Assembly Format

SCHOOL ATTENTION, STAND AT EASE, ATTENTION. Good Morning to one and all present here. I am Shivangi Goswami of Class 8 A standing before you to conduct today’s assembly. One man with courage is a majority. This famous quote was said by Thomas Jeffery, meaning one man who has courage can do anything and is capable enough to do any task at hand. So friends today the theme of our assembly is courage. The one who has the made the world, the one who has made us and the one who has blessed us with all our abilities is none other than our Almighty Father.So to acknowledge him for his deeds and blessings, I would like to call some of the boys of our class. Thank you for your acknowledging world. The love, affection, respect and devotion for god cannot be expressed only through words. To thank god in a wonderful way I present my class with the choir. That was indeed melodious. A class without a teacher, a flower without petals and a day without a thought is incomplete. So Nabin and Nih arika are here with a charming and delightful thought on courage. Thank you Nabin and Niharika.N for north, E for east, W for west and s for south. All these letters together makes the news. So to update us with the latest happenings around the globe, I call upon our young reporters Harpal, __________and____________ with the news. Thank you Harpal, ___________ and __________. Courage is not the absence of fear but rather the judgment that something else is important than fear. To through some more light on the assembly’s theme Courage, may I call upon Swaraj for the special assembly speech.Thank you Swaraj. Birthdays come once in a year. So we should celebrate it enthusiastically. May I call upon all the birthday students at the center stage as it is time to wish them a very happy birthday. On behalf of Class 8 A, I wish all the birthday students a very happy birthday. May I call upon our class teacher for making some announcements. Thank you madam. SCHOOL ATTENTION, STAND AT EASE, ATTENTION Now it’s time for the national anthem and the national anthem begins.

Participative Leadership Essay

In taking the online quiz required for this assignment I found myself to be a participative leader. This type of leader fits me perfectly and I was not surprised to see the answer. I try to engage each team member in identifying necessary goals and developing procedures or strategies for reaching those goals . Nursing management is a challenging and difficult task. The style of the manager can be important for employees’ as well as other members of the healthcare team’s acceptance of change and in motivating them to achieve a high quality of care. From this view, participative leadership can be seen as a leadership approach that relies greatly on the leader functioning as a facilitator and mentor rather than simply issue orders or make assignments. Participative leadership theories recommend that the model guidance approach is one that takes the involvement of each member of the team concerned into consideration. I encourage participation and contribution from members of the group. This helps them feel more significant and committed to the decision-making process. In participative leadership, however, the leader retains the right to allow the participation of others and eventually has the final say for the best interest of the group and entice teamwork. Teamwork is established through effective communication and a shared vision that reinforces an environment of collaboration with a constant free-flow of ideas. The leader must communicate a clear vision of where the organization is headed and how the team is going to attain this goal. I find myself trying to take complete control and responsibility for the team. I have a hard time letting go and giving in to new ideas. I need to develop better listening and compromising skills. I am not a shy or quiet spoken person/leader. I do think I am fair, honest and take pride in maintain integrity. Taking a different approach and keeping an open mind would be a good place for me to start. I most definitely will be watching for the leadership skills needed for advanced practice nurses in my clinical phase of courses. I am open to suggestions now as a leader in management in my current role. I feel it is always most important to do what is safe for the patients, the team and the organization. I am always watching the leaders of my organization and picking up skills I see as note worthy. Unfortunately, each organizations has leaders with attributes that should not be a part of leadership qualities. The most important quality that a leader can possess is honesty. The process of becoming a leader starts with honesty and builds into a trusting relationship between leader and followers. If this quality is lacking no amount of team building will be successful. Honesty is the building block of any healthy relationship. â€Å"Honesty is the most powerful weapon in business† (Fralic, 2011, p. 447). â€Å"Leaders must have a sense of one’s own character and be able to accept no less than what is beneficial for the whole group†(Fralic, 2011, p. 447) In order to function with total honesty and integrity each leader must have the mind set of what is beneficial for the whole group not just the select few or the leader (Fowler, 2010).

WASH ASSISTANT Personal Statement Example | Topics and Well Written Essays - 250 words - 1

WASH ASSISTANT - Personal Statement Example tional Rescue Committee (IRC) based in Garowe in Somalia because I possess the potential, prerequisite knowledge and experience required to make a difference. According to Godfrey (2005), the IRC responds to the worst humanitarian crisis in the world by helping people survive and rebuild their lives. The IRC’s objectives and goals inspire me to contribute to alleviating the suffering of people afflicted by calamities, and in the process acquire more experience and knowledge with regard to disaster management. My training on several essential WASH courses with redr.uk on mock WASH cluster gives me an added advantage. This is borne out of the fact that during these training sessions I have to collaborate with other WASH actors in identifying and addressing gaps in an emergency response. Given this opportunity to work with the IRC in Garowe in Somalia, I will be able to apply and test the viability of the proposed strategies to address the gaps in emergency response. My focus will be to address and enhance WASH protocols in a bid to improve disaster emergency responses by filling the gaps identified. This will include conducting household water and hygiene promotion and assessments to gauge the safety and appropriateness of available water sources in use during and after disasters. This will be in an effort to mitigate the effects of unsanitary water sources in calamities. To this effect, my experiences will enable me to easily identify WASH related factors needed to control and eliminate neglected tropical and respiratory diseases. This has also enabled me to formulate prevention strategies against water borne diseases and water related insect vector disease phenomena, which I can apply to improve the capacity of

Critical reading response Essay Example | Topics and Well Written Essays - 1000 words

Critical reading response - Essay Example He offers three possible solutions for these issues. He states that mandatory attendance should be abolished and replaced with policies allowing kids to attend classes only when they want to. He also suggests removing children from schools, declaring them to be prisons where learning is limited. Additionally, he views that abolishing the curriculum is also a possible solution because people merely remember what they believe is interesting and useful to them. In order to assess the veracity or, at least, appropriateness of Holt’s claims, the major points of his article will be analyzed. First, Holt states that learning is inherent in every human, and that babies learn the basics of living and survival from the day they are born. Without any formal instruction, kids learn to communicate and interact with people around them. They learn through discovery, association, application, and mistakes (Holt, â€Å"School is Bad for Children†). This is a very strong point. Yes we sh ould acknowledge that school provides specialized information of some subject matters, but it does not mean that learning the same is impossible outside school. To prove this, one can simply look at the greatest minds in man’s history like Albert Einstein, Blaise Pascal, Pierre Curie, the Wright brothers, Thomas Alva Edison, and Alexander Graham Bell. These great minds did not acquire their knowledge from traditional schools because they were all home-schooled (McKee 16). Therefore, with the undeniable inherent ability of man to learn coupled with proven achievements of those that never went to school, it is easy to agree with Holt on this matter. Another statement made by Holt is that school environment encourages passive learning, thereby decreasing the utilization of man’s inherent ability to learn through active discovery, association, application, and mistakes. It also encourages the thinking that to be wrong is a crime, and to be right is the only acceptable thin g. In school, students are dictated by the experts on what is important, what they need, and what they should do. Technically, everything is spoon-fed (Holt, â€Å"School is Bad for Children†). Holt is not exaggerating when he states school teaches kids to do something only if they are forced, bribed, or deceived, since school rewards excellence and correctness. Despite the idea that teachers encourage children to analyze and ask, at the end of the day, they still follow a pre-set standard of what is correct and incorrect. Knowing the correct and universally accepted answer is the only way to pass, and passing is the only way to move forward. These standards place children in categories --- stupid, average, or brilliant (McKee 21). Moreover, it gives a false idea that learning and living are separate things that cannot merge together. The live outside the school, and learn inside with the experts. It reinforces the belief that children cannot be trusted to learn on their own --- they need experts to tell them what they should know to be considered knowledgeable and learned (Holt, â€Å"School is Bad for Children†). Holt again presents unquestionably strong arguments on this matter. Everyone who experienced school can relate to a great chunk of Holt’s standpoints. Another controversial statement is Holt’s declaration that schools shut kids’ brains and lead them to vices, particularly drugs. Several people may react negatively

Marketing in Social Media (Facebook) Research Paper

Marketing in Social Media (Facebook) - Research Paper Example Social media is one of the latest marketing aid tools in the commercial sector. Facebook is a popular social network that enables people from all corners of the globe to create respective accounts and communicate to each other regardless the distance. The commercial sector has taken advantage of the popular network to advertise or create awareness of their products among other relevant information. This work focuses on Facebook, one of the most popular social networks, as an advertising tool in the commercial arena. There are over a million commercial pages in Facebook, hence, it is important to incorporate some attractive features to attract more people to the social networking community. The success of communication through Facebook could be measured by the number of likes or comments. Attractive photos or images attached to accounts play a significant role. From a psychological view, a normal human being would always be attracted by unique or colorful images, and this would make o ne read the content of the pages and finally like such pages. Bright colors like yellow, pink and white could be incorporated into the images to attract some attention and this would improve the chances of one to make positive comments or like a page. Business pages could also include the images of popular individuals like famous sportsmen, actors, models and comedians among others. However, it is important to consider all the legal and ethical implications before using anyone’s image; for instance, a company should enter into a contract with a preferred celebrity to have his/her photos used on such pages. People tend to associate themselves with celebrities, hence, more likes and positive comments, which is a good sign of an advert message. The use of simple appealing language could also attract more people to like or comment on such pages. For instance, adverts in Europe could be done in English or French as these are the two most spoken languages in the area (Arvind 19). I t is also important to incorporate current events like sports in such pages. For instance, such pages may contain images of the ongoing confederation cup and rugby sevens world cup among others. The advert information should be short and precise, meaning the core information should be easy to access. Recent business studies of hotel and tourism business in Taiwan recommend the industries to engage in more Facebook adverts to increase more clients or customers. Compared to their counterparts in Europe and other parts of the developed world, Taiwan hotels are not that well known due to poor advert or marketing strategies. The language barrier is another factor limiting effective communications through Facebook. Taiwan hotel market expect more customers from Europe, Africa, North America and South America among others whose main languages are French, English and Portuguese, which are not spoken in Taiwan. However, Taiwan hotel industry could create business pages in their native langua ge but have it translated into other languages to limit the issue of biases ((Hsu 972). The industry could also post images or photos of some of well established hotels among other tourism facilities to attract more clients from all corners of the globe. The pages should be interactive, meaning the clients or customers’ questions or concerns should be answered considering all important details in the most respective ways. The pages should have appropriate passwords to limit hackers from posting non-relevant information that could compromise the image and reputations of such hotels. Facebook has enabled e-commerce in several ways and this could be attributed by the fact that the majority of the youths' access the Facebook pages at

Takehome midterm Assignment Example | Topics and Well Written Essays - 750 words

Takehome midterm - Assignment Example Bus on the other hand reasons that males get jealous due to physical cheating since he may not be certain about the paternity of the child born out of the relationship. Therefore, the thought of not being the father is laced with jealousy. On the part of women, emotional jealousy springs up if the woman is not sure about protection of resources for the children. According to these thinkers and scholars, the brain is configured with inbuilt with innate or unchangeable parts or forms of computational intuitions. This is to say that human beings are born with some skewed form intelligence which is to imply that human minds are pre-disposed with some form of knowledge. For instance, if a person is born, he or she would intuitively know what plants, people, non-living things, living things are. However, if a physical impact or injury is occasioned to the brain, then it would mean that the brain would be in a position to recall all the things that it had learnt and knew prior to the injury. This is to imply that a brain damage or injury cannot erase all the things and concepts that the brain knew prior to the injury on it. 3) Pinker and Tomasello both address the issue of poverty of stimulus when trying to explain language acquisition. How does it support Pinker’s view, and what does Tomasello have to say about Pinker’s argument? According to Pinker, human brains are innately and unequipped with the ability of them to speak languages even if the people are not necessarily the taught. This is to say once a person is born, he or she would have the instinctive ability to speak a language regardless of the geographic environment in which the person is born into. According to his line of thoughts and arguments, a child once born would have the ability to speak instinctive languages, but since their brains develop, it becomes difficult for their developing brains to grow accordingly since there are not educated on

Colonial America to Road to Revolution Essay Example | Topics and Well Written Essays - 250 words - 1

Colonial America to Road to Revolution - Essay Example The slave trade was not an output of any raids by Europeans bur Africans themselves were sellers of other Africans and Europeans were purchasers. Slavery was not something new for Europe as Christians and Moslems enslaved each other in wars. However, the slaves were considered the members of society and slavery was not shifted to their children. With the passage of time, Europeans were in need of labor due to which, they moved towards Africa for black gold, a term that they used of African slaves. Africans were transported to European colonies for the labor needs. Black slaves were considered the strength of English men. Black slaves increased in number in white populations and the white population started considering that the Africans are naturally slaves. Soon, the slaves gained the status of chattels that had no rights of their own. Due to mass enslavement, the white man became more and more prejudiced racially. I like the essay as a detailed history is given about the slavery and the practices of Europeans towards African slaves. The writer has given the detailed account of the arrival of black people in a white people’s country in a persuasive

Business Research Essay Example | Topics and Well Written Essays - 1250 words

Business Research - Essay Example Speaking in the terms of economics we need to strengthen first the factors of production to set up a new venture namely land, labour, capital and organization; be it either service oriented or manufacture based or even trading. The first and foremost necessity is the project with clear layers of strategic growth. One has to acquire land that covers building and machinery for the initiation. After the acquisition of the land, the entrepreneur has to move on proper legal documentation such as â€Å"Registration of the Firm†. Once the registration is done furnishing its source of fund, annual estimated turn over, chain of man power and delegation of responsibilities we can precede further. Then it is important needs to the source of raw materials that have to be procured from the possible cheapest region with the lowest cost of transportation. Eventually we need a clear road map to market our product. Thus, every entrepreneur set the bridge of profit across the flow of the possib le consumers.

Multispecies Models as an Improvement on Single Species Models for Mea Assignment

Multispecies Models as an Improvement on Single Species Models for Measuring Fishing Impacts on Marine Ecosystem - Assignment Example The study is thorough and provides a deep insight of the multispecies modeling tools along with the single species models and their impacts. In the more recent studies on the topic of multispecies fish modeling and harvesting the factors that can impact the rate of harvesting is usually considered. The purpose is to target and examine the sources. Another study is conducted in the year 2013 in which the authors tried to find the cooperative and non-co operative harvesting in the multispecies fish war models. This paper emphasizes on the role played by support for the sustainable supervision of a broken ecosystem. The authors Daniel Pauly, Villy Christensen and Carl Walton in their study named as the â€Å"Ecopath, Ecoism and Ecospace as tools for Evaluating Ecosystem Impacts of Fisheries† thoroughly studied the key features for the reconceptualized approach. Not only this, they designed two indices based theorem in which they tried to qualify the impacts of an ecosystem on the fisheries. In the research, they used the truth based statistics collected from the users of the Eco Path and extracted from their feedbacks. They further discussed the implementation made up to the date and the limitations of the Eco System. They commented that some of the implementations have been made but the process of up gradation is very slow and it requires quite an effort. In another recent study, the authors studied the statistical and empirical identification of the multispecies fish harvesting Zones. The purpose of the study was to discuss the factors that can help in improving the monitoring and the management of the specific multispecies fish zones. The impacts and the ideas are not only the main theme of the recent researches but  some researchers also conducted the studies on the issues of the multispecies fish modeling and harvesting. Like in a paper the author from India highlighted the problem of harvesting two competing fish species together. For this, he designed a bioeconomic model. Also, the Marine Fisheries Service published their report on the topic of optimal multispecies harvesting in the presences of the nuisance species.  

Educational Website Evaluation Research Paper Example | Topics and Well Written Essays - 750 words

Educational Website Evaluation - Research Paper Example Before healthcare professionals recommend any websites to patients, the must make sure of the quality of content and information is accurate to serve the purpose. Based on the given references, â€Å"accuracy† is a key factor to check the sources for content. The information may also come from more than one source. If the information comes from a reputed source, then it is good to use. For example, websites like www.cdc.gov gives users ample information on health topics. Within the site one can find links that provide information in details on recent outbreaks in the country, health and safety topics related to all diseases. Accuracy of particular site deals with the updating of the site, the quality of language, authentication of the site, appropriate links within the site, etc. In CDC on the home page itself the visitors can view â€Å"Health and Safety Topics† that takes them to a vast array of information on various diseases and prevention methods. They can also get A-Z information on all health topics as each topic is provided with featured links and sub-topics making the information easily accessible. For example, the â€Å"heart disease† topic will give the visitors links for coronary artery disease, symptoms and recommendations. However, relying on the internet for health information is a risky proposition as one cannot blindly believe on all the sites. Many times, people end up with websites giving them irrelevant or false information. Fortunately, the users can verify the contents of CDC and it is accurate. Regular users of internet can easily identify the genuineness of this website. While searching for right health information few aspects needs to be considered. These include whether the site is authorized, does it ask for personal information or whether it makes unbelievable claims. It is also desirable to check the â€Å"About Us† page of the site for finding the answers about the questions relating to the promoters of the sites. To a certain extent, the â€Å"site map† can also be helpful. In the â€Å"About Us† page of CDC one can get to know about CDC organization, mission and vision, their training and education and how they are connected with social media. These points are enough to answer the authorization of the site. Second factor is the author of the website, who must have â€Å"verifiable credentials† (Website Evaluation Guide, n.d., p.1). The author must be easily accessible through e-mail address or other contact details provided on the site. CDC gives the users the complete postal address and how to contact the owner through twitter and FaceBook – CDC tweets and CDC FaceBook Posts. Evaluating health websites is impossible without authorization and details of sponsor. When a person checks on the authority, two important things must be noted such as (a) why the site is created and (2) which sponsor runs the site? If the site is making unwanted claims to the u ser that means the site does not have a sponsor or proper author. If one takes the example of the earlier mentioned site he or she can find that the site is run by the Center for Disease Control and Prevention. In the â€Å"About CDC† page of the site, there is a link for â€Å"CDC 24/7† which gives you information on how â€Å"CDC officials† work with other health care providers to spread health awareness. This provides clear details of who runs the site and what is its purpose. Another important

History Behind Moulin Rouge the Movie Essay Example for Free

History Behind Moulin Rouge the Movie Essay It was 1899 in Paris, France, it was the time of the Bohemian Revolution, and it was the summer of love. Christian, played by Ewan McGregor, was a writer and came to Paris to experience this revolution and be surrounded by the artists, singers, and dancers of this new Bohemian world. Little did he know that he would experience something he had never felt before but always believed in: love. Moulin Rouge, directed by Baz Luhrmann, is an exquisite movie musical based off of a real life cabaret called Moulin Rouge in Montmartre. The movie tells the story of the love triangle between Christian, Satine aka the â€Å"Sparkling Diamond† of the Moulin Rouge, played by Nicole Kidman, and The Duke. Although Christian and Satine are fictional characters, the story includes real life characters such as Harold Zidler, the co-mastermind of the Moulin Rouge and Toulouse-Lautrec, a famous French artist. Moulin Rouge is a great look into what life was like back in Paris in 1900, but also adds in the love story between Christian and Satine to make for a great movie musical. In the beginning of the movie, Christians optimistic love shines some light into Satines dark materialistic reality. To make a living, Satine became a courtesan at the Moulin Rouge. She gets paid for making men believe what they want to believe, so she sells her body to make money. She mistakenly became attracted to Christian for his pure and optimistic belief in love. Seeing that Christian did not have a lot of money, she becomes hesitant of loving him because he would not be able to support her and her dreams of being an actress. With Christians pure and optimistic belief of love, he captures Satines heart by loving her for who she really is, not for what she is. Although Satine dies in the end of the movie, Christian learns that true love lasts forever even through death. Harold Zidler, who is not a fictional character, is the man who helped to run the real Moulin Rouge cabaret. In the film, and in real life Paris, Zidler was the man who was, â€Å"a ‘brother’ to the artists and the man in the shadows who watched over the dancers and the rest of the personnel with a benevolent eye and ruled with an iron fist† (History). In the film he is the one who is in charge of making sure everything goes perfectly at the cabaret and makes sure all his dancers, especially Satine, know what they are supposed to do and who they should impress that night. Not only did he run the Moulin Rouge he was also a showman and performed with his dancers in the shows. Toulouse-Lautrec was also an important person when it comes to the cabaret in Paris. In the film he does not have a huge role other than help Christian get inside the Moulin Rouge and find a way for him to meet Satine. In Paris in the 1900’s, though, he is said to have been â€Å"the eyes of the Moulin Rouge.† Toulouse-Lautrec attended every evening show when the cabaret opened; and as mentioned before he was an artist, so every night he would sit in a corner and draw the dancers accompanied by a glass of absinthe (History). The fact about the absinthe is also in the movie; Toulouse-Lautrec, Christian, and a few others take a shot of absinthe before they head to the Moulin Rouge one night and the next few minutes of the film are just filled with pure craziness and hallucinations. His artwork, though, was extremely important in the success of the Moulin Rouge. â€Å"In 1891, he drew the first advertising poster for the Moulin Rouge, which today remains the best known image of the Moulin Rouge around the world† (History). His work is still famous today and without him the Moulin Rouge in Paris would not be as well known as it is today. The dancers of the Moulin Rouge were masters of the â€Å"cancan.† One of the stars and also known as â€Å"Queen of the Cancan† was Louise Weber, but her nickname was â€Å"La Goulue.† She is not specifically in the film, but in a biography about her, it states that, â€Å"one evening when she was dancing a frenetic cancan, between two cartwheels she spotted the Prince of Wales, who had come to spend an evening on his own at the Moulin Rouge, and called out, with the Parisian cheek for which she was well know, ‘Hey, Wales! The champagne’s on you?’† (History). La Goulue is relatable to Satine in the film, because Satine was also the star and best dancer and she spotted Christian the first night he was there and while she was dancing called him out in front of everyone who was in attendance at the Moulin Rouge that evening. Moulin Rouge is one of Baz Luhrmann’s best films. The movie came out in June 2001 and has won many awards and is one of the best movies in the musical genre. The set design, costumes, casting of roles, and music all is so perfectly put together to create this brilliant film. Luhrmann, who also co-wrote the movie with Craig Pearce, traveled to Paris with Pearce and the production designer to conduct historical research and write the synopsis for the movie. â€Å"To find ways to depict 19th century Paris and the Moulin Rouge as it may have felt to its audience then at the cutting edge of sex, music, dance, theater and modern thinking the filmmakers immersed themselves in the neighborhood, venues and culture of their story† (Luhrmann). Through their research and learning about the culture, they came to understand that the Moulin Rouge was a club that brought all different classes together and Pearce quotes that is the equivalent of â€Å"Studio 54 in New York in the late 70’s; a place where the rich and the powerful can mix with the young, the beautiful and the penniless† (Luhrmann). This is shown in the movie because we see the powerful, such as The Duke, and then Christian who is just a writer, come to the same club to experience th e same thing, women and entertainment. The first half an hour of the movie is nonstop music, dancing, lights, and just absolutely craziness. Audiences are not given a chance to â€Å"relax† and just slowly take the movie in; it is fast paced and keeps the movie viewer on their toes just waiting for what will come next. In a movie critique, shortly after it came out in 2001, the movie reviewer describes Moulin Rouge as â€Å"grandiose, glorious, absinthe-soaked excess.† When filming, Luhrmann wanted everything to be over the top and wanted more out of the production; more songs, more sound, more color, more everything (Kaplan C.D.). This is what it was like in the real cabaret, the dancing and songs were all so intense and crazy so the men would be fully entertained and never get bored. There was a lot going on in Paris in the late 1880’s and 1890’s. The Eiffel Tower was built, the first cinematographic screening was shown by the Lumiere brothers, and the most famous cabaret opened its doors. â€Å"The public came in mass to discover this extravagant place with its huge dance floor, mirrors everywhere, and galleries that were the last word in elegance, to mix with the riffraff and girls of easy virtue† (History). The Moulin Rouge was a place for the rich and poor men to come for dancing, music, and entertainment from the ladies; it is said to have been an atmosphere of â€Å"total euphoria.† This was a time where workers, aristocrats, artists, and the middle-class could all gather together to experience cabarets, music-halls, and other night time activities. As mentioned before, this movie takes place during the Bohemian Revolution. This revolution was not a revolution of fighting, but a revolution of art and culture. It was a time for artisits, poets, writer, singers, dancers, and anyone else who wanted to express themselves to show off their talents and be recognized. These were the â€Å"children of the revolution† (Moulin Rouge). In the beginning scenes of Moulin Rouge, Christian is told that to really be a child of the revolution, he has to believe in beauty, freedom, truth, and most importantly love. Which of course he believes in love, it is what he lives for and as stated earlier, he is given the chance to experience love for the first time. Not only is the movie based off of the real cabaret in Paris, but it is also partly based on the Greek myth of Orpheus and partly on the opera La Traviata by Giuseppe Verdi (IMDb). The Greek myth of Orpheus and Eurydice is somewhat like the story between Christian and Satine. Orpheus is said to have been the best musician that ever lived and until he met Eurydice, he lived his simply and carelessly. Orpheus and Eurydice fell in love and it meant everything to both of them but someone else wanted Eurydice’s beauty and wanted her but she did not care for this other man. To make a long story short, she ends up dying and Orpheus tries to get her back from the underworld but could not save her; all he had left was the love they once had (â€Å"Orpheus†). For Christian, he lost Satine and would never get her back again but what he got from her death was a story of true love that he has to share with the world. Satine was already dying before she fell in love with Christian, but at least she was able to die knowing what it was like to be in love. The opera La Traviata is another love story that ends tragically. Violetta, who is a courtesan, claims that love means nothing to her until she meets a young man named Alfredo which makes her then wonder if he could be the man that she could love. In the end of the story, though, Violetta is diagnosed with tuberculosis and does not have long to live and dies at Alfredo’s feet (â€Å"La Traviata†). This opera, the myth of Orpheus, and Moulin Rouge, are all similar in the way that the woman never really believed in love until they met that one man that changed their views on love, there are challenges to face one the man and woman fall in love, and then it is the woman who dies in end leaving their lovers all alone. Each story is a little different but the same basic idea, from the opera and Greek myth, are apparent in the film. From twentieth century Paris, the Bohemian Revolution, the myth of Orpheus, Harold Zidler, and other historical moments, Moulin Rouge is a one of a kind musical film that is an amazing piece of work put together by Luhrmann. Knowing the history behind the film makes it exciting to watch and understand what it was like back in Paris in 1899. Works Cited â€Å"The History of the Moulin Rouge and its Shows.† Moulin Rouge.fr. Le Bal du Moulin Rouge, n.d. Web. 17 Nov. 2011. Kaplan, C.D. Rev. of Moulin Rouge, by Baz Luhrmann. Louisville Eccentric Observer, Louisville, Ky.: 30 May 2001. Vol. 11, Iss. 30; pg. 21 â€Å"La Traviata.† The Metropolitan Opera. N.p., n.d. Web. 18 Nov. 2011. Luhrmann, Baz,, and Craig Pearce, commentary. Moulin Rouge. Dir. Baz Luhrmann. Perf. Nicole Kidman and Ewan McGregor. Twentieth Century Fox, 2001. Film. Moulin Rouge. Dir. Baz Luhrmann. Perf. Nicole Kidman and Ewan McGregor. Twentieth Century Fox, 2001. Film. â€Å"Moulin Rouge.† IMDb. IMDb.com, Inc., n.d. Web. 17 Nov. 2011. â€Å"Orpheus and Eurydice.† Paleothea Myths. N.p., 10 Jan. 2008. Web. 18 Nov. 2011.

Psychology Debate Essay Example for Free

Psychology Debate Essay Psychology is a human science and should thereby leave the study of biology to the biologists. Psychology, as defined by the APA is, ‘the study of the mind and behaviour’(APA, 2013), this definition states that psychology is indeed separate to that of biology as biology by definition is ‘the branch of science concerned with the structure, function, growth, evolution, and distribution of living and non-living organisms’ (biology online, 2013), this implies that the two are indeed two different disciplines which do not require interaction, as they are simply focusing on different things. A good example of the two disciplines being separate, is psychoanalysis. Psychoanalysis, a method of therapy developed by Freud and still used widely today, focuses on the subconscious and says that mental illness is caused by underlying traumas, repressed memories and unconscious desires. If these are brought to the surface, by the patient verbalising under hypnosis of these repressed, unconscious and underlying issues, it is thought that by uncovering them they will find answers. Psychoanalysis has no foundations in biology and even as it has been expanded upon by people such as Adler and Jung, still does not believe that biology is relevant to psychology (Kandel, 1999). The simple fact that they are, still to this day, separate disciplines again reinforces that they are separate spheres of study and should remain that way. AGAINST: Psychologists need an understanding of biology in order to treat patients, and understand concepts fully.  Psychology could not be practiced if it was not for the fundamental biology that sets human beings apart from any other species. An understanding of the brain, body and how they function and there interactions and co-existence with psychological concepts such as mood, personality, emotions are integral and in fact, psychology needs a biological foundation and understanding to even begin to interpret psychological concepts (Weiten, 1992). When taking a closer look at the definitions mentioned previously, they both study life. Since biology is the study of life psychology fits into this definition as psychologists too study life. In saying that, the study of life should not be left up to the biologists as they are typically concerned with the structure, function, growth, evolution and distribution of living and non-living organisms, whereas psychologists look deeper into the study of life, not just seeing it as a science but seeing it as an avenue to help and better people’s lives through understanding the fundamental biological workings of the brain. But without an understanding of the human brain and body and how it functions psychologists would not be able to put these two disciplines together to achieve their outcomes. It is crucial for a psychologist to understand the work of biology in order to be an effective psychologist. Without a biological basis, there would be no way that psychology would even be a pro-active discipline. Diagnosing a patient today, requires the psychologist to be able to understand the biological forces which influence behaviour (Weiten, 1992).

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