1.
Insulin
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Insulin is a peptide hormone produced by beta cells of the pancreatic islets. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats via lipogenesis, or, in the case of the liver, Glucose production by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells, low insulin levels in the blood have the opposite effect by promoting widespread catabolism. Pancreatic beta cells are known to be sensitive to concentrations in the blood. When glucose concentrations in the blood are high, the pancreatic β cells secrete insulin into the blood, glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin. If pancreatic beta cells are destroyed by an reaction, insulin can no longer be synthesized or be secreted into the blood. This results in type 1 diabetes mellitus, which is characterized by high blood glucose concentrations. In type 2 diabetes mellitus the destruction of cells is less pronounced than in type 1 diabetes. Instead there is an accumulation of amyloid in the pancreatic islets, Type 2 diabetes is characterized by high rates of glucagon secretion into the blood which are unaffected by, and unresponsive to the concentration of glucose in the blood glucose. Insulin is still secreted into the blood in response to the blood glucose, as a result, the insulin levels, even when the blood sugar level is normal, are much higher than they are in healthy persons. There are a variety of treatment regimens, none of which is entirely satisfactory, when the pancreas’s capacity to secrete insulin can no longer keep the blood sugar level within normal bounds, insulin injections are given. The human insulin protein is composed of 51 amino acids, and has a mass of 5808 Da. It is a dimer of an A-chain and a B-chain, which are linked together by disulfide bonds, insulins structure varies slightly between species of animals. Insulin from animal sources differs somewhat in effectiveness from human insulin because of these variations, porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies. The crystal structure of insulin in the state was determined by Dorothy Hodgkin. It is on the WHO Model List of Essential Medicines, the most important medications needed in a health system
2.
Infusion set
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An infusion set is used with an insulin pump as part of intensive insulin therapy. The purpose of a set is to deliver insulin under the skin. It is a tubing system to connect an insulin pump to the pump user, it includes a subcutaneous cannula, adhesive mount, quick-disconnect. Firstly, the user must attach a reservoir of insulin to the set, the set is then primed - the pump pushes insulin quickly through the tubing and the cannula to ensure no air is in the system before insertion. Note that it is vital that the set is not inserted into the skin when the set is being primed. The user then peels off the paper protecting the adhesive pad, the cannula is usually made of flexible plastic, which allows it to move without causing discomfort to the patient. The needle is pushed into the layer of fat below the skin, the needle is then removed, leaving the cannula in place below the skin. Insertion should be done in a swift movement to avoid the cannula bunching up around the needle. A few pump users prefer an infusion set with a steel needle instead of a cannula, the cannula surrounds a steel needle similar to that found on a hypodermic syringe. The same used device cant be reused for the other patient, as it is not a surgical instrument. It is for use only. Some pump users prefer to use a device to insert their sets. These are spring-loaded and are designed to push the needle into the skin quickly and painlessly, the user simply loads the primed set into the insertion device, peels off the paper protecting the adhesive pad, places the device against the skin and presses a button. This may be an advantage for those with needle phobia, many pump users site their infusion sets on the abdomen, in a roughly semicircular area around and below the navel. Other sites include the upper leg, upper buttocks, hips, upper arms, insulin absorption may vary from site to site, so it is important that patients are advised of the most effective sites to use by their diabetes adviser. The infusion set must be replaced regularly, usually every 2–3 days, insulin absorption becomes less effective the longer the set is left in place, leading to poorer control of blood glucose. For this reason, the site of the set is moved when the set is changed. Often a number of sites for the infusion set are used on a rotation basis
3.
Cannula
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A cannula is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of data. In simple terms, a cannula can surround the inner or outer surfaces of a trocar needle thus extending the effective needle length by at least half the length of the original needle and it is also called as IV cannula. Its size mainly ranges from 14 to 24 gauge, different sized cannula have different colours on it. Decannulation is the permanent removal of a cannula, especially of a tracheostomy cannula, cannulae normally come with a trocar attached, which allows puncturing of the body in order to get into the intended space. Many types of cannulae exist, Intravenous cannulae are the most common in hospital use, a variety of cannulae are used to establish cardiopulmonary bypass in cardiac surgery. A nasal cannula is a piece of tubing that runs under the nose and is used to administer oxygen. A venous cannula is inserted into a vein, primarily for the administration of fluids, for obtaining blood samples. Insertion of the cannula is a painful procedure that can lead to anxiety. Use of a vapocoolant immediately before cannulation reduces pain during the procedure, selection of an appropriate vein and gently applying pressure slightly above the insertion point on removal of the cannula may prevent this. Infiltration, when infusate enters the subcutaneous tissue instead of the vein, to prevent this, a cannula with accurate trim distances may be used. It is essential to fix the cannula in place firmly, Embolism, this can be caused by air, a thrombus, or fragment of a catheter breaking off and entering the venous system. It can cause a Pulmonary Embolism, air emboli can be avoided by making sure that there is no air in the system. A thromboembolism can be avoided by using a smaller cannula, phlebitis, an inflammation of the vein resulting from mechanical or chemical irritation or from an infection. Phlebitis can be avoided by choosing the site for cannulation. The removal of a tube is referred to as decannulation. Cannulas are a component used in the insertion of the Verichip, much larger cannulas are used to research about the digestive system of cows. Depending on the size of the diameter, it can be used either for the injection of cosmetic wrinkle fillers like hyaluronic acid, collagen, poly-L-lactic acid, CaHA. The advantage of using these is that they are painful, have less risk of bruising, have less swelling
4.
Syringe
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A syringe is a simple reciprocating pump consisting of a plunger that fits tightly within a cylindrical tube. The plunger can be pulled and pushed along the inside of the tube, allowing the syringe to take in. The open end of the syringe may be fitted with a hypodermic needle, syringes are frequently used in clinical medicine to administer injections, infuse intravenous drugs into the bloodstream, apply compounds such as glue or lubricant, and draw/measure liquids. The word syringe is derived from the Greek σύριγξ via back-formation of a new singular from its Greek-type plural syringes, sectors in the syringe and needle market include disposable and safety syringes, injection pens, needleless injectors, insulin pumps, and specialty needles. Hypodermic syringes are used with hypodermic needles to inject liquid or gases into body tissues, the barrel of a syringe is made of plastic or glass, usually has graduated marks indicating the volume of fluid in the syringe, and is nearly always transparent. Glass syringes may be sterilized in an autoclave, reuse of needles and syringes has caused spread of diseases, especially HIV and hepatitis, among intravenous drug users. Syringes are, however, commonly reused by diabetics, and this is if the syringe is only used by one person. In medical settings, single-use needles and syringes effectively reduce the risk of cross-contamination, syringes come with a number of designs for the area in which the blade locks to the syringe body. Perhaps the most well known of these is the Luer lock, bodies featuring a small, plain connection are known as slip tips and are useful for when the syringe is being connected to something not featuring a screw lock mechanism. Similar to this is the tip, which is essentially a slip tip but longer and tapered. These can also be used for rinsing out wounds or large abscesses in veterinary use, there is also an eccentric tip, where the nozzle at the end of the syringe is not in the centre of the syringe but at the side. This causes the blade attached to the syringe to lie almost in line with the walls of the syringe itself, syringes for insulin users are designed for standard U-100 insulin. The dilution of insulin is such that 1 mL of insulin fluid has 100 standard units of insulin, since insulin vials are typically 10 mL, each vial has 1000 units. Low dead space to reduce complications caused by improper drawing order of different insulin strengths, there are needle syringes designed to reload from a built-in tank after each injection, so they can make several or many injections on a filling. These are not used much in human medicine because of the risk of cross-infection via the needle, an exception is the personal insulin autoinjector used by diabetic patients. Venom extraction syringes are different from standard syringes, because they usually do not puncture the wound. The most common types have a nozzle which is placed over the affected area. Attempts to treat snakebites in this way are specifically advised against, as they are ineffective, syringes of this type are sometimes used for extracting human botfly larvae from the skin
5.
Insulin pen
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An insulin pen is used to inject insulin for the treatment of diabetes. Insulin is a produced by the pancreas. It is composed of a cartridge and a dial to measure the dose. It was introduced and marketed as NovoPen by the Danish company Novo Nordisk in 1985, a number of companies make insulin pens including Novo Nordisk, Aventis and Eli Lilly. These companies produce pens for most of their insulins, including NovoLog/NovoRapid, Humalog, Levemir, there are two pen systems, durable and prefilled, A durable pen uses a replaceable insulin cartridge. When the insulin cartridge is empty, the empty cartridge is disposed of, a prefilled pen is entirely disposable. The pen comes pre-filled with insulin, and when the cartridge or reservoir is empty. They are currently underutilized but growing in use in the United States, Insulin pens offer several significant advantages over insulin syringes, ease of handling, accuracy, and they are more discreet to use and easier to transport. Screw or click on a new pen needle, a healthcare provider helps determine the best injection site for a patient. In general, recommended injection sites include the abdomen, parts of the buttocks, parts of the upper arms, unlike with the traditional syringe, two different insulins cannot be mixed by the user in an insulin pen. On the other hand, some of the newest types of insulin cannot be mixed at all, technology has not changed much since the launch of the first insulin pen over 25 years ago by Novo Nordisk. A number of independent companies have created accessories to help people using insulin pens better manage their insulin intake. - Timesulin is a cap that works with all major insulin pen types to show users how long it has been since their insulin pen injection to help avoid missed or accidental double doses. - Bee by Vigilant the Diabetes Smart Tracker serves as a cap for most insulin pens and transmits insulin injection data and glucose levels via Bluetooth to smartphones, Insulin Pen Users group Insulin Pen Reviews Insulin pump Insulin syringe Insulin port Injection port Pen needles
6.
Dean Kamen
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Dean L. Kamen is an American engineer, inventor, and businessman. He is most known for his invention of the Segway and he is the son of Jack Kamen, an illustrator for Mad, Weird Science and other EC Comics publications. The device is balanced on two wheels and is controlled by moving body weight. Kamen was already a successful and wealthy inventor, after inventing the first drug infusion pump and starting a company, AutoSyringe, to market and he hopes the project will help improve living standards in developing countries. Kamen has a patent issued on his water purifier, U. S, patent 7,340,879, and other patents pending. In 2014, the film SlingShot was released, detailing Kamens quest to use his vapor compression distiller to fix the water crisis. In 2009 Kamen claimed his company DEKA was now working on solar power inventions, Kamen and DEKA also developed the DEKA Arm System or Luke, a prosthetic arm replacement that offers its user much more fine motor control than traditional prosthetic limbs. It was approved for use by the U. S. Food and Drug Administration in May 2014, in 1989, Kamen founded FIRST, a program for students to get people interested in science, technology, and engineering. One competition started and run by FIRST is the FRC or FIRST Robotics Competition, in 2011, it held 55 regional competitions around the globe, and one international competition in St. Louis, Missouri. FIRST has many programs, including the FLL JR. and the FLL for younger students, and the FTC. During his career Kamen has won numerous awards and he was elected to the National Academy of Engineering in 1997 for his biomedical devices and for making engineering more popular among high school students. In April 2002, Kamen was awarded the Lemelson-MIT Prize for inventors, for his invention of the Segway, in 2003 his Project Slingshot, a cheap portable water purification system, was named a runner-up for coolest invention of 2003 by Time magazine. In 2005 he was inducted into the National Inventors Hall of Fame for his invention of the AutoSyringe, in 2006 Kamen was awarded the Global Humanitarian Action Award by the United Nations. In 2015, Kamen received an honorary Doctor of Engineering and Technology degree from Yale University, Kamen received the prestigious Stevens Honor Award on November 6,2009, given by the Stevens Institute of Technology and the Stevens Alumni Association. On November 14,2013, he received the James C. Morgan Global Humanitarian Award and his residence is a hexagonal, shed style mansion he dubbed Westwind, located in Bedford, New Hampshire, just outside Manchester. Kamen owns and pilots an Embraer Phenom 300 light jet aircraft and he regularly commutes to work via his helicopters and had a hangar built into his house. In 2016 he piloted a B-2 Spirit bomber at Whiteman AFB and his company, DEKA, annually creates intricate mechanical presents for him. The company has created a chess player, which is a mechanical arm attached to a chess board, and a vintage-looking computer with antique wood
7.
National Institute for Health and Care Excellence
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The National Institute for Health and Care Excellence is an executive non-departmental public body of the Department of Health in the United Kingdom. It serves both the English NHS and the Welsh NHS and these appraisals are based primarily on evaluations of efficacy and cost–effectiveness in various circumstances. One aspect of this is the determination of cost–benefit boundaries for certain technologies that it assesses. NICE also plays an important role in pioneering technology assessment in other systems through NICE International. The NSC aimed to ensure that evidence-based medicine informed policy making on what national screening programmes were approved for funding, the idea of what was originally termed a National Institute for Clinical Excellence took root when Labour came to power having in 1997. Frank Dobson became Secretary of State and was supported by a team of Ministers keen on introducing clinical and health measures to achieve improvements in the quality. The team included Alan Milburn, Baroness Margaret Jay, and Tessa Jowell, riley led the team that developed the policy for NICE and which managed the legislation through Parliament in addition to formalising the new institute as a Special Health Authority. Riley joined Sir Michael Rawlins at the Health Select Committee in February 1999 where questions were raised as to whether NICE was just a means to ration healthcare, Sir Michael Rawlins presented a compelling case that positioned NICE as a standards setting body first and foremost. This controversial policy shift meant that NICE was critical for decisions on drug reimbursement, indeed, the first drug appraisal by NICE was on the drug Relenza which was turned down amidst criticisms from Glaxo-Wellcome that the appraisal had been fast tracked. Since January 2005, the NHS in England and Wales has been obliged to provide funding for medicines. Before an appraisal, the Advisory Committee on Topic Selection draws up a list of topics of clinical significance for appraisal. The Secretary of State for Health or the Welsh Assembly must then refer any technology so that the process can be formally initiated. Once this has been done NICE works with the Department of Health to draw up the scope of the appraisal, NICE then invites consultee and commentator organisations to take part in the appraisal. A consultee organisation would include patient groups, organisations representing health care professionals, Consultees submit evidence during the appraisal and comment on the appraisal documents. Commentator organisations include the manufacturers of products to which the product undergoing appraisal is being compared and they comment on the documents that have been submitted and drawn up but do not actually submit information themselves. An independent academic centre then draws together and analyses all of the information on the technology under appraisal. This can be commented on by the Consultees and Commentators, comments are then taken into account and changes made to the assessment report to produce an evaluation report. An independent Appraisal Committee then looks at the report, hears spoken testimony from clinical experts, patient groups
8.
Diabetes management software
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There are many products available to help maintain records and analyze trends related to diabetes care. Some support a single diabetes tool such as one manufacturers glucose meter, some diabetes management software is free to download or can be used on-line, while others are for sale. Some are simple and easy to use for a single user, example 1 shows a logbook can combine readings from multiple meters in one place. Breakfast, lunch, and dinner readings are lined up vertically to look for trends. The logbook automatically colors the box red for a low blood sugar, in the example chart, a pattern is easy to visualize, mornings tend to be a bit high and there is a pattern of lows occurring after dinner. The Standard day data plots, see example 2, shows that trends are easy to see, the blood glucose readings are plotted at their level versus the time of day. Multiple days are plotted on top of other, creating a scatter of points. In the example shown, it is easy to see the glycemic excursions to high blood sugars following breakfast and lunch. Once identified, this can be improved by using a faster acting insulin, or injecting insulin 20 minutes before eating, or by selecting carbohydrates to eat that are slower to peak in the bloodstream. Example 3 shows that pie charts are a way to judge performance of insulin doses throughout the day relative to the goal of keeping 75% of premeal blood glucose readings within boundaries. Sub-charts automatically break down to breakfast, lunch, dinner, and late night, in the example pie chart shown, it appears there is an opportunity to improve morning lows and afternoon highs with insulin adjustments. Example 4 evaluates the delivery from a pump, showing blood glucose plots along the top, carbohydrates eaten, basal. In this chart, it is easy to see that the pump user had a meal at 3pm. Example 5 shows a screen for basal delivery from an insulin pump. Time of day and basal rate in units per hour can be modified to create a custom basal rate pattern to match the needs of the pump user. Icons are shown which save or read data from the PC, example 6 shows bolus control on this screen. The insulin to carbohydrate ratio is stored in the pump as a function of the meal eaten, example 7 shows a data plot from a continuous glucose monitoring system. This plot shows the blood sugar levels between meals and also during the night, when other BG testing methods using a finger prick sample would typically miss the data available between samples and this curve also illustrates the dawn effect
9.
Medtronic
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Medtronic is a medical device company headquartered in Dublin, Ireland. Their operational headquarters is in Fridley, Minnesota, Medtronic is the worlds largest standalone medical technology development company. In 2015, at the time of its acquisition of Covidien, Medtronic operates in more than 140 countries, employs over 85,000 people and has more than 53,000 patents. Medtronic was founded in 1949 in northeast Minneapolis by Earl Bakken, through their repair business, Bakken came to know Dr C. Walton Lillehei, a doctor in the field of heart surgery then at the University of Minnesota Medical School, the deficiencies of the pacemakers of the day were made painfully obvious following a power outage over Halloween in 1957 which affected large sections of Minnesota and western Wisconsin. As a direct result of this blackout, a pacemaker-dependent paediatric patient of Lillehei died, the next day, Lillehei spoke with Bakken about developing some form of battery-powered pacemaker. Stemming from this need, Bakken modified a design for a metronome to create the first battery-powered external artificial pacemaker. The company expanded through the 1950s, mostly selling equipment built by other companies, Bakken built a small transistorised pacemaker that could be strapped to the body and powered by batteries. Work into this new field continued, producing an implantable pacemaker in 1960 and it built a headquarters in the Minneapolis suburb of St. Anthony in 1960 and moved to Fridley in the 1970s. Medtronics main competitors in the cardiac rhythm field include Boston Scientific, in 1998, Medtronic acquired Physio-Control for USD538 million. In 2005,2008, and 2010 PETA threatened to submit a resolution in order to improve animal welfare standards in the company. In 2005, PETA attempted to stop five specific animal experiments which they deemed crude, in 2008, PETA protested the outsourcing of animal testing to countries with lax animal welfare laws such as China. In 2010, PETA attempted to stop Medtronics reported use of animals in testing and training. In response Medtronic conducted a feasibility study to see whether banning the use of animals was practical. This study concluded that it was not and Medtronic continues to use animals for testing and training. In each case PETA withdrew its resolution after talks with Medtronics leadership. After 2008 and the financial crisis, Medtronic stock value dropped dramatically. In May 2014, Medtronic agreed to pay over USD1 billion to settle patent litigation with Edwards Lifesciences after years of protracted legal battles, in June 2014, Medtronic announced its acquisition of Covidien, plc of Ireland for USD42.9 billion in cash and stock
10.
Minimed Paradigm
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MiniMed Paradigm is a series of insulin pumps manufactured by Medtronic for patients with diabetes mellitus. The pump operates with a single AAA battery and uses a pump to infuse a programmed amount of insulin into the patient through a length of tubing. The Paradigm uses a wireless radio frequency link to receive blood sugar measurements from select glucose meters. The Paradigm RT series adds the ability to data from a mated continuous blood-glucose monitor. Although the pump can use these measurements to assist in calculating a dose of insulin, in the United States, the device is regulated by a branch of the Food and Drug Administration. Insulin pumps are drug delivery devices used to treat patients with type 1, the Minimed Paradigm REAL-Time and Continuous Glucose Monitoring system, which received FDA clearance in 2006, uses tubing and a reservoir with rapid-acting insulin. This infusion set is patient-connected via a catheter to the abdomen region, the infusion set can remain in the place for 3 days while the pump is clip-belt worn. There is a feature for the tubing. The pump delivers insulin in two modes, in Basal rate mode, the delivery is continuous in small doses similar to a pancreas, for example 0.15 units per hour throughout the day. Basal rates are set to meet individual metabolic rates, in Bolus mode, the delivery is programmed to be a one-time delivery prior to eating or after an unexpected high, for example 18 units spread out to several hours. This type of treatment is in contrast to traditional multiple daily injections that use slower-acting insulin. The Paradigm system consists of two parts, an insulin pump and an optional glucose sensor CGM worn for up to 3 days. So any change in basal or bolus is patient-driven by programming the pump using the Bolus WizardTM, the latest model pumps are the MiniMed Paradigm 522 and 722 which differ in reservoir size,176 versus 300 units, respectively. In 2007 the FDA approved a model for patients 7 to 17 years old. If using OneTouch UltraLink meter, readings are sent wirelessly to the pump, the development history of the Minimed pump goes back to the 1980s. The objective of CSII is to reduce the variability of blood glucose by increasing the frequency of infusion. In 1995 the ADA issued the statement, CSII is an alternative to multiple injection therapy in the management of Insulin Dependent Diabetes Mellitus. The Diabetes Control and Complications Trial study showed that CSII patients achieved an A1c of 7. 3% and this large and controlled study also showed that improvement in glycemic control could reduce the incidence of microvascular complications for type 1 diabetes by 60%
11.
Artificial pancreas
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There are several important exocrine and endocrine functions of the pancreas, but it is the lack of insulin production which is the motivation to develop a substitute. While the current state of insulin replacement therapy is appreciated for its life-saving capability, different approaches under consideration include, the medical equipment approach—using an insulin pump under closed loop control using real-time data from a continuous blood glucose sensor. The bioengineering approach—the development of a bio-artificial pancreas consisting of a sheet of encapsulated beta cells. When surgically implanted, the sheet will behave as the endocrine pancreas. The gene therapy approach—the therapeutic infection of a person by a genetically engineered virus which causes a DNA change of intestinal cells to become insulin-producing cells. When islet cells have been transplanted via the Edmonton protocol, insulin production was restored at the expense of immunosuppression, one concept of the bio-artificial pancreas uses encapsulated islet cells to build an islet sheet which can be surgically implanted to function as an artificial pancreas. Islet sheet research is pressing forward with large animal studies at the present, technology for gene therapy is advancing rapidly such that there are multiple pathways possible to support endocrine function, with potential to practically cure diabetes. Gene therapy can be used to manufacture insulin directly, a medication, consisting of viral vectors containing the insulin sequence, is digested. Those intestinal cells will then behave like any viral infected cell, the virus can be controlled to infect only the cells which respond to the presence of glucose, such that insulin is produced only in the presence of high glucose levels. Due to the numbers of vectors delivered, very few intestinal cells would actually be impacted. Therefore, by varying the amount of medication used, the amount of insulin created by gene therapy can be increased or decreased as needed. As the insulin-producing intestinal cells die off, they are boosted by additional oral medications, gene therapy might eventually be used to cure the cause of beta cell destruction, thereby curing the new diabetes patient before the beta cell destruction is complete and irreversible. Gene therapy can be used to turn duodenum cells and duodenum adult stem cells into beta cells which produce insulin and amylin naturally. By delivering beta cell DNA to the cells in the duodenum, a few intestine cells will turn into beta cells. This makes the supply of beta cells in the duodenum self replenishing, and these capabilities suggest that a stream of real-time data can be used to close the loop and control the insulin pump directly. As the state of the art for blood glucose monitoring continues to advance, the first step in controlling an insulin pump based on continuous blood glucose data is to automatically control the basal rate of the insulin pump. In France, a clinical trial of an artificial pancreas is underway. The system is automated by combining Medtronic MiniMeds long-term glucose sensor
12.
Amylin
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Amylin, or islet amyloid polypeptide, is a 37-residue peptide hormone. It is cosecreted with insulin from the pancreatic β-cells in the ratio of approximately 100,1, amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels. IAPP is processed from an 89-residue coding sequence, proIAPP consists of 67 amino acids, which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence. The human sequence is, TPIESHQVEKR^ KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTYG^ KR^ NAVEVLKREPLNYLPL, once released from the signal peptide, it undergoes additional proteolysis and posttranslational modification. 11 amino acids are removed from the N-terminus by the enzyme proprotein convertase 2 while 16 are removed from the C-terminus of the molecule by proprotein convertase 1/3. At the C-terminus Carboxypeptidase E then removes the terminal lysine and arginine residues, the terminal glycine amino acid that results from this cleavage allows the enzyme peptidylglycine alpha-amidating monooxygenase to add an amine group. Finally, a bond is formed between cysteine residues numbers 2 and 7. After this the transformation from the precursor protein proIAPP to the biologically active IAPP is complete, insulin and IAPP are regulated by similar factors since they share a common regulatory promoter motif. The IAPP promoter is activated by stimuli which do not affect insulin, such as tumor necrosis factor alpha. One of the features of Type 2 diabetes is insulin resistance. Although little is known about IAPP regulation, its connection to insulin indicates that regulatory mechanisms that affect insulin also affect IAPP, thus blood glucose levels play an important role in regulation of proIAPP synthesis. Amylin functions as part of the pancreas and contributes to glycemic control. The peptide is secreted from the islets into the blood circulation and is cleared by peptidases in the kidney. It is not found in the urine, amylins metabolic function is well-characterized as an inhibitor of the appearance of nutrient in the plasma. It thus functions as a partner to insulin, with which it is cosecreted from pancreatic beta cells in response to meals. Appearance of new glucose in the blood is reduced by inhibiting secretion of the hormone glucagon. These actions, which are carried out via a glucose-sensitive part of the brain stem. They collectively reduce the total insulin demand, amylin also acts in bone metabolism, along with the related peptides calcitonin and calcitonin gene related peptide
13.
Postprandial
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Postprandial means after eating a meal while preprandial is before a meal. The term postprandial is used in many contexts, refers to activities performed after a meal, like drinking cocktails or smoking. A common use is in relation to blood sugar levels, which are normally measured 2 hours after and this is because blood glucose levels usually rise after a meal. The American Diabetes Association recommends a postprandial glucose level under 180 mg/dl, other uses of postprandial include, Postprandial dip is a mild decrease in blood sugar after eating a big meal. Postprandial hyperglycemia is high blood sugar following a meal and it can be evaluated in a postprandial glucose test. Postprandial hypotension is a decline in blood pressure which happens after eating a meal. Postprandial regurgitation is a symptom of rumination syndrome. Postprandial thermogenesis is heat production due to metabolism after a meal, Postprandial abdominal distension usually refers to bloating of the abdomen following a meal, especially a large one. It is generally harmless, but tends to be uncomfortable, instances of its sudden onset or prolonged duration can, however, be symptoms of certain severe adverse gastro-intestinal conditions such as irritable bowel disease. Postprandial abdominal distension is also a side effect of some medications. In the postprandium, there is digestion of food in the tract, followed by uptake and various metabolic processes. The postprandium is characterized by an activity of the parasympathetic nervous system
14.
Diabetes management
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The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentration of a sugar called glucose in the blood. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance, the pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the forms of maturity onset diabetes of the young, may represent some combination of insufficient insulin production. Some degree of resistance may also be present in a person with type 1 diabetes. The main goal of management is, as far as possible. To achieve this goal, individuals with a deficiency of insulin require insulin replacement therapy. Insulin resistance, in contrast, can be corrected by dietary modifications, other goals of diabetes management are to prevent or treat the many complications that can result from the disease itself and from its treatment. The treatment goals are related to control of blood glucose, blood pressure and lipids. They are suggested in clinical practice guidelines released by various national and international diabetes agencies, the targets are, HbA1c of 6% to 7. 0% Preprandial blood glucose,3.9 to 7. The primary issue requiring management is that of the glucose cycle, checking cholesterol, LDL, HDL and triglyceride levels may indicate hyperlipoproteinemia, which may warrant treatment with hypolipidemic drugs. Checking the blood pressure and keeping it within strict limits protects against the retinal, renal, regular follow-up by a podiatrist or other foot health specialists is encouraged to prevent the development of diabetic foot. Annual eye exams are suggested to monitor for progression of diabetic retinopathy, late in the 19th century, sugar in the urine was associated with diabetes. Frederick Madison Allen studied diabetes in 1909-12, then published a volume, Studies Concerning Glycosuria. He invented a fasting treatment for diabetes called the Allen treatment for diabetes and his diet was an early attempt at managing diabetes. Modern approaches to diabetes primarily rely upon dietary and lifestyle management, diet management allows control and awareness of the types of nutrients entering the digestive system, and hence allows indirectly, significant control over changes in blood glucose levels. Blood glucose monitoring allows verification of these, and closer control, other approaches include exercise and other lifestyle changes which impact the glucose cycle. In addition, a partnership between the patient and the primary healthcare provider – general practitioner or internist – is an essential tool in the successful management of diabetes. Often the primary care doctor makes the diagnosis of diabetes and provides the basic tools to get the patient started on a management program
15.
Glucagon
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Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It works to raise the concentration of glucose in the bloodstream and it is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers the glucose, the pancreas releases glucagon when the concentration of glucose in the bloodstream falls too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream, high blood-glucose levels, on the other hand, stimulate the release of insulin. Insulin allows glucose to be taken up and used by insulin-dependent tissues, thus, glucagon and insulin are part of a feedback system that keeps blood glucose levels stable. Glucagon increases energy expenditure and is elevated under conditions of stress, Glucagon belongs to the secritin family of hormones. Glucagon generally elevates the concentration of glucose in the blood by promoting gluconeogenesis and glycogenolysis, glucose is stored in the liver in the form of the polysaccharide glycogen, which is a glucan. When glucagon binds to the receptors, the liver cells convert the glycogen into individual glucose molecules and release them into the bloodstream. As these stores become depleted, glucagon then encourages the liver, Glucagon turns off glycolysis in the liver, causing glycolytic intermediates to be shuttled to gluconeogenesis. Glucagon also regulates the rate of production through lipolysis. Glucagon induces lipolysis in humans under conditions of insulin suppression, Glucagon production appears to be dependent on the central nervous system through pathways yet to be defined. In invertebrate animals, eyestalk removal has been reported to affect glucagon production, excising the eyestalk in young crayfish produces glucagon-induced hyperglycemia. Glucagon binds to the receptor, a G protein-coupled receptor. The conformation change in the receptor activates G proteins, a protein with α, β. When the G protein interacts with the receptor, it undergoes a change that results in the replacement of the GDP molecule that was bound to the α subunit with a GTP molecule. This substitution results in the releasing of the α subunit from the β and γ subunits, the alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase. Adenylate cyclase manufactures cyclic adenosine monophosphate, which activates protein kinase A and this enzyme, in turn, activates phosphorylase kinase, which then phosphorylates glycogen phosphorylase b, converting it into the active form called phosphorylase a. Phosphorylase a is the responsible for the release of glucose-1-phosphate from glycogen polymers
16.
Novo Nordisk
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Novo Nordisk is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in eight countries, and affiliates or offices in 75 countries. Novo Nordisk is controlled by majority shareholder, Novo A/S, which holds approximately 25% of its shares, Novo Nordisk manufactures and markets pharmaceutical products and services. Key products include diabetes care medications and devices, Novo Nordisk is also involved with hemostasis management, growth hormone therapy and hormone replacement therapy. The company makes several drugs under various names, including Levemir, NovoLog, Novolin R, NovoSeven, NovoEight. Novo Nordisk employs more than 40,000 people globally, the corporation was created in 1989 through a merger of two Danish companies which date back to the 1920s. The Novo Nordisk logo is the Apis bull, one of the animals of ancient Egypt. Novo Nordisk is a member of the European Federation of Pharmaceutical Industries. The company was ranked 25th among 100 best companies to work for in 2010 by Fortune, in January 2012, Novo Nordisk was named as the most sustainable company in the world by the business magazine Corporate Knights while spin-off company Novozymes was named fourth. Novo Nordisk was ranked 72nd on “Fortune’s 100 Best Companies to Work For®” list within the U. S. state of New Jersey as of January 2014, behind Novo Nordisk lies a story about two Danish firms - Nordisk Insulinlaboratorium and Novo Terapeutisk Laboratorium. Nordisk Insulinlaboratorium was founded by Hans Christian Hagedorn, August Krogh, in 1922, August Krogh and his wife Marie Krogh travelled to the US. The couple had heard reports of people with diabetes being treated with insulin – a hormone discovered in 1921 by two Canadians, Frederick Banting and Charles Best, Marie Krogh was a doctor herself and also had type 2 diabetes. The couple returned to Denmark with permission to manufacture and sell insulin in Scandinavia, with the economic help from August Kongsted – the owner of Leo Pharmaceutical Products - Insulin Leo was marketed in 1923. When Krogh and Hagedorn started manufacturing insulin, they hired Thorvald Pedersen, however, Thorvald Pedersen was fired from Nordisk and the two brothers decided to try to manufacture insulin themselves. Thorvald and Harald Pedersen managed to produce a stable liquid insulin, the brothers named their firm Novo Terapeutisk Laboratorium. Over the next decades the products were further improved, e. g, in 1982, Novo succeeded and launched the world’s first insulin preparation identical to human insulin. In 1989, Novo Industri A/S and Nordisk Gentofte A/S merged to become Novo Nordisk A/S, in 2000 the company demerged into NovoZymes A/S and Novo Nordisk A/S. In 2015, the company announced it would collaborate with Ablynx, jesper Brandgaard is the Executive Vice President and CFO of the global healthcare company Novo Nordisk A/S. Brandgaard has been the Vice Chairman of the board of directors in the Danish company SimCorp since 2007, Tresiba - is a Diabetes mellitus type 1 and Type 2 diabetes drug
17.
Blood sugar level
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The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. The body naturally tightly regulates blood glucose levels as a part of metabolic homeostasis, with some exceptions, glucose is the primary source of energy for the bodys cells, and blood lipids are primarily a compact energy store. Glucose levels are usually lowest in the morning, before the first meal of the day, Blood sugar levels outside the normal range may be an indicator of a medical condition. A persistently high level is referred to as hyperglycemia, low levels are referred to as hypoglycemia, Diabetes mellitus is characterized by persistent hyperglycemia from any of several causes, and is the most prominent disease related to failure of blood sugar regulation. Intake of alcohol causes a surge in blood sugar. Also, certain drugs can increase or decrease glucose levels, the international standard way of measuring blood glucose levels are in terms of a molar concentration, measured in mmol/L. In the United States, West-Germany and other countries mass concentration is measured in mg/dL, since the molecular weight of glucose C6H12O6 is 180, the difference between the two units is a factor of 18, so that 1 mmol/L of glucose is equivalent to 18 mg/dL. Normal value ranges may vary slightly among different laboratories, many factors affect a persons blood sugar level. A bodys homeostatic mechanism, when operating normally, restores the blood sugar level to a range of about 4.4 to 6.1 mmol/L. The normal blood level for non-diabetics, should be between 3.9 and 5.5 mmol/L. The mean normal blood glucose level in humans is about 5.5 mmol/L, however, Blood sugar levels for those without diabetes and who are not fasting should be below 6.9 mmol/L. The blood glucose target range for diabetics, according to the American Diabetes Association, should be 5. 0–7.2 mmol/l before meals, and less than 10 mmol/L after meals. Despite widely variable intervals between meals or the consumption of meals with a substantial carbohydrate load, human blood glucose levels tend to remain within the normal range. However, shortly after eating, the glucose level may rise, in non-diabetics. The actual amount of glucose in the blood and body fluids is very small. In a healthy adult male of 75 kg with a volume of 5 liters. Part of the reason why this amount is so small is that, to maintain an influx of glucose into cells, in general, ranges of blood sugar in common domestic ruminants are lower than in many monogastric mammals. However this generalization does not extend to wild ruminants or camelids, a 90 percent reference interval for serum glucose of 26 to 181 mg/dL has been reported for captured mountain goats, where no effects of the pursuit and capture on measured levels were evident
18.
Basal rate
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In biology, basal rate is the rate of continuous supply of some chemical or process. In the case of diabetes mellitus, it is a low rate of continuous insulin supply needed for such purposes as controlling cellular glucose, together with a bolus of insulin, the basal insulin completes the total insulin needs of an insulin-dependent person. An insulin pump and wristop controller is one way to arrange for a closely controlled basal insulin rate, the slow-release insulins can provide a similar effect. In healthy individuals, basal rate is monitored by the pancreas, the body requires this flow of insulin to enable the body to utilize glucose in the blood stream, so the energy in glucose can be used to carry out bodily functions. Basal rate requirements can differ for individuals depending on the activities they carry out on that particular day. For example, if one is not highly active on a certain day, on the other hand, basal rate increases dramatically when an individual is highly active. Basal rates often even vary from hour to hour throughout the day, for example, one’s insulin needs vary from activity to activity. Activities, such as sports, housework, shopping, gardening, tidying the house and these activities all require energy and, thus, use glucose, basal rate must decrease in order to keep glucose levels high enough to be used as fuel for the body. On the other hand, fevers, having a cold, taking a nap, taking cortisone-containing medication, in these instances, the body has an overwhelming supply of glucose, and glucose levels need to decrease. To induce this decrease, basal rate needs to increase to increase insulin release to some of the excess glucose from the blood stream. Those with diabetes mellitus must be aware of their basal rates, Basal rate can be raised and lowered through various methods. For example, individuals with diabetes mellitus often use a pump to supply an increased amount of insulin into the blood stream. Those with diabetes also may eat carbohydrates or sugars to account for low blood sugar, however one monitors and regulates their blood sugar levels and basal rates, it is important to make changes gradually. An initial lowering in basal rate should be no more than 10% of the original, after the initial lowering point, one must note the factor by which one’s blood sugar changes. If blood sugar levels decreased, one should lower their basal rate by 20% next time, if their blood sugar levels increased, a lowering of 10% was too great, and one should not lower their basal rate at all next time. If blood sugar levels remained constant, a drop in basal rate of 10% was sufficient. Just as the action to change basal rate should be gradual in nature, a change in basal rate is felt around two hours after the action is done. This is especially important for those with diabetes to note, as it affects when they should act to monitor their basal rates, the liver is the primary contributing organ which produces glucose continuously even when nothing is being eaten
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Puberty
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Puberty is the process of physical changes through which a childs body matures into an adult body capable of sexual reproduction. It is initiated by signals from the brain to the gonads, the ovaries in a girl. In response to the signals, the gonads produce hormones that stimulate libido and the growth, function, and transformation of the brain, bones, muscle, blood, skin, hair, breasts, and sex organs. Physical growth—height and weight—accelerates in the first half of puberty and is completed when a body has been developed. Until the maturation of their capabilities, the pre-pubertal physical differences between boys and girls are the external sex organs. On average, girls begin puberty around ages 10–11, boys around ages 11–12, girls usually complete puberty around ages 15–17, while boys usually complete puberty around ages 16–17. In the 21st century, the age at which children, especially girls, reach puberty is lower compared to the 19th century. Puberty which starts earlier than usual is known as precocious puberty, Puberty which starts later than usual is known as delayed puberty. Two of the most significant differences between puberty in girls and puberty in boys are the age at which it begins, and the sex steroids involved, the testosterones. Although there is a range of normal ages, girls typically begin the process of puberty at age 10 or 11. Girls usually complete puberty by ages 15–17, while boys usually complete puberty by ages 16–17, girls attain reproductive maturity about four years after the first physical changes of puberty appear. In contrast, boys accelerate more slowly but continue to grow for about six years after the first visible pubertal changes, any increase in height beyond the post-pubertal age is uncommon. For boys, an androgen called testosterone is the sex hormone. While testosterone is produced, all changes are characterized as virilization. The conversion of testosterone to estradiol depends on the amount of body fat, the male growth spurt also begins later, accelerates more slowly, and lasts longer before the epiphyses fuse. Although boys are on average 2 centimetres shorter than girls before puberty begins, the hormone that dominates female development is an estrogen called estradiol. While estradiol promotes growth of the breasts and uterus, it is also the principal hormone driving the growth spurt and epiphyseal maturation. Estradiol levels rise earlier and reach higher levels in women than in men, the hormonal maturation of females is considerably more complicated than in boys
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Corticosteroid
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Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Some common naturally occurring steroid hormones are cortisol, corticosterone, cortisone and aldosterone, the main corticosteroids produced by the adrenal cortex are cortisol and aldosterone. Glucocorticoids such as cortisol affect carbohydrate, fat, and protein metabolism, and have anti-inflammatory, immunosuppressive, anti-proliferative, anti-inflammatory effects are mediated by blocking the action of inflammatory mediators and inducing anti-inflammatory mediators. Immunosuppressive effects are mediated by suppressing delayed hypersensitivity reactions by direct action on T-lymphocytes, anti-proliferative effects are mediated by inhibition of DNA synthesis and epidermal cell turnover. Vasoconstrictive effects are mediated by inhibiting the action of inflammatory mediators such as histidine, synthetic pharmaceutical drugs with corticosteroid-like effects are used in a variety of conditions, ranging from brain tumors to skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone, hydrocortisone is typically used for replacement therapy, e. g. for adrenal insufficiency and congenital adrenal hyperplasia. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists, typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushings syndrome. Typical mineralocorticoid side-effects are hypertension, hypokalemia, hypernatremia without causing peripheral edema, metabolic alkalosis, there may also be impaired wound healing or ulcer formation because of the immunosuppressive effects. Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing central serous retinopathy, a variety of steroid medications, from anti-allergy nasal sprays to topical skin creams, to eye drops, to prednisone have been implicated in the development of CSR. Corticosteroids have been used in treating people with traumatic brain injury. A systematic review identified 20 randomised controlled trials and included 12,303 participants, the authors recommended people with traumatic head injury should not be routinely treated with corticosteroids. There is some basis for genetic variation in response to inhaled corticosteroids. Two genes of interest are CHRH1 and TBX21, both genes display some degree of polymorphic variation in humans, which may explain how some patients respond better to inhaled corticosteroid therapy than others. Use of corticosteroids has numerous side-effects, some of which may be severe, Neuropsychiatric, steroid psychosis, therapeutic doses may cause a feeling of artificial well-being. The neuropsychiatric effects are mediated by sensitization of the body to the actions of adrenaline. Therapeutically, the bulk of corticosteroid dose is given in the morning to mimic the bodys diurnal rhythm, if given at night, an extensive review is provided by Flores and Gumina. Cardiovascular, Corticosteroids can cause sodium retention through an action on the kidney. This can result in retention and hypertension
21.
Ketone bodies
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These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above as a result of intense gluconeogenesis and they are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted. When two acetyl-CoA molecules lose their -CoAs, they can form a dimer called acetoacetate, beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol group. Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, ketone bodies have a characteristic smell, which can easily be detected in the breath of persons in ketosis and ketoacidosis. It is often described as fruity or like nail polish remover, fats stored in adipose tissue are released from the fat cells into the blood as free fatty acids and glycerol when insulin levels are low and glucagon and epinephrine levels in the blood are high. This occurs between meals, during fasting, starvation and strenuous exercise, when glucose levels are likely to fall. Fatty acids are very high energy fuels, and are taken up by all metabolizing cells which have mitochondria and this is because fatty acids can only be metabolized in the mitochondria. Red blood cells do not contain mitochondria and are entirely dependent on glycolysis for their energy requirements. In all other tissues the fatty acids enter the metabolizing cells are combined with co-enzyme A to form acyl-CoA chains. These are transferred into the mitochondria of the cells, where they are broken down into units by a sequence of reactions known as β-oxidation. The acetyl-CoA produced by β-oxidation enters the citric acid cycle in the mitochondrion by combining with oxaloacetate to form citrate and this results in the complete combustion of the acetyl group of acetyl-CoA to CO2 and water. The energy released in this process is captured in the form of 1 GTP and 11 ATP molecules per acetyl group oxidized and this is the fate of acetyl-CoA wherever β-oxidation of fatty acids occurs, except under certain circumstances in the liver. Under these circumstances acetyl-CoA is diverted to the formation of acetoacetate and beta-hydroxybutyrate, acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone, are frequently, but confusingly, known as ketone bodies. The ketone bodies are released by the liver into the blood, acetoacetate has a highly characteristic smell, for the people who can detect this smell, which occurs in the breath and urine during ketosis. On the other hand, most people can smell acetone, whose sweet & fruity odor also characterizes the breath of persons in ketosis or, especially, ketone bodies can be used as fuels, yielding 2 GTP and 22 ATP molecules per acetoacetate molecule when oxidized in the mitochondria. Ketone bodies are transported from the liver to other tissues, where acetoacetate and beta-hydroxybutyrate can be reconverted to acetyl-CoA to produce reducing equivalents, ketone bodies cannot be used as fuel by the liver, because the liver lacks the enzyme β-ketoacyl-CoA transferase, also called thiophorase. Acetone in low concentrations is taken up by the liver and undergoes detoxification through the pathway which ends with lactate
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Menstruation
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Menstruation, also known as a period or monthly, is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The first period usually begins between twelve and fifteen years of age, a point in time known as menarche, however, periods may occasionally start as young as eight years old and still be considered normal. The average age of the first period is later in the developing world. The typical length of time between the first day of one period and the first day of the next is 21 to 45 days in young women, bleeding usually lasts around 2 to 7 days. Menstruation stops occurring after menopause, which occurs between 45 and 55 years of age. Periods also stop during pregnancy and typically do not resume during the months of breastfeeding. Up to 80% of women report having some symptoms prior to menstruation, common signs and symptoms include acne, tender breasts, bloating, feeling tired, irritability, and mood changes. These may interfere with life, therefore qualifying as premenstrual syndrome. In 3 to 8%, symptoms are severe, a lack of periods, known as amenorrhea, is when periods do not occur by age 15 or have not occurred in 90 days. Other problems with the cycle include painful periods and abnormal bleeding such as bleeding between periods or heavy bleeding. Menstruation in other animals occurs in primates, such as apes and monkeys, as well as bats, the menstrual cycle occurs due to the rise and fall of hormones. This cycle results in the thickening of the lining of the uterus, the egg is released from an ovary around day fourteen in the cycle, the thickened lining of the uterus provides nutrients to an embryo after implantation. If pregnancy does not occur, the lining is released in what is known as menstruation, the first menstrual period occurs after the onset of pubertal growth, and is called menarche. The average age of menarche is 12 to 15, however, it may start as early as eight. The average age of the first period is later in the developing world. The average age of menarche has changed little in the United States since the 1950s, Menstruation is the most visible phase of the menstrual cycle and its beginning is used as the marker between cycles. The first day of bleeding is the date used for the last menstrual period. The typical length of time between the first day of one period and the first day of the next is 21 to 45 days in young women, the medical definition of menopause is one year without a period and typically occurs between 45 and 55 in Western countries
23.
IBM
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International Business Machines Corporation is an American multinational technology company headquartered in Armonk, New York, United States, with operations in over 170 countries. The company originated in 1911 as the Computing-Tabulating-Recording Company and was renamed International Business Machines in 1924, IBM manufactures and markets computer hardware, middleware and software, and offers hosting and consulting services in areas ranging from mainframe computers to nanotechnology. IBM is also a research organization, holding the record for most patents generated by a business for 24 consecutive years. IBM has continually shifted its business mix by exiting commoditizing markets and focusing on higher-value, also in 2014, IBM announced that it would go fabless, continuing to design semiconductors, but offloading manufacturing to GlobalFoundries. Nicknamed Big Blue, IBM is one of 30 companies included in the Dow Jones Industrial Average and one of the worlds largest employers, with nearly 380,000 employees. Known as IBMers, IBM employees have been awarded five Nobel Prizes, six Turing Awards, ten National Medals of Technology, in the 1880s, technologies emerged that would ultimately form the core of what would become International Business Machines. On June 16,1911, their four companies were amalgamated in New York State by Charles Ranlett Flint forming a fifth company, the Computing-Tabulating-Recording Company based in Endicott, New York. The five companies had 1,300 employees and offices and plants in Endicott and Binghamton, New York, Dayton, Ohio, Detroit, Michigan, Washington, D. C. and Toronto. They manufactured machinery for sale and lease, ranging from commercial scales and industrial time recorders, meat and cheese slicers, to tabulators and punched cards. Thomas J. Watson, Sr. fired from the National Cash Register Company by John Henry Patterson, called on Flint and, Watson joined CTR as General Manager then,11 months later, was made President when court cases relating to his time at NCR were resolved. Having learned Pattersons pioneering business practices, Watson proceeded to put the stamp of NCR onto CTRs companies and his favorite slogan, THINK, became a mantra for each companys employees. During Watsons first four years, revenues more than doubled to $9 million, Watson had never liked the clumsy hyphenated title of the CTR and in 1924 chose to replace it with the more expansive title International Business Machines. By 1933 most of the subsidiaries had been merged into one company, in 1937, IBMs tabulating equipment enabled organizations to process unprecedented amounts of data, its clients including the U. S. During the Second World War the company produced small arms for the American war effort, in 1949, Thomas Watson, Sr. created IBM World Trade Corporation, a subsidiary of IBM focused on foreign operations. In 1952, he stepped down after almost 40 years at the company helm, in 1957, the FORTRAN scientific programming language was developed. In 1961, IBM developed the SABRE reservation system for American Airlines, in 1963, IBM employees and computers helped NASA track the orbital flight of the Mercury astronauts. A year later it moved its headquarters from New York City to Armonk. The latter half of the 1960s saw IBM continue its support of space exploration, on April 7,1964, IBM announced the first computer system family, the IBM System/360
24.
McAfee
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Intel Security Group is an American global computer security software company headquartered in Santa Clara, California, and the worlds largest dedicated security technology company. The company has been a wholly owned subsidiary of Intel since February 2011, on September 7,2016, Intel announced a strategic deal with TPG Capital to convert Intel Security into a joint venture between Intel and TPG Capital called McAfee. TPG Capital will be the majority owner with 51% of McAfee, the company was founded in 1987 as McAfee Associates, named for its founder John McAfee, who resigned from the company in 1994. McAfee was incorporated in the state of Delaware in 1992, Network Associates was formed in 1997 as a merger of McAfee Associates, Network General, PGP Corporation and Helix Software. The company restructured in 2004, beginning with the sale of its Magic Solutions business to Remedy, the FSA team also oversaw the creation of a number of other technologies that were leading edge at the time, including firewall, file encryption, and public key infrastructure product lines. While those product lines had their own individual successes including PowerBroker and it is fair to say that McAfee remains best known for its anti-virus and anti-spam product lines. On August 19,2010, Intel announced that it would purchase McAfee for $48 a share in a deal valued at $7.68 billion. On January 6,2014, Intel CEO Brian Krzanich announced during the Consumer Electronics Show the name change from McAfee Security to Intel Security, the companys red shield logo will remain and the firm will continue to operate as a wholly owned Intel subsidiary. John McAfee, who no longer has any interest in the company, I am now everlastingly grateful to Intel for freeing me from this terrible association with the worst software on the planet. These are not my words, but the words of millions of irate users, however, as of 2016 the products still bear the name McAfee. McAfee products are primarily digital security tools for personal computers and server devices, Stonesoft acquisition On July 8,2013 McAfee completed the tender offer for Finnish network firewall design company Stonesoft Oyj worth $389 million in cash, or about $6.09 a share. The Next Generation Firewall business acquired from Stonesoft was divested to Forcepoint in January 2016, ValidEdge acquisition On February 26,2013 McAfee announced it had acquired the ValidEdge sandboxing technology. NitroSecurity solutions reduce risk exposure and increase network and information availability by removing the scalability, the acquisition closed on November 30,2011. The acquisition enables McAfee to extend its database security portfolio, the acquisition closed on April 6,2011. The acquisition allowed McAfee to complete its diversification into the mobile security space, the acquisition closed on August 25,2010. Trust Digital acquisition On May 25,2010, McAfee announced an agreement to acquire Trust Digital. The acquisition allowed McAfee to extend its services beyond traditional endpoint security, the acquisition closed on June 3,2010. The price for Trust Digital was not disclosed MX Logic acquisition On July 30,2009, McAfee announced plans to acquire managed email, the acquisition provided an enhanced range of SaaS-based security services such as cloud-based intelligence, web security, email security, endpoint security and vulnerability assessment
