Top Court in India Rejects Novartis Drug Patent - NYTimes.com Low-Cost Drugs in Poor Nations Get a Lift in Indian Court NEW DELHI — People in developing countries worldwide will continue to have ac-cess to low-cost copycat versions of drugs for diseases like H.I.V. and cancer, at leastfor a while. Production of the generic drugs in India, the world’s biggest provider of cheap medi-cines, w
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Swen1997.woelmuis.nl1.1 Nerve cells The technical name for a nerve cell is a neurone. These are the basic units of the nervous system. The connections between these nerve cells are called synapses. Nerve impulses travel like waves through this system. These waves are electrical signals that arise when tiny channels open in the cell membrane allowing ions (electrically charged atoms) to move in and out of the cell. The cell body of a neurone gets it’s information through it’s dendrites and gives it out again to other neurones through it’s axon. Synapses and neurotransmitters Nerve impulses do not just travel from neurone to neurone. The signals first have to cross synapses by means of a chemical neurotransmitter. Neurotransmitters are released by one neurone and taken in by another neurone again. The neurotransmitters that are released make contact with receptor molecules on the synapse of another neurone. This makes the receiving neurone more or less active then it was before. Neurotransmitters are made in the cell body and are transported to synapses along tiny tubes inside dendrites and axons. The first neurotransmitter that was discovered was acetylcholine (neurotransmitter between nerve axons and muscles). The main neurotransmitter that excites neurones in the brain is glutamate. GABA and glycine help to bring precision to nervous activity in the brain by suppressing activity in some neurones while other neurones are excited. Other examples of neurotransmitters are dopamine, serotonin and noradrenaline. The structure of the human brain Nobody’s brain is exactly the same and everyone’s brain is changing all the time. Your brain consists of different parts. Spinal cord; Contains axons that transmit nerve impulses between the brain and your Cerebrum; Consists of two hemispheres. Contains neurones and synapses. Cerebral cortex ; The outer few millimetres of the cerebrum Brainstem ; controls all your unconscious functions as heartbeat, breathing, digestion Corpus callosum; Contains axons that connect the two different hemispheres Cerebellum; coordinates fine movements and balance 1.2 Parkinson’s disease Symptoms Neurodegenerative disease (caused by breakdown of neurones). Usually developes in people aged 50 or over. Shaking/tremor in the limbs, movement becomes slow and limbs feel stiff, pause between the patient deciding to move and being able to get going. Dopamine In most patients that suffer from Parkinson’s disease the treatment with levodopa works. It reduces the stiffness and tremors. Levodopa probably helps to restore the level of dopamine in the brain. Long axons supply the dopamine to synapses across many different brain areas. The main cause of Parkinson’s disease is the worsening of the cells that produce dopamine. Dopamine is responsible for normal control of movement. The drug levodopa enters the brain where it is converted into dopamine. Describing the drug is different because the amount needs to be very precise. Too little does not help a patient, but too much messes up the level of dopamine in the brain. This can cause muscle spasms, depression and psychosis. There is a membrane around the blood vessels in the brain that prevents selected molecules and ions from passing between the blood and the brain cells. This is called a blood-brain barrier. Dopamine is unable to pass this blood-brain barrier but levodopa is. This is the main reason for prescribing levodopa instead of dopamine itself. Levodopa pills are usually taken at intervals throughout the day. This causes side effects by high and variable levels of dopamine in the brain. Because of this there is an urgent need for better treatment for this disease. Deep brain stimulation This is another way to help people with Parkinson’s disease. Surgeons insert electrodes into the brain through the skull. The electrodes are connected to an electrical pulse generator attached to the chest. This reduces abnormal neurone activity, preventing tremors. This is risky and can cause bleeding in the brain, heart attack, fits or infection. Beyond levodopa Until recently people thought that taking levodopa could damage the cells that produce dopamine. Recently it has been proved that although levodopa may not harm these cells, it does nothing to slow their degeneration. The causes of the disease are still largely unknown. Alzheimer’s disease Gradual loss of short-term memory. Leading to general impairment of thinking, reasoning and perception. In Alzheimer’s disease there is a build up of two abnormal proteins called amyloid and tau. Something triggers the deposition of these proteins, particularly in the hippocampus and cortex regions of the brain. These parts of the brain are involved in memory and higher thought processes. The accumulation of the proteins impairs cellular function and causes cell death. Main treatment available on the market inhibits the breakdown of the neurotransmitter called acetylcholine that is involved in learning, memory and attention. Schizophrenia Classed as a severe mental disorder characterized by delusions, hallucinations, psychosis, paranoia, disorganized thinking, perception and speech, physical agitation. Increase in the neurotransmitter dopamine, treatment is often with antipsychotic drugs that either inhibit dopamine release or suppress dopamine function. Random stuff In vitro = experiments using radioactive isotopes In vivo = experiments on animals 1.3 Drugs and dopamine Dopamine acts as a transmitter between several brain areas. Dopamine is very important in drug taking and drug addiction because it is involved in the reward pathway. This pathway comes from the brainstem and extends into the prefrontal cortex. It is activated when people seek a reward or are motivated to do something. Three parts of the brain are involved in this reward pathway; dopamine production centre, nucleus accumbens prefrontal cortex. The neurones of the dopamine production centre produce dopamine, which is released in the nucleus accumbens and in the prefrontal cortex. These particular pathways are activated by a rewarding stimulus and make us feel good. Almost all recreational drugs raise dopamine
levels in our brain. The dopamine reward system is present in all mammals and rewards us for
feeding, drinking and sex. It makes it pleasurable and therefore it will be repeated. Getting a
reward when you do something good is called positive reinforcement.
Dependence, tolerance and addiction
Drug users become dependent on a drug when they suffer unpleasant physical or
psychological withdrawal symptoms if they stop taking the drug. People are addicted to drugs
when they have lost control over drug taking. Addicts continue to take drugs compulsively
despite harmful effects on health and social relationships. Drugs tend to have less effect the
longer people take them and then they need a higher dose. The drug user craves higher doses
of the drug in order to bring back the effects experienced when it was first used.
Illegal drugs are classified as A, B or C. A is the most harmful and addictive. Some people
argue that this classification system is bad because doctors are allowed to prescribe harmful
drugs to patients and then it is no longer illegal.
First cannabis was an A drug, then it turned into a C drug and later it was classified as a B
drug because some evidence of a link was found between cannabis abuse and mental ill
health, particularly schizophrenia. Our brain is full of cannabinoid receptors. We do not really
know what these do but we think that they have a role in neurotransmitter release. So, if you
smoke cannabis it locks onto these receptors. This alters the release of neurotransmitters
causing a number of different reactions. Cannabinoids can protect against programmed cell
death, where DNA signals cells help precent a state where too much of the neurotransmitter
glutamate excites nerve cells to death.
Attention deficit hyperactive disorder (ADHD)
Hyperactive, inattentive and impulsive. Behavior usually hinders progress at school. More
common in boys than in girls. Children with ADHD often don’t know that their behavior
bothers other people and don’t know how to change. This can cause children to be isolated,
disaffected and do bad at school. Boys tend to quit school early, drift from job to job and
show an attention to risk .There are no specific laboratory tests to show if someone as ADHD.
Diagnosis is made by a child psychiatrist educational psychologist or a pediatrician. This
person watches the child closely and gathers information from parents, teachers and other
adults. In making the diagnosis, other mental disorders must be ruled out.
No clear understanding of the cause of ADHD. Both genetic and environmental factors are
important. Probably a number of genes instead of one single gene involved. Probably
something wrong with the genes involved in dopamine pathways in the brain.
Psychological therapy, behavior management, counseling, change of diet, educational support
and medication. Main drug used to treat ADHD is Ritalin (a type of amphetamine). Ritalin
makes children calmer and more attentive. Ritalin is thought to work by raising the levels of
dopamine in the brain, perhaps compensating for a natural deficit. However, what it exactly
does is unknown. Some side effects including; psychosis, mood swings and difficulty
Feelings of worthlessness, hopelessness and self-hatred. Leads to an inability to cope with
daily life, this form is known as clinical depression. This goes beyond sadness and upset
however, this does not mean that people with milder symptoms are not depressed. Diagnosis
of depression by a doctor is based on three things.
1. How serious it is; mild depression , moderate depression or severe depression. 2. physical symptoms; loss of interest and pleasure, weight gain, loss associated with a changed appetite, loss of energy and extreme tiredness, feelings of guilt, poor self-esteem, problems sleeping, agitated behavior, difficulty making decisions, difficulty concentrating, thoughts of death and suicide. 3. psychotic symptoms; hallucinations or delusional behavior. Postnatal depression; exhausted, difficult to fall asleep, when you wake you feel to tired to cope with life, irritable, anxious, very tearful, distorted sense of time. Manic depression/bipolar disorder; usually first affects a person when they are in the late years of their teens. Extreme mood swings, altered thought patterns, emotions and physical health. Recurs at intervals. Seasonal affective disorder (SAD); depressed at particular times of the year (especially late autumn and winter). Symptoms are varied. Sleep and eating problems, lack of energy for everyday tasks, anxiety or other changes of mood. Causes; Environmental factors. Physical activity: people who exercise more tend to be less depressed. Depression often runs in families. This might have something to do with genetics but members of the same family are likely to live together in similar circumstances and acquire common learned behavior. Treatment; Mild depression; self help techniques. Healthy diet, someone to talk to, herbal More severe depression; drug treatments and electroconvulsive therapy. Bipolar disorder; Mood stabilizers (containing lithium). They work in part by Most people think that if you are depressed there is something wrong with the levels of dopamine, serotonin and noradrenaline in the brain. Antidepressants are used to increase the activity of the neurotransmitters that control mood, serotonin in particular. Selective serotonin reuptake inhibitors (SSRI) such as Prozac are widely prescribed for depression. Side effects; blurred vision, constipation, sexual problems and aggression. MDMA (ecstasy) greatly increases the levels of serotonin but is too powerful to treat depression. Cognitive behavioral therapy (CBT) is talking therapy is used to change peoples behavior; helped to think more positively , particularly about themselves. More expensive than drug treatment but longer lasting than drug treatment. Electroconvulsive therapy (ECT) is a controversial treatment that involves giving the patient an electrical shock to the brain. Usually used as emergency treatment or when every other way of treating a patient didn’t work. Serious side effects that include memory loss. 1.5 Therapy or enhancement Drugs that used to be used to help patients suffering from ADHD or depression are now often used to enhance performance in people without these disorders. The definition of what counts as a good health has changed. For example; People would have accepted it that if they get older they would get more forgetful but now people see these changes as something that they need medical treatment for. Drugs to enhance brain performance Modafinil Modafinil was originally developed and used as a sleep-regulating drug to improve wakefulness in people with narcolepsy. Side effects that you get from taking modafinil can include; headaches, dizziness, blurred vision, depression and suicidal thoughts. Nowadays this drug is used by the military to stay awake for 40 hours in a row. Scientist are worried about the long-term affect of this medication because your body goes without sleep for a long period. Antidementia drugs Donepezil is an example of a drug developed to help people with Alzheimer’s disease. The drug blocks the action of the enzyme that breaks down the neurotransmitter acetylcholine in synapses. It lifts the patients confidence, improving mood and drive and reduces delusions and hallucinations. Individual benefits and risks All drugs have side effects. Improving your memory could have some unexpected consequences. For example; we all have unpleasant moments that we want to forget. If we use a drug to enhance our memory we might not be able to forget these things anymore. Social benefits and risks Society benefits from smart people but society also needs the dumb people. 3.1 Brain injuries Phineas Gage once got a spike through the head in an accident and still was able to live on. His coworkers said that he wasn’t the same anymore since this accident. This is because the spike passed through the part of his brain just behind his forehead. This is the prefrontal cortex and had overall control of everything we do, it defines our personality and makes us individuals. Animal models The best animal model for the human brain is the chimpanzee. The chimp brain is very like ours in structure though it is much smaller and the cortex is also a lot smaller. Lobotomy = using a surgical knife to cut nerve fibers connecting the prefrontal lobe, or section of the cortex to other parts of the brain. After lobotomy some patients with severe mental disorders were quieter and easier to control, however it became clear that the benefits of the treatment to patients were questionable and the side effects could be severe. Many patients became changed characters. They were less responsive to emotions and unable to think ahead. The cerebral cortex The cerebral cortex covers the surface of two cerebral hemispheres. Within the cortex there are millions of neurones. During human evolution the forebrain has greatly expanded and folded back over the top of the rest of the brain. The contorted (=gekronkeld) brain surface allows a very large area of cortex to be packed inside the protective skull. The cortex provides the thinking or computing power of the brain and is also known as grey matter. Inside the cortex there are a lot of axons linking neurones together. The axons are coated with a layer of fatty insulation called myelin, which is white. The axons are therefore called the white matter. The cortex has three main functions; Sensory areas receive and process nerve impulses from sensory receptors in the eyes, Association areas are regions which receive information from the sense areas and organize a response via the motor areas. These areas integrate incoming sensory information with stored memories to make decisions. Parts of the association areas are probably responsible for conscious thoughts. Motor areas send out nerve impulses to the muscles and glands, causing them to take The cortex maps things upside down and back to front. The left side of the brain controls movement in the right side of the body and the other way around. The motor areas are arranged with the toes near the top of the brain and the head near the bottom. The more sensitive areas of the skin are served by a bigger area of the cortex than the less sensitive parts. Parts of the body that contain lots of muscles have more cortex controlling them than parts of the body that don’t contain a lot of muscles. 3.3 Humans and animals can respond to stimuli simply and quick. These reflexes help us avoid danger. Much of our behaviour is inborn and no conscious thought is required. There are also a lot of impulses that don’t cause a reflex. Scientists suggest that when we learn something new synapses are made in our brains and this changes our responses to future stimuli. Some types of learning involves the cerebellum. Things like riding a bike, typing or playing a music instrument. We do not have conscious memories of how to move our muscles, once we’ve learned it we just remember it. Deception and lie detectors It takes a lot of mental effort to tell a consistently false story. That’s why when the police interrogates people they might ask them to tell the story backwards or from the point of view of a bystander. One type of instrument for detecting lies is based on the effects of the stress involving lying. When people lie we make more of the hormone adrenaline which makes us sweat, cause our hearts to beat faster and our rate of breathing increases. The polygraph is an instrument designed to detect these changes, so the polygraph has been used as a lie detector. MRI and fMRI scanning MRI depends on the magnetic properties of nuclei of hydrogen atoms in water molecules. The subject is placed in a tunnel inside a very powerful electromagnet. As the instrument carries out a scan a beam of radio waves pick up a series of signals from the nuclei of the hydrogen atoms as the resonate with the magnetic field. The signals vary with the type of tissue surrounding the water molecules. The signals are then send to a computer which creates an image of the tissues in the body. These images are very useful for investigating brain injury and brain tumors. MRI has been extended to allow scientists to compare the activity of different areas of the brain. This technique is called fMRI. fMRI shows which areas of the brain are actually working as we carry out different mental processes. This works by detecting changes in blood flow in the brain. When a particular area of the brain becomes active the neurones send out more electrical impulses and start to use more oxygen for respiration. This means that more blood is sent to the active area. Oxygenated blood has less magnetic effect than deoxygenated blood so when a part of the brain becomes active it’s magnetic signals change. An fMRI scanner can track activity in the brain very shortly after it happens. fMRI to detect lies In order to tell a lie, the prefrontal cortex must work harder to suppress the truth and construct a lie. A lie can be detected in this way because telling a lie involves more brain regions than telling the truth. fMRI has a lot of practical disadvantages; It takes many hours to analyse the results of a scan. The apparatus is bulky and claustrophobic and requires the cooperation of the person fMRI measures blood flow to different parts of the brain. This is an indirect measurement of brain activity and may not be a real reflection of the neurological functioning of the brain. There is a time lag between the start of mental activity and changes in blood flow, and The images from the scans are subject to many different interpretations. Who is to know whether a part of the brain becoming active really indicates a lie? The uncertainties surrounding the significance of a scan could lead to deliberate misinterpretations in an attempt to obtain convictions. Brain imaging and mental illness Brain imaging can help compare healthy brains to brains that suffer from a mental disorder. This way scientist can see in which part of the brain diseases like Alzheimer’s start. Brain imaging, language and hearing As we listen to someone talking it is not just the parts of the brain associated with hearing that light up, also parts that we use in speaking. Similarly when we speak, parts of the brain associated with hearing also light up. Sounds and emotions Scientists have found that hearing someone make an emotional noise activates the parts of the brain we would use to make that sound oneself. Restoring hearing Cochlear implants are becoming a more frequent was of restoring hearing in both young and old people. In those born deaf and those who have lost their hearing later in life. But the sound the implants provide is very different from sound we usually heart through our ears. If you lose your hearing and have a cochlear implant you have to learn to listen all over again. 3.4 Right and left brain The two hemispheres of your brain connect using a band of nerve fibres called the corpus callosum which carries nerve impulses backwards and forwards between the two sides of the brain using a lot of nerve axons. Cutting the corpus callosum can help prevent the excessive brain activity which cause epileptic fits. Split brain patients In all people the axons in the optic nerves running from the eyes to the brain connect to the visual cortex in such a way that images from the left half of the screen go to the right hemisphere and images from the right half of your visual field go to the left hemisphere. Your language ability is controlled by your left hemisphere. The right hemisphere is better at the tasks that cannot easily be put into words like remembering faces, music or copying a picture. Split brain patients and false memories Adding extra details to improve a story is called confabulation. It seems that our left hemisphere is very adept at confabulation and that we may be unaware of the extent to which we are doing it. Male & female brain Most female brains are focused on empathy and most male brains are focused on systemizing. Empathisers are sensitive to other people’s emotions and thoughts. They respond to these with an appropriate emotion. This means that empathisers intuitively figure out how people are feeling and how to treat people with care and sensitivity. Systemisers have a drive to analyse and explore. They try to figure out how things work. This theory suggests that males are more likely to be autistic than females. Lateralisation in male and female brains It is found that women tend to have less language impairment after strokes than men, and this is explained by the theory that language functions are more lateralized in men’s brain. 3.5 States of consciousness Clinical state Brain stem death The development of life-support machines has made decisions about death more difficult. Although the functions of the lungs, heart and kidneys can be taken over by machines, that of the brain cannot. Keeping the heart beating is essential so that the rain continues to be supplied with oxygen. If the brain stem is damaged so severely that it dies then there is little point in stimulating the heart to keep it beating. This is because the brain stem controls essential internal reflexes which keep the body alive. After a brain injury the cerebral hemispheres may become inactive, yet they may regain function if the brain stem is still intact. To tests if someone’s brain stem is dead they carry out tests to see if the normal reflexes that involve the brain stem are still working. In one test they shine a torch into both eyes to see if the pupils react to the light. Patients who do not respond to tests like these are brain stem death. Brains of premature babies When a baby is born early some brain damage is common, usually caused by internal bleeding. Doctors can use ultrasound to obtain an image of the brain but this technique cannot reveal detailed internal structures. MRI gives a much better image but requires the patient to be still and that doesn’t work for babies. A new recent technique to discover brain damage in babies is to use optical tomography which scans the brain surface using flashes of infrared light. The scan shows whether any brain areas are becoming deoxygenated, allowing doctors to give immediate treatment. The decision to withdraw treatment When babies are born with a severe handicap the question arises as to whether life-saving treatment should be given. This also applies to adults in permanent vegetative state. Withdrawing treatment is different from euthanasia which means assisting a person to die. A person in pvs is unable to give consent for treatment or its withdrawal and this poses a moral dilemma for carers.
VÄYLÄT YHDISTÄVÄT ALUEET PORI TAMPERE SALO HELSINKI TOIMITUSJOHTAJAN KATSAUS VUOTEEN 2007 Vuosi 2007 oli Loimaan seutukunnan kehittämiskeskukselle vakiintuneet muodot saanutta yritysneuvontaa, jossa painopiste oli uuden yritystoiminnan neuvonnassa. Vuosi oli kuntakentässämme myös PARAS -uudistuksen aikaa. Alastaro ja Mellilä tekivät yhdistymispäätöksen Loimaan kaupunk