Assignment 1 Example | Topics and Well Written Essays - 250 words - 14

1 - Assignment Example Such confusion happens because speech sounds and meanings relate in an arbitrary manner. In other words, there is no rational and logical relationship between speech sounds and meanings. The Portuguese model can best illustrate language arbitrariness. Similarity in words should not be an issue, and neither should the words be understandable to a foreigner. However, the tribesmen need to understand what words mean. The Portuguese words tigre-dente-de-sabre mean a sabre toothed tiger. These words are the signifier. Suppose one was to go back 40 years and ask a Portuguese where to find a tiger with a sabre tooth, he or she would have no idea about it. The reason is that there is no connection between the words and the animal in question. Maybe one would wonder how the words are signified or related to the animal. According to Tomasello, every sign is arbitrary and has conventional associations, which have been established by a social rule (Tomasello 87). At first, one could argue that the statement is completely flawed, especially when onomatopoeic words are concerned. However, when one looks gives a detailed look at specific languages, one will notice certain differences. For instance, cock-a-doodle-doo is the English representation of a cock’s crowing whereas cocorico is the French version of the same. It is unlikely that cocks in Britain and France crow differently. In conclusion, all languages are arbitrary but it does not mean they are unpredictable. Precisely, arbitrariness means that one cannot exactly predict specific features that can be found in a language. It is impossible to predict what sounds will occur. Languages have their systems that differentiate sounds and meanings. Not every new concept necessitates the creation of a new word. The wing of a plane, for instance, was lifted from the wing of a bird. Moreover, a banker and a baker sound almost the same

Training & Development Essay Example | Topics and Well Written Essays - 3000 words

Training & Development - Essay Example Consequently, there is a need to ensure that the company remains ahead of the competition. Management realised that there is no better way to achieve this rather than through the use of training and development. (Paisley, 1999) Policies at M&S will be measured against the backdrop of ‘best practise’ models. The model is based upon the belief that when organisations adopt certain human resource strategies, they are able to make their employees highly motivated. As a result, those employees will become more efficient and they will help in the realisation of competitive advantage within the organisation. Best practice applies to various sectors that include retention of employees, performance improvement, enhancing and promoting training and development, enhancing corporate culture, enforcing organisational structure and also in the determination of pay costs. However, for purposes of this report, we shall mainly focus on training and development. The Research primarily focuses on the use of secondary sources of data. This is because secondary data gives an overall picture of the situation at Marks and Spencer. It allows one to obtain all the relevant information to the research question and compile them to come up with new answers. If primary sources like interviews had been used, it would have been difficult to see the overall picture as results are mostly person centred. (Schutt, 2006) Secondary data allows comparisons between different elements of the research that would otherwise have been too complex to collect using primary sources. Consequently, there are very accurate results that come out of the usage of such a source of data. (Banta, 2007) However, one must not under look the disadvantages of this method of data collection. First of all, it does not allow the progression from developing a research question, collecting data and formulating a hypothesis

Classification of Milk Essay Example for Free

Classification of Milk Essay Milk is important for both children and adults because it is a source of minerals, calcium, protein and phosphorus. Currently, there are different kinds of milk products in the market. Here are some types of milk based on the manufacturing process: -UHT Liquid Milk UHT is stands for Ultra High Temperature Processing or Ultra Heat Treatment. It is a way to sterilize food through to high heat process about 24 seconds at 135-140 degrees Celsius which the spores of milk is destroyed completely in that temperature. The high temperature pasteurization processes was first discovered in the 1960s by used with the milk know as UHT milk. UHT milk can be stored at room temperature for 6-10 months compared with pasteurized milk. UHT milk free of preservatives because the package is made in six layers to keep the milk remains in a sterile condition within a specified period without other chemicals. -Milk Pasteurization Pasteurized milk is raw milk that passed through the heat of not less than 60 Celsius for at least 30 minutes or uses the heat of not less than 73 degrees Celsius for 15 seconds. Pasteurized milk is only lasted for 14 days if not stored in the refrigerator with a temperature of 5-7 degrees Celsius. Pasteurized milk has fresh taste and features as the natural milk. -Milk Sterilization The milk will be sterilized by high heat at 120 degrees Celsius for 15 minutes and caused the whole bacteria die but the spores will still be growing. The sterilized milk is not suitable for children because some nutrients like Vitamin B1, Vitamin B2 and Vitamin C disappear during the heating process. The sterilized milk is usually packed in sealed metal cans so it can be kept up to 1-2 years and should be stored in the refrigerator after you open it to maintain the quality of milk. -Sweetened Condensed Milk 80 degrees Celsius warming conducted over three hours. It is condensed milk from which water has been removed and to which sugar has been added. It can last for year without refrigeration if unopened. Sweetened Condensed Milk is used for cooking rather than drinking. And it contains very high sugar so it should not to use to feed the baby. -Milk Powder It is a manufactured dairy product made by evaporating milk to dryness with a spray dryer or roller dryer is 200 degrees Celsius for two hours. The purpose of drying milk is to preserve it. It can be kept longer than the liquid milk and does not need to be refrigerated. Milk has been one of the most widely consumed foods since a long time. However, it may not be benefiting us much, or may even be harming us. This paper of the advantages and disadvantages of milk can help you decide what kind of milk is the best for yourself and your family. Reference Admin (JUNE 6, 2011),Various Types of Milk : Based on The Manufacturing Process. Retrieved November,17 ,2011 from http://gorgeoushealthyme. com/various-types-of-milk-based-on-the-manufacturing-process/.

Cyclo-oxygenase inhibitors of human diseases

Cyclo-oxygenase inhibitors of human diseases Historical background Cyclooxygenase (COX) inhibitors are a widely prescribed group of antipyretics and analgesics worldwide and are important component in the treatment of inflammatory conditions. Although first COX inhibitor was discovered more than a decade ago their origin dates back to ancient Mediterranean descent1. Back and other body pains where treated using extracts of poplar tree bark and leaves of myrtle. Use of willow bark emerged far more lately and its first appearance was reported in England in 17631. As was later discovered, the essence of the willow bark possessing anti-inflammatory and antipyretic properties was salicin. Further modification of its structural properties allowed generation of salicylic acid that eventually was developed via Kolbe reaction using phenol1,3. In 1899 Bayer company went ahead in synthesising more susceptible derivative of it, acetylsalicylic acid and named it aspirin. Following this phenylbutazone (1949) and indomethacin (1963) came along however the mystery of mechanism of their action in the body was not yet developed. It was not known until 8 years later when an idea surrounding the synthesis of prostaglandins within body was revealed and for which a Nobel Prize in physiology and medicine was awarded (1982)1. It was proposed that first non-steroidal anti-inflammatory drug (NSAID), aspirin, acted upon inhibition of an enzyme that played role in utilising unsaturated fatty acids into biochemical molecules exerting their action in conditions such as inflammation, pain, and fever and platelet synthesis. It was accepted that during changes occurring within stimulated cells and tissues prostaglandins synthesis was taking place 1,3. Structure of COX was isolated in 1976 and its second isoform was confirmed around 14 years later by few different laboratory investigations; investigations which greatly allowed appreciating the nature of first nonselective cox inhibitors NSAIDs in the treatment of human diseases1. 1.1 The pharmacology and chemistry of cyclooxygenase enzyme Cyclooxygenase (COX aka PGG2/H2 synthase) belongs to the family of enzymes known as myeloperoxidases and it is the crucial enzyme in the synthesis of prostaglandins, prostacyclin and tromboxane A2 resullting from the conversion of arachidonic acid (AA) 2,4. This heme-containing COX enzyme is a bifunctional biocatalyst with two interconnected active sites: cyclooxygenase and peroxidase which action involves generation of hydroperoxy endoperoxide PGG2 via cyclooxygenase cycle (Fig.1.) into its reduced form of hydroxy endoperoxide (PGH2) (Fig. 2.) 2,4. Both isoforms of COX enzyme are expressed in endothelial, monocytic and renal cells with COX-2 being more profound in inflammatory and cancer tissues. Both enzymes are characterised by signal peptide, endothelium growth like factor (EGF) region, membrane in-bound domain, catalytic part, interface between monomers and N-linked polysaccharides residues2. The signal peptide in COX-1 consists of 23 residues whereas COX-2 has only 17. The EGF like region constitutes a major part of the interface and is not found in other myeloperoxidases. It is involved in Cys-Cys cross linked bridges with lack of Cys9 in COX-1 and Cys512 in COX-2. The membrane in-bound domain accounts for 33% of overall similarity and 24% of identity within membranous face. This domain is described as consisting of 4 amphipathic a helices that surround the entry to the COX site. The catalytic part is known to be the largest part of the enzyme with remained homology between other myeloperoxidases. 180Â ° rotation between subunits is preserved with chemical interaction between polar, ionic and hydrophobic moieties. Differences in residue positioning prevent heterodimerization and dissociation from facial interaction inactivates the enzymes overall catalytic activity 1,2,3,4,5. Figure 1. Mechanism of COX cycle in cyclooxygenase active site showing free radicals formation denoted by ? prior to PGH2 synthesis in POX pathway (not shown) 2. Attraction of hydrogen atom from Tyr385 by peroxyl radical of PGG2 allows for the regeneration of the steps of the reaction in the COX cycle of prostanoid biosynthesis. The coloured boxes are to indicate the origin of oxygen atoms. PLA2 phospholipase A2, S secretory, C cytoplasmic. Figure 2. A diagram summarising changes made to AA in the distinct active sites of the PGG2/H2 synthase and products formed via action of each catalytic active site 2. 1.2 The nature of cyclooxygenase inhibition in the human body Inhibition of cyclooxygenase action is desired in the treatment of human diseases. Not only because it suppresses the inflammatory production of prostaglandins in the conditions such as: dysmenorrhoea, rheumatoid arthritis, osteoarthritis but also because it prevents platelet aggregation, suppresses tumour growth and prevents cancer5. Until 1994 it was not clear by which mode, mechanism or process inhibition of COX was carried out. Just complexation studies between COX and flurbiprofen allowed insight into molecular basis of COX inhibition. The investigation led by Garavito and his colleagues proposed such model of inhibition. In his model it was suggested that the enzyme in question possesses long hydrophobic path that originates from in-membrane bound moiety up to the heart of the dimer subunit. Blocking this channel stops the endogenous substrate (AA) from binding hence possible intervention in the process of prostaglandins biosynthesis5. 1.3 The types of cyclooxygenase inhibitors in the treatment of human diseases There are several types of COX inhibitors available in the treatment of human diseases. The very first one, aspirin, is known to act through non-selective and irreversible manner. As this manner suggests aspirin binds to both types of COX enzyme by acetylating Ser530 residue upon covalent modification. Consequently effects such as risk of excessive bleeding, ulcer formation or foetal deformation limit the use of aspirin in dealing with long term diseases. Nowadays it is mainly considered as the important component in the treatment of cardiovascular conditions due to its anti-platelet activity 1,3. Other types of non-selective NSAIDs such as piroxicam, ibuprofen or diclofenac, constitute majority of therapeutic agents being prescribed however due to harmful effects they are being considered less effective in the long term treatment. The damage to the gastrointestinal (GI) system is due to inhibition of COX-1 expressed in GI mucosa which results in formation of ulcers with associated bleeding. Therefore since the main target for choosing those drugs is found to be of inflammatory nature (inhibition of COX-2) they are nowadays preferred in topical dosage forms 1,3,5. The consequence of the undesired effects caused by non-selective COX inhibitors targeted new approach towards development of more specifically acting agents. The era began on discovery of the second isoform of cyclooxygenase and introduction of first COX-2 selective agent (1999) was introduced to the market within 10 years since its discovery with celecoxib and rofecoxib for the treatment of arthritis. The discovery proposed mechanism of actions of both enzymes within the body with COX-1 possessing more constitutive effects especially in GI tract. It was therefore suggested that COX-2 was an inducible form in conditions such as inflammation and pain, symptoms desired in treatment of human diseases associated with the effects of COX-2 isozyme 1,3. 2. ASPIRIN THE ORIGINAL COX INHIBITOR (Joyce) 2.1. Pharmacology and chemistry of Aspirin Plant ingredient salicin was discovered in the willow bark and leaves in the 17th century by a greek physician (Hippocrates) who prescribed it as an analgesic and antipyretic. Further into the 17th century a crude form of salicylic acid was made by a German scientist (Charles Frederic von Gerhardt). This was followed by production of a purer form of salicylic acid by another German chemist (Karl Johann Kraut). Finally in 1897 a German chemist Felix Hoffmann, who worked for the pharmaceutical company Bayer, was assigned the task to find a better derivative of salicylic acid. He also had his own personal reasons for wanting to find a better derivative. His father had been taking salicylic acid for his arthritis pain but could no longer take it without vomiting3,7. In 1889 Hoff man then found a way of acetylating the hydroxyl group on the benzene ring of salicylic acid to form acetylsalicylic acid. Hoffman father tried the new derivative and it was pronounced effective. The name ‘ASPIRIN was given to the drug by Bayer chief pharmacologist Henrich Dreser7. Aspirin was found to have antipyretic, analgesic and anti-inflammatory effects. It does this by inhibiting cyclo-oxygenase(COX) or prostaglandin endoperoxide synthase(PGHS) enzyme irreversibly. COX is responsible for cyclizing arachidonic acid and adds the 15-hydroperoxy group to form PGG2 which is the precursor to prostaglandins. An enzyme perioxidase is responsible for reducing the hydroperoxy group of PGG2 to the hydroxyl group of PGH2.(4)(See Figure 15- prostaglandins synthesis) Prostaglandins can be described as chemical mediators that produce a variety of strong physiological effects in the body. Most importantly they are responsible for the activation of the inflammatory response, production of pain, and fever. There are three isoforms of the COX enzyme of which aspirin has an effect on two which are COX-1 and COX-2. Aspirin binds covalently modifiying COX-1 through acetylation of its Ser-530 and COX-2 through acetylation of its serine 516 residue by placing a bulky constituent (acetyl) and this directly inhibits binding of arachidonic acid. Aspirins action is more potent against COX-1 than against COX-2. This difference in inhibition of the two COX enzymes by aspirin is due to the larger volume of the COX-2 active site produced by the Val-523 substitution at the side pocket. (1,7, 9) The difference in the size of the active site has been exploited by pharmaceutical companies to develop selective COX-2 inhibitors (section 4) COX-1 is an essential enzyme expressed in majority of tissues and also in platelets. It is responsible for prostaglandin production involved in homeostatic mechanisms e.g. platelet aggregation, gastric wall protection, regulation of renal blood flow and initiation of labour in childbirth. In contrast, COX-2, is an inducible form which becomes up regulated by inflammatory mediators such as cytokine (Interleukin and tumour necrosis factor). 2.2 The problems associated with aspirin(1, 10) a. Unwanted effects GASTRIC PROBLEMS The inhibition of COX 1 can produce gastric disturbances as an unwanted effect because the prostaglandin production in the GI tract is a homeostatic mechanism to protect the gastric mucosa. It causes inherent symptoms like heartburn; dyspepsia, nausea, and abdominal pain. (1, 10)This effect can cause Aspirin users to change or discontinue its use. Some of these inherent symptoms are quite common for most NSAIDs. Secondly it can also causes gastro duodenal mucosal lesions such as erosions and asymptomatic ulcers, which may or may not heal spontaneously; and finally more serious gastro ulcers with life-threatening complications like perforation, symptomatic ulcers, and bleeding ulcers. Symptoms of this could be black, bloody, or tar like stools or vomiting/coughing up blood REYES SYNDROME Reyes syndrome is a collection of symptoms consisting of altered consciousness, convulsions, low blood glucose, and enlargement of the liver associated with fatty infiltration of the liver. It is a deadly disease, which can strike any child, teenager, or adult without warning. All body organs are normally affected, but the liver and brain are antagonised the most. In 1965 it was stipulated that Reyess syndrome can be caused by the administration of aspirin in children under 16years of age. There is no discovered mechanism for the role of salicylate in this but it is thought that aspirin enhances the release of tumour necrosis factor which induces apoptosis of cells which can cause inflammation, viral replication e.t.c. SALICYLISM This is caused by the excessive ingestion of aspirin. There are two main pathways in the metabolism of aspirin. (10)Phase 1 reaction that involves the oxidation of aspirin to salicylic acid by a cytochrome P450 monooxygenase. By addition of a reactive group (OH) to get it ready for conjugation to a soluble component and hence aid excretion. This conjugation involves the attachment of small polar molecules glycine and gluconoride to salicylic acid. This results in further deactivation of the aspirin and the production of water-soluble metabolites that will be readily excreted in the urine or bile. The pathway conjugated with glycine, is the one that is easily overloaded in cases of toxicity. Thus elimination of salicylic acid slows down and accumulation leads to a variety of side effects. Below are the pathways showing oxidation and conjugation. This excess salicylate produces toxic effects include below. Ringing in ears Hyperventilation which causes increase in CO2- respiratory alkalosis, Dehydration: increased water loss due to hyperventilation Loss of carbonic acid metabolic acidosis. This in turn will reduce the blood pH, and make aspirin return to its non-ionised form allowing free aspirin in the blood stream. Hyperthermia. These pathways overload uncouples the energy producing processes (oxidative phosphorylation) of the mitochondria thus causing production of heat rather than ATP. Fatality especially in children Interactions with other drugs Reduced effect of aspirin if given with ibuprofen and avoid concomitant use of aspirin with NSAIDS due to increased side effects. Increase risk of bleeding when aspirin is given with coumarins, SSRIs, clopidogrel, illoprost, and sibutramine, Aspirin enhances effect of Heparins, Phenytoin, Valporate, Aspirin antagonises effect of Spirolactone, Sulfinpyrazone and Probenacid Rate of excretion of aspirin is increases by some antacids. The effect of aspirin on the gastrointestinal tract may be enhanced by the intake of alcohol and corticosteroids. 3. NON STEROIDAL ANTINFLAMMATORY DRUGS NON SELECTIVE COX INHIBITORS (Christina) 3.1 Isozymes of Cyclooxygenase Cyclooxygenase has various isozymes. The main isozymes are COX-1 and COX-2, however there is now evidence of a third form- COX-3. COX, originally known as prostaglandin H synthase is responsible for the oxidation of arachadonic acid to prostaglandin G2 and prostaglandin H2. It catalyses the reaction in which the arachadonic acid substrate and two molecules of O2 are converted to prostaglandin G2 and then in the perioxidase reaction Prostaglandin G2 is reduced to PGH2 by a 2 electron reduction. The COX isozymes are heme containing enzymes that are homodimers. Each monomer contains three main domains; A membrane binding domain, a N-terminal epidermal growth factor domain and a C-terminal catalytic domain. COX-1 is made up of 602 amino acids while COX-2 is comprised of 604.3 The catalytic reaction in COX takes place in a hydrophobic channel in the core of the enzyme while the peroxidise reaction takes place in the heme containing region near the surface of the enzyme. The membrane binding domain consists of four alpha helices with one helix that fuses with the catalytic domain. These helices congregate around an opening and through these openings fatty acids and NSAIDS are considered to enter the active site. The COX-1 isozyme is considered a constitutive enzyme. It is present in high volumes in most cells and tissues i.e. renal collecting tubules, monocytes, endothelium etc. However COX-2 is hardly noticeable in most cells, it is an inducible enzyme so it becomes more abundant in cells or tissues when macrophages are activated or by any other inflammation mediators e.g. TNF-a (tumor necrosis factor-alpha) or IL-1 (interleukin-1).5 Both COX-1 and COX-2 isozymes are attatched to the endoplasmic reticulum and nuclear envelope. The COX isozymes need to be N-linked glycosylated to enable them to be folded and attatched to the endoplasmic reticulum and nuclear envelope. The COX isozymes have very similar structures for their binding site, catalytic mechanisms and produce the same biosynthetic products3 COX-3 COX-3 a third isozyme was discovered in 2002 by Simmons and co-workers. They conducted a study on dogs and this resulted in them discovering a novel COX-1 splice variant termed COX-3 that was sensitive to acetaminophen (paracetamol). It was suspected for a while that acetaminophen worked by inhibiting a different specific isozyme due to the fact that it did not directly inhibit COX-1 and COX-2 very effectively at therapeutic concentrations but it generated prostanoids in neuronal systems. 3, 15 The Simmons and co-worker group showed that acetaminophen was the actual target for COX-3, and that it acted separately from COX-1 and COX-2. 3 Canine COX-3 is a membrane bound protein consisting of 613 amino acids with a molecular weight of ~65 kDa. It has a high expression in cells and tissues like COX-1 suggesting it may be a constitutive enzyme. However the question that needs to be asked is if generalisations can truly be made on the presence of COX-3 in humans based on Canine studies, so future experiments need to be designed to clarify whether a human COX-3 actually does exist that acts independently from COX-1 and COX-2 in vivo. 14 NSAIDs are known to inhibit COX in order for them to exhibit their anti-inflammatory actions, a structural NSAID binding study was carried out. The COX-1 active site contains a long hydrophobic channel that extends from the membrane binding domain to the core of the COX monomer. The tip of the COX active site houses Tyr385 that is located near the heme iron. Ser530 is positioned just below Tyr385 and that is the site for aspirin acetylation. Glu524 and Arg120 are positioned at the mouth of the COX-1 channel. A typical NSAID such as fluobriprofen, when introduced to the COX enzyme, its carboxylate moiety is usually directed towards the mouth of the COX-1 channel in order for it to be positioned in the most ideal place that will allow it to interact with the two polar residues Glu524 and Arg120. From these studies a better insight into the binding profiles of NSAIDs were observed. Non selective NSAIDs can bind in three different ways: Reversibly (e.g. Ibuprofen) Fast, low affinity reversible binding followed by a higher affinity, time dependant slowly reversible binding (e.g. fluobriprofen) Rapid, reversible binding followed by a covalent modification of the enzyme (e.g. Aspirin) 3 Arg120, Glu524, Tyr355 and His90 form a network of hydrogen bonds at the entrance of the COX channel acting like a gate to the binding site. NSAIDs generally bind between the upper portion of the COX channel near Tyr 385 and Arg 120 which is at the mouth of the COX channel. 3 Through the use of hydrogen bonding and electrostatic interactions, the carboxyl moiety of acidic NSAIDs like fluoribiprofen interact with Arg120 in both COX isozymes. The significant differences in the structure of the binding sites for both COX isozymes has been manipulated to enable the design of selective COX-2 inhibitors. In the COX-2 active site there is an extra accessible pocket due to the presence of a smaller valine amino acid residue at position 523 and a valine substitution at position 434, unlike COX-1, this difference increases the overall volume at the COX-2 active site by about 20%. 1 This means that due to reduced steric and ionic crowding at the mouth of the channel by Arg120, non acidic selective COX-2 inhibitors can show an enhanced and specific binding to the COX-2 enzyme. Another structural difference exists at the amino acid residue 513 where COX-1 has a histidine residue and COX-2 has an arginine moiety. 1 These small differences provides flexibility in the substrates that can be utilised in the COX-2 active site. 3.2 Problems Associated With Non Selective Non Steroidal Anti-Inflammatory Drugs NSAIDs are one group of drugs that are regularly used by the worlds population to relieve pain, reduce inflammation and lower temperature. They are COX inhibitors and act to inhibit the catalysation of arachadonic acid to PGH2. COX-1 is constitutively present in most cells while COX-2 is induced by chemical mediators of inflammation and activated macrophages.13 COX-1 and COX-2 as mentioned above have 2 specific roles. The 1st role gives PGG2 and the other role is in the peroxidise reaction that gives PGH2. Both COX-1 and COX-2 inhibitors work by inhibiting the 1st and main role i.e. inhibiting the conversion of arachadonic acid to PGG2. COX-1 and COX-2 possesses hydrophobic channels within their core. The classical NSAIDs exhibit their effects by blocking these enzymes halfway down the COX channel near Tyr385 and the Arg120 which is at the mouth of the COX channel by hydrogen bonding to the Arg120 residue. This results in the prohibition of any fatty acid substrates from entering the catalytic domain of the COX enzyme.3 In COX-1, these drugs tend to inhibit the enzyme quickly yet generally the inhibition is often reversible, however in COX-2 the inhibition is time dependant and often results in irreversible inhibition. As mentioned before, the COX-1 and COX-2 isozyme differ slightly. In the COX-2 active site there is an extra accessible side pocket due to the presence of a smaller valine amino acid residue at position 523 instead of isoleucin as in COX-1. This is important for understanding why some NSAIDs are selective for the COX-2 isozyme.13 There are a number of side effects associated with traditional NSAID therapy. NSAIDs can cause renal failure, liver damage/disorders, aseptic meningitis, skin reactions and bone marrow disturbances which can interfere with bone fracture healing. However amongst them all gastrointestinal (GI) toxicities is amongst the most common. These are believed to arise from the inhibition of COX-1 in the gastric mucosa.14 GI toxicities In humans and other species it has been shown that COX-1 not COX-2 is constitutively expressed throughout the GI tract.13 COX-1 is responsible for the synthesis of prostaglandins like PGE2 and PGI2 which are responsible for protecting the GI mucosa by reducing acid secretion in the stomach by the parietal cells, increasing blood flow in the mucosa and stimulating the release of viscous mucous. This leads to conditions of ulcers, dyspepsia, diarrhoea, nausea and vomiting and can even lead to gastric bleeding in some cases. These undesirable side effects have led to the development of COX-2 selective inhibitors. These drugs are effective anti-inflammatorys and reflect good analgesic effects. They have considerable less gastric damage due to the fact they selectively inhibit COX-2 with minimal action on COX-1. Unfortunately the use of COX-2 selective drugs has been associated with increased incidence of myocardial infarction and stroke.3 Renal effects Prostaglandins especially PGE2 and PGI2 are involved in regulating renal blood flow and vascular tone. Recent studies have shown that COX-2 is constitutively expressed in the macula densa, epithelia cells lining the ascending loop of henle and medullary interstitial cells of the renal papillae, while COX-1 is constitutively expressed in the collecting ducts, loop of henle and in the vasculature. The COX-2 enzyme is associated with normal renal function and inhibition of COX-2 results in NSAID-induced sodium retention while inhibition of COX-1 results in a disease in glomerular filtration rate.3 This conclusively tells us that both COX-1 and COX-2 are involved in the physiology of the kidneys. However therapeutic doses in patients with normal renal function are at little risk of renal complications. It is mostly neonates and the elderly who are more susceptible as well as patients with heart, liver or kidney disease. 4. SELECTIVE COX 2 INHIBITORS (Nadine) 4.1 Reasoning behind selective inhibition 4.2 Benefits and risks 5. MECHANISM OF ACTION OF COX INHIBITORS IN HUMAN DISEASES 5.1 Analgesic (Joyce) Pain can be defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a self protection mechanism which helps of forces us to identify danger and move away from it. It is one of the main symptoms used to identify a condition in medicine. Removing pain is very essential in terms of either eliminating the disease or condition or in fact suppressing its effect. This can be done by the use of medicines called analgesics. Pain receptors also called nociceptors are present on special nerve fibres that are sensitive to noxious of harmless stimuli. The stimulation of these receptors are on A-delta and C-fibers which are located in skin, connective tissue, viscera, muscle e.t.c. COX inhibitors act by blocking transmission to peripheral nerves. Pain associated with I. Arthritis Arthritis is the inflammation of joints. The inflammation and movement of the joints cause extreme pain in the sufferer. There are two major types a. Osteoarthritis(10) This is a chronic disease that features the breakdown of the joints cartilage. Cartilage is flexible connective tissue found in between joints that cushions or protects the ends of the bones and allows easy mobility of joints. This breakdown of cartilage causes the bones to rub against each other creating friction, causing joint tension, pain and loss of mobility in the joint. There are different types of arthritis of which osteoarthritis is most common; it can also be referred to a degenerative joint disease. There are two types of osteoarthritis, primary of which is associated with old age, general wear and tear of the cartilage. And secondary where it occurs where there is a cause example obesity, trauma, or hereditary. Treatment: Paracetamol may be considered as first line therapy for Osteoarthritis patients with mild to moderate pain. If the pain does not respond to paracetamol or patient has severe symptoms then other traditional NSAIDs like Ibuprofen, diclofenac or coxibs should be used. Coxibs have shown to produce reduced GI side effects. However they have the probability of increasing cardiovascular risk because they inhibit prostacyclin production in endothelial cells but not thromboxane in platelets, hence this can increase the chance of a thrombus formation. The choice of a coxib or a specific NSAID should be based on the patient characteristics and risk factors. b. Rheumatoid arthritis(12 ) This is an autoimmune disease of unknown origin whose major characteristic is the inflammation and erosion of the synovial membrane or synovium. This membrane lines and surrounds the joint and synovial cavity. The synovium secretes a slightly viscous, clear fluid known as synovial fluid, which lubricates cavity that lies between the cartilage and joint on the bone. In Rheumatoid arthritis accumulation of the synovial fluid builds up within the joint space and causes inflammation. This makes the joint look and feel swollen. Rubor occurs do to the increased blood flow to the area because of inflammation. In conditions of long-term RA, joint degeneration can occur causing mobility to be very painful and restricted. Treatment: Aspirin used to be used to treat RA but because of its GI toxicity. The use of aspirin as first line of therapy has been superceded by other NSAIDs. There are a large number of NSAIDs that have been invented since aspirin, but have similarities in toxicities e.g. Ibuprofen, naproxen meloxicam, etodolac selective COX-2 inhibitors have been invented to control inflammation. These drugs were designed to combat the gastrointestinal risk of NSAIDS, but there are concerns of increases in cardiovascular risk. II. Cancer (11) Can be defined as an abnormal growth of cells as when a group ofcellsdisplayuncontrolled division,invasion, and sometimesmetastasis. Cells become cancer cells because of its damaging effect to the DNA of the cell. A normal cell will try to repair damaged DNA but in a cancer cell it replicates with the damaged DNA. The cancer cell continues making new cells that the body does not require. The most common cause of cancer pain is infiltration of the tumour into bone. Bone metastases occur as a consequence of different types of cancer. Another mechanism of pain apart from bone metastasis is the secretion of Prostaglandins by carcinomas. For this reason, NSAIDs should be included in any regimen to control pain associated with bone metastasis. Because NSAIDs do not activate opioid receptors, they can provide additional pain relief when combined with an opioid analgesic. Thus, combining an NSAID with an opioid analgesic may provide adequate pain control with a clinically significant reduction in opioid dose. This opioid-sparing effect of NSAID therapy allows the clinician to diminish the side effects associated with opioid therapy without sacrificing pain control. Coxibs: Another Option for Cancer Pain Management(11) The recent introduction of the coxibs, on their use in cancer patients is still being studied. Oncologists are replacing NSAIDs, with the use of coxib, because of the improved safety profile compared to traditional agents. Surgical oncologists are exploring the use of coxibs both preoperatively and during the post-operative period to reduce opioid usage in order to speed the recovery process 5.2 Anti-pyretic (Nadine) 5.3 Anti-inflammatory (Christina) To date there are over 100 inflammatory diseases- each of which causes the degeneration of connective tissue in one or more parts of the body. These include: Rheumatoid Arthritis Osteoarthritis Atherosclerosis Irritable Bowel Disease Alzheimers and many more. Inflammation is characterised by dolor, rubor, calor and tubor, its one of the bodys ways of responding to harmful stimuli, pathogens, injury or disease. These usually initiate an acute or chronic inflammatory response. Arthritis is a general term used to characterise inflammation in the joints. Rheumatoid arthritis describes arthritis that occurs on both sides of the body i.e symmetrical. These usually occur in the wrists, hands and knees. It is not known what causes this disease many theories have been put forward but it happens when the immune system begins to attack the joints. A number of anti-inflammatory drugs are available worldwide and are widely used to relieve pain, swelling and inflammation associated with soft tissue inflammation. A number of these drugs act via the inhibition of COX. When you experience pain and inflammation from arthritis, an increase in microvascular permeability occurs selectively in post-capillary venules. The endothelial cells undergo conformational change leading to vascular leakage through gaps between the adjacent endothelial cells. At the site of injury phagocytes are attracted and move into the affected tissue along with plasma. The plasma causes the associated swelling observed in inflammation and the phagocytes engulf dead cells and bacteria. Prostanoic acids are

Physics of the Human Body in Earths Gravitational Field :: physics human gravity

No Conclusion The force of gravity affects all "bodies" in the universe. How well each human falls into the imaginary line of gravity determines the energy they must have to expel to live within this force. The ideal axis for obtaining the greatest balance is one that is a strait line through the center mass of the body. This line should be identical to the one between the gravitational force between the body and the earth. The human body has adapted over many generations and there are markers that will show where a strait line should form to be properly aligned. This imaginary line connects points at the top of the head, middle of the ear, middle of the shoulder, midpoint of the hip joint, center of the knee joint, and center of the ankle joint. Finding the angles that this line forms from unevenness will explain some things about the amount of energy and mobility this person spends to stay upright. If a person is not consciously holding their muscles to stay up, they must have chronic tension in their muscles to even themselves out. Over time this tension has been programmed into their brain and the connective tissue has been bundled up to help hold the tension. This tension has most definitely limited mobility of the antagonist muscles because they must now use extra force to move. These tensions are most likely formed from the overall function of the individual. For example, if a person is a shot-putter they will build up connective tissue to reinforce themselves from the large amount of torque placed on their bodies outside of their Center of Mass. Over time, their body will adapt to resist the forces its put on it but outside of shot-put, those tensions will remain as part of the person. Eventually, the chronic torque t hat the tensions of the muscles put on the body will deform the lines of symmetry and be detrimental to the person. When people lift weights, it is almost impossible to isolate the lifting to a specific muscle due to the body's make up and connections in the brain. Phisiologicly, there are limitations to each muscle. When an isolated lift is attempted and one muscle can't do the job and more are called in that might not act directly on the lift but help in some way, it is called recruitment. Recruitment generally involves using more superficcial muscles than inferior ones and will result in a greater torque beacuse of this.

A Career as a Public Health Specialist Essay -- Occupational Issues

There is no doubt with the advances in technology that, as a population, we are continuing to live longer; yet with the cost of medical care constantly on the raise, is it any wonder an industry would develop out of the concept of â€Å"preventative† maintenance? We are after all, all too aware of this concept; from large corporations who strive to maintain their expensive equipment in an attempt to secure the bottom line, to the local neighbor who would rather afford the costs of preventative maintenance over the expense of replacing a broken down vehicle. To that effect, automobile manufacturers have even begun to include major necessary â€Å"preventative maintenance† items in their â€Å"owner’s manuals.† For instance, I have to replace my timing belt and water pump every 75k miles in my Nissan. Interestingly enough, while we were focused on maintaining everything else around us, somehow we forgot to consider our most valuable complex asset, our bo dies. How is it that the maintenance of a human health and its performance somehow got left over looked and left to fall through the cracks? The need for public health specialists†¦ Until till recent years the thought of humans not only living well in to their 80’s and 90’s, but living vibrant lives was concept that did not appear to go hand-n-hand. However, today the thought is not only real but, the concept and relevance of â€Å"quality of life,† both before and well into the twilight years, is more important than ever before thus making the demand for, and need, of educators and health advocacy even greater. So, what is public health†¦? The concept of public health is not a foreign one; it ultimately emerged from the practice of heroic medicine. Yet today it has evolved into something ... ... us, knowingly or unknowingly, at greater risk that can and possibly will lead us to a dark place. If this trend is allowed to continue or, perhaps revelation through education suffices and people start making their health a priority, one thing is for sure, either way, the future of the public health professional is not only bright but it will only continue to get brighter. Sources: 1. www.whatispublichealth.org/what/index.html; Title: What is Public Health 2. www.healthstate.mn.us/pathways/specialtyareas.html ; Title: Public Health Career Specialty Areas; Sub-Specialties of Public Health 3. www.whatispublichealth.org/faqs/index; Title: What is Public Health? – Frequently Asked Questions 4. www.pzfizerpublichealth.com/publichealthbooks.aspx 5. www.whatispublichealth.org/impact/achievement.html; Title: What is Public Health? – Impact of Public Health

Anne Hathaway

â€Å"Anne Hathaway† by Carol Ann Duffy, the current poet laureate, is a strikingly poignant poem. It is in the persona of Anne Hathaway, Shakespeare’s wife, and is perceived to be the opinion of what she thinks about when she is left the second best bed in his will. The sonnet explores the loss felt by Hathaway as she grieves for her husband. Throughout the poem Duffy effectively uses poetic techniques to explore the feeling of loss felt by Hathaway as she is now a widow. The sonnet form allows Duffy the opportunity to discuss the emotion of loss as it highlights the grief felt by Hathaway perfectly. The title of the poem is interesting as it directly quotes from Shakespeare’s will â€Å"Item I gyve unto my wife†. Using the sonnet form effectively allows the feeling of loss to flow through the poem. Duffy emphasises the words â€Å"living laughing love† by putting stresses on them. This highlights the feeling of loss that she has for her dead husband. Duffy wrote the poem in the persona of Anne Hathaway but did not follow the rules of the sonnet form. If Duffy followed the rules of the sonnet form then the work â€Å"rhyme† would fall on a stress but it doesn’t and this illustrates the flow of the emotion of loss. Duffy describes the bed that Hathaway and Shakespeare made love in as a â€Å"Spinning world†. This gives the idea of it being magical and exciting. Duffy uses metaphors such as â€Å"forests†¦Ã¢â‚¬  to indicate the romance that they shared as it is no longer there and now there is only the feeling of loss. Duffy uses the words â€Å"my lover’s words† and this instantly illustrates the feeling of loss because Hathaway would never be able to hear him speak to her again during romance. Enjambment is effectively used to convey the spilling over of emotions of loss felt by Hathaway as she remembers the romance and the kisses they shared. Duffy creates the idea that there relationship was bright, exciting and out of this world by using the words â€Å"shooting stars†. Duffy reinforces the emotion of loss felt by Hathaway with the words â€Å"these lips†. This highlights the fact that they will never be able to share the magical times they had together again. Duffy does not always stick to the iambic pentameter such as when it comes to the word â€Å"kisses†. This highlights the fact that these are personal and they will never be able to do this again so creating the feeling of loss for her husband. Duffy makes a reference to literature to create the idea that they were made for each other. She uses the words â€Å"a verb dancing in the centre of a noun†. This highlights the fact she will never be able to feel like this with anyone else because Shakespeare was the verb and she was the noun. The poet uses senses to reinforce the importance of the shared experiences Hathaway and Shakespeare had together. Duffy uses the phrase â€Å"by touch, by scent, by taste†. This brings their relationship to life and reinforces the idea that they won’t be able to share this romance again. Although other people sleep in the best bed they will never be able to reach the same level of excitement and romance that Hathaway and Shakespeare shared. Now that Shakespeare is no longer there Hathaway herself will no longer be able to reach the same level of romance and excitement in that bed. The poignant use of alliteration â€Å"my living laughing love† heightens the readers understanding of the emotion of loss felt by Hathaway as it makes the reader realise that she is sad at the death of her husband. In the beginning the poem talks about the bed that they shared and where exciting and magical happened but at the end it tells us of the bed where she was â€Å"held†. This instantly makes the reader feel sad as Hathaway has to deal with the emotion of loss and grief. Throughout the poem Duffy effectively creates the emotion of loss. The emotion of loss is illustrated through the bed that they shared and where all the magical and exciting moments happened. This creates the emotion of loss because she will no longer be able to relive those moments but instead only has the memories of them and the loss of her husband.