How To Take Creatine

Creatine Practical Guide.

Creatine: A practical guide evolved from the thousands of questions asked by professional and amateur athletes from around the globe. Learn How To Most Effectively Combine Exercise, Nutrition And Smart Creatine Use For Explosive Muscle Growth And Improved Overall Health. Here is just a small sampling of the many questions addressed by this e-book How long can I keep creatine on the shelf? Will I lose muscle after I stop supplementing? Not all creatine brands recommend the same amount. What gives? Is mixing creatine with protein powder a bad idea? Why do so many creatine brands contain so much dextrose? Is loading really necessary? Im currently taking Accutane for nodular acne. Is it safe for me to supplement? Will creatine stunt my growth? Im training twice as much these days and Im still not making any gains! Why? If creatine isnt a steroid, then how come it gave me a positive doping result? Will creatine shrink my package?!

Creatine Practical Guide Overview

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Creatine Kinase

Creatine phosphate serves as a cellular storage species of high-energy phosphate that is readily available for the formation of ATP from ADP by the action of creatine kinase (EC 2.7.3.2). Creatine phosphate is a high-energy phosphate (AG' -10 kcal mol-1 for hydrolysis) by virtue of being a phosphoramidate. The reversibility of the reaction of creatine kinase (eq. 10-5), allows creatine phosphate to be formed whenever the concentration of ATP is high, and it makes creatine phosphate an efficient reserve of high-energy phosphate to generate ATP under conditions of high-energy demand. The action of creatine kinase requires a divalent metal ion, either Mg2+ or Mn2+ in complex with ADP. The more prevalent Mg2+ is the likely activating metal ion in cells. Structurally and stereochemically distinct complexes of divalent metal ions with ADP or ATP exist in solution, and species that bind to a particular enzyme can be determined in various ways. For example, the following two structures of...

Arginine Citrulline Ornithine and Proline Figure

In addition to synthesis of NO, urea, and ornithine, arginine is used for synthesis of creatine, which is an important constituent of skeletal muscle and neurons and acts as an energy source for these tissues. Furthermore, arginine may be catabolyzed to agmatine, which acts as a cell-signaling molecule. Arginine not only acts as an intermediate in the

Cysteine Cystine Methionine and Taurine Figure

Methionine is converted to cysteine and its dipeptide cystine. In addition methionine is a precursor for creatine (see arginine). The potential for formation of disulfide bonds between its thiol (-SH) groups makes protein-bound cysteine important in the folding and structural assembly of proteins. Reduced cysteine thiol groups are found in protein (albumin), free cysteine, and in the principal intracellular anti-oxidant tripeptide glutathione (see glycine, glutamic acid) for which free cysteine is the synthesis rate-limiting constituent. Through the formation of disulfides (e.g., cystine, cysteinyl-glutathione, glu-tathione disulfide, mercaptalbumin) thiol-containing molecules can scavenge oxygen-derived free radicals. The ratio between oxidized and reduced thiol groups reflects the cellular redox state. Owing to its small pool size cysteine deficiencies rapidly occur during malnutrition. Arginine Creatine

Left ventricular function

Kinetics of creatine kinase (CK) release (left) and ST resolution (right) in response to coronary reperfusion. Sequential coronary arteriograms 90 minutes apart in 41 patients presenting with acute coronary syndromes and ST elevation permitted identification of three groups group 1 patency of infarct related artery at first arteriogram before thrombolytic treatment (n 12) group 2 early recanalisation of the infarct related artery within 90 minutes of thrombolytic treatment (n 10) group 3 persistent occlusion of infarct related artery (n 19). Serial CK analysis showed early peaking in groups with coronary recanalisation (groups 1 and 2). Cumulative CK release was considerably greater in patients with failed recanalisation (group 3). Serial ECGs showed rapid resolution of ST segment elevation in patients in groups 1 and 2, while in those patients with persistent coronary occlusion (group 3), ST elevation persisted considerably longer. Reproduced from Timmis et al6 with...

Chapter References

Puleo PR, Meyer D, Wathen C, et al Use of a rapid assay of subforms of creatine kinase- MB to diagnose or rule out acute myocardial infarction. N Engl J Med 331 561, 1994. 15. Marin MM, Teichman SL Use of rapid serial sampling of creatine kinase MB for very early detection of myocardial infarction in patients with acute chest pain. Am Heart J 123 354, 1992. 20. Hedges JR, Gibler WB, Young GP, et al Multicenter study of creatine kinase MB use Effect on chest pain clinical decision making. Acad Emerg Med 3 7, 1996. 22. Pettijohn TL, Doyle T, Spiekerman AM, et al Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris. Am J Cardiol 80 510, 1997.

Clinical Features and Diagnosis

The chest roentgenogram is usually normal, and reported abnormalities (cardiomegaly and pulmonary venous hypertension and or pulmonary edema) vary with disease severity and are nondiagnostic. Reported ECG changes include nonspecific ST-T-wave changes, ST-segment elevation (due to associated pericarditis), atrioventricular block, and prolonged QRS duration. Levels of cardiac enzymes (creatine kinase and CK-MB) and troponin may be elevated. 16 Echocardiographic studies may reveal depressed systolic function in severe cases.

Use of enzymes for diagnostics

Many enzymes occur only in certain specialised cells in our body. If those cells are damaged, enzyme molecules are released into the circulation. Thus determination of enzyme activities is an important diagnostic tool in the clinical laboratory. For example creatine kinase (CK) is prevalent in muscle cells. Destruction of heart muscle cells in an acute myocardial infarct or of skeletal muscle cells in DuCHENNE muscular dystrophy leads to the appearance of CK in the blood. Interestingly, different organs contain different isoforms of CK, so that it is possible to tell from which organ an increased blood CK activity originated.

Chronic Renal Disease

Maternal risks associated with renal disease are linked to the degree of renal compromise. As renal function diminishes, fertility decreases. Pregnancy rarely occurs in women who have a preconception serum creatine of > 3 mg dL. Preterm delivery and superimposed preeclampsia frequently complicate pregnancies of patients with underlying renal disease. Patients with chronic pyelonephritis may have an increased number of recurrences due to bacteriuria, increased glucosuria, and mechanical compression of the ureter in the third trimester pregnancy. Those with a history of reflux nephropathy are at increased risk of sudden escalating hypertension and worsening renal function. Urolithiasis is associated with more frequent urinary tract infections. Patients with lupus nephropathy are at greatly increased risk for exacerbations of the disease and superimposed preeclampsia, particularly if their disease was not in remission for at least 6 months prior to conception.

Clinical Findings

Clinical symptoms usually appear in adulthood and are characterized by exercise intolerance with muscle cramps that can be accompanied by attacks of myoglobinuria. Serum creatine kinase is usually elevated and increases after exercise. Avoidance of strenuous exercise can prevent major episodes of rhabdomyolysis.

Clinical Features

Hypocalcemia may develop secondary to precipitation of calcium as calcium oxalate and may be severe enough to cause tetany and prolongation of the QT interval. Elevated serum creatine phosphokinase levels may accompany and explain the generalized myalgias experienced by some patients.

Loss of Lean Body Mass

Document the loss of muscle mass over an extended period of time. Dietary creatine and creatinine intake has only a minor influence (< 20 ) on urinary creatinine in the normal eating individual. Changes in dietary intake may influence the accuracy of the collection, but repeating the values over 3 days will help average variations in dietary intake. Impairment of renal function reduces the normal creatinine excretion and excludes the creatinine height index as a marker of muscle mass.

Box 152 Working In Biochemistry

Glucokinase Hexokinase

Shortly after a heart attack, the blood level of total LDH increases, and there is more LDH2 than LDH1. After 12 hours the amounts of LDH1 and LDH2 are very similar, and after 24 hours there is more LDH1 than LDH2. This switch in the LDH1 LDH2 ratio, combined with increased concentrations in the blood of another heart enzyme, creatine kinase, is very strong evidence of a recent myocardial infarction.

Biocompatibility and Toxicity

Biocompatibility of injectable formulations with tissues can be tested by observing microscopic histology of the tissues so exposed, or by using erythrocyte hemolysis as a surrogate for these other tissues. Alternatively, one can measure the level of the cytosolic enzyme creatine phosphokinase that is released from damaged tissues (18).

Chlorophenoxy Herbicides

DIAGNOSIS Diagnosis is based on the history of exposure. Ancillary tests generally are nonspecific but may demonstrate a metabolic acidosis and evidence of hepatorenal dysfunction. Toxin levels are not immediately available. Myoglobinuria and an elevated creatine phosphate level indicate rhabdomyolysis. Differential diagnosis includes other causes of acute myopathy.

Atp Hydrolysis In Two Steps

Ionization, as for ATP, acyl phosphates, and thioesters (3) the products are stabilized by isomerization (tau-tomerization), as for phosphoenolpyruvate and or (4) the products are stabilized by resonance, as for creatine released from phosphocreatine, carboxylate ion released from acyl phosphates and thioesters, and phosphate (Pj) released from anhydride or ester linkages.

Biotargetsdirected Design And Discovery Of Bioactive Compounds

G-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, has been the target of extensive pharmacological research. GABA reuptake from the synaptic cleft is an important mechanism in the regulation of GABA activity, which is effected by a selective transporter named a GABA transporter (GAT) (Radian et al., 1986). GAT, together with the betaine, taurine, and creatine transporters, belongs to a subfamily of Na+- (and Cl_) ion-dependent transporters. The human GAT proteins consist of 599 amino acids and a putative structure (Nelson et al., 1990 Kanner, 1994 Gao et al., 1999), as shown in Fig. 10.10.

Initial Resuscitation

Diagnostic studies necessary to detect the end-organ sequelae of heatstroke include a complete blood cell count, comprehensive metabolic profile, hepatic panel, coagulation profile (prothrombin time, partial thromboplastin time, and international normalized ratio), creatine kinase, urinalysis, toxicology screen, ECG, and chest radiograph. Computed tomography of the head and lumbar puncture may also be indicated as part of the evaluation of altered mental status.

TABLE 1875 Complications of Heatstroke

Centrilobular necrosis due to direct thermal injury results in abnormal liver functions, although jaundice is unusual. Recovery is to be expected. Renal injury is manifested by microscopic hematuria, proteinuria, and hyaline and granular casts. Patients with hypovolemic complications and decreased renal blood flow may develop acute tubular necrosis. Exercise-induced heatstroke is often complicated by rhabdomyolysis, sometimes with massive myoglobinuria and renal failure. This complication may not develop until several days after the initial injury, so that careful monitoring of creatine kinase levels and renal function is necessary. Occasionally, a patient may present to the emergency department with the dark urine of myoglobinuria and should be questioned about recent heat exposure or heavy exertion.

Black Widow Latrodectus

Muscle groups, although physical examination of the cramping extremity rarely exhibits rigidity, and serum creatine kinase concentrations do not appear to be significantly elevated. The pain often increases progressively, becomes generalized, and can involve the trunk, back, and abdomen. Involvement of the abdominal wall musculature with severe pain and cramping has been mistaken for peritonitis.

Emergency Department Management

Routine laboratory tests including a CBC, electrolytes, BUN, creatinine, and glucose should be obtained. In patients with suspected inhalation injury, arterial blood gases, carboxyhemoglobin, chest radiograph, and ECG should be obtained. Fiberoptic bronchoscopy is indicated where there is a suspicion of inhalation injury and in intubated patients, as this is both diagnostic and therapeutic in clearing the airways. A urinalysis, urine for mycoglobin and creatine kinase (CK) levels are obtained along with an electrocardiogram (ECG) in patients with electrical injury to assess muscle or cardiac injury. Additional radiographs should be taken as indicated for other suspected trauma.

Cardiovascular Injury

The immediate cause of death due to a lightning strike is usually direct current depolarization of the myocardium and sustained cardiac asystole. Although cardiac automaticity may spontaneously return, concomitant respiratory arrest due to medullary respiratory center paralysis may outlast cardiac arrest and ultimately lead to a hypoxic cardiac arrest. The duration of apnea, rather than the duration of asystole, appears to be a critical prognostic factor. Patients may suffer a variety of other cardiovascular effects, including direct myocardial damage, coronary artery spasm, cardiac contusion from blunt trauma, acute global cardiac dysfunction, atrial and ventricular dysrhythmias, pericardial effusion, and transient hypertension and tachycardia. The electrocardiogram (ECG) may show acute injury with ST-segment elevation and a prolonged QT interval. T-wave changes may be seen especially in the presence of cerebrovascular injuries. Although creatine kinase (CK) and CK-MB (isoenzyme)...

Echocardiography in acute coronary syndromes key points

The study by Trippi and colleagues15 is an example of how echocardiography might be aggressively used in the emergency room. These authors enrolled 163 patients with no evidence of MI on initial cardiac markers or ECG, who were recommended for admission. If rest echocardiographic images were normal, dobutamine stress echocardiography was performed, initially supervised by a cardiologist and, in later stages, by a trained nurse. Echocardiographic images were transmitted by tele-echocardiography and interpreted off-site. In the first three stages, all patients were admitted. In the final stage, patients were discharged if the stress echocardiogram was negative. Average length of stay was only 5.4 hours. In the third and fourth stages recruitment was less selective, so that in the final phase mild residual chest pain, a non-diagnostic rather than normal ECG, and mild elevation of initial creatine kinase (CK) with normal CK-MB were permitted. The negative predictive value of dobutamine...

Clinical Description Dm1

Ninety percent of DM1 patients present at adulthood with delayed muscle maturation, distal muscle weakness, wasting, myotonia, cataracts, cardiac abnormalities, smooth muscle dysfunction, insulin resistance, daytime sleepiness, testicular atrophy (low reproductive fitness), ''difficult'' personality, neuropsychiatric disturbances, and frontal balding. 1 Ten percent of the patients present at infancy with hypotonia (floppy infant), oromotor dysfunction, tent-shaped mouth, feeding and respiratory insufficiency (diaphragmatic hypoplasia), arthrogryposis, and mental retardation in those who survive until adulthood (congenital DM). 1 All manifestations show a progressive course. Usually, creatine kinase is elevated. Muscle biopsy shows type 1 predominance, centrally located nuclei, severe fiber atrophy with nuclear clumps, hypertrophic and angulated fibers, and occasionally, necrotic fibers, fibrosis, or fat deposits. Cardiac involvement comprises conduction defects (mostly HV...

Muscle Fiber Types and Their Physiological Role

Although all striated muscles contract, the time course of contraction in the living animal varies with the muscle fiber type (fast twitch, slow twitch), substrate (ATP, creatine phosphate, protein, fatty acid, or glycogen), and the amount of oxygen available. Slow-twitch fibers (Type I fibers or red fibers) are mainly postural and are dominant in aerobic or endurance activity, whereas fast-twitch fibers (TVpe IIA and IIB fibers) are mainly fast acting and are involved in anaerobic activity. Type IIB muscles can take on a greater aerobic role than Type IIA muscles. Most body muscles consist of different proportions of all types, although instances of pure Type IIA (m. cutaneous trunci) or Type I (m. masseter) do exist in various parts of the body (7).

Muscle Energy Supply and Changes During Rigor

In a living muscle, or a muscle just at animal death, the immediate source of energy for contraction comes from ATP. Muscle ATP is quickly used up in two to five contractions, whereupon creatine phosphate immediately becomes dominant. Upon depletion of this source, glycogen takes over. Depending on the intensity and duration of muscle activity, and on the presence of blood circulation, either anaerobic or aerobic glycolysis occurs to sustain activity. Although protein or fat can be useful energy sources in sustained aerobic activity, glycogen is the only fuel that can be used for anaerobic activity. Therefore, glycogen is the only available energy source in postmortem muscle. It is metabolized when the muscle is triggered to contract via physical effects such as cold, and it is also metabolized slowly in noncontracting muscle. Without an intact circulation, lactic acid, a by-product of anaerobic glycolysis, accumulates in the tissue, causing the pH to fall (for reviews, see Ref. 6)....

TABLE 2075 Clinical Presentation of Myxedema Coma

Laboratory evaluation of patients with suspected myxedema coma may reveal anemia hyponatremia hypoglycemia elevated transaminases, creatine phosphokinase, and lactate dehydrogenase levels hypercholesterolemia and arterial blood-gas abnormalities (decreased P o2 and increased Pco2). The electrocardiogram may demonstrate sinus bradycardia, prolongation of the QT interval, and low voltage with flattening or inversion of T waves. A chest radiograph may demonstrate an enlarged cardiac contour caused by a pericardial effusion. 910

Inhibition Of Activator Binding By Formation Of A Nondna Binding Complex

Differentiation of 10TO cells into myoblasts by 5-azacytidine and then into myotubes by removal of growth factors. Note that the MyoD-dependent induction of genes encoding terminal differentiation markers such as creatine kinase (CK), which occurs in myotubes, occurs without an increase in MyoD concentration. Differentiation of 10TO cells into myoblasts by 5-azacytidine and then into myotubes by removal of growth factors. Note that the MyoD-dependent induction of genes encoding terminal differentiation markers such as creatine kinase (CK), which occurs in myotubes, occurs without an increase in MyoD concentration.

Neurobiological Aspects

Another study using magnetic resonance spectroscopy (MRS) found that bipolar offspring with bipolar disorder had decreased N-acetyl-aspartate (NAA) to creatine (Cr) ratios in the right dorsolateral prefrontal cortex (DLPFC), while bipolar offspring with mood and disruptive behavioural disorder but not bipolar disorder had unchanged NAA Cr ratios in the same cerebral region 91 . Information about the NAA before the onset of bipolar disorder and before the onset of pharmacological treatment was not available. The NAA Cr ratio tends to decrease as illness duration increases 91 .

Huntingtons disease also known as Huntingtons chorea

The main neurochemical deficit occurs in the GABA enkephalin neurons in the striatum, particularly in the neurons that project to the external globus pallidus which forms part of the indirect striatal pathway. As a consequence, the direct pathway, in which the GABA dynorphin-contain-ing neurons predominate, becomes dominant which provides the neurochemical basis for the dyskinesia. Thus, unlike Parkinson's disease, there is no loss of dopaminergic neurons but a primary deficit in GABA, the opioid peptide and substance P. So far, it has not been possible to counteract the symptoms by replacing the defective neurotransmitters. In the early stages of the disease in which the dyskinesia predominates, antipsychotic drugs blocking the D2 receptors may offer some relief by reducing the inhibitory input to the GABA enkephalin neurons and thereby help to restore the balance between the direct and indirect pathways. However, such treatments are usually only marginally effective and there is a...

Localization Of Neurologic Disease

Once a peripheral disorder has been established, it is necessary to determine which part of the peripheral nervous system is involved. A localized process, such as numbness and tingling of the fifth and half of the fourth digits of one hand, strongly suggests a focal lesion (ulnar nerve). The lesion may involve the nervous system at a number of locations the nerve, plexus, or root. Basic knowledge or the aid of an anatomy text or neurology handbook should be sufficient to accurately localize focal lesions of these types. Figure22.5-1 shows a schematized view of the peripheral nervous system and illustrates the signs associated with disease of specific parts of the neuromuscular system. Most muscle-related processes result in weakness of large proximal muscles, and patients may have a difficult time lifting their arms over their heads or arising from a seated position. Pain and tenderness of the muscles occur commonly (although usually these are not predominant symptoms and if not...

Subcellular Systems For Studying Pglycoprotein

Plasma membrane vesicles have also proved useful in studies of Pgp-mediated drug transport. Most vesicle preparations consist of a mixture of right-side-out and inside-out vesicles,54 and if they are well sealed, the latter population can transport drug from the external medium into the vesicle lumen when provided with ATP. When using a vesicle system where other membrane-bound ATPases are present, it is often necessary to add an ATP-regenerating system, such as creatine kinase and creatine phosphate, to prevent rapid depletion of ATP in the external solution. Substrate uptake into the vesicle interior can be measured in one of two ways. If drug is available in radioactive form (e.g., 3H colchicine, 3H vinblastine, 125I peptide), it is added to the vesicle preparation at time zero, together with ATP and a regenerating system, and vesicles are removed at various times (typically, ranging up to 30 minutes) and collected by rapid filtration.54 Drug uptake into the vesicles increases with...

Calcium Phosphate Interrelationships

Hormones, such as PTH and 1,25-dihydroxyvitamin D, on bone, the gut, and the kidneys. Adequate phosphorus and calcium intakes are needed not only for skeletal growth and maintenance but also for many cellular roles, such as energy production (i.e., adenosine triphosphate (ATP)). Phosphate ions are incorporated in many organic molecules, including phospholipids, creatine phosphate, nucleotides, nucleic acids, and ATP.

Statistical Approaches for Data Analysis

Duchenne muscular dystrophy (DMD) on the basis of serum creatine kinase (CK) measurements, we developed a procedure to combine independent serial measurements of CK on individuals into a single index which then was combined with family history information to yield the probability that the individual being tested was a carrier of the DMD gene (299). In order to efficiently distinguish female carriers of hemophilia from healthy normal individuals, logistic coefficients were derived from the ratio of measurements of factor VIII activity (which is defective in hemophilia A) and von Willebrand factor (to which factor VIII binds) into a single index which was combined with family history information to yield the probability that the individual being tested was a carrier of hemophilia A (300).

Neuromuscular and Cutaneous Syndromes

Polyneuropathy, polymyositis, and myopathy are all known to occur with RCC. The myopathy is characterized by involvement of proximal muscles and association of elevated serum levels of creatine kinase and aldolase (Solon etal. 1994 Evans etal. 1990). In each condition, there are reports of resolution after nephrecto-my. With the development of metastatic disease, poly-myositis and polyneuromyopathy have recurred.

Copper Mediated Mutant SOD1 Neurotoxicity

G93A SOD1 transgenic mice have been used to test a variety of therapeutic approaches. Vitamin E and selenium modestly delay the onset and progression of disease without affecting survival in contrast, riluzole and gabapentin do not influence onset progression but do slightly increase survival. Although initial studies showed that oral administration of d-penicillamine delays the onset of disease, recent results revealed no significant effects. Overexpression of Bcl-2 extends the survival of these transgenic mice, but the presence of the gene does not change the progression of the disease. Recently, the level of Bax, a molecule that promotes apoptosis, was shown to be increased in G93A mice. However, this increase in Bax was augmented by an increase in Bcl-2 Bax heterodimers in G93A mice overexpressing Bcl-2. Interestingly, there is evidence that an apoptotic mechanism may be involved in motor neuron loss in ALS. In a small group of G93A SOD1 mice overexpressing a dominant-negative...

Idiopathic inflammatory myopathy

The idiopathic inflammatory myopathies, which include polymyositis, dermatomyositis and inclusion body myositis, are inflammatory diseases of muscle which cause weakness, and less frequently pain, of the large proximal muscles of the trunk and limbs. The inflammatory lesion with primarily lymphocytes results in damage and subsequent attempts at repair of the muscles with release of the muscle enzymes creatine kinase, aldolase, aspartate aminotransferase and lactate dehydrogenase. The muscle damage also results in characteristic changes on electromyography.

Haemodynamic and Coronary Vascular Effects of ACE Inhibition

Cardioprotective effects of ACE inhibition that were attenuated by icatibant included the reduction of arrhythmias, reduction of lactate, lactate dehydrogenase, and creatine kinase release, and increase in myocardial contractility and myocardial levels of glycogen, adenosine triphosphate and creatine phosphate during reperfusion of the ischaemic isolated working rat heart (Linz et al 1992). Icatibant attenuated the ACE inhibitor-induced increase in coronary flow and nitric oxide levels in dogs with myocardial ischaemia (Kitakaze et al 2002). Icatibant also prevented the potentiation of ischaemic preconditioning by ACE inhibition in human atria (Morris et al 1997). The post-ischaemic anti-arrhythmic effect of ACE inhibition may be mediated by kinin-induced suppression of endothelin release (Brunner et al 1996).

Neuroimaging Studies

Magnetic resonance spectroscopy (MRS) has emerged as a possible sensitive measure of the structural and functional abnormalities associated with central nervous system dysfunction. It is an advanced level of the technology used in conventional MRI, which can detect chemical characteristics in addition to image data. Three main peaks reflecting the concentrations of N-acetyl-L-aspartate (NAA), creatine-phosphocrea-tine (Cr), and choline-containing compounds (Cho) are recorded from selected areas of interest. NAA is present within all neurons, and its concentration is elevated in several degenerative neurological conditions including amyotrophic lateral sclerosis. The Cr peak seen on MRS reflects levels of creatine and phosphocreatine, which serve as a reserve for high-energy phosphates in the cytosol of neurons. The Cho peak represents choline-containing compounds. The value of MRS in the diagnosis of exposure to neurotoxicants has not been fully elucidated, but published reports...

Magnetic Resonance Imaging

Adem Mri Findings

Newer techniques add to our understanding of why T2-weighted images may not correlate well with clinical disability. Magnetization transfer imaging (MTI) relies on a different relaxation time of protons bound to macromolecules versus that ofthose protons that are freely moving in water. The normal appearing white matter of T2 weighted scans is abnormal when assessed with MTI, implying a more diffuse process than demonstrated by conventional T2 images. Magnetic resonance spectroscopy (MRS) uses MRI to generate a spectra of hydrogen or high energy phosphorus-containing metabolites. The spectra is used to define pathology of lesions, including tumors and demyelination. The spectra reveal major resonances from choline, creatine and phosphocreatine, and N-acetylaspartate (NAA). Choline is present in membranes and also present with increased myelin breakdown products. Creatine and phosphocreatine tend to be stable in MS other than acute lesion. NAA is present only in neurons and neuronal...

Natrual Food Ventricle Wall Motion

A number of factors, including the presence of ischemia, stunning, or overload, confound the relationship between the size of regional wall motion abnormalities and the amount of infarcted myocardium. When compared with pathologic examination, echocardiography tends to overestimate the amount of necrosed myocardium early in the course of myocardial infarction. Despite this limitation, echocardiographic estimation of the extent of myocardial infarction correlates well with infarct size as determined by peak creatine kinase, radionuclide imaging, and contrast ventriculography. Echocardiographic evaluation of left ventricular function early in the course of myocardial infarction has been found to be a better predictor of in-hospital mortality than the prognostically strongest clinical parameters. An echocardiographically determined ejection fraction of greater than 40 percent has correlated with a low short-term mortality and could potentially be used to select low-risk patients for...

Myocardial Infarction

The majority of these infarctions are of the non-Q-wave type, are asymptomatic, and remain undiagnosed. Many of these patients cannot complain of chest pain or dyspnea due to a variety of factors. In other patients, presentation may be very subtle. For example, a change in mental status may herald a perioperative MI. A postoperative workup may identify an ongoing MI in the absence of clinical symptoms in high-risk patients. Diagnosis is best confirmed by electrocardiogram and serial-elevated creatine kinase-MB enzyme and troponin levels.

High Intensity Exercise and Strength Training

Metabolic In addition to the neuromuscular alterations that occur with high-intensity and strength training, several metabolic adaptations improve the ability of the muscle to resynthesize ATP from anaerobic sources. Intramuscular stores of the anaerobic energy intermediates, such as creatine phosphate (CP) and glycogen, increase after a period of supramaximal training. The activity of enzymes involved in anaerobic production of energy, such as creatine kinase and myokinase, is also increased.

Hormonal Interactions During Exercise

For the few seconds of the 100-yard dash, endogenous ATP reserves in muscle, creatine phosphate and glycogen, are the chief sources of energy. For short-term maximal effort, energy must be released from fuel before circulatory adjustments can provide the required oxygen. Breakdown of glycogen to lactate provides the needed ATP and is activated in part through intrinsic biochemical mechanisms that activate glycogen phos-phorylase and phosphofructokinase. For example, calcium released from the sarcoplasmic reticulum in response to neural stimulation not only triggers muscle contraction but also activates glycogen phosphorylase. These intrinsic mechanisms are reinforced by epinephr-ine and norepinephrine released from the adrenal medullae and sympathetic nerve endings in response to central activation of the sympathetic nervous system.

Glycine Serine and Threonine

Thought to possess anti-inflammatory properties, but to date these properties have only been demonstrated in the test tube. Furthermore, glycine can react with arginine and methionine to form creatine (see section on arginine). Finally, glycine, like taurine, is a conjugate for bile acids.

Analyses of human plasma and serum proteomes using HUPO filter criteria

Well with peptide sequences assigned by SEQUEST. Examples of the MS MS spectra for single-peptide proteins identified in both data sets are shown in Fig. 7. All of the major peaks in both MS MS spectra can be accounted for by fragment ions from the predicted peptide sequences, indicating that the peptide assignment is correct. Of particular interest is the protein creatine kinase M which, in the MB isoform, is an important serum marker for myocardial infarction 31 . Therefore, even though the single-peptide protein category contains the most false positives, it also contains many important correct entries that cannot be ignored.

Supplementation

Using citrulline as an arginine-delivering substrate has been suggested, but has not been applied clinically. Ornithine is supplied as part of the ornithine-a-ketoglutarate molecule (see glutamine). Creatine is widely used by professional and recreational athletes as a nutritional supplement, although the ascribed performance-enhancing effects have not been proven.

Clinical Diagnosis

Serum creatine kinase (CK) is markedly increased. This marked elevation of serum CK is the most important hallmark for the diagnosis of BMD, but the level of elevation of serum CK is not so high compared to DMD. During the asymptomatic period, elevation of serum CK is the sole sign for BMD. Some BMD patients are identified accidentally because of elevations of AST or ALT which are commonly examined for liver function as serum CK elevation is accompanied with elevations of AST and ALT.

Biochemical factors

Enzymes released from cardiac myocytes have long been used as markers of injury to confirm myocardial infarction in patients presenting with acute coronary syndromes (fig 4.3). Creatine kinase and its more specific MB fraction remain widely used, but in recent years a number of novel biochemical markers (my-oglobin, troponin I and T) have been developed that are more sensitive and appear in the blood earlier after the onset of symptoms. Almost regardless of which biochemical marker is used, increased concentrations are associated with an increased risk of recurrent ischaemic events. Myoglobin peaks particularly early and is reliably detected within four hours of injury, making it potentially useful for very early diagnosis. However, myoglobin is relatively non-specific and it is troponin I and T (regulatory proteins with isoforms found only in cardiac myocytes) that have emerged as the most useful biochemical markers for diagnostic and prognostic purposes. Raised concentrations of...

Myocardial Markers

CREATINE KINASE (CK), CK ISOENZYMES, AND ISOFORMS CK (adenosine triphosphate creatine -phosphotransferase) is an intracellular enzyme involved in the transfer of high-energy phosphate groups from ATP to creatine. Although found in small quantities in many tissues, CK is present in large concentrations in cardiac and skeletal muscle as well as brain. The enzyme is a dimer composed of two subunits, each of which may be either the M (muscle) type or the B (brain) type, thus creating three distinct dimers, or isoenzymes cK-BB, predominantly found in brain tissue CK-MM, the predominant isoenzyme in skeletal muscle (although CK-MB is also found there in small amounts) and CK-MB, accounting for 14 to 42 percent of the total enzyme activity present in cardiac muscle (the predominant enzyme remaining CK-MM).

Clinical Experience

Taking into account the expectations of off-pump bypass surgery, these findings were somewhat disappointing. The study, however, was conducted in patients of whom 50 had two vessel disease with a normal ventricular function and little comorbidity. This is also reflected by the low incidence of complications in patients who underwent on-pump bypass surgery. Two findings, however, favour off-pump CABG there was a reduced need for blood products in the off-pump group, and there was a 41 reduction in postoperative creatine kinase MB release. The former is a consistent finding in most of the observational studies summarised in table 5.4. The latter suggests that avoiding CPB reduces the degree of myocar-dial necrosis which is in accordance with a significant reduction in troponin I release in off-pump patients reported previously.1314 Apparently local ischaemia during clamping of the coronary arteries is less harmful than global cardiac ischaemia. The clinical importance of this finding is...

Eukaryotic Genes

The existence of introns allows for the creation of multiple proteins from one gene, by the use or exclusion of different exons. Such alternative splicing gives rise to protein isoforms, highly similar but slightly different proteins, with functions that vary as well. Isoforms are typically tissue-specific. For example, the muscle enzyme creatine kinase exists in one form in the heart, and another form in the skeletal muscles (such as the biceps), which have different ends formed through use of different exons. Even though it codes for two or more proteins, most scientists call such a DNA sequence a single gene.

Muscle Metabolism

Muscle tissue is specialized for movement in humans and animals. The compound adenosine triphosphate (ATP) contains high-energy phosphate bonds, and these bonds can be broken to convert chemical energy into work by the myofibrils. Muscle contraction occurs when a nerve signal causes the depolarization of the muscle cell membrane and the release of calcium from the sarcoplasmic reticulum to activate the myofibril contractile proteins. Adenosine triphosphate is required to power the contraction as well as to pump the calcium back into the sarcoplasmic reticulum and restore the sodium and potassium at the cell membrane. 1 A diagram showing the pathways for ATP production and utilization is shown in Fig. 1. In the living animal, the most efficient pathways of ATP production involve conversion of pyruvate into carbon dioxide in the mitochondria. However, after the animal dies, substrates such as glucose, fatty acids, and oxygen from the bloodstream are no longer available. Creatine...

Muscular System

The ATP for muscle contractions can come from four sources aerobic oxidation, or glycolysis with fermentation to lactic acid, creatine phosphorylation, and free ATP. Under resting conditions, muscle cells produce ATP from the oxidation of fatty acids via aerobic respiration. Because it requires oxygen, this mechanism can provide energy only as fast as the required amount of oxygen can be provided to the muscle by the bloodstream. Although this is most efficient, aerobic respiration does not provide ATP fast enough for continuous contractions such as those during athletic performances. It can, however, support moderate continuous activity such as hiking or, literally, aerobic exercise. For very brief, explosive activity, such as a single leap or a throw, the muscle cell has two immediate sources of ATP. One is the small amount of free ATP always present in cells. This can support about 2 seconds of contractions. The second immediate source is a high-energy compound called creatine...

Renal System

Freshwater fishes are hyperosmotic regulators. That means that the concentration of ions and other solutes is greater in the blood than in their surrounding water, which in most cases is very dilute. The fish will thus absorb water osmotically from their environment through all permeable epithelia such as the gills, skin, and gut. The regulatory problem is one of getting rid of the excess water and the kidney plays that important role. A large amount of urine is produced, which is dilute and contains creatine, uric acid, and some ions. The volume of urine produced must balance the quantity of water entering the body. Sodium (Na+) and chloride (Cl ) ions passively diffuse out of the body across permeable epithelia and are actively taken up, to a large extent, across the gill epithelium. Electrolyte reabsorption out of the urine takes place across the renal tubule. Na+ is actively extracted and it appears that Cl passively follows. Calcium (Ca2+), magnesium (Mg2 +), and other divalent...

Clinical Application

When treating healthy kidneys of eight patients with extracorporeally applied HIFU in a phase 1 study, Vallancien et al. 19 did not observe any significant changes in the usual laboratory parameters, except for a transient increase in creatine phosphokinase after a long pulse. Side effects included skin burns. Kohrmann et al. 41 applied HIFU to healthy kidney tissue of 24 patients immediately before nephrectomy. In 19 out of the 24 cases, hemorrhage or necrosis was detected macroscopically. Histologically, interstitial hemorrhages and fiber rupture, as well as collagen fiber shrinkage with eosinophilia, were detected in the focal area.

Metabolic Activity

The cellular mechanisms underlying the adaptation to altered gravity require energy consumption. This consumption can directly be determined by glucose utilization. Marker enzymes can also be used to study the energy demands during adaptation. For example, Ghicose-6-Phosphate Dehydrogenase (G6P-DH) and Succinate Dehydrogenase (SDH), which are the limiting enzymes of the Krebs' cycle, are important to maintain energy availability in the cells. There is also the creatine kinase involved in the mechanism of ATP-regeneration, or the cytochrome oxidase that characterizes basic metabolic activity. Using these markers, space studies revealed that brain metabolism was strongly affected by a change in gravity level. In immature and adult aquatic animals, modifications occurred mostly in vestibular related structures of the developing brain or in the sense organs. After the 20-day Cosmos-782 biosatellite mission, creatine kinase activity was increased in the cortex of the vestibular cerebellum...

Renal Failure

Acute renal failure is rare after NSAID overdose, but NSAID overdose may place a stressed renal system at risk for failure. Clinical presentation may include hematuria, elevations in blood urea nitrogen creatine, and oliguria. The mechanism of renal insufficiency in acute overdose is believed to be renal vascular changes secondary to COX-mediated prostaglandin inhibition. Patients with underlying renal insufficiency appear to be at greatest risk for acute renal failure. Most patients have recovery of renal function, but the need for long-term dialysis has been reported.

Aminoglycosides

Animoglycosides are bactericidal agents that bind to the 30 S bacterial ribosome and inhibit protein synthesis. Agents include gentamicin, tobramycin, amikacin, kanamycin, streptomycin, spectinomycin, and netilmicin. Aminoglycosides have a low therapeutic to toxic ratio, with ototoxicity and nephrotoxicity being common adverse effects. All aminoglycosides have the potential to damage vestibular and cochlear sensory cells, but neomycin is by far the most ototoxic. The incidence of hearing loss related to aminoglycoside has been reported to be between 2 and 25 percent. Hearing loss correlates closely with high-dose or prolonged therapy. Nephrotoxicity results from damage to the proximal renal tubules and correlates with drug dose, therapy duration, volume status, and extremes of age. Mild renal insufficiency may result in 10 to 25 percent of patients using aminoglycosides, as reflected in elevations in serum creatine. Renal damage is largely reversible with cessation of therapy, but...

DB immunoassays

DB immunoassays (see Supplemental Tab. 1, http www.vai.org vari labs haab. asp) were performed on a Behring Nephelometer (BN) II (2.2 D, serial no. 330135) and on a Dimension (DIM) RxL (serial no. 970933-AX) from DB (Deerfield, IL) with the HUPO PPP specimens 8 . Most tests performed are approved by the Food and Drug Administration (FDA) only for serum samples, as outlined in the manufacturer data sheets. Tests for ferritin (FERR), soluble transferrin receptor (sTfR), cardiac troponin I (cTNI), and myoglobin (MYO) on the Dimension system are also approved for heparinized plasma. Tests for C-reactive protein (CRP), IgE, b2-micro-globulin, and MYO on the BN system are also approved for EDTA and heparinized plasma. The creatine kinase MB (mass assay, MMB), human chorionic gonadotropin (HCG), and thyroid stimulating hormone (TSH) assays are FDA-approved for use in serum, EDTA-plasma, and heparin-plasma samples. The fibrinogen, plasminogen, antithrombin III, and fibronectin tests are...

Myopathies

Polymyositis is an inflammatory myopathy that affects individuals over the age of 30, with a slight propensity for women.1 Usually, patients present with chronic complaints of proximal symmetric weakness, although the disorder occasionally presents subacutely. Some patients will have dysphagia, and a few will progress to respiratory failure. There may be muscle pain and tenderness. On examination, there is reduced proximal strength, which may best be tested by asking the patient to arise from a chair with his or her arms crossed or to lift a light object over his or her head. There is no sensory loss, and unless weakness is profound, reflexes should be intact. If deep tendon reflexes are diminished, neuropathy should be considered. Laboratory testing may reveal an elevated erythrocyte sedimentation rate (ESR), leukocytosis, and creatine kinase. The differential diagnosis includes Lambert-Eaton myasthenic syndrome, inclusion body myositis, toxic myopathies, dermatomyositis,...

Investigations

Evidence of myocyte necrosis may be found with an increase in creatine kinase or appearance of troponin, indicating myocytolysis. The highest enzyme concentrations occur early and will probably have returned to normal by about a week after onset.6 Cardiac autoantibodies can be demonstrated only later in the disease process.

Dietary Supplements

Athletes have not been well researched, and both safety and efficacy remain open to question for many of these products. Anyone seeking to improve health or performance would be better advised to ensure that they consume a sound diet that meets energy needs and contains a variety of foods. A recent development of concern to athletes is the finding of various prohibited doping agents in what should be legitimate sports nutrition products. Supplements for which there is good evidence of beneficial effects on performance include caffeine, creatine, and bicarbonate, but the risk of an inadvertent positive doping result must always be considered.

Figure

Like gene activation by MyoD, repression of the c-fos promoter is dependent on DNA binding which, in this case, prevents the binding of a positively acting factor to a site known as the serum response element which overlaps the MyoD binding site in the c-fos promoter (Fig. 7.6). Obviously, in contrast to its binding to the creatine kinase enhancer, MyoD must bind to its binding site in the c-fos promoter in a form which cannot activate transcription. Hence, like the glucocorticoid receptor, MyoD can have different effects on gene expression depending on the nature of its binding site (see Chapter 6, section 6.2.1 for discussion of the mechanism of transcriptional repression by the glucocorticoid receptor). In both cases, however, DNA binding by MyoD is dependent upon a basic region of the protein which binds directly to the DNA and an adjacent region which can form a helix-loop-helix structure and is

Metabolism

Adenosine triphosphate (ATP) provides the energy for muscle contraction, just as for other cellular functions. ATP can be generated most efficiently by oxidative phosphorylation, but it can also be generated by anaerobic glycolysis. Anaerobic glycolysis uses glucose or glycogen stores in muscle to generate ATP and is useful at the immediate onset of exercise and for short periods of time. The major muscle store of high-energy phosphate necessary to generate ATP from adenosine diphosphate (ADP) is phosphocreatine. Dietary supplementation with creatine phosphate may slightly enhance short bursts of high-intensity exercise, but sustained levels of exercise depend on oxidative phosphorylation. Hence, maximal oxygen consumption, or VO2 max, is the best measure of absolute exercise capacity.

Heart Disease

The ability of PA to chelate iron and possibly reduce its free radical generating potential and subsequent lipid peroxidative damage Figure 14.3(C) may also protect the heart from ischemic and reperfusion injury 113 . Rao et al. 113 intravenously injected rats with saline or PA at levels up to 15 mg per 100 g of BW. Shortly after, the hearts were excised, and reperfusion injury was induced in vitro. The higher levels of injected PA resulted in lessened reperfusion injury by significantly reducing creatine kinase release, decreasing lipid peroxidation

Scientific Basis

When muscles of freshly slaughtered animals are electrically stimulated, they contract. There is a concomitant increase in biochemical reactions in the muscle cells leading to an accumulation of lactate and resulting in an immediate drop in the muscle pH (zlpH). After stimulation, the rate of pH fall (dpH dt) as the muscles go into rigor is increased (Fig. 5) (40). If a muscle is free, it will contract during stimulation. When stimulation ceases, the muscle will partially relax but unless the muscle is subjected to some force, either restrained or tensioned, it will remain in a shortened state. Stimulation of suspended bodies or sides with a balanced arrangement of opposing muscle systems ensures that there is sufficient physical force to pull most muscles back to rest length. If muscles have been freed from their natural attachments soon after stimulation, however, as occurs with hot boning, there may be no restraining force to return stimulated muscles to their natural length. The...

Nematodes Roundworms

TRICHINELLA SPIRALIS Trichinosis is common in Mexico and the United States and results from the consumption of infected pork and, less commonly, bear and walrus meat. In the early stages of infection with Trichinella spiralis, the patient may present with acute myocarditis, nonsuppurative meningitis, bronchopneumonia, or catarrhal enteritis. The primary lesions are in striated muscle. Clinical symptoms depend on the site of invasion. Patients may present with nausea and vomiting, diarrhea, fever, urticaria, periorbital edema, (pathognomonic) splinter hemorrhages, myalgia, muscle spasm, stiff neck, headache, and psychiatric disturbances. Laboratory manifestations of trichinosis include leukocytosis, eosinophilia, elevated creatine phosphokinase and electrocardiographic changes. The diagnosis can be confirmed with latex agglutination, skin test, and a bentonite flocculation test. Biopsy of tender muscle may be helpful after the fourth week. Since T. spiralis encysts in striated muscle,...

Designer Foods

Sports nutrition is another established arena for designer foods. Specific nutritional measures and dietary interventions have been devised to support athletic performance and recuperation. Oral rehy-dration products for athletes were one of the first categories of functional foods for which scientific evidence of benefit was obtained. Oral rehydration solutions must permit rapid gastric emptying and enteral absorption, improved fluid retention, and thermal regulation, to enhance physical performance and delay fatigue. Carbohydrates with relatively high glycemic index combined with whey protein concentrates or other sources of branched chain amino acids have been shown to enhance recovery of athletes. Caffeine, creatine, ribose, citrulline, L-carnitine, and branched chain amino acids have each been shown to improve exercise performance or diminish postexercise fatigue. Whether combinations of these ingredients, blended into foods or beverages, will perform better than the individual...