The Approaches and Methodologies of New Product Development

Insulin resistance may gradually become worse as time goes Essay Example

Insulin resistance may gradually become worse as time goes Essay Example Insulin resistance may gradually become worse as time goes Paper Insulin resistance may gradually become worse as time goes Paper To understand what is occurring in the cellular level in type 2 diabetes we must first understand how the pancreas, blood glucose and insulin are related to diabetes. The condition known as diabetes mellitus occurs when there is too much glucose in the blood and this is also reflected in the abnormal amount of sugar in the urine (Layman 275). Type 2 diabetes usually occurs later in life and is believed to be the result of insulin resistance, among others (Mathur, â€Å"Insulin Resistance,† par. 4). After eating a meal that is rich in sugar or carbohydrates, the glucose level in the blood goes up and this stimulates the beta cells in the pancreas (Layman 273). What is the result of this excitation of the beta cells? The answer is that they speed up the release of insulin into the blood and these act as messengers to the fat cells, liver cells, and   the skeletal muscle cells (Layman 274). There is a certain mechanism by which the insulin molecules are able to send their message to the cells regarding the increase in glucose in the blood. When the insulin molecules bind to the surface of the cell, they are able to activate an intracellular molecule that initiates changes in how the cell makes use of glucose (Layman 274). This intracellular molecule causes two essential adjustments to cell metabolism. It hastens up the activity of the glucose carrier proteins that play an important role in transferring the glucose from the blood to the target cells, and then it also sets off an enzyme that plays a key role in the conversion of glucose into energy (Layman 274). Thus, in the normal process, the extra glucose in the blood is used up by the target cells for the production of energy. However, in type 2 diabetes in which there is insulin resistance the cells fail to properly respond to the message from the insulin molecules, and because of this abnormal situation, more insulin is required to be able to cause the necessary effects ( Mathur, â€Å"Insulin Resistance,† par. 2). Insulin resistance may gradually become worse as time goes by until such time that the pancreas are no longer able to secrete the required amount of insulin to trigger the appropriate response in the cells ( Mathur, â€Å"Insulin Resistance,† par. 7). Because the amount of insulin is no longer able to sufficiently activate the use of the glucose in the blood for cell energy, glucose begins to accumulate in the blood and we now have type 2 diabetes (Mathur, â€Å"Insulin Resistance,† par. 7). Studies have revealed there is a relationship between insulin resistance and obesity, high blood pressure, arteriosclerosis, high blood cholesterol, and having family members who have type 2 diabetes, among others (Mathur, â€Å"Insulin Resistance,† par. 17). Therefore, studies have focused on these conditions to find a cure or to prevent type 2 diabetes. Some clinical trials have demonstrated the importance of strictly controlling the amount of blood sugar as a way to avoid or delay the onset of serious complications (â€Å"Type 2 Diabetes Fact Sheet† p. 2). Other studies have concentrated on the production of glucose monitors that continuously indicated sugar levels and still others have focused on oral drugs that target the abnormalities in how the cells use glucose (â€Å"Type 2 Diabetes Fact Sheet† p. 2). Some of these oral agents try to decrease the amount of insulin that is required while others attempt to regulate the amount of blood glucose. Future research are being prepared to determine those genes that make a person more susceptible to type 2 diabetes, the molecular mechanisms that cause obesity to be related to insulin resistance, and the preemption of diabetes as an effort to avoid complications that could result to death (â€Å"Type 2 Diabetes Fact Sheet† p. 2). Layman, Dale Pierre. Biology Demystified. New York: 2003. Mathur, Ruchi. â€Å"Insulin Resistance.† Eds. Jay W. Marks and William C. Shiel. MedicineNET. 27 Jun. 2009. medicinenet.com/insulin_resistance/article.htm Type 2 Diabetes Fact Sheet. National Institutes of Health. Bethesda, MD: 2008.

Gender inequalities in the Middle East Essay Example | Topics and Well Written Essays - 1500 words

Gender inequalities in the Middle East - Essay Example On addressing the impact of poverty and microfinance on gender/power relations and women’s empowerment,this study engraves itself into broader discourses and debates on gendered inequalities in the Middle East.Introducing the context that Saudi Arabia is an undisguised,self-evident patriarchal state,this study aims at investigating the positive and negative implications on female clients. By studying the microfinance initiatives and examining the underlying principles of Bab Rizq Jameel (BRJ), the positive and negative implication on female clients are analyzed, particularly in terms of its effects on their decision-making and bargaining power in the household. This case study on microfinance in the kingdom of Saudi Arabia aspires to unfold an important and lacking dimension to the current debates surrounding gender and development in developing countries. Keywords: Microfinance, Saudi Arabia, Bab Rizq Jameel (BRJ), gender relations, women’s economic/social empowerment, bargaining power, decision-making and household. Introduction Microfinance institutions vary in terms of their goals, agenda’s and assumptions. There have been continual debates on whether microfinance can be considered as a savior to poverty-stricken women from oppression and gendered inequalities or whether having access to micro-financial resources can empower women economically. There are studies which argue that microcredit helps to empower women thus promoting gender-equality and improving household well-being while microfinance ‘does not directly challenge any official views that subjugate women’ (Aminul et al., 2011). Women are treated as second-class citizens and are chiefly oppressed by the laws and constraints imposed on them through patriarchal states such as Sharee’a law in the kingdom of Saudi Arabia. There are also the traditions and customs that give rise to inequalities and gendered division of roles that are produced and reinforced from ‘relationships that are intrinsically gendered’ within the household (Khateeb, 2011). This study being the vanguard of research on gender and development through microfinance, it felt natural that the appropriate start should be from the grass root’s level, the household. Gender-related rigidity in the intra-household is the core institution where the microfinance women clients spend most of their time. This study primarily deals with investigating the impact of microfinance on gender relations in the household. Professor M. Khateeb (Khateeb, 2011) in her lecture about gender, household and domestic domain points out that there is an explicit focus on the household because ‘it is the site of the earliest socialisation processes and gender identity formation. Secondly, it is central to the analysis of the organisation of production and reproduction in different societies. The gender division of roles, responsibilities and resources within the household play an important role in shaping what men and women are able to do beyond the household. And finally a great deal of policy, both economic and social, is premised on assumptions about how gender relations are organised within households’. This study ultimately aims at assisting and enabling the policy makers of BRJ Microfinance programme to create policies that prioritise the impact of microfinance on gender relations in intra-household. On having a wider examination of BRJ’s assumptions, rationale and process coupled with gender power relations within household, policy makers would be able to arrive at a more accurate representation of the graving issue of unemployment and would also travel at a more effective outcome. Aims 1. How does microfinance impact gender relations in Saudi Arabia? 2. Effects of micro-financial resources in Saudi Arabia on women empowerment both in household and in society?1 3. How do micro-financial resources effect on the well-being of the famili es in Saudi Arabia in terms of survival, security, financial self-reliance and autonomy on various levels (Kabeer, 1994:304)? Objectives This

THE PERIOD 18811919 MARKED A FUNDAMENTAL CHANGE IN AMERICAN FORIENG Essay

THE PERIOD 18811919 MARKED A FUNDAMENTAL CHANGE IN AMERICAN FORIENG POLICY. EXPLAIN THE CHANGES THAT OCCURRED IN THIS PERIOD. WHY DID THESE CHANGES OCCUR THE - Essay Example They were so diverse that to unite them was very difficult. They engaged in strikes, politics to live better life. The industrialists employed low wage workers from small areas of the country and rest of the world. The low class people also needed some work to earn their living. This made people from various countries to migrate to United States. This migration caused a point of concern for the local skilled worker class. Thus protests were carried out against the migration and foreign policies to make some changes. Thus the worker class was divided into northern European skilled workers and southern and eastern unskilled European workers. This diversification was not only among the worker class but also in the educated service class. The racial difference was set between the white native Americans and the black African Americans. Racism was started among white and black people. Poverty was so increased that women and children were also supposed to work in factories to satisfy the basic needs. In the late nineteenth century a new managerial class evolved. This class comprised of white collar people and army people. The major population of this group was from middle class and basically were those people who work between executives of the company and white collar workers. As new technology introduced typewriters in the offices the office work was increased. Women were given more preference because they work for low wages and also can earn more money in shorter time. The late nineteenth century was the era of progressivism. The progressive movement was based on the concepts of social justice, greater efficiency in government and social control. The people thought that the government should become more active regarding democratic reforms and in protecting laborers. William McKinley was the president at that time. McKinley was the 25th president of United States Of America. To increase the American colonial power he fought Spanish American war. The main point of attraction of progressive movement was cities. Civilized cities was the main aim of progressive movement. The urban population wanted cities to be better and safer place to live. The progressive movement was started from the local government and then moved to the upper level government. Theodore Roosevelt, a young man with a great political experience became 26th president of United States Of America. He was the youngest president with age of forty only. His personality reflected as activist and moralist due to his policies. He won a noble peace prize for negotiating an end to Russo-Japanese war and preserving open door policy in China. The foreign policies like Monoroe doctrine and open door policy were proved to be beneficial for American trade. In late nineteenth

Philosophy Essay Example | Topics and Well Written Essays - 3250 words

Philosophy - Essay Example ture prevails as man is covetous and motivated by desire, appetite and avarice who justifies the employment of violence to protect his treasures or holdings. Violence is thus a means to an end. Left on their own stratagems, men would fight to death even for the slightest reasons. Therefore, man’s propensity to pander his cravings and indulgences makes him evil but these vices likewise impel men to consider peace as medium of self-preservation. A covenant of peace among the protagonists is fragile as any perceived breach rescinds the covenant and hostilities resumes. Hobbes then espoused the creation of State which extracts obedience from the citizenry as it exercises absolute power to maintain the peace but bona fide power resides in the citizenry who can confer power or withdraw recognition at will in case of abuse. On the other hand, Rousseau (1761) submits that men are inherently good but as men began to journey from solitude and sought out humanity, the relatively peaceful, morally balanced and virtuous man was corrupted by arts and sciences. Conversely, when men gained knowledge and social interactions progressed, they begun to conform to certain standards which would dictate their actions. The acquiescence of men therefore to the common consciousness gave rise to a social contract which guarantees freedom under the regime of law. Another view towards the attainment of perpetual peace was advocated by Immanuel Kant (1795), in his treatise, the Second Definitive Article of Perpetual Peace, it was proffered that â€Å"the law of nations shall be founded on a federation of free states† thus the objective of this paper is to probe into the two centuries old exposition, its influence in the creation of the United Nations (UN) and whether the Utopian concept envisage by Kant was fulfilled by the UN in its role towards the prevention of war. The utopian concept was born in the year 1515 when Thomas More drafted his book entitled Utopia published in the year 1562.

Biotransformation And Elimination Of Drugs Biology Essay

Biotransformation And Elimination Of Drugs Biology Essay Liver plays a significant role in the metabolism of a large number of drugs and toxins. Hepatic drug metabolism involves various processes, broadly classified as Phase 1 (functionalisation) and Phase 2 (conjugation). Glucuronidation catalysed by UDP-glucuronosyl transferase (UGTs) plays a key role in the Phase 2 metabolism of a large number of drugs as well as many endogenous substrates, like bilirubin, steroids etc., by increasing the hydrophilicity and clearance. UGTs are versatile enzymes, in terms of broad, yet overlapping substrate specificity, presence of numerous isoforms, genetic polymorphisms etc. Biological systems are recognised to be stereoselective in nature. A large number of drugs, nearly 50% of all marketed drugs exist as either single enantiomers or racemates. Therefore stereoselective behaviour of drugs plays an important role in drug action as well as disposition (Absorption, Distribution, Metabolism and Elimination). The aim of this project is to identify the enantio-selectivity of drugs towards glucuronidation by UGT and also to identify whether enantio-selectivity is linked to specific isoforms of UGT. Furthermore, predicting the enantiomeric behaviour of drugs may also aid in rationalising in-sillico modelling of drug metabolism and thereby predicting metabolism of new chemical entities (NCEs) 1. INTRODUCTION Biotransformation and elimination of drugs from the body involves several different metabolic routes. These metabolic pathways are broadly classified into Phase 1 (functionalisation) and Phase 2 (conjugation) drug metabolism. Phase 1 metabolic pathway involves transforming the drug into a more polar functionality, through various reactions like, oxidation, reduction, hydrolysis, isomerisation and so on depending on the chemical nature of the drug. These reactions are catalysed by enzymes such as: Cytochrome P450, NADPH-cytochrome P450 reductase, acetlycholineestrase etc. Product of Phase 1 drug metabolism may then act as a substrate for Phase 2 metabolism. This phase consists of conjugation of the drug substrate with endogenous ligands leading to increased polarity, hydrophilicity and thereby elimination of the drug from body through bile or urine. Conjugation reactions include glucuronidation, glycosidation, sulfation, methylation etc. These reactions are catalysed by UDP-Glucuronosyltransferase, UDP-Glycosyltransferase, Sulfotransferase, Methyltransferase respectively. Among these, glucuronidation is the most prevalent conjugation reaction in the body. [1] 2. GLUCURONIDATION Glucuronidation is the most common reaction in Phase 2 drug metabolism. This conjugation reaction which is catalysed by UDP- glucuronosyl transferase, forms about 35% of all drugs metabolised by conjugation. This is primarily due to the abundance in living systems of UDP-glucuronic acid, the co-factor for the reaction, as well as due to the pervasive nature of the enzyme, UDP-glucuronosyl transferases (UGTs). [1] [2] The process of glucuronidation involves: I. Formation of co-factor (UDP-glucuronic acid) II. Conjugation of UDP-glucuronic acid with substrate The formation of co-factor (UDP-glucuronic acid) This consists of a two step process: 1. Formation of UDP-glucose Glucose-1-phosphate is present in high concentrations in almost all cells of the body. The first stage of glucuronidation is related to glycogen synthesis through the common intermediate, UDP-glucose. The formation of UDP-glucose occurs by addition of a Uridine 5- diphosphate (UDP), a pyrophosphate nucleotide in cells, to a molecule of Glucose-1-phosphate. The reaction is catalysed by UDP-glucose pyrophosphorylase enzyme. [1] [3] 2. Dehydrogenation of UDP-glucose to UDP-glucuronic acid The above step is followed by dehydrogenation of UDP-glucose to UDP-glucuronic acid, catalysed by the enzyme UDP-glucose dehydrogenase, in the presence of NAD+ co-factor. [3] Conjugation of the substrate with UDP-glucuronic acid Conjugation reaction involves transfer of one ÃŽÂ ±-D-glucuronic acid moiety from the co-substrate UDP-glucuronic acid (UDPGA), which act as an energy rich intermediate, to form the glucuronide conjugate of the drug molecule. The reaction is catalysed by UDP-glucuronosyl transferase (UGT) enzyme. The reaction is found to be a bimolecular nucleophilic substitution (SN2), whereby the C1 carbon of glucuronic acid, which is in ÃŽÂ ±-configuration, during its reaction with the substrate inverts to form a ÃŽÂ ²-D-glucuronide. [3] [4]. The glucuronide formed is excreted via urine or bile, depending on the chemical nature and molecular weight of the conjugate. [1] [2] The entire reaction is summarised below: Figure: 1: Glucuronidation Pathway leading to formation of ether glucuronide. [3] 2.1 PHARMACOLOGICAL RELEVANCE Based on the functional group of the substrate molecule, the following types of glucuronide conjugates may be formed; [1] O-Glucuronide They are formed from Phenols, alcohols, carboxylic acids. O-gulcuronides are chiefly excreted in to bile and may undergo entero-hepatic circulation. Examples of drugs: Morphine, Chloramphenicol, Salicylic acid, Clofibrate. Figure: 2 O- Glucuronidation of Morphine [5] [6] UGT Enzyme UDPGA N-glucuronide They are formed by the reaction of UDP-glucuronic acid (UDPGA) with amines, amides etc. E.g. Sulfanilamide, Cyproheptidine, Dapsone S-Glucuronide Reaction of thiol groups with UDPGA in presence of UDP-gucuronosyl transferase results in S-glucuronides. E.g.Disulfiram, 2-Mercapto benzothiazole C-glucuronide It is an uncommon metabolic pathway that occurs due to the direct attachment of UDPGA to the carbon skeleton of drugs. E.g. Sulfinpyrazone [1] [3] 3. UDP-GLUCURONOSYL TRANSFERASE (UGT) ENZYMES 3.1 SITE UGT enzymes are present in human beings and most other mammals. The enzyme is located in many tissues of the body, mostly in liver but also in kidney, lungs, small intestine, spleen, adrenals and skin, to a lesser extend. Inside the cell, UGTs are bound to the membranes of endoplasmic reticulum. Most of the Phase 1 metabolic enzymes, including cytochrome P450s, are located in the endoplasmic reticulum. Therefore endoplasmic reticulum is regarded as an ideal site for UGT enzymes, as it facilitates glucuronide conjugation of Phase 1 substrates. [1] 3.2 STRUCTURAL ASPECTS UDP-glucuronosyl transferase enzyme does not contain a prosthetic group. The monomeric molecular weight of the enzyme if found to be between 50- 60 kilo Daltons. The protein sequence of the enzyme shows slight variations between each individual form. A full length crystal structure of UGTs is yet to be resolved, although crystal structure of the binding domain for UDP-glucuronic acid in human UGT2B7 has been published (by Miley et.al. 2007) [1] [2] 3.3 PHYSIOLOGICAL RELEVANCE In addition to being a major enzyme involved in Phase 2 drug metabolism, UGT enzymes play a number of other roles in the body. Many endogenous compounds such as bilirubin, steroid hormones (e.g. thyroxine, triiodothyronine) and catechols (derived from catecholamine metabolism), act as substrates for UGT enzymes. All these compounds are potentially hazardous if accumulated in the body. Deficiency of UGT enzyme results in hyperbilirubinaemia. Hereditary diseases like Gilberts syndrome and Cringler-Najjars syndrome are associated with genetic polymorphisms of UGT gene [7]. Apart from disposition of endogenous toxins, the enzyme also catalyses glucuronidation of various exogenous chemicals and helps in bodys defence against toxic principles [1] [8] 3.4 MULTIPLE FORMS Various forms of UDP-glucuronosyl transferase (UGT) enzymes have been identified with the help of studies based on purification, characterization of enzymes, molecular cloning, DNA sequencing etc. About 50 vertebrate UGTs have been identified among which 19 are found in humans. UGT enzymes are divided in to families and sub-families based on similarity of their amino acid sequences. Two enzymes are in the same family if the similarity of their amino acid sequences is more than 50% and will be grouped into the same subfamily is similarity is greater than 60%. [1] [2] Nomenclature Divergent evolution and sequence similarity forms the basis of nomenclature of UGT enzymes. Name of the enzyme consists of 4 parts: [1] Root Symbol The root symbol UGT stands for UDP- glucuronosyl transferase. Family It is denoted by Arabic number. E.g. 1, 2 etc Sub-family Designated by an upper-case alphabet Individual Form An Arabic numeral is used for unique identification of the individual form of the enzyme. E.g. UGT2B4, UGT1A6 [1] Mammalian UGTs are divided in to four families: UGT1, UGT2, UGT3 and UGT8. Among these, only UGT1 and UGT2 catalyses conjugation of glucuronide and hence are discussed further. UGT1A family of enzymes are found to contain 9 functional proteins and are coded for by a single gene complex located at chromosome 2q37. The genes coding for this enzyme have common exons 2-5 (region of gene which codes for the carboxyl terminus of the enzyme) and a variable exon 1. The first exon is responsible for coding the N-terminal domain of the protein and this explains why the enzymes are substrate specific in spite of have a common C-terminal [1] [2] UGT2 enzyme family, especially UGT2B plays a vital role in the metabolism of xenobiotics and endogenous ligands. Genes coding for UGT2 family enzymes are situated on chromosome 4q13. In the case of UGT2B sub family, protein sequences at the C-terminal, gives rise to the UDP-glucuronic acid binding domain as well as helps in anchoring of the protein to membrane of endoplasmic reticulum. UGT2A subfamily is less studied and do not play a significant role in systemic metabolism. UGT2A1 is present in olfactory epithelia and to a lesser extend in cells of brain and lungs. UGT2A2 in liver and small intestine, while UGT2A3 in small intestine, liver and adipose tissue. [2] Figure: 3: Shows the Phylogenetic tree of different UGT isoenzymes. %values indicate the homology between two groups or single isoenzymes at the amino-acid level. [9] 3.5 TISSUE SPECIFICITY The various forms of UGT enzymes show tissue specificity in man. Majority of these enzymes occur predominantly in the liver, (E.g. UGT 1A1, 1A4, 1A6, 2B7 etc) while some others are found in various extrahepatic sites. An example is UGT1A10, which is present in the cells of all areas of gastrointestinal tract and hence accounts for its wide range of substrate specificity, from phenol molecules to steroids. [1] 3.6 SUBSTRATE SPECIFICITY UGTs show a wide, yet overlapping, range of specificity towards drugs and endogenous ligands. For example, glucuronidation of bilirubin is preferred by UGT1A1 and that of morphine by UGT2B7. [1] [6] Table: 1: Showing Substrate Specificity of UGT enzyme isoforms. [6] Sl.No Substrate Max. Specific enzyme activity / pmol.min-1.mg protein-1 1A1 1A3 1A4 1A6 1A8 2A1 2B4 2B7 2B15 2B17 1. Phenols 1900 239 30 2400 5300 735 0.4 5 167 38 2. Amines 1 84 540 10600 1800 22 3 0 3 Opioids 0 130 0 0 0 73 0 3462 0 4. Carboxylic acids 0 121 0 170 68 0 2 0 5. Bilirubin 400 0 2 0 0 0 0 0 0 3.7 INTERINDIVIDUAL VARIATIONS Several genetic polymorphisms in UGTs may lead to variations between individuals in the ability to glucuronidate drugs and endogenous substrates. Mutations in genes coding for UGT1 enzyme family has been identified as the cause for hereditary hyperbilirubinaemia, characterized by jaundice due to high levels of unconjugated bilirubin in the body. Further, several genetic diseases- Gilberts syndrome and Cringler-Najjars syndrome, may occur due to mutations in genes coding for UGT1A1 isoform. [1] 4. ENZYME KINETICS: Study of enzyme kinetics helps to understand the catalytic mechanism of the enzyme; role played by the enzyme in metabolism as well the rate and activity of enzyme. Michaelis Menten equation is used to describe enzyme substrate interaction and is given by: [2] k1 k 2 E + S ES E + P k-1 Where E = Enzyme, S = Substrate, P = Product Michaelis Constant Km is given by: Km = (k 2 + k -1) / k 1 Michaelis Constant Km is an indicator of affinity of substrate for the enzyme as well as the rate of enzyme activity. The kinetics of drug metabolism can also be defined using Michaelis Menten equation and may be plotted in a graph of Rate of reaction (Velocity) vs. Concentration of Substrate. Although not all enzyme substrate reactions are best described by this equation, a typical model of Michaelis Menten plot is shown below: [2] Figure: 3 Michaelis Menten hyperbolic kinetic profile. [10] Here Vmax is the maximum velocity of enzyme action. Vmax / Km is an indicator of the catalytic efficiency of the enzyme. 5. STEREOISOMERISM Molecules having the same constitution of atoms and sequence of covalent bond, but differ in their three-dimensional arrangement of atoms in space are known as stereoisomers. Stereoisomers are classified in to geometrical (cis/trans) isomers, enantiomers and diastereoisomers. Stereoisomers that are mirror images of each other and hence are not superimpossible are called enantiomers. They differ from each other only by one chiral centre. Isomers that are not mirror images are diastereoisomers. They may contain more than one chiral centre. [2] [11] While geometrical and diastereoisomers are chemically different molecules, enantiomers have identical chemical and physical properties, except for the way in which they rotate plane polarized light. Enantiomers are of great significance in therapeutics as all biological systems represent a chiral environment. Hence drug action as well as disposition (absorption, distribution, metabolism and elimination) may differ between enantiomers. [2] 5.1 DRUGS AS ENANTIOMERS As discussed above, the pharmacokinetic and pharmacodynamic properties may vary for each individual enantiomer. In 1992, United States Food and Drug Administration (US FDA) published a policy for development of new stereoisomeric drugs. Approximately 50% of all marketed drugs are found to be racemates. Although many drugs can be safely administered as racemates, some others show better efficacy and fewer side effects when administered as a single enantiomer. For example, cardiac toxicity of the local anaesthetic agent, Levobupivacaine is chiefly associated with R-enantiomer. Further, some drugs undergo chiral inversion inside the body to the other enantiomer (e.g. Ibuprofen: Non-steroidal anti-inflammatory agent) and some others undergo racemisation after administration. This is of particular concern, especially if one of the enantiomers is toxic. Hence evaluating drugs for their stereochemistry is gaining importance. [2] [12] Some examples of some single enantiomeric drugs which have gained importance, compared to their racemate counterparts are given below, due to their improved pharmacodynamic- pharmacokinetic profiles: L-DOPA: The use of levo dopa instead of racemic dopa has resulted in reduction in dose and adverse effects (nausea, vomiting, anorexia, granulocytopenia) Figure: 4: Levodopa [13] ESOMEPRAZOLE: This proton-pump inhibitor, which is the S-enantiomer of Omeprazle has shown lower first pass effect and higher plasma half life compared to the R-enantiomer, thus maintaining the intra-gastric pH above 4 for a longer duration. S-enantiomer also showed reduction in variability of response between patients. Figure: 5: Esomeprazole [14] LEVOFLOXACIN: It is a Quinolone antibiotic. As there are slight differences in disposition between enantiomers of this drug, a single S-enantiomer is preferred. Figure: 6: Levofloxacin [15] R-SALBUTAMOL (LEVALBUTEROL): S-enantiomer has shown increased hyper responsiveness of airway, sensitivity to allergens and some decrease in bronchodilator potency. While R-Salbutamol gives significantly higher bronchodilator effect and lesser side effects Figure: 7: R-Salbutamol [16] R, R-METHYLPHENIDATE: This drug is found to be ten-fold more potent than its S-enantiomer when used to treat attention deficit hyperactivity. The presystemic metabolism and disposition of the drug is enantioselective in nature. Further, the R-enantiomer shows rapid onset of action and reduced adverse effects Figure: 8 R, R-Methylphenidate [17] 6. AIM OF THE PROJECT This project aims to determine the rates of glucuronidation of enantiomeric pairs, of a wide range of drugs, to identify differences in metabolism between enantiomers of a drug and also to find out whether enantioselectivity is related to a particular family of UDP-glucuronosyl transferase (UGT) enzyme. Experiment may be done by in-vitro incubations of human recombinant UGTs or human liver microsomes with the selected substrates, followed by analysis using liquid chromatography (HPLC) equipped with a mass spectrometer for detection. [14] Laboratory analysis of enantiomers is usually done using any one of the following two methods: Chiral Chromatography, which make use of a chiral column or chiral mobile phase to separate the enantiomers. Derivatisation, of the analyte using a chiral derivative followed by separation of the resulting diastereoisomers using standard, achiral chromatographic method. But in the case of separation of drug conjugates, the analytical process is relatively simple, as the glucuronide conjugates behave just like derivatised diastereomers and hence may be separated by conventional liquid chromatography. 7. FUTURE DIRECTIONS Many late stage failures in drug development process are due to inability to predict the pharmacokinetic properties of new chemical entities (NCE) before obtaining data from clinical trials. Hence in-vitro approaches like computational (in-sillico) modelling of drug metabolism is gaining acceptance in the recent times. Many approaches such as 2D-Quantitative Structure Metabolism Relationship (2D- QSMR), 3D-Quantitative Structure Metabolism Relationship (3D- QSMR), Pharmacophore Identification as well as Non-linear pattern recognition techniques are being studied to model drug metabolising enzymes. Although predictive models for metabolism of drugs by the Phase 1 metabolising enzyme, Cytochrome P450 are widely accepted, development of effective models for UDP-glucuronosyl transferases (UGTs) catalyzed Phase 2 metabolism has received much less attention. [15] Versatility of these group of metabolic enzymes, in terms of broad but overlapping substrate specificity, drug-drug interactions, genetic polymorphisms as well as presence of a large number of isoforms are some of the challenges facing the development of predictable models for UGTs. Furthermore, apart from a few catalytically relevant amino acids, the full X-ray crystal structure of UGT enzyme is not yet elucidated. [15] [18] Depending on the parameters being modelled (e.g. Km, Vmax etc.) a number of physico-chemical and molecular descriptors, such as molecular size, shape, lipophilicity, hydrogen bonding etc., are required to model molecular recognition of substrates and catalysis by UGTs. Apart from this, study of electronic nature of the nucleophile and pKa is also significant. Since chirality plays an important role in determining metabolic behaviour of drugs, design tools may be developed that address the issue of chirality. While 2D-descriptors will only predict molecular connectivity, 3-D models predicting the enantiomeric properties of enzyme-substrate interactions might significantly improve the future of drug development process. [16] [17] 8. CONCLUSION In conclusion, many biological systems represent a chiral environment. Therefore assessing the enantioselectivity of drug metabolising enzymes plays a significant role in predicting pharmacokinetic behaviour of drugs. The present project aims at identifying the enantio-selectivity of drugs in UDP-glucuronosyl transferase (UGT) metabolism, which is an important Phase 2 (conjugation) process of drug metabolism. Furthermore, knowing the enantiomeric behaviour may help in the development of 3D-Quantitative Structure Metabolism Relationship (3D-QSMR) models for predicting drug metabolism.

Personal Narrative: My Run Away Dog :: essays research papers

"Honey," my mom yelled to me one sunny afternoon, "Go out and feed Sugar." Sugar was our dog, a big, husky lap dog. I went to our kitchen, and got some food. Then I stepped outside, into the warm, fresh August air, looking for Sugar. I glanced to where I kept Sugar, and couldn't believe my eyes. Sugar was not there. I ran to the place where Sugar slept, I saw that the leash was elegantly coiled up. I knew that Sugar could not have run away. I thought that she must have chased a deer or another animal. Then a disturbing thought hit me, Sugar might have been abducted. As I tried to push that thought out of my mind, I thought that my mom could have put Sugar out in the garage. I went to the garage to check, but unfortunately Sugar wasn?t there. ?Mom,? I cried after a couple of seconds, ?Do you know where Sugar is?? ?Check the garage,? was all my mom replied. As soon as she said this, I knew that my beloved dog was gone. I had never been a dog lover. Matter of fact, I hated dogs, cats, and other animals. My Grandmother is a great animal lover, but she has a soft spot for dogs. One of her first dogs was an enormous, white, Sonoma named Coda. Coda enjoyed licking my face and then knocking me over. With Coda, my fear of animals started. For the next 11 years, I despised dogs. I refused to be near one. I cried, yelled, and trembled as if a monster was coming, anytime I thought a dog was near. It all changed with Sugar. The day Mom got Sugar was somewhat frightening for me. Obviously, I wanted nothing to do with the dog, I never planned to be in the same room as the dog, much less, take care of the dog. After all, Mom was supposed to take care of the dog. Slowly, I fell in love with her. She looked stern and loving. Her warm, brown eyes and pearly white smile only helped me fall in love with her. Not long after that I started to enjoy her company. Sugar was a loyal dog, she wanted to please everyone. When we went for a walk Sugar would come with us. We kept her on a leash, yet she never strayed from us.

Genetically organism Essay

Everyone in the world competes in his/her way to maintain standards through which he/she can feed themselves and their loved ones with food. It is the basic necessity every human being requires daily from birth until death. Today in the modern days different forms of many foods have evolved ranging from organic foods to genetically modified foods. Since the genetically modified foods have taken over the market they are known to be greater in resistance to pesticides and viruses, provide higher nutritional value and have a longer expiration date. Lastly, these foods are sold at cheaper prices in comparison to the organic foods. However, the potential risks of these foods are still being debated all over the world. The three reasons why the genetically engineered food should be labeled separately are the health hazards, religious – ethical concerns, and economic concerns involved. The reason why genetically modified foods should be labeled separately from organic foods are the health hazards involved in the production. The major health hazard involved in the non-labeling of genetic foods is that people all over the world have allergies to particular types of ingredients used in the manufacturing of the foods. The genetically modified foods include soybean, maize, chicory, potato, squash, oilseed rape (canola), pineapples, and strawberries. [1] Genetically modified foods can cause health diseases such as cancers, a newly discovered disease Morgellons, and other allergies. Without any specific labeling, the rate at which these diseases can occur doubles because people allergic to certain genes used in these foods, and there is no other way to determines these foods contain these genes or not. A recent article published in Lancet examined the effects of GM potatoes on the digestive tract in rats. This study claimed that there were appreciable differences in the intestines of rats fed GM potatoes and rats fed unmodified potatoes. Many children in the US and Europe have developed life-threatening allergies to peanuts and other foods. There is a possibility that introducing a gene into a plant may create a new allergen or cause an allergic reaction in susceptible individuals. (Raab, Grobe; 2009) [2] The quoted article above examines the differences between the Rats that fed on organic produce of potatoes and the ones’ that fed on the GM potatoes. The rats that fed on GM foods developed precancerous cell growth in their digestive tracts, inhibited developments of their brains, livers, and testicles. They also faced enlarged pancreas and intestines, and suffered immune system damage. The quote also demonstrates the possibility of the harmful side effects that GM foods can cause to future human generations. The possible solution to minimize these side effects is that Extensive testing of GM foods should be required to avoid the possibility of harm to consumers with food allergies. Labeling of GM foods and food products will acquire new importance. Before buying a certain GM product, people will be able to determine if they are allergic to its ingredients or not. Another reason why genetically modified foods should be labeled separately from organic foods is the religious – ethical concerns involved in the production. Different religious groups prohibit themselves from eating certain types of animal products. For example, Muslims do not eat any type of enzymes extracted from Pork. [3] Thus, using genes to create traces of genetic material from pork in GM foods and plants without labeling them could cause a stir in the Muslim sect. Another ethical concern is that Animal rights can harmfully be affected by excessive manufacturing of Genetic Foods. For example, Sheep given more powerful hormones could suffer problems relating to growth and problems in digestive systems. Without specific labeling on foods, animals being tested cannot be identified, and this could lead to further malpractices by large corporations. Ethical and religious concerns include the belief that the technology involved is unnatural, and preoccupations regarding the consumption of religiously forbidden ingredients from certain animals. These new technologies, it is argued, violate religious freedom by placing a burden on those who follow strict religious dietary laws. The government is not constitutionally obligated to make accommodations in favor of religious groups that are incidentally affected by neutral rules. Accordingly, the neutral decision of not labeling genetically modified foods met this constitutional standard and was not subjected to a more rigorous constitutional adjudication test. (Lietz, 2000) [4]. The quoted excerpt above from the Harvard law review emphasizes the importance of the labeling on genetically modified foods because without explanation of how these foods are manufactured, it is unethical and unfavorable to religious and cultural groups that restrict themselves from practices in consumption of certain ingredients included in these foods. In other words, the use of these technologies is harming the religion freedom of people. [4] The government of United States protects the non-labeling by not passing laws that require rigorous tests on GM foods because it is believed that there are already laws that protect religious groups. The third reason why genetically modified foods should be labeled separately is the economic concerns involved in the production. The main economic concern is that the world food market could be monopolized by large multinational corporations that control the production and distribution of genetically manufactured seeds. If this happens, they would be able manipulate governments to pass laws that don’t require companies to label their GM foods. [5] Monopolization will increase prices of seeds and eliminate small level farming. GMOs are the products of large corporations and considered intellectual property. Thus, they are protected by patents and copyrights. This means that if farmers want to use genetically modified crops, they must buy it from a corporation. If the world relies solely on GMOs, this means that these corporations will control the world’s food supply, leading to the monopolization of food. The use of GMOs is driving out the need for small farmers. These small farmers are forced to switch to GMOs in order to compete with other GMO farmers, but in the process, they are subjugated to the control of the corporation that produced the GMOs. (Barton, 2002) [6] The above passage was taken from a research about non labeling consequences published in the Harvard Law Review that extrapolates the consequences if the food industry is monopolized. It explains that if this happens, the patents and copyrights will increase prices of foods massively and abolish the system of low scale farming. Each and every farmer will need to rely on large corporations to grow crops, and GM foods will be seasonal that means in every season the seeds will expire and costs of storage and harvesting will sky rocket. All in all, the corporations will completely take over the food sourcing misleading people in what they produce for the sole purpose of profits. Thus, it will be considered legal and ethical. Regulations should be passed by governments all around the world that strictly insist on the labeling of genetically manufactured foods. Without labeling on the Genetically Modified Foods the health hazards, religious – ethical concerns, and economical concerns will increase over time. Therefore, instead of looking at the future from the eyes of the economic benefit, the world should look at the consequences this evolution could lead. Works Cited Page 1. â€Å"Genetically Modified Food. † Crowdsourcing Questions & Answers. N. p. , n. d. Web. 18 May 2011. 2. [6]Barton. â€Å"GMF Labeling Issues. † Harvard Law Review, Winter 2002. Web. 18 May 2011. . 3. Daneil, â€Å"Genetically Modified Foods | Better Health Channel. † Home | Better Health Channel. Deakin University. Web. 18 May 2011. . 4. [2]Grobe, and Raab. â€Å"Genetically Modified Foods | Better Health Channel. † Home | Better Health Channel. Deakin University. Web. 18 May 2011. . 5. [4] Lietz, supra note 11, at 416; Julie Teel, Regulating Genetically Modified Products and Processes: An Overview of Approaches, 8 N. Y. U. ENVTL. L. J. 649, 660-61 (2000) 6. â€Å"Genetically Modified Food. † Crowdsourcing Questions & Answers. N. p. , n. d. Web. 18 May 2011. .

Mental Health Field essays

Mental Health Field essays For many years, people who had mental health issues were locked away in institutions and spent their lives within the confines of that setting. There was little hope of ever having a normal life let alone a productive one and family members accepted the fact that their family member was substandard. Today that belief has been has been destroyed and millions of people with mental illness are contributing positively to society while enjoying their life. The changes that have taken place within the field have allowed professionals to diagnose mental illness and treat many of them on an outpatient basis. Just as alcoholism is considered a disease(Davis, 1998), so is mental illness. The key to success in this endeavor is careful, accurate diagnosis and consistent treatment plans. The agency that will be included as the focus to the case study will be Health and Education Services Inc. This is an agency that provides a wide range of community based mental health and substance abuse assistance. Its location is the Greater North Shore area of Massachusetts as well as the Lower Merrimack Valley area. I am a student intern from Boston University. My primary intern responsibilities include the provision of individual and family therapy sessions. My role in relations to the client is that she was assigned to me to interview and provide a preliminary diagnosis based on her narrative and her symptoms. The client is a female who is currently 48 years old. She is heterosexual though she did participate in a homosexual relationship during her college years. She has three children who are 10, 12, and 15 years old and she is married. She is white, does not identify with any particular culture at this time and is in the upper middle class income bracket. She and her family have been Catholic her entire life though her husband is Protestant. Until recently the client worked full time in the insurance industry as a licensed insurance agent...

Free Essays on Organization Theory And Design

Organization Theory and Design What is an "Organization†? Basically, an organization is a group of people intentionally organized to accomplish an overall, common goal or set of goals. Business organizations can range in size from two people to tens of thousands. Members of the organization often have some image in their minds about how the organization should be working, how it should appear when things are going well. An organization operates according to an overall purpose, or mission. Values All organizations operate according to overall values, or priorities in the nature of how they carry out their activities. These values are the personality, or culture, of the organization. Strategic Goals Organizations members often work to achieve several overall accomplishments, or goals, as they work toward their mission. Strategies Organizations usually follow several overall general approaches to reach their goals. Organization as a System It helps to think of organizations is systems. Simply put, a system is an organized collection of parts that are highly integrated in order to accomplish an overall goal. The system has various inputs which are processed to produce certain outputs that together, accomplish the overall goal desired by the organization. There is ongoing feedback among these various parts to ensure they remain aligned to accomplish the overall goal of the organization. There are several classes of systems, ranging from very simple frameworks all the way to social systems, which are the most complex. Organizations are, of course, social systems. Systems have inputs, processes, outputs and outcomes. To explain, inputs to the system include resources such as raw materials, money, technologies and people. These inputs go through a process where they're aligned, moved along and carefully coordinated, ultimately to achieve the goals set for the system. Outputs are tangible results produced b... Free Essays on Organization Theory And Design Free Essays on Organization Theory And Design Organization Theory and Design What is an "Organization†? Basically, an organization is a group of people intentionally organized to accomplish an overall, common goal or set of goals. Business organizations can range in size from two people to tens of thousands. Members of the organization often have some image in their minds about how the organization should be working, how it should appear when things are going well. An organization operates according to an overall purpose, or mission. Values All organizations operate according to overall values, or priorities in the nature of how they carry out their activities. These values are the personality, or culture, of the organization. Strategic Goals Organizations members often work to achieve several overall accomplishments, or goals, as they work toward their mission. Strategies Organizations usually follow several overall general approaches to reach their goals. Organization as a System It helps to think of organizations is systems. Simply put, a system is an organized collection of parts that are highly integrated in order to accomplish an overall goal. The system has various inputs which are processed to produce certain outputs that together, accomplish the overall goal desired by the organization. There is ongoing feedback among these various parts to ensure they remain aligned to accomplish the overall goal of the organization. There are several classes of systems, ranging from very simple frameworks all the way to social systems, which are the most complex. Organizations are, of course, social systems. Systems have inputs, processes, outputs and outcomes. To explain, inputs to the system include resources such as raw materials, money, technologies and people. These inputs go through a process where they're aligned, moved along and carefully coordinated, ultimately to achieve the goals set for the system. Outputs are tangible results produced b...

Science Essay Example | Topics and Well Written Essays - 1750 words

Science - Essay Example Once in the sea, they typically stay there around 4 years before returning up the rivers they came from to spawn. 3. Wildebeast – nomadic migration, performed by wildebeasts as a function of seeking out new grazing and better sources of drinking water; this typically is a relatively short migratory route. Occurs on a seasonal basis and is dependent upon the quality of grass and the availability of water within the affected regions. Other species such as the impala accompany the wildebeasts in this mass migration pattern. 4. Humback Whales – seasonal migration. Humpback whales spend the winter months in warmer climates while during the summers they hunt for krill and small fish in polar climates. Performed on a seasonal/yearly basis; this typically is a relatively long migratory route. Humpback whales are known not to eat while in the warmer waters closer to the equator during the winter months. 5. Dall Sheep – altitudinal migration. Dall sheep typically spend the winter months in lower elevations where they can dig through the snow to find patches of existing grass. However, once the summer months appear, they climb back up into higher elevations; both for protection and due to the fact that food is also abundantly available there; this typically is a relatively short migratory route. ... The average arctic tern lives about 20 years and during this time can cover over 1.5 million miles! 7. Golden Eagles-partial migration. The golden eagles ultimately a bird that exhibits a partial migration in the fact that not each and every one of the species leaves it habitat as part of the migration. The migration itself is a medium to long migratory route that has as its purpose breeding in the sub Arctic regions of Alaska and Canada; returning to warmer climates once the summer is at an end. The golden eagle is the emblem of perhaps more countries than any other animal. It is officially the emblem of Albania, Kazakhstan, Mexico, Austria, and Germany. 8. Sea Turtles (pick any one of the 8 species) – reproductive migration. Green sea turtles travel vast distances from their feeding grounds to the beaches that they will ultimately deposit their eggs upon. Currently, green sea turtles, like the other sea turtles, are endangered due to human activity and the overall lack of en vironmental conditions that they can lay their eggs unadulterated. 9. Locusts – is a type of animal that exhibits an interruptive migration. These migrations are incumbent upon the region that the locust is in and the availability of the food source within this region. The distances traveled are usually not as far as many of the other species that have been discussed. Locust migration has been known to cause vast amounts of damage and ultimately the deaths of tens of thousands of people throughout history as the result of famine caused by the destruction in crops and grassland that they can effect. 10. Great Gray Owls- are indicative of a nomadic migration. The nomadic patterns of the great grey owl are little understood;

Hofstede's dimension in Korea Essay Example | Topics and Well Written Essays - 1750 words

Hofstede's dimension in Korea - Essay Example Korean is the main and highly used language of the country. The language is used together with Korean and Hangul alphabet. Korea is an export driven country, focusing on the export of electronics and automobile goods and services. Figure 1: Hofstede's Five dimension in Korea There are five dimensions of Korea’s Hofstede, such as Power Distance, Masculinity vs. Femininity, Individualism, Long Term Orientation and Uncertainty Avoidance. If the essay explores the culture of Korea through the Hofstede’s Five Dimension Model lenses, then an effective overview of the deep drive of the country’s culture can be attained relative to the world’s culture. Power Distance This particular dimension deals with the fact that each and every individual in society cannot be equal. Especially, it expresses the cultural attitude of people towards the inequalities among the people in a society. Power distance can be defined as the extent to which limited powerful individuals of an organization or an institution within a society accept and expect that power is not equally distributed. The power distance score of Korea is 60. The people within the societies and communities of Korea always maintain and give value to the people who are in the top of hierarchy. Therefore, regulations and norms take huge account as the people of Korea accept a hierarchical order. Each and every individual within the society has a place that does not need further justification. Hierarchy in an institution or an organization is seen as reflecting intrinsic inequalities. In addition to this, people within the organization follow centralized structure or order. Boss or top management in an organization decides what to do. The subordinates always expected to do what their top management wants in the organization. The employees or subordinates do not raise their voice against the opinion of the boss or the top management. In a single word, people in Korean organizations give high res pect to the authority and the decision making process in business management organization is totally centralized. Individualism The basic issue addressed by this particular dimension is the degree of interdependence that is maintained by a society among its each and every member. This dimension has to deal with whether the self image of people within a society is defined in terms of â€Å"WE† or â€Å"I†. There are two types of dimensions of the society, such as individualist society and collectivist society. According to the concept of individualistic society, people only can look after their direct family and themselves. On the other hand, people of collectivist society can look after or take care of the people who are belonging to the group and exchange loyalty. In terms of individualism, Korea has a score of 18. It means that the people of Korea follow collectivistic social structure and values. People of Korea have close long-term commitment to each and every memb er of the group (Greet-Hofstede, 2012, p.1). Loyalty in the collectivist culture over-rides several societal rules and regulations. In addition to this, this collectivist culture is considered as paramount. A particular society fosters strong relationship where each and every member within a group takes significant responsibility for fellow group members. Koreans always like to follow the collective decision of family (Lee and Boster, 1992, pp. 11-13). The