The activities of CK and its isoenzymes were determined in the sera of six test subjects just before, and 6 and 24 h after, alcohol intake. The CK activity was higher after alcohol intake, but the change was not significant. CK-MB isoenzyme was not observed. The activities of CK and its isoenzymes were also determined in serum from 14 chronic alcoholics, who had consumed alcohol for several days before the blood sampling. Pathologically high activity of creatine kinase was found in six of them, but CK-MB and CK-BB isoenzymes were not found.

We have established previously that rat bone tissue, as well as rat and human-derived bone cells in culture, show a sex-specific response to gonadal steroids in stimulation of the specific activity of the BB isozyme of creatine kinase (CK) and DNA synthesis. This response could be modified by manipulation of the endocrine environment during early stages in rat development. To further examine the influence of changing hormonal steroid milieu and vitamin D status on the action of gonadal steroids in developing bone tissue, we used two models of ectopic bone formation: demineralized tooth matrix (DTM) implanted under the skin, and femoral bone marrow (BM) transplanted under the kidney capsule of a syngeneic recipient mouse. The response to gonadal steroids in ossicles developed from implanted DTM depended on the recipient's gender; injection of estradiol 17beta (E2; 5 microg) into young female mice 21 days after DTM implantation increased, 24 h later, CK activity in the newly formed ossicles by approximately 60%, whereas injection of dihydrotestosterone (DHT; 50 microg) had no effect on CK activity. In contrast, in male mice, DHT but not E2 increased CK activity in the ossicles by approximately 50%. This sex-specific response was abolished in gonadectomized mice resulting in a similar response of the ossicles to both E2 and DHT. When DTM was implanted into vitamin D- deficient female mice, there was a lower basal CK activity and a significantly diminished response to E2 in the newly formed bone tissues. When BM, which contains mesenchymal and stromal cells and committed osteoprogenitor cells, was transplanted into 6-week-old intact or gonadectomized female or male mice, the response of the newly formed bone ossicles, 21 days after transplantation, to E2 or to DHT was according to the gender of the donor. Bone formed from BM obtained from female mice responded to E2 only and those formed from male BM responded to DHT only. Ossicles developed from BM obtained from gonadectomized mice showed lack of response to either gonadal steroid. Furthermore, only approximately 25% of the BM transplants obtained from castrated (CAST) male donors developed into ossicles. Ossicles formed from BM obtained from vitamin D-deficient female donors showed lack of response to gonadal steroids. These findings suggest that the manipulation of the hormonal milieu in early stages of the differentiation sequence of bone cells modifies the subsequent selective responsiveness of the developing bone tissue to gonadal steroids.

By differentiation of creatine kinase isoenzyme activities in sera using immunological methods the published data about occurrence of creatine kinase BB activities in patients with different diseases or after surgical treatment, respectively, cannot be verified in general. With a frequency in the order of magnitude of 1 : 1000 in the serum of old patients (age 57 to 85 years with one exception), however, creatine kinase BB activities can be measured. The range of activities is 15 to 234 U/1, or 19 to 94% of total creatine kinase activities, respectively. At the present time there is no possibility to correlate this phenomenon to any specific disease. These cases are detected by abnormally high results of CK-MB activity measurements with the immunoinhibition test (range 60 to 202% of total creatine kinase activities) which lead to a repeated analysis using immunoprecipitation. The results of all CK-BB patients investigated till now are presented and discussed.

Creatine kinase (CK) activity was determined in the seminal plasma of 169 men divided in a) 11 groups according to etiological diagnosis of infertility and b) 2 groups on the basis of the normal or abnormal spermiogram. Electrophoretic separation of CK isoenzymes on agarose gel was also performed. We found that: 1) in seminal plasma enzyme activity is 4.2 times higher than the upper limit in normal serum, 2) CK activity in seminal plasma is exclusively due to the isoenzyme BB (CKCK activity and the variables of the spermiogram, as well as between enzyme activity and fructose or acid phosphatase in seminal plasma.

This study was designed to determine the effects of dexmedetomidine on perioperative myocardial injury by observing peripheral circulatory changes in response to tracheal intubation and extubation, myocardial enzyme levels, myocardial ischaemia improvements, cardiovascular adverse events and cytokines in patients with coronary heart disease (CHD) undergoing non-cardiac surgery. This study was a prospective, randomized, double-blind trial. Eighty patients having CHD were scheduled for elective hip-replacement surgery and randomly allocated to receive a loading dose of 1 μg/kg dexmedetomidine followed by a 0.2 μg/kg per h infusion (Dex group; n = 40) or normal saline (control group; n = 40). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, rate-pressure product and changes in ST-T segment on the electrocardiogram were recorded every 5 min during surgery. Serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), glycogen phosphorylase BB (GP-BB), interleukin (IL)-6 and tumour necrosis factor (TNF)-α protein levels were determined preoperatively, at the end of surgery and 12 and 24 h after surgery. The improvement rate of myocardial ischaemia was higher in the Dex than control group (87.5% vs 32.5%, respectively; P < 0.05). In addition, the Dex group had lower serum CK-MB, IL-6, cTnI and GP-BB concentrations than the control group (P < 0.05). There was no significance difference in TNF-α between the two groups (P>> 0.05). Dexmedetomidine can reduce myocardial injury and cytokine levels in patients with CHD undergoing non-cardiac surgery.

Serum creatine phosphokinase (CK) and alkaline phosphatase (ALP) rise after mesenteric infarction; it is not known which one rises earlier or which one has the greater elevation. This experiment compared and contrasted the elevations in both these enzyme systems after acute small bowel infarction. Isoenzymes of both systems were analyzed to determine if any qualitative changes occurred. After baseline blood samples had been drawn, 10 dogs had midline laparotomies under general anesthesia. Each was assigned to one of two groups according to a randomized block design. Controls (CON) were closed after exploration (N = 5). The infarction (INF) group had ligation and division of the arteries to the jejunum and ileum (N = 5). Blood samples were obtained from both groups at 3, 6, 9, 12, 24, and 27 hr after surgery. Sera were analyzed for total CK and ALP activity by automated spectrophotometry. Isoenzymes were determined by agarose gel electrophoresis. Serum CK rose faster and to a higher level than ALP after small bowel infarction (470 +/- 181 vs 196 + 28 IU/liter). CK-BB was a better marker of small bowel necrosis than was intestinal ALP. The elevation of both CK and ALP by 12 hr after infarction may be a diagnostic aid if similar changes occur in humans.

Enzymatic determinations in cerebrospinal fluid (CSF) of lactic dehydrogenase (LDH), creatine phosphokinase (CPK) and creatine kinase BB (CK-BB) were performed on 94 patients presenting with a range of disorders of the central nervous system. Enzyme results from 37 patients undergoing myelography were used as controls. The highest concentration of these enzymes appeared in patients with the most severe brain injury. In head-injured patients with a Glasgow Coma Score (GCS) of 3 to 7, only the CK-BB correlated with the degree of injury and with the ultimate outcome. Within the subgroup of spinal cord injuries none of the enzymes correlated with the severity of neurological injury. However, patients with acute spinal cord trauma who demonstrated CSF CK-BB values greater than 10 U/litre had never recovered. The present study confirms that CSF CK-BB seems to be a sensitive index of acute brain damage, but it reflects best the extent of CNS tissue disruption rather than the severity of neurological deficits.

Blood serum and cerebrospinal fluid from a 4.5-year-old girl suffering from convulsive episodes of toxic origin were investigated for lactate dehydrogenase (LDH) and creatine kinase (CK) activities. Elevated levels of both enzymes were found. Furthermore CK was higher in the CSF (680 I.U./1) than in blood serum (160 I.U./1). The CSF activity was demonstrated mainly as the BB form (96%) for CK and H4 (63%) was the predominant form for LDH. Identical investigations were performed 45 h later and results compared with the first set. These data provide an additional example of interest in CSF enzymatic studies as a brain damage index.

We have developed an equilibrium radioimmunoassay for creatine kinase BB (CK-BB) isoenzyme in serum. We used as antibody a CK-BB binding immunoglobulin G isolated from serum of a patient with macro CK-BB. Free and antibody-bound tracer were separated by anion-exchange chromatography. The affinity constant, Keq, for the binding of CK-BB to immunoglobulin was calculated as 1.4 X 10(11) L/mol, which suggests that the immunoglobulin was an autoantibody. The assay may detect 1 microgram of enzyme per liter in a 100- microL sample. CK-MM and CK-MB isoenzymes did not cross react in the assay. Within-assay precision (CV) was 5%; between-assay precision was 14 and 15% at 6 and 14 microgram of CK-BB per liter, respectively. Of 45 sera from blood donors, 95% contained < 1.8 microgram of CK-BB per liter, whereas of 19 sera from unselected patients the corresponding figure was 2.8 microgram/L.

Epitopes differing among isoenzymes of creatine kinase (CK) are apparently limited in number and poorly immunogenic in vivo. Especially for the BB-CK isoenzyme, very few monoclonal antibodies (mAb) are available. Here, we use in vitro selection with a synthetic human phage display antibody library and develop isoenzyme competition and peptide panning strategies to obtain human single chain Fv (scFv) antibodies against specific CK isoenzymes. We isolated and characterized seven scFv clones that recognize native as well as denatured cytosolic BB-CK in ELISA, immunoblot, immunofluorescence histochemistry and surface plasmon resonance (SPR) spectroscopy. To a variable but minor degree, they also react with cytosolic MM-CK, but not with mitochondrial CK isoenzymes. Epitope mapping revealed that the scFv antibodies recognize different BB-CK epitopes, including the N-terminus and the isoenzyme-specific box, a highly conserved sequence of unknown function for which no mAb were available so far. With a K(D) of 3.5-9.6 x 10(-7) M, the isolated scFv compare favorably with mouse mAb and may overcome certain of their limitations. Our results demonstrate the advantages of in vitro antibody selection for the generation of isoenzyme-specific antibodies.

Creatine kinase (CK) isoenzymes are essential for storing, buffering and intracellular transport of "energy-rich" phosphate compounds in tissues with fluctuating high energy demand such as muscle, brain and other tissues and cells where CK is expressed. In brain and many non-muscle cells, ubiquitous cytosolic "brain-type" BB-CK and ubiquitous mitochondrial CK (uMtCK) act as components of a phosphocreatine shuttle to maintain cellular energy pools and distribute energy flux. To date, still relatively little is known about direct coupling of functional dimeric BB-CK with other partner proteins or enzymes that are important for cell function. Using a global yeast two-hybrid (Y2H) screen with monomeric B-CK as bait and a representative brain cDNA library to search for interaction partners of B-CK with proteins of the brain, we repeatedly identified the cis-Golgi Matrix protein (GM130) as recurrent interacting partner of B-CK. Since HeLa cells also express both BB-CK and GM130, we subsequently used this cellular model system to verify and characterize the BB-CK-GM130 complex by GST-pulldown experiments, as well as by in vivo co-localization studies with confocal microscopy. Using dividing HeLa cells, we report here for the first time that GM130 and BB-CK co-localize specifically in a transient fashion during early prophase of mitosis, when GM130 plays an important role in Golgi fragmentation that starts also at early prophase. These data may shed new light on BB-CK function for energy provision for Golgi-fragmentation that is initiated by cell signalling cascades in the early phases of mitosis.

We have previously reported that human cultured bone cells (hObs) respond to estradiol-17β (E2) by stimulating DNA synthesis, creatine kinase BB specific activity (CK) and other parameters sex-specifically. We now investigate the sex specificity of the response of these hObs to estrogen receptor (ER) α and ERβ specific agonists. Real time PCR revealed that all cells express mRNA for both ERs. ERα mRNA but not ERβ mRNA was stimulated by all estrogenic compounds in both pre- and post-menopausal hObs with no effect in male hObs. Cells treated with E2, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; ERβ specific agonist) and 4,4',4″-[4-propyl-(1H)-pyrazol-1,3,5-triyl] tris-phenol (PPT; ERα specific agonist) showed increased DNA synthesis and CK in all female but not male hObs. Raloxifene (Ral), a specific ERα antagonist, inhibited the stimulation of DNA synthesis and CK by E2 or PPT, but not by DPN. DPN and PPT like E2 modulated the expression of both 12 and 15 lipooxygenase (LO) mRNA in both female but not male hObs. 12 and 15 HETE production was modulated only by DPN and PPT in these cells. The LO inhibitor baicaleine inhibited only E2 and PPT but not DPN effects in both female hObs. In conclusion, we provide herein evidence for the separation of age- and sex-dependent mediation via both ERα and ERβ pathways in the effects of estrogens on hObs, with a yet unknown mechanism.

Theophylline toxicity has been recognized since its introduction into clinical medicine. Clarithromycin is a new oral macrolide antibiotic with excellent antibacterial activity and rare adverse effect. Patients with upper respiratory infection are often treated with theophylline and clarithromycin concurrently. We report a case of acute renal failure due to acute rhabdomyolysis caused by the interaction of theophylline and clarithromycin. A 72-year-old man visited our hospital because of coughing and a sore throat continuing for 1 week. He was diagnosed as having the common cold with a bronchial asthmatic symptom and was prescribed 200 mg/day of sustained-release theophylline for the treatment of asthma for 7 days. One week later, he visited our hospital again. Radiographic study of the chest revealed mild interstitial pneumonia and 200 mg/day of sustained-release theophylline and 400 mg/day of clarithromycin were administrated concomitantly. Five days after the second visit, the patient was admitted to our hospital because of generalized twitching, muscular weakness, high fever and serious general condition. He experienced generalized muscular twitching and tremor. Blood urea nitrogen was 106.1 mg/dl, serum creatinine was 7.4 mg/dl, serum creatinine kinase (CK) was 36,000 IU/l (normal 15-130 IU/l), CK isozyme revealed the following ratio: BB 0%, MB 1% and MM 99%. He was diagnosed as having acute renal failure with rhabdomyolysis caused by the interaction of theophylline and clarithromycin. Hemodialysis therapy was started. After 5 weeks, his serum creatinine was markedly decreased. It is well-known that clarithromycin enhances the serum concentration of theophylline by inhibition of the cytochrome P450-dependent pathway in hepatocytes. Theophylline toxicity may be enhanced when clarithromycin is administrated concomitantly, especially to elderly patients with dehydration.

The dog's precordial region at the sternum was impacted with a mechanical elastic-cord propelled impactor at the velocity of 8.0 m/s. The left and right intraventricular pressures and electrocardiogram (ECG) were monitored continuously for 60 min after the impact. The micro- and ultra-structure of myocardium were examined. Localization of myocardial myoglobin (Mb), creatine kinase BB (CK-BB) and creatine kinase MM (CK-MM) as well as plasma membrane permeability were studied by immunohistochemical and lanthanum probe techniques. Upon the impact, abrupt over-pressures within both ventricles were recorded with transient depression of the left ventricular systolic pressure. In all the dogs, some rhythm- and conduction-disorders were noted, which lasted transiently and resumed to normal sinus rhythm. At autopsy, no gross injuries of the heart were detected, and microscopic examination showed no visible myocardial lesions. However, immunohistochemically, focal patchy loss of myocardial Mb, CK-BB and CK-MM was identified with scattered deposition of these substances between myocardial fibers elsewhere. Such changes as relaxed myofibrils with widened I band, contracted myofibrils and broken cristae of the mitochondria were observed in myocardial ultrastructure. Lanthanum particles deposited inside the mitochondria. These results indicate that increase in cardiac cell membrane permeability and ultrastructural damage in myocardium may be involved even in cardiac concussion.

Measurements of cerebrospinal fluid (CSF) creatine kinase (CK, EC 2.7.3.2) isoenzyme activity have been used to predict outcome in patients with acute brain injury following cardiac arrest. We identified two CK isoenzymes previously unreported in CSF from 16 patients with hypoxic-ischemic brain damage. Prior to analysis, the CK in the CSF samples was reactivated with dithiothreitol. CK isoenzymes were identified using electrophoretic and immunologic methods. Total CK activity ranged from 23 to 924 U/L (mean 452). CSF-CK-BB was the predominant isoenzyme present in all cases. In addition to CSF-CK-BB, the authors identified CSF-CK-MM in 6 cases, CSF-CK-MB in 8 cases, and CSF-mitochondrial-CK in 14 cases. The presence of CSF-CK-MM was significantly related to blood contaminating the CSF (P less than 0.02). It is proposed that CSF-CK-MB results from recombination of CK-MM and CK-BB in CSF and that mitochondrial CK is released with CK-BB into the CSF from the damaged brain tissue.

Early changes of the activity of enzymes such as creatine kinase in the cerebrospinal fluid (CSF) or serum are often investigated after head injuries to assess the extent of brain damage and establish a reliable prognosis. The purpose of the present study was to determine levels of creatine kinase isoenzyme CK-BB in the CSF of rats after experimental head injuries. External head injuries of different severity were inflicted on rats, immediately after which CSF was collected for isoenzyme activity determination. It was found that the levels of CK-BB were significantly elevated immediately after the head injury and that the greater the degree of external cranial injury inflicted, the higher the isoenzyme activity was. The results seem to provide evidence that CK-BB activity is an early indicator of brain damage and that its level may reflect the extent of cerebral damage involved.

A 14-month-old girl with infantile osteopetrosis had hematologic and neurologic complications with severe brain atrophy. Although serum contained high creatine kinase brain isoenzyme activity (CK-BB), CK-BB activity was not detected on repeated cerebrospinal fluid examinations. After frequent blood transfusions and steroid therapy, hematologic involvement improved gradually and disappeared finally at age 11 months; serum CK-BB tended to show a concomitant proportional increase in activity. A 111Indium chloride scan was performed at age 4 weeks when the patient had relatively low serum CK-BB activity. It indicated active extramedullary hematopoiesis in the liver and spleen. The second scan was performed at age 12 months when she had high serum CK-BB activity and indicated active medullary hematopoiesis in the cranium. The tests disclosed that the elevated serum CK-BB activity was the result of bone marrow serum leakage, and not leakage from brain tissue. This finding may be a good marker of medullary hematopoietic activity in patients with osteopetrosis. Meanwhile, biopsied sural nerve revealed storage of cellular debris, including myelin figures in the Schwann cells, which suggested increased degradation process in the cells or lysosomal enzyme deficiency.

In order to determine skeletal muscle and serum enzyme activities following exercise, six adult Landrace pigs were submitted to 10 min running on a treadmill (0.5 m/s, on a 12% gradient) and compared to six controls. Blood samples were obtained just before the exercise, immediately after, and 24 h, 48 h and 144 h after exercise. Muscle biopsies were taken from the longissimus dorsi and biceps femoris 24 h after exercise. Total lactic dehydrogenase (LDH) and LDH isoenzymes in muscle and serum were unchanged. In muscle homogenates, there was no difference in total creatine phosphokinase (CK) activity between the two groups. Total CK activity in the biceps femoris muscle represented only 59% of that observed in the longissimus dorsi muscle. A mean CK-MB value of 2.5% was found in the control group for both muscles but after exercise it was 9.5% (p less than 0.05) for the biceps femoris and 12.2% (p less than 0.01) for the longissimus dorsi muscle. In serum, the total CK (p less than 0.05), CK-MM (p less than 0.05) and CK-BB (p less than 0.05) increased immediately after the exercise, followed by a progressive decrease.

In patients with intracranial tumors (ICT) and acute cerebral infarctions (CI), both necrosis and reversible changes occur in central nervous system (CNS) tissue. The damaged CNS cells release specific substances into the cerebrospinal fluid (CFS). Radioimmunoassay (RIA)-determined myelin basic protein (MBP) and RIA-determined creatine kinase BB (CK-BB) are markers of damage to CNS specific structures. The elevated CSF level of MBP is considered a marker of myelin damage and the increased concentration of CSF CK-BB may be of combined neuronal and astrocytic origin. CSF was collected from 57 patients with the diagnosis of CI (n = 30) and ICT (n = 27) and the concentration of MBP and CK-BB were measured by RIA. Our study shows increased CSF levels of MBP and CK-BB in patients with CI and patients with ICT. We have also found a linear correlation between MBP and CK-BB in both CI and ICT, and for a given CK-BB level, MBP was significantly higher in patients with ICT than in patients with CI. These facts suggest that lesion markers behave differently in the different pathologic processes affecting the CNS.

BACKGROUND

Activation of the endothelium, complement activation and generation of cytokines are known events during ischemia-reperfusion (I/R) that mediate tissue injury. Our aim was to elucidate their respective participation at the onset of the reperfusion phase. Tourniquet application in hand surgery causes short-term ischemia, followed by reperfusion and was therefore used as the model in this study.

METHODS

Ten patients were included in the study after obtaining informed consent. A tourniquet was placed on the upper arm and inflated to 250 mmHg for 116 ± 16 min, during which the surgery was performed. Venous blood and tissue samples from the surgical area were taken at baseline as well as 0, 2, and 10 min after reperfusion and analyzed for the following parameters: Endothelial integrity and/or activation were analyzed by measuring heparan sulfate and syndecan-1 in serum, and vWF, heparan sulfate proteoglycan as well as CD31on tissue. Complement activation was determined by C3a and C4d levels in plasma, levels of C1-inhibitor in serum, and IgG, IgM, C3b/c, and C4b/c deposition on tissue. Cytokines and growth factors IL-5, IL-6, IL-7, IL-8, IL-10, IL-17, G-CSF, GM-CSF, MCP-1, TNFα, VEGF, and PDGF bb were measured in the serum. Finally, CK-MM levels were determined in plasma as a measure for muscle necrosis.

RESULTS

Markers for endothelial activation and/or integrity as well as complement activation showed no significant changes until 10 min reperfusion. Among the measured cytokines, IL-6, IL-7, IL-17, TNFα, GM-CSF, VEGF, and PDGF bb were significantly increased at 10 min reperfusion with respect to baseline. CK-MM showed a rise from baseline at the onset of reperfusion (p < 0.001) and dropped again at 2 min (p < 0.01) reperfusion, suggesting ischemic muscle damage.

CONCLUSIONS

In this clinical model of I/R injury no damage to the endothelium, antibody deposition or complement activation were observed during early reperfusion. However, an increase of pro-inflammatory cytokines and growth factors was shown, suggesting a contribution of these molecules in the early stages of I/R injury.

Three creatine kinase isozymes (CK-BB, CK-MB and CK-MM) were estimated by immunoassay in tumor tissues and in sera of patients with various lung carcinomas. CK-BB was increased in small cell carcinoma, but not in other lung carcinomas. CK-MM and CK-MB were not increased in any types of carcinoma. Serum CK-BB was increased in all types of lung carcinoma examined, while serum CK-MM and CK-MB were within normal limits in all patients. Serum CK-BB of healthy adults was estimated as 0.32 +/- 0.14 (mean +/- SD) ng/ml, ranging from 0.11-0.68 ng/ml. If CK-BB values above 1.0 ng/ml were considered abnormal, elevation occurred in 28/40 (70%) of patients with small cell carcinoma, 25/67 (37%) with adenocarcinoma, 21/51 (41%) with squamous cell carcinoma, 4/11 (36%) with other carcinoma of the lung and 10/42 (24%) with lung tuberculosis. Since serum CK-BB with lung cancer changed in parallel with the clinical course, this isozyme may be a marker for monitoring the clinical course, especially in small cell carcinoma of the lung.

Total creatine kinase and its isoenzymes CK-MB and CK-BB were measured in the serum of patients admitted with acute abdominal pain or signs suggestive of an intraabdominal catastrophe. Total creatine kinase was measured by automated spectrophotometry, CK-MB by chemiluminescent assay, and CK-BB by radioimmunoassay. Patients were grouped according to their final diagnosis: intestinal infarction (N = 8); all other diagnoses (N = 22); controls (N = 20). CK-BB in the infarction group (22.3 +/- 5.3 ng/ml, mean +/- SE) was significantly greater (P less than 0.01) than in the noninfarction or the control groups (11.0 +/- 0.8 ng/ml and 5.8 +/- 0.7 ng/ml, respectively). There were no differences in total creatine kinase and CK-MB in the three groups. Stepwise deletion multiple regression analysis of 26 independent regressors showed that among a cluster of six significant variables (R2 = 0.92, P less than 0.005), CK-BB greater than 20 ng/ml was the best predictor of intestinal infarction. Results of this study indicate that CK-BB isoenzyme measurement may be useful in the diagnosis of intestinal infarction in man.

Brain energy disorders and oxidative stress due to chronic hypoperfusion are considered to be major risk factors in the pathogenesis of dementia. The aim of our study was to evaluate changes of the brain creatine kinase (BB-CK) reaction and mitochondrial respiratory chain function in male Wistar rats exposed to chronic cerebral hypoperfusion. Three-vessel occlusion (3-VO) was accomplished without thoracotomy using a minimally-invasive surgical approach for the occlusion of the brachiocephalic trunk and the left common carotid artery (CCA). The forward rate constant of creatine kinase (k(for)) was measured in vivo by saturation transfer of (31)P magnetic resonance spectroscopy (MRS) at 2 and 10 weeks of permanent 3-VO. The function of the mitochondrial respiratory chain in vitro was assessed polarographically at 10 weeks after 3-VO. When compared to the controls, the significant 42% reduction of k(for) at 2 resp. 10 weeks indicated disorders in brain energy metabolism, which is in agreement with the 12% decrease of the oxidative phosphorylation coefficient (ADP:O) and with the 14% decrease of the oxidative phosphorylation rate (OPR) measured in isolated mitochondria. Oxidative modification of the creatine kinase system (inactivation of enzymes) and metabolic disorders due to chronic 3-VO, thus, may participate in vascular cognitive impairment and neuronal degeneration.

OBJECTIVE

We performed a prospective study of 72 preterm neonates with high-risk predisposing them to necrotizing enterocolitis (NEC) in which isoenzyme CK-BB activity in serum was measured at birth and after establishment of feeding with the purpose being to investigate whether CK-BB isoenzyme measurement may be useful in the diagnosis of NEC and an efficient marker in the evolution of the disease.

METHODS

In 12 neonates with NEC, CK-BB was measured in serum, at the beginning of symptoms and every 48 hours until remission of the acute episode. Control data were obtained from 26 healthy preterm and 20 preterm neonates with diarrhoea of several etiologies. Fourteen infants were excluded from the study due to complications. Electrophoresis on an agarose gel was used determine CK isoenzymes and these are expressed as the percentage of total CK activity.

RESULTS

There were no differences in CK-BB values between the control groups. At the beginning of symptoms, the CK-BB in serum was significantly greater in neonates with NEC (p < 0.001) than in the control groups and were continuously elevated until complete recovery from NEC.

CONCLUSIONS

The CK-BB was shown as a useful marker in the diagnosis and evolution of NEC.