Interpetive Essay Example | Topics and Well Written Essays - 750 words

Interpetive - Essay Example In the beginning, the streets of London are represented by Woolf as amazingly pleasing and interesting to people. Walking around the city of London arouses the imaginations and discoveries of identity where people are unbound to shortly become â€Å"a nomad wandering the desert, a mystic staring at the sky, a debauchee in the slums of San Francisco, a soldier heading a revolution, a pariah howling with skepticism and solitude† (Woolf 3). This sense of liberty and independence while walking the streets of London somehow manages to merge the individual identity of the narrator to those of the passing crowd. The narrator is simply carried away by the exquisiteness and magnificence of the city that dissolves any form of her hang-up into a â€Å"central oyster of perceptiveness† (Woolf 1). Her character then becomes identity-less as she absorbs the color and light of the city roads. But when the door shuts on us, all that vanishes. The shell-like covering which our souls hav e excreted to house themselves, to make fro themselves a shape distinct from others, is broken, and there is left of all these wrinkles and roughness a central oyster of perceptiveness, an enormous eye. How beautiful a street is in winter. (Woolf 1) In addition, the freedom that the modern city of London offers to the narrator allows her to lose herself in the crowd, and thus discovers herself inquiring about the everyday life of a dwarf (reference)? This event of losing oneself while exploring the streets of modern London is the fundamental reason that haunts the narrator. As she walks around the city, she witnesses different disturbing realities: a dwarf woman, two blind men, a retard, and the limping ludicrous dance of â€Å"the humped, the twisted, and the deformed† (Woolf 2). These realities have brought deep thinking to the narrator that makes her feel so lost in the modern world. The monstrosities that the narrator has witnessed and the beauty that she has experienced shake her identity and left her unstable. All the way through the narration of Wolf in her essay â€Å"Street Haunting† this feeling of uncertain identity is stressed out by referring to her narrator as â€Å"we† instead of â€Å"I†: â€Å"We shall never know† (Woolf 4) and â€Å"We are no long quite ourselves† (Woolf 1). The very instance of the narrator stepping out her door and into the modern city of London immediately strips off her individuality for anonymity. She can no longer identify herself with the different oddities and, at the same time, beauty that she is witnessing around the streets of modern London. The narrator becomes estranged to herself because she cannot connect anymore to the outside world that is entirely different to her inside world. Indeed, the various technological advances and behavioral changes brought by the rapid modernization of the London’s society highly contribute to the new definition and understanding of mobility, communication, time, and speed. Contrastingly, these advances and changes have also expanded the modern London outside the limits of coherent perception making the city unfathomable and too intricate for people to figure out. The enormity of the modern society and how it has become incomprehensible is repeatedly expressed in the essay. The narrator’s encounter at the second-hand bookstore conveys how she finds it

Anti-copper Therapy among Pregnant Women Can Lower the Risk of Wilsons Research Paper

Anti-copper Therapy among Pregnant Women Can Lower the Risk of Wilsons Disease in Their Children - Research Paper Example Therefore, the physicians encourage the pregnant women to use zinc in reducing the amount of copper in their neurological system in a mild way that would not affect the unborn child. Trientine can also be highly effective in treating copper toxicity, while protecting the expectant mothers and her unborn child’s life (Walshe, 129). Some of the measures which health experts would take are a screening test falsification ring assessment and ceruloplasmin serum copper assays. The test relies on a liver biopsy using quantitative copper assays. Immediately a pregnant woman is diagnosed with such symptoms the siblings might be genotyped via making comparison. Medical practitioners advocate for proper use of anti copper therapy. Anti –copper drugs widely used include Trientine, zinc and tetrathiomolybdate. Penicillamine is often administered to pregnant women. Despite its toxicity, it is proven to be the best. Trientine is alternatively used to people who not tolerate Penicillamine and the body responds better notably there is lower quantity of urine copper, which gently reduces to insignificant levels (Schilsky and Scott, 214). In reality, compliance with the recommended therapy and close monitoring of the copper status are the most beneficial practices that patients should observe during treatment. Similarly, the most effectively monitoring tool is used non-ceruloplasmin plasma copper though it also has some side effects; their frequency and impact are minimal. In addition, the neurological worsening especially in the patients using Trientine for the first time is less severe as in Penicillamine. Zinc, it is extremely vital for the maintenance of the therapy. It reduces mettallothionein in the cells. When using copper, urinary secretion of harmful copper is similar to the normal body loading system (Schilsky and Scott, 220). Tetrathiomolybdate, is also used to eliminate copper out of the body, it forms a complex tripartite of

Efficacy of Growth Factors Concentration after PRP

Efficacy of Growth Factors Concentration after PRP Efficacy of growth factors concentration (hGH, IGF-1, FGF-2, PDGF, VEGF) after autologous Platelet-rich plasma injection (PRP) on accelerating healing of proximal hamstring tear for athletes. Ahmed Gaballah 1- Department of Sports Health Sciences, Damietta University, Damietta, Egypt. 2- Kinesiology and Health Sciences Department, Utah State University, Logan, UT, USA Abstract Platelet rich plasma (PRP) become popular biologically method used to accelerate healing in sports medicine and orthopaedic surgery field. PRP is concentrate the human platelets to supra-physiologic levels. It is an autologous producing high level of the platelets concentration centrifuged from the peripheral vein. Then it re-injected under the ultrasound gaudiness during surgery or at a site of injury. METHOD: Seventeen physically active males (age 22.0 ±0.6) with acute hamstring strain injuries divided to 8 case group and 9 matched controls (age 21.6 ±2.8) were recruited as research participants. Case group participants were injected with single 3 ml of extracted PRP under ultrasound gaudiness. However, Blood samples were collected by venipuncture at standardized time points: before the injection and 24, 48, 72, and 96 hours after for case group and 4wks. and 8wks for both groups. RESULTS: there was significantly difference between the growth factors results of the case group a fter 4 weeks compared with the 8 weeks result of the control group. Additionally, the same significant results between the two groups after the 8 weeks. Nevertheless, the physical measurements related with hamstring Strain and Knee flexion range of motion between the two groups were not significant after 4 weeks or 8 weeks. CONCLUTION: a single 3-mL injection of autologous PRP combined with a rehabilitation program was effective in time return to play and reducing the severity of pain after an acute grade 2 hamstring injury. Additionally, increase in circulating concentrations of VEGF, IGF-1, PDGF and FGF-2. Key Words: Platelet rich plasma (PRP), Human Growth Factors, Hamstring Tear. 1. Introduction: Skeletal muscle injuries are up to 55% of all sports injuries and causes excessive long term pain and physical disability, Muscles strains and contusions representing more than 90% of all sports related injuries and are the most muscular injuries frequent. [1] [2]   Proximal hamstring tear injuries are common in athletes and frequently result in prolonged rehabilitation, time missed from play, and a significant risk of re-injury. Reports of acute hamstring strains without avulsion in dancers have suggested recovery times for return-to-play ranging from 30 to 76 weeks [3]. Platelet rich plasma (PRP) become popular biologically method used to accelerate healing in sports medicine and orthopaedic surgery field. PRP is concentrate the human platelets to supra-physiologic levels. It is an autologous producing high level of the platelets concentration centrifuged from the peripheral vein. Then it re-injected under the ultrasound gaudiness during surgery or at a site of injury [4] [5]. As a result of the lack side-effect and the autologous nature of PRP, it has utilized exponentially over the last few years in sports medicine and orthopaedic. Historically, since the 1950s the platelet-rich plasma (PRP) has been used to dermatological conditions and manage maxillofacial as well [6]. Furthermore, Platelet-derived preparations including PRP were first regulated by WADA under the 2010 Prohibited List because of concerns that the elevated concentrations of growth factors in PRP may confer an unfair advantage to treated athletes. However, WADA lifted the ban on PR P in 2011 in recognition of the lack of evidence to support a systemic performance-enhancing effect and to allow further research in the field [7]. Indeed, the blood contains 6% platelets, 1% white blood cells, and 93% red blood cells.   The PRP technique aims to reverse the concentration of the platelet in lieu of red cells to increase the growth factors that more useful in accelerating the healing. [8] However, Platelet rich plasma (PRP) is a centrifuged blood product that contains a supraphysiologic amount of platelets. Therefore, the preparation process to product concentrative platelet above the baseline values have started with an autologous extraction of patients` blood, then by plasmapheresis centrifuged to obtain a concentrated suspension of platelets. It then separates the solid and liquid components of the anticoagulated blood after a two-stage of centrifugation process [9]. The initial phase separates the plasma and platelets from the erythrocytes and leucocytes. The second stage concentrates the platelets further into platelet-rich and platelet-poor plasma components [10] [11]. Platelet rich plasma (PRP) contains some biologic factors which have been enhanced the proliferation and collagen secretion of tenocytes. These factors including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF2), and transforming growth factor ÃŽ ² (TGF ÃŽ ²) [12] [13]. There is an increasing the stimulus response of PDGF and TGF-ÃŽ ² in the early stages of tendon and muscles healing after PRP injection resulting in new vessel formation and collagen synthesis. [14]. In addition to decrease oxidative stress that could lead to cell apoptosis, PRP has been promoted tendon and muscles cell growth [15]. This is evidenced and reinforced by release of inflammatory meiators such as COX-1 and2, PGE-2 [16] [17]. Recently, there are various approaches reported the benefits of treating the soft tissue injuries such as muscles tears and tendinosis by injecting platelet rich plasma (PRP). Despite this popularization and increasing use in soft tissue injuries, its efficacy still not clear and remains controversial. It has been previously established that platelets provide regenerative potential by the process of chemo-taxis [18] [19] [20]. The use of PRP in order to accelerate recovery time after muscle injury has become a relatively common practice in sports medicine. Several studies represent that PRP can improve skeletal muscle healing after acute injury. In particular, local PRP which increased expression of several myogenic factors at mRNA level acting on modlating the inflammatory response and myogenesis in the early stages after acute injury [21] [22]. Rossi L, et al. reported the effects of an autologous PRP injections on time to return to play in randomized controlled study conducted on 75 patients. The study represented time to return to play for recreational and competitive athletes and recurrence rate after acute muscle injuries as well. The main result in the study that PRP injection significant reduction of re-injury rates at 2 years. Additionally, it was decreased the pain severity score and significantly decreased the time of return to sports as well [23]. One more study reported that 14 professional athletes were treated with ultrasound-guidance injections of PRP after acute muscle injuries. The athletes showed a quick return to activity and improved healing in muscle tears [8]. Similar results have represented in Sanchez et al study, which conducted on 20 athletes. These results supported the benefits of PRP and its role in muscle healing. The patients recovered in half of the expected time [24]. Figure 1. Process of platelet activation (PDGF, platelet derived growth factor). Source [25] Platelet Activity in muscles: (Figure 1,) represents the released serotonin contributes to vasoconstriction. The conversion of ATP into ADP releases the energy necessary to establish and maintain the aggregation. The release of the calcium ions inside the platelet makes the myofibril within it contract, thus allowing the aggregation and release of the content of the granules. This is serum calcium, which is necessary for the formation of the fibrin network [26]. The presence of the Ca2+ ions in the plasma makes the coagulation factors activate and group, forming the fibrin network, which is stabilized by factor XIII and transformed in a stable clot. The calcium ions also inhibit the anticoagulant activity of heparin, preserving the clot [27]. The PRP and the growth factors: The functions of these growth factors are presented in Table 1. It should be noted that the mechanism of action of platelet-rich plasma does not differ from the physiological healing process, but allows for obtaining higher concentrations of growth factors. As a result, the process of tissue regeneration is accelerated [28] [29] [30]. Platelet ÃŽ ±-granules are comprised of haemostatic factors, regulators inflammation, and wound healing. Substances stored in dense granules are thrombocyte-activating factors. Platelets also contain lysosomal granules, which secrete acid hydrolases [31] [32]. Platelet activation results in growth factor release. Platelet growth factors include platelet-derived growth factor (PDGF), transforming growth factor ÃŽ ² (TGF-ÃŽ ²), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) [33] [8]. Table 1. Growth Factors function Growth factor Abbreviation Functions Transforming growth factor TGF-ÃŽ ² A mitogen for fibroblasts, smooth muscle cells, osteoblasts Angiogenesis promotion, extracellular matrix production Platelet-derived growth factor PDGF Chemotactic effect on monocytes, neutrophils, fibroblasts, mesenchymal stem cells and osteoblasts A mitogen for fibroblasts and smooth muscle cells Angiogenesis promotion, formation of fibrous tissue, re-epithelialization Vascular endothelial growth factor VEGF Angiogenesis promotion Chronic wound healing promotion Inhibition of bone formation Epidermal growth EGF factor A mitogen for fibroblasts, endothelial cells, keratinocytes Chronic wound healing promotion Insulin-like growth factor IGF-1 Regulation of bone maintenance Modulator of cell apoptosis Stimulation of bone tissue regeneration Platet derived endothelial growth factor PDEGF Promotes wound healing by stimulating the proliferation of keratinocyes and dermal fibroblasts Endothelial Growth Factor EGF Cellular proliferation Differentiation of epithelial cells Figure 2. Platelet degranulation and action of the released cytokines in the process of formation of new bone and muscle tissue (VEGF, vascular endothelial growth factor; PDGF, platelet derived growth factor; BMP, bone morphogenetic protein; TGF-b, transforming growth factor). 2. Methods 2.1. Participants: This study was approved by Damietta University, Egypt, Alexandria University, Egypt and Utah state University, UT, USA. Twenty-three physically active males with acute grade 2 hamstring tear were voluntarily recruited for data collection (age 21.8  ± 2.64y, mass 71.52 ±2.74 Kg, height 175.4 ±2.32). All patients receiving local ultrasound-guided intratendinous PRP injection at our institution between September 2014 and December 2016 were screened for eligibility to participate in the study, and 17 patients were ultimately enrolled. Exclusion criteria included five participants with previous injury or diagnoses in hamstring. 8 physically active males (age 22.0 ±0.6) with acute hamstring strain injuries and 9 matched controls (age 21.6 ±2.8) were recruited as research participants. The case and control groups were performed rehabilitation program included aquatic exercise for 8 weeks. The history of pain data and the daily hours of using the smartphones were collected by surve y. Furthermore, the procedures were explained to the subjects and their written signatures were obtained on the informed consent. 2.2. Platelet rich plasma preparation and injection: In accordance of GPSTM III Systems instruction the blood collected for PRP was prepared by (Biomet Biologics, Inc., Warsaw, Ind) and standard 60 ml GPSTM III kit. Approximately of 7 ml of PRP was prepared in 30 minutes. Furthermore, single 3 ml of extracted PRP were injected under ultrasound gaudiness after adding 8.4% sodium bicarbonate buffered PRP for increasing the pH to normal physiological levels. The sodium was added in a ratio 0.05 ml to 1 ml of PRP. All the participants blood samples were stored in -25 ° Celsius and were analyzed to determine the concentration of the growth factors. The PRP injection of the current study were injected directly into the injured area under aseptic technique. The case group participants only received the single autologous PRP combined with the rehabilitation program. The participants were kept under observation for 96 hours and were performed the rehabilitation program after 5-7 days of PRP injection. Blood samples were collected by venipuncture at standardized time points: before (baseline) and 24, 48, 72, and 96 hours to 4wks. and 8wks. after administration of PRP. blood was drawn at precisely the same time each morning and at least 3 hours after eating and exercising per WADA standards Figure 3. PRP set up. 2.3. Growth Factor Quantification: Six growth factors and related molecules that are concentrated in PRP preparations were quantified in PRP and blood by direct immunoassay using the Quantikine enzymelinked immunosorbent assay (ELISA kit), as outlined   the Growth factors studied were: human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), basic fibro blast growth factor (bFGF or FGF-2), vascular endothelial growth factor (VEGF), and platelet-derived growth factor- BB (PDGF-BB). Because bFGF is present in the blood only at very low concentrations, a high-sensitivity ELISA kit was used to ensure accurate detection [34] [35] [5]. Figure 4. PRP injection under ultrasound guidance. 2.4. Rehabilitation program: A Physical rehabilitation program was performed for six weeks and designed for lower limb. In particular, hamstring muscles. both groups participants (8 case and 9 control) performed the exercises protocol once a day for 55 minutes for each training session and 5 times a week (275 M. / week). The exercise protocol was consisted of aquatic exercise and strength exercises and was divided to tree stages, the first stage was focused on the flexibility and isotonic strength exercise with 5 sets and 12-15 1RM intensity. While, the second stage was designed for strength exercises with 3 sets and 8-10 1RM intensity. While the third stage for endurance and exercise related of activity performance. Aquatic pool, Machine weights and The Thera-Band resistance bands exercises were used during the 6 weeks especially the colors (red, blue, black, silver). The red and blue bands were used in the first stage and the black and silver used in second stage. Furthermore, all the exercises were performed by stretching the band between 75 100 %. knowing that, the weight of stretching in Thera-Band between 75-100% is red 3.3-3.9kg, blue 5.9-7.1kg, black 8.1-9.7, and silver 11.1-13.2kg. 2.5. Statistical Analysis The paired t-test was used to compare the collected data before performing the exercise protocol (Pre-test) and those which were obtained after the 6 and 8-weeks training period (Post-test). The differences between the samples were significant at the t = 1.740 p < 0.05 level. All the analyses were performed by using SPSS 21 software for Windows 7 (SPSS Inc. Chicago, IL, USA). Additionally, all values within the text and table are observed as standard deviation and mean (mean  ± SD). 3. Results: Table 2, 3 illustrate the large variations in growth factor concentrations between participants in the two groups before and after PRP injection. Regarding growth factor (GF) trajectories for the case group participants are shown in Figure 3, and data are summarized in Table 2, the human growth hormone increased dramatically within the first 24 hours after PRP injection while these results were not significant after the 4 weeks and 8 weeks.   Moreover, IGF-1 increased relative to baseline within 24 hours after PRP and remained elevated at all-time points thereafter, and the change was statistically at 24 until 96 hours as well after 4 weeks and 8 weeks. Likewise, VEGF and PDGF were significantly elevated at 24 hours and at all-time points thereafter and were significant after 4 and 8 weeks.   Furthermore, FGF-2 rose at the point between 24 to 96 hours after PRP injection but not significantly, while it was elevated significantly after 4 week and 8 weeks. It obviously represented in table 3, the spectacular significantly difference between the growth factors results of the case group after 4 weeks compared with the 8 weeks result of the control group. Additionally, Figure 6, reveals the same significant results between the two groups after the 8 weeks. Nevertheless, the physical measurements related with hamstring Strain and Knee flexion range of motion between the two groups were not significant after 4 weeks or 8 weeks. Table 1. Data Summary for the Growth Factors after PRP Injectiona unit   Ã‚  Ã‚   Pre-test 24 h 48 h 72 h 96 h 4 weeks 8 weeks hGH   pg/mLpg/mL pg/mL 1.927  ± 0.67 8.117  ± 2.414 2.276  ± 0.030 2.776  ± 0.180 5.597  ± 1.910 2.321  ± 0.554 2.175  ± 0.651 IGF-1 pg/mL 0.577 ±0.283 1.078  ± 0.914 1.101 ±0.341 1.122  ± 0.239 1.133  ± 0.165 0.817  ± 0.844 0.793  ± 0.141 FGF-2 pg/mL 2.233  ± 1.22 2.105  ± 0.772 2.292  ± 0.736 1.911  ± 0.201 2.314  ± 0.877 3.652  ± 0.567 3.921  ± 0.822 VEGF pg/mL 0.346  ± 0.18 1.313  ± 0.42 1.544  ± 0.463 1.836  ± 0.463 1.554  ± 0.419 0.784  ± 0.098 0.749  ± 0.077 PDGF pg/mL 0.352 ±0.11 0.884  ± 0.949 1.702 ±1.572 1.602  ± 2.021 1.262  ± 1.423 0.856  ± 0.108 0.807  ± 0.133 aPRP, platelet-rich plasma; hGH, human growth hormone; IGF-1, insulin-like growth factor-1; FGF-2, basic fibroblast growth factor; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor. Table 2. Difference of the Growth Factors concentration between the Case and Control group Case Group (N=8) Control Group (N = 9) Unit Pre-test 4 weeks 8 weeks Pre-test 4 weeks 8 weeks P ≠¤ 0.05 hGH   pg/mLpg/mL pg/mL 1.927  ± 0.67 2.321  ± 0.554 2.175  ± 0.651 1.941  ± 0.201 1.997  ± 0.088 2.063  ± 0.477 1.215 IGF-1 pg/mL 0.577 ±0.283 0.817  ± 0.844 0. 793  ± 0.141 0.582  ± 0.247 0.633  ± 0.145 0.637  ± 0.114 1.760 * FGF-2 pg/mL 2.233  ± 1.22 3.452  ± 0.567 3.921  ± 0.822 2.228  ± 0.721 2.593  ± 0.687 2.627  ± 0.514 2.046 * VEGF pg/mL 0.346  ± 0.184 0.784  ± 0.098 0.749  ± 0.077 0.341  ± 0.163 0.384  ± 0.187 0.396  ± 0.106 2.584 * PDGF pg/mL 0.352 ±0.117 0.856  ± 0.108 0.807  ± 0.133 0.358  ± 0.121 0.421  ± 0.633 0.429  ± 0.008 2.632 * PRP, platelet-rich plasma; hGH, human growth hormone; IGF-1, insulin-like growth factor-1; FGF-2, basic fibroblast growth factor; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; N, Number; * Significant difference P ≠¤ 0.05, t =1.740 (N= 17). Table 3. Difference of Hamstring Force and Knee Flexion (ROM) between the Case and Control group Case Group (N=8) Control Group (N = 9) Unit Pre-test 4 weeks 8 weeks Pre-test 4 weeks 8 weeks P ≠¤ 0.05 HF N 26.62  ± 4.67 104.32  ± 5.67 107.06 ±1.64 25.31  ± 3.41 102.71  ± 4.75 105.75  ±3.18 0.743 KF(ROM) Deg. ËÅ ¡ 51.72  ± 5.17 147.92  ± 0.43 148.62  ± 0.78 52.04  ± 2.43 147.02  ± 0.14 147.36  ± 0.88 0.632 aPRP, platelet-rich plasma; HF, Hamstring Force; KF(ROM), Knee Flexion range of motion. N, Number. P ≠¤ 0.05, t =1.740 (N= 17). 4. Discussion: There is little published evidence to support whether a statistically significant increase in growth factors with performance-enhancing potential, including IGF-1, hGH VEGF, PDGF and FGF-2, necessarily leads to clinically relevant ergogenic effects. This is further complicated by evidence from some animal studies that local IGF-1 overexpression enhances local muscle mass and strength without systemic increases in IGF-1. The current study aims to determine the effect of PRP in accelerate the healing of hamstring strain. Moreover, to identify potential molecular markers that could be used to distinguish athletes who have been treated with local PRP injections from those who have not. Figure 5, The concentration of the growth factors after the PRP injection. PRP, platelet-rich plasma; hGH, human growth hormone; IGF-1, insulin-like growth factor-1; FGF-2, basic fibroblast growth factor; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor. The performance of the growth factors after a single PRP injection was enhanced and increased significantly from 24 until 96 hours.   Indeed, hGH was peaked within the 24-hour window, although the results were not significant after 4 weeks or 8 weeks. Similarly, IGF-1 is significantly increased by 24 until 96 hours after PRP, while its activation was decreased after 4 weeks and 8 weeks but with significantly difference compared with the pretest and the control group 8 weeks test. Furthermore, IGF-1 is generated in the liver in response to hGH, is the primary downstream mediator of hGH, and is the most specific marker of supraphysiological hGH exposure [36] [37]. Figure 6. Difference between the case and control group in the concentration of the Growth Factors after 8 weeks. hGH, human growth hormone; IGF-1, insulin-like growth factor-1; FGF-2, basic fibroblast growth factor; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor. Despite that both groups performed the same rehabilitation program, our study reported a significant increase in the growth factors for the control group after 4 and 8 weeks (Table 3, figure 6). However, the values of the case group after 4 weeks for the case group were more advanced than the 8 weeks values of the controlled (Figure 7,8). Therefore, the PRP injection enhanced the concentration of the growth. It is notably that the physical measurements of hamstring force and knee flexion range of motion were not significant at either 4 or 8 weeks. Wallace et al demonstrated that an acute bout of exercise increases total circulating IGF-1 by only about 20% [38] [9]. Figure 7, Difference between the case and control group in (NFROM) Knee flexion range of motion after 8 weeks. Figure 8, Difference between the case and control group in (HF) Hamstring Force after 8 weeks.          By comparison, participants in case group who treated with PRP and exercise program. Our study demonstrated a 38% increase in IGF-1 in case group and 9.5% in control group. Relative to baseline, suggesting that PRP treatment activates the hGH-IGF-1 pathway but that a single PRP injection is important to combined with the exercise to maximally stimulate. [39] [9] (Table 3) (Figure 6). We also observed FGF-2 and VEGF also peaked after treatment with PRP.   Fibroblast growth factor contributes to angiogenesis by stimulating the proliferation of endothelial cells to enhance the proliferation of satellite cells, which are the stem cells of mature muscle [40]. Basic fibroblast growth factor may enhance athletic performance by inducing muscle hyper- trophy and increasing oxygen transport. Vascular endothelial growth factor is a powerful stimulator of angiogenesis and could have noteworthy performance-enhancing effects if it entered systemic circulation and exerted its effects in tissues o ther than the site of injury [41]. The potential effects of autologous biological substances to hasten muscle healing were reported in several case reports [34] [42] [43]. Borrione et al [34] noted that athletes with grade 3 muscle strains treated with PRP showed earlier functional improvement and more complete recovery than those treated nonoperatively. Hamid et al   [44] demonstrated that a single PRP injection was effective in accelerating recovery for grade 2. However, the PRP Group achieved full recovery significantly earlier than controls and returned to play after 27 days while control group returned after 43 days. Another approach successfully treated an athlete with a grade 2 semimembranosus muscle injury with a single 3-mL infiltration of platelet-enriched plasma under ultrasound guidance. The athlete was pain free and allowed to train at the preinjury intensity 21 days after treatment [45]. The effect of a preparation rich in growth factors (PRGF) to hasten muscle recovery was reported in a 35-year-old pr ofessional bodybuilder diagnosed with a right adductor longus rupture. The athlete successfully returned to competitive training within 1 week after the third PRGF injection [43]. The effect of PRP in accelerated and associated a hamstring injury was also observed in the current study. The PRP preparation contained a high concentration of several growth factors including TGF-b, FGF-2, and insulin-like growth factor-1, but the amount of platelets and WBCs present was not stated. Additionally, the actual effect of PRP on soft tissue healing is not fully understood,22 our findings supported the possible role of higher growth factors (concentration level) in hastening recovery as postulated by previous researchers [46] [47] [42]. Sanchez et al reported full functional recovery of hamstring and adductor muscle injuries 2 times faster in 20 professional athletes treated with a PRGF [24]. Similar designed study by Rettig et al was investigated the effects of an autologous PRP injection and was retrospective case-control study conducted to determine the effect of the PRP on return time to play after acute hamstring injuries. The study included 10 professional National Football League (NFL) players with acute hamstring injury. The participants were divided equally into PRP and Control groups. Under ultrasound guidance the PRP group patients were injected once with 6 mL of PRP. Both groups were performed the same rehabilitation program. Several differences were identified between the study by Rettig et al and the current study. For instance, the

The Strength of Uncle Toms Cabin by Harriet Beecher Stowe :: Uncle Toms Cabin

The Power of Uncle Tom’s Cabin  Ã‚   Harriet Beecher Stowe’s novel, Uncle Tom’s Cabin, has had a tremendous impact on American culture, both then and now.   It is still considered a controversial novel, and many secondary schools have banned it from their libraries.   What makes it such a controversial novel?   One reason would have been that the novel is full of melodrama, and many people considered it a caricature of the truth.   Others said that she did not show the horror of slavery enough, that she showed the softer side of it throughout most of her novel.   Regardless of the varying opinions of its readers, it is obvious that its impact was large.   Ã‚  Ã‚  Ã‚  Ã‚   For instance many of the characters in the book have become the stereotypes of slavery in the South.   An example of this is Uncle Tom himself, whose name was eventually degraded into a nickname for blacks who were too subservient to whites.   He became the stereotype of the passive slave who would do anything his master told him, because it was his duty as a slave.   However few remember how the strength of his faith was what allowed him to tolerate the horrors that were enacted upon him.     Ã‚  Ã‚  Ã‚  Ã‚   Another example of the stereotyping of Stowe’s characters is Aunt Chloe, Uncle Tom’s wife, and her children.   Aunt Chloe is an excellent example because she has become the â€Å"Aunt Jemima† stereotype.   She had a â€Å"round, black, shining face† and wore a checkered headscarf, and she worked in the kitchen, took care of the kitchen, and basically ran the household.   Not to mention for many years black children were still stereotyped as mischievous like Mose, Pete, and, later in the novel, Topsy.     Ã‚  Ã‚  Ã‚   Even the slave owners and traders are stereotypes now.   Mr. Shelby and his wife have become the â€Å"gentlemen and lady† slave holders, who see themselves as good Christian people and attempt to take good care of their slaves, but still don’t see black people as equal to whites.   Simon Legree has become the stereotypical cruel master, who let his estate go to hell, but continued to work his slaves too hard and beat them senseless (or, in Tom’s and other’s cases, to death) when they did not behave as he thought they should.     Ã‚  Ã‚  Ã‚  Ã‚   However there are other ways this novel has been influential to American culture.   After its publishing it helped spread the ideas of the abolitionist movement.

Nike – good or bad?

Nike is good: A factory called Samyang in Vietnam (a factory under Nike contract) seems to be keeping satisfactory working levels within the building. It employs 5,200 people, most of them being women. The factory is made up of six big buildings with well-kept surroundings. Inside, there are fans keeping the workers cool, fire extinguishers about in the case of an emergency, and workers can easily access goggles, masks and gloves if they need them. Workers get double the local average of $54 per month and an annual bonus of at least one month's salary. Other factories get a lot less – in rural areas, factories pay $35 per month, in suburbs they pay $40 per month, and in cities, $45 per month. In state-owned factories (factories owned by the government), workers get a surprisingly low $15 per month! All this money they are getting has allowed most of them (three quarters) to buy a television, many to have a motorbike, some to have phones, etc. Not only does this improve their life, but it also allows other businesses such as petrol stations, electronic repair shops, etc. to function properly and make money too. This is called the multiplier effect. Nike has made changes to improve health and safety. In 1998, it replaced the very hazardous petroleum-based solvents with less harmful water-based ones. In 1999, an expert in the field went to verify Nike had actually done this at the Tae Kwang Vina factory in Vietnam. The investigator found that Nike had indeed replaced the compound and had also installed local exhaust ventilation systems. They also discovered that Nike had trained certain staff personnel aspects of health and safety. Nike is bad: Nike does not own the factories their clothes are manufactured in. This means they can leave at any time, leaving thousands of workers unemployed and fighting for their life while they find another job. For example, on February 22nd 2008, the BJ&J factory in the Dominic Republic announced that it was going to slowly fire workers and close. The factory, owned by Korean company called Yupoong, was making Nike caps at the time. In the Tae Kwang Vina factory mentioned earlier, some health and safety issues remained. Some sections of the factory were still exposed to hazardous chemicals, and to high heat and noise levels. In 1997, it was found that workers in a different factory were being exposed to 100 times the legal limit of Toluene, a toxic gas. Nike gets its clothes made in countries with free trade zones where it is illegal or extremely difficult for workers to organise into trade unions. It is practically impossible for workers to get better conditions (such as better pay, improved health and safety, etc.) when they cannot get together and form a united group to approach their boss. However, this said, some factory workers have done it before and achieved what they were protesting for. The Ching Luh Nike factory has 21,000 employees, and in June 2008, after going on strike for 2 days, they managed to get Nike to increase their wages by $6 a month. Some people think that the minimum wage in countries is enough to survive because the cost of living in that particular country is lower too. The chart below proves this to be wrong with three primary countries that Nike manufactures in. Nike doesn't pay lots to its workers. In many countries, they live way under the predicted living wage. The table shows the average wage of all the factories in that country, and the living wage in each. The data presented is only an average. Some factory workers earn only $1.60 a day, where the price of three meals a day is $2.00.

Book Report on “Fathers and Sons” by Ivan Turgenev Essay

â€Å"Fathers and Sons† is, perhaps, the most interesting book by the Russian writer Ivan Turgenev, which gained international recognition. It has been first published in 1862 and concurred with a complicated period of Russian history, known as the â€Å"Great Reforms†. Abolition of serfdom, reforms of administrational system, industrialization and raise of revolutionary ideas caused profound changes in the Russian society and in the minds of people. Turgenev’s book is devoted t this dramatic mental and psychological break. â€Å"Fathers† are old generation who share conservative views and â€Å"sons† are youth, dreaming of revolution and demonstrating nihilism and disrespect towards traditional values. The narrator of the story – Nikolai Petrovitch Kirsanov, is a son of a general, who has been a hero of Napoleonic wars. His life is rather unremarkable. Being unable to serve in the army because of the childhood trauma, he has married and lived happily with his wife till her early death. After that he devoted all his life to his only son Arcady. The novel opens when the older Kirsanov stands before the door of his dominion waiting for his son returning from the university. Finally the son comes back, but he is not alone, he is accompanied by his new university friend Yevgeny Vasil’evich Bazarov. Soon Nikolai Kirsanov finds out, that his son has completely fallen under influence of Bazarov’s nihilistic and realistic views. He dreams of bloody revolutionary changes and disputes with Kirsanov about the future of Russia: â€Å"Aristocracy, liberalism, progress, principles,† said Bazarov. â€Å"Just think what a lot of foreign . . . and useless words! To a Russian they’re no good for anything! â€Å", says he. Further along the novel Bazarov continues to play a role of a â€Å"revolutionary demon†. He is pretty charismatic, so such miserable people as Sitnikov and Kukushkina fall under his influence. Those two are represent a sort of â€Å"progressive thinkers† whose â€Å"progrogressism† comes to be reduced to absurd. They are ready to admire any new nihilistic ideas being completely unable to think of them critically and add any own reasoning to them. Bazarov openly contemns Sitnikov and flirts with Kushkina to allay his boredom. What is really interesting for Bazarov are his disputes with Pavel Petrovitch Kirsanov, older brother of Nikolai Kirsanov They feel antipathy from the very first moment of their acquaintance. Pavel Kirsanov speaks of Bazarov’s nihilism as of an unfounded doctrine existing in vacuum. Bazarov’s manner of thinking is purely utilitarian: â€Å"We act by virtue of what we recognize as useful,† went on Bazarov. â€Å"At present the most useful thing is denial, so we deny†. Pavel strongly disagrees â€Å"But allow me,† began Nikolai Petrovich. â€Å"You deny everything, or to put it more precisely, you destroy everything . . . But one must construct, too, you know. † [33] But Bazarov remains sure, that to construct something it is first necessary to â€Å"Clean the ground†. Perhaps this dispute between Pavel Kirsanov and Bazarov puts forth the basic idea of the book: conflict of conservatism and revolutionary doctrine. In order to iron out the differences between Pavel Kirsanov and Bazarov Arcady tells Bazarov the story of Pavel’s life. Once Pavel was a luminous officer, but love to a woman, duchess R† ruined his life and left him completely drained. Pavel only retained his sophisticated taste, fair manners and Anglomania. Although she is not present in the novel, duchess R† seems to be one of the characters because even after years she continues to determine Pavel’s actions. He asks for satisfaction from Bazarov, when he sees him kissing Fenichka, but the real reason is not Bazarov’s behavior, but that Fenichka somehow reminds Pavel duchess R†. While men in the story are symbols of social classes and positions, women represent something, what can be called â€Å"normal life†, whether it is duchess R† – a symbol of Russian magnificent nobility, Fenichka – a symbol of common sense, or Mme Odintsov. Mme Odintsov is a very special character. On the one hand she is perfectly educated and progressive woman, on the other she does not in any way share Bazarov’s enthusiasm about social cataclysms. She is sure, that society is to be bettered by bettering of human, but not by reconstruction of it’s formation. She asks Bazarov a question which he is unable to directly answer: â€Å"And you suppose,† said Anna Sergeyevna, â€Å"that when society is reformed there will be no longer any stupid or wicked people? † [56] Bazarov starts explaining that a proper society will make no difference, but inside he feels, that Odintsova is right. Love to a woman is so contrary to Bazarov’s views, that he is unable to accept it, putting cynicism on himself, and then leaving her house. He attempts to find some occupation for himself, flirts, fights at a duel and tries to speak about his ideas with peasants. The peasants are in fact those, who are to be enthusiastic about the revolution, at least as Bazarov thinks. So he is unhappily surprised to find out, that peasants do not want to understand complicated teaching and think of him as of a cheat. Bazarov’s ideas collapse: he finds no support both with educated and common people, so he has to recognize, that revolution is actually unnecessary to anyone and that it is nothing more, than a fashionable game. Pavel Kirsanov is right: doctrines of Bazarov exist in vacuum. It is not clear whether Bazarov’s death was a suicide, but his behavior itself is suicidal, and he accepts the certainty of death calmly. The only thing he wants is to say farewell to Odintsova. At his deathbed he openly confessed, that all his prod ideas went down to the pan. He continues to speak of himself as of a giant, but now the only task he puts for himself is to die with dignity. Six month after his death the two couples married: Nikolai Kirsanov to Fenichka and Arcady to Kate – Odintsova younger sister. The normal life continues even after Bazarov’s death, and Arcady, his former confederate, becomes a wealthy landowner, representing an antithesis to Bazarov’s views. Bazarov’s grave is almost forgotten, and only his parents sometimes come to shed tears over it. Although â€Å"Fathers and Sons† is a novel about pre-revolutionary Russia, it’s lesson is useful for all generations. Sons always rise against their fathers, willing to change this world and create a totally new one for themselves. And Turgenev demonstrates how mental dissoluteness and spiritual weakness can destroy even the most sharp-minded person. The whole revolutionary fervor of Bazarov is destroyed by romantic love – the real motivation of the world. At the end of his life â€Å"the demon† feels lost and betrayed, while conservatism triumphs over his grave. Works cited: Ivan Turgenev (1998) Fathers and Sons. Oxford: Oxford University Press

Globalisation essay

Globalisation essay Globalisation essay Globalisation essayThe development of the world economy and international relations becomes vulnerable to the overwhelming impact of globalisation which affects all countries, even though they conduct isolationist policies, such as North Korea, for instance. Moreover, once started, the process of globalisation is likely to be irrevocable. Globalisation is the process of the international economic, political and cultural integration of nations. The economic integration is the major driver of the process of globalisation. Even though many researchers (Dunning, 1998) insist that globalisation has a positive impact on the economic development of the world because the emergence of international trade stimulates the economic growth worldwide, but long-run effects of globalisation may be negative, especially for the poor nations which cannot compete with well-developed nations in the global market.Background of globalisationGlobalisation has started as the increasing economic cooperation b etween nations at the regional level and steadily evolved into the global trend. The economic cooperation between countries was the result of the accumulation of capital by leading companies operating in the national market. The accumulation of capital made national markets inattractive for companies because they have saturated them and they needed further export of capital and international market expansion. In such a situation, the international market expansion prior to the globalisation era was not always profitable because of high costs of such expansion. The high costs of international market expansion and, therefore, international economic cooperation between nations, was the result of high fiscal barriers, which local governments introduced to support their domestic economies. The process of globalisation emerged after the beginning of the elimination of fiscal barriers to developer free trade between countries. The free trade implied the elimination of fiscal barriers that stimulated companies operating in different countries expand their business internationally. At the dawn of globalisation, there were interstate agreements involving two or three states, as was the case of the NAFTA signed by the US, Canada and Mexico, but soon such agreements involved multiple parties and, today, free trade agreements involve the majority of nations. At this point, it is worth mentioning the EU as one of the most advanced and integrated international community that united European nations and evolved from the economic union into the supranational political union which unites European countries, members of the EU.Therefore, the process of globalisation involves the elimination of fiscal barriers and limitations on the movement of capital, goods, commodities, and human resources. The increasing economic cooperation between nations stimulated the development of multinational corporations which operated globally. The overwhelming majority of multinational corporations were based in well-developed countries. Multinational corporations in their turn encouraged governments to eliminate fiscal barriers and develop free trade further to facilitate their further international market expansion. At the same time such policy resulted to the consistent strengthening of the process of globalisation which has become the mainstream trend in the contemporary economic development of the world.Effects of globalisation on developed nationsGlobalisation has had a considerable impact on developed countries. In this regard, one of the effects of globalisation was the development of trade between well-developed nations mainly. In fact, the trade between developed nations comprises the larger share in the total world trade. Moreover, developed nations focus on the trade with each other rather than with under-developed nations which they tend to use as suppliers of natural resources, such as fossil fuels, for instance.The economic cooperation is beneficial for develope d nations because they have technology, capital and well-qualified human resources which are key factors contributing to the competitive advantage of companies in the global market (Martin Van Gunten, 2002). Developed nations and companies based in developed countries use their technologies to enter new markets and take the dominant position in international markets. They often take the leading position in the global market as is the case of Microsoft, for instance, and develop their business successfully. More important, globalisation involving the free trade opened large opportunities for companies based in developed countries to purchase natural resources and other basic supplies from developing countries. As a result, companies based in developed countries have got an opportunity to decrease costs of production due to the elimination of fiscal barriers and low price of supplies from developing countries. Moreover, they accelerated the consumption of natural resources and other basic supplies from developing countries but purchasing raw materials mainly they sold high tech products to developing as well as developed countries which price was often tenfold higher than the price of raw materials the products were made of.Foreign direct investment flow also tends to the investment of capital into developed countries mainly, while investments in developing countries turn out to be secondary. Therefore, developed countries prefer to invest into other developed countries because they believe such investments and reliable and safe. In addition, investors investing in developed countries can count on low risk of investment and stable level of income. Such investments are stable and profitable.Even emerging economies are secondary targets for investors from developed countries. Instead, the US investors prefer to invest into the EU economy, while the EU investors prefer to invest into the US economy. At this point, it is worth mentioning the fact that the investmen ts between developed countries contribute to their accelerated economic growth that allows them to outpace the rest of the world consistently. Developed nations apparently benefit from such mutual investments because they stimulate their economic growth. One of the reasons why investors from developed nations prefer investing in developed economies than in emerging and developing economies is the risk of such investments. In fact, they do not want to take a risk and invest into unstable countries.  Globalisation   essay part 2

Married life Essay Example

Married life Essay Example Married life Essay Married life Essay Marriage is the third main ideal to be presented in Act 1 of the play. Whilst it is not strictly an ideal in itself, the manner in which it is presented leaves a sense of mocked ceremony. The female leads treat marriage with a deadly seriousness in all respects, with Lady Bracknell saying: an engagement should come on a young girl as a surpriseIt is hardly a matter that she could be allowed to arrange herself this seeming dedication to the meticulous arrangement of a marriage in order to achieve the best results ironically destroys any romantic element, and in that aspect chances of true love. The male attitude to marriage is quite different. When talking with Jack in private, Algernon takes a rather dismissive stance on marriage: A man who marries without knowing Bunbury has a very tedious time of it, this negative view is also shown in In married life three is company and two is none. This is again representative of a characters embodiment of an ideal, or the anathema to one in this case. The attitude of the men changes when in the company of the women, in order to appear courteous and honourable, as the woman superficially believe they are. This pretence of behaviour is something of a microcosm for the ideal of marriage itself. The explicit female view of marriage is dismantled with various epigrams, for instance Lady Bracknell saying that after her husbands death, Lady Harbury looks quite twenty years younger. Again Gwendolens statement that her ideal has always been to love some one of the name of Ernest, is obviously facetious, and through that it is clear that the women have an equally sceptical view of marriage as the men. Yet they are inexorably drawn towards it because of the perceived duty to live up to the romantic ideal of marriage. Wildes satire of this situation again helps to dismiss the validity of the ideal presented. Marriage is probably the most complex of all the ideals presented in Act One of the play, in that the view presented very much depends on the interaction of the two sexes, which in itself is a questionable motif, consequently a definite opinion can not be drawn from it. Ultimately, the presentation and satire of the age of ideals is light hearted and insincere, however there are several poignant facets of this dissection of society that are worthy of note. The duality of human nature, whilst being an over-used speculation is particularly applicable in the play, as it is the habit of the characters to have sincere feelings and yet be incapable of showing them at all. The motiveless and consequently worthless existence of the upper classes is starkly compared to the diligence of a few hard working men of the lower echelons measures up unfavourably. Whereas the objectification of women is quite clearly the biggest irony in the play; as is quite clear from the actions of Gwendolen and Lady Bracknell, they are in fact the ones in charge.

Chicago Referencing †Citing a Newspaper (Footnote Style)

Chicago Referencing – Citing a Newspaper (Footnote Style) Chicago Referencing – Citing a Newspaper (Footnote Style) News flash! Citing sources is vital in academic writing. But what should you do if you need to cite a newspaper in your work? This all depends on the referencing system you’re using. With Chicago referencing, you have two options: author–date referencing or footnote citations. In this post, though, we’re looking specifically at citing a newspaper with Chicago-style footnotes. Footnote Citations The first time you cite a newspaper article, give full publication information in the footnote. The format for doing this is: n. Author Name, â€Å"Title of Article,† Title of Newspaper, date of publication, page number. In practice, then, the first citation of a newspaper article would look like this: 1. James V. Koch, â€Å"No College Kid Needs a Water Park to Study,† New York Times, January 9 2018, 65. This citation points to an article on page 65 of the New York Times, published on January 9. Online articles won’t have page numbers, though. Instead, give a URL and date of access. For instance: 2. James V. Koch, â€Å"No College Kid Needs a Water Park to Study,† New York Times, January 9 2018, accessed 2 April 2018, https://www.nytimes.com/2018/01/09/opinion/trustees-tuition-lazy-rivers.html. If you need to cite the same article again, you can use a shortened format. To do this, just give the author’s surname, a shortened version of the title, and (if relevant) a page number. Bibliography In Chicago footnote referencing, all cited sources are listed in a bibliography at the end of the document. The format to use for a newspaper article here is: Surname, First Name(s). â€Å"Title of Article.† Title of Newspaper, date of publication. As with footnote citations, you should also give a date of access and URL for online articles. For instance, if citing a print article and an online article, the bibliography entries would look like this: Koch, James V. â€Å"No College Kid Needs a Water Park to Study.† New York Times, January 9 2018. Selingo, Jeffrey J. â€Å"You Got into the College of Your Dreams. But Will You Actually Go There?† The Washington Post, March 29 2018. Accessed 2 April 2018. https://www.washingtonpost.com/news/grade-point/wp/2018/03/29/you-got-into-the-college-of-your-dreams-but-will-you-actually-go-there/?utm_term=.7ba14166f003

Discussion 5 Assignment Example | Topics and Well Written Essays - 750 words

Discussion 5 - Assignment Example He followed the Lebensraum policy, living room, in order to snatch lands outside Germany and let the German people expand their territory (Spielvogel,1988). In chapter seven the leaders of France and Britain met Hitler to discuss his demands of expanding Germany. They granted him control over a part of Czechoslovakia and in return Hitler pledged to leave the other parts of Czechoslovakia. Hitler broke his promise and took the rest of Czechoslovakia and invaded Poland. This caused the start of World War two. This occurred in September 1939 when German troops invaded Poland and Britain and France declared war. Adolf Hitler’s dream of building a German Empire across Central and Eastern Europe could not be established only through Lebensraum. Lebensraum could only be established by waging a war against the Soviet Union. Hitler’s racial ideology required it, hence the conclusion that World War two was Hitler’s war. Asia, Japan and China also were already at war. More than fifty million people lost their lives during the war, including Germans and also non-Germans In chapter eight Germanies continue with the war and Hitler brought Nazi to power. Hitler enforces his new rules with a secret police, the Gestapo. He formed camps which organized the murder of Gypsies, Jews and political opponents. There was also resistance in the war and the home front was preparing adequately for war (Spielvogel, 1988). In chapter nine the Holocaust took place. It refers to the extensive murders Hitler and his Nazis were accountable for. It involved the formation of squads that followed Hitler’s army to murder Jews and those who were not of German descent. Many camps were set up around Europe and several were determined to murder people. In the years 1939 and 1940, the Nazi army was responsible for the deaths of around fourteen million people which included six million European Jewish people. They

Developing a Health Advocacy Campaign , Prostate Cancer Research Paper

Developing a Health Advocacy Campaign , Prostate Cancer Funding - Senator Boxer introduced the Prostate and Mens Education Act, - Research Paper Example The cause of prostate cancer is not clearly understood, but researchers argue that issues like race, family and age are beyond ones’ control. But some risk factors like avoiding fatty foods can be avoided as one is advised to eat more fruits, unsaturated foods, whole grains and intake of less red meat. Some medication from well equipped health centers helps reduce the spread of the cancer in the body. Drugs like; finastede have shown to reduce the prostrate cancer risk (John, 2008). California population is the most affected with cancer cases with 1,277,200 people affected with different types of cancer. The state projects that in 2012, more than 144,800 new cases will occur. The patients with prostate cancer include 20,195 new cases that makes up to 28% and 3,085 deaths occurs. The survivors of prostate cancer are 240,200 that accounts for 42%. Although from 1988 to 2009, 11% reduction has been reported as mortality reduces by 23% (CCR, 2012). The advocacy that have been effective include the â€Å"Us too advocacy† that uses the prostate cancer survivors and victims to spread the awareness creation. They give speeches in forums, hold door to door awareness creations and attended screening centers to help explain to the attendees the screening environment. The attributes that makes this advocacy campaign is that it involves survivors, volunteers and experts to spread the required awareness messages. The volunteers take their time to deliver the message of the benefits of early screening, explaining the screening environment to the people so that they attend the screening exercise and encouraging people the people to attend the screening centers. The other attribute makes this advocacy to be effective is the involvement of medical experts on comprehensive research and provision of a variety of advanced treatment (CCR, 2012). The other advocacy campaign that is effective is the â€Å"Zero prostate cancer†

Reviewing of articles Literature review Example | Topics and Well Written Essays - 1250 words

Reviewing of articles - Literature review Example Adoption of new or modified accounting control can have meaningful changes on organizational strategies and the general perception of organizational purpose (Ahrens, T. & Mollona, M. 2007, 306). Addressing the cultural dimension of organizational control technologies is key just like the practices that engage technologies. The study of control as a cultural practice lies in exploring relationships between the diverse aspects of organizing. This includes work processes and their technologies, organizational members’ values, beliefs and social relationships. The cultural analysis aims at clarifying the sources of ambitions of the organizational members and how they are shared in competition with each other. It also evaluate their contributions in making the practices unfit or subjective to technical discussions and struggles over organizational purpose (Ahrens, T. & Mollona, M. 2007, 312). Comparative account of organizational subcultures, based on detailed observations of activities and how they consist of specific practices helps to shed more light. It involves the adoption of anthropological approaches to the study of organizational control. This entails the study of how management strategies and production strategies affect the control practices of different organizational subcultures. It also digs deep into determining how the social relations between organizational members and their social backgrounds can give rise to different cultural practices of control. Adoption of the anthropological method in the study of culture is a useful tool for producing longitudinal observations of everyday operations through which the study of accounting and control is studied. This mode of studying the everyday functioning of accounting is a key tool in providing detailed insights into the ways in which accounting makes possible and becomes part of specific forms of organization.

The C.I.A Research Paper Example | Topics and Well Written Essays - 750 words

The C.I.A - Research Paper Example so coincided with the alleged UFO crash in Roswell, New Mexico, causing many people to believe that the creation of the agency also had to deal with the probability of extra terrestrial visitors. The main task of the Central Intelligence Agency is to gather, process and analyze situations or people, both inside and outside of the United States, that can be threatening or harmful to the United States. If the agency comes upon any information that suggests that someone is doing something harmful at the expense of the United States, they take the proper actions to ensure that nothing comes of these actions and that the person is dealt with accordingly. The agency also looks for threats that may come to an interest that the United States has in the world. In essence, the Central Intelligence Agency seeks out threats and dangers to the United States and the world and does what need to be done to prevent both negative actions and the leaking of the threat to the general public. The CIA also monitors activities that have the potential of turning dangerous, such as a foreign country creating a new nuclear power plant to produce electricity. The CIA would monitor the progress of this plant to ensure that it really is being created for the intended purpose and not for something that can prove to be harmful. The Central Intelligence Agency, in their mission of protecting the United States and the places of interest throughout the world, also helps in making the important decisions surrounding national security. The agency does not make the policies, they simply provide foreign intelligence information for the agencies and groups that do make the policies based on the information provided (Weiner, 2008). At times the agency is allowed to suggest possible policies or changes to current policies as starting points for the groups actually able to make the changes. Their sole job is gathering the information needed to make the decisions that can help keep the United States and

Reflective practice Essay Example | Topics and Well Written Essays - 2000 words - 2

Reflective practice - Essay Example Reflective practice is one of the most important concepts in contemporary management in various contexts (Arnold & Development Research, 2012). From schools, businesses, personal initiatives, group projects, and healthcare facilities, reflective practice has been used to enhance the assimilation and comprehension of initiatives. Apart from providing a retrospective angle of a particular initiative, which involves â€Å"retreat in order to advance† mentality, reflective practice gives teams and individuals a critical perspective of a process that enables the transmission of knowledge to other people. For example, reflective practice is highly to the business effective in educational settings where students’ comprehension can be significantly enhanced by looking back at past lessons (Tarrant, 2013). Reflective practice is desirable for the MEGA experience because it enables greater understanding of the plans put forward by the team members and, consequently, promotes a po sitive contribution from all participants. Since the activities involved in the experience are business-oriented, reflective practice enabled the team members to identify potential mistakes in projections, goals, and budgets (Roffey-Barentsen & Malthouse, 2013). In terms of analysis, it provides the team members with an opportunity to refine the three aspects based on the corrective measures adopted, and significantly improves the team’s analytic capacity with regards to the business.

Reasons why a Large Company in One Country Might Wish to 'Go Global' Essay

Reasons why a Large Company in One Country Might Wish to 'Go Global' and the Various Ways it Could Expand its Operations Oversea - Essay Example Going global has become the norm because it offers the companies a range of opportunities to move ahead further and increase their profits in the long run (Orr & Sohal). It makes them realize their due potential and the risks that they could take to achieve supremacy within their line of business. Nearly all companies wants that it expands its operations within the far flung areas of the world in order to increase its sales and bring new customers into the equation. The large companies are no exception to this rule as they look to exploit the weaknesses of their competitors and build upon the strength that possesses within their folds. What is even more significant is the fact that these companies have started to understand the nuances related with growing far and wide which essentially allows them to develop in an out and out manner. The senior management domains within these companies are looking at exploring newer markets because they believe that the unique customers provide a go lden opportunity for the company under consideration and the outsourcing debates are also settled in an amicable way (Townsend, Cavusgil & Yeniyurt, 2004). This is indicative of the numerous discussions that are being done within the going global perspectives and which have more or less touched upon the new understandings of growth and development for the sake of the companies in the modern times. These companies are doing their best to find out where the opportunities lie and what is it like to tap them before their competitors are able to do just the same. Hence the intention is to bring along all the necessary resources and find new avenues and routes which will eventually build upon the profits and expand left, right and center around the world. The companies are therefore looking at areas from where they can cut down on costs and bring in more profits. This debate comes directly under the realms of the outsourcing ones because third world countries are seen as the most helpful ones, where they bring cheap labor with them yet look at establishing offices which cut down on costs immensely. In essence, the entire world has come out as a whole new ball game for the companies which earlier used to believe in a single local marketplace. Now the times have changed and that too for all the right reasons as has been evidenced by recent examples of some companies which have made it big around the world by exploring newer markets (Gregory & Shi, 1998). One of the other reasons behind companies going the global way is because they have started to realize that just being limited to a single place would not allow them to grow beyond a certain measures. Thus they need to enact strategies and find pathways which will double or tripe their expected sums in the coming times. This is the reason why these companies are always on the look out for newer markets, diversified product forms tailored for new and potential customers, and local market suited products and services. I n essence, the role of the companies within such a fray is a precisely sensitive one since they have to decide who to hire, where to purchase all the resources and how to go about doing operations within a new country which effectively is quite a risky process. The companies have also realized the fact that the local laws and regulations are also something which must be

Reflective practice Essay Example | Topics and Well Written Essays - 2000 words - 2

Reflective practice - Essay Example Reflective practice is one of the most important concepts in contemporary management in various contexts (Arnold & Development Research, 2012). From schools, businesses, personal initiatives, group projects, and healthcare facilities, reflective practice has been used to enhance the assimilation and comprehension of initiatives. Apart from providing a retrospective angle of a particular initiative, which involves â€Å"retreat in order to advance† mentality, reflective practice gives teams and individuals a critical perspective of a process that enables the transmission of knowledge to other people. For example, reflective practice is highly to the business effective in educational settings where students’ comprehension can be significantly enhanced by looking back at past lessons (Tarrant, 2013). Reflective practice is desirable for the MEGA experience because it enables greater understanding of the plans put forward by the team members and, consequently, promotes a po sitive contribution from all participants. Since the activities involved in the experience are business-oriented, reflective practice enabled the team members to identify potential mistakes in projections, goals, and budgets (Roffey-Barentsen & Malthouse, 2013). In terms of analysis, it provides the team members with an opportunity to refine the three aspects based on the corrective measures adopted, and significantly improves the team’s analytic capacity with regards to the business.

Consolidated Life Case-Business Ethics Essay Example for Free

Consolidated Life Case-Business Ethics Essay Consolidated life is a prestigious insurance company however, due to the nature of the establishment the duties required by the worker neither required minimal knowledge nor did you have to have a high level education in order to obtain a position at the company. Mr. Mike Wilson however, obtained a business degree in administration. He was hired by Consolidated Life as simply as you can put a clerical worker. He worked in the policy issue department which main duties included processing or in taking clients orders for insurance, customer service, and client services. One would say that working for them; your performance required little to no creativity. It was the same day-to-day work load. Because it required so little creativity, daily routines were repetitive and can be done basically, with your hands tied to you back. Mike Wilson demonstrated how an effective a leader can be in the workforce rather than just a manager by title. He portrayed in existence of â€Å"high fidelity† which is the best experience you can have in a workplace. In the book Trade Off, by Author Kevin Maney, the word fidelity deals with â€Å"the total experience of something† (Maney, 2009). The author also says that â€Å"aura† can also provides an advantage to fidelity. With that being said Mr. Wilson influenced his co-workers with providing them with incentives and rewards in which they can gain a reward at the end of the task but most importantly he provided the right tools and motivations in order for his employees to work in a positive mind frame. This created a system of mutual bipartisanship between supervisor and employee. Model: based on the Organizational Model Behavior Mikes drive and motivation can be comparable to a person with theory y attributes. The theory Y concept displays how an employees work is as natural as play. Also a person with this characteristic has a huge sense of self-direction and self-control. Mr. Wilson showed this by cultivating a modern management technique that motivated its workers rather than coerced them which a person who you can place in this. Whereas, a person with the characteristics of theory x† carries the opposite attractions. The individual is not seen as enthusiastic about their job. They are mainly threatened or told â€Å"do it or else† and as stated before, lack the ability and drive to overachieve. They usually follow the motto, overpromise-under deliver. Mikes performance ultimately won him a promotion working in the supervisory assignment area. He won this promotion just six weeks after promise. Mike brought a sense of modern culture although it was seen as unorthodox or non-traditional. When comparing the delegation of authority in the levels of management the organization structure clearly shows that the establishment followed an authority oriented program in which Presidents are first to make decisions for the overall â€Å"vision† for the company in which it then trickles down to the VP who implements the President’s strategy by orchestrating a staff of supervisors to oversee the execution. Situation: There seems to be a drastic change to the division in which Mike supervised some time ago. When Mike realized his unhappiness at his new division he sought a remedy for disaster by returning to his old division forcing him under new terms and most importantly, a new boss. The performance value of his once over exceeding staff was now dwindled and unmotivated. The new way in which they worked became stricter and more inflexible. It was stale and there was no aura of high fidelity being promoted. Problems: The problem of this case has to do with mis-delegation of roles and mis-clarification for all parties. Not only that, the fact is the company as a whole has not identified its mission statement for their employees. With that being said the transition from the time Mike left became a tragedy. As stated before, the culture of the environment was slated after Mike left. It became from being a collegial environment to an autocratic environment once new vice president Jack Greely took over. Not only did he change the environment of the company, he basically dismantled the structure and rebuilt it based on his power. Until Mike was promoted the managerial style approach was not identified and supervisors, at this early time wanted a change and that’s why Mike was chosen to become supervisor. However, when Jack took Mike’s former supervisor’s place, the organization became, autocratic. An autocratic person can be defined as an employee that is dependent tot tally on a supervisor. This person has no other desire than to do what is only required out of the task and only the minimum. Usually in an autocratic setting the boss expects pure obedience from their employees and rely straight on authority from higher ups with no regard to any self-drive for themselves and lacks the qualities and abilities to take on initiatives and providing an entrepreneurial attitude about themselves. This can be explained by using the Abraham Maslow’s Theory found in an essay article written by Janet Simmons, Donald Irvin, and Beverly Drinnien which it states he says accordingly â€Å"that the only reason that people would not move well in direction of self-actualization is because of hindrances placed in their way by society† (Janet A. Simons, 1987). Also saying â€Å"We must see that the persons basic needs are satisfied. This includes safety, belongingness, and esteem needs† (Janet A. Simons, 1987) A person in the Consolidated Life organization that can be also skewed towards the autocratic style is Mr. Rick Belkner. Mike’s former boss. This, for lack of a better term, lazy supervisor (whom he was Mikes supervisor initially) illustrated as a person who rather do crossword puzzles during his work shift then to lead by example, what a competent Vice President of their division; shy 40,000 of a six-figure salary. The point was clearly made by Mr. Greely when he assumed that Mikes management style would still be undermined no matter how good of his performance. He even went to the extent of assuring that Mr. Wilson will fail no matter how high you move up in the establishment. It is almost agreeable to say that Mr. Speelys choose of words were not only rude but shows a poor and ineffective leader. Mr. Greely does not seem to be results-driven but ego-driven as his defense for Mikes work style was inarguable and measured his own assumption to Mikes performance rather than just judging an employee on what he does best, his/her performance. Reading how Mike handled it; amazingly enough. In the chart featured on page-You can see simple comparing of the two different types of behavioral patterns by identifying the qualities, organizational and environmental forces that are represented by the 2 behavior patterns. You will see the differences between a workers operating in an autocratic setting versus a person who operates under the collegial or supportive setting(s). By identifying the contrast you are able to see what kind of modifications or structures that would have to be put in place based on a employees attitude. The attitude in which comes from probably stems from personal goal, motivations, or self desires a person may have in their work space. Some individuals dont possess the willingness to achieve and be a leader. Some individual are quite happy with just being an average worker and moving up in the corporate latter is something that does not motivate them. Autocratic Environment Vs. Collegial /System Environment Base Questions for Case 1. Describe ALL the factors that contributed to Mike’s lack of promotion at the end. Was his lack of promotion fair? When Mike left the division, he left the process in which he created, to be altered by the new president upon his departure. The flexible leadership that led to the team success came to a halt when divisional vice president, Jack Greely; who’s reputation was described as tough but fair. Mike accepted the position at the old division again without really investigating the provisions in which he was now to work under. He loss total control when he noticed that co-workers were actually more inclined to follow Mr. Greelys direction because the employees knew the order of hierarchy and knew the consequences of action should one follow anyones demands except for Mr. Greelys. 2. Using your knowledge of culture, explain in detail Consolidated Life’s culture when Mike was first hired and then when he returned. There was a transition in the organization which proved to have opportunities due to the position void. Such example shows that Mike (when he was first hired by Consolidated Life) he was promoted to his position because of the opportunities of change. Mike’s style was not really favored by his â€Å"higher-ups† but because he manages to increase workflow and reduce errors, which created more performance his flexible style was overlook which sends a sign of â€Å"inconsistency†. If you are going to allow a manager to take over the project then let them take over. As long as they don’t compromise the integrity of the company or do anything illegal. 3. What actions could Consolidated Life have taken to prevent Mike’s problems? There should have been more flexibility granted for Mike to effectively coordinate his team. Mr. Wilsons track record clearly shows that as a supervisor he is competent to make educated decisions and lead a staff with ease. An employee is always happy when they are not pressured nor stressed. Most important of all, when a leader shows reciprocity, more than likely there would be a win-win. For Example, Mikes strategy to reward his co-workers in exchange for hard work showed the worker was not working out of vain and in fact he/she was being acknowledged and rewarded for the hard efforts being put forth. 4. Who do you think was at fault for Mike’s problems, Mike or his supervisors (e. g. , Jack) or others? Completely justify your opinion. The fault of Mike problems was his free spirited style which usually offends conservatives. Jack implemented a â€Å"corporate† style setting upon Mike’s return.

Methadone Pharmacology and Its Mechanism of Action

Methadone Pharmacology and Its Mechanism of Action Table of Contents (Jump to) 1. Goal 2. Aims and Objectives 3. Background 4. Methadone Pharmacology and Its Mechanism of Action 4.1 Methadone History Background 4.2 Benefits of Methadone 4.3 Deaths Involving Methadone 4.4 Pharmacokinetics and Metabolism of Methadone 4.4 Cytochrome P450 4.5 Cytochrome P450 Polymorphism and Adverse Drug Reactions 1. Goal Methadone is the most common and widely used drug for the opioid dependence in Ireland as in most of the countries in the E.U. Methadone treatment is undoubtedly effective however; the reports on methadone related mortalities have definitely stirred the public concern. The challenge for biotechnologists is to determine whether the application of pharmacogenomics can solve this dispute. The fact regarding any drug or opioid is that they affect different individuals in a different way. To solve this â€Å"Biological Puzzle† this case study links the role of methadone and CYP2D6 gene variations with the metaboliser status of individuals, which may serve as an adjunct in methadone related fatalities. CYP2D6 is a member of cytochrome P450 mixed oxidase system, which is involved in the metabolism of many toxicologically important drugs that commonly implicates in fatal poisoning. CYP2D6 gene is located on chromosome 22 and is highly polymorphic in nature. Single Nucleotide Polymorph ism (SNP) variation at the exon 4 position of the gene results in a single nucleotide change of G to A, which ensue in poor metabolism of the drug. This variation is amongst 5 to 10% of the Caucasian population. 2. Aims and Objectives The specific aims of this report are as follows: Describe the methadone pharmacology and its mechanism of action, which will include the pharmacokinetics and the pharmacodynamics of the drug. The role of cytochrome P450 in the metabolism of methadone. The focus will be on the genetic polymorphism and the adverse drug reaction. This research will further investigate on methadone’s safety profile and mortalities associated with the drug. 3. Background Methadone is a synthetic opioid, invented during the Second World War (White Torres, 2010). The first chemical synthesis of the drug was in 1939 at the pharmaceutical laboratories of I.G. Farbenkonzern, Germany. Methadone was introduced to the market during 1960’s and since then it is one of the most valued drug which has proved its effectiveness from the prevention of abstinence syndrome that occurs after rapid interruption of continuous opioid administration (Zweben Payte, 1990; Dole Nyswander, 1965). Methadone is also one of the most common medications administered for the treatment of heroin addiction, however; there are many fatal poisonings reported over the years (Bunten et al 2010). Methadone is a liposoluble basic drug, often administered orally as a racemic mixture of two enantiomers i.e. R-Met and S-Met (Garrido Troconiz, 2000). It has a long plasma elimination half-life that lies between 13 and 55 hours and a high bioavailability of 70% 90% when administered orally (Moffet et al, 2004). It is extensively metabolised in liver and is converted into its primary metabolite which is 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) (Crettol, Monnat Eap, 2007) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) (Lugo et al, 2005). Blood methadone concentration in drug tolerant individuals reaches >0.84 mg/l, whereas in cases of fatality or poisoning concentrations typically range from 0.4 mg/l to 1.8 mg/l. Fatalities have also been reported with concentrations as low as 0.05 mg/l which is significantly lower than the average concentration in blood (Caplehorn, Drummer Fatal, 2002). Studies suggests that the largest patient associated deaths are during t he drug induction phase, when either individual drug tolerance is overestimated or the presence of other drugs are also found in the system (Bunten et al 2010; CSAT, 2004). The revolutions in the molecular techniques in postgenomic era provide us a significant platform for the diagnostics and clinical purposes. Pharmacogenomics is the study of the impact of heritable traits on pharmacology and toxicology that acts as bridge to certify opioid fatalities (Wong et al 2002). The significant inter-individual variation in blood methadone concentrations and individual susceptibility to methadone toxicity might be explained through genetic variations of the genes encoding the drug metabolism enzymes. Pharmacogenomics acts as the linkage between an individual’s genotype and individual’s ability to metabolise a foreign compound (Linder, Prough Valdes 1997). Most xenobiotics, including therapeutic drugs, are metabolised by cytochromes P450 to some extent (Guengerich, 2006). The metabolism of these drugs results in detoxification and elimination of drug or activation of the prodrug to its biologically active form. Cytochrome P450 (CYP450) shows a wide interindividual variation in their protein expression and/or catalytic activity, which results in unique drug metabolism (Jannetto et al 2002). Among the P450 subfamilies, CYP2D6 plays a critical role in determining the response to several drug groups/families (Sadee 1999). CYP2D6 gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are mono-oxygenases, consisting of more than 30 enzymes (Schur et al 2001) which catalyze many reactions involved in drug metabolism. This protein localizes to the endoplasmic reticulum and is known to metabolise as many as 20% of commonly prescribed drugs. CYP2D6 gene substrates include debrisoquine (Wennerholm et al, 1999) an adrenergic-blocking drug; sparteine and propafenone, both anti-arrythmic drugs; and amitryptiline, an anti-depressant. CYP2D6 gene is highly polymorphic in population (Neafsey et al, 2009); certain alleles result in the poor metaboliser phenotype, characterized by a decreased ability to metabolise the enzymes substrates. The polymorphism is due to multiple mutations of the gene, which result in absent, functionally deficient, under-expressed or over-expressed protein (Shiran et al, 2003). The gene is located near two cytochrome P450 pseudogenes on chromosome 22q13.1 (Gouch et al, 1993). Alternatively spliced transcript variants encoding different isoforms have been found for this gene (Toscano et al, 2006). CYP2D6 is a polypeptide of 497 amino acids that accounts for only small a percentage of all hepatic P450s but its role in drug metabolism is extensively higher than its relative content (Zanger et al, 2010). 4. Methadone Pharmacology and Its Mechanism of Action 4.1Methadone History Background Methadone was introduced to the market in 1960’s (Serban, 2011; Liebrenz et al, 2010). The drug was approved by the Food and Drug Administration (FDA) in 1947 as an analgesic; by 1950 it was used for the treatment of painful symptoms from heroin withdrawal and other opioids (SAMSHA, 2004). In 1964, researchers discovered that continuous, daily maintenance doses of oral methadone allowed opioid-addicted patients to function more normally in the process of their recovery (Payte, 1991; Zweben and Payte, 1990; Dole, 1988; Gearing and Schweitzer, 1974). Fig: 2 Methadone Chemical Structure Methadone in the modern medicine is used both as an analgesic for severe pain relief as well as in the treatment of opioid dependence (Rowley, 2011; Potter, 2010). Many scientific articles reviewed methadone to be the currently preferred drug of choice for the treatment of opioid dependence in many countries, including the U.K. (Nosyk et al, 2010; Verster and Buning, 2000). Fredheim et al, (2008) in their review reported that currently, methadone has had a renaissance in the treatment of pain because it has proven its usefulness as a second line drug in opioid switching when other opioids fail to show their effectiveness. Methadone has also been found to be the valued medication for its effectiveness in reducing the number of deaths associated with opioid addiction as well as various medical and behavioural prevalence of diseases associated with addictive disorders (Maxwell, Pullum Tannert 2005; Sheilds et al. 2007). However, the news headlines of many prominent newspapers including the New York Times and the Washington Times, in 2002 and 2003 hyped its publicity by reporting the opioid medications were the major cause of deaths in drug abuse treatment (Belluck, 2003a, 2003b, 2003c; Associated Press, 2002; Washington Times, 2003). New York Times even mentioned methadone as a â€Å"Killer Drug† which is widely abused and dangerous (Washington Times, 2003). After these issues it was decided by the U.N. to put methadone in the class of controlled drug. Methadone was declared in a controlled drug category by the United Nations convention and placed under the controlled substances (â€Å"narcotics†) by the Single Convention on Narcotic Drugs, 1961 (Single Convention) (Bosnjak et al,2011). However, it can only be prescribed in the UK, as in most countries, by prescription till present (Verster Buning, 2000; CSAT 200b). 4.2 Benefits of Methadone Methadone is one of the most preferred drugs not only in Ireland but also across several continents around the globe. In the report published by European Monitoring Centre for Drugs and Drug Addition (EMCDDA), there is a seven fold increase in the opioid treatment between 19993 -2000. The drug is widely recognised amongst doctors and patients due to its several socio-economic reasons. It is observed that there is a significant decrease in the crime graph and a noticeable increase in the employment services amongst the patients undergoing methadone maintenance treatment. No doubt, there is a reduction in illicit drug use by the opiate users and increase in social integration is one of the benefits of methadone. In addition, methadone also helps in reducing morbidity and mortality among opiate users. 4.3 Deaths Involving Methadone Methadone is a highly potent drug for the treatment of opioid dependence and acts as an analgesic for second line management of chronic pain. However, increase in mortality due to methadone administration has instigated controversies regarding the drug use (Lowe, Brooks Petry, 2010; Bunten et al 2010). Law enforcement agencies in the United States (U.S.) and the Drug abuse Warning Network (DAWN) ranked methadone as the third most apprehended analgesic used in the treatment of pain management, fourth among all controlled pharmaceuticals, and eighth among all controlled substances (Fig:2.1.1) (SAMSHA, 2007). Various researches conducted amongst patients undergoing addiction treatment shows that the majority of methadone related deaths occur during the drug induction phase. Post-mortem sample predicts either an overestimation of the drug or combined usage of various other central nervous system (CNS) depressant in addition to the prescribed methadone (Bunten et al, 2010; Lowe, Johnson Petry, 2007). Fig: Methadone as the third most apprehended analgesic, fourth among all controlled pharmaceuticals, and eighth among all controlled substances (SAMASHA, 2007) The side effects associated with methadone overdose includes nausea, vomiting, dizziness, clouding of consciousness and pruritus (itching) (Davis Walsh, 2001). However, the primary toxic effect of excessive methadone is respiratory depression and hypoxia, sometimes accompanied by pulmonary edema and/or aspiration pneumonia (White and Irvine, 1999; Harding-Pink, 1993). Methadone related deaths during later phases of the additiction treatment mainly signify the presence of other illicit drugs. Researchers generally use the term â€Å"poison cocktail† describing the fatality due to intake of multiple psychotropic drugs (Borron, et al., 2001) such as alcohol, benzodiazepines, and other opioids. Several opioids when used or prescribed alone are relatively moderate respiratory depressants; however, when combined with methadone, their additive or synergistic effects can be lethal (Kramer, 2003; Payte and Zweben, 1998). Safety Information and Adverse Event Reporting Program a subsidiary of Food and Drug Administration (FDA) confirms 1,114 cases of methadone-associated fatalities in adults from 1970 through 2002. Critically, a greater number of deaths were reported in 2001 alone than during the entire period from1990 through 1999; the number doubled itself in 2002. In the U.K. 225 individuals died whilst undergoing methadone treatment in 1993. In 1997, data confirms 449 deaths due to the same cause. However, the mortality graph went down in 2001 by reporting 279 deaths caused by methadone but in 2002, it again rose to 316. Therefore, we can conclude that there is no regular trend in methadone related deaths. However, Corkery et al (2004), mentions that it is always not necessary for methadone to be the cause of death even according to the death certificate of the individuals. In an individual study, methadone was detected in the post-mortem blood of 352 unexplained sudden deaths in Scotland between 1 991 and 2001. 23 % of these deaths were not directly linked with methadone. However, there were other drugs and/or alcohol found in the blood sample of the individuals. The Substance Abuse and Mental Health Services (CSAT) in 2004 states that all methadone related poisoning eventually leads to cardio-toxicity and respiratory depression. Methadone deaths expressed as Percent of all poisoning deaths (CSAT, 2007). United States Poison Control Centres states that the overall number of opioid-related deaths has been on the rise, with many cases involving other opioids that include oxycodone and hydrocodone (Litovitz, et al., 2002; Florida Department of Law Enforcement, 2002) 4.4 Pharmacokinetics and Metabolism of Methadone Methadone is a liposoluble basic drug with a pKa of 9.2 and is usually administered orally as a recemic mixture of two enantiomers: R-methadone (R-Met) and S-methadone (S-Met) (Fig.2.2) (Trescot, 2010). The plasma half-life of the drug is highly variable and is between 13 and 55 hours but it is usually assumed to be an average of 25 hours (Letsky et al, 2011; Albion et al, 2010; Wolff et al, 2002). The bioavailability is 70% to 90% when administered orally (Bunten et al, 2010; Lowe, Brooks Petry, 2010). Studies indicate that in drug naive individuals, a single dose of methadone can show its clinical effects up to 72 hours in duration (Olsen et al, 1997). However, the peak plasma concentration reaches in 2 to 4 hours. The analgesic effect of the drug sets in about 15 minute after the subcutaneous injection (Eap et al, 2002). The chemical structure of r-(-)-methadone and s-(+)-methadone (asterisk (*) denotes chiral centre). There is a wide distribution of methadone amongst tissues, which generally range from 60 to 90%. As a result, the drug shows slow elimination and cumulative effect. Methadone is mostly metabolised in liver. The primary metabolite of the drug is 2-ethylidene-1, 5- dimethyl-3, 3-diphenylpyrrolidine (EDDP) (Fig) (Bunten et al, 2010) and to some extent 3, 3-diphenyl-1-pyrroline (EMDP) (Corkery et al, 2004). However, both of these metabolites are inactive and elimination of these inactive metabolies is through urine and faeces. Anggard and Inturrisi et al. (1975) (1990) mentioned that as a result of the basic (pKa =9.2) and lipophylic properties, methadone undergoes a hepatic metabolism and renal excretion. Fig: 4 Metabolic Conversion of Methadone to EDDP 4.4 Cytochrome P450 Cytochrome P450 (P450) is a large superfamily of enzymes. The origin of P450’s superfamily is since prokaryotes much before the existence of eukaryotes (Omura, 2010). The gene P450, commonly known as â€Å"CYP† is present in the genomes of virtually all organisms. Moreover, studies suggest that heme proteins are the building blocks of CYP450 enzymes. These enzymes play a crucial role in the metabolism of the various xenobiotics, steroids and other chemicals. Most of the drugs and chemicals are lipophilic to become more water soluble before excretion. Therefore, P450 superfamily of hemoproteins serves as terminal oxidases of the mixed function oxidase system (Wrighton and Stevens, 1992). The heme prosthetic group binds oxygen after electron transfer reactions from the reduced form of 24 nicotinamide adenine dinucleotide phosphate (NADPH). This reaction incorporates a single atom of molecular oxygen into a substrate with the concomitant reduction of the other atom to wate r (Synder, 2000; Omura, 1999). In cytochrome P450, ‘P’ denotes the pigment and the number ‘450’ is the spectral properties for the absorption band at 450 nm of the reduced CO-bound complex (Benhardt, 2006; Reichhart Feyereisen, 2000). However, according to the nomenclature society, the term â€Å"CYP† is followed by number of families which are generally group of proteins with more than 40% amino-acid sequence identity, a letter for subfamilies and a number for the gene e.g. – CYP2D6. Studies indicate that P450 superfamily is highly diverse (Mathew, 2010). Diversity of P450’s is mainly due to the extensive process of gene duplications. However, gene amplifications, conversions, genome duplications, gene loss, and lateral transfers are certain scenarios that are less documented. 4.5 Cytochrome P450 Polymorphism and Adverse Drug Reactions Drugs affect different individuals in a different way. Genetic variations, which affect the response of the drug metabolism, can be of the most probable reasons (Mayer Zanger, 1997). Johansson Sunderberg (2010) also reported that the difference in drug metabolism among individuals might be due to several factors e.g. epigenetic, pathophysiological, or it might be due to some environmental factors. In a population, genetic polymorphism is divided according to individual ability to perform drug transformation reaction (Srivastava, 2003). Moreover, polymorphic trait is also noticed due to certain mutation in the genes and/or a single nucleotide polymorphism (SNP) which results in the enzyme variation and leads towards higher or lower activity. As a result, there is a partial or complete absence of an enzyme protein in the system. (FIG:) Fig: Polymorphism of Drug Metabolism Enzymes (Evans Relling, 1999). As we can see from the above figure that the genetic polymorphism applies for a wide range of drugs and xenobiotic metabolizing enzymes. Identification of these variations were by the occurrence of adverse reactions after normal doses of drugs in patients or volunteers. In adverse drug reactions, drug-drug interactions have its key role. In fact, adverse drug reactions (ADRs) are one of the major causes of death which is reported in many scientific articles, reviews and even government scripts. According to Substance Abuse and Mental Health Administration (SAMSHA) (2007), there is a record of approximately 100,000 deaths in the United States due to drug toxicity. In addition, Eichelbaum et al., (2006) stated that ADRs is also responsible for up to 7% of hospitalizations and the number has increased to > 30% in the elderly population (> 70 years of age) (Paul et al., 2008). ADRs mainly affect cardiac function or cause liver toxicity (Need et al., 2005). The CYP families metabolises approximately, 75% of all clinically used drugs (Bertz and Granneman, 1997; Evans and Relling, 1999).The human genome contains 115 CYP genes, out of which 57 are found to be functional and the rest are reported as pseudogenes (Johansson Sundberg, 2010; Wang et al,2003). Among CYP families, there are 22 different P450 isoforms, which shows a high degree of polymorphism. Therefore, we can divide the polymorphic xenobiotic metabolizing CYP enzymes into two classes according to their interindividual susceptibility for xenobiotics: Class I: Composed of CYP1A1, CYP1A2, CYP2E1, and CYP3A4 without important functional polymorphism and active in metabolism of drugs. Class II: Composed of CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP2D6, which are highly polymorphic and are important for the metabolism of drugs.