Observations on a Relationship between Steroid Metabolism and the Concentration of Plasma Fibrinogen

1963 ◽  
Vol 10 (02) ◽  
pp. 400-405 ◽  
Author(s):  
B. A Amundson ◽  
L. O Pilgeram
Keyword(s):  
Blood Coagulation ◽  
Methyl Ether ◽  
Broad Spectrum ◽  
Human Subjects ◽  
Plasma Fibrinogen ◽  
Steroid Metabolism ◽  
Specific Site ◽  
Chain Reaction ◽  
Normal Human ◽  
A Chain

SummaryEnovid (5 mg norethynodrel and 0.075 mg ethynylestradiol-3-methyl ether) therapy in young normal human subjects causes an increase in plasma fibrinogen of 32.4% (P >C 0.001). Consideration of this effect together with other effects of Enovid on the activity of specific blood coagulatory factors suggests that the steroids are exerting their effect at a specific site of the blood coagulation and/or fibrinolytic system. The broad spectrum of changes which are induced by the steroids may be attributed to a combination of a chain reaction and feed-back control.

Implications for Risk Assessment of Host Factors Causing Large Pharmacokinetic Variations

1985 ◽  
Vol 1 (4) ◽  
pp. 135-152 ◽  
Author(s):  
Elliot S. Vesell
Keyword(s):  
Risk Assessment ◽  
Cigarette Smoking ◽  
Safety Factor ◽  
Oral Contraceptives ◽  
Broad Spectrum ◽  
Human Subjects ◽  
Environmental Chemicals ◽  
Host Factors ◽  
Normal Human ◽  
Genetically Determined

Normal human subjects vary widely in their capacity to eliminate many drugs and environmental chemicals. These variations range in magnitude from fourfold to fortyfold depending on the drug and the population studied. Pharmacogenetics deals with only one of many host factors responsible for these large pharmacokinetic differences. Age, sex, diet and exposure to other drugs and chemicals, including oral contraceptives, ethanol and cigarette smoking, can alter the genetically determined rate at which a particular subject eliminates drugs and environmental chemicals. These elimination rates, therefore, are dynamic and change even in the same subject with time and condition. Regulatory legislation has only recently begun to recognize this very broad spectrum of human susceptibility and the existence of multiple special subgroups of particularly sensitive subjects. In setting standards for environmental chemicals, EPA and NIOSH have attempted to protect the most sensitive humans and should be encouraged to continue this policy. For some drugs and environmental chemicals, the commonly used safety factor of 100 may be too low; for these chemicals large, interindividual pharmacokinetic variations produced by pharmacogenetic and other host factors may make a safety factor of 400 or 500 more adequate.

Compartmentalization of the acute cytokine response in humans after intravenous endotoxin administration

1993 ◽  
Vol 74 (6) ◽  
pp. 3027-3033 ◽  
Author(s):  
A. J. Boujoukos ◽  
G. D. Martich ◽  
E. Supinski ◽  
A. F. Suffredini
Keyword(s):  
Polymerase Chain Reaction ◽  
Mrna Expression ◽  
Human Subjects ◽  
Peak Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chain Reaction ◽  
Cytokine Mrna ◽  
Cytokine Mrna Expression ◽  
Normal Human ◽  
Polymerase Chain

Lung cytokine production was examined after the intravenous administration of endotoxin to 23 normal human subjects. Bronchoalveolar lavage (BAL) was performed 7 days before and 1.5 or 5 h after endotoxin (4 ng/kg). Cytokine mRNA was evaluated in cell pellets (> 98% macrophages) by use of reverse transcription and the polymerase chain reaction. Immunoreactivity was measured by enzyme-linked immunosorbent assay of 20- to 40-fold concentrated BAL. Interleukin- (IL) 8 was detected in BAL (4–130 pg/ml) but not in the serum at baseline. Few neutrophils were found in BAL (< 1%) despite this IL-8 gradient. Peak serum IL-8 levels occurred 2 h after endotoxin (3,930 +/- 241 pg/ml), but BAL neutrophils and IL-8 did not increase. Peak serum tumor necrosis factor (TNF) levels occurred 1.5 h after endotoxin (1,844 +/- 210 pg/ml), but TNF was detected in only 1 of 20 BAL samples. TNF and IL-8 mRNA were detected by polymerase chain reaction in > 70% of the BAL samples before endotoxin, whereas IL-1 alpha, IL-1 beta, and IL-6 were detected in < 25% of the BAL samples. After endotoxin, no change was detected in cytokine mRNA expression. Actinomycin D treatment of the BAL did not alter the pattern of cytokine mRNA expression. These data suggest that mechanisms exist to insulate the alveolar space from the stimulatory effects of endotoxin and high circulating levels of cytokines. Additional factors appear to control the chemotactic effects of IL-8 on neutrophils in the air spaces during acute systemic inflammation.

Relationship Between Mepacrine-Labelled Dense Body Number, Platelet Capacity to Accumulate 14C-5-HT and Platelet Density in the Bernard-Soulier and Hermansky-Pudlak Syndromes

1979 ◽  
Vol 42 (02) ◽  
pp. 694-704 ◽  
Author(s):  
F Rendu ◽  
A T Nurden ◽  
M Lebret ◽  
J P Caen
Keyword(s):  
Dense Body ◽  
Human Subjects ◽  
Human Platelets ◽  
Dense Bodies ◽  
Storage Organelle ◽  
Hereditary Disorders ◽  
Labelling Procedure ◽  
Normal Human ◽  
Hermansky Pudlak Syndrome ◽  
Bernard Soulier Syndrome

SummaryWe have used the mepacrine-labelling procedure to measure the dense body (serotonin storage organelle) content of the platelets of 2 hereditary disorders where abnormalities in dense body number were suspected. The platelets were incubated with mepacrine and examined by fluorescence microscopy. A mean number of 5.4 ± 0.8 (SD) dense bodies per platelet was calculated from the data obtained using platelets isolated from 40 normal human subjects. In contrast the platelets of 2 patients with the Bernard-Soulier syndrome contained an average of 14 and 17 labelled granules. This increase was associated with a much greater capacity of the platelets to accumulate 14C-5-HT. The opposite result was obtained using the platelets from 2 patients with the Hermansky-Pudlak syndrome which contained few granules labelled by mepacrine and took up less 14C-5-HT than normal human platelets. Centrifugation of the patients’ platelets on discontinuous sucrose gradients showed that the platelets of the 2 Bemard-Soulier patients were much denser than normal whereas a high proportion of low density platelets was observed in the Hermansky-Pudlak syndrome. These results further define the platelet abnormalities in the two syndromes and suggest that dense body number may be one of the factors governing platelet density.

ADRENERGIC CONTROL MECHANISM FOR ACTH SECRETION IN MAN

1973 ◽  
Vol 74 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Yoshikatsu Nakai ◽  
Hiroo Imura ◽  
Teruya Yoshimi ◽  
Shigeru Matsukura
Keyword(s):  
Intravenous Infusion ◽  
Human Subjects ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Glucose Levels ◽  
Alpha Receptors ◽  
Normal Human ◽  
Adrenergic Blocking

ABSTRACT In order to determine if an adrenergic mechanism is involved in the secretion of corticotrophin (ACTH), the effect of adrenergic-blocking or -stimulating agent on plasma ACTH, cortisol and glucose levels was studied in normal human subjects. The intravenous infusion of methoxamine, an alpha adrenergic-stimulating agent, caused a rise in plasma ACTH and cortisol. This increase in plasma ACTH and cortisol was significantly inhibited by the simultaneous administration of phentolamine, an alpha adrenergic-blocking agent, in combination with methoxamine. The intravenous infusion of propranolol, a beta adrenergic-blocking agent, caused no significant change in plasma ACTH and cortisol, although it enhanced the plasma ACTH response to insulin-induced hypoglycaemia. On the other hand, alpha adrenergicblockade by intravenous infusion of phentolamine significantly suppressed the plasma ACTH response to insulin-induced hypoglycaemia. These studies suggest a stimulatory effect of alpha receptors and a possible inhibitory effect of beta receptors on ACTH secretion in man.

Specialized systems for the processing of mnemonic information within the primate frontal cortex

1996 ◽  
Vol 351 (1346) ◽  
pp. 1455-1462 ◽  
Keyword(s):  
Frontal Cortex ◽  
Specific Activity ◽  
Human Subjects ◽  
Long Term Memory ◽  
Executive Processing ◽  
Severe Impairment ◽  
Normal Human ◽  
Short And Long Term ◽  
Cortical Association Areas

The lateral frontal cortex is involved in various aspects of executive processing within short- and long-term memory. It is argued that the different parts of the lateral frontal cortex make distinct contributions to memory that differ in terms of the level of executive processing that is carried out in interaction with posterior cortical systems. According to this hypothesis, the mid-dorsolateral frontal cortex (areas 46 and 9) is a specialized system for the monitoring and manipulation of information within working memory, whereas the mid-ventrolateral frontal cortex (areas 47/12 and 45) is involved in the active retrieval of information from the posterior cortical association areas. Data are presented which support this two-level hypothesis that posits two distinct levels of interaction of the lateral frontal cortex with posterior cortical association areas. Functional activation studies with normal human subjects have demonstrated specific activity within the mid-dorsolateral region of the frontal cortex during the performance of tasks requiring monitoring of self-generated and externally generated sequences of responses. In the monkey, lesions restricted to this region of the frontal cortex yield a severe impairment in performance of the above tasks, this impairment appearing against a background of normal performance on several basic mnemonic tasks. By contrast, a more severe impairment follows damage to the mid-ventrolateral frontal region and functional activation studies have demonstrated specific changes in activity in this region in relation to the active retrieval of information from memory.

scholarly journals Pathogenesis and Management of COVID-19

2021 ◽  
Vol 11 (2) ◽  
pp. 77-93
Author(s):  
Khalid O. Alfarouk ◽  
Sari T. S. AlHoufie ◽  
Samrein B. M. Ahmed ◽  
Mona Shabana ◽  
Ahmed Ahmed ◽  
...  
Keyword(s):  
Multiple Organ Failure ◽  
Human Body ◽  
Inflammatory Mediators ◽  
Expression Patterns ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Chain Reaction ◽  
Road Map ◽  
A Chain ◽  
Global War

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.

Effect of Age on Oxygen-Binding in Normal Human Subjects

1976 ◽  
Vol 51 (2) ◽  
pp. 185-188
Author(s):  
P. M. Tweeddale ◽  
R. J. E. Leggett ◽  
D. C. Flenley
Keyword(s):  
Oxygen Saturation ◽  
Oxygen Tension ◽  
Inorganic Phosphate ◽  
Human Subjects ◽  
Oxygen Binding ◽  
Corpuscular Haemoglobin ◽  
Positive Correlation ◽  
Normal Human ◽  
Mean Corpuscular Haemoglobin ◽  
Effect Of Age

1. Oxygen-binding, plasma and intra-erythrocytic pH, and haemoglobin, 2,3-diphosphoglycerate and inorganic phosphate concentrations were measured in sixty-two healthy non-smokers aged between 18 and 89 years. 2. P50 (oxygen tension at 50% oxygen saturation) expressed at plasma pH 7·40 and Pco2 5·33 kPa showed a positive correlation with age. 3. This correlation of P50 with age was closer when P50 was expressed at a constant intra-erythrocytic pH 7·20. On average P50 at intra-erythrocytic pH 7·20 increased from 3·59 kPa at 20 years to 3·96 kPa at 90 years of age. 4. 2,3-Diphosphoglycerate, inorganic phosphate, haemoglobin and mean corpuscular haemoglobin concentrations did not correlate with P50 or with age.

Influence of initiation mode on stability and control of a chain reaction

1980 ◽  
Vol 20 (18) ◽  
pp. 1197-1204 ◽  
Author(s):  
H. T. Chen ◽  
P. A. Chartier ◽  
S. Setthachayanon
Keyword(s):  
Chain Reaction ◽  
Stability And Control ◽  
A Chain ◽  
And Control
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