explore the cell's role in mediating adverse reactions 7 c09
TRANSCRIPT
a scientific discussion on metabolic, immunologic
and pharmacologic mediators
Explore the cell’s role in mediating adverse reactions:
Roger Davis Deutsch is one of the pioneers of food and chemical sensitivities testing with involvement in this field since 1986. He has been responsible for the commercialization of the Alcat Test throughout the world. He is the co-author of Your Hidden food Allergies are Making You Fat. Roger serves as the Founder and CEO of Cell Science Systems.
About our Speakers
J Allergy Clin Immunol. 2001 Jan;107(1):129-34.
Distinct patterns of neonatal gut microflora in infants in whom
atopy was and was not developing.
Kalliomaki M, Kiriavainen P, Eerola E, Kero P, Salminen S, Isolauri E.
RESULTS: • Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks,
the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing (P =.005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 x 10(7) [3.8-22.9 x 10(7)] vs 3.3 x 10(7) [1.8-6.1 x 10(7)], P =.04) and tended to have fewer bifidobacteria (1.8 x 10(9) [0.4-7.6 x 10(9)] vs 6.1 x 10(9) [2.5-14.6 x 10(9)], P =.11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia (P =.03).
CONCLUSION: • Differences in the neonatal gut microflora precede the development of
atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode.
Distinct Patterns of IgG and IgA against Food and Microbial
Antigens in Serum and Feces of Patients with Inflammatory
Bowel Disease
PLOS ONE Sept, 12, 2014 Lisa Freh, et. al.
• We therefore aimed at comprehensively investigating local or systemic levels of anti-microbial and anti-food Abs in IBD patients. For this purpose, we analyzed in parallel serum and fecal Abs specific for dietary and microbial antigens in a cohort of IBD patients and controls.
Figure 2. Anti-food and anti-microbial serum IgG and IgA levels in CD patients with or without stricturing/penetrating disease and controls.
Frehn L, Jansen A, Bennek E, Mandic AD, Temizel I, et al. (2014) Distinct Patterns of IgG and IgA against Food and Microbial Antigens in Serum and Feces of Patients with Inflammatory Bowel Diseases. PLoS ONE 9(9): e106750. doi:10.1371/journal.pone.0106750 http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0106750
Distinct Patterns of IgG and IgA against Food and
Microbial Antigens in Serum and Feces of Patients
with Inflammatory Bowel Disease PLOS ONE Sept, 12, 2014 Lisa Freh, et. al. Department of Internal Medicine III, University Hospital Aachen, RWTH University, Aachen, Germany
Results • Serum anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-B.
fragilis IgG and IgA levels were increased in CD patients whereas antibody (Ab) levels against E. coli and food antigens were not significantly different within the patient groups and controls
• One important finding of our study is that we did not find any correlation between food-specific Ab levels and clinical symptoms. Our data does not support the idea that measurements of anti-food specific IgG or IgA is of any clinical relevance for patients suffering from CD or UC. In particular, it does not predict the presence of food intolerance.
Distinct Patterns of IgG and IgA against Food
and Microbial Antigens in Serum and Feces of
Patients with Inflammatory Bowel Disease
PLOS ONE Sept, 12, 2014 Lisa Freh, et. al.
Distinct Patterns of IgG and IgA against Food and
Microbial Antigens in Serum and Feces of Patients
with Inflammatory Bowel Disease
PLOS ONE Sept, 12, 2014 Lisa Freh, et. al.
• Acute exacerbation of disease does not correlate with antibody levels, however enhanced ASCA and other anti-microbial Ab levels correlate with more complicated disease courses and anti-TNF-α therapy, It has been shown that microbial-specific IgA mediates gut homeostasis in animal models and might therefore have anti-inflammatory functions in IBD.
Distinct Patterns of IgG and IgA against Food and
Microbial Antigens in Serum and Feces of Patients
with Inflammatory Bowel Disease
PLOS ONE Sept, 12, 2014 Lisa Freh, et. al.
• In summary, our study reveals that CD, UC and AGE
patients as well as non-inflammatory controls have distinct patterns of IgG and IgA against food and microbial antigens in serum and feces suggesting differentially regulated immune responses towards intestinal antigens. However, food-specific Abs have not yet been proven to be a valuable biomarker for IBD or food intolerance.
RESEARCH ARTICLE
Gliadin Induces Neutrophil Migration via
Engagement of the Formyl Peptide Receptor,
FPR1.
Results In vivo intestinal luminal injection of PT-gliadin induces an immediate and substantial recruitment of neutrophils. Increased intestinal permeability favors the access of gliadin and other macromolecular antigens from the intestinal lumen into the lamina propria where the host, by interpreting them as danger signals, will respond with first-line defense mechanisms such as neutrophil recruitment to the site of exposure.
CXCR3-/- neutrophil chemotaxis using EZ-TAXIScan chemotactic assay. The EZ-TAXIScan chemotactic assay was used for direct visualization of chemotaxis of CXCR3-/- neutrophils to either PT-gliadin (lower panel) or fMet-Leu-Phe (middle panel). PBS (upper panel) was used as a negative control. PT-gliadin and fMet-Leu-Phe induced similar chemotactic responses as C57BL/6 wild-type neutrophils (see S2 movie), indicating that neutrophil chemotaxis is independent of PT-gliadin binding to CXCR3. Frames were taken every 15 seconds.
Macrophage activity in semen is significantly
correlated with sperm quality in infertile men.
“The presence of leucocytes within semen has the potential to impair sperm function. Neutrophils and macrophages make up 95% of seminal leucocytes, with both having the ability to damage sperm via the generation of reactive oxygen species, proteases and the induction of apoptosis…..We were able to confirm for the first time that seminal plasma does indeed contain neopterin and that the levels of this macrophage activity marker are threefold higher in infertile than fertile men.”
Tremellen K, Tunc O. Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia. Int J Androl. 2010 Jan 28.
Neutrophils in local and systemic antibody-
dependent inflammatory and anaphylactic reactions
Friederike Jönsson,*,1,2 David A. Mancardi,*,1,2 Marcello Albanesi,*,† and Pierre Bruhns*
* Institut Pasteur, Département d’Immunologie, Laboratoire Anticorps en Thérapie et Pathologie, and INSERM, U760, Paris,
France and;† Université Pierre et Marie Curie, Paris, France
RECEIVED SEPTEMBER 28, 2012; REVISED MARCH 7, 2013; ACCEPTED MARCH 11, 2013. DOI: 10.1189/jlb.1212623
• It is, however, difficult to discriminate between the consequences of the activation of resident macrophages and the activation of infiltrating neutrophils: these two cell types can secrete similar panels of molecules and antimicrobial products. Nonetheless, the severity of IC induced inflammation is closely linked to the extent of neutrophil infiltration, suggesting that this cell type is responsible for most of the observed symptoms.
alpha(4)-integrin mediates neutrophil-induced
free radical injury to cardiac myocytes
…circulating neutrophils adhere to cardiac myocytes and cause cellular injury… emigrated PMNs have the capacity to injure cardiac myocytes
Poon BY, Ward CA, Cooper CB, Giles WR, Burns AR, Kubes P. Immunology Research Group, University of Calgary, Calgary, Alberta T2N 1N4, Canada. J Cell Biol. 2001 Mar 5;152(5):857-66.
Changes of neutrophil myeloperoxidase in coronary circulation among patients with acute
coronary syndrome
“MPO is a better marker for inflammation of the local plaques. It may be one of the mechanisms that MPO induces the transforming from LDL to ox-LDL in plaques vulnerability.”
Li L, Zhang Y, Chen YG, Li GS, Wang Y, Ma X, Li JF, Zhong M, Zhang W. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China.
Chronic activation of the innate immune
system may underlie the metabolic syndrome
Most importantly, activation of this system leads to fundamental changes in body metabolism. In this regard, it is notable that pro-inflammatory cytokines are major stimulants of the hypothalamic-pituitary-adrenal axis, leading to increased cortisol secretion and inhibition of sex hormone production.
Sao Paulo Med. J. Vol. 119 no.3 Sao Paulo May 2001 Social Medicine Department, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Increase in fragmented phosphatidylcholine
in blood plasma by oxidative stress.
Oxidatively modified phospholipids have attracted much interest because of their pro-inflammatory activity and their potential involvement in atherosclerosis…The increase coincided with a surge of circulating neutrophils.
Frey B, Haupt R, Alms S, Holzmann G, Konig T, Kern H, Kox W, Rustow B, Schlame M. Department of Anesthesiology and Intensive Care Medicine, University Hospital Charite, Humboldt University, Berlin, Germany. J Lipid Res. 2000 Jul;41(7):1145-53
Adaptive Metabolic Leukocyte Activation
“Careful study of diet-induced obesity has identified chronic leukocyte-mediated low grade inflammation within professional metabolic tissues as the characteristic pathophysiology of metabolic syndrome.”
J. Olefsky, C. Glass, Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 72,219 (2010). 10.1146/annurev-physiol-021909 A. Chawla, K. D. Nguyen, Y. P. Goh, Macrophage-mediated inflammation in metabolic disease. Nat. Rev. Immunol. 11, 738 (2011).
Amy Pieczarka, RD is a dietitian/nutritionist, in practice for over 26 years. She is delighted to be a part of the PreviMedica team of exceptional professionals, dedicated to promoting optimal health through customized nutrition. Amy received her Bachelor of Science degree in Nutrition and Medical Dietetics from the Pennsylvania State University. Currently, Amy serves as the creator and manager of PreviMedica Nutrition Services.
About our Speakers
-Philip Regal, Biologist
“Plants are little biochemical factories that produce scores of bioactive compounds in order to mess up the metabolism of a great variety of predators and pathogens. That’s why all the first drugs were discovered in plants. Even in small amounts some plant chemicals are good for us and some are dangerous, so ethnobotanists seek knowledge from local tribal people about which are which.”
• Tryptamine • Gluten • Lectin • Aflatoxin • Lactose • Chlorogenic Acid • Solanine
“Pilot study into the Effect of Naturally
Occurring Pharmacoactive Agents on the
Alcat Test” - P.J. Fell, MD
• Dopamine • Histamine • Lactoglobulin • Octopamine • Phenylethylamine • Serotonin
• The white cell can act as a model of activity by either a toxic or pharmacological effect. This effect produces a change in size of parts of the white cell population which the Alcat Test can detect.
About our Speakers
Craig Koniver, MD is a Board Certified Family Medicine Physician who has extensive experience and interest in the field of natural and organic medicine. Dr. Koniver completed his undergraduate degree at Brown University and received his Medical Doctorate from Jefferson Medical College. He opened Primary Plus Organic Medicine, LLC in Charleston, South Carolina in 2006 and has been utilizing the Alcat Test since.
The Alcat Test
• NOT just for GI issues • Symptomatic vs. Preventive (Optimizing Health) • Everything we interact with in life, affects our biochemistry
So, stop having
unrealistic expectations
No Test is Perfect
>50% of adults are tired,
depressed and obese
>50% of adults take more than
1 prescription medication
100% of all of these
people eat food
“In diagnosis, think of the easy first.”
…Martin H. Fischer, 1944
Case Studies
• Chemically Sensitive Patient • GI Health Issue • Metabolic Issues
Chemical Sensitivity
• JS, 53 y/o female presented with c/o mouth sores, joint pain • Ran full Alcat Test Panel
GI Issues
• TS is a 43 y/o male with no significant medical problems • 9 month h/o gas, bloating, constipation, rash on LE,
difficulty gaining weight, fatigue • Ran 200 Food Panel • After 1 month of being very strict with both elimination
and rotational diet, he reported that his symptoms were 90% better
Metabolic Issues
• CB, 56 y/o female with c/o fatigue, inability to lose weight, diabetes, on multiple medications
• Ran 200 Food Panel • After just three weeks of changing her diet, she reported
that her normal fasting AM glucose level was 86. Followed by several in the 90’s and then several in the 80’s (her norm was 120’s).
