Answers from 13D for the scientific article questions

1) Parkinson’s disease is a degenerative disorder of the central nervous system caused

by the death of dopamine-secreting neurones in the basal ganglia. Dopamine is a
neurotransmitter found throughout the frontal cortex, the brainstem and the spinal
cord.
The neurones that die normally provide dopamine to the motor cortex, so Parkinson’s
patients’ motor cortexes receive little dopamine.
The motor cortex describes the areas of the cerebral cortex that are involved in the
control of voluntary motor movements, so a lack of dopamine in the area causes a loss
of control of muscular movement.

The main symptoms of Parkinson’s disease are; stiffness of muscles, muscle tremors,
slowness of movement, poor balance and trouble walking.
Other symptoms can include depression as well as breathing and speech problems.
The disease mainly affects those over the age of 50, though it is possible to suffer
from the disease at a younger age.

Traditionally the disease has considered a non-genetic disorder, however a number of

genes have been found that play a role in the development of the disease.
Toxins in the environment and previous head trauma have been hypothesised to the
related to the development of Parkinson’s, but evidence from studies on the subjects
has been inconclusive.

There are a number of drug treatments that can be used to slow the progression of the
disease and make it easier for people to live with the effects.
The drug selegiline can be used to slow the loss of dopamine as it inhibits the enzyme
monoamine oxidase, which is used to break down dopamine in the brain.
Dopamine itself cannot be given directly to the patient as it cannot cross into the brain
from the bloodstream. Instead L-dopa, a precursor in the manufacture of dopamine, is
used as it can pass from the blood into the brain. Once it enters the brain it is
converted into dopamine, increasing the concentration of dopamine in the area.
Dopamine antagonists are drugs that activate the dopamine receptors directly. These
drugs mimic the effect of dopamine in the brain, binding to dopamine receptors at
synapses and releasing action potentials. This treatment is particularly useful as it
avoid having large amount of dopamine in the brain, which is related to
schizophrenia.

Gene therapy trials in animals and phase 1 trials in humans show promise. This
therapy involves genes for proteins that increase dopamine production and nerve cell
survival being inserted into the brain. Cell therapy, which involves the proteins
themselves being inserted, is also being trialled.

2. Across a neurone

Our ability to react rapidly to external stimuli is due to our extensive

nervous system. This system is able to conduct nerve impulses and
relay them to various reflexive and decision making centres. This
system is composed of nerves, bundles of neurones that span the
extent of the body and carry action potentials.

All cells have a potential difference across their surface membrane.

There are Sodium-Potassium pumps in the cell membrane that carry
Na+ out and move K+ in. Due to the energy produced by the
hydrolysis of ATP, these pumps can work against their respective
concentration gradients. A neurone is usually at resting potential,
-70 mV, this means that the inside of the neurone, when at rest, is
more negative than it is outside.

Neurones are electrically excitable, meaning that the potential

difference across their membrane changes when they conduct an
impulse. When one such impulse is stimulated voltage dependent
Na+ channels open allowing the positive Na+ ions to travel into the
neurone, down a concentration and electrochemical gradient. The
inside of the neurone is now more positive, making the neurone
Depolarised. Furthermore the more the membrane depolarises the
greater number of channels open, this is called Positive Feedback
and it rapidly accelerates the depolarisation.

The change in potential difference in a section of membrane

adjacent to the first action potential triggers a second action
potential, and the depolarisation travels up the neurone.

After 0.5 ms and having done their job, the Na+ channels close and
the new voltage causes K+ channels to open. The K+ ions travel down
the electrochemical and concentration gradient out of the
membrane and cause Repolarisation. This ensures that the impulse
does not travel backwards.

Across a synapse

The action potential arrives and depolarises the membrane of the

presynaptic membrane. This opens Calcium Channels and allows
Ca+ ions to move into the presynaptic membrane. This influx in Ca+
ions causes synaptic vesicles to fuse with the presynaptic
membrane and expel neurotransmitters into the synaptic cleft.
When these neurotransmitters meet receptors on the postsynaptic
membrane, cation channels are opened. Na+ ions flow in and cause
a depolarisation, which initiates the action potential on the post
synaptic neurone.

3. Explain how a nerve impulse causes muscle contraction.

A nerve impulse arrives at a neuromuscular junction. This is the point where a nerve
ending meets muscle tissue. The nerve endings and muscle fibres are separated by a
synapse one 10,000th of a mm wide. When an impulse arrives at the neuromuscular
junction the depolarisation causes calcium channels to open. This causes vesicles
containing acetylcholine (a neurotransmitter) to migrate and fuse to the presynaptic
membrane. Neurotransmitter is released into the synaptic cleft and binds to the
complementary receptor molecules on the post synaptic membrane. This causes a
conformational change of the receptor molecule, opening cation channels, allowing
sodium ions to pass into the muscle fibre. This causes depolarisation of the muscle
fibre. Depolarisation of the membrane causes calcium ions from the sarcoplasmic
reticulum into the sarcoplasm. Within the sarcomere, the calcium ions bind to the
troponin molecule on the actin filament, causing the troponin and tropomyosin to shift
their position –exposing the myosin binding site. The myosin head binds to the
binding site on the actin filament, forming cross bridges. ADP and Pi are released
from the myosin head. This causes a conformational change to the myosin head. The
myosin head nods forward causing the two protein filaments to slide past one another
(actin slides over myosin). This shortens the sarcomere. The coordinated movement
of many myosin heads results in coordinated muscle contraction. ATP then binds to
the myosin head, causing it to detach and the cross bridges are broken. Using ATPase
ATP is hydrolysed into ATP, Pi and energy. The hydrolysis of ATP causes the
myosin head to change shape and return to its upright position. When nerve impulses
stop being received, calcium ions return to the sarcoplasmic reticulum.
N.B. In rigor mortis, there is no ATP as there is no respiration. Thus the cross bridges
remain attached, and muscles remain contracted.

4. What are sledgehammer drugs?

Sledgehammer drugs are designed to target a specific type of cell but also affect many
other cells as well. This can cause many severe side effects. The benefits of
sledgehammer drugs are thought to be equal to their risk. They are very powerful and
usually only administered in hospitals. Chemotherapeutic agents used in the treatment
of cancer are an example of a sledgehammer drug. Whilst the chemotherapy destroys
the cancerous cells, they also harm your “good” cells in the process causing adverse
side effects such as hair loss, immune deficiencies, vomiting and weight loss.

A way to think about sledgehammer drugs is to imagine that you own a house that is
absolutely perfect and beautiful with all the necessities, except that it has some
rodents inside. When you call the exterminators, they tell you that they won't be able
to target just the rodents, as these rodents are of an especially stealthy breed. They tell
you they're just going to set off a series of explosions in your house that may kill the
rodents. They warn you, "Oh yeah, it may destroy some of your house in the process,
but, hey, you want those rodents out of your house, right?"

5. Explain how genes are a) isolated and b) inserted into other

cells.

a) Before genes can be manipulated they must be identified. This is the

task of the Human Genome Project who are deciphering the sequence of
bases, identifying what each gene codes for and the functions of the
product they code for. Much of this work is done by studying DNA
sequence patterns alongside that of other organisms.
Once a gene has been identified it can be isolated using treatment with
restriction enzymes which originate from bacteria. (They are sometimes
referred to as restriction endonucleases as they are found in the cell
nucleus.) Restriction enzymes are specific to particular sequences of
bases, known as recognition sites. The restriction enzymes will only ‘cut’
DNA at these sites, leaving the required fragment of DNA or desired gene
intact.

b) Genes are often inserted into plant cells to create genetically modified
plants (plants which have had new genes with alleles for desired
characteristics incorporated into their DNA). GM plants can be used in
different ways; to yield a greater mass of crop, to produce medicines and
chemicals or to manufacture proteins for treating diseases.

Before genes can be inserted into plant cells the cell wall must be
removed. Enzymes remove the wall by digestion, creating a plant
protoplast. Genes can be inserted into the plant protoplasts via 3 routes;
one of these is using genetically modified viruses. The viruses used are
usually bacteriophages; those which infect bacteria. The section of viral
RNA which allows it to replicate is removed and replaced with the desired
gene and a promoter sequence to initiate transcription and translation.
The viral genetic material (the desired gene) becomes incorporated into
the plant DNA. Bacteria can also be used. The bacterial plasmid is
extracted and cut using restriction enzymes. The desired gene is then
spliced into the bacterial plasmid using DNA ligase (an enzyme used to
bind DNA). The modified plasmid is inserted back into the bacterium.
When the bacterium invades the plant protoplast, the plasmid DNA
becomes incorporated into the plant DNA. Another method involves a
‘DNA gun’. Tiny bullets are coated with DNA including the desired gene
and are shot into the plant protoplast. The gene is integrated into the
plant DNA.

With all of these methods there is not a 100% success rate. One way in
which the modified plants can be identified is with the use of a marker
gene, which is often a gene coding for antibiotic resistance. This marker
gene is inserted into the plant protoplast at the same time as the desired
gene. All of the plant protoplasts are then cultured to allow the re-growth
of the cell walls. They are then incubated with the antibiotic, killing off any
plant cells which do not contain the new gene. After screening, the
resistant plant cells (those which have been successfully genetically
modified) are cultured on nutrient agar with a plant growth substance.
This process is known as micropropagation and firstly calluses (masses of
plant cells) are produced. These then differentiate into plantlets which
grow into the GM plants.

Genes can also be inserted into human cells using the same methods.
Another method can also be used where a plasmid of DNA containing the
desired gene is combined with a liposome and the positively charged
heads of the liposomes combine with the DNA of the cell. Gene therapy
using human cells is only in the early stages of trials but is thought to be a
possible treatment for conditions such as cystic fibrosis.

6) Explain how genes can be switched on or off? (Refer to super-coiling, repressor

molecules ECT)
Not all genes can be switched off, some genes remain permanently switched on
because they contain the information that is necessary for the formation of vital
metabolites (primary metabolite are small molecules directly involved in normal
growth, development, and reproduction); for instance (enzymes required for
respiration). This is how cells become specialised in multi-cellular organisms (like
us), because only some genes are switched on and produce active mRNA which is
translated into proteins within the cell.
Genes in uncoiled accessible regions of the eukaryote DNA can be transcribed
into messenger RNA. The enzyme RNA polymerase binds to a section of the DNA
adjacent to the gene to be transcribed. This section is known as the promoter region.
Only when the enzyme has attached to the DNA will transcription take-place. The
gene remains switched on or off until the enzyme attaches to the promoter region
successfully. This attachment of a regulator protein is usually also required at the start
of transcription. The
Transcription of a gene can be prevented by protein repressor molecules
attaching to the DNA of the promoter region, blocking the attachment site.
Furthermore the protein repressor molecules can attach directly to the regulator
proteins, preventing them from attaching and forming the transcription initiation
complex. In either case the gene is switched off; and is not transcribed or translated in
the cell.
Genes can be switched on by the successful formation of the transcription
initiation complex to promoter region.

Super coiling allows for easy manipulation and so easy access to the information
coded in the DNA. When a cell is copying a DNA strand it will uncoil a strand, copy
it and then recoil; this means a more workable interpretation of the stresses in the
DNA can be created. However sometimes super coiling can coil DNA too tightly
this also prevents DNA polymerase from binding to the promoter region and therefore
will not form a transcription initiation complex  and ultimately transcription and
translation of the gene will not take place.

Question 7
Transcription of a gene can be prevented by protein repressor molecules attaching to
the promoter region. This blocks the attachment sites for the transcription factors,
preventing the formation of transcription initiation complex. Hence turning the gene
off as this transcription initiation complex allows transcription to happen. The
structure and function of a cell is determined by the proteins it contains. The control
of the transcription factors is key to this.

Peptide hormones are protein chains. They cannot get into the cell easily as they are
charged. They instead bind to a receptor on the cell membrane releasing a secondary
messenger – a molecule in the cytoplasm. This brings around chemical changes in the
cell, such as activating transcription factors or enzymes so a gene can be expressed.
Examples of peptide hormones would be EPO or insulin.

A steroid hormone, like testosterone binds directly to a receptor molecule within the
cytoplasm. Once this is activated, it brings around the characteristic response resulting
in it becoming a transcription factor, switching enzyme syntheses on or off.
Steroids directly affecting gene transcription where as Peptides affect it via a
secondary messenger indirectly.

DNA begins to uncoil revealing DNA sequences. Regions on the DNA can then be
transcribed into mRNA. The enzyme RNA Polymerase binds to the adjacent section
of DNA (promoter region) that we want to transcribe. To turn off a gene a repressor
molecule blocks the promoter region stopping the RNA polymerase binding hence the
transcription cannot commence.

Transcription takes place in the nucleus. The DNA double helix uncoils, allowing
strands to part. One strand becomes a template. Free RNA nucleotides line up along
the DNA. Complementary base pairing ensures the order of the bases on RNA. The
mRNA molecules are joined together by condensation reactions and phosphodiester
bonds are formed. The single stranded mRNA then leaves the nucleus via a pore in
the nuclear envelope.

Translation then happens in the cytoplasm of the cell. The mRNA strand attaches to
ribosomes which are found either on the Rough ER or free in the cytoplasm. From
here transfer RNA molecules use the anti codon of three bases to complementary base
pair with the codon strand of the mRNA. Also on the tRNA there is an amino acid
attached to the bases. The Transfer RNA fit into place dragging in an amino acid that
is complementary to the base pairs. Amino acids join via peptide bonds. The peptide
bond is a condensation reaction between the amine group of one amino acids and the
carboxylic of another, forming a dipeptide bond. The ribosome moves along the
mRNA creating a chain of amino acids behind it until it until a stop code is reached.
This is three base pairs that cause the chain of amino acids to break off and a new one
can begin. This is the primary protein structure.
Secondary structure is when the amino acids twist to form an a-helix. Within this
helix, hydrogen bonds form between the C=O of the carboxylic acid and the –NH of
the amine group of different acids. These may be linked together with hydrogen bonds
forming a pleated sheet.
The tertiary structure is when the shape becomes three dimensional due to the polar
within the amino acid chains. The polar groups attract each other like water, where as
the non polar groups are arranged so they face inside away from any water. If a
tertiary structure has an R-polar molecule that has a sulphur attached, it can link via a
disulfide bond to another r group, changing the structure further still.
Protein trafficking then is the final process where the proteins get transformed into a
tertiary structure and are packaged to leave the cell. The protein goes into the
Endoplasmic reticulum and travels through it gaining a three dimensional shape en
route. Vesicles the pinch of the rough ER containing the protein. They then fuse with
the Golgi apparatus (body), releasing the protein into it. The proteins travel through it
being modified as they go. The vesicles are then pinched of the GA and travel though
the cell. When the vesicles reach the surface, they fuse and release the protein
(possible an enzyme) out the cell. This process is called Exocytosis. Or it can be used
inside the cell to permanently modify it making it specialised.

8. How do the algae mentioned in the article use light to produce

Algae use photosynthesis to produce sugars. The algae contain chloroplasts which is
the site of photosynthesis. Photosynthesis takes place in two phases, the first of which
is the light dependant. This occurs in the thylakoid membrane. The light energy is
 absorbed by chlorophyll and excites two electrons in each chlorophyll molecule and
raises them to a higher energy level. These are then taken by electron carriers where
they are transported to the electron transport chain. The electrons are passed down the
electron transport chain in a series of REDOX reactions. The energy released causes
photophosphorylation, the process in which ATP is synthesised from ADP + Pi.
Photolysis is catalysed by an enzyme in the thylakoid space, splitting water into
oxygen and hydrogen ions and electrons. The electrons replace those that were
emitted from the chlorophyll molecule, which means it is no longer positively
charged. The hydrogen ions combine with the electrons from the electron transport
chain to reduce NADP.
The next stage of photosynthesis is the light independent reaction (or Calvin cycle)
that takes place in the stroma. RuBISCO catalyses CO2 joining the 5 carbon
compound RuBP. As this is a 6 carbon compound it is unstable and so immediately
breaks down into 2 x 3 carbon compounds known as GP. These are then reduced
using the hydrogen from the oxidation of NADP and the energy from ATP from the
light dependant phase to form GALP. Out of every 12 GALP, 2 form hexose (a 6
carbon sugar) and the other 10 are used to make 12 RuBP. We say that CO2 has been
reduced to form sugar.

9) The Pros and Cons of animal testing including the ethics

involved.

Pros:
• It aids researchers in finding and developing drugs and
treatments to improve health and medicine.
• Many treatments have been developed with the use of animal
testing such as cancer and HIV drugs, insulin, antibiotics and vaccines.
• As well as finding and developing drugs and treatments,
testing on animals ensures the safety of the drugs and substances so
humans avoid danger.
• Animals are used as they are thought of as being similar to
humans and although there are limitations and differences, they are
useful when gathering data that will be applied to humans.

Cons:
• Countless numbers of animals used in testing are
experimented on and then killed/die. Others may be injured or damaged
by testing yet live out the full capacity of their lives.
• Animals may feel pain and suffering, but to what degree is
debatable.
• Many of the tests carried out resulting in the death of many
animals will not reach approval or public consumption so in effect died in
vain as there was no human benefit from its testing.
• The controlled environment that animals have to be kept in is
very expensive to run.
• Animal testing can be unreliable because reactions in an
animal’s blood may be different from that in a human’s blood. Also they
may be under stress because they are in an unnatural environment.
Ethical views:
Animal Rights and Welfare
It is not acceptable to have humans as slaves or held in captivity, so why
is it acceptable for this to be the case with animals? If humans have
certain rights to freedom etc, this should be the right of animals as well.
Animals should have the right to the same considerations as human
beings. On the other hand animals cannot make moral choices in society
and so should not be considered to be possessors of rights. Animal
welfare is widely regarded as a compromise stating that there is nothing
wrong with using animals as resources provided that there is no
unnecessary suffering.

Utilitarian
The idea that the moral worth of an action is determined solely by its
utility in providing happiness or pleasure as summed among all sentient
beings. It is thus a form of consequentialism, meaning that the moral
worth of an action is determined by its outcome. Often described by the
phrase "the greatest good for the greatest number of people”, in this
case it would be how many animals would suffer for the benefit of how
many human lives.

10. Name the light detecting cells in the retina and explain how they
respond to light.
In the human retina, there are two types of photoreceptor cells that respond to
light. These are called rods and cones. Light hits the sclera, and here it will be sent
through a series of rods and cones. After these, a bipolar neurone will send an
impulse, which in turn will stimulate a neurone that is part of the optic nerve.
There are a number of rods connected to a single bipolar neurone. This makes
them suited to creating less precise images that are black and white. They are also
suited to working in dim light. Cones on the other hand are more suited to working
accurately in colour vision and bright light. This is because for every cone that is
stimulated, one bipolar neurone is stimulated. A more precise picture is created.
In rods, there is a photochemical pigment that absorbs light called rhodopsin.
This is affected differently in light and dark situations. In the dark, sodium ions flow
into the outer segment through non-specific cation channels. They then move down
the concentration gradient into the inner segment. Here pumps continuously
transport them back out of the cell. This creates depolarisation of the cell (-40mV).
This depolarisation triggers the release of a neurotransmitter called glutamate from
the rod cells. In the dark, glutamate is continuously released. It binds to the bipolar
cell, and prevents it from depolarising, so no action potential is created. However in
the light, the rhodopsin in the outer segment is broken down into retinal and opsin.
This closes the cation channels, so the volume of sodium diffusing into the cell
decreases. The inner segment continues to pump sodium out though, so the inside
of the cell becomes more and more negative. The membrane becomes
hyperpolarised, so no neurotransmitter (glutamate) is released into the synaptic
cleft. Cation channels in the bipolar cell open, and the sodium flows into those
instead, the membrane becomes depolarised. An action potential is sent.
Q11) The clinical trial on p6 only tested 6 patients. Discuss the
possible reliability of data from this trial and explain what variables
should be considered for the future.
The very small sample suggests low level of reliability associated with the
findings. It also indicates minimal population validity (the degree to which
the results can be generalised from the sample to other populations) and
therefore caution should be taken when generalising the findings to a wider
population.
The article doesn’t imply that individual differences were taken into account
during the trials and therefore variables, such as weight, age and gender
may have affected the findings. Such factors should be considered when
conducting future studies and whilst generalising the finding to populations.
New knowledge only becomes public knowledge when it is published in a
journal. Peer review (the scrutiny of research by independent experts) acts
as a quality control mechanism used to regulate the introduction of new
knowledge. Outline of process:
1. Manuscript of research is prepared and sent to editor of
journal
2. Editor examines the topic of the manuscript and sends it to
other experts in that field- these experts act as peer reviewers
3. Peer reviewers read manuscript and send it back to the editor
with comments and recommendations about its suitability for
publication.
4. Editor decides whether research is suitable for publication
The clinical trial on p6 was published in a journal, so it has under
gone extensive peer review and therefore the data is likely to be
valid.
12) Cystic Fibrosis is a common hereditary disease which affects the entire body,
causing progressive disability and often early death. Difficulty breathing is the most
serious symptom and results from frequent lung infections that are treated, though not
cured, by antibiotics and other medications. A multitude of other symptoms, including
sinus infections, poor growth, diarrhea, and infertility result from the effects of Cystic
Fibrosis on other parts of the body.
CF is caused by a mutation in the gene for the protein cystic fibrosis
transmembrane conductance regulator (CFTR). Although most people without CF
have two working copies of the CFTR gene, only one is needed to prevent cystic
fibrosis because Cystic Fibrosis is a recessive disease. The CFTR channel allows Na+
to enter into the cell form the mucus. The Cl- ions are then secreted into the mucus.
This process reduces the viscosity of the mucus. However people with Cystic Fibrosis
don’t have this channel or it doesn’t function correctly, so the direction of osmosis
can’t be reversed in response to dehydrated mucus.
The CFTR gene is inserted into the faulty cell (target cell) by gene therapy.
Normal alleles are inserted into the target cell, by modifying a virus and removing the
RNA which allows it to replicate itself. Then the normal alleles are inserted into the
virus. Then the virus is inserted into the hosts target cells. A promoter region
sequence is then added this sequence initiates transcription and translation. This is
then given to the suffer through a spray, however because these cells don’t replicate
this treatment isn’t permanent and needs to be continued.
A copy of the normal DNA is inserted into a plasmid. The plasmids then
combine with liposome’s, this then forms a liposome complex. These are then
breathed in through aerosols, then in the body it will be transcribed and translated and
will produce a functioning protein from the target cells.
Another treatment would be to insert stem cells from an embryo into the
persons Cystic Fibrosis sufferer’s lungs. Then temporarily the stem cell would
differentiate into normal lung tissue and reduce the symptoms.
13. Briefly describe the possible causes and symptoms/effects of CVD.

CVD generally is a definition of any disease relation to the cardiovascular system, but
is most commonly related to the causes and effects of atherosclerosis; diseases of the
arterial systems.

Causes
There are a huge number of risk factors that can cause CVD, but they are generally
classified into certain categories:

Diet: A persons’ diet has a huge effect on their likelihood of developing CVD in their
lifetime. A diet high in saturated fats, sugar, and processed foods, and low in fruits
and vegetables is one of the greatest risk factors for causing CVD. This is due to the
large amounts of High Density Lipoproteins and cholesterol contained within them.
High triglyceride levels from sugary foods is also a confirmed cause for CVD. High
Low Density Lipoprotein levels and cholesterol are also a cause for poor heart health.
But these LDLs can be removed from the blood using the liver if HDLs are present. A
lack of HDL is also a risk factor for heart disease due to the resulting inefficiency at
removing LDL from the blood.

Smoking and substance abuse: Smoking cigarettes causes corrosive and dangerous
chemicals such as nicotine to build up to dangerous levels in the blood. These
increase blood pressure by causing the blood to thicken and prefer to clot easily,
which wears down the arterial walls and encourages atherosclerosis. As an added side
effect, it reduces the tolerance for exercise within the coronary system, so when
exercise is attempted the heart and lungs get overworked, adding to the high blood
pressure problems. Drugs such as ecstasy cause the heart to race and blood pressure to
rise very sharply, adding to the damage.

Lack of exercise: Exercise helps the body to break down toxins in the blood and
tissues more quickly and efficiently but working the body hard at a higher metabolic
rate. If a body isn’t worked, it will not be able to break down toxins that enter the
body through other risk factors such as poor diet and smoking, and therefore
compound the effect of these chemicals over time.

Genetics: An individuals’ genes can be one of the chief causes in determining if they
will develop CVD at a later age. Over 5% of all genes in a human are thought to be
crucial to the correct development of the cardiovascular system as a whole, so the
genetic tendencies to CVD are actually quite high. Different forms of the genes for
production of Homocysteine, Fibrinogen, Apolipoprotein B and Apolipoprotein E are
key in causing CVD, but a small mutation in any gene that affects the CV system can
directly cause, or increase the chance of developing, CVD. Further to this, heavy
mutations to these genes can mean a person will die of severe and instant heart failure
as young as 20 years old.

Symptoms/Effects:
Each of these risk factors can affect the CV system as a whole, or specific parts of it:
Atherosclerosis: This is the most common of the CV diseases. This is where an
atherosclerotic plaque builds up on the inside of the artery. First, damage to the inner
lining of the artery must occur. This can be from atherogenic chemicals within the
blood such as nicotine corroding and inflaming the area, or the normal wear on the
artery walls due to constant blood flow. Atherosclerosis actually starts at a very young
age, but the effects aren’t cumulatively large enough to have an effect on the health of
most average people. When the damage is done to the artery, the non-specific immune
response is triggered and the area inflames. Platelets enter the area and start to bind
together, and macrophages ingest LDLs from the bloodstream to form engorged foam
cells which causes fatty deposits to form around the damaged area. The platelets
attached to the area release chemicals that attract more platelets to from a ‘scab’ over
the area which is the basis of the atherosclerotic plaque. The release of calcium ions
from the blood is triggered and these catalyse the conversion of prothrombin into
thrombin, which further catalyses the fibrinogen -> fibrin change. This insoluble
fibrin binds the plaque over the damaged area. This plaque constricts the artery, which
greatly increases blood pressure in the area. As high blood pressure is a precursor for
atheromas to form this results in a very damaging cascade of negative feedback.

Heart attacks/Myocardial infarction: If these atheromas form in the coronary arteries

(a process called arteriolosclerosis) then they can constrict blood flow to areas of the
heart. As the heart needs a constant and reliable flow of blood to stay alive,
arteriolosclerosis can result in the death of large tracts of cardiac tissue, affecting the
rhythm and effectiveness of the heart as a pump. This irregular heart rhythm
(arrhythmia) can cause the further death of other tissues around the body due to
interrupted blood supply, and so is a very damaging condition, particularly if the
blood flow to vital organs such as the brain and lungs is affected.

Aneurysm: These are ‘bubbles’ of blood formed when an artery is completely

blocked, most likely due to an atherosclerotic plaque. The pressure build up behind
the blockage causes the artery to bulge out and fill with blood. These aneurysms can
then burst if the pressure gets too high or even if the afflicted suffers a knock. The
preceding rupture can cause the patient to bleed out of the artery and haemorrhage,
particularly if the aneurysm is in a high blood traffic area such as the aorta or the base
of the brain. These bleeds can result in instant death of the patient and are very hard to
treat, but if diagnosed early they can be cured through surgery.

Stroke: A stroke is also caused by a blockage in the arteries at the base of the brain,
but unlike an aneurysm, the blood doesn’t pool behind the blockage, it just flows
around other arterioles. A stroke is where reduced blood pressure (ischemia) in the
brain results in the loss of brain tissues, and by extension, brain and bodily functions.
This can be caused by high blood pressure and atheromas in the brain supply arteries.
Strokes are one of the major causes of adult disabilities worldwide and it is the second
most common cause of death in the world. If strokes are detected early they can be
treated with blood thinners and thrombolysis but if missed the effects can be very
severe and life threatening. There are two different types of stroke; ischemic and
hemorrhagic. The ischemic variety are caused by a fall in blood flow most likely due
to arterial plaques forming, and subsequent tissue death, and the hemorrhagic strokes
are caused by a leaking of blood into either the brain tissue or the skull itself. These
are significant differences and are both treated differently, but they both result in loss
of blood flow to the brain.
 14. Adrenaline is a hormone that has an effect on heart rate and breathing rate.
What is this effect and how is it brought about?
Adrenaline is a released in response to anxiety, exercise or fear. There are usually two
reactions known as the “fight or flight” reaction. Both of these reactions require extra
supplies of blood and oxygen to muscles. The brain sends signals to the adrenal
glands in the kidney where adrenaline is produced. This causes large amounts of
adrenaline to be pumped into the bloodstream. The brain also sends an impulse via the
sympathetic nerve to the SAN (sinoatrial node). Stimulation of the SAN by the
sympathetic nerve causes an increase in heart rate. Adrenaline has a direct effect on
SAN very similar to that of the sympathetic nerve. The SAN generates an electrical
impulse that spreads across the right and left atria causing them to contract at the
same time. The impulse also travels to the AVN (atrioventricular node). The impulse
is conducted to the ventricles after a delay. Due to increased heart rate this delay may
be shorter. There may also be a smaller stroke volume as there is less time for the
ventricles to fill completely with blood. The signal will then reach the purkyne fibres
which conduct impulses rapidly to the apex of the ventricles. The right and left bundle
of fibres are known collectively as the bundle of His. The purkyne fibres continue
around each ventricle and branch into the muscle in order to carry the impulse to the
inner cells of the ventricle. The first ventricular cells to be depolarised are at the apex
of the heart and so contraction travels upwards towards the atria. Adrenaline also
causes dilation of the arterioles supplying skeletal muscles, and constriction of
arterioles going to the digestive system and other non-essentials organs; this maximise
blood flow to the active muscles causing an anticipatory increase in heart rate.
Adrenaline also causes an increase in breathing rate and depth. The ventilation centre
in the medulla sends nerve impulses to the external intercostal muscles and diaphragm
muscles causing them to contract. As the lungs inflate, stretch receptors in the
bronchioles are stimulated. The stretch receptors send inhibitory impulses back to the
ventilation centre. As a consequence, impulses to the muscle stop and the muscles
relax, stopping inhalation and allowing exhalation. Exhalation is caused by the elastic
recoil of the lungs and gravity helping lower ribs. Not all air is removed from the
lungs, however during deep exhalation there is less residual air in the lungs. With
increased and deeper breathing, a steep concentration gradient of carbon dioxide
between alveolar air and the blood is maintained. This ensures an efficient removal of
carbon dioxide and uptake of oxygen.

15. A neurotransmitter is chemical that is responsible for carrying a nerve impulse

across a synapse and are usually released following the arrival of an action potential at
the synapse, examples of neurotransmitters are dopamine, serotonin, histamine,
adrenaline and noradrenalin.

16: Explain how cells would manufacture and release Noradrenaline.

Production:
Noradrenaline is synthesized by a series of enzyme catalysed stages in the adrenal medulla
and postganglionic neurons of the sympathetic nervous system from the amino acid
tyrosine.
The first stage is the hydroxylation into dihydroxyphenylalanine (L-DOPA). The enzyme
used to catalyze this stage is called tyrosine-hydroxylase.
This is followed by decarboxylation into the neurotransmitter dopamine, catalyzed by
pyridoxal phosphate & DOPA decarboxylase.
Last is the final β-oxidation into noradrenaline by dopamine beta hydroxylase, requiring
ascorbate as a cofactor (electron donor).

Transport/ Release:
Between the decarboxylation and the final β-oxidation, noradrenaline is transported into
synaptic vesicles. This is accomplished by vesicular transporter in the phospholipid-bilayer.
This transporter does not show any preference for noradrenaline, adrenaline and
isoprenaline.
To perform its functions, noradrenaline needs to be released from synaptic vesicles. Many
substances modulate this release, some inhibiting it and some stimulating it.

17. A second messenger that is used for intracellular signal transduction, such as
transferring the effects of hormones that cannot pass through the cell membrane and
upon reaching their target cells, the hormones activate adenylate cyclase a catalytic
enzyme for the production of cyclic AMP. It then activates the enzymes of the
reaction induced by the hormone concerned.

18. Glucocorticoids are steroid hormones that affect the metabolism of carbohydrates
and are part of the feedback mechanism in the immune system that turns immune
activity down such as inflammation. They affect the glucocorticoid receptor which
controls the up-regulate the expression of anti-inflammatory proteins and down-
regulate the expression of pro-inflammatory proteins. It is also involved in metabolic
process such as producing glucose from non-carbohydrate and inhibition of glucose in
muscles.

19: Which Pain relieving drugs are more effective: (a) for women (b) for men

(a) The most effective pain relief medication for women in a study drug test found that
strong painkillers related to morphine, called kappa-opioids, were most effective at
numbing pain. However the same drugs didn’t work for the men at all. In fact, the doses
used in the clinical trial made pain worse for the men.

(b) A recent study showed that ibuprofen, a widely used anti-inflammatory drug, can be
much less effective for women than for men. Researchers at the University of New South
Wales found that when they used mild electric shocks to induce pain in healthy young
people, only the men got any relief with ibuprofen. It was only a small study, but still
worrying, as the drug is often marketed with women in mind.

20) Clinical trials involving new drugs are commonly classified into four phases, with
each phase treated a separate clinical trial.
The drug will usually be approved by the national regulatory body for use in the
general population after passing the first three phases, with phase 4 acting as a ‘post
approval’ study.

Before clinical trials begin pharmaceutical companies conduct extensive pre-clinical

studies. Pre-clinical trials involve in vitro (test tube) and in vivo (animal or cell
culture) experiments using a wide range of doses in order to obtain information about
 the efficiency, toxicity and pharmokinetics of the drug. These tests allow companies
to decide whether or not it is worth developing a particular drug.

Phase 1 trials are the first stage in the testing of human subjects. They are performed
using a small number of healthy volunteers (20-100) and are used to test the safety,
tolerability, pharmokinetics and pharmodynamics of the drug when taken by humans.
The phase 1 trials also include dose ranging in order to work out the appropriate
dosage for therapy.

Phase 2 trials are performed once the phase 1 trials have confirmed the drug to be
safe. These trials are performed on a larger group of volunteers (20-300) and are
designed to asses how well the drug works, as well to continue with the safety
assessment from the first trial.

Phase 3 trials are randomized controlled multicenter trials on large groups of patients
(300-3000 or more) and air aimed to be the definitive assessment of how effective the
drug is. It is typically expected that a drug passes two phase 3 trials in order to obtain
approval from the appropriate regulatory agency.

Phase 4 trials, also known as post marketing assessment trials, involve the safety
surveillance and ongoing technical support of a drug after it receives permission to be
sold. The safety surveillance is designed to detect any rare or long-term adverse
effects over a much larger patient population and time period than was possible
during the phase 1-3 trials.

21. Explain the term “inflammation”. How is it caused?

Inflammation is part of the non-specific immune response which works at the sight of
the wound to destroy invading microbes. It is characterised by redness and swelling.

Damaged white blood cells and mast cells in the connective tissue below the skin
release a chemical called histamine. Histamine causes the surrounding arterioles to
dilate, increasing blood flow to the site. Histamine also increases the permeability of
capillaries. Plasma fluid, white blood cells and antibodies leak from the blood into the
tissue causing swelling (oedema). The chemicals released attract white blood cells
called phagocytes that "eat" microorganisms and dead or damaged cells. This process
is called phagocytosis. Phagocytes eventually die. Pus is formed from a collection of
dead tissue, dead bacteria, and live and dead phagocytes.

The main symptoms of the inflammatory response are:

• The tissues in the area are red and warm, as a result of the large amount of
blood reaching the site.
• The tissues in the area are swollen, again due to the increased amount of blood
and proteins that are present.
• The area is painful, due the expansion of tissues which put pressure on nerve
cells

Q22) Which organ produces oestrogen?

Both men and women produce oestrogen hormones. The hormones are
responsible for female sexual development i.e. breast development and
the menstrual cycle. In women, oestrogens are produced mainly in the
ovaries and in the placenta during pregnancy. Small amounts are also
produced by the adrenal glands. In men, small amounts of the hormone
are produced by the adrenal glands and testicles.

Like all steroid hormones, oestrogens readily diffuse across the cell
membrane. Once inside the cell, they bind to and activate estrogen
receptors resulting in the expression of many genes.

Yey women!: In both humans and mice, oestrogen has been shown to help promote the
healing of wounds. (http://www.woundsresearch.com/article/5190)

23) Which organ produces progesterone? What effect does progesterone have on an
individual’s experience of pain?
Progesterone is a potent anesthetic and the breakdown products have an
analgesia effect (a pain relieving effect which allows the women to stay conscious).
Progesterone is released around labor as it increases the female’s pain threshold.
Progesterone is a female sex hormone that plays an important physiological role to
regularize and rebuild changes to the body caused by estrogen as well as in the luteal
phase of the menstrual cycle. Progesterone helps prepare your body for conception
and pregnancy and regulates the monthly menstrual cycle. It also plays a role in
sexual desire. Low progesterone levels can cause uncomfortable symptoms such as
insomnia, dizziness, irritability, difficulty concentrating, extreme changes in mood,
bloating, weight gain, muscle pain, joint pain, and urinary incontinence. Other
possible symptoms of low progesterone may include frequent urinary tract infections,
interstitial cystitis, and changes in appetite, hot flashes, cold chills, night sweats, and
vaginal dryness. Symptoms in hormone fluctuations should be brought to a doctor's
attention for treatment.
Progesterone is a steroid hormone secreted by the corpus luteum of the ovary
and the placenta, which prepares the uterus for implantation of the fertilized ovum,
helps maintain pregnancy, and promotes development of the mammary glands.
However during pregnancy the progesterone is produced by the placenta. The
hormone is produced during the second half of a woman's menstural cycle. It thickens
the lining of the uterus to prepare it to acceptimplantation of a fertilized egg. It is
released in pulses, so the amount in the bloodstream is not constant. Like other
steroids, progesterone consists of four interconnected cyclic hydrocarbons. Like all
steroid hormones, it is hydrophobic. Progesterone production is high during the luteal
phase (second portion) of the menstrual cycle and low during the follicular phase
(first portion), as well as being low before puberty and after menopause.
Supplemental sources of progesterone are available in oral and cream forms, as well
as lozenges, suppositories, and injectable forms.

24) Analgesia
The relief of pain without the loss of consciousness. An ‘analgesic’ is the name for pain
relieving drugs (or ‘painkillers’). They work by interrupting the nervous system between
the sense organ and the brain. They do this by acting in different ways on the peripheral and
central nervous system. Non-steroidal anti-inflammatory drugs (such as aspirin) inhibit
cyclooxygenases which results in a reduction in prostaglandin production. This reduces
pain and inflammation.

26. Which organ produces testosterone? What effect does this have on an
individual’s experience of pain? How can the environment influence a
male’s pain threshold?
Primarily, testosterone is secreted by the testes in males, and by the ovaries in
females. A small amount is secreted from the adrenal glands. Testosterone has
been proven to decrease the feeling of pain, so men are thought to be less
susceptible to pain. The environment can increase a male’s pain threshold - if he is
taking part in sport, or trying to impress someone, he may have a higher level of
testosterone. So he will have a higher pain threshold.

27) Explain why women may be given the advice to abstain from hot curries in the last few
weeks of pregnancy?

In the third trimester of pregnancy women’s pain thresh-holds increase and said to be in as
‘induced state of profound analgesia’, this is because of the hormone PROGESTERONE.
When not pregnant most women’s pain thresh holds are much lower than that of men; it is
believed this is this the case because the visceral organs talk to one another so that pain
spreads between organs (because of linked nerve supplies between the organs) resulting in
quicker identification of a problem.
Capsaicin is the chemical in chillies that give them there hot taste. It is thought that
when we ingest this chemical the normal affect of progesterone is blocked and we become
more susceptible to pain. This is why women are often advised not to eat hot curries in the
last few weeks of pregnancy because of the high chilli content and therefore a high content
of capsaicin blocks the excess amounts of progesterone that occurs when pressure is applied
to the cervix  resulting in a more painful labour.

28) Discuss the advice “Reduce your cholesterol levels” with

reference to CVD and analgesia.

Cholesterol is a short lipid molecule. A vital component in cell

membranes, and the production of progesterone and testosterone.
For these reasons among others cholesterol is essential for good
health. Cholesterol is synthesised in the liver from the saturated fats
we ingest from food. However there are concerns that high
cholesterol levels are non conducive to human health.

Cholesterol is transported through the blood in conjunction with

Lipoprotiens.

LDL (Bad) Cholesterol

When too much LDL cholesterol circulates in the blood, it can slowly
build up in the inner walls of the arteries that feed the heart and
brain. Together with other substances, it can form atheroma, a
thick, hard deposit that can narrow the arteries and make them less
flexible. This condition is known as atherosclerosis. If a clot forms
and blocks a narrowed artery, heart attack or stroke can result.
HDL (good) Cholesterol
About one-fourth to one-third of blood cholesterol is carried by high-
density lipoprotein (HDL). HDL cholesterol is known as “good”
cholesterol, because high levels of HDL seem to protect against
heart attack. Low levels of HDL (less than 40 mg/dL) also increase
the risk of heart disease. Medical experts think that HDL tends to
carry cholesterol away from the arteries and back to the liver, where
it's passed from the body. Some experts believe that HDL removes
excess cholesterol from arterial plaque, slowing its build up.

This shows that the advice to reduce our cholesterol levels to

prevent CVD is not entirely accurate. Although LDL Cholesterol is
detrimental to human health, HDL Cholesterol has proven beneficial.
This means that reducing all cholesterol levels may not be as
appropriate a course of action as a greater control on the type of
cholesterol that is taken.

However, reductions in cholesterol intake can also prove

detrimental. The aforementioned by-products of cholesterol,
progesterone etc, could not be produced in sufficient amounts if
cholesterol intake were to be reduced. Progesterone is a potent
analgesic (pain killer) that is produced from cholesterol. This means
that a low cholesterol diet can result in a lower threshold to pain.