Changing Marketing Strategies of Pharmaceutical Companies

Changing Marketing Strategies of Pharmaceutical Companies Abstract Pharmaceutical companies spend large sums of money in the time-consuming research and development of new drugs and the new classes of drugs. Each company marketing in the US seeks the possible payoff of staggering high profits which is possible on their patented medicines. Because of the lack of price regulation in the marketing environment in the United States, the United States has become a premium sales market targeted by all pharmaceutical companies. This explains the continued willingness of each pharmaceutical company to persist through the entire long process of idea, creation, development, testing, approval, marketing and distribution despite the high possibility of product failure. The pharmaceutical companies have had to additionally contend with more US federal FDA rules, regulation and oversight in the United States for the entire process before receiving clearance to start marketing their drug product. Other influences like HMOs and Social Security cap limits affect prof itability structure. Over the last fifty years newer marketing strategies by pharmaceutical companies on prescription drugs include a directive appeal to the end consumer to increase the odds of making corporate profits and a marketing focus on social and internet interaction. Introduction Pharmaceutical companies produce specialized medical drug material designed to fill a need. These pharmaceutical companies are usually multinational operations located in key countries around the globe. Many have grown to become complete facilities that attempt to do the entire spectrum of research, develop, test and finally market the subject drug in order to reap the whole benefits possible from the entire cycle (Kaitin, 2010). The pharmaceutical industry has shown over time that they have the capability to increase consumer perceived value with their unique drug products using their own successful plans for timely marketing. But because of these old and new factors causing cumulative hurtles, a new trend in marketing in the pharmaceutical industry is now to additionally market direct to the customer, for example: TV advertising spots showing a new superior drug product which has special features making it directly appealing to a consumer. Changes in basic marketing structure tacti cs will be evaluated for the key levels of pressure from these internal and external factors as these pharmaceutical companies seek to address continuing ongoing product failure rates, increasing US regulation and the ever present potential competition from others inside their own industry. This trend has been a natural development over the last hundred years or so. This is reasonable because the same research that produces one drug may produce an entire class of drugs for market. Confidentiality, control, patents and oversight give these pharmaceutical companies the oversight. It also allows each pharmaceutical company to keep maximum control of all their connected environments. And by controlling these the final marketing each company achieve continues the cycle of giving the most control over the drug for the marketing campaign. The drug industry often competes worldwide and on different economic levels but in some specific territorial markets like the United States, pricing structures are not preset by the government and therefore the free market sets its own competitive standards for pricing giving the possibility and most often the probability of higher drug prices with the resultant bigger profit level opportunities. However these are offset by rigorous structural standard guidelines set by the FDA that must be complied with for any drug sold or marketed to the US public. In the past, drug companies in United States, marketed to doctors, hospitals, nursing homes and sometimes middleman companies as transitional handlers of the newest product. Marketing drugs in the United states has now changed as developers are now targeting consumers directly through television spots, online advertising and in print ads. The direct appeal is to make the end point consumer aware of the name of the drug and its benefits. The object is to have the consumer become familiar with the trade name, ask for the drug directly from their doctor thus boosting the initial sales of the new product and creating a ready market. Industry History Marchetti Schellens (2007) outline the structures of development showing it to be complex and expensive. Not only does the potential class or specific drug have to be discovered or created, it has to show promise for certain illness or disease, then pharmaceutical research can proceed through certain phases. Pharmaceutical companies have a history of costly product failures. Generally theres three clinical phrases and all this can take upwards of 15 years to complete. Additionally the FDA has trended over the last decade to creating higher pressures against drug companies by not approving as many new drugs for marketing. The probability odds are that any specific drug in early clinical phase has only 8% chance or less of ever becoming public (Food and Drug Administration, 2006) (Kummar, 2007). In the United States the U.S. Food and Drug Administration (FDA) has sought to control the drugs available to Americans because of the number of tragedies that have resulted in birth defects o r deaths. The most highly publicized incident was in the mid-1960s and the drug was called thalidomide which for pregnant women often resulted in severe birth defects. As an end result of public outrage creating governmental pressures, the pharmaceutical companies are overseen at all levels and must now successful clinical trials. Lamb(1998) writes that testing protocols have been standardized and once clinical trials are completed there is a analysis period with the end result being an application to the FDA called an NDA ( new drug application) which contains all the technical information. Over the last forty years (1970s -2010) and now in 2011 differential forces are in opposition to the ends of pharmaceutical companies. Environmental and safety issues, new technologies, mergers and the rise of managed care and health maintenance organizations (HMOs) have all effectively changed the environment thats pharmaceutical companies operate in. additionally in 1997 the FDA changed regulations relating to the presentation of risk level. This action in the United States opened the door for pharmaceutical companies to directly market to the public .This freedom for the pharmaceutical companies is offset by the FDA still having oversight surveillance of the specific phases and clinical approval. The FDA must approve the drug. After the drug is marketed there is oversight for continued compliance by the pharmaceutical companies to ensure a low-level of side effects during marketing. Post approval by the FDA comes solely after this period (Silverman, 2011). Pharmaceutical company spending on marketing exceeds that spent on research.[3][22] In 2004 in Canada $1.7 billion a year was spent marketing drugs to physicians and in the United States $21 billion were spent in 2002.[4] In 2005 money spent on pharmaceutical marketing in the US was estimated at $29.9 billion with one estimate as high as $57 billion.[3] When the US number are broken down 56% was free samples, 25% was detailing of physicians, 12.5% was direct to consumer advertising, 4% on hospital detailing, and 2% on journal ads.[4] In the United States approximately $20 billion could be saved if generics were used instead of equivalent brand name products.[3] Although pharmaceutical companies have made large investments in marketing their products, overall promotional spending has been decreasing over the last few years, and declined by 10 percent from 2009 to 2010. Pharmaceutical companies are cutting back mostly in detailing and sampling, while spending in mailings and print advertising grew since last year.[23] Historical Marketing Pharmaceutical companies have employed various methods of marketing their products and this idea can be understood by the phrase â€Å"How would you like to be in an industry where your buyers are uninformed about your product and almost 100 per cent insensitive to its price?† (The Business Edge Consortium, 2010). For many decades this was true. Around the mid 80s this started to change â€Å"The result of these industry conditions was impressive profit growth through the middle of the 1980s. With significant barriers to entry, docile suppliers, powerless buyers, almost no threat of substitutes, and little rivalry, the pharmaceutical industry in the 1980s was just about as perfect an industry as one could imagine. Given its attractiveness, the industry attracted the attention of genetic and molecular biology scientists and the venture capital community, who saw its appeal and thought their revolutionary approaches to drug therapy could attract enough money to overcome the for midable entry barriers the industry enjoyed. Thus, as scientific advances in biotechnology took hold, numerous entrepreneurial companies like Genentech and Amgen were founded to commercialize new scientific breakthroughs. Genentech, the first biotech firm having commercial success, developed a protein that broke up blood clots. Amgens famous molecular biology used recombinant DNA to produce erythropoietin, a hormone that increases the supply of red blood cells in anaemic patients under treatment for cancer and other diseases. By 2000, erythropoietin was generating $2 billion in sales and another $3 billion in licensing revenue for Amgen. Both of these new entrants fared very well in this attractive industry:Genentech went public in 1980, and by 2001 its shares had appreciated 2700 per cent since its IPO. Amgen shares, first offered in 1983, soared more than 16,000 per cent. Starting in the mid-1980s, the barriers to enter the pharmaceutical industry began to show cracks. New legislation made it easier for generic drug companies to enter the market. In the USA, the 1984 Waxman-Hatch Act, which changed the rules for generic drug manufacturers, reduced the barriers to generic entry. Instead of having to prove the generic drugs safety and efficacy, the act required companies only to prove their formulas were equivalent to that of the brandname drug. The subsequent growth in generic drugs was profound. By 1996, generic drugs accounted for more than 40 per cent of pharmaceutical prescriptions. Aside from the influx of generics, the pharmaceutical companies also saw a wave of biotechnology competitors enter their industry Genentech, Amgen and many others suggesting that economies of scale meant less than they used to, and that barriers to entry, while still high in absolute terms, were dropping, thanks in part to the availability of venture capital. Further, the biotech companies new science-focused research model, known as rational drug design, stood the traditional approach to drug discovery on its head. These drug companies worked backwards from known disease biochemistry to identify or design chemical ‘keys to fit the biochemical ‘locks of that disease.† Traditionally they employed very effective strategies that includes educational sponsorship to cover the costs of continuing instruction for top medical personnel, sponsorship of articles in well-respected journal publications, providing free drugs samples to doctors and promotional gifts that include a corporate logo or specifics about a drug the idea behind the promotional marketing is to simply connect the new drug with an old medical symptom and encourage the writers of the prescription to fulfill the marketing cycle. Promantally pharmaceutical samples are still given out to doctors as a promotion and marketing tactic and it works (Alexander, Zhang Basu, 2008). A few generations ago these forms of marketing worked well for the pharmaceutical companies. However circumstances have changed. The FDA seeks to discourage the intimate connection between pharmaceutical companies and their pharmaceutical representatives is the connection to the doctors prescribing medicines, these days d octors see more patients and fewer pharmacy drug representatives, additionally there is a continuing trend by hospitals, doctors and pharmacies towards being conservative in their recommendations and prescriptions because of lawsuits of all kinds (Pharmaceutical Industry History, 2007). Medical drug malpractice suits in the US are rising. Fiscus (2008) writes that â€Å" In the United States, the growing use of DTC advertising has raised challenges to one of the strongest defenses available to drug manufacturers against failure to warn allegations in product liability suits for prescription drugs and medical devices: the learned intermediary doctrine. Under this doctrine, a manufacturer fulfills its duty to warn by adequately informing a learned intermediary, typically a physician.† Current Marketing .In 2010 the global pharmaceutical market is worth over 825 million with a large percentage of this comes from newer and mature drug products and there are over 100,000 health-related websites (The Business Edge Consortium, 2010). The statistics show that marketing by pharmaceutical companies is changing because of external pressures. There has been a dramatic rise in U.S. physicians routinely using d the web to check or research information making the relevance of digital promotion all the more important Pharmaceutical companies have risen to the changing challenge of Internet marketing and now promote and advertise doctor friendly physician and customer service online portals like PubMed, the U.S. National Library of Medicine, National, and Physicians Interactive (Kaitin, 2010). Pharmaceutical marketers are relying more on connecting digital medical information to their target audience through focused marketing, interactive social media campaigns, and cell and mobile linked advertising all targeted to connect to the 145 million + U.S. adults who go online for health answers . The old saying â€Å" time is money† is accurate in the case of pharmaceutical companies as it takes upwards of 15 years to develop a potential drug which only has a 8% probability of getting out of trials and going to market. Therefore it is a necessity to carefully control costs and expenses where possible. One major area of expense has been having marketing representatives which were costing out as high as15 to 20% of a pharmaceutical companies annual drug product revenues. As pharmaceutical company overall expenses and costs have additionally escalated over the last few generations there is a need to reduce expenses down where possible. So the switch from costly pharmaceutical representatives to cheaper graphic marketing is easily understood. Finkelstein (1997) wrote that Competitive and technological changes in the pharmaceutical industry-from powerful new drug chemistries to innovative RD partnerships and marketing plans-are reshaping the business strategies of many phar maceutical and biotechnology companies Given these cost pressures it is understandable that the pharmaceutical companies are looking for better ways to market their drugs. The newest strategy is now to promote what is known as marketing blockbuster medical drugs directly to the consumer public. The idea was to empower the consumer. Right now only the United States and New Zealand allow pharmaceutical products promoted by DTC (Pharmaceutical Drug Manufacturers, 2011). When an individual consumer requests information and the medicine by name by their Doctor some of the responsibility while also applying pressure on the doctor to prescribe the new medicine. Additionally both the small and large pharmaceutical companies are now using digital media to promote their products. From TV and cable to Internet ads consumers are constantly being made aware of the virtues and minor drawbacks of a number specific pharmaceutical drugs. The reasoning behind this strategy by the pharmaceutical companies is relatively simple, if they can promote their products and make its trade name and cure synonymous with the ongoing medical complaint in the publics mind, then they can create momentum utilizing the end customer. Another reason for doing this is to get any of their major blockbuster drugs to pay for the company costs for their other company made drugs sold in smaller volumes Another reason for marketing these blockbuster drugs as to make a success of these drugs synonymous with the company name creating consumer goodwill towards the next product. The latest trend is for reduction in the number of blockbuster drugs and pharmaceutical companies delvin g back into their former research to find potential missing new specialized drugs, .this can be seen clearly by the reduction in applications to the FDA showing ever reducing numbers of new drugs. Another complication that pharmaceutical companies must contend with is the ever-growing number of over-the-counter substitutes (OTCs) that the consumers choose to purchase as an alternative. Over a period of 20 years Naprosyn was widely prescribed as an arthritis remedy but now is available as an over-the-counter drug. A whole spectrum of drugs from arthritis to antihistamines are now available without prescription providing relief to customers but adding little to the economic bottom line of pharmaceutical companies that originally developed these drugs. Another complication in drug marketing is the force exerted by HMOs on doctors and what doctors prescribe .Generally the majority of HMOs are not big on covering high prescription costs for new medicines recently brought to market. The economics are easily understandable because it is not about a single client which needs a single drug but the numbers are multiplied by the potential hundreds of thousands. Therefore HMOs seek to be conservative. And because of that they create a potential customer roadblock for pharmaceutical companies with the new drug on the market at a very high price. Because of the HMO will not cove r the price then the customer must, which generally means the consumer settles for less than the newest product. managed care organizations (MCO), compared with 5 per cent of the US population covered in 1980. These MCOs typically provided full coverage for prescription drugs. But, because of their sheer mass, these institutions had considerable bargaining power with drug companies If present industry overview is taken into consideration then the global pharmaceutical market in 2010 is projected to grow 4 6% exceeding $825 billion. The global pharmaceutical market sales is expected to grow at a 4 7% compound annual growth rate (CAGR) through 2013. This industry growth is driven by stronger near-term growth in the US market and is based on the global macroeconomy, the changing combination of innovative and mature products apart from the rising influence of healthcare access and funding on market demand. Global pharmaceutical market value is expected to expand to $975+ billion by 2013. Different regions of the world will influence the pharmaceutical industry trends in different ways. http://www.da-group.co.uk/index.php?option=com_contentview=articleid=31%3Amicro-and-macro-environmentscatid=2%3Amarketing-lecturesItemid=3 CURRENT CHALLENGES FOR THE RESEARCH-BASED INDUSTRY To understand why â€Å"business as usual† is no longer an option for the research-based drug industry, it is worth considering some of the myriad challenges that drug companies currently face. At the top of the list is the upcoming onslaught of patent expirations of many highrevenue- generating branded medicines. Between 2009 and 2012, worldwide sales for these products will exceed $112 billion (Table 1). Included in this list are 36 blockbusters (drugs with annual sales of $1 billion or more). Some important examples include Singulair (montelukast), with more than $4 billion in annual sales (patent expiration in 2012); Plavix (clopidogrel), with more than $8 billion in annual sales (patent expiration in 2011); and Lipitor (atorvastatin), with an industry-leading $13.7 billion in annual sales (patent expiration in 2010). Given that only 3 in 10 new products, on average, generate revenues equal to or greater than average industry RD costs,1 the loss of patent protection on the se blockbusters represents a very real threat to the industrys ability to sustain its own growth. Without question, many of the large pharma mergers and acquisitions announced in 2009 reflect the industrys desire to avoid the imminent danger of the patent cliff, rather than an interest in enhancing RD capabilities or scope. The current environment for innovation presents formidable economic, regulatory, and political challenges for the research-based pharmaceutical industry. In particular, the growing time, cost, and risk related to drug development are stubborn obstacles to filling industry pipelines and boosting the output of new pharmaceutical and biological products. Presented here is a model of an innovation network. Although structures may vary, the innovation network offers the best mechanism to ensure viability and economic success for all sectors of the pharmaceutical and biotechnology industry, as well as the uninterrupted flow of innovative lifesaving and life-improving medicines for waiting patients. The Rise of Contract Research Organizations Clinical trials are administered by investigators at hospitals, academic institutions or managed sites. The investigators find and enroll healthy and symptomatic volunteers, each of whom is required to sign an informed consent acknowledging acceptance of the drug and its potential side effects. The testing protocol and informed consent form are monitored by Institutional Review Boards (IRBs) in the sites where the trials are conducted. In essence, the IRB acts as an ethics committee to ensure the safety of patients and volunteers. Once clinical trials are completed, the data are subjected to biostatistical analysis over a 6 to 12 month period.3 If the data yield promising results, the sponsor seeks final approval though a New Drug Application (NDA). The NDA must contain all scientific information the sponsor has gathered and typically fills 100,000 pages or more.4 During the review period, the FDA assesses the safety and effectiveness of th e drug, the manufacturing process, and the risk-benefit calculus.5 By law, the FDA has 180 days to either approve the application or notify the sponsor of the opportunity to request a hearing on the merits of the application.6 In practice, however, the FDA review process takes more than two years; in 1996, for example, the mean approval time for NDAs was 17.8 months, down from over 30 months during the late 1980s.7 Following approval, the FDA may require additional post-market research. Post-market surveillance regulations require the sponsor to collect and periodically report additional safety and efficacy data.8 In addition, the FDA may request further clinical research (Phase IV) to find new uses for the drug, test dosage formulations, compare the drug to competitors treatments, and assess long-term effects.9 Finally, pharmaceutical Conclusions A continuous call for ethical standards by pharmaceutical companies that market in the United States is often put aside because company marketing and business model of making profits matter more.(Pharmaceutical Drug Manufacturer, 2011). Brezis (2008) writes that the US public will lose out in the long run because the pharmaceutical companies are more focused on marketing and profits than about public health. Drug trial deaths still happen and have been described as a trade secret. It is not just one of the big pharmaceutical companies by Johnson Johnson, Merick and others whose own safety documents raise concerns that are buried in stacks of papers while marketing continues (Brezis, 2008). But this is offset by the ability of both the doctor and patient to use the Internet to search out the detailed information and become truly informed. Each of them can then make an informed decision about the benefits and potential drawbacks of using pharmaceuticals.

Nanotechnology

Nanotechnology is a new multidisciplinary science interfering with many research areas and aspects. This technology deals with so small particles ranges from 1 to 100 nm (Birla et al., 2009; Husseiny et al., 2015). Nanoparticles of some metals like Au, Ag, Pt and Cu have paid more attention because of their biotechnological benefits (Rai and Duran, 2011). Research revealed the multiapplication of nanoparticle due to their unique properties in electronics, medicine, agriculture, pharmaceutic and environment (Nanda and Majeed, 2014; Dasgupta et al., 2015). Metal nanoparticles emerged as an alternative variety of antibacterial agents against strains of high resistance to the classical antibiotics (Naseem and Farrukh, 2015). Nanoparticles were used as antiviral agents (Gaikwad et al., 2013), effective antibacterial (Singh et al., 2013), cancer cells and antitumor (Daenen et al., 2014). Many researches have been directed to apply the nanoparticles of metals as anthelmintic (Garga and Chandrab, 2012), antifungal (Kim et al., 2012), antiprotozoal (Said et al., 2012), , acaricidal (Marimuthu et al., 2013) and larvicidal (Muthukumaran et al., 2015). Nanoparticles have many chemical and physical characteristics that differ from the metallic particles. Specific characteristics of nanoparticles such as their optical, physicochemical, mechanical properties make them crucial in many applications. Therefore, nanoparticles could be the key factor for the future technologies. Scientific as well as public associations are paying their attention for nanoparticles technology as a good investment source. Nanoparticles could be produced via physical, chemical or biological methods (Haider and Kang, 2015; Ebrahiminezhad et al., 2017). Both chemical and physical methods use reducing agents such as sodium borohydride, sodium citrate and alcohols (Rai and Duran, 2011). However, using of microorganisms in synthesis of nanoparticles represents another great achievement because of the economic and ease production (Shelar and Chavan, 2014; Patel et al., 2015). Research revealed that biological methods is an inexpensive and eco-friendly way for synthesis of nanoparticles. This method used biological agents including bacteria, fungi, yeast and plants (Mourato et al., 2011). Recently, emerging such microorganisms as eco-friendly nano-factories to manufacture inorganic nanoparticles was attractive (Lee et al., 2004; Lengke et al., 2007). Fungi were mentioned as excellent candidates for metal nanoparticle synthesis because they contain many of enzymes that induce the production (Sastry et al., 2003). It was assumed that the mechanism involved in nanoparticles production by fungi was due to cell wall sugars that could reduce the metal ions (Mukherjee et al., 2002) and because they have the high cell wall binding capacity, metal uptake and secrete more amounts of proteins lead to the higher productivity of nanoparticles (Vahabi et al., 2011). Fungi have some advantages over the other microorganisms regarding the synthesis of NPs, because fungal mycelia are able to resist pressure, high temperature and easy storage in the laboratory (Kiran et al., 2016). There are many of metals for biosynthesis (NPs) such as copper, zinc, iron, iron trichloride, lead carbonate, gold and silver (Siddiqi and Husen, 2016). In addition, silver NPs could be synthesized by fungi either intracellularly or extracellularly but the extracellular biosynthesis downstream process much easier and showed more activities against many pathogens (Ahmad et al., 2003). Among the active fungi that were reported to produce nanoparticles; Rhizopous oryzae produced nanoparticles intracellularly of gold (Das et al., 2012), Verticillium sp extracellularly peodcued gold and silver nanoparticles (Soni and Prakash, 2014) in the size range of 20–51 nm. However, F. oxysporum produced nanoparticles of silver of 5–15 nm and 8-14 nm in diameter extracellularly (Ahmad et al., 2003; Senapati et al., 2005). Many other fungi were approved for their productivity of nanoparticles of different metals either extracellularly or intracellularly including: Phoma sp. (Chen et al., 2003), the endophytic fungus Colletotrichum sp. (Shankar et al., 2003), Aspergillus fumigatus (Kuber and D'Souza, 2006) , Fusarium acuminatum (Ingle et al., 2008) , Trichoderma asperellum (Mukherjee et al., 2008), F. semitectum (Sawle et al., 2008), Phoma glomerate (Birla et al. 2009), F. solani (Ingle et al., 2009) , plant pathogenic fungi Aspergillus niger (Gade et al., 2008; Jaidev and Narasimha, 2010), Aspergillus flavus (Vigneshwaran et al., 2007; Jain et al., 2011) , Paecilomyces lilacinus (Devi and Joshi, 2012), endophytic fungus Pencillium sp. (Singh et al., 2013), Aspergillus foetidus (Roy and Das, 2014), Rhizopus stolonifer (AbdelRahim et al., 2017), Penicillium Oxalicum (Bhattacharjee et al., 2017) and Trichoderma atroviride (Saravanakumar and Wang, 2018). Many recent reports have shown that production of nanoparticles by fungi are could be affected by various condition of temperature, biomass weight, time and pH ( Balakumaran et al., 2016; Liang et al., 2017; Othman et al., 2017). Husseiny et al. (2015) reported that most important factors that were affecting the biosynthesis of AgNPs were the temperature, pH, time, the concentration of AgNO3 and amount biomass. Narayanan and Sakthivel (2010) approved that incubation at 27 0C for 72 h with 7 pH and 10 g of the fungal biomass and 1mM concentration of AgNPs were considered the optimum conditions for production of AgNPs from AgNO3 by fungi. Researches showed some variations in the characteristics of the biosynthesized AgNPs by different fungal species. These variations could be due to the source of fungal isolates or strains and types of medium (Devi and Joshi, 2012; Roy and Das, 2014). When Alam et al. (2017) compared the different types of media, they found Czapex dox broth was a good medium to produce enough mycelial biomass to synthesize AgNPs. This because this medium contains essential carbon and nitrogen source along with other vital macro and micronutrients such as magnesium, sodium, calcium, potassium, iron and zinc which are vital for fungal growth.Nowadays, application of AgNPs confirmed their effectiveness in treatment of cancer, bone implant, anti-inflammatory and their biocidal activity against many bacteria and pathogens (Husseiny et al., 2015; Majeed et al., 2016). The antibacterial properties of AgNPs are due to the oxidation and liberation of Ag+ ions into the environment that makes it an ideal biocidal agent (Sivakumar et al., 2015). It is expected that the large surface area to volume ratio as well as high fraction of the surface atoms of the nanoparticles increase their antimicrobial activity as compared with bulk silver metal (Joy and Johnson, 2015). Moreover, the small size of the nanoparticles facilitates their penetration inside the cell. Additionally, excellent antibacterial properties exhibited by AgNPs are due to their well-developed surface which provides maximum contact with the environment (Mitiku and Yilma, 2017). Recent research approved the antibacterial activity of the silver nanoparticles against many bacteria especially those having the capability to cause severe disease for the human such as Salmonella enterica, Enterococcus faecalis, Streptococcus, Proteus mirabilis, Staphylococcus aureus, Escherichia coli, Staphylococci and Pseudomonas sp (Devi and Joshi, 2012; Shelar and Chavan, 2014; Muhsin and Hachim, 2016; Madakka et al., 2018; Saravanakumar and Wang, 2018). However, shape, dimension, and the exterior charge as well as the concentration of the AgNPs are important factors that affect the antimicrobial activity the nanoparticles against the tested bacteria (Madakka et al., 2018). Devi and Joshi (2012) approved the antibacterial activity of AgNPs comparing with erythromycin, methicillin, chloramphenicol and ciprofloxacin agents Staphylococcus aureus, Streptococcus pyogenes, Salmonella enterica and Enterococcus faecalis. They showed that the diameter of inhibition zones obtained by the silver-nanoparticles, with 5-50 nm in diameter, were more than those obtained by the antibiotics. Shelar and Chavan, (2014) showed that Bacillus subtilis and Staphylococcus sp were inhibited by silver nanoparticles with diameter of 17-32 nm in very close pattern to the standard antibiotic streptomycin. Muhsin and Hachim (2016) reported the best concentration of silver nanoparticles with diameter 8-90 nm that showed strong antibacterial activity against Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi and Staphylococcus aureus streptomycin was 100 Â µl/ ml. Based on the above-mentioned information, we assume that fungi as bio-factories for the biogenic synthesis of the silver nanoparticles are very interesting during eco-friendly and safe technology, also for future application as antimicrobial agents. Nanotechnology Nanotechnology is a new multidisciplinary science interfering with many research areas and aspects. This technology deals with so small particles ranges from 1 to 100 nm (Birla et al., 2009; Husseiny et al., 2015). Nanoparticles of some metals like Au, Ag, Pt and Cu have paid more attention because of their biotechnological benefits (Rai and Duran, 2011). Research revealed the multiapplication of nanoparticle due to their unique properties in electronics, medicine, agriculture, pharmaceutic and environment (Nanda and Majeed, 2014; Dasgupta et al., 2015). Metal nanoparticles emerged as an alternative variety of antibacterial agents against strains of high resistance to the classical antibiotics (Naseem and Farrukh, 2015). Nanoparticles were used as antiviral agents (Gaikwad et al., 2013), effective antibacterial (Singh et al., 2013), cancer cells and antitumor (Daenen et al., 2014). Many researches have been directed to apply the nanoparticles of metals as anthelmintic (Garga and Chandrab, 2012), antifungal (Kim et al., 2012), antiprotozoal (Said et al., 2012), , acaricidal (Marimuthu et al., 2013) and larvicidal (Muthukumaran et al., 2015). Nanoparticles have many chemical and physical characteristics that differ from the metallic particles. Specific characteristics of nanoparticles such as their optical, physicochemical, mechanical properties make them crucial in many applications. Therefore, nanoparticles could be the key factor for the future technologies. Scientific as well as public associations are paying their attention for nanoparticles technology as a good investment source. Nanoparticles could be produced via physical, chemical or biological methods (Haider and Kang, 2015; Ebrahiminezhad et al., 2017). Both chemical and physical methods use reducing agents such as sodium borohydride, sodium citrate and alcohols (Rai and Duran, 2011). However, using of microorganisms in synthesis of nanoparticles represents another great achievement because of the economic and ease production (Shelar and Chavan, 2014; Patel et al., 2015). Research revealed that biological methods is an inexpensive and eco-friendly way for synthesis of nanoparticles. This method used biological agents including bacteria, fungi, yeast and plants (Mourato et al., 2011). Recently, emerging such microorganisms as eco-friendly nano-factories to manufacture inorganic nanoparticles was attractive (Lee et al., 2004; Lengke et al., 2007). Fungi were mentioned as excellent candidates for metal nanoparticle synthesis because they contain many of enzymes that induce the production (Sastry et al., 2003). It was assumed that the mechanism involved in nanoparticles production by fungi was due to cell wall sugars that could reduce the metal ions (Mukherjee et al., 2002) and because they have the high cell wall binding capacity, metal uptake and secrete more amounts of proteins lead to the higher productivity of nanoparticles (Vahabi et al., 2011). Fungi have some advantages over the other microorganisms regarding the synthesis of NPs, because fungal mycelia are able to resist pressure, high temperature and easy storage in the laboratory (Kiran et al., 2016). There are many of metals for biosynthesis (NPs) such as copper, zinc, iron, iron trichloride, lead carbonate, gold and silver (Siddiqi and Husen, 2016). In addition, silver NPs could be synthesized by fungi either intracellularly or extracellularly but the extracellular biosynthesis downstream process much easier and showed more activities against many pathogens (Ahmad et al., 2003). Among the active fungi that were reported to produce nanoparticles; Rhizopous oryzae produced nanoparticles intracellularly of gold (Das et al., 2012), Verticillium sp extracellularly peodcued gold and silver nanoparticles (Soni and Prakash, 2014) in the size range of 20–51 nm. However, F. oxysporum produced nanoparticles of silver of 5–15 nm and 8-14 nm in diameter extracellularly (Ahmad et al., 2003; Senapati et al., 2005). Many other fungi were approved for their productivity of nanoparticles of different metals either extracellularly or intracellularly including: Phoma sp. (Chen et al., 2003), the endophytic fungus Colletotrichum sp. (Shankar et al., 2003), Aspergillus fumigatus (Kuber and D'Souza, 2006) , Fusarium acuminatum (Ingle et al., 2008) , Trichoderma asperellum (Mukherjee et al., 2008), F. semitectum (Sawle et al., 2008), Phoma glomerate (Birla et al. 2009), F. solani (Ingle et al., 2009) , plant pathogenic fungi Aspergillus niger (Gade et al., 2008; Jaidev and Narasimha, 2010), Aspergillus flavus (Vigneshwaran et al., 2007; Jain et al., 2011) , Paecilomyces lilacinus (Devi and Joshi, 2012), endophytic fungus Pencillium sp. (Singh et al., 2013), Aspergillus foetidus (Roy and Das, 2014), Rhizopus stolonifer (AbdelRahim et al., 2017), Penicillium Oxalicum (Bhattacharjee et al., 2017) and Trichoderma atroviride (Saravanakumar and Wang, 2018). Many recent reports have shown that production of nanoparticles by fungi are could be affected by various condition of temperature, biomass weight, time and pH ( Balakumaran et al., 2016; Liang et al., 2017; Othman et al., 2017). Husseiny et al. (2015) reported that most important factors that were affecting the biosynthesis of AgNPs were the temperature, pH, time, the concentration of AgNO3 and amount biomass. Narayanan and Sakthivel (2010) approved that incubation at 27 0C for 72 h with 7 pH and 10 g of the fungal biomass and 1mM concentration of AgNPs were considered the optimum conditions for production of AgNPs from AgNO3 by fungi. Researches showed some variations in the characteristics of the biosynthesized AgNPs by different fungal species. These variations could be due to the source of fungal isolates or strains and types of medium (Devi and Joshi, 2012; Roy and Das, 2014). When Alam et al. (2017) compared the different types of media, they found Czapex dox broth was a good medium to produce enough mycelial biomass to synthesize AgNPs. This because this medium contains essential carbon and nitrogen source along with other vital macro and micronutrients such as magnesium, sodium, calcium, potassium, iron and zinc which are vital for fungal growth.Nowadays, application of AgNPs confirmed their effectiveness in treatment of cancer, bone implant, anti-inflammatory and their biocidal activity against many bacteria and pathogens (Husseiny et al., 2015; Majeed et al., 2016). The antibacterial properties of AgNPs are due to the oxidation and liberation of Ag+ ions into the environment that makes it an ideal biocidal agent (Sivakumar et al., 2015). It is expected that the large surface area to volume ratio as well as high fraction of the surface atoms of the nanoparticles increase their antimicrobial activity as compared with bulk silver metal (Joy and Johnson, 2015). Moreover, the small size of the nanoparticles facilitates their penetration inside the cell. Additionally, excellent antibacterial properties exhibited by AgNPs are due to their well-developed surface which provides maximum contact with the environment (Mitiku and Yilma, 2017). Recent research approved the antibacterial activity of the silver nanoparticles against many bacteria especially those having the capability to cause severe disease for the human such as Salmonella enterica, Enterococcus faecalis, Streptococcus, Proteus mirabilis, Staphylococcus aureus, Escherichia coli, Staphylococci and Pseudomonas sp (Devi and Joshi, 2012; Shelar and Chavan, 2014; Muhsin and Hachim, 2016; Madakka et al., 2018; Saravanakumar and Wang, 2018). However, shape, dimension, and the exterior charge as well as the concentration of the AgNPs are important factors that affect the antimicrobial activity the nanoparticles against the tested bacteria (Madakka et al., 2018). Devi and Joshi (2012) approved the antibacterial activity of AgNPs comparing with erythromycin, methicillin, chloramphenicol and ciprofloxacin agents Staphylococcus aureus, Streptococcus pyogenes, Salmonella enterica and Enterococcus faecalis. They showed that the diameter of inhibition zones obtained by the silver-nanoparticles, with 5-50 nm in diameter, were more than those obtained by the antibiotics. Shelar and Chavan, (2014) showed that Bacillus subtilis and Staphylococcus sp were inhibited by silver nanoparticles with diameter of 17-32 nm in very close pattern to the standard antibiotic streptomycin. Muhsin and Hachim (2016) reported the best concentration of silver nanoparticles with diameter 8-90 nm that showed strong antibacterial activity against Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi and Staphylococcus aureus streptomycin was 100 Â µl/ ml. Based on the above-mentioned information, we assume that fungi as bio-factories for the biogenic synthesis of the silver nanoparticles are very interesting during eco-friendly and safe technology, also for future application as antimicrobial agents.

Author Sophocles Displays A Conflict - Free Essay Example

Sample details Pages: 2 Words: 610 Downloads: 5 Date added: 2019/05/20 Category Literature Essay Level High school Tags: Antigone Essay Did you like this example? Most teenagers disobey their parents, break rules every once in a while, or rebel out of anger, stupidity, boredom or just impulsiveness. In the Greek play, Antigone, author Sophocles displays a conflict among Antigone, a teenage girl and her tyrannical, ruling uncle, Creon. When Antigoners determination and impulsiveness results in her breaking the law to bury her beloved brother, Creon, with no remorse, automatically sentences Antigone to death. Don’t waste time! Our writers will create an original "Author Sophocles Displays A Conflict" essay for you Create order Despite the fact that many characters in the play are flawed, Antigoners impulsiveness results in Haemonrs death, Creonrs downfall, and her own death. Antigoners actions have caused things to spiral out of control, and lives have been lost including Haemonrs; her future husband. When Haemon cant choose between his tyrannical, autrocious, father and his lover, he commits suicide, and soon after, so does Tiresias, his mother. When standing up for Antigone to his father, Haemon exclaims, Were you not my father, I would call you a fool (Sophocles 779). Before exiting, Haemon argues, No- not in my sight- never think this can happen! Shell not die beside me, and you will never lay your eyes upon my face again, so rage with any of your friends who can bear it (Sophocles 776). Those are Haemonrs last words before he takes his own life. If Antigone hadnt acted on Polyneices death, Haemon, and even Tiresias could still be alive, but when Haemon is put in the middle of his lover and father, it is impossible for him to decide where to stand. Creon doesnt know that by putting Antigone to death after she breaks the law, that it will lead to his downfall. Miserably, Creon says, Woe is me, these things will never fall on another person so as to exonerate me, for I killed you, O unhappy I, I claim truly. Servants, take me away right now, take me out of the way. I dont exist any more; Im no one (Sophocles 1323). A very arrogant King Creon wants to remain ?loyal and maintain his laws, however, itrs at the end when he realizes that by doing that, his sonrs and his wifers lives are taken. Before exiting, Creon exclaims, Let this rash man be led out of the way, who, my child, unwillingly slew you, and this woman, you, too- alas! I have no where to turn to, nothing to lean on, for everthing goes cross in my hands, and a difficult fate falls on my head (Sophocles 1247). It is only after his downfall that he realizes the mistakes he has made. However, by then itrs much too late to fix anything and he has lost everything. Pride and arrogance had overcome Creon, and played a huge role in his downfall. Antigone caused her own demise. Antigone is a bit too prideful and does not obey the law that King Creon has set: that no one can bury Polyneices body. Instead of following the rules, Antigone decides to bury Polyneices because he is family and she loves him. However, she doesnt see the bigger picture: death. Ill bury my brother- your brother too, too, though you refuse! Ill not be found a traitor (Sophocles 47). However, Antigone isnt a traitor. She, on the other hand, thinks otherwise. She doesnt listen to obediant sister Ismene either, who tells her she should follow the rules. Antigone argues with Ismene when Ismene says no to help bury Polyneices and states, Use that excuse, if you like, but I indeed will go and heap and tomb for my dearest brother (Sophocles 81). Antigone is being ignorant of her consequences and doesnt take them very seriously until she does. Antigoners teenage impulsivness has resulted in 3 downfalls, two of which being death.

Smog How it Is Formed and How to Protect Yourself

The formation of smog is hazardous to your health especially if you live in a big sunny city. Find out now how smog is formed and how you can protect yourself. The sun gives us life. But it also can cause lung cancer and heart attacks as it is a primary factor in creating smog. Learn more about this hazard. The Formation of Smog Photochemical smog (or just smog for short) is a term used to describe air pollution that is a result of the interaction of sunlight with certain chemicals in the atmosphere. One of the primary components of photochemical smog is ozone. While ozone in the stratosphere protects earth from harmful UV radiation, ozone on the ground is hazardous to human health. Ground-level ozone is formed when vehicle emissions containing nitrogen oxides (primarily from vehicle exhaust) and volatile organic compounds (from paints, solvents, and fuel evaporation) interact in the presence of sunlight. Therefore, some of the sunniest cities are also some of the most polluted. Smog and Your Health According to the American Lung Association, your lungs and heart can be permanently affected by air pollution and smog. While the young and the elderly are particularly susceptible to the effects of pollution, anyone with both short and long-term exposure can suffer ill health effects. Problems include shortness of breath, coughing, wheezing, bronchitis, pneumonia, inflammation of pulmonary tissues, heart attacks, lung cancer, increased asthma-related symptoms, fatigue, heart palpitations, and even premature aging of the lungs and death. How to Protect Yourself From Air Pollutants You can check the Air Quality Index (AQI) in your area. It may be reported on your weather app or local weather forecast or you can find it at the AirNow.gov website. 0 to 50: Green. Good air quality.51 to 100: Yellow. Moderate air quality. People who are unusually sensitive to ozone may experience respiratory symptoms.101 to 150: Orange. Unhealthy air quality for sensitive groups including people with lung disease or heart disease, older adults, and children.151 to 200: Red. Unhealthy for everyone, with special concern for sensitive groups.201 to 300: Purple. Health alert level indicating very unhealthy conditions, everyone may experience serious health effects.301 to 500: Maroon. Hazardous, an emergency condition for the entire population. Air Quality Action Days When air quality gets into unhealthy levels, local air pollution agencies declare an action day. These have different names depending on the agency. They may be called a Smog Alert, Air Quality Alert, Ozone Action Day, Air Pollution Action Day, Spare the Air Day, or many other terms. When you see this advisory, those sensitive to smog should reduce their exposure, including refraining from prolonged or heavy exertion outdoors. Become familiar with what these days are called in your area and pay attention to them in weather forecasts and on weather apps. You can also check the Action Days page at the AirNow.gov website. Where Can You Live to Avoid Smog? The American Lung Association provides air quality data for cities and states. You can check different locations for air quality when considering where to live. Cities in California lead the list due to the effects of sun and high levels of vehicular traffic.