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

Les Misérables Essay

Victor Hugo – Les Miserables BACKGROUND : Victor Marie Hugo was the son of a general in Napoleon’s army, and much of his childhood was therefore spent amid the backdrop of Napoleon’s campaigns in Spain and in Italy. The first three years of his life were spent in Elba, where he learnt to speak the Italian dialect spoken in the island in addition to his mother tongue. Victor got a little education in a small school. At the age of eleven, Hugo returned to live with his mother in Paris, where he got a little education in a small and where he also became infatuated with books and literature. By the time he was fifteen, he had already submitted one poem to a contest sponsored by the prestigious French Academy. There he learnt much from an old soldier, General Lahorie, who, obnoxious to Napoleon for the share he had taken in Moreau’s plot, lived secretly in the house, and from an old priest named Lariviere, who came every day to teach Victor and his two brothers. In 1815, at the age of thirteen, he was sent to a boarding school to prepare for the Ecole Polytechnique. But he devoted himself, even at school, to verse-writing with greater ardour than to study. He wrote in early youth more than one poem for a prize competition, composed a romance which some years later he elaborated into the story Bug Jargal, and in 1820, when only eighteen, joined his two brothers, Abel and Eugene, in publishing a literary journal called Le Conservateur Litteraire. Hugo published his first novel the year following his marriage (Han d’Islande, 1823) and his second three years later (Bug-Jargal, 1826). By the end of 1822 Victor Hugo was fully launched on a literary career, and for twenty years or more the story of his life is mainly the story of his literary output. Because of his successful drama Cormwell, the preface to which, with its note of defiance to literary convention, caused him to be definitely accepted as the head of the Romantic School of poetry. The revolution of 1830 disturbed for a moment his literary activity, but as soon as things were quiet again he shut himself in his study with a bottle of ink, a pen, and an immense pile of paper. For six weeks he was never seen, except at dinner-time, and the result was : The Hunchback of Notre-Dame (1831). During the next ten years four volumes of poetry and four dramas were published in 1841 came his election to the Academy, and in 1843 he published Les Burgraves, a drama which was less successful than his former plays, and which marks the close of his career as a dramatist. In the same year there came to him the greatest sorrow of his life. His most famous poem was ‘Demain, des l’aube’ in which he describes the crucial moment where he visits his daughters grave. As Hugo grew older, his politics became increasingly leftist, and he was forced to flee France in 1851 because of his opposition to the monarch Louis Napoleon. Hugo remained in exile until 1870, when he returned to his home country as a national hero. He continued to write until his death in 1885. He was buried with every conceivable honor in one of the grandest funerals in modern French history. The Book – Les Miserable : Hugo began writing Les Miserables twenty years before its eventual publication in 1862. His goals in writing the novel were as lofty as the reputation it has subsequently acquired; Les Miserables is primarily a great humanitarian work that encourages compassion and hope in the face of adversity and injustice. It is also, however, a historical novel of great scope and analysis, and it provides a detailed vision of nineteenth-century French politics and society. By coupling his story of redemption with a meticulous documentation of the injustices of France’s recent past, Hugo hoped Les Miserables would encourage a more progressive and democratic future. Driven by his commitment to reform and progress, Hugo wrote Les Miserables with nothing less than a literary and political revolution in mind. Les Miserables employs Hugo’s style of imaginative realism and is set in an artificially created human hell that emphasizes the three major predicaments of the nineteenth century. Each of the three major characters in the novel symbolizes one of these predicaments: Jean Valjean represents the degradation of man in the proletariat, Fantine represents the subjection of women through hunger, and Cosette represents the atrophy of the child by darkness. In part, the novel’s fame has endured because Hugo successfully created characters that serve as symbols of larger problems without being flat devices.

Natural Tendency To Do Good Essay

Being around different people can make a human behave or act in ways that they normally would not. This is true in many possible ways and experiences that people go through. Mencius said, â€Å"Persons may be brought to do evil, and that is because the same is done to their nature.† This shows that being in a circumstance of force can make the natural tendency to do good be flawed through whatever it is that is shadowing the mind to make clear judgment. â€Å"The tendency of human nature to do good is like that of water to flow downward.† I believe human nature is to do good based upon the right surroundings because things that go on in an exosphere can make one think that certain choices are acceptable in society. What shows how human nature is to do good is how a human has a want to help out another human when they are in a time of need or desperation. Such as to donate food to a homeless shelter, or to give someone who is down and out a cup of coffee or a dollar. Human nature is to do good based upon the right surroundings in the exosphere and is supported where Mencius said, â€Å"Now you may strike water and make it splash over your forehead, or you may even force it up the hills. But is this the nature of water?† This is what shows that natural tendency to do good is what humans were created to do. I have been in times in life where I made poor decisions based on the forceful circumstances that I chose to be around. There were people around that had addictive criminal thinking where it clouded my mind and was ultimately making me not choose the most logical choice to progress in life positively, rather negatively. These people that were indirectly giving influences toward my life, that fostered an environment that made it seem acceptable to break the law, and gave me an evil action. What I realized is that the choice in having the wrong set of people around me was affectively making me have a circumstance that was progressing into evil actions. Where Mencius said, â€Å"People tend by their nature toward goodness, and it is only the adverse circumstances of their nurture that erode goodness and engender evil.† This fully supports natural tendency is to do good. People must think in a manner that will allow them to be of the right path and do what is righteous. Human nature has a distinctive tendency towards goodness, but ethical rightness cannot be initiated down to the last element. This is why simply external governors always breakdown in enlightening society. True progress results from learning education in constructive atmospheres. Human nature is to do good based upon the right surroundings in the exosphere. Having bad circumstances tend to degrade the human will. However, this is not confirmation of natural evil because a pure thinking person would escape causing harm to other people. So without having a negative external exosphere the simplicity of natural tendency to do goodness will come easily than thinking about it. I have since after putting myself in a negative environment that caused my mind to think that doing evil was something that was tolerated in society, it has now given me options to progress in life. Being around more positive people makes the natural come forth in choices, decisions, and actions. With the rightness inside of someone it makes evil be present, but it does not let the evil pass through and have its way with the individuals mind and action. I think it is significant that Mencius credits that human beings have certain natural abilities for goodness. If we did not have these abilities, I do not think any quantity of education could enforce these onto us. In this regard, I do think that education is a kind of attentive attending goodness. Mencius establishes that all people have hearts by engaging to the example of a child about to fall into a well. Mencius says that as soon as people see the child about to fall â€Å"they will feel a sense of unease and compassion.† It is critical to notice that Mencius is not speaking about any kind of action here but about the instant response. These feelings of distress and empathy are not due to pursuing approval or wanting to reduce frustration. This response justifies Mencius’ claim that â€Å"People all have hearts that do not tolerate the suffering of others†. I feel that this falls in with what I have been addressing because in both ways it is what you are taught and what is naturally inside of a humans’ mind. It helps to prove that human nature is to do good based upon the right surroundings in the exosphere. The human only wants a good way of life and not an evil way that only brings despair and anguish through wrong actions. A human’s natural and taught ways of goodness to live and learn through lessons, whether it is through teachings or of actions. I have lived through life having those negative attributes that made me realize it is not an aspect of life I would like to have of being an evil person while going through the journey. That is how I see that the unease and compassion come into play with the natural tendency to do good. â€Å"When left to follow its natural feelings human nature will do good.† Mencius said that which helps support this argument of human nature is to do good based upon the right surroundings in the exosphere. If not putting yourself into a position to make you strive forward in the direction of virtuous instead of the wicked. With a clear peace of mind it helps to enfold life as it should be and have that natural tendency to do good. Where Mencius says, â€Å"If it becomes evil, it is not the fault of our original capability.† This shows that another man or woman influences a humans thoughts. This proves that the exosphere can have a projection of a negative force behind it creating a circumstance that is not of the capability that the human should have. Mencius noted through these examples of senses: Sense of mercy, sense of shame, sense of respect, sense of right and wrong. He said, â€Å"seek and you will find them, neglect and you will lose them.† I feel that this is another reason proving the argument that has been stated throughout this paper to prove that human nature is to do good based upon the right surroundings because things that go on in an exosphere. A humans’ natural tendency is to do good based upon the right surroundings because of things that go on in an exosphere. This has been proved through the evidence that has been shown though experiences that I have gone through and not only me, but many other people as well. With having the righteous path you can have the fullest extent of your original capability and that is to have the natural human nature to do good based upon the right surroundings because of the things that go on in an exosphere which can make one choose choices that are acceptable in society. Novak, Philip. The World’s Wisdom. 1st ed. New York: HarperCollins, 1995. Print.

A Comparative Review of the Vascular System in Seed Plants...

A comparative review of the vascular system in seed plants and humans In the evolutionary tree of life, all biotic organisms are believed to have derived from a common ancestor. The organisms falling under the eukaryotic kingdom of Plantae are known to have arisen in the same time period as those in the eukaryotic kingdom of Animalia—the Paleozoic era, about 500 million years ago (MYA) (Raven et al., 2008). Despite their chronological resemblance, their evolutionary diversity is especially great in their most advanced organisms—humans and seed plants. One key system that illustrates this diversity is the vascular system (or the cardiovascular system in humans). The vascular system of the respective lines of†¦show more content†¦While xylem transports water and nutrients that generally originate at the roots, phloem transports food (in the form of sugars), hormones, and mRNA which generally originate in the leaf of the plant. Additionally, while water is moved through passive transport, food requires energy to be driven throughout the length of the root and shoot, and is thus carried through active transport. Food transport is said to go from a source (where it is made) to a sink (where it is needed) (Vaucher, 2003). Humans use a more intricate network of systems to keep the internal body conditions moist and nourished. The cardiovascular system is the primary network of tubules responsible for molecular transport. Humans extract nutrients, vitamins, and other vital compounds from food in the gastrointestinal tract; extraction of minerals, vitamins, blood, and vital compounds from liquids is done primarily in the glomerulus of the kidney (Raven et al., 2008). Once the necessary molecules are in the blood stream, the cardiovascular system delivers it to the desired tissue through diffusion. The cardiovascular system of humans uses the heart to circulate blood throughout the body. The human heart is composed of four chambers; the left atrium and left ventricle transport oxygenated blood from the heart to the r est of the body, incoming deoxygenated blood filters from the superior and inferior vena cava to right atrium andShow MoreRelatedBanana Used as Fertilizer11002 Words   |  45 PagesTHE EFFECTIVENESS BANANA (MUSA X PARADISIACA) PEELS USED AS FERTILIZER APPLIED IN DIFFERENT KINDS OF PLANTS SAMPLES RESEARCHER: BERLENE GAIL H. LAMA CHAPTER I INTRODUCTION Background of the study A  banana peel, known as a  banana skin  in British English, is the  outer covering  of the  banana  fruit. As bananas, whether eaten raw or cooked, are a popular fruit consumed worldwide, with yearly production over 145 million tonnes in 2011, there is a significant amount of banana peel waste beingRead MoreDarden Mba Resumes16768 Words   |  68 PagesStrathclyde, UK; GPA: 4.0 EXPERIENCE 2007-2009 Credit Lyonnais Securities Asia (CLSA/Calyon) Singapore Equity Research Associate (Oil Gas) ï‚ · Led a project across seven countries to create a unified platform for investment idea generation using comparative valuations of over 300 energy stocks; Clients (fund managers) voted the team 1st in Asiamoney Broker Polls 2008 ï‚ · Initiated the Asian coverage of a UK based oil gas exploration company; first in the team to prepare valuation models for Indonesian