Advanced article 2018 Flashcards
What are the 3 main focuses/aspects of clinical trials?
o Toxicity: whether or not they might cause harm
o Efficacy: how well they work
o Dose: how much needs to be taken for the best results
Give 3 advantages of using human embryonic stem cells
- are capable of dividing without differentiating for a prolonged period in culture
- can develop into cells and tissues of the three primary germ layers: ectoderm, endoderm, and mesoderm
- can be grown in labs by transferring cells from a preimplantation-stage embryo into a laboratory culture dish that contains a nutrient broth known as culture medium
Define the term paraplegic
all or part of the trunk, legs and pelvic organs
How are preclinical trials carried out?
On cells then tissues and 2 then different types of live mammals
What is in the cell body of a neurone?
Contains nucleus surrounded by cytoplasm
Cytoplasm contains large amount of ER mitochondria for production of neurotransmitters
Also contains other cell organelles
What is a blastocyst?
early-stage pre-implantation embryo which is typically 4–5 days post fertilisation, at which time they consist of 50–150 cells
State 3 possible causes for demyelination
injury to the oligodendroglial cells
demyelinating diseases e.g. multiple sclerosis
trauma to the body e.g. SCI can also cause demyelination
What is a placebo?
tablets/capsules that look identical to the new drug
but contain no active ingredient
i.e. they are a dummy tablet with no actual drug in them
What is a stem cell?
- unspecialised i.e. undifferentiated cell
- which can proliferate to make large numbers of new cells
- differentiate into several types of specialised cells
- large nuclear:cytoplasmic ratio
What is meant by the term spinal cord injury?
damage to the spinal cord that causes changes in its function, either temporary or permanent
Why to brain cells only respire glucose?
Brain tissue is separated from the blood by the blood-brain barrier.
Fatty acids and glycerol can’t pass through this barrier due to their size.
Define the term tissue
- group of similar cells
- consisting of one or more than one type
- with any extracellular material they secrete
- which are specialised to carry out a specific function
State 4 different diagnostic tests that can be used for SCI
CT scan
MRI
X-ray
Neurological examination
Give a source of pluripotent stem cells
Inner cell mass of the blastocyst i.e. embryos that are between the 50-100 cell stage and are ~5 days old
What is the purpose of a blind trial?
it allows for the placebo effect
i.e. when the patient expects to feel better as they are taking medication, and also prevents subconscious bias from doctors when reporting how effective the drug has been
Define a multipotent stem cell
Adult SC that can give rise to a limited number of cell types, related to their tissue of origin
Typically round cells with very little cytoplasm in relation to the size of their nuclei
What is the benefit of transplanting OPCs?
OPC transplants contribute to remyelination
Hence they can potentially be used to treat disorders where symptoms are caused by demyelination
What are the functions of vertebrae?
- Support - form the vertebral column to support the body (part of skeletomuscular system)
- Protection - contain a vertebral foramen (hole) for the passage of the spinal canal & protection of spinal cord.
- Movement – vertebrae have openings which allow the entry and exit of the spinal nerves. Vertebral column also allows controlled movement and flexibility
Give 3 sources of mesenchymal stem cells
Bone marrow (most common source)
Adipose tissue (very rich source)
Cord blood (youngest source)
What are mesenchymal stem cells
multipotent stem cells that can differentiate into a variety of cell types
e.g. osteoblasts (bone cells),
chondrocytes (cartilage cells),
myocytes (muscle cells) and
adipocytes (fat cells which give rise to marrow adipose tissue)
What is a reflexive bowel?
when there is no control over when a bowel movement occurs
Suggest other possible complications as a result of a SCI
muscle atrophy, pressure sores, infections, and respiratory problems
State the 4 beneficial effects of scar tissue in the CNS
function of the glial scar is to re-establish the physical & chemical integrity of the CNS scar forms a barrier across the injured area that seals the nervous/non-nervous tissue boundary
allows for the regeneration of the selective barrier to prevent further microbial infections and prevent spread of cellular damage
glial scar also stimulates revascularisation of blood capillaries to increase the nutritional, trophic, and metabolic support of the nervous tissue
Give 3 uses of immunosuppressants
o anti-rejection drugs = reduce the chance of a transplanted organ being rejected e.g. liver, heart, or kidney.
o treat autoimmune disorders e.g. rheumatoid arthritis
o treat some other non-autoimmune inflammatory diseases e.g. long term allergic asthma control
What are the effects of having a SCI in the low cervical region?
Often result in shoulder and biceps control, but no control at the wrist or hand
A person with this level of injury may be able to breathe on their own and speak normally
What are the effects of having a SCI in the sacral region?
Injuries generally result in some loss of function in the hips and legs.
Little or no voluntary control of bowel or bladder, but can manage on their own with special equipment
Most likely will be able to walk
State the 4 different types of immune cells
lymphocytes (B and T) memory cells
phagocytes i.e. macrophage, neutrophils,
dendritic cells
mast cells
What structures form the central nervous system?
Brain
Spinal cord
remember both include grey and white matter
How are Schwann cells and oligodendrocytes similar?
Both add myelin to the axon to form an axon sheath
Both are glial cells
What are neurone axons?
Singular, elongated nerve fibre extending from cell body
Transmits impulses away from cell body
Vary in length but can be ~1m long
Fibre is very narrow ~1 micrometre
Surrounded by plasma membrane
Other than paralysis, what are the other effects/symptoms of SCI?
o low blood pressure
o inability to regulate blood pressure effectively
o reduced control of body temperature due to inability to sweat below the level of injury
o chronic pain
Define paralysis
loss of muscle function for one or more muscles
What is the function of a motor neurone?
carries impulse from motor neurone to effector (muscle or gland)
Give 4 types of cells found in the brain
o neurones
o glial cells – important in supporting role for neurones and tissue repair
o astrocytes – important in repair and scarring formation after trauma/SCI
o oligodendrocytes – important in myelination of axons & mainly found in white matter
What are the effects of having a SCI in the upper/high cervical region?
Most severe of the spinal cord injury levels
Paralysis in arms, hands, trunk and legs
Patient may not be able to breathe on his or her own, cough, or control bowel or bladder movements
Requires 24-hour-a-day personal care
What is the function of astrocytes?
astrocytes secrete several growth-inhibitory molecules that chemically prevent axonal extensions
Give 2 advantages of sourcing stem cells from the umbilical cord
* umbilical cord is normally discarded after birth and therefore is available easily
* there is no risk to the collector they are the youngest source of stem cells and most primitive source
What are the effects of having a SCI in the thoracic region?
Injuries usually affect the abdominal and lower back muscles and the legs
Typically result in paraplegia
Arm and hand function is usually normal
Little or no voluntary control of bowel or bladder, but can manage on their own with special equipment
What is the function of a relay neurone?
carries impulse from relay neurone to motor neurone
Define a pluripotent stem cell
SC that can give rise to any cells of the organism except extra-embryonic cells e.g. placenta & chorion
What are the two types of SCI?
Complete and incomplete paralysis
What are embryonic stem cells?
primitive (undifferentiated) cells that are derived from derived from the inner cell mass of a blastocyst
Give 3 uses of pluripotent stem cells
Cell replacement therapies
e.g. produce pancreatic β-cells to treat type I diabetes
or to treat Parkinson’s disease
or to produce cardiac muscle cells to treat heart disease
What are oligodendrocyte progenitor cells (OPCs)?
- subtype of glial cells in CNS
- precursors to oligodendrocytes
- they can differentiate into neurons & astrocytes
Why are neurological examinations delayed until a few days after a SCI?
‘Delay’ allows any swelling to subside which leads to a more accurate diagnosis of the severity of the SCI and predict the likelihood of recovery and the possible outcomes from treatment
What are immunosuppressants?
class of drugs that suppress or reduce the strength of the body’s immune system
What is meant by the term ‘adverse event’ in the medical field?
an unusual and unexpected medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment
How is scar tissue formed in the CNS?
• formed by glial cells
What are oligodendrocytes?
- specialised type of glial cells
- formed from oligodendrocyte precursor cells
- closely related to nerve cells
- provide a supporting role for neurones
Give 3 uses of multipotent stem cells
Used to treat leukaemia & other blood cancers & bone cancers
Possible future use for nervous system diseases e.g. Parkinson’s & Alzheimer’s disease
Give 2 examples of animal tissue and 2 examples of plant tissue
Animal: squamous epithelium, ciliated epithelium,
Plant: xylem tissue, phloem tissue
What are stromal cells and where are they found?
- they form connective tissue cells of any organ
- they are located adjacent to the epidermis
What are glial cells?
Non-neurone cells found in the nervous system
E.g. Schwann cells, oligodendrocytes
What is the function of a myelin sheath?
- increases impulse speed (increases linearly with the axon diameter) - due to saltatory propagation of action potentials at the Nodes of Ranvier in between Schwann cells and oligodendrocytes
- acts as insulation layer –> improved & faster passage of electrical signals along the nerves
Give an example of combination therapy
transplanted stem cells AND administration of therapeutic drugs (e.g. painkillers, anti-inflammatories)
State the negative effects scar tissue has in the CNS
glial scar also prevents neuronal regrowth after trauma to the CNS
axons begin to sprout and attempt to extend across the injury site in order to repair the damaged regions
but scar prevents axonal extensions via physical and chemical means
How do cells become specialised?
through a process called gene expression
How do stromal cells play a role in the development and spread of cancer?
- release growth factors that promote cell division
- certain types of skin cancers (basal cell carcinomas) cannot spread throughout the body because the cancer cells require nearby stromal cells to continue their division
- loss of these stromal growth factors when the cancer moves throughout the body prevents the cancer from invading other organs i.e. they do not become metastatic
What is meant by “peer review”?
This is when other scientists check the work of the original scientists to make sure the testing has been rigorous enough.
This helps prevent false claims.
What is the spinal cord?
- long, thin, tubular bundle of nervous tissue and support cells
- extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column
What are the two key features of stem cells?
- have self renewal ability i.e. ability to divide many times while maintaining an unspecialised state
- are potent i.e. have ability to differentiate into specialised cells (depending on state of origin)
What are the 5 main regions of the brain?
cerebrum
cerebellum
brain stem.
pituitary gland
hypothalamus
Explain why SCI can result in loss of sexual function
ability to get a reflexogenic erection or spontaneous erection is controlled by nerves found in the lowest part of the spinal cord segments (S2, S3 and S4)
very few men with a complete SCI have ejaculations
sometimes SCI prevents the bladder sphincter from closing and seminal fluid (semen) will be ejaculated into the bladder instead of out the penis = retrograde ejaculation.
How are Schwann cells and oligodendrocytes different??
o oligodendrocytes found in CNS vs Schwann cells found in PNS
o Schwann cell usually myelinates a single axon, completely surrounding it
o oligodendrocytes usually myelinate several axons - sending out thin projections of their cell membrane which envelop and enclose the axons
Suggest 3 common causes of SCI
o vehicle accidents
o falls
o gunshot wounds
o sports injury
o medical / surgical complications
o spinal tumours
o multiple sclerosis
o inflammation of the spinal cord
o arthritis
o spinal stenosis
o blood loss
Suggest how stem cells can be used in repair
- Replacement of nerve cells
- Reformation of myelin
- Regrowth of axons
- Release of growth factors
- Absorption of toxins
- Suppression of inflammation
Why does demyelination cause impulses to travel slower?
lack of myelin or if the myelin sheath is broken down means there is no insulation
hence the axon becomes permeable to Na+ and K+ ions
hence no saltatory conduction can occur
this results in shorter local circuits which slows transmission
What is the function of glial cells?
To surround neurons and hold them in place
To supply nutrients and oxygen to neurons
To insulate one neuron from another
To destroy pathogens and remove dead neurons
State 3 common side effects of taking immunosuppressants
immunodeficiency – most are non-selective so lead to increased susceptibility to infections and decreased cancer immunosurveillance
hypertension
hyperglycemia
peptic ulcers
possible interactions with other medicines and affect their metabolism and action
What are astrocytes?
astrocytes (star shaped glial cells found in brain and spinal cord) form a dense network of gap junctions that generates a physical barrier to axonal regrowth
Define a totipotent stem cell
SC that can differentiate into all the types of cell within an organism
What is an impulse?
A signal transmitted along a nerve fibre
It consists of a wave of electrical depolarisation that reverses the potential difference across the nerve cell membranes
Give 2 sources of totipotent stem cells
Very early embryos in animals (i.e. before 50 cell stage)
Meristematic tissue in plants
Why are further clinical trials carried out once the drug has been found to be safe?
to find the optimum dose for the drug
i.e. the dose that has the best effect with minimal (preferably no) side effects
What is meant by a ‘incomplete SCI’?
some function below the primary level of injury
person may be able to move one limb more than another, may be able to feel parts of the body that cannot be moved, or may have more functioning on one side of the body than the other
incomplete SCI are becoming more common due to advances in acute treatment of SCIs
List some concerns that people may have with stem cell therapy
- Could be used for reproductive cloning i.e. cloning humans requires destruction of human embryo some believe this to be a human life
- Human embryos have the same rights as an individual
- ESC research hasn’t (yet) produced any viable long term treatment SC transplants have the potential to produce tumours
Describe a single-blind trial
the patient doesn’t know if they are being given a drug or a placebo but the doctor knows what the patient takes
What is meant by ‘combination therapies’?
treatment in which a patient is given two or more drugs (or other therapeutic agents) for a single disease
What is a flaccid bowel?
- when there is no bowel movement stools remains in the rectum
- mucus and fluid will sometimes leak out around the stool and out the anus the person has fecal incontinence
When are drug tests and trial results published?
Only after scrutiny by peer review
Define the term tetraplegic
arms, hands, trunk, legs and pelvic organs are all affected
What is meant by a ‘complete SCI’?
- no function below the level of the injury – no sensation and no voluntary movement
- both sides of the body are equally affected
What are neurone dendrons?
- Short extensions of the cell & cytoplasm from the cell body
- Increase SA to receive nerve impulses from other neurones into the cell body
- Subdivide into smaller and smaller branches = dendrites
- Function = transmit electrical impulses towards cell body (i.e. deliver impulse to cell body)
What is the function of a sensory neurone?
carries impulse from receptor to relay neurone
What is meant by the term gene expression?
gene expression = specific combination of genes that are turned/”switched on” or “switched off” (expressed or repressed)
gene expression results in transcription and translation
Give an example of an adverse event in the medical field
an injury resulting in prolonged hospitalisation, disability or death, caused by healthcare professional
Give 4 sources of multipotent stem cells
- Haemocytoblasts (bone marrow SC) – rounds cells which have large nuclei & little cytoplasm
- Epithelial SC
- Bone SC
- Umbilical cord blood
Describe a double-blind trial
some patients are given a placebo and some get the new drug
neither the patient or the doctor knows what the patient takes until the trial is complete
Why are new drugs given to healthy individuals?
Initially new drugs are given to healthy individuals (to see if any side effects occur)
What are the 4 main regions of the cerebrum?
- frontal
- parietal
- temporal
- occipital
Other than SCi, suggest other possible causes of paralysis
stroke, trauma with nerve injury, poliomyelitis, cerebral palsy, Parkinson’s disease, botulism, spina bifida, multiple sclerosis
What structure protects the brain?
Cranium (skull)
Describe a triple-blind trial
some patients are given a placebo and some get the new drug
neither the patient or the doctor or the statistician knows what the patient takes until the trial and data processing is complete
Where can OPCs be found?
higher number of OPCs in white matter than in grey matter due to a higher rate of proliferation in white matter
What is an action potential?
the change in electrical potential associated with the passage of an impulse along the membrane of a neurone.
Why are very low doses of the drug given at the start of a clinical trial?
to determine if there are any side effects
