Platelet catecholamines and platelet function in normal human subjects

1987 ◽  
Vol 73 (1) ◽  
pp. 99-103 ◽  
Author(s):  
A. P. Wilson ◽  
C. C. T. Smith ◽  
B. N. C. Prichard ◽  
D. J. Betteridge
Keyword(s):  
Platelet Function ◽  
High Performance ◽  
Human Subjects ◽  
Normal Subjects ◽  
Noradrenaline Content ◽  
Collagen Concentration ◽  
Normal Human ◽  
Wall Interaction ◽  
Local Release

1. We have used high-performance liquid chromatography with electrochemical detection to measure plasma and platelet catecholamines in 24 normal subjects. 2. In the same subjects platelet function was assessed by measuring platelet aggregation in response to adenosine 5′-pyrophosphate, thrombin, adrenaline and collagen. Platelet sensitivity to prostacyclin was also examined. 3. Platelet noradrenaline showed a positive correlation with extent of aggregation induced by ‘low-dose’ collagen (1 μg/ml). No correlation was seen at the higher collagen concentration. 4. Platelet noradrenaline content also correlated with sensitivity of platelets to prostacyclin. High platelet noradrenaline concentrations appeared to result in decreased sensitivity to prostacyclin. 5. No other correlations were observed. 6. These data suggest that platelet noradrenaline rather than plasma levels may be involved in modifying platelet function in vivo. Local release of platelet catecholamines may affect the platelet/vessel wall interaction, the primary physiological step in platelet activation.

The Distribution of Catecholamines between Platelets and Plasma in Normal Human Subjects

1985 ◽  
Vol 69 (1) ◽  
pp. 1-6 ◽  
Author(s):  
C. C. T. Smith ◽  
L. D. Curtis ◽  
A. P. Delamothe ◽  
B. N. C. Prichard ◽  
D. J. Betteridge
Keyword(s):  
High Performance ◽  
Human Subjects ◽  
Normal Subjects ◽  
Plasma Noradrenaline ◽  
Plasma Catecholamine ◽  
Noradrenaline Content ◽  
Platelet Factor ◽  
Normal Human ◽  
Catecholamine Levels

1. We have used high-performance liquid chromatography with electrochemical detection to measure content of adrenaline and noradrenaline in platelets in 13 normal subjects at rest. 2. Subjects were exercised to raise plasma catecholamine levels and promote the platelet release reaction. 3. There was a significant positive correlation between plasma noradrenaline concentrations and platelet noradrenaline content. 4. Platelet/plasma concentration ratios were 1855 for noradrenaline and 268 for adrenaline at rest and 473 and 152 respectively after exercise. 5. Plasma noradrenaline levels positively correlated with age. 6. Determination of platelet factors released to the plasma showed increases of β-thromboglobulin and platelet factor 4 with exercise, whereas thromboxane B2 remained unchanged. No change in platelet catecholamine levels occurred with exercise and no correlations were observed between platelet catecholamines and released platelet factors. 7. These data suggest that plasma catecholamine levels influence platelet content and that noradrenaline and adrenaline are concentrated in platelets.

scholarly journals Lactitol, a new hydrogenated lactose derivative: intestinal absorption and laxative threshold in normal human subjects

1987 ◽  
Vol 57 (2) ◽  
pp. 195-199 ◽  
Author(s):  
Dharmaraj H. Patil ◽  
George K. Grimble ◽  
David B. A. Silk
Keyword(s):  
Side Effects ◽  
Maximum Dose ◽  
Human Subjects ◽  
Normal Subjects ◽  
Perfusion Technique ◽  
Double Blind ◽  
Gastrointestinal Side Effects ◽  
Normal Human ◽  
Jejunal Perfusion

1. In the first part of the study, the absorption of lactitol, a new disaccharide analogue of lactose, was studied using an in vivo jejunal perfusion technique in man. Intestinal uptake of lactitol from isotonic solutions containing 10, 30, 60, and 100 mmol lactitol/l was insignificant.2. In the second part of the study the laxative threshold of lactitol was determined and compared with that of sorbitol in a double-blind, randomized, cross-over study on twenty-one normal subjects. Laxative threshold was considered to be either the maximum dose tolerated without unacceptable diarrhoea or gastrointestinal side effects, or when the maximum dose in the study was reached. Increasing amounts of lactitol, sorbitol or placebo were administered in two divided doses each day until subjects developed diarrhoea or severe gastrointestinal side effects. The laxative threshold of lactitol (74 (SE 5) g/d) was similar to that of sorbitol (71 (SE 5) g/d).3. These findings indicate that lactitol is not absorbed by the human small intestine. Although diarrhoea or other gastrointestinal side effects occurred as the dose was increased, 40 g lactitol/d was well tolerated.

Nonadrenergic bronchodilator mechanisms in normal human subjects in vivo

1988 ◽  
Vol 64 (5) ◽  
pp. 1817-1822 ◽  
Author(s):  
J. W. Lammers ◽  
P. Minette ◽  
M. T. McCusker ◽  
K. F. Chung ◽  
P. J. Barnes
Keyword(s):  
Nervous System ◽  
Local Anesthesia ◽  
Ipratropium Bromide ◽  
Human Subjects ◽  
Normal Subjects ◽  
Respiratory Resistance ◽  
Leukotriene D4 ◽  
Normal Human ◽  
Oral Propranolol

In seven normal subjects we investigated whether a nonadrenergic bronchodilator nervous system is demonstrable in humans in vivo. After inhalation of leukotriene D4 (LTD4), respiratory resistance (Rrs) increased by 115 +/- 11% (SE). Subsequent inhalation of 2 nmol of capsaicin induced coughing and a fall in Rrs of 22.1 +/- 2% (P less than 0.01). However, inhalation of the diluent of capsaicin, 10% saline-ethanol, decreased Rrs similarly. These bronchodilator responses were not altered by inhaled ipratropium bromide (120 micrograms) and oral propranolol (80 mg). After ipratropium and propranolol, voluntary coughing alone decreased Rrs by 25 +/- 3% (P less than 0.05). We next investigated whether these bronchodilator responses could be blocked by anesthesia of the airways with inhaled lidocaine. After inhalation of lidocaine and LTD4, capsaicin aerosol induced coughing and a transient increase in Rrs of 18 +/- 6% (P less than 0.05) but no bronchodilation. Inhalation of saline-ethanol (n = 4) and a deep inhalation (n = 6) decreased Rrs by 18 +/- 4% (P less than 0.05) and 34 +/- 3% (P less than 0.001), respectively. We conclude that in normal subjects a nonadrenergic, noncholinergic bronchodilator mechanism exists, which can be activated by inhalation of capsaicin and inhibited by local anesthesia.

Evidence for an Increased Generation of Prostacyclin in the Microvasculature and an Impairment of the Platelet α-Granule Release in Chronic Renal Failure

1988 ◽  
Vol 60 (02) ◽  
pp. 205-208 ◽  
Author(s):  
Paul A Kyrle ◽  
Felix Stockenhuber ◽  
Brigitte Brenner ◽  
Heinz Gössinger ◽  
Christian Korninger ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Blood Clotting ◽  
Normal Subjects ◽  
Chronic Uraemia ◽  
Wall Interaction ◽  
End Stage ◽  
Granule Release

SummaryThe formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.

ANP kinetics in normal men: in vivo measurement by a tracer method and correlation with sodium intake

1993 ◽  
Vol 264 (3) ◽  
pp. F480-F489 ◽  
Author(s):  
G. Iervasi ◽  
A. Clerico ◽  
S. Berti ◽  
A. Pilo ◽  
F. Vitek ◽  
...  
Keyword(s):  
High Performance ◽  
Sodium Intake ◽  
Mean Transit Time ◽  
Normal Subjects ◽  
The Body ◽  
Metabolic Clearance ◽  
Healthy Human ◽  
Large Space ◽  
Wide Range

125I-labeled atrial natriuretic peptide (ANP) was bolus injected into seven healthy human male subjects on an unrestricted diet (sodium intake ranging from 80 to 300 mmol/day). A high-performance liquid chromatographic procedure was used to purify the labeled hormone and the principal labeled metabolites in venous plasma samples collected up to 50 min after injection. The main ANP kinetic parameters were derived from the disappearance curves of the 125I-ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large space (plasma-equivalent volume is 12.1 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this sampling space through both degradation and distribution in peripheral spaces, as indicated by the single-pass mean transit time through the sampling space (3.9 +/- 1.2 min). The mean residence time in the body (22.7 +/- 23.1 min) and the plasma-equivalent total distribution volume (30.9 +/- 12.0 l/m2) indicate that ANP is also widely distributed outside the initial space. Metabolic clearance rate (MCR) values were distributed across a wide range (from 740 to 2,581 ml.min-1 x m-2) and were shown to correlate strongly with the daily urinary excretion of sodium. These results indicate that: 1) newly produced ANP is rapidly distributed and degraded, 2) the body pool of the hormone can be considered as a combination of two exchanging spaces, 3) circulating ANP is < or = 1/15 of the body pool, and 4) MCR of ANP is closely related to sodium intake, at least in normal subjects on a free sodium intake diet.

Bronchoprotective and bronchodilatory effects of deep inspiration in rabbits subjected to bronchial challenge

2001 ◽  
Vol 91 (6) ◽  
pp. 2511-2516 ◽  
Author(s):  
S. J. Gunst ◽  
X. Shen ◽  
R. Ramchandani ◽  
R. S. Tepper
Keyword(s):  
Human Subjects ◽  
Inhibitory Effect ◽  
Airway Responsiveness ◽  
Deep Inspiration ◽  
Contractile Apparatus ◽  
Airway Reactivity ◽  
Airway Response ◽  
Normal Human ◽  
Airway Responses

The effect of deep inspiration (DI) on airway responsiveness differs in asthmatic and normal human subjects. The mechanism for the effects of DI on airway responsiveness in vivo has not been identified. To elucidate potential mechanisms, we compared the effects of DI imposed before or during induced bronchoconstriction on the airway response to methacholine (MCh) in rabbits. The changes in airway resistance in response to intravenous MCh were continuously monitored. DI depressed the maximum response to MCh when imposed before or during the MCh challenge; however, the inhibitory effect of DI was greater when imposed during bronchoconstriction. Because immature rabbits have greater airway reactivity than mature rabbits, we compared the effects of DI on their airway responses. No differences were observed. Our results suggest that the mechanisms by which DI inhibits airway responsiveness do not depend on prior activation of airway smooth muscle (ASM). These results are consistent with the possibility that reorganization of the contractile apparatus caused by stretch of ASM during DI contributes to depression of the airway response.

scholarly journals Noninvasive Measurements of Human Brain Temperature Using Volume-Localized Proton Magnetic Resonance Spectroscopy

1997 ◽  
Vol 17 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Ron Corbett ◽  
Abbot Laptook ◽  
Paul Weatherall
Keyword(s):  
Magnetic Resonance ◽  
Frontal Lobe ◽  
Mr Spectroscopy ◽  
Brain Temperature ◽  
Human Subjects ◽  
Normal Subjects ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Noninvasive Measurements

Elucidation of the role of cerebral hyperthermia as a secondary factor that worsens outcome after brain injury, and the therapeutic application of modest brain hypothermia would benefit from noninvasive measurements of absolute brain temperature. The present study was performed to evaluate the feasibility of using 1H magnetic resonance (MR) spectroscopy to measure absolute brain temperature in human subjects on a clinical imaging spectroscopy system operating at a field strength of 1.5 T. In vivo calibration results were obtained from swine brain during whole-body heating and cooling, with concurrent measurements of brain temperature via implanted probes. Plots of the frequency differences between the in vivo MR peaks of water and N-acetyl-aspartate and related compounds (NAX), or water and choline and other trimethylamines versus brain temperature were linear over the temperature range studied (28–40°C). These relationships were used to estimate brain temperature from 1H MR spectra obtained from 10 adult human volunteers from 4 cm3-volumes selected from the frontal lobe and thalamus. Oral and forehead temperatures were monitored concurrently with MR data collection to verify normothermia in all the subjects studied. Temperatures determined using N-acetyl-aspartate or choline as the chemical shift reference did not differ significantly, and therefore results from these estimates were averaged. The brain temperature (mean ± SD) measured from the frontal lobe (37.2 = 0.6°C) and thalamus (37.7 ± 0.6°C) were significantly different from each other (paired t-test, p = 0.035). We conclude that 1H MR spectroscopy provides a viable noninvasive means of measuring regional brain temperatures in normal subjects and is a promising approach for measuring temperatures in brain-injured subjects.

Catechol O-Methyltransferase in Red Blood Cells of Schizophrenic, Depressed, and Normal Human Subjects

1976 ◽  
Vol 128 (2) ◽  
pp. 184-187 ◽  
Author(s):  
Helen L. White ◽  
Malcolm N. McLeod ◽  
Jonathan R. T. Davidson
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Normal Subjects ◽  
Enzyme Preparations ◽  
Human Red Blood Cells ◽  
Schizophrenic Patients ◽  
Normal Human ◽  
The Mean ◽  
Isoelectric Ph

SummaryCatechol O-methyltransferase of lysed human red blood cells was assayed under optimal conditions, using saturating concentrations of the substrates, S-adenosyl-L-methionine and 3,4-dihydroxybenzoic acid. The mean enzyme activity found in 24 normal subjects was 29.2 nmol/hr/ml RBC. The mean activity in blood of 33 female unipolar depressives was not significantly different from normal. However, higher enzyme activities were observed in the blood of 11 schizophrenic patients (38.9 nmol/hr/ml RBC). Partially purified enzyme preparations from blood of normal and schizophrenic individuals were indistinguishable with respect to substrate specificities, isoelectric pH values, and ratios of the two O-methylated products. Therefore it is unlikely that any defect in O-methylation which may occur in schizophrenia can be attributed to a change in the intrinsic properties of erythrocyte catechol O-methyltransferase.

Lithium and erythrocyte membrane cation carrier studies in normal and manic depressive subjects

1977 ◽  
Vol 7 (2) ◽  
pp. 229-233 ◽  
Author(s):  
G. J. Naylor ◽  
A. Smith ◽  
L. J. Boardman ◽  
D. A. T. Dick ◽  
E. G. Dick ◽  
...  
Keyword(s):  
Erythrocyte Membrane ◽  
Human Subjects ◽  
Normal Subjects ◽  
Sodium Concentration ◽  
Manic Depressive Psychosis ◽  
Manic Depressive ◽  
Normal Human ◽  
Potassium Influx ◽  
Erythrocyte Sodium

synopsisChanges in the erythrocyte membrane cation carrier following lithium ingestion in normal human subjects were studied; ouabain sensitive potassium influx fell significantly during the lithium treated phase. Lithium was fed to rats and no change in erythrocyte Na-K ATPase was shown. These findings contrast with studies of lithium in manic depressive psychosis. The fluctuations in the erythrocyte membrane cation carrier were studied in 5 normal subjects over 12 weeks and the correlations between the parameters calculated. The erythrocyte sodium concentration correlated positively with the ouabain sensitive potassium influx. This too contrasts with findings in manic depressive psychosis.

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