Amin Maaloufs Idea Essay Example for Free

Amin Maaloufs Idea Essay My understanding of Amin Maalouf’s concept on identity is that human identity is based on an individual’s environment. He defines identity into two categories. One that is inherited through our elders and cultural beliefs â€Å"vertical†, and another that exist according to our generational influence, â€Å"horizontal†. The two categories create our identity as a human and is the source of our behavior. My experience with the vertical heritage is my belief in Christianity. My ancestors and the community I was raised in have traditionally taught me to celebrate religious holidays like Christmas and Easter. I also grew up in a small neighborhood with Christian peers. They have influenced the way I behave and interact by helping to shape my morals. My experience with the â€Å"horizontal† is the communities I have been introduced to, such as, the public and private school environments. They have broadened my personality with their social aspects. One example of what Maalouf is saying is my switch from public to private school. My personality was much different in public school than it was in private. In my public school the social standard for academic progress was average. The fact that there was no assigned dress code distracted me because I would attempt to impress others with my appearance. This influenced my train of thought, behavior and ultimately my identity, until I was placed into a different setting. When I made the switch to private school the distraction of looking different was taken away, and expectations were higher. My surrounding influenced me again and I became more focused on things that mattered and more questionable of my beliefs. What I gained from both these settings was my horizontal inheritance. For example, the music that I listen to and the hobbies I enjoy. Maalouf’s point is that no matter your vertical, your horizontal has a bigger affect on your identity, and since the horizontal is based on contemporaries, you are based on the subjects around you. He points out that there is a gap between what we think we are and what we actually are in reality. We may know we are different but what we don’t realize is in reality we are only becoming identical through arguing are differences. I believe this is a magnificent insight on identity. Mankind changes the world around us and if we all do the same, we end up in each other’s world. We are becoming more and more identical to each other through compromise from arguing our differences because we learn to live with each other. When we accept differences they soon become norms, and once they are norms, they become a standard. I agree with Amin Maaloufs concept on identity.

Communication Skills Required For Holistic Nursing Care Nursing Essay

Communication Skills Required For Holistic Nursing Care Nursing Essay The communication skills required for holistic nursing care of patients in adult nursing. The American Holistic Nurses Association (AHNA) defines holistic nursing as all nursing practice that has healing the whole person as its goal. Holistic nursing recognises that there is a connection between a persons mind, environment, culture, emotions and body. holistic nursing is not necessarily something that you do; it is an attitude, a philosophy and a way of being. American Holistic Nurses Association 1998. The Oxford online dictionary defines the word holistic as: medicine characterized by the treatment of the whole person, taking into account mental and social factors, rather than just the symptoms of a disease. Oxford Dictionary online 2010. There are two types of communication, verbal and non-verbal. Communication is the exchange of information, verbally or non-verbally. The Oxford dictionary defines the word communication as: the imparting or exchanging of information by speaking, writing, or using some other medium. Oxford Dictionary online 2010. verbal communication is speaking face to face to someone using words, sounds, speech and language. Verbal communication is separated into two types, public speaking and interpersonal communication. There are over 3000 languages spoken in the world and verbal communication is based largely on these as well as class, profession, age and social factors. some sources suggest that written communication is verbal as well as non-verbal. Non-verbal communication is email, letters, databases, social networking sites, text messaging as well as body language. Body language is an important means of communication, it includes gestures, eye contact, expressions and posture. How we communicate non-verbally is extremely important and sends strong messages as to whether you care and to what extent you are listening. We communicate this way by how we sit, the tone and pace of how we talk, how much personal space we use and the eye contact we make. There are five roles in non-verbal communication: Repetition the message we send can repeat the verbal message. Contradiction the message we send can contradict the verbal message. Substitution the message we send can be substituted by our body language. Complementing this adds to the verbal message e.g. a hug or a pat on the back. Accenting this underlines the message e.g. punching a wall or slamming a door. There are many barriers with communication such as: learning disabilities languages blindness/ deafness gender culture age professionalism the ability to digest information and bad news lost or incomplete records Language differences pose a large barrier in effective communication for nurses, although the option for a translator is often accessible, although it may not be readily at hand. There are also regional dialects that present barriers, for example, different regions refer to bodily parts and functions differently. Such as to pass urine may be commonly known as having a wee, taking a pee etc. Jemma Harrison 20174222 October 2010 cohort Adult Nursing 9th January 2011 Maintaining eye contact with someone who is blind or from a religion that doesnt allow this may also be a significant barrier. To overcome this you would need to ensure that the rest of your body language was correct and consistent. Asking questions that are open ended or asking the patient to repeat the question back would be the best way to ensure that the patient has clearly understood you and what information you are relaying to them. Another barrier may be if a patient had a learning disability and required a parent, guardian or advocate present. You need to ensure that you fully understand the disability your patient had and to what effect certain gestures may have, for example, eye contact with an autistic patient may be deemed aggressive. This is where a nurse needs to assess a patients holistic (or whole) needs, and what brings them to their care. A patient may have only been admitted with a knee injury but how was that injury sustained? This is were holistic nursing care is most important. A knee injury may not be a one off incident, it may be through lifestyle choices, e.g. are they sports fanatics, regular walkers etc. For a nurse to just assess that patients knee injury on face value may lead to the patient being readmitted with the same injury. Again, asking questions that require more than just a yes or no answer, these are called open questions, or asking the patient to non-verbally communicate how they sustained their illness or injury by filling out a questionnaire. The Nursing Times 2007 says that communicating correctly is a basic yet fundamental requirement of good nursing and the breakdown of communication can quickly ruin the already delicate nurse/patient relationship. Other barriers in nurse/patient communication is that nurses are often pushed for time, facing targets, have a lack of privacy or lack of training. This can often make holistic nursing impossible. The communication skills required for holistic nursing (given the correct conditions) are: having the correct patient information. Observe a patients body language. Maintain eye contact where possible. Listen properly. Avoid difficult to understand medical terminology. Be emotionally prepared. Be honest, empathise and show compassion. There has been extensive research into effective communication with patients Dougherty and Lister 2007 highlighted the importance of providing patients with the correct information, communicated in the correct way aided the patient to a quicker recovery. An article in the Nursing Times 2007 by Hamilton. S.J et al highlights a framework of communication skills effective in holistic nursing called the five Is. INTERACT with the patient. Establish the INTENTION of the interaction. Decide on the INTERVENTION to be used. Assess the IMPACT of the interventions. Evaluate the IMPLICATIONS of the subsequent information obtained and act accordingly. In order to get the patient to express their fears and anxieties a nurse needs to display strong and confident non-verbal communication skills and talk to the patient not at them, seeking as much information as possible. Most communication barriers can be overcome if the nurse (or any individual) is ready to try. Repeat open questions, make time for the patient and complete all patient notes thoroughly and to a Jemma Harrison 20174222 October 2010 cohort Adult Nursing 9th January 2011 standard that complies with NMC guidelines. Also remembering that a patients needs may change often but the level of communication should remain the same. On my placement I realised just how effective holistic nursing can be given the time and location. I observed a drug counsellor attempting to discuss a patients rehabilitation and how they intended to take it forward and at what pace and level. The drug counsellor had to find out if what type of drugs the patient was using, how often and were there any underlying physical or emotional reasons why the patient was a drug user. The patient was very withdrawn and didnt appear interested. The counsellor repeatedly asked him questions but the patient stared at his feet and didnt answer. He became noticeably agitated and his body language appeared to become aggressive (he folded his arms). The counsellor suggested they took a break and had a cup of tea. During the break the counsellor asked some indirect questions about the weather etc., I noticed the patient started to relax and build a rapport with the counsellor, this I feel was the counsellor gaining knowledge of the patients whole being not just his drug problem (this is a strong example of holistic care in an adult medical setting). On returning to the treatment room the patient seemed more relaxed and began to answer the counsellors questions whilst maintaining a good verbal and non-verbal communication. This was the first barrier I noticed being over come the second was the patients inability to read and complete a questionnaire. The counsellor sat and read the questions to the patient and then asked the patient to repeat the questions before answering them, ensuring that he had understood what she was asking. Jemma Harrison 20174222 October 2010 cohort Adult Nursing 9th January 2011

The chemistry of drug metabolism

The chemistry of drug metabolism Introduction To describe and explain the chemistry of drug metabolism a basic foundation of knowledge is needed to understand the concepts. Metabolism is one of the methods for analysing the effect of drugs or xenobiotics on the body. It is basically a process of converting lipophilic drugs into more hydrophilic drugs to decrease pharmacological effect and increase subsequent hepatic or renal elimination. So it is essentially a process of inactivation and detoxification of a drug and subsequent elimination of the metabolite formed. The basic knowledge involves the all time classical reactions such as oxidation and reduction and those more advanced reactions including glucuronidation and sulfation. Despite energy being needed to drive such reactions to be in favour, metabolism cannot occur without the complex nature of enzymes catalysing the process. However, metabolism of drugs in human is not solely dependent on the enzymes alone it can be affected by natural micro flora in the small intestines. In an in vitro experiment conducted on ranitidine, it was found that N-oxide was cleaved and is therefore a source of drug metabolism. An alteration in the population of micro flora can affect the of drugs efficacy this is a source of interaction between antibiotics and Microgynon ®. Furthermore, some drugs are bioactivated by metabolism to form active metabolites with a desirable pharmacological function i.e. prodrugs. Unfortunately metabolism can transform an inactive drug or xenobiotic into a biologically active compound which can be carcinogenic to humans. Phenol is a readily formed metabolite of benzene metabolism before catechol and hydroquinone 3,6 which poses a major health concern for humans because it can cause acute myelogenous leukaemia 6 As the great founding father of medicine Paracelsus once said â€Å"all drugs are poison†. Therefore humans and animals have adapted many mechanisms for detoxifying xenobiotics, and these processes are divided into two phases phase I and phase II. It is important to bear in mind that some phase II reactions can occur without phase I metabolism, but phase I and phase II reactions are complimentary and not mutually exclusive. This report describes the chemical reactions of drug metabolism and explains how they occur in vivo. 3.0 Phase 1 Phase 1 metabolism involves the direct enzyme activity on drugs P450 isoform enzymes and esterases are responsible for reduction and hydrolysis of drugs respectively. Each P450 isoenzymes genetic expression varies and can either be inhibited or induced. Knowledge of these drivers of metabolism is essential not only to optimise the use of drugs, reduce harm, maximise benefits in poly pharmacy but also to serve as a template for novel drug development10. P450 and esterase enzymes are mainly found in the liver. Phase I metabolism consists of 3 main reactions: oxidation, reduction and hydrolysis. 3.1 Oxidation 3.1.1 P450 mono oxygenase system 3.1.2 Other oxidation reactions 3.2 Reduction reactions Reduction reactions are mainly interconversion reactions that occur in azo, nitro and epoxide groups and conversion of carbonyl to its corresponding alcohol. Reduction reactions are carried out in the body by P450 isoenzymes, NADH/NADPH reduction systems, carbonyl reductase or aldo-ketone reductase. Azo compounds are generally used in pharmaceutical and cosmetic products. Reduction of an azo group is a classical example of a reduction metabolic reaction. This reaction occurs in the presence of other enzymes and is inhibited in the presence of molecular oxygen. Mechanism of Azo reduction Azo reduction can also occur in the presence of NADH/NADPH system alone within the pH range 3.5-6.08. An azo group can either be reduced by 2 hydrogens to form hydrozo compounds or 4 hydrogens to form two aromatic amines which usually results in a colour loss10 Mechanism of Nitro reduction Nitro groups also undergo reduction reactions and these are catalysed by the same NADP systems. 6 e- are donated to the NO2 to form amine functional groups as in chloramphenicol. This then undergoes acetylation conjugation in phase II metabolism. Conversion of carbonyl to corresponding alcohols Many different enzymes have been identified that catalyse carbonyl reduction of xenobiotics, but most of them catalyse other endogenous substances including sugars and prostaglandins7 Oracin, an anticancer drug with a pro-chiral carbon is metabolised by 11 ÃŽ ²-hydroxysteroid dehydrogenase type I in the microsomes. These metabolites are stereo specific to form DHO7 as shown below in figure 3.2.4. Much of what is known about Oracin metabolism is from phase II clinical trials as its not licensed for use in chemotherapy yet. Mechanism of epoxide reduction This reaction is catalysed by microsomal epoxide hydrolase, a catalytic triad that consists of His 431, Asp226 and Glu 404. Their activity is limited because of a narrow hydrophobic tunnel in the active site and water. A water molecule ionises to form a OH and H+ OH attacks the oxirane ring and thus opens it resulting in formation of vicinal dihydrodiol. This reaction is slow in vitro without acid but in this case epoxide hydrolase catalyses the reaction. Vicinal diols formed are more water soluble thereby terminating genotoxic potential. Hydrolysis Most hydrolysis reactions occur at the ester and amide functional groups, with ester more prone to hydrolysis than amide. Amides are more stable than esters because nitrogen is similar to carbon in size, but less electronegative than oxygen so electrons are pulled into the carbonyl Ï€ electron systems which stabilise its structure. The ease of hydrolysis of esters is used in the development of prodrugs to avoid first pass metabolism, a major problem in orally administered drugs. In vivo hydrolytic metabolism of drugs occurs in the presence of enzymes present in various parts of the body. Hydrolysis of drugs and xenobiotics is generally carried out by esterases mainly in the plasma and intestine and not by P450 systems. The blood, GI tract and liver have the highest hydrolysing capacity. The most significant hydrolysing enzymes are carboxylesterases, cholinesterases, arylesterases and serine endopeptidases. Carboxylesterase is one of the major esterases involved in drug metabolism and xenobiotic biotransformation of drugs with esters, amide and thioester functional groups. In figure 3.0 hydrolysis of ester bond results in benzoylecgonine, a carboxylic acid metabolite. But this is not the only ester group present in the structure. The group present next to the benzene can also undergo metabolism to form benzoic acid. Cocaine in the presence of heroine can generate the toxic metabolite cocaethylene in the presence of alcohol, from concomitant cocaine abuse. Carboxylesterase exists in two different forms hCE1 and hCE2. hCE1 is a more effective metabolic enzyme which transports protein to the endoplasmic reticulum and processes fatty acids and cholesterol in the liver alongside other cholesterol enzymes. The general mechanism of drug hydrolysis in esters and amides is by nucleophilic acyl substitution reactions as shown in figure 3.2.6. Minor structural differences exist between heroine and its metabolites, but their activity differs. Heroin (diamorphine) is converted by hydrolysis to 6-acetylmorphine and morphine. hCE1 mainly cleaves the 3-acetyl linkage to form 6-acetylmorphine. The 6-acetyl linkage is cleaved which later forms morphine with a phenolic -OH and secondary allylic -OH. Diloxanide furorate is a drug of choice and an antiparasitic agent for treating asymptomatic patients with E. histolytica cysts in the faeces and cryptosporidiosis, an acute intestinal amoebiaosis in HIV patients. The drug is orally administered and extensively metabolised by gastro intestinal esterase to form diloxanide and furoic acid, thereby diminishing its effectiveness. This problem is modified by using cyclodextrin that prevents excessive hydrolysis of the drug. Carboxylesterases ability to form a stable complex enhances its presence in the blood and makes it ideal for treating cocaine overdose. It is also considered that as an active site for drugs, this would make it ideal for drug discovery e.g. sarin and VX gas. 4. Phase II Conjugation pathway The phase II conjugation pathway is often a detoxification mechanism. It terminates drug pharmacological activity by changing or masking functional groups in the parent drug or phase I metabolite into a more ionic polar product which aids excretion. The processes that commonly occur in phase II metabolism can be fundamentally divided into 3 groups which are glucuronidation, sulfation and acetylation. The nature and functional group of a drug molecule will determine which one of these processes be in favour e.g. acetaminophen undergoes both glucuronidation and sulfation, however at high doses glucuronidation predominates and at low doses sulfation predominate (Airpine Choonara, 2009). 4.1. Conjugation with sugars Conjugation with various sugars is possible in nature, and novel pathways for xenobiotic metabolism are discovered frequently (Ikenakaa, Ishizakab, Miyabaraa, 2007). However the most important reaction in humans is glucuronidation. 4.1.1 Glucuronidation Glucuronidation is essentially conjugation of a substrate with ÃŽ ±-D-glucuronic acid, shown in figure 4.1.1.1. As the name suggests, glucuronic acid is a derivative of glucose with the 6th carbon being oxidised to a carboxylic acid group. This in combination with the many hydroxyl groups gives glucuronic acid a solubility of 1g/10mL in cold water, which the British Pharmacopeia would class as â€Å"freely soluble† (British Pharmacopeia Commission, 2009) Glucuronic acid is present in vivo as the co-factor uridine 5-diphosphate-glucuronic acid (UDP-glucuronic acid). The reaction of UDP-glucuronic acid with a xenobiotic substrate is catalysed by the enzyme UDP-glucuronosyltransferase (UGT) (Kaeferstein, 2009), and an example of a glucuronidation reaction is shown in figure 4.1.1.2 Figure 4.1.1.2 demonstrates how glucuronidation can occur with a xenobiotic containing an acceptor nucleophilic group (for example COOH, SH or NH2, but in this case OH) (Kaeferstein, 2009) (Sakaguchi, Green, Stock, Reger, King, 2004). The lone pair of electrons on the hydroxyl group attacks at the 1st carbon of the pyranose ring, which is activated because of the adjacent electron-withdrawing oxygens, in an SN2 nucleophilic substitution reaction. The UDP glycosidic bond is cleaved off owing to the good leaving group properties of the phosphate group, and the xenobiotic has reacted with the glucuronic acid to form a ÃŽ ²-D-glucopyranosiduronic acid conjugate. Note that the reaction is known to be SN2 because the formation of an intermediate leads to an inversion of stereochemistry at the anomeric carbon. The resulting glucuronide conjugate has improved solubility due to the hydroxyl and carboxylate groups, and is usually excreted in the urine, although there is evidence to suggest that conjugates with a high molecular weight are eliminated in the bile. However the glucuronides undergo some important reactions within the body which affects their metabolism. A spontaneous intramolecular reaction can lead to esterification of the glucuronide, as shown in figure 4.1.1.4. The newly formed ester carbonyl is capable of reacting with the N-terminal of a protein residue to form a stable imine, i.e. this can lead to irreversible protein binding. Alternatively, depending on which species the glucuronic acid is bound to, nucleophilic substitution can again occur and the xenobiotic will react with the N-terminal of the protein and regenerate free glucuronic acid (Zamek-Gliszczynski, Hoffmaster, Nezasa, Brouwer, 2006). Pharmaceutical companies may therefore try to avoid designing drugs which are predicted to be metabolised by the glucuronidation pathway, not just to increase the half-life of the drug by avoiding conjugation and excretion but also to avoid the potential side-effects that can occur as a result of protein binding, such as cirrhosis of the liver. Interestingly, glucuronidation can also lead not just to metabolites that lose their therapeutic use and are toxic, but some glucuronides can continue to be pharmacologically active and may even be more potent than their parent drug. Morphine-6-glucuronide (M6G) is one such example. M6G and morphine are both potent analgesics M6G, despite having been conjugated with a large polar molecule, still binds strongly to ÃŽ ¼ opioid receptors to provide pain relief to the same extent as morphine. Morphine-3-glucuronide, another metabolite, binds preferentially to NMDA receptors instead, and causes allodynia, myoclonus and seizures (the side-effects associated with opiate usage). Morphine and codeine are so far the only known examples of glucuronides with high activity (Kaeferstein, 2009). 4.2. Glutathione conjugation Glutathione serves as a substrate for electrophilic drugs because of the nucleophilic thiol moiety on the cysteine residue (thus glutathione can be referred to in reaction pathways as simply GSH). GSH conjugation therefore involves a nucleophilic attack of the sulphur atom onto drugs with electrophilic carbon atoms, i.e. those bound to good leaving groups such as halogens, sulphate and nitro, as well as activated carbon atoms in ring strained systems such as epoxides and ß-lactones (Zamek-Gliszczynski, Hoffmaster, Nezasa, Brouwer, 2006). Conjugation leads to a thioether bond being formed between GSH and the drug molecule. Following this reaction, conjugates are typically metabolised further to yield more polar molecules which are better excreted in the urine and bile (Zamek-Gliszczynski, Hoffmaster, Nezasa, Brouwer, 2006). Figure 4.2.4 shows the possible biotransformation reactions of a glutathione conjugate. Transpeptidase and peptidase convert glutamate to NH2 and remove glycine, respectively. NH2 is then a target for N-acetylation (mentioned in section 4.4). Alternatively, two molecules of glutathione can react together to form a disulfide bridge, in the process donating hydrogen atoms to reduce another molecule. This is usually utilised in vivo when glutathione acts as an antioxidant (Forman, Zhang, Rinna, 2009), but also plays a part in drug metabolism as seen in the denitrification of the antianginal drug, glyceryl trinitrate (GTN) in figure 4.2.5 (Ji, Anderson, Bennett, 2009). To reiterate, GSH reacts with highly electrophilic species in the body. This prevents drugs with electrophilic groups from attacking important nucleophilic centres in biological molecules, such as DNA and proteins, which could lead to toxicity. This is explored further in section 5 where the consequences of insufficient glutathione conjugation of paracetamol metabolites are looked at. 4.3. Sulfation Sulfation is one of the classical processes of phase II metabolism. It allows the biotransformation of numerous xenobiotics and metabolites from phase 1 (shown in figure 4.3.1) to be sulphate conjugates. This gives protection against toxicity or the potential toxic effects from the numerous xenobiotics and metabolites not being conjugated. It also produces more polar, more water soluble metabolites, which means they are more easily and readily excreted in urine or bile. The sulphate conjugate possesses such advantageous properties by having a low pKa, allowing an increased aqueous solubility and excretion. It is an important reaction for drugs and hormones that contain the phenolic functional group to be metabolised by conjugation to a sulphate group examples include steroid hormones, catecholamines, neurotransmitters, thyroxine, bile acids and phenolic drugs. Examples of drugs and xenobiotics with a phenolic group attached: The chemistry behind the sulfation conjugation reaction emphasizes the important key features of the system. This includes the two enzymes sulfatase and sulfotransferase, alongside the co factor 3†²-phosphoadenosine 5†²-phosphosulfate (3†²-phosphoadenylylsulfate, PAPS) which plays an important role in sulfation conjugation. The availability of PAPS and its precursor inorganic sulphate determines the reaction rate as the total amount of sulphate is limited and can be readily used up. PAPS is formed enzymatically by ATP and inorganic sulphate. The enzyme sulfotransferase transfers the active sulphate from PAPS to the xenobiotic or a phase 1 metabolite forming the sulphate conjugate (VL Verdugo D, 2004). Sulphate conjugation is a reaction principally of phenols and to a lesser extent alcohols to form highly ionic polar sulphates. Sulphate conjugation is also important for steroids because steroid sulphates are not capable of binding to their receptor and so this reduces its biological activity. Sulfation of alcohol generates a good leaving group and can be an activation process for alcohols to produce a reactive electrophilic species. Mechanism of sulfation conjugation an electrophilic substitution reaction: The oxygen of the OH has a negative inductive effect on the benzene ring so it withdraws electrons towards it making it a more reactive nucleophile It attacks the electrophilic sulphur of the sulphate group of PAPS The hydrogen of the OH bond leaves in exchange for the sulphate group and UDP acts as a good leaving group This forms the sulphate conjugate which is soluble and readily excreted via the kidneys 4.4. Acetylation Conjugation Acetylation is also an important reaction in phase II metabolism as the majority of drugs contain a primary amine functional group. It is a major route for the biotransformation of hydrazine and aromatic amines. This means that acetylation of the arylamine or phase 1 metabolites can occur more easily to reduce their biological activity (Garcia-Galan Diaz-Cruz, 2008). The limitation of acetylation is that it produces conjugates that are less water soluble (Zamek-Gliszczynski, Hoffmaster, Nezasa, Brouwer, 2006) as well as it does not work for drugs containing secondary amine groups. The aim of acetylation is to convert the primary amine moiety into an amide because amides are more stable as peptide bonds are more resistant to hydrolysis. Like glucuronidation and sulfation this reaction is highly specific because of the nature of the enzyme involved. The main players of acetylation conjugation are N-acetyltransferase and the co factor acetyl Coenzyme which is a thioester . The reactio n undergoes electrophilic substitution similar to Friedal-Craft acylation. The NH2 attached to the aromatic ring makes it much more reactive and electron donating. NAT helps to transfer the acetyl group (CH3CO) obtained from Co enzyme A (CH3COSCoA) to conjugate with the drug at the amine site forming the amide bond. H-SCo-enzyme acts as a good leaving group. Mechanism of acetylation conjugation: The lone pairs of the nitrogen of the primary amine of sulphonamide attack the carbonyl carbon of the acetyl group of the acetyl coenzyme A. In this reaction nitrogen acts as a nucleophile, donating the pair of electrons to the electrophilic carbonyl carbon. The carbonyl carbon (ÃŽ ´+) is activated by the electron withdrawing oxygen (ÃŽ ´-) making it more susceptible to nucleophilic attack. This forms a temporary tetrahedral intermediate, which falls back to form an amide bond and SH-CoA acts as a leaving group. As a result the acetyl conjugation of sulphonamide is formed, and this is readily excreted via the kidneys. 4.5 Stereo selectivity Stereo selectivity is classed as a fundamental aspect of drug metabolism ever since the tragic case of the drug thalidomide. This has provided a broader knowledge on the understanding of drugs and xenobiotics and also the importance of their stereochemistry properties. As mentioned in section 4.1.1 (glucuronidation), drug metabolism may lead to stereochemistry inversion of substrates during the various reactions that occur. An example of how the understanding of stereochemistry in xenobiotic metabolism has practical applications can be seen with the non-steroidal anti-inflammatory drug ibuprofen. It has been found that in vitro, only the S-isomer is pharmacologically active in inhibiting cyclooxygenase enzymes. However in vivo the metabolism of ibuprofen is complex, involving glucuronidation at the acyl group and hydroxylation at the 2 and 3 positions, but most importantly the metabolism of the 2 enantiomers differs because there is a unidirectional enzymatic conversion of the R-isomer to the active S-isomer. (Chang, et al., 2008). The metabolism of ibuprofen is summarised in figure 4.5.2. For this reason drug manufacturers typically produce a racemic mixture of ibuprofen for administration to patients, since the R-isomer will be converted within the body, and producing an enantiomerically pure sample would be needlessly expensive. 5. Micellaneous Amino acid conjugation is important for metabolising, solubilising and eliminating carboxylic acids through the urine because it produces very soluble conjugates. Amino acid conjugation mechanism e.g. benzoic acid (Xu, et al., 2007): The carboxylic group of the benzoic acid is first activated by ATP to the AMP ester This is then converted to the corresponding coenzyme A thioester with CoASH. These first two steps are catalysed by acyl Coenzyme A synthase enzyme The appropriate amino acid N-acyltransferase then catalyses the condensation of amino acid and Coenzyme A thioester to form the amino acid conjugate. Methylation conjugation: Even though it is not a common reaction for most drugs and xenobiotics, it is worth mentioning methylation because it is the most common biochemical reaction for endogenous compounds such as catecholamines (Strous, et al., 2009). Methylation plays a key role in the inactivation of amines such as norepinephrine, serotonin, dopamine and histamine, and is also involved in the biosynthesis of epinephrine and melatonin. A source of methyl comes from the high energy nucleotide S- adenosylmethionine (SAM) which is transported by cathecol-O- methyltransferase. However, it has been reported that methylated conjugates do not have improved water solubility (a similar disadvantage to acetylation). Methylation mechanism the nucleophilic substitution of norepinephrine: The lone pair on the electronegative oxygen of norepinephrine (R-OH) attacks the CH3 of SAM The bond between the sulphur and carbon breaks (S-C) Drug Toxicity The toxicity associated with acute paracetamol overdose is due to its metabolism processes. In the human body, paracetamol is mostly metabolised 30% by the sulfation pathway, 60% via glucuronidation and the remaining 10% being either excreted unchanged in the urine or undergoing CYP450-dependent oxidation as shown in figure 5.3 to form N-acetyl-p-benzoquinoneimine (NAPQI) (Airpine Choonara, 2009). NAPQI contains an electronically activated ring system, capable of attacking nucleophilic molecules such as N atoms in cellular macromolecules and causing cell damage. However NAPQI will preferably attack the more nucleophilic sulphur atom of glutathione and therefore will also undergo phase II metabolism to form inactive conjugates a schematic summary of the metabolism of paracetamo In overdose situations, the glutathione supply is used up as it is conjugated with the excessive NAPQI in the system. This leaves the rest of the NAPQI free to bind irreversibly to proteins in hepatic liver cells (since P450 metabolism occurs predominantly in the liver) and this cause liver necrosis. Without the detoxification capacity of the liver, the human body will typically die within 2 weeks (Airpine Choonara, 2009). With the chemistry of paracetamol metabolism in mind, it is easier to understand why some patients are classed as â€Å"high-risk† and thus more susceptible to paracetamol overdose: Recent alcohol (ethanol) consumption causes induction of the P450 enzyme involved in the formation of the NAPQI molecule; this leads to an increased quantity of NAPQI being produced and therefore the bodys supply of glutathione for conjugation is more rapidly used up leading to toxicity. Other drugs which induce the same P450 enzymes will have the same effect. Eating disorders such as anorexia nervosa lead to a poor diet and therefore decreased synthesis of glutathione in vivo, so NAPQI detoxification conjugation can be overwhelmed at lower concentrations of paracetamol consumption.

Essay --

Taylor Stoiber Mr. Dobberstein Research Essay 1/13/14 Rotten Apple Apple is a king in the technology world; poisoning every area of the industry that they have introduced a product too. They are slowly weeding their competition out. The only a company thrives in the thorn bush market is if they are in cahoots with apple. Apples co-founder Steve Jobs, started the company with all intention of dominating the market. The only obstacle for them is the Anti-trust law created ages ago. Apple, in their attempt to take the market over, has been racking up evidence against themselves. There reach has leaped boarders and even caught the attention of the European Union. Apple is pushing their boundaries and in the future will eventually cross the line in to monopolistic actions. Sir Steve Jobs, the almighty co-founder of Apple started apple dreaming big. The Harvard College dropout carried through with that dream. According to Leander Kahney, author of â€Å"Inside Steve’s Brain,† â€Å"apple went public 1980 with the biggest public offering since 1958† (2008), this offer proved successful as apple soon became a super power. Apple suffered a fall out though, but Steve Jobs came back and rescued them, reviving them to their previous stature. A stature limited by the law. The Anti- trust law to be exact. According to â€Å"The Fuller Court: 1888-1910† the Antitrust law was passed in 1904 (2005, p 2). This law was formed after a large legal case Northern Securities Co. v. United States where the Supreme Court sided with President Roosevelt (Flash Focus, 2005). This case has had major effects on today’s marketing techniques and monopolistic companies. Apple, being one of these monopolistic type companies, has had to deal with some scrutiny over t... ...ften times Apple will simply take the fine because it can afford to, and would rather pay the money then fairly open their trade secrets up to the world. This loophole in the law, if you will, is allowing for Apple to pay its way through anti-monopoly laws and regulations. Unfortunately Apple is able to buy its way out of trouble and slowly knock its competition. Apple needs new regulations enforced on it to keep the company in check. Especially because Steve Jobs went into the company with full intentions of domination and dominate he did. Apple was kept mildly in check by the Anti-trust law which Apple still managed to find loop holes in. Finally the evidence of a growing monopoly is there. Apple has even gained scrutiny on an international scale. Apple is pushing their boundaries and in the future will eventually cross the line in to monopolistic actions.

The Role of Women in Mary Shelleys Frankenstein Essay -- Frankenstein

The Role of Women in Mary Shelley's Frankenstein Whether an author is conscious of the fact or not, a fictional work cannot avoid reflecting the political, social, economic, and religious background of the author. Therefore, regardless of Frankenstein's categorization being that of science fiction, Mary Shelley reveals her own fears and thoughts, and, as a result, reveals a great deal about the time and place in which she wrote. She mentions specific geographical locations throughout Europe, she raises ethical questions concerning the synthesis of life, and she writes in the context of popular contemporary philosophy and the importance of environment vs. experiences. Most importantly to this essay, however, is the manner in which Shelley reflects the characteristics of the Romantic period in which it was written and its attitudes toward women. In an article that discusses female authors during this time period, we find that Romanticism was a male-dominated movement. The same article states that this dominance prevented female authors from being given the same consideration as males (Behrendt 147). Moreover, women who crossed this "culturally-imposed boundary" were routinely charged with "unnaturalness" or "monstrosity" (Ibid.). This is clearly portrayed through the author herself, particularly in the introduction of the novel where her introduction is full of apologies for her work. Despite the self-proclaimed pressure to become a writer in the expectation of continuation of her parents' writing, the story is wrought with marks of difficulties of having been taken less than seriously. One place where it is particularly evident is in the preface of the book, although parts were writte... ...ely, in the representation of Shelley herself in the monster. Works Cited and Consulted: Behrendt, Stephen C. "New Romanticisms for Old: Displacing Our Expectations and Our Models." Midwest Quarterly. Winter 2000: 145-159. Kelly, G. "Unbecoming a Heroine." Nineteenth Century Literature. September 1990: 220-242. Lowe-Evans, Mary. Frankenstein: Mary Shelly's Wedding Guest. New York: Twayne Publishers, 1993. Oates, Joyce Carol. "Frankenstein: Creation as Catastrophe." Mary Shelly's Frankenstein. Ed. Harold Bloom. New York: Chelsea House Publishers, 1987. Seymour, Miranda. Mary Shelley. Savannah, Georgia: Grove/Atlantic Publishers, August 2001. Shelley, Mary Wollstonecraft. Frankenstein. Edited by Johann Smith. Boston: St. Martin's Press, 1992. Tropp, Martin. Mary Shelly's Monster. Boston: Houghton Mifflin, 1976.

Archetypes and Their Influence on the Personality Essay

Carl Gustav Jung (1875-1961) was born on July 26, in the small village of Kesswil on Lake Constance. He was named after his grandfather, a professor of medicine at the University of Basel. He was the oldest child and only surviving son of a Swiss Reform pastor. Carl attended the University of Basel and decided to go into the field of psychiatry after reading a book that caught his interest. Jung became an assistant at the Burgholzli Mental hospital, a famous medical hospital in Zurich. He studied under, and was influenced by Eugen Bleuler, a famous psychiatrist who defined schizophrenia. Jung was also influenced by Freud, with whom he later became good friends. Their relationship ended when Jung wrote a book called â€Å"Symbols of Transformation. † Jung disagreed with Freud’s fundamental idea that a symbol is a disguised representation of a repressed wish (Heaney, 1994). After splitting up with Freud, Jung had a 2 year period of non-productivity, but then he came out with his â€Å"Psychological Types,† a famous work. He went on several trips to learn about primitive societies and archetypes. His explorations included trips to Africa, New Mexico to study Pueblo Indians, and to India and Ceylon to study eastern philosophy. He studied religious and occult beliefs like I Ching, a Chinese method of fortune telling. Alchemy became one of his interests during his journeys. His book, â€Å"Psychology and Alchemy,† published in 1944, is among his most important writings. In this study, he told about the human mind. One of his methods was word association. This is when a person is given a series of words and asked to respond to them. Abnormal response or hesitation can mean that the person has a complex about that word. His basic belief was in complex or analytical psychology. The goal is psychosynthesis, or the unification and differentiation of the psyche (mind). He believed that the mind started out as a whole and should stay that way. That answered structural, dynamic, developmental questions. Jung is best known for his theory of â€Å"The three levels of the mind† (Aurelio, 1995). Discussion The three levels of the mind theory includes the ego (conscious), personal unconscious, and collective unconscious. The conscious level serves four functions. It is the part of the personality that carries out normal daily activities: thinking, feeling, sensing, and intuiting. The personal unconscious contains an individual’s memories, and the collective unconscious is an inaccessible layer that contains universal experiences. Usually, one of the two classes usually dominates, and rarely does one see an individual with perfectly balanced classes of behavior (Nehr, 1996). Jung said that an ego is a filter from the senses to the conscious mind. All ego rejections go to the personal unconscious. The ego is highly selective. Every day we are subjected to a vast number of experiences, most of which do not become conscious because the ego eliminates them before they reach consciousness. â€Å"The personal unconscious acts like a filing cabinet for those ego rejections† (Jurkevich, 1991,p. 58). Clusters of related thoughts in the personal subconscious form complexes. Complexes are really suppressed feelings. Complexes are often highly visible to people, but unfelt by the individual who has the complex. Complexes can be revealed by word association, which will cause hang-ups if a certain word is mentioned. A strong or total complex will dominate the life of a person, and a weak or partial complex will drive a person in a direction of it, but not too strongly. A complex, as Jung discovered, need not be a hindrance to a person’s adjustment. â€Å"They can be and often are sources of inspiration and drive that are essential for outstanding achievement† (Aurelio, 1995, p. 351). â€Å"The collective unconscious is hereditary. It sets up the pattern of one’s psyche†(Kremer, 1990, p. 2). An inherited collection of primordial images are stored here. They are universal inclinations that all people have in common somewhere by means of heredity. The four important archetypes that play very significant roles in everyone’s personality are Persona, Anima(us), Shadow, and the Self. Persona is derived from the Latin word meaning â€Å"mask†. In Jungian psychology, the persona archetype serves a similar purpose; it enables one to portray a character that is not necessarily his or her own. The persona is the mask or facade one exhibits publicly, with the intention of presenting a favorable impression so that society will accept him (Nehr, 1996). Anima and Animus is what Jung referred to as the â€Å"inward face† of the psyche. The â€Å"inward face† he called the anima in males and the animus in females. The anima archetype is the female side of the masculine psyche; the animus archetype is the masculine side of the female psyche. Man has developed his anima archetype by continuous exposure to women over many generations, and woman has developed her animus archetype by her exposure to men (Heaney, 1994). According to Mannis (1997), the â€Å"Shadow† is what Jung referred to as â€Å"the negative side of the personality, the unpleasant qualities we like to hide†. When one is not conscious of their â€Å"shadow†, they give it more power. â€Å"Usually, the qualities we dislike the most in others, are the unknown qualities in our shadow† (Kremer, 1999, p. 4). â€Å"The self represents all archetypes working together† (Heaney, 1994, p. 29). Jung used the words extraversion and introversion to show how one’s personality is. Those who lean towards extraversion are usually socially accepted. They are outgoing and very sociable. Those who lean towards introversion tend to keep to themselves and are not very sociable. One’s psyche works together three ways. One structure may compensate for the weakness of another structure (Jurkevich, 1991). One component may oppose another component, and two or more structures may unite to form a synthesis. Compensation may be illustrated by the contrasting attitudes of extraversion and introversion. If extraversion is the dominant or superior attitude of the conscious ego, then the unconscious will compensate by developing the repressed attitude of introversion. Compensation also occurs between function. A person thinking or feeling in his conscious mind will be an intuitive, sensation type unconsciously. This balance is healthy and it prevents our psyches from becoming neurotically unbalanced. Opposition exists everywhere in the personality: between the persona and the shadow, between the persona and the anima, and between the shadow and the anima. The contest between the rational and irrational forces of the psyche never ceases. One’s integrity of â€Å"self† can actually determine whether or not this opposition will cause a shattering of a personality (Heaney, 1994). I decided to do my research on Carl Jung because he is not discussed much in the textbook. I find his theory of conscious and unconscious very interesting. I believe the thoughts of persona and ego without a doubt. When one’s ego is shot down, a person can tend to develop a complex about it. I also agree that people tend to have a different persona based on where they are at and how they are expected to act around certain people. References Aurelio, Jeanne M. (1995). Using Jungian archetypes to explore deeper levels of organizationalculture. Journal of Management Inquiry, 4, 347-369. Heaney, Liam F. (1994). Freud, Jung and Joyce: Conscious connections. Contemporary Review,265, 28-32. Jurkevich, Gayana. (1991). Unamuno’s intrahistoria and Jung’s collective unconscious: parallels,convergences, and common. Comparative Literature, 43, 43-60. Kremer, Jurgen W. (1999). Facing the collective shadow. Revision, 22, 2-5. Mannis, Robert F. (1997). Jung and his shadow. Utne Reader, 84, 91-94. Neher, Andrew. (1996). Jung’s theory of archetypes: a critiques. Journal of HumanisticPsychology, 36, 61-92.

How Has Music Marketing Changed over the Years and Where Does the Future of the Music Press Lie? Essay

In this day and age, technology is developing so rapidly that changes are occurring all across the board. Faster internet, digital photography, and interactive programs are all making advertising and marketing much easier in the ever expanding world of consumerism. With all these new advances, there are bound to be numerous changes. The music industry is a relatively modern concept. It originated from word of mouth and paper publications back before computers were even thought of. Many people nowadays act for the music press themselves by creating their own blogs/podcasts etc from their own music knowledge they have gained from websites and magazines. Although there are many technology based music industries there are still some simple publications that are still popular even though they have been around for the past 50 years such as NME magazine. As the music press progressed specific music genre specialisms such as Kerrang and TOTP have been introduced. Also, advertising elements such as billboards and posters still catch our attention as we are walking or driving past one. An eye catching mise en scene or new pictures of our favourite bands induce us to stop what we are doing and take notice in what they are doing or promoting. This shows how the music press operates according to the basic principles of advertising. For example A. I. D. A. The awareness is raised through apple symbols and artists which we trust to admire, acting as form of celebrity endorsement for the reader or viewer. The press follow the interest in an artist by using aesthetically pleasing photos of them making us aspire to look or be like our idols in the music industry. We cant help to desire to follow our favourite artist on twitter to get all the up to date gossip and information on them. We then take action by buying CD’s, gig tickets and merchandise in order to support our favourite bands but also as we aspire to fit in to the changing society. We do what is ‘the thing’ to do at the time. This relates to Maslow’s Hierarchy of Needs as group and self identity relate to our choices in music and say a lot about us as individuals. There are still many advantages of buying a traditional magazine in today’s society. You can pick it up anytime and take it anywhere with you. You know all the information will be reliable and trustworthy. Free CDs/booklets and posters are one of the biggest advantages. People are most likely to by a magazine with a freebie other than any other one. Since technology became so popular, the most common music marketing for music was magazines. People would go out and spend their hard earned money on a magazine which would fill them in and keep them updated on everything to do with their favourite genre of music. It was for some people the only way to find out about new information on their favourite bands etc. However, over time as technology has developed, new marketing ways have been introduced which are pushing music magazines to the back of the line. These new ways are quicker, cheaper and easier for people which is why they are becoming more popular. In the mid 1990’s things started to change. The advent of the Internet allowed music fans to change the way they consumed music. And as technology advanced, the music business began to rethink (or in some cases were forced to rethink) the tools they used to market music to consumers. For reasons both good and bad, the Internet has given nearly all consumers more information than they would get from things like magazines or the radio for free, which means that people wont bother spending their money buying a magazine. Online music magazines/websites have the opportunity to make more money from advertising etc. If things continue developing in this way, the future of the music press will all be technology based. Eventually music magazines wont be making enough money and will be taken off the shelves and more and more industries will be online based. What is certain is that the future of the music press will be tied to the idea of sharing ideas online and through word of mouth. Blogs like network. youthmusic. org. uk, viral marketing through facebook where artists have a bigger fan base will develop and expand.