Regional Economic Cooperation Essay

One of the most important developments in the world trade system in the 1990s has been the emergence of regional cooperation. The end of the Cold War reduced political tensions between countries in Asia as well as globalizing production processes and increasing vertical integration. Cities like Bangkok, Kuala Lumpur, and Singapore have been lifting their populations out of poverty in part through cooperative arrangements with neighboring countries. Transnational economic zones have utilized the different endowments of the various countries of East Asia, exploiting cooperative trade and development opportunities. Transfer of technology and manufacturing between nations has allowed them to develop sequentially. Information technology has improved linkages between economies and put remote regions in contact with the world. The private sector provides capital for investment; the public sector provides infrastructure, fiscal incentives, and the administrative framework to attract industry. Regional cooperation is now considered the means of enhancing economic development and providing economic security within the regions. Trade among ASEAN members accounted for more than 23% of all trade by member nations in 1994, topping that of any of the group’s major trading partners. Singapore has concentrated on becoming the technology center for Southeast Asia, sending labor-intensive operations to low-cost neighboring countries like Malaysia and Indonesia in special mutual cooperative trade and development arrangements known as growth triangles or growth polygons. The Southern Growth Triangle, also known as SIJORI (Singapore, the Johore state of Malaysia, and Riau Province of Indonesia), was formed in 1989 and covers a population of about 6 million people. It attracted $10 billion in private sector investments during its first five years. Such regional economic cooperation has occurred in other Asian regions as well, spurring economic development. Growth triangles are expected to be a continued driving force for growth in Asian economies throughout the 1990s. Four growth triangles have been established since 1989, involving parts of 11 countries. There are currently eight growth polygons in East and Southeast Asia, with additional triangles being planned. For example, Cambodia, Laos, Myanmar, Thailand, Vietnam, and China’s Yunnan Province have been discussing ways to develop the Mekong area since 1992. Regional cooperation provides a competitive model to attract investment and technology. According to the secretary general of ASEAN, Ajit Singh, â€Å"These growth areas will have to be flexible to change where necessary, innovative, and always attentive to the needs of the investors and the businessmen. They also have to be aware that they are competing with much larger countries such as China and India, whose capacities for attracting investors are much greater than their own† (Kruger 1996, 17). Asian capital markets are now watching the global economy, and large companies recognize their need to be involved in this fastest growing region in the world. The growth triangles typically group remote regions of the nations involved in an effort to exploit complementary assets within the groupings. For example, the Tumen Delta triangle integrates the capital and technology of Japan and the Republic of Korea with the natural resources of Russia and North Korea (i. e. , the People’s Democratic Republic of Korea) and the labor and agricultural resources of China. The governments of Brunei, East and West Kalimantan, and North Sulawesi of Indonesia; Sabah, Sarawak, and Labuan in Malaysia; and Mindanao and Palawan in the Philippines have given priority to expanding air and shipping routes within the East ASEAN Growth Area, another polygon. Where all parts of the polygon are at similar levels of development, growth is expected to be slower. Singapore has provided capital and technology for developments in Malaysia to support SIJORI. Thailand is expected to provide capital and experience in developing the Mekong polygon. It will encompass a population of over 400 million people offering low wages, rents, and land costs. The Southern China Growth Triangle The Southern China Growth area comprises Hong Kong, Taiwan, and the southern provinces of China (Thant et al. 1994). Because China lags behind Taiwan and Hong Kong considerably in economic development and has a very large population, growth in this triangle has enormous potential. Establishment of this triangle was spurred by market forces and private sector initiatives rather than by policy coordination among the countries. However, government policies have supported the economic links that were instituted. The PRC’s economic reforms and open door policy initiated in 1978 laid the foundation for economic success in Guangdong and Fujian provinces. Establishment of China’s first Special Economic Zone (SEZ) in 1980 provided for tax concessions, expanded land use rights, and simplified procedures for foreign investment. Policies for land use, finance, and trade were designed to reduce transaction costs and to provide greater access to the domestic as well as the world market. Policies formulated within the SEZs themselves have been even more liberal than those in other parts of the triangle. For China, the triangle has provided exports, foreign exchange, and employment as well as access to the larger global economy. Rapid economic growth and higher incomes have occurred in Guangdong and Fujian Provinces with materials and components from Taiwan’s manufacturing sectors and the support of Hong Kong’s advanced services sector. Geographical proximity and common language are the most compelling factors for capital to move across the border from Hong Kong into Guangdong Province, or for investment to flow across the Formosa Strait from Taiwan to Fujian Province. Cantonese is a Chinese dialect spoken in both Hong Kong and Guangdong, while Fujianese is spoken in both Taiwan and Fujian. For Hong Kong and Taipei, the triangle has provided a means of implementing structural changes in manufacturing and export patterns at minimal cost. In spite of recent political posturing on the part of China, economic planners in Hong Kong and Taiwan are optimistic that economic logic will continue to drive regional integration. Low-Cost Sourcing As Japanese and U. S firms seek to reduce the cost of their latest innovations, they are outsourcing production to low-cost contract manufacturers. China has a growing number of low-cost parts and components suppliers. With a minimum of overhead and a large pool of low-cost labor in China, there is a growing list of high-quality vendors in China. The continuing miniaturization of products has lead to joint ventures with companies from Japan, the United States, Taiwan, Hong Kong, and other Asian countries. The success of these firms is dependent upon providing competitive value in a timely manner. Low-cost board assembly operations in China utilize the latest SMT equipment required by new computer and telecommunications products. Capital intensity will increase as IC packaging and SMT assembly operations are installed. In the 1980s, Korea and Taiwan provided the first step in the cost reduction chain by providing the most advanced process capabilities. Singapore and Malaysia became additional sources for contract manufacturing with the establishment of global vendors like SCI and Solectron. Today, further cost reduction is possible by moving production to lower cost regions like China and the Philippines. Wong’s Electronics in Hong Kong provides a three-step process for cost reduction that includes low-cost labor, low-cost sourcing, and low-cost production designs. Hong Kong, Thailand, Malaysia, and China are considered the home of lowest-cost manufacturing competitors in the electronics industry today. They offer limited component technology or product design skills, but provide many low-cost suppliers of generic, low-technology components. Since low-cost manufacturing countries generally lack the technologies required to become industry leaders, they must follow the technology trends as quickly as possible. OEM competitors from Taiwan and Singapore are being forced to open branch plants in China or other Southeast Asian countries to produce the most labor-intensive, cost-driven products.

How to Write a Thesis Statement With Examples

How to Write a Thesis Statement With Examples A thesis statement provides the foundation for your entire research paper or essay. This statement is the central assertion that you want to express in your essay. A successful thesis statement is one that is made up of one or two sentences clearly laying out your central idea and expressing an informed, reasoned answer to your research question. Usually, the thesis statement will appear at the end of the first paragraph of your paper. There are a few different types, and the content of your thesis statement will depend upon the type of paper you’re writing. Key Takeaways: Writing a Thesis Statement A thesis statement gives your reader a preview of your papers content by laying out your central idea and expressing an informed, reasoned answer to your research question.Thesis statements will vary depending on the type of paper you are writing, such as an expository essay, argument paper, or analytical essay.Before creating a thesis statement, determine whether you are defending a stance, giving an overview of an event, object, or process, or analyzing your subject Expository Essay Thesis Statement Examples An expository essay exposes the reader to a new topic; it informs the reader with details, descriptions, or explanations of a subject. If you are writing an expository essay, your thesis statement should explain to the reader what she will learn in your essay. For example: The United States spends more money on its military budget than all the industrialized nations combined.Gun-related homicides and suicides are increasing after years of decline.Hate crimes have increased three years in a row, according to the FBI.Post-traumatic stress disorder (PTSD) increases the risk of stroke and arterial fibrillation (irregular heartbeat). These statements provide a statement of fact about the topic (not just opinion) but leave the door open for you to elaborate with plenty of details. In an expository essay, you dont need to develop an argument or prove anything; you only need to understand your topic and present it in a logical manner. A good thesis statement in an expository essay always leaves the reader wanting more details. Types of Thesis Statements Before creating a thesis statement, its important to ask a few basic questions, which will help you determine the kind of essay or paper you plan to create: Are you defending a stance in a controversial essay?Are you simply giving an overview or describing an event, object, or process?Are you conducting an analysis of an event, object, or process? In every thesis statement, you will give the reader a preview of your papers content, but the message will differ a little depending on the essay type. Argument Thesis Statement Examples If you have been instructed to take a stance on one side of a controversial issue, you will need to write an argument essay. Your thesis statement should express the stance you are taking and may give the reader a preview or a hint of your evidence. The thesis of an argument essay could look something like the following: Self-driving cars are too dangerous and should be banned from the roadways.The exploration of outer space is a waste of money; instead, funds should go toward solving issues on Earth, such as poverty, hunger, global warming, and traffic congestion.The U.S. must crack down on illegal immigration.Street cameras and street-view maps have led to a total loss of privacy in the United States and elsewhere. These thesis statements are effective because they offer opinions that can be supported by evidence. If you are writing an argument essay, you can craft your own thesis around the structure of the statements above. Analytical Essay Thesis Statement Examples In an analytical essay assignment, you will be expected to break down a topic, process, or object in order to observe and analyze your subject piece by piece. Examples of a thesis statement for an analytical essay include: The criminal justice reform bill passed by the U.S. Senate in late 2018 (The First Step Act) aims to reduce prison sentences that disproportionately fall on nonwhite criminal defendants.The rise in populism and nationalism in the U.S. and European democracies has coincided with the decline of moderate and centrist parties that have dominated since WWII.Later-start school days increase student success for a variety of reasons. Because the role of the thesis statement is to state the central message of your entire paper, it is important to revisit (and maybe rewrite) your thesis statement after the paper is written. In fact, it is quite normal for your message to change as you construct your paper.

Circus Show in Las Vegas Essay Example | Topics and Well Written Essays - 750 words

Circus Show in Las Vegas - Essay Example Before attending this circus show, I had a very blurred concept of circus shows. I used to think that circus shows are solely animal based. Some people have trained their pets in a particular fashion so the pets are able to perform certain tricks in front of the masses. A monkey dancing on a song or three lions standing upon one another were the particular images that used to flash in mind the very moment I would listen about a circus show. The idea of merely seeing some animals perform never attracted me enough to draw me towards a circus show until my friend, Tom almost dragged me to the show with him this April. Only as I appeared on the show last Saturday did I realize that circus was actually much more than what I knew about it. The whole scene was spellbinding. I can only try to narrate the scene in words, yet the whole feeling was too heavenly and magical to be captured into words. We arrived at the show at 3 pm. It was a big show with too many components. The show was organiz ed in the open, to lend the show the traditional touch. There were loudspeakers everywhere advertising different kinds of acts. We roamed about the place and saw different shows. I particularly liked the act of a motorcyclist who was making the bike go round and round along the inner walls of a deep well, which was called the well of sorrows. To add to the adventure, there were about a dozen snakes in the base of the well. The host told us that they were some of the most venomous and gigantic snakes to be found on the face of Earth. From the look of them, I could tell that the host was not lying. I was looking at the snakes from a distance of about 20 meters from the top, and they still seemed too gigantic to be anywhere less than 2 meters each. The 20 meters deep well was divided into 5 levels, each of which was 4 meters in depth. The motorcyclist was given the task to ride the bike to the lowest level. The lower he went, the more he earned. The scene of watching the motorcyclist w iggle through the cobras on the lowest level was one of the most breath-taking scenes of my life. After watching the well of sorrows, we headed over to the gymnastics section. This was the only section of the whole circus show that was organized in a hall. The gymnastics were performed by obese ladies. One lady that I was particularly astonished to watch do gymnastics was in her forties and from her look, it seemed as if she was about 140 kgs in weight. In normal life, I would hardly expect such an obese woman to walk, and to my uttermost astonishment, the lady was walking over a carbon wire tied between two stories of the circular hall in a diagonal fashion. As I saw the woman walk up the wire to the second level, I expected her to fall any moment, but she was too skilled and experienced to let imbalance. That was the most scaring, dreadful and yet, funniest moment of my life. After the gymnastics, Tom and I moved over to the ice cream parlor. We had some delicious vanilla scoops t opped with bittersweet chocolate sauce. That seemed like a nice full stop to the experience of watching the circus show.

The C.I.A Research Paper Example | Topics and Well Written Essays - 750 words

The C.I.A - Research Paper Example so coincided with the alleged UFO crash in Roswell, New Mexico, causing many people to believe that the creation of the agency also had to deal with the probability of extra terrestrial visitors. The main task of the Central Intelligence Agency is to gather, process and analyze situations or people, both inside and outside of the United States, that can be threatening or harmful to the United States. If the agency comes upon any information that suggests that someone is doing something harmful at the expense of the United States, they take the proper actions to ensure that nothing comes of these actions and that the person is dealt with accordingly. The agency also looks for threats that may come to an interest that the United States has in the world. In essence, the Central Intelligence Agency seeks out threats and dangers to the United States and the world and does what need to be done to prevent both negative actions and the leaking of the threat to the general public. The CIA also monitors activities that have the potential of turning dangerous, such as a foreign country creating a new nuclear power plant to produce electricity. The CIA would monitor the progress of this plant to ensure that it really is being created for the intended purpose and not for something that can prove to be harmful. The Central Intelligence Agency, in their mission of protecting the United States and the places of interest throughout the world, also helps in making the important decisions surrounding national security. The agency does not make the policies, they simply provide foreign intelligence information for the agencies and groups that do make the policies based on the information provided (Weiner, 2008). At times the agency is allowed to suggest possible policies or changes to current policies as starting points for the groups actually able to make the changes. Their sole job is gathering the information needed to make the decisions that can help keep the United States and

Eng lit Essay Example | Topics and Well Written Essays - 2000 words

Eng lit - Essay Example Victorian era, Rudyard Kipling’s â€Å"Man Who Would be King† from the later Victorian era and George Orwell’s 1984 written in the period known simply as the 20th century. Beginning with William Blake’s short poem â€Å"London†, written in 1794 and included in his collection entitled Songs of Experience, traces of political unrest can be found as the scenes and sounds of a walk down the London streets are reported. The first hints that something is not right within the city can be found in the first lines of the poem, â€Å"A mark in every face I meet, / Marks of weakness, marks of woe† (3-4). These comments wouldn’t necessarily suggest a poor political situation, except that the signs of decay and desperation are seen in every face encountered as the speaker walks down what is presumed to be an average London street. This is reinforced in the second stanza as the speaker says, â€Å"In every cry of every man, / In every infant’s cry of fear, / In every voice, in every ban, / The mind-forged manacles I hear† (4-8). In this, it is apparent that someone is controlling these people, although it remains unclear if the ‘mind-forged manacles’ are of their own creation or someone else’s. However, because of the inclusion of infants, who cannot possibly be imposing harsh times on themselves as well as the mention of bans, which are posted laws, it is indicated that the hardships being experienced are imposed from a higher source, such as the government. This is again reinforced in the third stanza when the speaker indicates that the decay of the city has reached even as far as the churches: â€Å"How the chimney-sweepers cry / Every blackening church appals† (9-10) and the city’s defenses as â€Å"the hapless soldier[‘s]† sigh is made visible as it â€Å"runs in blood down palace-walls† (12). Throughout the poem, then, although no specific mention is made of issues affecting the people, the affects are nevertheless made clear. Something is not working

Fantasy literature for children Essay Example for Free

Fantasy literature for children Essay Q (1). Fantasy literature means new ideas and deals with new images, fantasy includes literature, myths, legends, fairy tales, stories of super natural beings with super natural powers, fantasy creates an imaginative world in which the super natural is natural and plays a perfect part essential to the story to complete it, such literature is enjoyed by the children and adults. An example of such literature is L’Engle’s â€Å"A Wrinkle in Time† which can be read by both children and adults. This books heroine is Meg Murry who is an unhappy and clumsy high school student, she with her friend Calvin and her brother Charles undertake an adventurous journey into time and space to rescue her father from the evil force that is attempting to rule over the universe; her greatest drawback is her anger, impatience and lack of self confidence, during the travel and experience she learns to overcome her faults while rescuing her father. The symbols mentioned in this story are (1) The Dark Thing, it is the dark and cold symbol of evil forces that Meg,Calvin and Charles must fight in rescuing her father, the Dark Thing is evil and in the book there is constant battle between good and evil, and good is always successful over evil; (2) The second symbol is the IT, it is the bodiless brain of Camazotz, it controls all the creatures living in that planet, it identifies with the dark thing with its pulsating and revolting rhythm, it is the main body of evil in the planet, it is war of good and evil and love is successful over evil. 3) the book also has good symbols and one is Aunt Beast, she has many tentacles, she is tall and has fur all over, she is from the planet Ixchel and loves to look after travelers as she looks after Meg when during her travel she brushes with the dark thing, Aunt Beast is full of love but she is always in the dark as she has no eyes and has no idea of light or vision she shows her love and emotions by touching with her tentacles. The major theme of the book is Cosmology, other theme is human life and space travel to other planets and constant war of good against evil and ultimately love and goodness are successful. All these symbols show individuality. Meg rescues her brother Charles from IT through the power of love, LEngle makes her characters to travel through space and into other planets and there they communicate with each other without spoken language, the author is trying to show that speech is not the only way to communicate, and the universal theme is the struggle between good and evil, light against darkness, the author also emphasizes inadequacy of words, as sometimes feelings cannot be explained completely with words. All the symbols help Meg to learn the lessons of life as she cannot be aware of everything, she has learned patience, and she has also learned to understand situations as there is explanation for everything even if sometimes we do not understand the world. Q (2) Poetry appeals to the young people in many ways, as it is a way to express the feelings in words, and helps to understand others feelings also, poetry is called literary art, young people read and write poetry as it is away of relaxation, young people like poetry as it can be sung and people love to write songs; there are different kinds and styles of poetry. A study was conducted by Ann Terry in 1974 which shows what type of poetry is liked by children of different ages of elementary school, humorous poems appealed to a large age range of students, they mostly liked poems with musical qualities and disliked poems that they could not understand maturity plays an important part in understanding poetry, four of the poems were narratives, students of all ages did not like this type of poetry, twenty five poems were not popular poems and were not liked, the students liked rhymed poems. The use of poetry in the classroom is very beneficial as reading and learning poems helps the student’s language development, as it evokes emotions it encourages creativity, poetry develops reading habit and helps to increase vocabulary, poetry is a literary art it is a way to relax, it appeals to the young as it can be made into a song and the teenagers love romantic poetry. It is used in the classroom to teach young students to learn, like the alphabet song is used for teaching young students. Q (3) The â€Å"Monkey Island† written by Paula Fox, is a short novel about an eleven years old boy named Clay Garrity, who is left to live on his own as his father looses his job and cannot find another so he simply walks away from his only child and wife, they go to live in a welfare home as his mother is pregnant she disappears one day and Clay is left alone in the streets of New York , soon he finds Buddy and Calvin in a park and they become a family. If Clay leaves the streets he may never find his parents again and if he stays on the streets alone he might not survive as dangers are eminent. According to evaluation criteria it is a short and simple novel, and it is written for all ages as all can enjoy reading it, the book deals with the darkness and dangers of the night the child has to face, as Clay is left alone to survive he reaches a park where homeless people live and this is scornfully called ‘The Monkey Island’. Clay is a sensitive child who is facing harsh realities of life; he has to face hunger, fear and illness, he gets pneumonia and is in the hospital for ten days and then sent to a foster home and is reunited to his mother and baby sister. According to evaluation criteria this novel intrigues the mind of the child and young adults the title also fascinates the child; it is a simple straight, short novel which shows the harsh realities of life faced by the eleven year old. This novel has all the qualities of a good literature for children, in the view of evaluation, as the features of the book help to analyze the pure and clear title of the book that is composed into a quality literature for children and young adults. Q (4) The answer to this question, ‘who should write science books for children’ has an unlimited answer. Basically scientists should write science books for children, writers who write science books for children should be very clear in explaining and they should use accurate facts and figures, complicated writings scare the children as a result the child looses interest and shies away, science should not be complicated, facts must be presented in such a way that the child is encouraged to indulge in furthering reading. Every topic must have pictures to explain. The science books should be based on topics of universal and international appeal, so that it can be read by all the children over the world without clashes of cultures; the authors should write the text that is within the reach of the understanding power of the child; as illustrations immediately attracts the young mind it also sharpens the appetite of the child’s mind to grasp more and read more. The authors suited for writing science books for children should be aware of the needs and intellectual level of the young mind, therefore they should write about things that are interesting to the imagination of the child’s mind, as scientists are best suited to write science books for children they should emphasize and lay stress on meaningful observations, as it helps the student to master his patience through daily observation classes and become a good observer which is the main part of learning science, which also produces a spark of inspirational power to the reader. The science book must inform the reader not only of facts but must explain the beauty of complicated physical life; science books that teach the child to develop scientific language skills are of great help, in helping the child to discover the natural world around us. Authors who write scientific books for children must use easy and graceful language, they must have expertise on descriptive powers of the verbal text, and the design of the book cover is a source of great attraction for the child, writers must depend on illustrations for explanations, the book should be non-fictional and based only on facts that can be understood by the intellectual level of the young readers, accuracy of facts is the main point on which science books can depend so that a child does not have a con fused orientation of science. Authors who write with such accuracy and are careful in presentations and explanations in the books that are for the young mind, are suited to write science books for children, the books must present simple things for children to do alone and in a group as well, then there are things that the child must work on with the help of parents and together they create fun in learning for all ages, the last part of the book must have questions to be answered by the child, so that the child starts thinking about science around us in this world, and the science book should be appealing to the imagination of the child’s mind, the seventh edition of the text is a tool that can help the writers to be updated in research and utilization of technology, these help resources help to make the most of media available with text, as C. D. ROM; and online activities must be encouraged which help greatly in learning. Q (5) Books for children and young adults are banned and censored due to many reason s in some cases it creates awareness to avoid clashes of cultures and beliefs and sentiments of certain society. There are many reasons for banning a book; it depends on the material of contents which are not ‘anti Christian’ or the language used is objectionable and against the religious beliefs, these can be unsuitable for the young mind, books can be banned due to many reasons such as political reason or social grounds, or books are banned when a certain group of people or an influential person considers it to be controversial, immoral or inappropriate, corrupt, vulgar, violent or wicked, generally if the book contains socially unacceptable ideas, such books are banned as these views are made public. These books sometimes contain racial differences such racial slurs, some books contain depressing and alien material which is not good for the development of the young mind; some facts of history show disrespect to adults and elders which is not acceptable to the society, some books confuse fantasy with reality which is very confusing to the young mind, books depicting witchcraft su ch as J. K. Rowling’s book is under challenge as it creates confusion in the mind of the young, as the book mixes reality with fantasy and witchcraft. Parents play a significant part in banning books as they according to their own thinking accept or ban certain books and they also have their own reasons and view points, parents tend to over protect their children and think that reading certain bad books will lead the child to do bad things which may not be the case, some books are banned if the young try to copy certain acts mentioned in the book which are not acceptable in society, such as suicide stories. The text book on ‘through the eyes of a child’ is an introduction to child literature and is an excellent source of literature for children, no person can justify banning a book it simply depends on personal views and reasons. Today the society has changed and many controversial books are now regarded as classics, today people cannot be stopped from thinking, if thinking is allowed, they will speak and if they speak will write and what is written can be printed and published. Society has changed with time and people are becoming liberal minded and have started accepting books that were once banned. Every person has a right to freedom of thought, the young adults and children have the freedom to read and express their opinions and thoughts, people have different thoughts and these thoughts are valuable only to the individual himself but putting ban on such opinions will deprive the human race and society of its freedom rights. Today the society plays a great role in the development of the mental capabilities of the young, as thinking changes the society has also changed and allows the child some freedom, writing books for children and young adults is not an easy task as the writer has to see through the eyes of the child. Writing books for children and young adults is not an easy task as one has to see through the eyes of the child, books are ways to help the young to understand and appreciate their world. Today books are an integral part of young and children and adults alike each in their own capacity. The society has become more open minded, as less content is censored for viewing by the young, it is preferred that children be informed about all issues related to individuals and society itself, this is done so that children be able to have an understanding which would lead them to formulate their own opinion, excess to all information is important so that may be promoted amongst the young.

Folate-conjugated Therapeutic Agents for Arthritis

Folate-conjugated Therapeutic Agents for Arthritis IN VIVO STUDIES Consistent performance of a controlled release formulation upon dosing is critical to a quality product. In vivo evaluation of any drug delivery system is quite essential because many factors like pH of different biological organs, enzyme systems and variable affinity of carrier system for the various biological fluids including the tissues are expected to influence its performance. These factors affect the in vivo biological distribution and the drug release profile from a novel carrier system. In vivo studies are important in evaluating the bioavailability of drug from the designed formulations. Screening of the anti-inflammatory activity The screening methods for the evaluation of anti inflamatory activity have been classified as follows :- A. Nonimmunological methods 1. Evaluation of acute inflammation Carrageenan induced paw edema model (Winter et al.,1962) Histamine induced hind paw method. Carrageenan granuloma pouch technique. 2. Evaluation of chronic inflamation Formaldehyde induced arthritis. B.  Immunological methods 1. Adjuvant induced arthritis Complete Freunds adjuvant induced arthritic model. 2. Collagen induced arthritic model. 3. Borrelia burgdorferi induced arthritic model. C.  Miscellaneous U.V. erythema inflamatory model. MATERIAL AND METHODS Male albino rats In vivo study was performed on the albino rats (av.wt.100 ±20 g).The animal studies were conducted with the permission of Institutional Animal Ethical Committee of Dr. Hari Singh Gour University, Sagar (M.P.). Animals were housed in plastic cages in the thermoneutral environment, and were supplied with feed pellet and water ad libitum. Induction of arthritis Carrageenan induced arthritis method was selected for present study (Winter et al., 1962). Carrageenan acts as phlogistic agent which causes the formation of edema due to stimulation of release of various proinflamatory agents like prostaglandins, histamine and serotonin, bradykinin. tachykinins, reactive oxygen and nitrogen species etc. BIODISTRIBUTION STUDY The rats were divided into four groups with each group comprising of three animals and labelled properly. After induction of arthritis plain drug suspended in PBS (pH 7.4), ETX-NPs and f-ETX-NPs in a dose equivalent to etoricoxib of 0.5 mg/kg body weight were administered through tail vein to albino rats. After 6 hr following administration of formulation, blood of animals was collected from retro orbital plexus of the eye, the rats were sacrificed and various organs such as liver, lung, kidney, spleen and arthritic knee joint were isolated. The organs were weighed, washed in PBS (pH 7.4) and stored at -20 °C until further required. Table 7.1 Data of biodistribution of etoricoxib in albino rats after i.v. administration of formulations Organs System Distribution of % injected dose /whole organ or tissue at 6 hr Blood Plain drug 53.17 ±2.11 ETX-NPs 29.23 ±1.39 f-ETX-NPs 24.39 ±1.10 Liver Plain drug 17.0 ±2.10 ETX-NPs 18.21 ±2.43 f-ETX-NPs 21.25 ±2.11 Spleen Plain drug 10.69 ±1.13 ETX-NPs 12.43 ±1.47 f-ETX-NPs 11.45 ±1.25 Kidney Plain drug 9.08 ±0.49 ETX-NPs 6.60 ±0.65 f-ETX-NPs 6.20 ±0.68 Lung Plain drug 2.76 ±0.28 ETX-NPs 4.81 ±0.53 f-ETX-NPs 6.60 ±0.71 Non-inflamed joint Plain drug 0.106 ±.02 ETX-NPs 0.11 ±0.02 f-ETX-NPs 0.104 ±.017 Inflamed joint Plain drug 0.11 ±0.020 ETX-NPs 0.35 ±0.058 f-ETX-NPs 1.42 ±0.049 Each value is expressed as mean  ±SD (n=3) Figure 7.1(A) % concentration of etoricoxib in blood after 6 hr of i.v. injection         Figure 7.1(B) % concentration of etoricoxib in liver after 6 hr of i.v. injection Figure 7.1(C) % concentration of etoricoxib in spleen after 6 hr of i.v. injection Figure 7.1(D) % concentration of etoricoxib in kidney after 6 hr of i.v. injection Figure 7.1(E) % concentration of etoricoxib in lung after 6 hr of i.v. injection Figure 7.1(F) % concentration of etoricoxib in noninflamed joint after 6 hr of i.v. injection Figure 7.1(G) % concentration of etoricoxib in inflamed joint after 6 hr of i.v. injection PHARMACODYNAMIC STUDY Carrageenan-induced Paw edema in rats This model is based on the principle of release of various inflamatory mediators by carrageenan. Edema formation due to carrageenan in rat paw is biphasic event. The initial phase is attributed to the release of histamine and serotonin. The second phase of edema is due to the release of prostaglandins, protease and lysosome. Assay was performed by single subcutaneous injection of 1% (0.1 ml) carrageenan as phlogistic agent and inflamation was determined by measuring change in the volume of inflamed paw , using a well calibrated plethysmometer (UGO,BASILE 7140, Italy). The carrageenan edema test was performed for drug loaded BSA nanoparticles as described by (Winter et al., 1962). Albino rats selected for the present study were weighed, numbered and left paw was marked with ink at the level of tibiotarsic articulation, so that every time, the paw was dipped into the plethysmometer up to the fix mark to ensure the constant paw volume. Basal paw volume was measured plethysmographically by volume displacement method using Plethysmometer (UGO Basile 7140 Italy ) by immersing the paw till the level of tibiotarsic articulation The weight of each animal was taken, averaged and were found to be around 120 g .The day time was chosen for the study to avoid any significant changes in the circardian rhythyms. Animals were divided into four groups (n=3) including one controlled group starved overnight with water ad libitum prior to the day of experiment. Test formulation of drug loaded BSA NPs (0.2%w/v) and plain drug suspended in PBS (pH 7.4) in dose of 0.5 mg/kg body wt. was administered through iv route to albino rats of respective groups excluding control group. The co ntrol group was injected with normal saline (PBS, pH 7.4). After administration of test formulations of drug loaded NPs of BSA, the rats were challenged by a subcutaneous injection of 0.1 ml of 1% solution of carrageenan into the sub-plantar side of the right hind paw. The paw volume was measured every hour till 4th hr and subsequently readings were taken at 8, 12, 18, 24, 36, 48 and 72 hrs after challenge. The increase in paw volume was calculated as percentage compared with the basal volume. The difference of average values between treated animals and control group is calculated for each time interval and evaluated statistically. The percent Inhibition for each group was calculated using the formula as follows. Vcontrol -Vtreated % inhibition of edema = -χ 100 Vcontrol Where Vcontrol =mean edema volume of rats in control group, Vtreated mean edema volume of each rat in test group. The results are reported in the Table 7.2. A graph was plotted between % inhibition of edema Vs time ( Figure 7.2). Table 7.2 Screening Data for anti-inflamatory activity of plain drug solution, drug loaded nanoparticulate system and ligand conjugated drug loaded nanoparticulate system using carrageenan induced paw edema model. Time (hr) % Inhibition of edema Plain drug solution Drug loaded nanoparticulate system Ligand conjugated drug loaded nanoparticulate system 1/2 15.14 ±1.9 6.71 ±0.81 7.54 ±1.1 1 24.21 ±2.8 10.32 ±1.7 18.91 ±3.3 2 37.42 ±3.8 12.54 ±1.8 23.01 ±5.2 4 41.53 ±4.2 19.37 ±2.1 38.41 ±4.2 8 32.27 ±3.5 26.57 ±3.2 47.50 ±3.9 12 21.59 ±2.2 46.91 ±3.9 62.35 ±6.9 24 12.01 ±1.8 28.12 ±3.4 55.01 ±8.3 36 7.37 ±0.79 19.97 ±2.6 48.72 ±7.6 48 ND 12.10 ±1.9 24.59 ±3.3 60 ND 7.53 ±0.87 18.15 ±2.8 72 ND ND 7.78 ±0.89 ND= Not detectable; each value is expressed as mean  ±SD (n=3) Figure 7.2 Plot of % inhibition of edema Vs time Statistical analysis Results were expressed as mean  ±standard deviation (SD) and statistical analysis was performed with PSS 10.1 Chicago (USA). The biodistribution parameters were calculated with the help of (pk analyst) scientific programme from Micromath Inc. (UK). RESULTS AND DISCUSSION In vivo studies are important in evaluating the therapeutic efficacy of designed dosage forms and also help in establishing the correlation between the results obtained from the in vitro experimentation to that of in vivo conclusions. In order to understand the fate of drug loaded NPs in vivo, the biodistribution of drug in various major organs was investigated. The amount of drug in the body depends upon its release, distribution metabolism and excretion from body. The concentration of drug in inflamatory knee joint was found about 3 folds higher in case of drug loaded NPs and about 10 folds higher in case of folic acid conjugated system as compare to the free drug administration. These results evidenced the site specific targeting of drug in inflammatory region. Concentration of drug in blood was found to be 53.17 ±2.11 % in case of plain drug solution, while in case of ETX-NPs and f-ETX-NPs it was found to be about 29.23 ±1.39 % and 24.39 ±1.10 % respectively of the whole injected dose which proved the sustained effect of formulations. The concentration of drug in liver was found to be 17.0 ±2.10%, 18.2 ±2.43% and 21.2 ±2.119% of the whole injected dose in case of plain drug, ETX-NPs and f-ETX-NPs respectively. Slight increase in the amount of drug (although very less) in various organs from formulations ETX-NPs and f-ETX-NPs suggested the RES uptake of nanoparticulate formulations in those organs. Concentration of drug in inflamed joint was raised up to 3 fold in case of plain ETX-NPs and 10 fold in case of f-ETX-NPs as compared to plain drug administration. This proved the targeting efficiency of nanoparticulate formulations both uncoupled as well as folate conjugated nanoparticles. The % inhibition of edema was found to be significantly higher from f-ETX-NPs as compared to the ETX-NPs and plain drug .The folic acid (folate) attached to the surface of NPs might have carried the NPs to folate receptors over expressed on the activated macrophages that is responsible for the release of various inflamatory cytokines including prostaglandins (PGs). CONCLUSION The above data suggested that the development of folate-conjugated therapeutic agents in treatment of arthritis may further enhance its site specific drug delivery at inflamed joints and may also be used as sustained drug delivery system in rheumatoid arthritis.