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A product-inhibition study of bovine liver glutamate dehydrogenase.

1. Initial rates of oxidative deamination of L-glutamate with NAD+ as coenzyme, and of reductive aminiation of 2-oxoglutarate with NADH as coenzyme, catalysed by bovine liver glutamate dehydrogenase were measured in 0.111 M-sodium phosphate buffer, pH 7, at 25 degrees C, in the absence and presence of product inhibitors. All 12 possible combinations of variable substrate and product inhibitor were used. 2. Strict competition was observed between NAD+ and NADH, and between glutamate and 2-oxoglutarate. All other inhibition patterns were clearly non-competitive, except for inhibition by NH4+ with NAD+ as variable substrate. Here the extrapolation did not permit a clear distinction between competitive and non-competitive inhibition. 3. Mutually non-competitive behaviour between glutamate and NH4+ indicates that these substrates can be bound at the active site simultaneously. 4. Primary Lineweaver-Burk plots and derived secondary plots of slopes and intercepts against inhibitor concentration were linear, with one exception: with 2-oxoglutarate as variable substrate, the replot of primary intercepts against inhibitory NAD+ concentration was curved. 5. Separate Ki values were evaluated for the effect of each product inhibitor on the individual terms in the reciprocal initial-rate equations. With this information it is possible to calculate rates for any combination of substrate concentrations within the experimental range with any concentration of a single product inhibitor. 6. The inhibition patterns are consistent with neither a simple compulsory-order mechanism nor a rapid-equilibrium random-order mechanism without modification. They can, however, be reconciled with either type of mechanism by postulating appropirate abortive complexes. Of the two compulsory sequences that have been proposed, one, that in which the order of binding is NADH, NH4+, 2-oxoglutarate, requires an implausible pattern of abortive complex-formation to account for the results. 7. On the basis of a rapid-equilibrium random-order mechanism, dissociation constants can be calculated from the Ki values. Where these can be compared with independent estimates from the kinetics of the uninhibited reaction or from direct measurements of substrate binding, the agreement is reasonable good. On balance, therefore, the results provide further support for the rapid-equilibrium random-order mechanism under these conditions.

Ammonia↗

Effect of repetitive exercise testing on breathlessness in humans.

There are conflicting reports on the reproducibility of the visual analogue scale (VAS) and the modified Borg scale for the estimation of breathlessness during exercise. In an attempt to clarify the situation, two groups of healthy subjects undertook a progressive exercise test either daily (Group A) or weekly (Group B) on 10 separate occasions. Breathlessness was estimated every 1 min using the VAS. After 10 occasions, both Group A (P <0.05) and Group B ( P <0.01) showed a significant increase in the mean intercept of the breathlessness/ventilation (VAS/ V (I)) relationship. The increase was not progressive; using change point regression, reproducible values were found to occur after approximately the fifth occasion in both subject groups. As the slope of the VAS/ V (I) relationship was highly reproducible and did not change with repeat testing, it would appear that at least two mechanisms are involved in the generation of the sensation of breathlessness. A decrease in the exercise heart rate over the same time period was significantly correlated with changes in the VAS/ V (I) intercept in both groups (P <0.01 and P <0.005 respectively). The relationship is unlikely to be causal, but may be indicative of a common underlying mechanism. It is suggested that breathlessness scores are likely to decrease as a direct result of repetitive testing over, on average, the first five periods of assessment. On the basis of this study, it may be inferred that a physiological mechanism contributes to the modulation of breathlessness during repetitive exercise testing.

Adult↗

Consonant-vowel interdependencies in babbling and early words: preliminary examination of a locus equation approach.

Consonant-vowel productions at two distinct stages of language development were studied in a single female child. At 12 months canonical babbling syllables (N = 144) identified by a panel of listeners as comprising [bV], [dV], and [gv] tokens were acoustically analyzed by measuring F2 transition onset and F2 midvowel frequencies and plotting their relationship as locus equations for each stop category. A regression analysis performed on these scatterplots revealed differential slopes and y-intercepts as a function of stop place. The same analysis was performed 9 months later on CV utterances (N = 243) produced as syllable-initial segments of real words by the same child. Whereas labial and velar locus equation parameters moved toward more adult-like values, alveolar slope and y-intercept moved away from adult values and more in the direction of decreased coarticulation between vowel and consonant. There was greater scatter of data points around the regression line for production of words compared to babbling. These results are compared to locus equations obtained from 3-5-year-olds and adults. Locus equations appear to be useful as an empirical developmental probe to document how CV productions gradually approach adult categorical standards.

Cross-Sectional Studies↗

An examination of the degrees of freedom of human jaw motion in speech and mastication.

The kinematics of human jaw movements were assessed in terms of the three orientation angles and three positions that characterize the motion of the jaw as a rigid body. The analysis focused on the identification of the jaw's independent movement dimensions, and was based on an examination of jaw motion paths that were plotted in various combinations of linear and angular coordinate frames. Overall, both behaviors were characterized by independent motion in four degrees of freedom. In general, when jaw movements were plotted to show orientation in the sagittal plane as a function of horizontal position, relatively straight paths were observed. In speech, the slopes and intercepts of these paths varied depending on the phonetic material. The vertical position of the jaw was observed to shift up or down so as to displace the overall form of the sagittal plane motion path of the jaw. Yaw movements were small but independent of pitch, and vertical and horizontal position. In mastication, the slope and intercept of the relationship between pitch and horizontal position were affected by the type of food and its size. However, the range of variation was less than that observed in speech. When vertical jaw position was plotted as a function of horizontal position, the basic form of the path of the jaw was maintained but could be shifted vertically. In general, larger bolus diameters were associated with lower jaw positions throughout the movement. The timing of pitch and yaw motion differed. The most common pattern involved changes in pitch angle during jaw opening followed by a phase predominated by lateral motion (yaw). Thus, in both behaviors there was evidence of independent motion in pitch, yaw, horizontal position, and vertical position. This is consistent with the idea that motions in these degrees of freedom are independently controlled.

Humans↗

Retrospective population pharmacokinetic analysis of cetirizine in children aged 6 months to 12 years.

AIMS: To evaluate retrospectively the population pharmacokinetics of cetirizine, a second-generation antihistamine, in children. METHODS: Data were pooled from six clinical trials, in which cetirizine was administered orally in various formulations and in single and multiple dosage regimens. The population consisted of 112 children (33 female and 79 male) aged 6 months to 12 years. A one-compartment open model with first-order absorption and elimination was fitted to the plasma concentration-time profiles using nonlinear mixed effects modelling with first-order estimation. RESULTS: A linear association was found between apparent clearance (CL/F) and age with the former increasing by 0.12 l h(-1) per year. The intercept of the relationship was slightly lower for female children (0.59 vs. 0.77 l h(-1) in male). The population estimate of CL/F for an average age of 7 years was 1.61 and 1.43 l h(-1) for male and female children, respectively. A linear association was found between apparent volume of distribution (V/F) and age with the former increasing by 1.4 l year(-1), with an intercept of 4.0 l. The population estimate of V/F for an average age of 7 years was 13.9 l. The magnitudes of interpatient variability were 35.6% for CL/F and 19.7% for V/F. The magnitude of residual variability in cetirizine concentrations was 26.9%. CONCLUSIONS: Population analysis predicts a linear increase in cetirizine CL/F and V/F with age, with CL/F being slightly lower in female children, relative to males of the same age. However, this gender difference probably has no clinical consequences. Since V/F increased more rapidly with age than CL/F, a nonlinear increase in half-life was seen, from < 4 h in infants to near the adult value at 12 years of age. The current recommended dosing regimens that younger children should receive lower but more frequent doses, are confirmed by the present analysis.

Cetirizine↗

Validation of the FACSCount AF system for determination of sperm concentration in boar semen.

A flow cytometric method has been developed for rapid determination of sperm concentration in semen from various mammalian species.* All cells containing DNA are stained with SYBR-14 or propidium iodide (PI) and sperm concentration is determined in relation to an internal standard of fluorescent microspheres (beads). Satisfactory staining can be achieved within 2-3 min and the following flow cytometric analysis on the FACSCount AF System rapidly provides the user with a precise and accurate assessment of the sperm concentration. In this study, the FACSCount AF System and Sperm Counting Reagent (BD Biosciences) was compared with microscopic counting using a Bürker-Türk haemocytometer. In addition, sperm concentration was determined using the Corning 254 spectrophotometer which is used routinely by Danish artificial insemination stations for boars. The results show that the agreement between flow cytometry and microscopic counting is very high. The slope for the regression line was 1.12 (SE = 0.03) with an estimated intercept with the Y-axis of 22 x 10(6) sperm/ml (SE = 10 x 10(6) sperm/ml) and an estimated error of the model of 10 x 10(6) sperm/ml. For the spectrophotometer, the slope of the regression line was 1.09 (SE = 0.07) with an estimated intercept of 137 x 10(6) sperm/ml (SE = 25 x 10(6) sperm/ml). The average error made by the spectrophotometer was 55 x 10(6) sperm/ml. In addition, the results obtained using flow cytometry was highly repeatable (CV = 2.7%) in comparison with the spectrophotometric method (CV = 6.3%). These results indicate that the FACSCount AF System is a valuable tool for precise and accurate assessment of sperm concentration in boar semen and that use of this system may lead to production of more uniform insemination doses containing a specific number of sperm per dose.

Animals↗

Extrapolation of cardiac index from analysis of the left ventricular outflow velocities in children: implication of the relationship between aortic size and body surface area.

BACKGROUND: It has recently been reported in critically ill patients that a linear relationship exists between cardiac index (CI) measured with thermodilution and mean aortic blood flow velocity (MAFV). This hypothesis can be validated mathematically only if the aortic area (AA index) indexed to body surface area (BSA) remains constant and if the relationship between aortic diameter (PhiAo) and BSA is nonlinear. However, several other equations have described the relationship between BSA and, respectively, PhiAo and aortic area (AA) in children. The aim of this study was to determine if the relationships calculated between BSA and aortic size in children (without left ventricular outflow tract abnormality) could validate the hypothesis that MAFV and CI are well linked linearly, leading to its use to determine CI. METHODS: Two hundred and thirty-two measurements performed in 126 children and infants were retrospectively analysed. PhiAo was measured in the long axis view at the annulus using two-dimensional mode echocardiography with a 5-MHz transducer. Various linear and nonlinear relationships between BSA and, respectively, PhiAo, PhiAoindex, AA and AAindex were determined based on a nonlinear regression method with a model as follows: y=a(xc) + b. The comparisons between regressions were conducted based on the estimation error. RESULTS: The relationships between PhiAo and BSA appeared nonlinear and was well described by: PhiAo=2.96(BSA1/4) - 1.31 with a non-zero y-intercept and PhiAo=1.64(BSA1/2) with a zero y-intercept. In contrast, the relationships between AA and BSA were linear. The AAindex was not linked to BSA and can be considered as constant. The coefficient a of the equation appeared similar to those obtained mathematically with the relationship previously described between MAFV and CI. CONCLUSIONS: The hypothesis that CI can be extrapolated to the measurement of MAFV appears valid as regards the relationships calculated between aortic size and BSA in children without left ventricular outflow tract abnormality.

Adolescent↗

Rate responsive pacing using transthoracic impedance minute ventilation sensors: a multicenter study on calibration stability.

Previous studies showed that transthoracic impedance minute ventilation (IMV), as measured by a pacemaker sensor, is closely correlated to actual minute ventilation (VE) determined by standard methods. The aim of this study was to analyze the changes in the calibration between IMV and VE at rest and during exercise over time. Fifteen patients (age 60 +/- 13 years) with Medtronic Kappa 400 pacemakers completed a baseline visit followed by two visits separated by 1 month and 1 week, respectively. In each patient, VE (L/min) was monitored at rest in the supine and sitting positions and during graded bicycle ergometer exercise using a standard cardiopulmonary metabolic gas analysis system with simultaneous recording of IMV (omega/min) using DR-180 extended telemetry monitors. Calibration at rest was defined as the ratio of IMV to VE, calculated from 1-minute average values in the supine and sitting positions. Calibration during bicycle exercise was defined as intercept (IMV value at VE = 10 L/min-typical VE value at beginning of exercise), and slope of the IMV/VE regression line. The calibration of IMV showed individual variability over time. The magnitude (absolute value) of observed fractional changes in calibration at 1 month was 0.23 +/- 0.20 (rest-supine), 0.20 +/- 0.15 (rest-sitting), 0.18 +/- 0.19 (exercise-intercept), 0.28 +/- 0.35 (exercise-slope), and 0.18 +/- 0.15, 0.15 +/- 0.09, 0.28 +/- 0.39, and 0.27 +/- 0.15, respectively, at 1 week. The magnitude of change at 1 month was not statistically different from the magnitude of change at 1 week. In conclusion, the calibration of IMV, as measured by a pacemaker sensor, versus actual VE may demonstrate variability. However, this study also suggests that the observed changes are not cumulative over time. These results have implications for patient monitoring applications using these sensors and for development of future pacemaker rate response algorithms.

Arrhythmias, Cardiac↗

Stereological estimation of the volume weighted mean volumes of alveoli and acinar pathways in the rat lung to characterise alterations after ischaemia/reperfusion.

The aim of this study was to characterise pulmonary reimplantation injury in isolated, perfused rat lungs following 2 h of cold ischaemia, and 50 min. of in vitro reperfusion. The effects of 2 differently composed lung preservation solutions (low potassium Euro-Collins and Celsior; each n = 5) were examined in comparison with untreated, nonischaemic control lungs (n = 3). After fixation by vascular perfusion and tissue collection by systematic random sampling, the volume weighted mean volume (Vv) of alveoli and acinar pathways was estimated by light microscopic stereology using the method of point sampled intercepts in plastic embedded, Azan-stained material. Significantly higher Vv of alveoli and acinar paths was found in the Celsior group than in Euro-Collins preserved lungs. However, in the controls the size of acinar pathways was similar to Celsior preserved lungs whereas alveolar size was comparable to preservation with Euro-Collins. The between-animal coefficient of variation of alveoli was very low in controls and Celsior preserved but higher in the Euro-Collins group. Size distribution of alveoli and acinar paths in 15 size classes was largely homogeneous in all groups tested. In the Euro-Collins group the fractions of both class 1-alveoli and class 1-acinar paths significantly exceeded those of the other groups. Widely expanded alveoli (size classes 13-15) only occurred after preservation with Celsior whereas wider acinar paths (size class 15) were found in the Celsior group and in the controls. It is concluded that lung preservation with low-potassium Euro-Collins and Celsior solutions may act differently on distinct spaces in the distal gas-exchange regions of lungs. This may be due to selective effects on pulmonary surfactant activity and on elastic tissue elements in the alveolar ducts, respectively. Additionally, the method of point sampled intercepts is considered to be an efficient tool to evaluate the effects of different preservation solutions on lung parenchyma.

Animals↗

Stereological estimation of volume-weighted mean glomerular volume from arbitrary sections of the equine kidney.

Mean glomerular volume has previously been estimated, using stereological techniques, specifically the point-sampled intercept (PSI), either from isotropic or from vertical sections. As glomeruli are approximately spherical structures, the same stereological technique was carried out on vertical and arbitrary sections to determine whether section orientation had any effect on mean glomerular volume estimation. Equine kidneys from 10 individuals were analysed using the PSI method of estimating volume-weighted mean glomerular volume (MGV); for each kidney, arbitrary and vertical sections were analysed. MGVs were not significantly different between arbitrary and vertical sections (P = 0.691) when analysing the data with the paired t test; when plotting MGV estimates from arbitrary sections against those from vertical sections the intercept was found not to be significantly different from zero (P > 0.8) and the slope of the regression line not to be significantly different from 1.0 (P > 0.4). For the estimation of MGV in equine kidneys using PSI, arbitrary sections may be used if it is not possible to use isotropic or vertical sections, but some caution must be exercised in the interpretation of results so gained.

Animals↗

Validation of a noninvasive method to measure brain temperature in vivo using 1H NMR spectroscopy.

The goal of this study was to evaluate the potential of using the difference between the 1H NMR frequencies of water and N-acetylaspartic acid (NAA) to measure brain temperature noninvasively. All water-suppressed and non-water-suppressed 1H NMR spectra were obtained at a field strength of 4.7 T using a surface coil. Experiments performed on model solutions revealed a decrease in the difference between NMR frequencies for NAA and water as a linear function of increasing temperature from 14 to 45 degrees C. Changing pH in the range 5.5-7.6 produced no discernible trends for concurrent changes in the slope and intercept of the linear relationship. There were minor changes in slope and intercept for solutions containing 80 or 100 mg of protein/ml versus no protein, but these changes were not considered to be of sufficient magnitude to deter the use of this approach to measure brain temperature. The protein content of swine cerebral cortex was found to remain constant from newborn to 1 month old (78 +/- 12 mg/g; n = 41). Therefore, data collected for the model solution containing 80 mg of protein/ml were used as a calibration curve to calculate brain temperature in eight swine during control, hypothermia, ischemia, postischemia, or death, over a temperature range of 23-40 degrees C. A plot of 61 temperatures determined from 1H NMR versus temperatures measured from an optical fiber probe sensor implanted 1 cm into the cerebral cortex showed excellent linear agreement (slope = 1.00 +/- 0.03, r2 = 0.96). We conclude that 1H NMR spectroscopy presents a practical means of making noninvasive measurements of brain temperature with an accuracy of better than +/- 1 degree C.

Animals↗

Class differences in the effects of calcium channel blockers in the rat remnant kidney model.

BACKGROUND: Controversy persists as to the existence of class differences between calcium channel blockers (CCBs) in their ability to provide renoprotection and as to potential mechanisms involved. METHODS: Rats with 5/6 renal ablation were left untreated or received diltiazem, verapamil, or felodipine after the first week, and the relationship between continuous radiotelemetrically measured blood pressure (BP) and glomerulosclerosis (GS) was assessed at seven weeks. Additionally, the effects of these CCBs on renal autoregulation and hypertrophy were examined at three weeks after renal ablation. RESULTS: Although an excellent linear correlation was observed between the average BP levels and GS in all groups (r = 0.75 to 0.84, P < 0.01), significant protection was not achieved with any of the CCBs, but for different reasons. The antihypertensive effects of diltiazem were not sustained beyond the second week. Verapamil significantly reduced the average BP (144 +/- 4 mm Hg vs. 181 +/- 8 in untreated rats) but shifted the slope of the relationship between BP and GS (increase in percentage GS/mm Hg increase in average systolic BP) to the left (x intercept 121 vs. 144 mm Hg for untreated rats, P < 0.01) so that GS was not reduced. Felodipine also significantly reduced the average BP (144 +/- 3 mm Hg) and shifted the slope to the left (x intercept 123 mm Hg), but additionally made the slope steeper (2.3 +/- 0.5 vs. 0.82 +/- 0.2 in untreated rats). Because of these differing effects on the relationship between BP and GS, the rank order of GS for any given BP elevation was as follows: felodipine > verapamil > diltiazem = untreated. Felodipine, but not verapamil or diltiazem, caused additional impairment of the already impaired renal autoregulation in untreated rats, thereby explaining its adverse effects on GS. By contrast, the adverse effects of verapamil on GS were attributable to the greater amplitude of BP fluctuations that was observed in the verapamil-treated rats such that for any given average BP, these rats were exposed to greater peak pressures as compared with the other groups. None of the CCBs had a significant effect on glomerular hypertrophy. CONCLUSIONS: These class differences between CCBs in their relative impact on systemic BP profiles, renal autoregulation, and glomerular pressure transmission may have clinically significant implications and may account for the variable glomeruloprotection that has been observed with these agents in both experimental models and in humans.

Animals↗

Microaggregate blood filtration and the febrile transfusion reaction. A comparative study.

Seventy-four patients with chronic transfusion requirements and histories of repetitive febrile reactions were transfused with 1138 units of microaggregate-filtered red cells. The filtered blood was prepared using either a direct interception or a depth filter. One-half of the units were centrifuged immediately prior to filtration. Microaggregate filtration reduced the overall incidence of febrile transfusion reactions by 77 percent. The centrifugation-filtration protocol reduced the rate of reactions by 98 percent. There were no differences between the ability of the different filters to reduce the reaction rate; however, red cell loss was twice as large with the depth filter as with the direct interception filter. The numerical criterion for "leukocyte-poor blood" was met in all units processed by centrifugation-filtration. Only units processed during the last 2 weeks of shelf-life fulfilled this criterion when centrifugation was omitted from the procedure. The majority of the latter units were clinically tolerated well due to their reduced granulocyte content.

Cell Aggregation↗

Measurement of circulating red cell volume using biotin-labeled red cells: validation against 51Cr-labeled red cells.

BACKGROUND: Anemia is a serious problem in the fetus and preterm infant. To investigate the physiology and pathophysiology of anemia and to assess responses to blood transfusions or erythropoietin therapy, measurement of circulating red cell volume would be useful. Because the standard 51Cr method exposes the subject to radiation, a method of measuring circulating red cell volume without radiation exposure, sufficiently sensitive for use in fetuses and infants, was developed. STUDY DESIGN AND METHODS: In 10 healthy adults whose body mass ranged from 56.8 to 115.9 kg, aliquots of autologous red cells were labeled with biotin or with 51Cr, mixed, and transfused intravenously. Circulating red cell volume was measured in posttransfusion blood by quantitating the in vivo dilution of biotinylated red cells. Biotinylated red cells were detected by two methods: 1) 125I-streptavidin and 2) fluorescein-labeled avidin with flow cytometry. RESULTS: Circulating red cell volume measured by 125I-streptavidin detection agreed well with that measured by 51Cr (slope = 1.07, y-intercept = -97, correlation = 0.987). Similarly, circulating red cell volume measured by flow cytometry agreed well with that measured by 51Cr (slope = 1.05, y-intercept = -20, correlation = 0.987). CONCLUSIONS: Circulating red cell volume measured by the use of biotin with either 125I-streptavidin or flow cytometry agrees with that measured by 51Cr. Each system provides a method of performing these studies without exposing the subject to radiation.

Adult↗

Linearly scaled, rate-invariant normal limits for QT interval: eight decades of incorrect application of power functions.

INTRODUCTION: Normal limits for QT traditionally are derived as mean +/- 2*SD, with rate adjustment done by dividing QT values by power functions such as RR 1/2 (proportional scaling). METHODS AND RESULTS: We evaluated procedures for deriving normal limits by comparing adjusted QT distributions versus heart rate using ECG data of 11,739 normal men and women aged > or = 40 years. QT decreased as predicted by many power functions with heart rate but its SD remained relatively unchanged. Consequently, proportional scaling induced rate-dependent distortion of normal limits. Furthermore, QT distributions by heart rate were variably skewed and non-normal. Therefore, normal limits expressed as mean +/- 2*SD were misleading. Omission of regression intercept was an additional reason for failure of Bazett's and Fridericia's formulas. Regularized normal limits for adjusted QT (Qta) were obtained with linear instead of proportional scaling of type QTa = QT + k1*(1 - RR(k2)), for instance, with k2 = 0.5, k1 = 0.360 for males and 0.353 for females, or with k2 = 0.42, k1 = 0.414 for males and 0.420 for females. With linear scaling, QTa = 460 msec was established as the upper 2% normal limit, with 32 msec as the limit for a significant QTa increase from reference ECG in serial comparison. CONCLUSION: Traditional procedures for establishment of normal limits failed because of proportional scaling, assumption of normal QT distribution, or omission of regression intercept. Percentile distributions of linearly scaled adjusted QT produced regularized rate invariant normal limits within normal sinus rates.

Adult↗

[Orthodontics founded on "proof" or therapeutic decision making based on the literature].

Faced to an abundant literature and to various clinical situations, practitioners are nowadays invited to implement an evidence based approach. This methodology, initially developed in Canada in the 80's, is getting widely used and is perfectly suited for Orthodontics and particularly for the evaluation of interceptive treatments. It is defined as the conscentious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. This approach, which requires four different steps, will initially be presented. A methodological guide that allows to grade the evidence among different research protocols, will then be introduced. At the top of the hierarchy, randomized clinical trials have shown to be the best tools available to evaluate treatment efficiency. Different research designs are finally put forward to evaluate interceptive treatments.

Databases, Bibliographic↗

Assessment of the respiratory actions of intramuscular morphine in conscious dogs.

The actions on the respiratory system of 0.25, 0.5 and 1.0 mg kg(-1) morphine given intramuscularly were studied in conscious dogs. Dogs breathed oxygen with 0, 2 and 4 per cent CO(2), in that order, through a mask attached to a flow sensor and connected to a respiratory mechanics monitor. When a steady state period of respiration was reached breathing pure oxygen, respiratory rate, tidal volume, respiratory minute volume, peak expiratory flow rate and end tidal CO(2)(PetCO(2)) were measured. The respiratory minute volume and PetCO(2) were measured when the dogs breathed 2 and 4 per cent CO(2) in oxygen, the points plotted onto a graph and the gradient of the line, describing the PCO(2)/ventilation response, plus the intercept with the y-axis were determined. Measurements for each morphine dose were taken before injection and at 30 minutes, 1, 2, 3, 4, 6 and 8 hours post injection. The incidence of panting after morphine was dose related and it occurred in all dogs given the high dose. Morphine reduced the gradients of the PCO(2)/ventilation response lines and raised the intercept. Other changes were increased respiratory minute volume and peak expiratory flow and decreased PetCO(2) and tidal volume.

Analgesics, Opioid↗

The leptin-fat ratio is constant, and leptin may be part of two feedback mechanisms for maintaining the body fat set point in non-obese male Fischer 344 rats.

While plasma leptin and adiposity have been found to be strongly related, the specific nature of this relationship has yet to be clarified. Hence, plasma leptin and three indicators of adiposity were measured in adult male Fischer 344 rats on three different long-term diets: continuous ad libitum feeding; ad libitum feeding until early adulthood, then continuous 60% caloric restriction; and ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, then ad libitum feeding for 5 months. Body fat was found to be a good linear correlate of plasma leptin, with a zero Y-intercept, and a constant plasma leptin-body fat ratio. The number of adipocytes per rat and % body fat were strong quadratic correlates of plasma leptin. This study is the first to find a zero Y-intercept and constant plasma leptin-body fat ratio, probably because it is the first to simultaneously measure both plasma leptin and body fat accurately, and to account for confounders such as gender, genetic background, age, physical activity, and possibly obesity. The study also explored the effect of switching calorically-restricted rats to ad libitum feeding. This led to a rapid rise, and then synchronized up-down cycles in average daily food intake and body weight, with a steady upward trend toward a new stable body-weight set point. It is hypothesized that this pattern resulted from two simultaneous feedback mechanisms, possibly involving leptin. In conclusion, this study suggests that, under controlled conditions, the plasma leptin-body fat ratio is a constant for a particular mammalian strain, independent of dietary history.

Adipose Tissue↗