DISTRIBUTION PATTERN OF A NON-STEROID COMPOUND WITH ENDOCRINE ACTIONS, 14C-BIS(P-HYDROXYPHENYL)CYCLOHEXYLIDENEMETHANE (COMPOUND F6060) AND ITS DIACETATE (COMPOUND F6066)

1965 ◽  
Vol 50 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Å. Hanngren ◽  
N. Einer-Jensen ◽  
S. Ullberg

ABSTRACT While testing a series of unsymmetrical diphenylalkenes, it was observed that bis(p-hydroxyphenyl)cyclohexylidenemethane (compound F6060) and its diacetate (compound F6066) had an oestrogenic activity of about 1/1000 that of oestradiol benzoate. Further pharmacological investigations showed antioestrogenic (chicken oviduct test) and antigestagenic (Clauberg test) properties. The compounds had a low toxicity both in acute and chronic tests. In order to further elucidate the physiology of the compounds they were labelled with 14C and their distribution in the body was investigated by whole body autoradiography in male and female (pregnant and nonpregnant) mice. A rapid and selective accumulation of both compounds was observed in the corpora lutea. A selective and progressively increasing accumulation was also seen in the visceral yolk sac epithelium. A slight accumulation was also found in the hypophysis, the adrenal cortex, the endometrium, the interstitial tissue of the testis and ovary, the epididymis and the mucosa of the seminal vesicles. No accumulation was found in the prostate. There was a very low concentration in the foetus during the whole course of observation. In addition to the radioactivity in the liver, bile and intestinal lumen, the only organs showing any retention 24 hours after administration were the corpora lutea and yolk sac epithelium. The distribution pattern is in agreement with the physiological findings of an antigestagenic effect. The concentration in the yolk sac epithelium suggests further studies on the localization of the different steps in gestagen biosynthesis.

2005 ◽  
Vol 88 (3) ◽  
pp. 923-934 ◽  
Author(s):  
Malcolm F Fuller ◽  
Daniel Tomé

Abstract Because the digestion of many dietary proteins is incomplete, and because there is a continuous (but variable) entry into the intestinal lumen of endogenous protein and amino acid nitrogen that is also subject to digestion, the fluxes of nitrogen, amino acids, and protein in the gut exhibit a rather complicated pattern. Methods to distinguish and quantitate the endogenous and dietary components of nitrogen and amino acids in ileal chyme or feces include the use of a protein-free diet, the enzyme-hydrolyzed protein method, different levels of protein intake, multiple regression methods, and stable-isotope labelling of endogenous or exogenous amino acids. Assessment of bioavailability can be made, with varying degrees of difficulty, in man directly but, for routine evaluation of foods, the use of model animals is attractive for several reasons, the main ones being cost and time. Various animals and birds have been proposed as models for man but, in determining their suitability as a model, their physiological, enzymological, and microbiological differences must be considered. Fecal or ileal digestibility measurements, as well as apparent and true nitrogen and amino acid digestibility measurements, have very different nutritional significance and can, thus, be used for different objectives. Measurements at the ileal level are critical for determining amino acid losses of both dietary and endogenous origin, whereas measurements at the fecal level are critical in assessing whole-body nitrogen losses. A complementary and still unresolved aspect is to take into account the recycling of intestinal nitrogen and bacterial amino acids to the body.


1916 ◽  
Vol s2-61 (244) ◽  
pp. 433-473
Author(s):  
CHAS. H. O'DONOGHUE

The Corpus Luteum (a) Follicular Wall--The membrana granulosa in the three species, P. cinereus, T. vulpecula, and D. aurita, is composed of typical polygonal cells arranged three or four cells deep around the ripe follicle. The theca folliculi also calls for no special comment in any case. It is composed of internal and external layers, does not contain any included interstitial cells, and its cells are always readily distinguishable from membrana granulosa cells. (b) The Formation of the Corpus Luteum--The corpus luteum in P. cinereus is formed by the irruption of both layers of the theca folliculi, which burst through the membrana granulosa and form a lining on its inner side. This method of formation is similar to that in P. obesula, P. nasuta, and M. ruficollis. The ripe follicle in T. vulpecula collapses when the ovum is extruded, and the central cavity is at once obliterated. The theca folliculi is drawn in with the membrana granulosa, which it penetrates, and the connective tissue becomes irregularly distributed through the body. It is unlike the process in any other marsupial so far examined, but to a certain extent resembles that in the mouse. In D. aurita the thecal irruptions do not at once go through the membrana granulosa, but push it before them until the central cavity is practically filled in, and then they break through and form the central plug of connective tissue. In one example, a very early stage, mitoses were found in the cells of the membrana granulosa, as was also the case in P. obesula and P. nasuta. (c) The fully formed Corpus Luteum.--The corpus luteum in P. cinereus remains hollow even when fully grown, and the central cavity does not get filled in until some time after the birth of the young, apparently not until the gland has started to decline. This condition is apparently unique. In T. vulpecula the corpus luteum is fairly typical when full grown, save that its connective tissue is much more irregularly arranged than in other marsupials. The condition of the corpus in D. aurita is very similar to that in D. viverrinus In no case is the membrana granulosa shed, nor does the theca interna contribute to the lutein cells of the corpus luteum. The Interstitial Tissue. There is present in the ovary of certain species of marsupials a tissue which corresponds histologically to the interstitial tissue in the ovary of the higher mammals. The cells are always distinguishable from ordinary stroma cells, cells of the theca interna, old lutein cells, or the cells of an atresic follicle, and there is no evidence that any of the last three are at any time transformed into interstitial cells. Such cells are present in the pouch young of T. vulpecula before they could have been derived from any of the sources suggested above. Interstitial tissue is to be regarded as a tissue suigeneris, although it is possible that it may originate from modified stroma cells at a very early stage. The tissue is irregularly distributed in the various species of marsupials, and it is worthy of note that it is present in all the Diprotodontia and absent in the Polyprotodontia so far examined. It may be present only as a few small groups of cells or in such quantity as to form by far the largest part of the bulk of the ovary, excluding corpora lutea, as, for example, in P. penicillata. The tissue has a typical glandular appearance, but no satisfactory account of its function has yet been put forward, and in view of this and its irregularity it is preferable not to call it a gland, but retain the term interstitial tissue or cells.


1969 ◽  
Vol 62 (3) ◽  
pp. 505-512 ◽  
Author(s):  
Lars-Erik Appelgren

ABSTRACT Whole body autoradiography of 14C-4-testosterone in mice showed the same distribution pattern as earlier investigations by impulse counting on the accumulation of radioactivity in the liver and kidney and the remarkably low concentration in most male sex organs. One major exception was the high concentration of radioactivity found in the ductus deferens. In the testicle the radioactivity was mainly confined to the interstitial parts and in the adrenal a rather high concentration was registered in the cortex. An accumulation of testosterone and/or its metabolites in the corpora lutea of pregnant mice was observed. The findings of testosterone and/or its metabolites in the testicles, adrenals and ovaries are in agreement with the previously demonstrated abilities of these organs to metabolize testosterone.


2008 ◽  
Vol 294 (5) ◽  
pp. G1171-G1180 ◽  
Author(s):  
Heleen M. de Vogel-van den Bosch ◽  
Nicole J. W. de Wit ◽  
Guido J. E. J. Hooiveld ◽  
Hanneke Vermeulen ◽  
Jelske N. van der Veen ◽  
...  

Transporters present in the epithelium of the small intestine determine the efficiency by which dietary and biliary cholesterol are taken up into the body and thus control whole-body cholesterol balance. Niemann-Pick C1 Like Protein 1 (Npc1l1) transports cholesterol into the enterocyte, whereas ATP-binding cassette transporters Abca1 and Abcg5/Abcg8 are presumed to be involved in cholesterol efflux from the enterocyte toward plasma HDL and back into the intestinal lumen, respectively. Abca1, Abcg5, and Abcg8 are well-established liver X receptor (LXR) target genes. We examined the effects of a high-fat diet on expression and function of cholesterol transporters in the small intestine in mice. Npc1l1, Abca1, Abcg5, and Abcg8 were all downregulated after 2, 4, and 8 wk on a cholesterol-free, high-fat diet. The high-fat diet did not affect biliary cholesterol secretion but diminished fractional cholesterol absorption from 61 to 42% ( P < 0.05). In an acute experiment in which triacylglycerols of unsaturated fatty acids were given by gavage, we found that this downregulation occurs within a 6-h time frame. Studies in LXRα-null mice, confirmed by in vitro data, showed that fatty acid-induced downregulation of cholesterol transporters is LXRα independent and associated with a posttranslational increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity that reflects induction of cholesterol biosynthesis as well as with a doubling of neutral fecal sterol loss. This study highlights the induction of adaptive changes in small intestinal cholesterol metabolism during exposure to dietary fat.


Author(s):  
William P. Jollie

A technique has been developed for visualizing antibody against horseradish peroxidase (HRP) in rat visceral yolk sac, the placental membrane across which passive immunity previously has been shown to be transferred from mother to young just prior to birth. Female rats were immunized by injecting both hind foot pads with 1 mg HRP emulsified in complete Freund's adjuvant. They were given a booster of 0.5mg HRP in 0.1 ml normal saline i.v. after one week, then bred and autopsied at selected stages of pregnancy, viz., 12, 1 7 and 22 days post coitum, receiving a second booster, injected as above, five days before autopsy. Yolk sacs were removed surgically and fixed immediately in 2% paraformaldehye, 1% glutaraldehye in 0.1 M phosphate buffer with 0.01% CaCl2 at pH 7.4, room temperature, for 3 hr, rinsed 3X in 0.1 M phosphate buffer plus 5% sucrose, then exposed to 1 mg HRP in 1 ml 0.1 M phosphate buffer at pH 7.4 for 1 hr. They were refixed in aldehydes, as above, for 1 5 min (to assure binding of antigen-antibody complex). Following buffer washes, the tissues were incubated in 3 mg diaminobenzidine tetrahydrochloride and 0.01% H2O2 in 0.05 M Tris-HCl buffer for 30 min. After brief buffer washes, they were postfixed in 2% OsO4. in phosphate buffer at pH 7.4, 4°C for 2 hr, dehydrated through a graded series of ethanols, and embedded in Durcupan. Thin sections were observed and photographed without contrast-enhancement with heavy metals. Cytochemical reaction product marked the site of HRP (i.e., antigen) which, in turn, was present only where it was bound with anti-HRP antibody.


1976 ◽  
Vol 15 (05) ◽  
pp. 248-253
Author(s):  
A. K. Basu ◽  
S. K. Guha ◽  
B. N. Tandon ◽  
M. M. Gupta ◽  
M. ML. Rehani

SummaryThe conventional radioisotope scanner has been used as a whole body counter. The background index of the system is 10.9 counts per minute per ml of sodium iodide crystal. The sensitivity and derived sensitivity parameters have been evaluated and found to be suitable for clinical studies. The optimum parameters for a single detector at two positions above the lying subject have been obtained. It has been found that for the case of 131I measurement it is possible to assay a source located at any point in the body with coefficient of variation less than 5%. To add to the versatility, a fixed geometry for in-vitro counting of large samples has been obtained. The retention values obtained by the whole body counter have been found to correlate with those obtained by in-vitro assay of urine and stool after intravenous administration of 51Cr-albumin.


1963 ◽  
Vol 43 (4) ◽  
pp. 561-570 ◽  
Author(s):  
Gösta Bengtsson ◽  
Sven Ullberg

ABSTRACT The distribution in mice of 14C- and 3H-diethylstilboestrol has been investigated autoradiographically. The results have been compared with those which have been previously reported for natural oestrogens. Many similarities have been demonstrated between the synthetic and natural compounds. Thus a specific accumulation has been observed in the endometrium, the granulosa layer of large ovarian follicles, the adrenal cortex. the interstitial tissue of the testes, and the hypophysis. Natural and synthetic oestrogens differ widely concerning the penetration into and the distribution within the foetus.


Author(s):  
Kinesh V P ◽  
Neelam D P ◽  
Punit B ◽  
Bhavesh S.B ◽  
Pragna K. S

Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.


2008 ◽  
Vol 396-398 ◽  
pp. 569-572
Author(s):  
Fumio Watari ◽  
Shigeaki Abe ◽  
I.D. Rosca ◽  
Atsuro Yokoyama ◽  
Motohiro Uo ◽  
...  

Nanoparticles may invade directly into the internal body through the respiratory or digestive system and diffuse inside body. The behavior of nanoparticles in the internal body is also essential to comprehend for the realization of DDS. Thus it is necessary to reveal the internal dynamics for the proper treatments and biomedical applications of nanoparticles. In the present study the plural methods with different principles such as X-ray scanning analytical microscope (XSAM), MRI and Fluorescent microscopy were applied to enable the observation of the internal diffusion of micro/nanoparticles in the (1) whole body level, (2) inner organ level and (3) tissue and intracellular level. Chemical analysis was also done by ICP-AES for organs and compared with the results of XSAM mapping.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dmitry M. Davydov ◽  
Andrey Boev ◽  
Stas Gorbunov

AbstractSituational or persistent body fluid deficit (i.e., de- or hypo-hydration) is considered a significant health risk factor. Bioimpedance analysis (BIA) has been suggested as an alternative to less reliable subjective and biochemical indicators of hydration status. The present study aimed to compare various BIA models in the prediction of direct measures of body compartments associated with hydration/osmolality. Fish (n = 20) was selected as a biological model for physicochemically measuring proximate body compartments associated with hydration such as water, dissolved proteins, and non-osseous minerals as the references or criterion points. Whole-body and segmental/local impedance measures were used to investigate a pool of BIA models, which were compared by Akaike Information Criterion in their ability to accurately predict the body components. Statistical models showed that ‘volumetric-based’ BIA measures obtained in parallel, such as distance2/Rp, could be the best approach in predicting percent of body moisture, proteins, and minerals in the whole-body schema. However, serially-obtained BIA measures, such as the ratio of the reactance to resistance and the resistance adjusted for distance between electrodes, were the best fitting in predicting the compartments in the segmental schema. Validity of these results should be confirmed on humans before implementation in practice.


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