OESTRADIOL METABOLISM IN THE PREVIABLE HUMAN FOETUS AND IN THE FOETO-PLACENTAL UNIT

1964 ◽  
Vol 45 (2) ◽  
pp. 297-320 ◽  
Author(s):  
R. C. Haynes ◽  
G. Mikhail ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Five normal previable foetuses were perfused with tracer amounts of oestradiol-4-14C and the metabolism of the compound was investigated. This study was completed by 3 experiments in which the oestradiol-4-14C was introduced in situ into the intact foeto-placental unit via the umbilical circulation. More than 80 per cent of the radioactive material present in the various foetal organs in both types of experiments was in a conjugated form. In contrast, in the placentas, less than 10 per cent of the total radioactivity present was in a conjugated form. The bulk of the radioactive material present in the foetal tissues was identified as oestradiol 3-sulphate and oestrone sulphate. In addition, two minor fractions were detected in the perfused foetuses, one of which behaved in countercurrent distribution studies as »glucosiduronates«; the other resembled »sulphates«. The oestrogen moiety of these two fractions was neither oestradiol nor oestrone, but it appeared to be a complex mixture. Although some radioactive material was found which closely resembled oestriol, it was not possible to detect oestriol with certainty. No glucosiduronate-like material was found in the foetal tissues following the injection of oestradiol-4-14C into the intact foeto-placental unit. Also the quantity of the »sulphate-like« material different from oestradioland oestrone sulphates was greatly reduced: A number of unconjugated metabolites were also detected, among which oestrone was identified. A perfusion experiment with an anencephalic foetus indicated that this foetus was capable of forming conjugated metabolites from oestradiol-4-14C. The results obtained do not favour the view that oestriol is a major and instantaneously formed foetal metabolite of oestradiol. On the other hand, they lend additional support to the concept that oestrogens reaching the foetus are extensively sulphurylated by the foetus and that these oestrogen sulphates are hydrolysed by the placenta before transfer of the oestrogen moiety to the maternal circulation.

1971 ◽  
Vol 66 (4) ◽  
pp. 637-647 ◽  
Author(s):  
J. Schwers ◽  
T. Vancrombreucq ◽  
M. Govaerts ◽  
G. Eriksson ◽  
E. Diczfalusy

ABSTRACT Two midgestation placentas were perfused in situ with a combination of [7α-3H] dehydroepiandrosterone sulphate and [4-14C] oestrone sulphate and metabolites were isolated from the placentas, perfusates and maternal urine specimens. Approximately 70 per cent of the perfused radioactive material was recovered from these three sources. The bulk of the administered radioactive material was recovered in an unchanged form from the perfusates; some 2–4 per cent was excreted in the urine and less than 0.5% was found in the placentas. The tritium to carbon-14 ratio of the unconjugated material isolated from the perfusates and placentas was higher, and that of the conjugated material recovered from the same sources was lower than the ratio of the administered material. In addition, more tritium than carbon-14 labelled material was present in the urine. Approximately 2 per cent of the perfused dehydroepiandrosterone sulphate was recovered in the form of phenolic steroids, mostly from the urine. From this source double labelled oestrone, oestriol, 16α-hydroxy-oestrone and 16-epioestriol were isolated. The tritium to carbon-14 ratio of all oestrogens isolated from the urine was higher than that of the perfused material. From the urine specimens 10 to 15 times more double labelled oestriol than oestrone was isolated.


1967 ◽  
Vol 56 (1) ◽  
pp. 71-84 ◽  
Author(s):  
G. Zucconi ◽  
U. Goebelsmann ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Oestrone-6,7-3H-glucosiduronate-14C (OE1-3H-Gl-14C) has been prepared biosynthetically and its metabolism studied in two cases of therapeutic abortion following the administration of the tracer at laparotomy into the umbilical vein. The bulk of the radioactive material recovered was in the foetus and placenta; only small amounts were present in the urine of the mother. Minute quantities of the radioactive material recovered from any of these sources were in an unconjugated form. Following reduction with KBH4 of the extract of the foetal liver oestriol-3-glucosiduronate (OE3-3Gl) was isolated from this source with the same isotopic ratio as that of the injected material. Following hydrolysis with β-glucuronidase, 3H-labelled oestrone, 17β-oestradiol and oestriol were isolated in a radiochemically homogeneous form from the foetal liver and from the urine of the mother, and oestrone and 17β-oestradiol from the placenta. From the urine of the mothers OE1-3H-Gl-14C was also isolated. It exhibited the same isotopic ratio as the injected material. Following the intravenous infusion to two women at midpregnancy of a combination of 3H-labelled OE1-Gl and 14C-labelled oestrone sulphate (OE1-S), the tracer administered as OE1-Gl was eliminated in the urine far more rapidly than that infused in the form of OE1-S. It is concluded that at midpregnancy a) the foetus is capable of metabolizing OE1-Gl without any preceding hydrolysis, b) the placenta exhibits no β-glucuronidase activity, c) only a limited amount of OE1-Gl is transferred from the foeto-placental circulation to the mother and exclusively in an unchanged form, and d) OE1-Gl is eliminated from the maternal circulation much more rapidly than OE1-S.


1967 ◽  
Vol 55 (3) ◽  
pp. 401-414 ◽  
Author(s):  
S. Dell'Acqua ◽  
S. Mancuso ◽  
G. Eriksson ◽  
J. L. Ruse ◽  
S. Solomon ◽  
...  

ABSTRACT 16α-Hydroxy-dehydroepiandrosterone-7α-3H (16αHO-DHA), 16α-hydroxy-androstenedione-4-14C (16αHO-A) and 16α-hydroxy-testosterone-4-14C (16αHO-T) were synthesized. Human placentas were perfused in situ at midpregnancy with these steroids and the radioactive material recovered from the placentas and perfusates was analysed. In order to compare the aromatisation of 16α-hydroxylated and 16-desoxy precursors, in a second series of perfusions 16αHO-DHA was combined with differently labelled dehydroepiandrosterone (DHA) and 16αHO-T with testosterone (T). Following the perfusion of 16αHO-DHA, both 16αHO-A and oestriol (OE3) were isolated from the placentas and perfusates. No labelled androst-5-ene-3β,16α,17β-triol (Δ5-TRIOL) or 16αHO-T was detected in these sources. When 16αHO-A or 16αHO-T was perfused, OE3 was isolated from the placenta and perfusates. However, there was no interconversion between 16αHO-A and 16αHO-T. No oestrogenic ring D ketols were found in the placentas and perfusates in any of the experiments. The extent of aromatisation (judged from the amount of oestrogen isolated from the placenta and perfusate) was approximately the same following the perfusion of 16αHO-DHA, 16αHO-A, DHA and T, but was much lower when 16αHO-T was perfused. The low degree of aromatisation of 16αHO-T was associated with the presence of large amounts of unchanged 16αHO-T in the placentas as well as in the perfusates. The transfer of 16αHO-T to the maternal compartment was also much lower than that of the other precursors studied. It is concluded that the placental transfer and aromatisation of 16αHO-T is much lower than those of other oestrogen precursors. This condition might lead to the accumulation of this compound in the placenta. The placental metabolism of Δ5-TRIOL and 16αHO-DHA follow separate pathways with no interconversion until the stage of aromatisation, or possibly 19-hydroxylation.


Author(s):  
J. I. Bennetch

In a recent study of the superplastic forming (SPF) behavior of certain Al-Li-X alloys, the relative misorientation between adjacent (sub)grains proved to be an important parameter. It is well established that the most accurate way to determine misorientation across boundaries is by Kikuchi line analysis. However, the SPF study required the characterization of a large number of (sub)grains in each sample to be statistically meaningful, a very time-consuming task even for comparatively rapid Kikuchi analytical techniques.In order to circumvent this problem, an alternate, even more rapid in-situ Kikuchi technique was devised, eliminating the need for the developing of negatives and any subsequent measurements on photographic plates. All that is required is a double tilt low backlash goniometer capable of tilting ± 45° in one axis and ± 30° in the other axis. The procedure is as follows. While viewing the microscope screen, one merely tilts the specimen until a standard recognizable reference Kikuchi pattern is centered, making sure, at the same time, that the focused electron beam remains on the (sub)grain in question.


1964 ◽  
Vol 45 (4) ◽  
pp. 535-559 ◽  
Author(s):  
E. Bolté ◽  
S. Mancuso ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT In 15 cases of therapeutic abortion by laparotomy the placenta was disconnected from the foetus and perfused in situ with tracer amounts of radioactive dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), androst-4-ene-3,17-dione (A), testosterone (T) and 17β-oestradiol (OE2). Analysis of the placentas, perfusates and urine samples revealed an extensive aromatisation of DHA, A and T; more than 70% of the radioactive material recovered was phenolic, and at least 80 % of this phenolic material was identified as oestrone (OE1), 17β-oestradiol (OE2) and oestriol (OE3), the latter being detected only in the urine. Comparative studies indicated that A and T were aromatised somewhat better than DHA and that all three unconjugated steroids were aromatised to a much greater extent than DHAS. Radioactive OE1 and OE2 were isolated and identified in the placentas and perfusates, but no OE3, epimeric oestriols, or ring D ketols could be detected in these sources, not even when human chorionic gonadotrophin (HCG) was added to the blood prior to perfusion. Lack of placental 16-hydroxylation was also apparent when OE2 was perfused. Regardless of the precursor perfused, there was three times more OE2 than OE1 in the placenta and three times more OE1 than OE2 in the perfusate. This was also the case following perfusion with OE2. The results are interpreted as suggesting the existence in the pregnant human of a placental »barrier« limiting the passage of circulating androgen. The barrier consists of a) limited ability to transfer directly DHAS and b) an enzymic mechanism resulting in the rapid and extensive aromatisation of the important androgens DHA, A and T.


Author(s):  
Oliver D. Patterson ◽  
Deborah A. Ryan ◽  
Xiaohu Tang ◽  
Shuen Cheng Lei

Abstract In-line E-beam inspection may be used for rapid generation of failure analysis (FA) results for low yielding test structures. This approach provides a number of advantages: 1) It is much earlier than traditional FA, 2) de-processing isn’t required, and 3) a high volume of sites can be processed with the additional support of an in-line FIB. Both physical defect detection and voltage contrast inspection modes are useful for this application. Voltage contrast mode is necessary for isolation of buried defects and is the preferred approach for opens, because it is faster. Physical defect detection mode is generally necessary to locate shorts. The considerations in applying these inspection modes for rapid failure analysis are discussed in the context of two examples: one that lends itself to physical defect inspection and the other, more appropriately addressed with voltage contrast inspection.


2006 ◽  
Vol 6 (9) ◽  
pp. 2959-2966 ◽  
Author(s):  
Na Zhang ◽  
Qineng Ping ◽  
Guihua Huang ◽  
Xiuzhen Han ◽  
Yanna Cheng ◽  
...  

Wheat germ agglutinin (WGA) modified liposomes and solid lipid nanoparticles (SLNs) were evaluated for improving intestinal absorption of insulin. In an in situ local intestinal perfusion experiment, formulations containing 100 IU/kg insulin were administered to the duodenum, jejunum, and ileum of fasted rats. As hypothesized, ileum was the best intestinal location for the absorption of insulin-containing liposomes. Serum insulin concentrations decreased for the various formulations in different absorption sites according to the following trends: Duodenum > ileum > jejunum for WGA-modified insulin-containing liposomes; duodenum > jejunum > ileum for WGA-modified insulin-containing SLNs; ileum > jejunum > duodenum for insulin-containing liposomes; ileum > duodenum > jejunum for insulin-containing SLNs; and duodenum ≥ ileum > jejunum for aqueous solution of insulin. These results imply that the nanoparticle type and delivery site were important factors with respect to increasing the bioavailability of insulin following oral administration. The proteolytic degradation as well as the epithelial permeability were primary determinants influcing insulin mucosal absorption.


2000 ◽  
Vol 3 (6) ◽  
pp. 591-596 ◽  
Author(s):  
Virpi V. Smith ◽  
Amanda J. Williams ◽  
Vas Novelli ◽  
Marian Malone

We report two infants with the acquired immunodeficiency syndrome (AIDS) and rectal bleeding due to cytomegalovirus (CMV) ileitis and colitis with minimal focal mucosal ulceration but with extensive leiomyolysis of the muscularis propria. Immunostaining and in situ hybridization for CMV showed numerous viral inclusions in the myocytes of the muscularis propria and vascular endothelium/smooth muscle with only occasional inclusions present in the muscularis mucosae. Colectomy was curative in one patient; in the other the bowel was only examined at postmortem.


2000 ◽  
Vol 6 ◽  
pp. 171-182 ◽  
Author(s):  
Ben A. LePage ◽  
Hermann W. Pfefferkorn

When one hears the term “ground cover,” one immediately thinks of “grasses.” This perception is so deep-seated that paleobotanists even have been overheard to proclaim that “there was no ground cover before grasses.” Today grasses are so predominant in many environments that this perception is perpetuated easily. On the other hand, it is difficult to imagine the absence or lack of ground cover prior to the mid-Tertiary. We tested the hypothesis that different forms of ground cover existed in the past against examples from the Recent and the fossil record (Table 1). The Recent data were obtained from a large number of sources including those in the ecological, horticultural, and microbiological literature. Other data were derived from our knowledge of Precambrian life, sedimentology and paleosols, and the plant fossil record, especially in situ floras and fossil “monocultures.” Some of the data are original observations, but many others are from the literature. A detailed account of these results will be presented elsewhere (Pfefferkorn and LePage, in preparation).


1977 ◽  
Vol 24 (1) ◽  
pp. 113-116 ◽  
Author(s):  
F. J. Galindez ◽  
M. Prud'hon ◽  
G. Reboul

SUMMARYFifty-six Merino d'Aries and 56 Romanov × Merino crossbred lactating ewes were divided into two treatment groups, one (T1) with a ewe-to-ram ratio of 48: 1 (24 Merino and 24 crossbred) and the other (T2) of 64: 1 (32 Merino and 32 crossbred).Intravaginal sponges with 40 mg FGA (Searle) were inserted in two subgroups at 8-day intervals and withdrawn after 12 and 16 days in situ, in four equal groups at 4-day intervals. A dose of 400 IU pregnant mare's serum gonadotrophin (PMSG) was applied at sponge withdrawal.Fertility after two oestrous cycles was equally satisfactory in both treatments, though it was lower in treatment group T2. This could be due to the significantly low (P<0·01) number of Merino ewes raddled by the T2 ram (0·33 Merino against 0·92 crossbred) suggesting preferential behaviour by the ram in this treatment.Comparisons between breeds show a slight superiority in the fertility of crossbred ewes and a highly significant superiority in prolificacy These results suggest that using the described method, 2% of rams seems more than adequate to mate with progestagen-synchronized ewes with a satisfactory fertility level. It is, however, recommended to use homogeneous groups of ewes.


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