Imagery In A Good Man Is Hard To Find - Free Essay Example

Sample details Pages: 2 Words: 611 Downloads: 9 Date added: 2019/05/31 Category Literature Essay Level High school Tags: A Good Man is Hard to Find Essay Did you like this example? Flannery O Connor, was a strict Catholic from Georgia, O Connor often displayed a sense of spiritual corruption within the characters in most of her stories. One of O Connors well known stories, A Good Man Is Hard to Find, has a lot of imagery and foreshadows toward the characters who sadly meet never make it to Florida, yet instead meet their bloody end to a man named The Misfit. The grandmother was the one sign of foreshadowing within the novel as she stated on the first page. Don’t waste time! Our writers will create an original "Imagery In A Good Man Is Hard To Find" essay for you Create order There are also shown foreshadowing in the graveyard with there being 5 to 6 graves. The last sign of foreshadowing shown was as they were walking around they saw 6 columns. The Grandmother was the first to do any foreshadowing within the novel. She stated to John Wesley and June Star Yes and what would you do if that fellow, the Misfit, caught you? Even though she warning of the Misfit, her activities various signs of foreshadowing of their inevitable encounter with the Misfit. The grandmother warned about the Misfit in the first paragraph of the story: `Here this fellow calls himself the Misfit is loose from the federal pen and headed toward Florida and you read here what it says he did to these people.' This was the first sign of an obvious Foreshadowing within the novel itself. The grandmother is very hypocritical when it comes to following through with what she says or doing what she states to other people as she was the one who said Florida was dangerous. As the one who states such valuable information to the people you love you still disregard it and go to Florida to avoid being left behind. There were about six graves fenced in, which was a major indication of foreshadowing. John Wesley asked about where the plantation was, the grandmother replied, Gone with the Wind, which was foretelling their demise. Red Sammy also narrated about Two fellers come in here last week in an old beat up car. These people were the Misfits goons, and they were offered free gasoline from Red Sammys store, probably because of his fear that he was dealing with notorious killers. Red Sammys wife also gave a warning by saying, I wouldnt be a bit surprised if he didnt attack this place right here. This was a self-explanatory caution signal gave by the store owners which was ignored. The family was in a town named as Tombsboro, which name itself was a sign of foreshadowing. When the family finally meets the Misfit, he arrives in a hearse like vehicle which is foreshadowing death. The hearse is used to bring move coffins from place to place, while the misfit is considered the bringer of death within the story as all the death seems to come from him. Red Sammy tried to warn the family that the misfit may be in the area as the name of his restaurant is also the name of a card that represents warning and Sammy let two guys who were the misfits goons fill up gas on credit. This short story has many signs of foreshadowing within it that if known by the family could have been essential. The grandmother was the base off all the foreshadowing by talking about what if they ran into the misfit, which later occurs. There is also the graves and columns which just so happen to have the exact number for each of the family members. These are just a few of the examples of the foreshadowing that happens within the book of things that take place to the family until their death which I feel was undeserved.

Air Transport Management And Operations - 3094 Words

Air Transport Management and Operations Rachel Passmore Student Number: 2140479 Bucks New University Introduction Airline business models continuously evolve to respond to the ever changing nature of the airline industry. Good management involves responding to dynamic changes of the market by using effective and efficient ways to coordinate a business activities to be able to achieve the goals and aims. The principals of management will be defined and they re roles explained; both individually and as a whole to create a good management technique. Human resource also plays an integral role in the success of an organization, dealing with employee well-being. The variety of aspects that is included will be explored and the various strategies that are adopted will be scrutinized. Safety and security in the aviation industry is fundamental. The International Civil Aviation Organisation and the UK Civil Aviation Authority have a similar view in ensuring the safety of UK airports is at an acceptable standard. The aim is to explore how the organizations link, and how tasks related to transport security are designated and coordinated at UK airports. Principles of Management Organizational management requires decisive and theoretically thinking in order to achieve specific goals. The functions of management can be condensed into four broad categories: planning, organizing, leading and controlling. Each aspect builds on each other but can also be operational with just aShow MoreRelatedCase Study : Air Transport Management And Operations2889 Words   |  12 Pages Air Transport Management and Operations Module AT502 TASK 3 Ben Matthews 30/10/14 CONTENTS Task 3: Perform a strategic analysis of your chosen airline. The analysis should take appropriate consideration of factors both internal and external to the organization. 1. 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Industry Rivalry: Intense rivalry remains in the air transport industry, where a large number of airline operators, compete for customer loyalty. A number of factors affecting industry rivalry include pricing, service quality and level (Shchiglik Barnes, 2004)Read MoreLegal Landscape Of Air Charter Transportation1232 Words   |  5 PagesLANDSCAPE OF AIR CHARTER TRANSPORTATION The air transportation services in India are controlled by Directorate General of Civil Aviation (hereinafter â€Å"DGCA†), operating under the Ministry of Civil Aviation (MCA). According to Rule 134 of the Aircraft Rules, 1937, the DGCA is empowered to grant permission to individuals to operate an air transport service to, within and from India. The rules promulgated by DGCA for issuance of permits for air transport services are ensconced within Non-Scheduled Air TransportRead MoreAir New Zealand Board Of Directors Essay1408 Words   |  6 PagesAir New Zealand Board of Directors need to have the skills of top managers, such as leadership, strategic planning and risk management. In addition, they need to establish any negotiating ability is excellent and build relationships with other major airline alliances. b) Staff: Air New Zealand chief executive Christopher Luxon experience from other members of the January 2013 implementation of the team are: †¢ Cam Wallace - Chief Sales Commercial Officer †¢ Rob MacDonald - Chief Financial OfficerRead MoreEssay ICAO - The International Civil Aviation Organisation 1129 Words   |  5 Pagesfew seconds somewhere on the face of the earth. People on the ground and in the air handle each and every one of these flights in the same way and the organisation responsible for setting these complex standards and procedures is the International Civil Aviation Organisation, which is a part of the United Nations Organisation. The ICAO is working on, among other things, improving the safety of the African air transport sector and implementing a new navigation standard worldwide in an attempt to achieveRead MoreCase Study Of Volga Dnepr : A Heavy Lift Cargo Airline1122 Words   |  5 PagesVolga-Dnepr: A Heavy-Lift Cargo Airline History/Background As the air cargo industry grew after World War II, the need for large cargo aircraft increased worldwide. Items such as military tanks, aircraft engines, space station sections, satellites, factory power plants, and large construction equipment needed to be transported from manufacturing plants or job sites to locations around the world. This type of cargo, also known as oversized, outsized, or heavy-lift cargo, did not fit in conventionalRead MoreTransportation Problem and Solution in Case of Bangladesh1652 Words   |  7 Pages An adequate and efficient transport system is a pre-requisite for both initiating and sustaining economic development. Investment in improving transport efficiency is the key to expansion and integration of markets - sub-national, national and international. It also helps the generation of economies of scale, increased competition, reduced cost, systematic urbanization, export-led faster growth and a larger share of international trade. The transport system of Bangladesh consists ofRead MoreEssay on Transportation and How it Affects Logistics1139 Words   |  5 Pages In order for transportation and logistics to work together successfully, there must be good management between them. It plays a major role in connecting it all together. What is logistics? Logistics is the management of freights, warehousing of materials, production and inventory. Logistics and the supply chain work hand in hand. Supply chain management is defined as† a continuously evolving management philosophy that seeks to unify the collective productive competencies and resources of the business

Pioneer in Interactive Conflict Resolution †MyAssignmenthelp.com

Question: Discuss about the Pioneer in Interactive Conflict Resolution. Answer: Introduction: Analyzing the employee engagement is crucial for ensuring better productivity. Such important information should be well-organized and well-managed. Chris and I are entitled to analyze the progress employee engagement program as per the survey and making the necessary improvements. In order to respond assertively to Chriss criticism the following strategies can be adopted: In case of a situation of criticism, it is essential to understand the root cause of the criticism. It would be helpful to some extent if Chris is asked to state reasons for not agreeing with the decision. In the process, this would help me to understand the likes and dislikes of Chris regarding the employee engagement survey. This, in turn, would reduce the chances of conflict in the future. In instances where I strongly agree with my decision and ideas, I would try to convince Chris with the decision and also let him suggest some improvements related to the project. In the process, Chris might come up with better decisions related to the project. The third strategy that could be undertaken for dealing with Chris is to not respond anything immediately to Chris. In other words, taking time to acknowledge Chris's criticism would enable me to understand his reason for disapproval much effectively (Wallensteen, 2015). There might be a different perspective of Chris for not agreeing with my suggestion. Understanding the motive behind Chriss disagreement would help me to cope up with the conflicting situation (Fisher, 2016). Feedback technique to be incorporated Corrective feedback technique should be adopted considering the situation. In every work culture, it is essential to build a healthy relationship with the colleagues as this could surely improve the quality of decisions. Considering the aspect of my negotiation with Chris, it is necessary that both of us should handle the feedbacks in an assertive manner as this would provide a scope of improvement for both of us (Mackey, 2013). If the feedback of Chris is taken positively it could give me a scope for improvement also it is essential that Chris takes my suggestion positively. Corrective feedback will provide both of us with an equal opportunity to rectify our mistakes and manage the interaction process. Healthy interaction will surely help us in delivering the best results for employee engagement of the Western Sydney University. The other technique that can be used with respect to this situation is the Feedback Sandwich'. In this technique, at first, we can discuss the positive points from both of our suggestions and then we both can provide our feedback regarding various improvements that can be brought in the plan (Parkes, Abercrombie and McCarty, 2013). In the end, this will result in a positive interaction from both of our end. In this approach of feedback technique, both of our suggestions would get equal importance thus reducing the chances of conflict. This could possibly resolve the situation of conflict between us also in the process it might help me to establish a cordial working relationship with Chris. References Fisher, R.J., 2016. Third party consultation: A method for the study and resolution of conflict. InRonald J. Fisher: A North American Pioneer in Interactive Conflict Resolution(pp. 37-71). Springer, Cham. Mackey, A., 2013.Input, Interaction and Corrective Feedback in L2 Learning-Oxford Applied Linguistics. Oxford University Press. Parkes, J., Abercrombie, S. and McCarty, T., 2013. Feedback sandwiches affect perceptions but not performance.Advances in Health Sciences Education,18(3), pp.397-407. Wallensteen, P., 2015.Understanding conflict resolution. Sage.

Wendy Goes Adventuring free essay sample

There are two places I wanted to be as a child: Sherwood Forest at Robin Hood’s side or adventuring in Neverland with Peter Pan. Either way, I was bound to be cloaked in green and running about shooting arrows at some foe; whether they where sheriff or pirate made no difference to me. Both where elaborate fantasy lives but what made Never Land the more tempting was the promise of never having to grow up. My grandparents, generously, every birthday give their twelve grandchildren checks to add to our college accounts. It never seemed that impressive to me, just a slip of paper tucked into an envelope. I didn’t understand the value of the gift, and what’s worse, the seemingly useless present came with strings attached- strings of never-ending questions like â€Å"What do you want to do when you grow up?† or â€Å"Where are you going to college?† Traditionally, in the play, the actor who plays the Darling’s father also plays the dastardly Captai n Hook, for all adults are pirates. We will write a custom essay sample on Wendy Goes Adventuring or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page And it did feel like my own free will was being stolen from me and left to wreck on shore; I was told the professions I should do, the places I should go, even if they held no interest to me. I was Wendy, bright-eyed and imaginative, a story-teller; the girl on the cusp of growing up. And I hated it; I wasn’t ready to cross the threshold just yet. If my Mother would have let me, I would have left my windows open every night, in hopes Peter would visit. Surely he could save me from the terrible promise of my future, before I grew too old to save? But in the odd ways you don’t notice, I was growing up. I grew in and out of new clothes, tucked my dolls away in boxes, grew and settled into my role of the â€Å"mother hen† among my friends. The one childish impulse I couldn’t buck was my distaste for school and the urge to escape it. School was the portent that childhood would end, even the small scraps I clung to. I scoffed at fellow classmates who spoke in r everent voices of the colleges they would one day attend; more school was not an option I ever considered. The fact is, things change. Wendy runs to Never Land because she doesn’t want to grow up, but Never Land is the reason why she does. Maybe I really did fly away on pixie dust and happy thoughts. If that’s what it takes to change, I certainly have. I’ve ridden the Jolly Roger, searched for treasure on Marooner’s Rock, danced with Tiger Lily, and flown with Peter Pan and Tinker Bell- second star to the right and straight on till morning, because college is no longer the threat it once was. It’s a promise of adventure I could never see; where I can choose the ways I want to go. College means growing up, but growing up doesn’t mean washing all the color out of life. It just expands the fields you play on, unveils treasure maps of even greater value. I am Wendy, bright-eyed and imaginative, a story-teller, girl-grown-up. And this is just my next adventure.

Anorexia Nervosa Essays (1539 words) - Eating Disorders, Psychiatry

Anorexia Nervosa In American society women are given the message starting from a very young age that in order to be successful and happy, they must be thin. Eating disorders are on the rise, it is not surprising given the value which society places on being thin. Television and magazine advertising that show the image of glamorous and thin model are everywhere. Thousands of teenage girls are starving themselves daily in an effort to attain what the fashion industry considers to be the "ideal" figure. An average female model weighs 23% less than the recommended weight for a woman. Maintaining a weight 20% below your expected body weight fits the criteria for the emotional eating disorder known as anorexia (Pirke & Ploog, 1984). According to medical weight standards, most models fit into the category of being anorexic (Garfinkle & Garner, 1990). Physicians now believe that anorexia has existed for at least 300 years (Pirke & Ploog, 1984). It was however only about one hundred years ago that Professor Ernest Lasegue of the University of Paris finally identified anorexia as an illness (Pirke & Ploog, 1984). The term "anorexia nervosa" literally means nervous lose of appetite. Most researchers and physicians agree that the number of patients with this life threatening disease is increasing at an alarming rate. Garfinkle & Garner define anorexia as "an emotional disorder characterized by an intense fear of becoming obese, lack of self-esteem and distorted body image which results in self-induced starvation" (1990). The development of this disease generally peaks between the age of 14 to 18 but can occur later in life and is not uncommon to see it in women in to their early 40's. Recent estimates suggest that 1% of American girls between this age span will develop anorexia to some degree (Garfinkle & Garner, 1990). It has also propagated in many college campuses, and it is spreading. Studies have shown that nearly 20% of college women may suffer from anorexia or bulimia (Pirke & Ploog, 1984). The disease develops slowly over a period of months to years during which the sufferer changes her eating patterns to a very restricted diet. As stated previously above, an anorexic is diagnosed by having a body weight 20% below the expected body weight of a healthy person at the same age and height of the eating disorder patient. The anorexic may often becomes frightened of gaining weight and even of food itself. The patient may feel fat, even though their body weight is well below the normal weight for their height. Some may even feel they do not deserve pleasure out of life and will deprive themselves of situations offering pleasure, including eating. This fear becomes so difficult to manage that the sufferer will gradually isolate themselves from other people and social activities. This happens so the sufferer can continue the exhausting anorexic behaviors. Although the mortality rate is high (30% of anorexics will eventually die from the disease), approximately one third are able overcome the disease with psychiatric help (Pirke & Ploog, 1984). Warning signs to look for in someone you suspect of anorexia. Physical signs are intolerance of cold due to the absence of the body's natural insulator (fat), dizziness and fainting spells, dry skin, loss of muscle, and the most obvious, a weight loss of about fifteen percent. There are also behavioral changes in a person when they becomes anorexic including restricted food intake, odd food rituals, an increased fear of food, hyperactivity, dressing in layers, and regular weighing. Some "odd food rituals" include things like cutting food into small pieces, counting bites or even talking to their food. Anorexics are not repelled or revolted by food, in fact their minds are often dominated by thoughts of food. While the exact cause of anorexia is still unknown, a combination of psychological, environmental, and physiological factors is associated with the development of this disorder (Cove, 1998). The most common cause of anorexia in a woman is an incorrect self-perception of her weight. Anorexics feel as if they are heavier than the others around them, and believe the quickest way to lose weight is to simply stop eating. Anorexia survivor Nanett Pearson (Miss Utah 1996) explains "I became obsessed with body image. I kept journals and in one pathetic passage I described how I went for sixteen days on water, and only about two glasses a day" (1998). At first, this method may seem to work and the subject loses weight, but their bodies will soon adjust to the lack of food it learns to use the

Democracy and Jacksonian Democrats Essay Example

Democracy and Jacksonian Democrats Essay Example Democracy and Jacksonian Democrats Essay Democracy and Jacksonian Democrats Essay Jacksonian democrats viewed themselves as the guardians of the Constitution, political democracy, individual liberty, and equality of economic opportunity. In light of the documents and your knowledge of the 1820s and 1830s, to what extent do you agree with the Jacksonians view of themselves? Jacksonian democrats viewed themselves as the guardians of the Constitution, political democracy, individual liberty, and equality of economic opportunity. In light of the documents and your knowledge of the 1820s and 1830s, to what extent do you agree with the Jacksonians view of themselves? AP AM HISTORY DBQ 4 (An A+ Essays Original Paper, written by Zoo Patrol) Jacksonian Democrats viewed themselves as the guardians of the United States Constitution, political democracy, individual liberty, and equality of economic opportunity. In light of the following documents and your knowledge of the 1820s and the 1830s, to what extent do you agree with the Jacksonians view of themselves. Unlike previous presidents, Andrew Jackson represented the common men. He and his followers did not support the aristocrats, but instead favored the interests of farmers and urban workers. When they gained power, the Jacksonian Democrats brought about great advances in creating a more democratic and economically equal society. One of the most important changes that Jackson brought was a much more democratic society. You no longer had to be a rich landowner to be allowed to vote. Most of the states removed any religious or property qualifications for holding office. The number of voters increased nearly by seven times during Jacksons presidency. By 1832, nearly all states adopted a new system for choosing for choosing its electors. Before Jacksons presidency, the electors were chosen by state legislatures. Now all the states in the Union, except South Carolina, had adopted a more democratic method of allowing voters to choose their states electors. Also, during Jacksons era, many state and local officials were elected to office, instead of being appointed. This gave the voters more control of their local government, and increased participation in elections. Another principle of the Jacksonian Democracy was the rotation system. Jackson limited a persons stay in office to just one term, and then appoint another in his place. Jacksonian Democrats believed that any American was capable of holding government office. Jackson also said that if a man were to hold office for a lengthy period of time, he would be capable of tolerating conduct from which an unpracticed man would revolt. Along with rotation, the Jacksonian Democrats reestablished the spoils system. Jackson fired any previous office holder who was not a loyal Democrat. He would then appoint a Democrat to that position. The spoils system and rotation were advances toward greater political democracy, because they showed that one man is just as good as another is. In addition to creating a more democratic country, Jackson also tried to establish equal economic opportunity for the people of America. The best example of this is the vetoing of the charter of the Bank of the United States. The bank was a huge monopoly. It was ran by aristocrats, most of which were from England. Nicholas Biddle, who was the president of the bank, often used funds from the bank to lend money to the members of Congress, thus wining their support. In his veto message, Jackson wrote, It is to be regretted that rich and powerful too often bend the acts of government to their selfish purposes. This was true, since the bank was used to provide for the interests of the rich and not the common men such as the small farmers and urban workers. The attempt to create equality of economic opportunity is also evident in the Supreme Court case of Charles River Bridge vs. Warren Bridge. Chief Justice Roger B. Taney ruled that a single corporation does not have a right to collect toll and prevent other bridges from being built near it. Taney said, †¦we must not forget that the community also has rights, and that the happiness and well-being of every citizen depends on their faithful preservation. He did not want the bridge to become a monopoly and ruled that competition shall be allowed. Besides making progress toward greater democracy and equal economic opportunity, there was also greater equality of and individual liberty of the people. There was less poverty and the majority of people were middle-class citizens. Harriet Martineau wrote I had seen every man in towns as independent citizen; every man in country a landowner. This is true, because most of the white population lived in good conditions during Jacksons presidency. During Jacksons presidency there were many changes made toward a more democratic and economically equal society. The voting qualifications were abolished for white men, common people were allowed to hold office, and most of the citizens had equal economic opportunity.

Personal statement Example | Topics and Well Written Essays - 500 words - 45

Personal Statement Example I believe that good managers must have entrepreneurial qualities. Managers are always ahead of time and see things in the perspective of the business. In this regard, their decisions affect the performance of a company directly. The success or failure of a company is also attributed to the management. In this regard, I believe managers have the principal responsibility for ensuring survival optimal performance of a business. I am the vice president of an international club. Essentially, the responsibilities of the position demand sound management skills. The position has helped me prepare for my future role in the business world. I have observed that I must change my attitude towards people and business in order to survive in the competitive management jobs. Also, the position has enabled me learn how to deal with people of different origins and cultures. It has helped me appreciate that people are different and can be productive only if they are recognized and appreciated by the management. In the urge to enhance my skills in management, I undertook a part-time job in management. The job has enabled me see business processes in the perspective of a manager. I have come to understand that managers should carry out extensive research on the business situation and also have a hands on approach to solving any issues in the business. In my position, I have seen how managers engage other employees and stakeholders when making serious business decisions. The job has improved my management skills and revamped my urge to study management to a higher level. My hobbies also contribute towards my better understanding of people. I interact with people and share their stories. I believe communication is key in understanding people. Moreover, talking to people enhances my social life and also learning. Mostly, meeting and talking to people enhances my knowledge and learning of new things. When people share their situations, I evaluate them and emulate the strategies

A Brief Analysis of the Development of English as a Global Language Essay

A Brief Analysis of the Development of English as a Global Language - Essay Example As the report declares social change will contribute to change in status of a language, as Gerry Knowles implies in a study of the history of language. This paper stresses that medium can become the official language of a country when it is adopted as the mother tongue and used by â€Å"such domains as government, the law courts, media, and the educational system. English did not achieve global status by way of one or two variables: several factors contributed to the process and arrival, factors which are part of a slowly evolving phenomenon that parallels the social changes experienced by numerous cultures over many eras. The culture of nationalism and the revolutions lead to worldwide expansion, as does the Industrial Revolution: electricity, roads, railroads, and airways introduce and facilitate transportation, commerce, migration. The farmer, no longer isolated in rural domains, picks up the local dialect or brings his own to the towns. Tradesmen, needing a common medium, trade words. With the printing press, administrations, and the London-based dialect passing to greater reaches, the shifts and adaptations make English both l ocalized and â€Å"normalised†. With education, standardised English is formalised. With film, television, and satellite technology, a trend is clearly toward the globalised. And with language change facilitated by the development of new technology that leads to improved communications.

The Picture of Dorian Gray by Oscar Wilde Essay Example | Topics and Well Written Essays - 500 words

The Picture of Dorian Gray by Oscar Wilde - Essay Example Harry’s argument easily wins him over and he is totally changed person after the meeting. â€Å"The few words that Basils friend had said to him--words spoken by chance, no doubt, and with willful paradox in them--had touched some secret chord that had never been touched before, but that he felt was now vibrating and throbbing to curious pulses.† But the worldly and satanic wisdom of his mentor makes him break the heart of the innocent soul. He feels remorse at first but again justifies himself in the light of Machiavellian morality of Lord Henry. Lord Henry is the evil angel of the story .Every moment the hero is close to repentance, he appears from nowhere and through his devilish speech changes the mind of Dorian. One is wonderstruck at the callousness of both Henry and Dorian they show at the death of Sibyl. â€Å"What is done is done. What is past is past." The yellow book is another diversion provided to him by Lord Henry. This book further goads him to indulge in â€Å"all the passions and modes of thought that belonged to every century except his own.† Now Evil in him is in its true attire. Under his influence, the friends meet destruction. He murders his once beloved Basil as he exposed the ugliness of Dorian’s soul .The portrait is a surrogate of soul, so when he sins his soul is changed . Even in the end to avoid the pangs of consciousness, he resorts to opium. He seems to be following Henry’s philosophy â€Å"To cure the soul by means of the senses, and the senses by means of the soul.† When Dorian has ominous hallucinations about his possible end, all his fears are dispelled by Lord Henry who declares that destiny is too wise or cruel to send us omens. The bad influence of Lord Henry even subdues the feelings of guilt created in Dorian’s heart. His resolve to reform himself is diverted to some other thoughts. The damnation is complete .The inherent evil in the

Disease Caused by Parasite of Genus Trypanosoma

Disease Caused by Parasite of Genus Trypanosoma Human trypanosomiasis caused by Trypanosoma evansi and Trypanosoma lewisi in India : A matter of concern Introduction Disease produced by the parasite of genus Trypanosoma called as trypanosomiasis. It is one of the most important hemoprotozoan diseases, widely distributed in animals and human beings. It is endemic in Africa and America, are deadly pathogens that threaten millions of people in at least 36 countries in Africa. It is estimated that approximately 60 million people are at risk and 3, 00,000 new cases found every year in Africa (WHO Report 1998). Both African and American trypanosomes rank within the top 10 in terms of global impact. Despite the impact of these parasites, how they cause disease is relatively less is understood. In Africa, the disease is commonly known as human African trypanosomiasis (HAT) or sleeping sickness whereas the American trypanosomiasis recognized as Chagas disease. They not only infect vertebrates groups (amphibians, reptiles, birds, fish, and mammals) but also many invertebrates (Crithidia, Leptomonas). Human African trypanosomiasis belongs to genus Trypanoso ma, subgenus trypanozoon. Classification phylum sacromastigophora, order kinetoplastida and the family trypanosomatidae. Genus Trypanosoma includes subgenus which is divided into major group, salivaria and stercoraria that infect vertebrates (Hoare C. A.1964). Trypanozoon (T. brucei ssp, T. evansi, T. equiperdum), Duttonella (T. vivax,T. uniforme), Nannomonas (T. congolense, T. simiae), Pycnomonas (T. suis), Tejeraia (T. rangeli) belongs to salivaria group. Under stercoraria group Herpetosoma (T. lewisi, T. musculi,T. microti), Megatrypanum (T. theileri, T. melophagium), Schizotryponum (T. cruzi, T. dionisii) come. T. brucei. brucei, T. brucei. gambiense and T. brucei. rhodesiense are the subspecies of the Trypanozoon. Sleeping sickness is caused by T. brucei. gambiense, a chronic form of HAT in West and Central Africa lasting from months to years or T. brucei. rhodesiense, an acute form of HAT in East and Southern African with a duration of weeks to months. Whereas, closely relate d parasite T. brucei. brucei is non pathogenic to humans. The American trypanosomiasis is caused by T. cruzi. rhodesiense. These forms of the disease is deadly and develop within weeks to months, the gambiense form takes year. Trypanosomes cause animal trypanosomiasis has a wide geographic distribution. Surra is caused by T. evansi and infects mainly camels, cattle, buffalos, horses, deer and other wild animals. T. b. Brucei causes nagana in tropical Africa and affects only cattle; T. vivax and T. congolense infect domestic and small animals while T.lewisi is a commensally of rats. T. equiperdum causes dourine disease in horse and donkey of India, Europe, America and North Africa. African trypanosomes are transmitted by tsetse flies, a species of Glossina, and South American trypanosomes by reduvid bugs. Normally human are resistant to animal species of Trypanosoma due to the trypanolytic factor of human serum. However, there are several cases of human infection with animal trypanosomes such as Trypanosoma evansi; Trypanosoma lewisi and Trypanosoma congolense have been discussed later in this article. This proves not just a rare cases but the beginning of new era in the history of human trypanosomes, put in dilemma whether they develop potential of new diseases of humans or just a biological accidently transmission. In Asia, first documented evidence found in 1933, human trypanosomiasis in Malaysia, a four month old infant infected with T. lewisi (Johnson P. D, 1933). Later in 1974 K. Shrivastava and colleague reported T. lewisi-like Herpetosoma infection, diagnosed in two adult patients in India during malaria eradication program. All three human Herpetosoma infected patients were recovered without treatment. More recently the cases of a two-month-old infant in the Gambia (Howie, S. et al., 2006) and India (Kaur, R. et al., 2007) infected with T. lewisi-like trypanosome is reported but Gambian case has invasion of central nervous system. One more case in Thailand is reported; Trypanosoma lewisi-like infected 45-day-old male infant was recovered with the treatment of antibiotic gentamicin (Sarataphan, N. et al., 2007). Suspected case, 40 aged female in State of west Bengal of India, infected with trypanosomiasis in January 2005 however T. evansi was concluded by considering only the fact, specie s isolated from these area is T. evansi in cattle, buffaloes, and goats (see Ref. Meeting of the Ad Hoc Group of the World Organization for Animal Health (OIE), Paris 2006). Animal trypanosomiasis Trypanosoma evansi caused to human in India, state of Maharashtra. The patient was 45 year old man and veterinary quack from Seoni village in Taluka Shindevahi of District Chandrapur from Maharashtra State. He was admitted to rural hospital; initially symptoms observed were headache, intermittent fever, disoriented, sensory scarcity, saliva dribble from mouth and violent behaviour. Blood thick smear, stained by Fields stain, examination was done by local microbiologist Mrs. Bharti U Sable; she suspects trypanosome along with plasmodium falciparum (figure 01). He was treated with antimalarial drug along with oral hematenics. She marked as the founder of Indian trypanosome, T. evansi. Later patient was transferred to the Government Medical College and Hospital (GMC) in Nagpur, India. Stained blood smear shows numerous flagellated trypanosomes parasite only, was confirmed morphologically, position of nucleus and small kinetoplast at central and posterior respectively indicate that the contributory mediator was T. evansi (Joshi, PP. et al., 2005). Anoth er unique character of T. evansi has homogenous DNA minicircles (Borst et al., 1987; Songa et al., 1990; Masiga and Gibson, 1990; Lun et al., 1992) and absence of DNA maxicircles in the kinetoplast unlike T. brucei (Borst et al., 1987; Songa et al., 1990). Several methods has been evolvedmicroscopy, card agglutination test (C. Gutierrez et. al., 2000), microhematocrit centrifugation technique (Woo, PTK 1970), enzyme-linked immunosorbent assay (Indrakamhang, P et al.1996), DNA hybridization (Viseshakul, N., Panyim, S., 1990) and polymerase chain reaction (Wuyts, N.et.al. 1994; Wuyts, N.et al.1995; Omawa, S et al 1999) for detection of T. evansi infection. To confirm morphological identification of parasite, additional test of blood, serum and cerebrospinal fluid (CSF) was done in the Department of Microbiology, Government Medical College and Hospital, Nagpur and at the Institut de Recherche pour le Dà ©veloppement in Montpellier, France. Parasitological and serological tests conducted at GMC, Nagpur, are as followed (Joshi, PP. et al., 2005): Biochemical quantitative analysis of serum was performed with less tiny significance on lipid levels, indication of Tangier disease. Tangier disease is a rare autosomal recessive genetic disorder, high density lipoprotein deficiencies associated with this disease include dramatically lowered level of APO A1 (Von Eckardstein, A., et al., 1998), was found to be non trypanolytic (Rifkin, M R. 1978a), however controversial data, fresh sera of a patient with Tangier disease is trypanolytic exhibiting bothTLF-1 and TLF-2 activity, reported (Tomlinson et al., 1995). The demonstration of specific antibodies has been employed by using card agglutination test for trypanosomiasis (CATT) for T. evansi using whole blood and serum was conducted. CATT test initially developed for T. brucei. gambiense (Diall et al., 1994). Sensitivity of CATT for T. evansi in Kenya was 65.5% (Z.K. Njiru et al.2004) and 68.6% (Ngaira et al.2003).False positive result of CATT was reported (Stijn Deborggraeve et al.2008). Mini-anion centrifugation technique is used for purification and concentration of trypanosomes using heparinised blood before and after treatment of suramin A direct latex IgM agglutination test was conducted with CSF to reveal functionless of parasite in the blood brain barrier. Sediment of CSF after centrifugation was examined by bright field microscopy for the presence of trypanosomes. Thomas chamber is used to count lymphocytes in the CSF, presence demonstrate the incursion of parasite. Molecular technique and serological tests conducted at the Institut de Recherche pour le Dà ©veloppement in Montpellier, France, are as followed (Joshi, PP. et al., 2005). Three independent PCR assay were performed using DNA of trypanosome Related to the subgenus Trypanozoon using a seminested PCR method, primer used ITS1/2 based on internal transcribed spacer (ITS) of ribosomal DNA. Related to T.brucei group using a single PCR of the 177- basepair. Amplification of T. evansi was conducted using a 994- basepair mitochondrial kinetoplast minicircle template with the primer TEV 1/2. Reference strains used are T. b.gambiense Bat 6118 and T. evansi CIRDES. PCR provided high specificity and sensitivity molecular biology technique among others for diagnosis of infectious diseases and also permits identification of micro organisms such as mycobacterium (Garcia-Quintanilla, A et al., 2002) , detection and differentiation of Entamoeba histolytica and Entamoeba dispar (Gonin, P et. al.,2003), simultaneous detection of tick-borne hemoprotozoan parasites Babesia caballi and Babesia equi in horse blood (Alhassan, A. et. al., 2005) and detection of influenza A Virus (Nicole L. Z et. al, 2006). In spite of these, PCR are not usual in some countries (Holland et al., 2001). It has been reported about reproducibility problems, for diagnosis of both human and animal trypanosomes, of PCR results (Solano et al., 2002; Malele et al., 2003). Recently a new DNA amplification method, loop-mediated isothermal amplification developed for diagnosis of species and sub-species specific trypanosomes (Thekisoe OM et al., 2007). Disease developed due to absence of trypanolytic factor in normal human serum hence immune status of patient was checked to resolve possible infection with human immunodeficiency virus (HIV). Three tests were conducted to corroborate the results of Enzyme-linked immunosorbent assay (ELISA) in India. HIV 1/2 assay Specific enzyme-linked immunosorbent assay (ELISA) NNO-LIA HIV 1/2 Score test Investigation of parasite Unusual transmission of animal trypanosomiasis, T. evansi to human requires rationalization, for this P. Truc and collaborator, 2007 studied genetic characterization of T. evansi. Generally, genetic variability of T. evansi has been detected by using isoenzyme (Gibson et al., 1983; Stevens et al., 1989), restriction fragment length polymorphism (RFLP) (Songa et al., 1990), microsatellite (Biteau et al., 2000) and random amplified polymorphic DNA (RAPD) analysis (Lun et al., 2004; Ventura et al., 2002); all these above technique found isolated T. evansi were genetically homogenous. Micro heterogeneity reported (Gibson et al., 1983; Stevens et al., 1989), may due to low-resolution techniques and no genetic exchange of T. evansi in vector like others T. brucei ssp, that leads to absence of recombination which play role for micro heterogeneity (Jenni et al.1986). Nevertheless, some genetic variability of isolated T. evansi from Kenya reported through PCR (Ngaira et al.2004, 2005; Njiru e t al.2006) and amplified fragment length polymorphism (AFLP) along with RAPD. Among later, AFLP admittance more polymorphisms, was able to differentiate and separate the Type A T. evansi into two clades (Masiga et al., 2006). Direct comparison of high-resolution molecular techniques microsatellites or simple sequence repeats (SSR) and Inter-simple sequence repeats (ISSR) PCR revealed that latter technique demonstrate greater genetic variability of T evansi isolates from different geographical area (Z.K. Njiru et al 2007). Recently molecular analysis of T. b. brucei by PCR and microsatellite PCR of reported blood slides was successfully conducted (Stijn Deborggraeve et al.2008). Isolated T. evansi has been termed into type A and type B (Masiga and Gibson, 1990). Unlike to type B detected only from Kenya, isolates type A are most copious (Borst et al., 1987). It has been shown however, that most of T. evansi from South America are dyskinetoplastic- lacking both maxicircles and minicir cles (Masiga and Gibson, 1990; Ventura et al., 2000; Schnaufer et al., 2002). Normally T. evansi diagnosed through variant surface glycoprotein (VSG) Rode Trypanozoon antigen type (RoTat) 1.2, a diagnostic antigen. Songa and Hamers, 1988 developed CATT for veterinary use, which based on RoTat 1.2 gene (Songa and Hamers, 1988). Both PCR test and serological-CATT test are highly sensitive and specific in divergent geographical region (Verloo et al., 2000), former test can be trustworthy for detection of isolates of both dyskinetoplastic and DNA minicircles in kinetoplast of T. evansi (Claes et al., 2004) also it based on RoTat 1.2 gene (Urakawa et al., 2001). On the other hand, most of T. evansi from Kenya were not detected by test, which based on VSG of T. evansi RoTat 1.2 gene because few isolates lack both RoTat 1.2 gene and their linked protein-VSG while other isolates having only RoTat 1.2 gene (Ngaira et al. 2004). Characterization of non-RoTat 1.2 T. evansi, specific PCR test developed in these 273 base pair was present in disparity to RoTat 1.2 T. evans i (J.M. Ngaira et al., 2005). Microscopic examination of dissected organs of tsetse flies was done for identification of trypanosome infections (Lloyd and Johnson, 1924). Parasites are, generally indentified in the mouthparts, salivary glands and mid-guts. Trypanosome species from vector is isolated and employed in isoenzyme electrophoresis technique for identifications (Gashumba et al., 1986). Another approach as recombinant DNA probes have been used for the identification both mature and immature trypanosomes in tsetse fly (Gibson et al., 1988; Majiwa et al., 1993).Dot-ELISA is another technique used for detecting trypanosomes in tsetse flies (Bosompem et al., 1996; Ouma, J. O et al., 2000) How T. evansi differs from other Trypanozoon The subgenus Trypanozoon includes three species, namely Trypanosoma brucei, T. evansi and T. equiperdum. T. evansi is judge against, concerning their morphological, mode of transmission, biochemical and molecular characteristics, rest of species. Bloodstream stages of these three parasites are often morphologically indistinguishable (Brun R et al., 1998; Gibson, 2003). T. evansi is mechanically transmitted of infected blood through insects of the genera Tabanus, Stomoxys, Atylotus and Lyperosia. Horseflies (Tabanus spp), Stableflies (Stomoxys spp) are the most capable vectors for the transmission of T. evansi in Indonesia and China (Luckins, 1988; Lun et al., 1993). In Africa, south and Central America, tsetse fly (Glossina spp) and vampire bats Desmodus rotundus an extra host-vector-reservoir of the T. evansi, respectively can mechanically transmitted this parasite. Direct transmissions through milk or during coitus involved T. evansi (Wang, 1988). Besides mechanical and direct tran smission of T. evansi, T. equiperdum transmitted directly during coitus and with rare possibility through bloodsucking insects (see ref. Brun, R et al.,1998). Trypanosoma brucei gambiense, sleeping sickness parasites have been able to spread through tsetse flies of palpalis group (Glossina palpalis, Glossina tachinoides) while T. b. rhodesiense was generally transmitted by tsetse of the morsitans group (Glossina morsitans, Glossina pallidipes). All 31 species of tsetse flies are able to transmit trypanosomes (Aksoy S, et al., 2003). Other major parasites T. congolense, T. vivax and T. simiae that are pathogens of domesticated animals, transmitted by tsetse fly. Both parasites, T. evansi and T. equiperdum are closely related to T. brucei, most likely developed from Trypanosoma brucei by independently deletion of kinetoplast DNA and should be regarded as two subspecies Trypanosoma brucei evansi and Trypanosoma brucei equiperdum respectively (Lai et al., 2008). Absence of maxicircles in kinetoplast DNA explained inexistence of procyclic or insect stage in these parasites and can propagate only as the mammal-infective bloodstream form (Borst et al., 1987).This facilitate to explain wide range of mechanical transmission of T. evansi outside of Africa (Lun and Desser, 1995). Procyclic form (PCF) T.brucei strain cannot survival with a partial or complete loss of kinetoplast DNA as with some Blood stream form (BSF) strains. This kinetoplast DNA deficient T.brucei strains appear naturally or induced by drugs (Schnaufer A et al.2002). Drug inducers are acriflavine, ethidium bromide, methoxy-9-ellipticine, hydroxystilbamidine, berenil, pentamidine, an trycide, and para-rosaniline, grouped as DNA intercalators and non intercalating drugs (Hajduk, 1978). Nevertheless, the existence of T. equiperdum has been complexity; Claes et al. suggested that, in fact, some strains of Trypanosoma equiperdum are actually Trypanosoma brucei and all other remaining misidentified strains such as Swiss Tropical Institute Basel (STIB) 818 are Trypanosoma evansi. However, based on PCR amplification of the fragment of DNA maxicircles in the kinetoplast, T. equiperdum Onderstepoort Veterinary Institute (OVI) and Bordeaux Trypanosoma antigen type (BoTat) 1.1 strains are T. brucei and other STIB 818, STIB 841 and STIB 842 T. equiperdum strains are not cluster together with T. evansi as it maintains maxicircles and allied genes. (Li et al., 2006). Both parasites have homogeneous minicircles. Although in all T. evansi strains maxicircles are totally lost but T. equiperdum shows more assortment, some strains seems to bear complete maxicircles with no active essential gene; others are missing one of the genes; and a few devoid the entire maxicircles (Lai et al., 2008). Unlike other DNA, T. brucei mitochondrial DNA termed kinetoplast DNA include a network of interlocked DNA rings (Liu, B. et al. 2005). This network of T. brucei ssp. comprised of several thousands of heterogeneous minicircles and several dozen of homogeneous maxicircles (Borst and Hoeijmakers, 1979). T. evansi has largely homogenous and limited heterogeneous minicircles in kinetoplast DNA (Borst et al., 1987). Results (Joshi, PP. et al., 2005; P. Truc et al., 2007) A careful examination of morphological characteristic demonstrates the presence of T. evansi. Patient had normal level of APO A-1 indicate no sign of Tangier disease. The result of CATT for T. evansi was positive suspect stalwartly presence of RoTat 1.2 gene. Latex IgM test, a diagnostic for trypanosome invasion in CSF, and lymphocytes count in the CSF indicated no invasion of parasite. An attempt to isolate and propagate trypanosome in wistar rat was failed. For molecular diagnosis of T. evansi PCR conducted, test was positive. Results of ELISAs for HIV, conducted in France and India were negative. Genetic characterization, Indian patient has homogenous DNA minicircles in kinetoplast of T. evansi of type A and devoid of SRA gene. Treatment Treatment was started 109 days after initial admission to hospital using suramin. Suramin is manufactured by Bayer and donated to WHO as Germanin, used against sleeping sickness in 1922 (Voogd et al., 1993). Suramin was used as a first stage of treatment for HAT caused by Trypanosoma brucei gambiense (chronic form) or T. b. rhodesiense (acute form). Efficacy of suramin against T. evansi infection was studied in cattle by Gill BS, Malhotra MN, 1963. It was requested and provided by Department of Public Health, Government of Maharashtra State, India and World Health Organisation respectively. As patient falls under first stage of infection, drugs have to be used pentamidine or suramin sodium. Pentamidine has more adverse effect than suramin, according to author; hence suramin was used in this patient. Drug suramin acts by interfering with enzyme of glycolytic pathway (Wierenga RK, et.al., 1987) in trypanosomes and produce hot spot, function as a signal for import into glycosome. It is preferred to give slow intravenous injection as suramin is poorly absorbed from intestine and causes intense local irritation when given intramuscularly (Voogd TE, et.al., 1993). Suramin does not cross the blood-brain barrier to kill trypanosome in the CSF however able to cure model of stage 2 diseases at a high dose greater than 80 mg per kg (Jennings FW, et.al., 1995). Follow-up study was commenced after the end of treatment and at 3rd and 6th months, all previous tests-CATT for T. evansi, latex IgM agglutination test, Mini anion-exchange centrifugation technique and examination of CSF by bright field microscopy are repeated at GMC Nagpur excepts biochemical analysis of serum for Tangier disease (P. P. Joshi et al. 2006). Tests result indicates first patient of human trypanosomiasis infected with T. evansi was recovered, Joshi and collaborators concluded that same schedule would follow in treatment if more cases observed. Suramin Suramin is less active against procyclic form of trypanosomes than bloodstream form, former normally reside in the tsetse flies (Scott AG, et.al., 1996). Suramin inhibit number of glycolytic enzyme which is essential to bloodstream form rather than procyclic form (Fairlamb AH, et.al., 1977, Fairlamb AH, et.al., 1980). Hanau and colleagues proposed other likely target of drug, competitive inhibitor of an enzyme 6-phosphogluconate dehydrogenase of pentose phosphate pathway (Hanau S, et.al., 1996). Suramin is an effective microfilaricide for Onchocerca spp. and Brugia pahangi worms (Hawking, et al., 1981; Howells, et al., 1983). It is a known ATP/UTP purine receptor (P2 receptor) antagonist (V. Ralevic and G. Burnstock, 1998). Nevertheless suramin inhibit ample varieties of enzymes like reverse transcriptase, dihydrofolate reductase, furamse, glycerol-3-phosphate dehydrogenase, hexokinase, L-a-glycerophosphate oxidase, receptor mediated uptake of low density lipoprotein, RNA polymerase and kinases, thymidine kinase, trypsin (P ´epin and Milord, 1994; Wang, 1995). Besides its trypanocidal activity, suramin is also useful in hormone-refractory prostate cancer, however survival rate was not affected (Small et al., 2000; Ahles et al., 2004). Suramins antitumor activity has been attributed to its inhibition of various growth factors which include platelet-derived growth factor, fibroblast growth factor, transforming growth factors alpha and beta, insulin- like growth factors 1(Stein CA,1993). Osteosarcoma is the malignant tumor of the bone; suramin exerts an inhibitory effect on osteosarcoma cell growth of established cell lines (Benini et al., 1999), newly established osteosarcoma cell lines and stimulation of osteosarcoma cells by physiological compounds, such as 1, 25-dihydroxy-Vitamin D3 (K. Trieb, H. Blahovec, 2002). Furthermore, results in an inhibiting capacity of suramin on various cell functions include production of alkaline-phosphatase or telomerase activi ty (K. Trieb, H. Blahovec, 2002). Suramin blocked CD154 (Emilio Margolles-Clark et al., 2009) from interacting with its receptor CD40 (U. Schà ¶nbeck and P. Libby, 2001; I.S. Grewal and R.A. Flavell, 1998), costimulatory interactions are therapeutically important to modulate immune responses (C.P. Larsen et al., 2006; F. Vincenti and M. Luggen, 2007). Suramin inhibited the binding of TNF-a to its receptor TNF-R1 (F. Mancini et al., 1999) and its ability to inhibit CD40-CD154 interaction was 30 fold more active compared to it (Emilio Margolles-Clark et al., 2009). Suramin has also been shown to suppress T cell activity (C. Schiller et al., 1994), antiproliferative effects on lymphoid cells (Z. Spigelman et al., 1987). Suramin can causes toxicities which include adrenal and renal insufficiency, coagulation factor abnormalities and poly-neuropathy (T.E. Voogd et al., 1993; D.J. Cole et al., 1994), at relatively high concentration inhibited the binding of IL2 to its cell surface recept or (G.B. Mills et al.,1990), greater than therapeutic use (S.A. Grossman et al., 2001; S.T. Eichhorst et al., 2004). It concentration-dependently inhibited proteolytic and phospholipase A2 (PLA2) activities of Bothrops jararacussu venom- potential to be used as antivenom, suramin also antagonise the cardiotoxic effect of Bothrops jararacussu venom in rats heart (Daniel N. Sifuentes et al., 2008). Uptake of suramin by bloodstream form of trypanosome is through receptor mediated endocytosis which is most likely route of entry (Fairlamb AH, et al., 1980). Suramin intensively bound to plasma proteins such as low density lipoproteins, albumins, globulins, fibrinogen, etc. According to Bastin et al. 1996, Coppens and Courtoy 2000 and Green et.al 2003 suggested that suramin might enter while bound to low density lipoprotein (LDL), it has high affinity to bind many serum proteins including LDL (Vansterkenburg ELM, et al., 1993). The high rate of fluid-phase endocytosis occurs in the trypanosomes of bloodstream form (Engstler, et al., 2004). This mechanism could be involved in the uptake of suramin into T. brucei that does not require specialized receptors. Trypanosomes cannot synthesise their own fatty acid and cholesterol de novo hence LDL uptake is essential for propagation (Coppens I, et al., 2000). It does not make any worse however in procyclic form, uptake of suramin is through receptor mediated endocytosis and not coupled with LDL uptake (Pal A, et al., 2002). Suramin involves inhibition of various glycolytic enzymes, effects rates of respiration as aerobic glycolysis is closely related with it in bloodstream forms (Fairlamb AH, et al., 1980, Opperdoes, F.R. et al., 1989). Diminished growth rate of trypanosome in vivo is a consequence of decrease in respiration (Fairlamb AH, et al., 1980). Suramin is also used as veterinary trypanocide; report on resistance in T. evansi that infects animals is reported (El Rayah et al., 1999, Zhou, J.L. et al., 2004). Some cases have been described of drug resistance when suramin is used against Trypanosoma brucei rhodesiense in humans (W ´ery, M., 1994). Suramin reduced sensitivity towards T. b. rhodesiense (Bacchi et al., 1990) and failure of treatment up to 25-30% observed (P ´epin and Milord, 1994, Burri, C et al., 2004). Failures of treatment are common due to misdiagnosed late stage infection (Burri et al., 2004). De Koning argued one of the reasons of suramin resistance is associated with reduction in drug uptake; molecule is large and highly charged which plasma membrane transporter takes up. Role of apolipoprotein L-1 and haptoglobin-related protein T. evansi affects mainly domesticated animals such as camels, cattle and water buffalo, spread by mechanical transmission of infected blood through insect such as tabanid flies. Due to these, it spread apart from sub-Saharan Africa to South America, North America and Asia. Normally humans are resistant to animal trypanosomes, immunity against T.brucei brucei is due to trypanolytic activity of an apolipoprotein L-1 (APOL-1) bound to high density lipoprotein (HDL) (Vanhamme L. et al., 2003). Previously it was concluded that trypanolytic activity in normal human serum was due to immunoglobin M (Aaronovitch, S. Terry, R. J. 1972). Later in 1973, Hawking and colleagues resolute there were two trypanolyic factors. These two factors differ in their activity (in vivo and vitro), molecular mass, quantity in serum and sensitivity to antagonists (Hawking et al., 1973b). HDL was identified as trypanolyic factor by Rifkin in 1978, she also characterised the two trypanolyic factors determined by Hawking (Rifkin, M. R. 1978b). Trypanolyic factors in human serum shows inhomogeneous properties (Tomlinson et al., 1995; Raper et al., 1996b). Both TLF are a subset of HDLs commonly referred to as HDL3 (Lorenz et al., 1995), contain haptoglobin-related protein (Hpr) (Smith et al., 1995) and APOL-1 (Vanhamme, L. et al., 2003).TLF-1 is a 500 kDa lipid rich while TLF-2,1000 kDa protein complex containing IgM, lipid poor HDL particle (Raper, J. et al., 1999; Lugli, E.B. et al., 2004). Apolipop rotein A-1 (APOA-1) is a component of TLF-1(Smith et al., 1995) and, although previously reported that APOA-1 could not detected in TLF-2(Tomlinson, S. et al., 1995), is a component of TLF-2 (Raper, J. et al., 1999). Previously unknown proteins, human cathelicidin antimicrobial peptide (hCAP18), glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) and paraoxonase are associated with TLF-1(Smith AB et al., 1995; Lugil E et al., 2004). APOA-1 suggests a role in trypanolysis later controversial report supporting a lytic role (Gillett, M. Owen, J. 1992a) or not favor lytic role (Rifkin, 1991; Seed et al., 1993). Later it was confirmed that APOA-1 was not toxic (Tytler, 1995) but may indirectly play role of trypanolytic (Owen et al., 1996). For trypanosomes, HDLs contain 16,000-65,000 binding site per cell having moderate affinity (Gillett, M. Owen, J. 1992b). However, binding of lytic factor, TLF-1 appeared to involve two binding site, low affinity have 65,000 and high affinity 350 binding sites (Drain et al., 2001). Host macromolecules, interact with bloodstream trypanosomes, transferrin (Borst, P.1991) and low-density lipoprotein (LDL) (Coppens, I et al., 1987) through receptor-mediated endocytosis occur at the flagellar pocket of trypanosome (Gull, K., 2003). APOL-1 is a bacterial colicins and Bcl-2 family members like protein containing pore forming domain as well as a region for the membrane insertion of it (Pà ©rez -Morga D et al., 2005, Pays E et al., 2006). APOL-1 is taken up in the parasite by endocytosis, able to kill by the parasite by forming anion selective pores in the lysosomal membrane of parasite, this pore allows the influx of chloride ions into the lysosome, subsequent cell death as a consequence of entry of water and induces uncontrolled osmotic swelling of vacuole ((Pà ©rez-Morga D et al., 2005; Pays E et al., 2006; B. Vanhollebeke et al., 2007a). APOL-1 could not be involved in apoptosis but in programmed cell death (B. Vanhollebeke et al., 2006a). Resistance of T.brucei rhodesiense and T.brucei gambiense to APOL-1 is developed which allows these parasites to infect and cause HAT. Single protein termed serum resistance-associated protein (SRA) is main reason of resistance of T.brucei rhodesiense to APOL-1.SRAP interacts strongly with APOL-1 and provide specific resistance to T.brucei rhodesiense (Xong HV et al., 1998; Gibson WC, 2005). T brucei gambiense is also resistant to APOL-1; mechanism is not understood (Pays E et al., 2006). Indian case with T. evansi infection, human serum devoid of APOL-1, reason for the absence was due to independent frameshift mutation in both APOL-1 alleles (B. Vanhollebeke et al., 2006b). Another HDL component, plays a toxic role for full trypanolytic activity of normal human serum, haptoglobin-related protein (Hpr).Indian case has normal concentration of Hpr bound HDL but short of trypanolytic activity. Hpr is a haemoglobin (Hb) binding protein induces, within acidic lysosome of T.b.brucei, Fenton like reaction between H202 and iron that lead to formation of free hydroxyl radicals, which would prompt the reaction of lipid peroxidation of lysosomal membrane (Smith AB et al., 1995; Hager KM et al., 1994; Bishop JR et al., 2001; Justin Widener et al., 2007). Nevertheless action of trypanolysis of Hpr and APOL-1, biological function is not clear. Optimal trypanolytic activity requires presence of both APOL-1 and Hpr on same subset of HDL particle (B. Vanhollebeke et al., 2007b). Vanhollebeke et al. (2007b) reported trypanosome survival assay in normal as well as mutant human sera. Survival of trypanosomes occurs in human serum devoid of APOL-1 and fetal calf serum (FCS). FCS is nonlytic and contains neither APOL-1 nor Hpr. Human serum deficient of Hpr and haptoglobin (Hp) but with normal HDL b Disease Caused by Parasite of Genus Trypanosoma Disease Caused by Parasite of Genus Trypanosoma Human trypanosomiasis caused by Trypanosoma evansi and Trypanosoma lewisi in India : A matter of concern Introduction Disease produced by the parasite of genus Trypanosoma called as trypanosomiasis. It is one of the most important hemoprotozoan diseases, widely distributed in animals and human beings. It is endemic in Africa and America, are deadly pathogens that threaten millions of people in at least 36 countries in Africa. It is estimated that approximately 60 million people are at risk and 3, 00,000 new cases found every year in Africa (WHO Report 1998). Both African and American trypanosomes rank within the top 10 in terms of global impact. Despite the impact of these parasites, how they cause disease is relatively less is understood. In Africa, the disease is commonly known as human African trypanosomiasis (HAT) or sleeping sickness whereas the American trypanosomiasis recognized as Chagas disease. They not only infect vertebrates groups (amphibians, reptiles, birds, fish, and mammals) but also many invertebrates (Crithidia, Leptomonas). Human African trypanosomiasis belongs to genus Trypanoso ma, subgenus trypanozoon. Classification phylum sacromastigophora, order kinetoplastida and the family trypanosomatidae. Genus Trypanosoma includes subgenus which is divided into major group, salivaria and stercoraria that infect vertebrates (Hoare C. A.1964). Trypanozoon (T. brucei ssp, T. evansi, T. equiperdum), Duttonella (T. vivax,T. uniforme), Nannomonas (T. congolense, T. simiae), Pycnomonas (T. suis), Tejeraia (T. rangeli) belongs to salivaria group. Under stercoraria group Herpetosoma (T. lewisi, T. musculi,T. microti), Megatrypanum (T. theileri, T. melophagium), Schizotryponum (T. cruzi, T. dionisii) come. T. brucei. brucei, T. brucei. gambiense and T. brucei. rhodesiense are the subspecies of the Trypanozoon. Sleeping sickness is caused by T. brucei. gambiense, a chronic form of HAT in West and Central Africa lasting from months to years or T. brucei. rhodesiense, an acute form of HAT in East and Southern African with a duration of weeks to months. Whereas, closely relate d parasite T. brucei. brucei is non pathogenic to humans. The American trypanosomiasis is caused by T. cruzi. rhodesiense. These forms of the disease is deadly and develop within weeks to months, the gambiense form takes year. Trypanosomes cause animal trypanosomiasis has a wide geographic distribution. Surra is caused by T. evansi and infects mainly camels, cattle, buffalos, horses, deer and other wild animals. T. b. Brucei causes nagana in tropical Africa and affects only cattle; T. vivax and T. congolense infect domestic and small animals while T.lewisi is a commensally of rats. T. equiperdum causes dourine disease in horse and donkey of India, Europe, America and North Africa. African trypanosomes are transmitted by tsetse flies, a species of Glossina, and South American trypanosomes by reduvid bugs. Normally human are resistant to animal species of Trypanosoma due to the trypanolytic factor of human serum. However, there are several cases of human infection with animal trypanosomes such as Trypanosoma evansi; Trypanosoma lewisi and Trypanosoma congolense have been discussed later in this article. This proves not just a rare cases but the beginning of new era in the history of human trypanosomes, put in dilemma whether they develop potential of new diseases of humans or just a biological accidently transmission. In Asia, first documented evidence found in 1933, human trypanosomiasis in Malaysia, a four month old infant infected with T. lewisi (Johnson P. D, 1933). Later in 1974 K. Shrivastava and colleague reported T. lewisi-like Herpetosoma infection, diagnosed in two adult patients in India during malaria eradication program. All three human Herpetosoma infected patients were recovered without treatment. More recently the cases of a two-month-old infant in the Gambia (Howie, S. et al., 2006) and India (Kaur, R. et al., 2007) infected with T. lewisi-like trypanosome is reported but Gambian case has invasion of central nervous system. One more case in Thailand is reported; Trypanosoma lewisi-like infected 45-day-old male infant was recovered with the treatment of antibiotic gentamicin (Sarataphan, N. et al., 2007). Suspected case, 40 aged female in State of west Bengal of India, infected with trypanosomiasis in January 2005 however T. evansi was concluded by considering only the fact, specie s isolated from these area is T. evansi in cattle, buffaloes, and goats (see Ref. Meeting of the Ad Hoc Group of the World Organization for Animal Health (OIE), Paris 2006). Animal trypanosomiasis Trypanosoma evansi caused to human in India, state of Maharashtra. The patient was 45 year old man and veterinary quack from Seoni village in Taluka Shindevahi of District Chandrapur from Maharashtra State. He was admitted to rural hospital; initially symptoms observed were headache, intermittent fever, disoriented, sensory scarcity, saliva dribble from mouth and violent behaviour. Blood thick smear, stained by Fields stain, examination was done by local microbiologist Mrs. Bharti U Sable; she suspects trypanosome along with plasmodium falciparum (figure 01). He was treated with antimalarial drug along with oral hematenics. She marked as the founder of Indian trypanosome, T. evansi. Later patient was transferred to the Government Medical College and Hospital (GMC) in Nagpur, India. Stained blood smear shows numerous flagellated trypanosomes parasite only, was confirmed morphologically, position of nucleus and small kinetoplast at central and posterior respectively indicate that the contributory mediator was T. evansi (Joshi, PP. et al., 2005). Anoth er unique character of T. evansi has homogenous DNA minicircles (Borst et al., 1987; Songa et al., 1990; Masiga and Gibson, 1990; Lun et al., 1992) and absence of DNA maxicircles in the kinetoplast unlike T. brucei (Borst et al., 1987; Songa et al., 1990). Several methods has been evolvedmicroscopy, card agglutination test (C. Gutierrez et. al., 2000), microhematocrit centrifugation technique (Woo, PTK 1970), enzyme-linked immunosorbent assay (Indrakamhang, P et al.1996), DNA hybridization (Viseshakul, N., Panyim, S., 1990) and polymerase chain reaction (Wuyts, N.et.al. 1994; Wuyts, N.et al.1995; Omawa, S et al 1999) for detection of T. evansi infection. To confirm morphological identification of parasite, additional test of blood, serum and cerebrospinal fluid (CSF) was done in the Department of Microbiology, Government Medical College and Hospital, Nagpur and at the Institut de Recherche pour le Dà ©veloppement in Montpellier, France. Parasitological and serological tests conducted at GMC, Nagpur, are as followed (Joshi, PP. et al., 2005): Biochemical quantitative analysis of serum was performed with less tiny significance on lipid levels, indication of Tangier disease. Tangier disease is a rare autosomal recessive genetic disorder, high density lipoprotein deficiencies associated with this disease include dramatically lowered level of APO A1 (Von Eckardstein, A., et al., 1998), was found to be non trypanolytic (Rifkin, M R. 1978a), however controversial data, fresh sera of a patient with Tangier disease is trypanolytic exhibiting bothTLF-1 and TLF-2 activity, reported (Tomlinson et al., 1995). The demonstration of specific antibodies has been employed by using card agglutination test for trypanosomiasis (CATT) for T. evansi using whole blood and serum was conducted. CATT test initially developed for T. brucei. gambiense (Diall et al., 1994). Sensitivity of CATT for T. evansi in Kenya was 65.5% (Z.K. Njiru et al.2004) and 68.6% (Ngaira et al.2003).False positive result of CATT was reported (Stijn Deborggraeve et al.2008). Mini-anion centrifugation technique is used for purification and concentration of trypanosomes using heparinised blood before and after treatment of suramin A direct latex IgM agglutination test was conducted with CSF to reveal functionless of parasite in the blood brain barrier. Sediment of CSF after centrifugation was examined by bright field microscopy for the presence of trypanosomes. Thomas chamber is used to count lymphocytes in the CSF, presence demonstrate the incursion of parasite. Molecular technique and serological tests conducted at the Institut de Recherche pour le Dà ©veloppement in Montpellier, France, are as followed (Joshi, PP. et al., 2005). Three independent PCR assay were performed using DNA of trypanosome Related to the subgenus Trypanozoon using a seminested PCR method, primer used ITS1/2 based on internal transcribed spacer (ITS) of ribosomal DNA. Related to T.brucei group using a single PCR of the 177- basepair. Amplification of T. evansi was conducted using a 994- basepair mitochondrial kinetoplast minicircle template with the primer TEV 1/2. Reference strains used are T. b.gambiense Bat 6118 and T. evansi CIRDES. PCR provided high specificity and sensitivity molecular biology technique among others for diagnosis of infectious diseases and also permits identification of micro organisms such as mycobacterium (Garcia-Quintanilla, A et al., 2002) , detection and differentiation of Entamoeba histolytica and Entamoeba dispar (Gonin, P et. al.,2003), simultaneous detection of tick-borne hemoprotozoan parasites Babesia caballi and Babesia equi in horse blood (Alhassan, A. et. al., 2005) and detection of influenza A Virus (Nicole L. Z et. al, 2006). In spite of these, PCR are not usual in some countries (Holland et al., 2001). It has been reported about reproducibility problems, for diagnosis of both human and animal trypanosomes, of PCR results (Solano et al., 2002; Malele et al., 2003). Recently a new DNA amplification method, loop-mediated isothermal amplification developed for diagnosis of species and sub-species specific trypanosomes (Thekisoe OM et al., 2007). Disease developed due to absence of trypanolytic factor in normal human serum hence immune status of patient was checked to resolve possible infection with human immunodeficiency virus (HIV). Three tests were conducted to corroborate the results of Enzyme-linked immunosorbent assay (ELISA) in India. HIV 1/2 assay Specific enzyme-linked immunosorbent assay (ELISA) NNO-LIA HIV 1/2 Score test Investigation of parasite Unusual transmission of animal trypanosomiasis, T. evansi to human requires rationalization, for this P. Truc and collaborator, 2007 studied genetic characterization of T. evansi. Generally, genetic variability of T. evansi has been detected by using isoenzyme (Gibson et al., 1983; Stevens et al., 1989), restriction fragment length polymorphism (RFLP) (Songa et al., 1990), microsatellite (Biteau et al., 2000) and random amplified polymorphic DNA (RAPD) analysis (Lun et al., 2004; Ventura et al., 2002); all these above technique found isolated T. evansi were genetically homogenous. Micro heterogeneity reported (Gibson et al., 1983; Stevens et al., 1989), may due to low-resolution techniques and no genetic exchange of T. evansi in vector like others T. brucei ssp, that leads to absence of recombination which play role for micro heterogeneity (Jenni et al.1986). Nevertheless, some genetic variability of isolated T. evansi from Kenya reported through PCR (Ngaira et al.2004, 2005; Njiru e t al.2006) and amplified fragment length polymorphism (AFLP) along with RAPD. Among later, AFLP admittance more polymorphisms, was able to differentiate and separate the Type A T. evansi into two clades (Masiga et al., 2006). Direct comparison of high-resolution molecular techniques microsatellites or simple sequence repeats (SSR) and Inter-simple sequence repeats (ISSR) PCR revealed that latter technique demonstrate greater genetic variability of T evansi isolates from different geographical area (Z.K. Njiru et al 2007). Recently molecular analysis of T. b. brucei by PCR and microsatellite PCR of reported blood slides was successfully conducted (Stijn Deborggraeve et al.2008). Isolated T. evansi has been termed into type A and type B (Masiga and Gibson, 1990). Unlike to type B detected only from Kenya, isolates type A are most copious (Borst et al., 1987). It has been shown however, that most of T. evansi from South America are dyskinetoplastic- lacking both maxicircles and minicir cles (Masiga and Gibson, 1990; Ventura et al., 2000; Schnaufer et al., 2002). Normally T. evansi diagnosed through variant surface glycoprotein (VSG) Rode Trypanozoon antigen type (RoTat) 1.2, a diagnostic antigen. Songa and Hamers, 1988 developed CATT for veterinary use, which based on RoTat 1.2 gene (Songa and Hamers, 1988). Both PCR test and serological-CATT test are highly sensitive and specific in divergent geographical region (Verloo et al., 2000), former test can be trustworthy for detection of isolates of both dyskinetoplastic and DNA minicircles in kinetoplast of T. evansi (Claes et al., 2004) also it based on RoTat 1.2 gene (Urakawa et al., 2001). On the other hand, most of T. evansi from Kenya were not detected by test, which based on VSG of T. evansi RoTat 1.2 gene because few isolates lack both RoTat 1.2 gene and their linked protein-VSG while other isolates having only RoTat 1.2 gene (Ngaira et al. 2004). Characterization of non-RoTat 1.2 T. evansi, specific PCR test developed in these 273 base pair was present in disparity to RoTat 1.2 T. evans i (J.M. Ngaira et al., 2005). Microscopic examination of dissected organs of tsetse flies was done for identification of trypanosome infections (Lloyd and Johnson, 1924). Parasites are, generally indentified in the mouthparts, salivary glands and mid-guts. Trypanosome species from vector is isolated and employed in isoenzyme electrophoresis technique for identifications (Gashumba et al., 1986). Another approach as recombinant DNA probes have been used for the identification both mature and immature trypanosomes in tsetse fly (Gibson et al., 1988; Majiwa et al., 1993).Dot-ELISA is another technique used for detecting trypanosomes in tsetse flies (Bosompem et al., 1996; Ouma, J. O et al., 2000) How T. evansi differs from other Trypanozoon The subgenus Trypanozoon includes three species, namely Trypanosoma brucei, T. evansi and T. equiperdum. T. evansi is judge against, concerning their morphological, mode of transmission, biochemical and molecular characteristics, rest of species. Bloodstream stages of these three parasites are often morphologically indistinguishable (Brun R et al., 1998; Gibson, 2003). T. evansi is mechanically transmitted of infected blood through insects of the genera Tabanus, Stomoxys, Atylotus and Lyperosia. Horseflies (Tabanus spp), Stableflies (Stomoxys spp) are the most capable vectors for the transmission of T. evansi in Indonesia and China (Luckins, 1988; Lun et al., 1993). In Africa, south and Central America, tsetse fly (Glossina spp) and vampire bats Desmodus rotundus an extra host-vector-reservoir of the T. evansi, respectively can mechanically transmitted this parasite. Direct transmissions through milk or during coitus involved T. evansi (Wang, 1988). Besides mechanical and direct tran smission of T. evansi, T. equiperdum transmitted directly during coitus and with rare possibility through bloodsucking insects (see ref. Brun, R et al.,1998). Trypanosoma brucei gambiense, sleeping sickness parasites have been able to spread through tsetse flies of palpalis group (Glossina palpalis, Glossina tachinoides) while T. b. rhodesiense was generally transmitted by tsetse of the morsitans group (Glossina morsitans, Glossina pallidipes). All 31 species of tsetse flies are able to transmit trypanosomes (Aksoy S, et al., 2003). Other major parasites T. congolense, T. vivax and T. simiae that are pathogens of domesticated animals, transmitted by tsetse fly. Both parasites, T. evansi and T. equiperdum are closely related to T. brucei, most likely developed from Trypanosoma brucei by independently deletion of kinetoplast DNA and should be regarded as two subspecies Trypanosoma brucei evansi and Trypanosoma brucei equiperdum respectively (Lai et al., 2008). Absence of maxicircles in kinetoplast DNA explained inexistence of procyclic or insect stage in these parasites and can propagate only as the mammal-infective bloodstream form (Borst et al., 1987).This facilitate to explain wide range of mechanical transmission of T. evansi outside of Africa (Lun and Desser, 1995). Procyclic form (PCF) T.brucei strain cannot survival with a partial or complete loss of kinetoplast DNA as with some Blood stream form (BSF) strains. This kinetoplast DNA deficient T.brucei strains appear naturally or induced by drugs (Schnaufer A et al.2002). Drug inducers are acriflavine, ethidium bromide, methoxy-9-ellipticine, hydroxystilbamidine, berenil, pentamidine, an trycide, and para-rosaniline, grouped as DNA intercalators and non intercalating drugs (Hajduk, 1978). Nevertheless, the existence of T. equiperdum has been complexity; Claes et al. suggested that, in fact, some strains of Trypanosoma equiperdum are actually Trypanosoma brucei and all other remaining misidentified strains such as Swiss Tropical Institute Basel (STIB) 818 are Trypanosoma evansi. However, based on PCR amplification of the fragment of DNA maxicircles in the kinetoplast, T. equiperdum Onderstepoort Veterinary Institute (OVI) and Bordeaux Trypanosoma antigen type (BoTat) 1.1 strains are T. brucei and other STIB 818, STIB 841 and STIB 842 T. equiperdum strains are not cluster together with T. evansi as it maintains maxicircles and allied genes. (Li et al., 2006). Both parasites have homogeneous minicircles. Although in all T. evansi strains maxicircles are totally lost but T. equiperdum shows more assortment, some strains seems to bear complete maxicircles with no active essential gene; others are missing one of the genes; and a few devoid the entire maxicircles (Lai et al., 2008). Unlike other DNA, T. brucei mitochondrial DNA termed kinetoplast DNA include a network of interlocked DNA rings (Liu, B. et al. 2005). This network of T. brucei ssp. comprised of several thousands of heterogeneous minicircles and several dozen of homogeneous maxicircles (Borst and Hoeijmakers, 1979). T. evansi has largely homogenous and limited heterogeneous minicircles in kinetoplast DNA (Borst et al., 1987). Results (Joshi, PP. et al., 2005; P. Truc et al., 2007) A careful examination of morphological characteristic demonstrates the presence of T. evansi. Patient had normal level of APO A-1 indicate no sign of Tangier disease. The result of CATT for T. evansi was positive suspect stalwartly presence of RoTat 1.2 gene. Latex IgM test, a diagnostic for trypanosome invasion in CSF, and lymphocytes count in the CSF indicated no invasion of parasite. An attempt to isolate and propagate trypanosome in wistar rat was failed. For molecular diagnosis of T. evansi PCR conducted, test was positive. Results of ELISAs for HIV, conducted in France and India were negative. Genetic characterization, Indian patient has homogenous DNA minicircles in kinetoplast of T. evansi of type A and devoid of SRA gene. Treatment Treatment was started 109 days after initial admission to hospital using suramin. Suramin is manufactured by Bayer and donated to WHO as Germanin, used against sleeping sickness in 1922 (Voogd et al., 1993). Suramin was used as a first stage of treatment for HAT caused by Trypanosoma brucei gambiense (chronic form) or T. b. rhodesiense (acute form). Efficacy of suramin against T. evansi infection was studied in cattle by Gill BS, Malhotra MN, 1963. It was requested and provided by Department of Public Health, Government of Maharashtra State, India and World Health Organisation respectively. As patient falls under first stage of infection, drugs have to be used pentamidine or suramin sodium. Pentamidine has more adverse effect than suramin, according to author; hence suramin was used in this patient. Drug suramin acts by interfering with enzyme of glycolytic pathway (Wierenga RK, et.al., 1987) in trypanosomes and produce hot spot, function as a signal for import into glycosome. It is preferred to give slow intravenous injection as suramin is poorly absorbed from intestine and causes intense local irritation when given intramuscularly (Voogd TE, et.al., 1993). Suramin does not cross the blood-brain barrier to kill trypanosome in the CSF however able to cure model of stage 2 diseases at a high dose greater than 80 mg per kg (Jennings FW, et.al., 1995). Follow-up study was commenced after the end of treatment and at 3rd and 6th months, all previous tests-CATT for T. evansi, latex IgM agglutination test, Mini anion-exchange centrifugation technique and examination of CSF by bright field microscopy are repeated at GMC Nagpur excepts biochemical analysis of serum for Tangier disease (P. P. Joshi et al. 2006). Tests result indicates first patient of human trypanosomiasis infected with T. evansi was recovered, Joshi and collaborators concluded that same schedule would follow in treatment if more cases observed. Suramin Suramin is less active against procyclic form of trypanosomes than bloodstream form, former normally reside in the tsetse flies (Scott AG, et.al., 1996). Suramin inhibit number of glycolytic enzyme which is essential to bloodstream form rather than procyclic form (Fairlamb AH, et.al., 1977, Fairlamb AH, et.al., 1980). Hanau and colleagues proposed other likely target of drug, competitive inhibitor of an enzyme 6-phosphogluconate dehydrogenase of pentose phosphate pathway (Hanau S, et.al., 1996). Suramin is an effective microfilaricide for Onchocerca spp. and Brugia pahangi worms (Hawking, et al., 1981; Howells, et al., 1983). It is a known ATP/UTP purine receptor (P2 receptor) antagonist (V. Ralevic and G. Burnstock, 1998). Nevertheless suramin inhibit ample varieties of enzymes like reverse transcriptase, dihydrofolate reductase, furamse, glycerol-3-phosphate dehydrogenase, hexokinase, L-a-glycerophosphate oxidase, receptor mediated uptake of low density lipoprotein, RNA polymerase and kinases, thymidine kinase, trypsin (P ´epin and Milord, 1994; Wang, 1995). Besides its trypanocidal activity, suramin is also useful in hormone-refractory prostate cancer, however survival rate was not affected (Small et al., 2000; Ahles et al., 2004). Suramins antitumor activity has been attributed to its inhibition of various growth factors which include platelet-derived growth factor, fibroblast growth factor, transforming growth factors alpha and beta, insulin- like growth factors 1(Stein CA,1993). Osteosarcoma is the malignant tumor of the bone; suramin exerts an inhibitory effect on osteosarcoma cell growth of established cell lines (Benini et al., 1999), newly established osteosarcoma cell lines and stimulation of osteosarcoma cells by physiological compounds, such as 1, 25-dihydroxy-Vitamin D3 (K. Trieb, H. Blahovec, 2002). Furthermore, results in an inhibiting capacity of suramin on various cell functions include production of alkaline-phosphatase or telomerase activi ty (K. Trieb, H. Blahovec, 2002). Suramin blocked CD154 (Emilio Margolles-Clark et al., 2009) from interacting with its receptor CD40 (U. Schà ¶nbeck and P. Libby, 2001; I.S. Grewal and R.A. Flavell, 1998), costimulatory interactions are therapeutically important to modulate immune responses (C.P. Larsen et al., 2006; F. Vincenti and M. Luggen, 2007). Suramin inhibited the binding of TNF-a to its receptor TNF-R1 (F. Mancini et al., 1999) and its ability to inhibit CD40-CD154 interaction was 30 fold more active compared to it (Emilio Margolles-Clark et al., 2009). Suramin has also been shown to suppress T cell activity (C. Schiller et al., 1994), antiproliferative effects on lymphoid cells (Z. Spigelman et al., 1987). Suramin can causes toxicities which include adrenal and renal insufficiency, coagulation factor abnormalities and poly-neuropathy (T.E. Voogd et al., 1993; D.J. Cole et al., 1994), at relatively high concentration inhibited the binding of IL2 to its cell surface recept or (G.B. Mills et al.,1990), greater than therapeutic use (S.A. Grossman et al., 2001; S.T. Eichhorst et al., 2004). It concentration-dependently inhibited proteolytic and phospholipase A2 (PLA2) activities of Bothrops jararacussu venom- potential to be used as antivenom, suramin also antagonise the cardiotoxic effect of Bothrops jararacussu venom in rats heart (Daniel N. Sifuentes et al., 2008). Uptake of suramin by bloodstream form of trypanosome is through receptor mediated endocytosis which is most likely route of entry (Fairlamb AH, et al., 1980). Suramin intensively bound to plasma proteins such as low density lipoproteins, albumins, globulins, fibrinogen, etc. According to Bastin et al. 1996, Coppens and Courtoy 2000 and Green et.al 2003 suggested that suramin might enter while bound to low density lipoprotein (LDL), it has high affinity to bind many serum proteins including LDL (Vansterkenburg ELM, et al., 1993). The high rate of fluid-phase endocytosis occurs in the trypanosomes of bloodstream form (Engstler, et al., 2004). This mechanism could be involved in the uptake of suramin into T. brucei that does not require specialized receptors. Trypanosomes cannot synthesise their own fatty acid and cholesterol de novo hence LDL uptake is essential for propagation (Coppens I, et al., 2000). It does not make any worse however in procyclic form, uptake of suramin is through receptor mediated endocytosis and not coupled with LDL uptake (Pal A, et al., 2002). Suramin involves inhibition of various glycolytic enzymes, effects rates of respiration as aerobic glycolysis is closely related with it in bloodstream forms (Fairlamb AH, et al., 1980, Opperdoes, F.R. et al., 1989). Diminished growth rate of trypanosome in vivo is a consequence of decrease in respiration (Fairlamb AH, et al., 1980). Suramin is also used as veterinary trypanocide; report on resistance in T. evansi that infects animals is reported (El Rayah et al., 1999, Zhou, J.L. et al., 2004). Some cases have been described of drug resistance when suramin is used against Trypanosoma brucei rhodesiense in humans (W ´ery, M., 1994). Suramin reduced sensitivity towards T. b. rhodesiense (Bacchi et al., 1990) and failure of treatment up to 25-30% observed (P ´epin and Milord, 1994, Burri, C et al., 2004). Failures of treatment are common due to misdiagnosed late stage infection (Burri et al., 2004). De Koning argued one of the reasons of suramin resistance is associated with reduction in drug uptake; molecule is large and highly charged which plasma membrane transporter takes up. Role of apolipoprotein L-1 and haptoglobin-related protein T. evansi affects mainly domesticated animals such as camels, cattle and water buffalo, spread by mechanical transmission of infected blood through insect such as tabanid flies. Due to these, it spread apart from sub-Saharan Africa to South America, North America and Asia. Normally humans are resistant to animal trypanosomes, immunity against T.brucei brucei is due to trypanolytic activity of an apolipoprotein L-1 (APOL-1) bound to high density lipoprotein (HDL) (Vanhamme L. et al., 2003). Previously it was concluded that trypanolytic activity in normal human serum was due to immunoglobin M (Aaronovitch, S. Terry, R. J. 1972). Later in 1973, Hawking and colleagues resolute there were two trypanolyic factors. These two factors differ in their activity (in vivo and vitro), molecular mass, quantity in serum and sensitivity to antagonists (Hawking et al., 1973b). HDL was identified as trypanolyic factor by Rifkin in 1978, she also characterised the two trypanolyic factors determined by Hawking (Rifkin, M. R. 1978b). Trypanolyic factors in human serum shows inhomogeneous properties (Tomlinson et al., 1995; Raper et al., 1996b). Both TLF are a subset of HDLs commonly referred to as HDL3 (Lorenz et al., 1995), contain haptoglobin-related protein (Hpr) (Smith et al., 1995) and APOL-1 (Vanhamme, L. et al., 2003).TLF-1 is a 500 kDa lipid rich while TLF-2,1000 kDa protein complex containing IgM, lipid poor HDL particle (Raper, J. et al., 1999; Lugli, E.B. et al., 2004). Apolipop rotein A-1 (APOA-1) is a component of TLF-1(Smith et al., 1995) and, although previously reported that APOA-1 could not detected in TLF-2(Tomlinson, S. et al., 1995), is a component of TLF-2 (Raper, J. et al., 1999). Previously unknown proteins, human cathelicidin antimicrobial peptide (hCAP18), glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) and paraoxonase are associated with TLF-1(Smith AB et al., 1995; Lugil E et al., 2004). APOA-1 suggests a role in trypanolysis later controversial report supporting a lytic role (Gillett, M. Owen, J. 1992a) or not favor lytic role (Rifkin, 1991; Seed et al., 1993). Later it was confirmed that APOA-1 was not toxic (Tytler, 1995) but may indirectly play role of trypanolytic (Owen et al., 1996). For trypanosomes, HDLs contain 16,000-65,000 binding site per cell having moderate affinity (Gillett, M. Owen, J. 1992b). However, binding of lytic factor, TLF-1 appeared to involve two binding site, low affinity have 65,000 and high affinity 350 binding sites (Drain et al., 2001). Host macromolecules, interact with bloodstream trypanosomes, transferrin (Borst, P.1991) and low-density lipoprotein (LDL) (Coppens, I et al., 1987) through receptor-mediated endocytosis occur at the flagellar pocket of trypanosome (Gull, K., 2003). APOL-1 is a bacterial colicins and Bcl-2 family members like protein containing pore forming domain as well as a region for the membrane insertion of it (Pà ©rez -Morga D et al., 2005, Pays E et al., 2006). APOL-1 is taken up in the parasite by endocytosis, able to kill by the parasite by forming anion selective pores in the lysosomal membrane of parasite, this pore allows the influx of chloride ions into the lysosome, subsequent cell death as a consequence of entry of water and induces uncontrolled osmotic swelling of vacuole ((Pà ©rez-Morga D et al., 2005; Pays E et al., 2006; B. Vanhollebeke et al., 2007a). APOL-1 could not be involved in apoptosis but in programmed cell death (B. Vanhollebeke et al., 2006a). Resistance of T.brucei rhodesiense and T.brucei gambiense to APOL-1 is developed which allows these parasites to infect and cause HAT. Single protein termed serum resistance-associated protein (SRA) is main reason of resistance of T.brucei rhodesiense to APOL-1.SRAP interacts strongly with APOL-1 and provide specific resistance to T.brucei rhodesiense (Xong HV et al., 1998; Gibson WC, 2005). T brucei gambiense is also resistant to APOL-1; mechanism is not understood (Pays E et al., 2006). Indian case with T. evansi infection, human serum devoid of APOL-1, reason for the absence was due to independent frameshift mutation in both APOL-1 alleles (B. Vanhollebeke et al., 2006b). Another HDL component, plays a toxic role for full trypanolytic activity of normal human serum, haptoglobin-related protein (Hpr).Indian case has normal concentration of Hpr bound HDL but short of trypanolytic activity. Hpr is a haemoglobin (Hb) binding protein induces, within acidic lysosome of T.b.brucei, Fenton like reaction between H202 and iron that lead to formation of free hydroxyl radicals, which would prompt the reaction of lipid peroxidation of lysosomal membrane (Smith AB et al., 1995; Hager KM et al., 1994; Bishop JR et al., 2001; Justin Widener et al., 2007). Nevertheless action of trypanolysis of Hpr and APOL-1, biological function is not clear. Optimal trypanolytic activity requires presence of both APOL-1 and Hpr on same subset of HDL particle (B. Vanhollebeke et al., 2007b). Vanhollebeke et al. (2007b) reported trypanosome survival assay in normal as well as mutant human sera. Survival of trypanosomes occurs in human serum devoid of APOL-1 and fetal calf serum (FCS). FCS is nonlytic and contains neither APOL-1 nor Hpr. Human serum deficient of Hpr and haptoglobin (Hp) but with normal HDL b

Oscar Wildes The Importance of Being Earnest Essay -- Oscar Wilde Imp

Oscar Wilde's "The Importance of Being Earnest" In the closing lines of the first act of Oscar Wilde's "The Importance of Being Earnest," Algernon remarks, "I love scrapes. They are the only things that are never serious," to which Jack responds, "Oh, that's nonsense Algy. You never talk about anything but nonsense." Algernon caps off this exchange with a proclamation of the purpose of the whole work: "Nobody ever does" (1642). Wilde never allows anything in the work to conclude on a serious note. While Wilde repeatedly proclaims this direction for the play through his characters, he does not tell us the motivation for this direction. He never explains why there is this avoidance of earnestness. The most apparent answer lies in the veiled criticism of Victorian society contained at each level of the play. The quick paradoxical epigrams that form the core of the conversational comedy are pointed at Victorian society. Wilde also abuses the concept of characterization with paradox to create comical characters that expose Victori an deficiencies. Each of these criticisms relies upon the paradoxes that Wilde sets up on successively larger scales within the play. It is, in fact, this tool of humor, not the object of ridicule that truly defines this work. While each paradox is pointed at Victorian society, the individual paradoxes each take on a different element of Victorian society, thereby diminishing the pointedness of the overall criticism. The use of paradox allows Wilde to take this play beyond its narrow and somewhat scattered critique of Victorian society. The underpinning element then, is not Victorian society, but instead the paradox, the concept of dual, irreconcilable elements. This more lasting topic is, not co... ...man in prudish nineteenth century England Oscar Wilde never felt comfortably assimilated into the strait society that surrounded him. He was forced to assume a double identity to cope with his divergence from the norms of the day. This tax that the society levied upon Wilde undoubtedly engendered an animosity, an animosity that is reflected in his ironic, and sardonic treatment of Victorian society in "The Importance of Being Earnest". However, the multiple and irreconcilable identities that Wilde was forced into are the more significant driving force behind this work. This struggle with identities is seen in the paradoxes that pervade all levels of the work. In the end though, these large themes build upon, rather than overshadow Wilde's greatest genius which lies in his subtle turns of phrases and words that keep even the most earnest reader chuckling throughout. Oscar Wilde's The Importance of Being Earnest Essay -- Oscar Wilde Imp Oscar Wilde's "The Importance of Being Earnest" In the closing lines of the first act of Oscar Wilde's "The Importance of Being Earnest," Algernon remarks, "I love scrapes. They are the only things that are never serious," to which Jack responds, "Oh, that's nonsense Algy. You never talk about anything but nonsense." Algernon caps off this exchange with a proclamation of the purpose of the whole work: "Nobody ever does" (1642). Wilde never allows anything in the work to conclude on a serious note. While Wilde repeatedly proclaims this direction for the play through his characters, he does not tell us the motivation for this direction. He never explains why there is this avoidance of earnestness. The most apparent answer lies in the veiled criticism of Victorian society contained at each level of the play. The quick paradoxical epigrams that form the core of the conversational comedy are pointed at Victorian society. Wilde also abuses the concept of characterization with paradox to create comical characters that expose Victori an deficiencies. Each of these criticisms relies upon the paradoxes that Wilde sets up on successively larger scales within the play. It is, in fact, this tool of humor, not the object of ridicule that truly defines this work. While each paradox is pointed at Victorian society, the individual paradoxes each take on a different element of Victorian society, thereby diminishing the pointedness of the overall criticism. The use of paradox allows Wilde to take this play beyond its narrow and somewhat scattered critique of Victorian society. The underpinning element then, is not Victorian society, but instead the paradox, the concept of dual, irreconcilable elements. This more lasting topic is, not co... ...man in prudish nineteenth century England Oscar Wilde never felt comfortably assimilated into the strait society that surrounded him. He was forced to assume a double identity to cope with his divergence from the norms of the day. This tax that the society levied upon Wilde undoubtedly engendered an animosity, an animosity that is reflected in his ironic, and sardonic treatment of Victorian society in "The Importance of Being Earnest". However, the multiple and irreconcilable identities that Wilde was forced into are the more significant driving force behind this work. This struggle with identities is seen in the paradoxes that pervade all levels of the work. In the end though, these large themes build upon, rather than overshadow Wilde's greatest genius which lies in his subtle turns of phrases and words that keep even the most earnest reader chuckling throughout.