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PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed1984

Reaction rate studies of glucose-6-phosphate dehydrogenase in rat tracheal epithelium; the effect of section thickness.

The reaction velocity of glucose-6-phosphate dehydrogenase has been quantified by continuous monitoring on a Vickers microdensitometer of the reaction product as it formed in sections of different thickness of rat tracheal epithelium. Reaction velocity was directly proportional to section thickness when either tetranitro BT or neotetrazolium was used as the final acceptor; the rate was the same with each tetrazolium salt. However, the amount of formazan deposited in a given time was not proportional to section thickness. When tetranitro BT was employed the reaction became non-linear in the thicker sections due to the inability of the instrument to record beyond a certain absorbance value. Using neotetrazolium a lag phase, due to the failure to overcome the critical supersaturation level of the formazan, preceded the linear response. The duration of this phase decreased as section thickness increased. The implications of these findings on studies using conventional "end point" methods of measurement are discussed.

Animals↗
PubMed2004

Role of positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose in evaluating the effects of arterial infusion chemotherapy and radiotherapy on pancreatic cancer.

BACKGROUND: This study evaluated the usefulness of positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose (FDG-PET) in monitoring the response to continuous arterial infusion chemotherapy (CAI) combined with external radiation therapy (ERT) for unresectable pancreatic carcinomas. METHODS: Ten patients with unresectable pancreatic cancer were enrolled in this study. Computed tomography (CT) and FDG-PET were done before and after CAI (5-fluorouracil [FU], 500 mg/body per day) combined with ERT (50.4 Gy total dose). Tumor regression was evaluated by standardized uptake value (SUV) with FDG-PET, tumor size on CT, and changes in blood levels of carbohydrate antigen (CA) 19-9. The three methods of evaluation were compared. RESULTS: The ten patients were classified in three categories. In category I, tumor changes evident on CT and FDG-PET were consistent. In category II, CT could not accurately detect the area of the tumor. However, tumor uptake on FDG-PET decreased markedly after the treatment in category II patients. In category III, both CT and FDG-PET detected the tumor, as in category I. Although there was no definite change in tumor size on CT, FDG-PET uptake was markedly reduced immediately after the treatment. Reduction in tumor size did not appear on CT until 2 months later. CONCLUSIONS: FDG-PET aids in analysis of the effectiveness of chemotherapy and/or radiotherapy.

Aged↗
PubMed1983

Neurophysiological recovery after hypoglycemic coma in the rat: correlation with cerebral metabolism.

Recovery of electroencephalographic activity and somatosensory evoked responses was studied in paralyzed and lightly anesthetized (70% N2O) rats in which profound hypoglycemia had been induced by insulin administration. The duration of severe hypoglycemia was defined as the duration of a flat electroencephalogram (EEG) recording (5, 30, and 60 min, respectively) before restitution with glucose. The restitution period was followed by continuous EEG monitoring and repeated tests for evoked potentials. After 180 min of recovery, the brains were frozen in situ with liquid nitrogen and analyzed for energy metabolism. In accordance with earlier metabolic studies from this laboratory, the recovery after 60 min of severe hypoglycemia was incomplete, with signs of permanent failure of energy metabolism. There was persistent ATP reduction proportional to the duration of the hypoglycemia. The short-term recovery of EEG and sensory evoked responses was proportional to the duration of severe hypoglycemia. The neurophysiological recovery after 5 min of severe hypoglycemia was complete. After 30 min of severe hypoglycemia, the evoked responses recovered but showed a significant prolongation of latency, compared with normal. After 60 min of severe hypoglycemia, no early evoked response and scanty EEG activity were observed. The neurophysiological observations indicate a persistent deficit of synaptic transmission in the somatosensory pathway, including the cortical projection. This can be correlated with neuropathologic changes that are particularly prominent in intermediate cortical layers, as previously shown.

Animals↗
PubMed1986

A microcalorimetric study of heat production in resting skeletal muscle from human subjects.

Different microcalorimetric techniques have been compared for the assessment in vitro of the total metabolic activity of resting skeletal muscle. Human fibre bundles were suspended in Krebs-Ringer-phosphate buffer containing glucose and insulin and the heat evolution was continuously monitored for 2-6 h. Palmitate as substrate was also tested. The power signals declined rapidly when a static calorimetric method (A) was used. Two different perfusion methods (B, C) gave higher power values. Long-lasting steady states were observed with method C, where the sample was contained in a cage acting as a stirrer. Significant differences were found for fibre bundles from different human muscles as well as age- and sex-related differences. The heat production in samples from the rectus abdominis muscle (method B), 0.73 mW/g muscle wet wt., was significantly higher than for the obliquus internus muscle, 0.44 mW/g, and the vastus lateralis muscle, 0.55 mW/g, but not different from the heat production value of vastus medialis, 0.66 mW/g. In method C particularly, the fibre bundles are believed to be in adequate contact with the surrounding medium. With the use of a multi-channel calorimeter it is possible to perform up to four experiments simultaneously, e.g. involving the calorigenic effects of pharmacological substances. The technique provides a new approach for detailed studies of muscle metabolism in physiological and pathological conditions.

Adolescent↗
PubMed1990

Cocaine and lidocaine interfere with epinephrine-induced changes in intracellular calcium concentration and glucose efflux from rat hepatocytes.

The mechanism of cocaine-induced hepatotoxicity is not clearly understood. Recent studies show that fluctuations in intracellular Ca2+ ([Ca2+]i) and/or cyclic-AMP ([cAMP]) concentration play a major role in hormone action, and sustained elevations in [Ca2+]i may be involved in the initiation of hepatocellular damage. To evaluate the possible involvement of intracellular Ca2+ and/or cAMP, we investigated effects of cocaine and lidocaine on basal, epinephrine and dibutyryl cyclic-AMP (DBcAMP)-induced changes in [Ca2+]i and glucose efflux from isolated rat hepatocytes. [Ca2+]i was monitored continuously using a Ca2(+)-selective fluorescence indicator, Quin-2, and was calculated after correcting for autofluorescence. Neither cocaine nor lidocaine (0.1-5 mmol/l) affected basal [Ca2+]i, yet both agents decreased epinephrine (10 mumol/l) and DBcAMP (100 mumol/l)-induced increases in [Ca2+]i in a dose-dependent fashion. Half-maximal inhibition occurred at 0.75 mmol/l cocaine and 1.7 mmol/l lidocaine. Cocaine and lidocaine also decreased epinephrine and DBcAMP-induced glucose efflux. The dose-dependent effect on epinephrine-induced glucose efflux was similar to that of both anesthetics on epinephrine-induced increases in [Ca2+]i. However, 5 mmol/l cocaine or lidocaine decreased DBcAMP-induced glucose efflux by less than 50%, and [Ca2+]i by more than 80%. Taken together, these results indicate that cocaine and lidocaine decrease the ability of epinephrine to stimulate glucose efflux by interfering with the Ca2(+)-mediated, and not the cAMP-mediated intracellular pathway. It is therefore speculated that alterations in metabolic endocrine regulation may contribute to cocaine's hepatotoxic effect.

Animals↗
PubMed1996

Acute changes in intracranial pressure and pressure-volume index after forebrain ischemia in normoglycemic and hyperglycemic rats.

BACKGROUND AND PURPOSE: Hyperglycemia enhances the deleterious effect of global cerebral ischemia. One possible explanation is that increased anaerobic glycolysis leads to exaggeration of intracellular acidosis and increased postischemic edema. To examine the importance of this edema on postischemic cerebral perfusion dynamics, we measured acute changes in intracranial pressure (ICP), specific gravity, and the pressure-volume index (PVI) after forebrain ischemia in normoglycemic and hyperglycemic rats. METHODS: Rats underwent 15 minutes of forebrain ischemia and 90 minutes of reperfusion. ICP and mean arterial pressure were continuously monitored. Before ischemia, rats received either saline or glucose intravenously. Ninety minutes after ischemia, the specific gravity of the neocortex was measured. In a second experiment, the PVI was measured at 20 and 60 minutes after ischemia. RESULTS: Preischemic ICP (mean+/-SD) was 7 +/- 1 mm Hg in both groups. A peak ICP (approximately 11 mm Hg) occurred within 15 to 20 minutes after ischemia in both groups. Between 25 and 80 minutes after ischemia, ICP was significantly but only slightly greater in hyperglycemic than in normoglycemic rats. Cerebral perfusion pressure was similar between groups and remained greater than 100 mm Hg. Specific gravity was also similar for both groups but was less than normal values. The PVI in hyperglycemic rats was lower than in normoglycemic rats, indicating reduced compliance. CONCLUSIONS: These findings indicate that hyperglycemia-augmented intraischemic tissue acidosis does not contribute to worsened outcome by means of compromised cerebral perfusion pressure during the early stages of recovery. Nevertheless, evidence was found for decreased cerebral compliance, indicating an effect of hyperglycemia on intracranial volume compartments other than cortical parenchyma.

Animals↗
PubMed2004

Prevention of adverse events in juvenile diabetes.

The most severe adverse event of juvenile diabetes is death. Still these days it happens that children with diabetes die from diabetes before having received any treatment at all, sometimes probably undiagnosed. We have to improve the awareness and knowledge, both in the general population and also among health care staff and physicians. Retarded growth and development was seen earlier, but is now rare. But long-term complications affecting primarily blood vessels and nerves are still a real threat and may develop already after a few years. Unless diabetes is well treated, the disease is as dangerous as ever before. We know that a good metabolic control prevents complications, but not how to reach such control in many patients. Severe hypoglycemia has been feared to limit our possibilities to reach good metabolic balance. However, near-normal HbA1c must not be accompanied by increasing incidence of severe hypoglycemia. Too many patients are never offered an insulin treatment as physiological as possible. Adequate use of basal and bolus insulin is a prerequisite. Continuous adjustments should be monitored on the basis of glucose profiles, but without effective education and psychosocial support the treatment tends to fail. Intense treatment of diabetes may become a heavy burden, an "adverse event" in itself, for the patient and the parents of a diabetic child. Psychosocial support is often needed. Realistic information already from the onset of the disease is important, together with optimism, encouragement and not only criticism. Short-term goals and realistic agreements may help the patient to accept the disease. Independence and capacity to manage the treatment successfully contribute to a good metabolic control and also improves quality of life. Children with diabetes cannot expect a "normal" life, but they should be able to expect a long, active, exciting and happy life.

Child↗
PubMed2005

Using blood glucose data as an indicator for epidemic disease outbreaks.

In the future, transfer of vital sensor data from patients to the public health care system is likely to become commonplace. Systems for automatic transfer of sensor data are now at the prototype stage. As electronic health record (EHR) systems adapt such functionality, widespread use may become an actuality in the foreseeable future.To prevent spreading of diseases, an early detection of infection is important. At the time an outbreak is diagnosed, many people may already be infected due to the incubation period. This study suggests an approach for detecting an epidemic outbreak at an early stage by monitoring blood glucose data collected from people with diabetes. Continuous analysis of blood glucose data may have the potential to prevent large outbreaks of infectious diseases, such as different strains of Influenza, Cholera, Plague, Ebola, Anthrax and SARS.When a person gets infected, the blood glucose value increases. If the blood glucose data from a large number of patients with diabetes are collected in a central database, it may be possible to detect an epidemic disease outbreak at an early stage. Advanced data analysis on the data may detect predominant numbers of incidences, indicating a possible outbreak. This gives the health authorities the possibilities to take actions to limit the outbreak and its consequences for all the inhabitants in an affected area.At the Norwegian Centre for Telemedicine, a mobile system for automatic transfer of blood glucose values has been constructed. By using wireless communication standards such as Bluetooth and GSM, the system transfers blood glucose data to an electronic health record system. Combined with a system accessing and querying data from EHR systems for patient surveillance we are extending our work into an Epidemic Disease Detection using blood Glucose (EDDG) system.

Blood Glucose↗
PubMed1983

[Value of continuous registration of blood D-beta-hydroxybutyrate and glucose. Application in a case of acromegaly].

We describe the use of an autoanalyzer II for continuous whole blood D-beta-hydroxybutyrate and glucose monitoring. The former is analyzed by an enzymatic-fluorimetric determination. This method is simple, reliable and sensitive at low cost. It permits to record dynamic patterns of the two major energetic substrates in response to various stimuli, as shown in an acromegalic patient following a glucose load.

3-Hydroxybutyric Acid↗
PubMed2002

Carbohydrate administration during a day of sustained aerobic activity improves vigilance, as assessed by a novel ambulatory monitoring device, and mood.

BACKGROUND: The brain requires a continuous supply of glucose to function adequately. During aerobic exercise, peripheral glucose requirements increase and carbohydrate supplementation improves physical performance. The brain's utilization of glucose also increases during aerobic exercise. However, the effects of energy supplementation on cognitive function during sustained aerobic exercise are not well characterized. OBJECTIVE: The effects of energy supplementation, as liquid carbohydrate, on cognitive function during sustained aerobic activity were examined. DESIGN: A double-blind, placebo-controlled, between-subjects design was used. Young, healthy men (n = 143) were randomly assigned to 1 of 3 treatment groups. The groups received either a 6% (by vol) carbohydrate (35.1 kJ/kg), 12% (by vol) carbohydrate (70.2 kJ/kg), or placebo beverage in 6 isovolumic doses, and all groups consumed 2 meals (3200 kJ). Over the 10-h study, the subjects performed physically demanding tasks, including a 19.3-km road march and two 4.8-km runs, interspersed with rest and other activities. Wrist-worn vigilance monitors, which emitted auditory stimuli (20/h) to which the subjects responded as rapidly as possible, and a standardized self-report mood questionnaire were used to assess cognitive function. RESULTS: Vigilance consistently improved with supplemental carbohydrates in a dose-related manner; the 12% carbohydrate group performed the best and the placebo group the worst (P < 0.001). Mood-questionnaire results corroborated the results from the monitors; the subjects who received carbohydrates reported less confusion (P = 0.040) and greater vigor (P = 0.025) than did those who received the placebo. CONCLUSIONS: Supplemental carbohydrate beverages enhance vigilance and mood during sustained physical activity and interspersed rest. In addition, ambulatory monitoring devices can continuously assess the effects of nutritional factors on cognition as individuals conduct their daily activities or participate in experiments.

Acoustic Stimulation↗
PubMed1993

Use of the microdialysis technique in the monitoring of subcutaneous tissue glucose concentration.

For some time the subcutaneous (s.c.) tissue has been the target for continuous glucose measurement. The microdialysis technique permits an extracellular region approach, which has been used for about two decades for measuring various metabolites in dialysates obtained from different body regions. By connecting a s.c. implanted microdialysis probe to a flow chamber of an amperometric glucose sensor, the procedure of glucose sensing was transferred to ex vivo. Using this device it was possible to obtain, for up to 24 hours, s.c. tissue glucose profiles of healthy and diabetic people. The microdialysis theory, the calibration process and other microdialysis technique applications are discussed in this paper. Although the combination of the microdialysis technique and amperometric glucose sensing requires certain technical equipment, the combination of microdialysis and glucose sensor seems to be a promising approach to a continuously functioning glucose sensing system.

Blood Glucose↗
PubMed1990

Electrocardiographic abnormalities during ritodrine administration.

Electrocardiographic abnormalities have been reported during ritodrine tocolysis. No previous studies, however, have included controls. The purpose of this study is to evaluate the electrocardiographic tracings of patients receiving ritodrine tocolysis and compare them with those of matched controls. Holter monitors were placed on eight patients receiving ritodrine tocolysis and eight control patients for 24 hours to make continuous electrocardiographic records. Twelve-lead electrocardiograms, serum glucose, and electrolyte concentrations were monitored serially in all patients. Four of the eight patients receiving ritodrine tocolysis demonstrated ST segment depression, while none of the control patients manifested any electrocardiographic abnormalities. The observed ST segment depression appears to be related to the degree of maternal tachycardia and the level of hypokalemia and hyperglycemia that occurs during early ritodrine tocolysis.

Adolescent↗
PubMed1984

Seven years experience of home management in pregnancy in women with insulin-dependent diabetes.

Fifty-eight of a consecutive series of 75 pregnancies in women with insulin-dependent diabetes went into the third trimester. Diabetes was managed by home blood glucose monitoring and women were not routinely admitted at any stage before delivery. The mean number of in-patient days before delivery was 15 for the whole series but has been reduced to 9 during the past four years. Each woman performed an average of 171 blood glucose measurements during her pregnancy. Mean blood glucose (including post-prandial levels) fell significantly from 7.9 mmol/l in the first trimester to 7.3 in the second and 6.4 in the third. Mean percentage of haemoglobin A1 was within the normal range in the second and third trimesters. The cesarean section rate was high at 66% but there were no perinatal deaths. Three infants had congenital abnormalities. We conclude that home blood glucose monitoring is a safe and effective way of managing pregnant diabetic women as out-patients. The cost of meters and sticks is repaid many times over in the saving of hospital costs. In addition, home blood glucose monitoring is popular with the patients and many choose to continue it after delivery.

Blood Glucose↗
PubMed2004

Adverse biochemical and physiological effects of prostacyclin in experimental brain oedema.

BACKGROUND: Prostacyclin (PGI2) and its stable analogues are known to reduce capillary hydraulic permeability. This study explores the biochemical and physiological effects of i.v. infusion of low-dose PGI2 in an experimental model of vasogenic brain oedema. METHODS: Twenty-seven anaesthetized and mechanically ventilated piglets with brain oedema induced by intrathecal injection of lipopolysaccharide (LPS) were used. Five of the animals received a continuous infusion of PGI2 (1 ng kg(-1) min(-1)) i.v. Four microdialysis catheters were placed in the brain to measure interstitial concentrations of glucose, lactate, and glycerol. Mean arterial pressure (MAP), intracranial pressure (ICP) and temperature were monitored continuously. Low-dose infusion of PGI2 started 1 h before the LPS injection and was constant during the study period. RESULTS: Intracranial pressure increased significantly in animals treated with PGI2. The increase in ICP was associated with significant cerebral biochemical changes: decrease in glucose, increase in lactate, increase in lactate/glucose ratio and increase in glycerol. CONCLUSION: In LPS-induced brain oedema i.v. infusion of low-dose PGI2 caused a further increase in ICP and a perturbation of energy metabolism, indicating cerebral ischemia and degradation of cellular membranes.

Animals↗
PubMed1996

Non-invasive glucose monitoring.

Several recent reports claim success in measuring blood glucose non-invasively in human subjects with near-infrared spectroscopy. A critical examination of these published results suggests more fundamental research is needed to verify the validity of these claims. In addition, progress continues in assessing the utility of near-infrared spectroscopy as a non-invasive probe for continuous bioreactor monitoring during fermentation processes. Recent work demonstrates that five critical fermentation components, including glucose, may be measured simultaneously.

Biosensing Techniques↗
PubMed1997

Blood glucose monitoring devices.

Blood glucose monitoring can enable people to control their diabetes. People with diabetes will be motivated to continue monitoring only if it is seen to be effective. Patient education will significantly influence people's attitude to blood glucose monitoring, and must reflect individual needs and circumstances.

Blood Glucose Self-Monitoring↗