Allergic disorders are on rise with increase in urbanization, improved personal hygiene & more people migrating in search of jobs, better opportunities. Diagnosis of allergy can aid the clinician is appropriate counselling of the patient for avoidance of specific allergens & if required prescribe appropriate immunotherapy.
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.
Food “Allergy” Testing for Adverse Food ReactionsAugustin Bralley
Learn how to differentiate classes of adverse reactions to food, understand the mechanism of sensitivity reactions, and interpret reports of IgG4 food antibodies.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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
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.
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
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
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
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
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.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
2. Food-dependent exercise-induced
anaphylaxis ( FDEIA)
• First reported in 1979 triggered by a combination of shellfish ingestion
and exercise .
• FDEIA is IgE mediated; classical symptoms of type 1 hypersensitivity and
serum-specific IgE (ssIgE) to culprit allergens are detectable .
• Time between meal and exercise is usually between 30 and 120 min , and
the duration of exercise before the onset of symptoms last 10-50 min
• Causative foods shellfish, wheat products, vegetables, fruits,
nuts,egg,mushrooms,corn, garlic,pork, beef,rice,and cows milk
Gabriel K. Wong & Mamidipudi T. Krishna, Curr Allergy Asthma Rep (2013) 13:639–644
3. • Triggered by wheat ingestion only together with cofactors such as
physical activity
Wheat-dependent exercise-induced
anaphylaxis (WDEIA
4. Eishin Morita1, Hiroaki Matsuo, Food-Dependent Exercise-Induced Anaphylaxis―Importance of Omega-5 Gliadin and HMW-Glutenin as Causative Antigens for Wheat-Dependent
Exercise-Induced Anaphylaxis, Allergology International. 2009;58:493-498
Trigger factors in FDEIA
5. Schematic figures of food allergen absorption in
gastrointestinal tract in the patients with FDEIA
A: Ingested foods are digested in the intestine, and no immunoreactive allergens entered into circulation.
B: Exercise and/or aspirin enhance absorption of undigested immunoreactive allergens into circulation
Eishin Morita1, Hiroaki Matsuo, Food-Dependent Exercise-Induced Anaphylaxis―Importance of Omega-5 Gliadin and HMW-Glutenin as Causative Antigens
for Wheat-Dependent Exercise-Induced Anaphylaxis, Allergology International. 2009;58:493-498
6. Overview about WheatOverview about wheat
uca Elli, Federica Branchi, Carolina Tomba, Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity
7. Gregory J. Tanner, journal of the American Society of Brewing Chemists · February 2014
8. Wheat protein
Gliadins and glutenins have extremely imbalanced amino acid compositions with high proportions of glutamine (32–53 mol-%)
and proline (11–29 mol-%) and low contents (< 2 mol-%) of lysine, methionine, and tryptophan
9. Yuko Chinukiand Eishin Morita ,Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap
,Allergology International Vol 61, No4, 2012
10. A. S. Tatham and P. R. Shewryw , Allergens in wheat and related cereals , Clinical and Experimental Allergy,
38, 1712–1726
11. Overview about wheat
Kathrin Schalk, Barbara Lexhaller Isolation and characterization of gluten protein types from wheat, rye, barley and oats, February 24, 2017
12. K. A. Scherf1, K. Brockow,wheat-dependent exercise – induced anaphylaxis , Clinical & Experimental Allergy, 46, 10–20
Wheat
14. Rye g-70 and g-35 secalins and barley g-3 hordein cross-react with v-5 gliadin, a major allergen in wheat-dependent,
exercise-induced anaphylaxis , K. PALOSUO*†, H. ALENIUS†‡, E. VARJONEN*, N. KALKKINEN§ and T. REUNALA*¶
15. • Bakers’ asthma, inhalation of flour and dust during grain processing.
group of inhibitors of a-amylase (also called chloroform methanol
soluble, or CM, proteins) are the major components responsible for
this syndrome.
• Wheat-dependent exercise-induced anaphylaxis (WDEIA), with the
o5-gliadins (part of the gluten protein fraction) major group of
proteins which are responsible.
• Other forms of food allergy have also been reported, with the
proteins responsible including gluten proteins, CM proteins and
non-specific lipid transfer proteins
Wheat allergens
A. S. Tatham and P. R. Shewryw , Allergens in wheat and related cereals , Clinical and Experimental Allergy, 38, 1712–1726
16. Protein epitopes identified as associated with
associated with WDEIA
K. A. Scherf1, K. Brockow,wheat-dependent exercise – induced anaphylaxis , Clinical & Experimental Allergy, 46, 10–20
17. • When IgE binding epitopes were investigated using sera of WDEIA
patients,
• four epitopes consisting seven amino acids, QQIPQQQ, QQFPQQQ,
QQSPEQQ and QQSPQQQ, were found to be dominant epitopes
in omega-5 gliadin,
• and three epitopes QQPGQ, QQPGQGQQ and QQSGQGQ were identified in
HMW glutenin.
• Mutational analysis of the QQIPQQQ and QQFPQQQ peptides indicated
that five common amino acids at position 1 (Q), 4 (P), 5 (Q), 6 (Q) and 7
(Q) were critical for IgE-binding in omega-5 gliadin
CAUSATIVE FOODS AND ALLERGENS RESPONSIBLE FOR
WDEIA
Eishin Morita1, Hiroaki Matsuo, Food-Dependent Exercise-Induced Anaphylaxis―Importance of Omega-5 Gliadin and HMW-Glutenin as Causative
Antigens for Wheat-Dependent Exercise-Induced Anaphylaxis, Allergology International. 2009;58:493-498
18. • Symptoms of WDEIA are usually elicited by physical activity one to
four hours after wheat intake
• The frequency of WDEIA events varies
from patient to patient and ranges from a singular episode to multiple
episodes .
• The clinical manifestations and severity of allergic reactions from
urticaria to anaphylaxis also vary
Clinical features
K. A. Scherf1, K. Brockow,wheat-dependent exercise – induced anaphylaxis , Clinical & Experimental Allergy, 46, 10–20
19. K. A. Scherf1, K. Brockow,wheat-dependent exercise – induced anaphylaxis , Clinical & Experimental Allergy, 46, 10–20
IgE antibody levels
20. • In conclusion, omega5-gliadin(Tri a 19 ) and HMW-GS appear to be
the major allergens in WDEIA. However, other types of gluten
proteins such as a/b- and c-gliadins and LMWGS also can sensitize
WDEIA patients.
• Case report 9-kDa wheat lipid transfer protein (LTP) (Tri a 14 ) can
causative allergen .
Causative proteins in WDEIA
Ann Allergy Asthma 112(2014) 383-394
21. • Exercise : up-regulates intestinal resulting in increased amounts of
food antigens in the circulating blood.
: enhances the degranulation of mast cells in combination
with IgE cross-linking through an unknown mechanism.
• Aspirin : damage to the tight junctions in the gastrointestinal mucosa.
: degranulation of mast cells and accelerate histamine release
via increased Syk kinase activation
: PGE 1 may suppress allergen absorption
Cofactors
24. • Route of allergen sensitization : gastrointestinal tract , skin
• TG2 may become activated during exercise, which
results in conjugates between wheat peptides and TG2
followed by IgE binding
• Exercise mobilizes and activates immune cells from
gut-associated depots stimulating pro-inflammatory
responses that are normally countered by anti-inflammatory responses
• Noradrenaline may be involved in the onset of WDEIA, because it
selectively inhibits T helper 1 (Th1) functions while favouring Th2 and
humoral responses, or acts directly on both cellular and humoral immunity
Pathomechanism
29. • Elevated levels of IgE antibodies to CGE and purified Omega-5 Gliadin .
• IgA levels,especially to omega-5 gliadin ,were significantly elevated in
the patients .
• IgA is the most predominant immunoglobulin at mucosal surfaces,
where it is involved in protection against microorganism.
• Level of IL-10 mRNA significant lower in patients
• IL-10 can inhibit several activation and effector function of T cells,
monocytes and macrophages .
Humoral and Cellular responses
31. Yuko Chinukiand Eishin Morita ,Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap
,Allergology International Vol 61, No4, 2012
Hydrolyzed wheat Protein in Soap
32. Yuko Chinukiand Eishin Morita ,Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap
,Allergology International Vol 61, No4, 2012
33. Yuko Chinukiand Eishin Morita ,Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap
,Allergology International Vol 61, No4, 2012
34. • All allergy history Data , all factors relating
• Diagnostic tools :
- in vivo tests such as SPT and provocation tests
- in vitro tests including basophil activation test (BAT) ,histamine
release test (HRT) and wheat-specific IgE testing
Diagnosis
SPT using gluten had a sensitivity of 100% and a specificity of 96%
Specific igE antibodies to omega-5 gliadin sensitivity (78%-82%)and
specificity 100% for patients with WDEIA.
Knut Brockow, MD,a Daniel Kneissl,a Luzia Valentini, PhD , J ALLERGY CLIN IMMUNOLAPRIL 2015
35. antihistamines and leukotriene antagonists was stopped
3 days .
Aspirin (10 mg/kg, maximum500 mg) and the suspected
food(s) were administered 90 and 60 min before
exercise.
200–400 g Udon noodle (5.2–10.4 g wheat protein),
40–100 g shrimp, or one whole apple.
The exercise was started at 2.1 W/kg, and increased up
to 3 or 4 W/kg, and was conducted for 6 min or more
according to the patients’ athletic abilities, as
the level of exertion can influence the test results .
The target heart rate was >160 beats/min.
36. Challenge tests for WDEIA
• Wheat products included noodles, bread or pasta containing 60-135 g
of wheat flour.
• Thirty minutes after wheat ingestion, exercise was performed using a
treadmill for 15-20 min.
• Aspirin (500 mg) was administrated 30 min prior to wheat ingestion.
• A positive test was determined if allergic symptoms such as wheals
and or anaphylaxis were observed
Kunie Kohno1, Hiroaki Matsuo2, Hitoshi Takahashi ,Serum Gliadin Monitoring Extracts Patients with False Negative Results in Challenge Tests
for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis , Allergology International. 2013;62:229-238
Challenge test
37. Kunie Kohno1, Hiroaki Matsuo2, Hitoshi Takahashi ,Serum Gliadin Monitoring Extracts Patients with False
Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis ,
Allergology International. 2013;62:229-238
38. Kunie Kohno1, Hiroaki Matsuo2, Hitoshi Takahashi ,Serum Gliadin Monitoring Extracts Patients with False
Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis ,
Allergology International. 2013;62:229-238
39.
40. The challenge-confirmed sensitivity
and specificity of gluten skin prick
tests was 100% and 96%,
respectively.
Conclusion: Oral challenge with
gluten alone or along with ASA and
alcohol is a sensitive and specific
test for the diagnosis of WDEIA.
Exercise is not an essential trigger
for the onset of
symptoms in patients with WDEIA.
41. Eishin Morita1, Hiroaki Matsuo, Food-Dependent Exercise-Induced Anaphylaxis―Importance of Omega-5 Gliadin and HMW-Glutenin as Causative Antigens for Wheat-Dependent
Exercise-Induced Anaphylaxis, Allergology International. 2009;58:493-498
IgE measurement in WDEIA and AD
42. • Acute management - immediate termination of physical effort
- Pharmaceutics such as Adrenaline ,
Antihistamine
• Prevent further episode of WDEIA
-education and how to use adrenaline autoinjectors.
-written anaphylaxis management plan as well as dietary counselling
- classical recommendation of refraining from exercise for 4-6 h after wheat
intake may be insufficient because unexpected exercise,NSAIDs .
- a gluten – free diet recommended need to avoid wheat only or other
gluten- containing cereals .
TREATMENT OF WDEIA
K. A. Scherf1, K. Brockow,wheat-dependent exercise – induced anaphylaxis , Clinical & Experimental Allergy, 46, 10–20
48. Ketotifen is an orally active tricyclic benzocyclo-heptathiophene
Derivative and thus may be a useful medication in the treatment
and prevention of allergic responses.
Ketotifen is a potent H1 receptor antagonist which has properties
of mast cell stabilization and anti-inflammatory capabilities.
Ketotifen also has other anti-inflammatory properties, which include
reduced eosinophilic chemotaxis in eosinophilia and
diminished production of eotaxin and expression of CD29 in epithelial
cells.
Editor's Notes
WDEIA one to four hours after wheat intake , but maybe delay or soon after exercise
SemolinaSpelt flour
Increased gastrointestinal permeability , blood flow redistribution and increased osmolarity triggered by physical effort after exposure to a sensitizing food allegen
Albumins and globulins,predominantly present in the aleurone layer and thegerm, are mainly metabolic proteins. Gliadins and glutenins are storage proteins located in the starchy endosperm as a supply of nitrogen and amino acids for theseedling
Gliadins are mainly monomeric proteins (molecular weights: 30 000–50 000) and glutenins are polymeric proteins linked by interchain disulphidebonds (molecular weights: 600 000 to more than 10 million). The chemical reduction of disulphide bonds results in glutenin subunits (molecular weights: 30 000to 80 000). Based on similar amino acid sequences and molecular weights, gluten proteins can be classified into the following protein types [30]: a/b-, c-, x1,2-, andx5-gliadins, low-molecular-weight (LMW-GS), and high-molecular-weight glutenin subunits (HMW-GS).a/b-Gliadins, c-gliadins, and LMW-GS belong to themajor and x5-gliadins, x1,2-gliadins, and HMW-GS tothe minor components
Synthetic overlapping dodecapeptides spanning thecomplete sequences (Pepscan) were used to identify themajor immunogenic epitopes from a/b-gliadin, c-gliadin, x1,2-gliadin, and x5-gliadin [50]. All epitopeswere localized in the glutamine- and proline-rich repetitive domains of the proteins. Cross-reactivity of allergens from barley, rye, and oats was studied, and among23 patients with WDEIA, 21 showed IgE-binding toc-75k-secalin, 19 to c-40k-secalin, and 21 to c3-hordein; oat proteins did not cross-react
strenuous exercise such asjogging, dancing, or cycling triggered anaphylaxis afterfood ingestion, but milder exercise, for example walking or gardening, may be sufficient
Adaptive and innate immune responses to gluten in the gut. Ingested gluten is digested by gastrointestinal proteases in the small intestine to innocuous peptides or proteolytically resistant, glutamine (Q)-containing immunotoxic gluten peptides. Immunogenic gluten peptides access the lamina propria by unknown mechanisms. Their Q residues are deamidated to glutamic acid (E) by TG2, internalized by antigen-presenting cells (APC), and presented via HLA DQ2 (or DQ8) molecules on the surface of APC to gluten-specific, DQ2- and DQ8-restricted CD4+ T cells in the lamina propria. The subsequent activation and clonal expansion of the T cells results in a cell-mediated Th1 response that initiates destruction of the epithelial layer and villous flattening as well as a humoral response that stimulates gluten-specific and TG2-specific B cells to produce gluten- and TG2-specific antibodies. This renders the epithelium more permeable, facilitating increased access of immunogenic gluten peptides and propagation of disease. [Adapted from Bethune and Khosla (44).]
Wheat (e.g., spelt) and other cereal grains (e.g., rye, barley)belong to the Poaceae family and share a number of homologous proteins among themselves and with grass pollen.93 Cerealgrains are frequently implicated in foodallergic reactions inchildren with atopic dermatitis. On the basis of their solubility,wheat proteins can be classifed as water/saltsoluble albuminsand globulins and water/saltinsoluble gliadins and glutenins.94Among the major allergens identifed in the water/saltsolublefraction of wheat flour are the cereal αamylase inhibitors(AAIs) and αamylase/trypsin inhibitors (AATIs), which arecapable of sensitizing by oral and inhaled routes (importantallergens in baker’s asthma and rhinitis). The globulin and glutenin fractions are the major allergenic fractions in IgEmediatedreactions, as are gliadins in celiac disease and in foodassociated,exerciseinduced anaphylaxis (ω5 gliadin, Tri a 19).95,96 Lipidtransfer proteins have been identifed as allergens in cases ofreactions to beers brewed from barley and wheat. In a study ofpediatric patients, 70 of 225 children were found to have at leastone positive prick skin test to wheat, rye, oat, barley, rice, orcorn: 28 of 70 to one grain, 16 of 70 to two grains, 12 of 70 tothree grains, 6 of 70 to four grains, 6 of 70 to fve grains, and2 of 70 to six grains.97 However, only 15 patients had at leastone positive DBPCFC to a cereal grain; two children reacted toasthma. Gly m 1 (i.e., Gly m Bd30K/P34 or P34) is a soybeanvacuolar protein that belongs to the group of nonspecifc lipidtransfer proteins. Gly m 1 shares high sequence similarity tothiol proteinases of the papain family, which includes the majorallergen in dust mites, Der p 1.Gly m 3 and Gly m 4 are related to birch pollen. With anamino acid sequence identity of 73%, Gly m 3 is highly homologous with the proflin Bet v 2. The IgEbinding epitopes of Glym 3 are highly conformational, and fragments of Gly m 3 fail tobind IgE. Gly m 4, also called SAM 22 (starvationassociatedmessage 22), is a PR protein with a 50% homology with Bet v 1.Serum IgE from 85% of birch pollen–allergic patients react toGly m 4.72 About 10% of Central European patients sensitizedto birch pollen have concomitant soy allergy, mainly due tocrossreactivity with Gly m 4.73Gly m 5 (βconglycinin, 7S) and Gly m 6 (glycinin, 11S) arethe seedstorage proteins from the cupin family that were foundto be major allergens in a cohort of 30 patients with DBPCFCconfrmed soy allergy, suggesting that these molecules are gooddiagnostic markers of componentresolved in vitro testing. Glym 5 and Gly m 6 have been associated with anaphylactic reactions in Japanese children.74 The allergenic epitopes on the Glym 6 acidic chain are homologous with IgEbinding epitopes onpeanut Ara h 3. Similar to highly refned peanut oil, refned soyoil did not provoke allergic reactions to soy in eight patientsafter ingesting up to 8 mL of soy oil.75Tree nut allergies affect about 0.6% of the American population.3 In a national registry of peanut and nut allergic individuals, walnuts provoked the most allergic reactions (34%),followed by cashews (20%), almonds (15%), pecan (9%),pistachio (7%), and by hazel nut, Brazil nut, pine nut, andmacadamia nut (all <5%).76 Skin testing reveals extensive crossreactivity among tree nuts. Although individuals allergic to onenut can tolerate other nuts, too few patients have been systematically challenged to a variety of nuts to determine the extentof clinical crossreactivity. High immunologic and clinicalcrossreactivity has been found between cashew and pistachioand between walnut and pecan.77 Patients allergic to nuts do notnecessarily need to avoid peanuts (a legume) and vice versa.However, about 30% of peanutallergic patients also reacted toat least one tree nut.78,79Fish are a common cause of foodallergic reactions in adultsand in children.80 Edible fsh are found predominantly in thebony fsh class (Osteichthyes), in which there are hundreds ofspecies. The major allergen in cod, Gad c 1, is a parvalbuminthat has been isolated from the myogen fraction of the whitemeat. A similar protein, Sal s 1, has been isolated from salmon.It is heat stable and resistant to proteolytic digestion, has amolecular mass of 12 kD and an isoelectric point of 4.75, andis composed of 113 amino acids.81 Specifc IgEbinding epitopeshave been identifed in Sal s 1; two of them correlate with thosepreviously described in Gad c 1. The threedimensional structure of Gad c 1 is arranged in three domains, two of whichbind calcium. Using SDSPAGE and immunoblot analyses, 10common fsh species were shown to have a protein that issimilar to Gad c 1 and up to 29 protein fractions. Eleven patientswith histories of fsh allergy had multiple positive skin testresults for various fsh; 7 of 11 reacted to only one fsh speciesin DBPCFCs, 1 reacted to two fsh, 2 reacted to three fsh, and1 patient did not react to any fsh during blinded challenges.The relative content of parvalbumin may underlie differencesin allergenic potential, which is highest in white fsh (e.g.,1320 SECTION G Systemic DiseaseCARBOHYDRATE ALLERGENSThe carbohydrate moieties present on many foods can induceIgE responses.35 Because carbohydrate moieties share signifcantstructural homologies beyond that of proteins, they are proneto extensive crossreactivity and are referred to as cross-reactivecarbohydrate determinants. Approximately 15% to 30% of allergic patients generate specifc antiglycan IgE, but very fewdevelop clinical allergy. Bromelain was identifed as the frstfood antigen that contained an oligosaccharide with two structural features that had not been found in mammalian glycoproteins: core α1,3fucose and xylose. Galactoseα1,3galactose(αgal) has been identifed as a cause of serious, even fatal,anaphylaxis.99 In contrast to previously described crossreactivecarbohydrate determinants expressed in plants and insects, theoligosaccharide αgal is abundantly expressed on cells andtissues of nonprimate mammals. This expression pattern makesαgal potentially clinically relevant as a food allergen (e.g., beef,pork, lamb) or as an inhaled allergen (e.g., cat, dog).100 IgEantibodies to αgal are associated with an unusual form ofdelayed anaphylaxis, which occurs 3 to 6 hours after ingestionof mammalian meat that carries αgal. Patients with IgE toαgal describe generalized urticaria or frank anaphylaxis starting 3 to 6 hours after eating beef, pork, or lamb and have aconsistent pattern of skin testing (likelihood of positive resultsis increased by testing with freshly ground meat or with intradermal testing) and serum IgE antibody results. Most patientsdeveloped anaphylaxis to red meat in adulthood; some reportedreceiving multiple tick bites, suggesting that tick bites, especiallythe lone star tick (Amblyomma americanum) may predispose tosensitization to αgal.Food additives and colorings derived from natural sourcesthat contain proteins may induce allergic reactions. Theyinclude colors derived from turmeric, paprika, seeds (e.g.,annatto), and insects (e.g., carmine, cochineal). Chemical additives are not likely to cause IgEmediated food allergy, butsome may have drug effects that cause adverse reactions,including allergylike symptoms, or they may invoke immuneresponses. Tartrazine (yellow #5) is a synthetic color that hasbeen extensively investigated because of concerns that it maytrigger hives, allergic reactions, and asthma. However, wellconducted studies have not validated these concerns. Sulftesare added to foods as a preservative, an antibrowning agent,or a bleaching effect. In sensitive persons, sulftes may induceasthma.CROSS-REACTIVITYStructural homology among allergens underlies immunologicand clinical crossreactivity.101 More than 70% identity inprimary sequence is considered necessary for clinical crossreactivity. However, the expression of clinical crossreactivity ismodulated by additional factors, including: protein solubilityand digestibility, concentration and affnity of the specifc IgEantibody, and the dose and route of allergen exposure. Highrates of clinical crossreactivity are observed among milks fromcows, goats, and sheep (>90%); melons (90%); crustacean shellfsh (75%); Rosaceae fruits such as apple, pear, peach (55%);and bony fsh (50%). Lower rates are observed among tree nuts(37%), grains (20%), cow’s milk and beef (10%), and peanutsand other legumes (5%). The rates of pollenfruit crossreactivity are about 50% for birch pollen and Rosaceae fruits.two grains, and two reacted to three grains. SDSPAGE andimmunoblot analyses with patient sera revealed 27 to 31 proteinbands in the range of 7.866.5 kDa for each of the six cerealgrains studied. Nonspecifc binding to lectin fractions was seenwith each grain, and extensive immunologic crossreactivityoccurred among the cereals, as was seen with skinprick testing.Homologies to allergenic proteins in grass pollens account fora large number of clinically irrelevant positive skin tests towheat and other cereal grains. Wheat (e.g., spelt) and other cereal grains (e.g., rye, barley)belong to the Poaceae family and share a number of homologous proteins among themselves and with grass pollen.93 Cerealgrains are frequently implicated in foodallergic reactions inchildren with atopic dermatitis. On the basis of their solubility,wheat proteins can be classifed as water/saltsoluble albuminsand globulins and water/saltinsoluble gliadins and glutenins.94Among the major allergens identifed in the water/saltsolublefraction of wheat flour are the cereal αamylase inhibitors(AAIs) and αamylase/trypsin inhibitors (AATIs), which arecapable of sensitizing by oral and inhaled routes (importantallergens in baker’s asthma and rhinitis). The globulin and glutenin fractions are the major allergenic fractions in IgEmediatedreactions, as are gliadins in celiac disease and in foodassociated,exerciseinduced anaphylaxis (ω5 gliadin, Tri a 19).95,96 Lipidtransfer proteins have been identifed as allergens in cases ofreactions to beers brewed from barley and wheat. In a study ofpediatric patients, 70 of 225 children were found to have at leastone positive prick skin test to wheat, rye, oat, barley, rice, orcorn: 28 of 70 to one grain, 16 of 70 to two grains, 12 of 70 tothree grains, 6 of 70 to four grains, 6 of 70 to fve grains, and2 of 70 to six grains.97 However, only 15 patients had at leastone positive DBPCFC to a cereal grain; two children reacted toasthma. Gly m 1 (i.e., Gly m Bd30K/P34 or P34) is a soybeanvacuolar protein that belongs to the group of nonspecifc lipidtransfer proteins. Gly m 1 shares high sequence similarity tothiol proteinases of the papain family, which includes the majorallergen in dust mites, Der p 1.Gly m 3 and Gly m 4 are related to birch pollen. With anamino acid sequence identity of 73%, Gly m 3 is highly homologous with the proflin Bet v 2. The IgEbinding epitopes of Glym 3 are highly conformational, and fragments of Gly m 3 fail tobind IgE. Gly m 4, also called SAM 22 (starvationassociatedmessage 22), is a PR protein with a 50% homology with Bet v 1.Serum IgE from 85% of birch pollen–allergic patients react toGly m 4.72 About 10% of Central European patients sensitizedto birch pollen have concomitant soy allergy, mainly due tocrossreactivity with Gly m 4.73Gly m 5 (βconglycinin, 7S) and Gly m 6 (glycinin, 11S) arethe seedstorage proteins from the cupin family that were foundto be major allergens in a cohort of 30 patients with DBPCFCconfrmed soy allergy, suggesting that these molecules are gooddiagnostic markers of componentresolved in vitro testing. Glym 5 and Gly m 6 have been associated with anaphylactic reactions in Japanese children.74 The allergenic epitopes on the Glym 6 acidic chain are homologous with IgEbinding epitopes onpeanut Ara h 3. Similar to highly refned peanut oil, refned soyoil did not provoke allergic reactions to soy in eight patientsafter ingesting up to 8 mL of soy oil.75Tree nut allergies affect about 0.6% of the American population.3 In a national registry of peanut and nut allergic individuals, walnuts provoked the most allergic reactions (34%),followed by cashews (20%), almonds (15%), pecan (9%),pistachio (7%), and by hazel nut, Brazil nut, pine nut, andmacadamia nut (all <5%).76 Skin testing reveals extensive crossreactivity among tree nuts. Although individuals allergic to onenut can tolerate other nuts, too few patients have been systematically challenged to a variety of nuts to determine the extentof clinical crossreactivity. High immunologic and clinicalcrossreactivity has been found between cashew and pistachioand between walnut and pecan.77 Patients allergic to nuts do notnecessarily need to avoid peanuts (a legume) and vice versa.However, about 30% of peanutallergic patients also reacted toat least one tree nut.78,79Fish are a common cause of foodallergic reactions in adultsand in children.80 Edible fsh are found predominantly in thebony fsh class (Osteichthyes), in which there are hundreds ofspecies. The major allergen in cod, Gad c 1, is a parvalbuminthat has been isolated from the myogen fraction of the whitemeat. A similar protein, Sal s 1, has been isolated from salmon.It is heat stable and resistant to proteolytic digestion, has amolecular mass of 12 kD and an isoelectric point of 4.75, andis composed of 113 amino acids.81 Specifc IgEbinding epitopeshave been identifed in Sal s 1; two of them correlate with thosepreviously described in Gad c 1. The threedimensional structure of Gad c 1 is arranged in three domains, two of whichbind calcium. Using SDSPAGE and immunoblot analyses, 10common fsh species were shown to have a protein that issimilar to Gad c 1 and up to 29 protein fractions. Eleven patientswith histories of fsh allergy had multiple positive skin testresults for various fsh; 7 of 11 reacted to only one fsh speciesin DBPCFCs, 1 reacted to two fsh, 2 reacted to three fsh, and1 patient did not react to any fsh during blinded challenges.The relative content of parvalbumin may underlie differencesin allergenic potential, which is highest in white fsh (e.g.,1320 SECTION G Systemic DiseaseCARBOHYDRATE ALLERGENSThe carbohydrate moieties present on many foods can induceIgE responses.35 Because carbohydrate moieties share signifcantstructural homologies beyond that of proteins, they are proneto extensive crossreactivity and are referred to as cross-reactivecarbohydrate determinants. Approximately 15% to 30% of allergic patients generate specifc antiglycan IgE, but very fewdevelop clinical allergy. Bromelain was identifed as the frstfood antigen that contained an oligosaccharide with two structural features that had not been found in mammalian glycoproteins: core α1,3fucose and xylose. Galactoseα1,3galactose(αgal) has been identifed as a cause of serious, even fatal,anaphylaxis.99 In contrast to previously described crossreactivecarbohydrate determinants expressed in plants and insects, theoligosaccharide αgal is abundantly expressed on cells andtissues of nonprimate mammals. This expression pattern makesαgal potentially clinically relevant as a food allergen (e.g., beef,pork, lamb) or as an inhaled allergen (e.g., cat, dog).100 IgEantibodies to αgal are associated with an unusual form ofdelayed anaphylaxis, which occurs 3 to 6 hours after ingestionof mammalian meat that carries αgal. Patients with IgE toαgal describe generalized urticaria or frank anaphylaxis starting 3 to 6 hours after eating beef, pork, or lamb and have aconsistent pattern of skin testing (likelihood of positive resultsis increased by testing with freshly ground meat or with intradermal testing) and serum IgE antibody results. Most patientsdeveloped anaphylaxis to red meat in adulthood; some reportedreceiving multiple tick bites, suggesting that tick bites, especiallythe lone star tick (Amblyomma americanum) may predispose tosensitization to αgal.Food additives and colorings derived from natural sourcesthat contain proteins may induce allergic reactions. Theyinclude colors derived from turmeric, paprika, seeds (e.g.,annatto), and insects (e.g., carmine, cochineal). Chemical additives are not likely to cause IgEmediated food allergy, butsome may have drug effects that cause adverse reactions,including allergylike symptoms, or they may invoke immuneresponses. Tartrazine (yellow #5) is a synthetic color that hasbeen extensively investigated because of concerns that it maytrigger hives, allergic reactions, and asthma. However, wellconducted studies have not validated these concerns. Sulftesare added to foods as a preservative, an antibrowning agent,or a bleaching effect. In sensitive persons, sulftes may induceasthma.CROSS-REACTIVITYStructural homology among allergens underlies immunologicand clinical crossreactivity.101 More than 70% identity inprimary sequence is considered necessary for clinical crossreactivity. However, the expression of clinical crossreactivity ismodulated by additional factors, including: protein solubilityand digestibility, concentration and affnity of the specifc IgEantibody, and the dose and route of allergen exposure. Highrates of clinical crossreactivity are observed among milks fromcows, goats, and sheep (>90%); melons (90%); crustacean shellfsh (75%); Rosaceae fruits such as apple, pear, peach (55%);and bony fsh (50%). Lower rates are observed among tree nuts(37%), grains (20%), cow’s milk and beef (10%), and peanutsand other legumes (5%). The rates of pollenfruit crossreactivity are about 50% for birch pollen and Rosaceae fruits.two grains, and two reacted to three grains. SDSPAGE andimmunoblot analyses with patient sera revealed 27 to 31 proteinbands in the range of 7.866.5 kDa for each of the six cerealgrains studied. Nonspecifc binding to lectin fractions was seenwith each grain, and extensive immunologic crossreactivityoccurred among the cereals, as was seen with skinprick testing.Homologies to allergenic proteins in grass pollens account fora large number of clinically irrelevant positive skin tests towheat and other cereal grains.