By Y. Vigo. Saint Francis College, Brooklyn Heights, New York.
Compression may also enhance temperature reduction28 with the changes at 1 cm below the fat layer and at 2 cm below the fat layer being greater with compression at 12⋅8ºC and 10⋅1ºC cheap rogaine 2 60 ml prostate cancer xenograft mouse model. Subcutaneous fat buy rogaine 2 60 ml with amex prostate reduction, being an insulating material, inhibits the cooling effect and while significant cooling occurs with 10 minutes of ice application to a depth of 2 cm in those with less than 1 cm of fat,29 athletes with more than 2 cm of fat, required 20–30 minutes. There is an inverse relationship between adipose tissue and temperature decrease so that subcutaneous fat may mean that short duration ice application may be ineffective in cooling deeper tissue levels. The above paragraphs highlight only some of the studies on ice application. The consensus from studies of ice application, for periods varying from five minutes to 85 minutes, is that the temperature is reduced in the first 10 minutes with little further reduction from 10 to 20 minutes. The temperature drop is determined by the area of contact between the ice and the skin, the temperature difference and tissue conductivity but most published studies do not measure the area of ice application, subcutaneous fat, nor use comparable methods of calculating depth, or measuring temperature. Where temperature is 48 The role of ice in soft tissue injury management measured, in human and animal studies, there is wide variation in the temperature recorded at different depths in different studies with wide standard deviations. It is almost impossible to consider the dynamic effect of tissue movement and blood flow on temperature and experimental measurements of tissue temperature cannot be directly compared to the effect on the injured athlete. Summary Subcutaneous fat is an insulator so may impair cold conduction A barrier should be used to prevent ice burns A wet towel is a most effective barrier and conductor Ice therapy may cause temporary neurological impairment Ice may temporarily impair muscle strength Application of different modalities Ice, or cold, is used in different ways. The standard ice application of melting iced water ensures a constant temperature of 0ºC. Ice taken straight from a freezer may be considerably below freezing point and reusable chemical gel packs may be as cold as −5 to −15ºC. Iced water may also be used in different ways, such as frozen in paper cups or in moulded packs, and convenience packs (for example frozen peas) have also been recommended. A temperature of 0ºC is certain with melting iced water, which is important as there is a risk of tissue damage and frostbite with excess cold. The traditional method of cryotherapy is through melting iced water, but there are a number of proprietary preparations available including chemical packs, reusable gels, sprays and applications. There is little research on comparison of the various methods although one animal study gives us particular insight. Ice can cause burns if applied directly to the skin34 so a barrier is usually recommended. This can, of course, act as an insulator and prevent cold conduction but this depends on the nature of the barrier. The effect of different barriers was clear after 30 minutes of ice application. Repeated 10 minute applications through a wet towel are most effective. Ice taken straight from a freezer may be below freezing point. Reusable chemical gel packs, may be as cold as −5 to −15°C. There is little research on comparison of the various methods. Effect on blood flow Cold is a vasoconstrictor, but there is some discussion about the possible paradoxical effect of cold application. This is described as the “hunting reflex”, and it is a physiological protective reflex to protect tissue from ice damage. This has been studied by Knight and Londeree37 who compared blood flow to the ankle under six experimental conditions using a cold pack and concluded that there was no cold induced vasodilation. These findings have been confirmed by Baker and Bell. Possible adverse affects Cooling is used to reduce swelling and muscle damage after injury but there are potential adverse effects associated with ice application which may be important if an athlete wishes to compete or train immediately after injury. Muscle cooling may inhibit muscle strength40 and Meeusen and Lievens41 suggest that motor performance is impaired at a critical temperature of 18ºC. This finding has not been confirmed in other studies where there was no significant effect on peak torque but an increase in muscle endurance. Ice application reduces nerve conduction velocity,45 slowing of the stretch reflex, with an effect greatest with superficial 50 The role of ice in soft tissue injury management nerves.
Although power mobility is a wonderful functional en- hancement for appropriate children with CP rogaine 2 60 ml with visa prostate cancer death rate, it is an option only for the minority of children with CP who are wheelchair dependent 60 ml rogaine 2 with visa androgen hormone katy. The use of a power wheelchair comes with significant risks, problems, and dangers. Many children can manually learn to drive a car by the time they are 12 years old; however, our society does not allow driving on the road until children are 16 or 18 years of age because of the need for maturity in judgment and stability in behavior. Likewise, there are definite criteria that have to be present be- fore children can be given a power wheelchair (Figure 6. There are three major requirements that children have to meet before a power wheelchair should be prescribed. The first requirement is children need to have the motor ability to safely operate some switching mechanism to drive the wheelchair, have adequate eyesight, and be cognitively and be- haviorally reliable to understand the dangers, such as road traffic and stairs. They must follow commands reliably, such as stopping if they are told to stop. Because power mobility is very expensive, it is never considered for short-term use during several months of postoperative rehabilitation, or for children who are expected to progress to functional ambulation over the next year or two. Children have to demonstrate that they can physically operate the power chair, which means a mechanism for switch interfacing must be found that works. There are many options for switch access, the most com- mon being joystick use with the hand (see Figure 6. Head switches, or a combination of leg and head switches, are also available and useful for children with CP. Mouth joysticks and oral sip-and-puff controls have very little use in children with CP because of uniformly poor oral motor control 210 Cerebral Palsy Management A Figure 6. A power wheelchair provides a significant amount of independence for children with CP (A). The use of the chair, in the CP population with this level of motor involvement. These systems are however, requires specific criteria of cogni- mainly for use in high-level spinal cord injuries. It is not mandatory that the tive ability, behavioral stability, and motor exact control system be set up before a power mobility system is ordered; function. Specifically, the child has to be able however, it is not appropriate to order a power wheelchair with the goal of to control the chair through some controller seeing if a way can be found for children to access its controls. These sys- mechanism, with a joystick being the most tems are simply too expensive, and there is good expertise available to make common arrangement (B). The second obligatory factor related to physical ability requires that chil- dren be able to see where they are going. Ordering a power wheelchair for a blind child makes as much sense as giving a driver’s license to a blind person. For children with marginal eyesight, a training period should be performed so they can demonstrate that their sight is adequate to safely see where they are going. The third and very important factor in deciding if children are candidates for power mobility is their cognitive understanding and behavioral stability. Children need to understand the concept of backing up when in a corner, to learn to avoid stairs and other drop-offs, and to understand the danger of specific areas, such as roadways. They must reliably follow directions such as stopping when told to stop. Children must have enough behavioral sta- bility to not use the wheelchair as a weapon to injure caretakers or other children. Only when all these requirements are met is it reasonable to order a power mobility system for a child. For children with CP, this usually starts between 7 and 9 years of age. There are occasional children with athetosis who are ready as early as age 4 years. There has been discussion about fitting children as young as 2 or 3 years of age with power wheelchairs; however, this is almost never appropriate for children with CP.
Thrombin has the same transition state complexes was that they stretched the bonds or distorted the bond aspartate-histidine-serine catalytic triad angles of the reacting substrates order rogaine 2 60 ml androgen hormone balance. However buy 60 ml rogaine 2 visa mens health six pack challenge, most transition state complexes, such as found in chymotrypsin and works in essen- the oxyanion tetrahedral complex, are better described as showing “electronic tially the same way. Thrombin is also pres- strain,” an electrostatic surface that would be highly improbable if it were not sta- ent as an inactive precursor, prothrombin, bilized by bonds with functional groups on the enzyme. Stabilization of the transi- which is itself activated through proteolytic tion state complex lowers its energy level and increases the number of molecules cleavage by another blood coagulation ser- that reach this energy level. The covalent acyl–enzyme intermediate 195 195 Asp His Ser Asp His Ser C Gly C Gly CH2 N CH2 N – • N – • N O HN N• HN N• O H H H H O O O OO O N C H CC C C C H C C CH N NH2 CH2 N HO H NH2 H R R Tyr Tyr 2. Histidine activates serine for nucleophilic attack 6. Water attacks the carbonyl carbon 195 195 Asp His Ser Asp His Ser C Gly C N Gly CH2 N CH2 – • N – • N O HN N• HN N• O H H H H O O H OO N O CC C C H H CH N NH2 CH2 N R H H Tyr Tyr 3. The oxyanion tetrahedral intermediate is stabilized by 7. Second oxyanion tetrahedral intermediate hydrogen bonds 195 Asp His Ser 195 Asp His Ser Gly C CH N Gly 2 N C CH N – + 2 HN N O H – + N H O HN N O H –– H H OO O H OO–– HO CC N CC CH2 N C CH H H CH N H Tyr R Tyr 8. Acid catalysis breaks the acyl–enzyme covalent bond 4. Cleavage of the peptide bond 195 Asp His Ser 195 Gly Asp His Ser C CH N 2 N Gly – + C HN N CH2 N O H H – + N – O HN N O H O H H O H – HO CC O CH2 N N CC H C CH H CH N Tyr R H Tyr 9. The product is free to dissociate 195 Asp His Ser C Gly CH2 N – • N O HN N• H O H H O HO C CH2 N H Tyr CHAPTER 8 / ENZYMES AS CATALYSTS 123 Subsequently, the serine in the active site forms a full covalent bond with the car- To participate in general acid-base bon of the carbonyl group as the peptide bond is cleaved (covalent catalysis). The for- catalysis, the amino acid side chain mation of a stable covalent intermediate is a catalytic strategy employed by many must be able to abstract a proton at one stage of the reaction, and donate it back enzymes and often involves serine or cysteine residues. The dissociating products of an tonated at this low pH, and could not enzyme-catalyzed reaction are often “destabilized” by some degree of charge repulsion abstract a proton from a potential nucle- in the active site. In the case of chymotrypsin, the amino group formed after peptide ophile. However, aspartic acid, with a (pK of a bond cleavage is destabilized or “uncomfortable” in the presence of the active site his- about 2) can release protons at a pH of 2. The two aspartates work together to activate water through the removal of a proton to 3. HYDROLYSIS OF THE ACYL-CHYMOTRYPSIN INTERMEDIATE form the hydroxyl nucleophile. The next sequence of events hydrolyzes the acyl-enzyme intermediate to release the bound carbonyl-side peptide (Fig. The active site histidine activates water to form an OH for a nucleophilic attack, resulting in a second oxyanion tran- sition state complex. When the histidine adds the proton back to serine, the reaction is complete, and the product dissociates. Energy Diagram in the Presence of Chymotrypsin The number of steps in real enzymatic reactions results in a multi-bump energy dia- gram (Fig. At the initial stage of the reaction, a dip occurs because energy is provided by formation of the initial multiple weak bonds between the substrate and enzyme. As the reaction progresses, the curve rises because additional energy is required for formation of the transition state complex. This energy is provided by the subsequent steps in the reaction replacing the initial weak bonds with progres- sively tighter bonds. Semi-stable covalent intermediates of the reaction have lower energy levels than do the transition state complexes, and are present in the reaction diagram as dips in the energy curve. The final transition state complex has the high- est energy level in the reaction and is therefore the most unstable state. It can col- lapse back to substrates or decompose to form products.
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