Kinetic analysis of the cerebral creatine kinase reaction under hypoxic and hypoglycaemic conditions in vitro. A 31P-n.m.r. study.

1. The tissue concentration of phosphocreatine (PCr) and the pseudo-first-order rate constant of creatine kinase (kf) were monitored in superfused guinea-pig brain slices in vitro by using 31P-n.m.r. techniques. 2. Superfusion of slices in low oxygen partial pressure (pO2 approx. 16 kPa) decreased tissue PCr concentrations by 48% but ATP concentrations were unchanged. Regression analysis revealed a significant negative correlation between the PCr concentration in hypoxic tissue and the increase in the rate constant, kf. Nevertheless the forward flux through the enzyme (Jf = kf.[PCr]) declined under these conditions. 3. Lowering the glucose concentration to 0.2 or 0.1 mM decreased PCr concentrations by 29% and 48% respectively; here ATP concentrations as well as PCr concentrations also decreased. Only in the presence of the lower glucose concentration (0.1 mM) was kf increased. However, unlike the situation in hypoxic tissue, Jf was maintained at control rates. 4. In spectra obtained in the presence of low oxygen or low glucose concentrations, a resonance attributable to tissue inorganic phosphate became dectectable. This observation is discussed in terms of known changes in tissue phosphate concentrations and possible alterations in cytoplasmic pH.     

Blood glucose discrimination training in insulin-dependent diabetes mellitus (IDDM) patients

Self-management of insulin-dependent diabetes mellitus (IDDM) is dependent on a negative feedback loop of blood glucose (BG) fluctuations, which in turn directs treatment decisions to maintain normal BG. Although this feedback is typically accomplished by self-monitoring of blood glucose (SMBG), SMBG has limitations, and patients often rely on what their BG "feels" like. Two studies were performed to evaluate whether patients could learn to more accurately "feel"/discriminate their BG on the basis of internal cues or internal plus external BG cues. In Study I, BG Awareness Training significantly improved pre- to posttreatment BG estimation accuracy, relative to a control group. Study II replicated BG Awareness Training efficacy in improving BG estimation accuracy. Improvement in estimation accuracy was related only to initial accuracy; those who were initially less accurate improved the most. This improvement was represented in a 31% reduction in dangerous BG estimation errors and a 9% increase in accurate estimates. Resulting estimations were, however, still significantly less accurate than SMBG at the end of training.     

Tissue-specific variation in C4 and Slp gene regulation.

C4 and Slp are highly homologous mouse genes that differ in function and regulation. Allelic variants exist in quantitative regulation of C4 and in hormonal regulation of Slp. We have examined expression in several tissues, including liver and peritoneal macrophages which are the major sites of synthesis, using a probe that allows direct comparison of C4 and Slp mRNAs. Correctly-sized and initiated RNA, within an order of magnitude of liver levels, is found in mammary gland, lung, spleen, and kidney; lower levels are detectable in testis, brain, heart and submaxillary gland. By comparing expression in congenic mouse strains differing in C4 and Slp loci, regulation of these genes is seen to vary in different tissues. This provides a well-defined genetic system in which to examine cis-acting sequences and trans-acting factors that result in tissue-specific patterns of gene regulation.     

Studies of pituitary-adrenal-testis interaction in sheep. II. The effects of repeated injections of adrenocorticotrophic hormone outside the breeding season

The administration of 0.5 mg of long-acting adrenocorticotrophic hormone (ACTH, Synacthen-Depot) twice daily for 5.5 d to four rams outside the breeding season caused marked rises in plasma cortisol without any evidence of adrenal depletion. This treatment also caused marked rises in basal plasma follicle stimulating hormone (FSH) concentrations which remained high even after cessation of treatment. Plasma FSH responses to 5 ug of gonadotrophin releasing hormone (GnRH) were consistently observed and ACTH treatment increased the FSH response to GnRH. In contrast, spontaneous fluctuations in the plasma luteinizing hormone (LH) and testosterone concentrations were abolished by ACTH treatment. The quantity of testosterone released after GnRH (estimated by the maximum values reached and by the area under the response curve) was also suppressed while that of LH was only slightly lower. A comparison of the results of this experiment with those obtained in rams during the breeding season showed that the effects of ACTH on LH and testosterone were more marked during the breeding season. In contrast, the effect of ACTH on FSH is to increase the latter during the nonbreeding season, whereas no effect was observed during the breeding season.     

Blood glucose discrimination training in insulin-dependent diabetes mellitus (IDDM) patients

Self-management of insulin-dependent diabetes mellitus (IDDM) is dependent on a negative feedback loop of blood glucose (BG) fluctuations, which in turn directs treatment decisions to maintain normal BG. Although this feedback is typically accomplished by self-monitoring of blood glucose (SMBG), SMBG has limitations, and patients often rely on what their BG feels like. Two studies were performed to evaluate whether patients could learn to more accurately feel/discriminate their BG on the basis of internal cues or internal plus external BG cues. In Study I, BG Awareness Training significantly improved pre- to posttreatment BG estimation accuracy, relative to a control group. Study II replicated BG Awareness Training efficacy in improving BG estimation accuracy. Improvement in estimation accuracy was related only to initial accuracy; those who were initially less accurate improved the most. This improvement was represented in a 31% reduction in dangerous BG estimation errors and a 9% increase in accurate estimates. Resulting estimations were, however, still significantly less accurate than SMBG at the end of training.This research was supported by NIH grants AM282880, AM24177, AM22125, and RR00847 and by the Ames Company. The authors express their appreciation for the contribution made by trainers Leslie Butterfield and Linda Zimbelman, by the nursing staff at the University of Virginia's Clinical Research Center and the Diabetes and Nutrition Unit, and by Dr. James May from the Medical College of Virginia in soliciting subjects. We would also like to thank Andrea Snyder for her assistance.     

Impedimetric evaluation of the efficiency of disinfectants against biofilms

An impedimetric evaluation of disinfectant efficacy has shown that biofilms of Staphylococcus aureus, Escherichia coli, Salmonella enteritidis and Listeria mono-cytogenes attached to polyvinyl chloride (PVC), Teflon, Plexiglass, wood, rubber and stainless steel are more resistant than the same bacteria in suspension. Based on the activity against the test-organisms after 1, 3 and 5 min with exposures to 0.5, 1 and 2% of each disinfectant, the resistance towards disinfection was related to the type of hard-surface to which biofilms were attached.