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INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
3
INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
4
FACTORS INFLUENCING DISEASES IN ANIMALS AND CONSUMERS
PROBLEMS MAY OCCUR FROM START TO FINISH
GENETICS OF THE ANIMALCONTAMINATED RAW MATERIAL IN FEEDCONTAMINATION IN FEED PROCESSINGTRANSPORT AND STORAGE ON FARMNUTRITIONAL DEFICIENCIES OF FEEDMICROBIAL IMBALANCES IN THE ANIMALUNHYGIENIC FARM MANAGEMENTUNHYGIENIC SLAUGHTERHOUSE CONDITIONSTRANSPORT AND STORAGE AT THE DISTRIBUTORSTORAGE AND PROCESSING OF FOOD AT THE END-USER
PATHOGENS
THE FOOD CHAIN5
6
RAW MATERIALS
TRANSPORT
FEED COMPOUNDING
STORAGE AT MILL
TRANSPORT
STORAGE AT FARM
DISTRIBUTION ON FARM
CONSUMPTION BY ANIMAL
ANIMAL PERFORMANCE
ANIMAL
TRANSPORT
SLAUGHTER
MEAT
PACKAGING
STORAGE
TRANSPORT
RETAIL
STORAGE
CONSUMPTION
FACTORS INFLUENCING DISEASE IN ANIMALS
AND CONSUMERS
MAIN FOCUS IS THE HEALTH OF THE ANIMALS ON FARM
7
THE EVOLUTIONOF DISEASES
8
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1880 1997
OTHER DISEASES
INFECTIOUS AND PARASITIC DISEASES
DISEASES OF THE RESPIRATORY SYSTEM
DISEASES OF THE CIRCULATORY SYSTEM
NEOPLASM (CANCERS)
CAUSES OF DEATH IN ENGLAND AND WALES: 1880 AND 1997
THE EVOLUTION OF DISEASES
9
RISK FACTORS
SANITARY CONDITIONS
LITTER QUALITY TURNOVER TIME
DRINKING MANAGEMENT CLEANINGFACILITIES BACTERIAL CONTAMINATION
GENETICS
BREEDING
VACCINE CHALLENGE
DENSITY STRESS POOR IMMUNITY
DIETARY CHANGE
SEASON
NUTRITION
HIGH NUTRIENTDENSITY DIETS
DIGESTIBILITY PARTICLE SIZE
TYPE OF CEREALS
TOXINS
MICROBIALIMBALANCE
9
10
THE KEY OBJECTIVES IN ANIMAL HUSBANDRY
OPTIMISE THE EFFICIENCY OF FOOD PRODUCTION
PREVENT DISEASES
ANTIBIOTICS WERE USED INPREVENTION AND IN THERAPY
BUT………
1111
12
FEED ADDITIVES
1970 2006 2008 2012
ADDITIVES AUTHORISED
ANTIBIOTICGROWTH PROMOTERSBANNED
INCREASED USE OF VETERINARY MEDICINAL ANTIBIOTICS
COCCIDIOSTATSAND HISTOMONOSTATSTO BE BANNED?
VMP ONLYNUTRITIONALADDITIVESCHANGE FROMFEEDSTUFFS REGULATIONTO FEED ADDITIVES E.G. AMINO ACIDS
13
20.5
21
21.5
22
22.5
23
23.5
1150
1200
1250
1300
1350
1400
1999 2000 2001 2002 2003 2004 2005 2006 2007
BAN
USE OF ANITBIOTICS IN FRANCE (TONS)FEED PRODUCTION (MILLION TONS)
SOURCE: AGENCE FRANÇAISE DE SECURITE SANITAIRE DES ALIMENTS – AFSSA + FEFAC
14
USE OF ANTIBIOTICS IN FRANCE
AMINOGLYCOSIDES ± 5%ß-LACTAMINES ± 8%CEPHALOSPORINES < 1%OTHERS < 2%FLUOROQUINOLONES < 1%FURANES < 1%MACROLIDES 7%PHENICOLES < 1%POLYPEPTIDES 5%QUINOLONES < 2%SULPHONAMIDES ± 16%TETRACYCLINES ± 50%TRIMETHOPRIMES < 3%
SOURCE: AGENCE FRANÇAISE DE SECURITE SANITAIRE DES ALIMENTS – AFSSA
15
1930 1940 1950 1960 1970 1980 1990 2000
SULPHONAMIDES 1935 - 1950
PENICILLIN 1942 - 1946
STREPTOMYCINE 1943 - 1957
CHLORAMPHENICOL 1946 - 1957
TETRACYCLINE 1948 - 1953
ERYTHROMYCINE 1952 - 1988
VANCOMYCINE 1957 - 1987
METICILLIN 1960 - 1962
AMPICILLIN 1963 - 1973
CEPHALOSPORINES 1961 - 1969
LINEZOID 2000 - 2002
DAPTOMYCINE 2003 - 2005
TIME BETWEEN 1ST MARKETING AND 1ST RESISTANCE
SOURCE: SCIENCE & VIE
16
BALANCED HEALTHY ANIMAL/ HUMAN BEING
IMBALANCED UNHEALTHY ANIMAL/ HUMAN BEING
PATHOGENS
TREATMENT
PATHOGENS
THERAPEUTIC TREATMENTTREATED
BALANCED HEALTHY ANIMAL/ HUMAN BEING
GENERAL PERCEPTION: WHEN ILL TAKE MEDICINE
1717
BALANCED HEALTHY ANIMAL/ HUMAN BEING
PREVENTIVETREATMENT
(BALANCED) HEALTHY ANIMAL/ HUMAN BEING
PREVENTIVETREATMENT
PATHOGENS
BALANCED HEALTHY ANIMAL/ HUMAN BEING
PREVENTIVE TREATMENT
PREVENTIVETREATMENT
PATHOGENS
PREVENTIVE TREATMENT NOT WORKINGGENERAL PERCEPTION: WHEN NOT ILL PREVENTION IS ONLY A FEEBLE INSURRANCE POLICY
18
SO WHO OR WHAT ARETHOSE PATHOGENS
AND WHERE DO THEY COME FROM?
19
STROMATOLITES OF FOSSILIZED OXYGEN-PRODUCING CYANOBACTERIA HAVE BEEN FOUND FROM 2.8 BILLION YEARS AGO, POSSIBLY AS OLD AS 3.5 BILLION YEARS AGO.
Pre-Cambrian stromatolites in the Glacier National Park, Montana
THE OLDEST ORGANISMS ON EARTH
http://upload.wikimedia.org/wikipedia/commons/c/c0/Stromatolites.jpghttp://upload.wikimedia.org/wikipedia/commons/c/c0/Stromatolites.jpg
20
COST VERSUS EFFICACY
PARAMETERS TO CONSIDER
COST OF RAW MATERIALSCOST OF PRODUCTIONCOST OF DISTRIBUTION
IMPROVEMENTOBTAINED IN
VALUE
PERCEIVED OR ACTUAL
21
PRODUCTS IN PREVENTING DISEASEIN ANIMAL HUSBANDRY
ORGANIC ACIDS
PREBIOTICSOLIGOSACCHARIDES
PROBIOTICSYEASTSBACTERIA
PHYTO-THERAPEUTICSPLANT EXTRACTSESSENTIAL OILS
NUCLEOTIDES
NUTRIGENOMICS
THE TENDENCY IN EUROPE IS TO REPLACE ANTIBIOTIC GROWTHPROMOTERS BY A WHOLE RANGE OF PRODUCTS.
22
INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
23
ORGANIC ACIDS
ORGANIC ACIDS ARE USED SINCE THE EARLY DAYS OF INTENSIVE ANIMAL HUSBANDRY
SOME OF THE KEY ACIDS ARE:ACETICBENZOICFORMICFUMARICLACTICPROPIONIC
COMBINATIONS OF THE ABOVE AND THEIR RESPECTIVE SALTS
LET’S HAVE A LOOK AT SOME OF THE HISTORY
24
ACCORDING TO SHENNONG’S HERB CLASSIC, VINEGAR WAS INVENTED IN CHINA DURING THE XIA DYNASTY, AROUND 2000 BC.
SHENNONG TASTING HERBS TO DISCOVER THEIR QUALITIES
IN THE 8TH CENTURY THE MUSLIM ALCHEMIST JABIR IBN HAYYAN (GEBER) WAS THE FIRST TO CONCENTRATE ACETIC ACID FROM VINEGAR THROUGH DISTILLATION.
15TH-CENTURY EUROPEAN PORTRAIT OF "GEBER", CODICI ASHBURNHAMIANI1166, BIBLIOTECA MEDICEA LAURENZIANA, FLORENCE
HISTORY
http://upload.wikimedia.org/wikipedia/commons/c/c5/Shennong3.jpghttp://en.wikipedia.org/wiki/Shennonghttp://en.wikipedia.org/wiki/File:Jabir_ibn_Hayyan.jpg
25
HISTORY
26
HISTORY
27
BENZOIC ACID WAS DISCOVERED IN THE 16TH CENTURY. THE DRY DISTILLATION OF GUM BENZOIN FIRST DESCRIBED BY NOSTRADAMUS (1556).
GUM BENZOIN IS A BASLAMIC RESIN DERVIED FROM THE BARK OF DIFFERENT TREES OF THE GENUS STYRAX.
MICHEL DE NOSTREDAME
NOSTRADAMUS: ORIGINAL PORTRAIT BY HIS SON CESAR
(STYRAX BENZOIN) PARTS DRAWING.FRANZ EUGEN KÖHLER:
KÖHLER'S MEDIZINAL-PFLANZENIN NATURGETREUEN ABBILDUNGEN, ETC. (1887)
HISTORY
http://en.wikipedia.org/wiki/File:Koeh-133.jpghttp://en.wikipedia.org/wiki/Styrax_benzoinhttp://en.wikipedia.org/wiki/Styrax_benzoinhttp://en.wikipedia.org/wiki/Styrax_benzoinhttp://en.wikipedia.org/wiki/Franz_Eugen_K%C3%B6hlerhttp://en.wikipedia.org/wiki/Franz_Eugen_K%C3%B6hlerhttp://en.wikipedia.org/wiki/Franz_Eugen_K%C3%B6hlerhttp://en.wikipedia.org/wiki/Franz_Eugen_K%C3%B6hlerhttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plants
28
ORGANIC ACIDS
ORGANIC ACIDS ARE PRIMARILY USED IN PIG DIETS, WHEREBY THE ACIDS LOWER THE pH OF THE GUT, HENCE CREATING AN ENVIRONMENT WHICH DISCOURAGES THE GROWTH OFPATHOGENS
KEY ISSUES THE COMPANIES SELLING THESE PRODUCTS (SINGLE ORCOMBINED) HAVE AUTHORISED THESE AS TECHNOLOGICALFEED ADDITIVES WHILST THEIR MARKTING IS TO PROMOTETHEM AS ZOOTECHNICAL FEED ADDITIVES
THIS YEAR ALL DOSSIERS FOR ORGANIC ACIDS AS PRESERVATIVESWILL BE SUBMITTED TO EFSA BEFORE 8 NOVEMBER
29
LND: LOWER NUTRIENT DENSITY
BROILER TRIAL CONDUCTED IN TURKEYSPONSOR: BIOMIN
RESULTS IN THE FIELD
PIG TRIAL CONDUCTED IN ROMANIASPONSOR: BIOMIN
30
0
50
100
150
200
250
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
EUROPE
WORLDWIDE
FORMIC ACID SALES IN ANIMAL HUSBANDRY($ MILLIONS)
USE OF FORMIC ACID IN ANIMAL HUSBANDRY
APPROX. 40 000 TONS IN 2010
31
INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
PREBIOTICS AND PROBIOTICS
32
PREBIOTICS
PROBIOTICS
VIABLE VBNC* INACTIVATED COMPETITIVECELLS CELLS ** EXCLUSION
*VBNC = VIABLE BUT NON-CULTURABLE; ** CONSIDERED AS A RAW MATERIAL IN THE EU
OLIGOSACCHARIDES (FOS, MOS)
33
PREBIOTICS AND PROBIOTICS
PRE- AND PROBIOTICS ARE USEDIN ALL ANIMAL DIETS, MAINTAINING AN IMPROVED GUT MICROFLORA ANDCONSEQUENTLY BETTER GROWTH PERFORMANCES
KEY ISSUES IN THE 90 ‘S NUMEROUS PROBIOTICS WEREINTRODUCED IN A ME-TOO FASHION, CREATING A NEGATIVE IMAGE
IN THE LAST DECADE MORE SCIENTIFIC WORK WAS CONDUCTED .THE WORLDWIDE MARKET INCLUDING PRE- /PROBIOTICS + YEAST CELL WALLS (FEED INGREDIENT ACCORDING TO 767/2009)IS NOW OF THE ORDER OF WELL OVER US$ 1.5 BILLION
34
MARCEL ROBERFROID IN 1995
STUDIES HAVE DEMONSTRATED POSITIVE EFFECTS ON CALCIUM AND OTHER MINERAL ABSORPTION, IMMUNE SYSTEM EFFECTIVENESS, BOWEL pH, REDUCTION OF COLORECTAL CANCER RISK, INFLAMMATORY BOWEL DISORDERS (CROHN'S DISEASE AND ULCERATIVE COLITIS) HYPERTENSION (HIGH BLOOD PRESSURE) AND INTESTINAL REGULARITY.
PREBIOTICS
35
MODE OF ACTION OF OLIGOSACCHARIDES
36
PROBIOTICS
HISTORYELIE METCHNIKOFF, NOBEL PRIZE WINNER IN 1908 WAS THE FIRST PERSON TO INTRODUCE THE CONCEPT OF REPLACING HARMFUL BACTERIA BY USEFUL ONES
IN THE INTESTINE
MOREOVER HE PROPOSED THE CONSUMPTIONOF FERMENTED MILK CONTAINING LACTIC ACIDBACTERIA AND LOWERING THE INTESTINAL pH.
37
QPS granted micro-organisms
Bifidobacterium adolescentisBifidobacterium animalisBifidobacterium bifidumBifidobacterium breveBifidobacterium longum
Lactobacillus acidophilusLactobacillus amylolyticusLactobacillus amylovorusLactobacillus alimentariusLactobacillus aviariesLactobacillus brevisLactobacillus buchneriLactobacillus casei **Lactobacillus coryniformisLactobacillus crispatusLactobacillus curvatusLactobacillus delbrueckiiLactobacillus farciminisLactobacillus fermentumLactobacillus gallinarumLactobacillus gasseriLactobacillus helveticusLactobacillus hilgardiiLactobacillus johnsoniiLactobacillus kefiranofaciensLactobacillus kefiriLactobacillus mucosaeLactobacillus panisLactobacillus paracaseiLactobacillus paraplantarumLactobacillus pentosusLactobacillus plantarumLactobacillus pontisLactobacillus reuteriLactobacillus rhamnosusLactobacillus sakeiLactobacillus salivariusLactobacillus sanfranciscensis
Lactococcus lactis
Leuconostoc citreumLeuconostoc lactis Leuconostoc mesenteroides
Pediococcus acidilacticiPediococcus dextrinicusPediococcus pentosaceus
Propionibacterium. Freudenreichii
Streptococcus Thermophilus
Bacillus amyloliquefaciensBacillus atrophaeusBacillus clausiiBacillus coagulansBacillus fusiformisBacillus lentusBacillus licheniformisBacillus megateriumBacillus mojavensisBacillus pumilusBacillus subtilisBacillus vallismortisGeobacillus stearothermophillus
Debaryomyces hanseniiHanseniaspora uvarumKluyveromyces lactis Kluyveromyces marxianusPichia angustaPichia anomala Pichia jadinii.Saccharomyces bayanusSaccharomyces cerevisiae Saccharomyces pastorianus(synonym of Saccharomycescarlsbergensis)
38QPS: Qualified Presumption of safety
39
MODE OF ACTIONOF PROBIOTICS
NUTRITIONAL EFFECT
REDUCTION OF METABOLIC REACTIONS THAT PRODUCES TOXIC SUBSTANCESSTIMULATION OF INDIGENOUS ENZYMESPRODUCTION OF VITAMINS OR ANTIMICROBIAL SUBSTANCES
SANITARY EFFECT
INCREASE IN COLONISATION RESISTANCESTIMULATION OF THE IMMUNE SYSTEM
40
VIABLE BUT NON CULTURABLE BACTERIAMODE OF ACTION OF SORBIFLORE®
Metabolites produced byLactobacillus farciminis
andLactobacillus rhamnosus
Bacteriocin-likesubstances
Polysaccharides
Organic acids(Lactic & Acetic acid)
Hydrogen peroxide
Bacterial cellwalls
EnzymesLipolytic, esterolytic
amylolytic, andcellulolytic
Amino acidsand
vitamins
Anti-microbial activity Nutritional Immune stimulation
41
LACTOBACILLUS RHAMNOSUS ADHERES TO THE GUT WALL, HENCE PROVIDING A BARRIER
41
42
21.4
21.6
21.8
22
22.2
22.4
22.6
22.8
23
23.2
23.4
42 days
Control
Treated
365
370
375
380
385
390
395
400
405
410
415
42 days
Control
Treated
RESULTS IN PIGLETS
BODY WEIGHT (KG)
ADG (G)
43
2950
3000
3050
3100
3150
3200
3250
3300
3350
3400
3450
3500
49 days
Control
Treatment
BODY WEIGHT (KG)
27000 BROILERS PER TREATMENT49 DAYS
CELLS CONTACT BETWEEN LACTOBACILLI AND SPIROCHAETES
44
45
BRACHYSPIRA AND ITS EFFECT IN ANIMAL HUSBANDRY
BRACHYSPIRAAND EGG DROP SYNDROME
BRACHYSPIRA
BRACHYSPIRAAND DIARRHOEA IN PIGS
46
SACCHAROMYCES CEREVISIAE
47
RESULTS IN PIGLETSBODY WEIGHT (KG)
ADG AND FCR WERE ALSO SIGNIFICANTLY DIFFERENT
TRIAL WITH SACCHAROMYCES CEREVISAE
0
5
10
15
20
25
DAY 0 DAY 42
CONTROL
TREATMENT
4848
COMPETITIVE EXCLUSION
GEORGII FRANTSEVICH GAUSE
IN 1932, GAUSE PUBLISHED WHAT HAS BECOME KNOWN AS THE COMPETITIVE EXCLUSION PRINCIPLE
TWO SPECIES COMPETING FOR THE SAME RESOURCES CANNOT STABLY COEXIST
49
COMPETITIVE EXCLUSION
50
COMPETITIVE EXCLUSION
ANIMAL SPECIES PRODUCT DESCRIPTION USAGE/CLAIM TYPE
ACC TO EU
BEEF CATTLE Bovamine Lactobacillusacidophilus
Reduces Escherichia coli O157:H7
Probiotic
Probiotic
DAIRY CATTLE LiveBac Dried extract from yeast and bacterial fermentation
Reduces acidosis Probiotic
Raw material
LactoEdge L. acidophilus, Saccharomyces cerevisiae,MOS
Prevention of scours in calves
Competitive exclusion; probiotic; prebiotic
Probiotic + prebiotic
PRODUCTS ON THE USA MARKET
52
ANIMAL SPECIES PRODUCT DESCRIPTION USAGE/CLAIM TYPE
ACC TO EU
POULTRY Aviguard Freeze-dried product from healthy pathogen-free chickens
Protection against E. coli, Salmonella, Clostridia
Competitive exclusion
Competitive exclusion
Fastrack S. cerevisiae, Enterococcus faecium, L. acidophilus, amylase from Bacillus subtilis and Aspergillus oryzae, protease from B. subtilis, FOS
Performance and immune stimulation
Probiotic
Probiotic, zootechnical additives (enzymes) + prebiotic
PRODUCTS ON THE USA MARKET
53
ANIMAL SPECIES PRODUCT DESCRIPTION USAGE/CLAIM TYPE
ACC TO EU
PIG Biofeed Mixed bacteria and antibodies
Reduction of diarrhoea
Probiotic
Not accepted
Premidex Modified starch Improved performance and decreased pathogen colonisation
Prebiotic
If no GMO -> raw materialIf GMO possibly a zootechnical additive
PRODUCTS ON THE USA MARKET
54
INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
55
ESSENTIAL OILS AND PLANT EXTRACTS
PHYTO THERAPEUTICS HAVE BEEN USED FOR CENTURIES PRIMARILY IN HUMAN MEDICINE
IN THE EU THEY FALL UNDER THE CATEGORY OF “SENSORY ADDITIVES”
SINCE THE BEGINNING OF THIS CENTURY THEY BECAMEMORE COMMON IN ANIMAL HUSBANDRY
SOME ISSUES ARE: • THE EU LEGISLATION• ITS MODE OF ACTION• A LOT OF ME-TOO PRODUCERS
56
THE HISTORY OF PLANT EXTRACTS
GINGER EXTRACTS WERE USED TO ALLEVIATE ALIMENTARY TRACT PROBLEMSTHE BRITISH PHARMACOPOEIA IN 1885 CONTAINED MORE PLANT DERIVED PRODUCTSTHAN CHEMICALLY SYNTHESIZED
57
THE ASSYRIANS IN 8TH CENTURY BC USED A MIXTURE OF BELLADONNA,CANNABIS AND MANDRAKE ROOT (NIGHTSHADES – SOLANACEAE)AS PAINKILLER
THE HISTORY OF PLANT EXTRACTS
http://upload.wikimedia.org/wikipedia/commons/7/79/Cannabis_sativa_Koehler_drawing.jpghttp://en.wikipedia.org/wiki/File:Mandrake-roots.jpghttp://upload.wikimedia.org/wikipedia/commons/2/2b/Koeh-018.jpg
58
THE VEDIC TEXTS (VEDAS IN SANSKRIT = KNOWLEDGE) DATED 2ND – 1ST MILLENIUM BCLISTS 700 SUBSTANCES INCLUDINGCINNAMON, GINGER, CORIANDER, ETC.ALL THESE PRODUCTS ARE NOW USED INPHYTO-THERAPEUTICS
THE HISTORY OF PLANT EXTRACTS
http://upload.wikimedia.org/wikipedia/commons/e/ed/Koeh-193.jpghttp://upload.wikimedia.org/wikipedia/commons/e/e1/Cinnamomum_verum1.jpg
59
THE EU LEGISLATION
THEY ARE CLASSIFIED AS “SENSORY” ADDITIVES
NO CLAIM TO GROWTH PERFORMANCE
THE COMPLEX NATURE OF ONE OR MOREACTIVE INGREDIENTS
MAKES IT DIFFICULT TO PRODUCE A DOSSIERFOR A ZOOTECHNICAL ADDITIVE, ESPECIALLY THE PART CONCERNING SAFETY
EXAMPLE ON SUBSEQUENT SLIDES
Choleretic effect (increases biliary secretion and lipids release).
Foie
Artichoke Cynarin Boldo
Diuretic, choleretic and antioxidant effect
Boldin
RosemaryRosmarinic acid
Milk thistle
Silymarin (silybin)
Lipotropic effect and cellular protection of hepatocyt
Detoxifying (increases Glutathion-S-transferase activity)
PLANT EXTRACTS HAVING AN EFFECT UPONLIVER METABOLISM IN DAIRY
60
61
Artichoke
Cynarin
HPLC chromatogram
of the determination of the cynarin
content
Active component:
COMPONENTS OF THE PRODUCT
Rosemary
Active component: HPLC chromatogram
of the determination of the
rosmarinic acid content
COMPONENTS OF THE PRODUCT
62
63
milk thistle
Silymarin (a blend of 3 isomers)
and derivatives
Active component:
HPLC chromatogram
of the determination of the
silymarin content
COMPONENTS OF THE PRODUCT
Boldo
Boldine
Active component:
HPLC chromatogram
of the determination of the boldine
content
COMPONENTS OF THE PRODUCT
64
65
MEASURABLE RESULTS
IMPROVEMENT OF LIVER FUNCTIONS
REDUCTION OF SANITARY PROBLEMS AND INFERTILITY
Frequency of sanitary troubles
specific to steatosis
35.3%
17.1%
0%
10%
20%
30%
40%
interval calving- fertilizing insemination
122
106
95
100
105
110
115
120
125Reduction
by 50%
2 weeks improvement
Reduction of NEFA ( *) for cows
with high steatosis
-0.32
-0.48
-0.7-0.6-0.5-0.4
-0.3-0.2-0.10.0
Reduction of ketones ( **) for
cows with high steatosis
-0.25
-0.66-0.7-0.6-0.5-0.4-0.3-0.2-0.10.0
mmol / lmmol / l
Reduction of biliary acids for cows
with high steatosis
15.42
-26.30-30
-20
-10
0
10
20
µ mol / l
(*) : NEFA = Non Esterified Fatty Acids, one of the main parameters of steatosis.
(**) : Ketonic bodies are produced by free fatty acids . B OHC4 (beta hydroxy butyrate) is measured.
Results obtained by animals with high steatosis.
Control
Treated
days
•
PLANT EXTRACTS HAVING AN EFFECT UPONNECROTIC ENTERITIS IN BROILERS
MODE OF ACTION
INCREASED PERMEABILITY OF THE MEMBRANE
MODIFICATION OF THE ENZYMATIC ACTIVITY
EFFECT UPON MITCHONDRIA
66
ELECTRON MICROSCOPY REVEALS THAT THE MEMBRANE IS ATTACKED
C. albicans treated with 800 g/ml of cinnamaldehyde
Candida albicans (control)
C. albicans treated with 600 g/ml of cinnamaldehyde
GAP FORMATION AND STRUCTURAL MODIFICATION OF CELL WALL
CANDIDA ALBICANS WITH SEM*: EXTERNAL OBSERVATIONS
INCREASED PERMEABILITY OF THE MEMBRANE
SEM: SCANNING ELECTRON MICROSCOPY 67
SEPARATION OF PLASMA MEMBRANE
reservesNucleus
Cell wall
C. ALBICANS TREATED WITH 500 G/ML OF CINNAMALDEHYDE
CONTROL
CANDIDA ALBICANS WITH TEM*: INTERNAL OBSERVATIONS
INCREASED PERMEABILITY OF THE MEMBRANE
TEM: TRANSMISSION ELECTRON MICROSCOPY 68
DRASTIC INHIBITION OF ENZYMATIC ACTIVITIES
BIOCHEMICAL MODIFICATIONS
MODIFICATION OF ENZYMATIC PROFILE
MODIFICATION OF THE ENZYMATIC ACTIVITY
69
EFFECT OF CNMA ON THE MEMBRANE POTENTIAL OF B. CEREUSWITH GLUCOSE (GLU), NIGERICIN (NIG).
PERMEABILITY OF MEMBRANE IS AFFECTED WITH INCREASED LEVELS OF CNMA
MODIFICATION OF THE ENZYMATIC ACTIVITY
BIOCHEMICAL MODIFICATIONS
MODIFICATION MEMBRANE PERMEABILITY
70
CNMA: CINNAMALDEHYDE
MODIFICATION OF GLUCOSE PERMEABILITY
DECREASE OF ATP SYNTHESIS IN MITOCHONDRIA
ADP
ATP
EFFECTS OF AEN ON PLASMA MEMBRANE
EFFECT UPON MITOCHONDRIA
71
72
OVERALL RESULTS
EuronutritionFrance – 2002Trial AEN 700 at 500 g/Tonne
RESULTS
1580
1590
1600
1610
1620
1630
1640
1650
1660
1670
1680
Control AEN 350
Weight
1.78
1.8
1.82
1.84
1.86
1.88
1.9
1.92
1.94
Control AEN 350
Feed conversion
73
INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
74
NUCLEOTIDESNUCLEOTIDES ARE USED IN SOME PIG, HORSE DIETS, BUT PRIMARILY IN FISH.SOME WORK SHOWS PROLONGATION OF THE VILLIHENCE INDIRECT STIMULATION OF THE IMMUNE-SYSTEM
KEY ISSUES EXPENSIVE AND THE RESULTS ARE NOT ALWAYS OBVIOUS
URIDINE
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THE USE OF NUCLEOTIDES IN FEED CAN RESULT IN SIGNIFICANT DIFFERENCES IN VILLILENGTH WITH 28 DAY OLD PIGLETS.
Xavier Córdoba, Elisabet Borda, Daniel Martínez-Puig and GerardHinojo, Bioiberica, Spain
THE EFFECT OF NUCLEOTIDES UPON PIGLETS
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THE EFFECT OF NUCLEOTIDES UPON PIGLETS
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THE EFFECT OF NUCLEOTIDES UPON PIGLETS
Providing a nucleotide-enriched prestarter diet to piglets aged between 21 and 35 days,produced animals in which productive effects could be observed in the starter diet period of35-56 days of age, when the diet no longer contained nucleotides.Nucleotides improve the production parameters of animals by enhancing the development ofthe immune system and the intestinal mucosa of piglets, reducing the stress and delays thatthe animals may suffer as a result of various diseases or post-weaning stress. Furthermore, theeffect of nucleotides is long-lasting, in that they develop important tissues such as those of theimmune system and the intestinal mucosa.
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THE EFFECT OF NUCLEOTIDES UPON FISH
VANNAGEN ENHANCES THE PERFORMANCE OF ASIAN SEA BASS
UNIT CONTROL TREATMENT CONTROL = 100%
INITIAL WEIGHT g 34.4 34.4
FINAL WEIGHT g 252.1 275.7
WEIGHT GAIN g 217.8 241.3 110.8
DAILY WEIGHT GAIN g 2.27 2.51 110.7
FCR 2.60 2.01 77.3
TRIAL PERIOD 96 DAYS
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INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
NUTRIGENOMICS
• Study of molecular
relationships between genes
• Responses to specific biologically active nutrients
• Relationships that impact animal health and performance
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MICROARRAY TECHNOLOGY
• Discovered nutrients & compounds can “turn on” or “turn off” genes & gene expression
• Gene regulation impacts health of the animal
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Healthy Immune System
• Benefits
– Reduced mastitis
– Reduced metritis
– Lower somatic cell counts
– Less death loss
– Fewer culls
– Better reproduction efficiency
– Increased milk production
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Mode of Action
• OmniGen-AF is a proprietary formulation of specific biologically active nutrients that modulate the genetic expression of genes responsible for cellular health
• Normalize innate immune function– Increased neutrophil migration to infection site– Improved neutrophil killing capabilities
• Adaptive immune system modulation is under investigation
• Improved immune function can reduce disease & improve performance– Less mastitis – More milk
production– Reduced SCC – Better
reproduction– Less metritis– Lower death lose
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Powerful medicineThe Immune System
• It’s more cost effective to prevent disease than to treat it.
• The most powerful medicine is the cows own immune system
• Immune system has two parts
– Adaptive Immunity
– Innate Immunity (OmniGen-AF)
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Adaptive Immunity
– Very specific
– Long lasting
– Days or weeks to develop
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Innate Immune System
• Immediate response to invading organisms and infections
• Non-specific
– Bacteria
– Viruses
– Molds
– parasites
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Multi-Layered Protection• Skin• Epithelial linings
in gut and lungs• GI tract acids
and enzymes• Blood components
(white blood cells)– Neutrophils– Macrophagess– Dendritic cells
• Identify and kill pathogens until adaptive immune system is established
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Role of Macrophages • Monitor for all
invading pathogens
• Inhabit the alveolus in mammary gland
• Detection releases cytokines and chemokines into capillaries
• Signal Neutrophils moving through capillaries to stop and migrate to area
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Role of Neutrophils
• Neutrophils detect chemical and hormonal signals from Macrophages
• Neutrophils tether to the capillary wall using L-selectin
• They squeeze through capillary wall and enter mammary gland to find pathogens
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Phagocytosis
• Neutrophils
– identify pathogens
– engulf them
– destroy them with enzymes or reactive oxygen species (ROS)
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Summary
• OmniGen-AF is a proprietary blend of biologically active nutrients that support the innate immune system
• Prince has conducted approximately 170 trials demonstrating mode of action and benefits of feeding OmniGen-AF
• The benefits of a properly functioning immune system are numerous
– Reduced mastitis– Reduced metritis– Lower somatic cell counts– Less death loss– Fewer culls– Better reproduction efficiency– Increased milk production
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INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
93
QUORUM SENSING
9393
N-ACETYL HOMOSERINE LACTONE (AHL)
ACTIVATION TRANSCRIPTIONOF CERTAIN GENES
INDUCTION SYNTHESIS
FORMATION OF BIOFILM DISEASE
94
QUORUM SENSING
9595
QUORUM SENSING
N-ACETYL HOMOSERINE LACTONE (AHL)
ACTIVATION TRANSCRIPTIONOF CERTAIN GENES
INDUCTION SYNTHESIS
FORMATION OF BIOFILM DISEASE
QUORUM QUENCHING
96
INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
9797
LACTOCEUTICALSLACTOFERRIN AND LACTOPEROXIDASE ARE POTENT ANTIMICROBIAL AGENTS AND FOUND IN HUMANSIN MANY DIFFERENT BODY FLUIDS
LACTOFERRIN
USED IN ASIA IN INFANTMILK, IN COSMETICS,AS PRESERVATIVE ANDANTIOXIDANT
http://upload.wikimedia.org/wikipedia/commons/1/1f/Lactoferrin.png
98LACTOPEROXIDASE
LACTOCEUTICALS
H2O2 + SCN- OSCN- + H2O
PEROXIDE + THIOCYANATE HYPOCYANITE
LACTOPEROXIDASE
POWERFUL ANITMICROBIAL ACTION
USED TO PRESERVEFOODS, INCL. MEATMILK, VEGETABLES,ETC.
http://upload.wikimedia.org/wikipedia/commons/a/a2/Lactoperoxidase.png
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COULD THESE MOLECULES BE POTENTIALLY USED IN ANIMAL HUSBANDRY?
ONE OF THE LEADING DAIRY COMPANIES IN JAPAN, MORINAGA LOOKED AT THE POSSIBILITY TO USE THESE MOLECULES IN ANIMAL HUSBANDRY INTHE MID 90’S.
AT THE TIME THE MANUFACTURING COST WAS TOO HIGH
PRESENTLY LACTOFERRIN IS PRODUCED IN SEVERAL WAYS
hrLACTOFERRIN VIA TRANSGENIC COWS IN THE USAbLACTOFERRIN FOR THE USE IN INFANT MILK
hr: HUMAN RECOMBINANT; b: BOVINE
100
INTRODUCTION
ORGANIC ACIDS
PREBIOTICS AND PROBIOTICS
PHYTO-THERAPEUTICS
NUCLEOTIDES
NUTRIGENOMICS
QUORUM SENSING
LACTOCEUTICALS
AFTERTHOUGHTS
THE PREVENTION OF DISEASES IN FARM ANIMALS
101CYANOBACTERIA IN LAKE ATITLÁN, GUATEMALA
THE OLDEST LIVING ORGANISM VERSUS THE YOUNGEST
WE ARE FIGHTING THE OLDEST KNOWN ORGANISMSWITH TOOLS WE DEVELOPED IN THE LAST CENTURY ONLY
THESE ORGANISMS HAVE BEEN ABLE TO ADAPTTO THE MOST PRECARIOUS CONDITIONS FOR OVER2 BILLIONS OF YEARS
http://upload.wikimedia.org/wikipedia/commons/1/11/Harmful_Bloom_in_Lake_Atitl%C3%A1n,_Guatemala.jpg
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THE FUTURE
QUORUM QUENCHING
GMO ANIMALS – DISEASE FREE
GMO CROPS – USED AS PREVENTIVE MEDICATION
NUTRIENTS ACTING UPON ATP-RECEPTORS
LACTOCEUTICALS
DESIGNER PREVENTIVE DRUGS
NANOTECHNOLOGY
103
WHAT ARE THE HURDLES FORINNOVATION IN THE EU?
104104
105
THE MAJORITYARE ME-TOO COPIERS
THE REST SLEEPS
ORIGINALITYAND SCIENTIFICALLY BASEDPRODUCERS
HIGHLOW
PRODUCERS
FEW COMPANIESHAVE THE OVERALL
SKILLS
106
THE ROAD OF DISCOVERIES IS LONG AND NEVER
ENDING
ALTHOUGH SOME DISEASES WILL BE A THING OF THE PASSED
WE WILL ALWAYS HAVE TO FACE NEWCHALLENGES
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