By U. Osko. Daemen College.
The compound is stored in vesicles and later released material buy 50 mg penegra with amex man health doctor. The ultimate result of this, however, through calcium-mediated exocytosis. Choline is taken up by the presynaptic ter- is bronchospasm, which can lead to difficulty minal from the blood via a low-affinity transport system (high Km) and from the in breathing. In the brain, histamine is an synaptic cleft via a high-affinity transport mechanism (low Km). Antihistamines from the hydrolysis of phosphatidylcholine (and possibly sphingomyelin) in mem- block histamine from binding to its receptor. Thus, membrane lipids may form a storage site for choline, and their In the tissues, this will counteract histamine’s hydrolysis, with the subsequent release of choline, is highly regulated. The new generation of to the neurologic symptoms of vitamin B12 deficiency. The methyl groups for “non-drowsy” antihistamines have been choline synthesis are donated by SAM, which is converted to S-adenosylho- modified such that they cannot pass through mocysteine in the reaction. Recall that formation of SAM through recycling of homocys- the blood-brain barrier. Thus, the effects on teine requires both tetrahydrofolate and vitamin B12 (unless extraordinary amounts of the peripheral tissues are retained with no methionine are available to bypass the B12-dependent methionine synthase step). Synthesis and inactivation of histamine; note the different pathways for brain and peripheral tissues. Choline is a common component of the diet but also can be synthesized in the human as part of the pathway for the synthesis of phospholipids (see Chapter 33). The only route for choline synthesis is via the sequential addition of three methyl groups from SAM to the ethanolamine portion of phosphatidylethanolamine to form phosphatidylcholine. Phosphatidylcholine is subsequently hydrolyzed to release choline or phosphocholine. Conversion of phosphatidylethanolamine to phos- CH phatidylcholine occurs in many tissues, including liver and brain. CH3 SCoA + HO 2 CH2 3 The acetyl group used for acetylcholine synthesis is derived principally from CH3 glucose oxidation to pyruvate and decarboxylation of pyruvate to form acetyl CoA choline acetyltransferase The supply of choline in the brain can become rate-limiting for acetylcholine O CH3 synthesis, and supplementation of the diet with lecithin (phosphatidylcholine) + CH3 2 2 3 has been used to increase brain acetylcholine in patients suffering from tardive CH dyskinesia (often persistent involuntary movements of the facial muscles and tongue). High levels of phos- acetylcholinesterase phatidylcholine in the maternal milk and a high activity of a high-affinity transport O system through the blood-brain barrier for choline in the neonate help to maintain brain – + choline concentrations. The fetus also has a high demand for choline, and there is a high- CH3 O + HO 2CH2 N (CH3)3 Acetic acid Choline affinity transport system for choline across the placenta. The choline is derived from maternal stores, maternal diet, and synthesis primarily in the maternal liver. Acetylcholine synthesis and degra- choline synthesis is dependent on folate and vitamin B12, the high fetal demand may dation. CHAPTER 48 / METABOLISM OF THE NERVOUS SYSTEM 895 CoA via the pyruvate dehydrogenase reaction. This is because neuronal tissues An inherited pyruvate dehydroge- have only a limited capacity to oxidize fatty acids to acetyl CoA so that glucose nase deficiency, a thiamine defi- oxidation is the major source of acetyl groups. Pyruvate dehydrogenase is found ciency, or hypoxia deprives the brain of a source of acetyl CoA for acetyl- only in mitochondria. The acetyl group is probably transported to the cytoplasm choline synthesis, as well as a source of as part of citrate, which is then cleaved in the cytosol to form acetyl CoA and acetyl CoA for ATP generation from the TCA oxaloacetate. INACTIVATION OF ACETYLCHOLINE Acetylcholine is inactivated by acetylcholinesterase, which is a serine esterase that forms a covalent bond with the acetyl group. The enzyme is inhibited by a wide range of compounds (pharmacologic drugs and neurotoxins) that form a covalent bond with this reactive serine group. Neurotoxins such as Sarin (the gas used in Japanese subways by a terrorist group) and the nerve gas in the movie “The Rock” work through this mechanism. Acetylcholine is the major neurotransmitter at the neuromuscular junctions; inability to inactivate this molecule leads to constant acti- vation of the nerve–muscle synapses, a condition that leads to varying degrees of paralysis. SYNTHESIS OF GLUTAMATE Glutamate functions as an excitatory neurotransmitter within the central nervous system, leading to the depolarization of neurons. Within nerve terminals, glutamate is generally synthesized de novo from glucose rather than taken up from the blood because its plasma concentration is low and it does not readily cross the blood-brain barrier. Glutamate is primarily synthesized from the TCA cycle intermediate -ketog- lutarate (Fig.
Although this can occur in some situations penegra 50mg discount androgen hormone needed, most authors believe an injury occurs when the muscle cannot absorb the force applied to it and that the most important variable with respect to muscle injury is the energy absorbed by the muscle. When sarcomeres are stretched so that the actin and myosin filaments no longer overlap, the force is transmitted to the cytoskeleton of the muscle fiber and damage occurs. This can occur within the normal ROM because sarcomere length within the muscle is heterogeneous; some sarcomeres lengthen during a contraction at the same time others are shortening. Under this hypothesis, an increase in total muscle compliance is irrelevant. Third, because injuries are believed to occur when the muscle is active (i. However, we have seen that these two compliances are unrelated. This is because compliance of resting muscle is almost exclusively due to the muscle cytoskeleton22,23 whereas compliance of active muscle is directly dependent on the number of active actin-myosin cross bridges. Fourth, over-stretching a muscle can certainly produce damage. However, even strains as little as 20% beyond resting fibre length, as one would expect with “correct” stretching techniques, can produce damage in isolated muscle preparations. Fifth, we have seen that the increased range of motion with stretching is partly due to an analgesic effect. Nor does it mean that 111 Evidence-based Sports Medicine stretching shortens rehabilitation time and prevents re-injury following an injury. In the only clinical study directly comparing stretching to strengthening after injury,61 23/34 male athletes with over two months of groin pain who participated in a strengthening programme returned to pre-activity levels within four months, compared to only 4/34 of athletes who participated in a stretching program (multiple regression OR: 12·7, 95% CI 3·4–47·2). Further, the group that strengthened had the same increase in ROM as the stretching group even though they never stretched. Whether this is also true for acute injuries, or whether stretching adds additional benefit to a strengthening programme remains to be determined. Given these arguments about pre-exercise stretching, the reader should remember that stretching at other times may theoretically induce hypertrophy,30–32 and if future evidence suggests this occurs, an increase in strength is likely to decrease injuries. This may explain the results of Pope et al which showed an increased risk if ankle ROM was decreased, but no effect of pre-exercise stretching over 11 weeks. In conclusion, the clinical evidence is consistent with the basic science evidence and theoretical arguments; stretching before exercise does not reduce the risk of injury and stretching at other times may or may not be beneficial. Further Note: In a recent article (Br J Sports Med 2001;35:103–108), the authors suggested in the text that ankle injuries are more frequent in people who did not stretch immediately before a game. However, the results (Tables 3 & 4) suggest the opposite: people who stretch immediately before a game had 2·6 times the risk of injury. The simplest way to understand this is that the coding is Yes = 1 for stretching, which is the same as that for “history of ankle sprains”. Both history of sprain and stretching before exercise had odds ratios above 1. If the authors say a previous sprain increases the risk of injury, then so must stretching before exercise. The authors did not reply to a request for clarification. Sample examination questions Multiple choice questions (answers on p 561) 1 The original study by Ekstrand et al suggested that stretching immediately prior to exercise is associated with a decrease in injuries. Which of the following interventions that are likely to prevent injury were also included in the experimental group as co-interventions? A Shin guards B Supervised rehabilitation C Warm-up D Education E All or none of the above 2 With regards to the number of studies examining whether stretching outside periods of exercise prevent injury or minimise the severity of injury: A 2 found it does and 2 found it does not B 0 found it does and 2 found it does not C 2 found it does and 0 found it does not D All studies used a cohort design E All or none of the above 3 Theoretical reasons why stretching prior to exercise would not decrease injuries include all of the following EXCEPT: A Tissues that are more compliant are associated with a decreased ability to absorb energy B The compliance of active muscle is related to the compliance of muscle during normal stretches C Most injuries occur during eccentric activity of the muscle, within its normal range of motion D Overstretching a muscle is known to be a cause of muscle injury E All or none of the above Essay question 1 Discuss the evidence for and against the use of stretching immediately prior to exercise as an intervention to prevent injuries. Acknowledgements The author would like to acknowledge that some of this material has been previously published in the Clinical Journal of Sport Medicine Vol 9(4): 221–227, 1999, and in the Physician and Sports Medicine Vol 28(8): 57–63, 2000. Overall, stretching before exercise does not prevent injury. Note that most studies done on recreational athletes or military personnel. According to the basic science of injury, there is no reason why elite athletes would be expected to have different results. Does stretching outside 2 RCTs (n = 300–470), weaknesses in A1 periods of exercise follow-up and differences in baseline prevent injury? One study suggested a decreased injury rate and the other only decreased severity of injury.
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