trace minerals: physiology,immunity and diagnostics€¦ · 7/22/19. sure trace mineral supply by...
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7/22/19
SURE Trace Mineral Supply by Timed Injection
Trace Minerals: Physiology, Immunity
and Diagnostics
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RACE CE: 589-34601Jerry Rusch DVMDiplomate ABVP-Beef Cattle
SURE Trace Mineral S upply by Timed Injection 2
Mineral Units Feeder Dry Cow Lact. Cow Decimal Feeder
K % 0.60 0.60 0.60 0.00600000 thousandthsCa % 0.40 0.16 0.28 0.00400000P % 0.22 0.17 0.22 0.00220000S % 0.15 0.15 0.15 0.00150000Mg % 0.10 0.12 0.20 0.00100000Na % 0.07 0.07 0.10 0.00070000
Fe ppm 50.00 50.00 50.00hundred
0.00005000 thousandthsZn ppm 30.00 30.00 30.00 0.00003000Mn ppm 20.00 40.00 40.00 0.00002000Cu ppm 10.00 10.00 10.00 0.00001000
I ppm 0.50 0.50 0.50ten
0.00000050 millionthsCo ppm 0.10 0.10 0.10 0.00000010Se ppm 0.10 0.10 0.10 0.00000010Cr ppm 0.00 0.00 0.00 0.00000000Mo ppm 0.00 0.00 0.00 0.00000000Ni ppm 0.00 0.00 0.00 0.00000000
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Part 1Physiological Functions of Trace Minerals
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TRACE MINERALMETABOLISM
STORAGE & RELEASE & EXCRETION
SURE Trace Mineral Supply by Timed Injection
TRANSPORT
ENZYME
STRUCTURAL
EXCRETION
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• “Zinc is required for the structural and functional integrity of over 2000 transcription factors and almost every signaling and metabolic pathway is dependent on one or more zinc-requiring proteins.” (Beattie and Kwun,2004; Cousins et al., 2006).
SURE Trace Mineral Supply by Timed Injection
Enzyme Functions SignificanceGlycosyltransferase Cartilage proteoglycans, prothrombin
Skeletal malformations ,swollen joints,dwarfism, prolonged clotting time
Pyruvate Carboxylase Lipid and Carbohydrate Metabolism GluconeogenesisMn-Superoxide Dismutase O2- H2O2 Mitochondrial oxidation control
SURE Trace Mineral Supply by Timed Injection
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Enzyme Function SignificanceCaeruloplasmin ( ferroxidase) Iron Transport Anemia, Antioxidant
Cytochrome c Oxidase Cellular Respiration Anoxia, Impaired cellular immunityDopamine-B-mono oxygenase Catecholamine metabolism Behavior?
Hephaestin Export Fe from intestine AnemiaFerroxidase II Iron Oxidation Anemia
Lysyl Oxidases Desmosine cross linkages in connective tissueAortic Rupture, joint disorders,
osteoporosisMonamine Oxidase Oxidative deamination of monoamines Cell signaling, Leukocyte trafficking
Lipid Peroxidation, Vascular Tone, ImpairedSuperoxide Dismutases e.g. ZnCuSOD O2- H2O2 cellular immunity
Thiol Oxidase Disulfide bond formation Loss of wool and hair strengthTyrosinases Tyrosine to melanin Depigmentation
SURE Trace Mineral Supply by Timed Injection
Enzyme Functions ( location) Abbrev. Pathognomic Sig.Cytosolic glutathione Antioxidant, storage ( tissue cytosol,
peroxidases RBC,) GPX1Impaired Immunity, White
Muscle Disease,
Phospholipid hyperoxideAntioxidant ( intracellular
memebranes, testes)GPX2
cellular damage due to oxidative stress.
Plasma GPX Antioxidant (plasma,kidney, lung) GPX3
Gastrointestional GPX Antioxidant ( intestinal mucosa) GPX4
Epidydimal GPX Antioxidant (epididymus) GPX5iodthyronine (deiodinases)
Conversion T4-T3 (liver, kidney, muscle) Ruminants
ID1 Reduce basal metabolic rate
Conversion T4-T3 (BAT, brain) ID2Neonate resistance to cold
stressConversion T4-rT3 ( Placenta) ID3
Selenoprotein N
Selenoprotein P
Cell proliferation ( Muscle) SePN
Transport, Metal detox. ( Plasma) SePP
SURE Trace Mineral Supply by Timed Injection
SURE Trace Mineral Supply by Timed Injection
OXIDATIVE STRESS :
PRODUCTION OF ROS >>>> ANTIOXIDANT CAPACITY
Zn & CuSe
Fe
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Oxidative Stress Damage
SURE Trace Mineral Supply by Timed Injection
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SURE Trace Mineral Supply by Timed Injection
Clinical
Trac
e M
iner
alIn
take
Trace Mineral Functions
Normal
Immunity
Fertility
Growth
Clinical Signs
Normal Subclinical
Time
Wikse, 1992 Texas A&M Beef Cattle Short Course
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Part 2Trace Mineral Functions in Immunity
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Immune System Parts• Innate
• How the body is built
• How the body responds
• Acquired
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SURE Trace Mineral Supply by Timed Injection
Immune System Parts• Innate
• How the body is built• Anatomic or Physical Barriers (skin, mucous membranes)
• How the body responds
• Acquired
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SURE Trace Mineral Supply by Timed Injection
Immune System – Physical Barriers
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SURE Trace Mineral Supply by Timed Injection
Immune System Parts• Innate
• How the body is built• Anatomic or Physical Barriers (skin, mucous membranes)• Physiological Barriers (pH, bile acids, mucus, organic acids)
• How the body responds
• Acquired
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SURE Trace Mineral Supply by Timed Injection
Immune System – Physiological
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SURE Trace Mineral Supply by Timed Injection
Immune System Parts• Innate
• How the body is built• Anatomic or Physical Barriers (skin, mucous membranes)• Physiological Barriers (pH, bile acids, mucus, organic acids)
• How the body responds
• Acquired
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SURE Trace Mineral Supply by Timed Injection
Immune System Parts• Innate
• How the body is built• Anatomic or Physical Barriers (skin, mucous membranes)• Physiological Barriers (pH, bile acids, mucus, organic acids)
• How the body responds• Inflammation (vasodilators, complement, fibrin)
• Acquired
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SURE Trace Mineral Supply by Timed Injection
Immune System – Inflammation
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SURE Trace Mineral Supply by Timed Injection
Immune System – Inflammation
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SURE Trace Mineral Supply by Timed Injection
Immune System – Inflammation
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SURE Trace Mineral Supply by Timed Injection
Immune System Parts• Innate
• How the body is built• Anatomic or Physical Barriers (skin, mucous membranes)• Physiological Barriers (pH, bile acids, mucus, organic acids)
• How the body responds• Inflammation (vasodilators, complement, fibrin)• Natural Killer Cells
• Acquired
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SURE Trace Mineral Supply by Timed Injection
Immune System Parts• Innate
• How the body is built• Anatomic or Physical Barriers (skin, mucous membranes)• Physiological Barriers (pH, bile acids, mucus, organic acids)
• How the body responds• Inflammation (vasodilators, complement, fibrin)• Natural Killer Cells• Phagocytic Cells (neutrophils and monocytes)
• Acquired
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SURE Trace Mineral Supply by Timed Injection
Immune System Parts• Innate
• How the body is built• Anatomic or Physical Barriers (skin, mucous membranes)• Physiological Barriers (pH, bile acids, mucus, organic acids)
• How the body responds• Inflammation (vasodilators, complement, fibrin)• Natural Killer Cells• Phagocytic Cells (neutrophils and monocytes)
• Acquired• Humoral
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Immune System Parts• Innate
• How the body is built• Anatomic or Physical Barriers (skin, mucous membranes)• Physiological Barriers (pH, bile acids, mucus, organic acids)
• How the body responds• Inflammation (vasodilators, complement, fibrin)• Natural Killer Cells• Phagocytic Cells (neutrophils and monocytes)
• Acquired• Humoral• Cell-Mediated
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1. Ceruloplasmin (anti-inflammatory)
3.Antioxidant
2. Energy Production
Reduced T-cell response & Reduced Interferon production Decreased Neutrophil Phagocytosis & Killing
SURE Trace Mineral Supply by Timed Injectionhttp://theredish.com/imgs/showimg
AntioxidantEnergy metabol i sm of phagocytic cells
T-cell Proliferation
Reduced B-cell response- reduced Antibody production Depressed Neutrophil migration to target tissue
Depressed Neutrophil killing ability
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V i tamin A – Transport and uti l ization (Epi thel ium)
SOD
Ribonucleotide reductase
Zn deficiency: Reduction in T cell in number and maturation Decrease in Interferon-γ , TNF-α , Interleukins
Affects appetite, cortisol, balance between cell-mediated and humoral immunityhttp://www.nature.com/nrurol/journal/v10/n4/fig_tab/nrurol.2013.43_F1.html
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SURE Trace Mineral Supply by Timed Injection
SURE Trace Mineral Supply by Timed Injection
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ITM Effects Immune Response• Teixeira JDS 2014 v. 97 p.4216 Improved Phagocytosis• Arthington JAS 2012 v. 90 p. 1996 – Improved Humoral Response• Arthington JAS 2014 v. 92 p. 2630 – Improved Humoral Response• Roberts PNC 2015 poster – Improved Humoral Response• Palomares AABP 2015 poster – Improved Humoral and CMI• Palomares AVC 2015 presentation - Improved Humoral and CMI
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Improved Phagocytosis - Teixeira
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Improved Humoral – Arthington
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Improved Humoral - Arthington
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Improved Humoral - Roberts
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Improved Humoral - Roberts
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Improved Immune Response
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SURE Trace Mineral Supply by Timed Injection
VS
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Improved Humoral & CMI –Palomares
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- 0.50
-1.00
-1.50
2 .0 0
1 .5 0
1 .0 0
0 .5 0
0 .0 0
0 7 1 4 2 1 2 8 4 2 6 0 9 0
Mannheimia haemolytica titers
Palomares 2015 AVC
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Conclusion
1. ITM resulted in increased humoral and CMI responses to MLV vaccination
2. ITM induced Faster & Stronger immune response to BVDV, BRSV & P. multocida
3. ITM enhanced protection from BVDV-2 infection by MLV vaccine, helping to maintain adequate health and improving performance of growing calves.
4. ITM at the time of vaccination appear to mitigate the decrease in CD4+ and CD8+ T cells in calves challenged with BVDV five days after immunization
SURE Trace Mineral Supply by Timed Injection
SURE Trace Mineral Supply by Timed Injection
Group N Vaccine ITM BVDV / BHV1
IN booster + ITM 12 Yes Yes Yes
SQ booster + ITM 12 Yes Yes Yes
IN booster + Sal 12 Yes No Yes
SQ booster + Sal 12 Yes No Yes
Unvaccinated 12 No No Yes
BVDV-2
MLV booster + ITM on Protection against BVDV+ BHV1
* 60 Holstein calves* 3 months old* Booster 60 d after priming
with IN
0 7 14 21 28 35 42 49 56 63
Blood & Nasal swab samples, Clinical signs score
BHV1
Necropsy
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SURE Trace Mineral Supply by Timed Injection
Endoscopy Respiratory Score5 days after BHV1 challenge
30
40
60
50
End
osc
opy
Resp
irat
ory
Scor
e
Endoscopy Respiratory Score
ITM
Saline
Unvaccinated
b,c
b,d
20
10
0ITM Saline Unvaccinated
Treatment Groups
Statistical difference between groups a,b (P< 0.01) c,d (P< 0.05)
a
“ITM: lower level of inflammation and damage of the URT by IBR”SURE Trace Mineral Supply by Timed Injection
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n
BCNOT VACCINATED
C
Hoyos, Palomares, et al., 2018 SURE Trace Mineral Supply by Timed Injectio
n
PRIMER (IN) plus Booster (IN / SQ)
Hoyos, Palomares, et al., 2018 SURE Trace Mineral Supply by Timed Injectio
n
PRIMER (IN) plus Multimin® 90 plus Booster (IN/SQ) plus Multimin® 90
Hoyos, Palomares, et al., 2018 SURE Trace Mineral Supply by Timed Injectio
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SURE Trace Mineral Supply by Timed Injection
NO VACCINE Intra-Nasal Plus Booster Intra-Nasal Plus Booster Plus
SURE Trace Mineral Supply by Timed Injection
NO VACCINE Intra-Nasal Plus Booster Intra-Nasal Plus Booster Plus
SURE Trace Mineral Supply by Timed Injection
NO VACCINE Intra-Nasal Plus Booster Intra-Nasal Plus Booster Plus
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SURE Trace Mineral Supply by Timed Injection 55
Part 4Trace Mineral Patterns in Cattle Production
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Mineral status /needs vary
Fixing Deficiencies
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SURE Trace Mineral Supply by Timed Injection
Liver copper depletion
350
300
250
200
150
100
50
0Birth 56 days avg 205 days
Copper - ppm DM
Branum dissertation, 1999
Liver selenium depletion
Selenium – mg/kg DM
3
2
1
0150 days 200 days 250 days
SURE Trace Mineral Supply by Timed Injection
Arthington, et al. 2014 JAS
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Part 5Injectable Trace Mineral Supplementation for Cattle
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SURE Trace Mineral Supply by Timed Injection
Manganese
Selenium 5mg/ml
Copper 15mg/ml
provides Zinc, Copper, Manganese and Seleniumin a readily available injection
SURE Trace Mineral Supply by Timed Injection
SURE Trace Mineral Supply by Timed Injection
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SURE Trace Mineral Supply by Timed Injection
SURE Trace Mineral Supply by Timed Injection
With Injectable Multimin®90• You supplement every animal you inject• You provide supplementation quickly• You by-pass any antagonists• You target periods of high challenge and demand
for your cattle
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SURE Trace Mineral Supply by Timed Injection
Trace Minerals and Immunity• Immune system is complicated• Immune response demands trace minerals
rapidly provides available key trace minerals primes cattle to respond to vaccine & challenge
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SURE Trace Mineral Supply by Timed Injection
BQADesigned for either SQ injection
SURE Trace Mineral Supply by Timed Injection
11.43
13.82
8.675 7.557
10.8210.68
7.303
10.45
9.321 8.662
13.83
7.5
10.75
8.347 7.972
%PB
MC
TX 1
TX 2
TX 3
MLV + ITMMLV+ Sal
Control
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16
14
12
10
8
6-7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Days relative to the day of BVDV-2 inoculation
Shipping MLV BVDV-2 inoculation
P< 0.001
P= 0.0712.63
CD8 T Lymphocytes (Cytotoxic T cells)
Fig 11. Effect of ITM + MLV vaccine on CD8 T cell population after BVDV-2 inoculation
ITM helped mitigating the decrease of CD8+ T cells caused by BVDV15.66
15.18
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BOTTOM LINE
• Multimin®90 has been researched with several vaccines• Cattle has been shown to mount improved humoral and
cmi earlier• Several studies indicated increased proportions of
populations showing improved responses to BVDVvaccination
• Several studies have NOW shown improved clinicalprotection from BVDV challenge compared to vaccinealone
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VACCINES ADMINESTERED CONCURRENTLY WITH MULTIMIN®
• COVEXIN8• PYRAMID5• PRESPONSE SQ• TITANIUM 5• KILLED ANTIGEN• EXPRESS 5• ONCE PMH SQ• VISION 7• VISION 7 SOMNUS• BOVISHIELD GOLD 5• NUPLURA PH
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SURE Trace Mineral Supply by Timed Injection
?
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