scholarly journals The metabolism of14C-labelled α-methyldopa in normal and hypertensive human subjects

1972 ◽  
Vol 129 (1) ◽  
pp. 1-10 ◽  
Author(s):  
W. Y. W. Au ◽  
L. G. Dring ◽  
D. G. Grahame-Smith ◽  
P. Isaac ◽  
R. T. Williams
Keyword(s):  
Human Subjects ◽  
Normal Subjects ◽  
Main Metabolite ◽  
Hypertensive Patients ◽  
The One ◽  
Normal Men

1. The fate of orally administered14C-labelled l-α-methyldopa has been examined in three normal men and in eight hypertensive patients who responded to the drug and three who did not. 2. The output of14C in the urine in 2 days and in the faeces in 4 days was not very different in any of the subjects. The normals excreted about 40% of the dose in the urine and 60% in the faeces, the responders 52% (range 35–60%) and 45% and the non-responders 42% and 41%. Most of the urinary14C radioactivity was eliminated in 24h after dosing. 3. The main metabolite in the urine was free and conjugated α-methyldopa (normal men, 23% responders, 37% non-responders, 25% of the dose). Free and conjugated 3-O-methyl-α-methyldopa was about 4% in all subjects, total amines (α-methyldopamine and 3-O-methyl-α-methyldopamine) about 6% and ketones (mainly 3,4-dihydroxyphenylacetone) about 3%. 4. The output of α-methyldopamine (2–4% of dose), 3-O-methyl-α-methyldopamine (0.3%) and 3,4-dihydroxyphenylacetone (3–5%) was similar in the one normal and two responders examined. 5. The faecal14C in all subjects was unchanged l-α-methyldopa. 6. In general, the amounts of the metabolites in the urine in normal men and in responding and non-responding patients were quantitatively similar, except in one non-responding patient who converted nearly two-thirds of the absorbed drug into amines and ketones. There appeared to be no correlation between metabolites in the urine and response or lack of response to the drug. 7. In two normal subjects 70–80% of d-α-methyldopa was excreted unchanged in the faeces. Of the absorbed compound most (9–14% of the dose) was excreted as the free and conjugated drug together with a small amount (1–2%) of 3-O-methyl-α-methyldopa. No amines and only traces of ketone were excreted.

TESTOSTERONE 5α-REDUCTION IN THE SKIN OF NORMAL SUBJECTS AND OF PATIENTS WITH ABNORMAL SEX DEVELOPMENT

1975 ◽  
Vol 79 (1) ◽  
pp. 164-176 ◽  
Author(s):  
Frédérique Kuttenn ◽  
Pierre Mauvais-Jarvis
Keyword(s):  
Conversion Rate ◽  
Reductase Activity ◽  
Human Subjects ◽  
Sex Differentiation ◽  
Normal Subjects ◽  
Normal Male ◽  
Skin Sample ◽  
Reduction Activity ◽  
Sex Development ◽  
Normal Men

ABSTRACT Human pubic skin was obtained from normal subjects and patients with abnormal sex differentiation. Skin samples (200 mg) supplemented with NADPH, were incubated for 1 h with labelled testosterone. The conversion of testosterone to dihydrotestosterone1), 3α- and 3β-androstanediol was calculated. This conversion averaged 14.9 ± 3.4 % (se) in 11 normal men and 3.6 ± 1.4 % (se) in 8 normal women. In 4 children as in 4 young hypogonadotrophic hypogonadal men, the conversion rate of testosterone to 5α-reduced metabolites was low (0.8 to 3.5%) and increased at puberty (13.5 to 19.2%). After administration of HCG for 3 months to 1 of the hypogonadal men, it reached 30.2 %. Inversely, the formation of dihydrotestosterone and androstanediols from testosterone was suppressed in 2 men treated with large doses of oestrogen. In 3 subjects with an incomplete form of testicular feminization syndrome, the conversion rate of testosterone to 5α-reduced metabolites was in the normal male range (6.4 to 18.3%), whereas it was low in one case of the complete form of the syndrome (1.5%). In 9 women with idiopathic hirsutism the rate of 5α-reduced metabolites recovered from testosterone was close to that of normal men (13.5 ± 5.5% (se). From theseresults, it is postulated that in human subjects, there is a good correlation between hair growth in skin from a sexual area and the extent of testosterone 5α-reduction in this tissue. Such an enzymatic activity might be induced by active androgens; this latter hypothesis is in good agreement with the increase of 5α-reduction activity observed at puberty or after treatment of young hypogonadal males. In addition, it is pointed out that a positive correlation is observed between the 5α-reductase activity present in each skin sample studied and the urinary 3α-androstanediol found for the same individual. This confirms our previous findings suggesting that the determination of urinary 3α-androstanediol might prove of clinical interest in the evaluation of the androgenic status in human subjects.

ÉTUDES IN VIVO SUR LE MÉTABOLISME DES ANDROGÉNES APRES ADMINISTRATION DE STÉROÏDES INHIBITEURS DE L'OVULATION

1965 ◽  
Vol 50 (1) ◽  
pp. 131-144 ◽  
Author(s):  
P. Mauvais-Jarvis ◽  
M. F. Jayle ◽  
J. Decourt ◽  
J. Louchart ◽  
J. Truffert
Keyword(s):  
Luteinizing Hormone ◽  
Urinary Excretion ◽  
Normal Subjects ◽  
Hormone Activity ◽  
Testosterone Production ◽  
Normal Men ◽  
Ethinyl Oestradiol

ABSTRACT Normal subjects and hirsute women with micropolycystic ovaries were treated with ethinyl-oestrenol + 3-methoxy-ethinyl-oestradiol (Lyndiol®), in view of studying the action of this compound on the production of androgens and on the urinary excretion of their metabolites. In normal men, the production of testosterone and the excretion of androsterone and aetiocholanolone are suppressed, whereas the excretion of other 17-ketosteroids and the production of dehydroepiandrosterone sulphate are unchanged. Moreover, the luteinizing hormone activity (LH) in plasma is depressed. It seems that the preparation inhibits specifically the testicular androgen production, by suppressing the hypothalamo-hypophyseal control of LH. Testosterone production and urinary 17-ketosteroid excretion are modified in the same way in women with Stein-Leventhal's syndrome. Physiopathological and therapeutical implications which come from these results are discussed.

IMMUNOLOGICAL REACTIVITY OF INSULIN IN HUMAN SERUM

1966 ◽  
Vol 53 (4) ◽  
pp. 673-680 ◽  
Author(s):  
Torsten Deckert ◽  
Kai R. Jorgensen
Keyword(s):  
Normal Subjects ◽  
The Other ◽  
Human Pancreas ◽  
Porcine Pancreas ◽  
Crystalline Insulin ◽  
Endogenous Insulin ◽  
Significant Difference ◽  
Human Sera ◽  
Normal Human ◽  
The One

ABSTRACT The purpose of this study was to investigate whether a difference could be demonstrated between crystalline insulin extracted from normal human pancreas, and crystalline insulin extracted from bovine and porcine pancreas. Using Hales & Randle's (1963) immunoassay no immunological differences could be demonstrated between human and pig insulin. On the other hand, a significant difference was found, between pig and ox insulin. An attempt was also made to determine whether an immunological difference could be demonstrated between crystalline pig insulin and crystalline human insulin from non diabetic subjects on the one hand and endogenous, circulating insulin from normal subjects, obese subjects and diabetic subjects on the other. No such difference was found. From these experiments it is concluded that endogenous insulin in normal, obese and diabetic human sera is immunologically identical with human, crystalline insulin from non diabetic subjects and crystalline pig insulin.

SIMPLIFIED DEXAMETHASONE SUPPRESSION TEST

1969 ◽  
Vol 61 (2) ◽  
pp. 219-231 ◽  
Author(s):  
V. H. Asfeldt
Keyword(s):  
Cushing’S Syndrome ◽  
Normal Subjects ◽  
Cushing's Syndrome ◽  
Dexamethasone Suppression Test ◽  
Clinical Value ◽  
Suppression Test ◽  
The One ◽  
Steroid Excretion ◽  
Dexamethasone Suppression

ABSTRACT This is an investigation of the practical clinical value of the one mg dexamethasone suppression test of Nugent et al. (1963). The results, evaluated from the decrease in fluorimetrically determined plasma corticosteroids in normal subjects, as well as in cases of exogenous obesity, hirsutism and in Cushing's syndrome, confirm the findings reported in previous studies. Plasma corticosteroid reduction after one mg of dexamethasone in cases of stable diabetes was not significantly different from that observed in control subjects, but in one third of the insulin-treated diabetics only a partial response was observed, indicating a slight hypercorticism in these patients. An insufficient decrease in plasma corticosteroids was observed in certain other conditions (anorexia nervosa, pituitary adenoma, patients receiving contraceptive or anticonvulsive treatment) with no hypercorticism. The physiological significance of these findings is discussed. It is concluded that the test, together with a determination of the basal urinary 17-ketogenic steroid excretion, is suitable as the first diagnostic test in patients in whom Cushing's syndrome is suspected. In cases of insufficient suppression of plasma corticosteroids, further studies, including the suppression test of Liddle (1960), must be carried out.

scholarly journals THE EFFECT OF ADMINISTRATION OF EPINEPHRINE ON THE LEUKOCYTE COUNTS OF NORMAL SUBJECTS

Blood ◽  
1950 ◽  
Vol 5 (8) ◽  
pp. 723-731 ◽  
Author(s):  
COLIN WHITE ◽  
TSUIN HWA LING ◽  
ARNOLD M. KLEIN
Keyword(s):  
Eosinophil Count ◽  
Adrenocorticotropic Hormone ◽  
Leukocyte Count ◽  
Normal Subjects ◽  
Total Count ◽  
Subcutaneous Injections ◽  
History Of ◽  
Leukocyte Counts ◽  
Adrenocortical Hormone ◽  
The One

Abstract 1. Thirty-seven normal subjects were given subcutaneous injections of epinephrine, ranging from 0.25 to 0.5 mg., and the effects on the leukocytes were noted. 2. The neutrophils rose steadily for the three and one-half hours during which blood counts were made. The small lymphocytes rose in the first half hour, then fell below normal and finally returned towards normal. The eosinophils rose at first and then fell below normal for the remainder of the period. 3. The three doses of epinephrine used produced effects which differed quantitatively but not qualitatively. The most readily identified effect of the smallest dose was the one-half hour rise in lymphocytes or the one-half hour rise in total count. A dose of 0.5 mg. is satisfactory for work of this kind. 4. Subjects with a history of allergy showed a greater tendency than the remainder to exhibit a one-half hour rise in the eosinophil count. 5. The changes in the leukocyte count produced by epinephrine are similar to, but not identical with, those produced by adrenocortical hormone or adrenocorticotropic hormone.

Effects of galvanic mastoid stimulation in seated human subjects

2009 ◽  
Vol 106 (3) ◽  
pp. 893-903 ◽  
Author(s):  
Z. Ghanim ◽  
J. C. Lamy ◽  
A. Lackmy ◽  
V. Achache ◽  
N. Roche ◽  
...  
Keyword(s):  
Human Subjects ◽  
Normal Subjects ◽  
Standing Position ◽  
Reflex Response ◽  
Emg Activity ◽  
Free Standing ◽  
Vestibular Response ◽  
Vestibular Reflex ◽  
Tendon Jerk ◽  
Biphasic Responses

The vestibular responses evoked by transmastoid galvanic stimulation (GS) in the rectified soleus electromyogram (EMG) in freely standing human subjects disappear when seated. However, a GS-induced facilitation of the soleus monosynaptic (H and tendon jerk) reflex has been described in few experiments in subjects lying prone or seated. This study addresses the issue of whether this reflex facilitation while seated is of vestibulospinal origin. GS-induced responses in the soleus (modulation of the rectified ongoing EMG and of the monosynaptic reflexes) were compared in the same normal subjects while freely standing and sitting with back and head support. The polarity-dependent biphasic responses in the free-standing position were replaced by a non-polarity-dependent twofold facilitation while seated. The effects of GS were hardly detectable in the rectified ongoing voluntary EMG activity, weak for the H reflex, but large and constant for the tendon jerk. They were subject to habituation. Anesthesia of the skin beneath the GS electrodes markedly reduced the reflex facilitation, while a similar, although weaker, facilitation of the tendon jerk was observed when GS was replaced with purely cutaneous stimulation, a tap to the tendon of the sternomastoid muscle, or an auditory click. The stimulation polarity independence of the GS-induced reflex facilitation argues strongly against a vestibular response. However, the vestibular afferent volley, insufficient to produce a vestibular reflex response while seated, could summate with the GS-induced tactile or proprioceptive volley to produce a startle-like response responsible for the reflex facilitation.

Effect of protein restriction on15N transfer from dietary [15N]alanine and [15N]Spirulina platensisinto urea

2001 ◽  
Vol 281 (2) ◽  
pp. E349-E356 ◽  
Author(s):  
Mazen J. Hamadeh ◽  
L. John Hoffer
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Test Meal ◽  
High Protein Diet ◽  
Normal Subjects ◽  
Insulin Dependent Diabetes Mellitus ◽  
Protein Restriction ◽  
Dependent Diabetes Mellitus ◽  
Serum Amino Acids ◽  
Normal Men

Six normal men consumed a mixed test meal while adapted to high (1.5 g · kg−1· day−1) and low (0.3 g · kg−1· day−1) protein intakes. They completed this protocol twice: when the test meals included 3 mg/kg of [15N]alanine ([15N]Ala) and when they included 30 mg/kg of intrinsically labeled [15N] Spirulina platensis([15N]SPI). Six subjects with insulin-dependent diabetes mellitus (IDDM) receiving conventional insulin therapy consumed the test meal with added [15N]Ala while adapted to their customary high-protein diet. Protein restriction increased serum alanine, glycine, glutamine, and methionine concentrations and reduced those of leucine. Whether the previous diet was high or low in protein, there was a similar increase in serum alanine, methionine, and branched-chain amino acid concentrations after the test meal and a similar pattern of15N enrichment in serum amino acids for a given tracer. When [15N]Ala was included in the test meal,15N appeared rapidly in serum alanine and glutamine, to a minor degree in leucine and isoleucine, and not at all in other circulating amino acids. With [15N]SPI, there was a slow appearance of the label in all serum amino acids analyzed. Despite the different serum amino acid labeling, protein restriction reduced the postmeal transfer of dietary15N in [15N]Ala or [15N]SPI into [15N]urea by similar amounts (38 and 43%, respectively, not significant). The response of the subjects with IDDM was similar to that of the normal subjects. Information about adaptive reductions in dietary amino acid catabolism obtained by adding [15N]Ala to a test meal appears to be equivalent to that obtained using an intrinsically labeled protein tracer.

scholarly journals Reproducibility of Cerebral Glucose Metabolic Measurements in Resting Human Subjects

1988 ◽  
Vol 8 (4) ◽  
pp. 502-512 ◽  
Author(s):  
Elsa J. Bartlett ◽  
Jonathan D. Brodie ◽  
Alfred P. Wolf ◽  
David R. Christman ◽  
Eugene Laska ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Brain Metabolism ◽  
Human Subjects ◽  
Normal Subjects ◽  
Time Of Day ◽  
Cerebral Glucose Metabolism ◽  
Whole Brain ◽  
Positron Emission ◽  
Subcortical Regions ◽  
Regional Cerebral Glucose Metabolism

Positron emission tomography with 11C-2-deoxyglucose was used to determine the test-retest variability of regional cerebral glucose metabolism in 22 young normal right-handed men scanned twice in a 24-h period under baseline (resting) conditions. To assess the effects of scan order and time of day on variability, 12 subjects were scanned in the morning and afternoon of the same day (a.m.-p.m.) and 10 in the reverse order (p.m.-a.m.) with a night in between. The effect of anxiety on metabolism was also assessed. Seventy-three percent of the total subject group showed changes in whole brain metabolism from the first to the second measurement of 10% or less, with comparable changes in various cortical and subcortical regions. When a scaling factor was used to equate the whole brain metabolism in the two scans for each individual, the resulting average regional changes for each group were no mote than 1%. This suggests that the proportion of the whole brain metabolism utilized regionally is stable in a group of subjects over time. Both groups of subjects had lower morning than afternoon metabolism, but the differences were slight in the p.m.-a.m. group. One measure of anxiety (pulse at fun 1) was correlated with run 1 metabolism and with the percentage of change from run 1 to run 2. No significant run 2 correlations were observed. This is the first study to measure test-retest variability in cerebral glucose metabolism in a large sample of young normal subjects. It demonstrates that the deoxyglucose method yields low Intrasubject variability and high stability over a 24-h period.

Secretion rate of dehydroepiandrosterone and dehydroepiandrosterone sulfate in benign essential hypertension as compared to normal subjects

1970 ◽  
Vol 48 (12) ◽  
pp. 1308-1313 ◽  
Author(s):  
A. Shao ◽  
W. Nowaczynski ◽  
O. Kuchel ◽  
J. Genest
Keyword(s):  
Essential Hypertension ◽  
Isotope Dilution ◽  
Normal Subjects ◽  
Dehydroepiandrosterone Sulfate ◽  
Secretion Rate ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Hypertensive Patients ◽  
Double Isotope ◽  
Column Chromatographic

A study of the secretion rate of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) in normal subjects and patients with benign essential hypertension by a double isotope dilution method showed a fivefold increase in the secretion rate of dehydroepiandrosterone (from 9.8 mg/day ± 3.1 mg/day S.D. to 52.0 mg/day ± 15.5 mg/day S.D.), and a sixfold increase of dehydroepiandrosterone sulfate in hypertensive patients (from 10.7 mg/day ± 2.9 mg/day S.D. to 60.7 mg/day ± 18.6 mg/day S.D.). This study was carried out following the administration of 14C-labelled DHEA and 3H-labelled DHEA-S and involved an initial column chromatographic separation of urinary DHEA-glucuronide and sulfate.

Dependence of Transcutaneous Oxygen Tension on Local Arteriovenous Pressure Gradient in Normal Subjects

1981 ◽  
Vol 60 (5) ◽  
pp. 499-506 ◽  
Author(s):  
C. R. Wyss ◽  
F. A. Matsen ◽  
Racheal V. King ◽  
C. W. Simmons ◽  
E. M. Burgess
Keyword(s):  
Oxygen Tension ◽  
Pressure Difference ◽  
Venous Blood ◽  
Venous Drainage ◽  
Normal Subjects ◽  
External Pressure ◽  
Transcutaneous Oxygen Tension ◽  
Transcutaneous Oxygen ◽  
Normal Men ◽  
The Relationship

1. We studied the relationship between trans-cutaneous oxygen tension at the foot and local arteriovenous pressure difference in 15 normal men and women; arteriovenous pressure difference was varied by changing the height of the foot with respect to the heart and by applying external pressure to the foot. 2. Control transcutaneous oxygen tension was 67 ± 9 sd mmHg (8.9 ± 1.2 kPa) at a control arteriovenous pressure difference of 80 ± 6 sd mmHg (10.6 ± 0.8 kPa). 3. In every subject transcutaneous oxygen tension fell non-linearly with a decrease in arteriovenous pressure difference; transcutaneous oxygen tension was relatively insensitive to changes in arteriovenous pressure difference when arteriovenous pressure difference was high, but always fell sharply to zero at some positive arteriovenous pressure difference [range 13-34 mmHg (1.7-4.5 kPa)]. 4. An analysis of the data indicated that transcutaneous oxygen tension varied with arteriovenous pressure difference approximately as the oxygen tension of cutaneous venous blood under the sensor varied (in the absence of changes in cutaneous vascular resistance and oxygen consumption). 5. This analysis was supported by studies in three subjects in whom the oxygen tension of superficial venous drainage from a warmed hand or foot was measured along with Transcutaneous oxygen tension while arteriovenous pressure difference was varied.

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