Granulocyte margination in the human lung and its response to strenuous exercise

1992 ◽  
Vol 82 (2) ◽  
pp. 237-244 ◽  
Author(s):  
A. M. Peters ◽  
P. Allsop ◽  
A. W. J. Stuttle ◽  
R. N. Arnot ◽  
M. Gwilliam ◽  
...  
Keyword(s):  
Count Rate ◽  
Time Course ◽  
Normal Subjects ◽  
Whole Body ◽  
Strenuous Exercise ◽  
Lung Pathology ◽  
Total Blood ◽  
Significant Release ◽  
The Mean ◽  
Blood Granulocyte

1. It is widely believed that the lung is an important site of granulocyte margination and releases most of the granulocytes of the peripheral neutrophilia of exercise. 2. We measured granulocyte margination in the lung in terms of the lung total blood granulocyte pool and the lung circulating granulocyte pool in eight patients without inflammatory disease or evidence of lung pathology by comparing the regional γ-camera lung count rate of 111In-labelled granulocytes with that of 111In-labelled erythrocytes. According to the respective 111In activities in peripheral blood samples taken between 5 and 40 min after granulocyte injection, the lung marginating granulocyte pool was 0.78 (sem 0.045) of the lung total blood granulocyte pool or 4.6 (0.92) of the lung circulating granulocyte pool 5 min after injection, decreasing to plateau values of 0.57 (0.053) and 1.53 (0.28) from 20 min after injection. This compared with corresponding whole-body ratios of about 0.6 and 1.5, respectively. 3. After 4 min of maximal exercise in four normal subjects given 111In-labelled granulocytes 60 min before exercise, the 111In-labelled granulocyte count rate over the lung increased to 1.23 (0.05) of the pre-exercise value with a time course that was essentially identical with the time course of the peripheral native neutrophilia. The spleen 111In signal decreased with the same time course, reaching a minimum of 0.63 (0.05) of the pre-exercise level at 5–10 min after the end of exercise. 4. In a further four normal subjects given 99mTc-labelled erythrocytes, exercise resulted in an increase in the lung 99mTc count rate to 1.11 (0.05) of the pre-exercise value. This increase was maximal immediately after the end of exercise. Based on changes in peripheral haemoglobin, total blood volume decreased in the eight normal subjects to 0.89 (0.01) of the pre-exercise value. 5. Using (a) the mean increases seen in lung 111In and 99mTc count rates in the normal subjects, (b) the mean haemoconcentration recorded in the normal subjects and (c) the mean baseline ratio of lung marginating granulocyte pool/lung total blood granulocyte pool measured in the patients, we calculated that the lung marginating granulocyte pool after exercise declined to only 0.94 of the pre-exercise value in the four normal subjects given 111In-labelled granulocytes. 6. We conclude (a) that although granulocytes marginate in the lung, they do not do so to an extent greater than the average for the whole body, and (b) that there is no significant release of granulocytes from the lungs as a result of exercise.

EARLY VARIATIONS OF PLASMA CORTISOL AFTER PULSE INTRAVENOUS INJECTION OF DIBUTYRYL CYCLIC ADENOSINE 3′,5′-MONOPHOSPHATE IN NORMAL SUBJECTS

1973 ◽  
Vol 72 (4) ◽  
pp. 753-761 ◽  
Author(s):  
Alberto Angeli ◽  
Giuseppe Boccuzzi ◽  
Roberto Frajria ◽  
Daniela Bisbocci ◽  
Franco Ceresa
Keyword(s):  
Intravenous Injection ◽  
Plasma Cortisol ◽  
Time Course ◽  
Healthy Adult ◽  
Normal Subjects ◽  
Adult Women ◽  
Healthy Women ◽  
Adrenal Steroidogenesis ◽  
The Mean ◽  
Zero Time

ABSTRACT 10 mg/kg of dibutyryl cyclic adenosine 3′,5′-monophosphate (Db-cAMP) was iv pulse injected into twelve healthy adult women. The plasma cortisol levels were determined as 11-OHCS at zero time and then at 2.5, 5, 7.5, 10, 15, 30, 60 and 180 min after the injection. The data were compared with those obtained at the corresponding times in two groups of eleven and seventeen healthy women after the injection of 250 ng and 250 μg of synthetic β-1-24 corticotrophin performed in the same manner as the injection of the nucleotide. The mean increments in plasma cortisol were significantly lower after Db-cAMP than after ACTH. Differences were noted by analyzing the time course of the responses. In the case of stimulation with Db-cAMP the 11-OHCS levels rose progressively to a maximum at 15–30 min. By contrast, a peak of plasma cortisol was evident in most cases within a few min after the injection of ACTH; after a fall, a later rise was then observed starting from 15 min. The differences in the plasma 11-OHCS responses after the two stimuli may also be of interest clinically for the investigation of some aspects of adrenal steroidogenesis.

The Comparative Pharmacodynamics of Remifentanil and Its Metabolite, GR90291, in a Rat Electroencephalographic Model 

1999 ◽  
Vol 90 (2) ◽  
pp. 535-544 ◽  
Author(s):  
Eugene H. Cox ◽  
Mariska W. E. Langemeijer ◽  
Josy M. Gubbens-Stibbe ◽  
Keith T. Muir ◽  
Meindert Danhof
Keyword(s):  
Steady State ◽  
Time Course ◽  
Parent Drug ◽  
Volume Of Distribution ◽  
Pharmacodynamic Model ◽  
Pharmacokinetic Parameters ◽  
Maximal Effect ◽  
Total Blood ◽  
The Mean

Background The purpose of this study was to investigate the in vivo pharmacodynamics and the pharmacodynamic interactions of remifentanil and its major metabolite, GR90291, in a rat electroencephalographic model. Methods Remifentanil and GR90291 were administered according to a stepwise infusion scheme. The time course of the electroencephalographic effect (0.5-4.5 Hz) was determined in conjunction with concentrations of the parent drug and the metabolite in blood. Results Administration of remifentanil resulted in concentrations of remifentanil and GR90291 in the ranges 0-120 ng/ml and 0-850 ng/ml, respectively. When the metabolite was administered, concentrations of the metabolite in the range 0-220 microg/ml and no measurable concentrations of remifentanil were observed. The mean +/- SE values of the pharmacokinetic parameters clearance and volume of distribution at steady state were 920+/-110 ml x min(-1) x kg(-1) and 1.00+/-0.93 l/kg for remifentanil and 15+/-2 ml x min(-1) x kg(-1) and 0.56+/-0.08 l/kg for GR90291. The relative free concentrations in the brain, as determined on the basis of the cerebrospinal fluid/total blood concentration ratio at steady state, were 25+/-5% and 0.30+/-0.11% for remifentanil and GR90291, respectively. Concentration-electroencephalographic effect relations were characterized on the basis of the sigmoidal Emax pharmacodynamic model. The mean +/- SE values for the maximal effect (Emax), the concentration at which 50% of the maximal effect is obtained (EC50), and Hill factor for remifentanil were 109+/-12 microV, 9.4+/-0.9 ng/ml, and 2.2+/-0.3, respectively (n = 8). For GR90291, the mean +/- SE values for EC50 and the Hill factor were 103,000+/-9,000 microg/ml and 2.5+/-0.4, respectively (n = 6). Conclusions Analysis of the data on the basis of a previously postulated, mechanism-based pharmacokinetic-pharmacodynamic model for synthetic opioids revealed that the low in vivo potency of GR90291 can be explained by a low affinity to the mu-opioid receptor in combination with a poor brain penetration.

Granulokinetics in normal dogs

1964 ◽  
Vol 206 (1) ◽  
pp. 83-88 ◽  
Author(s):  
S. O. Raab ◽  
J. W. Athens ◽  
O. P. Haab ◽  
D. R. Boggs ◽  
H. Ashenbrucker ◽  
...  
Keyword(s):  
Whole Blood ◽  
Turnover Rate ◽  
Half Time ◽  
Total Blood ◽  
Mean Values ◽  
Hexadimethrine Bromide ◽  
The Mean ◽  
Blood Granulocyte ◽  
Number Of Cells

Dog granulocytes were labeled in vitro with radioactive diisopropylfluorophosphate (DFP32) and then returned to the circulation of the donor. Granulocytes were separated from whole blood by utilizing hexadimethrine bromide as the sedimenting agent and saponin as a lysing agent. The labeled granulocytes disappeared from the circulation in an exponential fashion with a mean (±1 sd) half-time disappearance of 5.6 ± 0.95 hr. The size of the total blood granulocyte ( TBGP), circulating granulocyte ( CGP), and marginal granulocyte ( MGP) pools, and the granulocyte turnover rate ( GTR) were measured in 31 normal, unanesthetized dogs. The mean values ± 1 sd, expressed as number of cells x107/kg body wt., were as follows: TBGP, 102 ± 34.8; CGP, 54 ± 20.7; MGP, 48 ± 23.4; and GTR, 305 ± 111.5 cells/kg day. The values observed in anesthetized and in unanesthetized, splenectomized dogs were not significantly different from the above values.

Absorption of Copper in Homozygotes and Heterozygotes for Wilson's Disease and Controls: Isotope Tracer Studies with 67Cu and 64Cu

1972 ◽  
Vol 43 (5) ◽  
pp. 617-625 ◽  
Author(s):  
G. T. Strickland ◽  
W. M. Beckner ◽  
Mei-Ling Leu
Keyword(s):  
Wilson’S Disease ◽  
Body Burden ◽  
Normal Subjects ◽  
Wilson's Disease ◽  
Cirrhosis Of The Liver ◽  
Whole Body ◽  
Faecal Excretion ◽  
Body Retention ◽  
Body Counting ◽  
The Mean

1. Absorption of copper was determined by the simultaneous administration of 64Cu orally and 67Cu intravenously to six patients with Wilson's disease (WD), eighteen of their parents and siblings, four normal subjects and three subjects with cirrhosis of the liver. Absorption was calculated by three methods: (1) the mean ratio of 64Cu to 67Cu body retention at 3 and 4 days as determined by whole-body counting; (2) the mean ratio of 64Cu to 67Cu at 3 and 4 days as determined by faecal excretion; and (3) the mean ratio of 64Cu to 67Cu plasma radioactivity 6–24 h after administration. 2. The total-body counting and faecal methods for determining copper absorption agreed with each other, demonstrating that the normal absorption of copper is 40–70% (mean 56%) of the dose and that absorption is not influenced by cirrhosis of the liver, age or sex; but it appears to be inversely related to the amount of carrier copper. The absorption of copper in both homozygotes and heterozygotes for WD did not differ significantly from that of the control subjects. Therefore, the increased body burden of copper in WD does not appear to be due to over absorption, but rather to decreased biliary excretion of copper.

Untersuchungen zur effektiven Halbwertszeit des 131J bei der Radiojodbehandlung der Schilddrüsenautonomie

1991 ◽  
Vol 30 (03) ◽  
pp. 71-76
Author(s):  
R. Bares ◽  
U. Büll ◽  
B. Müller
Keyword(s):  
Time Course ◽  
Whole Body ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Exact Determination ◽  
The Mean ◽  
Therapeutic Doses ◽  
Autonomous Adenoma ◽  
Benign Thyroid

In order to compute effective half-life of131I after application of therapeutic doses (Teff), the time course of whole-body radioactivity was evaluated retrospectively in 115 patients with benign thyroid diseases (multinodular autonomous adenoma, solitary autonomous adenoma or Graves’ disease). Because of a large overlap of Teff in the various diseases analyzed, courses of all patients who did (group Ts, 24 cases) or did not (group kTs, 91 cases) receive antithyroid drugs during therapy were summarized. In group Ts a mean Teff of 5.0 ± 0.9 d was found which was significantly (p <0.01) lower than the mean Teff of 6.3 ± 0.9 d in group kTs. We believe that the mean Teff is a practical alternative in radioiodine dosimetry if an exact determination of Teff cannot be performed because of shortage of time.

Tachyphylaxis to inhaled methacholine in normal but not asthmatic subjects

1990 ◽  
Vol 69 (3) ◽  
pp. 875-879 ◽  
Author(s):  
W. H. Stevens ◽  
P. J. Manning ◽  
R. M. Watson ◽  
P. M. O'Byrne
Keyword(s):  
Time Course ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Cyclooxygenase Inhibitors ◽  
Test Results ◽  
Methacholine Test ◽  
Series Of Experiments ◽  
The Mean

Methacholine inhalation tests measure airway responsiveness in asthmatic and normal subjects. Tachyphylaxis occurs with repeated methacholine inhalations in normal subjects. The purpose of this study was to examine the time course and mechanisms of methacholine tachyphylaxis in normal subjects and to determine whether this occurs in mildly asthmatic subjects. Fifteen normal and nine asthmatic subjects were studied on 2 study days, at least 48 h apart. Each day, two inhalation tests were carried out. On one day, subjects performed two methacholine inhalation tests 3 h later by a methacholine test. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1), (PC20). All normal subjects developed methacholine tachyphylaxis. The mean PC20 increased from 47.3 mg/ml (%SE 1.34) to 115.6 (%SE 1.51) (P less than 0.0001) in a 3-h interval. This increase lasted for greater than or equal to 6 h (P = 0.012). Asthmatic subjects did not develop methacholine tachyphylaxis. Their mean methacholine PC20s were 1.6 mg/ml (%SE 1.4) and 1.5 (%SE 1.4) (P = 0.75) 3 h later. In two other series of experiments, normal subjects were pretreated with the cyclooxygenase inhibitors indomethacin (100 mg/day) or flurbiprofen (150 mg/day) or a placebo for 3 days before two methacholine tests 3 h apart. Both indomethacin and flurbiprofen significantly inhibited the development of methacholine tachyphylaxis. These results confirm that methacholine tachyphylaxis occurs in normal subjects, lasts greater than or equal to 6 h, and may occur through the release of inhibitory prostaglandins. By contrast, methacholine tachyphylaxis does not occur in asthmatic subjects.

The Influence Of Physiological Parameters On The Plasma Concentration Of β-Thromboglobulin (β-TG) And Platelet Factor 4 (PF-4) In Normal Healthy Subjects

1981 ◽  
Author(s):  
A Duncan ◽  
P Didisheim
Keyword(s):  
Oral Contraceptives ◽  
Healthy Subjects ◽  
Normal Subjects ◽  
Physiological Parameters ◽  
Strenuous Exercise ◽  
Control Group ◽  
Normal Range ◽  
Platelet Factor ◽  
Normal Ranges ◽  
The Mean

The variability of normal ranges in different laboratories and the occurrence of occasional elevated values of β-TG and PF-4 in normal subjects are well established. We examined the influence of factors such as age, sex, smoking, exercise, oral contraceptives and day-to-day variation in 148 healthy subjects. The β-TG and PF-4 assays were performed by commercial RIA’s modified by utilizing an EDTA- PGE1 -theophylline mixture as anticoagulant.The statistical method used to compare our groups was a student t-test after log transformation of the data. Our baseline control group (N=63) were non smokers and not taking oral contraceptives (O/C) or any medications. There was no difference between sexes or a significant change with increasing age, although the mean β-TG and PF-4 does increase in cohosts of 20 years. [<30 years (21.65±8.35)(SD), 30-50 years (24.32±10.94) >50 years (27.88±14.3)-β-TG data].Women on O/C were significantly different from those not on O/C for β-TG [35.06±22.45 (O/C) and 23.67±9.38 (N)] but not for PF-4 values [3.79±1.77 (O/C) and 3.91±1.63 (N)].Strenuous exercise was the parameter that influenced both β-TG and PF-4 significantly, showing an elevated value after exercise for both β-TG [81.9±31.4 v 26.73±10.91] and PF-4 [7.08±1.71 v 3.73±1.91].Day-to-day variations in β-TG and PF-4 were examined in 10 subjects for 7-10 days. The coefficient of variation (CV) amongst these subjects was 21-51%. In athletes day-today variation was the same unless a change in pattern of exercise occurred [CV-49-132%].Our results confirm that parameters such as above do influence normal values and should be taken into consideration in establishing a normal range.It also indicates the β-TG is a more sensitive parameter for delineating differences in physiological parameters in normal subjects than PF-4, and this may be applicable to clinical studies.

Airway caliber and the work of breathing in humans

1987 ◽  
Vol 63 (1) ◽  
pp. 20-24 ◽  
Author(s):  
S. J. Jennings ◽  
J. B. Warren ◽  
N. B. Pride
Keyword(s):  
Work Of Breathing ◽  
Vagal Tone ◽  
Normal Subjects ◽  
Work Rate ◽  
Strenuous Exercise ◽  
Anticholinergic Agent ◽  
Airway Caliber ◽  
Before And After ◽  
The Mean ◽  
Reference Pressure

Mechanical work rate of breathing was measured in five normal subjects during voluntary eucapnic hyperventilation at rates of approximately 10, 20, 40, 60, and 80 l/min before and after inhalation of 1 mg of ipratropium bromide, an anticholinergic agent. Chest wall recoil pressure was measured over a range of lung volumes in each subject and was used as the reference pressure in the calculation of work rate. There was little change in elastic or resistive work rate at rest when vagal tone was reduced by ipratropium. The mean work at 40, 60, and 80 l/min was 8.9, 17.2, and 34.0 cmH2O.l–1.s before and 5.6, 12.4 and 25.8 cmH2O.l–1.s after ipratropium. This suggests that vagal tone significantly influences the work of breathing at high ventilatory rates, such as occur during strenuous exercise.

Iron Metabolism after Renal Transplantation

1973 ◽  
Vol 44 (1) ◽  
pp. 27-32 ◽  
Author(s):  
K. Boddy ◽  
G. Will ◽  
D. H. Lawson ◽  
Priscilla C. King ◽  
A. L. Linton
Keyword(s):  
Renal Failure ◽  
Renal Transplantation ◽  
Chronic Renal Failure ◽  
Iron Metabolism ◽  
Oral Absorption ◽  
Normal Subjects ◽  
The Body ◽  
Whole Body ◽  
The Mean

1. The oral absorption and the rate of loss from the body of radioactive iron were measured by whole-body monitoring in patients with functioning renal homografts. The incorporation of radioactive iron into erythrocytes was also measured. 2. The results were compared with corresponding values in normal subjects and in non-dialysed and dialysed patients with chronic renal failure. 3. The mean oral absorption and incorporation into erythrocytes of radioactive iron was intermediate between that of normal subjects and of both non-dialysed and dialysed patients with chronic renal failure. 4. The mean rate of loss from the body was not significantly different from that in normal subjects and non-dialysed patients with chronic renal failure but it was significantly less than that in dialysed patients.

Intrasplenic blood cell kinetics in man before and after brief maximal exercise

1992 ◽  
Vol 83 (1) ◽  
pp. 47-54 ◽  
Author(s):  
P. Allsop ◽  
A. M. Peters ◽  
R. N. Arnot ◽  
A. W. J. Stuttle ◽  
M. Deenmamode ◽  
...  
Keyword(s):  
Blood Cell ◽  
Peripheral Blood ◽  
Time Course ◽  
Maximal Exercise ◽  
Normal Subjects ◽  
Cell Type ◽  
Total Blood ◽  
Cell Counts ◽  
Before And After ◽  
Time Courses

1. After a 4 min period of maximal exercise in 10 normal subjects (14 studies), there was a consistent decrease in total blood volume and a consistent increase in erythrocyte indices, which were maximal immediately after exercise. Peripheral platelet and leucocyte counts increased, but did not reach maximal values until 5–10 min after the end of exercise. 2. The distributions of 99mTc-Iabelled erythrocytes (five studies), 111In-labelled platelets (five studies) and 111In-labelled granulocytes (four studies) were monitored with a γ-camera immediately after injection and before and after maximal exercise performed 60 min after injection. 3. Labelled erythrocytes equilibrated rapidly between the spleen and circulating blood after injection, whereas labelled platelets and granulocytes equilibrated more slowly. After exercise, each cell type was released from the spleen with a time course that was the reciprocal of the time course of the corresponding cell count in peripheral blood. Thus, whereas the radioactivity of 99mTc-labelled erythrocytes in the spleen, which fell to 0.46 (SD 0.09) of the pre-exercise value, increased towards its baseline value as soon as exercise was completed, the radioactivities of 111In-labelled platelets and 111In-labelled granulocytes decreased, to respective minimum values of 0.61 (0.09) and 0.63 (0.09) of the pre-exercise levels, 5–10 min after the end of exercise. The exercise-induced changes in lung radioactivity for each cell type, and their time courses, broadly reflected those in the corresponding cell counts in peripheral blood. Liver radioactivity tended to decrease for each cell type. 4. Because of the dissociation of the time courses of splenic expulsion of erythrocytes (intrasplenic transit time about 1 min) from those of platelets and granulocytes (intrasplenic transit times both of 8–10 min), we conclude that blood cell expulsion from the spleen in man is not the result of active splenic contraction but probably the passive result of a decrease in splenic blood flow.

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