These are notes of articles from Scientific American, mostly on the Biochemistry of Hormones and the Endricine glands, but also covering viruses, nerve and brain function, and a few other things.
Stressed rats (poisons) have 1) enlarged, discolored, adrenals 2) shrivaled thymous 3) ulcers. Similar results to non-chemical stresses. Adrenal cortex produces at least 20 hormones, encapsulated in lipids (fats). These 1) maintain the salt balance outside the cells 2) stimulate sugar production. Most endrochrine glads are controled by anterior pituitary. Without the pituitary's hormones the adrenals shrink. Effects of prolonged stress, "general adaption syndrome": * first growth and sex functions are impaired, also typical stress reactions (see above) * then if the animals survived, their systems recovered. but resistance to other stresses decreased! * eventually exhaustion leads to renewed stress symptoms and death. hypertension and hardening of the arteries and kidneys are results HT is cured by a salt free diet -- affects the adrenals a low protien diet -- related to pituitary
Adrenals: medulla cortex adrenin (epinephrine) 28 hormone like substances controlled by nerves by pituitary secretions the cortical hormones control salts (especially sodium and potasium) and sugar levels, they can break down white blood ceels to make sugar A schizophrenics unstressed hormone levels are normal, but they don't rise under stress as expected. Stresses tested included: environmental, chemical, and psychological Apparently the chemicals from the pituitary don't excite the adrenals Maybe related to faulty potassium matabolism. Potassium is involved in nerve function, and is affected by stress.
Living cells are generally charged with respect to their environment.
The pituitary gland is closely connected to the hypothalimus. ACTH is the pituitaries messanger to the adrenal cortex. 2 adrinal cortex hormones can cause diseases (eg arthritis, high blood pressure), but are counteracted by cortizone, so the adrenal cortex produces counterbalancing hormones.
The human pituitary is similar to that of reptiles. It is very old and essentially unchanged by evolution. Somatotrophin, STH (growth H) Thyroxin, Triodothyronine | | | | | | | Thyroid <------------------ Pituitary ----------------> Mamaries Thyrotropic H | | Lactogenic H | | / \ Andrenocorticotrophin / \ FSH ACTH / \ ICSH / \ / / \ Adrenal cortex / \ / Ovaries ---------- Testies / | | 11 Oxycorticoids Progesterone, Estrogen Tetosterone (some additions from Hormones below). Distruction of the pituitary leads to a general wasting and eventually death. The other glands shrival, liver, spleen, and kidneys srink. Major body functions are controlled by the anterior lobe. Growth hormone enters the body directly, not via controling some other gland.
New species produced by mating to different species generally have steril offspring, but sometimes these will double their chromosomes and become a fertile new species. If parents have 48(24) and 18(9) then the first generation has 33 and the second 66(33).
Removal, or lack of the cerebral cortex results in an animal (or person) that dosen't develope a regular sleep/wake pattern, but only wakes up when bodily needs arouse it. This is the state of an infant. When nerve connections to the subcortical regions are cut, only sleep patterns are found in the cortex. These also form an integral part of the process. There is two-way communication up to the cortex and down to the rest of the nervous system. In the absence of the cortex the subcortical centers can arouse the animal for bodily needs. Damage to the hypothalimus also induces sleep. The natural ratio of sleep/wake periods is 1/2, the length of the cycle is not as important. There is a daily pattern of temperature rise and fall, peaking during the day and hitting minimum in the early morning. This seems to develope after birth along with the regular sleep/wake cycle. This cycle is in phase with the alertness of a person, even during long periods of sleep deprivation. Range is 1.5-2 degrees. Theory that athletic types get up early, cerebral types late and work best in the evening. The first type has a peak temperature near noon, the latter, in late afternoon or evening. The author comments that the former type is more conforming to social norms. Although rythms can be shifted (as in overseas travel) there seems to be a preferred phase for each person. Both temperature and alertness are linked in feedback to the muscles. Suspect that the pituitary controls the sleep/wake cycle.
Normally axions are negatively charged inside, mainly potassium ions, but when a threshold stimulous is applied the membrane becomes permiable to sodium ions. These are more concentrated externally and flow inside reversing the relative interior charge, making it positive This is a transient change and after 1 or 2 milli seconds the membrane returns to blocking the sodium and being pourous to the potasium ions. When a nerve pulse is transmitted down a long axion, there is a traveling wave, in which the change in one section triggers the next section. If a blockage is made, then the pulse is interupted, unless the distance is narrow enough that the signal is attenuated by less than %90.
Viruses only have DNA, no RNA or other cell parts. They can only reproduce in cells or bacteria, by taking them over. Prophage: inserts itself into bacterial DNA, thus modifying it they are multiplied as the bacteria multiply. The site at which the prophage inserts itself is specific.They are sometimes fatal to the bacteria because they mess replace a critical portion of its own DNA, but this is not common. Full Virus: enters the bateria and uses the bacterial DNA to replicate itself. A prophage can later be activated and go back to being a full virus. This will eventual happen via some random or statistical process, or it can be triggered by stressing the cell or bacteria, as with x-rays or UV, carcinogens, or nitrogen mustard (??). Bacteria infect with a provirus are then immune to genetically related viruses, that would need to use the same section of the bacteria's DNA.
These are a class of life in between viruses and bacteria. They are not complete in themselves, but can perform some functions one their own. They are inbetween in size as well.
Bacteria can modify viruses, adapting them so they only grown in that type of bacteria. This process can be undone (sometimes) by other bacteria which can adapt them for themselves. Other cells or bacteria also modify viruses, but so that they can't grow in them.
Fear and anger trigger the "fit or flight" reaction via signals from the cerebral cortex down the sympathetic channels of the autonomic nervous system to the adrenals. This causes the release of adrenin from the adrenal medulla which leads to many physiological changes. Also released from the medulla is nor-adrenalin, which raises the blood pressure by constricting the small arteries. Adrenalin raises it by speeding up the heart. In animals there is anger or fear, in man anger can also be inward directed, becoming anxiety and depression. Experiments indicated that anger releases nor-adrenalin, while fear or depression (interior anger) releases adrenalin. This was tested in stressed interns, psycotic patients with dominent emotions, and normal students which had been given one or the other hormone. Other experiments which induced either fear or anger in the same subject indicated that even in the same person fear generated adrenalin and anger nor-adrenalin. Stimulation of different regions of the hypothalimus produces either adrenalin or nor-adrenalin. Animals show specific patterns as well: lions, more nor-adrenalin, rabbits, more adrenalin (which would be why they go into shock so easily). Domestic and social wild animals have more nor-adrenalin. Infants have more nor-adrenalin than older children. Paranoid patients are angrier and have more nor-adrenalin than depresive patients. The paranoid patients are generally more regressed. THE AUTONOMIC NERVOUS SYSTEM:
Discussion of the use of LSD to mimic psychosis. LSD reduces phosphates in urine, as in schizophrenics, whereas ACTH does the opposite.
Reference to viruses with RNA rather than DNA. Tests of different viruses show different proteins, with the degree difference roughly related to difference in viral action. Although differenecs in the RNA or DNA were harder to detect they were believed to exist. Examples of combinations of protein and nucleic acid from different viruses. Experiments that change protein fail to change the viral behavior. Nucleic acid controls viral type. This does not seem to have been fully appreciated.
Refers here to stress reactions being mediated by the hypothalimus. The drugs refered to (including thorozine) affect the hypothalimus and reduce the general metabolic rates. Stimulous sends signals to the thalamus which distributes them to the parts of the cerebral cortex. Also sends signlas to the "activating system" in the "reticular formation". The activating system is also affected by these drugs, though they do so differently. The drugs tend to offset LSD and mescaline. All of these affect the levels of serotonin, which is a neurohormone, that acts as a sedative in large doses. The new drugs reduce its affects.
There seems to be a barrier the seperates the brain from the blood and the rest of the body. Its chemistry is somewhat different from other cells. Most disorders of the nervous system involve a break down of this barrier.
The tobbaco mosaic virus consists of a tube of protein surrounding a helix ( they didn't know its form then) of nucleic acid. These may be broken down and seperated, the protein being broken into small pieces. These seem to naturally go back together into the full tube under the right conditions. If some of the nucleic acid is also mixed in whole active viruses may be reconstituted.
Previously sensory and motor centers of the brain had been mapped. Sleep/wake related to reticular system, fight/flight related to rear of the hypothalimus. Front portion has to do with rest, recovery, dirgestion and elimination. Hypothalimus and septum (further forward) related to automatic protective behavior. Rhinencephalon related to smell and posibly emotions. In this study Skinner boxes used to measure positive stymulus. Rats would self-stimulate to the exclusion of other things. In motor sensory areas stimulus had little effect (10-25 stimulae/hr). In the mid-line regions there was varied effect, sometimes quite large. In some parts of the lower ML system negative effect. Highest rates for probes in the hypothalimus and some mid-brain centers (500-5000 stim/hr). In these regions stimulus was more attractive than food. Rhinencephalon showed lower rates (200 stim/hr). Sometimes being hungry enhanced the desire. Castration could negate it.
Test subjects spend upto several days without patterned sensory stimulous. Tend to loose ability to focus, become irritable, to halucinate. When they come out they can be disoriented, visual discrimination and analysis impaired. Possible out of body experiences.
There are two types of message carriers, energitic impluses, as in electric currents in nerves, and chemical messangers, as in hormones. These can be interelated, ie the adrenals can be stimulated either by nerves or by chemicals in the blood. In the nervous system itself chemicals transmit messages between the nerve cells. Transmission across synapses is controled by adrenalin (inhibits) and acetylcholine (enhances). Relatives of these chemicals have similar effects. Relatives of adrenalin include: mescaline, lysergic acid, bufotenin ( aplant extract), serotonin (a brain hormone), and benzedrine. These inhibit to varying degress, serotonin the most. These inhibitors tend to produce mental "disease". All these substances initially produced enhanced `activity' due to the release of restraints, later depresent effects. Acetylcholine (and relatives) produces enhanced activity, eventual chaotic states, strangr behavior, and death. Nerve gases work to prevent acetylcholine's breakdown. They are counteracted by atropine which blocks acetylcholine's acces to the synapses.
Established hormone-secreting organs include: pineal, pituitary, thyroid, parathyroid, thymus, stomach, adrenals, pancreas, kidneys, duodenum, and gonads.
The class of hormones is defined by action. Chemically they are diverse: steroids, proteins, glycoproteins, polypeptides etc. A single hormone can act on many enzymes. Since the enzyme reactions take place without hormones it is unclear exactly how they function. Chemically similar hormones can have very different effects, and chemically different hormones can have similar effects. The pituitary is most important. The posterior lobe secretes hormones which stiluate uterine contractions during labor, and the release of milk from the mamories. Also the amount of fluid filtered by the kidneys. The anterior lobe produces hormones that control most of the other endrocrine glands (see Pituitary above). The pancreas produces insulin. The thyroid produces thyroxin and triodothyronine. Thyroxin is necessary for proper development of the dendrites and axions of nerves. The parathyroid control calcium and phosphorus metabolism (as does the adrenal cortex). It hormones are necessary for growth, and in fact life itself. Nearly all the endrocrine glands produce substances that guide and promote different phases of growth. Sugar Metabolism: 1) Rate of use as energy in the tissues. 2) Rate of absorption byt the blood in the gut, and of reabsorption from fluids passing through the kidneys. 3) Release of sugar from liver and muscles which store carbohydrates. 4) Formation of sugar from fats and proteins. Insulin transforms glygogen in the liver and muscles into glucose (#3). The anterior pituitary can stimulate the adrenals (via ACTH) to release hormones the promote synthesis of glycogen from protiens (#4). Adrenalin helps to trigger this release of ATCH, both directly and through action on the hypothalamus. The anterior pituitary also causes the thyroid to release a hormone promoting oxidation of sugar(#1), and the rate of absorption into the blood in the gut(#2). The actions of the adrenals, pituitary and the pancreas tend to balance. Protein metabolism is also controled by hormones. Water metabolism: The hormone Aldosterone (adrenal cortex) adjusts water metabolism by promoting retention of sodium and chloride and the expulsion of potassium (see also Nerve Impulse). Serotonin acts in the brain and some gut cells to retain water and the posterior pituitary produces an antidiuretic hormone. The glands seem to be controled by feedback loops connecting them to the pituitary which stimulates them to cat. Also glands produce hormones that offset the effects ofeach other, eg. estrogen and progesterone (from the overies). See Cortisone and ATCH above for another example. Evidence suggests that the hormones, oxytocin and vasopressin (which raises blood pressure and reduces excretion of urine) are produced in nerve cells in the hypothalamus and only stored in the posterior pituitary. The testes also produce estrogen. Many glands can produce hormones that are similar to the main theme of other glands.
Subjects tested under hypnosis, while asleep, and while awake. The responses under hypnosis and while asleep were essentially the same. The suggestability relative to other subjects while awake corresponded to that while asleep or under hypnosis.
The reticluar formation is a nerve network in the central brain stem. All sensory nerves feed directly into the cortex (where they are processed) but also into the reticular formation. It is this which wakes up the cortex so it can process the signals. Also keeps it awake. It reacts to selectively to signals, one can learn the sleep through anything. Crude wakefulness is possible without the cortex, as long as the reticular formation operates. But for sustained wakefulness the cortex is necessary. In combination with the cortex it seems to focus attention. It is affected by sleep inducing drugs ana also stimulants. It also seems involved with both voluntary and involuntary motor operations. Stimulating the upper part enhances reflex actions, the lower part damps them. Similar results for sensory signals. In general it seems to be a traffic controler for the nervous system.
The front of the hypothalamus is involved with controling over- heating. The rear part and the front of the mid-brain have centers involved with resisting cold. Evidence that a substance released from white blood cells acts on the hypothalamus.
Has affects on blood circulation. Also on muscles in the intestines, uterus, and broncai. It can be produced almost anywhere in the body. It is common in the brain. It cannot enter itself, but precusors can from which it is produced. Seems to be sedative in small amounts, but to excite in large amounts. It is related to lysergic acid, but seems to work counter to it.
Secreted by the corpus luteum, which develops from a ripened follicle in an ovary after it has discharged its egg. It helps prepare the uterus for gestation and also protects the developing embryo. When the corpus luteum is removed the embrio dies, is aborted, or delivered prematurely. Artificial administration of extract (progesterone) can prolong the pregnancy. Spontaneous abortion is due to contractions of the uterus. It is found that estrogen controls how much actomyosin (muscle proteins myosin and actin) and ATP are produced in muscle tissue. The ATP activates the actomyosin making the muscle contract. Estrogen controls the process of sexual maturation, of egg ripening and the cycle of ovulation. Then when the egg has ripened the corpus luteum forms and produces progesterone, which induces the uterus to prepare for the egg. Once the placenta has formed around the egg it produces both estrogen and progesterone. Estrogen prepares the uterine muscle tissue for birth, progesterone inhibits contractions. The contractions are blocked because progesterone prevents excitation of the muscle tissue and blocks the conduction of a stimulus. It does this by affecting the ion content of cell walls. Potassium and sodium gradients across the walls are lower and calcium is contained in the cell more strongly (see The Nerve Impulse). Unlike many hormones which are carried in the blood, progesterone produced by the placenta diffuses through the uterine muscle tissue.
Insulin is secreted by cells (the isles of langerhans?) in the pancreas. Insulin has no effect on the metabolism of sugar. What it does affect is the ability of certain cells (muscles, the connective tissues, and the cells that make fat) to absorb sugar.
The cerebellum does not directly monitor any physiological functions in the body, but serves to monitor and coordinate other areas of the brain that do, and to mediate between them and the body. It has a highly convoluted structure, with a much higher ratio of surface area to overall volumen than other parts of the brain. In comparing those of different species, it scale s with body mass. Removal of parts of the cerebellum in animals reduces muscle tone, coordination and equilibrium, but massive damage has to be done to induce preminent loss.The cerebellum receives signals from the motor centers in the brain and also from nerves in the muscles of the body. It compares these and then sends modified signals to the motor centers as appropriate, ensuring that the actual motions of the muscles match the intended motions. It is also the place that related muscle groups are coordinated, as in opposing muscles controling the extension of the arm etc. It also uses signals from the inner ear to maintain balance. And finally coordinates the other senses as well.
The signals from the muscle sensing nerves map onto two `humanoid' figures in the cerebellum, one face on, the other like two back to back siamese twins. Signals from the sensory nerves in the skin also map to these figures. Visual and auditory information map into a third, overlapping, region, with no special shape, that lies between them. These sensory areas are also linked to the corresponding cerebral areas.
The cerebellum generates the highest frequencies of the whole nervous system (200 to 400 Hz), but with a low voltage (200 micro V). Compare to the cerebrum: 20-40 Hz at 2 mille V. The cerebellum, however, tends to impose its own characteristics on signals that pass through it from other portions of the nervous system, modulating the slower, stronger, signals, as if they were carrier waves.
The full brain stem, cerebelluar system:
The cortex as a network of neurons. There are 10^7 neurons, each having input from ~100 other neurons via dendrites and sending output to ~100 via a single multibranching axion. Axions connect to dendrites or neurons at synapses, mediated by transmitter molecules. Both exitory and inhibitory signals come into the neuron, and these must sum above a threshold. Once the neuron has fired, it needs to rest briefly. Total brain power estimated at 10 watts. There are waves that flow in circles, or circuits, so that an excitation will continue to propegate for several seconds. Measured brain waves include: Alpha-waves, 10 Hz, are the wave of inattentive consciousness. They are feed by impulses from lower portions of the brain and fade during deep sleep. During mental activity higher frequency waves, of lower spacial coherence break up the larger scale slower alpha waves. Cortical activity that is either too weak, or too intense, will coorespond to some form of unconsciousness or fit. In fact much activity occurs at a subconscious level. Sensory signals enter the cortex at specific locations. It is assumed that they are then integrated into multisense perceptions physical objects. However, direct electrical stimulous, produces only fuzzy illdefined sensations. It is indicated that memory is related to the enlargement of synapses with recurring use. Memories involve millions of neurons, and appear to be `recorded as engrams' in multiple locations in the cortex. This requires individual neurons and even synapses to be involved in multiple engrams.
Humans can regenerate some tissues, notably bone, skin, muscles, and sometimes nerves, more or less easily. Even some organs, the liver, pancreas and saliva glands can regrow, but in general the more complex structures cannot. In simple animals the entire animal can regenerate from small parts. As the animals increase in complexity, and elevation up the evolutionary ladder, they can only regenerate some parts, then none at all. There is also a trend as the animal ages, more can be regenerated in infancy and youth, than in the adult. Frogs are particularly noted for this. In the salamander cells appear to return to the undifferentiated embrionic states in the earliest stages of limb growth, they then follow the original course of infant growth. A mojor difference in regeneration is that this occurs in conjunction with adult cells, e.g. skin, blood vessel, nerves etc. growing from the remaining part of the adult limb. The ability to regenerate is not apparently dependent on hormones in the blood supply. Regeneration does appear to require that healthy nerves are in contact with the growth interface. Extra limbs may even be grown if main nerves are diverted to fresh surface wounds. It is the presence of the nerve cells, not their conductive capacity that is necessary. The type of nerves is not important, but the quantity is, and it may be that a relative reduction in quantity with growth(age) is at least partly responsible for the loss of regenerative capacity in animals with age (e.g. the frog).
In which it is found that the periodicity of stressful situations is a factor in inducing ulcers, e.i. is matches some internal gastrointestinal rythm.
Viruses can invade bacteria, incorporate themselves into the bacteria's NDA and stay there for generations as `latent infections'. While they are there the bacteria's behavior will change. It is also possible for viruses to pick up bacteria DNA in one host and then deposit it into another, thereby modifying the recieving bacteria. This is called transduction. Bacteria can also affect each other through transformation, in which DNA from a dead, disrupted, bacteria is absorbed by another, and by mating, in which the DNA is passed from one live bacteria directly to another. This last process can transfer longer sections of DNA at one time.
When placed in an electric field that is tuned approprietly sperm that will produce male or female offspring move in opposite directions. YY sperm move to the positive pole and XY sperm move to the negative pole.
Egg cells are polarized, with a north and south pole. The pre-embryo (a small cluster of as yet undifferentiated cells) can be disected, and still produce a normal fetus, if the polar balance is maintained, either by taking an equitorial band or by combining the polar regions. Cells from a frogs stomach area transplanted to the mouth area of a salamander fetus become mouth cells, but they are still frog mouth cells. [This demonstrates the combination of DNA and morphogenic field.] However, some regions are dominent, i.e. the notocord (incipient spine) will continue to develop as a spine, even when placed in an already developing belly region, that region instead became a back. In termite colonies nymphs may develop into any of the casts, but if the necessary quota of the higher casts is filled they remain unspecialized nymphs. When embrios are grown in a culture including bits of brain, heart, or blood, etc., they tended not to form those parts. This is compared to the ability of a growing tip on plants to inhibit development of other potential growing tips behind it.
Nerve cells have an inner conductiong core, an outer insulating membrane, and are surrounded a low-resistance conducting medium filled with salt. There is normally a separation of sodium ions outside the cells and potassium ions inside the cells. There is also a steady potential across the membrane so that it is negative inside and positive outside. Nerve pulses are travelling waves (constant amplitude and velocity) of negative charge along the outside of the membrane and of positive charge along the inside of the membrane. The potential across the membrane changes from 50-100 milli V to 20-50 milli V in the opposite direction. This occurs due to a changes in the permiability of the membrane first to allow sodium ions into the cell, and then to allow potassium ions to exit the cell. The speed of the signal depends on the resistance of the external medium, being slower in damp air than in sea water. It also depends on having sodium ions in the external medium. The changes in potential in turn cause changes in permiability, and so the wave propegates.
It is found that the main danger in shock from wounds, burns etc. is due to increased potassium in the rest of the body. The wound area draws in large amounts of fluids and high concentrations of sodium, upsetting the ion balance in the rest of the body. This can be countered by administering large amounts of saline solution, in which any sodium salt has been used.
Experiments with perception, involving the perception of what is upright, found people relied on either the physcial sensations of the body (gravity on the inner ear) and visual cues from the environment. Further testing with diagrams etc. indicated that those who relied on visual cues had a generally harder time ignoring environmental cues of all kinds, of seeing something `out of context'. The amount of field-dependance or field-independance was smoothly graduated, not a bimodal distribution. Field-independent people will do better at analytical problems which require one to isolate elements and rearrange them in a new way. They will also tend to be more independent in social situations. Women are more often field-dependent than men. The field-dependance of preception is thus a reflection of a much broader sense of self. The level of average field-independance changes as children grow, being lowest when young and increasing with age, especially during the early teen years, then it levels off or perhaps dropping a little. There is a wide variation at any age, but individuals maintain their position relative to their peers, even as the average changes. The relative dependance or independance appears to develop fairly early, and correlates well with the complexity of personality and the level of independance or passivity of the children. This is all independent of overall mental health and adjustment, but does correlate with the nature of pathologies. It has also been found that it correlates with the nature of the mother-son relationship, with sons of `growth-restrictive' mothers being more field-dependent.
Polio is one of a class of some 50 enteroviruses, which normally live in the intestines. At times they invade other parts of the body, in particular the nervous system, where they cause great damage. Besides polio these viruses are also responsible for various forms of meningitus, and other disorders of the nerves and muscles. The different viruses may show a preference for cells from specific organs and species. An intestinal infection which does not spread appears to provide lifeitme immunity.
The change from a larval form to an adult insect is controled by a gland behind its brain. In the larval stage it secrets a hormone, neotenin, when it has fully grown this secretion stops and the transformation to the adult stage takes place. This compares to the changes between the male and female in many species when the sex hormones are changed. In insects, such as butterflys there are two transformations (larva, pupa, adult) and a two step drop in the secretion of the hormone. This hormone apparently acts as a switch between different sets of genes that define the different stages. The application of the hormone to some parts of the adult (e.g. skin/sheel) may induce them to revert to juvenile form. It is hypothesized (correctly) that these processes may relate to the differentiation of cells as an organism grows from the egg.
Melatonin is a hormone secreted by the pineal gland. Its secretion responds to the day/night light cycle. It is involved in timing the actions of many animals during the year as well as the day. A surge is produced at nightfall. Light on the retina sneds a message to slow production. It acts to regulate other hormones. Peak production is at about 10 years of age in humans, sharply declines entering puberty, and slowly falls of the rest of ones life. When oxygen is metabolized free radicals are produced. These are corosive to protien and DNA. This contributes to aging in general and a host of diseases in particular. Several enzymes inhibit oxydation and vitamins C & E and beta carotene provide extra protection. But these are active only in certain parts of cells. Melatonin can be found throughout all cells, and seems to help project cells from all sorts of assaults. Probable that melatonin keeps the thymus healthy. This means the immune system is healthy. In mice it seems to reverse some features of aging. Some evidence that pineal gland hardening conributes to breast cancer, or the lack of resistance to it. Early puberty, fewer pregnancies, and late menopause increase the cumulative estrogen exposure, which increases a woman's chances of breast cancer. Melatonin dampens the release of estrogen. Most commonly used now as a sleep aid. Interleuken-2 is a hormone that helps T cells (immune system cells) proliferate. When taken with melatonin much smaller doses are effective against cancer cells. Another hormone: DHEA (dehydroepiandrosterone) seems to have similar effects. Evidence for strengthening bones,muscles, and the immune system, works against lupus, cancer, and diabetes. This is an adrenal cortex product and helps regulate the sex hormones. It increases at puberty then also declines.
The sweet smell of lavender oil helped four elderly insomniacs fall asleep quicker and sleep longer said David Stretch, a researcher at the University of Leicester. Three of them stopped taking sedatives. His report is published in a letter in this week's edition of The Lancet. "The results ... very consistent with what we and others have found," said Dr. Alan Hirsch, director of the Smell and Taste Research Center in Chicago. ...the aroma of lavender...worked just as well as sleeping pills. Hirsch said the olfactory bulb, the nose's nerve center, lies close to the brain's reticular activating system, which controls the sleep-wake cycle. He speculated that chemicals in the lavender oil flowed through the nose into the brain, somehow altering the biology of the sleep center.
On anger: Popular wisdom argues for "letting it all hang out" and having a good cathartic rant. But Goleman cites studies showing that dwelling on anger actually increases its power; the body needs a chance to process the adrenaline through exercise, relaxation techniques, a well-timed intervention or even the old admonition to count to 10. On shifting emotions: Sadness and discouragement, for instance, are "low arousal" states, and the dispirited salesman who goes out for a run is triggering a high arousal state that is incompatible with staying blue. Relaxation works better for high-energy moods like anger or anxiety. Either way, the idea is to shift to a state of arousal that breaks the destructive cycle of the dominant mood.
Melatonin is produced by the pineal gland and functions as the body's own safe and highly effective sleeping potion. The brain produces melatonin in response to the setting of the sun. Elevated levels of melatonin in the blood lull the body into sleep, while reduced levels during the day help keep it awake. This has been used to help reset the body clock after long plane trips. It is also known that the body produces less melatonin as it grows older. Based on this and an experiment in which the pineal glands of old mice were transplanted into young ones, and vice versa, in which the glands of the younger animals seemed to rejuvenate the older ones, while the younger mice who had received the old glands aged rapidly and died prematurely, it is now being suggested that melatonin is a significant antiaging agent. However, the strains of mice used in those studies do not produce melatonin. So whatever rejuvenated the aging rodents, it wasn't melatonin. [This suggests perhaps something else in the pineal gland?]
Cocaine and amphetamines affect the neurotransmitter dopamine -- a chemical that regulates emotions and body movement. Higher levels of dopamine create feelings of euphoria. Scientists have deduced how neurotransmitters work by experimenting with drugs such as antidepressants and watching their effects. Neurotransmitters carry messages across the synapses or spaces between nerve cells. Once they attach to a cell they are "on" until they are turned "off" -- by breaking down or when they are removed by chemicals called transporters. It has now been shown that amphetamines and cocaine work by blocking the transporters for dopamine so that the transmitter stays on. This was done with a mouse that was bred to have a disrupted, or faulty, gene for the dopamine transporter, so they are "just like mice that are on cocaine or amphetamines"; they are hyperactive, they gained weight more slowly than normal mice, tended to die young and the mothers neglected their babies. The mice also had unusually low levels of dopamine. It seems that the mice's bodies sensed that the dopamine was stuck "on," so the nerve cells did not produce any more. This points to the key importance of the transporter. The mice will also be useful for research into diseases, e.g. Parkinson's disease (too little dopamine), which causes uncontrollable shaking, schizophrenia (too much dopamine) and other conditions believed to be caused by an imbalance of dopamine.
The rates of depression differ among countries, but depression symptoms are strikingly similar worldwide, based on a study of rates of depression and bipolar disorder, also known as manic-depression, in 38,000 people in 10 countries. For bipolar disorder, however, rates are generally the same. Rates of major depression ranged from 19% in Beirut, Lebanon; 16.4% in Paris; 12.4% in Florence, Italy; Christchurch, New Zealand, 11.6%; Edmonton/Alberta, Canada, 9.6%; West Germany, 9.2%; U.S.A., 5.2%; Puerto Rico, 4.3%; Korea, 2.9%; to 1.5% in Taiwan. Rates of depression in every country were higher among women. The disorders are biological, or genetic, but their expression, particularly that of major depression, depends on the environmental context. Major depression is 'heterogeneous,' whereas bipolar disorder seems to be more 'homogeneous,' probably less dependent upon the environment for its expression. Yet despite the cultural diversity, there were similarities in ages of onset, similar patterns of symptoms and accompanying problems -- alcohol abuse or dependence, panic disorder, and obsessive-compulsive disorder. Insomnia and loss of energy were the most common symptoms presenting in major depression, and difficulty with concentration and thoughts of death or suicide were also commonly found. The average age at onset of depression was generally in the mid to late 20s.
BY J. MADELEINE NASH Imagine you are taking a slug of whiskey. a puff of a cigarette. A toke of marijuana. A snort of cocaine. A shot of heroin. Put aside whether these drugs are legal or illegal. Concentrate, for now, on the chemistry. The moment you take that slug, that puff, that toke, that snort, that shot, trillions of potent molecules surge through your bloodstream and into your brain. Once there, they set off a cascade of chemical and electrical events, a kind of neurological chain reaction that ricochets around the skull and rearranges the interior reality of the mind. Given the complexity of these events--and the inner workings of the mind in general--it's not surprising that scientists have struggled mightily to make sense of the mechanisms of addiction. Why do certain substances have the power to make us feel so good (at least at first)? Why do some people fall so easily into the thrall of alcohol, cocaine, nicotine and other addictive substances, while others can, literally, take them or leave them? The answer, many scientists are convinced, may be simpler than anyone has dared imagine. What ties all these mood-altering drugs together, they say, is a remarkable ability to elevate levels of a common substance in the brain called dopamine. In fact, so overwhelming has evidence of the link between dopamine and drugs of abuse become that the distinction (pushed primarily by the tobacco industry and its supporters) between substances that are addictive and those that are merely habit-forming has very nearly been swept away. The Liggett Group, smallest of the U.S.'s Big Five cigarette makers, broke ranks in March and conceded not only that tobacco is addictive but also that the company has known it all along. While RJR Nabisco and the others continue to battle in the courts--insisting that smokers are not hooked, just exercising free choice--their denials ring increasingly hollow in the face of the growing weight of evidence. Over the past year, several scientific groups have made the case that in dopamine-rich areas of the brain, nicotine behaves remarkably like cocaine. And late last week a federal judge ruled for the first time that the Food and Drug Administration has the right to regulate tobacco as a drug and cigarettes as drug-delivery devices. Now, a team of researchers led by psychiatrist Dr. Nora Volkow of the Brookhaven National Laboratory in New York has published the strongest evidence to date that the surge of dopamine in addicts' brains is what triggers a cocaine high. In last week's edition of the journal Nature they described how powerful brain-imaging technology can be used to track the rise of dopamine and link it to feelings of euphoria. Like serotonin (the brain chemical affected by such antidepressants as Prozac), dopamine is a neurotransmitter--a molecule that ferries messages from one neuron within the brain to another. Serotonin is associated with feelings of sadness and well-being, dopamine with pleasure and elation. Dopamine can be elevated by a hug, a kiss, a word of praise or a winning poker hand--as well as by the potent pleasures that come from drugs. The idea that a single chemical could be associated with everything from snorting cocaine and smoking tobacco to getting good grades and enjoying sex has electrified scientists and changed the way they look at a wide range of dependencies, chemical and otherwise. Dopamine, they now believe, is not just a chemical that transmits pleasure signals but may, in fact, be the master molecule of addiction. This is not to say dopamine is the only chemical involved or that the deranged thought processes that mark chronic drug abuse are due to dopamine alone. The brain is subtler than that. Drugs modulate the activity of a variety of brain chemicals, each of which intersects with many others. "Drugs are like sledgehammers," observes Dr. Eric Nestler of the Yale University School of Medicine. "They profoundly alter many pathways." Nevertheless, the realization that dopamine may be a common end point of all those pathways represents a signal advance. Provocative, controversial, unquestionably incomplete, the dopamine hypothesis provides a basic framework for understanding how a genetically encoded trait--such as a tendency to produce too little dopamine--might intersect with environmental influences to create a serious behavioral disorder. Therapists have long known of patients who, in addition to having psychological problems, abuse drugs as well. Could their drug problems be linked to some inborn quirk? Might an inability to absorb enough dopamine, with its pleasure-giving properties, cause them to seek gratification in drugs? Such speculation is controversial, for it suggests that broad swaths of the population may be genetically predisposed to drug abuse. What is not controversial is that the social cost of drug abuse, whatever its cause, is enormous. Cigarettes contribute to the death toll from cancer and heart disease. Alcohol is the leading cause of domestic violence and highway deaths. The needles used to inject heroin and cocaine are spreading aids. Directly or indirectly, addiction to drugs, cigarettes and alcohol is thought to account for a third of all hospital admissions, a quarter of all deaths and a majority of serious crimes. In the U.S. alone the combined medical and social costs of drug abuse are believed to exceed $240 billion. For nearly a quarter-century the U.S. has been waging a war on drugs, with little apparent success. As scientists learn more about how dopamine works (and how drugs work on it), the evidence suggests that we may be fighting the wrong battle. Americans tend to think of drug addiction as a failure of character. But this stereotype is beginning to give way to the recognition that drug dependence has a clear biological basis. "Addiction," declares Brookhaven's Volkow, "is a disorder of the brain no different from other forms of mental illness." That new insight may be the dopamine hypothesis' most important contribution in the fight against drugs. It completes the loop between the mechanism of addiction and programs for treatment. And it raises hope for more effective therapies. Abstinence, if maintained, not only halts the physical and psychological damage wrought by drugs but in large measure also reverses it. Genes and social forces may conspire to turn people into addicts but do not doom them to remain so. Consider the case of Rafael Rios, who grew up in a housing project in New York City's drug-infested South Bronx. For 18 years, until he turned 31, Rios, whose father died of alcoholism, led a double life. He graduated from Harvard Law School and joined a prestigious Chicago law firm. Yet all the while he was secretly visiting a shooting gallery once a day. His favored concoction: heroin spiked with a jolt of cocaine. Ten years ago, Rios succeeded in kicking his habit--for good, he hopes. He is now executive director of A Safe Haven, a Chicago-based chain of residential facilities for recovering addicts. How central is dopamine's role in this familiar morality play? Scientists are still trying to sort that out. It is no accident, they say, that people are attracted to drugs. The major drugs of abuse, whether depressants like heroin or stimulants like cocaine, mimic the structure of neurotransmitters, the most mind-bending chemicals nature has ever concocted. Neurotransmitters underlie every thought and emotion, memory and learning; they carry the signals between all the nerve cells, or neurons, in the brain. Among some 50 neurotransmitters discovered to date, a good half a dozen, including dopamine, are known to play a role in addiction. The neurons that produce this molecular messenger are surprisingly rare. Clustered in loose knots buried deep in the brain, they number a few tens of thousands of nerve cells out of an estimated total of 100 billion. But through long, wire-like projections known as axons, these cells influence neurological activity in many regions, including the nucleus accumbens, the primitive structure that is one of the brain's key pleasure centers. At a purely chemical level, every experience humans find enjoyable--whether listening to music, embracing a lover or savoring chocolate--amounts to little more than an explosion of dopamine in the nucleus accumbens, as exhilarating and ephemeral as a firecracker. Dopamine, like most biologically important molecules, must be kept within strict bounds. Too little dopamine in certain areas of the brain triggers the tremors and paralysis of Parkinson's disease. Too much causes the hallucinations and bizarre thoughts of schizophrenia. A breakthrough in addiction research came in 1975, when psychologists Roy Wise and Robert Yokel at Concordia University in Montreal reported on the remarkable behavior of some drug-addicted rats. One day the animals were placidly dispensing cocaine and amphetamines to themselves by pressing a lever attached to their cages. The next they were angrily banging at the lever like someone trying to summon a stalled elevator. The reason? The scientists had injected the rats with a drug that blocked the action of dopamine. In the years since, evidence linking dopamine to drugs has mounted. Amphetamines stimulate dopamine-producing cells to pump out more of the chemical. Cocaine keeps dopamine levels high by inhibiting the activity of a transporter molecule that would ordinarily ferry dopamine back into the cells that produce it. Nicotine, heroin and alcohol trigger a complex chemical cascade that raises dopamine levels. And a still unknown chemical in cigarette smoke, a group led by Brookhaven chemist Joanna Fowler reported last year, may extend the activity of dopamine by blocking a mopping-up enzyme, called MAO B, that would otherwise destroy it. The evidence that Volkow and her colleagues present in the current issue of Nature suggests that dopamine is directly responsible for the exhilarating rush that reinforces the desire to take drugs, at least in cocaine addicts. In all, 17 users participated in the study, says Volkow, and they experienced a high whose intensity was directly related to how extensively cocaine tied up available binding sites on the molecules that transport dopamine around the brain. To produce any high at all, she and her colleagues found, cocaine had to occupy at least 47% of these sites; the "best" results occurred when it took over 60% to 80% of the sites, effectively preventing the transporters from latching onto dopamine and spiriting it out of circulation. Scientists believe the dopamine system arose very early in the course of animal evolution because it reinforces behaviors so essential to survival. "If it were not for the fact that sex is pleasurable," observes Charles Schuster of Wayne State University in Detroit, "we would not engage in it." Unfortunately, some of the activities humans are neurochemically tuned to find agreeable--eating foods rich in fat and sugar, for instance--have backfired in modern society. Just as a surfeit of food and a dearth of exercise have conspired to turn heart disease and diabetes into major health problems, so the easy availability of addictive chemicals has played a devious trick. Addicts do not crave heroin or cocaine or alcohol or nicotine per se but want the rush of dopamine that these drugs produce. Dopamine, however, is more than just a feel-good molecule. It also exercises extraordinary power over learning and memory. Think of dopamine, suggests P. Read Montague of the Center for Theoretical Neuroscience at Houston's Baylor College of Medicine, as the proverbial carrot, a reward the brain doles out to networks of neurons for making survival-enhancing choices. And while the details of how this system works are not yet understood, Montague and his colleagues at the Salk Institute in San Diego, California, and M.I.T. have proposed a model that seems quite plausible. Each time the outcome of an action is better than expected, they predicted, dopamine-releasing neurons should increase the rate at which they fire. When an outcome is worse, they should decrease it. And if the outcome is as expected, the firing rate need not change at all. As a test of his model, Montague created a computer program that simulated the nectar-gathering activity of bees. Programmed with a dopamine-like reward system and set loose on a field of virtual "flowers," some of which were dependably sweet and some of which were either very sweet or not sweet at all, the virtual bees chose the reliably sweet flowers 85% of the time. In laboratory experiments real bees behave just like their virtual counterparts. What does this have to do with drug abuse? Possibly quite a lot, says Montague. The theory is that dopamine-enhancing chemicals fool the brain into thinking drugs are as beneficial as nectar to the bee, thus hijacking a natural reward system that dates back millions of years. The degree to which learning and memory sustain the addictive process is only now being appreciated. Each time a neurotransmitter like dopamine floods a synapse, scientists believe, circuits that trigger thoughts and motivate actions are etched onto the brain. Indeed, the neurochemistry supporting addiction is so powerful that the people, objects and places associated with drug taking are also imprinted on the brain. Stimulated by food, sex or the smell of tobacco, former smokers can no more control the urge to light up than Pavlov's dogs could stop their urge to salivate. For months Rafael Rios lived in fear of catching a glimpse of bare arms--his own or someone else's. Whenever he did, he remembers, he would be seized by a nearly unbearable urge to find a drug-filled syringe. Indeed, the brain has many devious tricks for ensuring that the irrational act of taking drugs, deemed "good" because it enhances dopamine, will be repeated. pet-scan images taken by Volkow and her colleagues reveal that the absorption of a cocaine-like chemical by neurons is profoundly reduced in cocaine addicts in contrast to normal subjects. One explanation: the addicts' neurons, assaulted by abnormally high levels of dopamine, have responded defensively and reduced the number of sites (or receptors) to which dopamine can bind. In the absence of drugs, these nerve cells probably experience a dopamine deficit, Volkow speculates, so while addicts begin by taking drugs to feel high, they end up taking them in order not to feel low. PET-SCAN images of the brains of recovering cocaine addicts reveal other striking changes, including a dramatically impaired ability to process glucose, the primary energy source for working neurons. Moreover, this impairment--which persists for up to 100 days after withdrawal--is greatest in the prefrontal cortex, a dopamine-rich area of the brain that controls impulsive and irrational behavior. Addicts, in fact, display many of the symptoms shown by patients who have suffered strokes or injuries to the prefrontal cortex. Damage to this region, University of Iowa neurologist Antonio Damasio and his colleagues have demonstrated, destroys the emotional compass that controls behaviors the patient knows are unacceptable. Anyone who doubts that genes influence behavior should see the mice in Marc Caron's lab. These tireless rodents race around their cages for hours on end. They lose weight because they rarely stop to eat, and then they drop from exhaustion because they are unable to sleep. Why? The mice, says Caron, a biochemist at Duke University's Howard Hughes Medical Institute laboratory, are high on dopamine. They lack the genetic mechanism that sponges up this powerful stuff and spirits it away. Result: there is so much dopamine banging around in the poor creatures' synapses that the mice, though drug-free, act as if they were strung out on cocaine. For years scientists have suspected that genes play a critical role in determining who will become addicted to drugs and who will not. But not until now have they had molecular tools powerful enough to go after the prime suspects. Caron's mice are just the most recent example. By knocking out a single gene--the so-called dopamine-transporter gene--Caron and his colleagues may have created a strain of mice so sated with dopamine that they are oblivious to the allure of cocaine, and possibly alcohol and heroin as well. "What's exciting about our mice," says Caron, "is that they should allow us to test the hypothesis that all these drugs funnel through the dopamine system." Several dopamine genes have already been tentatively, and controversially, linked to alcoholism and drug abuse. Inherited variations in these genes modify the efficiency with which nerve cells process dopamine, or so the speculation goes. Thus, some scientists conjecture, a dopamine-transporter gene that is superefficient, clearing dopamine from the synapses too rapidly, could predispose some people to a form of alcoholism characterized by violent and impulsive behavior. In essence, they would be mirror images of Caron's mice. Instead of being drenched in dopamine, their synapses would be dopamine-poor. The dopamine genes known as d2 and d4 might also play a role in drug abuse, for similar reasons. Both these genes, it turns out, contain the blueprints for assembling what scientists call a receptor, a minuscule bump on the surface of cells to which biologically active molecules are attracted. And just as a finger lights up a room by merely flicking a switch, so dopamine triggers a sequence of chemical reactions each time it binds to one of its five known receptors. Genetic differences that reduce the sensitivity of these receptors or decrease their number could diminish the sensation of pleasure. The problem is, studies that have purported to find a basis for addiction in variations of the d2 and d4 genes have not held up under scrutiny. Indeed, most scientists think addiction probably involves an intricate dance between environmental influences and multiple genes, some of which may influence dopamine activity only indirectly. This has not stopped some researchers from promoting the provocative theory that many people who become alcoholics and drug addicts suffer from an inherited condition dubbed the reward-deficiency syndrome. Low dopamine levels caused by a particular version of the d2 gene, they say, may link a breathtaking array of aberrant behaviors. Among them: severe alcoholism, pathological gambling, binge eating and attention-deficit hyperactivity disorder. The more science unmasks the powerful biology that underlies addiction, the brighter the prospects for treatment become. For instance, the discovery by Fowler and her team that a chemical that inhibits the mopping-up enzyme mao b may play a role in cigarette addiction has already opened new possibilities for therapy. A number of well-tolerated mao b-inhibitor drugs developed to treat Parkinson's disease could find a place in the antismoking arsenal. Equally promising, a Yale University team led by Eric Nestler and David Self has found that another type of compound--one that targets the dopamine receptor known as d1--seems to alleviate, at least in rats, the intense craving that accompanies withdrawal from cocaine. One day, suggests Self, a d1 skin patch might help cocaine abusers kick their habit, just as the nicotine patch attenuates the desire to smoke. Like methadone, the compound that activates d1 appears to be what is known as a partial agonist. Because such medications stimulate some of the same brain pathways as drugs of abuse, they are often addictive in their own right, though less so. And while treating heroin addicts with methadone may seem like a cop-out to people who have never struggled with a drug habit, clinicians say they desperately need more such agents to tide addicts--particularly cocaine addicts--over the first few months of treatment, when the danger of relapse is highest. Realistically, no one believes better medications alone will solve the drug problem. In fact, one of the most hopeful messages coming out of current research is that the biochemical abnormalities associated with addiction can be reversed through learning. For that reason, all sorts of psychosocial interventions, ranging from psychotherapy to 12-step programs, can and do help. Cognitive therapy, which seeks to supply people with coping skills (exercising after work instead of going to a bar, for instance), appears to hold particular promise. After just 10 weeks of therapy, before-and-after pet scans suggest, some patients suffering from obsessive-compulsive disorder (which has some similarities with addiction) manage to resculpt not only their behavior but also activity patterns in their brain. In late 20th century America, where drugs of abuse are being used on an unprecedented scale, the mounting evidence that treatment works could not be more welcome. Until now, policymakers have responded to the drug problem as though it were mostly a criminal matter. Only a third of the $15 billion the U.S. earmarks for the war on drugs goes to prevention and treatment. "In my view, we've got things upside down," says Dr. David Lewis, director of the Center for Alcohol and Addiction Studies at Brown University School of Medicine. "By relying so heavily on a criminalized approach, we've only added to the stigma of drug abuse and prevented high-quality medical care." Ironically, the biggest barrier to making such care available is the perception that efforts to treat addiction are wasted. Yet treatment for drug abuse has a failure rate no different from that for other chronic diseases. Close to half of recovering addicts fail to maintain complete abstinence after a year--about the same proportion of patients with diabetes and hypertension who fail to comply with their diet, exercise and medication regimens. What doctors who treat drug abuse should strive for, says Alan Leshner, director of the National Institute on Drug Abuse, is not necessarily a cure but long-term care that controls the progress of the disease and alleviates its worst symptoms. "The occasional relapse is normal," he says, "and just an indication that more treatment is needed." Rafael Rios has been luckier than many. He kicked his habit in one lengthy struggle that included four months of in-patient treatment at a residential facility and a year of daily outpatient sessions. During that time, Rios checked into 12-step meetings continually, sometimes attending three a day. As those who deal with alcoholics and drug addicts know, such exertions of will power and courage are more common than most people suspect. They are the best reason yet to start treating addiction as the medical
By Maggie Fox. Psychiatrists said Tuesday there may be a physical basis linking stressed-out babies to personality disorders in adulthood. Babies lacking physical contact and emotional support may grow up susceptible to post-traumatic stress disorder (PTSD) and personality problems. Sleeping by yourself is very stressful, as shown by infants crying. The levels of the stress hormone cortisol are much higher in crying babies. Ongoing stimulation by cortisol produces physical changes in the brain which make one more prone to the effects of stress, illness, including mental illness, and make it harder to recover from illness. These are perminent changes. In cultures where infants sleep with the parents and are carried by parents, or other care takers, infants learn to stay close and look to others for emotional and physical support. The theory is that such constant support keeps down levels of cortisol, and helps the cortical structures in the brain develop better.
By Maggie Fox. New studies by Martin Gardiner showing that the study of art, as well as music helps students with other subjects such as math and reading. This appears to help at all ages, not just with the very young. He believes that both information intake and processing are improved, but also emotional skills.