How To Take Creatine
The amount of evidence on creatine kinase (CK) as a single test administered at presentation to patients in the ED is large (21) (Tables 11 and 12). 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.
CK is an 85-kDa enzyme found in all striated muscle cells, where it catalyzes the phosphorylation of creatine to creatine phosphate. There are three isoenzymes of CK, each composed of two subunits (M and B) CK-MM, the predominant form in striated muscle (cardiac and skeletal) CK-MB, most common in the heart and CK-BB, most common in the brain but also found in the gut and kidney. Sensitivity for acute MI is greater than 90 by 6 h, and total CK may be detectable in the serum as early as 4 h after the onset of symptoms. Because assays for total CK detect all three isoenzymes, however, total CK is not cardiac-specific.
During sustained muscle activity, ATP may be used faster than it can be produced through cell respiration. At these times, the rapid renewal of ATP is extremely important. This is accomplished by combining ADP with phosphate derived from another high-energy phosphate compound called phosphocreatine, or creatine phosphate. Within muscle cells, the phosphocreatine concentration is more than three times the concentration of ATP and represents a ready reserve of high-energy phosphate that can be donated directly to ADP (fig. 12.22). Production of ATP from ADP and phosphocreatine is so efficient that, even though the rate of ATP breakdown rapidly increases from rest to heavy exercise, muscle ATP concentrations hardly change During times of rest, the depleted reserve of phosphocreatine can be restored by the reverse reaction phosphorylation of creatine with phosphate derived from ATP. Remember that Maria had a normal blood level of creatine phosphokinase.
Metabolism of glucose by the brain releases energy, and also generates neurotransmitters such as gamma amino butyric acid (GABA) and acetylcholine, together with phospholipids needed for cell membrane synthesis. When blood glucose concentration falls, changes in the synthesis of these products may occur within minutes because of reduced glucose metabolism, which can alter cerebral function. This is likely to be a factor in producing the subtle changes in cerebral function detectable at blood glucose concentrations as high as 3 mmol l, which is not sufficiently low to cause a major depletion in ATP or creatine phosphate, the brain's two main sources of energy (McCall, 1993). Isotope techniques and Positron Emission Tomography (PET) allow the study of metabolism in different parts of the brain and show regional variations in metabolism during hypoglycaemia. The neocortex, hippocampus, hypothalamus and cerebellum are most sensitive to hypoglycaemia, whereas metabolism is relatively...
The accumulation of lactic acid is the largest contributor (more than 60 ) to oxygen deficit, which allows short-term anaerobic metabolism to take place despite a relative lack of oxygen. Other depleted muscle oxygen stores have a smaller capacity but can still participate in oxygen deficit. The largest of these is the creatine phosphate pool (approximately 25 ). Tissue fluids (including venous blood) account for another 7 , and the protein myoglobin can hold about 2.5 .
Four limbs, but the woman does not complain of muscular soreness. She is somewhat underweight, slightly short of breath, and speaks in a low voice. Laboratory tests show a moderately elevated creatine kinase level. There is no family history of muscle problems, and she is not currently taking any medication.
High-resolution XH NMR spectroscopic analysis of biofluids has proved to be one of the most powerful techniques for the investigation organism response to xenobiotics. Exposure of an organism to a xenobiotic results in subtle modifications in the biochemical composition of intra- and extracellular fluids as the organism attempts to maintain homeostasis (constancy of internal environment). This metabolic adjustment involves altering the composition of body fluids such as urine and plasma, and this change in biochemical composition can be rapidly profiled with XH NMR spectroscopic analysis. XH NMR spectral profiles of biofluids provide a unique fingerprint of the metabolic state of an organism, and can provide information on the nature of a drug or toxin to which an animal has been exposed 1,57,52-55 . The site or basic mechanism of toxicity can often be determined from characteristic changes in the concentrations and patterns of endogenous metabolites in biofluids (Figure 5.2). For...
The chemical shift of the nucleus of interest, therefore, provides biochemical information about its environment. A typical proton spectrum is shown in Fig. 2.3A. A chemical shift is seen in hydrogen nuclei from protons in fat, in metabolites such as choline, creatine, A'-acetyl-aspartate (NAA), and also from those in glutamate, lactate, and other substances. This provides the basis for the identification of these substances in living tissue. In a similar manner, a phosphorus spectrum provides information about important phosphorus-containing metabolites such as adenosine triphosphate (ATP) and phos-phoesters (Fig. 2.3B). Clinically relevant information is mostly obtained from this region of the proton spectrum.
However, when dietary measures have failed to normalize serum lipids, results from the landmark statin trials should make it abundantly clear that simple pharmacological interventions in those with low HDL, high LDL, or elevated triglycerides or TC may yield substantial reductions in cardiovascular morbidity and mortality. Nonetheless, undertreatment of hyper-lipidemia is an ongoing problem for many patients, even those without major mental illness who have established CHD (Smith 2000). Although mental health practitioners may not choose to institute lipid agents themselves, patients with established CHD or CHD-equivalent disorders (e.g., DM, severe atherosclerotic vascular disease) should be started on low-dose aspirin therapy (81 mg day, or one baby aspirin) this simple intervention has been proven to reduce important vascular events by 25 -33 (Braunstein et al. 2001). On the other hand, some psychiatrists may feel comfortable initiating treatment of hyperlipidemia under the...
After ruling out an AMI or an unstable angina, a graded exercise test (52) prior to discharge from the ED may assist in the diagnosis of coronary artery disease (CAD) and result in more appropriate referral (53-61). In a study of patients evaluated in a chest pain center located in the ED, 791 of 1010 patients underwent graded ECG exercise stress testing after 9 h of nondiagnostic serial ECG ST-segment trend monitoring 0-, 3-, 6-, and 9-h creatine kinase isoenzyme-cardiac muscle subunit (CK-MB) testing and resting echocardiography (41). None of the patients undergoing ECG exercise stress testing suffered an adverse event while being tested. Of these 791 patients, 782 (98.9 ) had a negative or nondiagnostic ECG stress test, and the positive predictive value was 44 (4 out of 9) for CAD. Thirty-day follow-up revealed a 0.1 AMI rate and 0.5 all-cause mortality rate. Two recent prospective studies have shown that this approach has high diagnostic accuracy and is cost-effective. In a study...
Beyond the importance of reestablishing TIMI 3 flow in the infarct-related artery, we became increasingly aware of the significance of the integrity of the microcirculation in immediate and long-term outcome after reperfusion therapy (68). In general, patients with acute MI experience a systemic hyperactivity of platelets, manifested by slower flow than normal in both the infarct and noninfarct arteries (69). Many retrospective analyses demonstrated worse outcome in patients with impaired microcirculation, even in the presence of adequate epicardial reperfusion (18,70-72). The no-reflow phenomenon typically results either from distal embolization of platelet and fibrin thrombus or from destruction of the capillaries by prolonged ischemia. Furthermore, there is spasm and endothelial dysfunction from secretion of vasoactive substances from embolized platelets, as well as reperfusion injury resulting from neutrophil and complement accumulation in the infarcted territory. Distal...
1H-MRS studies have also been carried out in Tg2576 83 and in PS2APP mice 74 . In vivo 1H spectra of the frontal cortex of 19-month-old Tg2576 mice revealed significant decreases of NAA and increased levels of taurine compared to wildtype control mice. Subsequent in vitro MRS in corresponding areas of the cortex showed in addition decreased levels of glutamate and glutathione 83 . The decreased levels of NAA and the increased level of taurine are consistent with neuronal variability and increased glial volume, being equivalent to findings of decreased NAA and increased myo-inositol in human AD 82,84 . Taurine is much more concentrated in the rodent than in the human brain and may serve a similar role as myo-inositol in the human brain. Decreased NAA creatine and glutamate creatine ratios have been found in the frontal cortex of 24-month-old double-transgenic PS2APP mice compared to age-matched controls 74 . In a longitudinal study in the same model from age 4 to 24 months, the...
Magnetic resonance spectroscopy is a new technique that may be helpful in both diagnosing brain tumors in children and during follow-up investigations. This technique is able to distinguish between malignant tumors and areas of necrosis by comparing creatine choline ratios with N-acetyl aspartate choline ratios. This technique in combination with tumor characteristics as identified by MRI, tumor site, and other patient characteristics may be able to more accurately predict the tumor type preop-eratively. In addition, it may be helpful in identifying postoperatively residual tumor from postoperative changes.
The b-blockers were among the first therapeutic interventions designed to limit the size of an AMI. In most of these studies, all patients with AMI were included together regardless of the direction of the ST-segment deviation on admission. Norris and colleagues in New Zealand (11,12) demonstrated in 1978 that early administration of b-blockers decreased the size of AMI measured enzymatically (as a function of creatine-kinase
HEP levels as indicator of tissue state have been shown to be of limited value due to highly efficient regulatory mechanisms only severe metabolic stress will lead to observable changes of HEP steady-state levels. As long as their synthesis rate accounts for the energy consumption, HEP levels will remain unchanged. HEP turnover, on the other hand, has to match the demands of tissue function thus, a direct assessment of turnover rates provides superior information. This has been demonstrated in normal rat brain exposed to various workloads. while cerebral steady-state ATP levels were not different for pentobarbital and isoflurane anesthetized rats and animals with mild epileptic seizures following administration of the 7 -butyric amino acid A (GABAa) receptor antagonist bicuculline, there was a high correlation between the forward rate constant, kf, for the creatine kinase reaction as a measure for ATP turnover, and the cerebral energy consumption as reflected by the integrated...
Postoperative surveillance for the development of cardiac ischemia or myocardial infarction is required for patients at high risk for these complications. Although creatine kinase levels are usually elevated in these patients because of the muscle trauma associated with surgery, serial electrocardiograms and determination of creatine kinase isoenzymes are useful in the detection of interval ischemia.
Today, MRS represents a most valuable clinical tool, due mainly to the rapid availability of data. For example, determining metabolite concentrations are vital when diagnosing many diseases, with proton spectra of the brain being used to monitor levels of N-acetyl-aspartate, creatine, phosphocreatine, trimethylamines, myo-inositol and amino acids associated with neuronal tissue loss in dementia and other brain diseases. In this respect, metabolic changes in the brain can be mapped using functional magnetic resonance spectroscopy (fMRS) imaging techniques, while multimodal imaging using electromagnetic, metabolic, and hemo-dynamic activity will increase our understanding of brain function and provide new means of experimental validation in neuroscience.
Optimal length (lo) creatine phosphate oxygen debt muscle fatigue central command fatigue fast fiber slow fiber oxidative fiber myoglobin Describe the effect of increasing the load on a skeletal-muscle fiber on the velocity of shortening. What is the function of creatine phosphate in skeletal-muscle contraction
Skeletal muscles generate ATP through aerobic and anaerobic respiration and through the use of phosphate groups donated by creatine phosphate.The aerobic and anaerobic abilities of skeletal muscle fibers differ according to muscle fiber type, which are described according to their speed of contraction, color,and major mode of energy metabolism.
C Celsius (centigrade), creatine, cytosine, carbon, capillary, cervical C clearance, concentration Ca calcium (Ca2+ calcium ion) cal calorie monophosphate CGRP calcitonin gene-related peptide C intracellular concentration CK creatine kinase CL lung compliance Cl chlorine (Cl_ chloride ion) cm centimeter CNS central nervous system CO carbon monoxide, cardiac output Co extracellular concentration CO2 carbon dioxide CoA coenzyme A CP creatine phosphate CPK creatine phosphokinase CPR cardiopulmonary resuscitation Cr creatinine
There are three ways a muscle fiber can form ATP during contractile activity (Figure 11-26) (1) phosphorylation of ADP by creatine phosphate, (2) oxida-tive phosphorylation of ADP in the mitochondria, and (3) substrate-level phosphorylation of ADP by the gly-colytic pathway in the cytosol. Phosphorylation of ADP by creatine phosphate (CP) provides a very rapid means of forming ATP at the onset of contractile activity. When the chemical bond between creatine (C) and phosphate is broken, the amount of energy released is about the same as that released when the terminal phosphate bond in ATP is broken. This energy, along with the phosphate group, can be transferred to ADP to form ATP in a reversible reaction catalyzed by creatine kinase Creatine kinase Although creatine phosphate is a high-energy molecule, its energy cannot be released by myosin to drive cross-bridge activity. During periods of rest, muscle fibers build up a concentration of creatine phosphate approximately five times...
Although ATP is the immediate fuel for the contraction process, its concentration in the muscle cell is never high enough to sustain a long series of contractions. Most of the immediate energy supply is held in an energy pool of the compound creatine phosphate or phosphocreatine (PCr), which is in chemical equilibrium with ATP. After a molecule of ATP has been split and yielded its energy, the resulting ADP molecule is readily rephosphorylated to ATP by the high-energy phosphate group from a creatine phosphate molecule. The creatine phosphate pool is restored by ATP from the various cellular metabolic pathways. These reactions (of which the last two are the reverse of each other) can be summarized as follows used, the ATP concentration has fallen by only 10 . This situation results in a steady source of ATP for contraction that is maintained despite variations in energy supply and demand. Creatine phosphate is the most important storage form of high-energy phosphate,- together with...
Coenzyme Q10 is given to substitute and supplement for endogenous coenzyme Q. Idebenone, a quinone compound similar to coenzyme Q10, has the theoretical advantage of crossing the blood-brain barrier. Vitamin C and vitamin K3 (menadione) are given to bridge a defect in the electron transport chain, as they accept and transport electrons. These drugs are given alone or in varying combinations. In patients with MELAS variable improvement has been reported, ranging from none to remarkable, but evidence for a consistent beneficial effect is lacking. Dichloroacetate inhibits the pyruvate dehydrogenase specific kinase, thereby activating the pyruvate dehydrogenase complex and reducing lactate levels. Oral creatine supplementation has been reported to lead to clinical improvement in incidental patients. Intravenous administration of L-arginine during acute stroke has also been reported to lead to improvement.
Acute and Chronic Exercise Increases Insulin Sensitivity Insulin Receptor Density and Glucose Transport into Muscle
Though skeletal muscle is omnivorous, its work intensity and duration, training status, inherent metabolic capacities, and substrate availability determine its energy sources. For very short-term exercise, stored phosphagens (ATP and creatine phosphate) are sufficient for crossbridge interaction between actin and myosin, even maximal efforts lasting 5 to 10 seconds require little or no glycolytic or oxidative energy production. When work to exhaustion is paced to be somewhat longer in duration, glycolysis is driven (particularly in fast glycolytic fibers) by high intramuscular ADP concentrations, and this form of anaerobic metabolism, with its by-product lactic acid, is the major energy source. The carbohydrate provided to gly-colysis comes from stored, intramuscular glycogen or blood-borne glucose. Exhaustion from work in this intensity range (50 to 90 of the maximal oxygen uptake) is associated with carbohydrate depletion. Accordingly, factors that increase carbohydrate availability...
Given that hypoxia likely triggers an increase in cellular AMP levels, it seems possible that the AMP-activated protein kinase (AMPK) may play a role in regulating the activity of 02-sensing cells. AMPK is a multi-substrate serine threonine kinase, which acts as a metabolic sensor and modulates many aspects of cell metabolism in eukaryotes (37,47). AMPK effectively detects metabolic stress through changes in the local ATP AMP ratio, and may be activated by vigorous exercise, nutrient starvation and hypoxia (37,47). AMPK is an a, 3,Y heterotrimer, and its activity is increased 2-4 fold by the association of AMP with an allosteric site. However, the AMPK activity is also regulated by an upstream kinase, namely AMPK kinase (39). AMPK kinase is also activated by AMP and regulates AMPK by phosphorylation of Thrl72 within the activation loop of the AMPKasubunit(37, 47). In response to hypoxia, AMPK acts to maintain ATP levels with the minimum amount of 02utilization. AMPK does so by...
Creatinine is an end-product of muscle metabolism, a derivative of muscle creatine phosphate. It is produced continuously in the body and is excreted in the urine. Long urine collection periods (e.g., a few hours) can be used because creatinine concentrations in the plasma are normally stable and creatinine does not have to be infused consequently, there is no need to catheterize the bladder. Plasma and urine concentrations can be measured using a simple colorimetric method. The endogenous creatinine clearance is calculated from the formula
Other laboratory investigations are helpful in defining organ system involvement (e.g., creatine phosphokinase and aldolase in patients with weakness and possible myositis, or urinalysis and serum creatinine to screen for renal involvement), or monitoring for toxicities of ongoing therapies.
Phosphate is an important intracellular buffer, however, for two reasons. First, cells contain large amounts of phosphate in such organic compounds as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and creatine phosphate. Although these compounds primarily function in energy metabolism, they also act as pH buffers. Second, intracellular pH is generally lower than the pH of ECF and is closer to the pKa of phosphate. (The cytosol of skeletal muscle, for example, has a pH of 6.9.) Phosphate is, thus, more effective in this environment than in one with a pH of 7.4. Bone has large phosphate salt stores, which also help in buffering.
Fascioscapulohumeral dystrophy is an autosomal dominant disease that affects female and male subjects equally. The usual age of onset is between 9 and 20 years, although adult onset has been recognized. The symptoms vary in severity thus, diagnosis may be difficult. Shoulder-girdle weakness and winged scapulae are usually the first findings. Facial muscles are involved and may be the first muscles affected in some patients. The face is flattened, and the mouth moves asymmetrically, unable to pucker or whistle. Axial and pelvic muscles may become involved late in the disease however, distal muscles are usually spared. Cardiac disease is rare, and patients usually live a normal life span. Serum muscle enzymes may be elevated slightly, and elevated urinary creatine is common.
Creatine kinase (or creatine Different organs, when they are diseased, may liberate different isoenzymatic forms of an enzyme that can be measured in a clinical laboratory. For example, the enzyme creatine phosphokinase, abbreviated either CPK or CK, exists in three isoenzymatic forms.These forms are identified by two letters that indicate two components of this enzyme. One form is identified as MM and is liberated from diseased skeletal muscle the second is BB, released by a damaged brain and the third is MB, released from a diseased heart. Clinical tests utilizing antibodies that can bind to the M and B components are now available to specifically measure the level of the MB form in the blood when heart disease is suspected. Remember that Tom had elevated blood levels of the MB isoform of creatine phosphokinase.
Creatine kinase (CK) and aldolase are the most common and sensitive indicators of muscle damage. Either may be elevated exclusively. In general, the CK level should be checked first and aldolase measured as needed if the CK level is not elevated and clinical suspicion is high. In the face of intercurrent infection, trauma, fever, or use of cocaine or alcohol, the CK level may become dramatically elevated. Typically, after the insult has been eliminated, CK will return to the normal range within a few days.
CPK-MB, creatine phosphokinase isoenzyme CAD, coronary artery disease PTCA, purcutaneous transluminal coronary angioplasty MI, myocardial infarction LMWH, low-molecular-weight heparin MD, medical doctor D, change. CPK-MB, creatine phosphokinase isoenzyme CAD, coronary artery disease PTCA, purcutaneous transluminal coronary angioplasty MI, myocardial infarction LMWH, low-molecular-weight heparin MD, medical doctor D, change.
Trimethoprim is contraindicated in patients with a hypersensitivity to the drug and in those with a creatine clearance of less than 15 mL min. The drug is used cautiously in patients with hepatic or renal impairment and in patients with megaloblastic anemia caused by folate deficiency. Trimethoprim is classified as a Pregnancy Category C drug, and its use is not recommended during pregnancy and lactation.
In order to compare outcomes in PCI across device strategies, it is necessary to use a common vocabulary. Outcomes in percutaneous coronary interventions are categorized in three ways angiographic success, procedural success, and clinical success. Angiographic success refers to the achievement of a residual stenosis diameter less than 50 in the presence of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow as defined by the TIMI Trial (5). In the modern era of scaffolding technology such as stents, an additional term, optimal angiographic result, was created to describe the achievement of a postprocedural minimum stenosis diameter of less than 20 . Procedural success requires that angiographic success be coupled to the absence of specific complications during hospitalization (MI, emergent CABG, death). In order to standardize the definition of periprocedural MI, the current American College of Cardiology American Heart Association (ACC AHA) Guidelines for Percutaneous Coronary...
Folin was the first to use the Duboscq colorimeter in a clinical chemistry procedure. He published methods for urine creatinine and creatine in 1904 based on the colorimetric alkaline picric acid reaction (5,6). Prior to the Duboscq, colorimetric clinical chemistry assays were read by holding the test tubes with the unknowns up against a white background and color matching them against tubes containing standards or up against colored glass filters previously matched against liquid standards for that assay. The Duboscq colorimeter replaced this with a quantitative measure of the difference in color intensity between samples. In addition, because of its optical design, it improved the ability to distinguish between weak differences in intensity. (7) Folin, O. (1914) On the determination of creatinine and creatine in blood, milk and tissues. Journal of Biological Chemistry. 17(4) 475-481.
There is ample experimental and some clinical evidence of an antiarrhythmic effect of ACE inhibition. For example, captopril administered before the start of or at the end of experimentally induced ischemia in isolated rat myocardium reduces reperfusion-induced ventricular fibrillation and decreases purine outflow and peak creatine phos-phokinase levels during reperfusion (76). Similarly, in the closed chest pig model, captopril (continued beyond the acute phase of experimentally produced ischemia) decreases the inducibility of ventricular arrhythmia by programmed electrical stimulation performed 2 wk after MI (77).
ATP has limited mobility within cells, and thus tends to be concentrated around the sites of production, with the sites of production being close to primary sites of utilization. However, ATP translocation is enhanced, indirectly, by the phosphocreatine shuttle. A high-energy bond is transferred from ATP to creatine at the site of ATP production to yield phosphocreatine. The greater mobility of phosphocreatine allows for the transfer of the high-energy bond to ADP at relatively distant sites of utilization. This reversible process is known as the creatine kinase reaction (16), and is catalyzed by creatine kinase ATP + Creatine
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