George V. LeRoy

Absorbability of β-sitosterol in humans

Abstract Tritium labeled β-sitosterol was administered orally to 5 normal humans and to 5 terminal patients. Isolation of tritium-labeled sterols from plasma and red blood cells of normal male subjects showed some absorption had occurred, but it was much less than for comparable doses of labeled cholesterol. The highest level observed after a single 50-mg. dose of β-sitosterol was about 0.015 mg. per 100 ml. of blood in the total sterol fraction. These values are uncorrected for dilution by any unlabeled β-sitosterol present in the diet and are therefore minimum values. The disappearance rate from blood was slightly higher than for labeled cholesterol. Larger doses of tritium labeled β-sitosterol administered to a series of terminal patients gave similar results for blood levels and disappearance rates. Isolation of sterols from a variety of tissues showed β-sitosterol to be widely distributed. High specific activity values were observed in bile sterols, suggesting that β-sitosterol is selectively excreted by this route. Aorta and other blood vessels had lower amounts of tritium labeled sterols than most other tissues. The total amount of β-sitosterol present in blood and principal visceral organs (excluding intestine) was estimated in one patient as about 0.5 per cent of a single dose of 258 mg. given 5 days previously. Although the distribution pattern of absorbed β-sitosterol was similar to that of fed labeled cholesterol, it did not become esterified to as great an extent.

Hormones in human reproduction

In undergoing this life, many people always try to do and get the best. New knowledge, experience, lesson, and everything that can improve the life will be done. However, many people sometimes feel confused to get those things. Feeling the limited of experience and sources to be better is one of the lacks to own. However, there is a very simple thing that can be done. This is what your teacher always manoeuvres you to do this one. Yeah, reading is the answer. Reading a book as this hormones in human reproduction and other references can enrich your life quality. How can it be?Abstract Following the administration of progesterone labeled with carbon 14 at position 21 to a patient with a normal pregnancy about 70 per cent of the administered radioactivity was recovered from the urine, feces, and expired air (22.62 per cent, 29.74 per cent, and 18.56 per cent, respectively). The excretion of radioactive metabolites by the skin was minimal. At present we have not accounted for the remaining 30 per cent of the administered radioactivity, but it seems likely that part of it is stored in the fat compartments of the body for a considerable length of time. There was no relationship between the urinary recovery of radioactivity and the pregnant and nonpregnant state, nor the viability of the fetus. The metabolites in urine and feces consist mainly of conjugated steroids, as pregnanediol, pregnanolone, and other unknown compounds. The elimination of tagged carbon dioxide after the administration of C 14 -21-progesterone indicates an oxidation of the side chain of the progesterone molecule, resulting in the formation of such steroids as androstenedione and related compounds which have androgenic properties. Determinations of radioactivity in the blood plasma following the intravenous and intramuscular administration of the labeled hormone demonstrated a rapid disappearance of the free steroid from the circulation due to (1) a speedy conjugation with glucuronic acid and (2) rapid diffusion into body tissues, mainly into the fat compartment. In contrast to the high concentration of radioactivity in the fat, only moderate amounts of radioactivity were demonstrated in the myometrium and the decidua of pregnant patients. Extremely low concentrations of radioactivity were found in the endometrium of non-pregnant women during the pre- and postovulatory phases of the menstrual cycle, and no radioactivity was demonstrable in the atrophic endometrium of 2 patients. The absence of estrogenic activity seems to prevent the entrance of the hormone into the cells of the mucosal layer of the uterus. This observation provides direct evidence that estrogens must prepare the endometrial cells in order that progesterone can exhibit its progestational effect. Apparently, only minimal amounts of progesterone and/or its metabolites are necessary to exert its biological effects on the endometrium. Preliminary studies on the biosynthesis of estrogens in human pregnancy revealed that cholesterol as well as testosterone can serve as a precursor of estrone. In a patient with choriocarcinoma C 14 -4-progesterone was converted into radioactive estrone. The data which we have presented here complete another milestone in the very long experimental road toward our understanding of the metabolism and biosynthesis of the steroid hormones in mammalian reproduction. It becomes increasingly apparent that our thorough understanding of their role in the normal reproductive process must precede an intelligent approach to the solution of many problems in obstetrics and gynecology.

American Gynecological Society Transactions of the Seventy-ninth Annual Meeting Washington, D.C., May 21–23, 1956Hormones in human reproduction: Part I: Metabolism of progesterone☆☆☆★

In undergoing this life, many people always try to do and get the best. New knowledge, experience, lesson, and everything that can improve the life will be done. However, many people sometimes feel confused to get those things. Feeling the limited of experience and sources to be better is one of the lacks to own. However, there is a very simple thing that can be done. This is what your teacher always manoeuvres you to do this one. Yeah, reading is the answer. Reading a book as this hormones in human reproduction and other references can enrich your life quality. How can it be?Abstract Following the administration of progesterone labeled with carbon 14 at position 21 to a patient with a normal pregnancy about 70 per cent of the administered radioactivity was recovered from the urine, feces, and expired air (22.62 per cent, 29.74 per cent, and 18.56 per cent, respectively). The excretion of radioactive metabolites by the skin was minimal. At present we have not accounted for the remaining 30 per cent of the administered radioactivity, but it seems likely that part of it is stored in the fat compartments of the body for a considerable length of time. There was no relationship between the urinary recovery of radioactivity and the pregnant and nonpregnant state, nor the viability of the fetus. The metabolites in urine and feces consist mainly of conjugated steroids, as pregnanediol, pregnanolone, and other unknown compounds. The elimination of tagged carbon dioxide after the administration of C 14 -21-progesterone indicates an oxidation of the side chain of the progesterone molecule, resulting in the formation of such steroids as androstenedione and related compounds which have androgenic properties. Determinations of radioactivity in the blood plasma following the intravenous and intramuscular administration of the labeled hormone demonstrated a rapid disappearance of the free steroid from the circulation due to (1) a speedy conjugation with glucuronic acid and (2) rapid diffusion into body tissues, mainly into the fat compartment. In contrast to the high concentration of radioactivity in the fat, only moderate amounts of radioactivity were demonstrated in the myometrium and the decidua of pregnant patients. Extremely low concentrations of radioactivity were found in the endometrium of non-pregnant women during the pre- and postovulatory phases of the menstrual cycle, and no radioactivity was demonstrable in the atrophic endometrium of 2 patients. The absence of estrogenic activity seems to prevent the entrance of the hormone into the cells of the mucosal layer of the uterus. This observation provides direct evidence that estrogens must prepare the endometrial cells in order that progesterone can exhibit its progestational effect. Apparently, only minimal amounts of progesterone and/or its metabolites are necessary to exert its biological effects on the endometrium. Preliminary studies on the biosynthesis of estrogens in human pregnancy revealed that cholesterol as well as testosterone can serve as a precursor of estrone. In a patient with choriocarcinoma C 14 -4-progesterone was converted into radioactive estrone. The data which we have presented here complete another milestone in the very long experimental road toward our understanding of the metabolism and biosynthesis of the steroid hormones in mammalian reproduction. It becomes increasingly apparent that our thorough understanding of their role in the normal reproductive process must precede an intelligent approach to the solution of many problems in obstetrics and gynecology.

Continuous measurement of specific activity of C14O2 in expired air

Abstract The majority of carbon compounds of metabolic interest ultimately are degraded to carbon dioxide and urea which are excreted. Following the administration of a tracer dose of a C14-labeled metabolite, there is assumed to be a pattern of elimination of C14O2 which is characteristic for the healthy state, and which is distorted in disease. This pattern is represented by the time-course of specific activity of C14O2 in expired air. Metabolic studies in human subjects and in animals are facilitated by the apparatus described in this report which permits the continuous measurement of radioactive C14O2 in expired air. The apparatus consists of an air-collection system, a ventilation meter, a C12O2 (infrared) analyzer, a 4π G-M counter with anti-coincidence circuitry, and a ratio analyzer to compute C14/C12. Analog data are printed out on a four-channel recording millivoltmeter at the rate of four items per minute on each channel. The data are in such a form that they can be converted readily to digital information for processing in a high-speed computer. Rapid estimates of the size and kinetics of the carbon dioxide pool are possible when labeled bicarbonate is used as the tracer.

THE CONSEQUENCES OF INGESTION BY MAN OF REAL AND SIMULATED FALLOUT

Abstract : Real and simulated particulate fallout and solutions of Sr85Cl2 and Cs(134)Cl2 were fed to 102 healthy volunteers. Absorption and retention of ingested radioactivity was measured by whole body counting using the gamma-ray spectrometer at the Argonne Cancer Research Hospital. An average of 3 per cent of the radioactivity of week-old local fallout was absorbed: the range was 0 to 9 per cent. Strontium and cesium leached or dissolved from simulated fallout behaved in the same way, metabolically, after absorption as they did when the tracer was swallowed in a solution or injected intravenously. The large number of subjects studied provided additional information on the range of variation of intestinal motility, biological availability of strontium, cesium and barium following ingestion of fallout, and retention of the radionuclides of these elements. (Author)

AEC Licensing of Radioisotopes for Clinical Research

The established policies of the Atomic Energy Commission are embodied in the Federal Register in 10 CFR 30 with which the reader is presumably familiar. The decisions and actions of the Advisory Committee on Medical Uses of Isotopes of the Division of Licensing and Regulation of the AEC contribute to the making of regulations, but it is neither possible nor desirable to attempt to spell out what the position of the Committee will be in a particular case. As a preface let me review briefly some of the history of the Subcommittee on Human Applications of the Isotopes Branch which was the precursor-so to speak-of the present Advisory Committee. The original group (usually dubbed the Subhuman Committee) first met on June 28, 1946, at Oak Ridge. Because the quantities of radioisotopes available were limited, the initial functions of the Subcommittee were, first, to recommend the relative production effort to be devoted to isotopes for therapy and diagnosis; and second, to make recommendations to the Isotopes Branch for the allocation of available materials for clinical use. As the demand for isotopes for medical use increased, production also increased so that allocation as such soon ceased to be an important problem. In 1948 the Subcommittee formulated certain broad objectives and criteria for its role in the authorization process. At this point I wish to make it quite clear that the role of the Subcommittee, and of its product the Advisory Committee, is to appraise applications and to make recommendations with respect to the human use of isotopes for the guidance of the appropriate agencies of the AEC. Authorizations have now been replaced by licenses to possess by-product materials, which are issued by the Division of Licensing and Regulation in accordance with the provisions of 10 CFR 30, and by internal rules, the making of which is a prerogative of the Licensing Division.

Immediate Decrease in Respiratory C14O2 Excretion Following Simultaneous Intravenous Administration of NaHC14O3 and Acetazoleamide in the Rat

Summary The effect of acetazoleamide on rate of expiration of carbon dioxide was studied in rats using carbon-14 labeled bicarbonate. A marked transient reduction in expired C14O2 was observed during the first 10 minutes after simultaneous intravenous injection of the drug (70 mg/kg) and NaHC14O3. The rate of appearance of C14O2 was reduced 35 ± 7% in the treated animals 5 minutes after injection. When the animals were pretreated (30 minutes) with acetazoleamide (20 mg/kg) and when the labeled NaHC14O3 entered the blood slowly as a result of intraperitoneal injection, the reduction in rate of C14O2 elimination was not nearly as marked.