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Clofibrate improves glucose tolerance in fat-fed rats but decreases hepatic glucose consumption capacity.

BACKGROUND/AIMS: High-fat (HF) diets cause glucose intolerance. Fibrates improve glucose tolerance. We have tried to obtain information on possible hepatic mechanisms contributing to this effect. METHODS: Rats were fed a HF diet, isocaloric with the control diet, for 3 weeks without or with clofibrate. Several parameters related to liver glucose and glycogen metabolism were measured. RESULTS: Clofibrate prevented the induction of glucose intolerance by 3 weeks HF feeding. Improved glucose tolerance by clofibrate was not due to increases in glucose phosphorylation or glycolysis in the liver, since both the HF diet and clofibrate suppressed glucokinase and pyruvate kinase activities with no effect on glucose 6-phosphatase. Clofibrate decreased glycogen storage in both control and HF rats. Clofibrate, with and without HF feeding, inhibited weight gain during the experimental period. Body temperature was significantly elevated by clofibrate, indicative of an increased basal metabolic rate. The capacity of liver mitochondria to oxidize long-chain fatty acids increased by clofibrate treatment. Mitochondria did not show uncoupling. CONCLUSIONS: Clofibrate does not improve glucose tolerance by improving hepatic glucose or glycogen metabolism. Peripheral glucose oxidation may be facilitated by increased energy dissipation.

Animal Feed↗

Luteal phase defect: the sensitivity and specificity of diagnostic methods in common clinical use.

OBJECTIVE: To assess the sensitivity and specificity of common clinical tests used for the diagnosis of luteal phase defect (LPD). DESIGN: The sensitivity and specificity of these tests for predicting low integrated P levels over the luteal phase were calculated. SETTING: Outpatient reproductive endocrinology and infertility clinic at a university medical center. PATIENTS: Fifty-eight strictly defined normal women were used to determine normal integrated luteal phase P levels. The study population was a separate 34 women who either were normal (n = 15) or were being evaluated for infertility or recurrent abortion (n = 19). These 34 study subjects all had the following tests performed in the same menstrual cycle: daily reproductive hormone levels, daily assessment of preovulatory follicle size, late luteal endometrial biopsies, and BBT charts. MAIN OUTCOME MEASURES: Basal body temperature, maximum preovulatory follicle size, dated endometrial biopsies, and serum P levels (single and multiple) were used in an attempt to predict which patients had low integrated P levels. RESULTS: Unacceptably low sensitivity and/or specificity levels were found for the following tests: appearance of BBT charts, luteal phase length, and preovulatory follicle diameter. Timed endometrial biopsy was found to have marginally acceptable sensitivity and specificity levels whether dated by next menstrual period or midcycle events. The best test for the prediction of low integrated P was a single serum P level from the midluteal phase that was < 10 ng/mL (31.8 nmol/L) or a sum of three random serum P measurements that was < 30 ng/mL (95.4 nmol/L) (also obtained in the midluteal phase). CONCLUSIONS: Luteal phase defect is a relatively uncommon but important cause of infertility and/or habitual abortion. The recommended test for the determination of LPD is a midluteal phase single serum P level < 10 ng/mL or the sum of three serum P levels that is < 30 ng/mL. The endometrial biopsy is a second line test that is only recommended when LPD needs to be evaluated in a treated cycle (ovulation induction or supplemental P).

Abortion, Habitual↗

Study on the ATPasic lymphocytic activity during menstrual cycle.

We previously studied ATPasic activity in the lymphocyte according to sex, age and in pregnant women. Now we considered it is interesting to go on with out study with the dosage of ATPasic lymphocytic activity during menstrual cycle, monitored with basal temperature method. The methodology we followed is Ellegaard and Dimitrov one of 1972, with modifications and simplifications while the proteins dosage in the supernatant has been effected with biuret method. Our data showed a decrease of the ATPasic lymphocytic activity at the middle of cycle for ovulatory cycles, while there is no difference between data at the middle of the cycle and in menstruation for cycle without ovulation. We suppose a connection between ATPasic lymphocytic activity and the hormones which stimulate ovulation.

Adenosine Triphosphatases↗

Distinct mutants of retrograde intraflagellar transport (IFT) share similar morphological and molecular defects.

A microtubule-based transport of protein complexes, which is bidirectional and occurs between the space surrounding the basal bodies and the distal part of Chlamydomonas flagella, is referred to as intraflagellar transport (IFT). The IFT involves molecular motors and particles that consist of 17S protein complexes. To identify the function of different components of the IFT machinery, we isolated and characterized four temperature-sensitive (ts) mutants of flagellar assembly that represent the loci FLA15, FLA16, and FLA17. These mutants were selected among other ts mutants of flagellar assembly because they displayed a characteristic bulge of the flagellar membrane as a nonconditional phenotype. Each of these mutants was significantly defective for the retrograde velocity of particles and the frequency of bidirectional transport but not for the anterograde velocity of particles, as revealed by a novel method of analysis of IFT that allows tracking of single particles in a sequence of video images. Furthermore, each mutant was defective for the same four subunits of a 17S complex that was identified earlier as the IFT complex A. The occurrence of the same set of phenotypes, as the result of a mutation in any one of three loci, suggests the hypothesis that complex A is a portion of the IFT particles specifically involved in retrograde intraflagellar movement.

Animals↗

Withdrawal of trihexyphenidyl.

Trihexyphenidyl, a synthetic anticholinergic, used to control extrapyramidal symptoms arising from neuroleptic drug therapy has been a subject of controversy regarding the need for continuous antiparkinsonian therapy. In a group of 22 psychiatric patients receiving long-term antipsychotic medication concurrently with trihexyphenidyl the effects of trihexyphenidyl withdrawal were studied double-blind and placebo controlled. Anxiety, psychotic symptoms, extrapyramidal symptoms and salivary flow were monitored. Blood pressure, pulse, sleep duration, weight and body temperature were recorded daily. The result was a recognizable withdrawal syndrome indicated by an increase in anxiety with various physical complaints, as well as evidence of orthostatic hypotension and tachycardia. A temporary deterioration was noted in psychotic symptomatology and extrapyramidal symptoms. The majority of the parameters regained baseline values, indicating the symptoms were related to the discontinuation of trihexyphenidyl and supporting the existence of a withdrawal syndrome.

Adult↗

Dose dependent reduction of glucose utilization by pentobarbital in rat brain.

A new method of determining the rate of glucose utilization in brain regions of individual rats has been used to measure the dose dependency of the reduction of the metabolic activity of the cerebral cortex by pentobarbital. Cerebral cortical glucose utilization is depressed to a basal level of 44% of the control rate when cerebral pentobarbital levels exceed 50 microgram per g of tissue. The major portion of this effect occurs between the cerebral pentobarbital range of 10--20 microgram per g, which can be achieved by 1/5 to 1/10 the normal anesthetic intraperitoneal dosage. If a depression of brain metabolism is responsible for the previously reported protection of the brain from ischemic damage, these data suggest a substantial reduction of brain metabolic rate is achieved in the rat at a barbiturate dosage which may be therapeutically relevant in the human after acute brain ischemia.

Animals↗

Dynamic in vivo measurement of erythrocyte velocity and flow in capillaries and of microvessel diameter in the rat brain by confocal laser microscopy.

A new method for studying brain microcirculation is described. Both fluorescently labeled erythrocytes and plasma were visualized on-line through a closed cranial window in anesthetized rats, using laser-scanning two-dimension confocal microscopy. Video images of capillaries, arterioles, and venules were digitized off-line to measure microvessel diameter and labeled erythrocyte flow and velocity in parenchymal capillaries up to 200 microm beneath the brain surface. The method was used to analyze the rapid adaptation of microcirculation to a brief decrease in perfusion pressure. Twenty-second periods of forebrain ischemia were induced using the tour-vessel occlusion model in eight rats. EEG, arterial blood pressure, and body temperature were continuously controlled. In all conditions, labeled erythrocyte flow and velocity were both very heterogeneous in capillaries. During ischemia, capillary perfusion was close to 0, but a low blood flow persisted in arterioles and venules, while EEG was flattening. The arteriole and venule diameter did not significantly change. At the unclamping of carotid arteries, there was an instantaneous increase (by about 150%) of arteriole diameter. Capillary erythrocyte flow and velocity increased within 5 seconds, up to, respectively, 346 +/- 229% and 233 +/- 156% of their basal value. No capillary recruitment of erythrocytes was detected. All variables returned to their basal levels within less than 100 seconds after declamping. The data are discussed in terms of a possible involvement of shear stress in the reperfusion period.

Animals↗

Transport and demand of oxygen in severe burns.

The balance equation or oxygen-conservation equation in which oxygen consumption is equal to cardiac output times the maximal oxygen binding capacity times the oxygen saturation difference between arterial and mixed venous blood shows the three factors by which the oxygen supply to the tissues can be regulated according to the need. The release of oxygen to the tissues is regulated directly through the venous oxygen tension and indirectly through cardiac output, the 2,3-DPG system, and erythropoietin. Of these indirect regulation mechanisms, cardiac output has the most rapid response and erythropoietin the slowest. As the pool of oxygen in the tissues is comparatively small, the transport and the demand of oxygen under normal conditions are approximately equal over a longer period of time. The tissue oxygen tension (Fig. 21) is thus directly a result of the flows (Fig. 21), solid lines) and indirectly a result of the regulation mechanisms (Fig. 21, broken lines). Hypermetabolism, weight loss, and severe protein wasting characterize the metabolic response to thermal injury. The increased adrenergic activity following severe burns signifies a shift of flow of body substrate from storage to utilization and an increase in energy requirements. The greater the stress, the greater the response. All systems operate at maximal or near maximal levels. The critically injured patients have an accelerated glucose turnover and increased nitrogen loss; the main source of catabolized protein seems to be from skeletal muscle. The metabolic wheel has a tremendous speed. It is thus essential to feed the patient. Energy support with heat supply and nutrition must equal energy demand to avoid weight loss. Most important is to avoid loss of "lean body tissue." No hypermetabolism was found in burned patients when the patients themselves controlled the heat supply from infrared heaters. The metabolic rate corrected for rectal temperature was independent of the total body surface burned. The energy expenditure of patients with burns was studied during the daily treatment routine and showed that it is important to avoid hypovolemia, underhydration, pain, fear, and anxiety, all of which increase the metabolic demands. To prevent hypermetabolism, infrared radiation is a practical way of distributing energy from the environment to the patient. Weight loss can be essentially prevented as energy support equals energy demand (Fig. 20). Furthermore, the method has the advantages that many patients can be treated individually, the method is inexpensive, and the ambient air temperature can be kept normal. From the results of the present investigation, it may be concluded that in patients with burns treated with infrared heaters the energy intake can be predicted in an appropriate way from the calculated basal metabolism, the rectal temperature, and the activity of the patient. The effect of storage of blood on oxygen, proton, and carbon dioxide transport is mainly mediated over the concentration of 2,3-DPG...

Adolescent↗

Simultaneous estimation of blood flow rate and tissue temperature.

A new method for simultaneously estimating blood flow rate and tissue temperature under a RF hyperthermia treatment is presented. In this method the finite element method is used to solve the two-dimensional Laplace equation for a specific absorption rate (SAR) distribution and the two-dimensional bioheat transfer equation for a tissue temperature distribution from the SAR pattern over a cross-section of a patient-specific model input from computer tomography images. Blood flow rates used in the temperature distribution computation are determined from basal values given for respective types of tissues and tissue temperatures through an assumed function that is intended to represent the temperature dependence of the blood flow rate. The tissue temperature computation procedure is iterated until the estimated temperature at a given sampling point matches a measured value at that point. This iterative procedure allows one to simultaneously estimate blood flow rate and tissue temperature. This paper describes the numerical method along with results of rudimentary in vivo measurements made in a human brain, where blood flow rate was measured by the single photon emission computed tomography (SPECT) imaging technique and tissue temperature was measured by an invasive probe technique.

Blood Flow Velocity↗

[Brain thermo-pooling is the major problem in pediatric influenza encephalitis].

The prognosis of pediatric encephalitides, such as infantile influenza encephalitis, is still poor because of the rapid progression, severe brain edema, selective bilateral basal ganglia necrosis, and a poor immune function, the mechanism of which is still unknown. Especially, little is known about virus es in CSF and brain tissue with influenza encephalitis, which hampers successful treatment of this condition. Recently, hypothermia treatment has attracted attention as the management of infantile influenza encephalitis to prevent severe brain edema. Recent clinical studies have revealed brain thermo-pooling (elevation of brain tissue temperature) with damage of blood-brain barrier (BBB). We then studied brain injury mechanism after severe brain injuries, cerebral strokes, reperfusion after shock, and high fever with lower cerebral perfusion pressure in our ICU. The brain thermo-pooling phenomenon results from body temperature higher than 38 degrees C, systolic blood temperature lower than 90-100 mmHg, and cerebral perfusion pressure (CPP) lower than 70 mmHg that hinders washout of brain tissue temperature by cerebral blood flow. We have recorded of brain tissue temperature of 40-44 degrees C in various brain injured patients. Some pathophysiological changes in infantile influenza encephalitis may be explained on the basis of this brain thermo-pooling phenomenon. In systemic infection, it causes severe brain edema by activation of cytokines and destruction of BBB, bilateral basal ganglia necrosis by acute severe brain hypoxia, resulting in poor prognosis without control of brain temperature. In other words, brain thermo-pooling, is the major target of treatment for infantile influenza encephalitis. In this paper, new concepts of the brain injury mechanism and methods of brain hypothermia treatment of pediatric influenza encephalitis are presented.

Albumins↗

L-Bupivacaine 0.5% vs. racemic 0.5% bupivacaine for caudal epidural analgesia in horses.

Bupivacaine is available as a racemic mixture of its enantiomers, d-bupivacaine and l-bupivacaine (LB). The aim of this randomized, double-blind study was to investigate the clinical efficacy and safety of S(-)-bupivacaine compared with standard racemic bupivacaine (RB) in horses under caudal epidural analgesia. Two treatments were administered to each horse, with a 2-week interval between subsequent treatments. Treatment 1 consisted of 0.5% LB at a dose of 0.06 mg/kg of body weight, and treatment 2 consisted of 0.5% RB at a dose of 0.06 mg/kg of body weight. Epidural injections were given in all animals between the first and second coccygeal vertebra. Heart rate (HR), arterial pressures, respiratory rate (RR), rectal temperature (RT), analgesia, and motor blocking were determined before drug administration (basal) and 5, 10, 15 and 30 min after drug administration, and at 30 min intervals thereafter. There were no significant differences between the two treatments in the quality of sensory and motor block. The duration of analgesia was 320 +/- 30 min (mean +/- SD) for RB and 360 +/- 42 min for LB. HRs and RRs, arterial pressures and RT did not change (P < 0.05) significantly from basal values after epidural administration of LB or RB. This study supports that 0.5% LB is an effective alternative to RB in caudal epidural analgesia in conscious, standing horses. The use of LB vs. RB warrants further investigation, particularly for long-lasting surgery in the perineal region.

Analgesia, Epidural↗

The reliability, acceptability and applications of basal body temperature (BBT) records in the diagnosis and treatment of infertility.

The possibilities and limitations of basal body temperature (BBT) records as an adjunct in the management of infertility were re-evaluated. To assess its accuracy as an index of ovulation, 172 charts were analyzed by three different physicians. While the average true positive rate was 90%, the false negative rate was only 2%. The remaining graphs (8%) were classified as non-interpretable, probably reflecting measurement problems. Retrospective assessment of 210 biphasic records showed the thermal nadir to occur within 1 day of the urinary luteinizing hormone (LH) surge in 75% of the cases, and in 90% when 2 days where considered. This confirms BBT as a relatively accurate guide for retrospective identification of the periovulatory period. Moreover, results of a study conducted to investigate how patients experienced daily recording of BBT graphs suggest that the method is well accepted by a high proportion of women. From all these it appears that there are many indications where BBT graphs can still be applied. Development of new electronic devices may further improve the reliability, acceptability and applications of the BBT records in the fertility investigation.

Adult↗

[Prognostic factors associated with community-acquired aspiration pneumonia].

BACKGROUND: Aspiration pneumonia (AP) represents about 5-24% of community-acquired pneumonias. This condition mainly affects elderly patients and causes a high mortality. Our objective was to quantify the AP mortality rate and to identify prognostic factors upon patients admission. PATIENTS AND METHOD: We underwent a retrospective observational study of a cohort of AP patients admitted to a tertiary care hospital during a 29 months period. The in-hospital mortality rate was calculated. To identify prognostic factors, basal characteristics of patients as well as their clinical presentation and complementary tests performed on admission were studied and analyzed by univariate and multivariate techniques. Odds ratios and 95% confidence intervals were estimated. RESULTS: Thirty six out of 105 admitted patients with AP died (cumulative mortality incidence rate 34%, 95% CI 25-44%). In the univariate analysis, demographic, clinical and complementary test variables were associated with mortality. Final logistic model revealed the following independent variables: living in a nursing home (OR = 3.4; 95% CI 1.1-10.9), high degree of dependence (OR = 0.3; 95% CI, 0.1-0.9), body temperature (OR = 0.5 per Celsius degree; 95% CI, 0.3-1.0), serum creatinine levels (OR = 2.2 per mg/100 ml; 95% CI, 1.2-4.1) and LDH serum concentrations (OR = 1.5 per 100 IU/L; 95% CI, 1.1-2.0). CONCLUSIONS: The mortality of community-acquired AP is very high. In addition to clinical and biological parameters on admission such as body temperature and LDH and creatinine serum concentrations, living in a nursing home and having a high degree of dependence for the basic daily activities were identified as independent prognostic factors. An in-depth knowledge of prognostic factors related to pre-admission care and assistance is needed to decrease the mortality in these patients.

Activities of Daily Living↗

Effect of subcutaneous sumatriptan on head temperature in migraines.

Sumatriptan, a selective 5-hydroxy-triptamine (5-HT1) receptor agonist, has been used recently in the treatment of acute migraine. Some in vitro experiments suggested that sumatriptan has vasoactive properties in vascular beds distinct from cerebral circulation. In view of this we investigated the vascular effects of the standard 6 mg subcutaneous (s.c.) dose of sumatriptan, on the surface areas of the head using thermography, a simple and reliable method for detecting temperature changes. The head temperature of 127 patients (double-blind), 102 migraines (52 during headache attack and 50 headache-free) and 25 healthy control subjects were evaluated using thermography in basal condition and 30, 60, 90, and 120 min after s.c. sumatriptan injection of placebo. During the entire observation period systemic blood pressure (SBP), heart rate (HR) and continuous electrocardiogram (ECG) were detected automatically. A significant head temperature decrease was observed after s.c. sumatriptan administration, in both healthy controls and migraine subjects; placebo administration did not show any change of temperature. In migraine patients during headache attack, head temperature reduction corresponded to the relief of headache symptoms. This vasoconstrictor effect detected with thermography is not isolated to cranial circulation but it is also systemic. In fact, we observed a significant increase (p < 0.05) in both systolic and diastolic systemic blood pressure. No significant changes in heart rate and ECG abnormalities were otherwise detected. These findings suggest that sumatriptan is effective in the treatment of migraine attack, but it must be used with caution in migraines with concomitant hypertension.

Adult↗

Variations in the resting oxygen consumption of small babies.

Over 200 measurements of the resting rate of oxygen consumption using an open-circuit method were made on 15 small babies nursed in their usual clinical setting during the first month of life. There were striking and persistent variations between babies that could not be explained by postnatal age, relationship to feed, sleep, or time of day. It was not possible from clinical examination to predict which babies had the higher or lower metabolic rates, except that babies who were light-for-dates generally had higher values. Because of these variations the appropriate thermal temperature for small babies cannot be predicted from average values adjusted for body weight and postnatal age alone.

Age Factors↗

Rapid urinary LH assay for prediction of ovulation.

The results of the cervical mucus score (CMS), basal body temperature (BBT) and a rapid urine luteinizing hormone (LH) assay by haemagglutination immunoassay were compared with plasma LH radioimmunoassay in 28 ovulatory cycles. There was good correlation of the CMS peak with the plasma LH peak while the urine LH peak usually occurred one day later. The first day when the CMS was greater than or equal to 8 occurred within +/- 1 day of the plasma LH peak in 89.3% of cycles. The first day when the urine LH was greater than or equal to 100 iu/l occurred within +/- 1 day of the plasma LH peak in all the cycles. BBT nadir could be identified in only 82% of cycles and it coincided with the plasma LH peak in only 28.6% of cases. These findings suggest that both the CMS and the rapid urine LH assay are acceptable methods for determining the time of ovulation while the BBT is not useful.

Body Temperature↗

Functional consequences of the repeated administration of Delta9-tetrahydrocannabinol in the rat.

The repeated administration of Delta(9)-tetrahydrocannabinol (THC) results in tolerance to many of its behavioral and physiological effects. It also produces changes in the functionality of cannabinoid receptors. What is not completely understood is how these cellular events translate into the behavioral and physiological changes that are associated with repeated cannabinoid agonist treatment. The purpose of these studies was to determine the development of changes in the patterns of functional activity, as measured by the 2-[14C]deoxyglucose method (2DG), associated with repeated THC exposure. Male Sprague-Dawley rats (n=4-5) were administered THC (vehicle or 10 mg/kg, intraperitoneally), daily for 7 or 21 days. Fifteen minutes following the final THC treatment the 2DG procedure was initiated. In separate sets of rats similarly treated with THC, locomotor activity and core body temperature were measured at corresponding time points in order to establish the behavioral profile of repeated THC administration. The acute administration of THC following 7 or 21 days of drug exposure resulted in a significant attenuation of changes in rates of glucose utilization throughout the majority of brain regions analyzed when compared to the large global decreases observed following a single administration of THC. After 7 and 21 days of treatment, cerebral metabolic rates were no longer different from vehicle-treated controls in most cortical, thalamic and basal ganglia regions. This attenuation closely paralleled the development of tolerance to the effects of THC on locomotor activity and core body temperature. However, glucose utilization remained altered in the nucleus accumbens, mediodorsal thalamus, basolateral amygdala, portions of the hippocampus and median raphe. These data suggest that the development of tolerance to the cerebral metabolic effects of THC is regionally specific and temporally distinct. The persistence of effects in limbic areas as well as portions of the hippocampal complex, however, suggests that processes such as stress, reward, and aspects of memory mediated by these brain regions may continue to be affected by THC even after prolonged THC exposure.

Animals↗

Computational verification of anesthesia effect on temperature variations in rabbit eyes exposed to 2.45 GHz microwave energy.

This paper computationally verifies the effect of anesthesia on temperature variations in the rabbit eye due to microwave energy. The main reason for this investigation is that our previous paper suggested a reduction in blood flow due to the administration of anesthesia, resulting in an overestimated temperature increase. However, no quantitative investigation has yet been conducted. The finite-difference time-domain (FDTD) method is used for calculating power absorption and temperature variation in rabbits. For this purpose, we used a computational rabbit phantom, which is comprised of 12 tissues (including 6 eye tissues) with a resolution of 1 mm. Thermal constants of the rabbit were derived by comparing measured and calculated temperatures. For intense microwave exposure to the rabbit eye, time courses of calculated and measured temperatures were in good agreement for cases both with and without the administration of anesthesia. The point to be stressed is that under anesthesia the thermoregulatory response was inactivated and blood flow and basal metabolism was reduced.

Absorption↗