Serum creatine phosphokinase activity in asthma

Serum creatine phosphokinase activity was measured in 2 groups of asthmatics. The first group consisted of 12 asthmatics followed as outpatients for periods of up to 16 months. Serum creatine phosphokinase activity increased in 8 patients and correlated with the severity of subjective symptoms and objective measurement of airway obstruction, as represented by the forced expiratory volume in 1 second. In the second group, consisting of 5 asthmatic patients studied during hospitalization for acute exacerbations of asthma, serum creatine phosphokinase activity was increased on admission in all the patients and decreased as symptoms and airway obstruction improved and alveolar ventilation decreased. Analysis of creatine phosphokinase isoenzymes showed the increase in every instance to be due entirely to skeletal muscle isoenzyme. The results of additional laboratory tests and further evaluation suggested that the increased serum creatine phosphokinase activity was not derived from the myocardium and was not related to parenteral therapy, specific drugs, hyperthermia, or hyperkalemia. The increase in serum creatine phosphokinase during exacerbations of asthma is probably derived from respiratory muscles, owing to the increased work of breathing.     

Cerebrospinal fluid creatine phosphokinase in the normal dog

Sixty-seven cerebrospinal fluid samples obtained from 44 healthy dogs were assayed for creatine phosphokinase enzyme activity. All samples contained 1 Sigma unit or less of creatine phosphokinase. Temporal variability within individuals was minimal. The biological characteristics and potential use of this enzyme in neurologic disease are discussed.     

Observations on plasma creatine phosphokinase activity in dogs

Plasma creatine phosphokinase (PCPK) activity was determined in 14 clinically normal adult pedigree dogs of various breeds with an activated enzyme assay medium. PCPK levels were not significantly influenced by the time of sampling, body mass or eating, but there was a significant correlation (P is less than 0.05) between PCPK levels and moderate physical activity. The mean enzyme activity was 22.9 iu/litre at 30 degrees C. The PCPK levels are 10 times greater than those obtained by other authors with the non-activated enzyme assay method.     

Effects of isometric exercise on serum creatine phosphokinase activity

The effect of isometric exercise on serum creatinine phosphokinase (CPK) activity in 14 psychotic patients in remission and ten normal controls was studied. The increases in serum CPK activity at 18 and 42 hours after exercise were no significantly different in patients and controls. The postexercise serum CPK activities in the patients were significantly less than the peak serum CPK levels when they were psychotic. There were no significant correlations between postexercise serum CPK activity and preexercise or peak serum CPK activity in the patient group. It is unlikely that increased isometric muscle tension is a major causative factor in the increased serum CPK levels frequently found in psychotic patients.     

Occurrence of free creatine, phosphocreatine and creatine phosphokinase in adipose tissue

We evaluated brown and white adipose tissues for the presence of creatine, phosphocreatine and creatine phosphokinase activity. In rats 3.6 and 0.4 mumol of total creatine were found per g wet weight of brown and white adipose tissues, respectively. We were able to identify creatine by thin-layer chromatography after a pulse label of [14C]creatine had been given in vivo. Free creatine and phosphocreatine were shown to occur by column chromatography. Of the total creatine of brown adipose tissue, approximately one third to one half were attributable to phosphocreatine. The activity of creatine phosphokinase was demonstrated in both white and brown adipose tissue, the values of the latter prevailing over those of the former by a factor of 200, if based on wet weight, or 50, if expressed as specific enzyme activity. The labeling of total creatine in vivo proceeded much faster in adipose tissue than in skeletal muscle. The results strongly suggest that the energy metabolism of adipose tissue is closely dependent on the presence of creatine. The specific activities of free creatine and phosphocreatine of brown adipose tissue differed strikingly as long as 24 h after radioactive creatine was injected; this difference points to a metabolic or structural compartmentation of creatine.     

Mobility of creatine phosphokinase and beta-enolase in cultured muscle cells

The diffusion of beta-enolase and creatine phosphokinase in muscle cells has been studied by modulated fringe pattern photobleaching. Beta-enolase is mobile in the sarcoplasm. At 20 degrees C, the diffusion coefficient is 13.5 +/- 2.5 microm2 s(-1) in the cytosol and 56 microm2 s(-1) in aqueous media. As in the case of dextrans of the same hydrodynamic radius, its mobility is hindered by both the crowding of the fluid phase of the cytoplasm and the screening effect due to myofilaments. A fraction of creatine phosphokinase is mobile in the sarcoplasm. Its diffusion coefficient in the cytosol, 4.5 +/- 1 microm2 s(-1), is lower than that of the dextran of equivalent size. The other fraction (20 to 50%) is very slightly mobile, with an apparent diffusion coefficient varying from 0.0035 to 0.043 microm2 s(-1). This low mobility might be attributed to exchange between free and bound creatine phosphokinase. The bound fraction of the endogenous enzyme was localized by immunocytofluorescence on the cultured muscle cells. Our results favor a localization of bound cytosolic creatine phosphokinase on the M-line and a diffuse distribution in all myotubes.     

Mitochondrial contact sites detected by creatine phosphokinase activity in the hearts of normal and diabetic rats: is mitochondrial contact sites formation a calcium-dependent process?

Reovirus type 2 (Reo-2) infection in DBA/1 sucking mice causes pancreatic islet-cell destruction, which results in a diabetes-like syndrome. To investigate the role of reactive oxygen species (ROS), the protective effect of dimethylthiourea (DMTU) was examined, this substance being an effective scavenger of hydroxyl radicals. The degree of cellular infiltration in and around pancreatic islets was the same in mice receiving either virus only or virus and DMTU. The latter had no effect on (1) the number or type of white blood cells, (2) lymphocyte function-associated antigen 1-alpha-positive splenocytes, or (3) viral multiplication in the pancreas. However, treatment with DMTU inhibited the elevation of blood glucose concentrations and reduced pancreatic islet-cell damage (beta-cell degranulation and necrosis). These results suggest that ROS play a role in the pathogenesis of Reo-2-induced diabetes-like syndrome.     

Serum creatine phosphokinase concentrations after intramuscular chlordiazepoxide and its solvent

Serum creatine phosphokinase (CPK) concentrations were determined in healthy volunteers for the first 48 hours after intramuscular injection of 50 mg chlordiazepoxide hydrochloride or of its solvent alone. Intramuscular injection of both the drug solution and its solvent was painful and caused CPK elevations. The CPK rise due to the drug solution was 33 per cent higher than that due to the solvent alone, but the difference was not significant. The pH of the solvent preparation is low and it contains high concentrations of propylene glycol. The pain and muscle damage due to injection of the solvent could be due to its acidity and its high osmolarity. Problems associated with intramuscular injections of water-insoluble drugs are not resolved by the use of such solvent preparations.     

Insulin-like growth factor-I expression in normal and diseased endometrium

While the role of steroid hormones in the regulation of endometrial proliferation and differentiation is well established, the effects of growth factors and their receptors in normal and neoplastic endometrium remain a matter of debate. Previous studies have documented the positive effects of insulin-like growth factor-I (IGF-I) on epithelial cell proliferation and the active production of this growth factor in endometrial tissues. In view of decreased expression of transforming growth factor-beta1 (TGF-beta1), an antagonist of IGF-I, in endometrial carcinoma, we investigated the expression of IGF-I, at both the mRNA and protein levels, and the immunoreactivity for type I IGF-I receptor in 30 formalin-fixed, paraffin-embedded tissue samples of normal and neoplastic endometrium, in order to possibly clarify the role of IGF-I in endometrial proliferation and differentiation. Our results demonstrate a reduced expression of IGF-I mRNA in endometrial carcinomas compared with non-neoplastic tissues, despite equivalent immunohistochemical expression of IGF-I and IGF-I receptor. Our data suggest that IGF-I and its corresponding receptor may not be directly involved in endometrial cancer cell proliferation and differentiation in vivo, though other components of the IGF-I system (e.g., IGF binding proteins) may affect endometrial malignant transformation and tumor progression.     

Increase in serum creatine phosphokinase concentrations after suxamethonium during sevoflurane or isoflurane anaesthesia in children

We have studied whether sevoflurane or isoflurane anaesthesia modulates the effect of suxamethonium on serum concentrations of enzyme markers of skeletal muscle function in paediatric patients. Eighty patients undergoing bilateral tonsillectomy, aged 5-12 yr, were allocated randomly to receive anaesthesia with either sevoflurane and nitrous oxide or isoflurane and nitrous oxide. Serum creatine phosphokinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) concentrations were measured before, and at 30 min and 20 h after induction of anaesthesia. Mean CK concentrations increased from 97.0 (SD 17.3) to 478 (170) iu litre-1 in the sevoflurane group and from 86.9 (22.4) to 628 (223) iu litre-1 in the isoflurane group, 20 h after induction of anaesthesia. Mean peak serum CK concentration in the sevoflurane group (478 (170) iu litre-1) was significantly less (P < 0.05) than that in the isoflurane group (628 (223) iu litre-1). Mean serum AST concentration increased from 17.5 (4.9) to 31.7 (3.5) iu litre-1 in the sevoflurane group and from 17.3 (2.4) to 34.8 (5.7) iu litre-1 in the isoflurane group, 20 h after induction of anaesthesia. Mean peak serum AST concentrations in the sevoflurane group were significantly lower (P < 0.05) than those in the isoflurane group. There were no significant differences in serum ALT or LDH concentrations between the groups either before or after anaesthesia. We conclude that administration of suxamethonium during either sevoflurane or isoflurane anaesthesia caused a marked increase in serum CK concentrations in paediatric patients. The clinical significance of this finding is uncertain.     

Plasma MB creatine kinase activity and other conventional enzymes. Comparison in patients with chest pain and tachyarrhythmias

We studied 67 patients with tachycardia and chest pain admitted with suspected myocardial infarction; 29 had myocardial infarction (20 transmural, nine subendocardial) with elevated MB creatine kinase (CK) activity, as well as elevated total CK and lactate dehydrogenase (LDH) levels. However, hydroxybutyric dehydrogenase and SGOT activity remained normal in three and four patients, respectively. Despite abnormal ECGs in 84% and typical chest pain in 54%, 38 patients had normal MB CK activity. However, 15 of them had elevated MM CK levels, presumably due to release from skeletal muscle. In total, 29 patients had elevated activity of MM, CK, LDH, or SGOT, but 72% of these patients had cardiac failure, hypotension, or skeletal muscle trauma due to cardioversion. Eleven patients with normal MB CK had elevated hydroxybutyric dehydrogenase activity. Despite elevated activity of other enzymes, MB CK remained normal. Thus, elevated plasma MB CK activity appears to remain a good diagnostic marker of myocardial necrosis in patients with tachyarrhythmias.     

Incomplete development of human spermatozoa is associated with increased creatine phosphokinase concentration and abnormal head morphology

Our previous creatine phosphokinase (CK) activity studies in human sperm revealed differences among men and among sperm populations within the same specimen. Samples with low sperm concentrations, high incidence of abnormal sperm morphology, and diminished fertility had higher per sperm CK activity. In the present work, we demonstrated, with 14C-FDNB covalent CK active site modification and with direct CK immunocytochemistry, that the higher CK activity is related to an increased content of CK and of other proteins in sperm. Also, sperm heads with higher CK content were significantly larger and rounder and showed a higher incidence of amorph configuration. We suggest that these biochemical and morphological irregularities are related and are due to a failure of spermatogenesis, more specifically, to a higher retention of cytoplasm, which in normal sperm development is lost to the Sertoli cells as residual bodies. Thus higher CK activity and larger or irregular head size in human sperm signify cellular immaturity and a failure to complete spermatogenesis.     

Massive myoglobinuria precipitated by halothane and succinylcholine in a member of a family with elevation of serum creatine phosphokinase

Massive myoglobinuria developed in a patient given halothane and IV succinylcholine, Marked elevations of serum CPK were found in the patient and several family members. Myopathic changes in electromyogram and lack of neuromuscular symptoms and physical findings prompted the diagnosis of familial nonprogessive muscular dystrophy. Other hereditary muscular diseases were eliminated by medical workup. It is recommended that patients with known myopathy or unexplained elevations of serum CPK not receive the combination of halothane and succinylcholine.     

Activity of glutathione-dependent enzymes in long term diabetes. II. Glutathione contents and activity of glutathione-dependent enzymes: S-transferase and peroxidase in the kidney cytosol of alloxan induced diabetic rats

To better understand the uptake of oligonucleotides into cells, we have studied the labeling of cell surface proteins by an oligonucleotide conjugated to a radiolabeled photoactivatable crosslinker (Denny-Jaffe reagent). When HL60 cells are treated with the conjugate for 2 hours in a medium containing bovine serum albumin (BSA), almost all of the cell-associated label is found in one protein, which we identify as BSA. Cells grown and treated in a serum-free medium do not show this protein, whereas it is plainly seen in cells that are grown in serum-containing medium but then treated in serum-free medium. Overall association of the oligonucleotide with cells is much higher in serum-free medium than in BSA-containing medium, but the oligonucleotide is mostly not protein-associated in the absence of BSA. We conclude that (1) BSA from the medium serves to block overall association of oligonucleotide with cells, and (2) BSA is the main cell surface protein binding oligonucleotides. We discuss the possible role of albumin in endocytic uptake of oligonucleotides in the cell and in the biodistribution of oligonucleotides in vivo.     

Maintained coupling of oxidative phosphorylation to creatine kinase activity in sarcomeric mitochondrial creatine kinase-deficient mice

The importance of mitochondrial creatine kinase (mi-CK) in oxidative muscle was tested by studying the functional properties of in situ mitochondria in saponin-skinned muscle fibres from sarcomeric mi-CK-deficient (mutant) mice. Biochemical analyses showed that the lack of mi-CK in mutant muscle was associated with a decrease in specific activity of MM-CK in mutant ventricle, and increase in mutant soleus (oxidative) muscle. Lactate dehydrogenase activity and isoenzyme analysis showed an increased glycolytic metabolism in mutant soleus. No change was observed in ventricular muscle. In control animals, the apparent K(m) of mitochondrial respiration for ADP in ventricle and soleus (232 +/- 36 and 381 +/- 63 microM, respectively) was significantly reduced in the presence of creatine (52 +/- 8 and 45 +/- 12 microM, respectively). There was no change in the K(m) in oxidative fibres from mutant mice (258 +/- 27 and 399 +/- 66 microM, respectively) compared with control, though surprisingly, it was also significantly decreased in the presence of creatine (144 +/- 8 and 150 +/- 27 microM, respectively) despite the absence of mi-CK. It is proposed that in mutant (and perhaps normal) oxidative tissue, cytosolic MM-CK can relocate to the outer mitochondrial membrane, where it is coupled to oxidative phosphorylation by close proximity to porin, and the adenine nucleotide translocase. Such an effect can preserve the functioning of the CK shuttle and the energetic properties of mi-CK deficient tissue.