About Einstein719

Einstein 719 is currently a medical student in the UK. When he first wrote for this blog he was a sixth former at a state secondary school studying Chemistry, Biology, Maths and Further Maths. The opinions & experiences he discusses on this blog are his own. His posts are aimed at students applying for medical school & those currently studying medicine.

Alzheimers disease

Alzheimer’s disease is one of the most common diseases of the brain and whilst we may not yet have any decent therapies for preventing its progression, our understanding of its pathogenesis is growing and it seems likely that soon new pharmacotherapies will arrive. In this article I want to describe the process that leads to neurodegeneration in Alzheimer’s disease in all its gruesome biochemical detail and then highlight the points where future drugs may act.

So what causes Alzheimer’s disease? Well the only currently used method to diagnose a case of dementia as Alzheimer’s disease is post mortem histology (how jolly). If you look at the brain tissue of someone who had Alzheimer’s disease under the microscope, you see two characteristic features. The first is something called extracellular Amyloid Beta plaques.  These are effectively lumps of gunk amongst the neurons. The second key feature is that amongst the normal looking neurons you will see some neurons which have massively distorted cell bodies, which are bursting full of tiny fibres. These cells are known as neurofibrillary tangles. The Amyloid Beta plaques and Neurofibrillary tangles are the pathognomonic features of Alzheimer’s disease and are believed to be responsible for the cognitive and memory losses seen in people with Alzheimer’s disease.

I now want to try and explain what we know about where the Amyloid Beta plaques and Neurofibrillary tangles come from. It all starts with a protein called Amyloid Precursor Protein or APP for short. You can visualise APP as a rod. Now APP is usually cut in half by an enzyme called alpha Secretase. Now this is the good pathway. Indeed the two products as far as we know don’t cause any problems. However there is another enzyme given the fantastic name Beta Secretase, which again cuts the enzyme into two but it cuts it off centre so that one fragment is longer than it would be when alpha Secretase does the cutting and the other fragment is shorter. The fragment which is now shorter, which is called the sAPP for secreted Amyloid Precursor protein, doesn’t cause a problem. But the fragment which is now longer does. This longer fragment can be cleaved into two pieces again, by yep you’ve guessed it gamma Secretase and one of the final fragments it produces is the nasty bit which is going to form the Amyloid Beta plaques.

Now gamma Secretase can actually cut this final fragment in one of two places. If it cuts in the first place it produces Amyloid Beta 40 protein fragment along with a second piece that we’re not interested in. And if it cuts at the fragment at the second of the two places it produces a slightly longer fragment called Amyloid Beta 42 along with a slightly shorter second piece. It is these two proteins Amyloid Beta 40 and 42 which aggregate together to form Amyloid Beta plaques. It is speculated that Amyloid beta plaques form throughout your life and you only get symptoms of Alzheimer’s disease once you have enough neurodegeneration for deficits to begin. The tendency of Amyloid Beta 42 to form plaques is slightly greater than that of Amyloid beta 40. Hence the gamma Secretase enzyme which your body produces may determine whether you get Alzheimer’s disease in your life or not, since if your enzyme prefers to cleave at the second site over the first you will accumulate plaques quicker.

The first thing to say is that we could use this to diagnose someone with dementia with Alzheimer’s disease whilst they were alive. Indeed by taking a lumbar puncture and measuring levels of Amyloid beta 40 and 42 you could make that diagnosis. However this is not currently done because knowing that this process is the cause of their dementia would not effect the treatment that they receive. This is because at present all drug treatments is symptomatic rather than actually preventing the progression of the disease. It is hoped that in the future we will have drugs which can actually prevent the aggregation of Amyloid Beta 40/42 to form Amyloid Beta plaques. Current drugs which are not yet approved for human used which w believe do this are cyclohexanehexols, tramiprosate and Solanezumab. Solanezumab is a fully humanized monoclonal antibody (that’s what the umab on the end of its name means) which binds to Amyloid Beta 40/42 to hopefully prevent them aggregating. Unfortunately its recently failed phase 3 drug trials.

Ok so that is where the Amyloid Beta plaques come from, what about the Neurofibrillary tangles? Well the tangled fibres within neurofibrillary tangles are a protein called tau protein, more specifically they are phosphorylated tau protein. It is this phosphorylation which allows them to aggregate together in the way that they do within neurofibrillary tangles. When amyloid Beta plaques start forming it is speculated that their presence activates other enzymes called kinases, which add this phosphate group onto the tau proteins. Hence it is believed that the neurofibrillary tangles form as a result of the Amyloid Beta plaques.

Describe the components of an atherosclerotic plaque, indicating the factors which lead to plaque formation. Why are such lesions a threat to health?

Atherosclerosis is one of the major diseases of the western world. Indeed it is estimated that 50% of people in the western world die of atherosclerosis related complications. Atherosclerotic plaques consist of both an atheromatous component and a sclerotic component. The atheromatous component is a lipid core at the centre of the lesion which contains lipid filled cells called foam cells and crystals of free cholesterol. The sclerotic component consists of a tough fibrous cap which develops over the lipid core.

The Lipid core and its pathogenesis

The best theory of why atherosclerosis occurs is that of continued damage. The hypothesis is that prolonged and continuous damage to the endothelial lining of a blood vessel is what starts the process. When the endothelial cells become damaged they allow lipoproteins in the blood plasma called LDL to cross into the subendothelial space, which is the space in tunica intima between the basement membrane of the endothelium and the internal elastic lamina. In addition they start expressing surface molecules to which leukocytes and platelets can bind. The specific leukocytes which are very important in atherogenesis are monocytes. These monocytes bind to the surface molecules and translocate into the subendothelial space becoming macrophages.

The macrophages start releasing inflammatory cytokines and importantly oxidising agents. The inflammatory cytokines act as chemotaxic agents drawing more macrophages and other inflammatory cells into the atherosclerotic lesion. Whilst the oxidising agents convert the LDL molecules into oxidised LDL.

Macrophages have an uptake mechanism for LDL called the scavenger receptor pathway. In this pathway macrophages absorb LDL and store it within their cytoplasm. Molecules of oxidised LDL have a particularly high affinity for this pathway. Hence macrophages end up taking up a huge amount of this oxidised LDL. When looked at under the microscope these LDL filled cells look foamy and are hence referred to as foam cells. In addition the oxidised LDL is toxic to the macrophages which ingest it, so many of them undergo necrosis and release the lipid that they were storing into the subendothelial space. This free lipid, which in particular contains large amounts of cholesterol forms crystals in the subendothelial space which are again visible under the microscope. These are two of the main features of the lipid core of atherosclerotic plaques, i.e. the macrophages which have converted into foam cells along with deposits of free cholesterol.

The Fibrous cap

The damaged endothelial cells also start secreting growth factors such as endothelial derived growth factor (commonly referred to as EDGF). They also express a surface membrane protein called Von Willebrand Factor on their luminal membranes. Thrombocytes in the Blood adhere to this Von Willebrand factor and when they do they start secreting Platelet derived Growth factor (PDGF). Both of these growth factors diffuse into the artery wall, through the tunica intima to the tunica media. Here they trigger activity in the smooth muscle cells. They cause smooth muscle cells to dedifferentiate and digest away their contractile infrastructure. These modified cells then migrate along the chemotaxic gradient towards the source of the growth factors. Hence they migrate to just under the basement membrane of the endothelial cells of the blood vessel, i.e. over the lipid core. Some of the smooth muscle cells don’t make it all the way to the endothelium and instead end up absorbing LDL and converting into foam cells.

Once they arrive there, they begin fibroblast like behaviour. They proliferate to make a covering of these dedifferentiated smooth muscle cells over the lipid core and they also start secreting extracellular matrix proteins, such as collagen. Hence a fibrous layer containing these cells forms over the lipid core and this covering is known as the fibrous cap.


Another central feature of atherosclerotic lesions and one that is important with regards to the complications of atherosclerosis is Neovascularization. Indeed the damaged endothelial cells also start secreting vascular endothelial growth factor (VEGF), which causes the growth of new blood vessel towards the site of the cells which secrete it. Hence blood vessels present in the tunica adventicia, called vasa vasorum, begin to grow branches into the deeper layers of the blood vessel towards the atherosclerotic plaque. Eventually these blood vessels reach the plaque and they typically grow into the shoulder of the plaque. The shoulder refers to the periphery of the plaque, i.e. where it borders with the healthy endothelium.

Risk factors for atherosclerosis

The four main risk factors for the development of atherosclerotic lesions in the walls of your arteries are hypertension, smoking, diabetes mellitus and hyperlipidaemia and we will now address each of these in turn.

Hypertension means too high mean blood pressure. If your blood pressure is too high then your endothelial cells are constantly being exposed to a very large strain. So they are more likely to get damaged and activate the inflammatory response which leads to the formation of an atherosclerotic plaque. This is demonstrated by the fact that the most common site for atherosclerosis to occur is the posterior wall of the abdominal aorta. The pressure that the endothelial cells of the aorta have to endure is very large, because the aorta is the first blood vessel off the heart. But in addition this site is particularly at risk of damaged because it sits anterior to the vertebral column, so every time the heart beats blood is crushing the posterior wall of the aorta against the solid vertebral column and this leads to endothelial damage. If your blood pressure is raised then this crushing will be worsened.

Cigarette smoke contains a huge number of toxins, which the smoker and anyone unfortunate enough to be in their presence breathe in. These chemicals diffuse across the alveolar membrane and into the blood stream. Here they can lead to the damage of the endothelial cells.

In people who suffer from Diabetes mellitus, the blood glucose levels are often unstable and can reach dangerously high levels (hyperglycaemia), because of the lack of control by insulin. These elevated blood glucose levels can directly damage endothelial cells and begin the process of atherosclerosis. Diabetics are particularly at risk of getting atherosclerotic plaques developing in the popliteal arteries in the legs.

Finally Hyperlipidaemias result in much higher blood LDL levels. This means that if the endothelium does become damaged then more LDL will move into across the damaged endothelium into the subendothelial space and the resulting atherosclerotic plaque will be worse than if lipid levels were normal. People who are obese often have extremely high blood lipid levels as well as hypertension and are thus at high risk of atherosclerosis.

Complications of atherosclerosis

There are many ways in which atherosclerosis can lead to complications. Firstly the lesion can lead to stenosis or worse occlusion of blood vessels. It can do this in three ways; either the plaque can gradually grow and narrow the lumen. Or the plaque can ulcerate and then thrombosis can occur on the exposed surface. The resulting thrombus then limits blood flow through the vessel. Or the newly formed blood vessels in the shoulder of the plaque can rupture and lead to intraplaque haemorrhage. This leads to the lipid core swelling as it fills with blood and this swollen lesion can then limit blood flow.

The formation of an atherosclerotic plaque in the aorta is not going to significantly reduce blood flow through that vessel because the aorta is so large. But the second most common site for atherosclerosis to occur is within the coronary arteries and the fourth and fifth most common sites are the carotid arteries and the arteries of the circle of Willis respectively. These arteries have much smaller lumen and the presence of a growing atherosclerotic plaque can seriously limit blood flow to the heart and brain. Hence atherosclerosis in this way can lead to exertional angina pectoris and potential myocardial infarction. Or if the stenosis occurs in an artery supplying the brain then it can potentially lead to occlusive stroke.

The second major complication of atherosclerotic plaques is that they can ulcerate, which is where the fibrous cap becomes detached from the atheromatous portion of the lesion. The process of thrombosis commonly occurs on the exposed surface of the lesion and a thrombus hence forms. As previously discussed this then leads to the stenosis or potentially occlusion of the blood vessel and will result in ischemia and maybe infarction of the tissue which that blood vessel supplies, with serious consequences if it is the brain or the heart. However, another complication is that the thrombus can throw off thromboemboli which can circulate and lodge in other blood vessels. Commonly they lodge in pulmonary vessels causing a pulmonary embolism.

Finally, another complication is that atherosclerosis can lead to aneurysmal dilatation. The atherosclerotic plaque severely weakens the wall of the blood vessel on which it is established and if the blood vessel is under very high pressure from the blood, such as the aorta, this can lead to the blood vessel dilating to a massive size, such as is the case in a triple A. If this ruptures it can lead to major internal haemorrhage and death.


Atherosclerosis is dangerous and very common. By the late teenage years, individuals will have fatty streaks on their aortas, which are speculated to be the forerunners of atherosclerosis. Regular exercise and a healthy diet are thought to lower your risk for developing full-blown atherosclerotic plaques and there is a considerable body of evidence that moderate consumption of resveratrol in red wine also helps.

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Compare and contrast the role of endothelial cells and platelets in haemostasis and coagulation

Haemostasis is the process by which blood vessels with a hole in them produce a stable plug to fill in the hole and prevent haemorrhage. Coagulation is the process by which a soluble protein called fibrinogen, produced by the liver and normally present in the blood is converted into insoluble polymers of fibrin monomers. These fibrin polymers are interwoven into a plug to increase its stability. Both endothelial cells and platelets have essential roles in the processes of haemostasis and coagulation. But as we shall see the role of endothelial cells is more in signalling the need for the formation of a haemostatic plug, whilst platelets actually form the haemostatic plug.


The Primary Haemostatic plug

Healthy endothelial cells are incredibly important for preventing the formation of a haemostatic plug in a healthy blood vessel. But if for some reason the endothelial cells are damaged then a primary haemostatic plug forms. When endothelial cells are injured the collagen of the basement membrane of the endothelial cells and the collagen of the extra cellular matrix (depending on how severe the injury is) are exposed on the luminal surface of the blood vessel. In addition the injured endothelial cells begin to produce and secrete a protein called Von Willebrand factor onto the surface of the exposed collagen where it binds. Platelets, also called thrombocytes which are in the circulation possess a surface glycoprotein called gp1B which will bind to the Von Willebrand factor. Hence a layer of platelets will form over the exposed collagen. This is known as platelet adhesion.


In addition the exposed collagen will activate the platelets and cause them to secrete granules which are stored in their cytoplasm. These granules contain many substances but some particularly important ones are Thromboxane A2, Serotonin (also called 5-Hydroxytryptamine) and ADP. Both Thromboxane A2 and Serotonin are vasoactive and produce vasoconstriction of the arterioles leading to the damaged blood vessel. Hence less blood will be reaching the damaged wall and this will help to reduce blood loss due to the injury. Similarly injured endothelial cells also take action to try and reduce blood flow to the affected area, but rather than producing a vasoconstrictor, they instead stop secreting the vasodilator Prostacyclin.


The final of the products that platelets release is ADP. Platelets have on their surface receptors for ADP and when ADP binds to this receptor it activates the platelet. Activated platelets will then bind to other platelets; specifically they will bind to the platelets which have formed a layer over the exposed collagen, to produce a multilayered structure of platelets. This structure is known as the primary haemostatic plug. The antithrombotic drug Clopidogrel works by binding to the receptor for ADP on the surface of platelets and not stimulating it, i.e. it is an antagonist and simply prevents ADP binding and activating the receptor.


Overall with regards to the formation of the primary haemostatic plus we can see that platelets and endothelial cells have vastly different functions. The platelets actually form the structure which will plug the hole. Whilst endothelial cells are essential for preventing the formation of such a structure in healthy blood vessels and ensuring that it is only produced at sites of injury. So their role is more in coordinating haemostasis.




The purpose of the coagulation cascade is to transform the primary haemostatic plug into a secondary haemostatic plug. A primary haemostatic plug as previously described consists of a multilayered structure of platelets. Whilst a secondary haemostatic plug is a multilayered structure of platelets but with a dense meshwork of fibrin between the platelets holding them in position. The secondary haemostatic plug is far more stable than the primary haemostatic plug and prevents haemorrhage more effectively.


In order to produce such a dense meshwork of fibrin it is necessary to turn fibrinogen which is a soluble protein in the blood plasma into these fibrin strands. The enzyme which converts fibrinogen into fibrin monomers is called Thrombin and the inactive precursor of thrombin, called Prothrombin is constitutively present in the blood plasma. Another enzyme called Factor XIIIa then converts the fibrin monomers into Fibrin strands. Hence in order to produce the fibrin strands it is necessary for Prothrombin to be converted into thrombin and the series of reactions by which this conversion occurs is known as the coagulation cascade.


Similarly to in the formation of the primary haemostatic plug it is the damaged endothelial tissue which starts the coagulation cascade. Damaged endothelium does this in two ways. The first way is through the intrinsic pathway, when there is damage the protein HMW kinin, standing for heavy molecular weight kinin is produced. This converts factor XII into XIIa. The activated factor XII then in turn activates XI to XIa and XIa activates IX into IXa. Then comes the important stage which is the activation of factor X. Factor X is activated by factor IXa, but it must be in the presence of factor VIIIa, calcium and phospholipids. This is important because it is the activated platelets which release calcium ions and it is also the platelets which act as a surface of phospholipids on which this reaction can occur. Hence this stage means that the coagulation cascade can only occur on platelets surfaces, i.e. it ensures that the fibrin is going to be produced in the primary haemostatic plug.


Factor X has two stages of activation. The first we have just seen and the second is done by Factor Va. Once factor X is activated to factor Xa, it will catalyse the conversion of prothrombin to thrombin and hence coagulation can begin. Thrombin then further activated factor V to Va to produce a positive feedback loop.


The second pathway by which endothelial cells can activate the coagulation cascade is through the extrinsic pathway. In this pathway, the endothelial cells along with any damaged cells in the interstitum underneath produce a protein called tissue factor. Tissue factor converts factor VII to factor VIIa and factor VIIa can undertake the first portion of factor X activation. Again though this transformation must take place on a phospholipids surface and in the presence of calcium, which helps to ensure that fibrin deposition occurs actually within a primary haemostatic plug and not just in the free circulation.



Overall we have seen that in both the formation of the primary haemostatic plug and its conversion to a secondary haemostatic plug, via the coagulation cascade, endothelial cells have a regulatory function. Indeed they help in both cases to ensure that both processes only occur when there is damage. They do this by preventing exposure of the underlying collagen in the case of platelet adhesion and by expressing surface molecules like Antithrombin which inactivates thrombin in the case of coagulation. Platelets on the other hand play a more active role in the case of primary plug formation, since they are the structures which will actually bind together to form the plug. With regards to coagulation they are more similar to endothelial cells and play a guiding role, i.e. they ensure that fibrin deposition happens at the correct site.

The biochemistry of steroids-what are steroids and what are they used to treat medically ?

From school children to medics nearly everyone has heard of a subgroup of hormones known as steroids. However if asked to define what a steroid is, few would get further than: something that has an effect on the body. So what exactly is a steroid? 

Chemically a steroid is any molecule that has a specific arrangement of cyclic carbons. Namely a steroid contains 3 cyclohexane structures and 1 cyclopentane. These are arranged in a specific order and if you wish to see this order simple google it. However when most of us talk about steroids what we really mean is steroid hormones, i.e. human hormones within the body that are steroids. Steroid hormones are subdivided into three types: Glucocorticoids, Mineralocorticoids, Androgens, Estrogens and Progestogens.

Generally our body synthesizes mineralocorticoids and glucocorticoids in the suprarenal (Adrenal) glands, which sit atop the kidney. Whilst Androgens, Estrogens and Progestogens are synthesized in the Gonads/Genitals. All five are synthesized from the sterol: Cholesterol. A Sterol is a steroid with a hydroxyl (-OH) functional group attached to the steroid structure. This gives the sterol a amphiphillic structure, i.e. it is both hydrophobic and hydrophillic, which is extremely important for cholesterols use in the cell membranes of cells.

So steroid hormones have a specific chemical structure and are synthesized from cholesterol. But what do thay actually do? Well the answer to this questions is predictably different for each steroid. However the subgroups of steroid hormones divide steroids into categories based on the repercussions they induce within the body. So:

Glucocorticoids – Glucocorticoids are a branch of steroids produced in the adrenal cortex and which bind to the Glucocorticoid receptors, which are present in nearly all vertebrate cells. Glucocorticoids have two major functions within the body; firstly as their name suggests they play a role in the regulation of glucose metabolism. Indeed Cortisol, which is the primary (main) glucocorticoid stimulates several processes, which serve to increase and maintain the glucose levels within the body. The first process by which it achieves this is gluconeogenesis, which occurs in the liver and generates glucose from non-carbohydrate molecules, such as glycerol, lactate and amino acids. The second main process is the inhibition of glucose uptake by muscle and adipose tissue (N.B. Adipose tissue = fat tissue) and thus the catabolism of fatty acids within muscle tissue instead of glucose.

Glucocorticoids also have anti-inflamatory properties and hence are used in medicine to treat allergies, asthma, autoimmune diseases and sepsis. A particularly potent anti-inflamatory is Prednisone, the active metabolite of which is prednisolone. Glucocorticoids achieve their antiinflamatory nature through two methods – firstly they up-regulate the expression and consequent production of anti-inflamatory proteins. This is achieved when the glucocorticoid binds to the glucocorticoid receptor and thus triggers the expression of antiinflamatory proteins in the nucleus a process known as transactivation  Secondly they down-regulate the expression of pro-inflamatory proteins, by preventing the translocation of transcription factors from the cytosol/cytoplasm to the nucleus, a process known as transregression.

Mineralocorticoids – Mineralocorticoids are the second division of steroid hormones generated within the adrenal cortex, leading to the mineralocorticoids and the glucocorticoids collectively being refered to as corticosteroids. However their functions are very different – Mineralocorticoids regulate water and salt content of the blood plasma. The primary mineralocorticoid is Aldosterone, which plays a key role in the Renin-Angiotensin-Aldosterone-System, which is a system that modulates the water content of the blood. I could write a whole article on the RAAS, but that is not the focus of this blog – so back to the specific role of Aldosterone. Aldosterone production is triggered through the RAAS and it results in the kidneys reabsorping more sodium ions within the distal convulated tubule of the nephrons. This reabsorption of sodium leads to water more water moving via osmosis back into the capillaries. Aldosterone also leads to a greater excretion of H+ cations (protons) and potassium ions out of the medulla of the kidneys and into the urea collecting ducts. In short mineralocorticoids control the amount of water and mineral retention in the kidneys and hence the water and mineral content of the blood.

Androgens – These are the Steroid hormones which promote the development and maintenance male characteristics in humans, this includes the development of the male sex organs and also the secondary sex characteristics. The primary androgen is testosterone and is produced in the testes. The production of testosterone as discussed in an earlier blog is mediated by LH from the Pituitary. The original main bulk of anabolic steroids were androgens and androgens are also important precursors to estrogens. 

Estrogens – Estrogens are the female sex steroid hormones. There are three types E1 – Estrone, which is present in post menopausal woman. E2 – Estradiol, present in unpregnant woman and produced by the developing follicles during the menstrual cycle. E3 – Estriol, present in pregnant woman. Estradiol is crucial for the building up of the endometrium, in preparation for embryo implantation.

Progestogens – Progestogens are a group of carbons with a 21-carbon skeleton, known as a pregnane skeleton. The two major Progestogens are Progesterone, which mains pregnancy and Pregnenolone, which acts as a precursor in the production of all other Steroid hormones.

Diabetes – another disease that is a big problem in the Western world?

There are two types of Diabetes:

Type 1 Insulin dependant Diabetes. This is an autoimmune disease, which occurs because the body accidently creates antibodies against its own cells, specifically here the cells within the Pancreas which make insulin. These cells are called Beta cells and they synthesize the hormone insulin, which regulate blood glucose Level. This results in the Pancreas not being able to make insulin and blood glucose levels therefore rising.

Type 2 Diabetes is different in that it is not usually insulin dependant, i.e. sufferers don’t have to inject insulin into their bodies to treat it. Type 2 arises from insulin resistance. Insulin resistance is when the body cells become resistant to insulin and more insulin is therefore required to have the same effect. To understand this better we need to know more about the mechanism of insulin.

Insulin works, to downregulate glucose levels, by causing fat and muscle cells to take up the glucose and metabolise it. The insulin binds to insulin receptors on the cells surfaces and causes them to take in glucose. During insulin resistance this mechanism becomes weaker and the cells become less responsive to the insulin receptors – consequently more insulin is required. Willingly the pancreas responds and make more insulin. But gradually the insulin resistance increases and eventually the Pancreas can no longer continue increasing its production and the individual will develop diabetes

The causes of type 2 diabetes are varied – the most common ones are:

Obesity, Pregnancy (Gestational diabetes), Stress, infection or severe illness and certain medications (including steroids such as prednisone and HIV medications).

Obesity is the main one that is on the rise and many speculate that this is primarily the reason for the rise in type 2 diabetes in the west.

So why do higher blood glucose levels cause a problem? Well if the condition is chronic then it can damage the eyes, kidneys, nerves and heart. For the eyes it can cause blindness, the kidneys – kidney failure, neural damage and finally within the vascular system is can rapidify the development of arterosclerosis, which can lead to cerebravascular accident (stroke), coronary heart disease and myocardial infarction.

The good news is that we believe these diseases can be avoided, i.e. you can significantly reduce your chance of developing either type, by maintaining a healthy weight through a healthy diet and exercise. This is particularly important if you are pregnant, although gestational diabetes can occur in slim fit women who are pregnant!

How running has changed my life

At the start of this year I took up running after reading on the internet that it was a brilliant way to handle stress and improve your psychological health. I was never really in it for the physiological benefits.

At first I started with just walking and running a few short distances – then gradually I progressed and started being able to run further without a break. It gradually gets easier and easier, and I found it was a great was to release the stress accumulated from a school day. The psychologicasl benefits are great – its like going to sleep and waking up fully refreshed. Indeed exercise is speculated to downregulate cortisol, the hormone which is released into the blood stream in response to stress. The more precise mechanism is that stress causes the hypothalamus to release adrenocorticotrophic releasing hormone (ARH), which then causes the pituitary to release adrenocorticotrophic hormone (ACTH). The ACTH then travels in the bloodstream to the adrenal gland, located above the kidneys and causes it to release adrenaline (epinthrine) and Cortisol.

I have read that Cortisol is known to kill neurons (nerve cells) and this is believed to be why chronic stress gives rise to depression. Cortisol harms brain cells in three ways: firstly it interferes with the neurotransmitters, secondly it interferes also with the brains supply of glucose and thirdly it cause the calcium ion channels to open and therefore a sudden influx of calcium ions into the neuron. The calcium ions create free radical molecules which then kill or signifcantly damage the cell.

This loss of nerve cells has been linked to loss of concentration, which prevents adequate memory. So in fact less stress may = greater intelligence.

Im starting to get hooked on sport and have taken up rowing and badminton, as well as joining a running club, in which there is no stopping until  everyone stops.

Latest development in Neuroscience

Previously I had believed that synaptic pruning within the brain was something that happened only twice in your life: during the first years of life and during puberty. And that once this had happened your brain was moulded and set for life. However resent scientific advances, reported in the new scientist (20:08:11 edition) have suggested that this is not the case and in fact your brain is still remoulding its design, through synaptic pruning late into the twenties.

Moreover my belief that synaptic pruning was occuring in the first few years of life seems to have been wrong, as the article states that: “(dendritic) spine density increased rapidly during infancy reaching a peak before the 9th birthday”. Dendritic spines are small “door knob” shaped extensions of the dendrites, which have on their ends a PSD (post synaptic density). The role of the PSDs and therefore also the denritic spines is to recieve the incoming neurotransmitters, from an axon of another neuron and then send the message the signal to the neruon cell body (the soma).

By the age of nine then our brain has far too many connections between individual neurons. Over the next 20 years of our lives our brains are pruned so that half of these neurons are disconnected. this pruning is done to the crude: “Use it or loose it” principle. Therefore the neuron connectors we dont use – we loose. This neural pruning is believed to be crucial for learning and other cognative functions.

So whats the significance of this advancement? Well the disease schizophrenia is commonly developed whilst in the twenties. So now many neurologists and psychiatrists are theorizing that it may be due to a developmental complication, rather than a degenrative component. So we may be one step closer to curing a long incurable psychiatric disorder and who knows the further implications and applications this revelation could have – this is the beautiful ambiguity and mystery of science.

Asthma – the disease ensnaring the first world

As the medical world of the west grows ever more accomplished at fighting disease, there is one condition that seems to be just getting worse and worse – but is it? With statistics now calling it the most common chronic illness of the Western world I am going to examine the current and potential treatments for Asthma.

Although medicine has identified that asthma is triggered when an allergen, to which the sufferer is particularly sensitive to, is breathed into the airways, science is not yet able to explain, as with all allergies, how it is that that person ever became particularly sensitive to said allergen. It is also unexplained why the senistivity occurs particularly in the airways. So at present treatment revolves around getting asthma under control, and keeping it that way rather than curing it.

Once the allergen enters the bronchioles (smaller airways in the lungs) it triggers a collossal response and the bronchioles constrict, meaning that the inhaled air cannot then be exhaled. This means that fresh air cannot be inhaled and the sufferer of an asthma attack has extreme difficultly breathing. This often then triggers a panic attack sending the sympathetic nervous system into a state of flux and causing rapid shallow breathing which often makes things worse. The allergen also triggers lots of mucus to be made which further blocks the airways.

Some doctors believe that a person develops asthma when a viral infection damages lung tissue, leading to hypersensitivity to allergens. Other theorists believe that asthma is not understood because it is caused not only by the immune system, but also by the nervous system, the system of the body we arguably know least about.

Another theory is that asthma patients have too great a density of sympathetic neurons than parasympathetic neurons in the lungs. This means that they have more neurons which trigger a stress reaction, than neurons that trigger relaxation. Therefore potentially when the body gets stressed, i.e. during heavy exercise, the sympathetic nervous system goes into a state of high activity, including the neurons in the lungs. and this high activity then triggers the constriction of the airways and so an asthma attack. However the flaw in this theory is that it still does not explain how the neuron imbalance ever came to be and just points back to genetics, which is what happens a lot in biology, when no better answer is known.

So asthma genetic or not? – the difficultly I have with believing its genetic is surely it would have been eliminated hundreds of thousands of years ago by evolution and survival of the fittest. And so now we surface onto the centre of much of the research into asthma: is it caused by the modern western lifestyle? Unfortunately at present it does seem that way: the air pollution; the junk food and the incubated design of our homes which are perfect for breeding dust mites.

So asthma is at present an incurable disease in the clinical notebook, and maybe lifestyle changes, for instance eating fresh food as opposed to processed; eating organic over treated fruit and vegetables; maybe move to the countryside could help. So yes at present the “cure” for this fast spreading chronic disorder seems very wooley.

Blood type and its clinical implications

Easily the most common blood group system in the world is tha ABO naming system. This system refers to the different antigens on the surface of the red blood cells, also called erythrocytes. An antigen is a molecule (usually a protein) that causes an immune response when it enters the body. Cells present antigens on their surface – this is why invading bacteria cells cause an immune response.

There are two different antigens that can be presented on the cell surface of an erythrocyte and these antigens are labelled A and B. However there are four different blood types – this is because individuals red blood cells can either have A, B, neither or both.

Therefore the four blood groups are   A    B    O     AB

But the antigens comprise only half of the story – their second half is the antibodies, which attach to the antigens to form an antigen-antibody complex. Antibodies are made by white blood cells (Leukocytes). There are three types of Leukocytes – Phagocytes, B Lympocytes and T Lympocytes.

 B Lympocytes are the type which make antibodies and are very specific – each cell will only create one type of antibody against one non-self antigen. An individual will however not have antibodies against self-antigens, i.e. the antigens on ones own cells. So if you have blood group A you will have antibodies against antigen B but not against A and vice versa. If you are blood group O you will have antibodies against both A and B antigens and if you’re AB you will have antibodies against neither.

This is very important for blood transfusion as If you give someone a transfusion containing the wrong blood type then their immune system may attack the red blood cells. This causes agglutination (sticking together of the blood cells).

Whether agglutination will occur depends on the patients blood group and the blood type given to them. For example someone with blood type AB can recieve blood of all types as they have antibodies against neither antigen. On the contrary someone of blood group O can only recieve blood of type O as they have antibodies against both antigens.

Visit here for information about home blood group test kit

home blood group test

Applying to medical school – Where do I start?

Both of my parents went through UK medical school and went on to become GPs and their accounts of the application process made it seem frankly easy, indeed my dad got in with A level grades: BCC. So I relaxed myself on the notion that I would get in with no trouble at all – what could have changed in just 30 years?

How wrong we were. Competition for places has increased so dramatically, with nearly all applicants with at least AAA at A level and a long and impressive list of both work experience and voluntary work in the medical related field. Ive been told that they don’t even consider you unless you`ve done a lot of voluntary work.

Im currently in Year 12 so will be entering university in September 2012 and applying in a couple of months. I have at present done no work experience or voluntary work in the field, except for the work experience I did through school which was at the local dentists – so slightly related. So I went onto the www.do-it.org  – which is an absolutely fabulous website and Iive now got an interview tomorrow to see whether I’ll be suitable for a voluntary placement with a charity that looks after people who have just been discharged from hospital. So all smiles on that front.

As for work experience im hopefully going to do some over the summer holidays. My parents are no longer GPS but my uncle is a consultant at Edinburgh hospital. So theres a possibility I might be able to go there. If not I might just go to our local general practice.

Now onto another aspect of application – entrance exams. The medical schools I wish to apply for are: Oxford (would be absolutely lovely to get into this one), Imperial, UCL, Durham and Liverpool. I was going to apply to Warwick but I dont think they accept undergraduates for medicine. Now for Oxford, Imperial and UCL I need to sit and do well in the BMAT, whilst for Durham I need to sit the UKCAT and Liverpool mercifully requires no entrance exam. When researching this I thought for a while that I was also goiug to have to sit the 6 hour GAMSAT exam, but thankfully thats for graduate entry only. The BMAT seems quite easy, but the UKCAT has some really bizarre sections in it, one requires you to interpret codes and the other is abstract reasoning. Anyway I’m sitting that in July and have bought a practise book.

I havn`t even considered interviews yet – that will be a future hurdle.

Accutane – Month 4, Day 107 , week 16

7:06:2010 – Returned to the hospital to see the dermatologist, who increased my dose from 30mg a day to 60mg, which I still take in one go.

The affect has been very quick all the acne is starting to diminish under this heightened dose. I no longer have any active acne on my arms or chest and my back is clearing up also. Obviously along with this my skin has become very very dry and almost flaky. Im now using two moisturizers on my face along with aloe vera gel, which was a really useful tip from “highonhealth.com”.

I am not getting many adverse side effects from the drug. I certainly dont feel suicidal or even depressed. At some points, whilst I was on the lower dose I had some moments of feeling very down, but these were when I was very tired. I think being on the drug made those moments worse, rather than actually causing them.

Recently I have given up caffeine and am sleeping much better as a result of this and have not had one of these moments for a while. <(-_-)>

Still have not had a single nosebleed since applying vaseline constantly twice a day. Again <(-_-)>

 And my skin is looking is looking the best its looked for a very long time. <(-_-)>

Isotretinoin – Month 3, week 10, Day 68

7th May 2010: Roaccutane is working very well. All the huge cysts have gone from my face now and I have only small pimples, which come and go within a few days.

My lips are extremely dry and even excessive use of lipsyls wasn`t working – also I don`t like using vasaline. However I have found that one works very well now – called aloe lips, making the whole experience a lot more comfortable. My skin was becoming very dry as Istopped using the “simple” mositurizer, because it had stearic acid (comedogenic) within it. However one trip to Boots produced a non-comedogenic moisturizer, which has fixed this.

I have only a couple of tiny marks left on my chest now, which I’m pleased about and all the acne on my arms and back is drying! Hah! However it seems to mark the skin on my arms really badly – much worse than it marks my face. However other marks that I have had here have faded over time – so I remain confident.

The nosebleeds have stopped completely – with the use of vaseline on the inside of my nose.

A couple of weeks ago I got a strange rash on my arm- it was a patch of extremely dry skin and it looked very like eczema, which I have never had in my life. Thankfully it has gone , with the use of moisturizer on the spot.

 My GCSEs are approaching and the “stress” doesnt seem to be causing any breakouts. YEY!

 I return to see the dermatoligist, probably to get my dose upped – in exactly one month – 7th June.

Isotretinoin – Day 37

The Initital breakout sucked…

Between weeks 2-4 I developed many pus filled cysts, especially on  my cheeks. Now at the beginning of week 6 they are all going down: “slowly but surely” is an idyllic, apt thrase for the improvement.

My lips are incredibly dry (no matter how much vaseline I apply) and without the use of an intense moisturizer my skin gets very dry also – but those side effects were not unexpected and are in some ways reassuring as they show it is working.

The acne on my arms, back and chest is all reseading also. I love not having to use the blue light for hours and applying Benzoyl Peroxide (such a fowl chemical) to my skin, but my acne is still improving: at the moment I love this drug.

 Side effects so far; Dry skin and lips, headaches (occasionally), nose bleeds (from time to time – must remember to apply vaseline to the inside of my nose everyday – dont want to have one of these whilst at school), very dry hair, less reistance to disease ( I’ve had a lot of colds, which I usually dont get!).

Benzoyl Peroxide – “Digests Bacteria: But what is it doing to my skin?”

Many over the counter and prescription creams and gels, manufactured for the treatment of acne contain Benzoyl (or Hydrogen) Peroxide. Scientists and dermatoligists have found that this chemical reduces bacterial levels within the skin by 95%, after 5 days of usage. An achievement it would take tetracycline and erythromycin 2 months to achieve. No wonder then, that this is described as the “gold” of acne treatments.

I like many others, used this chemical (Benzoyl peroxide 2.5%) to treat my acne, for around 2 months. Whilst using I certainly saw its promised results: my acne did go down a lot ( but it never got me clear) – from huge ulcer like cysts to mere pimples.

However the damage this drug inflicted upon me, spolit the results. Initially, I was niave enough to believe that it wouldn’t dry my skin out that badly and dabbed it on liberally with no moisturizer – nothing. It turned me bright red and a couple of days later my skin wasn’t just flaking off (as mentioned could happen within the first days of use) but was rather peeling off – huge chunks at a time. After prolonged use the redness became less pronounced and the dryness went completely (with use of a moisturiser).

I found Benzoyl Peroxide to be a harsh topical treatment for acne, perhaps the harshest (although I’ve read thats Retin A) and my advice to anyone who is using it would be:

  1. Use only 2.5% gels and creams (5% and 10% literally do just burn you – this is a a face peel)
  2. Use tiny amounts and spread over large areas of skin
  3. Use a good moisturiser (one that doesn’t contain oil otherwise its counterproductive)
  4. Dont use a greasy “moisturising” soap  – I found it made my acne so much worse.
  5. Dont apply it with other creams ( I tried using it with adapalene to negliagable results)
  6. Wear  suncream if exposing skin to sun for a long session (Bp makes the skin a lot weaker and far more prone to sunburn)

Conclusion: I acknowledge that for many BP is a godsend. But for me the side effects so far from Roaccutane have been less than those I endured with BP.

Isotretinoin – Day 8

8 March 2010: Have now taken 240mg of Isotretinoin in total and can definately feel it within me. My lips are now really dry and begin to crack, without the use of vaseline. My skin feels more fragile – when I apply moisturisier it stings a little (the way it used to when I first started using benzoyl peroxide) and I can see now why the dermatoligist wanted me to stop all other treatments.

 Last week I suffered from a few minor headaches. I think this may have been whilst I still had moderately high doses of tetracycline in me, which increases the risk of “idiopathic intracranial hypertension” – basically headaches. These have now ceased, which has pleased me since it suggests that it wasnt accutane alone causing them.

Positive: My acne has not broken out as badly as I expected. I expected that it would return, as it was before christmas – severe nodulocystic. However since starting accutane I haven’t had a single cyst develop (on my face anyway – I don’t look at my back). I have had a lot of new spots come, but they are small, come to a head and heal very quickly. Much quicker than I think they would if I was not taking isotretinoin.

Isotretinoin – Day 1

March 1st 2010:

Returned to the dermatoligist today, with healthy blood tests, and was finally put on a generic form of Hoffman Laroche`s (Ro)accutane. I weigh 63kg and was therefore started on 30mg daily ( 0.5mg/kg/day).

Picked up the tablets from hospital pharamacy the same day and then returned to school. I was in an ecstatic state all day. Have disposed (finally) with my tetracycline tablets and benzoyl peroxide creams – it was a very good feeling.

I plan to continue using the blue light therapy (less frequently) throughout the first months of accutane use, to help it along a bit. I am a little nervous about the drying affect of Isotretinoin, but am confident that it cannot be much worse than what benzoyl peroxide did to me when I first used it.

Am about to take the first capsules with dinner now – I am sure that in 4/5 months time I will be extremely glad of my decision to take this drug.

Roche Accutane (isotretinoin) – “magic cure” or ”dangerous drug”

This is a matter which has concerned me for a long time – is Ro-accutane safe?

I, as I’m sure have many, have read a huge amount of content both pro and anti Ro-accutane.

There are many accounts of its success, but also its potential side effects. Some websites even seem to imply that there is a liklihood that it will kill you – this worried me hugely. But after speaking to a professional consultant dermatologist I am far less worried. He told me that he has treated thousands of people with isotretinoin and most experience only dry skin and chapped lips, with some occasionally getting joint aches.

Therefore to me it seems that the side effects of this drug are completely over hyped. The worst culprits for this, I feel are companies trying to sell you “acne vitamens”. To me this implies that if they feel the need to discredit Ro-accutane, it is most likely because it achieves better results than their product does. 

Therefore I have personally come to the conclusion that only one who has never suffered from acne would argue that Ro-accutane is definately not worth consideration. However I do acknowledge the very real danger posed to pregnancies, of those on this drug.

Isotretinoin – my only option.

Although the skin on my face is 100 times better, my back, chest and now arms also, are terrible. I cannot treat it with BP, for I would use a whole tube each time I applied it and the blue lamp is so time consuming already just using it on my face, so I cant use that either.

Feb 2010: I went to see an NHS dermatoligist (we decided against private as my skin was improving with topical treatments), with the intention of asking to be put on Ro-accutane (isotretinoin) or one of its generics. When I asked, and with only my newly improved face to go on, he looked very sceptical as to whether I needed Ro-accutane. But after I showed him my back and arms (my chest is not really that bad) he agreed instantly.

Now, in the UK, the prescription procedure for R`tane is much quicker (no i-ipledge), all I had to do was have my blood test fine. I had my blood taken, at the GPs a few days after and expect them to be fine. I return to see the dermatoligist on the 1st march 2010 and presuming my blood tests have been fine, i will be prescribed it and begin the course the same day. I dont yet know how long im going to be put on it for and at what dose – that will be determined 1st march. At present I am a little concerned as to what will happen to my face when I drop all other treatments ( as you have to when taking R`tane). Isotretinoin is suppose to cause an initial breakout anyway – so I am certainly not looking forward to the first month on it. My derm did say that if it gets really I can come back and be prescribed “emergency” steroids to prevent the inflamatory response.

Photo therapy and its dramatic effect on me

December 2009: Whilst my mother was trying to get me a private derm, my father was also spending money to try and solve this for me. It was really damaging my self esteem and I had no motivation to do anything other than watch tv and escape reality through computer games, such as Runescape.

At the time I was also doing my GCSE mocks, which didn’t help by adding to my stress. Anyway my dad bought an acne lamp, which effectively is just a blue lamp. You hold this to your skin and it activates some chemical in the bateria causing them to fry themselves. I`ve heard that if you have this treatment done prefessionally it hurts quite a lot, but I personally have noticed no side effects.

Within about three weeks the skin on my face was looking so much better I no longer had huge cysts and nodules and had fewer pimples. The change was incredible. However it would be unfair to attribute all this improvement to the blue lamp. I was still taking Lymacycline (although this is clearly not the reason for the improvement since I still have sever acne on my back and chest) and I was still using benzoyl peroxide. Together it seems BP and the acne lamp have cleared up my face considerably, to the point were I have no more acne than most people in my year at school (Year 11) and I was so much happier with my life, come new year.

2010 had started on a positive.

Severe Acne vulgaris and its affect on teenage psychological health

November 2009: My acne had become severe, I would have described it as acne fulminaris. My dermatolical appointment was not until february 2010. I was desperate and began to search the internet. I came across the website acne.org, which heavily recommends benzoyl peroxide. I had heard that this was extremely irritating and dryed your skin out terribly.

However i really didn’t care anymore so went to the chemist and bought BP 10%. My face went bright bright red and flaky and I immediatly abandoned BP and returned to adapalene.

December 2010: Acne getting really severe, with huge nodules and cysts starting to join together – to form like a riverworks of acne. I am forced to re-try BP. This time 2.5% and with a good mositurizer. It doesnt have the severe affect as it did the first time. It seemed to be drying the spots out effectively but I had so many at this point that I could see no dramatic improvement. My acne was so bad my mother thought that I could have a secondary infection and retruned me to the GP to ask to see a private dermatoligist.

Erythromycin for Acne treatment

September 2009: My acne was beginning to become nodular and it was covering my back and chest. Therefore my mother insisted that we return to see the doctor, although i at the time was adamate that commercial products would eventually work. The doctor kept my on adapalene, which i had continued to use with commercial products. But changed my antibiotic prescription to erythromycin.

I was sceptical at the beginning, thinking that this would do nothing – how wrong I was. Within 2 weeks I was completely, and I mean completely clear. I was ecstatic, unfortunately the results were short lived. The bacteria became resistant very quickly – in about 2 weeks my acne was descending back into its prior severity and the erythromycin was starting to have its common side effect of making my skin ridiculously greasy. Moreover I begun to acquire strange rashes on my arms ( target shaped), which on examination of the leaflet proved to be a known side effect of erythromycin. My doctor removed my prescription immediately and returned me to lymacycline. He then refered me to an NHS dermatoligist for stronger treatments.

Commercial treatments – creams/scrubs/washes/gels – CLEARASIL

August 2009: However no good thing lasts forever and in the summer of 2009 my acne entered a stage, which one would dub: moderate. I, in my ignorance, presumed that the medication prescribed by my GP, didnt work properly. I prefered, foolishly I see now, to place my trust and reliance in the hands of the commercial products.

I tried loads of exfoliating scrubs, ( the one i found worked best was St Ives), antiseptic washes (boots, clearasil, clearasil ultra ect). I must have spent hundreds of pounds and hours upon hours in the bath and shower, but nothing worked. I found however that my condition did inprove after strong exposure to sun light but I would not advise this as a treatment, as it can have disatrous long term affects.

Developing Acne Vulgaris

December 2008: Soon my skin condition began to get worse. It started getting worse as winter came and I spent less of my time exposed to UV (which is known to effectively kill proporibacterium – but which is never used as a treatment due to its long term damage on the skin). Therefore I once again returned to the doctor for a new treatment.

He gave me an adapalene gel (Differin) and an antibiotic (Lymacycline/ tetracycline 300mg). The combination had a miraculous effect and cleared most of the acne, within a month. I continued to use the treament for about half a year and although it never had me completely clear, I had only a couple of small pimples, which was commonplace within school.

Mild Acne, at the age of 13.

Guest blogger saying hello 

I am currently 15 years of age (15 and  1/2 to be precise) and I have suffered from acne for around 2 years. Originally it was extremely mild and my GP prescribed me Zineryt, which was intended to kill the proporibacteria. I do not fully know the effectiveness of Zineryt, since at the time, the acne was so mild, I thought it not worth my time trying to fight it. Therefore I only occasionally bothered to apply and consequently it had very little affect.