Colon Specific Drug Delivery

Colon Specific Drug Delivery ABSRACT The colon is a site where both local and systemic delivery of drugs can takes place. Colon specific drug delivery has achieved importance for the delivery of drugs for the treatment of local diseases associated with the colon like crohn’s disease, ulcerative colitis etc. as well as for the systemic delivery of proteins, therapeutic peptides, antiasthmatic drugs, antihypertensive drugs and antidiabetic agents. A drug need to be protected from degradation, release and absorption in the upper part of GIT and then to be ensured abrupt and controlled release in the proximal colon. This article reviews a detailed study about need of colon specific drug delivery, limitation and challenges, factors affecting colonic drug delivery, different approaches of colon including some successful novel approaches such as CODESTM, Pulsinicap system, Port system, Colal pred system, Multiparticulate system and also a study on evaluation for site specific drug delivery to colon. INTRODUCTION Drug administration through an oral route is the most convenient and important route of administering drugs for systemic effect. At about 50% of the drug delivery systems available in the market are oral drug delivery systems and these systems have more benefits due to patient acceptance and ease of administration. During the last decade considerable interest has been given in developing site-specific formulations for targeting drugs to the colon. Colon specific drug delivery has achieved increased importance not only for the delivery of the drugs for the treatment of local disorders associated with the colon like Crohn’s disease, ulcerative colitis, irritable bowel syndrome and constipation but also for the systemic delivery of proteins and peptides, antihypertensive drugs, antiasthmatic drugs and antidiabetic agents. The colon specific drug delivery system should have capability to protect the drug en route to the colon i.e. drug release and drug absorption should not occur in the stomach as well as the small intestine, and the bioactive agent should not be degraded in either of the dissolution sites but only released and absorbed once the system reaches the colon.1 Colon targeted drug delivery would additionally be valuable when a delay in absorption is desired from a therapeutically point of view in the treatment of diseases that have peak symptoms early in the morning, such as nocturnal asthma, angina or arthritis. The rapid advancement of biotechnology and genetic engineering resulted into availability of peptides and proteins at reasonable costs; there has been an increased interest in utilizing the colon as site for drug absorption. The potential candidates in this respect include analgesic peptides, oral vaccines, contraceptive peptides, growth hormone, insulin, erythropoietin, interferon, and interleukins (Saffran et al., 1988; Mackay and Tomlinson, 1993).2 The colon is a suitable absorption site for peptides and protein drugs due to: i) less diversity and intensity of digestive enzymes ii) less proteolytic activity of colon mucosa resulting in better prevention from hydrolysis and enzymatic degradation in duodenum and jejunum iii) increased systemic bioavailability iv) long colon residence time (5 days) and high responsiveness to absorption enhancers. There are number of methods or techniques through which colon drug targeting can be achieved, such as formation of prodrug, coating with pH sensitive polymers, coating with biodegradable polymers, designing formulations using polysaccharides, timed release system, pressure-controlled drug delivery systems, osmotic pressure controlled systems etc. Need of colon targeted drug delivery Colon targeted drug delivery system would asssure direct treatment at the disease site, lower dosing and fewer systemic side effects. Site-specific drug delivery system would allow oral administration of protein and peptide drugs, colon-specific formulation could also be used to prolong the drug delivery. Colon-specific drug delivery system is useful in the treatment of colon diseases. The colon is a site where both local or systemic drug delivery could be achieved. Topical treatment of inflammatory bowel disease, e.g. ulcerative colitis or Crohn’s disease. These inflammatory conditions are majorly treated with glucocorticoids and sulphasalazine (targeted). A number of others serious disorders of the colon, e.g. colorectal cancer, may also be capable of being treated more effectively if drugs were targeted to the colon. Formulations for colonic delivery are also suitable for delivery of drugs which are polar and/or susceptible to chemical and enzymatic degradation in the upper GI tract, highly affected by hepatic first pass metabolism, in particular, therapeutic proteins and peptides.3 Limitations and challenges in colon targeted drug delivery system A challenge in the development of colon specific drug delivery systems is to set up an appropriate dissolution testing method for in-vitro evaluation of the designed system. This is due to the rationale after a colon specific drug delivery system is quite different. As a site for drug delivery, the colon provides a near neutral pH, low digestive enzymatic activity, a long transit time and enhanced sensitivity to absorption enhancers; however, the targeting of drugs to the colon is very complicated. Owing to its location in the distal part of the alimentary canal, the colon is predominantly difficult to access. In addition to that the variation in pH values and different enzymes present throughout the gastrointestinal tract, through which the dosage form has to pass before reaching the target site, further complicate the consistency and delivery efficiency. Successful delivery through this site also needs the drug to be in solution form before it reaches the colon or alternatively, it should dissolve in the luminal fluids of the colon, but this can be a limiting factor for poorly soluble drugs as the fluid content in the colon is much lower and it is more viscous than in the upper part of the GI tract. The stability of the drug is also taken into consideration while designing a drug delivery system, because it may bind nonspecific way to dietary residues, intestinal secretions, mucus or faecal matter. Low surface area and relative tightness of the tight junctions in the colon can also limit drug transport across the mucosa and into the systemic circulation.4 Anatomy and physiology of colon The gastrointestinal tract is hollow muscular tube. It takes in nutrients and eliminate waste by such physiological processes as secretion, motility, digestion, absorption and excretion. Depending on structure and functions, the gastrointestinal tract is divided into the mouth, pharynx, oesophagus, stomach, small intestine and large intestine. The large intestine is approximately 1.5m in length and extends from the ileocaecal junctions to the anus. It is divided into four parts: caecum, colon, rectum and anal canal.5 The entire colon is approximately 5 feet (150 cm) long, and is divided into five major portions. Peritoneal folds called as mesentery which is supported by ascending and descending colon. The right colon consists of the caecum, ascending colon, hepatic flexure and the right half of the transverse colon. The left colon consists of the left half of the transverse colon, descending colon, splenic flexure and sigmoid. The rectum is the last anatomic segment before the anus. The human colon were shown in Figure1.The main functions of the colon is to make suitable environment for the growth of colonic microorganisms, storage reservoir of faecal contents, expulsion of the contents of the colon at an appropriate time and absorption of potassium and water from the lumen. The absorptive capacity is very high, at about 2000ml of fluid enters the colon through the ileocecal valve from which more than 90% of the fluid is absorbed6. The colon is involved in fermentation of polysaccharides and proteins, absorption of water and electrolytes and the formation, storage and elimination of faecal material. As a consequence of the functions of the colon, the colonic environment is generally viscous in nature. This could impact on the performance of drugs and delivery systems in this region of gut. Rapid water absorption in the ascending colon results in the distal colonic contents being more viscous. It has been estimated that the human colon contains only 220g of wet contents. In addition colon has a near neutral pH and is home to a viable microflora. These bacteria are involved in the fermentation of polysaccharides and proteins that have escaped digestion in the upper gut. Moreever the resident bacteria can also metabolize drug. The protein based drugs, insulin and calcitonin are rapidly degraded in simulated colonic contents5. Fig 1: Anatomy of colon Factors influencing colonic drug delivery: Physiological factors: 1. Transit through gastro intestinal tract Orally taken dosage forms first enters into stomach and small intestine via mouth and then reach colon. The nature and pH of the stomach affects the drug release and absorption. In order to effectively deliver tablet to colon in an intact form, the drug delivery systems should bypass the barriers in the stomach and small intestine. Gastrointestinal transit varies from 1 hr to 3 hrs depending upon the condition fasting or non-fasting respectively. In general, the small intestinal transit is not influenced by the physical state, size of the dosage form. The mean transit time of the dosage form is about 3-4 hours in order to reach the ileocecal junction and the time period is inconsistent. During this time the dosage form is exposed to enzymes present in small intestine. Compared to the other region of GIT, movement of material through the colon is slow. Total time for transit tends to be highly variable and influenced by number of factors such as diet particularly dietary fibre content , mobility, stress, disease condition and drugs. The colonic transit time is ranging from 20 to 30 hours, can be increase in presence of active disease 50 to 70 hours. Longer residence time with subsequent longer transit time and the contact of dosage form with micro flora in colon govern the release and improve absorption of drug from dosage form.7 Table 1: Transit time of dosage forms in GIT Organ Transit time(hr) Stomach >3 (fed) Small intestine 3-4 Large intestine 20-30 2. pKa of the drug, lipophilicity and gastrointestinal pH: The pH partition theory explains the process of drug absorption from the GIT and its distribution across all biological membranes. It states that for drug molecules of molecular weight greater than 100, which are mainly transported across the biological membranes by passive diffusion, the process of absorption is governed by: 1) The dissociation constant (pKa) of the drug. 2) The lipophilicity of unionized drug. 3) The pH at the absorption site. Since most of the drugs are weak electrolytes (weak acids or weak bases), their degree of ionization depends upon the pH of the biological fluid. If the pH on the either side of the membrane is different, then the compartment in which pH favors greater ionization of the drug will contain greater amount of drug, and only the unionized form of drug, if adequately lipid soluble, allowed to permeate the membrane passively until the concentration of unionized drug on both side of the membrane becomes equal i.e. until equilibrium is attained. The above statement of the hypothesis was on the basis of the assumptions that: 1) The GIT is a simple lipoidal barrier to the transport of drug. 2) Larger the fraction of unionized drug, faster the absorption(D. M. Brahmankar et al 2009). 3.pH of colon The pH of GIT varies in each individual. The food intakes, diseased state, etc.influences the pH of the GIT. This change in the pH in different regions of GIT is the basis for the development of colon targeted drug delivery systems. Coating with different polymers is done to target the drug to the site. Table 2: pH in different regions of gastrointestinal tract Part of GIT Ph Stomach (before meal) 1-2 Stomach (during digestion) 4 Smll intestine 6-7 Duodenum 6.6+0.5 Ileum 7.5+0.4 Caecum 6.4+0.4 Colon 5.5-7 Rectum 7 4. Colonic microflora A number of anaerobic and aerobic bacteria are present throghout entire length of the human GI tract. Over 400 different bacterial species have been found, 20-30% of which are of the genus bacteroids. The upper region of the GIT has a very small number of bacteria and predominantly consists of gram positive bacteria. The rate of microbial growth is greatest in the proximal areas because of high concentration of energy source. Concentration of microflora is generally about1011-1022 CFU/ml. It consists of Bacteroids, Bifidobacterium, Ruminococcus, Eubacterium and Clostridium. Chief metabolic reactions carried by the enzymes released from colonic microflora are hydrolysis and reduction. Table 3: Different microflora, enzymes and their actions Enzyme Microorganism Metabolic reactions catalysed Nitroreductase E. coli, Bacteroids Reduced aromatic and heterocyclic nitro compounds Azoreductase Clostridia, Lactobacilli, E.coli Reduced cleavage of azo compounds N oxide reductase, Sulphoxide reductase E. coli Reduced N oxides and sulphoxides Hydrogenase Clostridia, Lactobacilli Reduced carbonyl groups and aliphatic double bonds Esterases and amidases E. coli,P. vulgaris, B.subtilis, B. mycoides Cleavage of esters or amidases of carboxylic acid Glucosidase Clostridia, Eubacteria Cleavage of b- glycosidase of alcohols and phenols Glucoronidase E.coli, A. aerogenes Cleavage of b glycosidase of alcohols and phenols Sulphatase Eubacteria, streptococci Cleavage of O-sulfates and sulfamates Phamaceutical factors a) Drug candidate Drugs which show poor absorption in the stomach and intestine are most suitable for colon delivery. Drugs such as theophylline, nifedipine, diclofenac, ibuprofen, metoprolol, isoosorbide dinitrate, oxyprenolol and low molecular weight peptides and Peptide like drugs have been shown to be effectively absorbed from the colon. b) Drug carrier The selection of carrier for a particular drug candidate depends on the physicochemical nature of the drug as well as the disease for which the system is to be utilized. The factors such as chemical nature, stability and partition coefficient of drug and the type of absorption enhancers influences the carrier selection.9 Table 3: Drugs in colon targeted drug delivery Sr. No. Criteria Pharmacological class Drug and active agents 1 Drug used for local effect in colon Anti-inflammatory Drugs Oxyprenolol, Metoprolol, Nifedipine, Diclofenac, Sodium, Amylin, Antisense Oligonucleotide, 2 Drugs poorly absorbed from upper GIT Antihypertensive and antianginal drugs Ibuprofen, Isosorbides, Theophylline, Desmopressin Cyclosporine A, 3 Drugs for colon cancer Antineoplastics Pseudoephedrine, epoetin, Glucagon 4 Drugs that degrade in stomach and small intestine Peptides and proteins Bromopheniramine, 5 Flurouracil, Doxorubicin, Gonadoreline, Insulin, Interferones 5 Drugs that undergo extensive first pass metabolism Nitroglycerin and corticosteroids Nimustine, Bleomycin, Nicotine, Dexamethasone, protirelin, Sermorelin, Molgramoatim, Salotonin.

Behaviorism, Cognitivism and Constructivism

We study about three psychological school of thought Behaviorism, Cognitivism and Constructivism. In this reaction paper I notice my opinion and attitude and personal analyze about them briefly. One of the point that always think about it is that why some school of thought speak and focus on one factor of human being and deny many other factors of human nature as we see in BEHAVIORIST they believe that human nature like a tabula rasa and It assumes that each one behavior and acquisition either reflexes created by a response to sure stimulus within the environment. They didn't mention anything about inherited factors or inner of human obviously the environment, reinforcement and punishment play a great rule in acquisition but they ignore many aspect of human mind like creativity activity and looking a learner like automaton and passive creature. Radical Behaviorism maintain some important distinction with methodological form they acknowledge the view that organisms are born with innate behaviors, and also accept the role of genes and biological components in behavior. So it is more rational and moderate form of behaviorism. Cognitive theories center around the conceptualization of understudies learning procedures and address the issues of how data is gotten, sorted out, put away, and recovered by the mind. Learning is concerned not such a great amount with what students do but rather with what they know and how they come to get it. Cognitivism focus on that part of learning which deny in Behaviorism, mental activities of human mind they consider previous acquired knowledge, experiences and different abilities of each learners. They emphasize making learning significant furthermore, helping students sort out and relate new data to existing information in memory. The role of teachers in charge of helping students in sorting out that data in some ideal way. Originators utilize procedures, for example, advance coordinators, analogies, progressive connections, and grids to enable students to relate new data to earlier information. This school is more practical and flexible for considering the learner as active creature. Constructivism focus on learner and different aspect of attitude in every subject that learners can gain it. Individual and personal learning has a great role in their school. The learners in active mental process of learning should analyze and understand past experiences and adding them more details and knowledge through new experiences. We live in a real world we need practical knowledge that useful for our life so activity, knowledge, concept, culture, context are essential factors of process of learning. Plainly the focal point of constructivism is on making intellectual instruments which mirror the astuteness of the way of life in which they are utilized too as the bits of knowledge and encounters of people. There is no requirement for the mere obtaining of fixed, unique, independent ideas or subtle elements. Every different concept can be true and juxtaposition of individual ideas are gathering in social constructivism. In brief word we need all type of thinking in our world and combination of them are useful and meaningful to create more mature human being. In conclusion we can not select the best school of thought. Sometime we need to drill accents by repeation in some case we need to find out individual ability and rational and pragmatic analyze of our students. So I myself think all of them are effective in different situation and it depends on age and level of leaners and goals of lecturers. Combination of them can help us make an attractive method for language learner. Differ ideas and situation can challenge the students and help us to find out which one better work on every individual or group of learner.

The legal profession is a form of public trust

The legal profession is a form of public trust which is given only to those qualified enough to uphold the law and assist in the administration of justice. It is a duty of public service which involves sincerity, integrity and reliability, in which pecuniary considerations are a mere by-product, notwithstanding establishing lawyer-client relationships in the highest degree of fiduciary. The lawyer is an oath-bound servant of society whose conduct is clearly circumscribed by inflexible norms of law and ethics to which the ends of justice are the primary considerations. In rendering legal services to his clients, he must observe utmost fidelity to the cause of his client regardless of his personal beliefs on his client’s guilt or innocence, as even the most guilty of all criminals can still avail of the different protections afforded by the law. Sometimes, though, lawyers are faced with legal complications in providing the most adequate defenses for their clients especially when the latter are found to have deliberately violated the laws of the land. These acts do no include justifying circumstances in criminal prosecutions as these are been deemed lawful when convincingly proven in court. The acts contemplated here are acts which are considered, on its face, patent violations of the law bereft of any legal justification. However, these illegal acts do not preclude the rendering of legal services for the protection of their rights. Among the conditions and circumstances that utterly warrant the defense of illegal acts are those which are challenged based on constitutional issues involving the due process and equal protection clauses, and constitutionally-protected freedoms such as free expression and the right to privacy. The due process and the equal protection clauses have been two of the most important protections afforded by the US Constitution to the American people to safeguard them from the unwarranted intrusions of government into the free exercise of their democratic rights. As a result, many previously considered violations of the law were overturned by the US Supreme Court for abridging the due process and equal protection clauses of the constitution, to the extent that entire statutes were declared unconstitutional and taken off the statute books. In the case of Lawrence v. Texas, two gay couples were charged and convicted for â€Å"deviate sexual intercourse, namely anal sex, with a member of the same sex,† (539 U.S. 558) and violating the Texas Penal Code Ann.  §21.06(a), which provides that a person commits an offense if he engages in deviate sexual intercourse with another individual of the same sex. The homosexual couple asserted that their conviction was an infringement of the Equal Protection and Due Process Clauses of the Fourteenth amendment, in which the majority opinion answered thus These matters, involving the most intimate and personal choices a person may   Ã‚  Ã‚  Ã‚   make in a lifetime, choices central to personal dignity and autonomy, are central   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   to the liberty protected by the Fourteenth Amendment. At the heart of liberty is   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   the right to define one’s own concept of existence, of meaning, of the universe,    and of the mystery of human life. Beliefs about these matters could not define the   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   attributes of personhood were they formed under compulsion of the State.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚     Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Planned Parenthood of Southeastern Pa. v. Casey, 505 U.S. 833 (1992) Such homosexual acts in the privacy of a person’s home is subsumed in the concept stated above and their autonomy as persons to decide for themselves the concept of their own existence and meaning must be respected by the Court and the law. While convicted in the lower courts for violating the law, they were vindicated by the ruling of the Supreme Court based on their constitutional challenge. A case that was won based on procedural due process is the case of Tumey v. Ohio in which Tumey was arrested and charged with the unlawful possession of intoxicating liquor at White Oak, another village in Hamilton county, Ohio, on a warrant issued by the mayor of North College Hill. The mayor of the town then proceeded to try and convict Tumey under the existing law. His conviction was challenged based on the pecuniary interest of the mayor in convicting Tumey as he stood to gain from the amount of the costs in each case, in addition to his regular salary, as compensation for hearing such cases. There is, therefore, no way by which the mayor may be paid for his service as judge, if he does not convict those who are brought before him. The US Supreme Court looked favorably on the assertions of Tumey, reversed his conviction, and remanded the case for further trial, due to the utter lack of impartiality in the previous proceedings with the mayor sitting as a judge. This is proof once again that constitutional challenges protect the rights even of persons seen to have deliberately violated the law. In Lanzetta v. New Jersey, the appellants were indicted and convicted under the New Jersey Statute which prosecutes â€Å"any person not engaged in any lawful occupation, known to be a member of any gang consisting of two or more persons, who has been convicted at least three times of being a disorderly person, or who has been convicted of any crime, in this or any other State, is declared to be a gangster. The US Supreme Court declared the statute unconstitutional for being repugnant to the Fourteenth Amendment as the word â€Å"gang† and â€Å"gangster† is vague such that even those who belong to a group whose objective may be legal may unnecessarily be covered. Hence, due to vagueness, there is no sufficient warning to the public as to what exactly is proscribed by the law. The persons in this case, even if found to be true gangsters in a socio-cultural sense, had their convictions reversed simply due to the vagueness of the law. In the case of In Re Lynch, John Lynch was released from prison that supposedly condemned him for life behind bars as the US Supreme Court found the penalty for this offense of indecent exposure too cruel for such a light offense, relative to more heinous crimes with the same penalty. Lynch was definitely found guilty of his crime, yet the law still afforded him adequate protection despite his offenses when it was challenged based on the constitutional issue of disproportionate punishments which, although not cruel or unusual in its method, it is so disproportionate to the crime for which it is inflicted that it shocks the conscience and offends fundamental notions of human dignity. In New York Times v. Sullivan, the libel suit of L.B. Sullivan against the New York Times did not earn the affirmation of the US Supreme Court as it held that the interest of the public outweighs the interest of any other individual. While the New York Times might, on its face, erred in accurately reporting the facts of the civil rights demonstration involving Martin Luther King, the newspaper cannot be held for its criticisms of the official conduct of public officials.   In this case, the freedom of the press saved the New York Times from settling the multi-million dollar libel suit filed by Sullivan even if the lower courts found them guilty of the offense. In the famous case of Griswold v. Connecticut, Drs. Griswold and Buxton were found guilty of violating 53-32 and 54-196 of the General Statutes of Connecticut and fined $100 each for giving information, instruction, and medical advice to married persons as to the means of preventing conception, notwithstanding examining a married woman and prescribed the best contraceptive device or material for her use. The US Supreme Court reversed their convictions based on a discussion of the penumbra of rights which are formed by emanations from those constitutional guarantees that help give them life and substance. This is shown in past cases wherein, though not directly involved, the right to privacy was upheld. The court, in verbatim even said – The present case, concerns a relationship lying within the zone of privacy created   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   by several fundamental constitutional guarantees. And it concerns a law which, in   Ã‚   forbidding the use of contraceptives rather than regulating their manufacture or    sale, seeks to achieve its goals by means having a maximum destructive impact upon that relationship. Such a law cannot stand in light of the familiar principle, so often applied by this Court, that a â€Å"governmental purpose to control or prevent   Ã‚   activities constitutionally subject to state regulation may not be achieved by means which sweep unnecessarily broadly and thereby invade the area of   Ã‚  Ã‚  Ã‚  Ã‚   protected freedoms.† Yet again, the US Supreme Court intervened in expunging responsibility from individuals who were found to be in blatant violation of the existing laws of the land. In all of these, it is patently clear that individuals found to be in deliberate violation of existing laws can still be afforded protection by our system of laws. While many other conditions and exceptions exist to warrant the defense of supposedly erring individuals and groups, the best way of going around the violations of the law is through a sound constitutional challenge before the courts of law, from the lowest courts all the way up to the US Supreme Court. It must be remembered that these are done not only for the sheer obstinacy of defending the cause of the client but also in pursuit of upholding the rule of law, the integrity of the courts and assist in the administration of justice. The duties of the lawyers are not only to prosecute and defend, but also to ensure that justice is done to all those who deserve it. Cases Cited: Lawrence v. Texas, 539 U.S. 558 (2003) Tumey v. Ohio, 373 US 510 (1927) Lanzetta v. New Jersey, 306 US 451 (1939) In Re Lynch, 8 Cal 3rd 410 P. 2d (1972) New York Times v. Sullivan, 376 US 254 (1964) Griswold v. Connecticut, 381 US 47A (1965)   

Research On Diabetes And Its Effects On The Lives Of The...

Living in the 21st century, it may seem like a miracle that the people of the past survived at all. Medical procedures and beliefs at that time were often unscientific and illogical, and disease was rampant. However, new evidence suggests that our own modern understanding of medicine is also quite flawed. Research done on traditionally deadly diseases show that these illnesses may have given an evolutionary advantage to the people of the past. For one, research on hemochromatosis has not only shown that the disease helps to prevent infection, but has also challenged accepted medical processes. Research on diabetes has led to the discovery of another part of our history in which excess amounts of sugar would have been beneficial. Research on favism has shown both the dangers and benefits of plants and disease, especially among certain populations. Indeed, hemochromatosis, diabetes, and favism all have genetic components that played a role in early man’s survival and in our mode rn-day medical research. Rusting may seem like an issue specific to the Tin Man, but it is more common than most believe. Hemochromatosis is a hereditary disease that disrupts iron metabolism, leading to massive amounts of iron in the blood and the liver. Excess amounts of iron damages joints, major organs, and body chemistry, and can eventually lead to liver damage, heart failure, diabetes, arthritis and cancer. First described by Armand Trousseau in 1865, the disease was originally thought to beShow MoreRelatedDiabetes: Getting to Know it Better1435 Words   |  6 PagesDiabetes has become a prevalent disease, due to its drastic increase in diagnosis since the turn of the 21st century. People of all skin color, social class, or ethnicity can fall prey to this lifelong illness. 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It is too Quiet in the After - 2618 Words

The After Its too quiet. That was my first thought as I was aroused from my sleep on the first night. That silence, that eerie, distilled silence was what had woken me up. It was three o’clock in the morning and it was too quiet. There was no rustling of dead leaves in the wind, the constant blaring of my uncle’s flat screen TV was for the first time not seeping through the cracks of my bedroom walls, and my parent’s screaming voices where finally silent after years of arguing. Even the white noise from the broken radio that my grandmother refused to turn off because she claimed that my grandfather spoke to her through the chorus of static had finally ended. But that silence, that delightfully relieving silence was wrong somehow and I couldn’t put my finger on it. As I lay there in my bed, I noticed that this silence wasn’t normal. Its flavor was all wrong, it tasted slightly sweet yet to only have a bitter after-taste that left you will a foul odo r and lingered on the tip of your tongue and crept up your nose, kind of like when you smelled decaying flesh or the lingering scent of infection. It was not only quiet but cold and dark as well. It was too cold for the hot and steamy month of June. The chilly air was raw and jagged, like crisp snow on broken bones and the dark seeped into my white bedroom like bleeding ink on parchment paper. The only source of light was the faint grayish hue that the moon had casted, but even that was slowly melting away. Curious and aShow MoreRelatedComp Ii696 Words   |  3 Pagescolor shoes I wanted. 2. If a cat falls (of / off) the counter, it will land on its feet. 3. Make sure you do (your / you’re) homework right after school. 4. I talked (to / too / two) my brother yesterday. 5. (Are / Our) you going to be on (are / our) baseball team? 6. He bought (to / too / two) speakers (to / too / two) complete his stereo system. 7. I saw (their / there / they’re) mom sitting (their / there / they’re). 8. I think (their / thereRead MoreEssay The Shy Girl894 Words   |  4 PagesThe Shy Girl Ever since I can remember, I was naturally quiet and shy. I constantly repeated myself because people could not hear me the first time. Even then, I seldom made eye contact with others. When I entered high school, nothing changed. Soon afterward, I disliked the way my classmates thought of me. If someone had to make an announcement in class, I was not chosen; my classmates believed I was not vocal enough. If someone threw a party, I was not invited because they thought ShyRead MoreMy Experience At The Gym For A Physical Education ( P.e ) Essay988 Words   |  4 Pagesâ€Å"If everything is quiet, it is assumed that all is well. This is why many normal children-considering what kind of intelligence is expected and what till be rewarded here-becomes passive, quiet, obedient, dull. The environment practically demands it (Ayers, 64).† One thing that I don’t understand is why P.E. chose the field that they did, if they want and expect their students to be quiet during P.E. class. I personally believe that children are not meant to sit still and be quiet all day. When itRead MoreAll Quiet on the Western Front by Erich Maria Remarque781 Words   |  3 PagesAll Quiet on the Western Front is a short bo ok, but remarkably deep. More than 50 years after its jolting prose, haunting poetry, and powerful truths slashed their way into the consciousness of a worldwide readership, All Quiet still stands at the forefront of a host of novels on that most tragic recurrence in the history of human experience: war. All the aspects of trench warfare are present—excitement, boredom, horror, hunger, fear, dirt, alienation, imminent death, futility, to name a few. AllRead MoreInformative Speech : The Funny Thing About Introverts1144 Words   |  5 PagesAudience Relevance: Introversion is a personality trait, which is viewed as quiet. The words introversion and extroversion came from Swiss psychiatrist and psychotherapist, Carl Jung. C. Speaker Credibility: Remember in middle school and high school when you use to vote most likely or this person is? Remember there would be a category of who was shy or quiet? That would always be me. Or people would ask me why or say that I’m so quiet. Does it bother me? No not really, it’s true. It can be annoying thoughRead MoreInformative Speech : Introverts 1152 Words   |  5 PagesAudience Relevance: Introversion is a personality trait, which is viewed as quiet. The words introversion and extroversion came from Swiss psychiatrist and psychotherapist, Carl Jung. C. Speaker Credibility: Remember in middle school and high school when you use to vote most likely or this person is? Remember there would be a category of who was shy or quiet? That would always be me. Or people would ask me why or say that I’m so quiet. Does it bother me? No not really, it’s true. It can be annoying thoughRead MoreCharles Bukowski: Cynical Critic1054 Words   |  5 Pagesunderwear too, and quiet clean girls in gingham dresses. These poems reinforce Bukowski as a cynical critic of the bourgeois society, often targeting women; it would be foolish to blind ones opinion on whether he was anti-American or not, as such generalizations rarely fit an individual perfectly. Why Charles Bukowski criticizes and mocks conformed societies can be uncovered through the analysis of his life. Charles Bukowski (1920-1994) was born in post-World War I Germany, but soon after immigratedRead MorePersonal Essay : Running In Circles914 Words   |  4 PagesRunning in Circles The Place Right next to my school is a small, quiet, part of town. Only at night would it ever grow loud with fans and bright with lights. People gather and cheer their hearts out for their home team. The field was an outlet for the players. Yet no one ever noticed what surrounded the field; the track, a small, quiet part of the town where people go to think, train, or simply run. What I Notice Going to a track meet for the first time and watching runners pour their heartsRead More Comparing Do Not Go Gentle into That Good Night and After a Time823 Words   |  4 Pages Comparing Do Not Go Gentle into That Good Night and After a Timenbsp;nbsp;nbsp;nbsp;nbsp; nbsp; Dylan Thomas Do Not Go Gentle into That Good Night and Catherine Davis After a Time demand comparison: Davis poem was written in deliberate response to Thomas. Davis assumes the readers familiarity with Do Not Go Gentle, which she uses to articulate her contrasting ideas. After a Time, although it is a literary work in its own right, might even be thought of as serious parody--perhapsRead MoreHorror, Effects, And Nationalism1076 Words   |  5 PagesNationalism Today s horror came from the effects of nationalism that affects our country. Three themes in All Quiet on the Western Front are horror of war, effects on war on the soldier, and nationalism. World War I all started because of the assassination of Franz Ferdinand the archduke of Austria-Hungary. A group of alliances between major powers was blamed and went to war. All Quiet on the Western Front was about this teenager named Paul Baumer and several of his friends being enlisted into

Urbanization and Social Disparities in Cities, Questions...

Question 1: Cities as Locus for Political Debate Cities are plots of land, densely covered with built environment, inhabited by dwellers; however cities are also vast network hubs, linking social, economic and political flows. Cities possess enormous human capital: they encourage exchange of ideas and intellectual opportunities. Cities are conceived upon diversity – encountering individuals with different believes and points of view, coming from very different backgrounds one has a chance to test his own convictions against those of others. Cities therefore are constantly evolving subjects, where one continues to learn every minute; they also become arenas for political action and organization. In my essay I am going to discuss how through close spatial proximity and interrelation of different socio-economic groups important political questions are being raised. With examples from different world regions, such as India, US and Brazil it is possible to distill a trend that urban setting through compact spatial organization provides exposure to various viewpoints and encourages its dwellers to take action, to attempt to solve infrastructural problems and organize in political groups. It is both in the city center and the periphery where people become involved into performative politics. I would argue, that physical proximity and socio-economic difference present simultaneously in one space no matter whether in the center or in periphery foster one’s involvement inShow MoreRelatedRapid Urbanization And Violent Conflicts1282 Words   |  6 PagesIntroduction There are numerous social, economic, cultural, and political issues that accompany rapid urbanization. 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With the rise of modernism and various forms of reform, the public came to question the religious truth of the Bible and looked to philosophers for answers, re-evaluating the meaning of mankind andRead MoreAdaptation Of Climate And Simplifying Informal Settlements6860 Words   |  28 Pagesprogressive development of human societies, their ecological and environmental influence has been steadily increasing. The spatial expansion and higher population and housing density of cities with its multiplier effect on land use and land cover change (LUCC) have been recognized as the most important aspects of cities climate change which is triggered by the need for urban services provision for the influx of human population. 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EXECUTIVE SUMMARY Seven   global   megatrends   shape   the   face   of   the   world   in   2030 T1 CHANGING DEMOGRAPHICS T2 GLOBALIZATION FUTURE MARKETS

Reinventing Strategies Emerging Markets

Question: Discuss about the Reinventing Strategies for Emerging Markets. Answer: Introduction The Coca-Cola Company, being a global soft beverage industry leader in the market have been in control of the industry for a good time now. Things have taken shifts, and various factors have set in with each having a series of turns of events. Some of the known competitors of the company have since been outcompeted and as such, made the rivals to back and withdraw from the business environment. This paper sets out to discuss a new product that the Coca Cola Company intends to provide in India, the product in question being New Coke. Being that the produt had registered an all-time failure, the company has put in place measures like new tacts and strategies in order to make it a success. The Coca-Cola Company was established in 1886. The company was a brainchild of one Pharmacist by the name of Dr. John Pemberton who initially produced coke syrup for sale in the drinks. The world is dynamic, witnessing changes all around us. To see its success over the next years, it is important for the company to focus and shape up its game in in a bid to adjust to the ever changing scenarios in the business world. This is about the trends set by the business community. The mission of the company is to refresh the global market, inspire the moments of happiness and optimism, and to bring forth value and make the difference among customers. The core vision of the company serves to describe every aspect of consumers about people, partners, planet, profits, and productivity (London,and Hart, 2004, 350-370). The competition among soft drink manufacturers in India is one of the fiercest known. Some of the known traditional rival companies in the country included Pepsi and Parle. To survive this, Coca-Cola Company has to come up with top strategies that would make it easier for the enterprise to have a firmly rooted strategy that would outsmart these companies (Svensson, 2001, 6-18). One of the strategies that Coca-Cola Company can adopt while entering a new environment(India) with a new brand,( New Coke), includes the acquisition of Parle in a bid to taking advantage of the companys network and extensive customer base. This is the decision that can be deemed the best for the company since through this, the company commands access to over 2 million retailers plus the 60 bottles in the enterprises network. It remains a powerful call for the Coca-Cola Company to employ strategies that would then win the war of business establishments and make it successful (Cavusgil, et al., 2002, 3). It is quite useful for the Coca-Cola Company to employ the use of 4Ps of marketing. These include price, promotion, and place. This is done in such a manner that the quality of the product (soft drinks), as provided to the consumers is in a consistent state and price. This is geared towards making the brand attractive to the customers. Therefore, it will be for the best interest of the company to ensure that they spend a good amount of money in sales and advertisements plus other promotional errands (Svensson, 2001, 6-18). Coca-Cola is known to be one of the largest manufacturers, and distributors as well as marketers of non-alcoholic drinks and Cyprus in the whole world. Coca-Cola Company has its headquarters in Atlanta, Georgia. Known for its flagship brand, the company is by far the largest corporation in the US. In the present day, Coca-Cola has an international presence and is the all-time recognized beverage company with a range of plans that are aimed at promoting and growing the brand. The majority of the soft drinks bars, restaurants, and big hotels are coca cola products, thanks to the Coca-Cola Company. Some of the known companys product include Fanta, Oasis, Sprite and PowerAde among others (London,and Hart, 2004, 350-370). The coca cola company refreshes consumers with close to 500 sparkling brands with about 3,800 choices of beverages. This move makes the business, one of the worlds recognizable and valuable brands in the globe. As a matter of fact, the portfolio of the company boasts of close to 20 billion dollar brands in the beverage industry. It is important to note that just 18 out of the whole brands available are either reduced or no-calorie varieties. With the enduring commitment of coming up with the strategies of building business communities that are such sustainable, the company lays emphasis on some initiatives that are geared towards a reduction of environmental footprints. The other important considerations include the creation of a safe, all-inclusive environment for work as well as the enhancement of economic development for the business communities that Coke as a company operates (London,and Hart, 2004, 350-370). Region-wise growth patterns of Coke and its rival brands in India According to the Companys annual report, it boasts of a record sale in over 312 countries worldwide. When a company like Coca-Cola has made a decision to enter into new markets, otherwise known as overseas markets, there must be some considerations that fall into the bracket of open options. There are three main issues of concern that Coca-Cola has to deal with; marketing, sourcing and investment as well as control. Marketing regards what countries, what segments, the means and ways of managing as well as implementing the efforts of marketing and how to get to the new markets. However, some factors tend to deter such an entry process by various considerations. Some of these entry barriers or deterrents include intermediaries or direct entry with the necessary information. With regards to sourcing, the company needs to establish whether or not the company obtains the products, either by manufacturing or through purchase. Lastly, investment and control have everything to do with the di rection the company takes, whether a joint venture, acquisition or global partnership (London,and Hart, 2004, 350-370). With the view of winning a new market, it becomes necessary for any company of Cokes status to pay attention to such factors that tend to deter entry of companies of such magnanimity. The barriers to entry for the said companies often tends to prevent the smooth establishment of the said companies into these new markets. Some of the common barriers include network effects, control of the limited resources and the regulations as well as policies that govern the establishment of the business (Svensson, 2001, 6-18). According to economic models, lack of any barriers to entry makes it hard for any business to earn a credible and sustainable profit that goes beyond the cost of capital since the new companies entering the market gets attracted to the profits and tends to compete for the profits weighing them down to the capital cost (Foster, 2012, 7). As aforesaid, an example of a barrier to entry, in this case, is a brand. In this case, the best application would be a carbonated beverage. With this in mind, it becomes apparent that it takes billions of dollars plus the many years taken to manufacture and have the brand built. Regarding patents, it is important to note that the company has to spend millions as well as years to have its own RD or even a license for the same. With the slow trend of development and growth in developed markets, Coca-Cola is set to look for new and emerging markets in India for growth and expansion. The company looks forward to tripling its business and establishment in India over the course of five years while at the same time looking forward to setting up new leadership structures in the country (India) (Foster, 2012, 7). Coke has in place a new entrant strategy and as such, renewed the focus on such plots as semi-urban as well as rural markets in the country. Strengths Growth of carbonated soft drinks slated at between 10-15% The estimated PCC slated to increase to between 6-8 glass bottles Weaknesses Weaker infrastructure esp. refrigeration Small retailer base, and less self-space Massive custom and or excise duty that is close to 40% that have since been registered to come down considerably. High import rates of cans Problems of emptying bottles Opportunities An increase in the rural market about intermediate competition Cheap PCC in the new market compared to the ones in neighboring countries. Rise in disposable income The dynamic consumer trends as a result of satellite TV Threats Political uncertainties Pepsi and Coke rivalry. The target markets-rural setting The drinking of soft drinks in India is predominantly concentrated in the urban areas. The data from the study conducted in the industry suggest that consumers in the cities spend the better part of their time at a comfort that is ten times that of their counterparts in the rural areas. Nonetheless, Coca-Cola Company has had a new focus that is primarily targeted at the rural markets in India and as such shares in the belief that there is a great opportunity that encompasses loads of growth potential in the target markets. In India, Coke is laying focus on a small town like Agra, Lucknow, and Bilaspur plus other small markets in the rural setting in India (Shama, 1995, 90-109). Training of small towns Some of the best strategies that Coke as a company has adopted involves training of small retailers that are close to 6000 in number in the country. This is done through a program that was launched by the same University established by the company. The program is known as the parivartan, meaning change. Under this program, the retailers are taught on ways and means of stocking and displaying their products (Shama, 1995, 90-109). This program is aimed at providing the traditional retailers with the fundamental skills, techniques, and tools that are necessary to the success of the business in such a constantly changing business scenario. Under the program, the companies are meant to have presentations that include both visual and audio technologies that are done in the Hindi language so as to enable the retailers to have a better understanding of the concepts involved in the business. Having this in place, the company then provides each of the retailers with a Coke certified retailer c ertification that legitimizes them to deal in such products from the enterprise. Local culture and taste adoption The Coca-Cola Company set up an RD faculty in the country in a bid to develop beverages suited for localization of the company portfolio about beverage consumption. In earlier times, the Coca-Cola Company was known to outsource its RD roles from its establishment in Shanghai, China. Some of the known brand flavors include Maaza aam panna among other flavors. Some of the cultural challenges that the new product is likely to face in the new market includes overreliance of the local consumers on traditional beverages such as Pepsi and Parle, making it hard for the Coca Cola Company to firmly establish its roots in the new market. Initially, the Coca-Cola Company had set its target in the rural customers through bringing down the price at the time of entry. The company has now stepped up its distribution of the 200 ml beverage that is priced at between Rs 7 and 8. With this price in mind, the consumer returns the glass bottle after consuming the drink. As far as marketing decisions are concerned, the core focus that must be emphasized on is mainly value chain. The entry alternatives or the strategy that must make sure the activities in the chain are integrated or performed. Of the many factors that Coca-Cola Company has to pay attention to while entering a market is to come up with ways of creating global development strategies and the right selection of entry modes in the intended market in the targeted foreign market as well as its channel of distribution (Shama, 1995, 90-109). While the above mechanism can be deemed the best, other several strategies of entry can be paid attention to, that is, multinational enterprises that expand their international reach, with products and brands that are both new and diverse in the new economies and markets. As coca cola company attempts to expand its market in India having commanded a significant presence in Hong Kong. In this country, the company needs to come up with entirely new portfolio matching its competence in so far as the local needs are concerned. In any new markets, it is important that the foreign entrants come up with operational capacity for the appropriate context that calls for complementary assets that are controlled by the local firms. Coke is known to have a dying appetite for such foreign markets as India and Africa. Foreign direct investment of Coca-Cola The FDI means an investment in the manufacture and the service of facilities in the country that is considered foreign, with the sole intention of engaging the management of the facets that increasingly integrate national economies. Significant investments in the overseas markets are deemed to be the direct investments of the companies in the new country to (or intending to) developing the local products plus the means and ways of controlling the prices from the current set price. This fact brings us to the history of the establishment of the Coca-Cola Company that was established in the year 1981 in Beijing to the benefits of the investors. The company should operate in a joint venture, an arrangement that calls for partners to come together and collaborate without necessarily involving any returns of equity investments. Conclusion Conclusively, Coca-Cola has been viewed quite positively just as much as it has been projected. The consumers are quite aware of Coke as a brand plus its awareness that is quite high in the industry. with the right steps taken by the company to see New Coke gaining ground and stamping its authority in this new environment, it remains apparent that the new environment will find the product fulfilling.Whenever a product such as Coca-Cola is launched, the avid drinkers settle for the soda over the other competitors. When people settle for coke, they not only buy the product but also its image that goes with it. References CAVUSGIL, S.T., GHAURI, P.N. and AGARWAL, M.R., (2002).Doing business in emerging markets: Entry and negotiation strategies. Sage. FOSTER, R.J., (2012).Coca?Globalization. John Wiley Sons, Ltd. LONDON, T. and HART, S.L., (2004). Reinventing strategies for emerging markets: beyond the transnational model.Journal of international business studies,35(5), pp.350-370. SVENSSON, G., (2001). Glocalization of business activities: a glocal strategy approach.Management decision,39(1), pp.6-18. SHAMA, A., (1995). Entry strategies of US firms to the newly independent states, Baltic states, and Eastern European countries.California Management Review,37(3), pp.90-109.