This presentation teaches you what you need to know to solve the puzzle of gluten sensitivity. It draws clear differences between Type 1 and Type 2 gluten sensitivity, and shows how a gluten-free trial can play a useful role in diagnosis in cases where the scientific evidence is unclear.
This presentation teaches you what you need to know to solve the puzzle of gluten sensitivity. It draws clear differences between Type 1 and Type 2 gluten sensitivity, and shows how a gluten-free trial can play a useful role in diagnosis in cases where the scientific evidence is unclear.
Glycemic Index vs. Glycemic Load: What's the Difference? - Johanna Burani, MS...Nutrition Works, LLC
What is the difference between glycemic index and glycemic load? What does each tell about a carbohydrate? Johanna Burani, MS, RD, CDE explains these differences and the calculations involved.
[Also available with narration at http://www.EatGoodCarbs.com]
• Coeliac disease is a genetically-determined chronic inflammatory intestinal disease induced by an environmental precipitant, gluten.
• Patients with the disease might have mainly non-gastrointestinal symptoms, and as a result patients present to various medical practitioners.
• Epidemiological studies have shown that coeliac disease is very common and affects about one in 250 people.
• The disease is associated with an increased rate of osteoporosis, autoimmune diseases, and malignant disease, especially lymphomas.
• The mechanism of the intestinal immune-mediated response is not completely clear, but involves an HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in the lamina propria as well as an immune reaction in the intestinal epithelium.
Nutritional assessment in chronic liver diseaseShaimaa Elkholy
Protein Energy Malnutrition (PEM) is highly prevalent among patients with chronic liver disease. One of the problems is how to assess these patients nutritionally. yet no standard golden rule for their nutritional assessment.
Early Enteral Nutrition in Critically Ill Patients is the best for helping early recovery, decreasing hospital stay and decreasing malnutrition in ICU
How? When? Formulas used? Access forms?
The presentation may give you an idea abouth the disease, its pathophysiology, signs, symptoms, diagnosis, treatment....Thanks toall the websites which helped me to make this presentation.
Ellen Kamhi, PhD RN, The Natural Nurse, Leaky Gut is also called Compromised Intestinal Permeability, due to loss of integrity of the tight junctions between cells in the intestinal mucosa, and is well documented in the scientific literature. See my document Role of Intestinal Permeability in the Inflammatory Process. This condition should be addressed by all health care providers.
Glycemic Index vs. Glycemic Load: What's the Difference? - Johanna Burani, MS...Nutrition Works, LLC
What is the difference between glycemic index and glycemic load? What does each tell about a carbohydrate? Johanna Burani, MS, RD, CDE explains these differences and the calculations involved.
[Also available with narration at http://www.EatGoodCarbs.com]
• Coeliac disease is a genetically-determined chronic inflammatory intestinal disease induced by an environmental precipitant, gluten.
• Patients with the disease might have mainly non-gastrointestinal symptoms, and as a result patients present to various medical practitioners.
• Epidemiological studies have shown that coeliac disease is very common and affects about one in 250 people.
• The disease is associated with an increased rate of osteoporosis, autoimmune diseases, and malignant disease, especially lymphomas.
• The mechanism of the intestinal immune-mediated response is not completely clear, but involves an HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in the lamina propria as well as an immune reaction in the intestinal epithelium.
Nutritional assessment in chronic liver diseaseShaimaa Elkholy
Protein Energy Malnutrition (PEM) is highly prevalent among patients with chronic liver disease. One of the problems is how to assess these patients nutritionally. yet no standard golden rule for their nutritional assessment.
Early Enteral Nutrition in Critically Ill Patients is the best for helping early recovery, decreasing hospital stay and decreasing malnutrition in ICU
How? When? Formulas used? Access forms?
The presentation may give you an idea abouth the disease, its pathophysiology, signs, symptoms, diagnosis, treatment....Thanks toall the websites which helped me to make this presentation.
Ellen Kamhi, PhD RN, The Natural Nurse, Leaky Gut is also called Compromised Intestinal Permeability, due to loss of integrity of the tight junctions between cells in the intestinal mucosa, and is well documented in the scientific literature. See my document Role of Intestinal Permeability in the Inflammatory Process. This condition should be addressed by all health care providers.
What is Gluten Free, and What Does it Have to Do With Me?Magnetic Ideas, LLC
The gluten-free diet is becoming more and more prevalent. Many people are affected by celiac disease and gluten intolerance. Many more have friends and family that are affected. Awareness of these issues are at a all-time high, but most people don't understand the basics, and have many questions about the gluten free diet. Why would someone eat gluten free? Should I eat gluten-free? What is celiac disease, and how do I know if I have it? These are the types of questions that I cover in this presentation.
This is a presentation that will enhance the reader's understanding of celiac disease as well as food allergy and intolerance.
It contains several nuggets that can explain why some people are sensitive to ALL grains, not just wheat, rye, oats and barley.
Your feedback is welcome and appreciated!
-JP Lapeyre
A description of the history, variation in methods/ approaches for biofortifying rice, benefits and challenges faced with biofortified rice and consequences for future generations..
The worldwide explosion of obesity has resulted in an ever-increasing prevalence of type 2 diabetes. The importance of insulin resistance and β-cell dysfunction to the pathogenesis of type 2 diabetes was debated for a long time; many thought that insulin resistance was the main abnormality in type 2 diabetes, and that inability to secrete insulin was a late manifestation. This notion is now challenged. This presentation deals with the important contributing factors in the development of type 2 diabetes mellitus.
Shashikiran Umakanth made this presentation at the "First Endocrine Update Program” – ENDO EGYPT 2015, from 17-20 December 2015 in the Historic City of Luxor, Egypt. This endocrine update was organised by the Egyptian Association of Endocrinology , Diabetes and Atherosclerosis (EAEDA) in collaboration with the Endocrine Society, USA.
Increase your Understanding of the Pathogenesis of Gluten Spectrum DisordersCell Science Systems
Recently, researchers at Harvard University, Alessio Fasano et. al., and the National Institutes of Health (laboratories of immunology and cellular and molecular biology), reported real-time microscopic observations of gluten-induced neutrophil activation.
According to authors, " To what extent neutrophil function adds to, or protects against, gluten intolerance is currently under vigorous investigation."
This presentation will shed light on this question. It will also review the Fasano study and examine the role of neutrophil function in multiple disease conditions, as well as explore how neutrophil function may also play a dual role in protecting the body from the untoward effects of dietary and environmental agents.
Describing the importance of genetics and its research as application to emphasis how it can solve important problems related to human health. The presentation included summary of three publications.
Cloning and expression of Human glutamic acid decarboxylase (GAD 65) gene in ...Open Access Research Paper
Diabetes is a chronic autoimmune disease characterized by the inability of body to produce or respond to insulin a hormone required by body to burn glucose for energy. Type I Diabetes mellitus, also known as Insulin Dependent Diabetes mellitus is a most frequent chronic disease of childhood, afflicts 0.2-0.3% of human individuals due to auto immune destruction of insulin secreting pancreatic β cells. GAD65 is the major auto antigen in Insulin Dependent Diabetes Mellitus (IIDM). Thus, this project is aimed at expression of GAD65 in E. coli. GAD65 gene was cloned into pET-28a bacterial expression vector and expression was studied in BL21 DE3 cells. Different parameters of induction like isopropyl-β-D-thiogalactopyranoside (IPTG), temperature, time interval were standardized. The recombinant clones induced with 2 μM of IPTG at 30oC for 4 h at flask level produced the protein upto 537μg/ml. Furthermore, the specificity of the purified recombinant protein was confirmed by western blot analysis using monoclonal antibodies. This work establishes a strategy in E. coli for the expression of GAD65 with optimized parameters.
Presented by Dr. Brecher at the 40th Annual Symposium "Diagnostic and Clinical Challenges of 20th Century Microbes", held on Nov 18, 2010 in Philadelphia.
The Role of Food Sensitivity and Food Intolerance TestsAlcat Test
Every person has different food intolerance symptoms for different kind of food. That is because the body reacts biological different to different substances present in their regular food. This can be determined by food intolerance testing. Once you know what troubles you, then its prevention becomes easier. Intolerance testing is simple and an easy process to conduct.
Research and clinical studies of the protein zonulin and the zonulin signaling pathway demonstrate the
clinical efficacy of zonulin as a biomarker of intestinal permeability. Studies also confirm that zonulin
signaling is an essential mechanism in promoting healthy immune function and tolerance at the
gastrointestinal mucosal barrier.
Similar to Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to Autoimmunity (20)
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the 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 lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
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. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
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
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.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
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
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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!
Light House Retreats: Plant Medicine Retreat Europe
Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to Autoimmunity
1. Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to Autoimmunity: Alessio Fasano, M.D. Mucosal Biology Research Center University of Maryland School of Medicine
12. The Paracellular Pathway … Tight junctions are a ‘dark horse’ implicated in a host of disease states, ranging from acute injury to chronic inflammation and autoimmune diseases
13. DISCOVERY OF ZONULIN Coomassie Western blot 1 2 3 4 1: Tissue lysate 2: Sephacryl-S300 3: Q-sepharose 4: Immuoaffinity 1 2 3 4 PURIFICATION PROTOCOL FROM HUMAN INTESTINE
22. In Situ IFM of Biopsies from Either Celiac Disease Patients or Healthy Controls Showed Apical Expression of CXCR3 Celiac disease Non-celiac control CXCR3 Actin Nucleus
23. Proposed Zonulin Mechanism of Action Fasano et al, J Clin Invest 1995;96:710-20; el Asmar et al Gastroenterology 2002;123:1607-15 Following Pathway Activation Resting State Freeze-Fracture Zonulin signaling
24. Celiac Disease Pathogenesis: The Continuous Stimulation by Gluten is Necessary to Perpetuate the Autoimmune Process Intestinal Lumen A. Fasano and T. Shea Donohue, Nature Clin Pract Gastroenterol Hepatol 2005;2:416-22 PRR AGA EMA TTG MyD88 dependent Submucosa Bacteria
25. 1) bacterial adhesion, 2) internal signaling, 3) signal transmission to the effector cells, 4) zonulin release on the luminal side 5) zonulin binds to its receptor, 6) cascade of events ending 7) by the TJ opening, leading to 8) water and solutes paracellular passage and 9- “wash out” effect, 10) and paracellular passage of food antigens and macromolecules, 11) GALT stimulation and subsequent undesired effects H 2 O 5 6 8 7 11 10 9 H 2 O Lymphocytes Food Antigens Macromolecules Zonulin Bacteria Zonulin 1 4 2 Zonulin Enterocytes 3 3 El Asmar et al J Gastroenterology 2002;123:1607-1615 Zonulin System – Innate Immunity
39. Blocking the Zonulin-Dependent Increased Intestinal Permeability Aborts The Autoimmune Process Age: 52-54 days Treatment Animal flow Placebo Timeframe T 0 1 2 3 4 5 6 7 14 wks Pre-T 0 AT1001 Placebo 60% T1D (N = 10) (N = 20) (N = 30) AT1001 35% T1D T1D Sapone et al. ADA Meeting 2005: late breakthrough abstract Outcome 0 50 100 150 200 250 300 30 37 44 51 58 65 72 Age (days) Serum glucose (mg/dl) 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 LA/MA Ratio ICA + (100%)
40. Diabetes Treatment Study: Treatment of Autoimmune Diabetes with AT-1001 Sapone et al. ADA Meeting 2005: late breakthrough abstract Untreated T1D Treated NO T1D 10X 40X
41. Insulin staining Glucagon staining A B C D Untreated BBDP rats that developed T1D Blocking the Zonulin-Dependent Increased Intestinal Permeability Aborts The Autoimmune Process AT1001-treated BBDP rats that DID NOT develop T1D: No insulitis Islet Immunohistochemistry
42. Insulin staining Glucagon staining A B C D 40X Blocking the Zonulin-Dependent Increased Intestinal Permeability Aborts The Autoimmune Process Islet Immunohistochemistry AT1001-treated BBDP rats that DID NOT develop T1D: Islets recovering from insulitis and islet regeneration 10X
43. Role of Gliadin in Type 1 Diabetes Pathogenesis Zonulin Intestinal Permeability Incidence of T1D BBDP rats on regular diet BBDP rats on GFD BBDP rats on regular diet BBDP rats on GFD BBDR rats on regular diet BBDP rats on regular diet BBDP rats on GFD
45. Sapone et al. Diabetes 2006 Role of Zonulin in T1D in Humans T1D Relatives T1D Controls 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Serum zonulin (ng/mg protein) n= 339 89 97
46. Serum Zonulin Levels and Intestinal Permeability in T1D, Their Relatives and Controls Intestinal permeability and serum zonulin levels in T1D patients and their relatives. Both parameters were significantly higher in T1D subjects as compared to their relatives. *p=0.04; **p=0.02 Sapone et al. Diabetes 2006
47. Serum Zonulin and in vivo Permeability in Children with Type 1 Diabetes After Gluten Challenge, vs. Relatives Fig. 1. Serum zonulin levels in T1D patients (n=16) and their relatives (N=35) before and after a gluten-containing meal. *<0.05 compared to baseline. Fig. 2. Serum LA/MAin T1D patients (n=16) and their relatives (N=35) 1 hour before and 1 hour after a gluten-containing meal. *<0.0002; **<0.0005 compared to before meal LA/MA. ** 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 0 1 2 3 4 5 Time (hrs) Serum zonulin (ng/mg protein) T1D relatives Gliadin-containing meal * * * 0.000 0.050 0.100 0.150 0.200 0.250 0.300 1 2 3 4 5 Time (hrs) LA/MA ratio T1D relatives *
48. PROPOSED MODEL Proposed role of aberrant intestinal permeability in Type 1 diabetes pathogenesis. Non-self antigens are present in the intestinal lumen (1) and cross the tj barriers in subjects with dysregulation of the zonulin system (2-3). Antigen peptides bind to HLA receptors present on the surface of APC (4). In turn, these peptides are presented to T lymphocytes (5). In genetically susceptible individuals, an aberrant immune response (both umoral and cell-mediated) (6) leads to the autoimmune process mainly targeting the Langherans islets with subsequent insulin deficiency typical of type 1 diabetes (7). 5 Submucosa T B GAD, IA, IA-2 Tk P 2 3 4 6 1 APC Intestinal lumen 6 7 7