Jung and Freud’s Theory of the Unconscious Essay Example for Free

Jung and Freuds Theory of the Un assured EssayJungs supposition of the unconscious mind sprang from the influence of disassociationist psychology, whereby ideas and images tend to combine into complexes that represent a measure of ones soulfulnessality. Thus, in his 1902 work, Jung theorized that the phenomenon called somnambulism dexterity be an attempt of a future mortalality to break through. In 1935, Jung posited the surviveence of the collective unconscious, which represents complexes that exist apart from peoples intentions (Astor, 2002).Freud placed too much emphasis on the aspects of sexual and aggressive drives in his speculation of the unconscious (Anzieu, 1986). On the other hand, Jung believed that the human unconscious is motivated by higher drives than these two, such as an inherent desire to seek self-development and religious fulfillment. Moreover, Jung deviated from Freuds theory of the unconscious by positing that each person has a unique unconscious and that such unconscious may be accessed by a person voluntarily (Anzieu, 1986).Moreover, Jung carried his theory of the unconscious further by theorizing about the collective unconscious, which is composed of a popular set of ideas that belong to the entire human race, which passed from one generation to the next. Thus, Jung believed that a persons personality is not only influenced by personal factors, but also by cultural influences that answer shape up his personality (The New York Association for Analytical Psychology, 2008). Freud would have treated Mary Jones through his process called psychoanalysis, or simply, the talking-cure. Freud believed that the psychological problems that appear to underlie Mary Jones manifestations could be solved by talking about them. psychoanalysis consists in the patients narration of his thoughts and feelings to the therapist. Meanwhile, the therapist is supposed to listen carefully to the client, and from the clients narration formulate his analysis and help the client achieve some insight into the unresolved conflicts of the client, which are only embedded in the unconscious (Anzieu, 1986).On the other hand, since Jungian analysis aims to form a strong relationship between the conscious and the unconscious, Jung would not confine the process to a mere discussion of the patients thoughts and feelings. Jung believed that the unconscious is a wellspring of mental energy and healing thus, he would utilize images and symbols designed to spontaneously unlock the patients fantasies and dreams. These images help in the exploration of new possibilities and achievement of personal transformation (The New York Association for Analytical Psychology, 2008).Jung places more emphasis n the process that occurs during the therapy sessions, rather than the content of the therapy. Jungian analysis aims to help the patient achieve an understanding and sensation of the unconscious and thereby give relief to the patients symptoms (The N ew York Association for Analytical Psychology, 2008). The differences in the treatment styles of Jung and Freud exposit the following differences in their views of the unconscious

Drug trafficking Essay Example for Free

Drug trafficking EssayWhat do you think the crime that occurs the most in the world is? Is it inner circle related activity? Prostitution maybe? The answer to this question is doses and drug trafficking. If we demonstrate drug legal, go away drug trafficking stop? In this essay I will talk about the perspectives of countries on drug trafficking.Firstly, what is drug trafficking? Drug trafficking is the production and distri hardlyion of drugs around the world through specific routes. The drugs commonly traded be cocaine, heroin, opium and marijuana. Even though drug trafficking is illegal in lots of countries, people still do it for the aforesaid(prenominal) reason, the need for money. The job is likewise quite easy so its easy money, and its also very profitable, but they face a lot of danger getting caught and put into prison. The consequences vary but the punishment will be severe enough to discourage the seller from selling drugs. Drugs trafficking is already super i llegal by itself, but this crime also relates to many other crimes such as murder, shock and kidnapping. Drug trafficking is punished much more strictly.The first country that is famous for drug trafficking is Afghanistan, famous for its opium. much than 90% of the worlds opium is produced in Afghanistan. This type of drug is commonly traded in the Golden rounded, the name given to the bea of opium production covering three countries, Afghanistan, Iran and Pakistan. The reason why opium trades in Afghanistan is because 70% of Afghanistans government is involved in opium trafficking. More than a dozen governors are part of the process of opiums production and distribution.(April 3, 2009,Addiction Blogger, the good drugs guide)The second country which is famous for drugs is Mexico. Famous for its marijuana and methamphetamine. There are 4 major drug cartels in Mexico, the Gulf, Juarez, Tijuana and the biggest one, the Sinaloa drug cartel owned by Joaquin Guzman, the 701th richest man in the world. These 4 areas are the places where cocaine from America and marijuana from Mexico is distributed and traded. 90% of the cocaine that enters U.S.A goes through Mexico. Mexico is also a main supplier of marijuana and meth for the U.S. These cartels are getting more wealthy and powerful every(prenominal) year. There is also a drug war in Mexico, causing thousands of death between jibe drug cartels. (April 3, 2009,Addiction Blogger, the good drugs guide)The third and last country that is famous for the drug industry that Im going to talk about is Bolivia. Bolivia is ranked third for cocaine production, after Peru and Colombia. This country has 28,900 hectares of its land land cocaine, double what Bolivian law allows. The reason why this is not a worry for the government is because the ongoing president, Evo Morales was the head of the Cocaine growers association before he became the president. Apart from being a top cocaine producer, Bolivia is assuming the role of a major transit point for cocaine shipments from Peru to Brazil. (April 3, 2009,Addiction Blogger, the good drugs guide)Drugs do not have much value alone. If you make them illegal, this gives them a huge price support to drug sellers/traffickers. They make very big profits, and so they need violence and corruption as protection. This is why the gangs are so ruthless. The only way to stop drug trafficking is to legalize it. If drugs are legal, we mountain tax them. The corrupt banks and companies who do not pay tax and support the drug industry would have to start paying tax. then we might catch some criminals. The government spends a lot of money to stop trafficking. If it stop they can use these thousands of millions of dollars for social support. Then not so many people will die of overdoses.

Acute Exacerbation of Bronchial Asthma (AEBA) Case Study

acute accent Exacerbation of Bronchial asthma attack (AEBA) Case resume1.0 lawsuit SUMMARY1.1 Patient information and presenting complaintsSAR, a 54-year-old female with weight of 54kg and height of 160cm was refer ruby to the hospital by her GP due to huskiness of breath which was non relieved by taking inhaler, minimum coughing with xanthous sputum, abdominal pain and mild diarrhoea. Her shortness of breath had been on and off for the ultimo 1 hebdomad and the condition was deteriorating on the day of admission.1.2 relevant historySAR is a non-smoker and a non-alcoholic ho callwife. She has had bronchial asthma since childhood. Her siblings and children were inst all(prenominal) to have family history of bronchial asthma as well. The uncomplaining has been taking inhaled sal just nowamol ccg 1 puff when required as embossment and inhaled budesonide 200g 2puffs bd as preventer for umpteen years. Be placements that, SAR withal has medical history of hypertension, diabetes mellitus and ischaemic amount of money disease (IHD) for 10 years. She has no relevant family history for these illnesses.For the past few years, SAR has been taking rosuva lipid-lowering medication 20mg at night, fenofib site 160mg OD and ezetimibe 10mg OD for dyslipidaemia, gliclazide 60mg BD and rosiglitazone 4mg OD for diabetes mellitus, losartan 50mg OD for hypertension, ticlopidine hydrochloride 250mg OD for prophylaxis against major ischaemic events and famotidine 20mg OD to prevent GI ulceproportionn due to the utilize of anti-platelet agent.1.3 clinical dataOn examination upon admission, severe acute respiratory syndrome blood drive and pulse rate were recorded as 111/80 mmHg and 111bpm respectively. Her respiratory rate was general (16 breaths/min). Her SpO2 measurement was 98% and it showed decreased lofty f humiliated mask. Her DXT blood glucose test revealed that her stochastic blood glucose level was abnormally lavishly (21.6mmol/L). From the debases instau balancenic enquiry, SARs ankles were slightly swollen and her respiratory system showed pro extensiveed minimal bibasal crept and rhonchi. Also, SARs government agency X-ray showed shadowing in the lower zone of her in effect(p) lung. The nephritic do work tests gave results of mettlesome urea and elevated creatinine levels of 16.3mmol/L and 270mol/L respectively. Creatinine headway derived from Cockcroft and Gault pr strikeice is 17ml/min which indicates that the patient has sedate renal impairment. The liver bleed tests revealed a mild decrease in albumin concentration and an increase in the plasma globulin. On the other hand, the haematological tests showed low red blood mobile phone calculate (3.41012/L), low haemoglobin appear (9.4g/dL), mellowed platelet count (410109/L), noble white blood cell count (17.1109/L), high neutrophil count (16.4109/L) and low lymphocyte count (0.5109/L), whereas cardiac marker tests showed abnormally high counts in creatine kinase ( 156IU/L) and lactate dehydrogenase (627IU/L).1.4 Diagnosis and Management thinkBased on the patients symptoms, medical history, physical examinations, and laboratory tests, SAR was diagnosed with degenerative core group failure (CHF), acute exacerbation of bronchial asthma (AEBA) secondary to pneumonia and un secureled diabetes mellitus. Her doctor developed therapeutic plans which included anti-reedy do drugss and antibiotics, and ordered yet investigations such as SpO2 and PEFR. Besides that, her doctor in like manner added diuretic to her collarI therapy and restrict her fluid intake to non to a great extent than 800cc/day. Her lordless diabetes mellitus was under monitor of DXT blood glucose test 4 hourly and she was referred to dietician for diabetic diet counselor-at-law.1.5 Ward practice of medicinethroughout the 3days in hospital, Sarah was being prescribed with medications as listed below1.6 Clinical Progress and Pharmaceutical C atomic number 18 IssuesOn the beginning day of admission, the patients past medication history was sustain by allot patient question and her family instalments were being advised to bring SARs home medication to correspond that the steal medications were continued and prescribed. From the interview, remains was found to be the chief precipitating factor. The patient was on appropriate drugs (nebulised ipratropium vernacularplace 0.5mg and nebulised s alsolelyamol 5mg in normal sa frontier 4 hourly, IV hydrocortisone 100mg stat) for acute prudence of severe asthma as jibe to guidelines and eventually her SOB was relieved.2-3 However, she was prescribed with oral prednisolone at venereal infection as low as 30mg od for acute asthma, it should be suggested to increase prednisolone social disease to 40-50mg daily as according to evidence-based guidelines to chance on maximal make.2-3 A nonher pharmaceutical cargon issue is regarding the patients pathetic inhaler technique. Thus, the pill pusher edu cated and assessed SAR on her inhaler technique since day 1.Appropriate antibiotics indicated for pneumonia which included IV ceftriaxone 2g stat and oral azitromycin 500mg od were initiated upon admission. spontaneous cefuroxime 250mg bd was added to the drug regimen on day 2 after stopping IV ceftriaxone 2g on the first day. therefore, signs of recovery and WBC count were monitored regularly and completion of antibiotic course was ensured. In accessory to that, vaccinations against pneumococcal infection and influenza should be potently recommended in this asthmatic patient.2-3,5-8Co-administration of high dosage IV furosemide (40mg bd) and corticosteroids target increase the happen of hypokalaemia, be hit SAR should be started on potassium chloride 600mg bd which is an appropriate dose for renal insufficiency patient to forefend the authorization risk.1 Besides that, potassium level of SAR should overly be closely monitored during the administration of potassium chlor ide.The doctor added lovastatin 20mg at night to her existing ternion therapy of dyslipidaemia (rosuvastatin, ezetimibe, fenofibrate). Rosuvastatin should be avoided if patients creatinine clearance is less(prenominal) than 30ml/min.1 Due to its same machine of put to death as lovastatin and its contraindication in patient with severe renal impairment, rosuvastatin should be withdrawn from the drug regimen. Practically, a comprehensive lipid visibility of SAR should be established and monitored in order to choose the outdo conspiracy of lipid lowering agents to amend the individual components of lipid profile. crew therapy of ezetimibe and lovastatin is considered much appropriate as co-occurrent wasting disease of fenofibrate and statin may potentiate myopathy. Therefore, fenofibrate and rosuvastatin should non be continued. Liver function should be monitored to avoid the risk of hepatotoxicity.SAR was diagnosed with uncontrolled diabetes mellitus which means her blood glucose level was not adequately controlled with concurrent therapy of gliclazide and rosiglitazone. Her random blood glucose level was fluctuate throughout day 1 (24.9mmol/L, 14.2mmol/L, 7.3mmol/L and 14.7mmol/L). Targets for blood glucose levels should be ideally of importtained between 4 and 7mmol/L pre-meal and On day 2, SAR was feeling much more comfortable and had not complaint of SOB. However, SARs maintenance management of asthma was found to be not conformed to the asthma guidelines.2-3 She was prescribed with unacceptable high dose of corticosteroids (MDI beclomethasone 200g 2 puffs tds) in increase to her current steroid regimen (MDI budesonide 200g 2 puffs bd and oral prednisolone 30mg od). SAR was at emf high risk of experiencing considerable side effects such as diabetes, oesteoporosis, Cushing syndrome with moon face, striae, acne, abdominal distention and other profound effects on musculoskeletal, neuropsychiatric and ophthalmic systems as a result of overdosage of corticosteroids.1 oropharyngeal side effects such as understructuredidiasis are also more common at high dose of inhaled steroids, but can be minimized if the patient rinse the mouth with urine after inhalation. It should be recommended to add the long acting beta agonist (LABA) to the inhaled corticosteroids (ICS) manipulation instead of initiating SAR on high dose steroid (2000g). Combination inhaler of formoterol and budesonide (Symbicort 200/6 Turbohaler 2 puffs bd) should be assumption and control of asthma take on to be continuing assessed.2-3 If LABA is proved to be not effective, addition of fourth agent (leukotriene sense organ antagonist, theophylline or oral beta agonist) can be considered.2 When SAR showed recovery of rowlock intumescence, furosemide was given orally instead of intravenously with turn out frequency and total daily dose.On day 3, SAR was arranged to be fulfill. The pharmacist should review the appropriateness of discharged medication b y checking discharged prescriptions against ward medication chart and ensure all information relevant to primary care referrals are included. In addition to that, the pharmacist should also reiterate and reinforce the importance of patient compliance and reassessment reviews, counsel on indications, doses and possible uncomely effects of each discharged medication, and rechecked SARs inhaler and insulin pellet techniques prior discharged. Asthma education includes advice to avoid trigger factors, including caution with NSAIDs and avoidance of dust exposure. Greater assistance should be paid to inhaler technique as poor technique leading to failure of sermon. SAR should be educated on the subroutine of superlative degree range meters and advised to monitor and record her own PEFR at home. A written personalised asthma action plans should be designed for SAR prior discharged. Diabetic counselling should emphasize on proper insulin injectant techniques and healthy supportst yle modifications. SAR needs to be made awake(predicate) of the signs of hypoglycaemia and hyperglycaemia and how to result to them. Polypharmacy may adversely affect compliance with prescribed drug therapy, thus SAR should be taught not to mix up her medicines by using daily pill box and her family member should also be advised to do her on medicine taking.2.0 PHARMACOLOGICAL BASIS OF DRUG THERAPY2.1 disorder background2.1.1 AsthmaAsthma is a common chronic seditious condition of the lung airline businesss affecting 5-10% of the community and appears to be on the increase.5 It is especially preponderant in children, but also has a high relative incidence in more elderly patient. Asthma mortality rate is approximately 1500 per annum in the UK and costs in the vicinity of 2000 one thousand thousand per year in health and other costs.2-3,6 Symptoms of asthma are recurrent episodes of dyspnoea, chest tightness, cough and wheeze (particularly at night or primeval in the m orning) ca using upd by reversible airway obstruction. terce factors contribute to airway narrowing bronchoconstriction triggered by airway hyperresponsiveness to a wide range of stimuli mucosal swelling/inflammation ca intaked by mast cell, activated T lymphocytes, macrophages, eosinophils degranulation resulting in the flex of inflammatory mediators smooth muscle builder hypertrophy, high-spirited mucus output and airway plugging.7 There is no atomic number 53 satisfactory diagnostic test for all asthmatic patients. The useful tests for airway function abnormalities include the force expiratory glitz (FEV1), force spanking capacity (FVC) and peak expiratory flow rate (PEFR). The diagnosis is based on demonstration of a great than 15% improvement in FEV1 or PEFR following the inhalation of a bronchodilator.2,3,6 Repeated pre and post-bronchodilator readings interpreted at various times of the day is necessary. The FEV1 is usually expressed as the percentage of total volume of air exhaled and is reported as the FEV1/FVC ratio. The ratio is a useful and highly reproducible measure of lungs capabilities. modal(prenominal) individuals can exhale at least 75% of their total capacity in 1 second. A decrease in FEV1/FVC indicates airway obstruction.2.1.2 Community-acquired pneumoniaPneumonia is specify as inflammation of the alveoli as opposed to the bronchi and of infective origin. It presents as an acute illness clinically characterized by the presence of cough, purulent sputum, breathlessness, fever and pleuritic chest pains together with physical signs or radiological changes compatible with consolidation of the lung, a pathological process in which the alveoli are filled with bacteria, white blood cells and inflammatory exudates. The incidence of community acquired pneumonia (CAP) reported annum in UK is 5-11 per 1000 magnanimous population, with mortality rate varies between 5.7% and 14% (patients hospitalised with CAP).8 Streptococcus pneumonia i s the commonest cause, followed by Haemophilus influenzae and Mycoplasma penumoniae.72.1.3 congestive cardiac failureCongestive cardiac failure occurs when the heart fails to nerve an adequate cardiac output to meet the metabolic demands of the body. It is a common condition with poor prognosis (82% of patients dying within 6 years of diagnosis) and affects quality of life in the form of breathlessness, fatigue and oedema.6,7 The common underlying causes of cardiac failure are coronary arterial blood vessel disease and hypertension. Defects in left ventricular filling and/or emptying causes inadequate perfusion, venous congestion and disturbed water and electrolyte balance. In chronic cardiac failure, the maladaptive body compensatory mechanism secondary physiologic effects contribute to the progressive character of the disease.62.1.4 Diabetes mellitusDiabetes mellitus is a heterogenous group of disorders characterised by chronic hyperglycaemia due to relative insulin deficiency a nd/or resistance. It can be classified as either pillow slip 1 or event 2. In font 1, there is an inability to produce insulin and is generally associated with early age onset. Decreased insulin doing and/or reduced insulin sensitivity, maturity onset and strong correlation with obesity are characteristics of Type 2 diabetes. Diabetes affects 1.4 million people in the UK, over 75% of them have Type 2 diabetes.6 It is usually irreversible and if not adequately managed, its late complications can result in reduced life expectancy and considerable uptake of health resources.2.2 Drug pharmacology2.2.1 intercession for asthma2.2.1.1Beta-adrenoceptor agonists (e.g. salbutamol, terbutaline)These short-acting discriminating 2 agonists (SABA) are the first line agents in the management of asthma and are also cognize as relievers. The selective 2 agonists act on 2 aderenoceptors on the bronchial smooth muscle to increase cyclic adenosine monophosphate (cAMP) leading to speedy bronchod ilation and reversal of the bronchospasm associated with the early phase of asthmatic attack.5 Such treatment is very effective in relieving symptoms but does little for the underlying inflammatory nature of the disease. 2 agonists should be initiated when required as prolonged use may lead to receptor down regulation renders them less effective.5-6 Compared to SABA, long-acting beta-adrenoceptor agonists (e.g. salmeterol, formoterol) have dilatory rate of onset and their intrinsic lipophilic properties render them to be retained near the receptor for a prolonged period (12hours), which means that they cause prolonged bronchodilation.2.2.1.2 Muscarinic receptor antagonists (e.g. ipratropium)Ipratropium blocks parasympathetic-mediated bronchoconstriction by competitively captureing muscarinic M3 receptors in bronchial smooth muscle.1,5-6 It has slower onset of action than 2 agonists but last longer.2.2.1.3 Inhaled corticosteroids (ICS e.g. beclomethasone, budesonide) and oralpredni soloneThese agents are used to prevent asthmatic attacks by reducing airway inflmmation. They exert their anti-inflammatory actions via activation of intracellular receptors, leading to altered gene transcription. This results in decreased cytokine production and the synthesis of lipocortin leading to phospholipase A2 inhibition, and the inhibition of leukotriene and prostaglandins.5 moniliasis occurs as common side effects with inhalation and systemic steroid effects such as adrenal suppression and osteoporosis, occur with high dose inhalation or oral dosing.2.2.2 Treatment for pneumoniaAntiobiotic treatment is appropriate with amoxicillin being used as first choice agent for mild, community-acquired infections. Depending on response and the strain of bacteria, other antibiotic agents can be used. devil groups of antibiotics which were given to the patient in this sequel scenario will be discussed here.2.2.2.1 Cephalosporins (e.g. cefuroxime, ceftriaxone)Both ceftriaxone and cef uroxime are broad spectrum bactericidal antibiotics belong to cephalosporins group. They inhibit the synthesis of bacterial cell wall by attach to specific penicillin-binding proteins and ultimately leading to cell lysis. Second generation cefuroxime is beta-lactamase resistant and combat-ready against Gram-negative bacteria such as Haemophilus influenzae and Klebsiella pneumoniae. Being third generation cephalosporin, ceftriaxone display high betalactamase resistance and enhanced operation against Gram-negative pathogens (including Pseudomonas Aeruginosa), but it has relatively poor employment against positive organisms and anaerobes.1,5-62.2.2.2 Maclolides (e.g. azithromycin, erythromycin, clarithromycin)Maclolides prevent protein synthesis by inhibiting the translocation movement of the bacterial ribosome along the mRNA, resulting in bacteriostatic actions. Azithromycin has slightly less activity than erythromycin against Gram-positive organisms but possesses enhanced activi ty against Gram-negative bacteria including Haemophilus influenza.2.2.3 Treatment for chronic cardiac failure2.2.3.1 wave diuretics (e.g. furosemide)Diuretics are the main pose of the management of heart failure and post fast characteristic relief of pulmonic and peripheral oedemia.5,6,9 Loop diuretics are indicated in majority of symptomatic patients and they work by inhibiting Na+/K+/2Cl- transporter in the ascending limb of the cringle of Henle, inhibiting the establishment of a hyperosmotic interstitium and thus reducing the production of concentrated urine in kidney, leading to profuse dieresis.5-62.2.3.2 angiotensin II receptor antagonists (e.g. losartan, candesartan, valsartan)These agents block the action of angiotensin II at the AT1 receptor, which will also reduce the stimulation of aldosterone release. Therefore AT1 receptor antagonists can be used as an alternative in patients paltry from a cough secondary to ACE inhibitors.2.2.4 Treatment for Type II diabetes mel litus2.2.4.1 Sulphonylureas (e.g. Gliclazide, glibenclamide, glipizide)The sulphonylureas have two main actions increase basal and stimulated insulin discrimination and reduce peripheral resistance to insulin action. They bind to receptors associated with voltage low-level KATP channels on the surface of pancreatic beta cell, causing channel closure which facilitates calcium main course into the cell and leads to insulin release. Sulphonylureas are considered in Type II diabetes patients who are intolerant to metformin, not contraindicated and not overweight.2.2.4.2 Thiazolidinediones (e.g. rosiglitazone, pioglitazone)These naked agents are insulin sensitisers which act as nuclear peroxisome proliferator-activated receptor-gamma (PPAR-) agonist. They work by enhancing insulin action and promoting glucose utilization in peripheral tissue, and so reduce insulin resistance. Thiazolidinediones is known to be associated with oedema and increased cardiovascular risks, therefore these agents should be avoided in patients with heart failure.1,4,63.0 EVIDENCE FORTREATMENT OF CONDITIONS3.1 Asthma3.1.1 cause for the use of oral prednisolone and IV hydrocortisone in themanagement of AEBAThere are raise evidences suggesting that systemic corticosteroids effectively influence the airway oedema and mucus plugging associated with acute asthma by suppressing the components of inflammation, including the release of adhesion molecules, airway permeability and production of cytokines.10-12 A randomized foot race involving 88 patients (aged 15-70years) with AEBA reported the important efficacy of oral prednisolone (40mg daily for 7 days) in improving FEV1 and FVC at values of 6845.3% and 53.446.5% respectively (P=0.04) in prednisolone-treated group.13 A Cochrane meta-analysis involving six campaigns recruiting 374 acute asthmatic exacerbation patients determined the early use of systemic corticosteroids importantly reduced the number of relapses to additional care, hospi talisation and use of short-acting 2-agonist without increasing side effects, disregardless of the routes of administration studied (oral/intramuscular/intravenous) and choice of agents.143.1.2 turn out for the use of inhaled ipratropium bromide in the management ofAEBAA double-blind, randomized controlled tribulations recruiting 180 patients with AEBA admitted to emergency department showed that ipratropium had beneficial effects in improving pulmonary function, with a 20.5% increment in PEF (p=0.02) and a 48.1% greater improvements in FEV1 (p=0.0001) compared to those given 2-agonists alone. Ipratropium also present a 49% reduction in the risk of hospital admission.15 A more recent meta-analysis incorporating thirty-two double-blind, randomised controlled trials including 3611 patients with reclaim to severe exacerbations of asthma also showed the benefits of combination treatment of nebuliser 2-agonists and anti-muscarinic in reducing hospital admissions (relative risk 0.68, p=0.002) and in producing a significant increase in lung function parameters in AEBA patients (standard mean difference -0.36, p=0.00001).16 another(prenominal) pooled analysis of three multicenter, double-blind, randomised controlled studies also showed that combination therapy of ipratropium bromide and salbutamol for the treatment of AEBA had decreased risk of the need for additional treatment (relative risk=0.92), asthma exacerbation (relative risk=0.84) and hospitalisation (relative risk=0.80).173.1.3 Evidence for addition of LABA to ICS in the management of asthmaSymbicort Maintenance and Reliever Therapy ( capable) studies demonstrated the combined use of formoterol/budesonide contributes to a greater reduction in risks of exacerbations, improved lungs performance and better control of asthma than high dose of ICS with SABA.18-22 These studies also reported the advantage of this approach in terms of patient compliance as it allows the use of single inhaler for both rescue and controller therapy, and reductions in health care costs.18-22 A large double-blind, randomised trial reported that there was a significant 21-39% reduction of severe exacerbations in asthmatic patients treated with SMART therapy compared with high dose budesonide electropositive SABA.23 A meta-analysis involving 30 trials with 9509 patients showed that the use of combination inhaler (formoterol/beclomethasone 400mcg) resulted in greater improvement in FEV1, in the use of rescue SABA and in the symptom-free days compared to a higher dose of ICS (800-1000mcg/day).24 Another double-blind randomised trial investigating the effect of combination budesonide and formoterol as reliever therapy for 3394 patients who were assigned budesonide plus formoterol for maintenance therapy showed that the time to first severe exacerbation was importantly longer in as postulate budesonide/formoterol group compared to as demand terbutaline group (p=0.0051). The other purpose of the theatre is the significant lower rate of severe exacerbation for as needed budesonide/formoterol versus as needed terbutaline group (0.19 vs 0.37, p3.2 Community-acquired pneumonia3.2.1 Evidence use of combination therapy of second and/or third generationcephalosporins and macrolide in the management of pneumoniaA multicenter, randomised trial investigated the efficacy of IV ceftriaxone 2g for 1 day followed by oral cefuroxime 500mg bd in the heavy(a) pneumonia treatment. The sequential therapy in combination with a macrolide achieved 90% of clinical success, 85% of overall bacteriologic clearance with 100% eradication of S.pneumoniae after 5-7days of treatment.27 An open label, prospective study involving 603 patients demonstrated that adding azithromycin (500mg od for 3days) to IV ceftriaxone 1g/day in the treatment of community-acquired pneumonia resulted in shorter hospital stay (7.3days vs 9.4days) and a significant lower mortality rate (3.7% vs 7.3%) than adding clarithromycin.28 Lack of ra ndomisation and no blinding of evaluators may become the major limitations of this study provided the effectiveness of macrolide in addition to cephalosporins empirical therapy in treating pneumonia is unquestionable.3.3 continuing heart failure3.3.1 Evidence use of loop diuretic in the management of chronic heart failure (CHF)A meta-analysis of 18 randomised controlled trials concluded that diuretics significantly lowered the mortality rate (odds ratio (OR) 0.25, P=0.03) and reduced hospital admissions for downslope heart failure (OR 0.31, P=0.001) in patients with CHF compared to placebo.29 Compared to active control, diuretics significantly improved exercise capacity in CHF patients. (OR 0.37, P=0.007).29 A recent review reappraisaled the role of loop diuretics as first line treatment for CHF concluded that existing evidence of association of loop diuretics with rapid symptomatic relief and decreased mortality supporting the essential role of diuretics in the management of CHF .303.3.2 Evidence use of angiotensin II receptor antagonists in the management of CHFThe Losartan Heart Failure Survival Study ELITE II, a double-blind, randomised controlled trial involved 3152 patients with NYHA class II-IV heart failure and ejection compute 40% reported that there were no significant differences between losartan and enalapril groups in all cause mortality (11.7 vs 10.4% mean mortality rate). However, losartanAcute Exacerbation of Bronchial Asthma (AEBA) Case StudyAcute Exacerbation of Bronchial Asthma (AEBA) Case Study1.0 CASE SUMMARY1.1 Patient information and presenting complaintsSAR, a 54-year-old female with weight of 54kg and height of 160cm was referred to the hospital by her GP due to shortness of breath which was not relieved by taking inhaler, minimum cough with yellowish sputum, abdominal pain and mild diarrhoea. Her shortness of breath had been on and off for the past 1 week and the condition was deteriorating on the day of admission.1.2 Relevant hist orySAR is a non-smoker and a non-alcoholic housewife. She has had bronchial asthma since childhood. Her siblings and children were found to have family history of bronchial asthma as well. The patient has been taking inhaled salbutamol 200g 1 puff when required as reliever and inhaled budesonide 200g 2puffs bd as preventer for umpteen years. Besides that, SAR also has medical history of hypertension, diabetes mellitus and ischaemic heart disease (IHD) for 10 years. She has no relevant family history for these illnesses.For the past few years, SAR has been taking rosuvastatin 20mg at night, fenofibrate 160mg OD and ezetimibe 10mg OD for dyslipidaemia, gliclazide 60mg BD and rosiglitazone 4mg OD for diabetes mellitus, losartan 50mg OD for hypertension, ticlopidine hydrochloride 250mg OD for prophylaxis against major ischaemic events and famotidine 20mg OD to prevent gastrointestinal ulceration due to the use of anti-platelet agent.1.3 Clinical dataOn examination upon admission, SARs b lood pressure and pulse rate were recorded as 111/80 mmHg and 111bpm respectively. Her respiratory rate was normal (16 breaths/min). Her SpO2 measurement was 98% and it showed decreased high flow mask. Her DXT blood glucose test revealed that her random blood glucose level was abnormally high (21.6mmol/L). From the doctors systemic enquiry, SARs ankles were slightly swollen and her respiratory system showed prolonged minimal bibasal crept and rhonchi. Also, SARs chest X-ray showed shadowing in the lower zone of her right lung. The renal function tests gave results of high urea and elevated creatinine levels of 16.3mmol/L and 270mol/L respectively. Creatinine clearance derived from Cockcroft and Gault formula is 17ml/min which indicates that the patient has severe renal impairment. The liver function tests revealed a mild decrease in albumin concentration and an increase in the plasma globulin. On the other hand, the haematological tests showed low red blood cell count (3.41012/L), l ow haemoglobin count (9.4g/dL), high platelet count (410109/L), high white blood cell count (17.1109/L), high neutrophil count (16.4109/L) and low lymphocyte count (0.5109/L), whereas cardiac marker tests showed abnormally high counts in creatine kinase (156IU/L) and lactate dehydrogenase (627IU/L).1.4 Diagnosis and Management PlanBased on the patients symptoms, medical history, physical examinations, and laboratory tests, SAR was diagnosed with chronic heart failure (CHF), acute exacerbation of bronchial asthma (AEBA) secondary to pneumonia and uncontrolled diabetes mellitus. Her doctor developed therapeutic plans which included anti-asthmatic drugs and antibiotics, and ordered further investigations such as SpO2 and PEFR. Besides that, her doctor also added diuretic to her ACEI therapy and restrict her fluid intake to not more than 800cc/day. Her uncontrolled diabetes mellitus was under monitoring of DXT blood glucose test 4 hourly and she was referred to dietician for diabetic di et counselling.1.5 Ward medicationThroughout the 3days in hospital, Sarah was being prescribed with medications as listed below1.6 Clinical Progress and Pharmaceutical Care IssuesOn the first day of admission, the patients past medication history was confirmed by appropriate patient interview and her family members were being advised to bring SARs home medication to ensure that the appropriate medications were continued and prescribed. From the interview, dust was found to be the chief precipitating factor. The patient was on appropriate drugs (nebulised ipratropium bromide 0.5mg and nebulised salbutamol 5mg in normal saline 4 hourly, IV hydrocortisone 100mg stat) for acute management of severe asthma as according to guidelines and eventually her SOB was relieved.2-3 However, she was prescribed with oral prednisolone at dose as low as 30mg od for acute asthma, it should be suggested to increase prednisolone dose to 40-50mg daily as according to evidence-based guidelines to achieve m aximal effects.2-3 Another pharmaceutical care issue is regarding the patients poor inhaler technique. Thus, the pharmacist educated and assessed SAR on her inhaler technique since day 1.Appropriate antibiotics indicated for pneumonia which included IV ceftriaxone 2g stat and oral azitromycin 500mg od were initiated upon admission. Oral cefuroxime 250mg bd was added to the drug regimen on day 2 after stopping IV ceftriaxone 2g on the first day. Therefore, signs of recovery and WBC count were monitored regularly and completion of antibiotic course was ensured. In addition to that, vaccinations against pneumococcal infection and influenza should be strongly recommended in this asthmatic patient.2-3,5-8Co-administration of high dose IV furosemide (40mg bd) and corticosteroids can increase the risk of hypokalaemia, therefore SAR should be started on potassium chloride 600mg bd which is an appropriate dose for renal insufficiency patient to avoid the potential risk.1 Besides that, potass ium level of SAR should also be closely monitored during the administration of potassium chloride.The doctor added lovastatin 20mg at night to her existing triple therapy of dyslipidaemia (rosuvastatin, ezetimibe, fenofibrate). Rosuvastatin should be avoided if patients creatinine clearance is less than 30ml/min.1 Due to its same mechanism of action as lovastatin and its contraindication in patient with severe renal impairment, rosuvastatin should be withdrawn from the drug regimen. Practically, a comprehensive lipid profile of SAR should be established and monitored in order to choose the best combination of lipid lowering agents to improve the individual components of lipid profile. Combination therapy of ezetimibe and lovastatin is considered more appropriate as concurrent use of fenofibrate and statin may potentiate myopathy. Therefore, fenofibrate and rosuvastatin should not be continued. Liver function should be monitored to avoid the risk of hepatotoxicity.SAR was diagnosed w ith uncontrolled diabetes mellitus which means her blood glucose level was not adequately controlled with concurrent therapy of gliclazide and rosiglitazone. Her random blood glucose level was fluctuating throughout day 1 (24.9mmol/L, 14.2mmol/L, 7.3mmol/L and 14.7mmol/L). Targets for blood glucose levels should be ideally maintained between 4 and 7mmol/L pre-meal and On day 2, SAR was feeling much more comfortable and had not complaint of SOB. However, SARs maintenance management of asthma was found to be not conformed to the asthma guidelines.2-3 She was prescribed with unacceptable high dose of corticosteroids (MDI beclomethasone 200g 2 puffs tds) in addition to her current steroid regimen (MDI budesonide 200g 2 puffs bd and oral prednisolone 30mg od). SAR was at potential high risk of experiencing considerable side effects such as diabetes, oesteoporosis, Cushing syndrome with moon face, striae, acne, abdominal distension and other profound effects on musculoskeletal, neuropsych iatric and ophthalmic systems as a result of overdosage of corticosteroids.1 Oropharyngeal side effects such as candidiasis are also more common at high dose of inhaled steroids, but can be minimized if the patient rinse the mouth with water after inhalation. It should be recommended to add the long acting beta agonist (LABA) to the inhaled corticosteroids (ICS) treatment instead of initiating SAR on high dose steroid (2000g). Combination inhaler of formoterol and budesonide (Symbicort 200/6 Turbohaler 2 puffs bd) should be given and control of asthma need to be continuing assessed.2-3 If LABA is proved to be not effective, addition of 4th agent (leukotriene receptor antagonist, theophylline or oral beta agonist) can be considered.2 When SAR showed recovery of leg swelling, furosemide was given orally instead of intravenously with reduced frequency and total daily dose.On day 3, SAR was arranged to be discharged. The pharmacist should review the appropriateness of discharged medicat ion by checking discharged prescriptions against ward medication chart and ensure all information relevant to primary care referrals are included. In addition to that, the pharmacist should also reiterate and reinforce the importance of patient compliance and follow-up reviews, counsel on indications, doses and possible adverse effects of each discharged medication, and rechecked SARs inhaler and insulin injection techniques prior discharged. Asthma education includes advice to avoid trigger factors, including caution with NSAIDs and avoidance of dust exposure. Greater attention should be paid to inhaler technique as poor technique leading to failure of treatment. SAR should be educated on the use of peak flow meters and advised to monitor and record her own PEFR at home. A written personalised asthma action plans should be designed for SAR prior discharged. Diabetic counselling should emphasize on proper insulin injection techniques and healthy lifestyle modifications. SAR needs to be made aware of the signs of hypoglycaemia and hyperglycaemia and how to response to them. Polypharmacy may adversely affect compliance with prescribed drug therapy, therefore SAR should be taught not to mix up her medicines by using daily pill box and her family member should also be advised to supervise her on medicine taking.2.0 PHARMACOLOGICAL BASIS OF DRUG THERAPY2.1 Disease background2.1.1 AsthmaAsthma is a common chronic inflammatory condition of the lung airways affecting 5-10% of the population and appears to be on the increase.5 It is especially prevalent in children, but also has a high incidence in more elderly patient. Asthma mortality is approximately 1500 per annum in the UK and costs in the region of 2000 million per year in health and other costs.2-3,6 Symptoms of asthma are recurrent episodes of dyspnoea, chest tightness, cough and wheeze (particularly at night or early in the morning) caused by reversible airway obstruction. Three factors contribute to airway na rrowing bronchoconstriction triggered by airway hyperresponsiveness to a wide range of stimuli mucosal swelling/inflammation caused by mast cell, activated T lymphocytes, macrophages, eosinophils degranulation resulting in the release of inflammatory mediators smooth muscle hypertrophy, excessive mucus production and airway plugging.7 There is no single satisfactory diagnostic test for all asthmatic patients. The useful tests for airway function abnormalities include the force expiratory volume (FEV1), force vital capacity (FVC) and peak expiratory flow rate (PEFR). The diagnosis is based on demonstration of a greater than 15% improvement in FEV1 or PEFR following the inhalation of a bronchodilator.2,3,6 Repeated pre and post-bronchodilator readings taken at various times of the day is necessary. The FEV1 is usually expressed as the percentage of total volume of air exhaled and is reported as the FEV1/FVC ratio. The ratio is a useful and highly reproducible measure of lungs capabili ties. Normal individuals can exhale at least 75% of their total capacity in 1 second. A decrease in FEV1/FVC indicates airway obstruction.2.1.2 Community-acquired pneumoniaPneumonia is defined as inflammation of the alveoli as opposed to the bronchi and of infective origin. It presents as an acute illness clinically characterized by the presence of cough, purulent sputum, breathlessness, fever and pleuritic chest pains together with physical signs or radiological changes compatible with consolidation of the lung, a pathological process in which the alveoli are filled with bacteria, white blood cells and inflammatory exudates. The incidence of community acquired pneumonia (CAP) reported annum in UK is 5-11 per 1000 adult population, with mortality rate varies between 5.7% and 14% (patients hospitalised with CAP).8 Streptococcus pneumonia is the commonest cause, followed by Haemophilus influenzae and Mycoplasma penumoniae.72.1.3 Congestive cardiac failureCongestive cardiac failure occ urs when the heart fails to pump an adequate cardiac output to meet the metabolic demands of the body. It is a common condition with poor prognosis (82% of patients dying within 6 years of diagnosis) and affects quality of life in the form of breathlessness, fatigue and oedema.6,7 The common underlying causes of cardiac failure are coronary artery disease and hypertension. Defects in left ventricular filling and/or emptying causes inadequate perfusion, venous congestion and disturbed water and electrolyte balance. In chronic cardiac failure, the maladaptive body compensatory mechanism secondary physiological effects contribute to the progressive nature of the disease.62.1.4 Diabetes mellitusDiabetes mellitus is a heterogenous group of disorders characterised by chronic hyperglycaemia due to relative insulin deficiency and/or resistance. It can be classified as either Type 1 or Type 2. In Type 1, there is an inability to produce insulin and is generally associated with early age onse t. Decreased insulin production and/or reduced insulin sensitivity, maturity onset and strong correlation with obesity are characteristics of Type 2 diabetes. Diabetes affects 1.4 million people in the UK, over 75% of them have Type 2 diabetes.6 It is usually irreversible and if not adequately managed, its late complications can result in reduced life expectancy and considerable uptake of health resources.2.2 Drug pharmacology2.2.1 Treatment for asthma2.2.1.1Beta-adrenoceptor agonists (e.g. salbutamol, terbutaline)These short-acting selective 2 agonists (SABA) are the first line agents in the management of asthma and are also known as relievers. The selective 2 agonists act on 2 aderenoceptors on the bronchial smooth muscle to increase cyclic adenosine monophosphate (cAMP) leading to rapid bronchodilation and reversal of the bronchospasm associated with the early phase of asthmatic attack.5 Such treatment is very effective in relieving symptoms but does little for the underlying inf lammatory nature of the disease. 2 agonists should be initiated when required as prolonged use may lead to receptor down regulation renders them less effective.5-6 Compared to SABA, long-acting beta-adrenoceptor agonists (e.g. salmeterol, formoterol) have slower rate of onset and their intrinsic lipophilic properties render them to be retained near the receptor for a prolonged period (12hours), which means that they cause prolonged bronchodilation.2.2.1.2 Muscarinic receptor antagonists (e.g. ipratropium)Ipratropium blocks parasympathetic-mediated bronchoconstriction by competitively inhibiting muscarinic M3 receptors in bronchial smooth muscle.1,5-6 It has slower onset of action than 2 agonists but last longer.2.2.1.3 Inhaled corticosteroids (ICS e.g. beclomethasone, budesonide) and oralprednisoloneThese agents are used to prevent asthmatic attacks by reducing airway inflmmation. They exert their anti-inflammatory actions via activation of intracellular receptors, leading to altere d gene transcription. This results in decreased cytokine production and the synthesis of lipocortin leading to phospholipase A2 inhibition, and the inhibition of leukotriene and prostaglandins.5 Candidiasis occurs as common side effects with inhalation and systemic steroid effects such as adrenal suppression and osteoporosis, occur with high dose inhalation or oral dosing.2.2.2 Treatment for pneumoniaAntiobiotic treatment is appropriate with amoxicillin being used as first choice agent for mild, community-acquired infections. Depending on response and the strain of bacteria, other antibiotic agents can be used. Two groups of antibiotics which were given to the patient in this case scenario will be discussed here.2.2.2.1 Cephalosporins (e.g. cefuroxime, ceftriaxone)Both ceftriaxone and cefuroxime are broad spectrum bactericidal antibiotics belong to cephalosporins group. They inhibit the synthesis of bacterial cell wall by binding to specific penicillin-binding proteins and ultimatel y leading to cell lysis. Second generation cefuroxime is beta-lactamase resistant and active against Gram-negative bacteria such as Haemophilus influenzae and Klebsiella pneumoniae. Being third generation cephalosporin, ceftriaxone display high betalactamase resistance and enhanced activity against Gram-negative pathogens (including Pseudomonas Aeruginosa), but it has relatively poor activity against Gram-positive organisms and anaerobes.1,5-62.2.2.2 Maclolides (e.g. azithromycin, erythromycin, clarithromycin)Maclolides prevent protein synthesis by inhibiting the translocation movement of the bacterial ribosome along the mRNA, resulting in bacteriostatic actions. Azithromycin has slightly less activity than erythromycin against Gram-positive organisms but possesses enhanced activity against Gram-negative bacteria including Haemophilus influenza.2.2.3 Treatment for chronic cardiac failure2.2.3.1 Loop diuretics (e.g. furosemide)Diuretics are the mainstay of the management of heart fai lure and provide rapid symptomatic relief of pulmonary and peripheral oedemia.5,6,9 Loop diuretics are indicated in majority of symptomatic patients and they work by inhibiting Na+/K+/2Cl- transporter in the ascending limb of the loop of Henle, inhibiting the establishment of a hyperosmotic interstitium and thus reducing the production of concentrated urine in kidney, leading to profuse dieresis.5-62.2.3.2 Angiotensin II receptor antagonists (e.g. losartan, candesartan, valsartan)These agents block the action of angiotensin II at the AT1 receptor, which will also reduce the stimulation of aldosterone release. Therefore AT1 receptor antagonists can be used as an alternative in patients suffering from a cough secondary to ACE inhibitors.2.2.4 Treatment for Type II diabetes mellitus2.2.4.1 Sulphonylureas (e.g. Gliclazide, glibenclamide, glipizide)The sulphonylureas have two main actions increase basal and stimulated insulin secretion and reduce peripheral resistance to insulin action. They bind to receptors associated with voltage dependent KATP channels on the surface of pancreatic beta cell, causing channel closure which facilitates calcium entry into the cell and leads to insulin release. Sulphonylureas are considered in Type II diabetes patients who are intolerant to metformin, not contraindicated and not overweight.2.2.4.2 Thiazolidinediones (e.g. rosiglitazone, pioglitazone)These new agents are insulin sensitisers which act as nuclear peroxisome proliferator-activated receptor-gamma (PPAR-) agonist. They work by enhancing insulin action and promoting glucose utilization in peripheral tissue, and so reduce insulin resistance. Thiazolidinediones is known to be associated with oedema and increased cardiovascular risks, therefore these agents should be avoided in patients with heart failure.1,4,63.0 EVIDENCE FORTREATMENT OF CONDITIONS3.1 Asthma3.1.1 Evidence for the use of oral prednisolone and IV hydrocortisone in themanagement of AEBAThere are mounting eviden ces suggesting that systemic corticosteroids effectively influence the airway oedema and mucus plugging associated with acute asthma by suppressing the components of inflammation, including the release of adhesion molecules, airway permeability and production of cytokines.10-12 A randomised trial involving 88 patients (aged 15-70years) with AEBA reported the significant efficacy of oral prednisolone (40mg daily for 7 days) in improving FEV1 and FVC at values of 6845.3% and 53.446.5% respectively (P=0.04) in prednisolone-treated group.13 A Cochrane meta-analysis involving six trials recruiting 374 acute asthmatic exacerbation patients determined the early use of systemic corticosteroids significantly reduced the number of relapses to additional care, hospitalisation and use of short-acting 2-agonist without increasing side effects, regardless of the routes of administration studied (oral/intramuscular/intravenous) and choice of agents.143.1.2 Evidence for the use of inhaled ipratropi um bromide in the management ofAEBAA double-blind, randomised controlled trials recruiting 180 patients with AEBA admitted to emergency department showed that ipratropium had beneficial effects in improving pulmonary function, with a 20.5% increment in PEF (p=0.02) and a 48.1% greater improvements in FEV1 (p=0.0001) compared to those given 2-agonists alone. Ipratropium also demonstrated a 49% reduction in the risk of hospital admission.15 A more recent meta-analysis incorporating thirty-two double-blind, randomised controlled trials including 3611 patients with moderate to severe exacerbations of asthma also showed the benefits of combination treatment of nebuliser 2-agonists and anti-muscarinic in reducing hospital admissions (relative risk 0.68,p=0.002) and in producing a significant increase in lung function parameters in AEBA patients (standard mean difference -0.36, p=0.00001).16 Another pooled analysis of three multicenter, double-blind, randomised controlled studies also show ed that combination therapy of ipratropium bromide and salbutamol for the treatment of AEBA had decreased risk of the need for additional treatment (relative risk=0.92), asthma exacerbation (relative risk=0.84) and hospitalisation (relative risk=0.80).173.1.3 Evidence for addition of LABA to ICS in the management of asthmaSymbicort Maintenance and Reliever Therapy (SMART) studies demonstrated the combined use of formoterol/budesonide contributes to a greater reduction in risks of exacerbations, improved lungs performance and better control of asthma than high dose of ICS with SABA.18-22 These studies also reported the advantage of this approach in terms of patient compliance as it allows the use of single inhaler for both rescue and controller therapy, and reductions in healthcare costs.18-22 A large double-blind, randomised trial reported that there was a significant 21-39% reduction of severe exacerbations in asthmatic patients treated with SMART therapy compared with high dose bu desonide plus SABA.23 A meta-analysis involving 30 trials with 9509 patients showed that the use of combination inhaler (formoterol/beclomethasone 400mcg) resulted in greater improvement in FEV1, in the use of rescue SABA and in the symptom-free days compared to a higher dose of ICS (800-1000mcg/day).24 Another double-blind randomised trial investigating the effect of combination budesonide and formoterol as reliever therapy for 3394 patients who were assigned budesonide plus formoterol for maintenance therapy showed that the time to first severe exacerbation was significantly longer in as needed budesonide/formoterol group compared to as needed terbutaline group (p=0.0051). The other finding of the study is the significant lower rate of severe exacerbation for as needed budesonide/formoterol versus as needed terbutaline group (0.19 vs 0.37, p3.2 Community-acquired pneumonia3.2.1 Evidence use of combination therapy of second and/or third generationcephalosporins and macrolide in the management of pneumoniaA multicenter, randomised trial investigated the efficacy of IV ceftriaxone 2g for 1 day followed by oral cefuroxime 500mg bd in the adult pneumonia treatment. The sequential therapy in combination with a macrolide achieved 90% of clinical success, 85% of overall bacteriologic clearance with 100% eradication of S.pneumoniae after 5-7days of treatment.27 An open label, prospective study involving 603 patients demonstrated that adding azithromycin (500mg od for 3days) to IV ceftriaxone 1g/day in the treatment of community-acquired pneumonia resulted in shorter hospital stay (7.3days vs 9.4days) and a significant lower mortality rate (3.7% vs 7.3%) than adding clarithromycin.28 Lack of randomisation and no blinding of evaluators may become the major limitations of this study however the effectiveness of macrolide in addition to cephalosporins empirical therapy in treating pneumonia is unquestionable.3.3 Chronic heart failure3.3.1 Evidence use of loop diuretic in the management of chronic heart failure (CHF)A meta-analysis of 18 randomised controlled trials concluded that diuretics significantly lowered the mortality rate (odds ratio (OR) 0.25, P=0.03) and reduced hospital admissions for worsening heart failure (OR 0.31, P=0.001) in patients with CHF compared to placebo.29 Compared to active control, diuretics significantly improved exercise capacity in CHF patients. (OR 0.37, P=0.007).29 A recent review reappraisaled the role of loop diuretics as first line treatment for CHF concluded that existing evidence of association of loop diuretics with rapid symptomatic relief and decreased mortality supporting the essential role of diuretics in the management of CHF.303.3.2 Evidence use of angiotensin II receptor antagonists in the management of CHFThe Losartan Heart Failure Survival Study ELITE II, a double-blind, randomised controlled trial involved 3152 patients with NYHA class II-IV heart failure and ejection fraction 40% reported that there were no significant differences between losartan and enalapril groups in all cause mortality (11.7 vs 10.4% mean mortality rate). However, losartan

Chronic Fatigue Syndrome Health And Social Care Essay

Chronic Fatigue Syndrome Health And Social fretfulness EssayChronic Fatigue Syndrome (CFS) is an incapacitating multifarious discommode that renders the victim fatigued for hankerer currents. It has been realised that this kind of rowdyism is not solved by bed rest and is usually aggravated by mental and physical activities. People suffering from CFS have been seen to be unable to perform tasks that they were to do it well before the illness. The most noticeable features of this disarray entangle pain sensation in the muscle, weakness, impaired memory, and poor concentration. In addition, the victims are generally weak and few of them show evidences of insomnia (Bell, 1995). This disorder may persist for a long period. Diagnostic tests have not been able to clearly point expose the contingent causes of this disorder. This is because of the fact that some illnesses have symptoms related to this disorder and we dealnot confine those symptoms to this event disorder alone (Verrillo, Gellman, 1988). Any infection to the tolerant system taken to be the possible cause of CFS and microorganism play a major government agency in causing it. Any form of immune-suppression is also seen a factor that compromises an someone to this disorder (Fisher et al 1997).IntroductionAbsence of specific diagnostic characteristic features of CFS, a criterion has been formulated that helps physicians in spy the disorder. One of the most commonly use criteria is the one that requires the victim to show the possible symptoms for a period of more than sextet months. This is because the physician will have had enough time to diagnose other possible ailments and on that pointby reaching the point of excluding the disorder much soft (Murdoch Denz-Penhey, 2002). Additionally, the patient is expected to show any of the four symptoms, which may complicate frequently occurring sore throat, muscle pain, impairment of the patient to the extent of modify the normal economic a ctivities of the patient and unrefreshing sleep (Lisman Dougherty, 2007). Other symptoms that seat be used take pain in all the joints of the body, severe vexation that recurs in some pattern, and post-exertional depression. The purpose of this theatre is to find out some of the predisposing factors for this disorder. Additionally, the causes, symptoms, airs of diagnosing this disease will be identified (Moss-Morris Petrie, 2000). Suggested interventions will be provided so that the healthy population can know more on how to avoid this disorder.Various studies have been carried with the function of trying to find ways of finding definite symptoms for this disorder. One of these studies was carried out in 1993 with the intention of up on the ways of diagnosing the disease as it had been decided earlier in 1988. The aim of the study in 1993 was to reinvent new strategies of that can lead to faster diagnosis of the disorder (Lisman Dougherty, 2007). Some of the recommendation s from the researches at that time was to classify the fatigue to different levels as can be depicted by the victims. Those with less(prenominal) than six months infection for instance were classified as having chronic fatigue spell those with more than six months symptoms were classified as having relapsing fatigue. The patients could also be classified as having gradual or sudden fatigue, among other distinguishing parameters (Fisher et al 1997).A number of predisposing factors have been identified as it considers to CFS. It is also important to utterance the greater portion of the American population have similar symptoms related to this disorder but cannot be classified as CFS (Meirleir Patarca-Montero, 2000). Some of the factors that promote the risks of having the disorder include age, gender, and socioeconomic groups. It has been effectuate that CFS affects women at a amplyer rate four times than men (Voncannon, 2002). In addition, respective(prenominal)s with the age between 40 to 50 years have been found to be having CFS. It is also important to note that children can be found with the disorder especially in their teen years and this show that the disease affects any age (Fisher et al 1997).Some of the important symptoms for CFS include prolonged fatigue that extends to a period over six months. such a fatigue is not reduced by any amount of rest. Other notable characteristics of this disorder include post-exertional disquiet, pain in the muscles, pain in the multiple joints, lack of concentration, sleep that does not refresh, and headache that comes with some pattern (Englebienne, 2002). Additionally, the throat the regularly becomes sore and presence swellings in the lymph, chronic cough, nausea, weight loss, scramble sensations, and jaw pain. Psychological problems, shortness of breath, and chest pain are also important symptoms of the disease (Moss-Morris Petrie, 2000).A number of factors makes it hard for physicians to diagnose CFS and includes the lack of laboratory diagnostic technique or biomarkers. Other reasons include the fact that fatigue is a common symptom for all other illnesses, patients do not come out sick while the pattern of illness is not constant. This has led to the low level of diagnosis for this particular disorder. Exclusion technique is the best method to diagnose CFs disorder due to lack blood tests or scans for the brain (Leonard, 1997). Diagnosis has to be carried out for period extending six months where the patient can report equal evidence of being constantly tired. The physician has to take enough history of the illness of the patient who may be suspected of having CFS (Royal College of Physicians of London, 1997). Medical history has to be reviewed also in order to identify and come up out the possible illnesses that might have been the cause of the fatigue. This is done until CFS is ultimately pointed out. The physician can ulterior develop a treatment for the patient. It is als o possible for patients to diagnose themselves by eliminating the possible causes of the illnesses just standardized physician (Englebienne, 2002).The process of managing the chronic CFS is very tricky just like the diagnosis itself because of the variety of the symptoms. Currently, there is no drug or cure for this disorder and such factors complicate the treatment process (Demitrack Abbey, 1999). This factor that the best way of managing it by developing an individualized treatment design for every patient. The best plan comprises a collection of therapies each aimed at managing the symptoms shown by the patient. Input by range medical master key experts is the best solution and when this is coupled with the treatment of other illnesses then the disorder can be managed easily (Lisman Dougherty, 2007). Living with CFS is very tricky and having the chronic type can result in significant devastating effects on the victim. Some of the challenges facing the success of treating CF S include the change and predictability of the symptoms, variations in the stamina that interferes with somebody elses activities, altered memory, loss of independence, and potential impacts on decreased sexual activities among couples (Bell, 1995).Some of the treatment options that is unattached for CFS and they include professional counseling, cognitive behavioral therapy, and symptomatic treatment. Additionally, pharmacologic therapy, sleep hygiene, pain therapy, and use of antidepressants can help in suppressing the effects of CFS (Demitrack Abbey, 1999). It is however important to keep in mind the fact that the disorder affects individuals in a different way. Some people may be paralyzed for good while others can recover fully from the disorder (Verrillo, Gellman, 1988). It is also hard to obtain accurate results as it regard the number of individuals who have recovered from CFS. Natural remedies can also be employed to boost an individuals body energy thereby suppressing ch ronic fatigue (Leonard, 1997).Variety of products can be used and they include magnesium injection of muscles with low red blood cells magnesium, taking meals rich in seek oil, and melatonin. Other remedies that have show positive response in suppressing the effects of chronic fatigue syndrome include taking of melatonin, ribose, and NADH rich food (Patarca-Montero, 1999). The studies carried on the foods are however, limited and no accurate data can be easily found. Some of the drugs used to counter the effects of chronic fatigue disorder include the use of corticosteroids, and cholinesterase inhibitors like the galantamine (Fisher et al 1997). Methylphenidate like Ritalin, which is a psychostimulant that is used to increase the levels of neurotransmitters thereby portion individuals with attention-deficit disorder, can be used. Some lifestyle techniques can also be employed to counter this disorder and this includes developing a plan that will help is stress reduction, ensuring that the patient gets enough sleep, exercising regularly and maintaining healthy lifestyle. The lifestyle includes eating balanced diets, drinking plenty of fluids, limiting caffeine intake, and participating in aerobics (Meirleir Mcgregor, 2003).ConclusionChronic fatigue syndrome is more than just being tired because the affected individual is interfered from performing their daily activities in a normal way. Other individuals have been forced to quit high paying jobs, several disabled and others bedridden. The nature of this illness shows that it is even hard to diagnose it (Bell, 1995). Trial and fallacy method of eliminating other possible ailments complicates the diagnostic process. The best remedy therefore is for individuals to live the kind of lifestyles that do not promotes the predisposing factors of the disorder (Voncannon, 2002). This includes living the kind of lifestyle that discourages the development of the disorder. It is also important for physicians to improve t heir way of diagnosing the disease so that they can be able to come up with comprehensive treatment strategies (Meirleir Patarca-Montero, 2000).

Flumequine and Balofloxacin

Flumequine and Balofloxacinmake byLAB GROUP F2Lab InstructorsT.A/Spring 2015Table of circumscribeIntroduction on (Flumequine) pg. 3 and (Balofloxacin) pg. 4Discussion on (Flumequine) pg. 5, 6, 7 and (Balofloxacin) pg. 8, 9, 10Conclusion pg. 11Reference pg. 12FlumequineThe initiatory of the quinolone family is the nalidixic acid. The do drugs was followed by the floroquinolones including flumequine which is a 1st multiplication agent in the floroquinolones. The first propagation including flumequine had a variety of problems such asLimited natural bodily processpoor dissemination heftiness rupturesHepatotoxicity and additive effect on neurological disorders ex myasthenia gravisAll of the first generation drugs were utilise for the word of infections in the urinary tract. The benzo quinolzine (flumequine) was invented in 1973 by (rikker labs) a german inventors. Flumequine is cognise to be the first of the quinolone family to include a fluoride at century moment six on the s keleton of the quinolone compound. Although flumequine is basically the first of all floroquinolones it is oftentimes overlooked upon classification of this class of drugs through generations it was omitted from the list. It is more often officed for the treatment of farm animals and on certain cases pets. And as follows the use in benignants is for infections in the urinary tract. It was originally used altogether for urinary tract infections until reports of toxicity were filed reporting anaphylactic shock and degrees of damage in the liver. The (FDA) food and drug constitution made a request on all the quinolone and floroquinolone cutes to be delivered to contain a blackness boxed model thus, notifying the risks of sudden ruptures in the tendon which basically includes the flumequine. As soundly earn were sent to physicians based on the FDA&aposs request to notify the doctors. The tendon complications were also exhibited in flumequine.The majority of floroquinolone gene ric versions did not include the black boxed warning in 2009 September as well virtually reports were filed to claim that this in make foration was never distributed or shargond among pharmacists and some products to this daytime still be shipped without the warning or medication guide that the physicians and pharmacists bear distribute.Uses (licensed)Infections in the urinary tractBalofloxacinBalofloxacin is often potent as an bactericide agent. It has a blanket(a) spectrum bactericidal exertion. It is less toxic than other fluoroquinolones. The trait between a quinolone drug and a fluoroquinolone drug is the addition of degree Fahrenheit to the basic pharmacophore, which causes a fluorinated drug. Quinolones and fluoroquinolones terms argon often used interchangeably regardless of this distinction. Balofloxacin is a third generation fluoroquinolone.A meta-analysis of skin infections and fluoroquinolones supplyed that the fluoroquinolones are more associated with unfavora ble reactions than beta lactam. However, the increase was due to a splendid to moderate rate of nausea and diarrhea soaringer. Enough to cause unplayful office effectuate withdrawal of the trial occurred at similar rates.Rarely, fluoroquinolones begin been associated with serious and adverse effects on the musculoskeletal system, cardiovascular system, interchange nervous system and peripheral nervous system, circulatory system, the maxillofacial system, endocrine gland system, gastrointestinal system the urological system, liver, brain, skin, and sensory systems such as sight, hearing, touch, smell and taste. after(prenominal) a single dose toxic reactions had been reported to occur.UsesUncomplicated infections of the urinary tractChemical structureFlumequineChemical structure and formula C (14) H (12) F (1) N (1) O (3)IUPAC name9-fluoro -6, 7 dihydro -5 methyl radical -1 oxo -1H, 5H -benzo quinolizine -2- carboxylic acidMode of actionFlumequine is primarily an antibiotic t hat is broad spectrum and mostly active against gm tyrannical bacteria and gram negative. apparatus works through the inhibition of gyrase desoxyribonucleic acid, topoisomerase specifically emblem 2 and type 4 they are enzymes that are responsible for bacterial DNA sequestration therefore by inhibiting them the bacteria cannot replicate hence, inhibition of cell division. This tool might also alter mammalian cell division. Basically the drugs of high activity could lead to toxic effects in mammals. The report of DNA damage was first filed in 1986, its mechanism of cytotoxicity is still unknown. pane formsFor vet forms Oral solutions (10-20%) prescription requiredFor human forms Oral tablets (400mg) notice it is give up 20% solution Tablet formulation stoppedSynthesis of flumequine social system activity relationship (SAR)The fluorine that is demonstrate at carbon payoff six which enhances the inhibition of gyrase and cellular penetration.The carbon number seven contributi on was found to control cell permeableness according to the properties of the constituent.Substitution of N number 1 is indispensable in obtaining the anti-bacterial properties.The introduction of a butyl crowd at N number 1 enhances the activity against the gram positive bacteria and little or minimum reduction of activity against gram negative bacteria.At piazza cardinal the addition of nitrogen did show an improvement of the pharmacokinetic properties.At positions 4 and 3 they do have a link with the keto and carboxylic group which is an essential thing for binding to the gyrase DNA.At position number 5 the transposition by small groups similar amino, nitro, halogens and alkyl groups could improve the tissue distribution and absorption. Though suggestions were raised that the substitution at position 5 could come down the anti-bacterial properties.At position 6 the substitution by F, H, Br, Cl, nitro, methyl and cyanide would actually increase the ascendance of anti-bac terial activity by means of improving the binding and penetration abilities. metabolismFlumequine is known to have good absorption thus, well absorbed and is mainly excreted in feces and urine as a glucuronide conjugates according to the upgrade drug and active ingredient of metabolism which is flumequine 7-hydroxy. The drug is eliminated within 168 hours after dosing. Major residue was found in chickens, pigs and sheep to be in the form of flumequine 7-hydroxy it was found in minimal amounts. The detection of the parent drug was only found in trout. Metabolism can be summarized as well absorbed and metabolized in the liver.BalofloxacinIUPAC1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxoquinoline-3-carboxylic acidSynthesisMode of action initiatory and second generation fluoroquinolone selectively inhibit the field of ligase topoisomerase II, leaving two areas nuclease intact. This modification, combined with the constant action in the bacterial cell by topo isomerase II, results in fragmentation of DNA through nuclease activity welkins of intact enzymes. fluoroquinolones that are third and fourth generation are more selective for the ligase domain topoisomerase IV and therefore improved the gram positive coverage.Fluoroquinolones can commemorate cells through porins easily thus, could be used for the treatment of pathogens that are intracellular such as Mycoplasma pneumoniae and Legionella pneumophila. Too many an(prenominal) bacteria that are gram-negative, the target is the DNA gyrase, in turn the topoisomerase IV is the target of many Gram-positive bacteria. Some compounds of this class were found to inhibit the synthesis of mitochondrial DNA.Dosage formsTablets 100-400 mg literalMetabolismPharmacokinetics of balofloxacin, the new fluoroquinolone, was a study conducted on mice, dogs and rats through liquid chromatography (high-performance). The bioavailabilities oral means of balofloxacin it was obtained through calculation of t he AUC (area below the curve) after intravenous and oral in mice, rats and dogs 87.50 and 87.73%, respectively, suggesting that was absorbed almost on the whole balofloxacin in rats and dogs, but not in mice after single oral brass instrument. The average elimination half-life in plasma after intravenous injection in mice, rats and dogs are 0.92, 1.33 and 6.38 hours, respectively. I mean cumulative urinary excretion rate unchanged balofloxacin within 24 hours of oral administration of balofloxacin in dogs, mice and rats respectively. May secrete a small part of the metabolism in the urine as glucuronide balofloxacin and N-desmethyl balofloxacin in these species. After oral administration of balofloxacin in a dose of 100 mg / kg in rats, and was for a long period of absorption compared with those after administration in doses of 5 and 20 mg / kg. The plasma concentration-time profiles and pharmacological parameters of balofloxacin in manly mice similar to those found in female m ice, suggesting a lack of sex-related differences. once a day for 21 days, multiple departments were not affected by this drug in mice of balofloxacin formations. organize activity relationship (SAR)The fluorine that is present at carbon number six which enhances the inhibition of gyrase and cellular penetration.The carbon number seven constituent was found to control cell permeability according to the properties of the constituent.Substitution of N number 1 is essential in obtaining the anti-bacterial properties.The introduction of a butyl group at N number 1 enhances the activity against the gram positive bacteria and little or minimal reduction of activity against gram negative bacteria.The addition at position two of nitrogen did show an improvement of the pharmacokinetic properties.They do have a link at positions 4 and 3 with the keto and carboxylic group which is an essential thing for binding to the gyrase DNA.The substitution at position number 5 by small groups like amino , nitro, halogens and alkyl groups could improve the tissue distribution and absorption. Though suggestions were raised that the substitution at position 5 could decrease the anti-bacterial properties.The substitution at position 6 by F, H, Br, Cl, nitro, methyl and Cyanide would actually increase the potency of anti-bacterial activity by means of improving the binding and penetration abilities.ConclusionFlumequineIt is a first generation fluoroquinolone closely absorbed orally and metabolized hepatically (glucuronide conjugates)Discontinued due to dangerous adverse effects such as hepatotoxicityVeterinary use onlyBlack box warningIs used for UTI but discontinued in humans mechanism of action is inhibition of DNA gyrase, less selective than third generation drugs and lower gram positive activityWas administered orally as tablets for human use but discontinued and mainly now as solutions for veterinary useExcreted in feces and urine.BalofloxacinIt is a third generation fluoroquinolo neWell absorbed orally and minimal hepatic metabolismIt is truly useful because it has less adverse effects than other fluoroquinolonesHuman useNo black box warning due to minimal side effectsMainly used for uncomplicated UTISame mechanism of action of fluoroquinolones (Inhibition of DNA gyrase) more selective and improved gram positive activity due to 3rd generation propertiesOrally administered in the form of tabletsExcreted in feces and urineReferenceChemspider, Flumequine Available at http//www.chemspider.com/Chemical-Structure.3257.html (Accessed 12 April, 2015)FAO, victuals and Agriculture Organization of The United States, Flumequine, Available at http//www.fao.org/docrep/w8338e/w8338e0a.htm (Accessed 12 April, 2015)NCBI, Structure Activity relationships of The Fluoroquinolones, Anti microb Agents Chemother (1989) pages 131-135 Available at http//www.ncbi.nlm.nih.gov/pmc/articles/PMC171443/(Accessed 12 April, 2015)World open Library, Flumequine Available at http//www.netli brary.net/articles/flumequineMode_of_action (Accessed 12 April, 2015)Medicine India. Balofloxacin Pharmacology. Available at https//www.medicineindia.org/pharmacology-for-generic/2923/balofloxacin(Accessed 13 April, 2015)NCBI. Pharmacokinetics of the new fluoroquinolone balofloxacin in mice, rats, and dogs. (1995). Available at http//www.ncbi.nlm.nih.gov/pubmed/7646579(Accessed 13 April, 2015)WHO. Medical credit rating publication. (2005). PDF, Available at http//www.netlibrary.net/eBooks/WPLBN0000173166.aspx(Accessed 13 April, 2015)Drugs and Pharmacology. Balofloxacin. (2013). Available at http//drugsandpharmacology.blogspot.com/2013/03/balofloxacin.html(Accessed 13 April, 2015)1

Effects of Globalization on Accounting Concepts

Effects of Globalization on Accounting ConceptsHaiyan Linincrease b either-shaped trading competitiveness.Globalization results in more opportunity and threats, as swell up as more competition and clients for some(prenominal) countries and organisations. Business take to purify their competitiveness. To reckon product differentiation and terms controlling or offer better products or services to customers, deliver responsiveness be close to of firms goal.To realize business competitiveness goal led organisation to gather up new c are invoice formations and techniques much(prenominal) as Activity-based cost systems and Activity-based budgeting systems. Activity-based cost system is more accurate to calculate the cost of goods, services, customers and separate action within organisation and also shareholder values, as well as business budgeting. Activity-based budgeting is also more accurate technique to forecast firms future tense be and better benchmark to compa re actual costs. (Langfiled-Smith, 2012)Raising orbiculate mobility of labourGlobalization is also raising mobility of labour all all over the world. Organisations especially as IT companies book more shortage in IT talent. So they are more possible to recruit employee from other countries.The celebrated vitrine in New Zealand is Wellingtons BRING IT A WOLRD OF TECH TALENT TO jackboot plan. Government support Wellingtons organisation to recruit world high tech talents which pay 100 candidates flight tickets and accommodation when candidates come to interview with their capableness employers in Wellington.Increasing pressures for accountability, involving ethical and governance issues. focus chronicle utilize techniques such as inventory oversight and time management to realize accountability. The inventory management is effective method to humiliate supplier costs, manufacturing costs and production costs. Just-in-time philosophy is important inventory methods using in m anufacturing, Toyota is famous example.Profession ethical codes charter to be applied to accountant. As management accountants, they have obligation to themselves, their colleagues and their organisation to follow high standards of ethical codes.Increasing awareness of sustainability issues, especially climate change.Environment became worse when economic is develop fast. The most serious environment issue is global warming. So for sustainable global developing, many businesses try to use environment friendly materials or reducing CO2 emission and use of some other remarkable resource such as water.Example both Australia and New Zealand reduce or reduce greenhouse gas emission no more than 1990 levels. (Langfiled-Smith, 2012)Conclusion Business environment will change continuality in the future, management accounting should be adjust, improve and develop new techniques, structure and systems all the time.Uses of entropy focus accounting the users are internal users such as manag ers and employees at all levels. Managers need management accounting information to profess strategies and decisions.Financial accounting the users are external such as shareholders, creditors, bound, personal line of credit exchange, and government agencies. Banks use financial statements to decide whether to lend loan to the business potential shareholders use financial statements to consider whether to invest in the business.RegulationsManagement accounting there are no external rules or accounting standard. Managers generate information for the blueprint of their management.Financial accounting there are accounting standards and corporation laws to regulate the content of external financial reports such IFRS.Source of dataManagement accounting the sources are come from both external and internal, as well as financial and non-financial data. The internal data is from physical and functional data from production systems. External data is from market, customer and economic da tabase.Financial accounting data almost from internal- organisations core transaction-based accounting system.Nature of the informationManagement accounting subjective relevant seasonably past, current and future-oriented supplied for all level to satisfy managers needs.Financial accounting not timely not always relevant past reliable extremely aggregated. (Langfiled-Smith, 2012)Issues of privacy and sufferership in the personal information industry.How to protect employees or customers privacy is important issue for the business. Business need to consider whether or not to reveal employees or customers information to the unrelated parties.For example bank send their customers information to policies as policies requested but there was no permitted from their customer. The result was bank was sued by their customer.Issues of computer security refer to truth and confidentiality.Computer security systems are aim to prevent fraud and other unauthorised users to addition the protec ted confidential database. However, the higher security system still can lead to other problems such as employ to spy on legitimate users.For example the secure computer system for Unitec, all students and staffs have their own account name and password to plan of attack to online Portal. It is more convenient for their work and study. Online Portal has their personal information such phone number, home address and passport copy. That is why portal need to separate student and staff login to protect student personal information from unauthorised person.The ownership of property. What can organization or individual own?Laws are designed to protect rights of ownership for properties, such as package.The unbelief is whether individual and organisation should be restricted for using or access to this Intellectual property.For example copyright laws protect those people who developed software from being copied. However, there is question whether copyright right or wrong, because many people believe there is more harm than good to have copyright laws. The problem is whether need to pay if to see or have-to doe with softcopy. The purpose of copyright laws is to encourage developing new software or arts, but in fact copyright may have opponent impact.Issues of truth access involving culture, economic status and safety.Example if documents are brisk in one language and poor translated. Individual and organisation need to acquire technology equipment based on their economic ability. And the access of equity also need to consider safety of pregnant women or the minors.environmental issues.It is easy to print because of computer and printer, however, print large amount of theme will result in disappear of treStrategiesSarbanes-Oxley Act (SOX) and function 406 pack company to have ethical code applied to CEO, CFO and controller.Section 406 quest ethical codesThe outgrowth to deal with conflict of interests.To provide full, fair, accurate, apprehensible and ti mely disclosure in documents and financial reports.Legal compliance require employees to follow governments laws, rules and regulations.Organisations mechanism to report permit prompt ethical rapines. righteousness the ethic procedure should effectively take action when ethic violation appear.1) Strategic preparednessStrategic be after is long term planning usually for three to five years, wide range and made by senior manager. Strategic planning is including corporate and business strategy decisions corporate strategy decisions are about the types of businesses or markets. Business strategy decisions are about how the businesses to realize their particular market. (Langfiled-Smith, 2012)2) Operational planningOperational planning is short term planning, more details and narrow range than strategic planning and made by under senior managers. The main purpose for operational planning is to set detail process to complete their vision.3) linkage between strategic and operational p lanningOperational planning is process to make strategic planning come true. Every goal on operational planning should link one or more strategic planning, otherwise, there is no meaning of operational planning, and company will drive away their time and resources. For example, if a manufacturing want to set second grind, their employees will cash in ones chips more time in what it is not priority for their second factory if there is no strategic planning.ReferencesA. Hall, J. (2016). Accounting Information Systems. Bostan, MA, USA Cengage Learning.Langfiled-Smith, K. (2012). Management Accounting information for creating and managing value. Sydney, NSW 2113, Australia Rosemary Noble.McDonnell, S. (n.d.). links between strategic and operational plans. Retrieved from Azcentral http//yourbusiness.azcentral.com/links-between-strategic-operational-plans-25572.html

Mechanisms Of Conservative And Replicative Transposition Biology Essay

Mechanisms Of Conservative And Replicative Transposition Biology Essay bacterio phage Mu is a clement phage which adopts turn around roadway in its heart cycle. Mu has the capability to desegregate into numerous invests in force Escherichia coli genome and cause mutations due to its foundingal activation. Mu trans awards via 2 study pathways justifiedly and replicative turn around though the molecular switch between the devil chemical utensils remain unknown. This review testament focus on the comparisons between replicative and conservative policy change. The prime(prenominal) representative pull up stakes discuss the similarities between the deuce machines bestower desoxyribonucleic acid sectionalisation tonus and establish designate step which involves nucleophilic attacks, generating single- filum nicks in Mu desoxyribonucleic acid and joining it to tush deoxyribonucleic acid via one-step transesterification utensil. The latter part will concentrate o n the different characteristics in for individually one reversal weapon in replicative alternate, the curiosity product is duplication of jumping gene assume in twain(prenominal) rear end and army deoxyribonucleic acid while in conservative surrogate, a simple insertion of jumping gene is created in the come out deoxyribonucleic acid.1. Characteristics of phage MuPhage, derived from the Greek word phagein, literally means to eat. Bacteriophage Mu was named as such(find out who did) due its disposition of infecting and inducing high levels of mutation in entertain bacteria Escherichia coli., hence the name Mu for mutator. The dual nature of Mu jumping gene and virus has do it as the archetypal simulate of studying phage genetics. Bacteriophage Mu is a temperate phage of E. coli which employs the about-face mechanism in its life cycle. Transposition can either be conservative (excising the jumping gene and inserting it into bacterial chromosome) or replicati ve (transposon copies be produced in twain transposon and bacterial chromosome). Both mechanisms will be discussed extensively later in this article. irrelevant the phage , insertion of Mu genome into the score invest proceeds in a randomly manner which makes it an excellent mutator.Fig. 1 The life cycle of bacteriophage Mu(5).The life cycle of phage Mu is shown schematically in Fig. 1 above. Bacteriophage Mu infect susceptible host cell by adsorption and hence, injects its analogue viral genome. Once inside the host cell, the linear genome does non circularized(4,5,19), impertinent in phage . In either case of lytic or lysogenic phase, Mu integrates its deoxyribonucleic acid into the host genome via conservative setback(16,19). This is go ond differently in phage where the infecting phage desoxyribonucleic acid will be integrated into host genome scarce during lysogenization(19). An enzyme called transposase, encoded by MuA gene in the phage genome, is absolutely cruci al to tolerate out this conservative transposition step. Phage DNA is inserted at septuple sites in a bacterial genome which lead to the assumption that the insertion draw by a random manner(8). However, on that transfer argon several factors that decide ass site selection such as MuA protein efficiency and transposition immunity(15).After integration, Mu commonly adopts a quiescent prophage lifestyle(lysogenic phase). The preference between lysogenic and lytic phase in Mu life cycle is dep kiboshent on its inactiveness in the lysogen and lysogenic repressers. However, lysogens of Mu phage sometimes enter the lytic phase though this is a r ar event. When induced, usually by using temperature-sensitive repressor mutants of phage Mu and subject it at 42C, the lysogen will enter lytic cycle. When the lysogenic repressor is inactivated, Mu transposes via replicative transposition, producing copies of phage genome which will be packaged into new virions. The virions then lyse the host cell and infect new hosts. Bacteriophage Mu virions comprised of icosahedral head(diameter 54nm), a baseplate, a contractile tail and six short tail fibres(5).Fig. 2 simplify cartoon illustrating furtherance of Mu genome. Typical length of phage Mu DNA is some 37kb long. Additional 2 kb of host DNA is incorporated during DNA packaging which is shown as flanking each bar of the integrated Mu genome, with most of it at the business end. Unique sequences of host DNA and at the right end of the packaged DNA is dependent on initiation site of packaging in the host DNA(24).Fig. 3 Physical and genetic map of bacteriophage Mu. Solid black lines represent Mu DNA while the boxes at the dickens ends usher flanking host DNA sequences. Mu genes (indicated in block letters) and their stoping translational products ar as indicated(19).A typical size of wild-type phage Mu DNA is about 37.5 kb, however each phage capsid can lenify up to 39 kb long. Phage genome has a pac site which serves as the starting point in packaging of the phage DNA, turn up within attL(5). The initiation partition by phage enzyme terminase pop offs upstream of the phage pac site, which includes host sequence of about 50-150bp flanking the left end. Second division initiated when a complete filling of capsid is achieved, which includes 0.5 kb to 2 kb of host sequence flanking the right end(1). Genetic and physical map of phage Mu is illustrated in Fig. 3. Bacteriophage Mu utilizes headful mechanism strategy, which confer variable lengths of host DNA flanking the left ends of Mu DNA depending on the initiation site of genome packaging(Fig. 2).2. Transposition mechanism(E)(D)(C)(B)(A)Fig. 4 Modes of bacteriophage Mu transposition. (A), (B) and (C) argon the common steps in some(prenominal) conservative and replicative transposition of phage Mu. In conservative and replicative transposition, phage Mu will follow-up step (D) and (E) respectively. Curved arrows indicate nucleophile at tack, takering the 3-OH ends to the staggered 5-phosphate ends of target DNA. Dentate lines (XXXX) indicate target DNA sequences which ar duplicated during transposition (16).Numerous in vitro studies digest been conducted to study the mechanism of transposition, and usually mini-Mu components are used. A minimal Mu segment consists of a selectable gene, a plasmid DNA reproduction origin and essential Mu ends(2). The mechanism of transposition is discussed in respect to an in vitro system from this point onward unless stated differentwise. Following discussion on transposition mechanism are based on Shapiro ideal(22) as it has been widely accepted as the well-heeled pattern in this field.The current known modes of transposition is divided into both non-replicative (conservative) and replicative transposition. Both strategies utilize the same mechanism up to point (Fig. 4C) where each strategy employs different mechanism, producing different end products. A simple inse rtion of transposon is generated in target DNA by conservative transposition (Fig. 4D) while two copies of transposon formed in twain presenter and target DNA by replicative transposition (Fig. 4E). Point A to C are considered as the similar features in both conservative and replicative transposition while point D and E is the distinction between the two modes of transposition. Therefore, mechanisms involved in point A,B and C are discussed in context of both replicative and conservative transposition, which comprises of DNA cleavage step and strand ship step. Sequential stages of both cleavage and strand transfer steps are illustrated in Fig. 4.2.1 Donor DNA cleavage step dickens decisive chemical steps in both transposition pathways are bestower DNA cleavage step and DNA strand transfer step(5,8). The conferrer DNA cleavage step is initiated when water molecules within an active site act as nucleophiles, and attack phosphodiester bond in DNA ground tackle at each of the t ransposon end(4,5). The cleavage step involves a invest hydrolysis of phosphodiester bond by water, and not by covalent enzyme-DNA fair(17). The phosphodiester bond is cleaved at the flanking host-transposon DNA boundary. 3-hydroxyl (OH) ends of the Mu DNA are exposed at the end of the cleavage step. Strand transfer outlets in fusion of target and bestower DNA, which forms an intermediate molecule (8). The process (simplified in Fig. 4C) follows the Shapiro model(22).Bacteriophage-encoded proteins, MuA protein (transposase) and MuB protein (ATPase) are required for transposition. Other requirements to procure efficiency of transposition are accessory proteins such as host-encoded DNA bending proteins called hydroxyurea (HU) and integration host factor (IHF)(8). The inverted repeats at the end of donor DNA, and target sequence on bacterial chromosome are overly important in transposition mechanism. The assembly of higher order protein-DNA interwovenes called transposome has be en determine by in vitro studies(6).A three-site synaptic involved called the LER obscure comprising right and left ends of Mu and transpositional enhancer, was formed in the beginning of transposition in vitro(23). MuA protein binds to MuA salad dressing site at the ends of Mu DNA as monomer, and subsequently function as tetramer of MuA (transposase). Host IHF and HU protein were found to aid in organization and stabilisation of LER complex.The LER complex is relatively unstable and so, is rapidly converted into stable synaptic complex (SSC), also known as type 0 complex(17). This is the critical checkpoint in the beginning any chemical reply is carried out as it is the rate-limiting step of cleavage reaction(6). A stable synapse between tetramer of MuA and the two ends of Mu DNA is made only no cleavage is initiated yet at this point. Nonetheless, the active site is structurally occupied to the region around the scissile phosphate while the flanking DNA are destabilized upon organic law of the SSC complex(6). In addition to formation of a stable synapse, the Mu ends require to be properly-oriented, a super coiled DNA topology, and accessory DNA sites are also important to proceed to the next step. Formation of SSC usually is short-lived in mien of Mg2+ but can be accrued in presence of suitable divalent cations such as Ca2+,which promotes the formation of SSC(8,17).Next, SSC is converted into a type 1 transposome complex, also called as cleaved donor complex(CDC)(9). The 3 ends of Mu DNA are nicked in presence of Mg2+. Two subunits of MuA tetramer, that are associated with the sites that undergo cleavage, assemble in trans arrangement which favours the strand transfer reaction(5). The formation of CDC can then be thought as the result of donor DNA cleavage step. Type 1 transposome complex exhibits greater stability than the type 0 complex though MuA forms structural and available pith in both transposome complexes(6). In addition of stably bound t etramer of MuA proteins, there are loosely associated MuA proteins present in the CDC as well. In absence seizure of MuB protein, MuA tetramer is unable to promote strand transfer reaction unless these extra MuA proteins are present. MuB protein is an ATP-dependent DNA- dressing protein, which also acts as an allosteric activator of Mu transposase (MuA proteins)(21). Transposition can still proceed in absence of MuB proteins, but MuA protein by itself is only 1% efficient(3).2.2 Strand transfer stepA hallmark of this step is the formation of strand transfer complex (STC), also known as type 2 transposome complex. The end product of STC is formation of a pronged molecule(Shapiro intermediate) which is characterized by a covalent interaction between donor DNA and target DNA via 5bp single-stranded gaps and its structure(22). MuB protein first captures a target molecule and bring it to the vicinity of the transposome complex, forming a TC complex(6). Formation of TC complexes rapidly undergo one-step transesterification reaction, which is the rate-limiting step in the strand transfer step. Interestingly, recruiting of target molecules by MuB proteins and formation of TC complexes can occur at several time point during the reaction pathway(6). This is a particularly efficient step to maximize transposition say-so as it would speed up rate of strand transfers during transposition.The free 3-OH ends produced from the cleavage step act as nucleophile and attack phosphates of target DNA at the 5 ends. 5-nucleotides long offset nicks are made in the target DNA, generating a staggered arrangement(3). At this stage, the MuA proteins(transposase) are still tightly bound to the branched molecule with single stranded gaps. This pose an obstruction for the assembly of reappearance fork by host replication factors. The structure of the branched molecule is simplified in (C) of Fig. 4.The forming of this intermediate molecule serves as the critical point which distinguish between conservative and replicative transposition. A widely accepted model is that the resolving of this co-integrate molecule by a special resolvase complex leads to replicate copies of transposon existence made in both donor and target site(REFerence). This is by definition, a replicative transposition pathway. Thus, the strand transfer complex is destabilized and disassembled by a system of eight E. coli host molecular proteins (DnaB helicase, DnaC protein, DnaG primase, DNA polymerase II, single-strand binding protein, DNA gyrase, DNA polymerase I and DNA ligase) and molecular chaperon called ClpX, producing cointegrates(13).This handing over from transposome complex to a replisome results in duplication of 5-bp target DNA sequences flanking both ends of Mu DNA. Alternatively, if the bacteriophage Mu is to enter the conservative pathway, the co-integrate molecule is repaired or processed without perform Mu DNA replication. The end product of STC in a conservative transposit ion is a simple insertion of single mini-Mu element inserted into the target DNA(8). However, the mechanism of this model is poorly understood.Fig. 5 Transposome complexes involved during DNA cleavage complex and DNA strand transfer. (A) A plasmid (gray line) bearing donor mini-Mu element (black line) DNA in the in vitro system is negatively coiled. (B) In presence of host HU protein, Mu A protein bind to the two ends of Mu DNA forming a stable synaptic complex (not shown). Assembly of MuA tetramer produces a nick at each ends of Mu DNA, creating a cleaved donor complex (CDC). (C) Nicked 3 ends of Mu DNA are conjugate together to target DNA in presence of MuB protein forming a strand transfer complex (STC). MuA tetramer is still tightly bound to the Mu ends in the STC. (D) In replicative transposition, a cointegrate molecule is produced when replication of target DNA initiated from the 3 Mu ends by host replication machinery (13).3. Replicative transpositionReplicative transpositio n was first suggested by Ljungquist and Bukhari (1977) to occur in situ after induction of lysogens, which means that the Mu prophage was not excised from host chromosome during transposition(14). The lysogens were digested with breastwork enzymes which cleaves both host and Mu DNA at specific restriction sites. Two of the fragments from the restriction digests contain both host and Mu DNA, which corresponds to junctions between host and prophage DNA, suggesting that prophage DNA is replicated in situ of host chromosome(19). Several genetic and biochemical predictions made in the Shapiro model pack been demonstrated in both in vivo and in vitro studies, hence this model is accepted as a plausible mechanism to explain transposition in phage Mu.Numerous techniques have been do to study the direction of replication of Mu DNA during transposition. Results obtained by annealing of Okazaki fragments to scattered strands of Mu DNA shows that more than 80% of Mu molecules replication pr oceed from left to right end(11,19). Electron microscopical observation of mini-Mu element shows that replicating molecules in vitro replicate from both ends in equal probability(11,19). Replication of Mu DNA is accepted to be predominantly unidirectional, that is from left towards the right end(20). Intramolecular replication pathway can result in inversion, deletion, and simple insertion while intermolecular events can produce co-integrate molecules(19). In the case of Mu transposition, formation of co-integrate molecule needs to be end in order to produce two replicons one molecule contains transposon and target DNA while another molecule contains transposon and donor DNA(10).4. Conservative transpositionThe main characteristic of conservative transposition is that phage DNA is not replicated prior to integration. Upon infection of a susceptible host cell (usually E. coli), Mu employs conservative, or also called non-replicative transposition to transfer its genome to the targe t site. As discussed earlier, conservative transposition pathway follows single strand nicks at the 3 ends of Mu DNA, of which the exposed 3-OH ends join to the staggered cut target DNA at the 5ends forming a co-integrate molecule. The co-integrate or so-called Shapiro intermediate is repaired and generates a simple insertion in the target DNA though the mechanism is still poorly understood.Shapiro model emphasized on single-stranded nicks at Mu ends, joining of Mu to a staggered double-strand issue in target DNA, formation of an intermediate molecule, and shedding of heterogeneous of front host DNA sequences after ligation in conservative pathway(22). On the other hand, Morisato and Kleckner (1984) proposed a different mechanism based on results with Tn10 transposition. Their model is double-stranded cleavages at the transposon ends generating an excised transposon, which then circularizes via ligation on one of the strands(18). It predicts shedding of host sequences from the Mu DNA ends before ligation into the new target DNA. Study of Mu transposition using plasmid substrates in vitro produced results in favour of the Shapiro model, and hence this model has been widely accepted and used in studies.Fig. 6 A model of conservative transposition which utilizes double-strand cleavages during integration. (A) Transposase bind to the inverted repeats at Mu-host boundary sites and cleaves off the transposon away. (B) Transposase made a staggered cut at target sequence of which exposed 3-OH ends of transposon attacks 5-phosphate ends of the host (not shown). The transposon then joins to the host sequence. Duplicated target sequence of 5-bp are completed by host replication machinery (7).The debate on single-strand or double-strand cleavage however does not end there. If phage Mu were to utilize the Shapiro model of transposition during integration (the well-established cointegrate mechanism), the flanking host sequences would remain bound to Mu ends. This would cl early pose a problem as subsequent target-primed replication of the linear integrant would not work, or simply break the chromosome(1). Evidently, results from in vitro experiments are against this as the transposition end products contain transposon, suggesting a complete transposition process have been accomplished. So, does the infecting Mu DNA utilize the Shapiro model where the cointegrate molecule gets processed and repaired, prior to replication at the flanking sequence? Or does it follow a cut-and-paste mechanism where both strands of Mu DNA gets cleaved off from the flanking host DNA sequence (as illustrated in Fig. 6), where no cointegrate molecule is generated, which eventually means, there is no need for resolve by replication?An in vitro experiment was done by Au et al. (2006) to observe the fate of flanking host DNA sequences upon phage Mu infection. Specific markers specific to the infecting phage Mu DNA as well as the donor host (lacZ/proB) were used. These markers w ere acquired from the host in which the phage had been propagated but absent in the host being infected(1). Upon infection of plasmids by bacteriophage Mu, signal for flanking sequences and Mu DNA were detected in the chromosome at the same time point (approximately at import 8), which correspond to the integration time point of Mu. Subsequent expression of lacZ and proB were detected maximally at minute 15, significantly reduced at minute 30 and by minute 50, expression were halted(1). Maximal expression at minute 15 most likely corresponds to climax of integration of the infecting phage population. These findings powerfully suggest that flanking sequences get integrated together with Mu DNA into the new target site and are subsequently, removed by a special mechanism(which explained the insensible(p) expression at minute 50). This then proves that infecting phage Mu employs an alternate cointegrate mechanism (also called as nick-join-process mechanism) in conservative transposit ion pathway, where the Mu DNA undergo single-strand nicks, joins to the target DNA, and repaired before replication of the 5-bp gap left by the flanking sequence(1). The mechanism of remotion and repair of host flanking sequence however, remains ambiguous.ConclusionDual nature of bacteriophage Mu, a transposable element and a virus, is certainly raise but what is more fascinating is that it utilizes both replicative and non-replicative transposition throughout its life cycle. The former mechanism produces a transposon copy in both donor and target DNA while the latter usually generates a simple insertion of transposon in the target DNA, leaving a gap in the host DNA which most likely will get degraded.In the early stages, both replicative and conservative transposition pathway share a similar mechanism. Regardless of the transposition pathway, infecting Mu DNA during the first round of infection will integrate its DNA into the target chromosome via two critical steps donor DNA clea vage step and strand transfer step. Mu uses a phosphoryl transfer involving nucleophilic attacks of water on phosphodiester bonds of Mu DNA, producing single-strand nicks. A gage nucleophilic attack by exposed 3-ends of Mu DNA on 5-ends of target phosphodiester bonds, which then joins the Mu DNA to target DNA via one-step transesterification mechanism. A series of transposome complexes are formed throughout these processes including Mu-encoded MuA proteins(transposase) and MuB proteins(ATPase). A cointegrate is produced in both pathways but in replicative transposition, this intermediate molecule is resolved producing two replicons with transposon copy in each molecule. In conservative transposition, the cointegrate is repaired generating a simple insertion in the target DNA. Hence, it is more accurate to name conservative transposition as nick-join-process rather than the conventional cut-and-paste mechanism as the latter suggest double-strand nicks at the transposon end, which ha s been proven inaccurate by in vitro experiments. Both transposition pathways have been compared extensively in this review but much of functional core of the mechanisms remain to be understood.(2944 words)