Pick a controversial topic Essay Example | Topics and Well Written Essays - 750 words

Pick a controversial topic - Essay Example However many of these criminals are violent and have committed depraved murders without regard to their victims and their families. In these instances the death penalty may be an appropriate punishment. According to the Amnesty International website â€Å"The death penalty is the ultimate denial of human rights. It is the premeditated and cold-blooded killing of a human being by the state.† (â€Å"Abolish the Death Penalty†) The site claims that in 2011 there was an international movement toward abolishing the death penalty completely. It also has indicated aside from the United States only 20 regularly imposed the death penalty in murder cases. There are several articles found on the site which describe their efforts to ban the death penalty. For example in the article â€Å"Iran must halt executions amid fears of new wave of death penalties† it stated that Amnesty International asked Iranian authorities to put a stop to upcoming executions because many other Iranian prisoners may be at risk for execution pertaining to drug crimes without a fair trial. Amnesty International is calling for a stop to these executions until allegations of torture and other illega l practices perpetrated by Iranian authorities can be investigated. In a 2007 Washington Post article author Martin O’Malley discusses his reasons for believing that the death penalty should be abolished in his home state of Maryland. He indicates that it is not the most effective punishment for murder and does not necessarily discourage other people from committing murders. He cites the example of a case of a Maryland man who randomly shot and killed three teens. This person expressed no remorse and stated that he would do it again if he could. (O’Malley) He was eventually executed. However O’ Malley questioned whether or not the execution was appropriate retribution for the murders since the killer welcomed execution. O’ Malley also cites an example of another man who was

Marketing Management Strategic Issues Blue Dart Express

Marketing Management Strategic Issues Blue Dart Express On a beautiful sunny afternoon in April 2012, Ketan Kulkarni, Vice President and Head of Blue Darts Marketing, Corporate Communication Sustainability division, was waiting in the plush conference room of Blue Darts head office in Mumbai. As he waited for Tulsi Mirchandaney, Managing Director and Accountable Manager for Blue Dart Aviation, he once again looked at the notes on proposed future plans of marketing strategy and wondered whether the companys plans to address the intense competition will be enough to meet 2012s target. Looking outside through the clear windowpanes, Ketan thought about remarkable journey of Blue Dart. Blue Dart was the leading express company in India, engaged in door to door pick up and distribution of packages, documents, and shipments in India and overseas. From its inception in 1984, in its first decade Blue Dart became the dominant player in the courier industry and in the next decade it surpassed all the competition and became South Asias premier number one express company in air and integrated transportation, distribution and logistics. In India, Blue Dart was the only company providing an array of services in air express (both domestic and international through DHL), air freight, ground and charters. It was a one stop solution for any logistical requirement. Blue Dart enjoyed a 45.9% market share and gained a significant increase in both, volumes and value. In the ground segment, the company garnered a market share of 12.4%. Blue Dart not only offered secure and reliable delivery of consignments, but also managed to deliver impressively on the financial front with the help of its widespread infrastructure network and aggressive growth strategies. Rs.10 billion in annual revenues is a remarkable landmark for any logistics company. Blue Dart managed better, leaping over the 11-digit barrier to record Rs. 14.89 billion in top line during FY2011. The company was established with a vision to be the best and set the pace in the express air and integrated transportation and distribution industry, with a business and human conscience. A people-first company, Blue Dart continued to deliver value to its stakeholders through its people philosophy and corporate governance, based on distinctive customer service, business ethics, accountability and profitability. Blue Darts core competence lies in the business of superior express delivery services, maintaining reliability levels of 99.96%. With a dedicated air and ground network optimized by cutting-edge technology, Care Customer Addition, Retention Empathy summed up the marketing strategy of Blue Dart. Company History In November 1983, three young entrepreneurs, Clyde Cooper, Tushar Jani and Kushroo Dubash identified tremendous opportunities in Indias expanding exports market and came up with an idea of delivering small packages and samples. On that date, Blue Dart was established in a space of 200 square feet under a staircase, with a capital of Rs. 30,000. Grit, determination and hard work would propel the fledgling from sorting and delivering a few dozen packages outside Mumbai airport on that first night, to handling nearly 200,000 shipments each day through rain, hail, earthquake and snow. In a study conducted by Dhristi Strategic Research Services in 2007, Blue Dart emerged as one of the strongest brands in India with amongst the highest top of mind recall. In its early days, Blue Dart forged ties with Gelco Express International, UK to introduce an international air package express service from India and thus enhance the value offered to its customers. In 1993, foreseeing the potential in I ndia, Blue Dart decided to shift focus from international to domestic service. It went on to become the first Indian courier company to conceptualise domestic on-board couriers with a guaranteed 10:30 am delivery to major metros. In 1994, the company went public with an IPO of 2.55 million shares. In the same year Blue Dart launched its multi-modal, premium package delivery service DartApexà ¢Ã¢â‚¬Å¾Ã‚ ¢ (Air Package Express) and COSMATIIà ¢Ã¢â‚¬Å¾Ã‚ ¢, an advanced tracking and ERP system that redefined the industry. In that year, too, Blue Dart Aviation, a 100% subsidiary of Blue Dart Express, was incorporated and became the first private company to receive government approval for the operation of cargo aircraft in the country. In 1995, Blue Dart Aviation acquired two B737 aircraft and developed SMART (Space Management Allocation Reservations and Tracking), the first cargo reservations systems in India. The following year, Blue Dart launched the first jet express airline and also became the first express company to receive an ISO: 9001 Certification. 1995 was also momentous because in that year Blue Dart crossed Rs. 100 crore (US$ 25 million) in turnover for the first time. 1997 witnessed the launch of domestic charter operations and the signing of interline agreements with international airlines for distribution of bonded cargo within Blue Darts network. Today, these have extended to 26 operators and include bonded warehousing and transhipment facilities. In 1998, the company developed Indias first Load and Trim software for its aircraft, reducing handling time by 80%. In 1999, Blue Dart moved to its state-of-the art administrative, technology and operations Super hub and Headquarters, the Blue Dart Centre, in Mumbai. In 2001, a third Boeing 737 was added to the Blue Dart fleet. A year later, Blue Dart entered into a sales alliance with global leader DHL Express Worldwide. Today, DHL owns 81.03% stake in the company. In 2002, Blue Dart was re-certified as one of a handful of Indian companies to the new global ISO 9001 2000 standards for Design, management and operations of countrywide express transportation and distribution service within the Indian Subcontinent and to international destinations serviced through multinational express companies. Blue Dart signed a path-breaking Sales Alliance with the Worlds No. 1 international air express company, DHL Worldwide Express. Blue Dart also crossed 1,00,000 shipments per day. The fourth aircraft joined the fleet in 2004 and Blue Dart became the first private operator in India to receive approval from the Director General of Civil Aviation (DGCA) for undertaking heavy maintenance D-checks on its aircraft. Two B757 freighters the first in the Indian skies joined the Blue Dart fleet in 2006. In an effort to fortify its unique capability of offering the entire gamut of end-to end distribution solutions, Blue Dart launched its ground express service Dart Surface Line in September 2007 and inducted the third B757 freighter. By 2011, Blue Darts infrastructure comprised a fleet of three Boeing 737 and four Boeing 757 freighters operating each night to the 7 main metros in India and offering a revenue payload of over 370 tonnes per night. It owns a flotilla of over 6,272 vehicles, 365 facilities including 7 aviation hubs and bonded warehouses, 56 domestic warehouses and 12 express hubs delivering excellence. Current Operations Blue Dart is the largest player in the domestic segment of documents and non-documents with 26 per cent market share in terms of tonnage. In terms of overall (domestic plus overseas) market share, it is the largest express company in India with a share of about 45.9 per cent. The company had a turnover of Rs 14.89 billion in 2011 and has had an annual growth rate of about 50 per cent while the industry growth rate has been hovering around 35 per cent. Table 1 presents the breakup of revenues and costs for the year 2010-11 (see Exhibit 1). Administratively, the company is organized into regional centres at six major cities namely, Ahmedabad, Mumbai, Delhi, Chennai, Bangalore, and Calcutta. Each regional centre is responsible for a number of branch locations under which there are area locations. The company currently employees around 7,800 people. Each major branch has a team of operations personnel who manage the entire network, transportation and tracking of shipments. They also liaison with airline and transportation agencies and take care of scheduling out-bound couriers. Other responsibilities of the operations department include routing, sorting, security checking, fleet management, and customer billing. Commercial functions like finance and marketing are centralized at the head office in Mumbai. Its international out-bound gateways function at Dubai, Singapore, London, and Mumbai. The in-bound international gateway is at Mumbai which receives packages from London, Frankfurt, Singapore, and Dubai. The Company offers secure and reliable delivery of consignments to over 35,902 locations in India and to over 220 countries and territories worldwide through its integrated air support and ground network group company DHL Express. In 2011, Blue Dart operates through 1,342,677 sq. ft. of facilities and carried over 988.5 lacs domestic shipments and over 8 lacs international shipments weighing over 423,000 tonnes. The core function of Blue Dart is the physical transportation of a shipment from its origin to the destination which is performed by the operations department. The distribution system follows the hub-and-spoke concept, i.e., shipments picked up at a particular origin location are transported to the nearest hub, which in turn routes these shipments to the hub to which the destination location is attached. The destination hub routes the shipment to the specific destination location where the staff deliver the shipment to the consignee. (see Exhibit 2) The Express Industry Addressing a changing market The express industry is a key enabler in facilitating trade and commerce because of the time-sensitive nature of most goods and the increasing demand for reliability, efficiency and speed. The opportunities are aplenty for the express industry in India as the current logistics spend in India is 13% of the GDP compared to a notably lesser percentage of the same in more developed economies. The need for the highest levels of efficiencies still exists. The demand for express services is surging with each passing year and customer expectations have also risen tremendously. Today, the Indian express industry provides integrated, value-added, time-bound, door-to-door delivery of documents, parcels and merchandise. It supports industries such as electronics, telecommunication, IT, banking, retail, auto-components, textiles and apparels, gems and jewellery and pharmaceuticals. Moreover, with India recognized as an outsourcing destination, manufacturing sectors such as textiles, automobiles and pharmaceuticals are likely to witness increased activities in the medium to long term. In order to maintain competitiveness, companies operating in these industries are expected to outsource their logistics requirements to third-party logistics service providers and concentrate on their core-competency of manufacturing and marketing. Besides, the opening up of banking, insurance, telecom and retail sectors would boost the demand for value-added express services in India, as these are major user industries. Anil Khanna, managing director, Blue Dart, conveyed the same sentiment. In his opinion, the growth in the Indian economy and the overall economic scenario, fuelled primarily by domestic consumption, is promising. The Indian economy is poised to record robust growth between 8 and 9 per cent in the financial year 2011-12, the Indian express industry is expected to register double-digit growth over the next few years. This in itself is a strong indicator of the potential of the express industry. The organised domestic air express market is pegged at around ` 1,500 crore, which grew at a CAG R of 7-8 per cent in the last five years, while the domestic organised ground express market is pegged at around 1,700 crore, which grew at a CAGR of 14-15 per cent in the last 5 years, Khanna pointed out. Blue Dart is in the process of rolling out several sector-specific, innovative products and services in a phased manner, in line with specific needs and requirements of different industries. These products provide the much-required flexibility to the shipper and consignee. Some recent additions to the companys product portfolio include Express Pallet, Smart Box: Ground Express, Time Definite Delivery, etc. In its journey of last 20 years, Blue Dart had evolved from a being a document centric service to a critically supply chain support service in. The annual turnover of express industry in India was estimated to be Rs 8000 million in 1994-95. The industry players can be categorized into (i) organized sector, accounting for 50 per cent market share, (ii) EMS Speed Post, accounting for 6.5 per cent, and (iii) the unorganized sector, making up the remaining 43 per cent. The courier industry in India has expanded its horizon to provide a wider range of services. Whereas it started initially as a service provider for the document and samples demand of industry, it is now viewed as an important part of the supply chain for industries, which demand speed, reliability, security and just-in-time distribution, Though this market is still in its infancy in India, it is growing Tulsi Mirchandaney, Senior Vice President, Marketing and Projects Competitive edge: Building IT for Business Agility Companys information technology infrastructure remains one of its key differentiators and enabler to values. Blue Dart was always in the forefront of technology and its technology innovations have played a key role in the companys premium positioning and in bringing global standards to the Indian customers doorstep. Blue Dart has become an important part of the supply chain of many companies by providing integrated services. Blue Darts in-house IT team has constantly developed technology solutions over the past seventeen years. Such has been the ramifications of these offerings that more than 79% of Blue Darts regular customers use it actively. These Home grown innovations include COSMAT IIà ¢Ã¢â‚¬Å¾Ã‚ ¢ (the tracking and ERP system), TrackDartà ¢Ã¢â‚¬Å¾Ã‚ ¢ (monitoring shipment status), MailDartà ¢Ã¢â‚¬Å¾Ã‚ ¢ (tracking shipments over e-mail), InternetDartà ¢Ã¢â‚¬Å¾Ã‚ ¢ (memory bank for shipments), PackTrackà ¢Ã¢â‚¬Å¾Ã‚ ¢ (tracking software for medium and large customers), ShopTrackà ¢Ã¢â‚¬Å¾Ã‚ ¢ (tracking and CRM tool for e-business portals), ImageDartà ¢Ã¢â‚¬Å¾Ã‚ ¢ (online download of proof of delivery challans/documents, to speed up the customers bill process, waybill issuance capability, customer directory, data upload and download of tracking information). The company also provides e conomical packaging that facilitates customers sending documents at a price that includes door-to-door delivery service within India. These innovation solutions have enabled the weaving of thoughtful information management to the logistics business. With this advanced technology support Blue Dart delivers door-to-door to over 13,000 locations in the country with an in-house team of experts to handle inter-state regulatory requirements. Quality levels are at 99.95% and are monitored daily. No one else in the country offers this kind of integrated delivery capability. Marketing Strategies A combination of new product launches and tactical shift in focus across sectors helped Blue Dart register growth in spite of an overall slowdown in the economy. For instance, in order to lessen the impact of the slowdown in client verticals such as automobile and realty, it consciously improved its focus on sectors such as health sciences and the spare parts segment of the auto sector. It also built on its exposure to high-growth segments such as e-commerce and SMEs and high-growth potential Tier-II and III cities this year. These put together helped the company grow its revenues and profits by about 34 per cent and 42 per cent in the nine-months ended September 2011. On various other fronts the company has provided following marketing strategies. Offerings Blue Dart has a range of products and services that can be customised to address individual requirements. Blue Darts core business is domestic door-to-door and integrated (air and ground) express distribution. Each product has been developed with a customer centric approach. A combination of the right product mix and price has helped Blue Dart build a strong brand loyalty over the years. The products are ably supported by cutting-edge technologies. Blue Dart offers express, air freight, ocean freight, supply chain solutions, customs clearance, project handling, freight forwarding, and charters through its synergies with the three DHL Business Units DHL Express, DHL Global Forwarding and DHL Exel Supply Chain. The express services offer domestic priority for non-commercial domestic documents and small packages under 32 kilos. Dart Apexà ¢Ã¢â‚¬Å¾Ã‚ ¢ is a door-to-door, time-definite, supply chain and logistics distribution service for commercial shipments that require regulatory clearance. Smart Box is the convenient door-to-door service for cargo in two sizes 10 kilos and 25 kilos. Freight services include domestic, early morning airport-to-airport deliveries to the seven metros Mumbai, New Delhi, Kolkata, Chennai, Bangalore, Ahmedabad and Hyderabad serviced by Blue Dart aircraft. Charters offer palletised capacity for carriage of urgent and large volumes to eighteen airports in India and four international airports in the region. Blue Dart, in line with its focus on innovation, has also introduced several customised products -Rakhi Express and Student Express, for instance designed to meet specific needs. A recent addition to Blue Darts product portfolio is Import Express. It is the only service of its kind in India and offers door-to-door facility for importing shipments from over 200 countries. Services Blue Dart offers a range of services: Domestic Priority a fast reliable service for non-commercial documents and non-documents. Dart Apex to support reliable commercial distribution and supply chain requirements. Dart Surfaceline a reliable and secure surface option, and an airport to airport option which includes charter of our aircraft for large volumes and urgent shipments. Some of the best services offered by this company are: à ¢Ã¢â€š ¬Ã‚ ¢ Free computerized proof of delivery à ¢Ã¢â€š ¬Ã‚ ¢ Real Time tracking à ¢Ã¢â€š ¬Ã‚ ¢ Regulatory clearance à ¢Ã¢â€š ¬Ã‚ ¢ Free pick up from the location of the customer How does your service differ from competition? What added advantages do you provide your clients and what kind of message do you aim to send across? Blue Dart offer Solutions for Peace of Mind, and it has built extensively to deliver on that promise. Blue Dart are the only express cargo airline in the country today focused on handling packages. Connecting with Customers In an overcrowded, cluttered world, brand Blue Dart has exploited every opportunity to stand out. The core focus has been on strengthening customer relationship and on making more effective use of the 4800 plus vehicles as mobile touch points. Blue Dart constantly rolls out promotions for its customers to keep them updated on our various offerings. Apart from this, the company keeps on introducing several sector-specific, innovative products and services in a phased manner, in line with specific needs and requirements of different industries like BFSI, Pharmaceuticals, IT, Consumer Durables, FMCG, Automotive, Retail, Textiles, Telecommunications etc. The new initiatives will upgrade the product range and improve service quality, thereby offering customers state-of-the-art air and ground express solutions across the country. These products provide the much-required flexibility to the shipper and consignee. The most used features are real time tracking and Money Back Guarantee (MBG) offered on specific shipments. Company had a dedicated team of specialists who provide the expertise for customs as well as regulatory clearances at all States within the country, to support seamless service to the customer. India is known for its huge section of middle-class buyers. Blue Darts offerings though known to be reliable, are available at a higher price bracket. Isnt this an awkward pricing strategy for the Indian market Considering the fast paced, dynamic lifestyles our customers lead, Blue Dart deliver shipments as well as peace of mind. For our customers, aspects like service quality, consistency, responsiveness and reliability are of paramount importance because these dimensions directly impact their business outcomes. These values make excellent attributes to building a trusted brand. When our customers experience optimal service with Blue Dart, they do not mind paying a premium for our products. Customers Growth Strategy Our growth drivers are multi-dimensional but well defined. Blue Dart will be focusing on existing customers to scale our existing relationship with select high potential clients by offering them a lot more than what Blue Dart have been traditionally offering them. This will not only lead to revenue enlargement, but also give us an army of loyal customers. Positioning Designed to enhance the reliability of our operations and process efficiency, and add value to the customer through time and cost savings. The only one of its kind in the country today, that is focused on carriage of packages as its prime business, rather than as a by-product of a passenger airline. A dedicated aviation system to support Blue Darts services is self-sustaining, with its own bonded warehouses, ground handling and maintenance capability. Blue Dart envisioned itself as a warehouse in the sky creating a niche segment in supply chains that demand critical deliveries, low inventories and reliable and timely distribution. A strategic product mix, optimum utilization of aircraft space and committed people delivering at high reliability levels, Blue Dart is now strategically positioned as the market leader in the air express segment. Blue Darts competitive advantage lies in its vast and unparalleled Domestic Network Linked by some of the most advanced communications systems and positioned to offer a consistent, premium, standardized quality of service. Blue Dart is the only express carrier in the country today which offers an entire range of services that extend from a document to a charter-load of shipments Blue Dart has the only dedicated logistics infrastructure in the country today to provide a variety of logistics solutions for its customers. Blue Dart have an aviation system with an in-house ground handling and maintenance capability to provide confirmed uplift. Blue Dart have invested extensively in technology, currently the most advanced in the he domestic courier industry, for integration, data flow and customer software for greater customer convenience and efficiency. Blue Dart have stringent security and quality norms, our integrated network has the widest reach and our people are skilled and committed professionals. When others in the domain were still trying to find their bearings Blue Dart had already envisioned itself as a warehouse in the sky. It created a palpable differential for itself by arrogating a niche and a hard-to-emulate segment in supply chain management that demanded critical deliveries, low inventories and reliable and timely distribution. Your Company has been able to differentiate itself and has achieved scalability due to its focus on technology right from the early stages of its business. It is reflected in the way the Company moves its products, in a manner which is more cost-effective, more fuel-efficient and more environment friendly. Building strong brand Logistics or Couriers is a service industry where the service is the brand. The attributes of the product are not physically apparent. Demystifying each product to the customer and demonstrating, in simple terms, real benefits meaningful to him, therefore, assumes greater importance. This means translating each customer contact point into an experience representative of the brand. People who serve take on the mantle of the brand as opposed to an FMCG where you would buy your preferred cake of soap regardless of where or how it is served. Promotion Blue Dart is not known to be aggressive advertiser, but as aggressive marketer. Blue Dart has tried to focus on the total customer experience the brand tangibles such as the retail outlets (service counters), vehicles, signages, etc, as well as the intangibles at the customer contact point. Blue Dart has emphasized that the personal touch is essential and thus has also strengthened the areas of customer care centres. Even its TV commercials and print ads try to connect emotionally with customers. Blue Darts promotion method is to create a strong emotional connect with customers, in order to achieve brand strength, saliency and equity. Blue Darts prime communication vehicle is PR land direct mailers, with support from a large sales force across the country to directly engage the customer. Brand Values Blue Dart has always made a conscious effort to create a bond with its customers. Perhaps, because of this, the brand has, today, become synonymous with value, quality, speed, efficiency, responsiveness and service excellence. Financial credibility Fitch Ratings India Pvt. Ltd. has assigned the highest F1+ (Ind)[F one plus (Ind)] rating for their short term debt programme of Rs. 30crores. Further, ICRA Ltd. has also assigned the highest A1+ (pronouncedA one plus) Rating for their Commercial Paper Programme of Rs. 25 crores. New Areas Detecting opportunities vertical wise has helped us device sector specific solutions and this has helped the overall growth strategy of the Company, to a great extent. Demand for streamlined supply chains from the auto, pharma, hitech and retail sectors is expected to drive growth for us. Blue Dart perceive SMEs as an emerging opportunity and efforts have been underway to tap this segment across industry verticals, aggressively. In terms of new customers, tapping new geographies and segments continues to be our key focus area. New Products A combination of the right product mix and price has helped Blue Dart build strong brand loyalty over the years. Launching new products has been our response to any opportunity sensed in a new geography and new industry verticals. This approach has borne fruit. It pleases me to inform you that Blue Dart have successfully launched 25 new services since 2008. Some of our success stories in the Air Express segment include Time Definite Solutions (Domestic Priority 1030, Domestic Priority 1200, Dart Apex 1200) and Day Definite Solutions (Domestic Priority, Dart Apex, Dart Surfaceline). Packaging Solutions include Express Pallet: Air and Ground, Smart Box Air and Ground. The Company also offers Cargo Solutions like Airport to Airport, Interline and Charters besides offering Festive Solutions and discounted Student Solutions. Solutions like Temperature Controlled Logistics (TCL), Dart Surfaceline Plus, Point to Point (P2P) and a host of value added services like Demand Draft on Delivery (DOD), Freight on Demand (FOD), Freight on Value (FOV), Cash on Delivery (COD) etc. represent our tailor made services for specific industry requirements. Blue Dart will continue to focus on reach expansion, transit time improvements, small town (Tier-II and III) activation and strengthening channels. The strategy is in place to strengthen market share and deliver the Blue Dart promise. Achievements Attaining such stunning success wasnt easy. Along the way, Blue Dart endured formidable challenges and took bold steps to protect its hard-fought territorial gains. The list of awards and accolades is endless for Blue Dart. It has achieved many awards in all sectors such as Brand / Customer Service / Retail / Loyalty, Human Resources, Sustainability and Individual Blue Darts services have been recognized and rewarded time and again. Blue Dart was selected as a Business Superbrand from over 1,699 brands and received the Readers Digests Most Trusted Brand Award, for three years in a row and has been listed twice in the Dun Bradstreet top 500 companies in India. Blue Dart has been awarded the NDTV Business Leadership Award 2008 and the Asia Brand Congress Brand Leadership Award 2008. An Indian company benchmarked to international standards, Blue Dart has been recognised as one of the best and has been listed among the top 500 companies in India by Dun Bradstreet. Blue Darts aviation arm received the Centre for Asia Pacific Aviation (CAPA) Cargo Airline of the Year Merit Award in 2006. In the following year, Blue Dart was declared the Best Cargo Airline at the Express, Logistics and Supply Chain conclave. Over the years Blue Dart ha achieved SUPERBRAND Status, 6 times in a row, Pursuing Business growth and Expansion Blue Dart already has an aggressive market share plans which aim to increase its market share both in air and ground express divisions. For this, Blue Dart will have to grow faster than the industry. Blue dart has already identified some growth levers. One of these is adding lot of new products. The company has been regularly introducing new products such as the latest Go Green carbon neutral service and it intends to continue. The other growth lever is the sectoral focus there are certain sectors that do not get impacted by a slowdown sectors like health sciences and the spare parts segment of the auto sector. Third, Blue Dart is focussing on verticals which are high-growth verticals like e-commerce, where in it is targeting a large market share. Moreover, the company has also identified small and medium enterprises (SMEs) as another growth lever. For a company, which has probably focussed more on our large customers, SMEs thus offer an opportunity. Finally, the company is looking at geographic expansion. It intends to reach out to those towns and cities where it currently does not have any presence. Also, prior to this, in smaller cities, the company was more focussed on the in-bound side. It then realised that a lot of these tier-II and tier-III cities have a lot of out-bound potential. These provide additional opportunity for business expansion. Looking ahead Blue Dart Express net profit declines 19.47% in the March 2012 quarter Blue Dart faces the challenges of increase in fuel cost, inadequate infrastructure, and increasing competition. But of these the biggest challenges is Infrastructure of both air and surface. Space at airports, airside and city-side infrastructure are often inadequate. In addition, parking bays, air-side/city-side access and traffic congestion adversely impact costs as well as service quality. Air express companies are constrained by the sizes of the facilities at the airports, as they have remained the same while the loads have increased many folds. It is estimated that though 70% of the freight transportation in India is through roads, National Highways constitute merely 2% of the total road network in India. Fuel prices are also a concern. In an industry, where space is a highly perishable commodity, any disruption in services, due to either natural disasters or manufactured reasons, affects us adversely, as the days capacity inventory is lost forever. Exhibit Financial Summary of the last five years Particulars 2007 2008 2009 2010 2011 Income from Operati

The Concern of Deforestation in Todays Society Essay -- Deforestation

Deforestation is a major concern in today’s society. The destruction of the world’s forest areas are leaving millions of acres uninhabitable. The varied species of animals and insects that use to live and thrive from these forests are rapidly becoming extinct. The destruction of the forest is also having a detrimental effect on the people through displacement thus forcing them to seek new living accommodations. Many of these people are loosing their heritage and cultures leaving them with a sense of hopelessness. The barren land left by deforestation is also causing many ecological problems. Increased flooding and soil erosion are two of the other problems facing several countries like China, Brazil, and the Philippines. To gain a better understanding of the immense significance of this matter perhaps a look at the past, present and future are needed. Deforestation â€Å"Past† Since the beginning of time humans have used nature’s resources to exist. They have hunted for food, drunk the water, used animal hides for clothing and even used the timber for warmth and homes. It was not until the twentieth century that man began to realize the effects of their enormous usage on the environment. Although staples like food and water are a problem in them selves, large-scale logging brought deforestation to the forefront.  · The World Rainforest Movement suggests that Western Europe, for example, has lost over 70 percent of its forests since Roman times and argues that fully one-third of â€Å"temperate broadleaved forests have been lost since the dawn of agriculture† (Elliott, 1998).  · In 1901 President Theodore Roosevelt along with Gifford Pinchot and John Muir wrote the first pages of modern environmental history in the United States by moving environmental conservation to the center of national agenda and declaring public primacy over the nations resources (Shabecoff, 1993).  · In 1933 President Franklin Roosevelt shored up his cousins beliefs in the environment by including major conservation programs and projects such as The Civilian Conservation Corps (CCC), the Soil Conservation Service, and the Tennessee Valley Authority into his New Deal reforms (Theodore, Theodore 1996).  · The President’s Commission on Materials Policy in 1952 estimated that 90 percent of the virgin timber in the U.S. commercial forests had been cut, that reforestation ... ...ces that cause more severe environmental impacts or problems. The unanswered question is weather such a hope is realistic in the face of the impersonal, price-driven forces of global markets and the reality that even the best production processes today still require the use of growing amounts of materials, energy and the continued transformation of the landscape for the expanding human population. References Elliott, Lorraine. 1998. The Global Politics of the Environment. New York, N.Y. New York University Press. Shabecoff, P.A. 1993. Fierce Green Fire. New York, N.Y. Hill and Wang Mercuro, Nicholas. 1997. Ecology, Law and Economics, Lanham, Maryland. University Press of America, Inc. U.S. Council on Environmental Quality. 1990. Environmental Quality 1990. Washington, D.C. Government Printing Office Andrews, Richard N. L. 1999. Managing the Environment, Managing Ourselves. Binghamton, New York. Vail-Ballou Press Wagner, Richard H. 1998. Environment and Man (6th ed.). New York, N.Y. W.W. Norton & Company, Inc. Theodore, Mary K., Theodore, Lewis. 1996. Major Environmental Issues Facing the 21st Century. Upper Saddle River, New Jersey. Prentice-Hall, Inc. The Concern of Deforestation in Today's Society Essay -- Deforestation Deforestation is a major concern in today’s society. The destruction of the world’s forest areas are leaving millions of acres uninhabitable. The varied species of animals and insects that use to live and thrive from these forests are rapidly becoming extinct. The destruction of the forest is also having a detrimental effect on the people through displacement thus forcing them to seek new living accommodations. Many of these people are loosing their heritage and cultures leaving them with a sense of hopelessness. The barren land left by deforestation is also causing many ecological problems. Increased flooding and soil erosion are two of the other problems facing several countries like China, Brazil, and the Philippines. To gain a better understanding of the immense significance of this matter perhaps a look at the past, present and future are needed. Deforestation â€Å"Past† Since the beginning of time humans have used nature’s resources to exist. They have hunted for food, drunk the water, used animal hides for clothing and even used the timber for warmth and homes. It was not until the twentieth century that man began to realize the effects of their enormous usage on the environment. Although staples like food and water are a problem in them selves, large-scale logging brought deforestation to the forefront.  · The World Rainforest Movement suggests that Western Europe, for example, has lost over 70 percent of its forests since Roman times and argues that fully one-third of â€Å"temperate broadleaved forests have been lost since the dawn of agriculture† (Elliott, 1998).  · In 1901 President Theodore Roosevelt along with Gifford Pinchot and John Muir wrote the first pages of modern environmental history in the United States by moving environmental conservation to the center of national agenda and declaring public primacy over the nations resources (Shabecoff, 1993).  · In 1933 President Franklin Roosevelt shored up his cousins beliefs in the environment by including major conservation programs and projects such as The Civilian Conservation Corps (CCC), the Soil Conservation Service, and the Tennessee Valley Authority into his New Deal reforms (Theodore, Theodore 1996).  · The President’s Commission on Materials Policy in 1952 estimated that 90 percent of the virgin timber in the U.S. commercial forests had been cut, that reforestation ... ...ces that cause more severe environmental impacts or problems. The unanswered question is weather such a hope is realistic in the face of the impersonal, price-driven forces of global markets and the reality that even the best production processes today still require the use of growing amounts of materials, energy and the continued transformation of the landscape for the expanding human population. References Elliott, Lorraine. 1998. The Global Politics of the Environment. New York, N.Y. New York University Press. Shabecoff, P.A. 1993. Fierce Green Fire. New York, N.Y. Hill and Wang Mercuro, Nicholas. 1997. Ecology, Law and Economics, Lanham, Maryland. University Press of America, Inc. U.S. Council on Environmental Quality. 1990. Environmental Quality 1990. Washington, D.C. Government Printing Office Andrews, Richard N. L. 1999. Managing the Environment, Managing Ourselves. Binghamton, New York. Vail-Ballou Press Wagner, Richard H. 1998. Environment and Man (6th ed.). New York, N.Y. W.W. Norton & Company, Inc. Theodore, Mary K., Theodore, Lewis. 1996. Major Environmental Issues Facing the 21st Century. Upper Saddle River, New Jersey. Prentice-Hall, Inc.

Mexican Cuisine

Mexican Cuisine Mexican cuisine is a style of food that originates in Mexico. It is known for its varied flavors, colorful decoration, and variety of spices and ingredients, many of which are native to the country. What makes a meal distinctly Mexican, of course, are the lively seasonings. Not all Mexican recipes are fiery, though; while renowned for their heat, many subtle and intriguing spice combinations are also found in Mexican fare. The staples of Mexican cuisine are typically corn and beans. Corn, traditionally Mexico's staple grain, is eaten fresh, on the cob, and as a component of a number of dishes. Most corn, however, is used to make masa, a dough for tamales, tortillas, gorditas, and many other corn-based foods. Squash and peppers also play important roles in Mexican cuisine. The most important and frequently used herbs and spices in Mexican cuisine are chilli powder, oregano, cilantro, epazote, cinnamon, and cocoa. Chipotle, a smoke-dried jalapeno chilli, is also common in Mexican cuisine. Many Mexican dishes also contain garlic and onions. Next to corn, rice is the most common grain in Mexican cuisine. Mexican food varies by region, because of local climate and geography and ethnic differences among the indigenous inhabitants and because these different populations were influenced by the Spaniards in varying degrees. The north of Mexico is known for its beef, goat and ostrich production and meat dishes, in particular the well-known arrachera cut. Central Mexico's cuisine is largely influenced by the rest of the country, but has unique and tasty dishes such as barbacoa, pozole, menudo and carnitas. Southeastern Mexico, on the other hand, is known for its spicy vegetable and chicken-based dishes. The cuisine of Southeastern Mexico has a considerable Caribbean influence due to its location. Seafood is commonly prepared in states that border the Pacific Ocean or the Gulf of Mexico, the latter having a famous reputation for its fish dishes. In Pueblos or villages, there are also more exotic dishes, cooked in the Aztec or Mayan with ingredients ranging from iguana to rattlesnake, deer, spider monkey, chapulines, ant eggs, and other kinds of insects. Mexican Cuisine Mexican cuisine is a style of food that originates in Mexico. It is known for its varied flavors, colorful decoration, and variety of spices and ingredients, many of which are native to the country. What makes a meal distinctly Mexican, of course, are the lively seasonings. Not all Mexican recipes are fiery, though; while renowned for their heat, many subtle and intriguing spice combinations are also found in Mexican fare. The staples of Mexican cuisine are typically corn and beans. Corn, traditionally Mexico's staple grain, is eaten fresh, on the cob, and as a component of a number of dishes. Most corn, however, is used to make masa, a dough for tamales, tortillas, gorditas, and many other corn-based foods. Squash and peppers also play important roles in Mexican cuisine. The most important and frequently used herbs and spices in Mexican cuisine are chilli powder, oregano, cilantro, epazote, cinnamon, and cocoa. Chipotle, a smoke-dried jalapeno chilli, is also common in Mexican cuisine. Many Mexican dishes also contain garlic and onions. Next to corn, rice is the most common grain in Mexican cuisine. Mexican food varies by region, because of local climate and geography and ethnic differences among the indigenous inhabitants and because these different populations were influenced by the Spaniards in varying degrees. The north of Mexico is known for its beef, goat and ostrich production and meat dishes, in particular the well-known arrachera cut. Central Mexico's cuisine is largely influenced by the rest of the country, but has unique and tasty dishes such as barbacoa, pozole, menudo and carnitas. Southeastern Mexico, on the other hand, is known for its spicy vegetable and chicken-based dishes. The cuisine of Southeastern Mexico has a considerable Caribbean influence due to its location. Seafood is commonly prepared in states that border the Pacific Ocean or the Gulf of Mexico, the latter having a famous reputation for its fish dishes. In Pueblos or villages, there are also more exotic dishes, cooked in the Aztec or Mayan with ingredients ranging from iguana to rattlesnake, deer, spider monkey, chapulines, ant eggs, and other kinds of insects. The main characteristics of Italian cuisine is its extreme simplicity, with many dishes having only four to eight ingredients. Italian cooks rely chiefly on the quality of the ingredients rather than on elaborate preparation. Dishes and recipes are often the creation of grandmothers rather than of chefs, and this makes many recipes ideally suited for home cooking. This is one of the main reasons behind the ever increasing popularity of this cuisine, as cooking magazine in foreign countries popularize Italian recipes targeted at the home cook. Italian cuisine has a great variety of different ingredients which are commonly used, ranging from fruits, vegetables, sauces, meats, etc Italian cuisine is also well known (and well regarded) for its use of a diverse variety of pasta. Pasta includes noodles in various lengths, widths and shapes. Distinguished on shapes they are named — penne, maccheroni, spaghetti, linguine, fusilli, lasagne and many more varieties that are filled with other ingredients like ravioli and tortellini. The main characteristics of Italian cuisine is its extreme simplicity, with many dishes having only four to eight ingredients. Italian cooks rely chiefly on the quality of the ingredients rather than on elaborate preparation. Dishes and recipes are often the creation of grandmothers rather than of chefs, and this makes many recipes ideally suited for home cooking. This is one of the main reasons behind the ever increasing popularity of this cuisine, as cooking magazine in foreign countries popularize Italian recipes targeted at the home cook. Italian cuisine has a great variety of different ingredients which are commonly used, ranging from fruits, vegetables, sauces, meats, etc Italian cuisine is also well known (and well regarded) for its use of a diverse variety of pasta. Pasta includes noodles in various lengths, widths and shapes. Distinguished on shapes they are named — penne, maccheroni, spaghetti, linguine, fusilli, lasagne and many more varieties that are filled with other ingredients like ravioli and tortellini.

Cultures in the World Essay

To define culture is not easy because culture means different things to different people. Hence there many definitions of culture as there are many different cultures in the World. Anthropologists define culture as social behaviour of human beings. To others dance, music, theatre, artifacts and fashion constitute culture. On the other hand, fashion is a style characteristic of the social elite and is mainly associated with social class and is highly dynamic. Hence fashion should be in current mode for instance a garment. Fashion, style, vogue or even mode are used interchangeably to refer to a preferred type of dress, behaviour, adornment or a way of life at a given time span. In broadest terms fashion usually refers to conventions which are generally accepted by a society or by any culture or even a subculture. Style like mode often stresses the adherence to standards and elegance and should be socially accepted. For instance miniskirts were the mode in the late sixties. Vogue is applied to style or fashion that prevails widely but often suggests enthusiastic but short lived acceptance (The American heritage 2003). Wilson, further states that fashion is always in a continual change and sets the terms for all sartorial behaviour (Wilson 2003). The importance of fashion can never be overemphasized in the current world since fashion now is always around us from media to our daily lives in clothing and even automobile sector. Let it be clearly noted that fashion is for aesthetic as well as societal class, elegance and modesty. In the current years fashion has become a major factor affecting the psychosocial wellbeing of major cultures and subcultures in the world. This influences the life of people both in style and preferences and their economical sphere. The growth of fashion is linked with the development of cities and urban centres in the 14th century and the growing sophistication of the courts. But it is only in 15th and 16th centuries when people developed the culture of fashion and class such that they felt shameful to wear outdated clothes (Wilson 2003). The entrance of fashion led to increased spending on clothes and a clear cut class differences. The rise of bourgeoisie became so much crucial in the development of fashion and style. The poorest class received the cheapest clothing with the people in the highest level in class ladder wearing the most expensive clothes. With the rise of Industrial revolution came capitalism hence new markets for clothes in fashion and fashion became more and more important with the circulation of images in mass communication. GENDER AND FASHION In the current contemporary world, fashion has become the order of the day. Media houses and world class beauty and model centres have been developed all over the world especially in Europe and U. S. A. However, unlike the past where fashion was associated with female, this industry welcomes both genders nowadays. But because of the past skewed interest of ladies in the industry they are still the major players. Nevertheless, almost every one in the current society setting especially in urban areas appreciates fashion and style and is a product of the same in one way or another. People are more conscious when it comes to fashion and no one is willing to be left behind in the outdated world hence consumption of these fashion products has tremendously risen. ‘Dress is a practical negotiation between the fashion system, the social conditions of everyday life such as class and gender as well as rules or norm governing particular social situations. The outcome of this complex interaction cannot be known in advance precisely because the habitus will improvise and adapt to these conditions’. Thus dress is a personal attempt to orientate ourselves to particular circumstances and thus recognise the structural influences of the social world and the individual on the other (Entwistle 2000) FASHION AND MODERNITY Fashion has kept pace with modern life. It has followed every step the global world is making and is by itself part and parcel of the globalised world. From North to South, West to East fashion is seen to influence the global ways of life. However, this is bringing about similarity and extinction of cultures since fashion and culture are linked and the change of one leads to change of the other. Since fashion is dynamic it follows that the fashion of yester years is different from the fashion of today hence today’s fashion is new and can be termed as modern. Modern fashion has greatly been affected by the present technological advancement and the entrance of new marketing approach. For example, the use of internet has revolutionized this industry. It is not a wonder therefore what is considered modern in London today is even being used the following day in Washington. This has promoted customized fashion products to promote what many fashion stars look for in fashion; uniqueness and class. Fashion and style industry has in the recent decades been well established with increased sales as many people go for class and fashion. Also, the quality of the products has greatly developed thus fashion has become our way of life. FASHION, SUBCULTURAL & YOUTH STYLES It is important to distinguish between the concept of youth culture and youth subcultures. In general terms youth culture is more homogenous, doing similar things and being treated in the same way playing down aspects of differentiation. This idea was much popular with U. S sociologists in early 1960s. In modern youth culture emphasis is more on subcultures. Unlike the 20th c where fashion was highly linked with class, in 21st c the line of demarcation has narrowed and the mode of classification is not only on class lines but across a wide plane of social and cultural identities. Hence the youth even in ghettos are coming up with their modes of fashion. The issue of subcultures within the large framework of culture in a society is a major phenomenon. Hence these subcultures act as the seed bed for fashion that is embraced by the larger society. The link between class and identity is far less apparent in the 20th c, in particular since high fashion is democratised and not longer the prerogative of a small elite. In contemporary culture distinction does not run along class lines alone but across a wide plane of social identities. Thus, rather than being only imposed from the top, fashion is also ‘bubbling up’ from the street and youth cultures (Entwistle 2000). The use of style brings across clear identity within the youth and serves to sometimes oppose dominant values within the society. Youth tend to solve their problems of culture and fashion in their own unique understandable way hence they act against the main stream fashions of the old. However their fashions and style are dominantly affected by the media and celebrities entertainment industry. Fashion trends brought forward by top musicians come fast and go quickly. These fashions and styles linked with subcultures are known to be diverse as the youth are dynamic. Therefore the rate of change of any fashion within a subculture is higher than in the dominant cultures. The youth also customise fashions by either adding or removing some parts from the original fashion to create a different identity. And for sure youth have revolutionised the world of fashion and culture, in the contemporary world. Therefore fashion is regarded as a mode of identity by the youth and serves as the avenue through which the youth express themselves. EFFECTS OF FASHION ON CONSUMERISM The cycle of fashion in the modern times has been found to influence the level of consumerism in the current world. Fashion is fueled by change and conversion. Designers always persuade their customers that their new fashions are everything they need. In the next season the same designers convince their customers to bade farewell to outdated designs and instead embrace the new trends in their latest collections. Western society’s culture of mass consumerism has widely been influenced by the fashion cycle. Sociologist Stella C. (1993) likens fashion cycle with the rolling waves of the sea. As one fashion gains popularity and is outdated another style is gaining momentum and this change our modern culture. Today’s fashion is not only placed on the contest of youth, sexuality and historicism, but also previous culture movements and shows fashion reflects its surrounding, its subjects but ultimately itself. FASHION AND CLASS Fashion is known to influence lifestyle and how people relate within the society. However this relationship is both on the individual and societal levels. Fashion is a product of class division since many people want to be seen in a unique way within any given society and societies also show their class differences using fashion hence affecting the culture of present societies. CONCLUSION It is true that fashion and culture are highly interlinked. A culture that appreciates fashion is a culture that is dynamic and ready to follow where its fashion leads it to. Modern culture is hinged on the fashion of each passing day and unlike the past psychosocial behaviour is influenced by fashion on a larger scale. Youth subcultures promote their own form of fashion which may be interlinked with fashions within the larger sphere of culture. These fashions serve to show their rebellious identity. The cycle of fashion has seen unnecessary changes of fashion due to designers who look forward to make profits and are out to change fashions as quickly as practicably possible. Hence the world is supposed to be aware of these uncalled changes in fashions. Unethical issues are also related to fashion and culture. Therefore, some people see it like their religious and spiritual beliefs are affected by fashion. However on a global perspective fashion has promoted the entrance of more products in the world market leading to increased competitiveness. Modern global culture is a mirror of fashion and design. REFERENCES Bruzzi Stella, and Patricia Gibson, 2000, Fashion Cultures: Theories, Explorations, and Analysis. London; New York: Routledge. Craik, Jennifer, 1993, The Face of Fashion: Cultural Studies in Fashion. London; New York: Routledge. Entwistle, J. 2000, The Fashioned Body: Fashion, Dress and Modern Social Theory. Cambridge: Polity Press. Malossi, G. 2000, Material Man: Masculinity, Sexuality, Style. New York: H. N. Abrams. The American Heritage, 2003, Dictionary of the English Language, Fourth Edition by Houghton Mifflin Company. U. S. A.

Not Poor, Just Broke Essays

Not Poor, Just Broke Essays Not Poor, Just Broke Paper Not Poor, Just Broke Paper I learned most emotions from school. You would think I would have learned most of my feelings from my home life, but I think my parents did the best they could to cover them up and make it seem like everything was fine and dandy. I grew up in a museum of sorts, or a playhouse. Everything was staged and we had to act in a proper manner to make it look like we had a perfect life. When my mom was upset, she would pull herself together in a moments time and say we need to â€Å"keep up appearances† so no one was the wiser. I would pay close attention to my parents to try and iscover how they really felt, but they were remarkable actors. So I became a player, performing in my own life as well. It was in school where I learned what real emotion was. And how to handle it. How do you pretend one way when you feel another way? I would imagine that is why some of the other kids act out. They are in a certain life, pretending to be something they are not but don’t want to let on t o the truth of their real emotions. I remember this other student who went to school with me. I felt bad for him most of the time because he always came to school kind f dirty and shabby. His family barely had any money and I don’t think his father was around. One day in class, there was a big scene when the teacher made it a point to single him out as a needed student and mention that everyone knows he doesn’t have a father. I’m not sure about his family but he seemed to just barely be holding it together. The teacher picked on him a lot, which I know bothered him. It bothered me as well. I felt sad for Page 2 of 2 him, but then I would remember my mother and trying to keep up appearances. He had a crush on my friend. I don’t think e knew that we all knew he liked her. I felt ashamed that we would make fun of him behind his back and call him names. I think back about how I use to act differently with my friends at school than I did at home. I wish I had learned more from my patents because I know now that most of my childhood friends were not the best influence on my developing emotions. That day when the teacher picked on him, I felt asha med. But I just kept smiling and pretending nothing was wrong. I wish I would have reached out to him and been a little more nice. It was a lesson well learned.

Prostanoids Essays

Prostanoids Essays Prostanoids Essay Prostanoids Essay Introduction 1. The Prostanoids Prostaglandins, the cyclic lipid go-betweens that belong to the ace household of eicosanoids ( Gryglewski, 2008 ) are 20 C fatty acerb merchandises of the additive polyunsaturated Arachadonic Acid ( AA ) ( Dey et al,2006 ) ( a cis-5,8,11,14-eicosatetraenoic acid ) . Often referred to as local short scope endocrines due to their metabolic and chemical instability ( half lives of Pgs is 30 seconds ) ( Kazuhito et al, 2002 ) the prostaglandins can be found in about every mammalian organic structure tissue where they maintain local homeostasis. ( Tsuboi et al, 2002 ; Coleman et al,1984 ) Certain structural characteristics that are outstanding amongst the prostanoids include carboxylic acid ; a hydroxyl group at place 15 and 2 aliphatic side ironss ( Manabu et al. , 1995 ) ( Gryglewski, 2008 ( Narumiya et al, 1999 ) . Arachidonic acid, enzymatically released from the phospholipid shops by PLA2, figure 1, is metabolised by the PGH synthases, COX 1 and 2 ( Dey et al,2006 ) ( the former referred to as constitutive is found in blood thrombocytes, the latter is known as inducible and is found in inflamed tissues ) to bring forth the prostaglandin endoperoxides PGG2 and PGH2, which depending on the tissue will metabolize farther by either the thromboxane/ prostacyclin synthases to PGD2/PGE2/PG12/TXA2 or reductases ( to synthesis PGF2 i? ) . ( Gryglewski, 2008 ) Due to their synthesis from fatty acids in the cell membrane ( which allowed them to go through through the membrane and range neighboring cells ) the prostanoids were originally thought to be hydrophobic but subsequently surveies subsequently concluded this is nt wholly true and that prostaglandins like PGF2i?iˆ are really H2O soluble. Figure The synthesis of Prostanoids by the use of Arachidonic acid by assorted enzymes including the PGH/PGG synthases. Besides included are some of the signal transduction and physiological actions of the receptors. Prostanoids exert a assortment of actions including neuromodulation ( PGE2 ) and platelet collection ( TXA2 ) ( Negishi et al, 1995 ) ( Coleman et al, 1984 ) that are mediated by their receptors ( situated on the plasma membranes ) which belong to the G protein coupled visual purple type ace household ( Dey et al. , 2006 ) of cell surface receptors. Each receptor has 7 hydrophobic putative transmembrane spheres within which the 3rd/ 7th transmembrane spheres every bit good as the 2nd extracellular cringle are conserved. ( Manabu et al. , 1995 ) . Certain constructions thought to be of import for the binding of prostanoid molecules include Arginine. ( Negishi et al, 1995 ) . The of course happening prostanoid receptors ( briefly described in the undermentioned subdivision ) were originally characterised in bioassay systems on assorted smooth musculus readyings ( table 1 ) and so harmonizing to their sensitivenesss to the major prostaglandins ( table 2 ) ( Negishi et al, 1995 ) . Secondary courier systems ; MRNA splicing discrepancies ( Jones et al, 2009 ) and ligand adhering surveies have besides been used in both receptor word picture and the find of the EP receptors subtypes, EP 1-4 and their isoforms ( EP3 is thought to hold up to 7 isoforms ) . Function of cistrons encoding mouse TP ; EP ( 1-4 ) ; IP ; FP and DP receptors revealed they are on chromosomes 10, 3, 15,7, 3, 8 and 14 severally. ( Narumiya et al, 1999 ) Smooth musculus response to receptor activation Receptors involved Contraction TP EP1 FP EP3 Relaxation IP EP4 EP2 DP Table Word picture of the receptors harmonizing to the type of response elicited on a smooth musculus ( Walch et al, 1999 ) Receptors Prostaglandins which have the greatest activity Displaced person PGD2 EP PGE2 FP PGF2i? Information science PGI2 TP TXA2 and its precursor PGH2 Postpone The original word picture of the receptors harmonizing to their sensitiveness towards the prostaglandins. 1.2 Naturally happening Prostaglandin receptors PGD2, the major prostanoid for DP receptors is formed in many tissues and cells and produces a assortment of biological responses including suppression of thrombocyte collection ( other more powerful DP agonists moving in a similar mode include 9-Deoxy PGD2 ) ; relaxation of vascular and non vascular smooth musculus ; alteration of autonomic and centripetal nervus maps every bit good as the intercellular ordinance the liver cells map ( Manabu et al, 1995 ) . DP receptors mediate their relaxant actions by triping adenylate cyclase and increasing intracellular camp degrees ( Manabu et al, 1995 ) . The major prostanoid for the FP receptors is PGF2a, known as the primary PG. More powerful agonists, Cloprosterol and Fluprostenol, were developed by ICI Pharmaceuticals as possible preventive agents in adult females. PGF2a actions include compressing smooth musculus readyings ( bronchea and windpipe ) and bring forthing a mitogenic response in civilized cells ( e.g. Osteoblast cells ) . FP receptor adversaries may be used in bar of pre-term labor ( Jones et al, 2009 ) . Signal transduction surveies indicated cloned FP receptors couple Gq ensuing in the activation of PLC. PGF2a stimulated phosphoinositide metamorphosis and activation of PKC besides occurred through FP receptors and led to the initiation of programmed cell death in cells. Thrombosis/haemostasis are thought to be mediated by TP receptors ( Manabu et al, 1995 ) which come in 2 isoforms, i? and i?iˆÂ ¬ and were isolated from purified blood thrombocytes and placenta utilizing high affinity specific adversary ( S-145 ) . TXA2, the of course happening TP receptor agonist is involved in cardiovascular disease ( e.g Acute MI ) . For experimental intents more stable agonists such as U-44619 are frequently used. ( Jones et al, 2009 ) TP receptors are thought to match at least 4 G-proteins ( Gq/Gi/G12/G13 ) which in bend leads to the activation of the undermentioned 2nd couriers and effecters: Ca2+ ; IP3/DAG ; camp ; PKC and PKA which later can take to platelet aggregation/ form alteration. The TP adversary BMS 180,291 is normally used in surveies as it is both powerful and orally active in add-on to being long playing and extremely selective. ( Misra et al. , 1992 ) The IP receptor agonist PGI2 maintains homeostasis in the organic structure by opposing the actions of TXA2 ( e.g. platelet collection ) . PGI2 itself is labile hence the more stable Cicaprost is used in surveies ( Manabu et al, 1995 ) . IP receptor mediated actions include loosen uping arterial smooth musculus ; platelet aggregation/degranulation and form alteration suppression ; vasodilatation of the pneumonic beds and modulating nephritic blood flow. IP receptor is thought to match the undermentioned G protein ( ) exert its actions by assorted effecters as shown by the following signalling tract: IP receptor activation leads to stimulation of adenylate cyclase and later an addition in intracellular camp which at high degrees, through PLC activation, causes calcium mobilization or pkA cascase. IP adversaries could potentially be used for hurting direction ( Bailey et al, 1998 ) . Two lead IP adversaries include RO-1138452- portion of the 2- ( phenyl amino ) -imidazoline series- and compound 21 ( Clark et Al, 2004 ) . Functional surveies utilizing guinea hog aorta/human pneumonic arteria revealed pA2 values of 8.39/8.20 for RO-11384520. The equilibrium dissociation invariable: Schild Vs Cheng-Prusoff Isolated tissue checks are critical to the survey of adversaries ( this includes finding of their affinities ) every bit good as the pharmacological distinction of receptors. Some of import footings associating to this kind of survey are KB the equilibrium dissociation invariable ; pA2 the measuring for antagonist activity and must be a positive figure ; EC50 the agonist concentration required to bring forth a bomber maximal ( 50 per centum ) action on a concentration consequence curve in the absence of adversary and IC50 the concentration of adversary needed to cut down the consequence of an agonist by 50 per centum. The chief methods used to mensurate KB are the Schild and Cheng-Prusoff analysis nevertheless other theories include those by Gaddum ; Guarino and Bovet. Schild analysis Pharmacologists originally determined KB by using schild analysis ( Cheng, 2002 ) to concentration consequence curves constructed for an agonist in the presence and absence of several antagonist concentrations ( Arunlakshana and schild, 1959 ; Schild,1947 ) nevertheless a individual adversary concentration can besides find KB ( individual point finding ) ( figures 2 and 3 ) ( Van Rossum, 1963 ) . Schild s most of import finds are finding the affinity of a competitory adversary and recognizing the significance of the dosage ratio ( despite the agonist action being unknown ) . ( Calderone, 1998 ) The dose ratio ( A1/A0 ) is the factor by which agonist concentration A0 in the absence of an adversary must be increased by in order to bring forth the same response as concentration A1 in the presence of an adversary. ( Calderone, 1998 ) Figure: Dose response ( hypertext transfer protocol: //www.curvefit.com/schild.htm ) Figure: Schild secret plan ( hypertext transfer protocol: //www.curvefit.com/schild.htm ) The Schild secret plan was besides originally used to find KB ( kenakin, 1982 ; schild, 1947 ) from individual point finding surveies but was subsequently found to give the correct reply in a wider scope of state of affairss therefore connoting theoretically a typical competitory adversary should bring forth parallel displacements in agonist response concentration curves with no suppression of the soap response every bit good as a negative incline of integrity when log ( concentration ratio -1 ) is plotted against -log ( antagonist concentration ) . The Schild method is one of the nothing methods which are used in functional surveies and there are many advantages to this ; for one there are restrictions in functional surveies such as unknown agonist tenancy but the void method overcomes this as it considers that a certain response is elicited from a certain sum of agonist tenancy in malice of the antagonist tenancy. Looking at the equation, the concentration, affinity and efficaciousness of the agonist are all irrelevant plus the dose ratio does nt trust on the nature of the agonist and magnitude of response. Therefore one considers Schild to be simple yet effectual. Overall Schild is thought to be a pharmacologically valid yet robust ( Colquhon, 1987 ) method even when there are non adequate receptors to make a direct binding experiment or when the receptors are excessively heterogenous ( Kenakin, 1984a ) to enable reading of ligand binding experiments ( although if a specific agonist was available so Schild could be used to an alyze the receptors that elicit the response ) . ( Lazareno and Birdsall, 1993 ) Schild analysis still has flaws nevertheless and these include its inefficiency and demand for tonss of informations points. Cheng- Prusoff and the Inhibition curve Inhibition curves ( figure 3 ) are routinely used in 2nd courier checks and affect increasing concentrations of an adversary to cut down the agonist concentration. ( Bockaert et al,1990 ) . Important parametric quantities for an suppression curve include the location parametric quantity ( I50 ) -originally thought to depend on the agonist concentration used-which can be converted to the affinity changeless Ki ( appendix B ) by the original Cheng-Prusoff equation in a monosubstrate enzyme reaction. ( Cheng, 2002 ) Figure: Example of an Inhibition curve on which the Cheng-Prusoff analysis can be applied. The location parametric quantity ( IC50 ) can be determined and so converted to Ki. ( hypertext transfer protocol: //journals.sfu.ca/coactionbks/index.php/Bindslev/article/viewArticle/6/67 ) Cheng-Prusoff protocol ( see Appendices B and C for derivations ) applies chiefly to enzymatic reactions nevertheless few prostanoid receptor surveies have used it including Bley et Al ( 2006 ) who calculated pA2 values for IP antagonists RO-1138452 and RO-3244794. There are premises made from the equation such as both substances interact at a individual binding site harmonizing to the jurisprudence of mass action and besides the substance s free concentrations are known and changeless throughout the experiment. ( Lazareno and Birdsall, 1993 ) . The Cheng-Prusoff analysis is frequently criticised ( see Munson and Rodbard, 1988 ) yet in pattern is used alternatively of Schild as it allows a lower scope of concentrations to be used and the antagonist action can be seen clearly even when the steady province is easy reached for case by adversaries that have a high affinity ( Jones et al.,2009 ) or are extremely lipotropic ( Jones et al.,2008 ) . This is in add-on to the fact that is can be used for dearly-won or limited agonists. Furthermore the easiness of building an suppression curve makes it more appealing. The job with the analysis is the inappropriate interlingual rendition of the original equation from the linguistic communication of enzymology to pharmacological medicine and the uncertainness of whether the agonist affinity invariable is needed to find the adversary s affinity invariable, Ka ( something Craig,1993 found unneeded as KB was in existent fact independent of it ) . Radioligand adhering surveies ( see Appendix A ) are complicated by the fact that EC50 does non equal Ka. unless a additive receptor tenancy response relationship exists ( Craig, 1993 ) hence te look is altered and ( KB =I50/1+ ( A/ Ka ) is used to change over Ka to Ec50 ( when the interaction with the receptor follows bimolecular dynamicss ( Craig,1993 ) . Further jobs with this technique include the trouble in implementing the equation in fortunes where small information exists about the agonist ( for case its concentration ) . Leff and Dougall ( 1993 ) stated there were no set standards for Cheng- Prusoff to prove an adversary of true competitory nature unlike Schild, this is in add-on to the trouble in separating between a competitory and non competitory adversary if the suppression curve was used ( something evidently detected with a Schild secret plan ) . Eglen and Whiting ( 1989 ) suggested using Cheng- Prusoff at a high agonist concentration is invalid which contradicts Lazareno and Roberts ( 1987 ) theory. erroneous KB values ( Leff and Dougall, 1993 ) . It is critical hence to cognize how to construe the cheng prusoff equation in a pharmacological scene and to understand the importance of KB and I50 and their dependance on the form of the curve. ( see Appendix ) With their complex pharmacological medicine, possible curative value and appropriate mathematical agencies of characterizing receptor ( every bit good as finding agonist/antagonists authorities ) there has been a batch of involvement in the prostanoids. EP receptors The EP receptor system is of involvement in this survey, with 4 subtypes ( and a figure of isoforms ) identified and known to intercede actions of an opponent nature ( e.g. stimulation and suppression of neurotransmitter release or inhibition/stimulation of Na and H2O resorption in kidneys ) through assorted complex signalling transduction mechanisms, Negishi et Al ( 1995 ) some of which have still to be clearly identified, it is of no surprise that the EP receptor system is the Centre of many surveies including this 1. The EP receptor was pharmacologically divided into four subtypes ( EP1/ EP2/EP3 and EP4 ) based on their responses to assorted agonists and adversaries. Each subtype can match a member of the g-protein coupled receptor household in order to excite a signal cascade. EP1is best characterised by its limited tissue distribution and repressive actions on intestine and trachea smooth musculus. Northern Blot analysis revealed both EP1/3 receptors were expressed in the kidneys ; lungs and uterine. Protagonists known to adhere EP1receptors have been ranked in the undermentioned order harmonizing to their authorities: 17-phenyl-PGE2 A ; gt ; PGE2 A ; gt ; sulprostone A ; gt ; iloprost ( partial EP1 agonist ) . EP1 receptor adversaries include SC-51322 which has a pA2 of 8.8 and schild secret plan incline of 0.91 ( bespeaking competitory hostility ( Durocher et al, 2000 ) and ONO-8711 ( which besides shows some EP3 hostility ) . EP2/4 receptors are abundant in ileum, Thymus, kidneys and bosom severally and intercede vasodilatory actions on blood vass every bit good as loosen up the windpipe and ileum. ( Negishi et al,1995 ) Protagonists used to trip these receptors include Butaprost ( selective EP2 agonist which is insensitive to EP4 ) and PGE2 ( Negishi et al, 1995 ) . Adversaries for EP2/4 receptors are as follows: AH6809 ( EP2 adversary and its a weak ligand for murine EP1 and DP1 ) and AH-23848-the lead EP4 adversary which can distinguish between EP2/4 and IP agonism ( Jones and Chan, 2001 ) and CJ-023,423/L-161982 ( EP4 antagonists with a pA2 of 8.3 the latter portions some structural characteristics with ep3 adversaries ) . In footings of signal transduction it is thought that EP1 couples an unknown G protein which leads to PKC activation which later, when over expressed, leads to desensitisation of EP1 receptors. During its phosphorylation ( possibly in 3rd intracellular cringle ) in worlds nevertheless Calcium mobilization is inhibited. EP4 positively couples Gs taking to its relaxant actions and both EP 2/4 receptors stimulate Adenylate cyclase and later addition degrees of Ca managing taking to EP2 repressive actions. EP4 mediated PGE2 actions ( e.g. suppression of function/proliferation of T cells ) are via an intracellular camp. Unlike the other receptors EP3 has been extensively studied and is the subtype receptor we shall concentrate on for this undertaking. A widely distributed inhibitory receptor ( found in kidneys, encephalon, GI piece of land and womb ) it exerts assorted pharmacological actions including the contraction of smooth musculus ( vascular and uterine ) , suppression of lipolysis and sweetening of thrombocyte collection. These belongingss are of import as there is a strong deduction that ep3 receptors and their isoforms are involved in cardiovascular diseases ( e.g. MI/ tachycardia/ high blood pressure ) . EP3 has a complex pharmacological medicine as it mediates its actions through assorted effecters and secondary couriers including Adenylate cyclase ( its suppression takes topographic point when phosphoinositide metamorphosis is stimulated ) ; camp ; the initiation of Ca inflow ( which later leads to chloride channel suppression ) ; PLC activation and Ca mobilization. Noradrenaline/ serotonin release is besides thought to be affected by the ep3 receptor. The G-proteins that couple EP3 receptors are Gi and Gq. Protagonists most normally used in ep3 receptor surveies are TEI-3356 ( a selective EP3 agonist ) and sulprostone ; ONO-AE-248 ; PGE2 and 17-phenylPGE2. Compounds used to barricade EP3 agonists include lead compound DG-041 ( an AT1 adversary that has already been investigated in a stage 1 clinical test ( Heptinstall et al, 2008 ) which is thought to be a utile for future intervention of peripheral cardiovascular disease by suppression of adenylyl cyclase/priming of protein kinase C ( Matthews and Jones, 1993 ) and L-798106 which blocked pre synaptic EP3 inhibitory sulprostone actions in guinea hog vessel deferens ( pA2 values for this compound are 7.5 and 7.8 severally ) ( Jones et al.,2009 ) . In add-on to this it was found to hold caused a parallel supplanting of log concentration response curves for sulprostone mediated rat femoral arteria contraction ( Hung et al, 2006 ) . Schlemper et Al ( 2005 ) implied L-826266 had some indirect repressive actions on EP3 but this has nt been to the full demonstrated. Both L-826266 and L-798106 did nevertheless barricade EP3 contraction in guinea hog aorta but it s been suggested that the groun ds behind the oncoming of the obstruction being so slow are related to the high lipophilicity of the compounds as opposed to their affinity. ONO-AE3-240, another EP3 adversary was extremely EP3 selective compared to EP1. ( Amano et al, 2003 ) The job with EP3 and prostanoid adversaries in general has been in their word picture which is both hard and dearly-won. As possible medical specialties there are a batch of restrictions, for case belley et Al ( 2006 ) showed their adversaries to be extremely protein edge which accordingly decreased their activity SAR surveies have suggested that indole karyon incorporating compounds retain a high affinity for EP3 after inversion of the indole karyon. Indolones and hexahydro-indolones ( OConnell et al, 2009 ) were besides said to hold high EP3 affinity. In add-on to this saturating alpha-beta bond allows for a high authority of EP3 adversaries nevertheless farther impregnation of dual bonds in hexahydro-indolone residues consequences in reduced affinity. Despite the fact that there are chemicals available, research is still on traveling to happen for case a more selective agonist and adversary such as 3,7-dithiaPGE1, the lead ep4 receptor agonist that was discovered through structural alteration. 3,7-dithiaPGE1 is an acidic molecule derived from the PGE1 molecule. Using the basic PGE1 skeleton the heteroatom Sulphur was added to the 7 C place which led to potent affinity for assorted receptors ( ep4, ep3 and information science ) . Another sulfur was so introduced into the a concatenation at the 3 C place which resulted non merely in good ep4 receptor selectivity and agonist activity but besides powerful ep3 receptor activity with a qi of 220nM and ec50 of 1.1nM. The debut of a 2nd sulfur besides led to decrease affinity for the IP receptor. Although there is some ep4 activity the chief issue with 3, 7-dithiaPGE1 prevarications in ep3 receptor affinity and activity as the writers have stated contrasting values for the qi and EC50. The purpose therefore of this survey is to find the selectivity in relation to its ep3 activity. As there are few literature that have studied this chemical, the usage of tissues that are known to hold a great trade of ep3 receptors and can react good to them are needed, hence, usage will be made of the guinea hog vessel deferens and aorta. For vascular surveies the human pneumonic arterias are appropriate nevertheless they are prone to tachyphylaxis and so small information can be gained from them during check surveies therefore the Guinea Pig Aorta and Vas deferens are used routinely. Although there is small correlativity between the tissues in footings of agonist sensitiveness there is a strong nexus between the contractile authorities of EP3 on Aorta/vas and pneumonic arterias. In add-on to this the Guinea Pig is comparatively cheap compared to other animate beings. Furthermore Vas Deferens ( a good studied tissue in footings of nervus transmittal ) is thought to be more sensitive to EP3 agonists than aorta. In add-on to this it s thought that PGE2 synthesis and distinction of receptors took topographic point on Vas Deferens ( Trachea and Ileum are besides accountable for the latter ) ( Coleman et al, 1984 ; Jones et Al, 1986 ) . To research the EP3 effects of 3,7-dithiaPGE1 in isolation requires the usage of other agonists and adversaries and this is due to the fact that there is an copiousness of other receptors in both the aorta and vessel deferens for illustration TP/EP1/i?1 which are to be characterised in the tissues therefore the undermentioned agonists and adversaries will besides be used: 17-phenylPGE2 ; BMS-180291 ; Phenylephrine ; PGE2 and ASA-3ap. 2. Methods and Materials Isolated tissue readyings Forfeit of the lab animate beings was performed harmonizing to the UK Home office agenda 1 guidelines. Male Dunkin Hartley guinea hogs of 300-350 gms were euthanized by inhaling 100 % CO2. The tissues were so instantly dissected out. The falling thoracic aorta was removed and cut into rings, which were measured at about 3mm in length, and were stored in oxygenated Krebs buffer solution ( room temperature, gassed with 95 % CO2 and 5 % O2 at a changeless rate to keep a pH of 7.4 ) which was made of ( millimeter ) NaCl 118.4 ; KCL 4.7 ; NaHCO3 25 ; Glucose 11.1 ; MgSO4 1.2 ; NaH2PO4 1.2 ; CaCl2 2.5. The tissue was so transferred into a 20 milliliter bath and supported by two chromium steel steel wires in order to mensurate tissue tenseness. Isolating the Vas Deferens required the venters to be cut unfastened and the tissue removed from the testicle. Any extra fat, connective tissue, blood vass and mesentery were so removed suitably. The tissue was once more immersed in warm Krebs solution. On a gel home base the tissue was pinned down suitably in order to bind a knot at each terminal, a cringle was so made at one terminal in order to suspend the tissue ( in a conventional 10ml organ bath ) between the transducer and wire electrode. The readyings were ace fused at a changeless rate with oxygenated Krebs solution set at temperature of 37oc by the usage of gravitation provender setup. Prior to suspending the tissues the isometric transducer was calibrated and the resting tenseness applied to both vessel deferens and aorta was 1g. After the setup was set up with the tissues the necessary alterations to weave tenseness were measured in gms by the isomeric transducer ( Dynamometer UF1, Pioden Controls ) connected to a CED 1902 MK III amplifier ( CED Science Park, Cambridge, England ) . The Intracept- Chart V.4.8.1 bundle on a Dell desktop computing machine was used to enter the informations. Protocols Aorta. For every experiment once the tissue was set up on the setup a force of 1g resting tenseness was applied. Furthermore anterior to adding any other chemicals 100 nm BMS 180291 was added to the bath and allowed to incubate for 10 proceedingss in order to suppress TP receptor activity. The COX-2 inhibitor Indomethacin ( 0.5 milliliters of 20i? ­M used ) was besides added to the Krebs reservoir ( 10 L which was split between the pupils in the group ) in order to barricade any endogenous TP activity. A cumulative dosage response curve was foremost constructed by adding 100, 300, 1300 and 3300nm phenylephrine ( four- five proceedingss were left between each dosage in order to let for a full consequence to be seen ) so the dosage that gave a close maximal contractile response ( about 60-70 % ) of the tissue could be used for priming anterior to adding the prostanoid agonists and adversaries of involvement. The readying was so washed 3 times before go oning with the following measure. Once primed with 100nm of BMS 180291 and Phenylephrine ( usually 900nm -1i? ­M was added ) for about 15 proceedingss a cumulative dosage response curve was constructed utilizing 17- phenylPGE2 ( 1nm, 5nm and 25nm were added at 5 minute intervals ) in order to mensurate the contractile response. This measure was repeated except with the usage of 3, 7-dithiaPGE1 ( 100, 500 and 2500nm ) . ASA-3ap was besides added in the concluding measure. Vas Deferens. At the start of each experiment the resting tenseness was recorded in a similar mode to aorta. Prior to adding any drugs the stimulator was set as follows: group interval ( 40 seconds ) , pulses per group ( 10 ) , pulse frequence ( 10Hz ) , pulse breadth ( 1ms ) , pulse amplitude ( 5v ) and a filter was on if required. A scope of electromotive forces ( 30v-70v ) were applied to the tissue to see if it contracted ( anterior to adding any repressive agents ) and the electromotive force which gave a close maximal contractile response ( most frequently this was at 60v ) was used for future experimentation. Initially a individual electromotive force ( 60v ) applied to the tissue and so a individual dosage of PGE2 ( 5nm ) was added to see if the tallness of contraction decreased ( this indicated that the chemical did in fact inhibit tissue contraction as expected ) . The readying was so washed out ( this had to be done in the 40 2nd interval ) several times before go oning wi th the experiment. The first protocol involved the same electromotive force applied once more and PGE2 added in a cumulative mode ( 3, 10 and 30 nanometer ) to suppress the contractions. The protocol was repeated once more but with 3, 7-dithiaPGE1 ( 100, 300, 500 and 700nm ) added in a cumulative mode. The 2nd protocol involved adding ASA-3ap ( 100nm ) which was allowed to incubate for 10 proceedingss so PGE2 /3, 7-dithiaPGE1 were added in the hope to suppress the action of the adversary. Datas Analysis Data was collected and recorded via the Intracept chart V4.8.1 bundle. For each new experiment the tissue tenseness was measured before and after adding the tissue ( in gm ) . To cut down biological fluctuation between stray tissue readyings the consequences ( e.g. contractions inhibited by 3, 7-dithiaPGE1 ) were normalised by being expressed as per centums of the tissues maximal contractions ( this was determined by mensurating the tallness of the contraction ) in the absence of agonists and adversaries. Graph pad Prism version 4 was used to build log concentration dosage response curves. The curves were fitted utilizing the undermentioned options: variable sigmoidal dose response, restraining the curve to the initial tone at 100 % and if necessary at resting tenseness ( 0 % ) . Data was expressed as the mean iˆÂ «iˆ?iˆÂ ­ the standard mistake mean of n independent probes. Statistical analysis was besides carried out by utilizing Graph tablet Prism, version 4 and Graph pad instat 3. Statistical significance was assumed if P A ; lt ; 0.05. Chemicals used The chemical of involvement in this probe, 3, 7-dithiaPGE1, was supplied from Allergan, USA. Likewise PGE2 and 17-phenyl-w-trinor PGE2 were supplied from Cayman Chemical, USA. ASA-3ap ( 1- ( 3-methoxybenzyl ) -3a-methyl- [ 3, 3a, 4, 5, 6-hexahydroindol-2-one-7-acrylic acid, 3, 4-difluorobenzenesulphonamide, 10 i? ­M in DMSO ) was provided by Target Molecules, UK. BMS-180291 ( [ 1S- ( exo, exo ) ] -2- [ [ 3- [ 4- [ ( pentylamino ) carbonyl ] -2-oxazolyl ] -7-oxabicyclo [ 2.2.1 ] hept-2-yl ] methyl ] -benzenepropanoic acid, Ifetroban ) was provided from Bristol-Myers Squibb, USA. Indomethacin ( 20i? ­M ) in ethyl alcohol was bought from Sigma-Aldrich, USA. Phenylephrine was provided by the University of Strathclyde. The stock solutions were prepared by the undermentioned procedure ( this applied to all chemicals except ASA-3ap ) : Indomethacin was dissolved in ethyl alcohol to accomplish a concentration of 20i? ­M ; the prostanoid agonists and adversaries ( PGE2, 17-phenyl-w-trinor PGE2 and, BMS-180291 ) were besides prepared in a similar mode except to concentrations of 1mM ( BMS 180-291 ) ; 1, 10 and 100 millimeter ( PGE2 ) and 17-phenyl-w-trinor PGE2. Stock solutions were so diluted suitably with 0.9 % NaCl solution ( saline ) . For ASA-3ap the first dilution was solubilised with a hint of NAHCO3. Consequences Guinea Pig Aorta- conventional experiments Phenylephrine cumulative dose response curve. Phenylephrine was added cumulatively to the stray tissue to show the tissue s response to phenylephrine in a concentration dependent mode. Figure 1 Log concentration response curve for phenylephrine in stray guinea hog aorta. The consequences are expressed as a per centum of the maximum tissue response. Establishing the being of an EP3 receptor system in stray guinea hog aorta. Prior to cumulatively adding 3, 7-dithiaPGE1 a priming dosage of phenylephrine was established by gauging the dosage that gave an appropriate EC20 ( the dosage that produces a response that is 20 % of the maximal response ) . This frequently varied between 500nM and 1300 nanometer nevertheless more frequently than non 1000 nanomet

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