David Kossor, PhD, RPh, DABT, PMP Syncratic Therapies, LLC Presentation to AutismOne May 26, 2016
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1 David Kossor, PhD, RPh, DABT, PMP Syncratic Therapies, LLC May 26, 2016
2 INSPIRE EDUCATE MOTIVATE
3 Concept first appeared by Charles Darwin in 1857 Pertained to genetics Splitter = increased diversity Lumper = reduced diversity Has been expanded to describe research paradigms Splitter = divergent approaches (data-driven) Lumper = convergent approaches (concept-driven)
4 BOTH concepts are needed to advance science: Splitters generate the pieces of a puzzle Lumpers assemble the pieces to create a picture Splitters vastly outnumber Lumpers Splitters generate DATA that support GRANT FUNDING PEER-REVIEW Lumpers are PIONEERS By definition PIONEERS HAVE NO PEERS!!
5 Very important piece of the picture of autism Much more complicated than you have ever heard of
6 HISTORY OF MELATONIN SCIENTIFIC PRINCIPLES ACTIONS OF MELATONIN SIGNIFICANCE TO PATIENTS WITH AUTISM
7 Discovey by Aaron Lerner in 1958 Affected melanin deposition in skin Might be beneficial in treatment of skin disorders hormone of darkness Produced by pineal gland in brain Stimulus: reduced light during evening hours Dominated research efforts for 40+ years
8 Professor UT Health Sciences Center Dept. of Cellular & Structural Biology Functional significance of melatonin in aging processes Editor-in-chief Journal of Pineal Research Accomplished Splitter AND Lumper
9 Endogenous (= made inside the body) Pineal gland Gastrointestinal tract, retina, placenta, etc. Exogenous (= Taken in from the outside) Oral (food; pills) Parenteral (injection) Transcutaneous (skin patch )
10 What the CHEMICAL does to the BODY PHARMACOKINETICS What the BODY does to a CHEMICAL
11 ABSORPTION Rapid absorption across biological membranes (lipophillic!) DISTRIBUTION Rapid tissue uptake Biliary excretion HIGHEST CONCENTRATION IN BODY TIMES GREATER THAN BLOOD Enterohepatic circulation CYCLES BETWEEN THE GUT AND THE LIVER
12 PORTAL VEIN MESENTERIC VEINS
13 Maintain Circadian rhythms Sleep Body temperature Hormone regulation
14 Depends upon tissue location: PINEAL GUT timing night 24/7 stimulus light food location actions blood (central) sleep enterohepatic (local) pleitropic (metabolic)
15 PLEITROPIC ACTIONS Metabolism Immunoregulation Antioxidant Anti-inflammation Metallochaperone
16 Metabolism Infancy Melatonin is supplied by breast milk Health implication of premature weaning Melatonin is highest during pre-adolescence, then declines through life Diminished melatonin stimulates estrogen/testosterone production Diminished melatonin signals onset of puberty
17 Metabolism Supports MICROBIOME Bacterial flora in gut Enormous impact on health Digestion of food Controls growth of PATHOGENIC BACTERIA Prevents development of LEAKY GUT
18 Immunoregulation Supports Th1 phenotype (cell-based immunity) Maintains glutathione concentrations
19 Antioxidant More potent antioxidant than antioxidants Vitamin C or Vitamin E Reduces oxidant stress
20 Anti-inflammation Blocks cytokine production and signalling Reduces white blood cell (leucocyte) migration Maintains integrity of mitochondria
21 Metallochaperone Maintains trace metals nutriture Zinc, copper, selenium, manganese Zinc is most important trace metals
22 Essential for over 300 zinc-dependent enzymes DNA/RNA production & repair Carbonic anhydrases (ionic balance) Matrix metalloproteinases (collagen metabolism) Aminopeptidases/carboxypeptidases (protein digestion) Alcohol dehydrogenase (degrades ingested ethanol) ZINC FINGER PROTEINS (cytokines/growth factors) Tight junction proteins (prevents leaky gut )
23 Toxicants decrease melatonin in the gut Healthy people restore the intestinal pool Patients with autism can t restore the pool Deficient methyl transferase enzyme Deficient methyl donor Both
24 Typical oral melatonin tablets deliver melatonin to the blood may be helpful for insomnia Special formulation needed for gastrointestinal delivery Melascend = MEDICAL FOOD Defined by the Food & Drug Administration in 1990 Supervised by healthcare provider Specially formulated to restore the enterohepatic cycle of melatonin
25 Melatonin is produced at several locations in the body Melatonin has important pleitropic actions Melatonin is deficient in many patients with Autism Patients with Autism may benefit by taking Melatonin Melascend is needed to restore Melatonin in the gut We can work with healthcare provider s to develop specific dosage regimens for individual children
26 (please visit
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