CORTISONE & NSAID's

Cortisone is one of the most powerful anti-inflammatories that exists. This drug was never designed to treat eczema but is prescribed as a symptomatic relief of the inflammation by "switching off" the immune response causing the eczema. Once it has worn off the eczema returns. Cortisone was never intended to be prescribed for long term use and is not called the "medicine of last resorts" for nothing, as the side effects are horrific and can be fatal.

To understand what cortisone does, you need to understand a little about how the body functions. Simply, your entire body is controlled by different types of hormones called "eicosanoids". An eicosanoid is produced in every cell, unlike other hormones which are controlled by a specific gland. identify and eliminate possible triggers. he function of an eicosonoid is to be excreted by the cell to test the external environment and then report back what was just outside by interacting with the cells receptor on the surface. It then self destructs, and the whole process starts again. With the information the cell has received it can then take appropriate biological action to respond to the change in it's environment. You can now imagine how these hormones play such a vital role in our physiology. Because there is no gland controlling these hormones, nature provided us with a balance of "good" and "bad" so that an even axis was maintained. Most chronic diseases are a consequence of too many "bad" eicosanoids.

So what does cortisone do:
Ask any physician what happens when a high dose of corticosteroid is given to a patient for longer than 30 days. The answer will be physiological devastation, if not death. This occurs because cortisone knocks out all eicosanoid production both good and bad, by inhibiting the release of essential fatty acids from the cell membrane. Without eicosanoids you can't survive.
Long term use of cortisone lowers the response to your immune system, decreases cognitive function, increases fat stores, thins the skin and accelerates osteoporosis. If you give a single injection of corticoseroids to a healthy individual, within 24 hours their lympocytes will show a pattern very similar to that in AIDS patients.

How does topical cortisone affect the skin?
The key structural proteins that give your skin it's firmness and elasticity are called collagen and elastin. These proteins are stimulated by increased blood flow which also provides nutrients to your skins subcutaneous layer. Cortisone inhibits the function of collagen and elastin thereby reducing the blood flow required to provide the optimum amount of nutrients the skin requires. Try imagine that the skin as a fine mesh, which with constant use of cortisone starts to widen further apart. Skin cells are literally starved of nutrients by reduced blood flow and therefore inhibit the regeneration process. Cortisone is not the solution to eczema, if anything it can pose a major threat. [read more below the ads]

Cortisone  (17-hydroxy-11-dehydrocorticosterone) is a steroid hormone. Chemically, it is a corticosteroid closely related to corticosterone.

Production

Cortisone is one of several end products of a process called steroidogenesis. This process starts with cholesterol which then goes through a series of reactions in the adrenal gland to produce a variety of steroid hormones. One end product of this pathway is cortisol, which is then released from the adrenal gland by ACTH signaling from the anterior pituitary, which is stimulated by corticotropin-releasing hormone from the hypothalamus in the brain. In the peripheral tissues cortisol is converted to cortisone by 11-beta-steroid dehydrogenase. Cortisol has much greater glucocorticoid activity than cortisone and thus cortisone can be considered an inactive metabolite of cortisol. However 11-beta-steroid dehydrogenase can catalyze the reverse reaction as well and thus cortisone is also the inactive precursor molecule of the active hormone cortisol. Cortisone is activated through hydroxylation of the 11-keto-group by an enzyme called 11-beta-steroid dehydrogenase. The active form, cortisol, is thus sometimes referred to as hydrocortisone.

Effects and uses

Cortisol and adrenaline are the main hormones released by the body as a reaction to stress. They elevate blood pressure and prepare the body for a fight or flight response.

Cortisone is sometimes used as a drug to treat a variety of ailments. It can be administered intravenously or cutaneously.

One of cortisone's effects on the body, and a potentially harmful side effect when administered clinically, is the suppression of the immune system. This could be the explanation for the apparent correlation between high stress and sickness. The suppresion of the immune system may be important in the treatment of inflammatory conditions such as severe IgE-mediated allergies.

Cortisone is less important than a similar steroid cortisol. Cortisol is responsible for 95% of the effects of the glucocorticosteroids while cortisone is about 4 or 5%. Corticosterone is even less important.

Cortisone shots also may leave "dents" in the injection area, in some cases.

History

Cortisone was first discovered by the American chemist Edward Calvin Kendall. He won the 1950 Nobel Prize for Physiology or Medicine along with Philip S. Hench and Tadeus Reichstein for the discovery of adrenal cortex hormones, their structures, and functions. Cortisone was first produced commercially by Merck & Co. under the leadership of George W. Merck.

More Info

1. Corticosterone is a 21 carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. In many species, including rodents, corticosterone is the principal glucocorticoid, involved in regulation of fuel metabolism, immune reactions, and stress responses.

However, in humans, corticosterone is produced primarily in the zona glomerulosa of the adrenal cortex. It has only weak glucocorticoid and mineralocorticoid potencies in humans and is important mainly as an intermediate in the steroidogenic pathway from pregnenolone to aldosterone.

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2. Steroidogenesis is the process of steroid production in living organisms. The pathways of steroidogenesis can differ from organism to organism, but the pathways of human steroidogenesis are shown below.

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3. Cholesterol is a sterol (a combination steroid and alcohol), a lipid found in the cell membranes of all body tissues, and is transported in the blood plasma of all animals. Because cholesterol is synthesized by all eukaryotes, trace amounts of cholesterol are also found in membranes of plants and fungi.

The name originates from the Greek chole- (bile) and stereos (solid), and the chemical suffix -ol for an alcohol, as researchers first identified cholesterol in solid form in gallstones by François Poulletier de la Salle in 1769. However, it is only in 1815 that chemist Eugène Chevreul named the compound "cholesterine".

Most of the cholesterol is synthesized by the body and some has dietary origin. Cholesterol is more abundant in tissues which either synthesize more or have more abundant densely-packed membranes, for example, the liver, spinal cord, brain, and atheromata (arterial plaques). Cholesterol plays a central role in many biochemical processes, but is best known for the association of cardiovascular disease with various lipoprotein cholesterol transport patterns and high levels of cholesterol in the blood. Cholesterol is insoluble in blood, but is transported in the circulatory system bound to one of the varieties of lipoprotein, spherical particles which have an exterior composed mainly of water-soluble proteins.

In recent years, the term "bad cholesterol" has been used to refer to cholesterol contained in LDL (low-density lipoprotein) which, according to the lipid hypothesis, is thought to have harmful actions, and "good cholesterol" to refer to cholesterol contained in HDL (high-density lipoprotein), thought to have beneficial actions.

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4. In mammals, the adrenal glands (also known as suprarenal glands) are the triangle-shaped endocrine glands that sit on top of the kidneys; their name indicates that position (ad-, "near" or "at" + -renes, "kidneys"). They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines, including cortisol and adrenaline.

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5. Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide hormone produced and secreted by the pituitary gland. It is an important player in the hypothalamic-pituitary-adrenal axis. ACTH synthesised from pro-opiomelanocortin (POMC) and secreted from corticotropes in the anterior lobe of the pituitary gland in response to the hormone corticotropin-releasing hormone (CRH) released by the hypothalamus. It can be also produced by cells of immune system (T cells, B cells and macrophages) as a response to stimuli which go along with stress (including CRH).

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6. The anterior pituitary (also called the adenohypophysis, from Greek adeno, "gland"; hypo, "under"; physis, "growth"; hence, glandular undergrowth) comprises the anterior lobe of the pituitary gland and is part of the endocrine system. Unlike the posterior lobe, the anterior lobe is genuinely glandular, hence the root adeno in its name.  Under the influence of the hypothalamus, the anterior pituitary produces and secretes several peptide hormones that regulate many physiological processes including stress, growth, and reproduction.

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7. Corticotropin-releasing hormone (CRH), originally named corticotropin-releasing factor (CRF), and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response.

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8. The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). The hypothalamus, is located below the thalamus, just above the brain stem. This gland occupies the major portion of the ventral region of the diencephalon. It is found in all mammalian brains, including humans. It is roughly the size of an almond. The hypothalamus regulates certain metabolic processes and other autonomic activities. It synthesizes and secretes neurohormones, often called hypothalamic-releasing hormones, and these in turn stimulate or inhibit the secretion of pituitary hormones. The hypothalamus controls body temperature, hunger, thirst, and circadian cycles.

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9. 11-Beta Hydroxysteroid Dehydrogenase (HSD11B) is the name of a family of enzymes that catalyzes the conversion of inert 11 keto-products (cortisone) to active cortisol, or vice versa, thus regulating the access of glucocorticoids to the steroid receptors.

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10. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger similar effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by the specific receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Cortisol (or hydrocortisone) is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions. Glucocorticoid receptors are found in the cells of almost all vertebrate tissues.

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11. Cortisol is a corticosteroid hormone produced by the adrenal cortex (in the adrenal gland). It is a vital hormone that is often referred to as the "stress hormone" as it is involved in the response to stress. It increases blood pressure, blood sugar levels and has an immunosuppressive action. In pharmacology, the synthetic form of cortisol is referred to as hydrocortisone, and is used to treat allergies and inflammation as well as cortisol production deficiencies. When first introduced as a treatment for rheumatoid arthritis, it was referred to as Compound E.

12. Hydroxylation is any chemical process that introduces one or more hydroxyl groups (-OH) into a compound (or radical) thereby oxidizing it. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases.

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13. Enzymes are proteins that catalyze (i.e. accelerate) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products. Almost all processes in a biological cell need enzymes in order to occur at significant rates. Since enzymes are extremely selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that cell.

Like all catalysts, enzymes work by lowering the activation energy (Ea or ΔG‡) for a reaction, thus dramatically accelerating the rate of the reaction. Most enzyme reaction rates are millions of times faster than those of comparable uncatalyzed reactions. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the equilibrium of these reactions. However, enzymes do differ from most other catalysts by being much more specific. Enzymes are known to catalyze about 4,000 biochemical reactions. Although all enzymes are proteins, not all biochemical catalysts are enzymes, since some RNA molecules called ribozymes also catalyze reactions. Synthetic molecules called artificial enzymes also display enzyme-like catalysis.

Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease enzyme activity; activators are molecules that increase activity. Many drugs and poisons are enzyme inhibitors. Activity is also affected by temperature, chemical environment (e.g. pH), and the concentration of substrate. Some enzymes are used commercially, for example, in the synthesis of antibiotics. In addition, some household products use enzymes to speed up biochemical reactions (e.g., enzymes in biological washing powders break down protein or fat stains on clothes; enzymes in meat tenderizers break down proteins, making the meat easier to chew).

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14. Edward Calvin Kendall (b.8 March 1886, Norwalk, CT – 4 May 1972) was an American chemist who, together with Philip S. Hench and Tadeus Reichstein, won the Nobel Prize for Physiology or Medicine in 1950 for research at the Mayo Clinic on the structure and biological effects of adrenal cortex hormones. He was credited for the discovery of the hormone Cortisone. He earned his B.S., M.A. and Ph.D. from Columbia University in 1908, 1909 and 1910, respectively.

Kendall Elementary School, in Norwalk, is named after him.

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15. Philip Showalter Hench (28 February 1896 – 30 March 1965) was an American physician who, with E. C. Kendall, in 1948 successfully applied an adrenal hormone (later known as cortisone) in the treatment of rheumatoid arthritis at the Mayo Clinic. With Kendall and Tadeus Reichstein of Switzerland, Hench received the Nobel Prize for Physiology or Medicine in 1950 for discoveries concerning hormones of the adrenal cortex, their structure and biological effects.

He was born in Pittsburgh, Pennsylvania and died in Ocho Rios, Jamaica.

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16. Tadeusz Reichstein (20 July 1897 – 1 August 1996) was a Polish-born Swiss Nobel Prize-winning chemist.

He was born into a Jewish family at Włocławek, Poland. After passing his early childhood at Kiev, Ukraine, where his father was an engineer, Reichstein was educated, first at a boarding-school at Jena, Germany.

In 1933, working in Zürich, Switzerland, Reichstein succeeded, independently of Sir Norman Haworth and his collaborators in Britain, in synthesizing vitamin C (ascorbic acid).

Together with E. C. Kendall and P. S. Hench, he was awarded the Nobel Prize in Physiology or Medicine in 1950 for their work on hormones of the adrenal cortex which culminated in the isolation of cortisone.

He died in Basel, Switzerland. The principal industrial process for the artificial synthesis of Vitamin C still bears his name.

Reichstein was the oldest living Nobel laureate and is the oldest Nobel laureate ever.

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17. Merck & Co., Inc., also known as Merck Sharp & Dohme or MSD outside the USA and Canada, is one of the largest pharmaceutical companies in the world. The HQ of this huge company is located in Readington, NJ It was established in 1891 as the United States subsidiary of the German company now known as Merck KGaA. In common with many other German assets in the United States, Merck & Co. was confiscated in 1917 during World War I and set up as an independent company. It is currently one of the top 7 largest pharmaceutical companies in the world both by capital and revenue.

Merck & Co. or MSD describes itself as a “a global research-driven pharmaceutical company. Merck discovers, develops, manufactures and markets a broad range of innovative products to improve human and animal health, directly and through its joint ventures.” The Merck Company Foundation has distributed over $160 million to educational and non-profit organizations since it was founded in 1957.[citation needed]

Merck publishes the Merck Manual of Diagnosis and Therapy and the Merck Index, a collection of information about chemical compounds.

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18. George W. Merck (1894 - 1957), the son of George Merck, was an American scientist and president of Merck & Co.. Raised in Llewellyn Park, New Jersey, he attended Harvard College, graduating in 1915. World War I prevented him from pursuing an advanced degree in Germany; instead, he joined his father at the company. He was made president of the company in 1925, shortly before his father's death. During the interwar years, he oversaw Merck's involvement in the development of synthetic vitamins, sulfas, antibiotics, and hormones. During World War II, he led the secret American research program in germ weapons at Fort Detrick, and helped insure continuation of germ research into the Cold War era. Merck was on the cover of Time Magazine on August 18, 1952, illustrating a story about the American drug industry.

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