International Markets Essay

Once SAB Miller has decided to establish itself in the global market, it becomes necessary for the marketing manager to study and analyze the various options available to enter the international markets and select the most suitable one. The selection of the entry mode is one of the most significant decisions.SAB Miller takes in the process of internationalization, as it involves commitment of resources with long-term financial and structural implications. Mode of entry may be defined as an institutional mechanism by which a firm makes its products or services available to consumer in international markets. Root (1994) defines the market entry for international markets as a comprehensive plan which sets forth the objectives,goals,resources,and policies that guide a company’s international business operations over a future period long enough to achieve sustainable growth in world markets. FACTORS AFFECTING THE SELECTION OF ENTRY MODE EXTERNAL MODES MARKET SIZE:Market size is one of the key factors an international marketer has to develop to keep in mind when selecting an entry strategy.Countries with a large market size justify the modes of entry with investment,such as wholly owned subsiaries or equity participation. MARKET GROWTH:Most of the large,established markets,such US,Europe and Japan,have more or less reached a point of saturation for consumer goods such as automobiles,consumer electronics.Therefore,the growth of markets in these countries is showing a declining trend.For instance,the overall growth in most of the US and European market is about 7% while emerging markets like India and China is over 30% which indicates tremendous market potential in time to come. Therefore,from the perspective of long-term growth potential such as China,India,Thailand,Indonesia etc.These markets are also termed emerging markets. GOVERNMENT REGULATIONS:The selection of market entry modes to a great extent affected by the legislative framework of the overseas market,the government of most of the Gulf countries have made it mandatory for foreign firms to have local partner.For instance,the UAE is a lucrative market for Indian firms but most firms operate there with a local partner. Trade barriers such as ecological regulations and local content requirements also affect the mode of entry.It has been a major reason for  increased foreign investment in Mexico,which is a part of the North American Free Agreement(NAFTA),in order to cater to the US market. LEVEL OF COMPETITION:Presence of competitors and their level of involvement in an overseas market is another crucial factor in deciding on an entry mode so as to effectively respond to competitive market force.This is one of the major reasons behind auto companies setting up their operations in India and other emerging markets so as to effectively respond to global competition. INTERNAL MODES COMPANY OBJECTIVES:Companies operating in domestic markets with limited aspirations generally enter foreign markets as a result of a reactive approach to international marketing oppurtunities.In such cases,companies receive unsoliated orders from acquaintances,firms and relatives based abroad,and they attempt to fulfil these export orders.This casual approach to entering international markets by way of producing in the homemarket and exporting overseas translates into regular exporting if the firm has positive experience in its exports operation. AVAILABILTY OF COMPANY RESOURCES:Venturing into international markts needs substantial commitment of financial and human resources and therefore choice of an entry mode depends upon the financial strength of a firm.It may be observed that Indian firms with good financial strength have entered international markets by way of wholly owned subsidiaries or equity participation. LEVEL OF COMMITMENT:In view of the market potential,the willingness of the company to commit resources in a particular market also determines the entry mode choice.Companies need to evaluate various investment alternatives in a particular market also depends upon the way the company is willing to perceive and respond to competitive forces. INTERNATIONAL EXPERIENCE:A company well exposed to the dynamics of the international marketing environment would be at ease when making a decision regarding entering into international markets with a highly intensive mode of entry such as joint venture and wholly owned subsidiaries. Below are different modes of market entry and they include: EXPORTING Exporting is the simplest method of entering a foreign market.It is the  process of sending goods or services from country to other countries for use or sale there. By exporting to a foreign country,a company is able to enter this country without actually establishing itself in the country.The company must simply manufacture products that can be shipped to the foreign country.Export activities may take several forms,including indirect exporting,direct exporting,and intracorporate transfers. Direct exports represent the most basic mode of exporting, capitalizing on economies of scale in production concentrated in the home country and affording better control over distribution. Direct export works the best if the volumes are small. Types of direct exporting are: Sales representatives – that represent foreign suppliers/manufacturers in their local markets for an established commission on sales. Provide support services to a manufacturer regarding local advertising, local sales presentations, customs clearance formalities, legal requirements. Importing distributors – purchase product in their own right and resell it in their local markets to wholesalers, retailers, or both. Indirect Exporting Indirect export is the process of exporting through domestically based export intermediaries. Indirect methods of exporting requires less marketing investment, but, as the exporter has no control over its products in the foreign market, the company lose substantial control over the marketing process. Types or methods of indirect exporting are: Filling orders from domestic buyers who then export the product Seeking out domestic buyers who represent foreign customers Exporting through an Export Management Company (EMC) Exporting through an Export Trading Company (ETC) INTRACORPORATE TRANSFERS A third form of export activity is the intracorporate transfer,which has become more important as the sizes of MNCs have increased.An intracorporate transfer is the sale of goods by a firm in one country to an affiliated firm in another. LICENCING License is a contract to identify what is being licensed: trademarks, patents, designs, copyrights or software. Licensing allows rapidly entering into the chosen foreign market and reduces capital requirements to establish manufacturing facilities overseas. Your contract does not violation of the host country’s existing laws and regulations.a licensor in the home country makes limited rights or resources available to the licensee in the host country. The rights or resources may include patents, trademarks, managerial skills, technology, and others that can make it possible for the licensee to manufacture and sell in the host country a similar product to the one the licensor has already been producing and selling in the home country without requiring the licensor to open a new operation overseas. The licensor earnings usually take forms of one time payments, technical fees and royalty payments usually calculated as a percentage of sales. As in this mode of entry the transference of knowledge between the parental company and the licensee is strongly present, the decision of making an international license agreement depend on the respect the host government show for intellectual property and on the ability of the licensor to choose the right partners and avoid them to compete in each other market. Licensing is a relatively flexible work agreement that can be customized to fit the needs and interests of both, licensor and licensee. Franchising The franchising system can be defined as: â€Å"A system in which semi-independent business owners (franchisees) pay fees and royalties to a parent company (franchiser) in return for the right to become identified with its trademark, to sell its products or services, and often to use its business format and system. Compared to licensing, franchising agreements tends to be longer and the franchisor offers a broader package of rights and resources which usually includes: equipment, managerial systems, operation manual, initial trainings, site approval and all the support necessary for the franchisee to run its business in the same way it is done by the franchisor. In addition to that, while a licensing agreement involves things such as intellectual property, trade secrets and others while in franchising it is limited to trademarks and operating know-how of the business. TYPES OF FRANCHISES There are three available types of franchises.The first type is the dealership,a form commonly found in the automobile industry.Here,the manufacturers use franchises to distribute their product lines.These dealership act as the retail stores for the manufacturer.In some distance,they are required to meet quotas established by the manufacturers,but as is the case for any franchise,they benefit from advertising and management support provided by the franchisor.The most common type of franchise is the type that offers a name,image and method of doing business,such as McDonald’s,KFC,Holiday Inn. There are many of these types of franchises,and their listings,with pertinent information can be found in various sources. A third type of franchise offers services.These include personnel agencies,income tax preparation companies and real estate agencies.These franchises have established names and reputation and methods of doing business.In some distances,such as real estate,the franchisee has actually been operating a business and then applies to become a member of the franchise. CONTRACT MANUFACTURING Contract manufacturing refers to a situation where a business will engage the services of an independent party to perform a specified duty for the business. In terms of manufacturing, contract manufacturing refers to a situation where a manufacturer will engage the services of an independent party to perform a specified job. There are various reasons for this type of engagement by manufacturers, all of which involve the maximization of profit. The process of contract manufacturing also has some negative considerations that include the risk of uncertainty and lack of control over the process. WHOLLY OWNED SUBSIDIRIES Entering a foreign market with a wholly owned subsidiary involves creating a local firm without the aid of a local partner. There are two ways of doing this. The first is through what is called greenfield development. This involves creating a new organization in the foreign country from the ground up. The second method is what is referred to as brownfield development. This involves purchasing an existing company in a foreign country. Brownfield developments can be beneficial because they offer local expertise, but they can be difficult because there may be resistance from those in the company  to new ownership. JOINT VENTURE A market entry option which the exporter and a domestic company in the target country join together to form a new incorporated company. Both parties provide equity and resources to the JV and share in the management, profits and losses. The JV be limited to the life of a particular project. This option is popular in countries where there are restrictions on foreign ownership, eg. China and Vietnam PIGGYBACKING Piggyback marketing – low cost market entry strategy in which two or more firms represent one another’s complementary (but non-competing) products in their respective market. Or, in other words, it is an arrangement, where two or more companies help each other to market their products, where the products have to be complementary and not competing against each other. LEVEL OF INVOLVEMENT IN INTERNATIONAL MARKETS No direct foreign marketing: A company in this stage does not actively cultivate customers outside national boundaries; however this company’s products may reach foreign markets. Sales may be made to trading companies as well as foreign customers who come directly to the firm. Or products may reach foreign markets via domestic wholesalers or distributors who sell abroad without explicit encouragement or even knowledge of the producer. As companies develop web sites on the internet, many receive orders from international Web surfers. Often an unsolicited order from a foreign is what piques the interest of a company to seek additional international sales. Infrequent Foreign marketing: Temporary surpluses caused by variations in production levels or demand may result in infrequent marketing overseas. The surpluses are characterized by their temporary nature; therefore sales to foreign markets are made as goods are available, with little or no intention of maintaining continuous market representation. As domestic demand increases and absorbs surpluses, foreign sales activity is withdrawn. In this stage, little or no change is seen in company organization or product lines. However, few companies today fit this  model because customers around the world increasingly seek long term commercial relationships. Further, evidence exists that financial returns from initial international expansions are limited. Regular Foreign marketing: At this level, the firm has permanent productive capacity devoted to the production of goods to be marketed in foreign markets. A firm may employ foreign or domestic overseas intermediaries or it may have its own sales force or sales subsidiaries in important markets. The primary focus of operations and production is to service domestic market needs. However, as overseas demand grows, production is allocated for foreign markets, and products may be adapted to meet the needs of individual foreign markets. Profit expectations from foreign markets move from being seen as a bonus to regular domestic profits to a position in which the company becomes dependent on foreign sales and profits to meet its goals. International marketing International marketing is the export, franchising, joint venture or full direct entry of a marketing organization into another country. This can be achieved by exporting a company’s product into another location, entry through a joint venture with another firm in the target country, or foreign direct investment into the target country. The development of the marketing mix for that country is then required – international marketing. It can be as straightforward as using existing marketing strategies, mix and tools for export on the one side, to a highly complex relationship strategy including localization, local product offerings, pricing, production and distribution with customized promotions, offers, website, social media and leadership. Internationalization and international marketing meets the needs of selected foreign countries where a company’s value can be exported and there is inter-firm and firm learning, optimization and efficiency in economies of scale and scope. The firm does not need to export or enter all world markets to be considered an international marketer. Global Marketing Global marketing is a firm’s ability to market to almost all countries on the planet. With extensive reach, the need for a firm’s product or services is  established. The global firm retains the capability, reach, knowledge, staff, skills, insights, and expertise to deliver value to customers worldwide. The firm understands the requirement to service customers locally with global standard solutions or products, and localizes that product as required to maintain an optimal balance of cost, efficiency, customization and localization in a control-customization continuum to best meet local, national and global requirements to position itself against or with competitors, partners, alliances, substitutes and defend against new global and local market entrants per country, region or city. The firm will price its products appropriately worldwide, nationally and locally, and promote, deliver access and information to its customers in the most cost-effective way. The firm also needs to understand, research, measure and develop loyalty for its brand and global brand equity (stay on brand) for the long term. b)OULINE ADVANTAGES AND DISAVANTAGES OF EACH STRATEGY. Advantages of direct exporting: -Control over selection of foreign markets and choice of foreign representative companies. -Good information feedback from target market. -Better protection of trademarks, patents, goodwill, and other intangible property. – Potentially greater sales than with indirect exporting. Disadvantages of direct exporting: – Higher start-up costs and higher risks as opposed to indirect exporting; – Greater information requirements; – Longer time-to-market as opposed to indirect exporting. Advantages of the international franchising mode: -Low political risk -Low cost -Allows simultaneous expansion into different regions of the world -Well selected partners bring financial investment as well as managerial capabilities to the operation. Advantages of indirect exporting -It’s an almost risk-free way to begin. -It demands minimal involvement in the export process. -It allows you to continue to concentrate on your domestic business. -You  have limited liability for product marketing problems — there’s always someone else to point the finger at! -You learn as you go about international marketing. -Depending on the type of intermediary with which you are dealing, you don’t have to concern yourself with shipment and other logistics. Disadvantages of indirect exporting: -Your profits are lower. -You lose control over your foreign sales. -You very rarely know who your customers are, and thus lose the opportunity to tailor your offerings to their evolving needs. -When you visit, you are a step removed from the actual transaction. You feel out of the loop. -The intermediary might also be offering products similar to yours, including directly competitive products, to the same customers instead of providing exclusive representation. -Your long-term outlook and goals for your export program can change rapidly, and if you’ve put your product in someone else’s hands, it’s hard to redirect your efforts accordingly. Advantages of licensing -Obtain extra income for technical know-how and services -Reach new markets not accessible by export from existing facilities -Quickly expand without much risk and large capital investment -Pave the way for future investments in the market -Retain established markets closed by trade restrictions -Political risk is minimized as the licensee is usually 100% locally owned -Is highly attractive for companies that are new in international business. Disadvantages of licensing -Lower income than in other entry modes -Loss of control of the licensee manufacture and marketing operations and practices leading to loss of quality -Risk of having the trademark and reputation ruined by an incompetent partner -The foreign partner can also become a competitor by selling its production in places where the parental company is already in. -investment to attract prospects and support and manage franchisees. Advanatges of Frachising -Franchising provide knowledge of the local markets. A franchise provides franchisees with a certain level of independence where they can operate their business. A franchise provides an established product or service which may already enjoy widespread brand-name recognition. This gives the franchisee the benefits of a pre-sold customer base which would ordinarily takes years to establish. A franchise increases your chances of business success because you are associating with proven products and methods. Franchises may offer consumers the attraction of a certain level of quality and consistency because it is mandated by the franchise agreement. – Disadvantages of franchising: -Franchisees may turn into future competitors. -Demand of franchisees may be scarce when starting to franchise a company, which can lead to making agreements with the wrong candidates -A wrong franchisee may ruin the company’s name and reputation in the market -Dependence on franchisee. -Potential conflicts with franchisee. Advantages of Joint Venture: -Accessing additional financial resources – Asset sharing is one of the best advantages about joint venture. Since, you are able to use larger funds to facilitate the production and operation of projects and products, you facilitate growth. In other words, you increase profit margin and increase your revenue potential. -Sharing the economic risk with co-venturer – It pays to have someone sharing the responsibility with you in case you end up in deep troubles. This is also true with joint venture. Since you are sharing assets, the risk of losing a great deal of money is divided to both parties. -Widening economic scope fast – Building reputation is often difficult, not to mention time consuming and expansive. At a joint venture, you are able to widen your economic scope without spending too much money and waiting for a long time. – Tapping newer methods, technology, and approach you do not have – In order to grow and expand, you need resources in the forms of methods, technology, and approach. For that matter, it would help a lot if you will be able to partner with an entity that presently has the things you don’t and the things you need. Joint venture opens up the venue for such need. -Building relationship with vital contacts – Aside from economic territory, another advantage of joint venture is the ability to give you business relationships with vital contacts. This is just like automatically befriending your partner’s influential friend that can give you access to lots of things such as business opportunities and a pass to vital information. Disadvantages of Joint Venture: -Shared profit – Since you share assets, you also share the profit. The profit of both parties usually depends on the size of the share to the venture or may be defined on the agreement. -Diminished control over some important matters – Operational control and decision making are sometimes compromised in joint ventures. Since there is an agreement that divides which one will take over a particular operation, the other may not be satisfied with how the things are worked out with another. This leads us to another disadvantage of a joint venture. -Undesired outcome of the quality of the product or project – Since one party may not have control on the supervision of the production or the execution of one part of the system, this can happen. This often leads to disputes and lawsuits. To avoid this, both parties agree on specific details about the whole operation process. -Uncontrolled or unmonitored increase in the operating cost – Again, defined control over the operation may lead to this disadvantage. It is important therefore to make sure that all things are clarified on the paper before singing in the joint venture agreement. Advantages of contract manufacturing -Low financial risks – contract manufacturing allows companies to save costs by manufacturing a particular item at a cheaper rate than what it would cost them If they decided to undertake the manufacturing process themselves. – it allows the company doing the outsourcing to shave some time off the whole process, giving them quicker returns and turnovers. – Where a company is less effective than another in manufacturing an item, contract manufacturing will allow it to concentrate on that in which it is the most efficient. Disadvantages of contract manufacturing -Reduced learning potential -Potential public relations problems may need to monitor working conditions. -The company doing the outsourcing faces some degree of risk if it fails to do its research properly. This is because outsourcing the manufacturing to the wrong company could end up costing the company more, rather than less, if the outsourced company fails to deliver as expected. Advantages of wholly owned subsidiaries On the positive side, a wholly-owned subsidiary that does its business in a location different from the parent company’s is able to remain in its locale. With the business world spanning so many countries, this can serve as a great advantage in international situations. Name recognition is another positive reason for maintaining a wholly-owned subsidiary. If a particular brand name is well known and popular, the parent company has no reason to absorb the subsidiary entirely. Wholly-owned status allows the subsidiary to retain its name brand, thus avoiding hindering its sales. Diversity for the parent company is another perk created by maintaining a wholly-owned subsidiary. This status allows the parent company to branch out into different products and markets, building strength in diversification. Disadvantages of wholly owned subsidiaries a wholly-owned subsidiary are more business oriented. The holding company runs a definite risk in assuming control of another company while allowing its management to continue to operate independently of the parent company’s. The level of investment and allocation of funds and resources required is also very high. A parent company must spend a great deal of time and money to smoothly integrate the new subsidiary.All of these factors require commitment and dedication on the part of the holding company and willingness to form that partnership on the part of the subsidiary. Advantages of piggybacking reduced financial costs limited risk quick, easy access to the market. Generally, the supported company can make immediate profits on the new market. The SME can, thus save time (3-5 years), compared to the normal length of time necessary to establish itself ; reduced logistical and administrative operations ; benefit of the brand image that the supporting company brings to its products ; immediate availability of a sales force structure ; excellent market knowledge of the supporting company. Disadvantages of piggybacking weak motivation of large companies to become supporters ; difficulty in finding partners offering a compatible product and distribution network ; risk of market loss, which can be reduced due to the complementarity of the product, and commercial follow-up between the partners ; occasional difficult relations because of differences in size or culture ; risk of lack of mutual confidence and of lack of involvement ; risk of conflict of interest (e.g. local agents could systematically put the interests of the supporting company before those of the supported company) ; occasional very rigid requirements and conditions of access to the commercial networks of large companies. These conditions can be qualitative (e.g.: product quality) and quantitative (minimum level of annual turnover, high commissions, etc.). Macro Environmental Influences That Can Affect SAB Millers SABMiller’s origins date back to the foundation of Castle Breweries in 1895 as to serve a growing market of miners and prospectors in and around Johannesburg, South Africa. Two years later, it became the first industrial company to list on the Johannesburg Stock Exchange and the year after (1898) it listed on the London Stock Exchange. From the early 1990s onwards, the company increasingly expanded internationally, making several acquisitions in both emerging and developed markets. In 1999, it formed a new UK-based holding company, SAB plc, and moved its primary listing to London. In May 2002, SAB plc acquired Miller Brewing, forming SABMiller plc. It is very important that SAB Miller considers its environment before going into international the market. In fact, environmental analysis should be continuous and feed all aspects of their planning to go international The macro-environment refers to the major external and uncontrollable factors that influence an organization’s decision making, and affect its performance and strategies. These factors include the Political (and legal) forces, Economic forces, Sociocultural forces, and Technological forces. These are known as the PEST factors. PEST Analysis Political Factors: The political environment revolves around the current government in a particular country in which SAB Miller manufactures or trades, and also laws/legislation operate or within their home market as well as overseas. If their government is socialist then perhaps there is a policy to tax more and to invest in the public sector. On the other hand if SAB Millers have a more conservative or Republican government then the free-market is left to take control, taxation is less and there is often a smaller public sector. The political arena has a huge influence upon the regulation of the business, and the spending power of consumers and other businesses. SAB Miller must consider issues like: †¢How stable is the political environment in that country? †¢Will government policy of that country influence laws that regulate or tax SAB Miller? †¢What is the government’s position on marketing ethics? †¢What is the government’s policy on the economy? †¢Does the government have a view on culture and religion? †¢Is the government involved in trading agreements such as EU, NAFTA, ASEAN, or others? Economic Factors The economic environment is a direct influence on all businesses. Obviously if you are studying marketing there is a huge element of economics within the topic itself, and you should be no stranger to the principles of economics. As we saw from our lesson on the marketing environment there is a macro environment, and internal environment and the microenvironment. More specifically you’ll be at looking elements such as where a business is in terms of the current business cycle, and whether or not they are trading in a recession. SAB Millers marketers need to consider the state of a trading economy in the short and long-terms. This is especially true when planning for international marketing. You need to look at: 1. Interest rates. 2. The level of inflation Employment level per capita. 3. Long-term prospects for the economy Gross Domestic Product (GDP) per capita, and so on. Sociocultural Factors The Sociocultural environment embodies everything which is social and cultural within a nation or society. There are plenty of examples of society and culture on the marketing teacher website, so we recommend that you go to our lesson store and look through some of the consumer behaviour pages. Some notable examples would include the influence of learning, memory, emotion and perception, motivation, lifestyle and attitude and consumer culture. Have a look at the six living generations in America, social environment and class, the impact of your birth order on how you behave as a consumer and take a look at the eight types of online shoppers. In a more general sense consider influences such as the increase in life expectation of Western consumers, and demographics which is the study of populations. The social and cultural influences on business vary from country to country. It is very important that such factors are considered. Factors include: 1. What is the dominant religion? 2. What are attitudes to foreign products and services? 3. Does language impact upon the diffusion of products onto markets? 4. How much time do consumers have for leisure? 5. What are the roles of men and women within society? 6. How long are the population living? Are the older generations wealthy? 7. Do the population have a strong/weak opinion on green issues? Technological Factors Technological factors are a multifaceted influencer. Let’s just think about the sorts of technology that you come in touch with almost daily. Smart phones such as Android and iphone are now common – all – garden, and we are used to being able to access information and communication technology instantly no matter where we are. During studies or at work we have access to information on quick PCs and over the Internet, with faster broadband connections arriving in many parts of the world. Technology also surrounds business processes. As we saw from our lesson on the functions within an organisation all departments use information technology or technology in one form or another. Our manufacturing operations will use technology to produce goods and services. Our logistics and warehousing functions use forklifts and Lorries as well as order tracking technology and software. The customer service department will use communication technology to talk to customers but will also have access to internal systems, such as technology to simplify credit control and stock control for example. There are many, many more examples of technology. Technology is vital for competitive advantage, and is a major driver of globalization. Consider the following points: 1. Does technology allow for products and services to be made more cheaply and to a better standard of quality? 2. Do the technologies offer consumers and businesses more innovative products and services such as Internet banking, new generation mobile telephones, etc? 3. How is distribution changed by new technologies e.g. books via the Internet, flight tickets, auctions, etc? 4. Does technology offer companies a new way to communicate with consumers e.g. banners, Customer Relationship Management (CRM), etc?

Current Trends in the War on Terror Essay

As the world is cowering in terror from the 9/11 attacks and the bombing incidents in Indonesia and other parts of the world, the world’s attention is shifted now to where the attacks may occur next and what can be done to address the situation. Some suggest that the answer lies in being able to suppress and perhaps eliminate all of the terrorist cells all over the world. The problem there, however, is that any attack that is targeted at eliminating terrorist cells would necessarily involve any host country where they may be located and in any Middle Eastern country, such an attack could prove disastrous (Campbell & Flourney 372). The more practical and ideal solution to this problem therefore lies at a more fundamental level; a more basic level wherein the country has more controls and no international liability (Kochler 37). The solution to this problem is by improving border security in order to prevent the occurrence of these terrorist attacks while the international community seeks for answers to address this problem at a global scale. At this point in time, domestic policies would be the best option in fighting the war against terror. This short discourse will therefore seek to shed light on the issue of terrorism and the crucial role that the border security plays in such. To gain a better understanding of the problem, it is important to first analyze the current trends that have been taken relative to border security to ensure the safety of the public from terrorist attacks. This will then be supplemented by an explanation on how border security can take an even larger role. The most crucial aspect in relation to border security and its role in the war against terror concerns the aviation industry. Since the 9/11 attacks, the public confidence with regard to air travel has greatly been shaken (Taylor 2). The attacks had the effect of sending a message that now, even airplanes could be used as missiles to target buildings regardless of whether there were people on board the aircraft of not. Every plane crash that is reported on the news is suspected to have been caused by a terrorist attack rather than just an equipment malfunction or a pilot error. In response to these attacks, security has been considerably increased in airports all over the world. Every passenger is now subject to a full body search and every hand carried and checked in item is thoroughly inspected for any suspicious objects that can either cause an explosion or aid a hijacker in gaining control over the aircraft (Campbell & Flourney 52). The impact has not been limited to airport security as even airplane manufacturers and airlines have resorted to installing devices and taking precautions with regard to what to do in case an airplane is hijacked. One of the safety measures that have been suggested and is highly debated is the issuing of arms for the pilots so that they may be able to defend themselves against any terrorist hijackers that are able to force themselves into the cockpits (Lott 1). The current controversy with regard to airline security concerns the proposal to equip the pilots of airplanes with weapons in order to protect themselves from any hijackers that manage to enter the cockpit (Taylor 2). This proposal is of course faced with a lot of opposition because of the implications of allowing pilots to be armed in aircrafts. There is a lot of concern with regard to the security of the other passengers on board just in case the armed pilots do decide to turn on the other co-pilots and hijack the aircraft themselves or hold passengers as hostages for whatever purpose. The proponents for arming the pilots argue that it is the best option because the pilots need to defend themselves against the terrorist hijackers (Keeler 151). The problem with this is that it negates the training of the pilots which is that in times such as hijackings they are not supposed to deal with the terrorists but instead secure the cockpit and land the plane as soon as possible (Will 1). The concern here is that the plane should be landed right away in order to protect not only the passengers but also the people on the ground who may become targets or victims as the 9/11 experience has shown. The duty of the pilot is not concern himself with whatever goes on in the cabin but instead make sure that the plane is safely on the ground where there are more units who can deal with the situation properly. Pilots are not adequately trained to deal with hijacking situations in terms of dealing directly with the terrorist hijackers (Will 1). Another argument for the arming of the pilots is that such a measure is only designed to protect the pilots from terrorist hijackers who succeed in gaining entry into the cockpit (3). While there as some merit to this precautionary measure, there is no guarantee that the armed pilots will do just that. There are instances when certain people, pilots included, enter a â€Å"cowboys or renegade† mode (Will 1). Most of the pilots have received a degree of military training as fighter pilots and there is some truth to the profiling of fighter pilots â€Å"live wires and risk-takers† (Will 1). The end result in these situations could be that instead of protecting the cockpit and landing the plane like they are supposed to, a number of these former fighter pilots could engage the terrorist hijackers.

Respect and Sportsmanship

Every day you go through obstacles that will push you to show unfairness, disrespect for others and a â€Å"sore loser† type attitude. For sportsmanship that is just the opposite of its meaning. If you are aware you show sportsmanship every day, whether it is playing a friendly game of basketball in your backyard or being a part of a school spelling bee. For over a decade people around the world learn and show sportsmanship. In the dictionary sportsmanship means one who plays fairly and wins or loses gracefully.To me sportsmanship means a little more than just being nice after a game to the opposing team. It is the ability to keep composed when a situation arises. To be able to except a loss and not act out to make your team look bad. Sportsmanship helps maintain a good image in the competitive world today. It’s a value you have to have to show respect to your team and other teams. It’s your responsibility as a competitive person to show sportsmen like behavior. Outside the sports world you show sportsmanship everywhere.Recently I went around asking a couple students what sportsmanship meant to them. Each one said something different, but they all generally said to show respect whether you win or lose. A great thought was sportsmanship applies to all disciplines. This one individual stated musically speaking; it meant if you are better than your cohorts. You should still open your ears to advice. To encourage people not to bring others down if they do something wrong. Sportsmanship is a kind of style and attitude and it has positive influences on everyone around you. If you win through bad sportsmanship, that’s no real victory. † –Babe Didrikson Zaharias quotes. This is a great quote that really clarifies what sportsmanship is. Yes, winning is awesome but it isn’t awesome when you disrespect people and show childish behavior. That truly is not a real victory. You should win with passion, competiveness and drive. I f you show sportsmanship by being unfair and not respectful, then you are not showing sportsmanship at all.

Resistance during the Transatlantic Slave Trade Essay

Resistance during the Transatlantic Slave Trade - Essay Example The resistances in Africa were defensive, offensive and protective in nature3. These were meant not only to discourage the Europeans from getting more slaves from Africa but to somehow send a message to the Western world that slavery is really unnatural and that no one has the right to declare that a person can be someone’s property.  Some resistances in African in the 18th century were in the form of relocation, particularly by the West Africans. As the market for slaves increased, many West Africans tried to look for areas that were less accessible to the slave traders. These Africans moved to lake areas where it was difficult for the invaders to cross4. Nevertheless, although some were spared through this way, there was no stopping the European invaders from getting more slaves from Africa.  Another strategy of Africans is by architectural means like building homes and villages with labyrinths, as well as high walls and several points of ingress or entry points, and egr ess or exit points5. This further confused the slave traders as most of them did not know how labyrinths worked. There were no reports, however, regarding the true effectiveness of these architectural works in preventing European invaders from capturing slaves.  Aside from these, there were also protective strategies like captive redemption, or the system of helping each other avoid slavery by using cash protection. Mostly, these were secret societies like those of the Efik and Ekpe, although they were able to help protect the African slave traders6. Still, just like the other previously mentioned strategies, there was no way to account for the effectiveness of captive redemption. After all, it obviously could not accommodate everyone. There were protective strategies but there were also offensive ones. The offensive forms of resistance included several rebellions in Africa itself. Among these were the Mandingo Rebellion in Mali and Niger from 1785-1796, the Hubbu Rebellion in Guinea in the 1850s, and the Bilali Rebellion in Sierra Leone from 1838-1872. These were all armed resistances that helped resist slavery and assert the freedom of the Africans from slavery7. Other offensive strategies included forming alliances among communities in order to protect people from the slave traders; Africans deliberately dropping poisoned food, wine and water along the paths of the European slave traders for an obvious purpose; and young men undergoing military training in order to be able to protect their communities8. The problem is that in many parts of Africa, all cultural and religious movements instituted to counter transatlantic slavery were brutally quelled by the government. One example of this was the Congolese

Diabetes WA Research Paper Example | Topics and Well Written Essays - 500 words

Diabetes WA - Research Paper Example The 360 degree marketing approaches are important. The DAGMER (Defining Advertising Goals for Measured Advertising Rules) approach tells the effective advertising must be measurable (Altstiel & Grow 2006). However, the marketing are the ongoing process and financial support is very important for these campaigns. Most of the campaigns must reach the target audiences. The basic target audiences are the people who are in the middle age, staying nearby the town and the diabetes WA centers. However, Diabetes can happen to anyone irrespective of their earning capacity and even many time juvenile diabetic patents are also seen. The major concept about the campaigns must be to create a concern about the diabetes within the minds of the diabetic patients. And for the future patients the fear of losing the happy moments with the family must be focused. It means the advertising campaigns must tell the viewers about the importance of him or her being fit and diabetes free. Media Mix: Media is th e most important factor in this case. The media is the platform which can help the campaigns to reach the mass. That is the reason the media mix is very vital. The media mix is basically the combination of the proper Medias which supports the advertising campaign efficiently (Surmanek, 1996). In this case the television and the radio are very important as they reach to the mass in a very efficient way.

National Security Affairs of Iraq Research Paper

National Security Affairs of Iraq - Research Paper Example This conflict has greatly divided the national purpose of Iraq. The Iraq’s National Security Affairs can be termed as having a complex framework characterized by burdensome issues associated with untangling and security issues connected to terrorist groups. The country has also been linked to most of the criminal events in the Middle East. Despite the above situation, the Iraq’s political scene is trying its level best to keep afloat through associating with other nations such as the United States. Its internal security is under complete control by its army following the withdrawal of American troops. The government has however admitted that it has along way to go in terms of attaining a stable national security especially in relation to technical issues in its intelligence apparatus. The Iraq’s army is not yet qualified to maintain peace and order in the country as it is still unsuited for such duties. In relation to the international community especially other Arab Spring countries, its foreign policy has not yet been fully established and this has led to fluid situations in such Arab countries preventing Iraq from attaining a stable approach with regards to its foreign policy. Cases like those witnessed in Syria have resulted to a sectarian dimension that has resulted to an acute effect on Iraq following its diverse sectarian composition. Despite the American withdrawal from Iraq, the two countries have maintained a close tie especially when it comes to Iraq’s National Security with America in full support of her security affairs. IDEOLOGY The Ideology of Iraq stems from the radical Islamists who are pursuing a vision that they believed to be universalists with regards to Sharia Law. They came out strongly seeking the interpretation of this law with regards to the war. According to the Sharia Law, the people’s voice had no position in any political system that obey the rules made by God (Ali 2009). This conflicting position left the mood of the public to be variable yet the law was external. The war against liberalism believed to be waged by the al-Qaeda as well as its affiliates represents a political manifestation of the mindset that resisted Westernization and globalization. The al-Qaeda had a number of complains with regards to American culture and the impact it had on the Iraq people. The American culture was looked at as to be resulting in immorality, hypocrisy and polytheism among the Iraq people Iraq had been closely associated with the Activities of Osama Bin Laden and that led to most of the international countries to declare war on Iraq with the USA being on the fore front. The United States under President Bush was against the democracy principles employed in the country at that time as well as all the leaders who were out to enact it. The International community was agitating for democratic elections to be held which would ensure that the existing government as well as the popular soverei gnty was eliminated now that the two had led to deviation and infidelity to the true desirable path (Ali 2009). Consequently the international community was ready to fight any person or force that was after malicious ideology and referred to such forces as infidels.

Mother Teresas Style of Leadership Essay Example | Topics and Well Written Essays - 2000 words

Mother Teresas Style of Leadership - Essay Example According to the study  by the time Mother Teresa started her missionary work, she had little money in her hand, but she proved to the entire world that a person can achieve anything and flourish in  this world without money. Mother Teresa taught individuals that being wealthy does not necessarily mean everything. She proved to all that it is possible to prosper without money. Mother Teresa created a world full of love where the disadvantaged are cared for and showered with unconditional love. Mother Teresa was so caring to the extent that she used to beg others to give her food so that she can provide the orphan children dying of hunger with something to eat. Some of these individuals had no mercy on her and spit on her hand when begging but she would respond calmly that she would continue keeping the spit for herself and continue begging them to provide food for the poor and orphaned children. In addition, at the end, they realized her gentle character and donated something for the poor whenever she asked for. This shows her magnanimity, which is one of the best leadership qualities she possessed.From this paper it is clear that  Mother Teresa displayed a great mental strength by building homes for the destitute through fundraising and seeking support. Furthermore, Mother Teresa was a teacher and a caregiver who majorly focused on how to relieve suffering from the poor and the disadvantaged in the society      

TLMT312 WEEK 4 FORUM Assignment Example | Topics and Well Written Essays - 250 words

TLMT312 WEEK 4 FORUM - Assignment Example There is a distinction between rates and rating. Rate is the price per hundred weights to move an individual product between two locations. It is listed on pricing sheets or tariffs. Various products in different classes are charged different rates. Rate is determined by weight and size of the product. Rating involves determining the appropriate, legal, economical rates and routes for the transportation of foreign and domestic freight through any or all modes of transportation. These determinations are made according to published classification, tariff, and tariff routings. Rating also includes development of narratives and exhibit materials and similar information to be used by others to negotiate and requested rates. In addition, it may also include preparation of materials concerning rate matters in cases to be presented to representatives of the carriers, regulatory bodies, and the courts. The goal of the assessment is to establish the appropriateness of classification, routes, rates and carriers’ actions (Gianpaolo & Laporte, 2004). Classification and rate depend on the grade. Rating determines the appropriateness of classification and rates. Once products are shipped they must be classified for various reasons. Classification helps to determine the rates for each

Training call center personnel Essay Example | Topics and Well Written Essays - 250 words

Training call center personnel - Essay Example Sales made will help the company to develop better strategies for developing other sectors. The customer strategy shall include customer profiling, which involves identifying who the clients of the business are and what they need. Access channels are another consideration and for this case, the website and retail shops will stock the new products. The company also needs to determine the way of communication with customers (International Financial Corporation, 2013). The practice case will have the methods of management involved because management practices form a fundamental part of success in administration. The case will also outline the objectives of the call center department and the how personnel involved should operate. The case will also have a provision for continuous learning to ensure that the trained staff will pass the information to the untrained. Such a method will mean that the system will involve many employees, not just a few. It is necessary that the company embraces the use technology to reach and market the product. For instance, the website forms the essential component of the technological aspect of the case system. Implementation of the case will take differentiated teaching styles, but which should emphasize involvement. Participants will gain knowledge of creativity on how to tackle customer-related issues. The practice case should entail methods, approach targeted, the objectives, methods of delivery and the channels of passing information to others. For the launch of new products, both customer and product-centric approaches are essential. Involving a large number of participants gives a chance for developing untrained

Aboriginal Rights (Canada) Essay Example | Topics and Well Written Essays - 1250 words

Aboriginal Rights (Canada) - Essay Example They are separate entity rights in Canada that the aboriginal people have practiced and acclimatized to over time. Historically, the aboriginal rights merely protected the aboriginal people and their status in the society. However, the rights and freedoms accorded to the aboriginal people have taken a new shape in the recent times. The aboriginal people now enjoy more emphasized and cemented rights and freedoms, as do other people in Canada. This paper analyzes the aboriginal rights and freedoms from a political angle in order to determine their application in Canada. Past Application of Aboriginal Rights In the past, the aboriginal rights and privileges in Canada only applied within the borders of the country. Aboriginal politicians defended their countries especially when foreign countries infringed on the rights. Particularly, the aboriginal politicians complained to the international bodies like the United Nations over the imposition of the British crown rules on the aboriginal p eople (Panagos 407). The politicians argued that the aboriginal people were governed by the aboriginal laws hence the imposition of the British crown laws lacked meaningful ground for application. Many aboriginal groups however call upon the government to recognize the aboriginal laws. ... However, the government and colonial masters brought discriminatory pieces to the aboriginal rights hence the aboriginal people faced more discrimination even in the face of the new treaties. On such grounds, the aboriginal people in Canada are resistant to allow the government any point of disrespect to the aboriginal rights. Court Implementation and Application of the Aboriginal Rights In the existence of the aboriginal rights, the court has played a major role in solving disputes and aligning the aboriginal rights among the people. The courts have previously arbitrated the conflicts between the aboriginal politicians and the governmental agencies. According to Ray (400), in the recognition of the aboriginal rights by the government in 1982, the government did not define what these rights were. This brought a lot of confusion over the application and enjoyment of the rights. In a statement during the adoption of the aboriginal rights, the courts attained the power to determine the definition and jurisdiction of the aboriginal rights. In this sense, the courts would determine cases on grounds of whether the aboriginal rights applied to a case or not. The courts have also played a role in the aboriginal rights through the creation of the â€Å"sparrow test† in the case of the 1990 R v Sparrow decision. The case brought two factors into existence as regards the aboriginal rights (Collins 959). First, it defined the extent to which the aboriginal rights could apply and the pieces or parts that could be infringed by the government. The case also confirmed that the aboriginal rights were not absolute because the court, which

Marketing case analysis Essay Example | Topics and Well Written Essays - 500 words - 6

Marketing case analysis - Essay Example Accepting Sears’ proposal means that Goodyear would have to change its distribution policy. There can be certain changes such as including their own Goodyear seller that would carry this brand exclusively. The reason for doing this is that Goodyear would have their own channel through which it can sell more and more to its customers. The customers would not have to go anywhere else for buying Goodyear’s tires because Goodyear would have its stores made available everywhere within the customers’ reach. Also, it is said that channel of distribution must be selected carefully so that it is within access of most possible customers and provides a number of prospects (Linton, n.d.) . But there are some limitations as well. Firstly, the dealers might influence the customers to buy other brands because there are very few dealers who have the full knowledge of tires. Secondly, brand loyalty and tires have high tendency of being elastic in demand. One day, customer might w ant Goodyear but the other day the customer could decide to go for Sears or any other brand. Thirdly, product cannibalization might appear between Sears and the franchised dealers. Moreover, continuing sales to Sears would also trigger another concern that whether to sell the Eagle brand only or sell some other specific products as well. The other solution is to reject the proposal and maintain the status quo. This can cause a lot of problems. Already, Goodyear is facing decline in the current market position and loss of market share by 3.2%. There is high competition and Goodyear has no strong market share outside the American continent. The cut throat competition in both price and quality might cause greater problems for Goodyear. The conclusion lies with the decision of accepting the Sears proposal. By employing this action, there would be an increase in the distribution channel leading to an increment in the revenues for Goodyear. This would prove

Managing Diversity in South Africa Essay Example for Free

Managing Diversity in South Africa Essay Introduction In the workplace, diversity in terms of ethnicity, locality, education and skills, age, and gender exist. Managers or employers therefore require innovative ideas to successfully manage employees in the workplace. Diversity management is a relatively new field in the South African business environment. Managing employees and the work environment involves different aspects and is influenced by the internal environment such as in the mission, vision and goals of the organisation as well as the external environment. These aspects include areas where diversity management is important. Managers have various roles to carry out in an organisation in order to provide effective management and deal with the ethical issues. Factors such as changing structures and polices, providing diversity skills training, creating cross functional teams and employee network groups, building relationships, and providing complete managerial support are all factors that contribute towards effective diversity management. A successful diversity management approach must be more accommodating and more capable of promoting the diversity within an organization to bring everyone together and generate effective participation. This means that employees should be regarded as an organized whole that brings meaningful contributions from their social, political, economic, and geographical experiences. 2. Diversity Diversity can be defined as all the ways people differ, that is the different influences to approaching the workplace, communication between employees, satisfaction achieved from performance and identification in the workplace (Daft, Kendrick, amp; Vershinina, 2010). It is a commitment to distinguishing and appreciating the range of characteristics that make individuals unique in an atmosphere that supports and celebrates individual and collective achievement (Tennessee, 2003). Diversity â€Å"represents the multitude of individual differences and similarities that exist among people (Kreitner, 2001). According to Erasmus, diversity applies to all employees and does not only encompass certain differences but rather the entire spectrum of individual differences that make people unique. Therefore diversity cannot be viewed as only racial or religious differentiation but s all differences combined. The notion of diversity describes differences among people as well as similarities. The discipline of managing diversity requires that these two aspects are managed simultaneously. He further suggests that managers are expected to integrate the collective mixture of similarities and differences between workers into the organisation (Erasmus, 2007). Diver sity is more than being politically correct; it is about nurturing a culture that values individuals and their wide assortment of needs and contributions Diversity management is a moderately new field in the South African business environment. Diversity management is ensuring that the necessary factors are in place to provide for and to encourage the continuous development of diversity in the workplace, by incorporating actual and perceived differences to achieve the utmost efficiency (Bandyopadhyay, Hazra, amp; Goswami, 2007). Diversity management can also be defined as the commitment on the part of the organisations to recruit, retain, reward and promote a heterogeneous mix of productive, motivated and committed workers, including people of colour, whites, females and the disabled (Inancevich amp; Gilbert, 2000). The two areas where diversity management are particularly important include: * Workplace diversity. * Global diversity. Workplace diversity refers to the array of distinctions between people in an organisation. Some of the benefits of implementing workplace diversity are; increased adaptability which supplies a variety of solutions to problems in service, sourcing, and allocation of resources, various opinions which include ideas and experiences, and effectiveness in terms of employee performance to attain goals (Greenberg, 2005). Furthermore, enhanced use of employee capacity is encouraged. This involves competitive advantage over other organisations along with prospects and development of employees for retention purposes. Diversity initiatives retain a competitive advantage by improving employee confidence, decreasing interpersonal conflict, facilitating development in new markets and increasing creativity. It also includes the understanding of the marketplace in terms of the changing needs of consumers. Building workplace diversity will also result in the improved extent of understanding in leadership positions that encompasses a variety of skills. Better quality of team problem solving to bring in different perspectives resulting in creativity of ideas and solutions and lastly reduction of costs induce lower turnover, absenteeism and lawsuits (Daft, Kendrick, amp; Vershinina, 2010). Global diversity is more than just demographical factors (such as age, race, gender, ethnicity, disability and sexual orientation), it is about thinking, leadership, skills and style which integrates peoples differences to achieve all the goals planned and is acceptable universally, that is by breaking though barriers through globalisation (Dell, 2011). Globalisation refers to standardisation of products plan and marketing strategy throughout the world by assuming a homogeneous global market of consumers and industrial products (Daft, Kendrick, amp; Vershinina, 2010). A benefit of global diversity is broader services through customer satisfaction and product availability. By managing diversity, managers access a range of skills which the organisation has never had before and thus a broader array of individual strengths, experiences and perspectives. There is also a wider legitimacy and organisational image across a wider audience. Managers however should realise that managing diversity is fairly tough and cannot be implemented immediately. It is instead a long-term strategy in order to correct the imbalances in the workplace. 3. Mission, Vision and Goals A mission is defined as the organisations’ reason for existence. A mission statement is a broadly stated definition of the purpose of the company. Well designed mission statements can enhance employee motivation and organisational performance.

The Communication Process Cycle

The Communication Process Cycle The word communication derived from the Latin word communis that means to impart, to participate, to share or to make common. It is a process of exchange of facts, ideas, and opinions and as a means that individual or organization share meaning and understanding with one another. In the other words, it is a transmission and interacting of facts, ideas, opinion, feeling and attitudes. It is the ability of mankind to communicate across barriers and beyond boundaries that has ushered the progress of mankind. It is the ability of fostering speedy and effective communication around the world that has shrunk the world and made globalization a reality. Communication had a vital role to play in ensuring that people belonging to a particular country or a culture or linguistic group interact with and relate to people belonging to other countries or culture or linguistic group. Communication adds meaning to human life. It helps to build relationship and fosters love and understanding. It enriches our knowledge of the universe and makes living worthwhile. The Communication Process / Cycle The transmission of senders ideas to the receiver and the receivers feedback or reaction to the sender constitute the communication cycle. The process of communication begins when one person (the sender) wants to transmit a fact, idea, opinion or other information to someone else (the receiver). This facts, idea or opinion has meaning to the sender. The next step is translating or converting the message into a language which reflects the idea. That is the message must be encoded. The encoding process is influenced by content of the message, the familiarity of sender and receiver and other situation of factors. After the message has been encoded, it is transmitted through the appropriate channel or medium. Common channel in organization includes meeting, reports, memorandums, letters, e-mail, fax and telephone calls. When the message is received, it is decoded, by the receiver and gives feedback to the sender as the conformation about the particular message has been carefully understand or not. Furthermore, the process of communication involves that (sender, message, encoding, communication channel, receiver, decoding and feedback). Therefore, person who desires to convey the message is known as sender. Sender initiates the message and changes the behavior of the receiver. Message is a subject matter of any communication also might involve any fact, idea, opinion or information. It must exist in the mind of the sender if communication is to take place. For encoding the communicator of the information organizes his idea into series of symbols (Words, signs, etc.) which, he feels will communicate to the intended receiver or receivers. Moreover, communication channel be has to select the channel for sending the information. Communication channel is the media through which the message passes. It is the link that connects the sender and the receiver. For receiver person who receives the message is called receiver or receiver is the person to whom the particular message is sent by the transmitter. The communication process is incomplete without the existence of receiver of the message. It is a receiver who receives and tries to understand the message. Additionally, decoding is the process of interpretation of an encoded message into the understandable meaning. Decoding helps the receiver to drive meaning from the message. Lastly, is feedback in communication process / cycle. Communication is an exchange process. For the exchange to be complete the information must go back to whom from where it started (or sender), so that he can know the reaction of the receiver. The reaction or response of the receiver is known as feedback. Brain drain: On whole process there is a possibility of misunderstandings at any level and is called brain drain. It may arise on sender side if they do not choose the adequate medium for delivery of message, by using default channel and it may also arise when receiver does not properly decode the message. In other words, we can say that it is breakdown of cycle at any level. Refer below (figure1.0 figure2.0) the communication process. Verbal Interpersonal Communication Effective our verbal or spoken communication is dependent on a number of factors and cannot be full isolated from other important interpersonal skills such as. The process involved and the steps we can take that verbal communication are (speaking skills, listening skills, self-Disclosure, conflict and assertiveness, gender and verbal communication and barriers to effective verbal communication). 3.1 Speaking skills To communicate effectively, speakers need to consider background, needs, and abilities of listeners. Moreover, Messages conveyed more effectively when spoken in simple, concrete, and specific way and Good speakers make verbal and nonverbal messages consistent. 3.2 Listening skills Listening skills is also a very important in communication. By listening, the listener is able to interpret and understand what the speaker is trying to input to the listener. In order for the listener to get the information more effectively, the listener should not hog the conversation but should pay careful attention to the person talking. The listener also should use reflective listening and paraphrasing skill to respond back to the speaker. If ever the listener wants to give any feedback, the listener should give the feedback in a competent manner. However, listening is not the same as hearing. Listening means paying attention not only to the story, the use of language and voice, and hoe the other person uses his or her body. Adults spend average of 70% of their time some of communication, of this average of 45% of their listening compare to 30% speaking, 16% reading and 9% is writing. (Refer below figure 3.0) 3.3 Self-Disclosure The communication for self-disclosure is defined as a psychological term as sharing with someone information which helps them understands you. Moreover, for the several important factors that influences self-disclosure and the state of the relationship involve that speak for yourself offer your own thoughts, feeling and opinions. Use sense describes what we see, touch, taste and smell. Additionally, describe what you are feeling and what you do and how you behave. It is important to note that self-disclosure should be voluntary process. 3.4 Conflict and Assertiveness As you become more assertive, there are four basic ways to resolve conflict that is aggressive, manipulative, passive and assertive. The goal of aggressive behavior is to gain control or power. When you are aggressive, you express needs and want freely but in a hostile, tactless, or angry manner. For the manipulative refers to making attempts at indirectly influencing someone elses behavior or actions. As human beings, our emotions often cloud our judgments making it difficult to see the reality behind hidden agendas or motives in different forms of behavior. The controlling aspects or shrewdness linked to manipulation are sometimes very subtle and may be easily overlooked, buried under feelings of obligation, love, or habit. In this article youll learn some ways to pick up on manipulative behavior occurring around you, so that you can sort it rather than jump to it. Furthermore, the goal of passive behavior may result in a persons rights being violated. The passivity may consist of hesitant speech, and avoidance of eye contact. Passive behavior usually reflects the underlying belief that ones feelings arent important, or that one is too weak to act on those feelings. Lastly, the goal of assertive behavior is to resolve conflicts in a way that is satisfying for both you and others. When you are assertive, you express problems, feelings, needs, and wants in a way that is both self-satisfying and socially effective. 3.5 Gender and Verbal Communication Every race, culture, civilization, and society on this planet shares two things in common: the presence of both men and women, and the need to communicate between the two. Gender and verbal communication is how each biological sex use verbal communication. There are many differences in how of both men and women, and the need to communicate between the two. Men are found to speak more in general as women are found to speak more in detail and specific. For example, if a friend has a nice house, a man would say, This is a nice place. A women would say, This is such a nice place, the kitchen is nice, living room so huge, and the bathroom also neat. An experiment had shown verbal communication of both genders to be affected as early as birth and these differences last until passing away. Barriers of Communication There are many reasons why interpersonal communications may fail. In many communications, the message may not be received exactly the way the sender intended and hence it is important that the communicator seeks feedback to check that their message is clearly understood. There exist many barriers to communication and these may occur at any stage in the communication process. Barriers may lead to your message becoming distorted and you therefore risk wasting both time and money by causing and misunderstanding. Effective communication involves overcoming these barriers and conveying a clear and concise message. Moreover, a categories of language barriers to communication include that clearly, language and linguistic. Nevertheless, even when communication in the same language, the terminology used in a message may act as a barrier if it is not fully understood by the receiver. Conclusion Effective of communication is a major part in achieving your educational goals. Effectively communicating with your teachers and peers is essential when it comes to your learning. Many times your instructor is the sender. Her job is to send you messages that include information about the skill you need to learn. Your instructors messages might include lectures or handouts for you. Your peers can also be the senders of a message. Many times learners are asked to work together as a team. You might be asked to work on a specific activity that would require you to receive messages from other team members or an appointed leader. Sometimes you may be asked to be the sender. Remember that communication involves speaking, listening, and observing. Communication is a two-way process that involves getting your message across and understanding what others have to say. Communication involves active listening, speaking and observing. Now that you have learned the communication process, you can begin to evaluate your communication skills. Begin to watch yourself in action. Each time you communicate observe what you do, how it went, what went well, and what could have been better.

Septic Shock Case Study: Causes and Effects

Septic Shock Case Study: Causes and Effects Introduction Septic Shock is a serious circulatory disorder often characterised by a whole- body inflammatory state and the systemic response to infection (Titheradge, 1998), with the most common cause being the contamination of blood with bacteria. Septic shock is defined as sepsis with hypotension which develops in almost half of all septic patients as a complication with a mortality rate of 40-60% (Titheradge, 1998). Septic shock often results in a progressive failure of the circulation to provide blood and oxygen to vital organs of the body resulting in impaired tissue perfusion and oxygen extraction (Thiemermann, 1997). The key symptoms include a severe fall in blood pressure (hypotension) with hypo-reactivity to vasoconstrictor agents (vasoplegia) which may lead to the dysfunction or failure of major organs including lungs, liver, kidneys and brain (multiple organ dysfunction, MODS) and ultimately death (Goligorski et al., 1997). Presently it is widely assumed that septic shock rarely shows similar symptoms in affected individuals and therefore it is difficult to detect and then consequently treat it (Groeneveld and Thijs, 1986). It is, however, also agreed that most of the therapeutic interventions invariably focus on the primary aim of fighting the refractory hypotension by the use of aggressive fluid infusions, glucocorticoids, large doses of vasoconstrictors (Baumgartner and Calandra, 1999) and occasionally renal replacement therapy (Wheeler Bernard, 1999). Yet these interventions do not offer consistent success (Parratt, 1997). In recent times, our understanding of the pathophysiology of septic shock has developed significantly through experimental and clinical trials, though the discovery of a suitable treatment with therapeutic efficacy is proving elusive (Baumgartner and Calandra, 1999). This is probably because of the heterogeneity of the clinical situations and the differences in host response to i dentical pathogens. Moreover evidence suggests that different pathogens which cause septic shock respond differently to the conventional treatments. Still, no effort has been made to treat patients according to the nature of the infecting organism (Gao, Anonymous, 1992). During the early 1990s nitric oxide (NO) emerged as a potentially substantial step towards the treatment of septic shock. This finding directed scientists to carry out numerous clinical trials and animal experiments with the objective of finding out more about the interrelation of NO and Sepsis (Cobb, 1999; Kilbourn, 1999). Later, the discovery of nitric oxide synthase (NOS) made this enzyme the primary target of therapeutic agents (Rosselet et al., 1998). However, recently a substantial amount of literature has been published with evidence contradicting the discoveries of earlier studies. Today more than a decade has elapsed without any resolution to the matter and even in this 21st century Septic Shock is invading the developing countries rapidly (Cobb, 1999; Kilbourn, 1999). This problem of a lack of significant advances in this field can be highlighted by the fact that 17 years have passed since the final publication of the Consensus Conference on sepsis and sepsis related syndromes (Rangel-Frausto, 2005). This paper conclusively defined sepsis and its symptoms with the hope of finding a suitable treatment in order to eradicate the disease (Rangel-Frausto, 2005). Today, however, the situation has not changed significantly with up to 750,000 new sepsis cases every year and 215,000 annual deaths in the United States (Trzeciak et al., 2008, Mitchell M. Levy, 2007). Additionally, in the population that survives such attacks, there is considerable morbidity with many scoring low in health related quality of life assessments (Kaarlola et al., 2003, Perl et al., 1995). Hence the 5 million lives campaign instigated by the US Institute of Healthcare Improvements, aims to minimize the prevalence of nosocomial sepsis (sepsis originating in a hospital) (Gao et al., 2008). This campaign aimed specifically at increasing safety and transforming the quality of hospital care (McCannon et al., 2007). Moreover, the Surviving Sepsis Campaign aims to improve the quality of life of septic patients using the best evidence available currently (Dellinger et al., 2004). Though the world mortality rates have declined in recent times, sepsis is gradually becoming more prevalent in the elderly in the developing countries (Gao et al., 2008).This is mainly due to the extended longevity of patients with chronic illnesses, the increased occurrence of immunosuppression, and the more frequent use of invasive procedures (Bone, 1991; Parrillo, 1993). Sepsis, severe sepsis, septic shock and multiple organ failure still dominate the mass cases of non coronary intensive care units (ICUs). This essay will attempt to explore the fundamental mechanisms leading to tissue and organ damage in septic shock through the investigation of a case study. Following this, the discovery and general biology of nitric oxide (NO) shall be discussed, and the experimental evidence implicating NO as an effector in sepsis, will be examined in detail. The results obtained from various pharmacologic interventions directed at NO in animal studies will also be considered. This report will also give an account of conventional and innovative treatments for the management of septic shock. Finally, data from the few available relevant clinical trials will be reviewed and possible future avenues of interest will be discussed. Systemic Inflammatory response syndrome and Septic Shock (Clinical Manifestation) Sepsis, severe sepsis and septic shock were inaccurately defined until a recently reviewed consensus conference in 1992 (Bone et al., 1992, Dellinger et al., 2004). In this meeting the term systemic inflammatory response syndrome (SIRS) was invented insinuating a clinical response arising from a nonspecific tissue damaging event (insult) (Rangel-Frausto, 2005). Sepsis as mentioned earlier is the result of substantial release of inflammatory mediators in response to an infection. However, often the same mediators are released in the absence of a documented infected in several medical conditions such as cardiopulmonary bypass (Wan S. et al., 1997), pancreatitis and trauma (Shanley TP. et al., 2006). Due to this, the early definitions of sepsis or septic shock were found to be misleading hence a North American consensus conference proposed a new terminology. In this conference sepsis was defined as a condition in which critically ill patients meet criteria for SIRS, in the context of infection. SIRS was defined as two or more of the following: 1) heart rate >90/min; 2) temperature >38Â °C or 12,000 or 20/min or a PCO2 3.5 L min-1 M-23; 2) hyperglycaemia (plasma glucose >120 mg/dL) in the absence of diabetes; 3) significant oedema or positive fluid balance (20 mL/kg over 20 h); 4) inflammatory variables: plasma C-reactive protein >2 SD above t he normal value or plasma procalcitonin >2 SD above the normal value and 5) mixed venous oxygen saturation (SVO2) >70% . (Dellinger RP et al., 2004). SIRS is generally not considered as a disease and its recognition does not provide any clinical conclusion. However, since it has proven to be a very useful for the identification of sepsis and its sequelae namely severe sepsis and septic shock it is regarded as a very important tool (Shanley TP. et al., 2006). Case Study: A 3-year-old boy was admitted to the intensive care unit because of fever, hypotension, and lethargy. A purpuric rash was noted on his arms and legs. Arterial blood gas analysis demonstrated hypoxemia and metabolic acidosis. The arterial lactate level was 10 mmol/L. He was intubated, resuscitated with crystalloid solution, started on broad-spectrum antibiotic therapy, and given dopamine to maintain a MAP above 55 mmHg. His chest radiograph revealed bilateral interstitial-alveolar infiltrates with a left sided predominance. Gram stain of the cerebrospinal fluid showed gram-negative cocci. The dopamine infusion was increased to 18Â µg kg-1min-1 for persistent hypotension and oliguria. Pulmonary and radial arterial catheter data yielded the following blood pressure, 85/30 mm Hg; MAP, 48 mm Hg; heart rate, 140 beats per minute; CVP, 10 mm Hg; pulmonary artery pressure, 22/14 mm Hg; PCWP, 12 mm Hg; cardiac index, 2.5L min-1m-2; and SVRI, 1226 dyne-sec-cm-5m-2. The boy was treated with ad ditional saline and an epinephrine infusion, which increased the MAP, cardiac index, and urine output. Arterial lactate levels decreased over the next 12 hours. Subsequent cultures of blood and cerebrospinal fluid grew Neisseria meningitidis. In this case the patient with acute organ failure and hypotension was diagnosed with septic shock. The young boy with meningococcal septic shock had a borderline-low cardiac index. Due to this a decrease in the cardiac index in this patient by the administration of an NOS inhibitor might not be desirable. This is suggestive of the fact that NO or its synthesising means cannot always be targeted in order to battle septic shock. I will attempt to go into further details with regards to this statement as we go along the essay. Nitric Oxide discovery: Joseph Priestly first identified gaseous NO in 1772. NO also named Nitrogen Monoxide is a very simple and tiny molecule consisting of one nitrogen and one oxygen molecule. Unknown of its fundamental physiological roles in the mammals, until the 1980s NO was widely considered as a mere toxic atmospheric pollutant (Konstantin J. Ovodov et al., 2000). In the 1980s researchers were examining how blood vessels expand (dilate) hence regulate the mean arterial blood pressure. Dilation of blood vessels, also termed vasodilation is a very important physiological response which partly regulates the blood pressure. By increasing the diameter of blood vessels, vasodilation causes the blood to travel more freely due to lower resistance (RF Furchgott, 1980). Since the blood vessel lumen widens during vasodilation, the blood imposes less outward pressure on the vessel wall hence reducing the blood pressure. In opposition, vasoconstriction reduces the diameter of the lumen increasing the BP. These physiological responses occur all the time in the human body regulating the BP and therefore are one of the most fundamental mechanisms of the human body. Dr Robert Furchgott and his group, later in 1980s investigated the role of acetylcholine in the smooth muscle relaxation and found that relaxation only occurred if a special class of cells called endothelial cells were present (RF Furchgott, 1980). These cells line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Behind the endothelial cells are the smooth muscle cells which either relax or contract thus regulating the vascular tone (RF Furchgott, 1991). The same research group also discovered that smooth muscle were only able to vasodilate the blood vessels in the presence of endothelial cells. This indicated that there was some kind of factor that was being released by the endothelial cells which was involved in the dilation of the blood vessel. This factor was named Endothelium Derived Relaxing Factor (EDRF) and subsequently specified as NO (S Moncada et al., 1997). In 1977, Ferid Murad independantly investigated the mechanism of action of nitroglycerin and found that it worked by inducing the release of NO which in turn was able to cause relaxation of smooth muscle cells (F Murad et al., 1977). Louis Ignarro in 1986 finally resolved the whole perplex of EDRF and NO by declaring that EDRF was in fact NO. It was stated that both molecules showed identical properties when he compared gas Nitric Oxide and EDRF (Ignarro, L. J. Et al. 1987). In 1998, Nobel Prize in Physiology and Medicine was awarded to Drs. Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries that vascular endothelial cells make nitric oxide (NO) and that such endothelium-derived NO stimulates cyclic guanosine monophosphate (cGMP) synthesis in the underlying vascular smooth muscle, causing relaxation (Kilbourn, 1999). Since the discovery of NO, vast number of its physiological roles in normal conditions have been reported including in the immune system, nervous system, reproductive system and other cellular functions. It has also been found to play important roles in variety of species ranging from mammals, to insects and plants. Role of Nitric Oxide in Biology Since it was first discovered to play a role in the dilation of blood vessels many new roles for Nitric Oxide (NO) have been discovered. In human body, NO is metabolised by its diffusion into red blood cells where it oxidizes the ferrous iron of oxyhemoglobin yielding methemoglobin and nitrate ions (NO3-) (J.M. Hevel et al., 1994 and Konstantin J. Ovodov and Ronald G. Pearl, 2000). This meachanism limits local NO build up and is particularly important in keeping NO concentration in naomolar range, at least in nonhydrophobic compartments (i.e. outside cell membranes) (Beckman Koppenol, 1996). Nitric oxide has been found to be produced by effectively every cell type in vivo and plays an important role in both controlling the normal function of cells as well as in regulating larger scale processes such as the reproductive, immune and nervous systems. A few of these biological functions for NO are described in more detail below. The Immune System Nitric oxide plays many important roles in the immune system although it is expressed in many cell types following endotoxin or pro-inflammatory cytokine treatment (C. Nathan et al., 1991 and R.G. Knowles et al., 1994). NO, in immune system, is produced in high amounts from specific cells called macrophages. Proceedingly to an infection, chemicals known as cytokines are release in vivo which activate the cells of the immune system such as macrophages, and help guide them to the site of infection (S. Moncada et al., 1991 and C. Nathan et al., 1991). NO produced by the macrophages is toxic to the bacteria and play an important role in their destruction (Fig 1). The production of nitric oxide in this way also helps protect against other types of infection including parasites and viruses (S. Moncada et al., 1991). However, too much nitric oxide production can not only lead to septic shock but has also been implicated in conditions where the immune system is too active autoimmune diseases like arthritis (Jang D and Murrell G A, 1998). The Nervous System Nitric oxide has been shown to be involved in both the peripheral and central nervous system. The three nitric oxide producing isotypes of enzyme (iNOS, eNOS, nNOS) (see section) in humans, one isotype (neuronal NOS (nNOS)) is found almost exclusively in the nervous system (Forstermann et al., 1995). nNOS is thought to be involved in promoting the transfer of interneuronal nerve signals. This is thought to take place by the stimulation of exocytosis (release) of endogenous chemicals called neurotransmitters of one neurone (Moncada et al., 1991; Forstermann and Kleinert, 1995). These NT then diffuse across the synaptic cleft (gap between neuronal terminals) and stimulate the neighbouring nerve cell terminal to transmit the signal (Otto Loewi, 1961). NO has shown to play a substantial role in diseases of the nervous system like Alzheimers and Parkinsons. In both diseases, the inhibition of NO has shown to slow down the progression of the disease in mice (Weill Cornell Team, 2005 and Jo hns Hopkins et al., 2004). Reproductive Biology Nitric oxide is one of the most important molecule in the course of reproduction and is involved in many aspects of it. As well as dilating the blood vessels and thereby helping to regulate maternal blood pressure, NO is also involved in implanting the early embryo in the uterus (Rogers, 1995). During pregnancy, nitric oxide is also suggested promote angiogenesis (a process in which new blood vessels are formed) (RayChaudhury et al., 1996). It is also known to play a role in the survival of trophoblasts (form placenta) (Enders et al., 1978). Furthermore deficiency of NO has been found in patients with preeclampsia (a medical condition in pregnancy) suggesting its partial role in growth of embryo (Yallampalli et al., 1994; Liao et al., 1996). In addition, drugs (Viagra) used to treat erectile dysfunction also affect nitric oxide signalling. Cellular function A notable number of cellular activities can be controlled by nitric oxide including cell division, cell movement and cell survival. The majority of cells in human body have the ability to undergo programmed cellular death. This is a self-destructive mechanism usually called apoptosis which often occurs when a cell is damaged and beyond repair, infected with a virus, or undergoing stressful conditions such as starvation (Kerr et al., 1972). Cells in these conditions go through apoptosis so that they dont hinder the proper functioning of the rest of the tissue. During apoptosis, the structures of the cell break down in an organised manner, forming a packaged cell that is smaller in size so that it can be easily removed by the cells of the immune system (Kerr et al., 1972). Nitric oxide was first shown to inhibit apoptosis hence promoting cell survival in human B lymphocytes (Mannick, J. B. Et al., 1994). Subsequently similar finding were reported in an ample number of other cells. However, high doses of nitric oxide also have deleterious effects. They can be toxic to many cell types and can lead to septic shock and multiple organ dysfunction syndrome (MODS) in which case NO causes cell death instead of promoting cell survival (Beal Cerra, 1994). Nitric Oxide and Inflammation (Pathophysiology of septic shock) This section will deal with mechanism by which wall fragments of Gram-negative or Gram-positive bacteria and other inflammatory agents induce nitric oxide synthase (iNOS) in cells and tissues. Exogenous toxins which enter the circulation stimulate the synthesis and release of a number of endogenous cytokines. During a gram-negative infection which can lead to septic shock, lipopolysaccharide (LPS) and endotoxins present on bacterial wall and many other inflammatory agents bind to a co-receptor (CD14) on the surface of specific immune cells like macrophages, resulting in their activation (J.C. Lee et al., 1996). LPS also bind to LPS-binding proteins which are produced by the liver. These proteins facilitate LPS binding to the CD14 co-receptor of the macrophages. The CD14 co-receptor is activated through the binding of LPS to a toll-like molecule (TLR4), (Re F, Strominger J. Et al., 2001) which is responsible for initiating the transmembrane signaling. TLR2 molecules act in the same way as TLR4, (Leppper PM et al., 2002) though; these are activated by gram-positive bacteria, mycobacteria and yeast. Gram-positive bacteria such as Staphylococcus aureus have further additional wall fragments such as peptidoglycan (PepG) and lipoteichoic acid (LTA). Both PepG and LTA have been shown to synergise to produce the characteristic features of septic shock, MODS and ultimately death in rodent models (S.J. De Kimpe et al., 1995 and G.M. Millar et al., 1997). These effects were not observed with either LTA or peptidoglycan alone, although high doses of LTA can cause circulatory failure but not MODS (S.J. De Kimpe et al., 1995). Gram-positive bacteria may also release other enterotoxins and exotoxins, for example toxic shock syndrome toxin 1, which are involved in the pathogenesis of sepsis (reviewed in (R.C. Bone et al., 1994)). The additional fragments released by Gram-positive bacteria bind to unknown receptors however, like LPS binding, cause the release of proinflammatory cytokines TNF-a, IL-1ß, and IFN-? (Thiemermann, 1997, Titheradge, 1999). These cytokines as well as IL-6 are often produced in response to immune stimulation of macrophages and monocytes hence also in septic shock patients. IL-1 and TNF each occur in two forms, a and ß. TNF- a and both forms of IL-1 are made by activated monocytes and macrophages, whereas TNF- ß is made by activated T lymphocytes (Review by J. Saklatvala et al., 1996). There are two receptors for both IL-1 and TNF and the two forms of each cytokine interact with the same receptors. IL-1 a and ß interact with the type 1 IL-1 receptor for signal transduction, whereas type II does not appear to transmit any signal and functions as an inhibitor of IL-1 action (J. Saklatvala et al., 1996). The two types of TNF receptor, p55 (type I) and p75 (type II) have different end effects; p75 mediates the proliferative actions of TNF- a while p55 receptor signals the inflammatory response and apoptosis (J. Saklatvala et al., 1996). Complex interactions between these different mediators produce intense pathophysiological modification, which eventually lead to diffuse tissue injury and ultimately sequential system failure (multiple organ dysfunc tion syndrome), which accounts for the majority of deaths among patients with sepsis, severe sepsis and septic shock (Beal Cerra, 1994). IL-1ß and TNF-a have a very short half life compared to IL-6 and therefore IL-6 is a very good indicator of cytokinemia. The initial studies of septic shock, showed a very strong positive correlation between IL-6 levels and fatal outcome (Casey L. Et al., 1993). NO is equally a very short lived molecule with an estimated in vivo half life of only 0.1 seconds hence again it is hard to measure its levels in order to detect the severity of cytokinemia hence the severity of sepsis or septic shock. There are several molecules that contribute to the pro and anti-inflammatory responses in septic shock (Table 4); however I shall only focus on a few due to the limited word allowance. In response to inflammatory agents in septic shock, the released cytokines (TNF-a, IL-1ß, and IFN- ?), bind to their specific receptors activating a protein kinase called tyrosine kinase leading to both the activation of the nuclear factor-kB (NF-?B) (a transcription factor) and the phosphorylation of intracellular protein (Gao et al., 2008). A precise mechanism by which these cytokines act was proposed by J. Saklatvala et al. in 1996 however this has yet to be confirmed. Nitric oxide producing cells contain I-?B which is an inhibitor of NF-?B. For the activation of NF-?B, proteolytic cleavage of I-?B from NF-?B is required which forms NF-?B. This biological change allows the activated NF-?B to translocate to the nucleus, where it binds to the promoter region of the iNOS gene inducing transcription. It has also been reported to induce other inflammatory agents, such as cytokines and leukocyte-endothelial adhesion molecules (Janssen-Heininger et al., 2000). Tyrosine kinase present inside the cell acts as a messenger molecule involved in the proteolytic cleavage of I-?B/NF-?B and hence in the activation of NF-?B and iNOS expression (Hecker M, et al., 1996). In septic shock, the translated products of iNOS mRNA subsequently assemble forming the iNOS protein which in turn causes local NO proliferation (Thiemermann, 1997). Fig 2 shows the signal transduction pathway of iNOS expression in response to inflammatory agents. The physiological role of iNOS is to enhance the formation of NO (due to iNOS activity), which in turn may contribute to either the pathophysiology of septic shock (clinbical symptoms) or the host defence (Reviewed in Gao et al., 2008). Fig 3 shows a simplified schematic of the Anti Inflammatory cascade in the context of septic shock. Excess NO produced by iNOS has been reported to both induce and inhibit NF-?B (Kalra et al., 2000; Umansky et al., 1998). In year 2000, it was proposed that low levels of NO may induce further NO production while high concentrations do the opposite exhibiting a feedback mechanisms that would oppose the over expression of genes regulated by NF-?B (Janssen-Heininger et al., 2000). In addition NO at high concentrations competes with O2 at the active site of NOS, thus providing a feedback mechanism of its own synthesis (Griscavage et al., 1995; Rengasamy Johns, 1993). Biological Synthesis of Nitric Oxide (Nitric Oxide Synthases) NOS structure and substrates for NO production: In mammals, NO is exclusively formed from the enzymatic oxidation of one terminal guanidino nitrogen of the amino acid L-arginine. When expressed in moles, this reaction utilizes 1 mol each of arginine and O2, and 1.5 mol of NADPH, yielding 1 mol of NO, 1 mol of L-citrulline and 1.5 mol of NADP (R.G. Knowles et al., 1994). The reaction sequence involves the generation of an Ng-hydroxy-L-arginine intermediate, followed by the oxidation of Ng-hydroxy-L-arginine in presence of molecular oxygen to form L-citrulline and NO (Dennis J. Stuehr et al., 1991 and R.G. Knowles et al., 1994). The enzymes that accelerate the reaction above are a family of relatively large heme proteins known as NO synthase (NOS) which resemble cytochrome P450 structurally (M. M. Chan et al., 2001 and Francois Feihl, 2001) (The general mechanism of NO production from NOS is illustrated in Fig 4). All members of this family share a similar homodimeric structure, where each monomer consists of a an oxygenase domain and a reductase domain, separated by a short amino acids (30aa) sequence for the attachment of the Ca2+-binding protein calmodulin. In addition to calmodulin attachment, enzymatic activity requires the presence of four cofactors: FAD, flavin mononucleotide (FMN), tetrahydrobiopterin (BH4), and heme (Francois Feihl, 2001). Fig 5 shows the general structure of the NOS enzymes. Nitric Oxide Synthase isoforms and their locus in the Human Body: There are three known isoforms of NOS, each the product of a different gene: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2), and endothelial NOS (eNOS or NOS-3). nNOS and eNOS were first described in rat cerebellum and bovine aortic endothelial cells, respectively, but their tissue distribution is far wider than suggested by their names. eNOS and nNOS are involved in regulating vascular tone (R.G. Knowles et al.,1992 and S. Moncada et al., 1991) and neurotransmission respectively, whereas iNOS is involved in the immune defence although it is expressed in many cell types following endotoxin or pro inflammatory cytokine treatment (R.G. Knowles et al., 1994). nNOS is typically expressed in skeletal muscle and myenteric plexuses. eNOS is ubiquitous in vascular endothelium, but may also be found in the kidney tubular epithelial cells, placenta (Forstermann et al., 1995), and neurons (Nathan Xie, 1994). In these tissues, the expression of nNOS and eNOS is constitutive, although it may be regulated (Michel Feron, 1997). For instance, the levels of transcript for eNOS in vascular endothelial cells is increased by shear stress (Topper et al., 1996; Uematsu et al., 1995) and exercise (Wang et al., 1997), reduced by inflammatory stimuli such as TNF-a (Nathan Xie, 1994) and variably affected by hypoxia (Le Cras et al., 1998; Toporsian et al., 2000). In the physiological state, the iNOS isoform is only present at a few locations, notably the respiratory epithelium, the gravid uterus (Nathan Xie, 1994), and perhaps the ileal mucosa (Hoffman et al., 1997). iNOS expression has been demonstrated in numerous cell types including macrophages, neutrop hils, vascular endothelial (Hoffmann et al., 1999), smooth muscle cells, endocardium, myocardium, fibroblast, mesangial cells, renal tubular epithelium (Kunz et al., 1994), neurons, hepatocytes, pancreatic islet cells and astrocytes (Nathan Xie, 1994). iNOS can be induced by a number factors including UV light; cyclic AMP-elevating agents; trauma; ozone and bacterial products described earlier (see section). On the other hand, many endogenous agents may oppose cytokine induction of iNOS. These include anti-inflammatory cytokines such as IL-10, chemokines such as monocyte chemoattractant protein-1 and growth factors such as tumor growth factor-ß (Forstermann et al., 1995). In all NOS isoforms, calmodulin binding is an absolutely vital for enzymatic activity. In the cases of eNOS and nNOS, this binding necessitates relatively high concentrations of Ca2+ (see Fig 7), in the range of 0.1-1 mM (Forstermann et al., 1995). In contrast, iNOS is able to bind calmodulin virtually independ ant of Ca2+ (Table 2). Therefore, once iNOS is expressed, NO synthesis may only be limited by the availability of substrates and cofactors (J. Stuehr, 1990). As NO produced from iNOS predominantly depends only on iNOS expression, it lasts much longer than NO formed from the other isoforms of NOS. In addition iNOS produces much higher concentrations of Ca2+ compared to the consecutive forms of NOS (Cobb et al., 1996). The production of NO by eNOS and nNOS, compared to iNOS, can be controlled relatively easily by decreasing or increasing intracellular Ca2+, whereas iNOS can only be controlled through transcription (Cobb et al., 1996). In most cell types iNOS protein levels are either very low or undetectable. However, stimulation of these cells by cytokines or growth factors, can lead to increased transcription of the iNOS gene, with subsequent production of NO. On the other hand, for the prevention of iNOS expression through endotoxins, TGF-ß (Szabo, 1995) and anti inflammatory gl ucocorticoids can be administered which lower the magnitude of vascular hyporeactivity. Glucocorticoids such as Dexamethasone inhibit iNOS activity by blocking arginine transport and inhibiting tetrahydrobiopterin biosynthesis (A.J.B. Brady et al., 1992 and Thiemermann C et al., 1993). Regulation of NO production In the normal as well as in extreme physiological states (e.g. during infection), nitric oxide is considered as one of the most important signalling molecules in vivo. It is however also highly reactive and highly diffusible due to it being a free radical (one unpaired electron) (see fig 8). It is therefore important that there is strict control and regulation of nitric oxide production. The synthesis of NO within cells can be regulated in several ways such as the cellular distribution of NOS, changes in NOS gene expression, enzymatic activation by phosphorylation and the presence of cellular inhibitors NOS activity. Intracellular distribution of NOS Nitric oxide is principally regulated through strict control over the location of NO production. The NOS isoforms can be targeted to different regions of the cell, where NO will be produced in close contact with its target proteins. The image below shows the distribution of iNOS (shown in green in image 1) and eNOS (shown in red) in a trophoblast cell. The nucleus is shown in blue. Co-localisation between iNOS and eNOS will show up as a yellow colour (Phil Dash, University of Reading). The image shows that eNOS and iNOS are fairly variably distributed inside the cell, with hardly any yellow colour suggesting very little overlap in their cellular distribution (Phil Dash, University of Reading).Although both iNOS and eNOS produce NO it is likely that their different cellular distribution will lead to NO interacting with different targets and therefore having different effects (Phil Dash, University of Reading). It is very likely that the distribution of NOS isoforms is an important mechanism for regulating when and where NO is produced. Therefore the current research on NOS mainly focuses on how endogenous signals trigger NOS transport and redistribution (Rahul S. Koti et al., 2005). Activation of NOS activity NOS enzyme synthesis is principally regulated by changes in intracellular calcium levels. The constitutive isoforms of NOS, (eNOS and nNOS) have shown to proliferate following increases in Ca2+, and therefore calmodulin levels, in the cell (Rameau et al., 2003). Additionally both nNOS and