Biochemistry perspective Essay Example for Free

Biochemistry perspective Essay Diabetes is an ailment which is caused due to high amount of glucose (sugar) in the blood. The main reason for high glucose levels in blood is due to the inability of body to utilize it properly. Glucose comes from the digestion of sugar and foods rich in carbohydrates that enable the liver to create glucose. The high concentration level of glucose in blood is termed as Hyperglycemia. In 1910, Sir Edward Albert Sharpey-Schafer suggested people with diabetes were deficient in a single chemical that was normally produced by the pancreas. He proposed calling this substance insulin. The term is derived from the Latin insula, meaning island, in reference to the islets of Langerhans in the pancreas that produce insulin. (Patlak, 2002) Insulin: An Introduction Insulin is a polypeptide containing 51 amino acids arranged in two chains. The chain A contains 21 amino acids and chain B contains 30 residues. These two chains are cross linked by two sulphur bridges by cysteine residues. Insulin is formed by proteolytic cleavage of its 84 amino acid prescursor Proinsulin. Insulin has a molecular weight of 5808 Da. It has the molecular formula C257H383N65O77S6. Insulin structure varies slightly between species. Its carbohydrate metabolism regulatory function strength in humans also varies. Porcine which is pig insulin is close to humans. The image above is computer-generated image of insulin hexamers. The zinc ions holding it together and the histidine residues are involved in zinc binding. Insulin Action A pharmacological action of insulin includes carbohydrate metabolism, protein metabolism, lipid metabolism and other actions. Insulin increases the use of sugar in the tissue and stimulates transportation of glucose into the cells. Insulin also stimulates protein synthesis and growth. It increases synthesis of messenger RNA and decreases gluconeogenesis. A gluconeogenesis is a formation of glucose from glycogen. It also increases amino acid uptake in the muscle. In adipose tissues, insulin increases fatty acid synthesis, glycerol phosphate synthesis and triglyceride deposition. Other action of insulin includes prevention of ketone boy formation and increases potassium uptake. After the release of insulin from the pancreatic beta cell into the interstitial compartment, it enters the circulation after crossing endothelial barrier. Insulin action effect at the cellular level is achieved by activating and suppressing the activity of enzyme. It can also be achieved by changing the rate of synthesis of enzymes at the level of transcription and translation. Insulin stimulate glucose uptake into fat cells by glucose transporters. Glucose transporters are small vesicles which contain specific protein macromolecules. Insulin increases the rate of fusion of these vesicles with the plasma membrane, and activates the transporters to transfer glucose across the plasma membrane into the cell. Insulin synthesize hoxokinase, an enzyme which phosporylates glucose as soon as it enters the cell. Insulin is an anabolic hormone. It encourages the storage of fats and the synthesis of proteins. Each receptor of insulin contain a pair of alpha subunits, which are located on the outer surface of the membrane, and a pair of beta subunits which crosses the membrane and stick out at both the outer and inner surfaces. Both alpha and beta subunits are held together by disulphide (S-S) bonds to form an aggregate. In humans, the insulin receptor gene is located on chromosome 19. Insulin binds to the receptor at a specific site on the alpha subunit. This causes increased phosphorylation of the receptor by ATP, mostly tyrosine residues of the intracellular portion of the beta subunit. Increased phophorylation of these tyrosine residues activates the beta subunit to function as a kinase enzyme. Some intracellular effects of insulin that occur after insulin-receptor binding may be mediate through nucleotide regulatory proteins (G proteins) a family of proteins associated with the inner surface of the plasma membrane. Cyclic AMP also has some intracellular effects of insulin. The major function of insulin is to counter the concerted action of a number of hyperglycemia-generating hormones and to maintain low blood glucose levels. Because there are numerous hyperglycemic hormones, untreated disorders associated with insulin generally lead to severe hyperglycemia and shortened life span. In addition to its role in regulating glucose metabolism, insulin stimulates lipogenesis, diminishes lipolysis, and increases amino acid transport into cells. Insulin also modulates transcription, altering the cell content of numerous mRNAs. It stimulates growth, DNA synthesis, and cell replication, effects that it holds in common with the insulin-like growth factors (IGFs) and relaxin. Specific protease activity cleaves the center third of the molecule, which dissociates as C peptide, leaving the amino terminal B peptide disulfide bonded to the carboxy terminal A peptide. Insulin secretion from beta cells is principally regulated by plasma glucose levels. Increased uptake of glucose by pancreatic b-cells leads to a concomitant increase in metabolism. The increase in metabolism leads to an elevation in the ATP/ADP ratio. This in turn leads to an inhibition of an ATP-sensitive K+ channel. The net result is a depolarization of the cell leading to Ca2+ influx and insulin secretion. In fact, the role of K+ channels in insulin secretion presents a viable therapeutic target for treating hyperglycemia due to insulin insufficiency. Insulin, secreted by the beta-cells of the pancreas, is directly infused via the portal vein to the liver, where it exerts profound metabolic effects. These effects are the response of the activation of the insulin receptor which belongs to the class of cell surface receptors that exhibit intrinsic tyrosine kinase activity as shown in the figure. Insulin produces its action through specific insulin receptors which consist of two subunits ? and ?. Insulin receptor complex then initiates a chain of biochemical reaction involving cAMP, protein phosphorylase, protein kinase, phosphatase and lipase. A diabetic condition result when receptor of insulin is desensitization. Therefore, Insulin is used medically in diabetes mellitus. Patients with type 1 diabetes mellitus depend on insulin (commonly injected subcutaneously) for their survival because they make no hormone. Patients with type 2 diabetes mellitus have either low insulin production or insulin resistance or both. Therefore, they require insulin administration when other medications become inadequate in controlling blood glucose levels. Actions of insulin-insulin receptor interactions at the level of IRS1 and activation of the kinase cascade leading to altered activities of glycogen phosphorylase and glycogen synthase. The insulin receptor is a heterotetramer of 2 extra cellular alpha-subunits disulfide bonded to 2 transmembrane beta-subunits. With respect to hepatic glucose homeostasis, the effects of insulin receptor activation are specific phosphorylation events that lead to an increase in the storage of glucose with a concomitant decrease in hepatic glucose release to the circulation. Only those responses at the level of glycogen synthase and glycogen phosphorylase are represented. This image shows Insulin-insulin receptor actions on glycogen homeostasis showing the role of protein targeting glycogen, PTG in complex formations involving many of the enzymes and substrates together. Also diagrammed is response of insulin at the level of glucose transport into cells via GLUT4 translocation to the plasma membrane. GS/GP kinase = glycogen synthase: glycogen phosphorylase kinase. PPI = protein phosphatase inhibitor. Arrows denote either direction of flow or positive effects, T lines represent inhibitory effects. In most nonhepatic tissues, insulin increases glucose uptake by increasing the number of plasma membrane glucose transporters: GLUTs. Glucose transporters are in a continuous state of turnover. Increases in the plasma membrane content of transporters stem from an increase in the rate of recruitment of new transporters into the plasma membrane, deriving from a special pool of preformed transporters localized in the cytoplasm. GLUT1 is present in most tissues, GLUT2 is found in liver and pancreatic b-cells, GLUT3 is in the brain and GLUT4 is found in heart, adipose tissue and skeletal muscle. In liver glucose uptake is dramatically increased because of increased activity of the enzymes glucokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase (PK), the key regulatory enzymes of glycolysis. Lack of Insulin Usually the inefficiency and lack of insulin are bracketed together, as both situations result in diabetes. There are two types of diabetes, diabetes insipidus and diabetes melitus, which is by far, the most common. Diabetes mellitus in turn has two types: Type 1, also known as insulin dependent diabetes mellitus, IDDM Type 1 is characterized by decreased productions of insulin so must be treated with insulin. It is most often found in children and adolescents. Type 2, also known as non-insulin dependent diabetes melitus, NIDDM Type 2 is caused by either decreased insulin production or abnormal cell sensitivity to the insulin that is present. It may be treated with diet alone, with oral hypoglycemic agents, or with insulin. It is more commonly diagnosed in adults. (Perspective Press, 240-43) Insulin does not cure diabetes. It is merely a treatment for the diabetes. Over time, many complications can occur in diabetic patients taking insulin. Some of these are coronary heart diseases, peripheral vascular diabetes, eye disorders, renal failure, and limb amputations. Because of reduced circulation and nerve damage, diabetic patients are essentially prone to developing foot ulcers, a major cause of amputations. They are able to feel foot infections, which allow it to grow and cause permanent damage. Proper foot care is essential and includes avoiding injuries oral restricting circulations, cleaning wounds, controlling infections, relieving weight from the ulcer area, and improving circulation. A new genetically engineered drug, becaplermin, promotes the healing process in diabetic foot ulcer. Lack of insulin or ineffectiveness of it may trigger some response from the body. The predominant tissue responding to signals that indicates fluctuating blood glucose levels is the liver. One of the most important functions of the liver is to produce glucose for circulation. Both elevated and reduced levels of blood glucose trigger hormonal responses to initiate pathways designed to restore glucose homeostasis. Low blood glucose triggers release of glucagon from pancreatic Alpha-cells. High blood glucose triggers release of insulin from pancreatic Beta-cells. In elderly people pancreas either fails or does not secrete right amount of insulin. In this patient insulin per injection becomes drug of choice when oral antidiabetics have failed. Insulin was also used to induce shocks in schizophrenics. Insulin secretion is controlled by concentrations circulating glucose, amino acids, and fatty acids, various hormones and neuron-transmitter agents. In the fasting state, when glucose concentrations are low, insulin secretion is minimal. As glucose concentrations rise after the utilizing carbohydrates meal the raised glucose concentration stimulates insulin secretion. Insulin resistance develops over time. Therefore, doses have to be increased. This occurs because of the development of insulin antibodies in the blood. This also can be somewhat corrected by changing the type of insulin injection and by giving cortiscosteroids which are immunity suppressant drugs. Yet, it also produces negative effect by increasing blood sugar and this is why they are not used. Types of Insulin There are many types of insulin and many salt forms of it. It can be derived synthetically of from different animal sources such as beef and pork. There is now genetically engineered human insulin available. Different insulin differs in the onset of action and the duration of action. Some are mixed together to achieve a desired effect such as a quick onset but a longer duration of action. The most common mixtures is regular insulin with NPH insulin (70units NPH and 30 units regular insulin per milliliter) The different categories of insulin’s are: 1. Short-acting insulin types: regular insulin (crystalline zinc insulin), semilente insulin (prompt insulin zinc suspension), insulin lipsor; 2. Intermediate acting insulin types: NPH (isophane insulin suspension) and linte insulin (insulin zinc suspension); 3. Long-acting insulin types: PZI (protamine zinc insulin suspension) and ultralente insulin (extended insulin zinc suspension). Administration Insulin is injection instead of giving orally because it is destroyed in the gastrointestinal tract. Also, the molecule is too large to be absorbed by the intestinal membrane. Therefore, injection of soluble crystalline insulin is given by subcutaneous injection which is quickly absorbed. Peak effects of insulin are achieved quickly and also excreted quickly within a few hours. However some insulin such as simelente is absorbed slowly. The peak is reached slowly and is sustained. This type of insulin excretion is also very slow and sometimes partly destroyed by insulinase enzyme in the liver. Controlling glucose level with insulin injections is a complex task since: a) Glucose concentrations fluctuate based on food ingestion. b) Cell sensitivity to insulin changes. Exercise increases sensitivity while stress, pregnancy, and some drug decrease insulin sensitivity. As a result some diabetic patients take multiple injections for a short-acting insulin preparation to produce peaks in insulin concentrations and a long acting formulation to establish a baseline concentration. Variable rate infusion pumps are also used. Patients who use insulin need to be instructed on the rotation method of taking their medication. Insulin is absorbed more rapidly with administration in the arm or thigh, especially with exercise. The abdomen is used for more consistent absorption. Glucose levels should be checked as per physician orders. All insulin must be checked for expiration date and clarity of the solution. Insulin should not be given if it appears cloudy. Vials should not be shaken but rotated in between the hands to mix contents. If regular insulin is to be mixed with NPH or lente insulin, the regular insulin should be drawn into the syringe first. Unopened vials should be stored in the refrigerator, and freezing should be avoided. The vial in use can be stored at room temperature. Vials should not be put in glove compartments, suitcase, or trunks. Humulin is a new type of insulin and is often the patients preference because it can be taken orally. It is imperative that the physician be called if any adverse reactions to the medications are observed. (Jahangir Moini, P 150-154) Undesirable Effects Insulin The main undesirable effect of insulin is hypoglycemia. This is common, and can cause brain damage. Intensive insulin therapy results in a threefold increase in severe hypoglycemia. The treatment of hypoglycemic is to take a sweet drink or snack, or, if the patient is unconscious, to give intravenous glucose (50% w/v solution) or intramuscular glucagon. Rebound hypergly (Somogyi effect) can follow excessive insulin administration. This results from the release of the insulin-opposing or counter-regulatory hormones in response to insulin-induced hypoglycemia. This can cause hypercemia before breakfast following an unrecognized hypoglycemic attack during sleep in the early hours of the morning. It is essential to recognize this possibility to avoid the mistake of increasing (rather than reducing) the dose of insulin in this situation. Allergy to insulin is unusual but may take the form of local or systemic reactions. Severe insulin resistance as a consequence of antibody formation is rare. A high tire of circulating anti-insulin antibodies is more likely to occur with bovine than with porcine insulin. Note, however, that virtually all patients treated with animal insulin have antibodies against the hormone, albeit usually flow. Human insulin is less immunogenic than animal insulin but may still evoke an antibody response, since the source of the hormone is not the only determinant of immunogenicity; insulin undergo physical changes before and after injection which can increase their potential for provoking an immune response. (HP Rang et al, 200-270) References 1. Patlak M. 2002. New weapons to combat an ancient disease: treating diabetes. Available on http://www. fasebj. org/cgi/content/full/16/14/1853e 2. Perspective Press. 2003. The Pharmacy Technician 1st edition: Morton Publishers. P 240- 243. 3. Jahangir Moini. 2005. Comprehensive Exam Review for the Pharmacy Technician: Thomson Delmar. P 150-154 4. H. P. Rang, M. Maureen Dale, James M. Ritter, Philip Moore. 2001. â€Å"Pharmacology†: Churchill Livingstone. P 200-270

Franks Landing Essay -- Sociology, The Nisqually Culture

Fishing and hunting have been at the core of many American Indian cultures like the Nisqually since precontact. Indian hunting, fishing and gathering were conducted then—as they are now—not for sport, but for food and for a livelihood. This was well understood by the early colonists and later by the U.S. government. Thus, many of the treaties (e.g., Medicine Creek, 1854) negotiated between the federal government and Indian tribes in the nineteenth century contained provisions guaranteeing rights to hunt and fish. In the trea ¬ty negotiated by Isaac Stevens, the tribe ceded to the U.S. some of the Nisqually vil ¬lages and prairies, but Article Three reserved the tribe’s right to fish â€Å"at all usual and accustomed grounds and stations†¦in common with all citizens of the Territory.† (FL 12) But the growth of the European American population, and with it the proliferation of fenced lands, the destruction of natural habitat, and often the destructi on of wildlife itself, drastically curtailed the Indians' ability to carry on these activities. Charles Wilkinson’s thesis declares that the â€Å"messages from Frank’s Landing† are â€Å"messages about ourselves, about the natural world, about societies past, about this society, and about societies to come.† (FL 6) Billy affectionately described his homeland (the key component of â€Å"peoplehood† i.e., the Nisqually watershed on South Puget Sound of the Nisqually River, creeks (Muck Creek), rolling prairie and forestland as well as the foothills of the Cascades Mountains and Mt Rainier) as â€Å"a magical place† where his family â€Å"never wished for anything: fish from the water ¬shed, vegetables up on the prairie, medicines, shellfish, and huckleberries†¦clean water, clean air.† He describes the arrival of L... ...s preferred by them or by the state.† In 1974 Judge Boldt ruled that a â€Å"fair share† meant Indian fishers are entitled to half (50%) of the harvestable catch of salmon. (FL 50) After a short-term negative backlash, the long-term result has been cooperation between federal, state and tribal governments over fish harvests and resource management since the U.S. Supreme Court upheld the Boldt decision in U.S. v. Washington (1980). (FL 50) Billy’s commitment to his traditional way of life did not end with the stunning Boldt decision. (FL 56)He became chairman of the North ¬west Indian Fisheries Commission in order to â€Å"speak for the salmon† on behalf of treaty tribes in Western Washington. Under his leadership, and through his exceptional skills as a negotiator, the tribes gained a reputation for being unsurpassed in their abilities as natural resource managers.

Lockie Leonard Proflie Essay

Lockie Leonard is 13 year old boy but he turns 14 in the book. He lives in a small town called Angelus with his family of 5, his dad’s name is Sarge and his mum’s name is Joy, he has a little brother and sister named Phillip and Blob. Blob is just a todler who can not walk or talk yet, Phillip thinks heis a mad scientist and likes to check girls out â€Å"A note from the teacher saying that he was obsessed with sex†p. 184, and he also still wets the bed and he is 11 years old. His best friend is Egg but he moved away, but they still talk by letters. Lockie is in love with Viki Streeton, according to him she is the hottest girl in school. His mum was depressed and crying all the timeand no one had any idea what was going on especially Lockie, Lockie was very troubled by this he was confused. Joy used to do all the things around thehouse like clean, wash and cook dinner but after she left Lockie had do all these jobs. In doing all these jobs and doing them well and his mum being sick Lockie and Sarge grew closer in there relationship in trusting each and talking to each other. After a while in hospital his mum was gradually getting better, Lockie went to talk to her every day because he missed her and wanted to make sure she was alright. Eventually she got out and she was felling great and had never felt better so Lockie’s life was back to normal, his mum was alright and his relationship with his dad was great and him and Viki had sort of started things again so it was going perfect.

Cherokee peoples - Free Essay Example

Sample details Pages: 3 Words: 929 Downloads: 4 Date added: 2019/08/02 Category History Essay Level High school Tags: Trail Of Tears Essay Did you like this example? Often in discussions of United States history, mentions of the Trail of Tears come up as a considerable blight, as well as treatment of the native people on the whole. But we know that a great many things about U.S. history are blown far out of proportion to make the nation seem evil. So how horrible was the Trail really? Well, research reveals that not only was the Andrew Jackson-led U.S. seizing of Native American lands in the 1830s unimaginably brutal, senseless, and unjust, but it was outright illegal and nobody ever answered for it! In the early-mid 1800s, enterprise in the budding United States of America was rich. A new generation of thinkers, bankers, innovators, and entrepreneurs had swept the country, and with this growth in economic success came the directly proportional yearning for ever more, especially more land to own specifically, in the case of the growing America, the land beyond the states borders to the west, in Indian territory. The primary issue with this desire is that it was just that the land of the natives. Americans were not satisfied. Despite the existence of established treaties and borders, new settlers routinely ignored the agreements, crossing the border to claim their own territory and disregarding the native populations right to the land. When they were met with resistance, they stole livestock, burned and looted houses and towns, committed mass murder, and squatted on land that did not belong to them. Even state governments were joining and supporting this infringement of the indi genous population. Don’t waste time! Our writers will create an original "Cherokee peoples" essay for you Create order It did not seem to matter at all to the statesmen that the tribespeople they were assaulting were often just as civilized as themselves. During the early years of America, many leaders, including George Washington, stated their belief that they would like for the native tribes to become westernized to match the civilization of the previously-European U.S.A. A number of the tribes actually did, converting to Christianity, speaking and reading English, adopting western styles of property and law, newspapers, and a written constitution, among others and thus the Choctaw, Chickasaw, Seminole, Creek, and Cherokee peoples became known as the Five Civilized Tribes. Many proposals have been made to us to adopt your laws, your religion, your manners and your customs. We would be better pleased with beholding the good effects of these doctrines in your own practices, than with hearing you talk about them. ~Old Tassel, Chief of the Cherokee Naturally, such violations of their basic liberties did not sit well with tribes that conformed to many of the same western ideas as their attackers. One issue, however, was that the settlers did not know which tribespeople spoke for their whole crowd when making negotiations therefore, whichever one best fit the settlers plan was the one representatives tended to accept as legitimate. This can be seen in an incident in 1825, when a group of Creek Indians agreed to sell their tribes land for $5 million and support for the journey west despite not being actual representatives of the Creek. A petition to nullify the deal reached over 15,000 signatures, but it mattered little to the whites who had just gained hundreds of acres. When the Cherokee people were assaulted in the aforementioned fashion, they decided to sue for peace. In 1832, The Cherokee Nation v. Georgia case was presented to the Supreme Court. The Cherokee claimed that they were a sovereign nation, and the U.S. should treat them in the same manner that they would other foreign states. The Supreme Court rejected the appeal for sovereignty, as the Cherokee resided entirely within United States borders, however, they agreed to have a hearing on other grounds. Thus, in 1832, the Worcester v. Georgia case ruled in favor of the so-called Indians. The Court ruled that because the Cherokees land rights were protected by the jurisdiction of the federal government, the states had no right to infringe upon it. The main issue with this ruling is that president Andrew Jackson did not agree with it, reportedly muttering John Marshall has made his ruling, now let him enforce it. He then proceeded to completely disregard the ruling, sending General Winfield Scott and an army to forcibly evict the Cherokee in 1838. The chiefs attempted to plead against the removal, but it was entirely fruitless. The Cherokee were occasionally held in disease-ridden internment camps before being marched at bayonet-point along more than 1,200 miles of arduous trails to their designated reserve, often without food or assistance. From the combined effects of whooping cough, typhus, cholera, dysentery, starvation, and other similarly colorful causes, an estimated 4,000-5,000 of the 15,000 Cherokee died along the Trail of Tears and Death. Half the infants, six months or a year, and all the aged over 60 had been killed directly, and one fourth of the remainder. There seems to be no place, nor means, nor time for the recovery of any who are now sick. -Cherokee missionary Daniel S. Butrick on the prison camps The story is one of greed and injustice. The whites wanted land and didnt care about the harm caused in attaining it. Even treaties and pacts and the law of the land didnt affect anything, as president Jackson was well known for disregarding the law when it pleased him and he was never held accountable for this breach of rights. I could not but think that some fearful retribution would come upon us. The scene seemed to me like a distempered dream, or something worthy of the dark ages rather than a present reality.