The encapsulation efficiency of a targeted drug delivery system Literature review - 1

The encapsulation efficiency of a targeted drug delivery system consisting of Herceptin-loaded polymers, an evaluation and characterization - Literature review Example There is enough evidence on nature on nanotechnology. For instance, the DNA molecules width is about 2.5nm, the thickness of the human hair is about 10,000nm thick, and the diameter of a hydrogen atom is about 0.1nm that is too small to be seen by human eyes. Nature also produces nanostructures that offer functional proteins, which are of great significance at the cellular level. It is argued that one of the functions of these proteins found in cells is nanotechnological separations. Molecular motors that comprise the human muscles are complex nanomachines that convert chemical energy to mechanical energy with high efficiency. Ribosomes can also produce protein molecules with high precision and photosynthesis is carried out in plants by nanosize cells that use energy to synthesize organic compounds with the use of cheap raw materials (Bender & Nahta, 2008). Pharmacists have confirmed the effectiveness of using Herceptin. Although the medication has raised controversies among scholars, it is confirmed that the medication is of paramount importance in the process of healing. According to Sauter et al. 2009, Herceptinis anticancer medication used mainly to treat early stage malignant cancer of the breast and in some cases cancer of the stomach. This is a condition that has for a long time given medical researchers sleepless nights as many of the medications used currently have been found to have severe side effects. In the process of treatment, Herceptin acts on those tumors which produce the Human Epidermal growth Receptor (HER2 protein) more than the normal amount. Human Epidermal growth Receptor 2 is a protein which enhances the growth of cancer cells. The presence of the cancerous cells leads to excessive production of the HER2 protein hence promoting the metastasis of the cancerous cells to a larger part of the affected area. The

The UNCRC Organization Essay Example for Free

The UNCRC Organization Essay The UNCRC happened in 1989 and out of this came the children’s act 1989. The act was formally adopted in England and Wales in 1991. The most important aim of the act was to ensure that children’s views were of paramount importance and that the children thoughts and views about their future were taken into consideration. After this, the children’s act 2004 was formed. In this act the framework for the every child matters programme was set out. Every child matters was formed after the tragic death of Victoria Climbie. Victoria Climbie was failed by the very people who were supposedly looking after her. â€Å"It led to recommendations for a radical reform of services†. The aim of the act is to make sure that services work together a lot better and more efficiently than previously. Children’s should be listened to and their opinions valued. We need to listen to children carefully to understand what a child is trying to say. If they cannot be understood or do not feel listened to they may get upset, frustrated, angry or become withdrawn. They could show their upset by hitting, biting, shouting etc., and it will lower their self-esteem. A child may have something important to say that needs our attention for example safe guarding . â€Å"every child can be hurt, put at risk of harm or abused, regardless of their age, gender, religion or ethnicity.† (http://www.safenetwork.org.uk/getting_started/Pages/Why_does_safeguarding_matter.aspx) A change in behaviour, something a child says or how they act can also alert the practitioner to safe guarding issues or perhaps something else that is happening outside the child care setting. Therefore it is essential that we listen to children and build up the child’s trust in adults and â€Å"enable those c hildren to have optimum life chances and to enter adulthood successfully.† (http://www.safenetwork.org.uk/getting_started/Pages/Why_does_safeguarding_matter.aspx) If you cannot understand the child by listening ask them to draw what they want to tell you, act out what they want to tell you or if they use sign language get them to sign what they want to tell you as this may also help you . It is important for children to be given different options of what they want to tell us either through, verbal communication, acting, drawing or pointing. This will show them we do value them and we want to  listen and reach out to them. In contrast if a child is listened to and feels understood they are more likely to be happy and confident. We can also find out if the child has understood a lesson or what you have said by using questions and listening carefully e.g. after a story you might ask a question to see if they have understood. The children’s opinions should be valued so that they are encouraged to express themselves and have got a sense of individuality. It will also help them to build confidence and trusting people and also encourage their communication skills. Children will come from a variety of different cultural backgrounds and have been brought up by parents with many and varied opinions on everything from religion/non religion to food, clothing and what are deemed to be acceptable behaviour. We need to be aware of all these influences and respect the diversity of our society in a non judgemental way . By doing so children will feel that we comfortable in their thoughts and feelings to you without fear of being misunderstood. Children who have disabilities should be given the opportunity to express themselves in a way that they are comfortable or able to. A child who does not have speech may make different noises which can be interpreted as happy or sad. This form of communication should be valued and we should respond to it as we would to a child who has speech. A child who has physical disabilities should be given choices about how they complete tasks and their opinions respected. It is important that practitioners understand the limits and boundaries of their job roles when they work with children. This is to get the best outcomes and the best quality of care for the child. There are 4 main areas that which are â€Å"Particularly important when thinking about your role, boundaries and limits are; †¢Health and safety †¢Managing children’s behaviour †¢Child Protection †¢Confidentially† You should always follow the legislations (children’s act 1989 and children’s act 2004) and read them often to refresh your mind as they often change and then you are always aware of what your limits and boundaries are. It is very important to follow the policies and procedures set out at your place of  work, so that everybody is working in a consistent way. By following procedures everybody knows who is responsible for each task and important jobs do not get missed. Also this is a way of making things clear to everybody and prevents misunderstandings, allegations and it will also help with knowing what to do in certain situations, E.g., †¢Following the fire procedure- Where fire exits are, where the assemble points are, taking the register and alerting parents/carers †¢Missing child policy/ procedure- Who to contact †¢Suspecting any child abuse – who to speak to ( child protection officer) knowing how to react when the child tells you something ( do not look shocked, no leading questions, but tell them you’re going to have to tell someone) †¢What to do if you’re going on a school trip- head counts, booster seats, right number of adults to children †¢General security policy/procedures- shutting gates, identification cards, signing in/out, knowing who’s going to pick the child up It is also crucial to make sure the appropriate people are made aware of any allergies or anything deemed important e.g. if a teacher was going to give out cake for someone’s birthday and it had nuts in and they were unaware of a child with a nut allergy this would cause serious difficulties. You should understand that when you are told something in confidence you should keep it confidential as stated in the policies and procedures. â€Å"Everyone is entitled to their privacy† (http://www.reference.com/motif/health/why-is-confidentiality-important) and may not want personal information to be common knowledge. This could for many reasons including that it is embarrassing for the family and for child protection reasons. However in certain circumstances e.g. in relation to child protection and safe guarding issues it may be vital to share information with relevant professionals (child welfare officer, safe guarding officer, social services). For example if a child tells you that they get hit at home or that they get left home alone every night. At my placement, to ensure confidentiality they lock up any files about the children and only shown to people on a need to know basis. We should know how to look after child a without crossing the professional boundaries and  causing harm to a child. On the 14th of august it was reported in the mail online that a practitioner had physically abused some children where she worked at Small Talk Nursery in Birmingham. It was reported that she â€Å"could be seen throwing a 17-month-old girl onto a mattress, causing her to almost strike her head on a radiator.† (: http://www.dailymail.co.uk/news/article-2188314/Small-Talk-Nursery-Kehyren-Sajid-dragged-toddler-mat-like-rag-doll-mistreated-children care.html#ixzz2BetgdNPW) This is obviously very unprofessional and she crossed the professional limits and boundaries. Therefore you should know your limits and boundaries to keep the children safe and protected All practitioners should know what their job role and responsibilities are, and not try and do something that isn’t within their role. They may not be trained appropriately and this could cause problems if something goes wrong. Each person is accountable for their own actions and we all must take responsibility. Also if you do the job that is in your job description then it will prevent friction with other colleagues as you won’t be seen to be interfering with things. You should be mature and respectful even if you do not necessarily agree with what someone is saying. You have to liaise with parents and have a friendly relationship so they feel they can tell you things. However professional boundaries should be kept so that if you are concerned about something you are more able to deal with this situation appropriately. A child centred approach is important in an early years setting. This is because young children develop at different stages. It is important to find out as much as information about the child as possible, by interacting with them through play and chatting, so you can meet the children’s needs. Once you know the child well, you can starts to plan activities tailored to the child and start to build on their existing skills towards their next stage. Also when using a child centred approach children feel empowered and learn to make decisions for themselves and they also get the best experience out of their child care setting. In order to meet the individual needs of children a child centred approach is necessary. This requires planning, time, effort and patience. In the late 1940’s a town named Reggio â€Å"developed an approach to pre-school learning†.(Level 3 child care and education, Tassoni,2007, pg188) The approach believes â€Å"in the importance of discovery,  stimulating learning environments (both indoor and outdoor) , children reflecting on their own learning and documenting children’s learning as part of the process.†.(Level 3 child care and education, Tassoni, 2007, pg188) This approach is based on; †¢Ã¢â‚¬Å"creative thinking †¢Exploration and discovery †¢Free play †¢Following children’s interests †¢Valuing and encouraging all ways children express themselves †¢Asking children to talk about their ideas† (Level 3 child care and education, Tassoni, 2007, pg188) The above information is, I think, very important as it makes sure that the child and their needs are the priority. Tailoring activities to the interests of the child and getting their reactions from this will help to plan future sessions. . The child’s needs are put above anything else rather than sticking to a routine for the convenience of child care practitioner. The Reggio Emilio theory links to the EYFS as it is a â€Å"play-based and child-led framework†. (https://www.education.gov.uk/publications/eOrderingDownload/DFE-RB029.pdf) One approach used set out in the EYFS framework and in the reggio amellio theory is to allow play to develop and be led by the child rather than the play leader. At my placement, which is in a nursery , we actively encourage children to learn through play, and we get them to choose what they would like to play with Eg; sand, water, play dough and painting. The child centred approach is good for children who disconnect unless it is something they are interested in. For example if a child loves playing with trains, it would be used to capture a child’s interest in a subject such as singing instead of singing about cats You would sing songs about trains to engage the child and get his/her full attention. It is also good because a child centred approach gives a sense of inclusion, because for example, if you are in a wheelchair you will still be included in the activities as they have been planned to support your need. â€Å"The Child Centered Approach promotes the right of the child to choose, make connections and communicate. It allows freedom for children to think, experience, explore, question and search for answers† (http://www.growingplaces.org.uk/reggio.htm)

Effects of Exercise on the Human Body

Effects of Exercise on the Human Body Exercise represents one the highest levels of extreme stresses to which the body can be exposed. Exercise physiology is the study of the function of the human body during various acute and chronic exercise conditions. These effects are significant during both short, high intensity exercise as well as with prolonged strenuous exercise such as done in endurance sports like marathons, ultramarathons, and road bicycle racing. In exercise, the liver generates extra glucose, while increased cardiovascular activity by the heart, and respiration by the lungs, provides an increased supply of oxygen. When exercise is very prolonged and strenuous, a decline, however, can occur in blood levels of glucose. In some individuals, this might even cause hypoglycemia and hypoxemia. There can also be cognitive and physical impairments due to dehydration. Another risk is low plasma sodium blood levels. Prolonged exercise is made possible by the human thermoregulation capacity to remove exercise waste hea t by sweat evaporation. This capacity evolved to enable early humans after many hours of persistence hunting to exhaust game animals that cannot remove so effectively exercise heat from their body. In general, the exercise-related measurements established for women follow the same general principles as those established for men, except for the quantitative differences caused by differences in body size, body composition, and levels of testosterone. In women, the values of muscle strength, pulmonary ventilation, and cardiac output (all variables related with muscle mass) are generally 60-75% of the exercise physiology values recorded in men. When measured in terms of strength per square centimeter, the female muscle can achieve the same force of contraction as that of a male. The functions of muscle tissues assume roles in homeostasis, as follows: Excitability Property of receiving and responding to stimuli such as the following: Neurotransmitters: Acetylcholine (ACh) stimulates skeletal muscle to contract, electrical stimuli: Applying electrical stimuli between cardiac and smooth muscle cells causes the muscles to contract, Applying a shock to skeletal muscle causes contraction, Hormonal stimuli: Oxytocin stimulates smooth muscle in the uterus to contract during labor.Contractility Ability to shorten. Extensibility Ability to stretch without damageElasticity Ability to return to original shape after extensionThrough contraction, muscle provides motion of the body (skeletal muscle), motion of blood (cardiac muscle), and motion of hollow organs such as the uterus, esophagus, stomach, intestines, and bladder (smooth muscle).Muscle tissue also helps maintain posture and produce heat. A large amount of body heat is produced by metabolism and by muscle con traction. Muscle contraction during shivering warms the body. Skeletal muscle consists of fibers (cells). These cells are up to 100 Â µm in diameter and often are as long as the muscle. Each contains sarcoplasm (cytoplasm) and multiple peripheral nuclei per fiber. Skeletal muscle is actually formed by the fusion of hundreds of embryonic cells. Other cell structures include the following:Each fiber is covered by a sarcolemma (plasma membrane). The sarcoplasmic reticulum (smooth endoplasmic reticulum) stores calcium, which is released into the sarcoplasm during muscle contraction. Transverse tubules (T tubules), which are extensions of the sarcolemma that penetrate cells, transmit electrical impulses from the sarcolemma inward, so electrical impulses penetrate deeply into the cell. Besides conducting electricity along their walls, T tubules contain extracellular fluid rich in glucose and oxygen.The sarcoplasm of fiber is rich in glycogen (glucose polymer) granules and myoglobin (oxygen-storing protein). It also is rich in mitochondria. Each fibe r contains hundreds to thousands of rodlike myofibrils, which are bundles of thin and thick protein chains termed myofilaments. From a cross-sectional view of a myofibril, each thick filament is surrounded by a hexagonal array of 6 thin filaments. Each thin filament is surrounded by a triangular array of thick filaments.myofilaments are composed of 3 proteins: actin, tropomyosin, and troponin. Thick myofilaments consist of bundles of approximately 200 myosin molecules. Myosin molecules look like double-headed golf clubs (both heads at the same end). The heads of the golf clubs are called myosin heads; they are also called cross-bridges because they link thick and thin filaments during contraction. They contain actin andadenosine triphosphate (ATP) binding sites. Myosin heads project out from the thick filaments, allowing them to bind to the thin filaments during contraction. Actin is a long chain of multiple globular proteins, similar in shape to kidney beans. Each globular subunit contains a myosin-binding site. Tropomyosin is a long strand of protein that covers the myosin-binding sites on actin when the muscle is relaxed. Troponin is a polypeptide complex that binds to tropomyosin, helping to position it over the myosin-binding sites on actin. During muscle contraction, calcium binds troponin, which causes tropomyosin to roll off of the myosin binding sites on actin. A muscle action potential travels over sarcolemma and enters the T tubules, causing the sarcoplasmic reticulum to release calcium into the sarcoplasm. This triggers the contractile process.Myosin cross-bridges pull on the actin myofilaments, causing the thin myofilaments of a sarcomere to slide toward the centers of the H zones.Deep fascia is a broad band of dense irregular connective tissue beneath and around muscle and organs. Deep fascia is different from superficial fascia, which is loose areolar connective tissue.Other connective-tissue components (all are extensions of deep fascia) include epimysium, which covers the entire muscle; perimysium, which penetrates into muscle and surrounds bundles of fibers called fascicles; and endomysium, which is delicate, barely visible, loose areolar tissue covering individual fibers (ie, individual cells).Tendons and aponeuroses are tough extensions of epimysium, perimysium, and endomysium. Tendons and aponeuroses are made of dense regular co nnective tissue and attach the muscle to bone or other muscle. Aponeuroses are broad, flat tendons. Tendon sheaths contain synovial fluid and enclose certain tendons. Tendon sheaths allow tendons to slide back and forth next to each other with lower friction. Tenosynovitis is inflammation of the tendon sheaths and tendons, especially those of the wrists, shoulders, and elbows. Tendons are not contractile and not very stretchy; furthermore, they are not very vascular and they heal poorly. Nerves convey impulses for muscular contraction. Nerves are bundles of nerve cell processes. Each nerve cell process (ie, axon) divides at its tip into a few to 10,000 branches called telodendria. At the end of each of these branches is an axon terminal that is rich in neurotransmitters.Blood provides nutrients and oxygen for contraction. An artery and a vein usually accompany a nerve that penetrates skeletal muscle. Arteries in muscles dilate during active muscular activity, thus increasing the supply of oxygen and glucose.A motor nerve is a bundle of axons that conducts nerve impulses away from the brain or spinal cord toward muscles. Each axon transmits an action potential (ie, nerve impulse), which is a burst of electricity. The nerve impulse travels along the axons at a steady rate, like fire travels along a fuse; however, nerve impulses travel extremely fast. Each axon has 4-2000 or more branches (ie, telodendria), with an average of 150 telodendria. Each separate branch suppli es a separate muscle cell. Thus, if an axon has 10 branches, it supplies 10 muscle fibers. Small motor units are for fine control of muscles; large motor units are for muscles that do not require such fine control.The neuromuscular junction is made of an axon terminal and the portion of the muscle fiber sarcolemma it nearly touches (called the motor endplate). The neurotransmitter released at the neuromuscular junction in skeletal muscle is ACh. The motor endplate is rich in thousands of ACh receptors; the receptors are integral proteins containing binding sites for ACh and sodium channels. Nerve impulse (action potential) reaches the axon terminal, which triggers calcium influx into the axon terminal.Calcium influx causes synaptic vesicles to release ACh via exocytosis. ACh diffuses across synaptic cleft.ACh binds to theACh receptor on the sarcolemma. Succinylcholine, a drug used to induce paralysis during surgery, binds to ACh receptors more tightly than ACh. Succinylcholine initially causes some depolarization, but then itbinds to the receptor, preventing ACh from binding. Therefore, it blocks the muscles stimulation by ACh, causing paralysis. Another drug that acts in a similar fashion is curare. These drugs do not cause pain relief or unconsciousness; thus, they are combined with other drugs during surgery. When ACh binds the receptor, it opens chemically regulated ion channels, which are sodium channels through the receptor molecule. Sodium, which is in high concentration outside cells and in low concentration inside cells, rushes into the cell through the channels.The cell, whose resting membrane potential along the inside of the membrane is negative when comparedwith the outside of the membrane, becomes positively charged along the inside of the membrane when sodium (a positive ion) rushes in. This change from a negative charge to a positive charge along the inner membrane is termed depolarization. The depolarization of one region of the sarcolemma (the motor endplate) initiates an action potential, which is a propagating wave of depolarization that travels (propagates) along the sarcolemma. Regions of membrane that become depolarized rapidly restore their proper ionic concentrations along their inner and outer surfaces in a process termed repolarization. (This process of depolarization, propagation, and repolarization is similar to dominoes that topple each other but also spring back into the upright position shortly afterward.)The action potential also propagates along the membrane lining the T tubules entering the cell. This action potential traveling along the T tubules causes the sarcoplasmic reticulum to release calcium into sarcoplasm.Calcium binds with troponin, causing it to pull on tropomyosin to change its or ientation, exposing myosin-binding sites on actin. An ATPase, which also functions as a myosin cross-bridging protein, splits ATP into adenosine diphosphate (ADP) + phosphate (P) in the previous contraction cycle. This energizes the myosin head. The energized myosin head, or cross-bridge, combines with myosin-binding sites on actin. Power stroke occurs. The attachment of the energized cross-bridge triggers a pivoting motion (ie, power stroke) of the myosin head. During the power stroke, ADP and P are released from the myosin cross-bridge. The power stroke causes thin actinmyofilaments to slide past thick myosin myofilaments toward the center of the A bands.ATP attaches to the myosin head again, allowing it to detach from actin. (In rigor mortis, an ATP deficiency occurs. Cross-bridges remain, and the muscles are rigid.)ATP is broken down to ADP and P, which cocks the myosin head again, preparing it to perform another power stroke if needed. Repeated detachment and reattachment of the cross-bridges results in shortening without much increase in tension during the shortening phase (isotonic contraction) or results in increased tension without shortening (isometric contraction).Release of the enzyme acetylcholinesterasein the neuromuscular junction destroys ACh and stops the generation of a muscle action potential. Calcium is taken back up (resequestered) in the sarcoplasmic reticulum, and myosin cross-bridges separate. ATP is required to separate myosin-actin cross-bridges. The muscle fiber resumes its resting state. The chemical energy that fuels muscular activities is ATP. For the first 5 or 6 seconds of muscle power, muscular activity can depend on the ATP that is already present in the muscle cells. Beyond this time, new amounts of ATP must be formed to enable the activation of muscular contractions that are needed to support longer and more vigorous physical activities. For activities that require a quick burst of energy that cannot be supplied by the ATP present in the muscle cells, the next 10-15 seconds of muscle power can be provided through the bodys use of the phosphagen system, which uses a substance called creatine phosphate to recycle ADP into ATP.4 For longer and more intense periods of physical activity, the body must rely on systems that break down the sugars (glucose) to produce ATP. The complete breakdown of glucose occurs in 2 ways: through anaerobic respiration (does not use oxygen) and through aerobic respiration (occurs in the presence of oxygen). The anaerobic use of gluco se to form ATP occurs as the body increases its muscle use beyond the capability of the phosphagen system to supply energy. In particular, the glycogen lactic acid system, through its anaerobic breakdown of glucose, provides approximately 30-40 seconds more of maximal muscle activity. For this system, each glucose molecule is split into 2 pyruvic acid molecules, and energy is released to form several ATP molecules, providing the extra energy. Then, the pyruvic acid partially breaks down further to produce lactic acid. If the lactic acid is allowed to accumulate in the muscle, one experiences muscle fatigue. At this point, the aerobic system must activate.The aerobic system in the body is used for sports that require an extensive and enduring expenditure of energy, such as a marathon race. Endurance sports absolutely require aerobic energy. A large amount of ATP must be provided to muscles to sustain the muscle power needed to perform such events without an excessive production of la ctic acid. This can only be accomplished when oxygen in the body is used to break down the pyruvic acid (that was produced anaerobically) into carbon dioxide, water, and energy by way of a very complex series of reactions known as the citric acid cycle. This cycle supports muscle usage for as long as the nutrients in the body last. The breakdown of pyruvic acid requires oxygen and slows or eliminates the accumulation of lactic acid. In summary, the 3 different muscle metabolic systems that supply the energy required for various activities are as follows: Phosphagen system (for 10- to 15-sec bursts of energy)Glycogen lactic acid system (for another 30-40 sec of energy)Aerobic system (provides a great deal of energy that is only limited by the bodys ability to supply oxygen and other important nutrients) Many sports require the use of a combination of these metabolic systems. By considering the vigor of a sports activity and its duration, one can estimate very closely which of the ene rgy systems are used for each activity. During muscular exercise, blood vessels in muscles dilate and blood flow is increased in order to increase the available oxygen supply. Up to a point, the available oxygen is sufficient to meet the energy needs of the body. However, when muscular exertion is very great, oxygen cannot be supplied to muscle fibers fast enough, and the aerobic breakdown of pyruvic acid cannot produce all the ATP required for further muscle contraction. During such periods, additional ATP is generated by anaerobic glycolysis. In the process, most of the pyruvic acid produced is converted to lactic acid. Although approximately 80% of the lactic acid diffuses from the skeletal muscles and is transported to the liver for conversion back to glucose or glycogen, some lactic acid accumulates in muscle tissue, making muscle contraction painful and causing fatigue. Ultimately, once adequate oxygen is available, lactic acid must be catabolized completely into carbon dioxide and water. After exercise has stopped, extra oxygen is required to metabolize lactic acid; to replenish ATP, phosphocreatine, and glycogen; and to replace (pay back) any oxygen that has been borrowed from hemoglobin, myoglobin (an iron-containing substance similar to hemoglobin that is found in muscle fibers), air in the lungs, and body fluids. The additional oxygen that must be taken into the body after vigorous exercise to restore all systems to their normal states is called oxygen debt. The debt is paid back by labored breathing that continues after exercise has stopped. Thus, the accumulation of lactic acid causes hard breathing and sufficient discomfort to stop muscle activity until homeostasis is restored.5 Eventually, muscle glycogen must also be restored. Restoration of muscle glycogen is accomplished through diet and may take several days, depending on the intensity of exercise. The maximum rate of oxygen consumption during the aerobic catabolism of pyruvic acid is called maximal oxygen uptake. Maximal oxygen uptake is determined by sex (higher in males), age (highest at approximately age 20 y), and size (increases with body size). Highly trained athletes can have maximal oxygen uptakes that are twice that of average people, probably owing to a combination of genetics and training. As a result, highly trained athletes are capable of greater muscular activity without increasing their lactic acid production and have lower oxygen debts, which is why they do not become short of breath as readily as untrained individuals. The best examples of light exercise are walking and light jogging. The muscles that are recruited during this type of exercise are those that contain a large amount of type I muscle cells, and, because these cells have a good blood supply, it is easy for fuels and oxygen to travel to the muscle. ATP consumption makes ADP available for new ATP synthesis. The presence of ADP (and the resulting synthesis of ATP) simulates the movement of hydrogen (H+) into the mitochondria; this, in turn, reduces the proton gradient and thus stimulates electron transport. The hydrogen on the reduced form of nicotinamide adenine dinucleotide (NADH) is used up, nicotinamide adenine dinucleotide (NAD) becomes available, and fatty acids and glucose are oxidized. Incidentally, the calcium released during contraction stimulates the enzymes in the Krebs cycle and stimulates the movement of the glucose transporter 4 (GLUT-4) from inside of the muscle cell to the cell membrane. Both these exercise-induced respon ses augment the elevation in fuel oxidation caused by the increase in ATP consumption. An increase in the pace of running simply results in an increased rate of fuel consumption, an increased fatty acid release, and, therefore, an increase in the rate of muscle fatty acid oxidation. However, if the intensity of the exercise increases even further, a stage is reached in which the rate of fatty acid oxidation becomes limited. The reasons why the rate of fatty acid oxidation reaches a maximum are not clear, but it is possible that the enzymes in the beta-oxidation pathway are saturated (ie, they reach a stage in which their maximal velocity [Vmax] is less than the rate of acetyl-coenzyme A [acetyl-CoA] consumption in the Krebs cycle). Alternatively, it may be that the availability of carnitine (the chemical required to transport the fatty acids into the mitochondria) becomes limited. Whatever the reason, the consequence is that as the pace rises, the demand for acetyl-CoA cannot be met by fatty acid oxidation alone. The accumulation of acetyl-CoA that was so effective at inhibiting the oxidation of glucose is no longer present, so pyruvate dehydrogenase starts working again and pyruvate is converted into acetyl-CoA. In other words, more of the glucose that enters the muscle cell is oxidized fully to carbon dioxide. Therefore, the energy used during moderate exercise is derived from a mixture of fatty acid and glucose oxidation. As the intensity of the exercise increases even further (ie, running at the pace of middle-distance races), the rate at which the muscles can extract glucose from the blood becomes limited. In other words, the rate of glucose transport reaches Vmax, either because the blood cannot supply the glucose fast enough or the number of GLUT-4s becomes limited. ATP generation cannot be serviced completely by exogenous fuels, and ATP levels decrease. Not only does this stimulate phosphofructokinase, it also stimulates glycogen phosphorylase. This me ans that glycogen stored within the muscle cells is broken down to provide glucose. Therefore, the fuel mix during strenuous exercise is composed of contributions from blood-borne glucose and fatty acids and from endogenously stored glycogen.Being fit (biochemically speaking) means that the individual has a well-developed cardiovascular system that can efficiently supply nutrients and oxygen to the muscles. Fit people have muscle cells that are well perfused with capillaries (ie, they have a good muscle blood supply). Their muscle cells also have a large number of mitochondria, and those mitochondria have a high activity of Krebs cycle enzymes, electron transport carriers, and oxidation enzymes. Individuals who are unfit must endure the consequences of a poorer blood supply, fewer mitochondria, less electron transport units, a lower activity of the Krebs cycle, and poorer activity of beta-oxidation enzymes. To generate ATP in the mitochondria, a steady supply of fuel and oxygen and decent activity of the oxidizing enzymes and carriers are needed. If any of these components are lacking, the rate at which ATP can be produced by mitochondria is compromised. Under these circumstances, the production of ATP by aerobic means is not sufficient to provide the muscles with sufficient ATP to sustain contractions. The result is anaerobic ATP generation using glycolysis. Increasing the flux through glycolysis but not increasing the oxidative consumption of the resulting pyruvate increases the production of lactate. The purpose of respiration is to provide oxygen to the tissues and to remove carbon dioxide from the tissues. To accomplish this, 4 major events must be regulated, as follows: Pulmonary ventilation. Diffusion of oxygen and carbon dioxide between the alveoli and the blood, Transport of oxygen and carbon dioxide in the blood and body fluids and to and from the cells, Regulation of ventilation and other aspects of respiration: Exercise causes these factors to change, but the body is designed to maintain homeostasisWhen one goes from a state of rest to a state of maximal intensity of exercise, oxygen consumption, carbon dioxide formation, and total pulmonary and alveolar ventilation increase by approximately 20-fold. A linear relationship exists between oxygen consumption and ventilation. At maximal exercise, pulmonary ventilation is 100-110 L/min, whereas maximal breathing capacity is 150-170 L/min. Thus, the maximal breathing capacity is approximately 50% greater than the actual pulmon ary ventilation during maximal exercise. This extra ventilation provides an element of safety that can be called on if the situation demands it (eg, at high altitudes, under hot conditions, abnormality in the respiratory system). Therefore, the respiratory system itself is not usually the most limiting factor in the delivery of oxygen to the muscles during maximal muscle aerobic metabolism. VO2 max is the rate of oxygen consumption under maximal aerobic metabolism. This rate in short-term studies is found to increase only 10% with the effect of training. However, that of a person who runs in marathons is 45% greater than that of an untrained person. This is believed to be partly genetically determined (eg, stronger respiratory muscles, larger chest size in relation to body size) and partly due to long-term training. Oxygen diffusing capacity is a measure of the rate at which oxygen can diffuse from the alveoli into the blood. An increase in diffusing capacity is observed in a state of maximal exercise. This results from the fact that blood flow through many of the pulmonary capillaries is sluggish in the resting state. In exercise, increased blood flow through the lungs causes all of the pulmonary capillaries to be perfused at their maximal level, providing a greater surface area through which oxygen can diffuse into the pulmonary capillary blood. Athletes who require greater amounts of oxygen per minute have been found to have higher diffusing capacities, but the exact reason why is not yet known. Although one would expect the oxygen pressure of arterial blood to decrease during strenuous exercise and carbon dioxide pressure of venous blood to increase far above normal, this is not the case. Both of these values remain close to normal. Stimulatory impulses from higher centers of the brain and from joint and muscle proprioceptive stimulatory reflexes account for the nervous stimulation of the respiratory and vasomotor center that provides almost exactly the pr oper increase in pulmonary ventilation to keep the blood respiratory gases almost normal. If nervous signals are too strong or weak, chemical factors bring about the final adjustment in respiration that is required to maintain homeostasis. Regular exercise makes the cardiovascular system more efficient at pumping blood and delivering oxygen to the exercise muscles. Releases of adrenaline and lactic acid into the blood result in an increase of the heart rate (HR). Basic definitions of terms are as follows:VO2 equals cardiac output times oxygen uptake necessary to supply oxygen to muscles. The Fick equation is the basis for determination of VO2. Exercises increase some of the different components of the cardiovascular system, such as stroke volume (SV), cardiac output, systolic blood pressure (BP), and mean arterial pressure. A greater percentage of the cardiac output goes to the exercising muscles. At rest, muscles receive approximately 20% of the total blood flow, but during exercise, the blood flow to muscles increases to 80-85%. To meet the metabolic demands of skeletal muscle during exercise, 2 major adjustments to blood flow must occur. First, cardiac output from the heart must increase. Second, blood flow from ina ctive organs and tissues must be redistributed to active skeletal muscle. Generally, the longer the duration of exercise, the greater the role the cardiovascular system plays in metabolism and performance during the exercise bout. An example would be the 100-meter sprint (little or no cardiovascular involvement) versus a marathon (maximal cardiovascular involvement). The cardiovascular system helps transport oxygen and nutrients to tissues, transport carbon dioxide and other metabolites to the lungs and kidneys, and distribute hormones throughout the body. The cardiovascular system also assists with thermoregulation.The pumping of blood by the heart requires the following 2 mechanisms to be efficient:Alternate periods of relaxation and contraction of the atria and ventriclesCoordinated opening and closing of the heart valves for unidirectional flow of blood The cardiac cycle is divided into 2 phases: ventricular diastole and ventricular systole.This phase begins with the opening of the atrioventricular (AV) valves. The mitral valve (located between the left atrium and left ventricle) opens when the left ventricular pressure falls below the left atrial pressure, and the blood from left atrium enters the left ventricle.Later, as the blood continues to flow into the left ventricle, the pressure in both chambers tends to equalize.At the end of the di astole, left atrial contractions cause an increase in left atrial pressure, thus again creating a pressure gradient between the left atrium and ventricle and forcing blood into the left ventricle.Ventricular systole begins with the contraction of the left ventricle, which is caused by the spread of an action potential over the left ventricle. The contraction of the left ventricle causes an increase in the left ventricular pressure. When this pressure is higher than the left atrial pressure, the mitral valve is closed abruptly.The left ventricular pressure continues to rise after the mitral valve is closed. When the left ventricular pressure rises above the pressure in the aorta, the aortic valve opens. This period between the closure of the mitral valve and the opening of the aortic valve is called isovolumetric contraction phase.The blood ejects out of the left ventricle and into the aorta once the aortic valve is opened. As the left ventricular contraction is continued, 2 processe s lead to a fall in the left ventricular pressure. These include a decrease in the strength of the ventricular contraction and a decrease in the volume of blood in the ventricle.When the left ventricular pressure falls below the aortic pressure, the aortic valve is closed. After the closure of the aortic valve, the left ventricular pressure falls rapidly as the left ventricle relaxes. When this pressure falls below the left atrial pressure, the mitral valve opens and allows blood to enter left ventricle. The period between the closure of the aortic valve closure and the opening of the mitral valve is called isovolumetric relaxation time. Right-sided heart chambers undergo the same phases simultaneously. Most of the work of the heart is completed when ventricular pressure exists. The greater the ventricular pressure, the greater the workload of the heart. Increases in BP dramatically increase the workload of the heart, and this is why hypertension is so harmful to the heart.Arterial BP is the pressure that is exerted against the walls of the vascular system. BP is determined by cardiac output and peripheral resistance. Arterial pressure can be estimated using a sphygmomanometer and a stethoscope. The reference range for males is 120/80 mm Hg; the reference range for females is 110/70 mm Hg. The difference between systolic and diastolic pressure is called the pulse pressure. The average pressure during a cardiac cycle is called the mean arterial pressure (MAP). MAP determines the rate of blood flow through the systemic circulation.During rest, MAP = diastolic BP + (0.33 X pulse pressure). For example, MAP = 80 + (0.33 X [120-80]), MAP = 93 mm Hg. During exercise, MAP = diastolic BP + (0.50 X pulse pressure). For example, MAP = 80 + (0.50 X [160-80]), MAP = 120 mm Hg. The heart has the ability to generate its own electrical activity, which is known as intrinsic rhythm. In the healthy heart, contraction is initiated in the sinoatrial (SA) node, which is often called the hearts pacemaker. If the SA node cannot set the rate, then other tissues in the heart are able to generate an electrical potential and establish the HR.The parasympathetic nervous system and the sympathetic nervous system affect a personsHR. Parasympathetic nervous system: The vagus nerve originates in the medulla and innervates the SA and AV nodes. The nerve releases ACh as the neurotransmitter. The response is a decrease in SA node and AV node activity, which causes a decrease in HR. Sympathetic nervous system: The nerves arise from the spinal cord and innervate the SA node and ventricular muscle mass. The nerves release norepinephrine as the neurotransmitter. The response is an increase in HR and a force of contraction of the ventricles.At rest, sympathetic and parasympathetic ne rvous stimulation are in balance. During exercise, parasympathetic stimulation decreases and sympathetic stimulation increases. Several factors can alter sympathetic nervous system input.Baroreceptors are groups of neurons located in the carotid arteries, the arch of aorta, and the right atrium. These neurons sense changes in pressure in the vascular system. An increase in BP results in an increase in parasympathetic activity except during exercise, when the sympathetic activity overrides the parasympathetic activity. Chemoreceptors are groups of neurons located in the arch of the aorta and the carotid arteries. These neurons sense changes in oxygen concentration. When oxygen concentration in the blood is decreased, parasympathetic activity decreasesand sympathetic activity increases. Temperature receptors are neurons located throughout the body. These neurons are sensitive to changes in body temperature. As temperature increases, sympathetic activity increases to cool Effects of Exercise on the Human Body Effects of Exercise on the Human Body Exercise represents one the highest levels of extreme stresses to which the body can be exposed. Exercise physiology is the study of the function of the human body during various acute and chronic exercise conditions. These effects are significant during both short, high intensity exercise as well as with prolonged strenuous exercise such as done in endurance sports like marathons, ultramarathons, and road bicycle racing. In exercise, the liver generates extra glucose, while increased cardiovascular activity by the heart, and respiration by the lungs, provides an increased supply of oxygen. When exercise is very prolonged and strenuous, a decline, however, can occur in blood levels of glucose. In some individuals, this might even cause hypoglycemia and hypoxemia. There can also be cognitive and physical impairments due to dehydration. Another risk is low plasma sodium blood levels. Prolonged exercise is made possible by the human thermoregulation capacity to remove exercise waste hea t by sweat evaporation. This capacity evolved to enable early humans after many hours of persistence hunting to exhaust game animals that cannot remove so effectively exercise heat from their body. In general, the exercise-related measurements established for women follow the same general principles as those established for men, except for the quantitative differences caused by differences in body size, body composition, and levels of testosterone. In women, the values of muscle strength, pulmonary ventilation, and cardiac output (all variables related with muscle mass) are generally 60-75% of the exercise physiology values recorded in men. When measured in terms of strength per square centimeter, the female muscle can achieve the same force of contraction as that of a male. The functions of muscle tissues assume roles in homeostasis, as follows: Excitability Property of receiving and responding to stimuli such as the following: Neurotransmitters: Acetylcholine (ACh) stimulates skeletal muscle to contract, electrical stimuli: Applying electrical stimuli between cardiac and smooth muscle cells causes the muscles to contract, Applying a shock to skeletal muscle causes contraction, Hormonal stimuli: Oxytocin stimulates smooth muscle in the uterus to contract during labor.Contractility Ability to shorten. Extensibility Ability to stretch without damageElasticity Ability to return to original shape after extensionThrough contraction, muscle provides motion of the body (skeletal muscle), motion of blood (cardiac muscle), and motion of hollow organs such as the uterus, esophagus, stomach, intestines, and bladder (smooth muscle).Muscle tissue also helps maintain posture and produce heat. A large amount of body heat is produced by metabolism and by muscle con traction. Muscle contraction during shivering warms the body. Skeletal muscle consists of fibers (cells). These cells are up to 100 Â µm in diameter and often are as long as the muscle. Each contains sarcoplasm (cytoplasm) and multiple peripheral nuclei per fiber. Skeletal muscle is actually formed by the fusion of hundreds of embryonic cells. Other cell structures include the following:Each fiber is covered by a sarcolemma (plasma membrane). The sarcoplasmic reticulum (smooth endoplasmic reticulum) stores calcium, which is released into the sarcoplasm during muscle contraction. Transverse tubules (T tubules), which are extensions of the sarcolemma that penetrate cells, transmit electrical impulses from the sarcolemma inward, so electrical impulses penetrate deeply into the cell. Besides conducting electricity along their walls, T tubules contain extracellular fluid rich in glucose and oxygen.The sarcoplasm of fiber is rich in glycogen (glucose polymer) granules and myoglobin (oxygen-storing protein). It also is rich in mitochondria. Each fibe r contains hundreds to thousands of rodlike myofibrils, which are bundles of thin and thick protein chains termed myofilaments. From a cross-sectional view of a myofibril, each thick filament is surrounded by a hexagonal array of 6 thin filaments. Each thin filament is surrounded by a triangular array of thick filaments.myofilaments are composed of 3 proteins: actin, tropomyosin, and troponin. Thick myofilaments consist of bundles of approximately 200 myosin molecules. Myosin molecules look like double-headed golf clubs (both heads at the same end). The heads of the golf clubs are called myosin heads; they are also called cross-bridges because they link thick and thin filaments during contraction. They contain actin andadenosine triphosphate (ATP) binding sites. Myosin heads project out from the thick filaments, allowing them to bind to the thin filaments during contraction. Actin is a long chain of multiple globular proteins, similar in shape to kidney beans. Each globular subunit contains a myosin-binding site. Tropomyosin is a long strand of protein that covers the myosin-binding sites on actin when the muscle is relaxed. Troponin is a polypeptide complex that binds to tropomyosin, helping to position it over the myosin-binding sites on actin. During muscle contraction, calcium binds troponin, which causes tropomyosin to roll off of the myosin binding sites on actin. A muscle action potential travels over sarcolemma and enters the T tubules, causing the sarcoplasmic reticulum to release calcium into the sarcoplasm. This triggers the contractile process.Myosin cross-bridges pull on the actin myofilaments, causing the thin myofilaments of a sarcomere to slide toward the centers of the H zones.Deep fascia is a broad band of dense irregular connective tissue beneath and around muscle and organs. Deep fascia is different from superficial fascia, which is loose areolar connective tissue.Other connective-tissue components (all are extensions of deep fascia) include epimysium, which covers the entire muscle; perimysium, which penetrates into muscle and surrounds bundles of fibers called fascicles; and endomysium, which is delicate, barely visible, loose areolar tissue covering individual fibers (ie, individual cells).Tendons and aponeuroses are tough extensions of epimysium, perimysium, and endomysium. Tendons and aponeuroses are made of dense regular co nnective tissue and attach the muscle to bone or other muscle. Aponeuroses are broad, flat tendons. Tendon sheaths contain synovial fluid and enclose certain tendons. Tendon sheaths allow tendons to slide back and forth next to each other with lower friction. Tenosynovitis is inflammation of the tendon sheaths and tendons, especially those of the wrists, shoulders, and elbows. Tendons are not contractile and not very stretchy; furthermore, they are not very vascular and they heal poorly. Nerves convey impulses for muscular contraction. Nerves are bundles of nerve cell processes. Each nerve cell process (ie, axon) divides at its tip into a few to 10,000 branches called telodendria. At the end of each of these branches is an axon terminal that is rich in neurotransmitters.Blood provides nutrients and oxygen for contraction. An artery and a vein usually accompany a nerve that penetrates skeletal muscle. Arteries in muscles dilate during active muscular activity, thus increasing the supply of oxygen and glucose.A motor nerve is a bundle of axons that conducts nerve impulses away from the brain or spinal cord toward muscles. Each axon transmits an action potential (ie, nerve impulse), which is a burst of electricity. The nerve impulse travels along the axons at a steady rate, like fire travels along a fuse; however, nerve impulses travel extremely fast. Each axon has 4-2000 or more branches (ie, telodendria), with an average of 150 telodendria. Each separate branch suppli es a separate muscle cell. Thus, if an axon has 10 branches, it supplies 10 muscle fibers. Small motor units are for fine control of muscles; large motor units are for muscles that do not require such fine control.The neuromuscular junction is made of an axon terminal and the portion of the muscle fiber sarcolemma it nearly touches (called the motor endplate). The neurotransmitter released at the neuromuscular junction in skeletal muscle is ACh. The motor endplate is rich in thousands of ACh receptors; the receptors are integral proteins containing binding sites for ACh and sodium channels. Nerve impulse (action potential) reaches the axon terminal, which triggers calcium influx into the axon terminal.Calcium influx causes synaptic vesicles to release ACh via exocytosis. ACh diffuses across synaptic cleft.ACh binds to theACh receptor on the sarcolemma. Succinylcholine, a drug used to induce paralysis during surgery, binds to ACh receptors more tightly than ACh. Succinylcholine initially causes some depolarization, but then itbinds to the receptor, preventing ACh from binding. Therefore, it blocks the muscles stimulation by ACh, causing paralysis. Another drug that acts in a similar fashion is curare. These drugs do not cause pain relief or unconsciousness; thus, they are combined with other drugs during surgery. When ACh binds the receptor, it opens chemically regulated ion channels, which are sodium channels through the receptor molecule. Sodium, which is in high concentration outside cells and in low concentration inside cells, rushes into the cell through the channels.The cell, whose resting membrane potential along the inside of the membrane is negative when comparedwith the outside of the membrane, becomes positively charged along the inside of the membrane when sodium (a positive ion) rushes in. This change from a negative charge to a positive charge along the inner membrane is termed depolarization. The depolarization of one region of the sarcolemma (the motor endplate) initiates an action potential, which is a propagating wave of depolarization that travels (propagates) along the sarcolemma. Regions of membrane that become depolarized rapidly restore their proper ionic concentrations along their inner and outer surfaces in a process termed repolarization. (This process of depolarization, propagation, and repolarization is similar to dominoes that topple each other but also spring back into the upright position shortly afterward.)The action potential also propagates along the membrane lining the T tubules entering the cell. This action potential traveling along the T tubules causes the sarcoplasmic reticulum to release calcium into sarcoplasm.Calcium binds with troponin, causing it to pull on tropomyosin to change its or ientation, exposing myosin-binding sites on actin. An ATPase, which also functions as a myosin cross-bridging protein, splits ATP into adenosine diphosphate (ADP) + phosphate (P) in the previous contraction cycle. This energizes the myosin head. The energized myosin head, or cross-bridge, combines with myosin-binding sites on actin. Power stroke occurs. The attachment of the energized cross-bridge triggers a pivoting motion (ie, power stroke) of the myosin head. During the power stroke, ADP and P are released from the myosin cross-bridge. The power stroke causes thin actinmyofilaments to slide past thick myosin myofilaments toward the center of the A bands.ATP attaches to the myosin head again, allowing it to detach from actin. (In rigor mortis, an ATP deficiency occurs. Cross-bridges remain, and the muscles are rigid.)ATP is broken down to ADP and P, which cocks the myosin head again, preparing it to perform another power stroke if needed. Repeated detachment and reattachment of the cross-bridges results in shortening without much increase in tension during the shortening phase (isotonic contraction) or results in increased tension without shortening (isometric contraction).Release of the enzyme acetylcholinesterasein the neuromuscular junction destroys ACh and stops the generation of a muscle action potential. Calcium is taken back up (resequestered) in the sarcoplasmic reticulum, and myosin cross-bridges separate. ATP is required to separate myosin-actin cross-bridges. The muscle fiber resumes its resting state. The chemical energy that fuels muscular activities is ATP. For the first 5 or 6 seconds of muscle power, muscular activity can depend on the ATP that is already present in the muscle cells. Beyond this time, new amounts of ATP must be formed to enable the activation of muscular contractions that are needed to support longer and more vigorous physical activities. For activities that require a quick burst of energy that cannot be supplied by the ATP present in the muscle cells, the next 10-15 seconds of muscle power can be provided through the bodys use of the phosphagen system, which uses a substance called creatine phosphate to recycle ADP into ATP.4 For longer and more intense periods of physical activity, the body must rely on systems that break down the sugars (glucose) to produce ATP. The complete breakdown of glucose occurs in 2 ways: through anaerobic respiration (does not use oxygen) and through aerobic respiration (occurs in the presence of oxygen). The anaerobic use of gluco se to form ATP occurs as the body increases its muscle use beyond the capability of the phosphagen system to supply energy. In particular, the glycogen lactic acid system, through its anaerobic breakdown of glucose, provides approximately 30-40 seconds more of maximal muscle activity. For this system, each glucose molecule is split into 2 pyruvic acid molecules, and energy is released to form several ATP molecules, providing the extra energy. Then, the pyruvic acid partially breaks down further to produce lactic acid. If the lactic acid is allowed to accumulate in the muscle, one experiences muscle fatigue. At this point, the aerobic system must activate.The aerobic system in the body is used for sports that require an extensive and enduring expenditure of energy, such as a marathon race. Endurance sports absolutely require aerobic energy. A large amount of ATP must be provided to muscles to sustain the muscle power needed to perform such events without an excessive production of la ctic acid. This can only be accomplished when oxygen in the body is used to break down the pyruvic acid (that was produced anaerobically) into carbon dioxide, water, and energy by way of a very complex series of reactions known as the citric acid cycle. This cycle supports muscle usage for as long as the nutrients in the body last. The breakdown of pyruvic acid requires oxygen and slows or eliminates the accumulation of lactic acid. In summary, the 3 different muscle metabolic systems that supply the energy required for various activities are as follows: Phosphagen system (for 10- to 15-sec bursts of energy)Glycogen lactic acid system (for another 30-40 sec of energy)Aerobic system (provides a great deal of energy that is only limited by the bodys ability to supply oxygen and other important nutrients) Many sports require the use of a combination of these metabolic systems. By considering the vigor of a sports activity and its duration, one can estimate very closely which of the ene rgy systems are used for each activity. During muscular exercise, blood vessels in muscles dilate and blood flow is increased in order to increase the available oxygen supply. Up to a point, the available oxygen is sufficient to meet the energy needs of the body. However, when muscular exertion is very great, oxygen cannot be supplied to muscle fibers fast enough, and the aerobic breakdown of pyruvic acid cannot produce all the ATP required for further muscle contraction. During such periods, additional ATP is generated by anaerobic glycolysis. In the process, most of the pyruvic acid produced is converted to lactic acid. Although approximately 80% of the lactic acid diffuses from the skeletal muscles and is transported to the liver for conversion back to glucose or glycogen, some lactic acid accumulates in muscle tissue, making muscle contraction painful and causing fatigue. Ultimately, once adequate oxygen is available, lactic acid must be catabolized completely into carbon dioxide and water. After exercise has stopped, extra oxygen is required to metabolize lactic acid; to replenish ATP, phosphocreatine, and glycogen; and to replace (pay back) any oxygen that has been borrowed from hemoglobin, myoglobin (an iron-containing substance similar to hemoglobin that is found in muscle fibers), air in the lungs, and body fluids. The additional oxygen that must be taken into the body after vigorous exercise to restore all systems to their normal states is called oxygen debt. The debt is paid back by labored breathing that continues after exercise has stopped. Thus, the accumulation of lactic acid causes hard breathing and sufficient discomfort to stop muscle activity until homeostasis is restored.5 Eventually, muscle glycogen must also be restored. Restoration of muscle glycogen is accomplished through diet and may take several days, depending on the intensity of exercise. The maximum rate of oxygen consumption during the aerobic catabolism of pyruvic acid is called maximal oxygen uptake. Maximal oxygen uptake is determined by sex (higher in males), age (highest at approximately age 20 y), and size (increases with body size). Highly trained athletes can have maximal oxygen uptakes that are twice that of average people, probably owing to a combination of genetics and training. As a result, highly trained athletes are capable of greater muscular activity without increasing their lactic acid production and have lower oxygen debts, which is why they do not become short of breath as readily as untrained individuals. The best examples of light exercise are walking and light jogging. The muscles that are recruited during this type of exercise are those that contain a large amount of type I muscle cells, and, because these cells have a good blood supply, it is easy for fuels and oxygen to travel to the muscle. ATP consumption makes ADP available for new ATP synthesis. The presence of ADP (and the resulting synthesis of ATP) simulates the movement of hydrogen (H+) into the mitochondria; this, in turn, reduces the proton gradient and thus stimulates electron transport. The hydrogen on the reduced form of nicotinamide adenine dinucleotide (NADH) is used up, nicotinamide adenine dinucleotide (NAD) becomes available, and fatty acids and glucose are oxidized. Incidentally, the calcium released during contraction stimulates the enzymes in the Krebs cycle and stimulates the movement of the glucose transporter 4 (GLUT-4) from inside of the muscle cell to the cell membrane. Both these exercise-induced respon ses augment the elevation in fuel oxidation caused by the increase in ATP consumption. An increase in the pace of running simply results in an increased rate of fuel consumption, an increased fatty acid release, and, therefore, an increase in the rate of muscle fatty acid oxidation. However, if the intensity of the exercise increases even further, a stage is reached in which the rate of fatty acid oxidation becomes limited. The reasons why the rate of fatty acid oxidation reaches a maximum are not clear, but it is possible that the enzymes in the beta-oxidation pathway are saturated (ie, they reach a stage in which their maximal velocity [Vmax] is less than the rate of acetyl-coenzyme A [acetyl-CoA] consumption in the Krebs cycle). Alternatively, it may be that the availability of carnitine (the chemical required to transport the fatty acids into the mitochondria) becomes limited. Whatever the reason, the consequence is that as the pace rises, the demand for acetyl-CoA cannot be met by fatty acid oxidation alone. The accumulation of acetyl-CoA that was so effective at inhibiting the oxidation of glucose is no longer present, so pyruvate dehydrogenase starts working again and pyruvate is converted into acetyl-CoA. In other words, more of the glucose that enters the muscle cell is oxidized fully to carbon dioxide. Therefore, the energy used during moderate exercise is derived from a mixture of fatty acid and glucose oxidation. As the intensity of the exercise increases even further (ie, running at the pace of middle-distance races), the rate at which the muscles can extract glucose from the blood becomes limited. In other words, the rate of glucose transport reaches Vmax, either because the blood cannot supply the glucose fast enough or the number of GLUT-4s becomes limited. ATP generation cannot be serviced completely by exogenous fuels, and ATP levels decrease. Not only does this stimulate phosphofructokinase, it also stimulates glycogen phosphorylase. This me ans that glycogen stored within the muscle cells is broken down to provide glucose. Therefore, the fuel mix during strenuous exercise is composed of contributions from blood-borne glucose and fatty acids and from endogenously stored glycogen.Being fit (biochemically speaking) means that the individual has a well-developed cardiovascular system that can efficiently supply nutrients and oxygen to the muscles. Fit people have muscle cells that are well perfused with capillaries (ie, they have a good muscle blood supply). Their muscle cells also have a large number of mitochondria, and those mitochondria have a high activity of Krebs cycle enzymes, electron transport carriers, and oxidation enzymes. Individuals who are unfit must endure the consequences of a poorer blood supply, fewer mitochondria, less electron transport units, a lower activity of the Krebs cycle, and poorer activity of beta-oxidation enzymes. To generate ATP in the mitochondria, a steady supply of fuel and oxygen and decent activity of the oxidizing enzymes and carriers are needed. If any of these components are lacking, the rate at which ATP can be produced by mitochondria is compromised. Under these circumstances, the production of ATP by aerobic means is not sufficient to provide the muscles with sufficient ATP to sustain contractions. The result is anaerobic ATP generation using glycolysis. Increasing the flux through glycolysis but not increasing the oxidative consumption of the resulting pyruvate increases the production of lactate. The purpose of respiration is to provide oxygen to the tissues and to remove carbon dioxide from the tissues. To accomplish this, 4 major events must be regulated, as follows: Pulmonary ventilation. Diffusion of oxygen and carbon dioxide between the alveoli and the blood, Transport of oxygen and carbon dioxide in the blood and body fluids and to and from the cells, Regulation of ventilation and other aspects of respiration: Exercise causes these factors to change, but the body is designed to maintain homeostasisWhen one goes from a state of rest to a state of maximal intensity of exercise, oxygen consumption, carbon dioxide formation, and total pulmonary and alveolar ventilation increase by approximately 20-fold. A linear relationship exists between oxygen consumption and ventilation. At maximal exercise, pulmonary ventilation is 100-110 L/min, whereas maximal breathing capacity is 150-170 L/min. Thus, the maximal breathing capacity is approximately 50% greater than the actual pulmon ary ventilation during maximal exercise. This extra ventilation provides an element of safety that can be called on if the situation demands it (eg, at high altitudes, under hot conditions, abnormality in the respiratory system). Therefore, the respiratory system itself is not usually the most limiting factor in the delivery of oxygen to the muscles during maximal muscle aerobic metabolism. VO2 max is the rate of oxygen consumption under maximal aerobic metabolism. This rate in short-term studies is found to increase only 10% with the effect of training. However, that of a person who runs in marathons is 45% greater than that of an untrained person. This is believed to be partly genetically determined (eg, stronger respiratory muscles, larger chest size in relation to body size) and partly due to long-term training. Oxygen diffusing capacity is a measure of the rate at which oxygen can diffuse from the alveoli into the blood. An increase in diffusing capacity is observed in a state of maximal exercise. This results from the fact that blood flow through many of the pulmonary capillaries is sluggish in the resting state. In exercise, increased blood flow through the lungs causes all of the pulmonary capillaries to be perfused at their maximal level, providing a greater surface area through which oxygen can diffuse into the pulmonary capillary blood. Athletes who require greater amounts of oxygen per minute have been found to have higher diffusing capacities, but the exact reason why is not yet known. Although one would expect the oxygen pressure of arterial blood to decrease during strenuous exercise and carbon dioxide pressure of venous blood to increase far above normal, this is not the case. Both of these values remain close to normal. Stimulatory impulses from higher centers of the brain and from joint and muscle proprioceptive stimulatory reflexes account for the nervous stimulation of the respiratory and vasomotor center that provides almost exactly the pr oper increase in pulmonary ventilation to keep the blood respiratory gases almost normal. If nervous signals are too strong or weak, chemical factors bring about the final adjustment in respiration that is required to maintain homeostasis. Regular exercise makes the cardiovascular system more efficient at pumping blood and delivering oxygen to the exercise muscles. Releases of adrenaline and lactic acid into the blood result in an increase of the heart rate (HR). Basic definitions of terms are as follows:VO2 equals cardiac output times oxygen uptake necessary to supply oxygen to muscles. The Fick equation is the basis for determination of VO2. Exercises increase some of the different components of the cardiovascular system, such as stroke volume (SV), cardiac output, systolic blood pressure (BP), and mean arterial pressure. A greater percentage of the cardiac output goes to the exercising muscles. At rest, muscles receive approximately 20% of the total blood flow, but during exercise, the blood flow to muscles increases to 80-85%. To meet the metabolic demands of skeletal muscle during exercise, 2 major adjustments to blood flow must occur. First, cardiac output from the heart must increase. Second, blood flow from ina ctive organs and tissues must be redistributed to active skeletal muscle. Generally, the longer the duration of exercise, the greater the role the cardiovascular system plays in metabolism and performance during the exercise bout. An example would be the 100-meter sprint (little or no cardiovascular involvement) versus a marathon (maximal cardiovascular involvement). The cardiovascular system helps transport oxygen and nutrients to tissues, transport carbon dioxide and other metabolites to the lungs and kidneys, and distribute hormones throughout the body. The cardiovascular system also assists with thermoregulation.The pumping of blood by the heart requires the following 2 mechanisms to be efficient:Alternate periods of relaxation and contraction of the atria and ventriclesCoordinated opening and closing of the heart valves for unidirectional flow of blood The cardiac cycle is divided into 2 phases: ventricular diastole and ventricular systole.This phase begins with the opening of the atrioventricular (AV) valves. The mitral valve (located between the left atrium and left ventricle) opens when the left ventricular pressure falls below the left atrial pressure, and the blood from left atrium enters the left ventricle.Later, as the blood continues to flow into the left ventricle, the pressure in both chambers tends to equalize.At the end of the di astole, left atrial contractions cause an increase in left atrial pressure, thus again creating a pressure gradient between the left atrium and ventricle and forcing blood into the left ventricle.Ventricular systole begins with the contraction of the left ventricle, which is caused by the spread of an action potential over the left ventricle. The contraction of the left ventricle causes an increase in the left ventricular pressure. When this pressure is higher than the left atrial pressure, the mitral valve is closed abruptly.The left ventricular pressure continues to rise after the mitral valve is closed. When the left ventricular pressure rises above the pressure in the aorta, the aortic valve opens. This period between the closure of the mitral valve and the opening of the aortic valve is called isovolumetric contraction phase.The blood ejects out of the left ventricle and into the aorta once the aortic valve is opened. As the left ventricular contraction is continued, 2 processe s lead to a fall in the left ventricular pressure. These include a decrease in the strength of the ventricular contraction and a decrease in the volume of blood in the ventricle.When the left ventricular pressure falls below the aortic pressure, the aortic valve is closed. After the closure of the aortic valve, the left ventricular pressure falls rapidly as the left ventricle relaxes. When this pressure falls below the left atrial pressure, the mitral valve opens and allows blood to enter left ventricle. The period between the closure of the aortic valve closure and the opening of the mitral valve is called isovolumetric relaxation time. Right-sided heart chambers undergo the same phases simultaneously. Most of the work of the heart is completed when ventricular pressure exists. The greater the ventricular pressure, the greater the workload of the heart. Increases in BP dramatically increase the workload of the heart, and this is why hypertension is so harmful to the heart.Arterial BP is the pressure that is exerted against the walls of the vascular system. BP is determined by cardiac output and peripheral resistance. Arterial pressure can be estimated using a sphygmomanometer and a stethoscope. The reference range for males is 120/80 mm Hg; the reference range for females is 110/70 mm Hg. The difference between systolic and diastolic pressure is called the pulse pressure. The average pressure during a cardiac cycle is called the mean arterial pressure (MAP). MAP determines the rate of blood flow through the systemic circulation.During rest, MAP = diastolic BP + (0.33 X pulse pressure). For example, MAP = 80 + (0.33 X [120-80]), MAP = 93 mm Hg. During exercise, MAP = diastolic BP + (0.50 X pulse pressure). For example, MAP = 80 + (0.50 X [160-80]), MAP = 120 mm Hg. The heart has the ability to generate its own electrical activity, which is known as intrinsic rhythm. In the healthy heart, contraction is initiated in the sinoatrial (SA) node, which is often called the hearts pacemaker. If the SA node cannot set the rate, then other tissues in the heart are able to generate an electrical potential and establish the HR.The parasympathetic nervous system and the sympathetic nervous system affect a personsHR. Parasympathetic nervous system: The vagus nerve originates in the medulla and innervates the SA and AV nodes. The nerve releases ACh as the neurotransmitter. The response is a decrease in SA node and AV node activity, which causes a decrease in HR. Sympathetic nervous system: The nerves arise from the spinal cord and innervate the SA node and ventricular muscle mass. The nerves release norepinephrine as the neurotransmitter. The response is an increase in HR and a force of contraction of the ventricles.At rest, sympathetic and parasympathetic ne rvous stimulation are in balance. During exercise, parasympathetic stimulation decreases and sympathetic stimulation increases. Several factors can alter sympathetic nervous system input.Baroreceptors are groups of neurons located in the carotid arteries, the arch of aorta, and the right atrium. These neurons sense changes in pressure in the vascular system. An increase in BP results in an increase in parasympathetic activity except during exercise, when the sympathetic activity overrides the parasympathetic activity. Chemoreceptors are groups of neurons located in the arch of the aorta and the carotid arteries. These neurons sense changes in oxygen concentration. When oxygen concentration in the blood is decreased, parasympathetic activity decreasesand sympathetic activity increases. Temperature receptors are neurons located throughout the body. These neurons are sensitive to changes in body temperature. As temperature increases, sympathetic activity increases to cool

Two Sides of Billy Pilgrim in Kurt Vonneguts Slaughterhouse Five :: Slaughterhouse-Five Essays

Two Sides of Billy Pilgrim in Kurt Vonnegut's Slaughterhouse Five War can destroy. War can teach. In Kurt Vonnegut's book Slaughterhouse Five, the central character, Billy Pilgrim, is the outcome of a test. In creating and developing Billy Pilgrim, Vonnegut's intention is to show the effect of modern war on a sensitive person who tries to play the game the way society expects. This, along with family influence, shapes how Billy acts in his two different lives: life in the military and life alone. Torn inside and out, Billy Pilgrim was forced to make a choice. He had to choose the way he would live his life. Learning from his father, Billy could respond by taking his father's drive toward dominance over people and environment. Billy could also follow his mother, confusing him with her excessive demands for gratitude. Forced to decide, Billy chooses neither, which to him, is the easiest way to survive. He yields to his father's attitude without adopting it as a model, while withdrawing from his mother without complaint, without hurting her. He believes that sharing the guilt of aggression is more complicated than simply turning the other cheek, which shines through in moments under pressure. Denial is also crucial to Billy Pilgrim's character. The Dresden bombing intensifies the damage to his personality. He can survive only by denying his experiences at Dresden and he divides himself into two halves: a social half that says, "Yes," and a private half that says, "No." His conflicts force his "surrender to the world," first with a mental breakdown, then with an escape into fantasy. Publicly, he agrees with the Marine major who wants more bombing, more Green Berets, while internally, he sees a war-film backwards, in which he wishes to undo the ravaging effects of war. Looking for an outlet, Billy discovers science fiction, which gives him perspective and consolation. This perspective forces him to teach others, to improve not people's physical sight but their spiritual vision, which eventually leads to his commitment.

Imaginary friend

Imaginary friend Dear Imaginary friend I hope this letter could make up for the past years, because ever since you've came back to my life I feel completed , because you have been the only one that I could tell my little dirty secret and not feel the urge to feel ashamed because you would never In a million years Judge me , you were my only true friend that knew who I truly was, and have never ratted me out that why I have love you more than anything In this oral for this long.Nevertheless, this past few days It feels Like part of you haven't forgiving me yet for the ways I treated you back then when I was still a little boy.I neglected you like you were nothing compared to something, the distress and shame I caused you, and also putting everyone else needs before yours especially my selfish self centered girlfriend who want it all , but don't blame her blame me because I was the stupid one who never knew wrong from right like I said I was still a little kid, but owe that I am all gr own up I realize my mistake for letting you go I should have fight for you, for us because back then I never realize how much you meant to me until you left, because each day that you were gone and not by my side I felt really lonely even my girlfriend and family could bring back the Joy and happiness that we had, but I never meant to hurt you I Just thought because no one could see you I could treat you any how I want, and since you were on my head I never thought you could leave me, and am really sorry for that. I know having an imaginary friend at the age of 35 might seem crazy to other people who don't understand but I don't care because with you I feel comfortable an safe, and all I have ever wished for is that one day you would come back.In conclusion, now that you are back I want to make up for the past 23 years ,and even it mean by leaving my girlfriend am ready to make the sacrifice I Just want everything to go back to the way they were except for the neglecting part, and I promise you would always come first no matter the circumstances I am In. His has being really tough for me, but I Just want to ask why did you ever left me was It the stuff I did to you, because If It Is I take full responsibly for my action, or If It something else let me know so I don't go through life feeling guilty for something I never did. Tell me what can I do to make the pain go away, or at least could you tell me how feel towards me because am done being kept In the dark. Please Just forgive me because I really missed you so much, and now that you are back I just want to everything Sincerely,

Democracy in India Essays

Democracy in India Essays Democracy in India Essay Democracy in India Essay An era of change has begun. In 1950, a democratic government in India was formed. Democracy a form of government which is for the people, of the people and by the people. Democracy a form of government where the ultimate power resides with the people. Democracy a gift to our country. Most people reading this would by now have added another exclamation. Democracy – What a joke. In today’s day and time the idea of democracy is dead in the minds of the people. We have forgotten that the reason why the people in power are in power is because of us. We vote for them, and still cower in submission from them. Have we not realized that all the government employees, be it the top officer in the police or any politician, they are all â€Å"PUBLIC SERVANTS†? They are given these â€Å"lucrative† government posts to serve us. We the citizens, the active taxpayers, fund every government institution. It is with our hard earned money with which the roads are supposed to be built. So, if the money that is supposed to be used to build the roads is going elsewhere then, oh innocent taxpayer, you cannot shrug you shoulders when you read this in the morning paper saying â€Å"it’s not my problem†. It is your problem. It is more of your problem than of the poor contractor who commits the thievery, because it is you who is being swindled. Why is this mentality prevalent in our country? I just finished the internationally acclaimed â€Å"The White Tiger† and was disturbed at the cynical and dark outlook the writer had of Indian democracy. But then it struck me that most Indians do feel this way and it’s not some solitary case. Most of us feel that democracy is useless; only a fancy word for something that does not apply to our daily lives. Most of us feel that democracy is dead. But what we don’t realize is that a democracy is always constituted of its people and that until the idea of democracy is not revived in our minds our country will continue to see the dark side of the moon. Quite frankly, we ourselves are the reason that the progress of our country has stagnated. All we do is sit back, criticize and point fingers. But no one wants to pull this old cow called India by the leash and lead it to greener pastures. All we can do is sit on the cow’s back or hang by its tail like useless parasites screaming â€Å"I contribute to the national income!! † I believe I was a bit cynical there myself. Our country has the potential; we can reach new heights if everyone in this country feels the same. Politicians, doctors, lawyers, educationists, actors, even the person who lives under the Safdarjung flyover. I’m not asking you to leave everything and become social workers; I’m asking you to what you are supposed to do but please do it with a touch of honesty, with a social outlook to it and just by being a little selfless. According to me if we start to think about the welfare of this country, it will be much easier for us to realize this dream. One more thing I am a bit concerned about is the educational system of our country. Is our epistemological setup conducive for the creation of young leaders who can take this country forward? Or are we creating useless rote machines that can rattle chemical formulae at the drop of a hat? When I speak of the educational system I do not only mean the schools which are imparting such forms of â€Å"knowledge†, but most of us today believe that getting a 95% in our 12th boards is all we go to school for. Our parents, teachers, peers, everyone believes the same. It is bred into us and our puny little minds that education translates to a high percentage and nothing else. Even the whole system is to blame. We have to change this outlook to create new leaders; we have to redefine our sense on knowledge and our perception of an educated person. Only then will our system yield better, thinking citizens for this country. How is it that when we speak of reform, inevitably, the first groups of people that come to our minds are the politicians? Why not? † you might ask, â€Å"They are the people who are responsible for running the country, for serving us; as you mentioned. † Yes; correct you are. You have the right, as a citizen of this wonderful country; you can question them on any issue you want. But what I intend to say is that when will start to look at our responsibilities as an individual on the ground level? We cast millions of aspersions on the government about some or th e other thing the government is supposed to do but did not. When will we begin to reconcile ourselves to the fact that when we have the so called right to question the â€Å"public servants†, we also on the other hand have some duties to fulfill, to help them run the country. How many of us use the trash cans wherever available? How many of us have voted for the general elections this year? How many of us still use plastic bags? How many of us dutifully pay the taxes on time? We do have a list of endless rights, but do we all fulfill our duties? Time for some self-reflection, isn’t it, oh great â€Å"Janta-e-Hindustan†