15 Questions
What is the effect of Phospolipase A2 in snake venom?
Local and systemic myotox, pain, damage to lymphatic vessels, oedema, neurotox, and hemolysis
The symptoms of evenomation include skin necrosis and paralysis of eye muscles.
True
What is the purpose of capturing snake venom?
To develop antivenom and to obtain qualitative and quantitative information about the toxins present.
TGN1412 is a medicine supposed for treatment of ___________ and rheumatoid arthritis.
B-cell lymphatic leukemia
What is the class of the antibody TGN1412?
IgG4
Cytokine storm is a rare side effect of TGN1412.
False
What is the structure of the CD28 superagonist antibody?
The CD28 superagonist antibody binds exclusively to the laterally exposed C”D loop of the Ig like domain.
Match the following toxins with their effects:
Phospolipase A2 = Local and systemic myotox, pain, damage to lymphatic vessels, oedema, neurotox, and hemolysis Snake venom metalloproteinases (SVMP) = Hemorrhage, myonecrosis, extracellular matrix degradation, blistering, pain, oedema, cardiovascular shock, nephrotox, and coagulopathy Three finger toxins = Cytotox, necrosis, and neurotox Dendrotoxin = Neurotox
TGN1412 is a ___________ of CD28.
superagonist
Snake venom can be used for the treatment of cancer.
True
What is the main source of human exposure to aflatoxins?
Food consumption
Aflatoxins are a type of genotoxin.
True
What is the main mechanism of aflatoxin B1 leading to hepatocellular carcinoma (HCC)?
p53 mutations and inactivation, leading to proliferation and loss of growth control
The compressor muscle in the 'cheek' of venomous snakes is responsible for the release of _______________ into the venom duct.
venom
Match the following organ-specific toxins with their effects:
Aflatoxins = Hepatocellular carcinoma (HCC) Snake venom = Tissue damage and inflammation Coumarin derivatives = Blood clotting disorders Polycyclic compounds = Genetic mutations
Study Notes
Aflatoxins
- Aflatoxins are polycyclic, unsaturated, and coumarin derivatives from yeast (Aspergillus flavus and A. parasiticus)
- Human exposure to aflatoxins occurs through food consumption, particularly through contaminated groundnuts (green) and maize (brown spots)
- Aflatoxin B1 is a co-factor in 60% of liver cancer cases in Sudan, leading to Hepatocellular carcinoma (HCC)
- MOA: Aflatoxin B1 causes p53 mutations, leading to p53 inactivation, proliferation, loss of growth control, and genetic alterations resulting in HCC
- Visible as yellow patches in the liver, causing damage to DNA
Mechanisms of Tox
- Genotox
Degradation Methods
- Extruder
- Ammonia
Snake Venom
Anatomy of Venomous Snakes
- Venom glands release venom through pressure on compressor muscle (in the ‘cheek’) and via venom duct into fangs and into tissue
- Examples: Rattle snakes, black mamba
Toxins in Snake Venom
- Phospholipase A2: local and systemic myotox, pain, damage to lymphatic vessels, oedema, neurotox, nephrotox, and hemolysis
- Snake venom metalloproteinases (SVMP): hemorrhage, myonecrosis, extracellular matrix degradation, blistering, pain, oedema, cardiovascular shock, nephrotox, and coagulopathy
- Hyaluronidases: ECM degradation
- Three finger toxins: cytotox, necrosis, and neurotox
- Dendrotox: neurotox
- Snake venom serine proteinases (SVSP): coagulopathy, oedema, and hypotension
- Vasoactive peptides: hypotension
- Disintegrins: inhibition of platelet aggregation
- C-type lectin like proteins: inhibition or promotion of platelet aggregation and thrombocytopenia
- Cysteine-rich secretory proteins: smooth muscle paralysis
- Natriuretic peptides: hypotension
- Sarafotoxins: cardiotox
Symptoms of Envenomation
- Swelling and blistering
- Gangrene
- Bleeding gums
- Skin necrosis
- Paralysis of eye muscles and upper eyelid
Mechanism of Neurotox
Capturing Snake Venom
- Snake venom milking
- Advantages: qualitative and quantitative information about toxins present, development of antivenom
- Capturing toxins: antivenom immobilization, column with venom Ab, toxins bind, rest goes through, elution, and further characterization
- Toxins are promising for treatment of cerebro and cardiovascular diseases, arteriosclerosis, blood clotting diseases, wound healing, hypertension, cancer, and viral infections
TGN1412
- Medicine supposed for treatment of B-cell lymphatic leukemia and rheumatoid arthritis
- MOA: normal trigger of immune response, Ag binds T-cell R, co-stimulatory molecule (CD28) for the activation of immune cells
MOA for Disease
- Activation of CD4+ T-cells, no longer tolerance to leukemic B-cells, elimination of leukemic B-cells
- Activation of T-reg (also have expression of CD28)
- Activation of other lymphocytes T4
MOA of Tox
- Cytokine storm: very high number of cytokines (first days after infusion), headache, hypotension, tachycardia, fever, lymphopenia, monocytopenia
- Cortico injection (reduction of immune response) = transient improvement
- Multi-organ failure, ↑ ALT (liver damage), necrosis of extremities
This module covers the toxicity of aflatoxins, including their sources, human exposure, and health effects such as hepatocellular carcinoma. Aflatoxins are polycyclic, unsaturated coumarin derivatives from Aspergillus flavus and A. parasiticus.
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