Revenged

biochemical starvation mode starts about eight hours of not eating food... normal metabolism we rely on our glycogen stores in the liver and glucose from digested food replaces them: carbohydrates ingested -> digested to glucose in gut -> absorbed into blood -> utilised as energy or converted to glycogen store biochemical starvation mode starts after about eight hours of not eating food... this is where glycogen stores start to become depleted and are used in metabolism and are not replaced sijnce no food has been eaten... since glycogen stores run out fats (and to a lesser extent protein) are utilised instead... as for ketogenesis i'll explain fat metabolism basics... fat molecule broken down in the liver {triglyceride -> fatty acid + glycerol} fatty acids can be used as energy source but since there is excess fatty acids within the liver and not enough for the muscles the liver converts fatty acids into ketones... ketones can be used as an energy source for the muscles... your metabolic rate decreases with such a long periods (i.e. 12 hours) without food so 'starvation' diets do not work !!! metabolic rate falls so dramatically since humans have evolved over thousands of years to not lose weight during periods of starvation/low food intake... ketogenic diets - e.g. Atkin's diet - is what a lot of people use... this is where restrict the amount of carbohydrates and so you intake so you utilise fat and protein intake... the calories are often the same but you feel fuller... so there is a biochemical basis for this but it is not popular in the medical field as it's most diets advocate low fat and calorie constriction... this is a debate in itself...

one equation can explain it best: CO2 + H2O <=> H2CO3 <=> H+ + HCO3- respiratory acidosis more CO2, equilibria shift to the right, high [H+], pH of blood reduced (acidosis), respiratory alkalosis less CO2, equilibria shifts to the left, reduced [H+], pH of blood increased (alkalosis) metabolic alkalosis increased [HCO3-], equilibria shifts to the left, reduced [H+], pH increased (alkalosis) metabolic acidosis reduced [HCO3-], equilibria shifts to the right, increase [H+], pH decreased (acidosis) to answer the original question: during anaerobic exercise you have a mild form of respiratory acidosis due to increased CO2 in being carried in the blood... the change in pH is detected the body and then body then counteracts this mild acidosis by increasing the removal of carbon dioxide... you could also counteract respiratory acidosis by increasing HCO3- levels into the blood... one way this could be done by giving a sodium biocarbonate (NaHCO3) injection... hope that is clear...

I think it would be good to add how opioids inhibit pain... The major pain pathway is the spinothalamic tract... It goes like this: Sensory nerve -> Spinal cord -> Brain (Thalamus + Somatosensory cortex) Opioids work on by binding to (mu) opiods receptors in the spinal cord. These receptors are inhibitory receptors. When they are activated they prevent the activation of the pain neurones in the spinal cord. It prevents the "pain" message from reaching the brain. Opioids are addictive but the evidence has found that people who are given it in chronic pain do not easily become addicted. It is thought that this is because pain inhibits the reward centres of the brain. The addictive effects of heroin (and other opioids) are due to activation of the reward centres of the brain. It is caused since opioids cause release of a chemical - dopamine, in the brain. Also, the withdrawal effects of heroin are also very important. It is probably the most addictive substance in the world and the cravings you get when you aren't taking it are dramatic. ps. i think you misunderstand some points about the drugs... 1) opioids do not treat sickel cell anaemia... they are given only for pain relief in when sickel patients have crisis... (a sickel cell crisis is when blood supply to parts of the body are blocked due to the shape of the red blood cells getting stuck in capillaries)... 2) levodopa is the precursor to dopamine... it must first be converted to dopamine in the brain before it is active... humans nerves do the same process... they produce dopamine, adrenaline and noradrenaline all from an amino acid tyrosine... levodopa is an intermediate in the biochemical pathway... tyrosine -> levodopa -> dopamine -> noradrenaline -> adrenaline* (*dopamine neurones can only do the first 2 steps, noradrenaline neurones can do 3 steps but only some places in the body (adrenal medulla) can do all 4 steps) i'm not really sure you understand what you have written... steroids and many licensed drugs have high immunosuppressive effects... exercise, chocolate and even sex activates the HPA axis... and has the medical profession restricted these? no, it's nothing to do with why medical profession restrict opioids... (side effects - respiratory depression, tolerance to drug, need to increase doses, addictiveness, contraindications...etc.) ps. be careful how you write essays... what you have written looks like you have just done a bad job in paraphrasing wikipaedia... soz if that's harsh... THAT'S INSANE ! Where did you get this study from?! Even in Sri Lanka that's bound to be illegal ! No doubt the Sri lankan government's too busy fighting the tamil tigers to care...

codeine, morphine and diamorphine are all analgesics... and very good ones - opioids are the gold standard pain killers... the difference is metabolism... codeine is metabolised slowly and only 10% ever forms morphine... morphine is already morphine and doesn't need metabolising - but it takes time to pass the blood brain barrier... diamorphine is morphine made more lipid soluble so it can rapidly enter the brain where it is converted to morphine pretty instantly... levodopa on the other hand is the precursor for dopamine... it is the main treatment for parkinson's disease... i think it would be very interesting to include this - i had no idea levodopa came from the opioid poppy...

cheers for your helpful replys

but how do you know that the knock out mice will breed knock out children? couldn't the genetics change down the generations - (e.g. two people with IaIo type A blood have a 25% chance of giving birth to type O blood children) is there any way to prevent such changes?

remember that blood leaving the R ventricle goes into the pulmonary artery...

Let's say I want to have 50 mice with a certain gene knocked out for an experiment. How would you make this many knock out mice in the lab? Thanks

couldn't you buy a shoulder support to stop the chance of dislocations?...

inflammatory factor in apples... hahaha... such an apricot...

Fruit doesn't cause inflammation... You pineapple... ;/

I thought the clinical definition of chronic pain is pain lasting more than 6 months... That include everything pretty much...

Chronic pain is different as a constant nociceptive stimulus can cause different levels of pain since the pain pathway can be both upregulated or downregulated... Although psychological methods (i.e. distraction) can have a part in reducing pain - if you are in a lot of pain i doubt that thiss will work alone and you will have to take some sort of pain killer. So why is it you can have different levels of pain for a constant pain stimulus? You can have peripheral sensitisation - i.e. activation of sensory nerves (Ad and C fibres) causes these nerves to be more easily stimulated... [i.e. if you cut yourself you have hyperalgesia in the surrounding area, even light touch in that area will be painful] Peripheral sensitisation can also cause cental sensitisation - i.e. activation of NMDA receptors (wide up) in the spinal cord. This will increase the activity of the spinothalamic (pain) pathway. However, this will be counteracted by downstream pathways. Activiation of the limbic system changes neurotransmitter levels in the pain (e.g. serotonin and noradrenaline are particularly relavent in pain)... [edit: this can both up or downregulate pain... as a general rule serotonin tends to decrease pain + noradrenaline increases pain - this is why SSRIs are not a treatment for chronic pain whereas tricyclics are...] It also causes release of other endogenous painkillers e.g. enkephalins (an engogenous opioids)... You can increase this counteraction by drugs... a) centrally acting pain killers - reduce central sentisation Opiates (Codeine / Morphine / Diamorphine) Low dose tricyclic antidepressants (e.g. amitriptylline) NMDA antagonists (Ketamine - not really used for obvious reasons) Ca2+ channels (Gabapentin) or you can reduce inflammatory stimulus (note - not all pain states have an inflammatory cause so these not always effective) b) Peripheral acting pain killers - anti-inflammatory agents NSAIDs (ibuprofen / aspirin), Corticosteroids (hydrocortisol)... For chronic pains you are probably prescribed a mixture of central and peripherally acting pain killers. i.e. co-codamol (coedine and paracetamol), co-dydramol, co-proximol (now withdrawn)...etc But the majority of people feel better once the pain is removed simply by pain killers. With chronic pain the problem is different as side effects of the drugs may mean that taking the drugs for years is a bad idea (e.g. long term intake of opiates or steroids)

Animals are used all the time to model pain... As someone mentioned before when we are in the clinic we ask people to state their pain between 1 and 10. But this method is rubbish, especially if you want to invest money into a costly clinical trial. This is why most of the evidence from the effectiveness of pain killers is from animal models (before they ever reach clinic) since it is hard to read people's pain and it is very subjective, varies dramatically and can be influenced by hundreds of other factors. Fortunately animals are actually extremely good models, which is rare when you deal with the nervous system. Most disorders of the CNS are impossible to model in animals - Alzheimers, Parkinson's, schizophrenia (the models used are very poor)... The exception may be epilepsy (but even with best knock-out mice studies and EEG recordings it is difficult to come to any firm conclusions)... This is perhaps one of the reasons why we have had no major breakthrough in treatments for epilepsy. The first line drugs (valproate, ethosuximide, carabamazepine) have been around for decades. However, with pain many new drugs are available and widely used. e.g. Gabapentin development for neuropathic pain (i.e. nerve pain)... it is making zillions because most of the drugs (NSAIDs, glucocorticoids) are only effective in inflammatory pain and it was the only real treatment for nerve pain (e.g. diabetic neuropathy, spinal cord damage, sciatica...etc.)... pretty surprising considering it was discovered by chance... the drug company developing it made gabapentin to act on GABA receptors... it worked on neropathic pain but after a few years of work it was found to acts on calcium channels and not GABA... it was pretty damn surprising...) There is also a lot of research occurring in the area of pain e.g. research looking into selective sodium channel blockers that can be taken orally... currently we only use local anasthetics (non-selective sodium channel blockers in injections or creams)... but there are currently clinical trials carried out into selective sodium channel blockers (Nav1.7 and 1.8) that can be taken orally... if effective clinically and side effects are low (as have been in animal models) - these drugs will be massive...

Health care is free but the standard of that health care you get is much lower than you get in america. We have one of the worst health services in europe despite being one of the richest. There is a massive shortage of health care workers and of money and there is a lot of bureaucracy and targets that can be counter-productive. For example, one target used in england (but not in scotland or wales) is that you needed to have 98% of people processed through accident and emergency in 4 hours in order to get paid. What happens in practice is that A+E docs panic when the 4 hour target nears and instead of keeping people in to monitor how they are - most are admitted to wards in the last 10 minutes just to meet a target. That's one of many examples. Another one in the news is that many new cancer drugs won't be funded by the NHS because they are too expensive. What is worse is that if you want to pay for these treatments privately then you will have to pay for ALL your cancer care treatments privately. This will cost about £10,000 a month so that's ~£120,000 (and if you imagine that the average wage in the UK is ~£18,000 a year) you can see how crazy it is that you aren't allowed to just pay for Avastin therapy privately (~£5,000 a year) and have the rest of the treatment on the NHS.