How to Melt Aluminum Cans at Home

Aluminum is a common and useful metal, known for its corrosion resistance, malleability, and for being lightweight. Its safe enough to be used around food and in contact with skin. Its much easier to recycle this metal than it is to purify it from ores. You can melt old aluminum cans to get molten aluminum. Pour the metal into a suitable mold to make jewelry, cookware, ornaments, sculptures, or for another metalworking project. Its a great introduction to home recycling. Key Takeaways: Melt Aluminum Cans Aluminum is an abundant and versatile metal that is easily recycled.The melting point of aluminum is low enough that it can be melted with a hand-held torch. However, the project goes more quickly using a furnace or kiln.Recycled aluminum can be used to make sculptures, containers, and jewelry. Materials for Melting Aluminum Cans Melting cans is not complicated, but its an adult-only project because high temperatures are involved. Youll want to work in a clean, well-ventilated area. Its not necessary to clean the cans before melting them since organic matter (plastic coating, leftover soda, etc.) will burn off during the process. Aluminum cansSmall furnace of the electric kiln (or another heat source that reaches the appropriate temperature, such as a propane torch)Steel crucible (or other metal with a melting point much higher than aluminum, yet lower than your furnace—could be a sturdy stainless steel bowl or a cast iron skillet)Heat-resistant glovesMetal tongsMolds into which youll pour the aluminum (steel, iron, etc.—be creative) Melting the Aluminum The first step youll want to take is to crush the cans so that you can load as many as possible into the crucible. Youll get about 1 pound of aluminum for every 40 cans. Load your cans into the container youre using as a crucible and place the crucible inside the kiln. Close the lid.Fire up the kiln or furnace to 1220 °F. This is the melting point of aluminum (660.32  °C, 1220.58  °F), but below the melting point of steel. The aluminum will melt almost immediately once it reaches this temperature. Allow half a minute or so at this temperature to assure the aluminum is molten.Put on safety glasses and heat-resistant gloves. You should be wearing a long-sleeve shirt, long pants, and covered toe shoes when working with extremely hot (or cold) materials.Open the kiln. Use tongs to slowly and carefully remove the crucible. Do not place your hand inside the kiln! Its a good idea to line the path from the kiln to the mold with a metal pan or foil, to aid in clean-up of spills.Pour the liquid aluminum into the mold. It will take about 15 minutes for the aluminum to solidify on its own. If desired, you can place the mold in a bucket of cold water after a few minutes. If you do this, use caution, since steam will be produced.There may be some leftover material in your crucible. You can knock the dregs out of the crucible by slapping it upside down onto a hard surface, such as concrete. You can use the same process to knock the aluminum out of the molds. If you have trouble, change the temperature of the mold. The aluminum and mold (which is a different meta) will have a different coefficient of expansion, which you can use to your advantage when freeing one metal from another.Remember to turn off your kiln or furnace when youre done. Recycling doesnt make much sense if youre wasting energy, right? Did You Know? Re-melting aluminum to recycle it is far less expensive and uses less energy than producing new aluminum from the electrolysis of aluminum oxide (Al2O3). Recycling uses about 5% of the energy needed to make the metal from its raw ore. About 36% of aluminum in the United States comes from recycled metal. Brazil leads the world in aluminum recycling. The country recycles 98.2% of its aluminum cans. Sources Morris, J. (2005). Comparative LCAs for curbside recycling versus either landfilling or incineration with energy recovery.  The International Journal of Life Cycle Assessment, 10(4), 273–284.Oskamp, S. (1995). Resource conservation and recycling: Behavior and policy. Journal of Social Issues. 51 (4): 157–177. doi:10.1111/j.1540-4560.1995.tb01353.xSchlesinger, Mark (2006). Aluminum Recycling. CRC Press. p. 248. ISBN 978-0-8493-9662-5.

The History of Algebra - 916 Words

The History of Algebra The history of algebra has been around for several decades, this method of mathematics has been used during the beginning of time. The development of algebraic notation progressed through out three stages: the rhetorical stage, the syncopated stage, and the symbolic stage with which we are use to using in our daily usage of algebra. In ancient civilization math was used to help leaders to strategically form how their troops should be lined up for battle and help decide how to attack their enemies. Algebra was used in the many of these civilizations: Egypt, Babylon, Greece, India, Europe, and most parts of the Middle East. In Egypt, the Egyptians used mathematics which included Algebra to solve equivalent to a†¦show more content†¦They also were able to prove that the quadratic equations have two roots, and included the negative as irrational roots. The Hindus used the astrology and astronomy to help determine directions in which they should live their lives as if it was an almanac. The Hindus used this method of algebraic equations to determine directions, farming, and behavior among their peers. The Arabs in the Middle East helped improve the Hindus number symbols and was able to adopted the same method of algebraic reasoning as the Greeks they reject the negative solutions that the Hindus were using and would solve the quadratic equations by recognizing two solutions, possibly irrational. The algebra of the Arabs in the Middle East was entirely rhetorical and like the Hindus, the Arabs worked freely with irrationals. The Arabs used and improved the Hindus number symbols and the idea of positional notation. These numerals (the Hindu-Arabic system of numeration) which are used throughout the world today, however the Arabs contribution to the methods that are used in algebra is the solution of cubic equations by geometric methods involving the intersection of conics. In the 16th century of the European nations there were great theories about algebra, they rejected the method that negative numbers could be used in an algebraic equation and many of the mathematicians would q uickly accepted zero as a number butShow MoreRelated history of algebra Essay1199 Words   |  5 Pages Unlike geometry, algebra was not developed in Europe. Algebra was actually discovered (or developed) in the Arab countries along side geometry. Many mathematicians worked and developed the system of math to be known as the algebra of today. European countries did not obtain information on algebra until relatively later years of the 12th century. After algebra was discovered in Europe, mathematicians put the information to use in very remarkable ways. Also, algebraic and geometric ways of thinkingRead MoreThe History Of Algebra, How It Started, The Most Study Mathematical Subject Around The World1750 Words   |  7 PagesThis paper will show the history of algebra, how it started, and how it grew to be what it is today. It will show that it started it developments from the basic arithmetic operations that first were used to solve simple addition, subtraction, multiplication, and division and how it went incorporating more operations that permitted it to solve problems that involve abstract concepts. It will show that the recorded history begins mostly with the Egyptian papyrus, and how it went passing from one civilizationRead MorePlan-Do-Study-Act (Pdsa): the Deming Cycle906 Words   |  4 Pagesstudents to complete End-of-Course exams at the completion of English 1, Physical Science, U.S. History, and Algebra 1. 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After some time â€Å"Finger reckoningRead More The Important Role of Mathematicians in Society Essay1653 Words   |  7 PagesImportant Role of Mathematicians in Society Thesis Statement This report will focus on the professional field of mathematicians. It will highlight some of the history, responsibilities, opportunities, and requirements of this occupation. Outline I.nbsp;nbsp;nbsp;nbsp;nbsp;Introduction A.nbsp;nbsp;nbsp;nbsp;nbsp;A condensed history of mathematics B.nbsp;nbsp;nbsp;nbsp;nbsp;Famous mathematicians and their accomplishments II.nbsp;nbsp;nbsp;nbsp;nbsp;Body A.nbsp;nbsp;nbsp;nbsp;nbsp;OpportunitiesRead MoreThe Contributions Of Islamic Mathematicians1329 Words   |  6 Pagesmathematicians, with particular attention to The Father of Algebra and his contributions. As the reader will notice, the contributions of Islamic mathematicians reached the major branches of mathematics of their era by building upon the work of mathematicians of other cultures and leaving detailed records of their achievements and those of cultures past. Key-Words: - Al-khwarizmi, algebra, Khayyam, Al’Kashi. 1 Introduction Although world history books have documented the period of the Dark Ages inRead MoreEssay Boolean Logic1555 Words   |  7 PagesBoolean Logic Many of our computer databases utilize boolean logic as the basis of querying the database. Boolean logic has a much older history than most computer users imagine. It is helpful to understand the background and theory behind this concept, because this theory is the foundation on which contemporary computer science and information technology has been built. George Boole was an English mathematician. Born in 1815, he had no formal higher education, but had a natural gift for mathematicsRead MoreThe Common Core State Standards982 Words   |  4 Pagesat the Common Core State Standards’ stance on algebra, which is taught in the eighth grade. According to the Common Core, students who take algebra can become familiar with more complex math courses as they progress through school, and will have more knowledge when they enter college. However, the infographic points out that childhood brain development tends to plateau in the eighth grade, which makes it harder to learn and retain new concepts. Algebra at an early age can discourage students and leadRead MoreThe Benefits of a Liberal Arts Education797 Words   |  3 Pagesrelationships and similarities making innovations more attainable. The reason algebra is so conveniently practical in relation to science, for example, is because it was developed as a tool for science. Algebra, as it is, would not be existent were it not for Diophantus, the Greek scholar who developed algebra. He was likely aware what his studies meant for future generations, mathematical and scientific alike (OConnor, Robertson). Algebra serves society through science and its accomplishments. From nuclearRead MoreInstructional Sequence Is Useful For Teachers Of Secondary Mathematics Learners1485 Words   |  6 Pagesit is important for teachers to be aware of it and use it in their classroom. Description of Strategy Graduated instructional sequence is useful for teachers of secondary mathematics learners. Especially helpful for those having difficulty in algebra, this strategy is potentially more effective on those who struggle with conceptual understanding of numbers, symbols, and the relationship between them. However, it is useful for teaching fractions, percentages, geometry, and many other concepts as

What Are Sheet-Molding Compounds (Smc) Bulk-Molding Compounds (Bmc) Free Essays

(5). a) What are sheet-molding compounds (SMC)? Bulk-molding compounds (BMC)? Sheet-molding compound (SMC) is a fiber glass reinforced thermosetting compound in sheet form, usually rolled into coils interleaved with plastic film to prevent auto adhesion. Made by dispensing mixed resin, fillers, maturation agent, catalyst and mold release agent onto two moving sheets of polyethylene film. We will write a custom essay sample on What Are Sheet-Molding Compounds (Smc)? Bulk-Molding Compounds (Bmc)? or any similar topic only for you Order Now The lower one also contains chopped glass roving or glass mat. SMC can be molded into complex shapes with little scrap. Sheet molding compound (SMC) is fiberglass reinforced composite material, produced in a â€Å"sheet† format Bulk-molding compound (BMC) is a combination of chopped glass strands and  Resin  in the form of a bulk  pre-preg. BMC is suitable for either compression or injection molding. Injection molding of BMC is used to produce complex components such as electrical equipment, car components, housings for electrical appliances and tools, in large industrial volumes. Unlike SMC, it is not necessary to include a maturation stage. Consequently, BMC pre-preg formulations contain higher filler contents. The chopped glass strands vary in length depending on the level of performance required. Reinforcement content generally ranges between 15 and 20 percent; however, it may reach 25 percent for the highest performance. BMC uses lower reinforcement content than SMC and permits higher filler loadings with lower costs. b) List FOUR (4) types of the forms in which reinforcement fibers appear in composite materials? Based on the form of reinforcement, common composite materials can be classified as follows: 1. Fibers as the reinforcement (Fibrous Composites) a. Random fiber (short fiber) reinforced composites b. Continuous fiber (long fiber) reinforced composites 2. Particles as the reinforcement (Particulate composites) 3. Flat flakes as the reinforcement (Flake composites) 4. Fillers as the reinforcement (Filler composites) c) Describe the problems involved in recycling products made from reinforced plastics. The main problems are that recycling usually requires the use of a single type of material, and that some plastics (mainly hard and brittle polymers) are more difficult to chop into small pieces for further processing than others. With reinforced plastics, this requires that the reinforcement be separated from the matrix, a very difficult task and uneconomical task. Note that matrices are often thermosets, so it is not practical to melt the matrix and separate the fibers from a molten phase. How to cite What Are Sheet-Molding Compounds (Smc)? Bulk-Molding Compounds (Bmc)?, Papers

Contingent Convertible Capital Structure -Myassignmenthelp.Com

Question: Discuss About The Contingent Convertible Capital Structure Decisions? Answer: Introduction Rivett, Australia. The company carries on the activities related to exploration of the mineral resources in Australia. The company primarily explores for the copper, silver, lead, gold, Zinc, Uranium, Platinum, thorium, earth elements and other metal in south Australian auditing South Wales (Capitalmining.com.au 2018). Ownership structure Major substantial shareholders More than 20% shareholding among the shareholders of the company no one is holding greater than 20% shares More than 5% holding of shares HSBC Custody Nominees Australia Ltd falls under the substantial shareholder as out of total shares it holds 80,000,000 shares that is, 5.28% (Capitalmining.com.au 2018). Name of main people Chairman Robert McCauley Board members Peter Torney Non-executive director Anthony Dunlop Non-executive director Peter Dykes Non-executive director Robert McCauley Executive Director James Ellingford Non-executive Director CEO Robert McCauley (Capitalmining.com.au 2018). Key ratios Return on assets (ROA) = (NPAT / Total Assets) Return on Equity (ROE) = (Net profit after tax / Ordinary equity) Debt ratio = Total liabilities / Total assets EBIT/TA * NPAT/EBIT * TA/OE = NPAT/OE EBIT/TA * NPAT/EBIT * TA/OE = -37,36,555/37,70,735 * -37,36,555/-37,36,555* 37,70,735/35,16,843 = -1.06 NPAT/OE = -37,36,555 / 35,16,843 = -1.06 Hence, it can be proved from the above that EBIT/TA * NPAT/EBIT * TA/OE = NPAT/OE Phenomenon of TA/OE It analyses the insolvency risk and leverage level of the company with the help of the total assets as compared to the owners equity. It also present the percentage of asset held by the shareholders of the company. If the ratio goes up it represent that the companys equity portion will go down and debt portion will go up (Scholes 2015). Therefore, the company may reach to unsustainable level as additional debt will increase the interest cost and will deteriorate the financial status of the company. However, various factors on which the ratio depends are industry status, present economic scenario and the assets and liability of the company. Reasons why ROE being higher than ROA The biggest factor that segregates the ROE and ROA is the financial leverage or the debt. The fundamental equation of balance sheet that is (Assets = Liabilities + Equity) represent that if the company has no debt then the total asset will be equal to total equity which in turn will increase the ROE. Apart from that, when debts are available at the rate that is lower than ROA it will increase ROE (Albul, Jaffee and Tchistyi 2015). Therefore, the interest is lower against ROA, will results into higher ROE ASX website information Monthly stock movement 2 years time period Stock movement graph Report on stock movement Looking at the above stocks movement, it is recognized that the stock of Capital Mining Limited before 2 years though started from 0.08, it fell to 0.005 that is almost to zero over the times of 2 years. It has sharp downward moving trend and will be considered as volatile. However, marketing stocks of All Ordinary Stock slowly moving upward and will be considered less volatile as compared to Capital Mining Limited. The correlation among 2 stocks are computed as -0.807. Therefore, the stocks are negatively correlated (Titman, Keown and Martin 2017). Recent announcement The company started the drilling at Scotia Cobalt Nickel Project in the Eastern area of Goldfields of WA. It is expected that the acquisition of the project will increase the share price of the company as the performance of the company will be improved. Peter Torney and Mr. Anthony Dunlop agreed to the termination from their agreement and role. There are 2 risks associated with the stock of Capital Mining Limited. 1st risk is can be diversified through investing in other stock and the 2nd one cannot be diversified as it is the market risk. Stock field Beta of Capital Mining Ltd is 2.41 Risk free rate = Rf = 4%, Market risk premium = Rm = 6% Therefore, required rate of return of the companys share = R = Rf + ( Rm Rf ) R = 4% + 2.41* (6% 4%) = 4% + 4.82% = 8.82% Conservative investment The conservative investment is the investment that gives maximum return with lowest level of risk. Generally, the conservative investors are afraid of risk and do not want to take up higher level of risks. The other type of investors can be moderate, conservative, moderately aggressive and aggressive (Brooks 2015). The type of the investors can be assessed on the basis of their risk taking approaches. From above calculation it can be recognized that the risk association that is the beta of the company is 2.41 which is quite high. Therefore, the stock of the company is not a conservative investment. WACC (weighted average cost of capital) Computation of WACC WACC = E/V * Re +D/V * Rd * (1-Tc), Where, E/V = Equity percentage in the capital structure D/V = Debt percentage in the capital structure Re = Cost of equity Rd = Rate of debt Tc = corporate tax rate It is identified from the annual report of the company that they did not have any borrowing or debt in their capital structure. Therefore, the cost of equity of the company itself will be the WACC (weighted average cost of capital). The calculated cost of equity of the company is 8.82%. Therefore, WACC of Capital Mining Limited will be 8.82% Impact of higher WACC has on management evaluation Higher WACC represents that the stock of the company is associated with higher risk and the investors need more return to absorb the higher level of risk. Another factor represented by the higher WACC is that whether the stock is able to earn more return as compared to the WACC (HA Davis and Lleo 2015). However, the higher WACC is optimized through adjustment of debt component in the capital structure. Further, the higher level of WACC will reduce the value of the company. Optimal debt structure Optimal structure for capital It is the capital structure at which the value of the company is maximized at minimum cost. It can be identified from the above table that the debt ratio of the company for the year 2015 the debt ratio of the company is 73% whereas for 2016 it is 6.7%. Therefore, the debt ratio of the company is significantly high and for 2016 is low as the ratio around 40% is considered as idea (Peirson et al. 2014). Hence, it is suggested that if the company wish to raise additional fund it shall raise through debt and not through equity. Gearing ratio To adjust the gearing ratio the company paid off their obligations and reduced the liabilities from $ 11,91,065 to $ 253,892 over the years from 2015 to 2016. Further, they increased the equity from $ 14,410,056 to $ 21,221,826. However, directors report did not depict anything regarding this. Dividend policy As it can be found from the annual report of the company that the company did not earn any positive income during last 4 years, it did not pay or declare any dividend. Further, the directors did not recommend any dividend for the year ended 2016 (Marx 2013). Recommendation It can be suggested based on the above analysis that if the risk and return aspect of the stock is taken into consideration, the stock shall not be included under the investment portfolio. The reason is that the ROA and ROE both are in negative figures as the company could not earn positive income over last 4 years. Further, stock is involved with higher risk as the beta of the company is 2.41. Further, Reference Albul, B., Jaffee, D.M. and Tchistyi, A., 2015. Contingent convertible bonds and capital structure decisions. Brooks, R., 2015.Financial management: core concepts. Pearson. Capitalmining.com.au., 2018. Home. [online] Available at: https://www.capitalmining.com.au/ [Accessed 30 Jan. 2018]. HA Davis, M. and Lleo, S., 2015.Risk-Sensitive Investment Management. Marx, J. ed., 2013.Investment management. Van Schaik. Peirson, G., Brown, R., Easton, S. and Howard, P., 2014.Business finance. McGraw-Hill Education Australia. Scholes, M.S., 2015.Taxes and business strategy. Prentice Hall. Titman, S., Keown, A.J. and Martin, J.D., 2017. Financial management: Principles and applications. Pearson.

The Hamlet In Me Essays - Fiction, Characters In Hamlet, Literature

The Hamlet in Me Whether we are planning to build a boat or hoping to write a good essay, the only way to go about these tasks is to make a detailed plan of all the steps that need to be taken in order to get the desired result. If you spontaneously decide to build a boat, the result may be a plywood tub that leaks from all sides, let alone hold anyone in it. Hamlet, a seventh century story put to life through the amazing writing of Shakespeare, is a play that shows how meticulous and well thought out plans will bring about the desired result. The plays main character, Hamlet, is a Renaissance man that struggles with the corrupt world around him. He must deal with such issues like "blood for blood revenge" when his own uncle kills his father and takes his place as king. A ghost king appears to Hamlet and catalyzes the events that follow in the play. Hamlet must devise a plan to take revenge for his father and bring to justice all the people who have marred the situation. Though the church mandates through its moral code that Hamlet not take revenge, Hamlet tries to find the worst fate for his devious uncle possible: "Now might I do it, now he is a-praying, And now I'll do't and so he goes to heave?When he is drunk asleep, or in his rage, or in th' incestuous pleasure of his bed?Then trip him?And that his soul may be as damned and black As hell, whereto it goes" (3.4.77-100). Hamlet finally gains the nerve to kill his uncle, but sheaths his sword when he realizes that if he kills him while he is praying, his uncle will ascend to heaven. He ultimately decides to kill his uncle when he commits a sin, so that his soul "may be as damned and black as hell." He goes through a meticulous thought process, which shows him both his options and when to act to give his uncle the most cruel and horrible death he deserves. His actions also bring in a conflict between church and the revengeful calls of his families past. If he revenges his father's death then he wil l be damned to hell according to the church. Without Hamlet's patient and meticulous thought process he would not be able to outwardly expose the king of his wrong doings to Horatio: There is a play tonight before the King. One scene of it comes near the circumstance Which I have told thee of my father's death. I prithee,?Observe my uncle. Hamlet devises a well thought out plan of exposing the King's fault in his father's death. Hamlet uses the advantage of having a wonderful acting troop with him to put on a play for the King and other nobility that greatly resembles the circumstances in which Hamlet's father was killed. Hamlet's hard work is rewarded when the King storms out of the performance as a result of his own guilt and wrong doings. Hamlet also devised this plan to fully prove to himself that the ghost was a trustworthy advocate and not a damned spirit from hell, trying to disrupt and corrupt the Danish court. The through well thought out plans of Hamlet ultimately give him his revenge but also bring the consequence of death by the treachery he creates through the story. Like Hamlet, I use often a long thought process to plan projects that I wish to do. We both are not quick to act, but rather devise a plan to attain our goal. Spontaneous thinking can bring about undesired and sometimes deadly results. A careful thought process is a safer, but not as exhilarating and self-fulfilling way of confronting life without being spontaneous. A balance between the two thought processes would produce the most desirable result.

Mr. and Mrs. and More

Mr. and Mrs. and More Mr. and Mrs. and More Mr. and Mrs. and More By Mark Nichol This post details the permutations of abbreviations for courtesy titles. As mentioned in this post, mister developed as a variant of master. (Interestingly, the newer title came to pertain to married men, while master, once a title of respect for a social superior, was reserved for unmarried men and boys.) Originally, both master and mister were abbreviated Mr. before a person’s name as a courtesy title, but as master fell out of use, Mr. came to be applied solely as an abbreviation for mister. Mrs. was originally a generic abbreviation of mistress before a name, but it developed into a courtesy title specifically for a married or widowed woman, while Miss, with no abbreviation, was adopted as an honorific for unmarried women. Ms. began as a variant abbreviation of mistress as a courtesy title in the 1600s but fell out of favor. (At the turn of the twentieth century, it was proposed as a substitute form of address for a woman whose marital status is unknown, but the idea did not gain traction, nor did the abbreviation catch on fifty years later when a couple of business publications brought the issue up again. However, after feminist and journalist Gloria Steinem adopted the abbreviation as the title of a new magazine for women in 1972, its use quickly spread.) Because no native plural form of Mr. or Mrs. developed in English, the French abbreviations Messrs. (Messieurs) and Mmes. (Mesdames) were borrowed; Mses. developed in imitation, and the plural form of Miss, Misses, like the singular form, did not acquire an abbreviation. Because of the decline in use of such honorifics, the plural forms are rarely seen anymore. As a reference to a man who embodies a certain quality, Mr. appears in such references as â€Å"Mr. Right† (the ideal man for a woman to marry) or â€Å"Mr. Big† (a man of significant authority and/or status). Missus, a derivative of mistress based on a casual pronunciation of the latter word, and Miz, a spelling based on the pronunciation of Mrs. or Miss in the southern United States, should generally be used only in dialogue in historically or geographically appropriate fiction. However, â€Å"the Mrs.† or â€Å"the missus,† spelled as shown as humorous references to one’s wife, are appropriate in informal writing. Want to improve your English in five minutes a day? Get a subscription and start receiving our writing tips and exercises daily! Keep learning! Browse the Style category, check our popular posts, or choose a related post below:100 Mostly Small But Expressive Interjections"Confused With" and "Confused About"The Difference Between "Phonics" and "Phonetics"

A persuasive postion paper on Fast food, burger king VS McDonalds Essay

A persuasive postion paper on Fast food, burger king VS McDonalds - Essay Example Others would counter that the discerning diner will detect real differences between fast food franchises when flavor, promotions and dining experience are considered. As one of these discerning consumers, I feel considerable differences can be found when comparing two fast food franchises such as Burger King and McDonalds. McDonalds is truly a ground –breaking enterprise. Global in scope and backed by decades of success, this fast food giant has set the standard for all others for many years. This fact is apparent in McDonald’s popularity and profits (Associated Press). But like an old shoe that’s been worn too much, McDonald’s has a sole that is wearing thin. The greatest problem is flavor of the food. True, it has been consistent for many decades, but that’s the problem. While other eateries have been innovative in positive ways, McDonalds seems to be stuck in a flavor rut. They are constantly introducing new items, like burritos and iced coffee, but they just seem to taste like everything else they already sell. Perhaps this can be attributed to the predictability of the promotions McDonalds tend to run. Cheap plastic gizmos of the latest blockbuster movie for the kids and sweepstakes games like monopoly are old and tired. They just add to a dated feeling present on the menu and in the store. McDonalds seems to have kept none of the nostalgia that has made it a traditional favorite while at the same time not really moving forward with anything truly innovative for years. Burger King, on the other hand, has made great strides in producing outstanding flavor results on its menu. The best innovation isn’t really an innovation at all. They simply offer fresh tomatoes, lettuce and onions on all of their burgers as a standard feature. They haven’t started making new products. Instead, they focus on doing a better job on giving their existing products the best flavor possible. Burger King also offers fewer promotional items and the

The Woman's Role in the Islam Religion Essay Example | Topics and Well Written Essays - 2250 words

The Woman's Role in the Islam Religion - Essay Example val of Islam. Similar to other religious, Islam has stipulated a certain position of women in society including their role and social status. The Islam tradition goes back to the 7th century when the revelations transmitted to the Prophet Muhammad who emphasized Islam’s continuity with earlier Semitic traditions. During this period of time, the patriarchal nature of most Islamic societies reinforced the pervasive belief that Muslim women were more subject to the control of men than were women in most other societies. This control was dramatic in the case of Muslim women during the 7-10 centuries. They were secluded immediately upon marriage; that was, they were removed from contact with men (other than relatives) and rarely allowed to move about in public. Islam stated that "marriage is the only road to virtue and that in marriage wives must be submissive and obey their husbands† (Roded 1999, p. 57). Girls generally married between the ages of ten and twelve. Scholars have argued that the definition of power should be broadened to include the invisible control of events by women, which gave them a certain stat us and position. In Muslim societies, kinship and lines of descent were important, and consequently women's power was most visible as they matured and developed the ability to influence the lives of others in their immediate kin and descent groups. In these societies, high-status aristocratic women in particular had power in their ability to influence the actions of their sons, husbands and other male relatives (Roded 1999). Quran and its laws had the profound impact n position and status of women in society and their relations with men. In general, Muslims affirm the Quran to be God's actual words; Muhammad is neither author nor editor, for no human agency influenced the formation of the text. Muhammad does not, therefore, function in the way, for example, the Evangelists do in Christianity. The Islamic tradition is reluctant to allow even this modicum of human involvement in the production of the Quran. Muhammad is not a partner but a go-between, chosen from among men to transmit verbatim God's Word communicated to him through the angel Gabriel. The role of women is to listen and obey, to live the life outlined for them in the revelation and the traditions, and made specific in the law. During the Middle Ages, the role of women in society did not change greatly affected by strict social laws and religious traditions. A blend of Islam and local cultural prescriptions shaped women's lives. In Muslim societies, the local culture was clearly patriarchal, making it difficult to distinguish what part of current culture came from Islam and what pre-Islamic influences remained (Roded 1999). The pre-Islamic record in Iran, Afghanistan and Iraq suggested important public and political roles for royal women. It was clear from historical accounts that the incorporation of Islam into the society profoundly changed the cultural, political, and social conditions under which women lived and worked. Prior to the coming of Islam, women of aristocratic origin had participated in public affairs (Nashat and Beck, 2003). Since the inception of the Islam religion, women were instructed to dress simply and modestly, while all men

Abnormal Psych DQ Questions Essay Example | Topics and Well Written Essays - 500 words

Abnormal Psych DQ Questions - Essay Example The low functional levels due to the profound mental retardation makes it difficult to assess for the key characteristics of autism and so diagnostic instruments are likely to throw up spurious results. This makes diagnosis of autism a challenge and calls for clinical experience (Brasic, 2006). Autism was initially believed to be associated with higher social classes, but is now known to afflict all social classes in an equal manner. Motion abnormalities are a striking feature of autism and may provide the means for the identification of autism in early infancy, prior to the other manifestations. In children the motion anomalies demonstrated are also highly characteristic and can be easily identified. An example of such an abnormal motion typical to autism is the placing of the hand with fingers outstretched by the child before the eyes, with rapid back and forth movement. This action of the child is considered as self-stimulation, as it produces a visual sensation. Many of such abnormal motions typical to autism appear like attempts to provide sensory input to the self in barren environments (Brasic, 2006). The cause of autism still remains unknown, but there are several hypotheses that include exposure to toxic agents and infections, and possibly vaccinations for diseases like measles, mumps and rubella. The treatment of autism is essentially directed towards the associated behavioral problems and so includes intensive behavioral, educational, and psychological components. The use of serotonin in the treatment of autism is under investigation. The earlier the diagnosis and use of intervention strategies the more favorable the outcome and so regular screening of infants and toddlers for signs and symptoms of the disorder is useful (Brasic, 2006). The definition of oppositional defiant disorder (ODD) provided by the American Psychiatric Association’s Diagnostic and Statistical Manual, Fourth Edition (DSM IV) is that it is â€Å"a recurrent

Aetiology of Gestational Diabetes Mellitus

Aetiology of Gestational Diabetes Mellitus Abstract Gestational Diabetes is a condition present in the later stages of pregnancy where the mother has insulin resistance leading to glucose intolerance. The aetiology of Gestational Diabetes Mellitus is largely unknown but several theories include autoimmune destruction of the beta cells, monogenic mutations and insulin resistance. In pregnancy it is normal for there to be some levels of insulin resistance and it is thought that the products of the placenta contribute to the state of insulin resistance as GDM usually subsides after pregnancy. GDM in pregnancy can lead to an increased risk of cardiovascular disease in the offspring such as hypertension and atherosclerosis. This is due to the increased levels of oxidative stress and inflammatory mediators present during pregnancy. The placenta is very important as it is able to control and buffer the amount of glucose that is delivered to the fetus but if this level is too high then it is out of the placentas control and the fetus may have increased rate of growth due to this extra glucose. The current focus of research in this area seems to be into finding ways to diagnosis GDM earlier in the pregnancy and to try and reduce the amounts of oxidative stress. Gestational diabetes: consequences for fetal programming of vascular disease in adulthood Introduction Gestational Diabetes Mellitus (GDM) occurs when there is a glucose intolerance that is first detected during pregnancy. It is a form of hyperglycaemia (Buchanan and Xiang 2005). The aetiology of the condition is unknown but there have been many suggestions as to the cause of it, including autoimmune destruction of the ß pancreatic cells and the possibility of a genetic predisposition to the condition. Hormones that are produced in pregnancy help contribute to the insulin resistant state which characterises diabetes. In recent years, there has been an increase in the cases of Obesity and this is a risk factor for both Diabetes Mellitus and Cardiovascular Disease. The intrauterine environment can affect fetal programming and development. This essay will look into how the placenta and its products can affect the insulin resistant state and how this resistance effects programming as well as the role of oxidative stress and inflammation in making the offspring more susceptible to cardi ovascular disease. Gestational Diabetes Mellitus (GDM) GDM is a state of insulin resistance which disturbs the intrauterine environment and can lead to accelerated fetal growth (Radaelli et al 2003).It effects approximately 7% of pregnant women with approximately 200,000 cases seen each year (Schillan-Koliopoulos and Guadagno 2006). The term GDM is applicable when the onset is during the second and third terms of the pregnancy, but it does not exclude the possibility that the insulin resistance was undiagnosed before the pregnancy. If this is the case and is found to occur in the earlier stages of pregnancy then the mother should be treated the same as mothers who are known to have diabetes before pregnancy (Metzger, Coustan 1998). There is a degree of insulin resistance in normal pregnancy which begins towards the middle of the pregnancy but during the later part of the second and the final trimester these can increase to levels of insulin resistance that are associated with type 2 diabetes (Yogev et al 2008 Chapter 10). Insulin resista nce is when the tissues do not produce a response to insulin due to problems with the secretion of insulin or where the tissues are desensitised to insulin and therefore lack the ability to produce a response (Catalano et al 2003). In a normal pregnancy, the mother changes her metabolism to allow a constant supply of nutrients to reach the fetus to support its rapid growth. Among these nutrients is glucose, which is the main energy source used by the fetus. During the later stages of pregnancy the mother becomes hypoglycaemic and although there is increased gluconeogenesis, the hypoglycaemia still occurs because there is a high rate of transport of glucose to the fetus (Herrera 2000 cited in Herrera and Ortega 2008). GDM can have effects that impact the development of the fetus such as hypoglycaemia and macrosomia, which is an increase in body weight and has the possibility of leading to problems when giving birth, such as shoulder dystocia (Schillan-Koliopoulos and Guadagno 2006). During the second trimester of pregnancy there is peripheral insulin resistance but there is also the possibility that hepatic insulin sensitivity is altered in pregnancy, although few studies confirm this. By the end of the pregnancy the levels of insulin that are circulating are thought to be double those at the start (Redman 2001). Insulin Resistance Insulin resistance in GDM can occur in two forms. The first is where it develops in late pregnancy and it has been postulated that there is a post-receptor mechanism that may influence the insulin signalling pathway which leads to a reduced glucose uptake. The second form is where there is already a degree of resistance before the pregnancy but the changes that occur in normal pregnancy aggravate this (Metznger et al 2007). The insulin resistance that develops in pregnancy is much needed to allow the flow of nutrients, from the mother, directly to the fetus to allow for growth (Radaelli 2003). Increased insulin resistance leads to an increase in insulin secretion by the ß pancreatic cells (Buchanan and Xiang 2005). The insulin resistance is thought to be caused by increased adiposity and as the insulin resistance usually stops after pregnancy this suggests that there is a possibility that the products of the placenta are a potential cause of the resistance. During the course of th e pregnancy the actual changes in glucose levels are very small. It would be assumed that the glucose levels would rise due to the increased insulin resistance but the pancreatic ß cells increase their secretion of insulin to maintain homeostatic glucose levels (Yogev et al 2008 Chapter 10). GDM occurs because there is an increased demand for insulin which under normal circumstances can be met unless there are problems with the secretion of insulin leading to the development of hyperglycaemia. The majority of mothers who develop GDM have been discovered to have a degree of insulin resistance before they became pregnant. Therefore, with the insulin resistance that occurs in normal pregnancy it can be said that GDM occurs with a greater insulin resistance than normally present in gestation (Yogev et al 2008 Chapter 10). Insulin resistance causes a decreased uptake of glucose into skeletal muscle, adipose tissue and liver as well as a decreased production of hepatic glucose. (Catala no et al 2003). One suggestion for insulin resistance looks into the possible role of the mitochondria. Studies using Magnetic Resonance Spectroscopy (MRS) have shown that in normal offspring of parents with type 2 diabetes, there is an increased amount of intramyocellular lipid. This has been shown to cause a reduced function in mitochondria which suggests that mitochondrial dysfunction may play a part in insulin resistance (Petersen et al 2004 cited in Morino et al 2005). It has been suggested that this increase in intramyocellular lipid activates a serine kinase cascade which causes an increase in the Insulin Substrate Receptor 1 (IRS-1), which inhibits insulin receptor phosphorylation on tyrosine sites. This can cause a decrease in the effects and utilisation of glucose. One study showed that in the insulin resistant offspring the mitochondrial density was reduced by just over a third to that of a normal offspring. This suggests that offspring who are insulin resistant may inher it a condition that causes a reduction in rate oxidative phosphorylation in mitochondria (Griffin et al 2009 cited in Morino et al 2005). Detection of GDM Diagnosis of GDM helps to identify pregnancies that are at risk of fetal morbidity as well as obesity and glucose intolerance in the offspring (Buchanan and Xiang 2005). GDM is hard to diagnose as it is asymptomatic. Normal diabetes could be diagnosed by glycosuria but in pregnancy the renal threshold to glucose is lowered so that glycosuria doesnt give a true representation of hyperglycaemia (Redman 2001). There are several risk factors of GDM which can be classified into three groups and help in the screening process. Low risk factors include women who are younger than 25, normal weight at conception, no known family members with diabetes and no history of glucose intolerance. High risk factors include obesity of the mother, diabetes in close relatives, a history of glucose intolerance, current glycosuria and previous pregnancies with GDM (Metzger and Coustan 1998 Chapter 25). Causes of Diabetes There are several theories as to why diabetes occurs and this has been thought to be similar to the underlying mechanisms that cause gestational diabetes. Diabetes is a result of pancreatic beta-cell dysfunction which can present in three main ways: autoimmune, a genetic cause and on top of already present insulin resistance (Buchanan and Xiang 2005). Autoimmune diabetes accounts for approximately 5-10% of all diabetic cases (American Diabetes Association 2010). There are circulating antibodies to the ß cells of the Islet of Langerhans. In GDM, there are a small number of women who have with these antibodies present in their circulation. It is thought that these cases present with GDM due to problems with insulin secretion caused by destruction of the Islets by the autoantibodies (Buchanan and Xiang 2005). This form is similar to type 1 diabetes. The Islet Cell Autoantibodies (ICA) have been shown to have four major molecular targets: Insulin, Glutamic acid decarboxylase (GAD 65), Insulinoma-associated antigen-2 (IA-2) and Zinc Transporter 8 (ZnT8) (Tree 2010). Monogenic diabetes has 2 general forms, one where there are mutations in autosomes and the other where there are mutations in the DNA of mitochondria. The first form is commonly referred to as Maturity Onset Diabetes of the Young (MODY). In both cases onset tends to be at a young age and the patient doesnt present with insulin resistance or obesity (Buchanan and Xiang 2005). Mutations that cause MODY have been found in some women with GDM and commonly occur in genes coding for glucokinase, hepatocyte nuclear factor and insulin promoter factor, MODY is associated with beta cell dysfunction (Weng et al 2002). Chronic insulin resistance with beta-cell dysfunction seems to be the most common cause of GDM. As mentioned before there is an increase in insulin resistance in normal pregnancy but if this develops with background insulin resistance then there is an even greater insulin resistance which can lead to GDM. An established suggestion is that women who are unable to increase their secretion of insulin to cope with the insulin resistance developed in late pregnancy are more susceptible to developing GDM (Buchanan and Xiang 2005). However there could be various environmental processes that are involved in the underlying pathophysiology of GDM. The products of the placenta may also have a role in increasing or decreasing insulin resistance and these will be discussed later. Placental Function The placenta is an organ that has many roles during the development of the fetus. One of these functions is that it acts as a barrier to separate the maternal and fetal surfaces such that the syncytiotrophoblast surface exposes the placenta to the maternal circulation and the endothelium is exposed to the fetal circulation. This position between the two circulations means that the placenta is influenced by molecules from both circulatory systems, including cytokines, hormones and growth factors. The placenta produces molecules which can separately affect the maternal and fetal circulation and it expresses a large number of cytokines including leptin, resistin and tumour necrosis factor. However it has been discovered that these molecules are also produced by adipocytes. All molecules that are going from the mother to the fetus have to cross the placenta. Here they are either modified, for example lipids or like glucose, they are metabolised for placental purposes (Desoye et al 2008). The placenta plays an important role in fetal growth and the regulation of pregnancy (Giachini 2008). The placenta acts to sustain normal homeostatic levels and to carry out the functions of the vital organs. It also provides an immunological defence to the fetus and allows the exchange of molecules vital to its development (Jansson and Taylor 2007). Placental Development Approximately 4-5 days after conception, the process of cleavage causes rapid cell divisions and one of the groups of cells to form are called trophoblast cells. Further developmental processes form the blastocyte which is surrounded by an outer layer of the trophoblast cells. As the pregnancy progresses, the trophoblast cells develop into the placenta while the inner parts of the blastocyte form the embryo and umbilical cord (Huppertz 2008). The blastocyte implants itself onto the epithelium of the uterus where it differentiates into a syncitiotrophoblast which is able to implant itself in the epithelium leading to it being embedded into the decidual part of the uterus (Huppertz 2008). After the attachment of the blastocyte, the trophoblast layer divides very quickly and changes into 2 layers; the inner cytotrophoblastic layer and the outer syncytiotrophoblastic mass (Gude et al 2004).The whole implantation process takes 12 days to complete and after this the fetus is fully embedded into the endometrial layer (Huppertz 2008). The chorionic plate is the surface of the placenta that faces the fetus and this is where the umbilical cord inserts. The basal plate is the surface that faces the mother which contains many types of cells including immune cells such as macrophages and killer cells to carry out the placentas immunological function. The maternal basal plate and the fetal chorionic plate converge to form the smooth chorion which is composed of three layers (Huppertz 2008). When the trophopblast invades the endothelium there is a remodelling of the uterine spinal arteries which is necessary to ensure that the fetus and the placenta receive an adequate blood and nutrient supply and is able to remove any waste materials. This direct supply of blood and nutrients to the placenta can define it as being haemochorial villous organ (Gude et al 2004). After the rapid divisions of the trophoblast and development into 2 layers there are two pathways that can occur, th e villous and extravillious pathways. The extravillious pathway results in the trophoblast being able to invade into the decidua and cause the remodelling of the uterine arteries to increase blood supply to the placento-fetal unit. The villious pathway has a transportation function as well as having endocrine and protective functions (Gude et al 2004). Normal Placentation Placentation involves the structure and function of the placenta. The process of placentation is helped by the composition and arrangement of the extracellular matrix (ECM) of the endometrium. Studies on rats induced with diabetes provided results that showed that diabetes has an effect on the distribution of the ECM molecules. This study by Giachini et al illustrates that Types I and III collagen as well as other molecules, such as proteoglycan molecules decorin and biglycan were distributed throughout normal and diabetic placentas. It was shown that diabetes affects the expression of fibronectin and an increase in deposition of fibronectin may cause changes to the ECM structure which could affect the transfer of molecules from the mother to the fetus. One way in which changes in the ECM can be overcome is to test blood glucose levels frequently during the pregnancy and if kept in normal ranges this can dramatically decrease the prevalence of diseases and disorders present in the fe tus (Giachini et al 2008). As the pregnancy progresses the size of the placenta increases which also means an increase in the amount of products that the placenta produces therefore increasing in the insulin resistance (Schillan-Koliopoulos and Guadagno 2006). This is because the net effect of the products of the placenta is to increase insulin resistance. The increase in size of the placenta means that it needs an increased blood supply. Failure of the mother to increase its blood supply to the placenta can lead to placental insuffiency which if exacerbated can be attributed to be a cause of intrauterine growth restriction (IUGR). This growth restriction is more related to poor maternal nutrition rather than to a cause of GDM. GDM have been associated with an increased fetal and placental weight (Jansson and Taylor 2007). One of the reasons why GDM and increased insulin resistance affects the fetus is that while glucose can cross the placenta, insulin is unable to. This means that the fetal pancreas has to compensate by producing more insulin to prevent high blood glucose levels. The fetal pancreas is capable of doing this and the liver responds to the higher levels of insulin by increasing its production of glucose (Schillan-Koliopoulos and Guadagno 2006). Offspring who have an increase in birth weight have been shown to be at risk of developing cardiovascular disease and diabetes later in life. The main risk factor for this is poor transfer of nutrients via the placenta (Jansson and Taylor 2007). How dramatic these changes are depends on how good the control of blood glucose levels have been during the development of the placenta, if any treatment has been received and if there were any periods of away from normal glucose levels (Desoye 2006). How does diabetes affect Placentation? Diabetic insults at the beginning of the pregnancy can have long last effects of the placenta. One of the roles of the placenta is that it is able to buffer excess maternal glucose which can help to keep the fetal glucose levels within range However if the insult lasts longer than the placenta is able to compensate for then excessive fetal growth may occur (Desoye Mouzon 2007). In diabetes there is endothelial dysfunction which can lead to vascular disease. The endothelial cells help to control the vascular tone of the smooth muscle lining the vasculature. They do this by producing substances that help to vasodilate the smooth muscle including Nitric Oxide, Prostacyclin and Endothelium-Derived Hyperpolarising Factor (EDHF). There have been several studies to suggest different mechanisms of how diabetes affects the endothelium including impaired release of these vasodilating molecules, faults with signal transduction and increased release of constricting mediators of the endothelium. The dysfunction of the endothelium in diabetes is thought to be caused by activation of protein kinase C (PKC) as well as increased oxidative stress, non-enzymatic glycation and an increased activation of the polyol pathway (De Vries et al 2000).The main reason why these effects occur is thought to be due the activation of the protein kinase C pathway and the increased oxidative stress. This can cause early damage to the development of vascular vessels (Roberts and Raspollini 2008). These mechanisms will be discussed later. The effect of hormones produced in pregnancy Pregnancy causes changes in the circulating hormones and cytokines which can all have different effects on insulin resistance and this may help explain the mechanism underlying the resistance that is found in pregnancy and in GDM. Cytokines produced in pregnancy, such as TNF-a, Adiponectin and Leptin have been found to cause an increase in the insulin resistance (Gao et al 2008). In early pregnancy, the levels of oestrogen and progesterone rise but no net effect is seen as the two have antagonistic effects. Oestrogen increases the binding of insulin to its receptor whereas progesterone reduces the ability of insulin to bind (Ryan and Enns 1988). Cortisol levels in pregnancy increase so that by the end of the pregnancy the levels are three times that of what they were at the beginning (Gibson and Tulchinski 1980 cited in Yogev et al Chapter 10). Studies have shown that with increased amounts of cortisol there was a decrease in insulin sensitivity causing insulin resistance (Rizza et a l 1982 cited in Yogev et al 2008 chapter 10). During pregnancy the levels of prolactin increase up to ten times the normal amount (Yogev et al 2008 chapter 10). Studies have shown that in a culture of pancreatic beta cells, prolactin can cause an increase in levels of secreted insulin (Sorenson et al 1993 cited in Yogev et al 2008 Chapter 10). However, high levels of prolactin are not seen to be a pathological cause of GDM (Yogev et al 2008 chapter 10). Human placental lactogen (HPL) is a hormone, and its levels rise during the second trimester of pregnancy. This causes a decrease in the phosphorylation of insulin receptor substrate (IRS1) which can lead to significant insulin resistance (Ryan and Enns 2008 cited Yogev et al 2008 ch 10). Leptin is associated with obesity and concentrations of leptin have been shown to be related to the concentration of insulin in the plasma. In pregnancy the leptin levels increase dramatically. During pregnancy the mother uses her fat stores to supp ort fetal growth and it is thought that the leptin levels increase with the mobilisation of these fat stores. Leptin levels relate to the body mass of the individual (Sattar et al 1998). Placental Leptin is the same in structure and charge to the one produced by adipose tissue (Ashworth et al 2000). One study showed that high leptin concentrations in the umbilical cord increased the likelihood of developing fetal macrosomia (Wiznitzer et al 2000). It is also thought that leptin effects insulin sensitivity by effecting glucose metabolism in both skeletal muscle and in hepatocytes. Rats that received an external source of leptin were found to have an increase in gluconeogenesis which accounted for the majority of hepatic glucose production (Rossetti et al 1997). In GDM there is a greater secretion of TNF-alpha in response to glucose. TNF-alpha functions to regulate metabolism of glucose and lipids as well as being involved in insulin resistance. Many studies suggest that TNF-alpha is involved in the progression to GDM. They found that an increase in glucose cause the placenta and adipose tissue to increase production of TNF-alpha in some cases up to 4 times more than non-diabetic pregnant(Coughlan et al 2001). One study showed that the increases in the levels of TNF-alpha during pregnancy increased consistently with increases in body weight (Catalano et al cited in Yogev et al 2008). Adiponectin is a protein derived from adipose tissue and its function is to regulate insulin resistance and maintains levels of glucose. During pregnancy it has been found that its levels drop and could therefore lead to the increase insulin resistance found in GDM (Gao, Yang, Zao 2008). Adiponectin has also been found to decrease the secretion of TNF-alpha which as stated above can lead to insulin resistance (Hotamisligil 1999 cited in Yogev et al Chapter 10 2008). Adiponectin may cause increased insulin sensitivity as its concentration decreases throughout the gestational period ( Desoye and Mouzon 2007). Resistin is a protein that is produced by adipose tissue and is thought to be involved in insulin resistance in diabetes and is associated with obesity (Steppan and Lazar 2002) In pregnancy, resistin is secreted by the placenta and this secretion reaches its peak by the last trimester (Yura et al cited in Megia et al 2008). Studies show that TNF-alpha is an important factor in insulin resistance during pregnancy and with inputs from leptin and cortisol there is altered glucose metabolism whereas inputs from oestrogen, progesterone and prolactin had little significant effects (Kirwan and Mouzon 2002). There are many hormones produced during pregnancy, mainly by the placenta and adipose tissue that have varying affects but with the overall impact being insulin resistance. Inflammation in Diabetes There are genes in the placenta which regulate reorganisation of the endothelium and inflammatory responses and in GDM these were found to be altered. The increase in leptin receptors suggests that in the placenta this can cause proinflammatory responses (Radaelli 2003). One of the current theories is that the abnormal metabolic environment in GDM can lead to increased production of cytokines and inflammatory mediators. Molecules such as TNF-alpha, Resistin and Leptin increase during pregnancy and these increases in these inflammatory mediators produce metabolic changes by increasing insulin resistance (Desoye and Mouzon 2007). Leptin and TNF-alpha activate phospholipase A2 which are a family of eicosanoid precursors that go on to produce essential fatty acids such as w3 polyunsaturated fatty acids (Desoye Mouzon 2007). There has been a recent investigation which found that with increased adiposity at birth there has been an increase in w3 fatty acids in the placenta (Verastehpour et al 2005 cited Desoye and Mouzon 2007). As stated before, the placenta produces cytokines but it is also a site of action of the cytokines. It is the location of the receptors for these cytokines will influence if the cytokines act on the mother, the placenta or the fetus. With cytokines there is very little transfer across the placenta from mother to fetus and the origin of the cytokines in the fetus can be from either the placenta or from the fetus itself (Desoye and Mouzon 2007). Fetal Programming Many studies have highlighted the fact that events that occur while the fetus is developing can alter its developmental pathway and have adverse outcomes in later life. Fetal programming describes how the environment can affect certain developmental events of which the effects are permanent and can affect processes such as metabolism and the organisms physiology. Women with GDM have an increased risk of the fetus developing macrosomia (Catalano 2008 Chapter 11). The main factor that effects the growth of the fetus is the maternal environment and there is a strong association with the weight and height of the mother and the growth of the fetus such that mothers who are heavier and taller will produce heavy babies. (Love and Kinch 1965 cited in Catalano 2008 Chapter 11). The placenta and fetal programming The placenta is very important to the developmental processes of the fetus as it is able to change the quantity of signals and nutrients that the fetus receives. Deviation from normal would alter the fetal programming, thus making it more susceptible to disease in later life. Pregnancies that are complicated by GDM have excessive oxidative and nitrate stress which has been found to change the activity of certain proteins. Oxidative and nitrate stress alter the placentas function and may cause changes in the fetal programming. Nutrient transfer depends largely on the normal development of the vasculature to allow blood flow and this can be affected by GDM which can cause a decrease in the flow of substrates and is a mechanism in which fetal programming can be affected (Myatt 2006). Fetal programming involves a large amount of development plasticity and interruptions to this development may cause abnormalities in the development of certain cells which may progress to structural differe nces in organ development (Gluckman and Hanson 2004 cited in Jansson and Powell 2008 ref 16). Effects to the fetus exposed to GDM If a fetus is exposed to a diabetic environment during pregnancy then there can be certain long term effects. These effects can be classified into three groups; Anthropometric, Metabolic or Vascular and Neurological or Psychological. Anthropometric changes are concerned with the rates of growth for both height and weight and in a diabetic environment these can be excessive leading to macrosomia and obesity in later life. Metabolic and vascular changes that occur are abnormal glucose tolerance which can eventually lead to diabetes mellitus. Finally the neurological and psychological changes that can occur are usually minor but development of psychological and intellect can sometimes be deficient (Dabelea and Pettitt 2008). Potential problems that may arise with the fetus from an exposure to maternal diabetes include abnormal organ mass, altered angiogenesis and increased levels of fetal insulin (Fetita 2006). It has also been found that if there is an increase in weight during pregnan cy then there is usually a higher birth weight of the fetus (Humphreys 1954 cited in Catalano 2008 Chapter 11). The developing fetus cannot synthesise glucose and is dependent on the mother to produce it where it is transported to the fetus via facilitated diffusion through the placenta (Aerts et al 1996 cited in Mello, Parretti and Hod 2008). The result of decreased insulin sensitivity is that there is more glucose available to the developing fetus which can lead to a greater birth weight (Mello, Parretti and Hod 2008). Using animal models, it has been shown that exposure to high levels of glucose in utero can lead a diminished number of nephrons in the offspring (Amri et al 1999 cited in Fetita 2006 ref 68). This is important as nephrogenesis only occurs in the fetus and stops after birth (Gomez, Norwood 1999). It has been shown that a reduction in the numbers of nephron may affect the rate of progression of renal disease in adults due to an inability to secrete sodium. This may l ater develop into salt-sensitive hypertension (Brenner et al 1988). The mechanisms of reduced organ mass, high levels of fetal insulin and defects in angiogenesis may help explain how the fetus programs abnormal glucose tolerance in adulthood as a result of exposure to GDM (Fetita 2006). Transmission of diabetes from mother to offspring Exposure to gestational diabetes mellitus increases the risk of the fetus developing abnormal glucose tolerance which may develop into type 2 diabetes. (Fetita et al 2006). The association between greater incidences of the offspring having diabetes with a mother with GDM is greater than what would be predicted that could be passed on by maternal genetics (McLean et al 2006). One study showed that the phenotype for GDM/T2D was more common in daughters of mothers who were diabetic rather than daughters of fathers who were diabetic suggesting that the transmission is from mothers with GDM to their daughters. However there were limitations of the McLean study. Patients may not be aware of their fathers diabetes status due to men having lower inclinations to report symptoms and share illnesses with the family. One study showed that the mass of the pancreatic beta cells is relatively fixed by the end of fetal growth and this can be influenced by an intrauterine environment of hyperglycaema (McLean et al 2006). Congenital defects are more common in babies born to diabetic mothers (Farrel et al 2002 cited in Fetita et al 2006). There are many factors that can influence the prevalence of these malformations including the duration, severity and age of onset of GDM (Kousseff 1999). If the onset of GDM is at the beginning of development then development of some organs may be affected. However as said before, the majority of GDM develops during the second trimester. This can then lead to embryopathy which includes defects such as failure of neural tube closure and malformations in the Renal, Cardiac and Gastrointestinal systems which present in childhood (Fetita 2006). In diabetes the hexosamine pathway is activated and inhibits the pentose shunt pathway which decreases the production of antioxidants and therefore leads to an increase in oxidative stress. This oxidative stress has been found to disrupt gene expression and may contribute to congenital defects. One example is that oxidative stress inhibits a gene called pax-3 which is needed for neural tube closure and in diabetes there is an increased risk of neural tube defects (Horal et al 20 Aetiology of Gestational Diabetes Mellitus Aetiology of Gestational Diabetes Mellitus Abstract Gestational Diabetes is a condition present in the later stages of pregnancy where the mother has insulin resistance leading to glucose intolerance. The aetiology of Gestational Diabetes Mellitus is largely unknown but several theories include autoimmune destruction of the beta cells, monogenic mutations and insulin resistance. In pregnancy it is normal for there to be some levels of insulin resistance and it is thought that the products of the placenta contribute to the state of insulin resistance as GDM usually subsides after pregnancy. GDM in pregnancy can lead to an increased risk of cardiovascular disease in the offspring such as hypertension and atherosclerosis. This is due to the increased levels of oxidative stress and inflammatory mediators present during pregnancy. The placenta is very important as it is able to control and buffer the amount of glucose that is delivered to the fetus but if this level is too high then it is out of the placentas control and the fetus may have increased rate of growth due to this extra glucose. The current focus of research in this area seems to be into finding ways to diagnosis GDM earlier in the pregnancy and to try and reduce the amounts of oxidative stress. Gestational diabetes: consequences for fetal programming of vascular disease in adulthood Introduction Gestational Diabetes Mellitus (GDM) occurs when there is a glucose intolerance that is first detected during pregnancy. It is a form of hyperglycaemia (Buchanan and Xiang 2005). The aetiology of the condition is unknown but there have been many suggestions as to the cause of it, including autoimmune destruction of the ß pancreatic cells and the possibility of a genetic predisposition to the condition. Hormones that are produced in pregnancy help contribute to the insulin resistant state which characterises diabetes. In recent years, there has been an increase in the cases of Obesity and this is a risk factor for both Diabetes Mellitus and Cardiovascular Disease. The intrauterine environment can affect fetal programming and development. This essay will look into how the placenta and its products can affect the insulin resistant state and how this resistance effects programming as well as the role of oxidative stress and inflammation in making the offspring more susceptible to cardi ovascular disease. Gestational Diabetes Mellitus (GDM) GDM is a state of insulin resistance which disturbs the intrauterine environment and can lead to accelerated fetal growth (Radaelli et al 2003).It effects approximately 7% of pregnant women with approximately 200,000 cases seen each year (Schillan-Koliopoulos and Guadagno 2006). The term GDM is applicable when the onset is during the second and third terms of the pregnancy, but it does not exclude the possibility that the insulin resistance was undiagnosed before the pregnancy. If this is the case and is found to occur in the earlier stages of pregnancy then the mother should be treated the same as mothers who are known to have diabetes before pregnancy (Metzger, Coustan 1998). There is a degree of insulin resistance in normal pregnancy which begins towards the middle of the pregnancy but during the later part of the second and the final trimester these can increase to levels of insulin resistance that are associated with type 2 diabetes (Yogev et al 2008 Chapter 10). Insulin resista nce is when the tissues do not produce a response to insulin due to problems with the secretion of insulin or where the tissues are desensitised to insulin and therefore lack the ability to produce a response (Catalano et al 2003). In a normal pregnancy, the mother changes her metabolism to allow a constant supply of nutrients to reach the fetus to support its rapid growth. Among these nutrients is glucose, which is the main energy source used by the fetus. During the later stages of pregnancy the mother becomes hypoglycaemic and although there is increased gluconeogenesis, the hypoglycaemia still occurs because there is a high rate of transport of glucose to the fetus (Herrera 2000 cited in Herrera and Ortega 2008). GDM can have effects that impact the development of the fetus such as hypoglycaemia and macrosomia, which is an increase in body weight and has the possibility of leading to problems when giving birth, such as shoulder dystocia (Schillan-Koliopoulos and Guadagno 2006). During the second trimester of pregnancy there is peripheral insulin resistance but there is also the possibility that hepatic insulin sensitivity is altered in pregnancy, although few studies confirm this. By the end of the pregnancy the levels of insulin that are circulating are thought to be double those at the start (Redman 2001). Insulin Resistance Insulin resistance in GDM can occur in two forms. The first is where it develops in late pregnancy and it has been postulated that there is a post-receptor mechanism that may influence the insulin signalling pathway which leads to a reduced glucose uptake. The second form is where there is already a degree of resistance before the pregnancy but the changes that occur in normal pregnancy aggravate this (Metznger et al 2007). The insulin resistance that develops in pregnancy is much needed to allow the flow of nutrients, from the mother, directly to the fetus to allow for growth (Radaelli 2003). Increased insulin resistance leads to an increase in insulin secretion by the ß pancreatic cells (Buchanan and Xiang 2005). The insulin resistance is thought to be caused by increased adiposity and as the insulin resistance usually stops after pregnancy this suggests that there is a possibility that the products of the placenta are a potential cause of the resistance. During the course of th e pregnancy the actual changes in glucose levels are very small. It would be assumed that the glucose levels would rise due to the increased insulin resistance but the pancreatic ß cells increase their secretion of insulin to maintain homeostatic glucose levels (Yogev et al 2008 Chapter 10). GDM occurs because there is an increased demand for insulin which under normal circumstances can be met unless there are problems with the secretion of insulin leading to the development of hyperglycaemia. The majority of mothers who develop GDM have been discovered to have a degree of insulin resistance before they became pregnant. Therefore, with the insulin resistance that occurs in normal pregnancy it can be said that GDM occurs with a greater insulin resistance than normally present in gestation (Yogev et al 2008 Chapter 10). Insulin resistance causes a decreased uptake of glucose into skeletal muscle, adipose tissue and liver as well as a decreased production of hepatic glucose. (Catala no et al 2003). One suggestion for insulin resistance looks into the possible role of the mitochondria. Studies using Magnetic Resonance Spectroscopy (MRS) have shown that in normal offspring of parents with type 2 diabetes, there is an increased amount of intramyocellular lipid. This has been shown to cause a reduced function in mitochondria which suggests that mitochondrial dysfunction may play a part in insulin resistance (Petersen et al 2004 cited in Morino et al 2005). It has been suggested that this increase in intramyocellular lipid activates a serine kinase cascade which causes an increase in the Insulin Substrate Receptor 1 (IRS-1), which inhibits insulin receptor phosphorylation on tyrosine sites. This can cause a decrease in the effects and utilisation of glucose. One study showed that in the insulin resistant offspring the mitochondrial density was reduced by just over a third to that of a normal offspring. This suggests that offspring who are insulin resistant may inher it a condition that causes a reduction in rate oxidative phosphorylation in mitochondria (Griffin et al 2009 cited in Morino et al 2005). Detection of GDM Diagnosis of GDM helps to identify pregnancies that are at risk of fetal morbidity as well as obesity and glucose intolerance in the offspring (Buchanan and Xiang 2005). GDM is hard to diagnose as it is asymptomatic. Normal diabetes could be diagnosed by glycosuria but in pregnancy the renal threshold to glucose is lowered so that glycosuria doesnt give a true representation of hyperglycaemia (Redman 2001). There are several risk factors of GDM which can be classified into three groups and help in the screening process. Low risk factors include women who are younger than 25, normal weight at conception, no known family members with diabetes and no history of glucose intolerance. High risk factors include obesity of the mother, diabetes in close relatives, a history of glucose intolerance, current glycosuria and previous pregnancies with GDM (Metzger and Coustan 1998 Chapter 25). Causes of Diabetes There are several theories as to why diabetes occurs and this has been thought to be similar to the underlying mechanisms that cause gestational diabetes. Diabetes is a result of pancreatic beta-cell dysfunction which can present in three main ways: autoimmune, a genetic cause and on top of already present insulin resistance (Buchanan and Xiang 2005). Autoimmune diabetes accounts for approximately 5-10% of all diabetic cases (American Diabetes Association 2010). There are circulating antibodies to the ß cells of the Islet of Langerhans. In GDM, there are a small number of women who have with these antibodies present in their circulation. It is thought that these cases present with GDM due to problems with insulin secretion caused by destruction of the Islets by the autoantibodies (Buchanan and Xiang 2005). This form is similar to type 1 diabetes. The Islet Cell Autoantibodies (ICA) have been shown to have four major molecular targets: Insulin, Glutamic acid decarboxylase (GAD 65), Insulinoma-associated antigen-2 (IA-2) and Zinc Transporter 8 (ZnT8) (Tree 2010). Monogenic diabetes has 2 general forms, one where there are mutations in autosomes and the other where there are mutations in the DNA of mitochondria. The first form is commonly referred to as Maturity Onset Diabetes of the Young (MODY). In both cases onset tends to be at a young age and the patient doesnt present with insulin resistance or obesity (Buchanan and Xiang 2005). Mutations that cause MODY have been found in some women with GDM and commonly occur in genes coding for glucokinase, hepatocyte nuclear factor and insulin promoter factor, MODY is associated with beta cell dysfunction (Weng et al 2002). Chronic insulin resistance with beta-cell dysfunction seems to be the most common cause of GDM. As mentioned before there is an increase in insulin resistance in normal pregnancy but if this develops with background insulin resistance then there is an even greater insulin resistance which can lead to GDM. An established suggestion is that women who are unable to increase their secretion of insulin to cope with the insulin resistance developed in late pregnancy are more susceptible to developing GDM (Buchanan and Xiang 2005). However there could be various environmental processes that are involved in the underlying pathophysiology of GDM. The products of the placenta may also have a role in increasing or decreasing insulin resistance and these will be discussed later. Placental Function The placenta is an organ that has many roles during the development of the fetus. One of these functions is that it acts as a barrier to separate the maternal and fetal surfaces such that the syncytiotrophoblast surface exposes the placenta to the maternal circulation and the endothelium is exposed to the fetal circulation. This position between the two circulations means that the placenta is influenced by molecules from both circulatory systems, including cytokines, hormones and growth factors. The placenta produces molecules which can separately affect the maternal and fetal circulation and it expresses a large number of cytokines including leptin, resistin and tumour necrosis factor. However it has been discovered that these molecules are also produced by adipocytes. All molecules that are going from the mother to the fetus have to cross the placenta. Here they are either modified, for example lipids or like glucose, they are metabolised for placental purposes (Desoye et al 2008). The placenta plays an important role in fetal growth and the regulation of pregnancy (Giachini 2008). The placenta acts to sustain normal homeostatic levels and to carry out the functions of the vital organs. It also provides an immunological defence to the fetus and allows the exchange of molecules vital to its development (Jansson and Taylor 2007). Placental Development Approximately 4-5 days after conception, the process of cleavage causes rapid cell divisions and one of the groups of cells to form are called trophoblast cells. Further developmental processes form the blastocyte which is surrounded by an outer layer of the trophoblast cells. As the pregnancy progresses, the trophoblast cells develop into the placenta while the inner parts of the blastocyte form the embryo and umbilical cord (Huppertz 2008). The blastocyte implants itself onto the epithelium of the uterus where it differentiates into a syncitiotrophoblast which is able to implant itself in the epithelium leading to it being embedded into the decidual part of the uterus (Huppertz 2008). After the attachment of the blastocyte, the trophoblast layer divides very quickly and changes into 2 layers; the inner cytotrophoblastic layer and the outer syncytiotrophoblastic mass (Gude et al 2004).The whole implantation process takes 12 days to complete and after this the fetus is fully embedded into the endometrial layer (Huppertz 2008). The chorionic plate is the surface of the placenta that faces the fetus and this is where the umbilical cord inserts. The basal plate is the surface that faces the mother which contains many types of cells including immune cells such as macrophages and killer cells to carry out the placentas immunological function. The maternal basal plate and the fetal chorionic plate converge to form the smooth chorion which is composed of three layers (Huppertz 2008). When the trophopblast invades the endothelium there is a remodelling of the uterine spinal arteries which is necessary to ensure that the fetus and the placenta receive an adequate blood and nutrient supply and is able to remove any waste materials. This direct supply of blood and nutrients to the placenta can define it as being haemochorial villous organ (Gude et al 2004). After the rapid divisions of the trophoblast and development into 2 layers there are two pathways that can occur, th e villous and extravillious pathways. The extravillious pathway results in the trophoblast being able to invade into the decidua and cause the remodelling of the uterine arteries to increase blood supply to the placento-fetal unit. The villious pathway has a transportation function as well as having endocrine and protective functions (Gude et al 2004). Normal Placentation Placentation involves the structure and function of the placenta. The process of placentation is helped by the composition and arrangement of the extracellular matrix (ECM) of the endometrium. Studies on rats induced with diabetes provided results that showed that diabetes has an effect on the distribution of the ECM molecules. This study by Giachini et al illustrates that Types I and III collagen as well as other molecules, such as proteoglycan molecules decorin and biglycan were distributed throughout normal and diabetic placentas. It was shown that diabetes affects the expression of fibronectin and an increase in deposition of fibronectin may cause changes to the ECM structure which could affect the transfer of molecules from the mother to the fetus. One way in which changes in the ECM can be overcome is to test blood glucose levels frequently during the pregnancy and if kept in normal ranges this can dramatically decrease the prevalence of diseases and disorders present in the fe tus (Giachini et al 2008). As the pregnancy progresses the size of the placenta increases which also means an increase in the amount of products that the placenta produces therefore increasing in the insulin resistance (Schillan-Koliopoulos and Guadagno 2006). This is because the net effect of the products of the placenta is to increase insulin resistance. The increase in size of the placenta means that it needs an increased blood supply. Failure of the mother to increase its blood supply to the placenta can lead to placental insuffiency which if exacerbated can be attributed to be a cause of intrauterine growth restriction (IUGR). This growth restriction is more related to poor maternal nutrition rather than to a cause of GDM. GDM have been associated with an increased fetal and placental weight (Jansson and Taylor 2007). One of the reasons why GDM and increased insulin resistance affects the fetus is that while glucose can cross the placenta, insulin is unable to. This means that the fetal pancreas has to compensate by producing more insulin to prevent high blood glucose levels. The fetal pancreas is capable of doing this and the liver responds to the higher levels of insulin by increasing its production of glucose (Schillan-Koliopoulos and Guadagno 2006). Offspring who have an increase in birth weight have been shown to be at risk of developing cardiovascular disease and diabetes later in life. The main risk factor for this is poor transfer of nutrients via the placenta (Jansson and Taylor 2007). How dramatic these changes are depends on how good the control of blood glucose levels have been during the development of the placenta, if any treatment has been received and if there were any periods of away from normal glucose levels (Desoye 2006). How does diabetes affect Placentation? Diabetic insults at the beginning of the pregnancy can have long last effects of the placenta. One of the roles of the placenta is that it is able to buffer excess maternal glucose which can help to keep the fetal glucose levels within range However if the insult lasts longer than the placenta is able to compensate for then excessive fetal growth may occur (Desoye Mouzon 2007). In diabetes there is endothelial dysfunction which can lead to vascular disease. The endothelial cells help to control the vascular tone of the smooth muscle lining the vasculature. They do this by producing substances that help to vasodilate the smooth muscle including Nitric Oxide, Prostacyclin and Endothelium-Derived Hyperpolarising Factor (EDHF). There have been several studies to suggest different mechanisms of how diabetes affects the endothelium including impaired release of these vasodilating molecules, faults with signal transduction and increased release of constricting mediators of the endothelium. The dysfunction of the endothelium in diabetes is thought to be caused by activation of protein kinase C (PKC) as well as increased oxidative stress, non-enzymatic glycation and an increased activation of the polyol pathway (De Vries et al 2000).The main reason why these effects occur is thought to be due the activation of the protein kinase C pathway and the increased oxidative stress. This can cause early damage to the development of vascular vessels (Roberts and Raspollini 2008). These mechanisms will be discussed later. The effect of hormones produced in pregnancy Pregnancy causes changes in the circulating hormones and cytokines which can all have different effects on insulin resistance and this may help explain the mechanism underlying the resistance that is found in pregnancy and in GDM. Cytokines produced in pregnancy, such as TNF-a, Adiponectin and Leptin have been found to cause an increase in the insulin resistance (Gao et al 2008). In early pregnancy, the levels of oestrogen and progesterone rise but no net effect is seen as the two have antagonistic effects. Oestrogen increases the binding of insulin to its receptor whereas progesterone reduces the ability of insulin to bind (Ryan and Enns 1988). Cortisol levels in pregnancy increase so that by the end of the pregnancy the levels are three times that of what they were at the beginning (Gibson and Tulchinski 1980 cited in Yogev et al Chapter 10). Studies have shown that with increased amounts of cortisol there was a decrease in insulin sensitivity causing insulin resistance (Rizza et a l 1982 cited in Yogev et al 2008 chapter 10). During pregnancy the levels of prolactin increase up to ten times the normal amount (Yogev et al 2008 chapter 10). Studies have shown that in a culture of pancreatic beta cells, prolactin can cause an increase in levels of secreted insulin (Sorenson et al 1993 cited in Yogev et al 2008 Chapter 10). However, high levels of prolactin are not seen to be a pathological cause of GDM (Yogev et al 2008 chapter 10). Human placental lactogen (HPL) is a hormone, and its levels rise during the second trimester of pregnancy. This causes a decrease in the phosphorylation of insulin receptor substrate (IRS1) which can lead to significant insulin resistance (Ryan and Enns 2008 cited Yogev et al 2008 ch 10). Leptin is associated with obesity and concentrations of leptin have been shown to be related to the concentration of insulin in the plasma. In pregnancy the leptin levels increase dramatically. During pregnancy the mother uses her fat stores to supp ort fetal growth and it is thought that the leptin levels increase with the mobilisation of these fat stores. Leptin levels relate to the body mass of the individual (Sattar et al 1998). Placental Leptin is the same in structure and charge to the one produced by adipose tissue (Ashworth et al 2000). One study showed that high leptin concentrations in the umbilical cord increased the likelihood of developing fetal macrosomia (Wiznitzer et al 2000). It is also thought that leptin effects insulin sensitivity by effecting glucose metabolism in both skeletal muscle and in hepatocytes. Rats that received an external source of leptin were found to have an increase in gluconeogenesis which accounted for the majority of hepatic glucose production (Rossetti et al 1997). In GDM there is a greater secretion of TNF-alpha in response to glucose. TNF-alpha functions to regulate metabolism of glucose and lipids as well as being involved in insulin resistance. Many studies suggest that TNF-alpha is involved in the progression to GDM. They found that an increase in glucose cause the placenta and adipose tissue to increase production of TNF-alpha in some cases up to 4 times more than non-diabetic pregnant(Coughlan et al 2001). One study showed that the increases in the levels of TNF-alpha during pregnancy increased consistently with increases in body weight (Catalano et al cited in Yogev et al 2008). Adiponectin is a protein derived from adipose tissue and its function is to regulate insulin resistance and maintains levels of glucose. During pregnancy it has been found that its levels drop and could therefore lead to the increase insulin resistance found in GDM (Gao, Yang, Zao 2008). Adiponectin has also been found to decrease the secretion of TNF-alpha which as stated above can lead to insulin resistance (Hotamisligil 1999 cited in Yogev et al Chapter 10 2008). Adiponectin may cause increased insulin sensitivity as its concentration decreases throughout the gestational period ( Desoye and Mouzon 2007). Resistin is a protein that is produced by adipose tissue and is thought to be involved in insulin resistance in diabetes and is associated with obesity (Steppan and Lazar 2002) In pregnancy, resistin is secreted by the placenta and this secretion reaches its peak by the last trimester (Yura et al cited in Megia et al 2008). Studies show that TNF-alpha is an important factor in insulin resistance during pregnancy and with inputs from leptin and cortisol there is altered glucose metabolism whereas inputs from oestrogen, progesterone and prolactin had little significant effects (Kirwan and Mouzon 2002). There are many hormones produced during pregnancy, mainly by the placenta and adipose tissue that have varying affects but with the overall impact being insulin resistance. Inflammation in Diabetes There are genes in the placenta which regulate reorganisation of the endothelium and inflammatory responses and in GDM these were found to be altered. The increase in leptin receptors suggests that in the placenta this can cause proinflammatory responses (Radaelli 2003). One of the current theories is that the abnormal metabolic environment in GDM can lead to increased production of cytokines and inflammatory mediators. Molecules such as TNF-alpha, Resistin and Leptin increase during pregnancy and these increases in these inflammatory mediators produce metabolic changes by increasing insulin resistance (Desoye and Mouzon 2007). Leptin and TNF-alpha activate phospholipase A2 which are a family of eicosanoid precursors that go on to produce essential fatty acids such as w3 polyunsaturated fatty acids (Desoye Mouzon 2007). There has been a recent investigation which found that with increased adiposity at birth there has been an increase in w3 fatty acids in the placenta (Verastehpour et al 2005 cited Desoye and Mouzon 2007). As stated before, the placenta produces cytokines but it is also a site of action of the cytokines. It is the location of the receptors for these cytokines will influence if the cytokines act on the mother, the placenta or the fetus. With cytokines there is very little transfer across the placenta from mother to fetus and the origin of the cytokines in the fetus can be from either the placenta or from the fetus itself (Desoye and Mouzon 2007). Fetal Programming Many studies have highlighted the fact that events that occur while the fetus is developing can alter its developmental pathway and have adverse outcomes in later life. Fetal programming describes how the environment can affect certain developmental events of which the effects are permanent and can affect processes such as metabolism and the organisms physiology. Women with GDM have an increased risk of the fetus developing macrosomia (Catalano 2008 Chapter 11). The main factor that effects the growth of the fetus is the maternal environment and there is a strong association with the weight and height of the mother and the growth of the fetus such that mothers who are heavier and taller will produce heavy babies. (Love and Kinch 1965 cited in Catalano 2008 Chapter 11). The placenta and fetal programming The placenta is very important to the developmental processes of the fetus as it is able to change the quantity of signals and nutrients that the fetus receives. Deviation from normal would alter the fetal programming, thus making it more susceptible to disease in later life. Pregnancies that are complicated by GDM have excessive oxidative and nitrate stress which has been found to change the activity of certain proteins. Oxidative and nitrate stress alter the placentas function and may cause changes in the fetal programming. Nutrient transfer depends largely on the normal development of the vasculature to allow blood flow and this can be affected by GDM which can cause a decrease in the flow of substrates and is a mechanism in which fetal programming can be affected (Myatt 2006). Fetal programming involves a large amount of development plasticity and interruptions to this development may cause abnormalities in the development of certain cells which may progress to structural differe nces in organ development (Gluckman and Hanson 2004 cited in Jansson and Powell 2008 ref 16). Effects to the fetus exposed to GDM If a fetus is exposed to a diabetic environment during pregnancy then there can be certain long term effects. These effects can be classified into three groups; Anthropometric, Metabolic or Vascular and Neurological or Psychological. Anthropometric changes are concerned with the rates of growth for both height and weight and in a diabetic environment these can be excessive leading to macrosomia and obesity in later life. Metabolic and vascular changes that occur are abnormal glucose tolerance which can eventually lead to diabetes mellitus. Finally the neurological and psychological changes that can occur are usually minor but development of psychological and intellect can sometimes be deficient (Dabelea and Pettitt 2008). Potential problems that may arise with the fetus from an exposure to maternal diabetes include abnormal organ mass, altered angiogenesis and increased levels of fetal insulin (Fetita 2006). It has also been found that if there is an increase in weight during pregnan cy then there is usually a higher birth weight of the fetus (Humphreys 1954 cited in Catalano 2008 Chapter 11). The developing fetus cannot synthesise glucose and is dependent on the mother to produce it where it is transported to the fetus via facilitated diffusion through the placenta (Aerts et al 1996 cited in Mello, Parretti and Hod 2008). The result of decreased insulin sensitivity is that there is more glucose available to the developing fetus which can lead to a greater birth weight (Mello, Parretti and Hod 2008). Using animal models, it has been shown that exposure to high levels of glucose in utero can lead a diminished number of nephrons in the offspring (Amri et al 1999 cited in Fetita 2006 ref 68). This is important as nephrogenesis only occurs in the fetus and stops after birth (Gomez, Norwood 1999). It has been shown that a reduction in the numbers of nephron may affect the rate of progression of renal disease in adults due to an inability to secrete sodium. This may l ater develop into salt-sensitive hypertension (Brenner et al 1988). The mechanisms of reduced organ mass, high levels of fetal insulin and defects in angiogenesis may help explain how the fetus programs abnormal glucose tolerance in adulthood as a result of exposure to GDM (Fetita 2006). Transmission of diabetes from mother to offspring Exposure to gestational diabetes mellitus increases the risk of the fetus developing abnormal glucose tolerance which may develop into type 2 diabetes. (Fetita et al 2006). The association between greater incidences of the offspring having diabetes with a mother with GDM is greater than what would be predicted that could be passed on by maternal genetics (McLean et al 2006). One study showed that the phenotype for GDM/T2D was more common in daughters of mothers who were diabetic rather than daughters of fathers who were diabetic suggesting that the transmission is from mothers with GDM to their daughters. However there were limitations of the McLean study. Patients may not be aware of their fathers diabetes status due to men having lower inclinations to report symptoms and share illnesses with the family. One study showed that the mass of the pancreatic beta cells is relatively fixed by the end of fetal growth and this can be influenced by an intrauterine environment of hyperglycaema (McLean et al 2006). Congenital defects are more common in babies born to diabetic mothers (Farrel et al 2002 cited in Fetita et al 2006). There are many factors that can influence the prevalence of these malformations including the duration, severity and age of onset of GDM (Kousseff 1999). If the onset of GDM is at the beginning of development then development of some organs may be affected. However as said before, the majority of GDM develops during the second trimester. This can then lead to embryopathy which includes defects such as failure of neural tube closure and malformations in the Renal, Cardiac and Gastrointestinal systems which present in childhood (Fetita 2006). In diabetes the hexosamine pathway is activated and inhibits the pentose shunt pathway which decreases the production of antioxidants and therefore leads to an increase in oxidative stress. This oxidative stress has been found to disrupt gene expression and may contribute to congenital defects. One example is that oxidative stress inhibits a gene called pax-3 which is needed for neural tube closure and in diabetes there is an increased risk of neural tube defects (Horal et al 20