Metronidazole Retention Enema Experiment and Study

Metronidazole Retention Enema Experiment and Study 1. Introduction 1.1. Rectal dosage forms   The most common and usually most convenient route for administering conventional pharmaceutical dosage forms is orally, where the drug dissolves in the gastric and/or intestinal fluids and is absorbed to reach the site of action. Dissolution and absorption of the drug from the gastro-intestinal environment depends upon many factors e.g. the physico-chemical properties of the drug, enzymes, metabolism, pH of the fluids etc. and these are considered as major drawback when localized drug delivery in the colon is required. Colonic drug delivery system offers advantages over oral dosage forms in improving the efficacy and achieving high concentrations with minimal side-effects1. 1.1.1. Advantages and limitations of rectal dosage forms Advantages: Safe and painless form of administration. Drugs liable to degradation in the gastrointestinal tract can be administration. First pass elimination (drugs liable to degrade before reaching the site of action) of high clearance drugs is partially owing to bypassing the liver. Even larger doses can be administered. Drugs can be administered rectally in the long term care of geriatric and terminally ill patients. Administration of rectal suppositories or capsules is a simple procedure that can be under taken even by unskilled healthcare personnel and patients. Limitations: Patients acceptability and compliance is poor, especially for long term therapy. Suppositories can leak. Drug absorption from suppositories is slow in comparison to oral or intravenous administration. 1.2. Different rectal drug formulations Many formulations are developed for rectal use and these include suppositories (in the form of solid dose suspensions and emulsions), irrigations, gelatine capsules (used for non-steroidal anti-inflammatory drugs, encapsulated in a soft gelatine capsules as a reverse micellar solution for rectal application) 2, and enemas. Enemas are aqueous solutions are suspensions intended for instillation into the rectal region for evacuation of bowel and to treat microbial infections. Enemas are of two types macro enemas (100ml or more) and micro enemas ( 1.3. Anatomy of Rectum and lower colon The terminal 15- 19cm portion of the large intestine is rectum; it has a circumference of 15-35cm. The rectal pH is around 7-8. The absorptive area of rectum is less when compared to that of small bowel because the rectal surface area is 200-400cm2 compared to that 200m2 of small bowel, due to very much shorter surface area per unit length 4. Generally medications for rectal delivery are better absorbed as weakly alkaline solutions. For rapid absorption of the medication aqueous solutions are preferable rather than suppositories or suspensions. Rectal absorption takes place by active absorption and for maximum retention without any rectal urgency to vacate bowels small volume of the fluid is recommended5.The diagram with a section of colon is shown below in fig-1. 1.3.1. Physiological considerations of colon 1.3.1a. Intestinal colonic micro flora The human colonic atmosphere supports over 400 distinct species of bacterium with a population of 1011 to 1012 CFU/ml with mostly Eubacterium, Bacteriodes etc6. The enzymes produced by these bacterium has wide spectrum of action, that being hydrolytic and reductive in nature, these enzymes are actively involved in many processes, such as steroidal transformation, protein and carbohydrate fermentation, and destruction of mutagenic metabolism. Nitroreductase, azoreductases, and N-oxide and sulfoxide reductases are the most extensive reductive enzymes produced by the intestinal flora7. 1.3.1b. Colonic motility Under the normal physiological conditions the colonic motility is described as irregular alternation of inactive, non-propagative, segmental contractions and infrequent propagative contractions that can be further classified into high amplitude contractions (> 100 mmHg) and low amplitude contractions ( 1.3.1c. Ascending colonic volume The ascending colonic volume was found to be 170 ±40 ml as per the studies conducted on healthy subjects using single photon emission computed tomography11. Metronidazole Metronidazole is a nitro-imidazole bactericidal agent primarily used against obligate anaerobic bacteria including Bacteroides, Clostridium spp., and certain protozoal parasites like Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia, Blastocysistis hominis, Balantidium coli and also some of the facultative anaerobes Gardnerella vaginalis and Helicobacter pylori16. Gram negative anaerobes like bacteroides and fusobacterium species and the gram positive anaerobes like Peptosteptococci and clostridium species typically test sensitive to metronidazole. It is particularly used against Helicobacter pylori associated to duodenal ulcers and gastritis. Metronidazole is also used against anaerobic bowel flora for the prophylaxis and for the treatment of Crohns disease where patients might develop complications of infections in bowel12. Metronidazole supports the overgrowth of aerobic microbial flora of the large intestine by reducing the number of anaerobic micro-organisms with acceptable profile of adverse effects13. 1.4.1. Anti microbial action of Metronidazole Metronidazole as anti microbial agent was first introduced in 1959 for the treatment of Trichomonas vaginalis infections, and used subsequently for invasive giardiasis and amebiasis. Metronidazole is highly effective and show rapid onset of action against anaerobic infections. Antimicrobial action of Metronidazole is mainly due to the toxic intermediates which are produced during the reduction of the compound14. Interaction of these intermediates with deoxyribonucleic acid in protozoan inhibits nucleic acid synthesis and there by exerts antimicrobial effects15. Mechanism of action of Metronidazole is shown in the fig-2. 1.4.2. Physico-chemical properties Chemically metronidazole is 2-methyl-5-nitroimidazole-1-ethanol or 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole. Its formula is C4H9N3O and its chemical formula is in the fig-3. Metronidazole is white to pale yellow coloured, odourless, crystalline powder. It is sparingly soluble in water, alcohol and slightly soluble in ether16.It is generally stable in aqueous solutions of pH 2.0-7.017. 1.4.3. Metabolism of Metronidazole Metronidazole is metabolised in the liver into two metabolites. These metabolites include 2-hydroxy-methyl-5-nitroimdazole-1-acetic acid (HM) and 2-methyl-1-2-nitroimidazole-1-acetic acid (MAA). Hydroxy metronidazole is pharmacologically active with antimicrobial action and its potency is 30% to that of metronidazole and the acetic acid metabolite of metronidazole is pharmacologically inactive but its activity is noticed in patients with renal dysfunction, small amount of metronidazole is oxidised to acetamide18. The metabolization pathway and chemical formulas can be seen in the figure 419. Study objective Metronidazole is commercially available in the form Tablets, Suppositories, Gels, and suspensions20. But metronidazole in the form of enema is not available commercially. Olumide F et al. 1976, described metronidazole in the form of enema (2gm. of metronidazole in 200ml of normal saline) for management of severe intestinal amoebiasis21. No extensive pharmaceutical data about the formulation and stability of the metronidazole enema is available at this moment. Hence, the development of a metronidazole enema was undertaken. The present objective of the study is to formulate Metronidazole retention enema in a suitable aqueous media using carbopol and tragacanth as suspending and viscosifying agents. Chemical stability of the formulated enema is analysed with an analytical method: high performance liquid chromatography (HPLC) and viscosity of the formulation is checked by Brook field viscometer. Aim To formulate a metronidazole retention enema and analyze physico-chemically. 2.0. Materials and Method 2.1. Chemicals Metronidazole (98.9% pure) used is a gift sample from Thrope Laboratories (India) Ltd, Mumbai. 2-methyl-5-nitro-imidazole is used as a standard impurity. Cardopol (35% w/v), tragacanth, methyl paraben, propyl paraben, tris buffer were purchased from Aldrich. The methanol and acetonitrile used were of high performance liquid chromatography (HPLC) grade along with distilled water; other materials namely potassium hydrogen phthalate (KHP), sodium hydroxide (NaOH), sodium chloride (NaCl), potassium di-hydrogen phosphate (KH2PO4), acetic acid (CH3C OOH), sodium acetate (CH3COONa), sodium citrate (Na3C6H5O7) and 0.1M hydrochloric acid (HCl) were of analytical quality. 2.2. Instrumentation High Performance Liquid Chromatography apparatus and conditions The liquid chromatography used was a Varian Prostar HPLC system (Model 410), equipped with an auto sampler serial mode system with a 20 µl loop. Detection is accomplished with a UV-Visible detector. Integration and the system parameters were controlled by Galaxy software running on a PC. Viscometer The viscometer used was Brook field viscometer (Model LVDV II + PRO); displays temperature (C or F), viscosity, % scales, shear rate, shear stress, speed, % torque, and spindle. Technical specifications include 0.01 to 200/rpm, viscosity range of 1 6Million cP, with 4 supplied spindles. 2.3. Preparation of buffer solutions22, 23 2.3.1. Preparation of Phthalate buffer Phthalate buffer was prepared by dissolving 20.42g of potassium hydrogen phthalate in 1000ml of water (0.1M). The pH was adjusted with 0.1M hydrochloric acid, 0.1M sodium hydroxide. Preparation of different pH ranges of phthalate buffer is shown in the table-1: 2.3.4. Preparation of tris buffer Tris buffer was prepared by dissolving 12.11g of tris (hydroxymethyl aminomethane) in 1000ml of water (0.1M). The pH of the buffer was adjusted with 0.1M hydrochloric acid. Preparation of different ph ranges of tris buffer is shown in the table-4. 2.4. Pre-formulation studies 2.4.1. Pre-formulation solubility studies The main problem associated with developing any of the solution formulation of a compound is its aqueous solubility. Metronidazole is poorly aqueous soluble drug24. For enhancing the poorly aqueous solubility of drug there are several alternatives and these include pH manipulation, co-solvency, surfactants, chelating agents and emulsion formation25. In the present experiment the solubility of metronidazole, 2-methyl-5-nitro-imidazole in water, buffered solutions of phosphate, acetate and tris in various pH ranges were determined by adding a weighed amount of drug to the solvent by stirring with a glass rod at 20 ±2oC. Excess amount of solvent was added until the drug completely dissolved in that solvent. 2.5. Stability Indicating HPLC studies The stability studies are particularly demonstrated to analyse the quality, concentration and purity of the pharmaceutical dosage form. For demonstrating stability of pharmaceutical dosage forms HPLC is prominently used. Szepesi et al.26 described some special stability-indicating requirements for HPLC and these include: 2.5.1. Stability- indicating assay The peaks of the drug substance and its decomposition product should not elute at same time; any decrease in the active drug concentration should be detected by the method. Stability-indicating purity: The resolutions between the active component peak and the adjacent peak should be higher to identify any decomposition of the active component similar in its structure formed during different storage conditions. 2.5.3. The main impurity peak(s) should be separated from degraded product peak(s) of different chemical structure, so that evaluation of purity and assay are carried out together. 2.5.4. The peaks of the degraded products or secondary degraded products formed by the decomposition of by-product can also be separated from other peaks. 2.6. Stability-indicating purity: Pre-formulation stability studies were conducted to determine the stability of metronidazole in water and various buffered pH ranges using reverse phase high performance liquid chromatography (HPLC). All the solutions were stored at room temperature 20 ±2oC for approximately 20 days in glass beakers and then analysed for stability. Results and Discussion Solubility study of Metronidazole The aqueous solubility and pH solubility profiles for Metronidazole and 2-methyl-5-nitro-imidazole are shown in Table-7, 8, 9. Overall solubility of Metronidazole and 2-methyl-5-nitro-imidazole is determined at all pH values. Both Metronidazole and 2-methyl-5-nitro-imidazole exhibited high solubility at a pH range à ¢Ã¢â‚¬ °Ã‚ ¥4. For example, at room temperature the aqueous solubility of Metronidazole was 100mg/50ml, respectively. Metronidazole, being a weak base, appears to dissolve maximally at a pH à ¢Ã¢â‚¬ °Ã‚ ¥ 4.0. High performance liquid chromatography method development The new method developed in this present study was very closely related to that of British Pharmacopoeia. British pharmacopoeia specifies reverse phase chromatography carried out using stainless steel column (20cmÃÆ'-4.6 mm) packed with octadecylsilyl silica gel of particle size 10 µm (spherisorb ODS), using a mixture of 30 volumes of methanol and 70 volumes of 0.01M potassium di-hydrogen orthophosphate as the mobile phase with a flow rate of 1ml per minute and a detection wavelength of 315nm. To establish a new stability indicating chromatographic nature of the HPLC method, we have changed the column to 5 µm C18 (150 ÃÆ'- 4.60 mm i.d., Phenomenex) stainless steel column, packed with Sphereclone octadecylsilane (ODS) and an (eluent) mobile phase to carry out the stability analysis in the solution at ambient room temperature with a flow rate of 1.0ml/min and at a detection wave length of 325nm. Each chromatographic run required about 10 minutes and the elution time obtained for metronidazole and the standard impurity were different for different mobile phases. For methanol: KH2PO4 in the volume of 30:70v/v retention times of drug and the impurity was1.89min and 2.00min, for methanol: KH2PO4 in the volume of 80:20v/v retention times were very narrow, like wise all the mobile phase in different proportion showed a little retention time gap between drug and impurity. When acetonitrile and sodium citrate was used in the volumes of 10:90 v/v retention time gap of 2min was achieved. Elution of Metronidazole and 2-methyl-5-nitro-imidazole was achieved with a retention time of 3.19Min and 4.99Min respectively. Stability indicating solubility studies Metronidazole was observed to be relatively stable in water and buffer pH conditions. The results obtained in our stability indicating solubility study showed an agreement with solubility and studies conducted by Yunqi et al., 200527. Test for clarity and sedimentation Sedimentation was observed when the water (400C) solubilized metronidazole is stored for 20 days, this might be due to the super saturation of the solution during solubilization of the drug at high temperature. Rest of the solutions were free from particles and sedimentation when observed against a black and white back ground. Solubility studies of metronidazole and its standard impurity (2-methyl-5-nitro-imidazole), indicates solubility of metronidazole was more in aqueous solvents including various buffered pH systems. These solubility profiles help to understand the chemical nature (polarity) of drug and the impurity. Solubility of metronidazole was observed to be high in acetate buffer (100mg/30ml) than any other buffer solutions. Taking the solubility profiles and colonic pH (5.5-7) into consideration, acetate buffer of pH 6 was used to formulate enema 4. Formulation of enema Our aim to formulate retention enemas is based on the studies conducted by Nyman-Pantelidis et al., 1994. There study proved low viscous enemas superiority over high viscous enemas in retention and colonic spread28. 4.1. Preparation of metronidazole- tragacanth enema Metronidazole-tragacanth enema was prepared by simple titration technique using motor and pestle. Metronidazole retention enema prepared was an aqueous formulation with a viscosity of 6.00 cPas, containing metronidazole in a buffered pH. The formulation includes tragacanth as suspending and viscocifying agent. Methyl paraben as a preservative and NaOH (0.1M) was used to maintain the pH of the formulation. Metrinidazole was dissolved in buffered solution and then added to tragacanth gum, while triturating methyl paraben was added and pH of the final formulation is maintained at pH-6 using NaOH. The composition of the enema prepared in the study contains 1g of Metronidazole as shown in table 9. Preparation of metronidazole- carbopol enema For the treatment of anaerobic infection of colon we have formulated Metronidazole as enema using carbopol, a high molecular weight polymer of acrylic acid cross linked to allyl sucrose. Carbopol increases the viscosity of the enema and so help in retaining in the colon for maximum efficacy of metronidazole29. Metronidazole was dissolved in buffered solution 1.0g/300ml. This solution was added under constant stirring to carbopol. Methyl paraben was dissolved in water and under  constant stirring this mixture was added to the suspension. The pH of the final formulation is maintained at 6 by the addition of NaOH. The composition of the enema formulated is shown below in the table-10. Storage of enemas for stability and viscosity studies The formulated enemas were filled in 100 ml glass beakers and stored for 2 days at refrigerated conditions 40C, room temperature 200C and at accelerated conditions 400C and analysed for stability and viscosity. Stability studies of the formulated enemas Both the enemas were found to be stable for 3 days at various temperatures (2-100C, 25 ±20C, 40 ±20C). The chromatograms show no peak of degraded metronidazole. Chromatograms of both the enemas is shown in the fig-9, fig-10. Viscosities of the formulated enemas The viscosity measurements for both rectal enemas were performed by Brooks field viscometer, using spindle 62 revolving at 22 rpm. Both the rectal enemas were prepared with a viscosity of 6.0 cP using tragacanth and carbopol. The viscosities of both rectal enemas were then analysed after storage for 2 days at 2-100C, 20 ±20C, and 40 ±20C respectively and there results are shown in table-10. There was a little variation of viscosities in the formulated enemas after their storage at various temperatures, and this variation is seen especially in enemas stored at accelerated temperature (40 ±20C) for 3 day. Because viscosity is inversely related to temperature, as temperature increases viscosity decreases. Test for clarity and sedimentation Both the formulated enemas were clear without any particles when observed against a black and white background. When the enemas are further analysed, phase separation was observed in the enema formulated using tragacanth and stored at 2-100C, 20 ±20C, and 40 ±20C. Conclusion The solubility studies results indicate that metronidazole showed a good solubility at various pH levels (à ¢Ã¢â‚¬ °Ã‚ ¥4.0). Maximum solubility of metronidazole was shown in acetate buffer of pH 6 (100mg/30ml). The stability studies indicate that metronidazole was stable at all the pH ranges without any degradation. The Metronidazole enema formulated using tragacanth and carbopol was chemically stable with no degradation when stored for a period of 3 days at 2 ±100C, 20 ±20C, 40 ±20C respectively. And there is no remarkable effect on the viscosities and pH of the enemas when stored at these temperatures. Future work In the present study stability studies were conducted for only 3 days, the results would be more appropriate if the stability studies of the formulated enema were carried for some more days. The new methodology developed for demonstrating High Performance Liquid Chromatography indicating stability studies using acetinitrile and sodium citrate in the volumes of 10:90v/v should be validated.

Theories for Determinants of Emotional States

Theories for Determinants of Emotional States INTRODUCTION An individual fast asleep at night is suddenly awakened by a loud noise coming from somewhere within the house. He immediately becomes physiological agitated: the body begins to sweat, the heart beats faster, and hands begin to tremble. Does he experience fear, or perhaps another emotion such as anger, or even happiness? Schachter and Singer (1962) proposed a two-factor model that specifies the conditions under which people will experience one particular emotion or another when faced with an emotionally exciting event, such as impending danger. This model states that a person’s emotional response to danger is dependent on the interaction between their physiological arousal and cognitive appraisal of the situation (e.g. whether it is dangerous or not). Ordinarily, danger would trigger biological changes, such as increased heart rate, trembling, crying, and perspiration. These physiological changes in turn determine both the intensity (i.e. level) and quality (i.e. type) of our emotional response. However, the particular type of emotion experienced depends on how we cognitively perceive or ‘read’ the situation. For example, we experience fear if the situation is appraised as dangerous or life threatening, such as an approaching lion, or an imminent category 4 tornado. SUPPORTING ARGUMENTS In the scenario described at the beginning of this essay, the individual woken suddenly by a noise, and physiologically aroused will experience emotional arousal. The intensity of his emotions will be a direct function of his level of physiological arousal. So, for example, we will experience very strong emotions if his heart is beating extremely fast and he is sweating profusely. However, the type of emotion experienced will depend on how is appraises the situation. He will experience fear if for example he believes a burglar has broken into the house and is armed and dangerous. By contrast he may experience anger if he knows that his excitable pet dog probably knocked something down while chasing his cat around the house. Or he may experience happiness if he knows the noise was caused by his loving fiancà ©e who has just returned from the airport after long holiday her parents, and perhaps tripped over something when entering the darkened house. Schachter and Singers (1962) two- f actor model is actually a redevelopment of the James-Lange theory. James Lange originally proposed that emotional experience is contingent on the physiological changes induced by an event. Thus, for example, imminent natural disaster for example will first trigger an emotional response in an individual, for example anxiety. Because they feel anxious, the person will experience physiological changes consistent with this emotion, for example increased heart rate, and perspiration. ALTERNATIVE EXPLANATIONS Whether physiological changes precede emotional arousal, or vice versa, is a controversial subject. Psychologist Walter Cannon (1927/1987) proposed an model, known as the Cannon-Bard theory, which contends that physiological arousal is in fact contingent on emotional experience. It can be argued that human beings are not very good at monitoring physiological changes in their body. For example, subtle changes in heart rate, or mild increases in perspiration may go undetected (Chwalisz et al, 1988). If so, then people may simply fail to experience any emotion, regardless of their appraisals of the situation. Yet, people generally react instantaneously to danger, exhibiting signs of emotional disturbance, without necessarily being aware of an increase in heart rate or other physiological changes (Zillman, 1978, 1988). The emotional experience isn’t determined by our detection of biological changes, but rather may be contingent on how we appraisal of the stimulus, and our memory ( i.e. prior experience) and general knowledge about the stimulus. For example, an individual who suddenly comes face to face with a lion will correctly judge that this animal can kill and therefore his life is under threat. This appraisal in turn will produce fear. Similarly, the person may remember that he was viscously attacked the last time he met a lion, and/or more probably be aware of the fact that big carnivorous cats kill people. Another problem with the Schachter and Singer model is their failure to account for how people cope with threat or danger. They assume that physiological arousal elicits emotional arousal, so that they relationship between the two variables is always positive. However, theories on coping propose that two people confronted with the same stressful event may experience marked different intensities of anxiety. More specifically Janis and Mann’s (1977) conflict-theory argued that the level of intensity experienced varies depending on how people deal with stress generated by uncertainty what to do. Complacency results in little or no emotional arousal. Defensive avoidance refers to evasive strategies, such as denial, wishful thinking, and shifting responsibility -emotional arousal is generally low, but easily becomes intense when signs of the danger become salient. Hypervigilance denotes panic, and occurs when the danger seems highly imminent (e.g. an approaching tornado, or impendi ng illness). It is characterised by extremely high levels of emotional arousal. Finally, vigilance refers to a rational, and logical problem solving approach, and emotional arousal is considered to be ‘moderate’, rather than extremely high or low. The problem with Janis and Mann’s (1977) model is that to date there has been a paucity of experimental research testing the association between coping strategies and stress levels (but see Mann Tan, 1993). However, studies have demonstrated correlational relationships between coping styles and emotional arousal (Witte Allen, 2000), suggesting that the former should form an important element of Schachter and Singers (1962) model. More specifically, it is possible that physiological changes generate strong emotions when people cope in one particular way, and little or no emotion arousal when people cope another way. Stimulus Characteristics Schachter and Singers (1962) model makes no reference to features of the stimulus itself. Rogers (1983) argued that the way we respond emotionally to a stimulus, specifically a threatening communication such as a health warning, depends on how we perceive aspects of the stimulus. He argued that dangerous events, such as a probable illness or impending natural disaster contain cues as to the probability of the event, and its seriousness or magnitude. The greater our estimates of the seriousness of a threat, and its probability of occurrence, the greater the level of anxiety experienced. In other words, stimulus characteristics determine the intensity of our emotional experience. A large volume of research published since the mid 1970s has found ample evidence in support of Rogers (1983) ideas (see reviews by Eagly Chaiken, 1993; Milne et al, 2000). In fact Rogers formulations continue to influence professional thinking especially in trying to understand people’s emotional reac tions to threatening health communications. It can be argued that Rogers’s ideas do not invalidate Schachter and Singers (1962) model. Stimulus characteristics may simply be something else people consider, in addition to monitoring their physiological parameters, and trying to work out the situation. Or perhaps Rogers’s appraisals fit in with Schachter and Singers emphasis on appraisals of the situation. Thus, if people perceived the situation as highly dangerous, because of the high severity and probability of the danger, then they would interpret their physiological arousal as fear. METHODOLOGICAL AND ANALYTICAL ISSUES Critique of Schachter and Singers two-factor model requires closer scrutiny of the evidence they present in support of their model. Various methodological and analytic constraints limit the conclusions that may be drawn (Coolican, 1994). Firstly, the study design is questionable. This study was set up as a between-groups design with subjects assigned to either one of two physiological arousal conditions – a treatment group (injected with adrenaline), or placebo group (given a saline condition). There was no control group. The presence of a control group is significant because it allows the researcher to demonstrate that observed effects were not simply a result of the ‘anticipatory’ effects of interventions (treatment or placebo) given to subjects. Another problem with the design was the failure to control for background variables that may confound treatment effects. In particular, subjects baseline emotions prior to the study should have been accounted for in the analysis, in order to partial out any pre-intervention differences between groups. The population was a sample of introductory psychology students. This kind of sample is generally better informed that the average man on the street, and have been able to decipher the researchers’ hypotheses, and hence provide responses intended to confirm or refute the predictions. The sample size was also rather limited (just over a 100), making it more difficult to detect statistically significant differences between the groups. This may partly explain the absence of group differences in self-reports of anger between the adrenaline-ignorant and adrenaline-informed groups. The anger condition was problematic because it was felt that subjects didn’t want to display anger towards the experimenter regarding their participation in the experiment. The sample was not randomly recruited meaning that the findings may in fact be specific to the particular subjects used, and may not generalise accurate to the wider population. CONCLUSIONS Perhaps the best evidence in support of the two-factor model lies in the difference observed between the three ‘information’ conditions amongst subjects injected with adrenaline. Those in the adrenaline-ignorant and adrenaline-misinformed group reported the highest ‘happiness’ levels, presumably because, lacking information about why they were experiencing physiological arousal, there automatically assumed that they felt that way because they were happy. This demonstrates two things. Firstly, it shows that physiological arousal may elicit an emotional experience (intensity), and secondly that an understanding of the situation led to a particular type of emotional experience – happiness. This confirms supports the two-factor proposition that emotional experience is a function of the interaction between physiological and situational (i.e. cognitive) factors. Nevertheless, the evidence is questionable, largely due to the absence of a control group, and a lso the small sample size. Schachter and Singers analysis also fails to account for other factors that may moderate that may have an independent effect on emotional experience, regardless of physiological arousal, such coping strategy, memory, prior experience, and general knowledge. There is a strong possibility that the impact of physiological arousal may be significantly attenuated after accounting for additional factors. In essence, emotional experience in certain circumstances may be driven solely by cognitive factors (i.e. thoughts, perceptions, memory), with biological changes have little or no effect peoples emotional response. REFERENCES Cannon, W. (1927/1987) The James-Lange theory of emotions: a critical examination  and an alternative theory. Special issue: 100 years of the American Journal of  Psychology. American Journal of Psychology. 100, pp.567-586. Chwalisz, K., Diener, E. Gallagher, D. (1988) Autonomic arousal feedback and  emotional experience. Evidence from the spinal cord injured. Journal of  Personality Social Psychology. 54, pp.820-828. Coolican, H. (1994) Research Methods and Statistics in Psychology. London: Hodder   Stoughton. Eagly, A.H. Chaiken, S. (1993) The Psychology of Attitudes. Fort Worth, TX:  Harcourt Brace Jovanovich. Janis, I. Mann, L. (1977) Decision Making: A Psychological Analysis of Conflict,  Choice, and Commitment. New York: The Free Press   Mann, L Tan, C. (1993) The hassled decision maker: the effects of perceived time  pressure on information processing in decision making. Australian Journal of  Management. 18, pp.197-209. Milne, S., Sheeran, P. Orbell, S. (2000) Prediction and intervention in health related  behaviour: a meta-analytic review of protection motivation theory. Journal of  Applied Social Psychology. 4, 149-163. Rogers, R.W. (1983) Cognitive and physiological processes in fear appeals and  attitude change: A revised theory of protection motivation. In B.L. Cacioppo,   L.L. Petty, D. Shapiro (Eds), Social Psychophysiology: A Source Book  (pp.153-176). London, UK: Guilford. Schachter, S. Singer, J. (1962) Cognitive, social and physiological determinants of  emotional state. Psychological Review. 69, pp.379-399. Witte, K. Allen, M. (2000) A meta-analysis of fear appeals: implications for  effective public health campaigns. Health Education Behaviour. 27, pp.591-  615. Zilman, D. (1978) Attribution and mis-attribution of excitatory reactions. In J.H.  Harvey, WE.J.Ickes R.F. Kidd (eds) New Directions in Attribution  Research Vol 2. Hillsdale, New Jersey: Erlbaum. Zilman, D. (1988) Cognition-excitation interdependence in aggressive behaviour.  Aggressive Behaviour. 14, pp.51-64.

Billy Budd :: essays papers

Billy Budd Today’s society as well as the majority of our schools can definitely improve on how it encourages creativity and individuality in today’s youth. A lot of the time, it’s hard to do this, but with smaller classrooms, more qualified and devoted teachers, and more cooperation from the students, everyone’s needs could be met, and students would receive a better education. Many of today’s schools have no tolerance for anything that may go against the â€Å"norm.† Schools today can allow for individuality and differences in students, but they either choose not to or are not aware that anything is wrong with the way they do things. In Melville’s, Billy Budd, there are examples of this stifling of individuality. The crew members on board the â€Å"Avenger† are made to all conform and follow orders without question. Through Claggart, the men’s individuality and rights as people are taken away through fear. No matter what anyo ne is trying to accomplish, satisfying everyone is almost always impossible. It is no different in today’s school system, satisfying everyone is difficult. Students are not allowed to express themselves as freely as they should. This is not the case in all schools, but it is Especially since incidents like those at Columbine High School, schools now view acts of individuality and creativeness as those of malicious intent. There is a kind of intolerance for those who act differently from the majority. Ever since the two boys from Columbine murdered their classmates, everyone has been extremely cautious about everything from actual death threats, to mere heated discussion between classmates. It is almost to a point of overkill. How much regulation is too much regulation? In order for schools to be able to accommodate for everyone and their individual needs, they must first not punish students for being different from the majority. After there is an acknowledgment of the individuality of students, then you can start to help them learn better and on their own levels. If a student has no aspirations whatsoever to go to college, then after some persuasion for them to reconsider, they should not be expected to complete and be graded on the same set of requirements as other students. If a person is not as â€Å"capable†, or rather does not choose to use their abilities to their fullest, then they should be graded on what they are able to do, not what other people are capable of and what they are expected to be capable of.

Environmental Regulations as Non-Tariff Barriers Essay -- WTO Trade NA

Environmental Regulations as Non-Tariff Barriers The current debate about the dispute resolution of environmental regulations as non-tariff barriers is one that is hotly contested in the WTO. Compared to the European Union and NAFTA, the WTO’s mission, goals, diverse membership, and rule structure make it decidedly difficult to create decision rules for these disputes. This paper suggests criteria for dispute resolution of cases within Multilateral Environmental Agreements (MEAs) and between WTO members. There are several different types of disputes likely to come before the WTO; they include direct trade restrictions on specific goods, product standards, process standards, and the use of eco-labeling. The policy suggestions put forth in this paper are rooted in GATT Article XX as well as basic principles of sovereignty and economic incentives. Perhaps most importantly, the dispute resolution criteria must be accompanied by international cooperation that facilitates the transfer of environmentally friendly technology an d promotes sustainable development. I. Background: Trade and the Environment Under the direction of the World Trade Organization, the global economy is gradually breaking down its barriers to trade. Agreements on the elimination of quantitative trade restrictions, tariff rate reductions, and the removal of export subsidies are well underway. The stampede of global economic integration cannot be ignored, and its progress is at the heart of WTO negotiation rounds. At the same time, there is an increasing amount of attention drawn to the consequences of trade liberalization on the environment. Environmental advocates worry that the lure of wealthy international markets encourages behaviors d... ... of Rule Development.† American Journal of International Law. April 1997, Volume 91, Issue 2, pp. 231-268. Steinberg, Richard H., ed. The Greening of Trade Law: International Trade Organizations and Environmental Issues. New York: Rowman and Littlefield Publishers, 2002. Switzer, Jacqueline V. Environmental Politics: Domestic and Global Dimensions. Third ed. Pp. 219-241; 295-310. New York: Bedford/St. Martins, 2001. Vogel, David. Trading Up: Consumer and Environmental Regulation in a Global Economy. Cambridge: Harvard University Press, 1995. Vogel, David. International Trade and Environmental Regulation. In Vig, Norman J. and Kraft, Michael E. (eds) Environmental Policy. Fourth ed. Pp. 350-369. Washington, D.C.: CQ Press, 2000. World Trade Organization Committee on Trade and the Environment. http://www.wto.org/english/tratop_e/envir_e.htm

We Are Not the Greeks :: Argumentative Persuasive Argument Essays

Shelley once said, "We are all Greeks," a sentiment which was echoed by many of his contemporaries who shared his belief that theirs was an age of achievement comparable to the Greeks.[1] Even beyond that era, people today hold a widespread belief that, although we aren't quite Greek ourselves, we are quite capable of understanding them, and that we have an innate familiarity with the Greek tradition. Our claim of an affinity to Greek literature can be found almost anywhere in modern society; the intelligentsia sprinkle allusions to all things Greek in books and films; the reference to Homer is considered the calling card of academic legitimacy. We are the consumers of a dominant culture that is rife with references to Greek literature. Consumerism does not lead to understanding, however. Anyone could justifiably make the argument that people experience the same struggles and emotions no matter what years bookend their lives and regardless of what gadgets or people fill up the space between them. However, to say that an emotion finds expression equally well on a Greek face or an American face leads to a false sense of our affinity to the Greeks. The point is not whether we share the same range of human experience, but whether we are capable of understanding the same means of expression. Just as much as we accept that Greek is a language foreign to us, we must accept that cultural differences exist that make most of those familiar names and quotes merely accessible parts of a culture that is largely inaccessible to the masses today. The average American is separated from the Greek epic. Although the lowest man is as capable of tragic struggle and feeling as any Greek hero, he is not capable of comprehending the scale and scope of the epic in his own life. We have no way of grasping the gargantuan undertaking of an epic. The epic poem is nonexistent in modern literature, and the number who read epic poems is decreasing rapidly as well. We may read excerpts or quotes about famous works, and from those remarks be able to afford remarks of our own, but this is a form of Cliffs Notes to cultural fluency. The fact that these facile and passing acquaintances serve as the bulk of our culture's understanding reveals the imperfect nature of what we assume we know. We feel qualified to claim a connection with the Greeks, through no proper understanding of our own, but rather through an opinion about an interpretation of a translation.

Lesson questions

Write an explanation to someone who does not know how to make proper measurements on how to measure the following line with the ruler. To the untrained eye, the ruler may seem like a useless and mundane tool straight out of a crappy ass's movie. But in fact, resent studies have that the ruler has many functionally sign efficacy purposes other than the ones used by teenagers behind closed bathroom doors. This tool is used to measure objects in standard or metric measurements.Here are instructions on how to use this device: 1 . Put down the TV remote and the bag of extra cheesy Ghettos. 2. Find an object worth measuring (I. E. The length of your TV remote) 3. Align the far edge of the remote with the line that reads â€Å"O† on the ruler. 4. Scanning to your right, locate the opposite end of the remote and read the corresponding number found on the ruler. That's it! 5. Repeat when necessary or to resolve any bets between your roommates or friends.The ruler is so easy to use a fo eman can do it! Be safe and enjoy! Explain how you would gather data and calculate the density of an irregularly shaped rock. By the word â€Å"rock† can only assume that you are referring to the one and only Deanne Johnson, who is both extremely manly and slightly irregular. Taking this into consideration, lets discuss how we would measure his density (this technique will also work on regular rocks as well but are far less entertaining). Here are the steps: 1.First we need a vessel filled approximately halfway with water that also has markings of measurement on them. Note the original volume of water (this will be used later) 2. Carefully introduce the object (or person) into the vessel until the water is displaced. 3. Note the new water level on the measurement indicators of the vessel (This measurement is your objects volume). 4. Now divide the volume by the object mass and the answer will equal the objects density. 5. Finally, get Deanne Johnson a towel, he's cold!

Ky School for the Deaf Changes Essay

No one is sure exactly what will become of Kentucky School for the Deaf campus. The school is rich in history of Danville and even houses its own museum in one of the buildings. Kentucky School for the Deaf was first established in 1823 and although it is not the first school for the deaf in the United States it is the first state funded school for the deaf. Several books have been written about the history of KSD. The entire book, A Centennial History of the Kentucky School for the Deaf by Charles Paxton, can be viewed online through the Kentuckiana Digital Library. Another book, published in 1973, is the History of the Kentucky School for the Deaf, 1923-1973, written by James B. Beauchamp and published by the KSD Alumni Association. In the late 70’s and early 80’s Kentucky School for the Deaf was thriving when enrollment reached its high at 440 students. Most of these students lived on campus and only went home once a month. There was a staff of 220 at that time. Today’s enrollment is about 130 students, of which approximately 75 are dorm who live on campus during the week. The remaining are day students bused in from surrounding counties. Many deaf students who once attended KSD are now mainstreamed into public schools in their home counties. Staff has been cut to 150. KSD has a campus of approximately 166 acres near the center of Danville. Some of this land was declared surplus land by the Kentucky Board of Education several years ago. The proposal was made to reduce campus size to 50 acres and to demolish several buildings. The campus at one time had 14 buildings. These include Argo-McClure Hall, built in 1964. It houses Technology classes for middle and high school students. Kerr Hall houses high school and middle school classes and Walker Hall is a self contained elementary school. Middleton Hall is the boy’s dormitory while Brady Hall is the girl’s dorm as well as where the infirmary and office are located. Grow Hall is the cafeteria for high school and middle school. Thomas Hall is the high school gymnasium as well as containing the Student Grille, Swimming pool and Athletic offices Jacobs Hall is KSD’s historical museum and is one of the oldest buildings on campus. It is listed as a National historic Landmark (Bill Macentire, Kentucky Landmarks) and shows student dorms and classrooms from the 1850’s. Because of this it can not be sold or demolished. Beauchamp Hall and Fosdick Hall are empty buildings that once housed boys and girls dorms. Bruce Hall is currently being used as an alternative learning school by the Danville Independent and Boyle County Schools. Barbee Hall has been rented to Danville Independent Schools for offices for several years. Old Lee Hall, facing South Third Street was built in 1958 and used for girls vocational classes. It was razed in 2010. It had sat empty for many years and fallen into disrepair. It had become very much an eyesore to the community but was in such bad shape it could not be renovated. The newer Lee Hall, facing South Second Street, once housed the middle school. It has sat empty for many years after mold was discovered growing in the basement. Some say the building was cleaned and repairs made to heating and air conditioning system and that the third floor apartments are now used to house dignitaries who visit. But one never sees any activity happening at the building. There was some talk that the building may one day be renovated to use as the elementary school. In 2004 a Master Plan was developed for KSD. The plan recommended the number of buildings be reduced from 17 to seven. The new campus would include Argo-McClure, Brady, Jacobs, Kerr, Middleton and Thomas halls and a new elementary school would be built at a cost of 6. 5 million. Beauchamp, Fosdick and Grow Halls would be torn down. Barbee, Bruce, Lee, Rogers and Walker Halls, the laundry and power plant and engineers home would be sold and the proceeds used to fund future needs for the campus. Last week Rogers Hall demolition began. Rogers Hall has been closed for many years having been declared unsafe by the state. It was the elementary school gymnasium. Currently the elementary school does not have a gym and uses a large classroom as its gymnasium. Also last week asbestos was discovered at Grow Hall. Now the middle and high school students are having to walk half a mile to Walker Hall to eat their meals in the cafeteria there. Many are complaining about the long walk in the cold and icy conditions. No one is sure when Grow Hall will reopen. Although the state at one time had money set aside for the building of the new school this has not happened. Now they are looking to save money. A better solution might be to use the newer Brady Hall. It already contains dorms, classrooms, a large kitchen area, a gymnasium, offices, even an infirmary. It is quite a large building and would easily accommodate the 130 students currently enrolled at KSD. KSD future seems uncertain but there is always hope for a better tomorrow. Works Cited Fosdick, Charles P. Centennial. History of the Kentucky School for the Deaf, Danville, Kentucky. 1923. Web. 8 Feb2011 Hudson, John W. Jr. Special collections-Kentucky School for the Deaf. Grace Daughtery Library. Centre College. 2002. 8 Feb 2011 MacEntire, Bill. Kentucky Landmarks. 2009. 8 Web. 2011.