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Biomedical subjects

C Bulletti

Publications and source records attributed to C Bulletti.

At least 55 records · Page 3Linked to original sources
PubMed1991

Factors regulating interaction between trophoblast and human endometrium.

Implantation is a crucial step in human reproduction. Disturbances of this process are responsible for pregnancy failure after both in vivo and in vitro fertilization. The endometrium provides the implanting embryo with a unique substratum where the embryo communicates with biochemical signals, attaches itself, penetrates and grows without blood circulation. The highly proliferative phase of the cytotrophoblast, during early human embryogenesis, may be due to endogenous production of growth factors that may establish autocrine/short range paracrine stimulator loops which explain the tumor-like properties of these tissues. Endometrial BM penetration and stroma invasion may be due to the proteolytic capability of the human embryo. It is suggested that collagenase and the urokinase-like plasminogen activator are responsible for this activity. To clarify the molecular mechanisms involved in human embryo implantation several models are suggested: culture of blastocysts, culture of endometrial cells, and endometrial explant co-culture. Human blastocysts cultured with whole perfused human uteri make it possible to recognize some aspects of the entire implantation process and give us the possibility of improving the benefits provided by new technologies in reproductive medicine and reducing embryonic loss at an early stage.

Endometrium↗
PubMed1991

Tissue factors influencing growth and maintenance of endometriosis.

The unpredictable response of endometriosis to steroids and its recurrence after therapy, led us to hypothesize a possible further control of this pathology by factors other than steroids. The presence of estrogen, progesterone and epidermal growth factor receptors (ER, PR, EGFr) was evaluated using immunohistochemistry before and after therapy with Danazol or a gonadotropin-releasing hormone analogue (GnRHa), Buserelin. EGFr, ER and PR were present in 100% of endometrial specimens, and in 71%, 29% and 49% of endometriotic implants, respectively. Danazol and GnRHa reduced immunohistochemical staining for EGFr antisera in the endometrial and endometriotic specimens. About 21% of endometriosis were EGFr positive and ER negative, suggesting a potential role of epidermal growth factor in growth and maintenance of endometrial ectopia.

Adult↗
PubMed1991

Basement membrane in human endometrium: possible role of proteolytic enzymes in developing hyperplasia and carcinoma.

Basement membranes (BM) are elements of the extracellular matrix that are essential for growth and differentiation of tissues. Several collagenolytic enzymes of tumor cells are involved in degradation of the extracellular matrix; growth and inhibitor factors [e.g. Epidermal Growth Factor (EGF), Transforming Growth Factors alpha and beta (TGF-alpha, beta)] seem to be involved in the extracellular matrix formation and degradation. To establish a possible association between the presence of collagenase (C), urokinase-type plasminogen activator (uPA) and the neoplastic growth of the endometrium, 44 endometrial specimens (14 proliferative, 11 secretive, 7 adenomatous hyperplasia, 12 adenocarcinoma) were studied using immunohistochemistry with antisera for C, uPA, EGF receptors and TGF-alpha. Immunostaining for collagenase revealed a positive reaction in moderately differentiated adeno-carcinoma without staining the normal and hyperplastic endometrium. A progressive increase in uPA immunostaining was observed in proliferative and neoplastic endometrium. TGF-alpha and its receptor (EGFr) were stained in proliferative and more clearly in hyperplastic and carcinomatous endometrium. In conclusion, BM play an important role in proliferation and differentiation of human endometrium; their degradation influences estrogen transportation from blood to the stroma. Endometrial BM degradation is associated with the presence of collagenolytic enzymes and growth factors.

Adult↗
PubMed1991

The effect of progestin on factors influencing growth and invasion of endometrial carcinoma.

Progesterone (P) and progestins play an important role in the control of endometrial growth. We have investigated P and progestin effects on endometrial estrogen extraction, on basement membrane (BM) synthesis and on the presence of the epidermal growth factor receptor (EGFr) in normal and pathologic endometrium. E2 uptake, evaluated in human isolated perfused uteri is significantly decreased by P. BMs investigated using immunohistochemistry, with antisera to collagen IV and laminin, were found around stromal cells only in the luteal phase or during P or progestin administration. Glandular BM, discontinuous in hyperplastic and carcinomatous endometria, were restored to integrity only in typical hyperplasia after therapy with progestin. Endometrial EGFr is modified by P: revelation of this antigen is increased in proliferative phase and decreased in secretory phase. Similarly this molecule was present in hyperplastic and carcinomatous endometria. Only in benign hyperplasia did we observe no staining for the same antigen after progestinic therapy. These data suggest that P or progestins may also have an indirect influence through mechanisms such as estrogen uptake and tissue factor activity with important differences between normal and pathologic endometrium.

Adult↗
PubMed1991

Treatment of hirsutism by an association of oral cyproterone acetate and transdermal 17 beta-estradiol.

Twenty-four hirsute women were treated with an inversal sequential scheme of cyproterone acetate, 50 mg/d by oral route from the 1st to the 15th day of the menstrual cycle, along with 100 micrograms/24 h of 17 beta-estradiol transdermally administered from days 1 to 21, for nine cycles at weekly intervals. The acne and seborrhea as well as hirsutism showed a significant improvement in all subjects studied. The plasma testosterone and dehydroepiandrosterone sulfate decrease from 1.5 +/- 1.3 ng/mL and 6.9 +/- 1.3 micrograms/mL to 0.5 +/- 0.03 ng/mL and 2.7 +/- 1.7 micrograms/mL, respectively. Similar values were observed in subjects with idiopathic hirsutism during the treatment. The metabolic parameters, as well as the plasma levels of sex hormone-binding globulin, appeared unaffected by the therapy. Furthermore, the luteinizing hormone and follicle-stimulating hormone secretion was strongly inhibited from the first cycle of treatment. In conclusion, considering the good clinical results and the avoidance of any hepatic effect, this association should be taken into account in the treatment of hirsutism, especially in case of oral estrogen intolerance.

Administration, Cutaneous↗
PubMed1989

Rapid and specific RIA of serum estrone sulfate with selective solid phase extraction.

The methods commonly used to evaluate conjugated steroids require hydrolysis and chromatographic purification. To avoid these steps, a simple method involving selective solid phase extraction and RIA using a highly specific antiserum for estrone sulfate (E1S) has been evolved. A Bond-Elut C2 cartridge was used for solid phase extraction of estrone (E1) and E1S; recoveries were 80 and 90% respectively. The intra- and inter assay precision of the assay at 3 serum levels, were 6.5, 10.4 and 4.4 and 12.7, 13.9 and 7.4% respectively. Accuracy, tested by linearity and recovery tests, was acceptable. A good correlation exists between a conventional enzymatic method and the proposed method. The latter is less time consuming and more reliable, thus providing a rapid assay to evaluate E1 and E1S in the same serum sample.

Estrone↗
PubMed1989

[Hypothalamic phospholipid liposomes in the treatment of the climacteric syndrome].

Phospholipid liposomes have a dopaminergic effect on the human brain. Changes in prolactin and growth hormone secretion have been observed in humans given phospholipid liposomes. The authors have investigated the therapeutic efficacy of hypothalamic phospholipids in the menopausal syndrome. The study was an open trial on 37 outpatients treated with 1 and 2 ampoules i.m. of a preparation of phospholipids (in the form of unilamellar liposomes) for a period of six months. The therapeutic effects were assessed by means of the Hamilton rating scale, MMPI (Minnesota multiphasic inventory test), and a list of psychosomatic symptoms (LSP). In the patients no change in FSH, LH, PRL, or E2 secretion was observed, whereas the neurotic symptomatology appeared remarkably reduced.

Adult↗
PubMed1988

Basement membrane components in normal hyperplastic and neoplastic endometrium.

The major basement membrane (BM) components, laminin and type IV collagen, were studied by immunochemistry in normal, hyperplastic, and neoplastic endometrium. By immunoperoxidase technique, proliferative and secretive endometrium showed capillary and epithelial cell basement membranes with linear staining with antibodies to both laminin and type IV collagen. Immunostaining of laminin and type IV collagen showed that capillaries were surrounded by a continuous perivascular sheath of these matrices in specimens of adenomatous hyperplasia and in nearly all specimens of endometrial adenocarcinoma. Laminin and type IV collagen were found to accumulate around glandular epithelial cells of adenomatous hyperplastic endometrium, but in several specimens these linear surrounding formations were defective and discontinuous. In several areas of well-differentiated endometrial adenocarcinomas BM-like structures were found around glandular epithelial cells as shadows without staining for laminin and type IV collagen. These basement membrane components accumulate around stromal cells to encircle each cell with a gradual, progressive, and cyclic process depending on the phase of the menstrual cycle. Laminin and type IV collagen were clearly detected around stromal cells at days 20 to 22 of the menstrual cycle and more thickly at days 26 to 28. The accumulation of these matrices around stromal cells is a progesterone/progestin-related process. In the well-differentiated adenocarcinoma a mid-term treatment with progestin (Danatrol Maggioni-Winthrop, SPA, Milan, Italy) was found to be effective on laminin and type IV collagen accumulation around stromal cells.

Adenocarcinoma↗
PubMed1988

Biological and endocrine aspects of transdermal 17 beta-oestradiol administration in post-menopausal women.

The plasma protein distribution of oestradiol (E2) and oestrone (E1) during transdermal E2 administration (100 micrograms/24 hr) was studied in 12 post-menopausal women. The E2 and E1 levels observed were 43-83 pg/ml and 37-73 pg/ml, respectively. The levels of the free, albumin-bound and sex-hormone-binding globulin (SHBG) bound fractions were in the ranges 1.4-1.9%, 60-65% and 35-45%, respectively, in the case of E2, and 2.8-3.0%, 80-89% and 15-20%, respectively, in that of E1. The SHBG levels also remained unaltered. It was concluded that transdermal administration of E2 at the dosage employed produces a physiological plasma protein distribution of E2 and E1 and does not affect liver protein production.

Administration, Cutaneous↗
PubMed1988

Extraction of estrogens by human perfused uterus. Effects of membrane permeability and binding by serum proteins on differential influx into endometrium and myometrium.

The present study was undertaken to examine the extractions of estradiol, estrone, and estrone sulfate from the circulation of the human perfused uterus. The differential permeability of endometrial and myometrial vascular beds to estrogens was evaluated in uteri samples obtained during the proliferative and secretive phases of the menstrual cycle. The effects of binding by human serum proteins on estrogen influx into the endometrium and myometrium were also determined by the use of double-isotope, single-injection, timed tissue sampling techniques adapted to the extracorporeal perfusion of human uterus. Tritiated test estrogen was injected into the uterine artery as a mixture with 14C-butanol, a free diffusible reference substance. The influx of 14C-dextran (a membrane-impermeable compound) was used to test the aspecific influx from vasculature to extravascular space. Results show that in the human perfused uterus: (1) membrane permeability plays different roles in estrogen influxes between the endometrium and myometrium; (2) during the proliferative and secretive phase of the menstrual cycle the uterine microvessels are differently permeable to the free plus protein-bound estrogens; and (3) plasma proteins decrease the endometrial and myometrial uptakes of estrogens.

Blood Proteins↗
PubMed1988

Early human pregnancy in vitro utilizing an artificially perfused uterus.

The penetration of luminal epithelium in the uterine cavity represents the crucial event that triggers the failure of embryo implant, thus limiting the possibility of fertility control. The purpose of our study was to implant a human blastocyst, cultured in vitro, into a human uterus extracorporeally perfused with an oxygenated medium. For this purpose, human blastocysts, collected from patients who underwent IVF program because of irreparable tubal infertility, were injected under the luminal epithelium of human perfused uteri. Light and electron microscopy showed that human blastocyst can successfully undergo the stage of implantation and trophoblastic invasion in 52 hours of extracorporeal perfusion.

Blastocyst↗
PubMed1988

Increased extraction of estrogens in human endometrial hyperplasia and carcinoma.

The present study was undertaken to assess in vitro the endometrial extraction of natural estrogens. Normal, hyperplastic, and neoplastic endometria were studied. This was accomplished by the use of double isotope, single-injection techniques performed during the extracorporeal perfusion of human isolated uterus. The differential permeability of vascular beds in normal and neoplastic endometrium to estrogens was evaluated. The effects of binding by human serum proteins on estrogen influx into the endometrium were also determined. When protein-free Ringer's solution was used as an injection vehicle, both normal and abnormal endometrium permitted free diffusion of estradiol (E2), estrone (E1), and estrone sulfate (E1S). In contrast, the endometrial extraction of these estrogens from human female serum was significantly lower than that obtained with Ringer's solution. The extraction of E2, E1, and E1S from human serum was significantly higher in hyperplastic and carcinomatous endometria than in normal proliferative endometria. We conclude that 1) membrane permeability to estrogenic influxes differs between normal and abnormal endometria and 2) plasma proteins decrease the endometrial uptake of estrogens.

Adenocarcinoma↗
PubMed1987

Comparative metabolism of oestrone sulphate after oral and intravenous administration in post-menopausal women.

Oestrone sulphate (E1S) is currently used in hormone replacement therapy in post-menopausal women. While isotope studies have demonstrated that E1S is metabolised in a similar way after administration by either the oral or intravenous route, pharmacokinetic studies point to its efficient extraction and metabolism by the liver. E1S was accordingly administered orally and intravenously at pharmacological dosages in a group of post-menopausal women and its conversion to oestrone (E1) and oestradiol (E2) was determined. We were able to demonstrate that E1S may cross the splanchnic area unaltered, since its conversion to E1 and E2 was similar after administration by each of the routes investigated.

Administration, Oral↗
PubMed1987

A 48-hour preservation of an isolated human uterus: endometrial responses to sex steroids.

Human uteri were perfused with Krebs-Ringer bicarbonate-glucose buffer with and without estrogens and progesterone for a period of up to 48 hours to preserve a viable organ, which was responsive to hormones. Flow rates of 12 to 35 ml/minute per artery were fully distributed into the organ, with pressure values ranging from 80 to 120 mm Hg. Arteriovenous gradients of oxygen and carbon dioxide tensions as well as the levels of lactate, lactic dehydrogenase, and creatine kinase released in the perfusate, indicators of tissue ischemia or cell necrosis, showed a good preservation of the organ for up to 48 hours. The light- and electron-microscopic examinations of endometrial and myometrial tissues taken before and during perfusion confirmed this result. The extracorporeal perfusion of uteri with buffer containing estrogens plus progesterone exhibited secretive modifications of the proliferative endometrium, thus suggesting the viability of the organ and its responsiveness to sex steroids.

Adult↗
PubMed1986

Reduced conversion of dehydroepiandrosterone into estrogens in premenarchal girls.

The purpose of this study was to evaluate the increases in plasma levels of E1, E1S and E2 during constant infusion of dehydroepiandrosterone (D) in premenarchal girls (PG) and in normal menstruating women (AW). Unlabelled D was infused for 48 h in 10 premenarchal girls and in 10 normal menstruating women. Plasma levels of D, estrone (E1), estrone sulfate (E1S) and estradiol (E2) were measured before and during 48 h infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of E1, E1S and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of D were found significantly lower in premenarchal girls than in normal menstruating women. MCRD was found significantly higher in premenarchal girls than in normal menstruating women (2565 +/- 467 L/day versus 1317 +/- 242 L/day, p less than 0.01). Administration of D increased the plasma levels of E1 and E1S in the group of normal menstruating women but not in the premenarchal girls. Considering all subjects studied, the increases in plasma levels of E1 and E1S during the infusion of D were significantly correlated with body weight (p less than 0.01 and p less than 0.001, respectively). From these results, we conclude that in premenarchal+ girls there is: a reduced peripheral contribution of D to E1 and E1S, and/or a higher MCRE1 and MCRE1S than in normal menstruating women.

Adult↗
PubMed1986

Extracorporeal perfusion of the human uterus.

Uterine specimens specially prepared for extracorporeal perfusions (arterial and venous stumps available for catheterization) were perfused with oxygenated Krebs-Ringer bicarbonate-glucose buffer for periods of up to 12 hours to investigate the feasibility of obtaining constant flow, stability of biochemical parameters, and adequate distribution of the perfusion fluid. Flow rates of 10 to 30 ml/min per artery could be maintained at pressures ranging from 80 to 120 mm Hg. Arteriovenous gradients of oxygen and carbon dioxide tensions were relatively stable and levels of lactate, lactic dehydrogenase, and creatine kinase released to the medium, indicators of tissue hypoxia or cell lysis, declined after 30 minutes of perfusion, remaining low and stable up to 12 hours. Distribution of methylene blue and radiopaque solutes was practically complete throughout the fundus and upper two thirds of the uterus. A mixture of tritium-labeled estrone sulfate and carbon 14-labeled estrone was injected as a bolus through an arterial catheter during perfusion. Perfusate samples were collected for 30 minutes, and tissue samples were taken at the end of this period. Tritium/carbon 14 ratios in myometrium and perfusate indicated preferential uptake of the unconjugated estrogen. Tritium/carbon 14 ratios were higher in endometrium than in myometrium, which suggests an enhanced permeability of endometrial capillaries to estrone sulfate.

Catheterization↗