Methadone Pharmacology and Its Mechanism of Action

Methadone Pharmacology and Its Mechanism of Action Table of Contents (Jump to) 1. Goal 2. Aims and Objectives 3. Background 4. Methadone Pharmacology and Its Mechanism of Action 4.1 Methadone History Background 4.2 Benefits of Methadone 4.3 Deaths Involving Methadone 4.4 Pharmacokinetics and Metabolism of Methadone 4.4 Cytochrome P450 4.5 Cytochrome P450 Polymorphism and Adverse Drug Reactions 1. Goal Methadone is the most common and widely used drug for the opioid dependence in Ireland as in most of the countries in the E.U. Methadone treatment is undoubtedly effective however; the reports on methadone related mortalities have definitely stirred the public concern. The challenge for biotechnologists is to determine whether the application of pharmacogenomics can solve this dispute. The fact regarding any drug or opioid is that they affect different individuals in a different way. To solve this â€Å"Biological Puzzle† this case study links the role of methadone and CYP2D6 gene variations with the metaboliser status of individuals, which may serve as an adjunct in methadone related fatalities. CYP2D6 is a member of cytochrome P450 mixed oxidase system, which is involved in the metabolism of many toxicologically important drugs that commonly implicates in fatal poisoning. CYP2D6 gene is located on chromosome 22 and is highly polymorphic in nature. Single Nucleotide Polymorph ism (SNP) variation at the exon 4 position of the gene results in a single nucleotide change of G to A, which ensue in poor metabolism of the drug. This variation is amongst 5 to 10% of the Caucasian population. 2. Aims and Objectives The specific aims of this report are as follows: Describe the methadone pharmacology and its mechanism of action, which will include the pharmacokinetics and the pharmacodynamics of the drug. The role of cytochrome P450 in the metabolism of methadone. The focus will be on the genetic polymorphism and the adverse drug reaction. This research will further investigate on methadone’s safety profile and mortalities associated with the drug. 3. Background Methadone is a synthetic opioid, invented during the Second World War (White Torres, 2010). The first chemical synthesis of the drug was in 1939 at the pharmaceutical laboratories of I.G. Farbenkonzern, Germany. Methadone was introduced to the market during 1960’s and since then it is one of the most valued drug which has proved its effectiveness from the prevention of abstinence syndrome that occurs after rapid interruption of continuous opioid administration (Zweben Payte, 1990; Dole Nyswander, 1965). Methadone is also one of the most common medications administered for the treatment of heroin addiction, however; there are many fatal poisonings reported over the years (Bunten et al 2010). Methadone is a liposoluble basic drug, often administered orally as a racemic mixture of two enantiomers i.e. R-Met and S-Met (Garrido Troconiz, 2000). It has a long plasma elimination half-life that lies between 13 and 55 hours and a high bioavailability of 70% 90% when administered orally (Moffet et al, 2004). It is extensively metabolised in liver and is converted into its primary metabolite which is 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) (Crettol, Monnat Eap, 2007) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) (Lugo et al, 2005). Blood methadone concentration in drug tolerant individuals reaches >0.84 mg/l, whereas in cases of fatality or poisoning concentrations typically range from 0.4 mg/l to 1.8 mg/l. Fatalities have also been reported with concentrations as low as 0.05 mg/l which is significantly lower than the average concentration in blood (Caplehorn, Drummer Fatal, 2002). Studies suggests that the largest patient associated deaths are during t he drug induction phase, when either individual drug tolerance is overestimated or the presence of other drugs are also found in the system (Bunten et al 2010; CSAT, 2004). The revolutions in the molecular techniques in postgenomic era provide us a significant platform for the diagnostics and clinical purposes. Pharmacogenomics is the study of the impact of heritable traits on pharmacology and toxicology that acts as bridge to certify opioid fatalities (Wong et al 2002). The significant inter-individual variation in blood methadone concentrations and individual susceptibility to methadone toxicity might be explained through genetic variations of the genes encoding the drug metabolism enzymes. Pharmacogenomics acts as the linkage between an individual’s genotype and individual’s ability to metabolise a foreign compound (Linder, Prough Valdes 1997). Most xenobiotics, including therapeutic drugs, are metabolised by cytochromes P450 to some extent (Guengerich, 2006). The metabolism of these drugs results in detoxification and elimination of drug or activation of the prodrug to its biologically active form. Cytochrome P450 (CYP450) shows a wide interindividual variation in their protein expression and/or catalytic activity, which results in unique drug metabolism (Jannetto et al 2002). Among the P450 subfamilies, CYP2D6 plays a critical role in determining the response to several drug groups/families (Sadee 1999). CYP2D6 gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are mono-oxygenases, consisting of more than 30 enzymes (Schur et al 2001) which catalyze many reactions involved in drug metabolism. This protein localizes to the endoplasmic reticulum and is known to metabolise as many as 20% of commonly prescribed drugs. CYP2D6 gene substrates include debrisoquine (Wennerholm et al, 1999) an adrenergic-blocking drug; sparteine and propafenone, both anti-arrythmic drugs; and amitryptiline, an anti-depressant. CYP2D6 gene is highly polymorphic in population (Neafsey et al, 2009); certain alleles result in the poor metaboliser phenotype, characterized by a decreased ability to metabolise the enzymes substrates. The polymorphism is due to multiple mutations of the gene, which result in absent, functionally deficient, under-expressed or over-expressed protein (Shiran et al, 2003). The gene is located near two cytochrome P450 pseudogenes on chromosome 22q13.1 (Gouch et al, 1993). Alternatively spliced transcript variants encoding different isoforms have been found for this gene (Toscano et al, 2006). CYP2D6 is a polypeptide of 497 amino acids that accounts for only small a percentage of all hepatic P450s but its role in drug metabolism is extensively higher than its relative content (Zanger et al, 2010). 4. Methadone Pharmacology and Its Mechanism of Action 4.1Methadone History Background Methadone was introduced to the market in 1960’s (Serban, 2011; Liebrenz et al, 2010). The drug was approved by the Food and Drug Administration (FDA) in 1947 as an analgesic; by 1950 it was used for the treatment of painful symptoms from heroin withdrawal and other opioids (SAMSHA, 2004). In 1964, researchers discovered that continuous, daily maintenance doses of oral methadone allowed opioid-addicted patients to function more normally in the process of their recovery (Payte, 1991; Zweben and Payte, 1990; Dole, 1988; Gearing and Schweitzer, 1974). Fig: 2 Methadone Chemical Structure Methadone in the modern medicine is used both as an analgesic for severe pain relief as well as in the treatment of opioid dependence (Rowley, 2011; Potter, 2010). Many scientific articles reviewed methadone to be the currently preferred drug of choice for the treatment of opioid dependence in many countries, including the U.K. (Nosyk et al, 2010; Verster and Buning, 2000). Fredheim et al, (2008) in their review reported that currently, methadone has had a renaissance in the treatment of pain because it has proven its usefulness as a second line drug in opioid switching when other opioids fail to show their effectiveness. Methadone has also been found to be the valued medication for its effectiveness in reducing the number of deaths associated with opioid addiction as well as various medical and behavioural prevalence of diseases associated with addictive disorders (Maxwell, Pullum Tannert 2005; Sheilds et al. 2007). However, the news headlines of many prominent newspapers including the New York Times and the Washington Times, in 2002 and 2003 hyped its publicity by reporting the opioid medications were the major cause of deaths in drug abuse treatment (Belluck, 2003a, 2003b, 2003c; Associated Press, 2002; Washington Times, 2003). New York Times even mentioned methadone as a â€Å"Killer Drug† which is widely abused and dangerous (Washington Times, 2003). After these issues it was decided by the U.N. to put methadone in the class of controlled drug. Methadone was declared in a controlled drug category by the United Nations convention and placed under the controlled substances (â€Å"narcotics†) by the Single Convention on Narcotic Drugs, 1961 (Single Convention) (Bosnjak et al,2011). However, it can only be prescribed in the UK, as in most countries, by prescription till present (Verster Buning, 2000; CSAT 200b). 4.2 Benefits of Methadone Methadone is one of the most preferred drugs not only in Ireland but also across several continents around the globe. In the report published by European Monitoring Centre for Drugs and Drug Addition (EMCDDA), there is a seven fold increase in the opioid treatment between 19993 -2000. The drug is widely recognised amongst doctors and patients due to its several socio-economic reasons. It is observed that there is a significant decrease in the crime graph and a noticeable increase in the employment services amongst the patients undergoing methadone maintenance treatment. No doubt, there is a reduction in illicit drug use by the opiate users and increase in social integration is one of the benefits of methadone. In addition, methadone also helps in reducing morbidity and mortality among opiate users. 4.3 Deaths Involving Methadone Methadone is a highly potent drug for the treatment of opioid dependence and acts as an analgesic for second line management of chronic pain. However, increase in mortality due to methadone administration has instigated controversies regarding the drug use (Lowe, Brooks Petry, 2010; Bunten et al 2010). Law enforcement agencies in the United States (U.S.) and the Drug abuse Warning Network (DAWN) ranked methadone as the third most apprehended analgesic used in the treatment of pain management, fourth among all controlled pharmaceuticals, and eighth among all controlled substances (Fig:2.1.1) (SAMSHA, 2007). Various researches conducted amongst patients undergoing addiction treatment shows that the majority of methadone related deaths occur during the drug induction phase. Post-mortem sample predicts either an overestimation of the drug or combined usage of various other central nervous system (CNS) depressant in addition to the prescribed methadone (Bunten et al, 2010; Lowe, Johnson Petry, 2007). Fig: Methadone as the third most apprehended analgesic, fourth among all controlled pharmaceuticals, and eighth among all controlled substances (SAMASHA, 2007) The side effects associated with methadone overdose includes nausea, vomiting, dizziness, clouding of consciousness and pruritus (itching) (Davis Walsh, 2001). However, the primary toxic effect of excessive methadone is respiratory depression and hypoxia, sometimes accompanied by pulmonary edema and/or aspiration pneumonia (White and Irvine, 1999; Harding-Pink, 1993). Methadone related deaths during later phases of the additiction treatment mainly signify the presence of other illicit drugs. Researchers generally use the term â€Å"poison cocktail† describing the fatality due to intake of multiple psychotropic drugs (Borron, et al., 2001) such as alcohol, benzodiazepines, and other opioids. Several opioids when used or prescribed alone are relatively moderate respiratory depressants; however, when combined with methadone, their additive or synergistic effects can be lethal (Kramer, 2003; Payte and Zweben, 1998). Safety Information and Adverse Event Reporting Program a subsidiary of Food and Drug Administration (FDA) confirms 1,114 cases of methadone-associated fatalities in adults from 1970 through 2002. Critically, a greater number of deaths were reported in 2001 alone than during the entire period from1990 through 1999; the number doubled itself in 2002. In the U.K. 225 individuals died whilst undergoing methadone treatment in 1993. In 1997, data confirms 449 deaths due to the same cause. However, the mortality graph went down in 2001 by reporting 279 deaths caused by methadone but in 2002, it again rose to 316. Therefore, we can conclude that there is no regular trend in methadone related deaths. However, Corkery et al (2004), mentions that it is always not necessary for methadone to be the cause of death even according to the death certificate of the individuals. In an individual study, methadone was detected in the post-mortem blood of 352 unexplained sudden deaths in Scotland between 1 991 and 2001. 23 % of these deaths were not directly linked with methadone. However, there were other drugs and/or alcohol found in the blood sample of the individuals. The Substance Abuse and Mental Health Services (CSAT) in 2004 states that all methadone related poisoning eventually leads to cardio-toxicity and respiratory depression. Methadone deaths expressed as Percent of all poisoning deaths (CSAT, 2007). United States Poison Control Centres states that the overall number of opioid-related deaths has been on the rise, with many cases involving other opioids that include oxycodone and hydrocodone (Litovitz, et al., 2002; Florida Department of Law Enforcement, 2002) 4.4 Pharmacokinetics and Metabolism of Methadone Methadone is a liposoluble basic drug with a pKa of 9.2 and is usually administered orally as a recemic mixture of two enantiomers: R-methadone (R-Met) and S-methadone (S-Met) (Fig.2.2) (Trescot, 2010). The plasma half-life of the drug is highly variable and is between 13 and 55 hours but it is usually assumed to be an average of 25 hours (Letsky et al, 2011; Albion et al, 2010; Wolff et al, 2002). The bioavailability is 70% to 90% when administered orally (Bunten et al, 2010; Lowe, Brooks Petry, 2010). Studies indicate that in drug naive individuals, a single dose of methadone can show its clinical effects up to 72 hours in duration (Olsen et al, 1997). However, the peak plasma concentration reaches in 2 to 4 hours. The analgesic effect of the drug sets in about 15 minute after the subcutaneous injection (Eap et al, 2002). The chemical structure of r-(-)-methadone and s-(+)-methadone (asterisk (*) denotes chiral centre). There is a wide distribution of methadone amongst tissues, which generally range from 60 to 90%. As a result, the drug shows slow elimination and cumulative effect. Methadone is mostly metabolised in liver. The primary metabolite of the drug is 2-ethylidene-1, 5- dimethyl-3, 3-diphenylpyrrolidine (EDDP) (Fig) (Bunten et al, 2010) and to some extent 3, 3-diphenyl-1-pyrroline (EMDP) (Corkery et al, 2004). However, both of these metabolites are inactive and elimination of these inactive metabolies is through urine and faeces. Anggard and Inturrisi et al. (1975) (1990) mentioned that as a result of the basic (pKa =9.2) and lipophylic properties, methadone undergoes a hepatic metabolism and renal excretion. Fig: 4 Metabolic Conversion of Methadone to EDDP 4.4 Cytochrome P450 Cytochrome P450 (P450) is a large superfamily of enzymes. The origin of P450’s superfamily is since prokaryotes much before the existence of eukaryotes (Omura, 2010). The gene P450, commonly known as â€Å"CYP† is present in the genomes of virtually all organisms. Moreover, studies suggest that heme proteins are the building blocks of CYP450 enzymes. These enzymes play a crucial role in the metabolism of the various xenobiotics, steroids and other chemicals. Most of the drugs and chemicals are lipophilic to become more water soluble before excretion. Therefore, P450 superfamily of hemoproteins serves as terminal oxidases of the mixed function oxidase system (Wrighton and Stevens, 1992). The heme prosthetic group binds oxygen after electron transfer reactions from the reduced form of 24 nicotinamide adenine dinucleotide phosphate (NADPH). This reaction incorporates a single atom of molecular oxygen into a substrate with the concomitant reduction of the other atom to wate r (Synder, 2000; Omura, 1999). In cytochrome P450, ‘P’ denotes the pigment and the number ‘450’ is the spectral properties for the absorption band at 450 nm of the reduced CO-bound complex (Benhardt, 2006; Reichhart Feyereisen, 2000). However, according to the nomenclature society, the term â€Å"CYP† is followed by number of families which are generally group of proteins with more than 40% amino-acid sequence identity, a letter for subfamilies and a number for the gene e.g. – CYP2D6. Studies indicate that P450 superfamily is highly diverse (Mathew, 2010). Diversity of P450’s is mainly due to the extensive process of gene duplications. However, gene amplifications, conversions, genome duplications, gene loss, and lateral transfers are certain scenarios that are less documented. 4.5 Cytochrome P450 Polymorphism and Adverse Drug Reactions Drugs affect different individuals in a different way. Genetic variations, which affect the response of the drug metabolism, can be of the most probable reasons (Mayer Zanger, 1997). Johansson Sunderberg (2010) also reported that the difference in drug metabolism among individuals might be due to several factors e.g. epigenetic, pathophysiological, or it might be due to some environmental factors. In a population, genetic polymorphism is divided according to individual ability to perform drug transformation reaction (Srivastava, 2003). Moreover, polymorphic trait is also noticed due to certain mutation in the genes and/or a single nucleotide polymorphism (SNP) which results in the enzyme variation and leads towards higher or lower activity. As a result, there is a partial or complete absence of an enzyme protein in the system. (FIG:) Fig: Polymorphism of Drug Metabolism Enzymes (Evans Relling, 1999). As we can see from the above figure that the genetic polymorphism applies for a wide range of drugs and xenobiotic metabolizing enzymes. Identification of these variations were by the occurrence of adverse reactions after normal doses of drugs in patients or volunteers. In adverse drug reactions, drug-drug interactions have its key role. In fact, adverse drug reactions (ADRs) are one of the major causes of death which is reported in many scientific articles, reviews and even government scripts. According to Substance Abuse and Mental Health Administration (SAMSHA) (2007), there is a record of approximately 100,000 deaths in the United States due to drug toxicity. In addition, Eichelbaum et al., (2006) stated that ADRs is also responsible for up to 7% of hospitalizations and the number has increased to > 30% in the elderly population (> 70 years of age) (Paul et al., 2008). ADRs mainly affect cardiac function or cause liver toxicity (Need et al., 2005). The CYP families metabolises approximately, 75% of all clinically used drugs (Bertz and Granneman, 1997; Evans and Relling, 1999).The human genome contains 115 CYP genes, out of which 57 are found to be functional and the rest are reported as pseudogenes (Johansson Sundberg, 2010; Wang et al,2003). Among CYP families, there are 22 different P450 isoforms, which shows a high degree of polymorphism. Therefore, we can divide the polymorphic xenobiotic metabolizing CYP enzymes into two classes according to their interindividual susceptibility for xenobiotics: Class I: Composed of CYP1A1, CYP1A2, CYP2E1, and CYP3A4 without important functional polymorphism and active in metabolism of drugs. Class II: Composed of CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP2D6, which are highly polymorphic and are important for the metabolism of drugs.

Ian Burumas Behind the Mask :: Ian Buruma Behind the Mask

Ian Buruma's Behind the Mask Ian Buruma was born in the Netherlands in 1951. He went to school in both Holland and Japan, and he has spent a great deal of time in Japan. Ian Buruma is an author, journalist and a professor at Bard College in New York. He sometimes writes for the New York Review of Books, the New York Times Magazine, the New Republic, the New Yorker, and the Guardian. The book, Behind the Mask, was a very interesting one. This book is filled with lots of Japans history that most people know nothing about. Much of the content in Behind the Mask is focused on sexuality and violence. The book has thirteen chapters each dealing with a different topic. It starts out with a kind of mythology about the origins of Japan. It is then followed by chapters on mothers in Japan and marriage. Some of the other topics focus on women, geisha, and yakuza. Behind the Mask is a great book explaining a great deal of the sexuality related to the culture and religion of Japan. To the Japanese, sex is a part of nature; it is not considered a sin. The worst thing that can happen to an individual in Japan is to be socially shamed or dishonored. The Japanese do believe in a sort of â€Å"pollution† though. They fear being unclean, death, and blood, among other things. Purification is a big deal in Japan. Ian Buruma, the author, not only explains in great detail much of the history and practices of the Japanese, but he also writes much about significant people and places dealing with the topic. There were many significant people who contributed a great deal to the practices in Japan. He also describes many of the important places where certain events occurred. He explains what the kabuki theaters looked like and also the famous strip clubs. The Washington Post Book World writes, â€Å"A fascinating exploration of Japanese culture: the fantasy life of the Japanese. It fishes its insights from the rich and muddy river of popular culture that the Foreign Ministry has always tried to screen from foreign view. Through skillfully chosen subjects – sex, gender, the mother – we find a comprehensible (if sometimes surprising) fantasy persona behind the inscrutable mask†¦fascinating, imaginative, highly polished, entertaining.

What is sociology, anyway? Why bother to study it?

The aspect of sociology mainly relates to the study of the human behavior, existence, and individual characteristics based on the collective perspective of the society. The importance of this field in science generally manifest in many ways varying from the views and interpretation of the person involved. In reply to the read article regarding a personal reflection towards sociology, this writer clearly understands that the author of the said article greatly appreciates the value of the aspect of sociology with its manifestation towards the said author’s life. Read also  Sociology and Social Integration. Parts of his realization are greatly inclined towards the aid of sociology for understanding the human behavior in the society and discovering the individual characteristics of each person in a collective perspective. By the inclusion of the sociological concepts, the author of the article was able to understand the individual differences in terms characteristics, behavior, intellect, and others relevant to his successful merge in his society. In agreement to the ideas presented of the author of the read article, indeed, the aspect of sociology explains that the individual differences of each person is rooted on the influence of numerous factors in the person’s development. Realizing this fact, it is important to acknowledge these factors in understanding the personal characteristics of each individual such as his or her opinion, values, perspective, behavior, and actions. Among these influential factors are the concepts of family background and culture wherein the former has changed significant in the present. Other than the traditional type of the family unit, new structure have already emerged in the present namely the extended and nuclear or modern type which also have significant influences in the personality development of the person involved in these family unit. The dominant culture existing inside the family also becomes a fundamental factor in the individual characteristic thus, should also be considered in the sociological analysis and understanding. Indeed, the factors of family background and culture significantly affect the development of individual personality and characteristics relative to understanding the differences of each person inside the collective group of their respective society. Being part of the broad field of sociology, indeed, it is important to consider this scientific field towards achieving development in the aspect of understanding social relationship and individual differences inside the organization of human society.

The Basic English Grammar Rules eBook (PDF)

The Basic English Grammar Rules eBook (PDF) The Basic English Grammar Rules eBook (PDF) The Basic English Grammar Rules eBook (PDF) By Daniel Scocco Last year we had a series called English Grammar 101, where the basic grammar rules were covered. Many readers asked if it was possible to transform that series into an ebook. We thought that the idea was good indeed, and started working on it. Maeve edited the whole thing, adding examples and formating the sections. The ebook (in PDF format) is finally ready, with 34 pages of content. You can download it free of charge. Below you will find the content of the e-book and the subscription form to request your download link. eBook Content Heres a breakdown of the sections you will find in the eBook: Introduction Section 1: Sentences The subject Predicate Praises and clauses The object The complement Section 2: Parts of speech Noun Pronoun Adjective Verb Adverb Preposition Interjection Conjunction In order to download the ebook you simply need to subscribe to DailyWritingTips email list. We only send out one email per week, on Tuesdays, and we only send useful content that will help you to improve your writing skills. Topics covered range from English grammar to punctuation and style. After subscribing your email address below you should receive the e-book download link within a couple of minutes. Subscribe below to receive a download link via email Heres how our email containing the download link looks like. Obviously joining our email list is free and you can unsubscribe anytime you want. Want to improve your English in five minutes a day? Get a subscription and start receiving our writing tips and exercises daily! Keep learning! Browse the Grammar 101 category, check our popular posts, or choose a related post below:Creative Writing 101Latin Plural Endings10 Tips for Clean, Clear Writing

Clausal Structure in English essay part 2

Clausal Structure in English essay part 2 Clausal Structure in English essay part 2 Clausal Structure in English essay part 2Clausal Structure in English essay part  1Adverbial clausesAdverbial clauses are clauses introduced by a subordinating conjunction, which explains the adverbial meaning of the clause. Conjunctions used in adverbial clause are as follows: when/before/after/while (time); because/since (reason); if/unless/lest (condition), etc. For exampleWhen your work day is over, you may go home.I cannot send you emails because I prefer using Skype.Unless you work hard, you will succeed in your life.At the same time, there are minor types of adverbial clause, which are inf. and -ing clauses:Inf. clause: I went to the bus stop to take the bus back home. (Clause introduced by to + infinitive).-ing clause: Jack lost his wallet while fighting. (Clause introduced by present participle).Types of adverbial clauses:Adverbial clauses may be time clauses, which use time-related conjunctions, such as when, whenever, before, after, since, while, as, until, once, as soon as. These clauses are used with regard to a specific period of time or to an event that occurs in the specific moment. For example, She started her career when she was a student. In addition, adverbial clauses are used in the following cases: before +-ing after +subject+verb For example: Before buying this car, make sure it is new. Tom left the house before Jane had realized what was going on.Conditional clauses involve the use of conjunctions, which indicate to the presence of certain condition or conditions, including the following conjunctions: if, unless, whether, provided/-ing (that)†¦, as/so long as, in case. Conditional clauses are used to describe a possible situation and its effects. For example: If they practice sport, they will be in the excellent physical shape.Adjectival clausesOne of the most widely-spread types of adjectival clauses is the relative clause, introduced by such relative pronouns as who, whom, whose, that, or which. For example:Here is the ma (whom) I saw last night, when the murder occurred.This is the car (which) I am using to get to my work.The movie (that) I most enjoy is American Beauty.At the same time, there are two types of adjectival clause which occur very seldom, which are -ing and -ed clauses.-ing clause: The train now standing at platform two is the 2.30 p.m. to New York.-ed clause: He is the pop star pursued by paparazzi.At this point, it is worth mentioning the fact that past participles do not all end in –ed. This is why other verb forms are used in such clauses. For example: The movie watched by the audience or the exam taken by the students.Furthermore, the transition from coordination to subordination may occur in adjectival clauses. Using adjectival clause it is possible to combine these two sentences:The national speed limit was repealed.Road accidents have increased sharply.One possible way to coordinate these two sentences is as followsThe national speed limit was repealed and road accidents have increased sharply. Coordination with the help of the conjunction ‘and’ allows connecting the two main clauses. On the other hand, such coordination does not clearly identify the relationship between the ideas in those clauses. Therefore, if it is necessary to clarify the relationship between the two ideas in the given example, it is necessary to change the first main clause into an adverb clause, for example:Since the national speed limit was repealed, road accidents have increased sharply.The adverbial clause indicates to the time relationship between two ideas of the sentence. By changing the first word in the adverb clause, which is called a subordinating conjunction, it is possible to establish a different relationship, for instance, the relationship of cause: Because the national speed limit was repealed, road accidents have increased sharply. However, it is worth mentioning the fact that an adverb clause, like an adjective clause, contains its own subject and pred icate, but it must be subordinated to a main clause to make sense.Furthermore, purpose clauses are clauses that use conjunctions or (finales) = subject. As a rule, the following conjunctions are used to convey the purpose: in order to, so as to (in order not to , so as not to) // subject: so that + can/will, so that + could/would, for fear that. These clauses are used to indicate the purpose of an action. For example: The police introduced automatic profile processing to identify suspects faster. They had to pass exams successfully so that they could continue their education at the University. The doctor explained the nature of my illness in medical terms so that I wouldn’t understand fully.Another type of adjectival clauses is reason clauses (causales), which use conjunctions that convey the reason of the action or event described in the sentence. The most widely-used reason conjunctions are as follows: because, since, as, (because of + (adj)noun,   due to/owing to+ (ad j)noun). These clauses are used to indicate the reason for something. I couldnt feel anger against him because I liked him too much. Because of the heavy traffic in cities, more people have started taking the train.In addition, there are comparison clauses (comparativas), which use comparative conjunctions, such as: as, than, the + comparative. Comparison clauses are used to compare two or more people, things or facts, for example: I cannot drive a truck as well as I can drive a car. Leila plays tennis better than her sister.Also it is worth mentioning the fact that there are result clauses (consecutivas), which use conjunctions that indicate to the result of the action or event: †¦, so (that)†¦ (Result clauses associated with degree: so + adj/adv + that (tan†¦que†¦) so much + noun(U) + that (tanto/a†¦que†¦) so many + noun(C) + that(tantos/asque†¦) such (a/an/-) + adj+ noun + that. Result clauses are used to indicate the result of something. For ex ample: I had some extra job to do, so that I had no time to call you back. The doctor explained the nature of my illness in medical terms, so that I didn’t understand fully.Furthermore, concessive clauses are another type of adjectival clauses which use concessive conjunctions, such as: although, though, even though, even if, while, whereas(mientras que†¦),   + noun despite + -ing, in spite of the fact that+subj+vb, (however + adj/adv + clause). Concessive clauses are used to communicate the idea of concession, when two statements, one of which contrasts with the other or makes it seem surprising. For example: I learned hard although I did not have money to continue my education. Although he is a good player, he has no stamina to keep on playing as he used to. In spite of / Despite his age, he kept on working in the construction.Another type of adjectival clauses is place clauses, which use conjunctions indicating to the specific place of action or event described in t he sentence. For example, the following are the most widely-spread place conjunctions: where, wherever. These clauses are used to talk about the location or position of something. For example: John believed he can succeed in the new city where he moved to last summer. Wherever she goes, she will always take her ‘lucky’ ring.Furthermore, there are also clauses of manner, which use conjunctions that reflect the manner, in which the action or event is carried out, for example: as, as if, the way, like. Clauses of manner are used to describe someones behavior or the way something is done. For example: I have never had a chance to do the things the way I wanted to do them. Jane did the job as no one has ever expected from her.In such a way, the diverse types of clauses identified by experts involved in the study reveal the clear trend to the close correlation between the main clause and finite or non-finite clause. However, the main clause is independent and may stand alone, while the finite or non-finite clause is coordinated or dependent on the main clause. At the same time, the researchers have proved that the relationships between the main and finite/non-finite clause depends on their function and purpose of the utterance.ConclusionThus, the analysis of the clausal structure in English reveals the fact that the diversity of clauses in English is mainly the result of the different purposes of utterances and the different relationship between the main and finite/non-finite clause. At the same time, the study has revealed the fact that the complex clausal structure depends on several factors, among which the function of the close, the purpose of the utterance and intention of the person making the utterance are key factors that determine the clausal structure.

Islamic Culture and Politics Essay Example | Topics and Well Written Essays - 750 words

Islamic Culture and Politics - Essay Example The similarities of the activities of these two groups is that they both aimed at instilling Sunnah (which are Prophet Muhammad’s living habits and sayings) and the Qur’an as the only points of reference for the ordering of life for all Muslim individuals, families, communities and nations (Mohammed 52). Activities by both groups fight for political reforms are driven by the belief in God (Allah) being their objective and the Qur’an the law. Funded by members’ contributions, who must assign a segment of their earnings to the movement, the Muslim Brotherhood in both the Arab and Western countries engages in political violence as they make Jihad their way of life. They believe that all Islamic countries must fight oppressors and Allah’s enemies as an overture to developing strong status as Islamic nations. For example, the Islamic Brotherhood in Egypt participated in violence, in the country, after the death of their founder al-Banna in 1949 for many years until they were suppressed forcibly and reemerged in 2011. However, the Muslim Brotherhood differs in its activities among the Arab and Western countries. In the Western world, the Brotherhood aims to end Western civilization from inside the countries they are present, and replace it with Islamic concepts. For example, in Belgium, the State Security observed that, from their presence since 1982, the Brotherhood has established an undercover structure with secretive membership that operates in discretion. Their key objective is to spread Islamic ideologies in Belgium and the surrounding regions then embed and expand a conformist Islamic syndicate in Western Europe (Sageman 74). This is in contrast to their activities in the Arab world where they have been fighting to remove the already Islamic authoritarian regimes in place. Therefore, within the Arab world, the activities usually are of a civil war nature. Examples are the recent Egyptian and Tunisian protest movements that to ppled the incumbent rulers. In that sense, it can be seen that the underlying difference is that, in Arab countries, the Muslim Brotherhood fights oppression from their governments while in the Western countries, they attempt to globalize their ideologies. Question Four Jihad is an Islamic term generally used to refer to holy war. The war is termed holy because it is believed to be a struggle for the way and cause of Allah. Both the Sunni and Shia sects of Islam believe that jihad is a religious obligation for all Muslims and have traditionally encouraged its use against non-Muslims. Both sects commonly accept two perceptions associated with jihad: that it entails a greater struggle which is an internal spiritual jihad, and a lesser struggle which is an external physical jihad. Both Sunni and Shia Muslims believe that the notion of jihad must always have an aspect of armed struggles to overcome oppression and persecution of Muslims (Sageman 92). A more contemporary understanding of jihad by the two sects is that the struggle must aim to build a better society by the Islamic community as a collective duty. This must be done by lodging valid protests for solving religious problems, acknowledgement of divine law and forbidding wrong conduct while commanding right conduct. To this end, a striking similarity between the two sects’ understanding of jihad is the way it is linked to martyrdom. They both believe that Muslims who die in the cause of executing jihad ascend into martyrdom, which gave rise to the phenomenon of suicide

World Population Growth and the Policy of Nations Research Paper

World Population Growth and the Policy of Nations - Research Paper Example This is a complex issue which involves privacy concerns, science concerns, and ethical concerns. This paper will first examine the technical issues with the science behind the issue of population control. Following that, I will elaborate more extensively by examining four separate studies on the subject and the arguments that each study presents. The debate over population growth control deals largely on the question if the potential benefits of preserving our environment; preventing poverty; and preventing slow economic development outweighs the problems posed by the government trying to correct these issues with intervention. By government trying to intervene, it is not certain in predictability or effectiveness of all their policies. In addition, fertility is a very personal issue to most all individuals and attempts to justify government intervention on that basis alone are quite problematic. One of the important science issues with overpopulation is that of water shortage as brought out in a study by Fredrickson. South Asia is a good example of a large water crisis area. As of the year 2009, the region has the largest number of malnourished children in the world in spite of recent economic growth. Approximately 45% of children in India, Nepal, and Bangladesh suffer from poor nutrition, with water shortage being a root cause. As the author brings out, there are 500 million people in three countries relying on the Ganges River. Another of the important science issues with overpopulation is in regards to poverty and famine. Young presents Malawi as a good case study of these issues. The author states that a fairly stable government is in place and the area has an aid present.