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 Summary

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Creatine ATP Creatine Phosphate ADP

The reaction is strongly endergonic as written. However, the level of ATP is very high in mitochondria, so the reaction proceeds to the right. Creatine phosphate then diffuses from mitochondria to the myofibrils, where it provides the energy for muscle contraction. High levels of ADP formed in the myofibrils during contraction favor the reverse reaction namely, resynthesis of ATP - at the expense of creatine phosphate cleavage to creatine. This example shows that one must consider not only the standard free energy change but also the actual concentrations of all reactants and products when predicting the direction of a reaction in vivo. Whether energy is stored as ATP or as a compound like creatine phosphate, that energy must eventually be made available as chemical energy, if it is to drive the synthesis of other high-energy compounds. It also can be transduced to other forms of energy, including mechanical energy or electrical energy. Transduction to mechanical energy occurs in...

Creatine ATP Creatine Phosphate ADP catalyzed by Creatine Kinase

The latter reaction is strongly endergonic as written. However, the level of ATP is very high in mitochondria, so the reaction proceeds to the right. Creatine phosphate then diffuses from mitochondria to the myofibrils (see here), where it provides the energy for muscle contraction. High levels of ADP formed in the myofibrils during contraction favor the reverse reaction namely, resynthesis of ATP - at the expense of creatine phosphate cleavage to creatine. This example shows that one must consider not only the standard free energy change but also the actual concentrations of all reactants and products when predicting the direction of a reaction in vivo.

Creatine

Creatine is an amin oacid derivative found in relatively large quantities in meat. It has been used in the last 10 years to improve exercise capacity in tasks that are brief but of high-intensity. Creatine acts to increase muscle phosphocreatine levels 105 and may increase the rate of phosphocreatine resynthesis 106 both of these effects result in improved, brief, high-intensity, intermittent exercise capacity 105 . Additionally, a combination of crea-tine ingestion and resistance exercise training has been shown to result in greater muscle-mass gains than resistance training alone in young individuals 107 . Creatine administration has been combined with resistance training in the elderly, with one investigation finding no effect 108 and others finding improvements in lean body mass and strength 109,110 . Thus, further investigation as to the potential anabolic actions of creatine and resistance training in older adults is warranted. There is one report of creatine supplementation...

Use of Biomarkers in the Emergency Department and Chest Pain Unit453

The use of biomarkers of cardiac injury in the emergency department (ED) and observation unit settings has several nuances that are different and, therefore, worthy of its own set of use guidelines. The markers that are used, however, are the same. The primary marker of choice continues to be cardiac troponin (Tn). Other markers that have been used because of the need in the ED for rapid triage have been myoglobin and fatty acid binding protein. In addition, some centers still prefer less sensitive and less specific markers such as creatine kinase myocardial band (CK-MB). More recently, a push has occurred to develop markers of ischemia, such as ischemia modified albumin (IMA), to determine which patients have ischemia, even in the absence of cardiac injury. As tro-ponin assays become more sensitive and method for use becomes better understood, the use of these other markers are being relegated to lesser and lesser roles. Markers of ischemia are useful, but at present, despite some...

Monitoring of renal function

Is a demonstrable rise in the serum creatinine concentration. A rise in the serum creatinine concentration that just exceeds the normal range may reflect as much as a 50 decline in the GFR. The failure of the serum creatinine to accurately reflect the degree of renal injury is particularly evident in patients with decreased muscle mass or those with chronic liver failure. Crea-tinine is produced from the metabolism of creatine in skeletal muscle. In turn, creatine is derived from the liver. In the setting of chronic liver disease or malnourished patients with decreased muscle mass creatinine synthesis becomes impaired. As a result more profound decreases in the GFR may occur before the serum crea-tinine concentration begins to rise above normal values 53 . By contrast, the serum creatinine concentration is a sensitive indicator of changing renal function in patients with chronic renal failure. In these patients a small decline in the GFR is associated with a large increase in the...

Diagnosis ofBlunt Cardiac Trauma

Concentrations of both cTnI and cTnT have been shown to be increased in trauma patients, especially following cardiac contusion (13-16). Blunt cardiac injury typically results from direct compression of the heart or decelerating forces delivered to the chest. Such cardiac injury may occur even after relatively low-energy trauma without other obvious injuries. In the large majority of patients with blunt chest trauma studied, small to moderate increases in cardiac troponin were found, implying that the extent of injury is small (14,15). The results of testing for cardiac troponin were able to differentiate the majority of patients with isolated increased creatine kinase-MB (CK-MB) values related to skeletal muscle damage from those with myocardial injury. In one representative study of 44 patients with blunt chest trauma, 37 trauma patients without cardiac contusion had increases in CK-MB without a rise in cTnI (15). In the six patients with evidence of cardiac injury by...

The Normal Adult Brain

Acute stimulation of the cerebral insulin receptor was achieved through a single intracerebroventricular injection of insulin. This procedure led to a dose-dependent stimulation of the glycolytic key enzymes hexokinase and phosphofructokinase in the cerebral cortex. Also, acute stimulatory effects of the hormone in the brain have been demonstrated for pyruvate dehydrogenase and choline acetyltransferase. These data may indicate that both glycolytic flux and pyruvate oxidation in the brain are stimulated by insulin paralleling the hormone's effect in non-nervous tissue. Short-term (1 day) or long-term (7 and 21 days) intracerebroventricular infusion of insulin have been found to exhibit a discrete anabolic effect on energy metabolism in the hippocampus as can be concluded from an 11 increase in the concentration of creatine phosphate, the storage form of ATP (Henneberg and Hoyer 1994). From animal studies, it may be deduced that in brain cortex and in some subcortical nuclei glucose...

Clinical challenges to the development of ischemia markers

The challenge of evaluating a new more sensitive and specific marker relative to an imperfect gold standard was observed in the development of cardiac troponin. Katus et al. (45) initially reported the specificity of troponin T to be only 78 when compared to a creatine kinase-MB (CK-MB) standard for AMI. This conclusion was not congruent with the hypothesis that troponin T was highly cardiac specific relative to CK-MB. However, when patients with a clinical diagnosis of unstable angina were excluded, the sensitivity

Klein LW Kramer BL Howard E Lesch M Reference

To assess the incidence and clinical significance of elevated total plasma creatine kinase (CK) and MB isoenzyme fraction after apparently successful coronary angioplasty, a prospective study of 272 consecutive elective procedures was undertaken. Total CK (normal < 200 lU liter) and CK MB isoenzyme (normal 4 ) were measured immediately after successful completion of the procedure and every 6h for 24 h. All nonelective procedures results not fulfilling all American Heart Association American College of Cardiology Task Force guideline criteria for a successful result were excluded from analysis. 2. Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG. Significance of mild transient release of creatine kinase-MB fraction after percutaneous coronary interventions. Circulation 1996 94 1528-1536.

Testing the Oocyte Extract for Chromatin Assembly

Creatine kinase (Boehringer Mannheim). 5. ATP buffer 10 min MgCl2, 30 mM ATP, pH 7.5, 800 mM creatine phosphate, 10 mM P-glycerol phosphate, 0.5 mM DTT, 1 mM EGTA, 5 mM KCl, 10 (v v) glycerol, 20 mM HEPES, 10 mg mL phenylmethylsulfonyl fluoride, 2 mg mL leupeptin, 2 mg mL pepstatin, pH 7.5.

Testing the DEAE Fraction for Chromatin Assembly

Creatine kinase (Boehringer Mannheim). 5. ATP buffer 5.0 mM MgCl2, 30 mM ATP, pH7.5, 450 mM creatine phosphate, 10 mM P-glycerol phosphate, 0.5 mM DTT, 1 mM EGTA, 5mMKCl, 10 (v v) glycerol, 20 mM HEPES, 10 mg mL phenylmethylsulfonyl fluoride, 2 mg mL leupeptin, 2 mg mL pepstatin, pH 7.5.

Classification Of Methods

A commercial serum creatine kinase assay8 employs the kinetic method for enzyme quantitation. This three-enzyme, coupled assay involves the following sequence of reactions . . creatine kinase . , Creatine phosphate + ADP -> Creatine + ATP (3.13) In this assay, diluted serum is preincubated with glucose, hexokinase, NADP+, and G6P dehydrogenase to allow any creatine phosphate and ADP present in the serum sample to be consumed. When a constant A340 value is achieved, a reagent solution consisting of concentrated creatine phosphate and ADP is added, and the increase in A340 is monitored as a function of time. A typical trace is shown in Figure 3.2. The slope of the initial linear section of this curve is directly proportional to enzyme concentration. Add creatine Figure 3.2. Kinetic trace for creatine kinase assay. Figure 3.2. Kinetic trace for creatine kinase assay.

Repair Synthesis and Supercoiling Assay

Set up a 25- L standard reaction with 300 ng of plasmid, 200-400 g of protein extract, 5 mM MgCl2, 40 mM HEPES-KOH, pH 7.8, 0.5 mM DTT, 40 mM phos-phocreatine, 4 mM ATP, 2.5 g creatine phosphokinase, 5 Ci a32PdCTP by adding the following reagents to an Eppendorf tube on ice, in the indicated order (see Note 5) 1 L creatine kinase,

Use of Biomarkers in the Emergency Department and Chest Pain Unit

The use of biomarkers of cardiac injury in the emergency department (ED) and observation unit settings has several nuances that are different and, therefore, worthy of its own set of use guidelines. The markers that are used, however, are the same. The primary marker of choice continues to be cardiac troponin (Tn). Other markers that have been advocated for use in the ED because of the need for rapid triage have been myoglobin and fatty acid binding protein. In addition, some centers still prefer less sensitive and less specific markers, such as creatine kinase myocardial band (CK-MB). More recently, a push has occurred to develop markers of ischemia, such as ischemia modified albumin (IMA), to determine which patients have ischemia, even in the absence of cardiac injury. As troponin assays become more sensitive and how to use them becomes better understood, the use of other markers are being relegated to lesser and lesser roles. Markers of ischemia would be useful but at present,...

Other Detection Methods

The sensitivity of this method is directly related to the apparent molar enthalpy of reaction, so that very endo- or exothermic reactions will be most readily followed. Examples of the application of this method to the determination of enzyme kinetic parameters include dihydrofolate reductase, creatine phosphokinase, hexokinase, urease, trypsin, HIV-1 protease, heparinase, and pyruvate carboxylase.

In Vitro Replication Assay with Chromatin Templates

L. 40 pL of 1 M creatine phosphate 400 mM. m. 1.2 pL of creatine kinase (10 pg pL) 12 pg. 3. DNA is assembled into chromatin by using Xenopus oocyte extracts (30 yL extract 150 ng DNA) for 6 h at 27 C in oocyte extraction buffer, in the presence of 3 mM ATP, 1 mM MgCl2, 40 mM creatine phosphate, creatine kinase (10 yg yL) and 10 yM aphidicolin (see Note 12).

Causes Of Hyponatremia

5.2 A 56-year-old man presents to the doctor for the first time complaining of fatigue and weight loss. He has never had any health problems, but he has smoked a pack of cigarettes per day for about 35 years. He is a day laborer and is currently homeless and living in a shelter. His physical examination is notable for a low-normal blood pressure, skin hyperpigmentation, and digital clubbing. He appears euvolemic. You tell him you are not sure of the problem as yet, but you will draw some blood tests and schedule him for follow-up in 1 week. The laboratory calls that night and informs you that the patient's sodium level is 126 mEq L, potassium level is 6.7 mEq L. creatine level is normal, and bicarbonate and chloride levels are low. What is the likely cause of his hyponatremia given his presentation

Involvement Of Calpains In Development And Differentiation

Expression is found in the heart and it disappears subsequently. Variants of capn3 generated by alternative splicing are also detected in smooth muscle (Fougerousse et al. 1998). The requirement of both calpain and the proteasome proteolytic systems in the differentiation of myoblasts is exemplified by the work of Ueda et al. (1998). L8 myoblast cells grown in the absence of mitogen show enhanced levels of creatine kinase together with the differentiation of myotubes. However, when calpain inhibitor and the proteasome inhibitor lactacystin are added to these cultures, creatine kinase levels are markedly reduced together with inhibition of myotube differentiation. Although calpains have been implicated in neurodegenerative diseases, a diametrically opposite view is held by some that calpains may contribute to processes such as the remodelling of neuronal dendritic structures after neuronal injury. In murine cortical cultures subjected to dendritic injury, calpain did not seem to...

Magnetic Resonance Imaging MRI and spectroscopy

Computed Tomography Fatty Liver

Differences in the magnetic properties of bulk cylinders like extramyocellular lipids (EMCL) and spherical vesicle-accumulated intramyocellular lipids (IMCL) give the potential to separate these two compartments. This phenomenon was observed for the first time in the early 1990s (Schicket al. 1993) and confirmed by theory (Boesch et al. 1997 Boesch & Kreis 2001) and model experiments (Szczepaniak et al. 2002) later on (Figure 13.7). Successful validation by histological and biochemical analysis of biopsies (Howald et al. 2002) and the increasing accessibility of MR equipment have led to numerous metabolic studies ever since (Krssak & Roden 2004 Boesch et al. 2006). For quantification purposes, the signal of tissue water (Boesch et al. 1997 Szczepaniak et al. 1999) or skeletal muscle creatine (Rico-Sanz et al. 1999) is taken as the internal reference. Lipid concentration can be given in these relative units (Krssak et al. 1999) or, assuming certain hydration or creatine...

Final results of the balloon vs optimal atherectomy trial BOAT

BACKGROUND Previous directional coronary atherectomy (DCA) trials have shown no significant reduction in angiographic restenosis, more in-hospital complications, and higher 1-year mortality than conventional balloon angioplasty (percutaneous transluminal coronary angioplasty PTCA ). DCA, however, has subsequently evolved toward a more optimal technique (larger devices, more extensive tissue removal, and routine postdilation to obtain diameter stenosis < 20 ). METHODS AND RESULTS The Balloon vs. Optimal Atherectomy Trial (BOAT) was conducted to evaluate whether optimal DCA provides short- and long-term benefits compared with balloon angioplasty. One thousand patients with single de novo, native vessel lesions were randomized to either DCA or PTCA at 37 participating centers. Lesion success was obtained in 99 versus 97 (p 0.02) of patients to a final residual diameter stenosis of 15 versus 28 (p < 0.001) for DCA and PTCA, respectively, the latter including stents in 9.3 of the...

Markers of ischemia

Commonly used biomarkers such as creatine kinase (CK), CK-MB, and troponin are not detected in blood until several hours after symptom onset, and their presence is almost always correlated with myocardial necrosis. The challenge is to identify patients who develop symptoms of ischemia, such as plaque rupture with partial occlusion of the vessel lumen, before myo-cyte death. In this early stage of ACS, traditional

Prognostic Role of BNP and NTproBNP Across Spectrum of ACS

Nstemi Troponin Bnp

A substudy ofthe Orbofiban in Patients with Unstable Coronary Syndromes-Thrombo-lysis in Myocardial Infarction 16 (OPUS-TIMI 16) trial was among the first to evaluate the prognostic capabilities of BNP in a large population of patients across the entire spectrum of ACS (45). In this study, BNP was measured in 2525 patients at a mean of 40 h after presenting with STEMI, NSTEMI, or unstable angina. BNP levels on admission correlated with age, male gender, white race, hypertension, CHF, peripheral vascular disease, hypercholesterolemia, and smoking status. In addition, elevated levels of BNP were associated with Killip class > 1, electrocardiogram (ECG) changes, elevated creatine kinase-MB, and chronic kidney disease. A plasma concentration of BNP > 80 pg mL was a powerful

Stone GW Rogers C Hermiller J et al Reference

348 grafts were randomized to the FilterWire EX compared to 319 patients with 334 grafts in the GuardWire group. All patients received 325 mg of aspirin and were loaded with either 300 mg of clopidogrel or 500 mg of ticlodipine within 4 h after the procedure. The use of glycoprotein Ilb IIIa inhibitors was left to the individual operator's discretion. Device success rates for the devices were 95 for the FilterWire and 97 for the GuardWire. There was no statistically significant difference in the end point between the two devices (Figure 1). Postprocedural measures of epicardial coronary blood flow, procedural complications, and postprocedural creatine kinase myocardial band (CK-MB) release were similar between the two groups however, the use of glycoprotein IIb IIIa inhibitors for bailout was slightly higher in the GuardWire group.

Section 2 Alternative Splicing

RNA splicing is very important for the maintenance of gene functions and regulation of the expression of certain genes. The mutations that affect RNA splicing can cause approximately 15 of all genetic diseases. The same pre-mRNA can be spliced variously in different tissues, cell types, and at different developmental stages, and react to various biological signals. So far only about 30,000 genes have been identified, compared with previous estimates of 100,000 or more. This indicates that one gene encodes more than one distinct mRNA hence, more than one protein may play a critical role in expanding the function of our genomes. The usage of alternative splicing can switch on and off the expression of a certain gene. In this case, one functional protein is produced by a splicing event, and the nonfunctional proteins resulted from other splicing events. A single gene can produce several different kinds of proteins, when different splicing possibilities exist. In one extreme case, the...

Exercise testing in chest pain units

The largest and most recent prospective, randomized trial comparing management by an ADP-stress test with regular inpatient care is that of Farkouh and co-investigators 42 . They studied 424 patients with a diagnosis of unstable angina based on symptoms and considered to be at intermediate risk. Patients with ECG evidence of ischemia were excluded. The observation protocol, which included ECGs, ST-segment monitoring, and serial serum creatine kinase-MB measurements, differed from prior studies in its duration of only 6 hours. Patients with negative ADP findings who were sufficiently ambulatory underwent exercise testing while pharmacologic stress imaging was performed in the others. No adverse events occurred with the stress tests but the proportion of patients receiving the various tests is not specified. Patients with negative tests were discharged and those with positive or equivocal results were admitted. Forty-six percent of patients in the ADP-stress test group had a negative...

Monocyteplatelet Aggregates As A Marker Of

Standard diagnostic markers of acute MI (AMI), such as the MB isoform of creatine kinase (CK-MB) and cardiac troponin, reflect the onset ofmyonecrosis rather than the early underlying etiological processes of plaque rupture, and platelet activation. Such markers of myonecrosis do not appear in the peripheral circulation until at least 4 hours after the onset of ischemic injury. However, monocyte-platelet aggregates are elevated < 4 h following the onset of symptoms of AMI (Fig. 2) (9) and thus serve as an early marker of AMI, potentially offering the opportunity to facilitate early treatment to reduce morbidity and mortality.

Creatinine Metabolism

Creatine is synthesized in the liver, pancreas, and kidneys from the amino acids arginine, glycine, and methionine. Creatine is transported through the circulatory system to muscle, brain, and other organs, where it is converted to phosphocrea-tine and acts as an energy reservoir much like ATP. Creatinine is produced as a waste product of creatine and phosphocreatine. Because much of the creatinine is produced in muscle, the amount of creatinine that is measured in blood is proportional to the patient's lean muscle mass. The waste product, creatinine, enters the blood supply, where it is removed through the kidneys.

And L Kristin Newby MD MHS

A significant proportion ( 20 ) of patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery develop elevated levels of creatine kinase MB isoform (CK-MB) afterward. Large increases in the concentration of CK-MB after PCI are associated with the risk of death, myocardial infarction, and repeat revascularization. However, the prognostic significance of modest elevations (less than five times the upper limit of normal ULN ) after PCI remains controversial. It has been shown in some studies have shown that even minor elevations in CK or CK-MB levels (more than one time the ULN) after PCI are associated with worse outcomes, but other studies have shown no association between small elevations in CK or CK-MB (less than five times the ULN) and recurrent cardiac events. Following CABG, almost all patients have elevated levels of CK-MB and the clinical significance is less well established. However, clinical studies show that large elevations...

PAPPA as a Marker for Plaque Stability

Icam Intracellular Cardiac

Pathophysiology ofatherosclerosis with respect to lesion development, progression, and destabilization. A variety of biomarkers with distinct pathophysiological profiles can be used to assess disease activity. ICAM-1, intracellular adhesion molecule-1 VCAM-1, vascular cell adhesion molecule-1 HGF, hepatocyte growth factor CKMB, creatine kinase-MB. Fig. 2. Pathophysiology ofatherosclerosis with respect to lesion development, progression, and destabilization. A variety of biomarkers with distinct pathophysiological profiles can be used to assess disease activity. ICAM-1, intracellular adhesion molecule-1 VCAM-1, vascular cell adhesion molecule-1 HGF, hepatocyte growth factor CKMB, creatine kinase-MB.

See also Glutamate as a Precursor of Other Amino Acids Tetrahydrofolate Coenzymes

Glutamate is one of the most metabolically active of all amino acids (Figure 21.1). It is a precursor to glutamine, arginine, creatine phosphate (Figure 21.3), proline, hydroxyproline, polyamines, glutathione, and T-aminobutyric acid (GABA). GABA (see here), is a neurotransmitter, and is also involved in the synthesis of glutathione. In addition, glutamate itself is a neurotransmitter. Creatine phosphate shuttles high-energy phosphate from mitochondria to sites of muscle contraction. Careful observation of ATP levels in red striated muscle has shown that the provision of energy is more complicated than it might appear at first. ** The amount of ATP needed for a single contraction may be greater than all the ATP immediately available to a sarcomere. Yet even after relatively long exercise, ATP levels in the sarcomeres remain essentially constant. Only after extreme exhaustion do ATP levels begin to fall. This finding suggests that ATP is an intermediary, and not the ultimate, energy...

See also Arginine Mitochondria Energetics in Muscular Motion

Guanidinoacetate is an intermediate in the biosynthesis of creatine, as follows Guanidinoacetate + S-Adenosylmethionine < > Creatine + S-Adenosylhomocysteine The high-energy compound steadily depleted during muscular activity is creatine phosphate (see here). Because the equilibrium for this reaction lies well to the right, virtually all of the muscle adenylate is maintained in the ATP form, rather than as ADP or AMP, as long as creatine phosphate is available. Thus, the energy source in red muscle is creatine phosphate, which regenerates ATP continually as it is depleted by muscle contraction.

Crosssectional Studies Of Quantitative Mr Techniques In People With The Clinical Diagnosis Of Ad

Proton MR spectroscopy (1H MRS) is a diagnostic imaging technique that is sensitive to the changes in the brain at the cellular level. With 1H MRS, several of the major proton-containing metabolites in the brain are measured during a common data acquisition period. The metabolite -acetyl aspartate (NAA) is a marker for neuronal integrity. NAA decreases in a variety of neurological disorders, including AD (15-19). The decrease of NAA or the NAA creatine (Cr) ratio shows a regional variation in AD (20-22). In patients with mild-to-moderate AD, NAA Cr levels are lower than normal in the posterior cingulate gyrus, whereas they are normal in the medial occipital lobe including the visual cortex (Fig. 2 ref. 23). This regional pattern is in agreement with the distribution of the neurofibril-lary pathology, and the associated neuron loss in people with mild-to-moderate AD, indicating that regional NAA Cr levels are potential surrogates for disease progression. Another metabolite that is...

See also ATP as Free Energy Currency Free Energy and Concentration from Chapter 3 Important Points about AG from chapter

Vn for breakdown of phosphoenolpyruvate (PEP), 1,3-bisphosphoglycerate, and creatine phosphate are -62, -49, and -43 kJ mol, respectively. Although the breakdown of super-high-energy compounds, such as PEP, is not used routinely in cells to drive endergonic reactions, these compounds are still important because they can be used to drive the synthesis of ATP from ADP + Pi. In fact, this coupling, called substrate level phospohorylation, is the process by which ATP is synthesized in glycolysis.

Immunoinhibition Technique

Uln Troponin

Cardiac MLC showed promise for risk stratification and as a biomarker of necrosis. Hillis et al. (17) measured cTnI, MLC1, and creatine kinase (CK)-MB mass at presentation and then 4, 8, 16, and 24 h later in 208 patients with chest pain without new ST-elevation. Both cTnI and MLC1 predicted the long-term outcome of patients with chest pain, and in this cohort MLC1 was a better predictor of mortality and nonfatal acute MI than the measurement of cTnI. Although MLC measurements were initially received enthusiastically by the cardiology and laboratory medicine communities (18,19), in the 1980s it was suspected and later verified that the apparent cardiac isoform of MLC is also produced by slow-twitch skeletal muscle, thus explaining the observed crossreactivity in some clinical samples (20). MLC measurements therefore fell out of favor compared with CK-MB and as assays for cardiac troponin were being developed. Creatine + ATP CK, Mg++ ADP + Creatine Phosphate pH 6.8 When cellular energy...

Importance of Novel Biomarkers

Proportion of patients with positive marker strategy at time of presentation (A) and risk of death or MI at 30 d (B) stratified by marker status in Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I study. Myo, myoglobin Freq, frequency. (Data are from ref. 20.)

Simple Multimarker Approaches Combining Markers of Necrosis

No available biomarker of necrosis offers the ideal properties of a very rapid early rise in conjunction with very high sensitivity and specificity (see Chapter 1). Thus, investigators have proposed the combined assessment of a marker with very rapid kinetics, such as myoglobin, along with a more specific marker of necrosis, such as troponin, to facilitate the diagnosis of MI. For example, in a study of 1005 patients with possible myocardial ischemia admitted to chest pain units, simultaneous quantitative testing for myoglobin, creatine kinase-MB (CK-MB), and cardiac troponin I (cTnI) reduced the time to detection of marker elevation (2.5 h) compared to either a strategy using only CK-MB and troponin (2.8 h) or local laboratory-based testing of CK-MB (3.4 h) (20). In addition, this multimarker strategy using markers of necrosis was positive in a larger proportion of patients (19 vs 5 ) at presentation (Fig. 2A) and showed a more robust discrimination of the risk of death or MI than...

Paul O Collinson Md Frcpath FACB

Point-of-care (POC) testing offers the opportunity to provide more rapid measurement of cardiac biomarkers in the environment in which clinical decisions about patient management are made. The technology of POC testing utilizes whole blood to measure one or more analytes including cardiac biomarkers such as creatine kinase-MB isoenzyme, myoglobin, cardiac troponins T and I, and B-type natriuretic peptide. Measurement methods include immunochromatographic separation usually combined with a quantitative reader, dedicated heterogeneous immunoassay systems, and those suitable for POC and emergency laboratory testing. Analytic performance of these systems approaches but does not always equal those of conventional laboratory methods. Evaluation of POC testing of cardiac biomarker measurement has shown good analytic and clinical diagnostic performance. These systems are entirely suitable for rule-in diagnosis of myocardial infarction (MI). Although POC testing has also been shown to be...

Methodological Aspects

The current available technology for POC testing can be divided into three categories (Table 1) visually read test devices, dedicated POC instruments, and instruments suitable for either POC testing or use in the emergency stat laboratory. The first developments in cardiac POC testing evolved from glucose test strip methodology using initially serum, then whole-blood measurements of creatine kinase (CK) and its MB isoenzyme (CK-MB). These methods were superseded by the development of immunoassay formats based on whole-blood separation and antigen-antibody complex formation, streptavidin-biotin binding ofthe complex, and visual detection. The antibody is labeled with gold (goldlabeled optically read immunoassay GLORIA ) or a dye. This produced the first generation of POC testing cardiac marker testing, often referred to as stick testing (Fig. 2). Although visually read test devices have been shown to be suitable for routine clinical use, they are more prone to operator error. Visually...

Synopsis of the Physiology of Sodium and Water

The major factor responsible for water movement into cells is intracellular potassium (K+) retention 6 . One reason for the retention is that the ICF anions are predominantly large macromolecular anions (organic phosphates) restricted to that compartment. Although these macromolecules do not exert a large osmotic pressure due to their small number, each of them bears a large number of anionic charges. Since the ICF macromole-cules are largely organic phosphate esters (e.g. ATP, creatine phosphate, RNA, DNA, phospholipids) and are essential for cell function, only small net changes in their content occur in most cells. It follows that the total number of ICF particles is relatively fixed in most cells 7 . Therefore, changes in the par

Cardiomyocytes And Endothelial Cells Derived From Human Es Cells

A-cardiac actin (8,11) atrial myosin light chain, ventricular myosin light chain, a-myosin heavy chain, atrial natriuretic peptide, cardiac troponin T and I, GATA-4, Nkx2.5 (30) a-myosin heavy chain, atrial natriuretic factor, Nkx2.5 (32) a, p-myosin heavy chain, cardiac troponin I, desmin, atrial natriuretic peptide, a-actinin (30) a-actinin (29) a, p-myosin heavy chain, cardiac troponin I and T, sMHC, desmin, tropomyosin, a-actinin, GATA4, MEF2, N-cadherin, creatine kinase-MB, myoglobin, a1 and p1 adrenoreceptors (32) Mononuclear and round or rod-shape (30) Immature phenotype of disorganized myofibrillar stacks in early stage EBs and more organized sarcomeric structure in older EBs, also Z bands and intercalated disks (30), poor sarcomeric banding pattern (29) 30 pulses min (8) 8.1 of 22-d-old EBs contained contracting areas, usually in the outgrowth of the EB with 94 33 pulses min (30) 60 pulses min (29) up to 70 of the EBs contained contracting areas, rate of 40 10 pulses min (32)...

Lesion Characteristics

In this experiment, as well as in many subsequent experiments in a number of different animal species, an attempt was made to identify a clinical pathology marker for myocardial injury that would allow for more rapid and sequential monitoring of lesion development. Unfortunately, to date no statistically significant increases in typical markers of myocardial injury, such as the myocardial isoenzyme of creatine kinase (CK-MB) or the lactic dehydrogenase isoenzyme LDH-1, were observed following infusion of large and repeated doses of DCLHb, even in sensitive species such as the rhesus monkey. The small percentage of myocardium involved in the monkeys is consistent with the observation that no significant levels of cardiac specific enzymes were identified in the plasma after hemoglobin infusion. In fact, to date no surrogate marker of

Alphaglucosidase inhibitor blocks hydrolysis of an

Nitrogen ingested and that excreted noncompetitive immunoassay - immunoassay that does not contain reagent antigen competing with patient antigen nonprotein nitrogen - catabolites of protein and nucleic acid metabolism, including urea, ammonia, creatinine, creatine, and uric acid

The Initial Assessment

Early in the course of evaluation in the ED, initial cardiac biomarkers of necrosis are obtained. Myoglobin, cardiac troponin T or cardiac troponin I (cTnl), and creatine kinase-MB (CK-MB) are commonly used to detect myocardial necrosis. However, the sensitivities of these cardiac biomarkers obtained on initial presentation may be poor and are dependent on the time from the onset of symptoms to presentation, the duration of ischemia, and the amount of myocardial tissue involved. Serial testing of cardiac biomarkers in the ED has substantially improved the detection ofmyocardial necrosis in this setting (9).

Proton Mr Spectroscopy

To our knowledge, only three reports on H-MRS in adult KD have been published. In 2000, De Stefano et al. (10) described symmetrical moderate choline creatine elevation in the voxels located inside, at the margin, and outside the T2-weighted MRI signal abnormality in the subcortical white matter of both motor strips. In this 44-yr-old female with slowly progressive gait disturbance since the age of 42, N-acetylaspartate (NAA) was still the dominant peak. The NAA creatine ratio was within normal values. In 2000, Farina et al. (11) described similar diffuse H-MRSI abnormalities in the white matter of the centra semiovalia in two siblings with adult KD. These two authors used the same multivoxel point-resolved spectroscopy (PRESS) technique with a nominal voxel resolution of 2 mL. The choline creatine ratio was elevated, and NAA was mildly decreased compared with the adjacent cortical gray matter. The choline NAA ratio was close to one not only in the voxel within the T2-signal...

See also Biological Fuel Hormonal Regulation of Fuel Metabolism Figure 234

Muscle has an additional energy reserve in creatine phosphate, which generates ATP without the need for metabolizing fuels (see here). This reserve is exhausted early in a period of exertion and must be replenished, along with glycogen stores, as muscle rests after prolonged exertion.

Oxidative Stress and Antioxidant Response

Using the same technique, Castegna et al. 48, 49 identified three specifically oxidized proteins in AD brain creatine kinase BB, glutamine synthase, and ubi-quitin C-terminal hydrolase L-1. Three other proteins exhibited increase in specific oxidation in AD brain dihydropyrimidinase-related protein 2, a-enolase, and the heat shock cognate 71. A similar study performed on plasma samples revealed that fibrinogen y-chain precursor protein and arantitrypsin precursor are more intensively oxidized in AD plasma samples than in controls 50 . These proteins exhibited a 2- to 6-fold higher oxidation index in plasma from AD subjects. Both proteins have been suggested to be involved in inflammation processes in AD.

See also Metabolism of Ornithine and Arginine SAdenosylmethionine and Biological Methylations Polyamines

Arginine is a precursor to nitric oxide, a novel second messenger and neurotransmitter. The complex conversion of arginine to citrulline and nitric oxide is shown in Figure 21.3 as is the conversion of arginine to creatine phosphate. Arginine is a precursor to nitric oxide and citrulline (Figure 21.3) and Arginine can be converted to creatine phosphate (Figure 21.3).

Neurochemistry Of Proton

Spectra acquired from white matter at (A) short echo time (TE 30), demonstrating NAA, choline, creatine, as well as a-glutamine glutamate, y-glutamine glutamate, and myo-inositol peaks and (B) long echo time (144 ms), demonstrating NAA, choline, and creatine. Fig. 2. Spectra acquired from white matter at (A) short echo time (TE 30), demonstrating NAA, choline, creatine, as well as a-glutamine glutamate, y-glutamine glutamate, and myo-inositol peaks and (B) long echo time (144 ms), demonstrating NAA, choline, and creatine. 3.2.3. Creatine 3.02 ppm Creatine is a measure of energy in brain tissue, serving as a buffer in the ATP-ADP reservoir and as a reserve of high-energy phosphates (17,18). It is a fairly stable metabolite and is often used in metabolite ratios as an internal reference. However, creatine levels too can drop, often in the setting of severe brain tissue damage. Choline is identified in elements needed for membrane synthesis and myelination, well as membrane...

Additional Technical Factors

Short echo time proton MRS allows for improved demonstration of peaks related to myo-inositol and glutamate glutamine. It can be helpful in distinguishing lactate from lipid signal and in the evaluation of macromolecular resonances. However, short TE proton MRS can be complicated by more baseline variability, making data processing more difficult. In addition, issues of peak overlap often render quantification efforts impossible for some peaks. Long TE MRS allows for the reliable demonstration of NAA, creatine, choline, and lactate lipid. At our institution, we routinely use a longer TE sequence unless metabolites identified with short TE imaging (a glutamine glutamate, p y glutamine glutamate, myo-inositol peaks) are of interest.

Future Strategies And Developments In Mrbased In Vivo Metabolic Imaging

In theory, higher field systems should provide improved spectral resolution and increased SNR (162) However, issues of shimming, coil design, and alterations in metabolite T1 T2 may degrade these advantages. Gonen et al. (163) found in a comparison of 3D-CSI of the brain with 1.5 T vs 3.0 T systems assuming similar sequence, shim, and anatomy, that SNR was improved 23-46 . This improvement in SNR could be used to increase sensitivity to changes in metabolites detected on MRS or be exchanged for shorter acquisition time. They also found that spectral resolution was improved, with improved peak discrimination, most notably between choline and creatine. At a TE of 135 or 144 ms, a generally flatter baseline was also noted, easing peak area estimation. The application of phased array coil technology has allowed for prominent gain in SNR. The application of a GRASE sequence has been discussed with dual advantages of significant improvement in acquisition time as well as effective...

Application Of Mri To Study Metabolic Disorders

MRS is a method whereby the chemical composition of magnetically active nuclei, such as H or 31P, within a tissue can be determined. The technique requires a large main magnetic field to orient the nuclear magnetic spins parallel or antiparallel with it. No magnetic field gradients are applied. The frequencies of the nuclei will differ depending upon what chemical group they are in. For example, protons on a methyl group, such as in lactate, will give an MRS signal at a slightly lower frequency than protons on an aromatic ring such as phenylalanine. The differences in frequency are small in the order of parts per million (ppm). 1H MRS is capable of producing information on a large number of brain chemicals. The most common chemicals studied via the identification and integration of the spectral peaks found in the proton (1H) spectra include N-acetyl- -aspartate (NAA), creatine, phosphocreatine, choline, myo-inositol, lactate, glutamate, and glutamine. In addition, amino acids, lipids,...

Peroxisomal Disorders

Brain involvement evidenced by MRI is rare in female subjects heterozygous for X-linked adrenoleukodystrophy, including those who have clinical evidence of spinal cord involvement, although in some cases, these females can have white matter abnormalities resembling homozygotes. 1H MRS in female heterozygotes have shown the NAA choline ratio to be significantly reduced in the parieto-occipital white matter, but NAA creatine and Cho creatine ratios are not significantly different from the normal range. In the frontal white matter the choline creatine ratio are significantly elevated, but other ratios did not demonstrate significant differences. NAA choline and NAA creatine ratios were significantly reduced along the white matter of the internal capsule and corticospinal projection fibers, suggesting that NAA was decreased. There were no significant differences in the calcarine or parietal gray matter (92).

Answers To Case 20 Chest Pain

Next diagnostic step Initial studies in the emergency room complete blood count (CBC). electrolytes, blood urea nitrogen (BUN), creatinine, prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR). glucose. 12-lead electrocardiography (EKG) and chest x-ray (CXR) markers of myocardial damage including creatine kinase (CK) and MB isoenzyme (CK-MB), troponin T and troponin I to be done stat and every 6-10 hours for 3 cycles. Oxygen saturation must be monitored, as well.

Creatinine Clearance

Ccr is the most widely used clinical estimate of GFR. Creatine is derived from the metabolism of creatine in skeletal muscle and from dietary meat intake, with about 1.6 of the creatine pool converted to creatinine. It is freely filtered at the glomerulus and not reabsorbed or metabolized. However, approximately 15 of the urinary creatinine is de

Mitochondrial Cytopathies

Several laboratory studies may be useful to screen for impaired energy metabolism such as serum lactate, pyruvate, plasma amino acids, complete blood count, electrolytes, car-nitine, acylcarnitine profile, ammonia, and creatine phospho-kinase. Renal tubular acidosis as part of a Fanconi syndrome may be seen, especially in patients with complex IV defects. Renal disease is more common in pediatric presentations. Elevated lactate is suggestive but not specific for mitochondrial disorders. Lactate levels are not entirely reliable markers of mitochondrial dysfunction. Many children do not have elevated serum lactate or may have elevations only under certain provocations, such as after glucose loading, illness, or exercise. Blood lactate values may be spuriously elevated when a tourniquet is used, or as a result of a child struggling with the venipuncture. In these cases, arterial lactate level may be more reliable. In infants and young children with encephalopathy, CSF lactate may be...

Carbohydrate Utilization in Exercise

Carbohydrate Utilization

Animals have a remarkable ability to shift gears metabolically during periods of strenuous exercise or activity. Metabolic adaptations allow the body to draw on different sources of energy (all of which produce ATP) for different types of activity. During periods of short-term, high-intensity exercise (e.g., a 100-m dash), most of the required energy is supplied directly by existing stores of ATP and creatine phosphate (Figure, part a). Long-term, low-intensity exercise (a 10-km run or a 42.2-km marathon) is fueled almost entirely by aerobic metabolism. Between these extremes is a variety of activities (an 800-m run, for example) that rely on anaerobic glycolysis conversion of glucose to lactate in the muscles and utilization of the Cori cycle.

Newer Imaging Methods for Triaging Patients Presenting to the Emergency Department with Chest Pain

McLaughlin and colleagues 14 evaluated 181 patients who were admitted to the hospital from the ED with chest pain of presumed cardiac origin. Patients were included if they had a normal or nondiagnostic ECG at presentation. Exclusion criteria were history of coronary artery disease (CAD) (MI, coronary bypass surgery, or percutaneous intervention), diagnostic ST changes or Q waves on electrocardiogram, weight more than 250 lb, initial elevated creatine kinase-myocardial band (CK-MB), and known or suspected pregnancy. Among those evaluated, 44 patients did not meet entry criteria and 4 patients did not give consent, yielding 133 patients in the final analysis. An EBCT was considered positive if the score was more than one the results of the scan were blinded to the responsible clinician.

Ghb With Synthetic Glycogen For Cancerous Cells

Glucose oxidase method, for glucose, 152 Glucose-6-phosphatase deficiency, 171 Glucose-6-phosphate, in creatine kinase in amylase measurement, 364-365 in creatine kinase measurement, 273, 274 Isoelectric point, of proteins, 20 Isoenzymes, 109, 244-245 alkaline phosphatase, 247, 248t creatine kinase, 272-274, 272f lactate dehydrogenase, 273-274, 275f, Labeling, of chemicals, 5-6, 5f Lactate, measurement of, 172-173 Lactate dehydrogenase (LD) in creatine kinase measurement, 273 isoenzymes of, 273-274, 275f, 292-293 measurement of

Brain Energy Metabolism In Bipolar Depression

Although the brain makes up about 2 of our total body weight, it consumes about 20 and 25 of total body dioxide and glucose, respectively. Neural activity is dependent upon energy metabolism mainly for the active transport of ions and other molecules through cellular membranes needed for neural excitation. Energy consumption is particularly high for Na+ K+-ATPase and Ca2+-ATPase in plasma and endoplasmic membranes. Brain energy metabolism is reflected in ade-nosine-triphosphate (ATP) turnover. ATP, an energy-rich molecule with two high-energy phosphoanhydride bonds, is the energy donor in most energy-consuming processes, and its production in the brain is highly regulated. Another energy-rich molecule with high-energy phosphate is creatine phosphate, which enables the production of ATP from ade-nosine diphosphate via the creatine kinase creatine phosphate system. This system may also function in regulating mitochondrial activity. Magnetic resonance spectroscopy (MRS) provides a...

CD36 Transgenic and Knockout Mice Models

Transgenic mice with muscle-targeted CD36 overexpression were generated by insertion of a CD36 gene under control of the muscle creatine kinase promoter 112 . The metabolic phenotype of these mice is consistent with greater peripheral FA utilization. These mice have less body fat and lower serum FA, triglyceride, and cholesterol. Blood glucose is significantly increased, while insulin levels are similar in the fed state and higher in the fasted state. Soleus muscle from these mice displays an enhanced ability to oxidize FA in response to stimulation contraction.

Mrs In The Developing Brain

Aside from differences of metabolite levels in different regions of the brain (decreased NAA in white matter and lower creatine in white matter (38), the evaluation of proton MR spectra in the pediatric patient is complicated by known developmental changes in metabolites. As such, quantified changes in spectra should be compared with known age-matched and regional controls to avoid misinterpretation of what may be normal changes in metabolite content. Reference to published quantitative data of normal individuals may be helpful in these regards (18,39). Regional NAA increases occur in concordance with neuronal density and myelination, which are seen in higher amounts in the thalami early, with subsequent increase in the occipito-parietal and periventricular white matter afterward (40). Newborn NAA is observed to be almost half that of adult values, with subsequent increase to adult levels. As a marker of cell membrane turnover and lipid metabolism, increased choline and myoinositol is...

Phase I Studies In Human Volunteers

In this study, exercise tolerance and diffusing capacity were similar to baseline after either autologous blood transfusion ( 150g Hb) or infusion with HBOC-201 ( 45 g Hb). Blood pressure was slightly higher ( 5mmHg) during the administration of HBOC-201 with a commensurate increase in total peripheral resistance, generally within the first 4 hours. Cardiac index declined during treatment with HBOC-201 ( 0.51 min M2) and pulse rate was about 5-10 beats lower.There were small but transient increases in alanine aminotransferase, aspartate aminotransferase, 5'-nucleotidase, lipase and creatine kinase after treatment with HBOC-201. Adverse events were mild and infrequent. Plasma lactate levels were lower and oxygen uptake and carbon dioxide production were greater after infusion with HBOC-201 than after blood transfusion, suggesting that HBOC-201 may promote improved oxygen metabolism at the cellular level. Furthermore, under the conditions of this study, a 45-g dose of HBOC-201...

Gg4g26624

Bioimaging is in the forefront of medicine for the diagnosis and treatment of neurodegenerative disease. Conventional magnetic resonance imaging (MRI) uses interactive external magnetic fields and resonant frequencies of protons from water molecules. However, newer sequences, such as magnetization-prepared rapid acquisition gradient echo (MPRAGE), are able to seek higher levels of anatomic resolution by allowing more rapid temporal imaging. Magnetic resonance spectroscopy (MRS) images metabolic changes, enabling underlying pathophysiologic dysfunction in neurodegeneration to be deciphered. Neurochemicals visible with proton H MRS include N-acetyl aspartate (NAA), creatine phosphocreatine (Cr), and choline (Cho) NAA is considered to act as an in vivo marker for neuronal loss and or neuronal dysfunction. By extending imaging to the study of elements such as iron elevated in several neurodegenerative diseases laser microprobe studies have become extremely useful, followed by X-ray...

The clinical problem

In the early 1990s, studies showed, for the first time, that creatine kinase (CK)-MB (mass) and troponins were frequently elevated in patients considered at the time to have presented with unstable angina, and that these elevations are associated with an adverse prognosis (4-6). Since then, markers of myocardial damage in general, and the troponins in particular, have become central elements in early risk assessment of patients with NSTEACS.

Mrs In Parkinsonism

Most clinical MRS studies have concentrated on the metabolites visible with proton (1H) spectroscopy and measured in single, localized tissue volumes in the brain. The metabolites of interest that can be most readily studied with 1H-MRS at long echo times include N-acetyl aspartate (NAA), creatine phosphocreatine (Cr), and choline (Cho). Altered neuronal membrane synthesis and degradation can produce changes in Cho (53). NAA is contained almost exclusively within neurons (54) and is therefore considered to act as an in vivo marker of neuronal loss or dysfunction. Reduced regional NAA concentration has been reported in conditions characterized by neuronal or axonal loss (55-59). Most frequently, NAA measurements have been based on the regional NAA Cr ratio. The rationale for the use of the Cr resonance as the denominator is based on the concept that creatine and phosphocreatine are in chemical equilibrium and that the total concentration of both compounds is expected to...

Cardiac Troponin

As a more sensitive biomarker of myocardial inury, cardiac troponin is elevated more frequently than creatine kinase (CK) or CK-MB in patients with PE. The release oftropo-nin in patients with PE is often quantitatively small, far less than typically observed in an ST-elevation MI (10). The release of troponin in this setting most likely results from acute RV pressure overload, impaired coronary blood flow, and severe hypoxemia that cause micronecrosis of the right ventricle.

Muscle Development

Differentiation to become mature muscle fibers (72). This process is under precise control through the interaction of muscle cells with the extracellular environment. Growth factors like FGF-2 and TGF-(3 are strong stimulators or inhibitors of muscle cell proliferation and differentiation, and interact with the cell by binding to proteoglycans. Syndecans-1 through -4 have been identified in skeletal muscle (42,73,74). In vitro studies with C2Q2 mouse skeletal muscle cells have shown that syndecan-1, syndecan-3, and syndecan-4 are down-regulated with muscle differentiation with expression being higher during the proliferation stage. Syndecan-2 expression remained constant during both in vitro muscle cell proliferation and differentiation. Larrain et al. (75) showed that C2Ci2 cells overexpressing syndecan-1 had a 6- to 7-fold increase in fibroblast growth factor responsiveness and a corresponding decrease in the expression of, myogenin, creatine kinase, and myosin, key factors...

Implementation

For these patients as creatine-kinase myocardial band (CK-MB) and, in particular, the troponins I (Tnl) and T (TnT) allow risk stratification to be performed expeditiously 16 . A collaborative relationship between emergency physicians and labo-ratorians can ensure a consistent and effective evaluation of patients in the CPU.

Case Scenario

Joe Smoker is an overweight 57-year-old white male who was mowing his lawn when he experienced a sharp chest pain along with pain in his left arm. His wife rushed him to the hospital, fearing that he was having a heart attack. In the clinic, the physician examined Joe and sent him for electrocardiogram (ECG) and blood work. The blood is processed in the clinical laboratory and the serum is tested for troponins, creatine kinase (CK), and creatine kinase isoenzyme MB (CK-MB).

Cardioplegia

Elert and Otterman (1979) perfused dog hearts with a solution of pyridoxylated hemoglobin and electrolytes. They induced cardiac arrest with this solution, and measured ATP and phospho-creatine. They were able to show a 20-minute gain in the length of time for which hearts could be stopped, and they had no difficulty in restarting them. On histologic examination, they found less endothelial swelling than in those hearts perfused without hemoglobin.

Sarcopenia

The causes of sarcopenia are multifactorial (Table 3). Aging itself is associated with a decline in physical activity. Small increases in cytokines, especially interleukin (IL)-6, have been implicated in the proteolysis of muscle involved in the pathophysiology of sarcopenia 32 . Decreased food intake can lead to loss of muscle protein, as it is broken down for use in more essential proteins. The amino acid creatine is found only in meat and is essential for muscle function. Older persons who are anorectic or vegetarian have inadequate crea-tine intake for muscle maintenance. Decreased creatine intake Peripheral vascular disease Hypogonadism Cytokine excess Myostatin excess

Crinoidea

Nitrogenous compound (NH2.C NH .N CH3 .CH2.COOH), derivative of arginine, glycine and methionine reversibly pho-sphorylated to phosphocreatine (see Fig. 33), which transfers its phosphate to ADP via the enzyme creatine kinase. Found in muscle. Its anhydride breakdown product, creatinine, is excreted in mammalian urine. See phosphagen, muscle contraction. Creatinine. See creatine .

Statins

Statins are well absorbed after administration orally, and are metabolised in the liver. They are well tolerated, the commonest adverse effect being transient, and usually minor abnormality of liver function tests in some 1 of patients. Asymptomatic elevation of muscle enzymes (creatine phos-phokinase, CPK) and myositis (with a generalised muscle discomfort) occur more rarely,5 but is more frequent when statins are combined with other anti-hyperlidaemic drugs such as fibrates and nicotinic acid patients should be counseled about myositis when these drugs are co-administered. Myositis is also more likely with co-administered anti-HIV protease inhibitors, and with drugs that interfere with metabolism of some statins, e.g. ciclosporin.

Additional Agents

Adenosine 5'-triphosphate has been studied with some evidence of benefit in patients with advanced lung cancer 160, 161 . Another way of increasing high-energy phosphate compounds may be by supplementing with oral creatine. This is recognised as having beneficial effects in certain types of athletic performance (although there are conflicting reports 162, 163 ), and in a clinical study of older men it improved their muscular performance 164 . There have been some concerns over safety, which has been reviewed recently 165 .

Diagnostic value

Confidence interval, 83 -94 ), similar to prior reported studies. As would be expected, patients who had negative MPI had small MIs as estimated by peak creatine kinase (CK) values, with an average CK of 313 + 227 U L, compared with 590 + 620 U L (P < .001) in those who had positive MPI 19 .

Other Agents

Tion, despite the fact that it has not yet been studied in cancer patients, is creatine. Commonly used by 'body builders', creatine is about to undergo active clinical investigation for the cancer anorexia weight loss syndrome. In a collaborative trial, the North Central Cancer Treatment Group and the National Cancer Institute of Canada are about to open a phase III, placebo-controlled trial to study this amino acid derivative. Although potential mechanisms of action have not been well characterised, over 50 clinical trials have investigated creatine supplementation in other disease settings. Empiric observations suggest that creatine merits testing in the clinical setting in cancer patients and in aggregate can be summarised with the five following observations 30,31 . First, creatine supplementation is associated with weight gain, including augmentation of lean tissue, in healthy individ-

Muscle Energetics

Deep in muscle tissue, key components have been stored for this moment. Adenosine triphosphate (ATP), the fundamental energy source for muscle cells, is at maximal levels. Also stored are significant amounts of creatine phosphate and glycogen. Initial replenishment of ATP occurs through the transfer of creatine phosphate (CP) into creatine. The resting muscle contains 4 to 6 times as much CP as it does ATP, but the total supply of high-energy phosphate cannot sustain muscle activity for more than a few seconds. When sufficient oxygen is available (aerobic conditions), either in muscle tissue or elsewhere, these processes are reversed. ATP is reformed from ADP and AMP (adenosine monophosphate), CP is reformed from creatine and phosphate (P), and glycogen is reformed from glucose or lactic acid. Energy for these processes is derived from the complete oxidation of carbohydrates, fatty acids, or amino acids to form carbon dioxide and water. These reactions can be summarized by the...

Tvt T1

Transcutaneous Pacing

In more than 40 years of experience, complications related to transcuta-neous pacing have been extraordinarily rare. Although limited areas of focal myofibrillar coagulation necrosis and perivascular microinfarcts have been demonstrated in dogs undergoing transcutaneous pacing, no such lesions have been described in humans.9 Transcutaneous pacing produces no measurable release of myoglobin, myocardial creatine kinase, or myocardial lactate dehydrogenase in normal individuals.3 There are no reports of damage to skeletal muscle, lungs, myocardium, or skin (other than mild erythema and irritation) associated with transcutaneous pacing in humans. Caution has been suggested in using

S100a11

S100A1 is released into the blood during ischemic periods and can serve as a marker for myocardial ischemia together with creatine kinase isoenzymes, myoglobin, troponin I and T (Kiewitz et al., 2000a). Extracellular S100A1 was reported to be endocytosed into the endosomal compartment of neonatal rat cardiomyocytes and to inhibit apoptosis via activation of extracellular signalregulated protein kinase 1 2 (ERK1 2) (Most et al., 2003a). Endocytosed S100A1 was further demonstrated to result in decreased diastolic Ca2+-concentrations and a diminished SR Ca2+ load (Most et al., 2005). In rodent cardiomyocytes, the extracellular application and subsequent endocytotic internalization of S100A1 resulted in increased L-type Ca2+ currents (IC+), accelerated fast inactivation kinetics of IC+ and a shift of the I V relationship of lC+ to negative potentials (Reppel et al., 2005).

Oxytocin

Amount of oxygen needed to oxidize the la c ti c a c i d produced in the anaerobic work done by muscle during vigorous exercise, and to resynthesize creatine phosphate used (see phos-ph agen) . Until then, oxygen intake remains above normal while lactic acid remains in the muscle and blood. May be oxidized to pyruvic acid, converted to carbohydrate by the liver in g llico neo -gene si s, or neutralized by blood bicarbonate- b uf fer and excreted 'as sodium lactate by the kidneys.

Abdominal aneurysm

Several published studies (Ma et al., 1997 Moreira et al., 1997 Wolthuis et al., 1999) have examined the effects of HBOC-201 on routine clinical laboratory tests however, since instruments and methodologies change as techniques are developed and advancements are made, these data should be verified with current instrumentation. Wolthuis et al. (1999) found that HBOC-201 did not interfere with routine hemocytometry, hemostasis analysis or detection of RBC agglutination. HBOC-201 was found to affect direct bilirubin, creatine kinase MB-fraction, creatine kinase, gamma-glutamyl transferase, magnesium and uric acid analysis. A second study examined the concentration dependence of HBOC-201 interference on 22 chemistry tests performed with Ektachem Vitros and Hitachi analyzers (Moreira et al., 1997). Assays that were not color-dependent (sodium, potassium, chloride) were not affected by the presence of HBOC-201 in the specimens. Measurement of aspartate aminotransferase, calcium, urea...

H2no2s

Autonomic Instability

In subjects with normal renal function, a 800 mg dose of the drug increased the excretion of water, chlorine, magnesium, potassium, and sodium without altering creatine clearance (294). In normal volunteers, a dose of 400 mg of etozolin was equipotent to 75 mg of a thiazide diuretic 1200 mg was 2.8 times more effective than the 75 mg of the thiazide. Diuresis starts within 1-2 h after dosing, reaches a peak after 2-4 h, and then gradually decreases over the next 6 h (295). Because of the long-lasting effect of eto-zolin, the compound would seem indicated for the treatment of cardiac and renal edema as well as for the treatment of hypertension (294). In hypertensive patients after a period of 2 weeks, treatment with 400 mg of etozolin daily significantly reduces systolic and dia-stolic blood pressure. The drug was introduced in 1977 as Elkpain.

Biochemical markers

Creatine kinase, single and serial measurements There is a large amount of evidence on creatine kinase (CK) as a single test administered at presentation to patients in the ED (see Tables 1 and 2) 57 . The evidence suggests that the sensitivity of a single CK reading for AMI is low (36 ), and specificity is modest (88 ). Limited evidence suggests that the sensitivity of the test depends on the duration of the patient's symptoms sensitivity increases with longer symptom duration. Test performance across studies did not appear to vary by type of hospital, inclusion criteria, AMI prevalence, or test threshold. Creatine kinase subunit, single and serial measurements

Chd Risk Factors

When lifestyle modifications are not enough to reach the LDL goal, multiple lipid-lowering medications are available. Table 46-2 lists their effects on lipids and their potential side effects. Side effects of statins are uncommon but include myopathy, which may manifest as muscle tenderness with elevated creatine kinase levels and may progress to rhabdomyolysis. Less commonly, elevated liver enzymes, or even severe hepatitis, has been reported. When these drugs are used, routine clinical or laboratory monitoring for these effects is advisable.