The invitro effect of sildenafil citrate on the outcome of pregnancy Literature review

The invitro effect of sildenafil citrate on the outcome of pregnancy in mice and offsprings - Literature review Example Other medications that can be put to use to make infertile women conceive a baby includes the controlled ovarian stimulation, intrauterine insemination (IUI), and ovulation induction. Although the use of ART can result to a successful pregnancy, not all women who undergo ART can become pregnant. Infertility may occur in all types of species; whether human or animals. This chapter tries to investigate the expression of PDE5 in the pre-implantation embryos and the effect of sildenafil citrate (Viagra) on pre-implantation murine embryo development in vitro. Sildenafil is a special drug with a nitric oxide effects on vascular smooth muscles. Randomly selected mice were divided into two groups. One group was hyper stimulated group whereas the other was hyper stimulated plus sildenafil citrate group. The mice were injected with human menopausal gonadotropin (HMG), and later they received human chorionic gonadotropic (HCG) hormones. Afterwards, two female mice were put in one cage with one male mouse for mating process (Rashidi, Rad, Roshangar, & Mira, 2012). For a period of three days, the hyper stimulated plus sildenafil citrate group was injected with three mg of sildenafil citrate after every 24 hours. This was done after the mice had received the HMG injection. Ninety six hours of HMG injection later a cervical dislocation was done, and their urine specimens were prepared for laboratory tests; electron microscope studies. After the study, it was realized that there was long and short microvilli in the control group while no observable pinopodes development. On the other hand, the other hyper stimulated plus sildenafil citrate group experienced pinopodes development after injecting the mice with HMG after four days. This study brings to the attention on how import hyper stimulation of mice with sildenafil citrate can be. For instance, it helps in formation of pinopodes and implantation. Failure of implantation is one of the major problems in infertility treatment. In addition, implantation is believed to be one of the most interesting biological events. Implantation failure can be as a result of impaired uterine receptivity caused by high concentration of serum estradiol, which is induced by an ovulation induction treatment. Appearance of pinopodes is a specific morphological marker that has been associated with window of implantation (Rashidi, Rad, Roshangar, & Mira, 2012). The pinopodes are found in mice and rats but lack in other animals and humans. These are surface projections of the endometrial cell, which are involved in uterine pinocytosis. These pinopodes are essential in the implantation window, and for this reason, it is of note for them to be developed in mice at-time to facilitate implantation. The use of sildenafil citrate can maintain effectively the vasodilatory effects of the Nitrogen Oxide by blocking the breakdown of cGMP. Reducing the problems associated with the development of a foetus is possible through proper facilita tion of blood to the endometrial lining. In addition, enhancing the flow of blood to the endometrium lining will help reduce the risk of maternal hemodynamic complications. Also known as Viagra TM or RevatioTM,

Land Law solve the problem with Sunnydale Cottage Essay

Land Law solve the problem with Sunnydale Cottage - Essay Example †¢In May 2006, Charlotte went abroad for a few months on holiday. She sent post cards to each of the other inhabitants of Sunnydale Cottage saying that she had met Costas, a Greek waiter, and wanted to marry him. Accordingly, she notified them all that â€Å"My one fifth share in Sunnydale Cottage is to be ring-fenced and should anything happen to me Costas is to get it.† The postcard to Barbara was lost in the post and never delivered. Charlotte has tried of Costas and has now returned to live in Sunnydale Cottage. The TLATA avoids this problem as there is no duty to sell under a trust of land, merely a power of sale. All land subject to a trust will be held on a "trust of land" (TLATA s 1). Existing settlements are excluded, but land already held on express or implied trusts for sale are included within the provision. Although it is still possible to create express trusts for sale, as a subset of the trust of land, this will rarely be appropriate for domestic situations, and even here the power to postpone sale cannot be excluded. This means that there is no longer a problem posed by an imperative duty to sell, in situations where that was the last thing intended. One of the most important features of the TLATA is the nature of the trust of land. No longer is there a duty on the trustees to sell the land, there is simply a power to do so if desired. This perhaps reflects the fact that the reasons why trusts are set up nowadays are not the same as in 1925. The trustees of land, when exercising any function relating to the land subject of the trust, are now under a duty (as far as practicable) to consult with beneficiaries of full age and beneficially entitled to an interest in possession in the land. They must give effect to the wishes of those beneficiaries, so far as they are consistent with the general interest of the trust. If there is a dispute among the

Tuberculosis: Prevention and Treatment

Tuberculosis: Prevention and Treatment Tuberculosis (TB) is an airborne infectious disease which is caused by strains of mycobacteria, mainly Mycobacterium tuberculosis1. There are roughly one third of the worlds population are infected with tuberculosis where nine millions of new cases reported annually2. Although tuberculosis can be prevented and treated, it continues to cause millions of deaths every year2. When infected individual coughs, sneezes or spits, M. tuberculosis is propelled into the air and infected those who breathed in the bacteria that existed in droplets of saliva3. Primarily, tuberculosis will affect the lungs, known as pulmonary tuberculosis3. It will also affect other parts of body, for instance lymph nodes, bones, brain and kidneys3. Once a person is infected with tuberculosis, there are basically three possible ways may occur. Firstly, the immune system plays a vital role and strong enough to kill the bacteria3. Secondly, immune system is not strong enough to fight off the bacteria but is able to b uild a defensive barrier against the bacteria3. Individuals who are latently infected with M. tuberculosis show asymptomatic where these bacteria lie dormant in the lungs and able to reactivate after years1. The disease is often reactivated in those who are immunocompromised or generally weakened. Lastly, the immune system fails to kill bacteria causing the bacteria to grow and spread towards other parts of body which is called active tuberculosis3. In the fight of tuberculosis, World Health Organisation (WHO) recommends universal Bacille Calmette-Guà ©rin (BCG) vaccination in the countries with high TB burdens4. BCG vaccine contains weakened form of M. tuberculosis which will induce human antibodies to fight against this type of bacteria. The efficacy of BCG vaccination can be ranging from 0% to 84%5. This may be due to the frequency of TB exposure and quality of vaccine used, leading to arguments on BCG vaccination efficacies4. One of the greatest arguments is that BCG vaccination causing positive reactions to tuberculin skin testing and hence interfere with the diagnosis of latent TB4. Existence of evidences showing the rates of efficacy also depends on geographical location, age at vaccination and form of TB further complicate the situation. Currently, TB chemotherapy is made up of combination of a list of first-line drugs isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (EMB) 6. If the treatment fails d ue to bacterial drug resistance, or patient unable to tolerate, second-line drugs for instance para-aminosalicylate (PAS), fluoroquinolones, ethionamide and cycloserine are introduced6. These are considered as second line drugs generally either less potent with larger doses regimen or more toxic with serious side effects6. Tuberculosis is presently treated in two phases, namely initial phase and continuous phase7. In initial phase, the patient will be treated with concurrent use of four first line drugs, with the aim to eradicate or control bacteria population to replicate in rapid motion and also avoid the emergence of bacteria resistance7. The treatment choices available for initial treatment include isoniazid, rifampicin, pyrazinamide and ethambutol7. Streptomycin is used rarely but can be used in patients who infected with bacteria that are resistant to isoniazid before the therapy is commenced7. The duration for initial phase is 2 months whereas the continuous phase takes 4 months7. During the four months of continuous phase, patients are treated with isoniazid and rifampicin at same doses7. Most of the TB treatment is supervised where drug administration needs to be fully supervised by healthcare professions since lengthy duration of treatment causing incompliance in patients7. These patients who are unlikely to be compliance will be given the drugs three times a week until the course is completed while patients who able to comply with the treatment will not be supervised7. Despite the chemotherapy treatment and BCG vaccine, TB remains as a significant infectious disease due to increasing emergence of drug resistant TB and co-infection with Human Immunodeficiency Virus (HIV) 6. Since the host defense in HIV patients is suppressed, they are more susceptible to TB infections. Moreover, drug- drug interactions between antiviral therapy and anti-TB also causing complications in treating co-infected patients6. Drug resistant TB has evolved mainly because of improper treatment or incompliance in patients who stop taking their medications before the bacteria is being fully eradicated since the duration of treatment is lengthy which takes 6-9 months8, 9. The mechanism involved includes chromosomal mutations in genes that responsible for drug targets encoding9. When there is a sequential accumulation of mutations, multi-drug resistant tuberculosis (MDR-TB) emerges where the M. tuberculosis strains will resistant to two of the most commonly used drugs, Isoniazid and Rifampicin9. Patients with MDR-TB are then relying on the second-line drug classes, fluoroquinolones and the three injectable agents namely amikacin, capreomycin, and kanamycin10, 11. The chances to cure would dramatically be reduced for patients who infected with extensively drug-resistant tuberculosis (XDR-TB), a situation where the isolated strains are resistant against any one of fluoroquinolones and at least one of three injectable drugs6. In order to combat with the MDR-TB or XDR-TB and optimize the tuberculosis drug regimen, it is crucial to understand the mechanism of action of current using first-line drugs and how resistance is developed against these drugs. Isoniazid (INH) or isonicotinic acid hydrazide is discovered in 1952, a bactericidal agent which active against organism of the genus Mycobacterium, especially M. tuberculosis, M. bovis and M. kansassi6, 12. In vivo, INH has shown to be bactericidal in culture over the first 48 hours which become bacteriostatic after this particular time frame12. This indicates that INH is bacteriostatic for slow replicating bacilli but is bactericidal against rapidly dividing mycobacterium. The minimal tuberculostatic concentration is 0.025 to 0.05ug/ml13. INH is a prodrug that needs to be activated by catalaseperoxide hemoporotein, KatG before acts by inhibiting mycolic acid synthesis and cell wall disruption in susceptible mycobacterium13, 14. This inhibitory action is only targeted to mycobacteria since other bacteria do not contain mycolic acid in the cell wall13. INH acts by inhibit enoyl acyl carrier protein (ACP) reductase, InhA, and a beta-ketoacyl-ACP synthase, KasA that are crucial in fatt y acid synthesis system for mycolic acid15. Resistance to INH is believed due to mutations in gene encoding catalaseperoxidase katG or InhA or lacking KatG 9, 14. Isoniazid is metabolised in the liver, mainly by acetylation and dehydrazination where slow acetylator may experience higher concentration leads to potential toxicity before excreted in the urine within 24 hours13. Rifampicin (RIF), discovered in 1963, is a lipophilic semisynthetic derivative of rifamycin antibiotic which is produced by the fermentation of a strain of Amycolatopsis mediterranei6, 9, 16. RIF has bactericidal activities against a broad spectrum of microorganisms including gram-positive and gram-negative. RIF will inhibit the action of DNA-dependent RNA polymerase of mycobacteria that is encoded by rpoB through formation of a stable drug-enzyme complex9. This will suppress the initiation chain formation in RNA synthesis and hence prohibit protein synthesis in M. tuberculosis9. Development of resistance to RIF is mostly due to mutation in 81 base pair region of rpoB gene thus facilitate a straightforward approach to detect MDR-TB since 85-90% RIF-resistant strains are also resistant to INH9. RIF produces peak plasma concentration of 7ug/mL in 2 to 4 hours after ingestion of 600mg17. It also distributed well to most of the body tissues and fluids, including cerebrospinal fluid since it is lipophilic17. Following absorption from the gastrointestinal tract, RIF is eliminated rapidly in the bile with fewer amounts excreted through urine17. Pyrazinamde (PZA) is discovered in 1954 and it produces excellent sterility effects against semidormant tubercle bacilli at slightly acidic pH6, 9. The antimicrobial activity of PZA is through interference with mycolic acid synthesis in M. tuberculosis by pyrazinoic acid, an active moiety of PZA9. Conversion of PZA to pyrazinoic acid is mediated by pyrazinamidase enzyme that is encoded by pncA gene in M. tuberculosis, thus indicating that these bacilli are sensitive to PZA9. Resistance against PZA evolved when mutation occur at pncA gene that is responsible for pyrazinamidase, hence affecting the activity of this enzyme9. PZA is well absorbed from gastrointestinal tract and is widely distributed to most tissues and fluid too17. The oral administration of 500 mg PZA produces plasma concentrations of 9-12ug/ml after two hours and 7ug/ml after 8 hours17. PZA is metabolized in liver whereas the metabolites are excreted through renal glomerular filtration17. Ethambutol (EMB) is discovered in 1962, acts as bacteriostatic agent and is active against undergoing cell division6, 18. EMB primarily targets on impairment of cell wall polymerization by inhibits arabinosy transferase, a vital enzyme responsible for mycobacteria cell wall biosynthesis9, 18. Since arabinosy transferase enzyme is encoded by embC-embA-embB genes, resistance against EMB evolved is believed due to mutation of these genes9. EMB is currently used as one of the first-line treatment for tuberculosis mainly because of its synergistic effect with other front-line drugs and its low toxicity property18. There is roughly 75-80% of an oral dose of EMB is rapidly absorbed in gastrointestinal tract with absorption unaffected when administered with foods19. In addition, EMB is distributed widely to body tissues and fluid, including cerebrospinal fluid before being metabolized in the liver and excreted in urine19. Streptomycin (SM) is an aminoglycoside antibiotic, used as first line treatment for TB when it first discovered in 19441, 6. Streptomycin is isolated from the bacteria Streptomyces griseus and its antimicrobial effects against M. tuberculosis is highly effective when use in combination with other first line agents20. However, SM is no longer considered as first line treatment as resistance against it has developed rapidly1. The optimum pH for SM is at pH8 where its bacteriostatic activity will reduce with increasingly acidic environment20. SM acts by binding tightly to A site of 16S ribosomal RNA subunit, interferes with mRNA translation, causing faulty protein being produced1, 9. Resistant emergence when the mutation occurs at gene rpsL and rrs that encoded for 16S and S12 ribosomal protein1, 9. Upon administration, SM is poorly absorbed from gastrointestinal tract and mostly administered parentally1. SM is mostly excreted in urine and patients with low renal profile might experienc e toxicity such as neurotoxic reactions1. When the first line treatment is no longer suitable for patients or patients develop multi-drug resistance TB, second line drugs will then be introduced in combating the TB. Second line drugs that are mostly used include Ethionamide (ETH), Cycloserine (CS), Para-Aminosalicylic Acid (PAS) and Fluoroquinolones (FQ). ETH has been in use since 1960s, is a structural analogue of INH and it targets at inhibition of mycolic acid biosynthesis in tubercle bacilli9, 21. INH however is much more potent than ETH since the minimal inhibitory concentration for ETH is 0.5-5.0ug/mL21. Resistance evolved due to mutation at gene InhA and ethA which encode for oxygenase enzyme in activation of ETH 9. In vitro, CS has inhibitory effect on M. tuberculosis at 5-200ug/mL and there is no cross resistance occurred between CS and other drugs13. CS acts by interfereing the biosynthesis of bacterial cell wall13. CS is well absorbed in gastrointestinal tract and also widely distributed to body tissues and fluid including cerebrospinal fluid13. PAS was first introduced as first line drug but being replaced by Ethambutol in 1960s1. It acts bacteriostatically with possessing inhibitory effect at concentration less than 1mg/ml by interfere with folic acid metabolism in bacteria1. PAS is readily absorbed from gastrointestinal tract and distributed well throughout the body. Approximately 80% of the drugs will be excreted via kidney after being metabolized to acetylated form1. Moxifloxacin and Gatifloxacin are both been synthesized and evaluated as excellent bactericidal agents through inhibiting DNA gyrase, an ATP-dependent enzymes topoisomerase II which is responsible in bacteria DNA transcription9. DNA gyrase is consisted of two subunits that is arranged in a complex, is encoded by two different genes, gyrA and gyrB where mutations at gyrA will normally cause bacteria resistance to these new generation of flouroquinolones9. Due to the increasing incidence of multidrug resistance TB, it is highly desirable to develop new drugs that are not only potent and effective against current resistant strains of M. tuberculosis but also possess shorter treatment duration since most of the incompliance of patients is brought up by lengthy TB treatment. Most of the mechanisms of action of current treatments are involved in interfering the bacterial DNA synthesis, protein and mycolic cell wall biosynthesis. The enzymes that participate in these pathways could also be the target of newly designed drugs such as TMC207, one of the new drugs which are currently under investigations and clinical trials. TMC207 is a member of diarylquinoline class of compound which target at adenosine triphosphate (ATP) synthase by binding to subunit C of the synthase, blocking the energy pathway of mycobacteria22, 23. In vitro, TMC207 not only possesses ability to inhibit both drug sensitive and resistant M. tuberculosis isolates, but also able to sterilize the patient through killing the dormant bacilli bactericidally22. TMC207 showed a minimum inhibitory concentration of 0.03ug/mL against M. tuberculosis, suggesting a more potent agent compared to current first- line treatments such as isoniazid and rifampicin23. Apart from that, its synergistic effect with pyrazinamide could promise as effective drug combination for sterilizing the patients against TB22. A phase I clinical trials which involved short terms administration of TMC207 in healthy individuals showing no adverse effects and the subjects are well tolerated with it23. However, it is essential to investigate the selectivity of TMC207 again st mammalian ATP synthase with longer periods to ensure the patients safety when administered with TMC207. Thiacetazone (TAC) is widely used as second line anti-TB agent against multiresistant tuberculosis at present24. TAC acts by interferes the biosynthesis pathway of mycolic acid in tubercle bacilli24. The fact that M. tuberculosis has been difficult to eradicate and remains persistent is due to its cell wall that composed of mycolic acid which is resistant against chemical injury, dehydration and also has low permeability to antibiotics24. Mycolic acid contains cyclopropane rings that is activated through cyclopropane mycolic acid synthase (CMASs), has a significant contribution to tuberculosis24. By inhibiting the cyclopropanation, the cell wall biosynthesis will then be interrupted, introducing the bactericidal effects24. The aim of this research is to synthesis and evaluates the analogues of Thiacetazone which might be potential anti tuberculosis agents. The analogues will be tested against different strains of mycobacteria in lab. The target actions of these analogues will also be identified based on the structure of the analogues. The above analogue is synthesized when a benzylaldehyde reacts with a primary amine. This is a condensation process and an imine is produced. The changes at position R1 to R3 with different electron withdrawing groups are first planned to be evaluated. However, the plan is prohibited since the corresponding structures are either unavailable or too expensive that falling outside the budget. After revised on the previous analogues that were discovered and their respective MIC values obtained from lab, the structures of new analogues that are going to be evaluated are finally sorted out. The R1 to R3 positions would be replaced by either a -chloro or a -methoxy with R8 position would either be an amine, a methyl or a benzene ring. A chloro is used at position R1 to R3 since it is electron withdrawing, big and lipophilic molecule whereas the methoxy group is electron donating, small and quite lipophilic. For R8 position, an amine is selected because it is electron withdrawing and small. A methyl is also selected since it is quite lipophilic, small and electron donating. On the other hand, benzene ring which is highly lipophilic, neither electron donating nor withdrawing group might have a different effect on the analogue synthesized. References: Patrick Brennan, Douglas Young (2008). Tuberculosis. 88(2), 85-86, 137-138, 162-163. Health Protection Agency. http://www.hpa.org.uk/HPA/ National Health Services. http://www.nhs.uk/Pages/HomePage.aspx Zaida Araujoa, Jacobus Henri de Waard, Carlos Fernà ¡ndez de Larrea, Rafael Borges, Jacinto Convit (2008). The effect of Bacille Calmette-Guà ©rin vaccine on tuberculin reactivity in indigenous children from communities with high prevalence of tuberculosis. Vaccine 26, 5575-5581. Hart and Sutherland (1977). BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. Br Med J2(6082), 293-295. Global Alliance for TB Drug Development. http://www.tballiance.org/home/home.php 57th edition of British National Formulary: Section on Tuberculosis drugs, 316-317. Blumberg, H. M. et al. (2003). American Thoracic Society/ Centers for Disease and Prevention/ Infectious Disease Society of American: treatment of TB. Am.J.Respir.CareMed.167, 603-662. Suhail Ahmad and Eiman Mokaddas (2009). Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis. Respiratory Medicine 103(12), 1777-1790. Frieden TR, Sherman LF, Maw KL, et al. (1996). A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes. JAMA 276, 1229-1235. Mukherjee JS, Rich ML, Socci AR, et al. (2004). Program and principles in treatment od multi-drug resistant tuberculosis. Lancet 363, 474-481. Zhang Y. et al. (2003). Isoniazid. Tuberculosis 2, 739-758. Hardmn, J.G., L.E. Limbird, P.B Molinoff, R.W. Ruddon, A.G. Goodman (2006). Goodman and Gilmans The Pharmacological Basis of Therapeutics. 9, 1164-1165. Zhang Y, Heym B, Allen B, Young D, Cole S (1992). The catalase-peroxidase gene and isoniazid resistance by Mycobacterium Tuberculosis. Nature 358, 591-593. Richard A. Slayden, Richard E. Lee and Clifton E. Barry (2002). Molecular Microbiology 38(3), 514-525. Rup Lal, Sukanya Lal (2005). Recent trends in rifamycin research. BioEssays 16(3), 211-216. Hardmn, J.G., L.E. Limbird, P.B Molinoff, A.G Gilman (2001). Goodman and Gilmans The Pharmacological Basis of Therapeutics. 10, 1278-1281. Raghunandan Yendapally and Richard E. Lee (2008). Design, synthesis and evaluation of novel ethambutol analogues. Bioorganic and Medical chemistry Letters 18(5), 1607-1611. McEvoy, G.K. (2007). Admerican Hospital Formulary Service. Besthesda, 551. Selman A. Waksman (1953). Streptomycin: Background, Isolation, Properties and Utilisation. Science, 118(3062), 259-266. Sampson AE, Barry CE (1999). Abstract General Meeting American Society Microbiology. 99, 635. Andreas H.D., Alexander Pym, Martin Grobusch et al. (2009). The Diarylquinoline TMC207 for Multidrug- Resistant Tuberculosis. 360(23), 2397-2405. Anna C. Haagsma, Rooda Abdillahi-Ibrahim, Marijke J. Wagner, Klaas Krab, Karen Vergauwen, Jerome Guillemont, Koen Andries, Holger Lill, Anil Koul, and Dirk Bald (2009). Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towardsthe Eukaryotic homologue. Antimicrobial Agents and Chemotherapy, 53(3), 1290-1292. Anuradha Alahari, Xavier Trivelli, Yann Guà ©rardel, Lynn G. Dover, Gurdyal S. Besra, James C. Sacchettini, Robert C. Reynolds, Geoffrey D. Coxon, Laurent Kremer (2007). Thiacetazone, an Antitubercular Drug that Inhibits Cyclopropanation of Cell Wall Mycolic Acids in mycobacteria. PloS ONE, 2(12): e1343. Mycolic acids are a complex mixture of branched, long-chain fatty acids, representing key components of the highly hydrophobic mycobacterial cell wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain cyclopropane rings. Double bonds at specific sites on mycolic acid precursors are modified by the action of cyclopropane mycolic acid synthases (CMASs). The latter belong to a family of S-adenosyl-methionine-dependent methyl transferases, of which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1 through A4, PcaA and CmaA2. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence of M. tuberculosis. While several antitubercular agents inhibit mycolic acid synthesis, to date, the CMASs have not been shown to be drug targets. We have employed various complementary approaches to show that the antitubercular drug, thiacetazone (TAC), and its chemical analogues, inhibit mycolic acid cyclopropanation. Dramatic changes in the content and ratio of mycolic acids in the vaccine strain Mycobacterium bovis BCG, as well as in the related pathogenic species Mycobacterium marinum were observed after treatment with the drugs. Combination of thin layer chromatography, mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses of mycolic acids purified from drug-treated mycobacteria showed a significant loss of cyclopropanation in both the ?- and oxygenated mycolate sub-types. Additionally, High-Resolution Magic Angle Spinning (HR-MAS) NMR analyses on whole cells was used to detect cell wall-associated mycolates and to quantify the cyclopropanation status of the cell envelope. Further, overexpression of cmaA2, mmaA2 or pcaA in mycobacteria partially reversed the effects of TAC and its analogue on mycolic acid cyclop ropanation, suggesting that the drugs act directly on CMASs. This is a first report on the mechanism of action of TAC, demonstrating the CMASs as its cellular targets in mycobacteria. The implications of this study may be important for the design of alternative strategies for tuberculosis treatment.

Free Essays - Role Playing in A Farewell to Arms :: Farewell Arms Essays

Role Playing in A Farewell to Arms In Hemingway's novel, A Farewell to Arms, the principle characters, Henry and Catherine, are forced by the war to face the fact of human mortality. As a defense mechanism, the two main characters, and several others, turn to "role-playing" as a way to escape reality. Hemingway utilized role-playing as a way to explore the strengths and weaknesses of the characters. By placing Henry's ordered life in opposition to Catherine's topsy-turvy one, and then letting each one assume a role which will bring them closer together, Hemingway shows the pair's inability to accept their own mortality. John Stubbs' has written an essay that examines the "role-playing" that Henry and Catherine use to protect themselves from the discovery of their insignificance and "powerlessness...in a world indifferent to their well being..." Stubbs begins by showing other examples, notably in In Our Time and The Sun Also Rises, in which Hemingway's characters revert to role-playing in order to escape or retreat from their lives. The ability to create characters who play roles, he says, either to "maintain self-esteem" or to escape, is one Hemingway exploits extraordinarily well in A Farewell to Arms and therefore it "is his richest and most successful handling of human beings trying to come to terms with their vulnerability." As far as Stubbs is concerned, Hemingway is quite blatant in letting us know that role-playing is what is occurring. He tells that the role-playing begins during Henry and Catherine's third encounter, when Catherine directly dictates what is spoken by Henry. After this meeting the two become increasingly comfortable with their roles and easily adopt them whenever the other is nearby. This is apparent also in that they can only successfully play their roles when they are in private and any disturbance causes the "game" to be disrupted. The intrusion of the outside world in any form makes their role-playing impossible, as evidenced at the race track in Milan, where they must be alone. The people surrounding them make Catherine feel uncomfortable and Henry has to take her away from the crowd. He goes on to describe how it is impossible for them to play the roles when they are apart and how they therefore become more dependent upon each other's company. Stubbs goes on to explain how, "neither mistakes role-playing for a truly intimate relationship, but both recognize that it can be a useful device for satisfying certain emotional needs.

Xacc 280 Financial Statement Analysis

Feedback is at the end of the paper. The three of financial statement analysis are horizontal analysis, vertical analysis, and ratio analysis. The function of all three analyses is to evaluate the significance of financial statements data. Horizontal analysis function is to evaluate and compare data given by the financial statement for at least two years with in its own company. Vertical analysis expresses the amounts of the financial statements as a percentage from the amounts given on the financial statements. Vertical analysis also makes it so that companies can compare how they are doing with competing companies. Ratio analysis is used to evaluate liquidity, profitability, and solvency. PepsiCo. Calculations: Ratio: 2005 Current Ratio: 1. 11:1 10,454/9,406=1. 1114 2004 Current Ratio: 1. 28:1 8,639/6,752=1. 2794 Vertical Analysis: 2005 current assets 10,454 / total assets 31,727=0. 3294 or 32. 9% 2004 current assets 8,639 / total assets 27,987=. 3086 or 30. 7% Horizontal Analysis: Assets increased in 2005 by 13% Total assets 2005 31,727-total assets 2004 27,987=3740/ 27,987=. 33 or 13% Liabilities increased by 21% Total liability 2005 17,476-total liability 2004 14,464=3012/14,464=. 208 or 21% Coca-Cola Calculations: Ratios: Current Ratio for 2005 1. 04:1 10,250/9,836=1. 042 Current Ratio for 2004 1. 10:1 12,281/11,133=1. 103 Vertical Analysis: 2005 Current Assets 10,250/total assets 29,427=. 348 or 35% 2004 current assets 12,281/total assets 31,441=. 390 or 39% Horizontal Analysis: Curre nt assets decreased by 17% Current assets in 2005 10,250-current assets 2004 12,281=-2031/current assets 2004 12,281=-. 65 or -17% Current liability decreased by 12% in 2005 Current liability in 2005 9,836- current liability in 2004 11,133=-1297/current liability in 2004 11,133=-. 116 or 12% Good Effort on the CheckPoint See more feedback below. | Â  | CheckPoint 25/points| Points Earned 21. 5/25| Â  | Write in 100 to 200 words an explanation of the three tools of financial statement analysis and the function of each. | 5/5 points| Â  | three tools of financial statement analysis| Â  | 3| The tone is appropriate to the content and assignment. Sentences are complete, clear, and concise. Sentences are well constructed, with consistently strong, varied sentences. Sentence transitions are present and maintain the flow of thought. Rules of grammar, usage, and punctuation are followed. Spelling is correct. | Â  | 1| The paper is 100 to 200 words in length. | Â  | 1| Feedback Concept seems to be learned. | Additional Comments:| Â  | Calculate the following for PepsiCo, Inc. and show your work and Calculate the following for Coca-Cola and show your work: | 19/20 points| Â  | Ratio analysis| Â  | Â  | Tool: Current ratio for 2005| Â  | Â  | Pepsico| Â  | 1| Coca-Cola| Â  | 1| Tool: Current ratio for 2004| Â  | Â  | Pepsico| Â  | 1| Coca-Cola| Â  | 1| | Â  | Â  | Vertical analysis| Â  | Â  | Tool: Current assets ? total assets in 2005| Â  | Â  | Pepsico| Â  | 2| Coca-Cola| Â  | 2| Tool: Current assets ? total assets in 2004| Â  | Â  | Pepsico| $8,639 ? $27,987 = 30. 9%| 2| Coca-Cola| $12,281 ? $31,441 = 39. 1%| 2| | Â  | Â  | Horizontal analysis| Â  | Â  | Tool :Percent change in total assets (2005 ? 2004)| Â  | Â  | Pepsico| Â  | 2| Tool :Percent change in current assets (2005 ? 2004)| ($10250-12281) ? $12281 = -16. 5 %| Â  | Coca-Cola| ($29,427 – $31,441) ? $31,441 = -6. %| 1. 5| Tool: Percent change in total liabilities (2005 ? 2004)| Â  | Â  | Pepsico| Â  | 2| Tool: Percent change in current liabilities (2005 ? 2004)| ($9836 – $11133) ? $11133 = -11. 65%| Â  | Coca-Cola| ($13,072 – $15,506) ? $15,506 = -16%| 1. 5| Â  | Â  | Â  | | Â  | Â  | Feedback: All figures looked good but you did the horizontal analysis on the Pepsico for the Total assest and did the current assets for Coca-Cola. You need to compare the same numbers in the companies to be able to complete a correct analysis. | Additional Comments:Â  | Â  | Late One Day 25 *. 0 | Â  | -2. 5| Total 25/Points | Points Earned 21. 5/25| Â  | | Â  | 21. 5| Overall Comments: Late assignments receive a 10% deduction for each day they are late. Assignments are late if they are not posted by midnight Arizona time (MST) of the day they are due. Assignments that are more than 4 days late will not be accepted unless we have negotiated and mutually agreed upon an alternative submission date in advance. Unless an Incomplete grade has been granted, student assignments submitted after the last day of class will not be accepted. | Â  | Â  | Â  | Â  | | | |

Freud’s Theory of Personality Essay

Sigmund Freud’s theory of personality is both relevant and non-relevant in today’s society. His theory of consciousness is very important as a foundation for understanding human thought and behavior. Freud looked beyond the effects of behavior and explored the unconscious. He significantly changed the way the world views behavior by explaining certain levels of consciousness, the components of the unconscious mind, and different developmental phases. Freud believed that many of our conscious thoughts and actions are motivated by unconscious fears and desires. Sigmund Freud is best known for his development and use of psychoanalysis. The theory of psychoanalysis focuses on the concept of how our unconscious thoughts, feelings, and emotions play an active role in our daily lives. The id, ego, and superego are the three mental zones and each has a specific function. The id functions on the pleasure principle; the ego on the protection of the individual; and the superego on protection of society. Every individual is composed of different amounts of each mental zone. The ultimate goal is to achieve the perfect balance of the three areas by understanding how each works alone and contributes to make the whole. The basis of psychoanalysis is that the unconscious mind determines behavior. One of the biggest concerns in Freud’s psychoanalytic theory is the inability to explain behavior in our modern culture. Freud lived in an era where women were believed to be inferior to men. Freud based his theories on his case studies and direct observations. These observations had limitations because his subjects were Viennese upper-class women; a small portion of society. He focused mainly on the male development; as he was part of a male dominated era which led to half of the population’s development being insufficiently accounted for. Freud lacked an  understanding of women which suggests that his theories involving women are not accurate. The prevalence of same-sex parents raising children in homosexual homes or single-parent households raises questions that psychoanalysis fails to answer and is not relevant in today’s society. Freudian theory suggests that as children develop they progress through a series of psychosexual stages. Each stage has a pleasure-seeking energy that is focused on a different part of the body. The successful completion of each stage leads to a healthy personality as an adult. However, if a conflict remains unresolved at any particular stage, the individual might remain fixated or â€Å"stuck† at that particular point of development. A fixation can involve an obsession with something related to that phase of development. Signs of an oral fixation might include an excessive reliance on oral behaviors such as smoking, biting fingernails or eating. In these modern times, there are over 45 million Americans who smoke and based on Freud’s theory it is a direct result of the way a child went through the teething phase. The idea that a parent who let their child teeth for too long could somehow lead to an individual developing an oral fixation is something that has lost credibility and not relevant today. There are millions of smokers in the United States and very rarely does the blame rest upon the parents who left their kids with a pacifier for too long. Defense mechanisms are a major aspect of psychoanalysis and are relevant in today’s society. When someone seems unwilling to face a painful truth, you might accuse them of being â€Å"in denial.† When a person tries to look for a logical explanation for unacceptable behavior, you might suggest that they are â€Å"rationalizing.† These things represent different types of defense mechanisms, or tactics that the ego uses to protect itself from anxiety. Today we recognize denial as the first and foremost defense mechanism which helps professionals understand an individual’s denial of addictions; such as drugs/alcohol, gambling, and shopping. In conclusion, the profession of psychology would not be where it is today without Sigmund Freud. His contributions to psychology are perhaps some of the most important. Freud’s early work on psychoanalysis as a treatment for  a â€Å"sick† mind paved the way for modern-day psychologists, psychiatrists, theorists, and analysts who are developing this treatment even further. However, he based his theories on events that were exclusive to his time period. In today’s society we have different stressors and live different lifestyles than those living in the 19th and early 20th centuries. They did not know road rage, chemical explosions, pollution, etc. Some changes to consider are focusing on the development of women, study of homosexual and single-parent households, variety of ethnicities/cultures, and environmental concerns just to name a few. References Feist, J., Feist, G., & Roberts, T. (2013). Theories of personality. (8ed., p.19). New York, NY: McGraw-Hill Companies. Lothane, Z. (2006). Freud’s legacy–is it still with us? Psychoanalytic Psychology, 23(2), 285-301. doi:10.1037/0736-9735.23.2.285 Psychoanalysis. (2013). Columbia Electronic Encyclopedia, 6th Edition, 1-2.