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Conference Series LLC Conferences Conference Series LLC is a pioneer and leading science event organizer, which publishes around 500 open access journals and conducts over 500 Medical, Clinical, Engineering, Life Sciences, Pharma scientific conferences all over the globe annually with the support of more than 1000 scientific associations and 30, 000 editorial board members and 3. 5 million followers to its credit. Conference Series LLC has organized 500 conferences, workshops and national symposiums across the major cities including San Francisco, Las Vegas, San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago, Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing, Hyderabad, Bengaluru and Mumbai.
CARNITINE DEFICIENCY AS THE CAUSE OF HIGHER AMMONIA LEVELS Cecilia Maldonado, Ph. D Pharmaceutical Sciences Department Universidad de la República Uruguay
3 MAPS • Football • Mate • Mujica • Marijuana
SYNTOMATIC HYPERAMMONEMIA WITH CHRONIC OR ACUTE VPA ADMINISTRATION Patient Sex Age Reason freatment (years) [VPA] [NH 4+] mg/L μg/d. L Comment 1 M 26 Epilepsy 80 235 Chronic treatment 1 M 26 Epilepsy ------ 86 Chronic treatment 2 F 16 Epilepsy 60 179 Chronic treatment 2 F 16 Epilepsy 75 200 Chronic treatment 3 F 37 Bipolar disorder 99 373 Chronic treatment 3 F 37 Bipolar disorder ------ 11 Chronic treatment 4 M 54 568 511 4 M 54 Psychiatric pathology 136 294 Acute ingestion 54 Psychiatric pathology 69 50 Acute ingestion 4 M TI DPA – 50 -100 mg/L. NR NH 4+ - 25 -94 μg/d. L
AMMONIA NH 4+ production • Protein catabolism NH 4+ elimination • Hepatic disease • Renal disease • Medicines • Age?
6 AMMONIA TOXICITY MILD – DROWSINESS/CONFUSION SEVERE – ENCEPHALOPATHY, EDEMA, COMA SEIZURES
CARNITINE HOMEOSTASIS Exogenous/Endogenous OCTN 2 ACYLCAR/CAR ratio – biomarker
CAR and ACETILCAR CAR/ACETILCAR β-oxidation Acyl-Co. A/Co. A ratio Acetilcholine
PATIENTS and METHODS 9 ▹Group A) Thirty-one epileptic adult patients (15 men -16 women), mean age 46. 2 years (range 18 -55) Blood CAR and ACYLCAR profiles and ammonia concentrations in blood were determined. ▹Group B) Twenty-eight patients treated with VPA (15 men - 13 women), mean age 45. 7 years (range 18 -55) Plasma VPA, blood CAR and ACYLCAR profiles, and ammonia blood concentrations were determined. ▹Group C) Forty-one elderly patients (21 men - 20 women), mean age 73. 8 years (range 65 -85). Blood CAR and ACYLCAR profiles and ammonia blood concentrations were determined. • • • VPA - HPLC. NH 4+ - Hitachi 911 Automatic Analyser, Laboratorios Roche. CAR / ACYLCAR - LC-MS/MS. • All statistical analyses were carried out using SPSS (version 17. 0 for Windows). • Means were compared using Student’s t-test for independent variables. • All p-values were two sided, using α = 0. 05 as the reference standard for determining the significance.
RESULTS CARNITINE – VALPROIC ACID 10
VPA - ACETYLCAR VPA - CAR VPA – NH 4+ 11 CORRELATIONS
12 MEAN COMPARISONS BETWEEN GROUPS
VPA INDUCED HYPERAMMONEMIA Valproil carnitine formation Butirobetaine hydroxylase inhibition OCTN 2 inhibition Carnitine depletion
β-OXIDATION ↓ Acetil-Co. A VPA ω-oxidation ↑ UREA CYCLE CPS-1 INHIBITION CPS-1 ALLOSTERIC REGULATION HYPERAMMONEMIA
RESULTS CARNITINE – AGE 15
Age - ACETYLCAR Age - CAR Age – NH 4+ 16 CORRELATIONS
17 MEAN COMPARISONS BETWEEN GROUPS
CARNITINE CAUSES OF HYPERAMMONIA IN THE ELDERLY CPS-1 OCTN 2 ACETYLCARNITINE Sexual hormones Elevated ammonia SIRT 5 Elevated ammonia
MEAN AMMONIA LEVELS IN THE THREE GROUPS 19
CONCLUSIONS Patients with VPA Elderly patients CAR deficiency No CAR depletion ACETYLCARdeficiency ACETILCAR deficiency Ammonia increase ACETYLCAR or CAR ACETYLCAR
NOW WHAT? ?
22 Any questions? You can find me at ▹ cmaldonado@fq. edu. uy THANKS!
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Let us meet again. . We welcome you to our future conferences of Conference Series LLC through 9 th International Conference and Exhibition on Pharmacovigilance July 17 -19, 2017 Munich, Germany http: //pharmacovigilance. pharmaceuticalconferences. com/
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