OBJECTIVETo study the effect of energy therapy on Ca2+ concentration and Ca2+ -ATP enzyme activity in rat master muscle after unilateral chew, and to discuss the protective action of the exogenous creatine phosphate on rat masseter muscle after unilateral chew.

METHODSThe 20 rats were randomly divided into 4 groups, A: Creatine phosphate normal control group; B: Creatine phosphate experimental group; C: Saline normal control group; D: Saline experimental group. The Ca2+ concentration were determined by atomic absorption spectrophotometry, the activity of the Ca2+ -ATP enzyme were determined by super-micro volume Ca2+ -ATP enzyme kit.

RESULTS(1) The Ca2+ concentration of the extraction side of group D which received the saline injection had significant difference compared with the non-extraction side (P = 0.007), the group C (P = 0.009) and the extraction side of group B (P = 0.01); (2) Ca2+ -ATP enzyme activity of group D were higher than its non-extraction side (P = 0.001), group C (P = 0.003) and the extraction side of group B (P = 0.001); (3) The ultrastructural changes of the rat masseter muscle under transmission electron microscope were as follows: The extraction side of group D have more severe pathological manifestations than non-extraction side. Both the extraction side and the non-extraction side of group B had a similar manifestation to the normal control group.

CONCLUSIONExogenous energy material, creatine phosphate, may have certain degree of protective effect on rat masseter muscles after unilateral chew. And it may become a possible way to improve the injury of the masseter muscle.

Animals ; Calcium ; metabolism ; Calcium-Transporting ATPases ; metabolism ; Masseter Muscle ; physiopathology ; ultrastructure ; Mastication ; Microscopy, Electron, Transmission ; Phosphocreatine ; pharmacology ; Rats

It has been postulated that central nervous system disorders characterized by convulsive seizures are caused by alterations in one or more cerebral metabolism especially in cellular energy metabolism, electrolyte metabolism and glutamate metabolism. In the present study, alterations in cerebral energy metabolism, cellular electrolyte metabolism and glutamate metabolism were studied to investigate biochemical nature of cerebral disturbances in rats injected intraperitoneally with massive doses of penicillin. Also carried out were in vitro experiments by which direct effects of penicillin on concentrations of high energy compounds and Na+, K+-ATPase activity in the brains were determined. Intraperitoneal injections of pencillin G sodium(1,000,000 I.U. per kg body weight) to rats twice daily for 3 to 5 days resulted in significant decreases in cerebral concentrations of ATP, phosphocreatine and lactate, suggesting that penicillin induces cerebral dysfunctions by inhibiting energy production. While cerebral Na+, K+-ATPase activity and brain K+ content were significantly decreased in rats with penicllin-induced cerebral dysfunctions, brain Na+ and water contents were significantly increased. Observations that, in rats with penicillin-induced cerebral dysfunctions, the fall in high-energy phosphate contents in the brain took place as rapidly as the cation shifts indicate that alterations in both energy metabolism and electrolyte metabolism in the brain may be responsible for cerebral dysfunctions induced by penicillin. These assumptions were further supported by the findings that Na+, K+-ATPase activity and high-energy phosphate contents in the isolated cerebral hemispheres were profoundly affected by the addition of penicillin to the medium in which in vitro experiment was carried out. While the activity of glutamine synthetase in the brain was increased in rats exhibiting cerebral dysfunctions induced by penicillin, the activity of glutamine dehydrogenase was significantly decreased. Significance of changes in activities of these two brain enzymes in penicillin-induced cerebral dysfunctions was not immediately understood. It may be possible, however, that penicillin may influence glutamate contents in the brain directly orindirectly through the alteration of these two brain enzyme activities so as to modify the cerebral functions.
Adenosine Triphosphate ; Animals ; Brain ; Central Nervous System Diseases ; Cerebrum ; Energy Metabolism ; Glutamate-Ammonia Ligase ; Glutamic Acid ; Glutamine ; Injections, Intraperitoneal ; Lactic Acid ; Metabolism ; Oxidoreductases ; Penicillins* ; Phosphocreatine ; Rats ; Seizures

Serum metabonomic profiles of the model of focal cerebral ischemia reperfusion is established with the suture-occluded method by Longa to study the effect of ginsenosides. In this study, 48 rats were randomly divided into six groups: sham-operated group, pathological model group, positive drug group(6 mg·kg~(-1)·d~(-1)) and high, medium, low-dose ginsenosides groups(200, 100, 50 mg·kg~(-1)·d~(-1)). They are given intragastric administration respectively with same amount of 0.5% CMC-Na,nimodipine and ginsenoside for 5 days. At 2 h after the final administration, the model was established with the suture-occluded method, and free radical-scavenging activity changes of ginsenoside were observed by maillard reaction, and Longa was possible used as a renoprotective agent-occluded method. At the end of 24 h after the reperfusion, the hemolymph of rats in each group was collected, and the ~1H-NMR spectrum was collected after being treated by certain methods, and analyzed by principal component analysis(PCA). Compared with sham-operated group, pathological model group showed significant increases in the levels of lactate, glutamate, taurine, choline, glucose and methionine, but decreases in the levels of 3-hydroxybutyrate and phosphocreatine/creatine in serum. After treatment with ginsenosides, lipid, 3-hydroxybutyrate and phosphocreatine/creatine were increased in the serum of ginsenosides group rats, but with decreases in lactate and glutamate. The results showed that ginsenosides could regulate metabolic disorders in rats with focal cerebral ischemia reperfusion, and promote a recovery in the process of metabolism. It's helpful to promote the metabolic changes in rats with focal cerebral ischemia reperfusion via ~1H-NMR, and lay a foundation to develop ginsenosides as a new drug to treat ischemic cerebral paralysis.
3-Hydroxybutyric Acid ; Animals ; Brain Ischemia/metabolism* ; Creatine ; Ginsenosides/pharmacology* ; Hemolymph ; Metabolome ; Phosphocreatine ; Proton Magnetic Resonance Spectroscopy ; Random Allocation ; Rats ; Reperfusion Injury/metabolism*

This study was performed to assess the accuracy of 31P magnetic resonance spectroscopy(MRS) in the evaluation of myocardial ischemia in cats. Twelve cats underwent myocardial ischemia and reperfusion induced by 90 minutes ligation followed by 90 minutes recirculation of the left anterior descending coronary artery (LAD). MRS was performed using a 4.7T Biospec MRS/MRI system (Bruker, Switzerland). An inner diameter 1.5cm-sized doubly tuned surface coli was used for the collection of the MR signal. The coli was implanted to the epicardial surface at the expected area of infarction. 31P MRS was acquired before and during the periods of ischemia and reperfusion with 5-minute to 30-minute of intervals. After completion of the 31P MRS study, animals were sacrificed and the hearts were excised for 2,3,5-triphenyl tetrazolium chloride (TTG0 histochemical staining. The area of infarct was measured on the photographs of TTG stained heart slices using a computer programmed planimetry and the results were compared with those of the 31P MRS study. The level of phosphocreatine (PCr) was decreased to 28.2±6.9% of the baseline level 90 minutes after occlusion and recovered to 43.8±4.8% of the baseline level at the end of the reperfusion. A 50% depletion of PCr was reached 5 minutes after the LAD occlusion. The ATP was decreased to a 26.6±3.6% of the baseline level 90 minutes after occlusion and recovered to a 35.9±6.0 of the baseline level 90 minutes after reperfusion. The decreasing rate of ATP was slower than that of PCr showing a 50% of depletion 15 minutes after occlusion. The PCr/ATP ratio was 1.16±0.09 at the baseline, decreased to 0.88±0.07 at 30 minutes of occlusion, and then progressively increased during the late ischemic and reperfused periods. The ratio of the infarcted area to the effective signal area of the surface coli was inversely correlated to the ATP (r=0.68) and PCr (r=0.40) levels obtained at the end of reperfusion. In conclusion, 31P MRS reflects the changes in myocardial high energy phosphorous metabolism during the actue ischemia and reperfusion. If on adequate localization technique is feasible, 31P MRS can be used clinically in the diagnosis and monitoring of the patients with acute myocardial infarction.
Adenosine Triphosphate ; Animals ; Cats* ; Coronary Vessels ; Diagnosis ; Heart ; Humans ; Infarction ; Ischemia ; Ligation ; Metabolism ; Myocardial Infarction* ; Myocardial Ischemia ; Phosphocreatine ; Polymerase Chain Reaction ; Reperfusion ; Spectrum Analysis*

Patients with chronic renal failure(CRF) suffer from muscular dysfunction of varying degrees. 31P-nuclear magnetic resonance(NMR) spectroscopic studies of skeletal muscle have shown that these patients have less energy reservoir. Chronic metabolic acidosis has been known to decrease intracellular pH in rat muscle. We investigated the effect of correction of metabolic acidosis with sodium bicarbonate on muscle energy metabolism. Eight patients(6M, 2F) with CRF(creatinine clearance <20ml/min/1.73m2) who were clinically stable and had serum bicarbonate level less than 18mEq/L were included. The median age was 48 years (range; 29-56 years). The patients were treated with daily doses of 3 gram sodium bicarbonate for 3 months. Phosphocreatine to inorganic phosphate ratio(PCr/Pi) and intracellular pH were measured with 31P-NMR spectroscopy, at resting, nadir and maximum recovery state after all-out exercise, before and after correction of acidosis. Plasma bicarbonate level increased from 16.2+/-0.9 to 21.9+/-1.1mmol/L(p<0.05). Creatinine clearance, hematocrit and serum albumin did not change during the study period. The exercise capacity, as measured by the time holding the weight, did not improve with sodium bicarbonate treatment. PCr/Pi ratio at resting state was 7.0+/-1.9 before treatment, which did not change after treatment, 6.2+/-0.8, although plasma bicarbonate level increased significantly. The ratio reached bottom immediately after the all-out exercise(the nadir state) and then recovered toward preexercise value. The PCr/Pi ratio at nadir and maximum recovery state were not different between before and after treatment. The intracellular pH became more acidotic immediately after exercise, but no difference was found between before and after sodium bicarbonate treatment in resting state, nadir or maximum recovery state. With our results, we conclude that the partial correction of acidosis does not improve energy reserve and serum albumin in CRF patients.
Acidosis* ; Animals ; Creatinine ; Energy Metabolism* ; Hematocrit ; Humans ; Hydrogen-Ion Concentration ; Kidney Failure, Chronic* ; Muscle, Skeletal ; Phosphocreatine ; Plasma ; Rats ; Serum Albumin ; Sodium Bicarbonate ; Spectrum Analysis

OBJECTIVEThis study examined the biochemical metabolism by proton magnetic resonance spectroscopy ('H-MRS) in order to explore the value of 'H-MRS in idiopathic epilepsy in children.

METHODSThirty-three children with idiopathic epilepsy (14 cases with history of febrile seizures and 19 cases without) and six normal controls experienced MRI of the skull and brain and single-voxel 'H-MRS examinations of the hippocampi-temporal lobe. The signal intensities of N-acetylaspartate (NAA), eatine+phosphocreatine (Cr), choline-containing compounds (Cho) and lactate (Lac) and the ratios of NAA/ (Cho+Cr) and Lac/Cr were compared between the patients and normal controls.

RESULTSMRI examination showed that only one child with epilepsy had myelin dysplasia. 'H-MRS examination showed that the ratio of NAA/ (Cho+Cr) in the epilepsy group was lower than that in the control group (0.64+/-0.07 vs 0.73+/-0.05; P<0.01). The epileptic children with history of febrile seizures had a more decreased ratio of NAA/ (Cho+Cr) compared with those without the history (0.61+/-0.07 vs 0.66+/-0.06; P<0.05). There were no significant differences in the ratio of Lac/Cr between the epilepsy and the control groups.

CONCLUSIONS'H-MRS may provide early information on brain injury sensitively and non-invasively in children with epilepsy. It may be used for diagnosis and prognosis evaluation of epilepsy.

Aspartic Acid ; analogs & derivatives ; analysis ; Child ; Child, Preschool ; Choline ; analysis ; Epilepsy ; diagnosis ; metabolism ; Female ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; methods ; Male ; Phosphocreatine ; analysis ; Protons

This study was conducted to investigate the metabolic changes in the motor and motor association cortices following axonal injury in the internal capsule that was caused by deep intracerebral hematoma. Using proton magnetic resonance spectroscopy (1H MRS), the authors studied the primary motor cortices (M-1) and sup-plementary motor areas (SMA) of 9 hemiparetic patients with documentable hemi-paresis of varying severity, and we studied 10 normal volunteers as controls. To measure the M-1 and SMA biochemical changes, 4 separate single volumes of inter-est(VOIs) were located bilaterally in the affected and unaffected hemisphere (AH and UH).1H MRS provided a neuronal and axonal viability index by measuring levels of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr). The M-1/SMA NAA/Cr ratios of the AH and UH in patients, and the AH and normal volunteers were com-pared. The NAA/Cr ratios of the M-1 and SMA in AH, and the SMA in UH were sig-nificantly lower than those of normal volunteers. These 1H MRS findings indicate that axonal injury in the descending motor pathway at the level of internal capsule could induce metabolic changes in the higher centers of the motor pathway.
Adult ; Aged ; Aged, 80 and over ; Aspartic Acid/*analogs & derivatives/metabolism ; Basal Ganglia Hemorrhage/metabolism/*pathology ; Creatine/metabolism ; Female ; Humans ; *Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Motor Cortex/metabolism/*pathology ; Paresis/metabolism/*pathology ; Phosphocreatine/metabolism ; Protons ; Pyramidal Tracts/metabolism/*pathology

OBJECTIVE: The purpose of our study was to evaluate the postmortem interval with multi-voxel 1H-MR spectroscopy. METHODS: Twelve healthy rabbits were studied and the quantities of N-acetylaspartate, total choline, phosphocreatine and creatine were measured by 1H-MR spectroscopy after death at 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 h. RESULTS: The levels of Naa/Cr and Naa/Ch decreased following death, while the level of Ch/Cr increased initially and then decreased following death. CONCLUSION Multi-voxel proton MR spectroscopy for Naa/Cr and Ch/Cr metabolic ratio could be used in future postmortem interval studies.
Animals ; Aspartic Acid/metabolism* ; Biomarkers/metabolism* ; Brain/pathology* ; Choline/metabolism* ; Creatine/metabolism* ; Disease Models, Animal ; Embolism, Air ; Female ; Magnetic Resonance Spectroscopy/methods* ; Male ; Phosphocreatine/metabolism* ; Postmortem Changes ; Protons ; Rabbits ; Regression Analysis ; Time Factors

BACKGROUNDPhosphorous magnetic resonance spectroscopy ((31)P-MRS) has been successfully applied to study intracellular membrane compounds and high-energy phosphate metabolism. This study aimed to evaluate the capability of dynamic (31)P-MRS for assessing energy metabolism and mitochondrial function in skeletal muscle from type 2 diabetic patients.

METHODSDynamic (31)P-MRS was performed on 22 patients with type 2 diabetes and 26 healthy volunteers. Spectra were acquired from quadriceps muscle while subjects were in a state of rest, at exercise and during recovery. The peak areas of inorganic phosphate (Pi), phosphocreatine (PCr), and adenosine triphosphate (ATP) were measured. The concentration of adenosine diphosphate (ADP) and the intracellular pH value were calculated from the biochemistry reaction equilibrium. The time constant and recovery rates of Pi, PCr, and ADP were analyzed using exponential curve fitting.

RESULTSAs compared to healthy controls, type 2 diabetes patients had significantly lower skeletal muscle concentrations of Pi, PCr and β-ATP, and higher levels of ADP and Pi/PCr. During exercise, diabetics experienced a significant Pi peak increase and PCr peak decrease, and once the exercise was completed both Pi and PCr peaks returned to resting levels. Quantitatively, the mean recovery rates of Pi and PCr in diabetes patients were (10.74 ± 1.26) mmol/s and (4.74 ± 2.36) mmol/s, respectively, which was significantly higher than in controls.

CONCLUSIONSNon-invasive quantitative (31)P-MRS is able to detect energy metabolism inefficiency and mitochondrial function impairment in skeletal muscle of type 2 diabetics.

Adenosine Diphosphate ; analysis ; Adenosine Triphosphate ; analysis ; Adult ; Diabetes Mellitus, Type 2 ; metabolism ; Female ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged ; Mitochondria, Muscle ; metabolism ; Muscle, Skeletal ; metabolism ; Phosphates ; analysis ; Phosphocreatine ; analysis ; Phosphorus ; chemistry

This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.
Adenosine Triphosphate ; blood ; pharmacokinetics ; Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Biotransformation ; Cardiotonic Agents ; administration & dosage ; blood ; pharmacokinetics ; Creatine ; administration & dosage ; metabolism ; pharmacokinetics ; Erythrocytes ; metabolism ; Injections, Intravenous ; Male ; Phosphocreatine ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley