V. Kalesch. Teikyo Post University.
A reactive depression was a response to a psychosocial precipitating factor discount januvia 100mg fast delivery diabetes insipidus pathophysiology and treatment, such as death of a spouse; an endogenous depression occurred in the absence of a pre- cipitating factor and arose from a biological predisposition cheap 100mg januvia fast delivery diabetes research. Since depression is a common and potentially life-threatening disorder, drug design of anti- depressants has been an ongoing activity for many decades. Unfortunately, this simple and attractive hypothesis cannot explain a number of facts: 1. The latency period of weeks or even months that occurs between the initiation of therapy and the antidepressant effect when tertiary tricyclics are used. Secondary amines act faster, but in both cases, although elevated neurotransmitter levels become rapidly apparent, the clinical improvement lags far behind. The problem with the tricyclic-based neurotransmitter–receptor hypothesis of antide- pressant activity is that it was based on observations in normal rat brain. Thus, it is likely that endogenous depression is a biologically heterogeneous syndrome; a single neurotrans- mitter hypothesis explaining the mode of action of all antidepressant drugs is not currently feasible. In the 1970s and 1980s, the tricyclic antidepressants dominated the clinical manage- ment of depression. Given their widespread use (and misuse), they were sometimes simply referred to as the “tricyclics. Various tricyclic drugs have anticholinergic properties, and people who attempt overdoses with tricyclic drugs experience life-threatening anticholinergic side effects. Recognizing that the interaction between a drug and its receptor is a precise dance between atoms and molecular frag- ments, we see that the three-dimensional interplanar orientation of the various rings is crucial to an appreciation of their varying modes of action. The tricyclics, however, do continue to be valuable in the management of chronic pain states such as headache or neuropathy. Apart from interferences with transmembrane ion fluxes (via ion channels and pumps), Li+ appears to facilitate membrane depletion of phosphatidylinositol bisphosphates, the principal lipid substrate used by various receptors in transmembrane signaling; blockade of this signal transduction pathway impairs the ability of neurons to respond to the activation of neurotransmitter receptors. The dopamine receptors have been studied extensively by classical pharmacological methods, receptor labeling techniques, and gene cloning experiments. D1-like receptors activate adenylate cyclase; D2-like receptors inhibit adenylate cyclase. The D1-like receptors, like the β-adrenergic receptors, are transcribed from intronless genes. Conversely, the D2-like receptors contain introns, thus providing an opportunity for alternatively spliced products. In terms of molecular mass, D1-like receptors are slightly larger than D2-like receptors. D1-like subtypes include the D1 (encoded on chromosome 5) and D5 (chromosome 4) receptors; D2-like subtypes include the D2 (chromosome 11), D3 (chromosome 3), and D4 (chromosome 11) receptors. D2-like receptors have smaller C-terminal intracellular segments but a larger intracellular loop between the sixth and seventh transmembrane segments. Two D2 receptor isoforms have been identified: D2 long and D2 short—D2 long has a 29 amino acid insert between the fifth and sixth membrane-spanning segments. A strong correlation exists between the clinical doses of antipsychotic drugs and their affinity for brain D2 receptors. This observation led to the hypothesis that psychotic dis- orders resulted from overactivity of the D2 receptor subpopulation. Therefore, the motor dysfunctions observed in patients chronically treated with antipsychotics are seemingly due to alter- ations in D2 receptor density. Presynaptic dopaminergic agonists These enable a logical, mechanistic understanding and will be discussed individually. In this case, α2-adrenergic receptor effects are irrelevant, and only the clas- sical competitive inhibitory effect is of any consequence. The exclusive peripheral mode of action of car- bidopa is due to its ionic character and inability to cross the blood–brain barrier. By affecting the enzyme through covalent binding, this compound completely inhibits both catecholamine and serotonin synthesis. Unlike 6-hydroxydopamine, α-fluoromethyldopa does not destroy the neurons, and unlike reserpine it does not deplete chromaffin tissue in the adrenal gland. High doses of amphetamines do deplete the storage vesicles, but this is not their principal mode of action. Interestingly, apomorphine is now also being evaluated as an oral agent for the treatment of erectile dysfunction. The ergot alkaloids and their derivatives are a rich source of catecholaminergic drugs. Ergot (Claviceps purpurea) is a parasitic fungus found on grasses and cereals (rye). Because the fungus is more valuable than the cereal crop, fields are artificially infected and the mixture of indole alkaloids is extracted from the ripe sclerotia. Other ergot alkaloids have a hypotensive effect and also cause smooth-muscle contraction, specifically in the uterus. Amides of lysergic acid are hallucino- gens and will be discussed among serotonergic drugs. A novel and very interesting group of compounds is represented by bromocriptine (4. It is used in parkinsonism and for inhibiting the excessive excretion of prolactin, a peptide hormone of the pituitary that regulates lactation. It also inhibits the secretion of growth hormone, another product of the anterior pituitary, and has been evaluated in the treatment of acromegaly, a form of gigantism arising from excessive growth hormone production. Psychosis is a severe psychiatric disorder in which mental functioning is suffi- ciently impaired to interfere with the patient’s capacity to meet the normal demands of everyday life. This impairment involves a marked inability to correctly interpret reality, and is often accompanied by severe distortions of perception, intellectual functioning, mood, motivation, and behavior, together with personality decompensation and regres- sion. The individual has little, if any, insight into either the nature or severity of his or her disturbance. There are many types of psychosis, including schizophrenia, paranoid psychosis and affective psychosis. Schizophrenia is a complex group of psychotic disorders manifested by typical dis- turbances of thinking, mood, and behavior. The associated disintegration of mental status is attributable to a thought disorder, accompanied by misinterpretations of reality and frequently by delusions and hallucinations (i. The term schizophrenia has generally been misinterpreted as meaning “splitting of the mind”; there is a popular misconception that this involves multiple, split personalities. Paranoid psychosis, on the other hand, is a psychotic disorder in which delusions, generally persecutory but sometimes grandiose, are the dominant abnormality (e. Finally, affective psychoses are a group of psychoses characterized by a single disorder of mood, typically extreme depression, which dominates the mental life of the patient, incapacitating the patient and sometimes culminating in suicide. Clearly, the psychoses are an exceedingly complex and heterogeneous array of mental state abnormalities. It is daunting to think that a single receptor (or family of receptors) can subserve such a complicated assortment of psychiatric illnesses.
A number of our physicians recognize this influence best buy for januvia diabetic diet handout in spanish, and my own experience confirms its value order discount januvia line diabetes diet hindi pdf. Those who have used all the heart remedies unite in the belief that for breadth of action, for specific directness, for reliability and smoothness and general trustworthiness, cactus takes preference over all the rest. Other remedies in some cases will do as much in single lines, but none will do more, and none will exercise all of its desirable influences. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 394 The writer has given it in valvular troubles, in weak and irregular conditions, depending upon muscular enervation, and in aortic regurgitation, and has seen cures accomplished that had been thought impossible. He was convinced of the fact ultimately and now finds excellent authority for his conclusion. Rubini, of Naples, claims that it is almost the counterpart of aconite in its action, differing in that it increases the strength and tone of the nerve centers instead of paralyzing them, as large doses of the latter agent does. Given a condition in which there is a rapid and feeble pulse, weak heart, weak and exhausted nervous system, cactus in small doses, frequently repeated, is a true sedative. Cactus as a powerful nerve tonic can be relied upon when there is any irregularity of the heart, demanding such a remedy in conjunction with general nervous weakness. It is especially indicated where there is mental depression with despondency and forebodings. It is combined with avena, nux or cimicifuga as I have often suggested with superb results. The above named combination will act as a tonic in a surpassing number of cases of nervous weakness without regard to the specific indications. It improves the nutrition of the brain by improving the circulation in that organ. In this it is of advantage in some cases of neurasthenia, especially in those in which there is a sensation of a band or cord around the body or chest or head, a symptom often spoken of in nervous exhaustion, and in forms of paralysis. Where feebleness is the cause of nervous excitement, cactus exercises a nerve sedative influence. In oppressive headache in the top of the head, causing nervousness, common to ladies at the menopause, resulting from irritation in the pelvic organs, or congestion, or menorrhagia with excessive losses of blood, it is of benefit. Where there is increased arterial tension, and exaltation of nerve force and excess of strength in the cardiac action, cactus is contraindicated. We have had several cases of palpitation, depending on exaltation of nerve energy, increased by cactus, and decreased by gelsemium, cimicifuga or the bromides. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 395 It may be given with excellent results combined with avena sativa in impotence accompanied with general nervous exhaustion, or in combination with avena sativa and saw palmetto in the feebleness and impotency of approaching age, or in the prostration following habits of dissipation, when it will accomplish most excellent results. It is given in endocarditis and in pericarditis following exhausting diseases as sequelae, With the most gratifying results. In a marked case of endocarditis following measles, with purple and bloated countenance, distressing dyspnea, and a pulse so rapid, feeble and fluttering that it could not be counted, the dyspnea was overcome, the heart beats reduced to 120, and regular, and every condition improved in the most satisfactory manner in twenty-four hours, incredible as it may seem, by the use of one drop of the fluid extract of cactus every hour. It is useful in valvular incompetency due to muscular weakness, in the feeble heart action following pneumonia, typhoid and other severe and prostrating diseases. In the feeble heart of exopthalmic goitre, it will do all that is expected of strophanthus. Lydia Ross, of Massachusetts, in the Eclectic Review, reports extensively concerning the action of cactus in the disorders of women. She claims it to be specific in that form of oppressive headache, occurring upon the top of the head, not uncommon at the menopause, resulting also from uterine malposition, or congestion. It is especially valuable in the hot flashes which are so disagreeable during the climacteric. Small doses of the remedy are advisable at that time, and their influence is often a surprise in controlling this otherwise intractable condition. Helleborus niger is an excellent remedy for this condition and they may sometimes be given in conjunction or in alternation. The melancholia, nervousness, irritability of temper, hypersensitiveness, neuralgia, vague fears and fancies, present during the menopause, are all influenced favorably by cactus. Its direct influence in strengthening the nervous system, and in toning the heart and circulatory organs, underlies its influence upon these conditions. Other conditions common to women, relieved by this remedy, are cerebral congestion, with weight and pain in the occiput, or in the vertex, numbness of the limbs, cough at the supra sternal notch, pain Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 396 behind the sternum, fear of death, general plethora and congestion. Irregularities of the menses, consisting of a flow too early, too dark and thick, too abundant-a flow which ceases upon lying down, with an inability to lie upon the left side, demand its use. In cardiac weakness of a less chronic or more acute character than those conditions affecting the aorta, the agent will be found serviceable, as in the threatened heart failure, due to violent over-exercise, as the bicycle heart, a condition not as common as it was when this work was written. It is of great value, as we have previously stated, in the tobacco heart of the cigarette fiend or inveterate smoker. In the treatment of heart weakness, common to masturbators, and in the feeble heart of the aged, where there are no great organic changes, the remedy is especially advised. The specific point present in nearly all of these cases indicating the remedy is a vise-like band around the organ affected. It may be the chest, or the stomach, or the heart, bladder, uterus or vagina, or it may be around the body. There is likely in the severe cases to be suffocation, faintness, cold perspiration and great fear of impending danger. If with the above symptoms, there be epistaxis, hematemesis, or hemorrhage from any organ or part, the agent is demanded. Lydia Ross in its use in hysterical conditions, and as a remedy to relieve the functional disturbances which the heart exhibits, from menstrual disorders. He believes it to be a most valuable remedy in the rapid and feeble heartbeat of anemia and chlorosis, greatly facilitating the influence of other indicated remedies. He reports a case of a gentleman of thirty who was suffering from cardiac irregularity of a mild type, accompanied with a persistent and almost excruciating pain in the deep muscles of the back, over the region of the kidneys. Cactus given for the heart symptoms relieved the pain permanently, in a very short time. I have used it in a few cases with good results, but unless given in large doses it will have to be given in conjunction with strychnine, nux vomica, or ignatia. It may be combined with cimicifuga or gelsemium for nervousness, with pulsatilla for hysteria, and may be given with an alkaline remedy in very feeble old ladies who suffer from vertigo and general heart feebleness. One doctor reports an increase of temperature from ten drops of cactus three times a day. Where there is a nervous hyperesthesia with excitable heart action cactus will aggravate the symptoms, I believe, whatever they may be. Cactus in the treatment of heart trouble where there is epilepsy as previously referred to, was fully enlarged on by a writer in the Eclectic Medical Journal for April, 1912. While the remedy is not always used alone in the treatment of epilepsy, it was cured. Carey, of Ohio, gives cactus with strophanthus in combination in cases where the circulation from heart fault is very imperfect, three or four drops of each. Physiological Action—Its specific influence is exercised upon the reproductive organs of the female, whether there be amenorrhea, Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 398 dysmenorrhea, menorrhagia or metrorrhagia—a disordered condition of the uterine functions—it is regulated by this agent; a general out-of-tone condition of the uterus or appendages, a relaxed condition of the supports to the womb, resulting in mild forms of displacement. In a general hyperaemic, irritable and atonic condition of the pelvic organs, it works to the best advantage.
It is much healthier to be warmly dressed and breathe cool air than to be lightly dressed in an 80°F room order januvia 100 mg with mastercard diabet-x body wash. Keep your elderly person warmly dressed purchase januvia on line diabetes insipidus adh, away from air conditioner or fan drafts, but keep it cool. Being comfortable, knowing you are there to care for them, brings out the best in your elderly person. This can be very rewarding if they are still able to communicate and distill their life experience into wisdom for you. If you can listen and be interested in their dis- tillations or their ramblings their longing for relationship will be fulfilled. Hearing Loss The hearing deficit in an elderly person is always much greater than they or you realize. The results of a hearing test, as it is told by a salesperson, is much more persuasive than you can be. Let the salesperson use his or her special talents to sell your loved one on hearing aids. Clogged hearing aids are the most troublesome feature of any of them—and never mentioned! Make it a rule to buy your batteries at the same hearing aid office where they are cleaned free of charge. Hearing loss is too subtle to leave to chance; have the hearing aids cleaned each time you buy fresh batteries (about three months). Take your loved one to a nurse for ear cleaning every six months after hearing aids are begun. With hearing aids that hear, and kidneys that flush and a heart that beats strongly, your elderly person may choose to attend concerts again, go to church or gatherings—and leave you out of the picture. If the excitement of a night out keeps him or her from sleeping use ornithine and valerian capsules. But if insomnia is the rule, not the exception, you need to go after it as a special problem. This leads me to believe it is their waste products, namely ammonia, that really causes insomnia. Your elderly person will have more energy throughout the day and a better mood if sleep was good. Limit bedtime supplements to magnesium, ornithine, valerian (6 capsules) taken with hot milk. Healthful Habits If your loved one had his or her way, they would drive the car forever, wear the same cosmetics forever, smoke or chew tobacco forever and eat their favorite dessert forever. You also know that gentle persuasion is useless; it merely erodes your relationship. Ask your loved one to ask their doctor (clinical doctor or trusted medical advisor) the following question: “Would it be better for my lungs to stop smoking? Let your family and other caretakers know you are no longer supplying these items (the car keys, the wine bottle, the codeine-containing pain pills). If you have managed to free your loved one from having to take pills or from certain disabilities that would soon require pills, you can give yourself great credit. Perhaps you, too, will find the needed natural help when you are aged and have lost your authority and your way mentally. The steer, too, has its feed provided, its water provided, its shelter for the night provided, seemingly the best time it ever had. Bacteria from the liver or your own intestines find these strained tissues immediately and intensify the pain. Kill the bacteria with a zapper, cleanse the liver, and start the Bowel Program if this has already happened to you. Surely it is keeping all your cells healthy so they can coordinate the constant tasks of nourishing themselves, removing their wastes, plus whatever job that cell was meant to do. Since your cells divide and therefore start again at age zero, even though you are 90, why do you age at all? So how could evolutionary forces have “learned” to establish death to prevent overpopulation? Unable to feed, to run, to call for help brings pain, fear, loneliness and finally, death. They may not have requested this, out of a sense of guilt or masochism, or plain dementia. But it is the most primitive of needs, the same as having a loved one nearby during childbirth. The good news is that it need not be you who attends your loved one every minute of the last week. No matter how much your loved one admonishes you to go about your business, you will know when you share the final minute that your presence helped. Give yourself the reward of knowing you shared the pain, fear and silent cry for help. Another Fluke Disease Cancer is so easily cured because it is a parasite-caused dis- ease. If the cancer damaged your ovaries or prostate, you still must heal these or- gans. It takes only 7 minutes to zap all the parasite adults and their stages which cause your cells to multiply. The responsible parasite is Fasciolopsis buskii, the human intestinal fluke, a flatworm. If the fluke eggs and other stages go through their develop- ment in your breast it can become breast cancer. Each different kind of cancer means the developmental stages of the intestinal fluke are present there. Only one more thing is needed to bring about an avalanche of reproduction, so that hundreds of little larvae turn into hundreds more in a short time: a growth factor. This growth factor, ortho-phospho-tyrosine (and possibly, also, epidermal growth factor and insulin-dependent growth factor) really begins your cancer. Teamed With A Solvent The good news is that this growth factor, which is essential for cancer to develop, cannot be made, without the presence of an abnormal solvent, propyl alcohol (or more exactly, isopropyl alcohol). It takes two things, together, to give you cancer: propyl alcohol and the human intestinal fluke parasite. Zap yourself every day for three seven minute periods, until after you are completely well. Once you have stopped using it, the last remnants leave your body within three days. Given half a chance your body will throw the rascals out and restore order in your tissues.
For all natural isotopes order januvia 100mg with amex diabetes mellitus in dogs treatment, electron capture is the usual process – because the energy between the par- ent and daughter is less than 2m c2 (m is the electron mass) generic 100mg januvia fast delivery diabetic diet percentages. However, for a number of artifcially e e induced isotopes positron emission takes place. The fate of the emitted positron is; after Illustration of the annihilation being slowed down, it will meet an elec- tron, and then either annihilate directly, or 511 keV photon form a short-lived “positronium atom”. The fnal process is an annihilation where the mass of the two particles is trans- formed into g-ray photons. A very important point is that the photons fy off in opposite directions (see the illustration to the right). We observe the two photons by detectors 180 degrees apart (coincidence measurements). We know Courtesy of Arnt Inge Vistnes from this observation that the annihilation process has taken place somewhere along the line shown in the illustration. One coincidence observation yield a line whereas two or more observations in other directions give a point (or a small area) where the radioactivity has its origin. Information on how tissue and organs functions on both the molecular and cell level. It is also possible to study changes in the brain that follows Alzheimer disease and epilepsy. Positron and positronium In connection to positron emission – we have to mention the “atom” positronium. When the positron has lost its kinetic energy and meet an electron, it is a possibility that they will exist for a short mo- ment almost like an atom (see illustration). It can be mentioned that the frst theoretical work on positro- nium was carried out by Aadne Ore in 1949. Ore was con- nected to the group of biophysics at the University of Oslo – in fact he was the one that started this group. Positronium can be either orto-positronium (parallel spins) or para-positronium (opposite spin). Aadne Ore Para-positronium decays in two photons, both with energy (1916 – 1980) 511 keV whereas orto-positronium decays in three photons (combined energy is 1. Modell av Positronium Ore published the work in two articles; “Annihilation of Positrons in Gases” and “Ortho-Parapositronium conversion”. Coinsidences for two opposite detectors are measured and a picture is recon- structed. The isotopes must be hooked on special chemicals that can transport the positron emitter to places of interest. C – 11 connected to acetate has been proposed as a tracer for prostate tumor cells. The use of F-18 F-18 can be made in a cylotron by irradiating O-18 enriched water with protons. The reaction can be written: 18 18 O +=p F +n 8 9 After the production of F-18 we have to work fast since the halfife is only a couple of hours. We know that the active cancer cells need more sugar than other cells in the body. There- fore, we hook on F-18 to glucose – and the sugar molecule will transport F-18 to the active cells – the cancer cells. Photons with energy 511 keV are measured in coinsidence by detectors 180 degrees from each other. Two different tumors were localized; a sarcoma in the right scapula (shoulder blade) and a lymphoma in the right axillary lymph. The cancers were treated by radiation and the result is seen on the series of pictures – the sarcoma to the left and the lymphoma to the right. You see that the large sarcoma in the right scapula is radioresistant – independent of the radiation dose given. The lymphoma in the right axillary lymph is however radiosensitive and is eliminated after a dose of 40 Gy. The images were taken before the start of radiotherapy (0 Gy), after 8 Gy (early treatment) and after 40 Gy (late treatment). For these methods no ionizing radiation is involved and no absorbed or scattered photons are making the pic- tures. However, Raymond Damadian in spite of this it was a sensation (born 1936) and a start of a technique that to- (photo from 2009) day is very important within med- ical diagnostics. The Nobel prize in physics for 1952 was awarded to Bloch and Purcell for nuclear magnetic resonance. Yevgeny Zavoisky Felix Bloch Edward Mills Purcell (1907 – 1976) (1905 – 1983) (1912 – 1997) 204 The physics of magnetic resonance In this book we are interested in the physical background for the different medical techniques rather than to the techniques themselves. Knowledge about x-rays and radioactive nuclides was important for the methods discussed so far. In the case of the electron it can be written as: Here b is the Bohr-magneton, S is the electron spin and “g“ is the spectroscopic splitting factor – which for free electrons is 2,0023. If these small magnets are placed in a magnetic feld B, they will attain an energy which depends on the spin state. B S S where mS is the spin quantum number for the electron, which can have two values; +1/2 and –1/2. The reonance phenomenon +1/2gbB Energy difference: hn = gbB –1/2gbB Increasing magnetic feld 205 The fgure show that all the small magnets have equal energy as long as the external magnetic feld is zero. However, in a magnetic feld the magnets will be oriented “with” or “against” the magnetic feld. The two states have different energies – and the energy difference increases with the feld B as shown. It is possible to induce transitions between the energy states by electromagnetic radiation. The condition for inducing transitions between the energy states is that the energy of the radiation (hn) is equal to the energy difference. The condition for an absorption can be written: hn = gbB for electrons and hn = g b B for protons N N The fgure indicates that we can have resonance at any given frequency as long as the magntic feld follows the resonance condition. However, it is a big difference since gb for electrons is much larger than g b for protons. The electromagntic radiation yields transitions in both directions with the same probability. Thus, if the populations of the two levels is equal, the net result would be nil – neither absorption, nor emis- sion. The population of the states follows a Boltzman distribution with the lowest level most popu- lated. In order to have a constant absorption, the difference in population must be kept. It appears that these relaxation times changes when going from normal to pathological tissue – and this can be used in diagnostics. It is therefore easy to understand that it is possible to fulfll the resonance condition for a small volume element.