By E. Shawn. Russell Sage College. 2018.
FAD synthetase then oxidation of succinate to fumarate (see Fig purchase 0.18mg alesse mastercard. Single electrons are transferred adds AMP to form FAD effective alesse 0.18 mg. FAD is the major from the two adjacent -CH2- methylene groups of succinate to an FAD bound to coenzyme in tissues and is generally found succinate dehydrogenase, thereby forming the double bond of fumarate. From the tightly bound to proteins, with about 10% reduced enzyme-bound FAD, the electrons are passed into the electron transport being covalently bound. An OH group and a proton from water add to the double bond of fumarate, body is very slow, and people can live for converting it to malate. In the last reaction of the TCA cycle, the alcohol group of long periods on low intakes without display- malate is oxidized to a keto group through the donation of electrons to NAD. There is no net consumption of oxaloacetate in the TCA cycle—the first step use an oxaloacetate, and the last step pro- II. The utilization and regeneration of oxaloacetate is the “cycle” part of the TCA The enzymes of the TCA cycle rely heavily on coenzymes for their catalytic func- tion. Isocitrate dehydrogenase and malate dehydrogenase use NAD as a coenzyme, cycle. Citrate synthase catalyzes a reaction that uses a CoA derivative, acetyl CoA. The -ketoglutarate dehydrogenase complex One of Otto Shape’s tennis part- uses thiamine pyrophosphate, lipoate and FAD as bound coenzymes, and NAD and ners told him that he had heard CoASH as substrates. Each of these coenzymes has unique structural features that about a health food designed for enable it to fulfill its role in the TCA cycle. The adver- tisement made the claim that succinate A. FAD and NAD would provide an excellent source of energy during exercise because it could be metabo- Both FAD and NAD are electron-accepting coenzymes. Why is FAD used in some lized directly without oxygen. Their unique structural features enable FAD and anything wrong with this statement? NAD to act as electron acceptors in different types of reactions, and play different physiological roles in the cell. FAD is able to accept single electrons (H•), and forms a half-reduced single electron intermediate (Fig. It thus participates in reactions in which single electrons are transferred independently from two different atoms, which occurs in double bond formation (e. When FAD and FMN accept single electrons, they are converted to the half-reduced semi- quinone, a semistable free radical form. They can also accept two electrons to form the fully reduced form, FADH2. However, in most dehydro- genases, FADH2 is never formed. Instead, the first electron is shared with a group on the protein as the next electron is transferred. Therefore, in this text, overall acceptance of two electrons by FAD has been denoted by the more general abbreviation, FAD(2H). CHAPTER 20 / TRICARBOXYLIC ACID CYCLE 365 – – The claim that succinate oxidation COO COO could produce energy without oxy- CH2 CH2 gen is wrong. It was probably Isocitrate CO2 α-Ketoglutarate – based on the fact that succinate is oxidized H C COO isocitrate CH2 to fumarate by the donation of electrons to H C H dehydrogenase C O FAD. However, ATP can only be generated – – from this process when these electrons are COO COO O H O donated to oxygen in the electron transport C NH2 C NH2 chain. The energy generated by the electron + H+ + transport chain is used for ATP synthesis in N N the process of oxidative phosphorylation. R R After the covalently bound FAD(2H) is oxi- + dized back to FAD by the electron transport NAD NADH chain, succinate dehydrogenase can oxidize Fig. The alcohol group (C—OH) is oxi- another succinate molecule. Subsequent electron shifts in the pyridine ring remove the positive charge. The H of the OH group dis- sociates into water as a proton, H. In contrast, NAD accepts a pair of electrons as the hydride ion (H ), which is attracted to the carbon opposite the positively-charged pyridine ring (Fig. This occurs, for example, in the oxidation of alcohols to ketones by malate dehydrogenase and isocitrate dehydrogenase. The nicotinamide ring accepts a hydride ion from the C-H bond, and the alcoholic hydrogen is released into the medium as a positively charged proton, H. The free radical, single-electron forms of FAD are very reactive, and FADH can lose its electron through exposure to water or the initiation of chain reactions. As a consequence, FAD must remain very tightly, sometimes covalently, attached to its enzyme while it accepts and transfers electrons to another group bound on the enzyme (Fig 20. Because FAD interacts with many functional groups on amino Succinate Fumarate acid side chains in the active site, the E0 for enzyme-bound FAD varies greatly and can be greater or much less than that of NAD. In contrast, NAD and NADH are His–FAD more like substrate and product than coenzymes. NADH plays a regulatory role in balancing energy metabolism that FAD(2H) cannot because FAD(2H) remains attached to its enzyme. Free NAD binds to a Fe–S dehydrogenase and is reduced to NADH, which is then released into the medium where it can bind and inhibit a different dehydrogenase.
AFO A solid AFO with an anterior calf strap and an anterior ankle strap is the most versatile orthotic design and is the orthosis most often prescribed for children at the preambulatory stage buy alesse 0.18 mg online, usually between the ages of 18 and 24 months (Figure 6 order 0.18 mg alesse with mastercard. This orthotic provides stability to the ankle and foot to give a stable base of support for children to stand. This orthosis is reasonably easy for caretakers to apply and is lightweight. As children gain better stability and start to walk using a walker, usually between the ages of 3 to 4 years, the ankle hinge can be added to allow dorsiflexion but limit plantar flexion. This transition to a hinged AFO is contraindicated if chil- dren have severe planovalgus or varus foot deformity (Figure 6. The hinge will allow movement through the subtalar joint rather than the ankle joint and, as a consequence, will allow worsening of the foot deformity in the orthosis. Also, the hinged AFO is contraindicated if the children are 6. Following removal, the casts are inspected to make sure they are developing increased knee flexion in stance or a crouched gait pattern. Most plantigrade and have the desired correction children who have good walking ability with diplegic and hemiplegic pat- (I). The cast is then filled with plaster to tern involvement benefit from the transition to a hinged AFO at approxi- make a positive mold, which has the relief mately 3 years of age. Most children who are marginal ambulators or non- areas increased further (J). The mold is then ambulators will be best served by staying in solid AFOs. Hinged AFOs are placed in a high-temperature oven over which a plastic cover is vacuum formed (K). The or- preferred for children who back-knee because of gastrocnemius contrac- thotic is then cut from the vacuum-formed tures. By setting the plantar flexion stop at 5° of dorsiflexion, these children plastic, trimmed, smoothed, and pads and will be forced into knee flexion in stance if they are independent ambulators. If they use assistive devices, such as walkers or crutches, they may still back- knee by allowing the forefoot to come off the floor. If this occurs, the shoe should have a good wide stable heel; however, in spite of this, some children will persist with back-kneeing and can be controlled only with a KAFO that blocks knee hyperextension directly. Ground Reaction AFO Controlling crouched gait with increased knee flexion and ankle dorsiflex- ion in stance phase is best done using solid AFOs with wide anterior proxi- mal calf straps until children weigh 25 kg, usually at about 8 to 10 years of age. For children who are over 25 kg, the solid ankle ground reaction AFO, which is rear entry in the calf, is recommended (Figure 6. The use of this orthosis requires that the ankle can be brought to neutral dorsiflexion with the knee in full extension. If this cannot be accomplished, the orthosis can- not work and these children first need gastrocnemius and hamstring length- ening before the orthosis can be used successfully. The successful use of this orthotic requires that there be very little knee flexion contracture. Because this orthosis depends on the mechanics of an effective ground reaction force, the foot-to-knee axis has to be in a relatively normal alignment, meaning less than 20° of internal or external tibial torsion. This solid ground reaction AFO does not work with severe internal or external tibial torsion or severe foot malalignments. The ground reaction AFO only works when children are standing on their feet, and as such is useful only for ambulatory children. As these children get heavier, this orthosis becomes more effective; however, it also has to become stronger. As children approach 50 to 70 kg, the orthosis 194 Cerebral Palsy Management Figure 6. The most basic AFO has a solid ankle, an anterior ankle strap, and an anterior calf strap. This is the preferred or- has to be constructed with a composite of carbon fiber or laminated copoly- thotic for preambulatory children and most mer to withstand the applied forces. As children gain am- bulatory ability and the main goal of the or- The ground reaction AFO may be hinged to allow plantar flexion but limit thotic becomes preventing plantar flexion, a dorsiflexion (Figure 6. This orthosis is primarily used after surgical re- plantar flexion-limiting ankle hinge joint can construction of the feet and muscle lengthening as a bridge to allow develop- be added. The remainder of the orthotic is ment of increased muscle strength in the plantar flexors, with the long-term similar to the solid ankle, with perhaps a flat goal of individuals being free of an orthotic. However, some individuals con- sole or additional arch molds added. These tinue to use this articulated ground reaction orthosis long term. The ortho- tone-reducing features have not been shown sis can be used before surgery on rare occasions; however, a prerequisite for to change gait in any measurable way. The ar- ticulated ground reaction AFO is entered posteriorly into a circumferentially Figure 6. The solid ground reaction AFO is entered from the rear at the calf level. If there is any planovalgus This is an anticrouching orthosis and has very or varus hindfoot deformity, the foot will deform even more severely into specific requirements to work. The knee must planovalgus or varus under the strong force of the ground reaction moment. Older children weighing more than 25 kg who meet the other cri- must be less than 30°. This orthosis depends teria will usually be very comfortable with the articulated ground reaction on the action of the ground reaction force, AFO, and the orthotic will be very effective in controlling crouched gait.
If the hip is normal discount alesse 0.18mg amex, defined as an MP of less than 25% or 30% discount alesse 0.18mg without a prescription, the risk of develop- ing hip subluxation in adulthood is virtually nonexistent. If the hip has mild to moderate subluxation, defined as 30% to 60%, there may rarely be some progression in adulthood. However, indi- viduals who reach adulthood with hip subluxation of greater than 60% will, slowly over time, go to full dislocation in almost all cases. As an example, it is very difficult to provide ade- quate perineal care during menstrual cycles for a young adult woman with severe hip adduction contractures from fixed hip dislocation. As outlined above, the subluxated and dislocated hips become arthritic and, like many arthritic joints, become painful. There is a myth in the medical community that the hips do not ever become painful in individuals who are noncom- municative. The fact that these individuals develop painful hips from neg- lected dislocations is absolutely clear to physicians who routinely care for these individuals; however, it is often difficult to determine how much pain individuals are experiencing. Just as with elderly individuals who have de- generative joints, sometimes individuals with severe changes on radiographs have only mild pain and others with mild radiographic changes have severe pain. This same discrepancy is seen in people with spasticity and hip dys- plasia. Although the published literature varies widely, probably 50% to 75% of individuals with spastic hip dislocation experience enough pain that it is recognized by the caretakers or medical personnel. Diagnostic Evaluations The most important work in evaluating the diagnostic monitoring of children with the typical posterosuperior spastic hip disease was done by Reimers. Hip 531 spastic hips at risk is the physical examination. This examination, which was popularized by Rang et al. All spastic chil- dren should have this measure of hip abduction monitored every 6 months during childhood at least to age 8 years. This monitoring can be performed by a trained physical therapist; however, we personally prefer to monitor this in the CP clinic and keep a diligent record in a database. For children who demonstrate some limitation of hip abduction, meaning less than 45° on each side, the secondary evaluation process is a supine anteroposterior radiograph of the pelvis. Hip Radiograph The standard anterosuperior supine radiograph of the pelvis with the legs in neutral or relatively neutral position should be obtained every 6 to 12 months if the hip abduction is less than 45°. The MP of this radiograph must be measured and recorded (Figure 10. It is not appropriate to only look at the radiograph, because it is impossible to tell the difference between an MP of 20% and one of 35% without measuring. It is no more appropriate to only look at an anteroposterior pelvis radiograph of a spastic child than it is to monitor idiopathic scoliosis by obtaining a scoliosis radiograph and only looking at it without measuring the curve. The measurement of the param- eter that is most predictive of outcome is clearly the MP, as demonstrated by Reimers. The center-edge angle is a poor measure for spastic hip disease and has a correlation coefficient of only 0. The reason the center-edge angle is not a good measure is that it requires defining a center rather than a line in the femoral head, and also requires defining a point in two-dimensional space of the lat- Figure 10. The primary screening and phys- ical examination method is to record the hip eral acetabulum. Both these points are often quite diffuse in these young and abduction with the hips and knees extended. The center-edge angle is also a measure that is not linear, but fol- tion measure to determine at risk and sub- lows the sine curve. Therefore, changes in the area of interest, between 20% luxated spastic hips. It is important to make and 40%, tend to fluctuate wildly based on these inaccuracies and make sure that asymmetric abduction is noted by monitoring for treatment methods extremely poor. In summary, the center- observing motion of the pelvis as the hip is edge angle has no role in the ongoing monitoring of spastic hip disease. Because these children often re- quire many radiographs over their lifetime, it is important to limit radio- graphs to only those that directly add to the clinical decision making, thereby limiting the radiation exposure of these children as much as possible. Computed Tomography Scans The use of computed tomography (CT) scan to evaluate hips with spastic hip disease has been extensively reviewed in the literature. It is important to note that not all hips have a typical posterosuperior subluxation of the femoral head, and by far the best mechanism for evaluating the direction of the hip dysplasia is the CT scan. Sometimes direct anterior subluxation or dislocation can have an almost normal radiographic appearance or a very minimal abnormality. At other times, the femoral head can be situated lat- erally so that it is very difficult to tell whether this is a lateral anterior sub- luxation or dislocation or a posterolateral subluxation or dislocation. The CT scan is extremely accurate in defining this position. Using the CT scan to evaluate the exact area of the deformity of the acetabulum is also useful; 532 Cerebral Palsy Management Figure 10. The most important measure to monitor on the radiograph for monitoring spastic hips is the Reimers migration percent- age (MP). This should be an anteroposterior supine radiograph with the child’s hips in the extended and relatively normal position. The hip should not be forced into abduction or external rotation if the child resists. The first line on the radiograph should be the transverse Hilgenreiner’s line (h), which goes through the center of the triradiate cartilages.
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