Personal Statement for Baccalaureate Child Welfare Education Program Essay

Personal Statement for Baccalaureate Child Welfare Education Program - Essay Example With more tasks and responsibilities relegated to parents, their role as the sole source of support had been scrutinized and evaluated to determine the effects on children’s welfare. The emergence of social worker’s critical roles in augmenting parental support continues to influence the design and delivery of services catered to children’s needs. I have been genuinely interested in working with children, specifically those with developmental and behavioral disabilities identified to be at risk. At Lakeside School, I was given the opportunity to work closely with special children and have encountered diverse factors that affect risk management. I became aware that parents, carers and social work practitioners are presented with the dilemma of either protecting children fully from risks by not exposing them at all or encourage them to develop appropriate skills in managing risks to some extent and enable them to develop effective skills to manage it for future use. This is just one of the challenging scenarios which enhanced my interest in child welfare. I recognized that inasmuch as parents, carers and social work practitioners all have one objective in common, that is, to ensure the safety and the normal development of children by protecting them from risks, it is evident that encouraging children to manage risks would be the most beneficial method for their holistic well-being. I want to be instrumental in the development of every special child’s welfare. As an effective social worker in child welfare, I possess the necessary knowledge and skills in assessment, active engagement, intervention, the use of authority, and an expert ability to negotiate and manage appropriate community resources. I am innately fond of children – ensuring that they are accorded the appropriate care using the most effective teaching methodologies that cater of each child’s individual needs. I am very patient, understanding but

A response to Generation Like Essay Example | Topics and Well Written Essays - 250 words

A response to Generation Like - Essay Example They could require brands to pay them for promotion, but they agree to work in exchange of goods and services. It turns out that teenagers underestimate their role in commercial culture today. Most of them tend to watch TV less and spend more and more time online using social media as a tool to express their identity. Brands cannot use conventional channels to reach and retain new audiences any more. They address Youtubers, fans, Twitter or Instagram celebrities to promote their products and they agree to do this for free. SMM advertising is very valuable because it is natural and it addresses loyal audience of viewers who identify with products liked by people they adore or follow. At the same time, kids learn fast and apply marketing strategies in their smaller channels in order to engage their fans and interact with them effectively. Overall, this documentary proves that social media marketing is not a game anymore and people engaged in it need to understand their value in

American Dream by James Truslow Essay Example for Free

American Dream by James Truslow Essay The ‘American dream’ is a term coined by James Truslow in his 1932 book Epic of America, but it is a concept as old as America itself: anything is possible if only the individual is willing to work hard. The dream draws immigrants to our shores and borders every year and keeps millions of Americans content in the idea that their toiling will pave the way to success for them and for their children. However, for every rags-to-riches story, there are thousands of other hard-working people who cannot get by, who do not have enough to eat, transportation, safe housing, or warm clothes in winter. There is much evidence that the American dream is little more than a myth, a false promise that keeps millions of people working themselves weary for a better tomorrow that will never come. The American dream is the promise of the Declaration of Independence, which indicates that our â€Å"inalienable rights† are â€Å"life, liberty, and the pursuit of happiness.† There is no single American dream, but Adams defines the concept in its most dignified sense: [It is the] dream of a land in which life should be better and richer and fuller for everyone, with opportunity for each according to ability or achievement†¦a dream of a social order in which each man and each woman shall be able to attain to the fullest stature of which that are innately capable, and be recognized by others for what they are, regardless of the fortuitous circumstances of birth or position. (qtd. In Ferenz) The lure of America for immigrants and the promise to its citizens is that, as Adams indicates, the individual is not held back by circumstances, but through individual efforts can pursue and attain whatever personal brand of happiness he or she desires. In the midst of the Great Depression, Franklin Roosevelt recognized the part the federal government needed to play in keeping the American dream alive-no longer was hard work the only factor involved in ensuring an acceptable standard of living. Under his administration, a number of social programs were put into place to help Americans achieve the dream, which Roosevelt described as â€Å"sufficiency of life, rather than†¦a plethora of riches [and] good health, good food, good education, good working conditions† (qtd. In Muir). Owing to these principles, Roosevelt’s New Deal included the Social Security Act, Fair Labor Standards Act that banned child labor and established a minimum wage, and a variety of programs that put Americans to work in civil service (Successes 4-6). Roosevelt’s programs and World War II helped drag the nation out of the Great Depression, but were not permanent solutions in making the American dream possible for all Americans. By the 1960’s, one in five Americans were living in poverty, and in his first State of the Union address in 1964, Lyndon Johnson declared, â€Å"an unconditional war on poverty in America.† (qtd. In Quindlen 1) Johnson, too, understood that the American dream was one not attainable through hard work alone. As Anna Quindlen, Pulitzer-prize winning journalist, notes in her 2004 editorial, â€Å"from [Johnson’s] declaration a host of government initiatives sprang, including Head Start, an expended food-stamp program, and sweeping reforms in health care for the needy† (Quindlen 2). Unfortunately, in spite of the attempts of Roosevelt, Johnson, and others to lend a hand to those Americans who need it most, the feeling that the poor are responsible for their own troubles always seems to creep its way back into the American mind. We’ve all heard the rumors that the poor are lazy, that welfare is just n excuse not to get a job. Quindlen comments that â€Å"part of the problem with a war on poverty today is that many Americans have decided that being poor is a character defect, not an economic condition† (Quindlen 2). Public policy of the last few decades seems to follow this line of thinking: the Federal minimum wage has not risen since 1997 even as welfare reform movements have forced millions of people, many single parents, off public assistance and into minimum wage jobs. Quindlen argues that â€Å"forty years after Johnson led the charge, the battle against poverty still rages. The biggest differences today if that there is no call to arms by those in power† (Quindlen 1). How does this shift in American policy affect the status of the American dream? Can we still call ourselves the land of opportunity when the American dream eludes so many of our citizens? Should the American dream exist and is it really worth it to try and live by the dream? In July 2000, Mortimer Zuckerman, editor-in-chief of U.S. News and World Report, wrote an essay about the success of the American dream. Zuckerman claims that â€Å"it is a dream on individual effort-talent, ambition, risk-taking, readiness to change, and just plain hard work-qualities that count more in America than social background of luck† (Zuckerman 120). That is a perspective that Zuckerman, a billionaire whose biography on the U.S. News and World Report website boasts he has substantial real-estate holdings, including properties in Boston, New York, Washington, and San Francisco can afford to have. The reality for most Americans, however, is not nearly so great. It is a reality where social background and luck play far too large a part in achieving the American dream. Two articles written a decade apart demonstrate that bitter reality. In USA Today in 1996, Charles Whalen writes that â€Å"beneath the misleading surface prosperity [of the 1990s] are numerous alarming trends,† among them â€Å"relentless downsizing, longer job searches and sluggish job creation, explosive growth in contingent work (part-time and temporary employment), and wage stagnation† (Whalen 2-3). One would be hard=pressed to find a list that better demonstrates the part luck plays in securing steady employment. Whalen also cites a survey, ironically conducted for U.S. News and World Report, that indicates â€Å"57% of those asked said that the American dream is out of reach for most families† (qtd. in Whalen 2). In 2006 in the Chicago Sun-Times, Clyde Murphy cites a â€Å"new report released by the Opportunity Agenda [that] measures the nation’s progress in living up to the American dream.† The findings? â€Å"That millions of Americans do not have a fair chance to achieve their full potential, despite their best efforts† (Murphy 33). Two of the reasons cited by the study are housing discrimination against blacks, Hispanics, and Asians are employment discrimination against women and minorities, which included favoring job candidates with â€Å"white-sounding† names. These findings clearly refute Zuckerman’s claim, demonstrating that background does in fact count more in America than individual effort when it comes to achieving certain aspects of the American dream. Another dubious claim in Zuckerman’s essay is that â€Å"anybody who wishes to work has the opportunity to move from the bottom of the ladder to a middle-class standard of life, or higher† (Zuckerman 120). As award-winning journalist Barbara Ehrenreich notes in her book Nickel and Dimed: On (Not) Getting By in America, the rhetoric surrounding welfare reform â€Å"assumed that a job was the ticket out of poverty and that the only thing holding back welfare recipients was their reluctance to get out and get one† (Ehrenreich 196). As a wealth of evidence suggests, this is the fundamental misperception surrounding the American dream. In her 2003 editorial A New Kind of Poverty, Anna Quindlen argues â€Å"America is a country that now sits atop a precarious latticework of myth. It is the myth that working people can support their families† (Quindlen 2). Quindlen interviews two women who run services for the homeless and impoverished in New York City, ant they note that more often they are seeing working families in dire need of their help. Indeed, according to the U.S. Census Bureau’s 2005 report on poverty, America’s poverty rate has been climbing, from 11.3 percent in 2000 to 12.7 percent in 2004, the latest for which data is available. This translates into 37 million people who live below the poverty line. This is further complicated, however, by the way that the Census Bureau calculates the poverty level. Barbara Ehrenreich explains that â€Å"[it] is still calculated by the archaic method of taking the bare-bones cost of food for a family of a given size and multiplying that number by th ree. Yet food is relatively inflation-proof† (Ehrenreich 200). This method results in a base calculation of $9,310 for one person, with $3,180 added for each additional person in the household. As anyone who has ever lived on his or her own understands, those poverty calculations are very low. Ehrenreich points out that â€Å"the Economic Policy Institute recently reviewed dozens of studies of what constitutes a ‘living wage’ and came up with an average figure of $30,000 for a family of one adult and two children† (Ehrenreich 213). When compared to the federal poverty calculation of $15,670, the gap becomes glaringly apparent. Anna Quindlen explains â€Å"when you adjust the level to reflect reality, you come closer to 35 percent of all Americans who are having a hard time providing the basics for their families† (Quindlen 2). As pioneering psychologist Abraham Maslow’s research reveals, psychological and safety needs-the â€Å"basics† referred to by Quindlen, such as food and housing-must be fulfilled before other needs, core components of the American dream such as belongingness and self-esteem, can be met (Abraham 2). This creates a basic gap between those who can reach for the American dream and those who cannot; if all someone’s energy is focused on providing food and shelter, there is nothing left to reach for higher goals. In a 2002 essay What’s So Great About America? Dinesh D’Souza, an Indian immigrant, makes assertions that demonstrate some common misconceptions about Americans meeting our basic needs. â€Å"The United States is a country where the ordinary guy has a good life,† (D’Souza 23). He even goes so far to say that â€Å"very few people in America have to wonder where their next meal is coming from† (D’Souza 23). Sadly, this is not true. Quindlen indicates â€Å"the U.S. Department of Agriculture notes that 1.6 million New Yorkers†¦suffer from ‘food insecurity,’ which is just a fancy way of saying they do not have to enough to eat† (Quindlen 1). Ehrenreich reports that â€Å"according to a survey conducted by the U.S. Conference of Mayors, 67 percent of the adults requesting emergency food aid are people with jobs† (Ehrenreich 219). Two other basic needs, safe housing and health care, are also beyond the reach of many Americans. â€Å"When the rich and the poor compete for housing on the open market,† writes Ehrenreich, â€Å"the poor don’t stand a chance. The rich can always outbid them, buy up their tenements and trailer parks, and replace them with†¦whatever they like† (Ehrenreich 199). This is exaggerated by the fact that â€Å"expenditures on public housing have fallen since the 1980s, and the expansion of public rental subsidies came to a halt in the 1990s† (Ehrenreich 201). Health care is another sad story. According to the U.S. Census Bureau, the number of Americans with no health insurance has been slowly rising, arriving at 15.7 percent in 2004, and as Quindlen observes, â€Å"poor kids are much more likely to become sick than their counterparts, but much less likely to have health insurance. Talk about a double whammy† (Quindlen 1). How can families dream big an d plan for the future as they worry about whether the next month will bring eviction or illness? Two people in particular have put a human face on the statistical evidence that the American dream remains out of reach for millions of hard-working Americans. At the urging of her editor at Harper’s magazine, Barbara Ehrenreich undertook a yearlong undercover investigation of living on low-wage jobs in Florida, Maine, and Minnesota. She waited tables, worked as a maid, and worked at Wal-Mart, never revealing her statue as a reported, but keeping careful private diaries documenting the details of her experience. In spite of working at least full-time, usually more, she was unable to get by. The most heartbreaking part of her journey, however, was the people she met, women who were not just experimenting with the low-wage life, but who were trapped by it. They were women who were victims of the affordable housing shortage, who lived in cars, or if they were lucky, weekly rental motel rooms. They walked, rode bikes, or bummed rides to work. Certainly among those who experience food insecurity, they skipped meals or ate nutritionally void foods like hot dog buns because they couldn’t afford to eat. They were women with raw hands and sore backs, balancing two or more jobs who would never, in spite of their work ethic, move off that bottom rung of the social ladder. In a similar experiment, Morgan Spurlock (of Super Size Me fame) and his fiancà ©e lived on minimum wage for thirty days in Columbus, Ohio and recorded the results for the premiere episode of his television series 30 Days. As Spurlock works eighteen-hour days making at least $7.50 per hour and Alex works for minimum wage at a coffee house, the pair is faced with a host of challenges that mirror the everyday trials of the working poor. Emergency room visits for a urinary tract infection and a sprained wrist cost them $1,217. D’Souza correctly comments that in America, â€Å"even sick people who don’t have money or insurance will receive medical care at hospital emergency rooms† (D’Souza 23), but he fails to take into account that suck care generates bills are equivalent to six weeks’ of full time minimum wage work. The most affordable housing they could find, a steal at $325 per month, has ant infestations, malfunctioning heat, and is upstairs from an apartment that was a crack house just the week before. Furthermore, their relationship is strained by the stress that results from the constant worrying about money. At the end of the month they find themselves hundreds of dollars in the hole, by permanently changed by their experience. When taken together, the accounts of Ehrenreich and Spurlock offer powerful insight into the everyday struggles of the working poor, those who are anything but lazy but still find themselves drowning financially, the American dream slipping further away all the time. Dinesh D’Souza claims that â€Å"in America your destiny is not prescribed. Your life is like a blank sheet of paper and you are the artist† (D’Souza 24). It is difficult to believe, however, that the millions of working poor are not trying to create a better destiny for themselves, only to find their dreams let down by the harsh realities of daily life. So why is the American dream still suck a pervasive part of our consciousness, even in the face of overwhelming evidence that hard work is not the ticket to prosperity, or even necessarily to a comfortable standard of living? In his â€Å"Critique of Hegel’s Philosophy of the Right,† Karl Marx wrote that â€Å"religion is the sigh of the oppressed creature, the heart of the heartless world, just as it is the spirit of a spiritless situation. It is the opium of the people. The abolition of religion as the illusory happiness of the people is required for the real happiness† (qtd in Cline). Marx’s clever observation is that religion, in keeping the focus on the afterlife, keeps people from demanding fair treatment in this world. D’Souza suggests, however, that â€Å"capitalism gives America a this-worldly focus that allows death and the afterlife to recede from everyday view†¦the gaze of the people is shifted to earthly progress† (D’Souza 25). If this the case, why is it that we are not more aware of (and enraged about!) the decided lack of â€Å"earthly progress† of so many of our friends and neighbors? Some believe that it is because the American dream has taken the place of religion as today’s â€Å"opiate of the masses.† So long as we all believe that there is a better life ahead, that is we only work harder, our dreams are within reach, it is easy to be lulled into satisfaction about the inequality that is so common in America today. Barbara Ehrenreich predicts that someday the working poor â€Å"are bound to tire of getting so little in return [for their labor] and to demand to be paid what they’re worth† (Ehrenreich 221). Some challenge, echoing Marx, that Ehrenreich’s predication will not come true until the American dream, â€Å"the illusory happiness of the people,† is abolished in favor of a more realistic world view that recognizes that more than hard work, a hel ping hand is needed to make America truly the land of opportunity. From the survey that I took in class, 14 out of 20 people were surveyed and said that they to, disagree that the American dream should exist. They believe as well that there should be a more realistic view in society that allows you to get what you work for. Of the people that did agree, most were people between the ages of 18 and 21, people who have not yet, most likely gotten out into the real world to experience what type of life they can actually work for. If you too, disagree with the American dream, I ask you to go to this website: http://www.thepetitionsite.com/3/the-american-dream-is-not-for-rent , sign the petition, and keep working hard at what you do! Work Cited â€Å"Abraham Maslow’s Hierarchy of Needs.† Shippensberg University Website. Sept. 2005: 2-3. Web. 16 June 2009. Cline, Austin. â€Å"Karl Marx on Religion.† About.com. 5 Apr. 2006: n.pag. Web. 16 June 2009. D’Souza, Dinesh. â€Å"What’s So Great About America?† The American Enterprise. May 2002: 22-25. Print. Ehrenreich, Barbara. â€Å"Nickel and Dimed: On (Not) Getting By in America.† New York: Owl Books. 2002: 20-38. Print. Ferenz, Kathleen. â€Å"What is the American Dream?† San Francisco State University Online Web Site. 31 Mar. 2005: n.pag. Web. 16 June 2009. Muir, Ed. â€Å"Narrowing the Highway to the American Dream.† American Teacher. Oct. 2004: 25. Print. Murphy, Clyde. â€Å"When Opportunity Knocks, It Skips Over Some Adresses.† Chicago Sun-Times. 14 Feb. 2006: 33. Web. 16 June 2009. Quindlen, Anna. â€Å"A New Kind of Poverty.† Newsweek. 1 Dec. 2003: 1-2. Web. 16 June 2009. Quindlen, Anna. â€Å"The War We Haven’t Won.† Newsweek. 20 Sep. 2004: 1-2. Web. 16 June 2009. â€Å"Successes and Failures of Roosevelt’s ‘New Deal’ Programs.† Bergen County Technical Schools and Special Services Web Site. 10 Mar. 2006: 4-6. 16 June 2009. U.S Census Bureau. 2005 Poverty Press Release. 30 Aug. 2005: n.pag. 16 June 2009. Whalen, Charles J. â€Å"The Age of Anxiety: Erosion of the American Dream.† USA Today. Sep. 1996: 1-3. Web. 16 June 2009. Zuckerman, Mortimer. â€Å"A Time to Celebrate.† U.S. News and World Report. 17 Jul. 2000: 120. Print.

Separate Peace Essay: Analysis of Marxism -- free essay writer

A Separate Peace:   Analysis of Marxism  Ã‚  Ã‚  Ã‚  Ã‚   A Separate Peace is an impeccable paradigm of critical mythology interpreted by philosophers such as Marx, Engels and Hegel.   The philosophy of Marxism serves as a basis for socialism and communism and is explicitly demonstrated by means of power, the understanding of human nature, and alienation.   Finny demonstrates authority and control over a lonely, alienated friend Gene, however, unitedly they discover friendship through the individuality possessed by one another.   Finny and Gene agonize with these eminent responsibilities and endeavor to uncover an inner peace within themselves as they evolve into young adults waking to the realities of life.   Their entity follows the social formation of their lives,   â€Å"men enter into definite relations that are indispensable and dependant of their will, relations of production ...development of their material productive forces.† (Tucker, 1978, pg.4) Therefore, by means of growth to maturity the two young men exemplify the challenges of manhood.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Power is an extremely dominant element that illustrates authority and control between the two young men Finny and Gene.   Throughout society, â€Å"the social power, i.e., the multiplied productive force, which arises through the co-operation of different individuals, since their co-operation is not voluntary but has come about naturally, not as their own united power.†(Tucker,   pg.161) Finny conducts himself as an authority figure, and an individualist with distinct and domineering characteristics.   He emphasizes his power as a perfect individual that is not concerned what other people conceive of ... ...monstrates his advantage to take control over every individual without any sincere emotions of any kind.   However, the companionship developed through the nature of man, although agonizing, has formed a special bond between the two boys.   Gene, nonetheless contends with feelings of alienation and self-estrangement indirectly generated by Finny.  Ã‚   The two young men persevere these responsibilities to initiate a sense of inner peace that transpires from adolescence to adulthood.   Their experience’s prove to be a symmetric accomplishment of manhood.      Works Cited Knowles, John. (1959) A Separate Peace London: Secker & Warburg Limited    Tucker, Robert. (1978) The Marx-Engles Reader (2nd ed.) New York: W.W. Norton & Company    Microsoft Encarta Encyclopedia 99. 1998 Microsoft Corporation      

Okonkwo Character Analysis

To help you, my dear clan, learn the importance of not letting your personal flaws be the reason for your downfall, I must tell you about our former clansman, Okonkwo. I watched as his weaknesses and pride brought him down to the point of suicide, which is the escape of cowards. He killed himself because he felt like he had nothing left to live for. Instead of facing a new, changed life in Umuofia, he escaped by taking his own. Before his downward spiral, Okonkwo was known as a self-determined and hard-working man who worked hard to earn many titles amongst our clan.Listen as I explain Okonkwo’s character. Okonkwo’s father was Unoka, who was loved by all amongst the clan. â€Å"He was tall but very thin and had a slight stoop. He wore a haggard and mournful look except when he was drinking or playing on his flute† (4). Unoka was lazy and had many debts that he didn’t pay off yet he was loved. Okonkwo grew up observing his dad mettle through life by living off others. â€Å"But Unoka was such a man that he always succeeded in borrowing more, and piling up debts† (5).Okonkwo watched his father be pitied because he couldn’t feed his wives or children. At his death, Unoka had no titles and he was still greatly in debt. â€Å"Any wonder then that his son Okonkwo was ashamed of him? † (7) Due to his father’s example, Okonkwo knew he wanted to achieve great things and he was determined he would become the opposite of his father. This aspect of Okonkwo’s character leads him to success. Okonkwo succeeded materially in our clan. One particular point of recognition happened when he fought Amanlize the Cat.Amanlize the Cat had not been defeated in seven years, and so when Okonkwo defeated him at the young age of eighteen he became well known throughout our nine villages. Okonkwo continued to grow into a great man. â€Å"He was tall and huge, and his bushy eyebrows and wide nose gave him a very severe look†¦. When he walked his heels hardly touched the ground and he seemed to walk on springs† (3). With his hard work he earned three wives, found financial security, ran a successful yam farm, produced multiple children, built several huts, and received many titles.Unfortunately, as sometimes happens with great men, Okonkwo had flaws. He had a temper, no self-control, he was over confidant, and he beat his poor wives. His most serious flaw was his pride. Just as he’d hoped, Okonkwo became the total opposite of his dad who had been a lazy debtor. His dad had also been a peace loving and kind man who was loved by all in our villages and Okonkwo could not say the same. An instance where Okonkwo let his pride cloud his judgment is when he participated in the killing of Ikemefuna, a boy he was raising as his own son. Okonkwo thought of Ikemefuna as the perfect son.Okonkwo liked that his biological son Nwoye and Ikemefuna were getting along because he was afraid of Nwoye’s lack of manliness. Okonkwo felt that Nwoye hanging around Ikemefuna would make him more of a man. Trouble arose when the Oracle in his village decided that Ikemefuna had to die because he was interfering with Okonkwo and his oldest son, Nwoye’s, relationship. Okonkwo was warned in advanced not to participate in the killing of Ikemefuna, but he did anyway because he was afraid of what the other men in the tribe would think of him if he didn’t participate.Okonkwo was too worried that he would be viewed as weak. His pride drove him to help kill a boy he loved as a son and this greatly harmed his relationship with Nwoye. Okonkwo was also too worried about Nwoye becoming â€Å"womanly† like his father, Unoka, and he didn’t realize how he was hurting his family with his violent and stubborn nature. Later on there was an instance when Okonkwo’s carelessness leads him to accidently kill a woman from our village.The custom in our village is to exile a man for seven years for such a crime and therefore Okonkwo went to his mother’s village, Mbanta. As the elders said, if one finger brought oil it soiled the others† (106). After seven long years of exile in his mother’s village, Okonkwo returned to his village eager to start his life by building more huts and showing his wealth. When Okonkwo came back to Umuofia he expected his wealth to place him in the same circumstances as before his exile. â€Å"The clan had undergone such profound change during his exile that it was barley recognizable† (150). You see, the missionaries had come into the church and attracted many of our people to it.This changed our clan remarkable with all the new people. â€Å"He knew that he had lost his place among the nine masked spirits who administered justice in the clan† (140). In addition to the new religion that is to this day so different and odd to us, they built a government. In his pride, Okonkwo figured that he could go to war with the new white people, but this turned out to be harder than he expected. Once he went to war he kept being defeated and eventually Okonkwo’s anger got the best of him and he actually killed another man. It was useless.Okonkwo’s machete descended twice and the man’s head lay beside his uniformed body† (168). Okonkwo felt worthless, like his life meant nothing any more. Instead of facing the new changes in his clan, he went the cowardly way out through suicide. This man of our clan who had worked hard to become great in order to overcome the shame from his childhood and who had built wealth in our village allowed his pride to be his ruin. What Okonkwo did to end his own life was incredibly selfish and he took the coward’s way out.He killed others in his violent temper, he killed a boy who was like a son to him, and in the end, he killed himself. The only last noble thing Okonkwo did was try and stand up to fight and save our clan from being taken over by the white people. Okonkwo was a fighter and a warrior, but in the end everything he worked for was meaningless. Heed my warnings. Learn from your past to improve your future, but don’t allow your past to cloud your judgment and make you too prideful about your own negative qualities.

Cloning Genetics and Society - Free Essay Example

Sample details Pages: 2 Words: 718 Downloads: 2 Date added: 2019/08/08 Category Science Essay Level High school Tags: Cloning Essay Did you like this example? Cloning is a very controversial topic, when Dolly the sheep was introduced people were amazed amazing, but the discussion on whether people should be able to be cloned is still at large. I say that plants and animals is safe enough but, people should not be cloned. The pros of cloning animals and plants is that they arent hurting anyone, cloning can bring back dying species and repopulate species with downing numbers, and it can be used with animals to create a better version of that species. Creating new plants and animals wont hurt anyone because it is different for the over population for animals and plants. For those, you could easily fix it with hunting or trimming. Cloning animals that are going extinct is helpful because they are dying it would be good to save the animals if anything its just balancing the scale of things. The last pro for animal cloning is that it can be used to make a better version of the animal. Say a bull has a specific gene or something that can help cure cancer, you would want to get more of it without losing the bull. Cloning would do that by creating multiple of the bull so you can get more.(Advantages and Disadvantages)(MacDonald)(Center for Genetics and Society) Don’t waste time! Our writers will create an original "Cloning: Genetics and Society" essay for you Create order The cons of animal cloning is that it is usually unsuccessful, it is very expensive, and its very unreliable in the form of reproduction. It is very unsuccessful as 95% of attempts usually end in failure. Cloning animals also has a high risk of birth defects or getting illnesses easier. Some animals who were cloned that seemed to have been healthy have required health complications. Viagen Pets has said that the cost to make a twin of a cat costs about 25,000 dollars, the clone a dog is around 50,000 dollars, and it is has been said that the cost of Dolly the Sheep was around 1 million dollars. If that is the cost to get something cloned, imagine the cost of the equipment and the time and the effort to create it. The reason it is an unreliable form of reproduction is because it can cause Large Offspring Syndrome, which can be fatal to the clone and the animal it came out of. For bovines that have been bred out of cloning, it can occur in around half of the attempts. Also, 1 in 4 bovi nes can also contract a disease called hydrops, which is when the animal swells with fluid it has retained.(Advantages and Disadvantages)(Center for Genetics and Society) This reasons for why human cloning is bad is because it will make overpopulation a bigger problem than it already is and egg extraction is very risky. It will make overpopulation a bigger problem because a women can only have one baby a year and if scientists have a bunch of womens eggs, they can create a lot more than just one. This leads me to my next issue with it as taking eggs from women is extremely risky. Paying women for their eggs can be damaging to them and some women might feel pressured to give them away if they need money. Otherwise, women wouldnt give away their eggs if they werent being paid for it. (The Case Against Human Cloning) Although, I am for animal and plant cloning, I can recognize when something is not all perfect. I still that plants and animals is safe enough but, people should not be cloned. Work Cited Animal Cloning: Old MacDonalds Farm Is Not What It Used To Be. Remedies From Native American Cultures, www.manataka.org/page1033.html. Animal Cloning: Old MacDonalds Farm Is Not What It Used To Be. Remedies From Native American Cultures, www.manataka.org/page1033.html. Burgstaller, Jerg Patrick, and Gottfried Brem. Aging of Cloned Animals: A www.karger.com/Article/FullText/452444. Crystal Lombardo. Vittana.org, 8 Nov. 2017, vittana.org/10-advantages-and-disadvantages-of-cloning-animals. Reproductive Cloning Arguements Pros and Cons. How Much Do Stem Cell Treatments Really Cost? | Center for Genetics and Society, 15 May 2006, www.geneticsandsociety.org/internal-content/reproductive-cloning-arguments-pro-and-con. Research Cloning Arguement Pros and Cons. How Much Do Stem Cell Treatments Really Cost? | Center for Genetics and Society, 2006, www.geneticsandsociety.org/internal-content/research-cloning-arguments-pro-and-con. The Case Against Human Cloning. RNA Editing Tools Could Create New Disease Therapies BioNews, 28 Sept. 2015, www.bionews.org.uk/page_95215

Haemoglobinopathies - Free Essay Example

Sample details Pages: 25 Words: 7474 Downloads: 5 Date added: 2017/06/26 Category Statistics Essay Did you like this example? Abstract Haemoglobinopathies or inherited disorders of haemoglobin are the most common monogenic disorders in humans. Red cell transfusion is a well accepted therapy for clinical management of the most severe form of haemoglobinopathies namely, sickle cell disease (SCD) and ÃŽÂ ²-thalassaemia major. Patients affected by SCD need red blood cell transfusions on a regular basis to reduce morbidity and mortality. Don’t waste time! Our writers will create an original "Haemoglobinopathies" essay for you Create order The transfusions are administered intermittently to control or prevent a serious complication of SCD, and as a perioperative measure. Or, as a chronic procedure, transfusion strategy is applied to prevent the recurrence, or the first occurrence, of stroke which is a major crisis in SCD, and to manage pulmonary hypertension and other sources of morbidity and mortality. Exchange transfusions are used to reduce the sickle cell haemoglobin (HbS) levels during crisis. Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudicious. Many side effects of transfusion have been identified and methods to overcome them have been developed. Iron overload (remedy: iron chelation), and alloimmunisation (remedy: phenotypical matching of transfused blood) are two notable examples. Association of haemoglobinopathies and neurologic sequelae after transfusion is also known. At the present time, bone marrow transplant is the only curati ve procedure available for both SCD and ÃŽÂ ²-thalassaemia major. Potential therapies involving stem cell transplantation and gene techniques are being vigorously researched. A detailed discussion of the current status of clinical management strategies as applied to inherited haemoglobin-related diseases in particular, sickle cell disease and the thalassaemias, is presented in this paper. 1. Introduction Anaemia is a syndrome characterised by a lack of healthy red blood cells or haemoglobin deficiency in the red blood cells, resulting in inadequate oxygen supply to the tissues. The condition can be temporary, long-term or chronic, and of mild to severe intensity. There are many forms and causes of anaemia. Normal blood consists of three types of blood cells: white blood cells (leucocytes), platelets and red blood cells (erythrocytes). The first generation of erythrocyte precursors in the developing foetus are produced in the yolk sac. They are carried to the developing liver by the blood where they form mature red blood cells that are required to meet the metabolic needs of the foetus. Until the 18th week of gestation, erythrocytes are produced only by liver after which the production shifts to the spleen and the bone marrow. The life of a red blood cell is about 127 days or 4 months (Shemin and Rittenberg, 1946; Kohgo et al., 2008). The main causes of anaemia are blood loss, product ion of too few red blood cells by the bone marrow or a rapid destruction of cells. Haemoglobin, a protein, present in the red blood cells is involved in the transport of oxygen from the lungs to all the other organs and tissues of the body. Iron is an important constituent of the haemoglobin protein structure which is intimately involved in the transport of oxygen. Anaemia is generally defined as a lower than normal haemoglobin concentration. The normal blood haemoglobin concentration is dependent on age and sex, and, according to the World Health Organisation (WHO) Expert Committee Report, anaemia results when the blood concentration of haemoglobin falls below 130 g/L in men or 120 g/L in non-pregnant women (WHO, 1968). However, the reference range of haemoglobin concentration in blood could vary depending on the ethnicity, age, sex, environmental conditions and food habits of the population analysed. According to Beutler and Warren (2006), more reasonable benchmarks for anaemia are 137 g/L for white men aged between 20 and 60 years and 132 g/L for older men. The value for women of all ages would be 122 g/L. Also, the lower limit of normal of haemoglobin concentrations of African Americans are appreciably lower than that of Caucasians (Beutler and Warren, 2006). Besides the well recognised iron deficiency anaemia, several inherited anaemias are also known. These are mostly haemoglobinopathies. Adult haemoglobin is a tetrameric haeme-protein. Abnormalities of beta-chain or alpha-chain produce the various medically significant haemoglobinopathies. The variations in amino acid composition induced genetically impart marked differences in the oxygen carrying properties of haemoglobin. Mutations in the haemoglobin genes cause disorders that are qualitative abnormalities in the synthesis of haemoglobin (e.g., sickle cell disease) and some that are quantitative abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall., 1969). In SCD, the missense mutation in the ÃŽÂ ²-globin gene causes the disorder. The mutation causing sickle cell anemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. The substitution converts a glutamic acid codon (GAG) to a valine codon (GTG). The form of haemoglobin in persons with sickle cell anemia is referred to as HbS. Also, the valine for glutamic acid replacement causes the haemoglobin tetramers to aggregate into arrays upon deoxygenation in the tissues. This aggregation leads to deformation of the red blood cell making it relatively inflexible and restrict its movement in the capillary beds. Repeated cycles of oxygenation and deoxygenation lead to irreversible sickling and clogging of the fine capillaries. Incessant clogging of the capillary beds damages the kidneys, heart and lungs while the constant destruction of the sickled red blood cells triggers chronic anaemia and episodes of hyperbilirubinaemia. Fanconi anaemia (FA) is an autosomal recessive condition, and the most common type of inherited bone marrow failure syndrome. The clinical features of FA are haematological with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML) being increasingly present in homozygotes (Tischkowitz and Hodgson, 2003). Cooleys anaemia is yet another disorder caused by a defect in haemoglobin synthesis. Autoimmune haemolytic anaemia is a syndrome in which individuals produce antibodies directed against one of their own erythrocyte membrane antigens. The condition results in diminished haemoglobin concentrations on account of shortened red blood cell lifespan (Sokol et al., 1992). Megaloblastic anaemia is a blood disorder in which anaemia occurs with erythrocytes which are larger in size than normal. The disorder is usually associated with a deficiency of vitamin B12 or folic acid . It can also be caused by alcohol abuse, drugs that impact DNA such as anti-cancer drugs, leukaemia, and certain inherited disorders among others (Dugdale, 2008). Malaria causes increased deformability of vivax-infected red blood cells (Anstey et al., 2009). Malarial anaemia occurs due to lysis of parasite-infected and non-parasitised erythroblasts as also by the effect of parasite products on erythropoiesis (Ru et al., 2009). Large amounts of iron are needed for haemoglobin synthesis by erythroblasts in the bone marrow. Transferrin receptor 1 (TfR1) expressed highly in erythroblasts plays an important role in extracellular iron uptake (Kohgo et al., 2008). Inside the erythroblasts, iron transported into the mitochondria gets incorporated into the haeme ring in a multistep pathway. Genetic abnormalities in this pathway cause the phenotype of ringed sideroblastic anemias (Fleming, 2002). The sideroblastic anemias are a heterogeneous group of acquired and inherited bone marrow disorders, characterised by mitochondrial iron overload in developing red blood cells. These conditions are diagnosed by the presence of pathologic iron deposits in erythroblast mitochondria (Bottomley, 2006).   2. Classification of anaemia Anaemia can be generally classified based on the morphology of the red blood cells, the pathogenic spectra or clinical presentation (Chulilla et al., 2009). The morphological classification is based on mean corpuscular volume (MCV) and comprises of microcytic, macrocytic and normocytic anaemia. (a) Microcytic anaemia refers to the presence of RBCs smaller than normal volume, the reduced MCV ( 82 fL) reflecting decreased haemoglobin synthesis.   Thus, it is usually associated with hypochromic anaemia. Microcytic anaemia can result from defects either in iron acquisition or availability (Iolascon et al., 2009), or disorders of haeme metabolism or globin synthesis (Richardson, 2007). The differential diagnosis for microcytic anaemia includes iron deficiency anaemia (IDA), thalassaemia, ACD, and rarely sideroblastic anaemia (Chulilla et al., 2009). Microcytosis without anaemia is characteristic of thalassaemia trait. The red blood cell distribution width (RDW) obtained with haematological analysers provides the index of dispersion in the erythrocyte distribution curve and complements MCV values. RDW is helpful to differentiate between thalassaemia and IDA. RDW is normal in thalassemia; on the contrary, microcytic anemia with RDW 15 would probably indicate IDA (Chulilla et al., 2009). In macrocytic anaemia, erythrocytes are larger (MCV 98 fL) than their normal volume (MCV = 82-98 fL). Vitamin B12 deficiency leads to delayed DNA synthesis in rapidly growing haematopoietic cells, and can result in macrocytic anaemia. Drugs that interfere with nucleic acid metabolism, such as.hydroxyurea increases MCV ( 110 fL) while alcohol induces a moderate macrocytosis (100-110 fL). In the initial stage, most anaemias are normocytic. The causes of normocytic anaemia are nutritional deficiency, renal failure and haemolytic anemia (Tefferi, 2003). The most common normocytic anaemia in adults is ACD (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anaemia, red blood cell membrane disorders and current or recent infections especially in the very young (Bessman et al., 1983). Homozygous sickle cell disease is the most common cause of haemolytic normocytic anemias in children (Weatherall DJ, 1997a). In practice, the morphological classification is quicker and therefore, more useful as a diagnostic tool. Besides, MCV is also closely linked to mean corpuscular haemoglobin (MCH), which denotes mean haemoglobin per erythrocyte expressed in picograms (Chulilla et al., 2009). Thus, MCV and MCH decrease simultaneously in microcytic, hypochromic anaemia and increase together in macrocytic, hyperchromic anemia. Pathogenic classification of anaemia is based on the production pattern of RBC: whether anaemia is due to inadequate production or loss of erythrocytes caused by bleeding or haemolysis. This approach is useful in those cases where MCV is normal. Pathogenic classification is also essential for proper recognition of the mechanisms involved in the genesis of anaemia. Based on the pathogenic mechanisms, anaemia is further divided into two types namely, (i) hypo-regenerative in which the bone marrow production of erythrocytes is decreased because of impaired function, decreased number of precursor cells, reduced bone marrow infiltration, or lack of nutrients; and (ii) regenerative: when bone marrow upregulates the production of erythrocytes in response to the low erythrocyte mass (Chulilla et al., 2009). This is typified by increased generation of erythropoietin in response to lowered haemoglobin concentration, and also reflects a loss of erythrocytes, due to bleeding or haemolysis. The r eticulocyte count is typically higher. Sickle cell disease is characterised by sickled red cells.   The first report of SCD was published a century ago noting the presence of peculiar elongated cells in blood by James Herrick, an American physician (1910). Pauling et al. (1949) described it as a molecular disease. The molecular nature of sickle haemoglobin (HbS) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of haemoglobin, causing red cells to sickle (Fig. 1). Sickling of cells occurs at first reversibly, then finally as a state of permanent distortion, when cells containing HbS and inadequate amounts of other haemoglobins including foetal haemoglobin, which retards sickling, become deoxygenated (Bunn, 1997). The abnormal red cells break down, leading to anaemia, and clog blood vessels with aggregates, leading to recurrent episodes of severe pain and multiorgan ischaemic damage (Creary et al., 2007). The high levels of inflammatory cytokines in SCD may promote retention of iron by macrophage/reticuloendothelial cells and/or renal cells. SCD care commonly depends on transfusion that results in iron overload (Walter et al., 2009). 3. Pathogenesis of anaemia Anaemia is a symptom , or a syndrome, and not a disease (Chulilla et al., 2009). Several types of anaemia have been recognised, the pathogenesis of each being unique. Iron deficiency anaemia (IDA) is the most common type of anaemia due to nutritional causes encountered worldwide (Killip et al., 2008). Iron is one of the essential micronutrients required for normal erythropoietic function While the causes of iron deficiency vary significantly depending on chronological age and gender, IDA can reduce work capacity in adults (Haas Brownlie, 2001) and affect motor and mental development in children (Halterman et al., 2001). The metabolism of iron is uniquely controlled by absorption rather than excretion (Siah et al., 2006). Iron absorption typically occurring in the duodenum accounts for only 5 to 10 per cent of the amount ingested in homoeostatis. The value decreases further under conditions of iron overload, and increases up to fivefold under conditions of iron depletion (Killip et al., 2008). Iron is ingested as haem iron (10%) present in meat, and as non-haem ionic form iron (90%) found in plant and dairy products. In the absence of a regulated excretion of iron through the liver or kidneys, the only way iron is lost from the body is through bleeding and sloughing of cells. Thus, men and non-menstruating women lose about 1 mg of iron per day while menstruating women could normally lose up to 1.025 mg of iron per day (Killip et al., 2008). The requirements for erythropoiesis   which are typically 20-30 mg/day   are dependent on the internal turnover of iron (Munoz et al., 2009) For example, the amount of iron required for daily production of 300 billion RBCs (20-30 mg) is provided mostly by recycling iron by macrophages (Andrews, 1999). Iron deficiency occurs when the metabolic demand for iron exceeds the amount available for absorption through consumption. Deficiency of nutritional intake of iron is important, while abnormal iron absorption due to hereditary or acquired iron-refractory iron deficiency anemia (IRIDA) is another important cause of unexplained iron deficiency. However, IDA is commonly attributed to blood loss e.g., physiological losses in women of reproductive age. It might also represent occult bleeding from the gastrointestinal tract generally indicative of malignancy (Hershko and Skikne, 2009). Iron absorption and loss play an important role in the pathogenesis and management of IDA. Human iron disorders are necessarily disorders of iron balance or iron distribution. Iron homeostasis involves accurate control of intestinal iron absorption, efficient utilisation of iron for erythropoiesis, proper recycling of iron from senescent erythrocytes, and regulated storage of iron by hepatocytes and macrophages (Andrews, 2008). Iron deficiency is largely acquired, resulting from blood loss (e.g., from intestinal parasitosis), from inadequate dietary iron intake, or both. Infections, for example, with H pylori, can lead to profound iron deficiency anemia without significant bleeding. Genetic defects can cause iron deficiency anaemia. Mutations in the genes encoding DMT1 (SLC11A2) and glutaredoxin 5 (GLRX5) lead to autosomal recessive hypochromic, microcytic anaemia (Mims et al., 2005). Transferrin is a protein that keeps iron nonreactive in the circulation, and delivers iron to cells possessing specific transferrin receptors such as TFR1 which is found in largest amounts on erythroid precursors. Mutations in the TF gene leading to deficiency of serum transferrin causes disruption in the transfer of iron to erythroid precursors thereby producing an enormous increase in intestinal iron absorption and consequent tissue iron deposition (Beutler et al., 2000). Quigley et al. (2004) found a haem exporter, FLVCR, which appears to be necessary for normal erythroid development. Inactivation of FLVCR gene after birth in mice led to severe macrocytic anaemia, indicating haem export to be important for normal erythropoiesis. The anaemia of chronic disease (ACD) found in patients with chronic infectious, inflammatory, and neoplastic disorders is the second most frequently encountered anaemia after iron-deficiency anaemia. It is most often a normochromic, normocytic anaemia that is primarily caused by an inadequate production of red cells, with low reticulocyte production (Krantz, 1994). The pathogenesis of ACD is unequivocally linked to increased production of the cytokines including tumour necrosis factor, interleukin-1, and the interferons that mediate the immune or inflammatory response. The various processes leading to the development of ACD such as reduced life span of red cells, diminished erythropoietin effect on anaemia, insufficient erythroid colony formation in response to erythropoietin, and impaired bioavailability of reticuloendothelial iron stores appear to be caused by inflammatory cytokines (Means, 1996;2003). Although iron metabolism is characteristically impaired in ACD, it may not play a key role in the pathogenesis of ACD (Spivak, 2002). Neither is the lack of available iron central to the pathogenesis of the syndrome, according to Spivak (2002), who found reduced iron absorption and decreased erythroblast transferrin-receptor expression to be the result of impaired erythropoietin production and inhibition of its activity by cytokines. However, reduced erythropoietin activity, mostly from reduced production, plays a pivotal role in the pathogenesis of ACD observed in systemic autoimmune diseases (Bertero and Caligaris-Cappio, 1997). Indeed, iron metabolism as well as nitric oxide (NO), which contributes to the regulation of iron cellular metabolism are involved in the pathogenesis of ACD in systemic autoimmune disorders. Inflammatory mediators, particularly the cytokines, are important factors involved in the pathogenesis of the anaemia of chronic disease, as seen in rheumatoid arthritis anaemia (Baer et al., 1990), the cytokines causing impairment of erythroid p rogenitor growth and haemoglobin production in developing erythrocytes.   Anaemia is also commonly found in cases of congestive heart failure (CHF), again caused by excessive cytokine production leading to reduced erythropoietin secretion, interference with erythropoietin activity in the bone marrow and reduced iron supply to the bone marrow (Silverberg et al., 2004). However, in the presence of chronic kidney insufficiency, abnormal erythropoietin production in the kidney plays a role in the pathogenesis of anaemia in CHF. The myelodysplastic syndromes (MDS) are common haematological malignancies affecting mostly the elderly as age-related telomere shortening enhances genomic instability (Rosenfeld and List, 2000). Radiation, smoking and exposure to toxic compounds e.g., pesticides, organic chemicals and heavy metals, are factors promoting the onset of MDS via damage caused to progenitor cells, and, thereby, inducing immune suppression of progenitor cell growth and maturation. TNF- and other pro-apoptotic cytokines could play a central role in the impaired haematopoiesis of MDS (Rosenfeld and List, 2000). Premature intramedullary cell death brought about by excessive apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).   SCD arising from a point mutation in the ÃŽÂ ²-globin gene and leading to the expression of haemoglobin S (HbS) is the most common monogenetic disorder worldwide. Chronic intravascular haemolysis and anaemia are some important characteristics of SCD. Intravascular haemolysis causes endothelial dysfunction marked by reduced nitric oxide (NO) bioavailability and NO resistance, leading to acute vasoconstriction and, subsequently, pulmonary hypertension (Gladwin and Kato, 2005).    However, a feature that differentiates SCD from other chronic haemolytic syndromes is the persistent and intense inflammatory condition present in SCD. The primary pathogenetic event in SCD is the intracellular polymerisation or gelation of deoxygenated HbS leading to rigidity in erythrocytes (Wun, 2001). The deformation of erythrocytes containing HbS is dependent on the concentration of haemoglobin in the deoxy conformation (Rodgers et al., 1985). It has been demonstrated that sickle monocytes are a ctivated which, in turn, activate endothelial cells and cause vascular inflammation. The vaso-occlusive processes in SCD involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall (Connes et al., 2008). Thus, inflammation, leucocyte adhesion to vascular endothelium, and subsequent endothelial injury are other crucial factors contributing to the pathogenesis of SCD (Jison et al., 2004). 4. Current therapies for clinical management of sickle cell disease including a critical appraisal of transfusion Between 1973 and 2003, the average life expectancy of a patient with SCD increased dramatically from a mere 14 years to 50 years thanks to the development of comprehensive care models and painstaking research efforts in both basic sciences especially molecular and genetic studies, and clinical aspects of SCD (Claster and Vichinsky, 2003). The clinical manifestations of SCD are highly variable. Both the phenotypic expression and intensity of the syndrome are vastly different among patients and also vary longitudinally within the same patient (Ballas, 1998). New pathophysiological insights available have enabled treatments to be developed for the recognised haematologic and nonhaematologic abnormalities in SCD (Claster and Vichinsky, 2003). The main goals of SCD treatment are symptom alleviation, crises avoidance and effective management of disease complications. The strategy adopted is primarily palliative in nature, and consists of supportive, symptomatic and preventative approaches to therapy. Symptomatic management includes pain mitigation, management of vasoocclusive crisis, improving chronic haemolytic anaemia, treatment of organ failure associated with the disease, and detection and treatment of pulmonary hypertension (Distenfeld and Woermann, 2009). The preventative strategies include use of prophylactic antibiotics (e.g., penicillin) in children, prophylactic blood transfusion for prevention of stroke in patients especially young children who are at a very high risk of stroke, and treatment with hydroxyurea of patients experiencing frequent acute painful episodes (Ballas, 2002). Currently, curative therapy for sickle cell anaemia is only available through bone marrow and stem cell transplantation. Hematopoietic cell transplantation using stem cells from a matched sibling donor has yielded excellent results in paediatric patients (Krishnamurti, 2007). Curative gene therapy is still at the exploratory stage (Ballas, 2002). 4.1 Current and potential therapies The potential treatment strategies basically target cellular dehydration, sickle haemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation (Claster and Vichinsky, 2003). HbS concentrations are essentially tackled through transfusions while approaches to reduce HbS polymerisation which is the main mechanism for the development of vaso-occlusion include (a) increasing foetal haemoglobin (HbF) concentration using hydroxyurea (Fig. 2), butyrate, or erythropoietin, and (b) preventing sickle cell dehydration using Clotrimazole (Fig. 3) or Mg2+pidolate. Hydroxyurea therapy increases the production of HbF in patients with sickle cell anaemia, and, thereby, inhibits the polymerisation of HbS and alleviates both the haemolytic and vaso-occlusive manifestations of the disease (Goldberg et al., 1990). Recombinant erythropoietin also increases the number of reticulocytes with HbF. Additionally, it has been observed that administration of intravenous recombinant eryt hropoietin with iron supplementation alternating with hydroxyurea enhances HbF levels more than hydroxyurea alone (Rodgers et al., 1993). As SCD is essentially characterized by an abnormal state of endothelial cell activation   that is, a state of inflammation, a pharmacologic approach to inhibit endothelial cell activation has proved clinically beneficial (Hebbel and Vercellotti, 1997). Thus, administration of sulfasalazine which is a powerful inhibitor of activation of nuclear factor (NF)-B, the transcription factor promoting expression of genes for a number of pro-adhesive and procoagulant molecules on endothelium to humans has been found to provide transcriptional regulation of SCD at the endothelium level (Solovey et al., 2001). 4.2 Red blood cell transfusion A key therapy that is applied regularly in the clinical management of patients with SCD is packed red blood cell transfusion. RBC transfusion improves the oxygen-carrying capacity which is achieved by enhancing the haemoglobin levels, causes dilution of HbS concentration thereby, reducing blood viscosity and boosting oxygen saturation. Furthermore, RBC transfusion is helpful in suppressing endogenous production of sickle RBCs by augmenting tissue oxygenation ( Josephson et al., 2007). There are two major types of RBC transfusion therapy: intermittent and chronic which are further classified as prophylactic or therapeutic. Intermittent transfusions are generally therapeutic in nature and administered to control acute manifestations of SCD whereas chronic transfusions are performed as general preventative measures to check complications of SCD. RBC transfusion given as a single dose is termed as simple transfusion. Exchange transfusion involves administration of a larger volume of RBCs replacing the patients RBCs that are simultaneously removed. Details of the various types of RBC transfusion and the major clinical indications for the same in SCD patients are listed in Table 1. 4.3 Indications for intermittent transfusions Indications for intermittent transfusions include acute manifestations of SCD, as indicated in Table 1, that require redressal through therapeutic transfusions. However, under certain circumstances intermittent transfusions could be prophylactic such as for instance, when SCD patients are transfused before specific surgeries viz., those related to pregnancy complications or renal failure (Table 1). Acute Chest Syndrome (ACS) describes a manifestation of SCD in which, due to sickling, infectious and noninfectious pulmonary events are complicated, resulting in a more severe clinical course. The diagnosis is the presence of a new infiltrate on chest radiography that is accompanied by acute respiratory symptoms. ACS accounts for nearly 25% of all deaths from SCD (Vichinsky, 2002). Repeated episodes of ACS are associated with an increased risk of chronic lung disease and pulmonary hypertension (Castro, 1996). The severe pulmonary events occurring in SCD may be precipitated by any trigger of hypoxia (Vichinsky, 2002). Transfusions are very efficacious and provide immediate benefit by reversing hypoxia in ACS. Transfusion of leucocyte-poor packed red cells matched for Rh, C, E, and Kell antigens can curtail antibody formation to below 1% (Vichinsky, 2002). Simple transfusions suffice for less severe cases; however, exchange transfusion is recommended to minimise the risk of increased viscosity. Also, chronic transfusion appears promising for prevention of recurrence in selected patients (Styles and Vichinsky, 1994). In a multicentre ACS trial, prophylactic transfusion was found to almost completely eliminate the risk of pulmonary complications (Vichinsky, 2002). Acute Symptomatic Anaemia arises in SCD as a result of blood loss, increased RBC destruction, suppression of erythropoiesis etc. and is effectively treated with intermittent transfusion of RBCs to relieve symptoms of cardiac and respiratory distress (Josephson et al., 2007). Aplastic Anaemia is commonly caused in SCD on account of infection of haematopoietic precursors in the bone marrow by Parvovirus B19 leading to a steep fall in RBCs. According to Josephson et al. (2007), therapeutic intermittent transfusion of RBCs is again the recommended first-line of treatment to improve total haemoglobin count and prevent cardiac decompensation. However, in those patients who are prone to fluid overload on account of cardiac or renal dysfunction an alternative transfusion strategy is to remove the whole blood and replace it with packed cells while avoiding the addition of excess volume (Josephson et al., 2007). Acute Stroke is a high risk especially in paediatric SCD cases because of elevated cerebral flow. Enormous decline in stroke rate have occurred in children receiving intermittent simple transfusion (Adams et al., 1998). However, the identification of the stroke type would be necessary in all SCD patients in order to determine the appropriate treatment approach since the occurrence of infarctive strokes is higher in children as opposed to a higher incidence of haemorrhagic strokes in adults (Adams, 2003). 4.4 Indications for Chronic Transfusions Prophylactic chronic RBC transfusion every 3 to 4 weeks to maintain HbS levels lower than 30% is crucial for preventing first as well as recurrent strokes in children (Johnson et al., 2007). The transfusions could either be chronic simple transfusion or prophylactic chronic RBC exchange transfusion. Prophylactic chronic transfusions are recommended for patients with chronic renal failure so as to avoid severe symptomatic anaemia and for those patients with SCD undergoing pregnancy with complications. However, prophylactic transfusion is not indicated for SCD patients with normal pregnancy (Tuck et al., 1987). 4.5 Controversial and indeterminate indications for transfusion Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudicious in SCD management. Some examples are indicated in Table 1. According to Hankins et al. (2005), chronic transfusion therapy is helpful in reducing the incidence of strokes in children but not the severity of strokes. In the case of acute priapism, improvement in patients has been observed after exchange or simple transfusion (Rifikind   et al., 1979). Yet, due to the ASPEN syndrome, transfusion therapy currently is only a second-line therapy in the management of priapism ( Miller et al., 1995). RBC transfusion is a vital component in the management of symptoms and complications of SCD. It has drastically reduced the morbidity and mortality of SCD. Yet, immune-related effects such as FNHTRs (Febrile Non-Haemolytic Transfusion Reaction i.e., fever resulting from a blood transfusion) and alloimmunisation to HLAs (Human Leucocyte Antigens),   and nonimmune-related effects e.g., iron overload and transfusion-transmitted infections are serious adverse effects of the transfusion therapy that need to be attended to in SCD patients receiving transfusion (Johnson et al., 2007). Chronic transfusions could result in an inexorable accumulation of tissue iron that could become fatal if not treated (Cohen, 1987). Excess iron damages the liver, endocrine organs, and heart and may be fatal by adolescence (Engle, 1964). 5. Critical review of thalassemias : (i) Molecular pathogenesis The large number of inherited haemoglobin disorders known today include (a) those related to anomalies in the haemoglobin structure e.g., sickle cell disease, and (b) the thalassemias whose hallmark is globin-chain deficiency of one or other of the globin chains of adult haemoglobin in erythroid cells. 5.1 ÃŽÂ ²-Thalassaemias These are a set of genetic disorders inherited as simple codominant traits affecting haemoglobin synthesis. Depending on the haemoglobin chain affected, 2 types of thalassemia are recognised: ÃŽÂ ±-thalassaemia and ÃŽÂ ²-thalassaemia. Homozygous ÃŽÂ ²-thalassaemia is marked by a quantitative deficiency of the ÃŽÂ ²-globin chains in the erythroid cells. A complete absence of the ÃŽÂ ²-globin chains occurs in homozygous ÃŽÂ ²o-thalassaemia whereas in homozygous ÃŽÂ ²+-thalassaemia the ÃŽÂ ²-globin chains are present at less than 30% of normal. Accounting for nearly 90% of the cases, ÃŽÂ ²+-thalassaemia is the most commonly observed form of ÃŽÂ ²-thalassaemia. The condition is termed thalassaemia major when there is microcytic hypochromic anaemia with severe haemolysis, hepatosplenomegaly, skeletal deformities and iron overload. ÃŽÂ ²-thalassaemia homozygotes exhibit severe transfusion-dependent anaemia in the very first year of life. Homozygotic individ uals having a relatively benign clinical phenotype and surviving with or without transfusion are described as thalassaemia intermedia (Weatherall, 1969). The thalassaemias, thus, encompass a wide gamut of clinical disability from intrauterine death to a mild anaemia with no overt symptoms (Weatherall, 1997b). The coexistence of   ÃŽÂ ± -thalassaemia leading to reduction in the synthesis of ÃŽÂ ±-globin chains, and a genetic predisposition to produce high levels of HbF, could be important factors for the extensive phenotypic variability described above (Weatherall, 1996). The milder form of thalassaemia intermedia is the result of a lesser imbalance in globin chain synthesis probably the result of residual ÃŽÂ ² -globin chain synthesis due to mild mutation or due to reduced synthesis of ÃŽÂ ±-globin chains due to co-inheritance of ÃŽÂ ±-thalassaemia (Nadkarni et al., 2001). Persons having the heterozygous form of the disorder are usually asymptomatic but can be recognised by typical abnormalities of red cell morphology (shown in Fig.4) and indices (Spritz and Forget, 1983). Compared to the heterozygous form of ÃŽÂ ²-thalassaemia, a larger imbalance exists in the ÃŽÂ ±- to ÃŽÂ ²-globin chain synthesis in the homozygous ÃŽÂ ²-thalassemia or Cooley anaemia. The excess ÃŽÂ ±-globin chains are liable to precipitate, causing damage to the ÃŽÂ ²-thalassemic red cell membrane and affecting erythropoiesis. Important manifestations of homozygous ÃŽÂ ²-thalassemia are severe chronic microcytic haemolytic anaemia and hepatosplenomegaly due to extramedullary haematopoiesis (Spritz and Forget, 1983). As many as 175-200 molecular mutations affecting the ÃŽÂ ²-globin gene complex are involved in creating the ÃŽÂ ²-thalassaemia syndromes with the resultant altered synthetic ratios of ÃŽÂ ±- to ÃŽÂ ²-globin chains, precipitation of excess unbalanced ÃŽÂ ±-globin chains, and programmed cell death of erythroid precursors (Steinberg and Rodgers, 2001; Gambari, 2010). Hence, the pathogenetic basis of the clinical diversity of the ÃŽÂ ²-thalassaemia syndromes essentially rests with the striking heterogeneity of mutations in the ÃŽÂ ²-globin gene (Thein, 1993). The -158 (C ÃÆ'   T) substitution in the GÃŽÂ ³ gene has been found to be linked to the increase in HbF synthesis leading to less severe disease in thalassaemia intermedia (Gilman and Huisman, 1985; Ragusa et al., 1992). 5.2 Red blood cell transfusion and iron overload Regular RBC transfusions have proved to be efficacious in the treatment of ÃŽÂ ²-thalassemia by nullifying the complications of anaemia and compensatory bone marrow (BM) expansion. However, thalassaemias are also complicated by physiological iron overload which gets exacerbated by blood transfusion and causes various endocrine diseases, liver cirrhosis, cardiac failure and also death (Engle, 1964). Complemented with iron-chelating therapy (e.g., deferoxamine) for iron overload, the prognosis of thalassemia major has become dramatic (Olivieri and Brittenham, 1997).  Ãƒâ€šÃ‚   Recently, the mechanism of iron overload in the absence of transfusion in thalassaemia has been unraveled by Tanno et al. (2007) who observed that the overproduction of the protein GDF15 suppresses the production of the liver protein, hepcidin in thalassaemia patients which eventually leads to an increase in the uptake of dietary iron in the gut. This information could translate into new diagnostic and therapeutic tools in the future. 6. Critical review of thalassemias : (ii) Clinical management therapies ÃŽÂ ²-thalassaemia syndromes are the most common genetic diseases worldwide. Improvements in treatment strategies have resulted in good prognosis. Yet, disease- and treatment-related complications get exacerbated over time, increasing morbidity and curtailing life expectancy of the patients. Currently, the only curative treatment available for thalassaemia is stem cell transplantation (SCT) (Gaziev et al., 2008) which is a gold standard in treating the disease. Many challenges exist for transplantation therapy including graft versus host disease (GVHD), rejection of the donated stem cells, and infections while a major limitation for SCT is finding HLA-matched blood-related donors viz., siblings. Currently available high-resolution HLA-typing could minimise rejection and GVHD by matching major as well as minor HLA (Gaziev et al., 2008). The advanced techniques of HLA-typing can also identify unrelated but suitable voluntary donors. Intermittent red blood cell transfusion is the recommended mode of treatment for people who have moderate or severe thalassaemias. ÃŽÂ ²-thalassemia major, or Cooleys anaemia require regular blood transfusions. 6.1 Emerging Therapies Gene therapy for treatment of thalassaemia is still evolving. Research is focussed on finding a potential treatment of ÃŽÂ ² -thalassemia based on globin gene transfer. One of the aims of the genetic research is to trigger the production of HbF in adults to make up for the lack of healthy adult haemoglobin. The molecular mechanisms that initiate the change in gene expression during the switch from foetal (HbF) to adult (HbA) have been partially elucidated. Several chemical compounds able to reactivate HbF synthesis in vitro and in vivo in adult bone marrow have been identified (Testa, 2009). Induction of HbF to treat thalassaemia is a novel therapeutic strategy especially for those patients who are resistant to conventional therapy that is, regular blood transfusions and chelation therapy (Gambari, 2010). In view of the fact that gene therapy could be inaccessible to many because of biological/genetic as well as economic constraints (Gambari, 2010), chemical inducers are being extensively studied. Hydroxyurea has already been used as HbF inducer in both moderate and severe forms of ÃŽÂ ²-thalassaemia (Testa, 2009). Some of the potential inducers of HbF are histone deacetylase inhibitors, DNA-binding drugs and inhibitors of the mammalian target of rapamycin or mTOR pathway (Gambari and Fibach, 2007). Also, according to Gambari and Fibach (2007) chemical inducers need to be used with caution since many of those used so far were potentially cytotoxic. Accelerated apoptosis has been observed in the erythroid progenitors of patients with ÃŽÂ ²-thalassaemia major (Silva et al., 1996). The hormone erythropoietin (Epo), which is the principal regulator of red blood cell production, is known to interact with high-affinity receptors on the surface of erythroid progenitor cells and promote cell viability. Epo has been shown to repress apoptosis via Bcl-XL and Bcl-2 during proliferation and differentiation of erythroid progenitors (Silva et al., 1996). Hence, recombinant human erythropoietin (rHuEpo) could have potential application in the treatment of transfusion-dependent thalassaemia patients as it promotes the differentiation and proliferation of erythroid cells, and stimulates the production of HbF (Makis et al., 2001). 7. Conclusion Inherited haemoglobinopathies including sickle cell disease and thalassaemias result from genetic abnormalities in the synthesis of globin protein chains. Sickle cell disease (SCD) is caused by structural defects in the haemoglobin molecule while thalassaemias occur due to reduced or absent globin chain. Only bone marrow or haematopoietic stem cell transplantation can cure patients with either disease. Clinical management of SCD generally involves supportive therapy consisting of pain relief, fluids and antibiotics, and folic acid supplements. Red cell transfusion is currently a well accepted therapy for clinical management of inherited haemoglobinopathies including SCD and the thalassaemias. Intermittent red cell transfusion is administered to most patients, pre-surgery and in specific cases of severe complications. Persons with severe complications such as stroke, acute chest syndrome or frequent painful sickling crises are treated with hydroxyurea. The only cure available currently for ÃŽÂ ²-thalassaemia major is haematopoietic stem cell transplantation from a compatible donor. Most thalassaemia patients require regular transfusions of red cells and all patients need iron chelation therapy to overcome iron overload. References Adams, R., 2003. Haemoglobinopathies. Haematology (Am Soc Haematol Educ Program) pp.14-39. Adams, R., McKie, V., Brambilla D, et al., 1998. Stroke prevention trial in sickle cell Anaemia. Control Clin Trials 19, pp.110- 129. Andrews, N.C., 1999. Disorders of iron metabolism. N Engl J Med, 341, pp.1986-1995. Andrews, N.C., 2008. Forging a field: the golden age of iron biology. Blood, 112(2), pp.219-230. Anstey, N.M., Russel, B., Yeo, T.W., et al., 2009. The pathophysiology of vivax malaria. Trends Parasitol., 25(5), pp.220-227. Aul, C., Bowen, D.T. Yoshida, Y., 1998. Pathogenesis, etiology, and epidemiology of myelodysplastic syndromes. Haematologica, 83(1), pp. 71-86. Ballas, S.K., 1998. Sickle cell disease: clinical management. Baillieres Clinical   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Haematology, 11 (1), pp.185-214. Ballas, S.K., 2002. Sickle cell anaemia: progress in pathogenesis and treatment. Drugs, 62(8), pp.1143-1172. Bertero, M.T. Caligaris-Cappio, F., 1997. Anemia of chronic disorders in systemic autoimmune disease. Haematologica, 82(3), pp.375-81. Bessman, J.D., Gilmer, P.R. Gardner, F.H., 1983. Improved classification of anemias by MCV and RDW. Am J Clin Pathol 80, pp.322-326. Beutler, E., Gelbart, T., Lee, P., et al., 2000. Molecular characterisation of a case of Atransferrinemia. Blood, 96, pp.4071-4074. Beutler, E. Waalen, J., 2006. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration?. Blood, 107(5), pp. 1747-1750. Bottomley, S.S., 2006. Congenital sideroblastic anemias. Curr Hematol Rep., 5(1), 41-49. Bunn H.F., 1997. Pathogenesis and treatment of sickle cell disease. N Engl Med.,337(11), pp.762-769. Castro, O., 1996. Systemic fat embolism and pulmonary hypertension in sickle cell Disease. Hematol Oncol Clin North Am. 10(6), pp.1289-1303. Centis, F., Tabellini, L., Lucarelli, G., et al., 2000. The importance of erythroid expansion in determining the extent of apoptosis in erythroid precursors in patients with beta- thalassaemia major. Blood, 96, pp.3624-3629. Chulilla, J.A.M., ColÃÆ' ¡s, M.S.R. MartÃÆ' ­n, M.G., 2009. Classification of anemia for Gastroenterologists. World J Gastroenterol. 15(37), pp.4627-4637. Claster, S. Vichinsky, E.P., 2003. Managing sickle cell disease. BMJ,327, pp.1151- 1155. Cohen, A.R., 1987. Management of iron overload in the paediatric patient. Haematol   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Oncol Clin North Am., pp. 521-544. Connes, P., Hue, O., Tripette, J., et al., 2008. Blood rheology abnormalities and vascular   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   cell adhesion mechanisms in sickle cell trait carriers during exercise. Clinical   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Hemorheology Microcirculation, 39(1-4), pp. 179-184. Creary, M., Williamson, D., Kulkarni, R., 2007. Sickle cell disease: current activities, public health implications, and future directions. J Womens Health, 16(5),575-582. Distenfeld, A. Woermann, U., 2009. Sickle Cell Anemia. Accessed 15 February 2010 https://emedicine.medscape.com/article/205926-overview. Dugdale, D.C., 2008. Megaloblastic anemia. Medline Plus, Accessed 28 Jan 2010  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   https://www.nlm.nih.gov/medlineplus/ency/article/000567.htm Engle, M.A., Erlandson, M. Smith, C.H., 1964. Late cardiac complications of chronic, severe, refractory anaemia with haemochromatosis. Circulation, 30, pp.698-705. Fleming, M.D., 2002. The genetics of inherited sideroblastic anemias. Semin Hematol.    39, pp.270-281. Gambari, R., 2010. Foetal haemoglobin inducers and thalassaemia: novel achievements. Blood Transfus. 8(1), pp. 5-7. Gambari, R. Fibach, E., 2007. Medicinal chemistry of foetal haemoglobin inducers for treatment of beta-thalassaemia. Curr Med Chem.14, pp.199-212. Gaziev J, Sodani P Lucarelli C, 2008, Haematopoietic stem cell transplantation in thalassaemia, Bone Marrow Transplantation, 42, S41. Gilman, J.G. Huisman, T.H.J., 1985. A sequence variation associated with elevated foetal GÃŽÂ ³globin production. Blood, 66, pp.783-787. Gladwin, M.T. Kato, G.J., 2005. Cardiopulmonary complications of sickle cell disease: role of nitric oxide and hemolytic anemia. Haematology (Am Soc Hematol Educ   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Program), pp. 51-57. Goldberg, M.A., Brugnara, C., Dover, G.J. et al., 1990. Treatment of sickle cell anaemia with hydroxyurea and erythropoietin. NEJM, 323(6), pp. 366-372. Haas JD Brownlie T, 2001, Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship, J Nutr., 131(2 Suppl): 676S-690S. Halterman, J.S., Kaczorowski, J.M., Aligne, C.A. et al., 2001. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics, 107, pp. 1381-1386.      Hankins J, Jeng M, Harris S, et al., 2005, Chronic transfusion therapy for children with sickle cell disease and recurrent acute chest syndrome, J Paediatr Haematol Oncol 27:158 161. Herrick JB, 1910, Peculiar elongated and sickle-shaped red corpuscles in a case of severe anemia, Arch Intern Med.6:517-521. Hershko C Skikne B, 2009, Pathogenesis and management of iron deficiency anaemia: Emerging role of Celiac disease, Helicobacter pylori, and autoimmune gastritis, Seminars in Hematology, 46 (4): 339-350.Iolascon A, De Falco L. Beaumont C, 2009, Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis, Haematologica 94(3): 395-408. Jison ML, Munson PJ, Barb JJ et al., 2004, Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease, Blood, 104(1): 270-280.   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Killip S, Bennett JM Chambers MD, 2008, Iron deficiency anemia, American Family Physician, 75(5): 671-678. Kohgo Y, Ikuta K, Ohtake T. et al., 2008, Body iron metabolism and pathophysiology of iron overload, Int J Hematol. 88(1): 7-15. Krantz SB, 1994, Pathogenesis and treatment of the anemia of chronic disease, Am J   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Med Sci.,307(5): 353-359. the art, Expert Opinion on Biological Therapy, 7(2): 161-172. Josephson CD, Su LL, Hillyer KL, et al., 2007, Transfusion in the Patient With Sickle Cell Disease: A Critical Review of the Literature and Transfusion Guidelines, Transfusion Medicine Reviews, 21(2): 118-133. MakisAC, ChaliasosN, Hatzimichael EC et al., 2001, Recombinant human   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   erythropoietin therapy in a transfusion-dependent ÃŽÂ ²-thalassaemia major patient,   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Annals of Haematology, 80(8):492-495. Means RT Jr., 1996, Advancement in the anemia of chronic disease: A cytokine- mediated anemia, Stem Cells, 13(1): 32-37. Means RT Jr., 2003, Recent developments in the anemia of chronic disease, Current   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Hematology Reports, 2(2):116-121. Miller S, Rao S, Dunn K, et al., 1995, Priapism in children with sickle cell disease, J   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Urol, 154:844- 847. Mims MP, Guan Y, Pospisilova D, et al., 2005, Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload, Blood,105:1337- 1342. MuÃÆ' ±oz M, Villar I GarcÃÆ' ­a-Erce JA, 2009, An update on iron physiology, World J Gastroenterol, 15(37): 4617-4626. Nadkarni A, Gorakshakar AC, Lu CY, et al., 2001, Molecular pathogenesis and clinical variability of ÃŽÂ ²-thalassaemia syndromes among Indians, American Journal of Haematology, 68:75-80. Olivieri NF Brittenham GM, 1997, Iron-chelating therapy and the treatment of   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   thalassaemia, Blood, 89(3): 739-761 Pauling L, Itano HA, Singer SJ, et al., 1949,   Sickle cell anemia: a molecular disease, Science, 110(2865):543-548. Quigley JG, Yang Z, Worthington MT, et al. 2004, Identification of a human heme exporter that is essential for erythropoiesis, Cell, 118:757-766. Ragusa A, Lambardo M, Beldjord C, et al., 1992, Genetic epidemiology of ÃŽÂ ²- thalassaemia in Sicily: do sequences 58 to the GÃŽÂ ³ gene and 58 to the ÃŽÂ ² gene interact to enhance HbF expression in ÃŽÂ ² -thalassemia?, Am J Hematol, 40:199-206. Richardson M, 2007, Microcytic anemia, Pediatrics in Review, 28:5-14. Rifikind S, Waisman J, Thompson R, et al., 1979, RBC exchange pheresis for priapism in sickle cell disease, JAMA, 242:2317 2318. Rodgers GP, Noguchi CT, Schechter AN, 1985, Irreversibly sickled erythrocytes in sickle cell anemia: A quantitative reappraisal, Am J Hematol., 20(1): 17-23. Rodgers GP, Dover GJ, Uyesaka N, et al., 1993, Augmention by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease, NEJM, 328(2): 73- 80. Rosenfeld C List A, 2000, A hypothesis for the pathogenesis of myelodysplastic syndromes: implications for new therapies, Leukemia, 14(1): 2-8. Ru YX, Mao BY, Zhang FK et al., 2009, Invasion of erythroblasts by Plasmodium vivax: A new mechanism contributing to malarial anaemia, Ultrastruct. Pathol., 33(5):236-42.   Shemin, D. Rittenberg D, 1946, The life span of the human red blood cell, J Biol Chem, 166: 627-636. Siah CW, Ombiga J, Adams LA, et al., 2006, Normal iron metabolism and the pathophysiology of iron overload disorders, Clin Biochem Rev. 27:5-16. Silva M, Grillot D, Benito A, et al., 1996, Erythropoietin can promote erythroid progenitor survival by repressing apoptosis through Bcl-XL and Bcl-2. Blood, 88:1576-1582. Sokol RJ, Booker DJ Stamps R, 1992, The pathology of autoimmune haemolytic anaemia, J Clin Pathol., 45: 1047-1052. Spivak, JL, 2002, Iron and the anemia of chronic disease, Oncology, 16(9 Suppl 10):25- 33. Spritz RA Forget BG, 1983, The thalassemias: molecular mechanisms of human genetic disease, Am J Hum Genet., 35:333-361. Steinberg MH Rodgers GP, 2001, Pharmacologic modulation of foetal haemoglobin, Medicine, 80:328-344. Styles LA Vichinsky E, 1994, Effects of a long-term transfusion regimen on sickle cell- related illnesses, J Pediatr., 125:909-911. Tanno T, Bhanu NV, Oneal PA et al., 2007, High levels of GDF15 in thalassemia   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   suppress expression of the iron regulatory protein hepcidin, Nature   Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚   Medicine, 13:1096 1101. Tefferi A, 2003, Anaemia in adults: a contemporary approach to diagnosis, Mayo Clin   Proc.78:1274-1280. Testa U, 2009, Fetal hemoglobin chemical inducers for treatment of   Haemoglobinopathies, Ann Hematol. 88:505-528. Thein SL, 1993, ÃŽÂ ²- Thalassaemia. In: Higgs DR Weatherall DA, editors, Baillieres clinical haematology: the hemoglobinopathis, Vol 6, Bailliere Tindall, London, p151-175. Tischkowitz MD Hodgson SV, 2003, Fanconi anaemia, J Med Genet 2003;40:1-10 doi:10.1136/jmg.40.1.1 Tuck S, James C, Brewster E, et al., 1987, Prophylactic blood transfusions in maternal sickle cell syndromes, Br J Obstet Gynaecol., 94:121 125. Walter PB, Harmatz P Vichinsky E, 2009, Iron metabolism and iron chelation in sickle cell disease, Acta Haematol., 122(2-3):174-183. Weatherall DJ, 1969, The genetics of the thalassaemias, British Medical Bulletin, 25(1): 24-29. Weatherall DJ, 1996, The molecular basis for phenotypic variability of the common thalassaemias, Mol Med Today 1:15-20.   Weatherall DJ, 1997a, ABC of clinical haematology. The hereditary anaemias, BMJ 314:492-496. Weatherall DJ, 1997b, Fortnightly review: the thalassaemias, BMJ, 314(7095):1675- 1678. WHO (1968), Nutritional anaemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser. 1968;405:5-37. Wun T, 2001, The role of inflammation and leukocytes in the pathogenesis of sickle cell disease, Hematology, 5(5): 403-412.