ASCOGEN

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ASCOGEN

• the natural choice
•  
•  
•  A unique natural feed supplement

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ASCOGEN

• Composition
• ASCOGEN is an optimally acting feed supplement.
• It is a powder made of natural substances.
• Its components play an essential role in the
  functions of cells. As a result increased overall
  resistance and an improved performance will be
  achieved.

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ASCOGEN

• The main active ingredients are
• RNA
• Nucleotides and precursors
• Specific organic acids
• Inactivated yeast

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ASCOGEN

• High performance is characterised by a quick cell
  proliferation.
• Most of the cells can produce the necessary
  molecules for the DNA and RNA for the cell
  division.
• This process however, is slow and requires high
  levels of energy.

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ASCOGEN

• But, by supplementing the cells with the
  constituent of DNA and RNA they can be more
  rapidly renewed and with lower energy
  requirements.

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ASCOGEN

• Nucleotides Mode of action
• Cell multiplication
• Cell division is central to life of all
  organisms. During the M-Phase all cell organelles
  are doubled and finally distributed between the
  two new sister cells.

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ASCOGEN
The multiplication of cells starts with a
doubling of the information stored in the DNA in
the cell nucleus during the interphase. This is
the longest part in the cell multiplication.
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ASCOGEN
The DNA is a linear sequence of nucleotides. A
typical DNA of one animal cell contains about
3x109 nucleotides and is about 1 meter long.
The basic constituents of DNA are nucleotides, as
amino acids are the building blocks of proteins.
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ASCOGEN
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ASCOGEN

• The production of nucleotides in the cells
  requires both time and energy

The synthesis of the purines in the cells is a
very complicated pro-cess and involves 14
different biochemical steps starting from
different amino acids (e.g. asparaginic acid,
glutaminic acid and glycine).
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ASCOGEN
The oral supplementation of nucleotides reduces
both energy and time for the cell proliferation
in the body.
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ASCOGEN

• Effect of the nucleotides on the proliferation
  of cells
• A normal DNA consists of about 3x109 nucleotides.
  
• It was assumed that all living cells are capable
  of covering their requirement for nucleotides by
  de novo synthesis. Studies revealed that in many
  tissues, except the liver, the requirement for
  nucleotides is covered not only by de Novo
  Synthesis but also by the Salvage Pathway.
• Important cells of the immune system, such as
  bone marrow cells, lymphocytes and erythrocytes
  are not able to syntheses the purines.

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ASCOGEN

• Other tissues, like intestinal mucosa cells, are
  not able to produce enough purines to cover their
  requirements.
• The nucleotides have an important function in all
  organs with a rapid cell multiplication, in
• Immuno-competent cells
• Gastrointestinal cells
• Cells of the intestinal flora
• Liver cells

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ASCOGEN

• Immune system and performance
• A strong immunity is of paramount importance for
  good health and performance in animals. Even a
  slight infection reduces the ability of the body
  to function at maximum performance. Therefore,
  good health and vigour is of greatest importance.
• The immune system is influenced continually
  either positively or negatively by a number of
  factors.

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ASCOGEN
Bacteria
Mycotoxins
Immune
Stress
Nutrition
System
Management
Viruses
Most of these factors are damaging to the immune
system and lead to immunosuppression, and
consequently to poor performance.
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ASCOGEN

• Immune system and stress
• Responses to stressful stimuli involve changes in
  the metabolic activity which results in a high
  biological cost. These may include both lower
  performance as well as changes in
  immuno-responsiveness.

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ASCOGEN

• Stress factors decrease the number of lymphocytes
• Damage to the immune system 
• Immunosuppression 
• Poor performance

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ASCOGEN

• Nutrition and immune system
• An adequate and well balanced diet is of most
  importance for the performance of animals.
• Exposure to disease-causing agent such as virus
  or bacteria does not always result in illness.
  The ultimate determining factor is the condition
  of the immune system. The more active and
  powerful the immune system, the less likely you
  are to contract disease.

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ASCOGEN

• The efficiency of the immune system depends
  greatly on the choices of nutrition.
• You can improve the immune systems response and
  power of animals
• by first being aware that one of the very
  important, but overlooked and neglected
  ingredients of the nutrition are the Nucleotides.

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ASCOGEN

• Effect of the nucleotides on the immune system
• Many investigations in animals and humans as
  described in various prestigious publications
  have shown that dietary supplementation of
  nucleotides has the following effects on the
  immune system

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ASCOGEN

• Effect on the humoral immunity
• Nucleotides accelerate the antibody production
• Increased resistance to challenge of bacterial
  and viral infections
• Lower mortality of infected animals.

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ASCOGEN

• Effect on the cellular immunity
• Acceleration of the proliferation of lymphocytes
• Reversal of malnutrition or starvation-induced
  immunosuppression
• Increase in natural killer (NK) cell activity and
  interleukin-2 production
• Increase in number of macrophages
• Increase in macrophage phagocytic activation
• Acceleration in bone marrow proliferation and
  peripheral neutrophil proliferation

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ASCOGEN

• Increase in resistance to pathogens
• Mortality of mice infected with 1 x 107
  Staphylococcus aureus
• Kulkarni et al, 1986
• Diet
• NF Basal diet (trace amounts of nucleotides)
• NFR Basal diet plus 0.25 RNA
• NFU Basal diet plus 0.06 Uracil

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ASCOGEN

• Results
•   No. of mice Mortality ()
• NF 15 100
• NFR 19 53
• NFU 19 58

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ASCOGEN

• General pathway of the immune response
• Foreign invader (i.e. virus, bacteria)
• RECOGNITION
• T-lymphocytes Macrophages
•  
• B-lymphocytes
•  
•  
• Cell division PROLIFERATION
•  
• B-lymphocytes T-lymphocytes CMI
  RESPONSE
• (cell mediated immune
  response)
• HUMORAL RESPONSE Plasma cells Activate
  Direct Macrophages
  intracellular
• Specific antibodies killing
• Invader destroyed ELIMINATION
•  
•  
• T and B Memory cells
  MEMORY

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ASCOGEN
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ASCOGEN

• Effects of nucleotides on the intestine
• Acceleration of growth and differentiation of the
  intestine and increase in the length of the
  villus
• Effect of nucleoside supplementation on
  intestinal morphometry
• Control Supplemented
• Number of animals 10 10
• Villus height (cells) 75 2.3 94
  4.7
• Muscle thickness (?m) 47.1 1.0 50.7
  3.3

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ASCOGEN

• Effects of nucleotides on the intestinal flora
• Dietary nucleotides stimulate the development of
  bifidobacteria in vivo.
• Riboflavin, nucleic acid bases and pyruvic acid
  are essential for the grow of Bifidobacterium
• Tanaka et al. 1980

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ASCOGEN

• Effects of riboflavin, nucleic acids and pyruvic
  acid on the growth of Bifidobacterium
•   No. of Not strains
  tested Supplemented Supplemented
• Bifidobacterias 162 114
  (70.4) 154 (95.1)

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ASCOGEN

• Effects on the liver
• Important organ
• The liver is one of the most important organs for
  maintaining the internal environment of the body.
• Significant damage can occur before clinical
  signs become apparent.
• Few animals die from hepatic disease, but many
  die with it.

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ASCOGEN

• Effects on recovery after liver injury
• Experiment
• Injection of 200 mg/kg galactosamine to induce
  liver injury
• Group S Standard total parenteral nutrition
  (TPN) with
• Glucose and amino acids
• Group OG Standard TPN with nucleoside/nucleotide
• Group U 1.2 g/kg uridine as a bolus dose

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ASCOGEN
The nucleotides have a protective effect on the
liver
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ASCOGEN

• Effects on detoxification of mycotoxins
• Effects of hepatoxins
• They cause degeneration, fat modifications,
  hemorrhage and necrosis in the liver. In some
  cases, hepatocytes and their nuclei are of
  abnormal size. Hyperplasia of bile ducts are
  often observed and some mycotoxins may induce
  haematoma.
• Acute toxicosis causes jaundice, hemolytic anemia
  and increased hepatic blood enzyme levels.
• Chronic toxicosis is characterized by low
  performance, impaired protein synthesis,
  hypoproteinemia, fibrosis and hepatic cirrhosis

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ASCOGEN

• Weight of the liver and mortality
• Average Mycotoxins Mycotoxins
  
• over 5 years during 3 month during 3
  month
• (DON, DAS F2) (DON, DAS, F2)
• 
  Nucleotides
• Liver weight 300 g 110 g
  320 g
• Mortality 4.2 12.1
  4.1

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ASCOGEN

• Effects on recovery from stress
• Nucleotide supplemented animals have significant
  lower creatine kinase, lactate dehydrogenase and
  aspartate animotransferase levels after stress
  than animals fed standard diet.

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ASCOGEN

• Dr. Zomborsky et al., 1995
• Animals 20 Norwegian Landrace Pigs in two
  identical groups
• Feeding Last 30 days of fattening
• Control animals standard pig feed
• Trial animals Standard pig feed
  supplemented
• with nucleotide mixture
• Stress Transport and slaughter set-up
• Blood samples 1. sample Two days before
  slaughter
• 2. sample during slaughter

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ASCOGEN

• Trial group Control group
• CK (U/L) 1. sample 206 225 2.
  sample 458 980
• LDH (U/L) 1. sample 641 766 2.
  sample 468 gt1600
• AST (U/L) 1. sample 20 23 2. sample 17 67

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ASCOGEN

• Effects on the lipid metabolism
• Effect on the metabolism of long chain
  polyunsaturated fatty acids (PUFA)
• Dietary nucleotides increase ?3 and ?6 PUFA in
  the lipids of the plasma and erythrocyte membrane
  in neonatal animals (Gil et al. 1985 Delucci et
  al. 1987)

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ASCOGEN

• Omega 6 polyunsaturated fatty acids gt18 carbon
  atoms in erythrocyte membranes in 58 healthy
  new-born infants
• Delucci et al. 1987
• HM Human milk
• MF Milk formula according to recommendations
  of the
• European Society for Pediatric Gastroenterology
  and Nutrition
• MNF MF plus 1.12 mg CMP, 1.32 mg AMP, 1,49 mg
  GMP,
• 3,42 mg UMP and 0,45 IMP

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ASCOGEN
PE Phosphatidylethanolamine PC
Phosphatidylcholine PS Phosphatidylserine SM
Sphingomyelin
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ASCOGEN

• Effect on the lipoprotein metabolism
• In the growing stage in rats, the group given a
  nucleotide rich diet showed significant increases
  in the concentration of plasma HDL cholesterol
  and decreases in the concentration of LDL
  cholesterol