens and to work as antibodies in tandem with the human immune system against them. Hybridoma technology was developed by Georges J.F. Kohler and Cesar Milstein. they made a hybrid cell that will make number of monoclonal antibodies against them.
Monoclonal antibodies (mAb or moAb) are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity, in that they bind to the same epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different plasma cell (antibody secreting immune cell) lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one single monoclonal antibody to two epitopes. Given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology, and medicine. When used as medications, non-proprietary drug names end in -mab and many immunotherapy specialists use the word mab anacronymically.
ProImmune Antigen Characterization Summit Johanna Olweusamandacturner
Johanna Olweus, Dept Immunology, Institute for Cancer Research, Radiumshospitalet, Oslo, Norway, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Cancer immunotherapy: finding allies among the "allos"
Fas signaling pathway is known to be engaged in elimination of unwanted cells by apoptosis, however, new discoveries presented its alternate face, namely FasR and FasL play pro-cancerous functions facilitating cancer progression, invasion and metastasis. Here, we provide a brief summary of knowledge concerning Fas signaling pathway merits and disadvantages in cancer. Fas molecules were found to be engaged in many pathways induced by different therapeutic compounds, such as aspirin and antibiotics. This suggest that Fas signaling pathway may be employed as adjuvant factor for immunotherapy of variable design. Although, the literature presents some first optimistic results, we must intensify efforts to finally introduce Fasassociated procedures into standard therapeutic options. The Fas signaling is known to exert very variable effects in wide spectrum of cells. The FasR/ FasL (CD95/ CD95L) proteins can be associated with both positive (physiological) and negative (pathological) effects. Nowadays, there is a growing interest in the elucidation of the Fas signaling role in the pathogenesis and progression of various cancers. Additionally, it was proven that the expression of FasR/ FasL in colorectal cancer is associated with worse prognosis, metastasis and recurrence [1-6] the aspects of cancer biology which cancer stem cells are responsible for [7].
Paludisme et infection à VIH - Présentation de la 3e édition du Cours international « Atelier Paludisme » - MADJI Nestor - Ministère de la Santé Publique et de la Population - République Centre Africaine - Chef de Section Laboratoire, Responsable de la Recherche Opérationnelle au PNLP - namssenmo@yahoo.fr
Génétique des populations de Plasmodium falciparum en Afrique - Conférence du 4e édition du Cours international « Atelier Paludisme » - Hervé BOGREAU - IMTSSA-URBEP - Parc du Pharo, Marseille, France - hervebogreau@yahoo.fr
Monoclonal antibodies are been developed an produced from some identical parental immune cells. they can be developed to target and identify specific cells and antigens and to work as antibodies in tandem with the human immune system against them. Hybridoma technology was developed by Georges J.F. Kohler and Cesar Milstein. they made a hybrid cell that will make number of monoclonal antibodies against them.
Monoclonal antibodies (mAb or moAb) are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity, in that they bind to the same epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different plasma cell (antibody secreting immune cell) lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one single monoclonal antibody to two epitopes. Given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology, and medicine. When used as medications, non-proprietary drug names end in -mab and many immunotherapy specialists use the word mab anacronymically.
ProImmune Antigen Characterization Summit Johanna Olweusamandacturner
Johanna Olweus, Dept Immunology, Institute for Cancer Research, Radiumshospitalet, Oslo, Norway, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Cancer immunotherapy: finding allies among the "allos"
Fas signaling pathway is known to be engaged in elimination of unwanted cells by apoptosis, however, new discoveries presented its alternate face, namely FasR and FasL play pro-cancerous functions facilitating cancer progression, invasion and metastasis. Here, we provide a brief summary of knowledge concerning Fas signaling pathway merits and disadvantages in cancer. Fas molecules were found to be engaged in many pathways induced by different therapeutic compounds, such as aspirin and antibiotics. This suggest that Fas signaling pathway may be employed as adjuvant factor for immunotherapy of variable design. Although, the literature presents some first optimistic results, we must intensify efforts to finally introduce Fasassociated procedures into standard therapeutic options. The Fas signaling is known to exert very variable effects in wide spectrum of cells. The FasR/ FasL (CD95/ CD95L) proteins can be associated with both positive (physiological) and negative (pathological) effects. Nowadays, there is a growing interest in the elucidation of the Fas signaling role in the pathogenesis and progression of various cancers. Additionally, it was proven that the expression of FasR/ FasL in colorectal cancer is associated with worse prognosis, metastasis and recurrence [1-6] the aspects of cancer biology which cancer stem cells are responsible for [7].
Paludisme et infection à VIH - Présentation de la 3e édition du Cours international « Atelier Paludisme » - MADJI Nestor - Ministère de la Santé Publique et de la Population - République Centre Africaine - Chef de Section Laboratoire, Responsable de la Recherche Opérationnelle au PNLP - namssenmo@yahoo.fr
Génétique des populations de Plasmodium falciparum en Afrique - Conférence du 4e édition du Cours international « Atelier Paludisme » - Hervé BOGREAU - IMTSSA-URBEP - Parc du Pharo, Marseille, France - hervebogreau@yahoo.fr
Plasmodium vivax, un parasite pas si banal - Séances Pratiques de la 5e édition du Cours international « Atelier Paludisme » - Stéphane PICOT - Hôpital E. Herriot, Lyon, France - picot@rockefeller.univ-lyon1.fr
Co-infections plasmodiales - Présentation de la 8e édition du Cours international « Atelier Paludisme » - RAZAFINDRAKOTO Hajasoa Nirina - Madagascar - hajasoanirinar@gmail.com
De l'ADN à la protéine - Présentation de la 3e édition du Cours international « Atelier Paludisme » - TRAORE Zoumana Isaac - MEDRU/MRTC/DEAP/FMPOS - BP : 1805, Point-G Bamako MALI - Biologiste (Assistant de Recherche) - zouisaac@usa.com
Diagnostic parasitologique des accès palustres: acquis et défis - Conférence de la 8e édition du Cours international « Atelier Paludisme » - D'ACREMONT Valérie - Suisse - valerie.dacremont@unibas.ch
Recombinant Fab fragments specific for the pfHRPII and pfHSP72 : implications for malaria diagnosis - Parole de junior de la 7e édition du Cours international « Atelier Paludisme » - Ravaoarisoa Elisabeth - Madagascar - elisa@pasteur.mg
Les anophèles transgéniques : Moyen de lutte ou miroir aux alouettes - Présentation de la 3e édition du Cours international « Atelier Paludisme » - SOANOMENA VALIKARA Jeannette MINISTERE DE LA SANTE ET DU PLANNING FAMILIAL DE MADAGASCAR CENTRE HOSPITALIER DE REFERENCE REGIONAL TOLIARA - Medecin, chef de service CRENI
Comment procéder pour traquer les marqueurs génétiques de résistance aux artemisinines et autres nouvelles molécules antipaludiques ? - Conférence de la 5e édition du Cours international « Atelier Paludisme » - Carol HOPKINS SIBLEY - University of Washington Seattle, USA - sibley@u.washington.edu
Conferencia de la Dra. Ana María Roa, Bióloga Molecular, sobre Epigenética, impartida en la Universidad Popular Carmen de Michelena de Tres Cantos el 1 de marzo de 2013.
Más información en:
http://www.universidadpopularc3c.es/index.php/actividades/conferencias/event/448-conferencia-una-revision-de-los-conocimientos-fundamentales-de-la-biologia-de-la-celula-la-epigenetica
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
Guide pour le suivi et l'évaluation des programmes - Séances Pratiques de la 5e édition du Cours international « Atelier Paludisme » - Luciano TUSEO - World Health Organization / Roll Back Malaria - Office for Madagascar and Reunion - Antananarivo, Madagascar - maloms@iris.mg
Monitoring and Evaluation Toolkit - Séances Pratiques de la 5e édition du Cours international « Atelier Paludisme » - Luciano TUSEO - World Health Organization / Roll Back Malaria - Office for Madagascar and Reunion - Antananarivo, Madagascar - maloms@iris.mg
Développement nouveaux médicaments - Séances Pratiques de la 5e édition du Cours international « Atelier Paludisme » - Pascal MILLET - Université Victor Segalen Bordeaux2, France - pascal.millet@u-bordeaux2.fr
Diagnostic biologique du paludisme - Séances Pratiques de la 5e édition du Cours international « Atelier Paludisme » - Didier MENARD et Vincent THONIER
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
2. Malaria’s facts
-About 3.3 billion people are at risk of malaria
-Every year: about 250 million malaria cases
2 and nearly one million deaths
3. Why studying malaria ?
1. Epidemiological transition of malaria
• Urbanization =>↓ rate of transmission
• Increased drug consumption
2. Antiparastic treatment: insufficient to control CM
Target : reduce mortality rates
=> Propose new strategies that can both eliminate
parasites and protect from the pathogenic
mechanisms induced by the parasite
4. Malaria complication: severe malaria
Severe malaria: characterized by cerebral malaria,
metabolic acidosis, renal failure, pulmonary oedema,
anemia, hypoglycemia, shock, and jaundice
Cerebral malaria (CM): the pathogenesis is
heterogenous and the neurological complications
are often part of a multisystem dysfunction.
=>CM characteristics : sequestration and Cerebral oedema
and/or micro-hemorrhages are features of endothelial
alteration in CM
6. Defined CM
Taylor et al, Nat Med. 10: 143‐145, 2004
In patients, CM-associated brain damage can be studied on only
post-mortem specimens and is the end-point of a fatal syndrome.
However, it is not known whether these alterations also are present
at the first stages of the disease.
7. Issues
• Post-mortem analyses = Study of severe malaria pathology at the
terminal stage
• Informative changes early in the disease process are inaccessible !!
• The mouse models for CM do not recapitulate human disease completely
• Understanding the pathogenesis of CM is important = can be achieved
through a combined approach involving ex vivo studies using patient
samples (blood cells, plasma), in vitro modelling of the interactions
between the various cells and their released mediators
7
9. Pathogenic mechanisms hypothesis
• Mechanical theory: sequestration ?
• Immunopathology theory: BBB alteration, effects of the
immune system and mediators ?
• Combination of both ?
• The fine mechanisms of this complex syndrome remain
incompletely understood.
9
11. Endothelial cells and P. falciparum infection
Jambou et al. Plos pathogen (2010)
al.
11 Immunology unit (IPM)
12. Gap of knowledge
• The fate and effects of Infected Red Blood Cells
uptake in endothelial cell are unknown
• Studies use up today P. falciparum lab strain
=> How about wild strain (large diversity)?
12
13. Objectives
To set up an in vitro model of BBB to study the effects
immune cells and the fate of red blood cells infected
with field isolates
of P. falciparum internalized in endothelial cells
13
14. Endothelial cells as APC
• Endothelial cells express MHC II in tissue culture (Leeuwenberg et al. 1988)
1988)
• Endothelial cells are able for cross Presentation (Rock el al . 2005)
• Antigen presentation by a continuous human microvascular
endothelial cell line (HMEC-1), to human T cells. (Bosse D, et al. 1993)
• Endothelial cells have capacity to costimulate T cells in vitro (Briscoe
DM et al . 1997)
• Presence of Immunoproteasome (Mishto et al.2006)
Endothelial cell act as an antigen presenting cell (APC)
14
15. Specific objectives
FIELD
Patient Healthy Immune villagers
Parasited red blood cell Immune cells
?
Antigen presentation
internalization
APOPTOSIS
JUNCTION OPENING
Analyze, on the field, the interaction of P. falciparum-sensitized endothelium
and immune cells and its role in the pathology
Analyzing BBB alteration induced by immune cells from healthy premunized donors
16. Methodology
In vitro model: Human Brain Endothelial Cells (HBEC-D3)+astrocytes
Co-cultivation with P. falciparum late stage (field isolate)
(positive magnetic selection: Miltenyi column and magnet)
Analysis of endothelium permeability Analysis of adhesion molecule expression
(Lucifer yellow diffusion) (qPCR)
assessment of Cytokine
CM model +Immune cells from health patients
production
Analysis of calcium flux
Quantification of adhesion Detection of apoptosis
(Fluo4-AM) (Tunnel assay, caspase 3,7,9 )
assay,
PKH labelling and fluorimetry
Fluorometry Flow cytometry
Immunology Unit
18. • Quantification of gene (required for antigen presentation)
expression changes by RT-qPCR
Tm CT values
HPRT 82,4 HPRT 21,71 CD80
CD83 86,6 CD83 27,83
CD86 83,2 CD86 26,01
CD80 82,9 CD80 32,93
CD83
CD86
HPRT
Run profile set up
19. Conclusion and perspectives
In vitro modelling in field: strengthening SOUTH
research capacity, hypothesis generation
Development of new therapeutic strategy to protect
BBB
the identification of antigens presented by the
endothelial cells to the immune system=> new
vaccine candidate
20. THANK YOU FOR YOUR ATTENTION
•Parteners
•University of Sydney (vascular immunology Unit : G. GRAU, V. COMBES, J. WHEWAY)
•Epidemiology unit – Institut Pasteur Madagascar
•Malaria Unit - Institut Pasteur Madagascar
•Dr COURAULT P.O ( HBEC-D3) Cochin Institut Paris