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Biomedical subjects

A Segre

Publications and source records attributed to A Segre.

At least 37 records · Page 2Linked to original sources

Human remains of Homo sapiens neanderthalensis from the pleistocene deposit of Santa [corrected] Croce Cave, Bisceglie (Apulia), Italy.

The paper deals with a Neanderthal human femur, recovered during excavations in Santa [corrected] Croce Cave, Bisceglie. The cave also yielded Mousterian lithic industry and fauna indicating a paleoclimate condition with dry-warm tendency and savannah landscape. Metrical, morphometrical, and morphological analysis, and the comparison with Neanderthal specimens show that the femur belonged to an adult individual. It particularly shows great affinities with the analogous specimens from La Ferrassie 1 and 2, Spy 2, and Fond de Forêt, which are similar in size and, above all, show similar archaic morphological traits.

Femur↗

Proopiomelanocortin-related peptides and methionine enkephalin in human follicular fluid: changes during the menstrual cycle.

Several studies indicate the presence of different pituitary hormones or neuropeptides in ovarian follicular fluid from various species. Recently our group showed that the ovarian follicular fluid of health women contains two of the endogenous opioid peptides, beta-endorphin and methionine enkephalin, in concentrations that are tenfold to twentyfold higher than in circulating plasma. The presence of immunoreactive beta-lipotropin was also shown. The aim of the present study was to evaluate whether adrenocorticotropic hormone, which in pituitary cells is synthesized from proopiomelanocortin such as beta-endorphin and beta-lipotropin, is also present in follicular fluid and the possible changes of proopiomelanocortin-related peptides during the menstrual cycle. Concentrations of beta-endorphin, methionine enkephalin, adrenocorticotropic hormone, and beta-lipotropin were measured in 60 healthy menstruating women at different periods of the menstrual cycle (20 during the follicular, 22 in the preovulatory days, and 18 during the luteal phase). Thirteen women participated in an in vitro fertilization program and thus received clomiphene citrate (100 mg/day from the fifth to the ninth day) plus 5000 IU human chorionic gonadotropin before starting the program. All samples were collected at laparoscopy under general anesthesia. In another eight patients fluid was collected from follicular cysts. Peptides were extracted on octadodecasilyl silica columns with 80% methanol in 0.5 mol/L acetic acid. The identity of follicular fluid beta-endorphin, methionine enkephalin, adrenocorticotropic hormone, and beta-lipotropin and standard peptides was demonstrated with high-pressure liquid chromatography. Peptide concentrations were measured in extracts by radioimmunoassays either directly by (methionine enkephalin and adrenocorticotropic hormone) or after (beta-endorphin and beta-lipotropin) gel filtration on Sephadex G-75. The concentrations of methionine enkephalin, adrenocorticotropic hormone, and beta-lipotropin were similar in the different periods of the cycle. Conversely, beta-endorphin concentrations were significantly higher in preovulatory days than in the other periods; no differences were evident between spontaneous and stimulated cycles. These results indicate that proopiomelanocortin-related peptides are present in the follicular fluid and that beta-endorphin concentrations change during the menstrual cycle, with the highest values occurring in the preovulatory follicle.

Adrenocorticotropic Hormone↗

Prostaglandin-induced mid-pregnancy abortion increases plasma and amniotic fluid levels of beta-lipotropin and beta-endorphin.

The continuous and progressive rise of beta-endorphin (B-EP), beta-lipotropin (B-LPH) and cortisol plasma levels during labor in term-pregnant women represents one of the most relevant maternal hormonal responses to the stress of parturition. The aim of the present study was to evaluate the changes of these hormones, both in plasma and amniotic fluid (except cortisol), in a group of pregnant women undergoing prostaglandin-induced therapeutic abortion at the 2nd trimester of pregnancy. B-EP, B-LPH and cortisol were measured by radioimmunoassay. Both plasma and amniotic fluid samples were purified through extraction and chromatography (Sephadex G-75 columns). The prostaglandin derivative, 16-phenoxy-PGE2-methylsulfonylamide (sulprostone, Schering, Berlin) (500 micrograms, i.m., every 4 h), caused a rapid and significant rise of plasma B-EP, B-LPH and cortisol levels in all subjects. The relative increase of the 3 hormones was less relevant after the 2nd and absent after the 3rd injection of PGE2. The amniotic fluid concentrations of B-EP and B-LPH were also raised 2 h after the 1st injection. These data indicate that sulprostone-induced abortion activates both maternal and fetoplacental release of opioids independently of the trend of uterine contractions. The pattern of pro-opiomelanocortin-related labor differs from spontaneous labor and can probably be linked to a direct effect of the drug.

Abortifacient Agents↗

Met-enkephalin enhances follicle-stimulating hormone-dependent progesterone production from cultured granulosa cells.

beta-Endorphin (beta-EP) and methionine-enkephalin (Met-Enk) have been detected in human follicular fluid in concentrations several times higher than those in plasma. These data stimulated us to study the possible physiological role of ovarian opioids. We, therefore, determined the effects of both beta-EP and Met-Enk, alone or in combination with naloxone, on FSH-induced progesterone (P) secretion by cultured granulosa cells. Granulosa cells were collected from follicular fluid recovered at laparoscopy in seven superovulated women. The cells were preincubated with RPMI-1640 medium containing 20% fetal calf serum in 5% CO2 for 48 h, followed by the addition of 100 mU purified FSH and the various test substances for 48 more h. beta-EP (10 nM to 1 pM) had no effect on P secretion either alone or in combination with FSH and/or naloxone. Micro- to picomolar amounts of Met-Enk increased FSH-induced P secretion up to 186.9 +/- 35.1% (+/- SEM). Met-Enk had no affect in the absence of FSH, and its action was significantly blunted by the concomitant addition of 10(-5) M naloxone. These data provide evidence for a dose-dependent naloxone-reversible synergistic action of Met-Enk and FSH on P secretion by cultured granulosa cells. This finding supports the hypothesis of the existence of an ovarian opioid system.

Cells, Cultured↗

Beta-endorphin and met-enkephalin in peritoneal and ovarian follicular fluids of fertile and postmenopausal women.

Immunoreactive (IR) beta-endorphin (beta-EP) and met-enkephalin (MET-ENK) have been found in peritoneal fluid (PF) and ovarian follicular fluid (FF). Gel chromatography also revealed the presence of coeluting IR beta-lipotropin and gamma-lipotropin. IR beta-EP and IR MET-ENK levels in healthy menstruating women were from 10 to 40 times higher than those present in circulating plasma, which indicated a possible local production. The highest concentrations of IR beta-EP in FF were found in the largest follicles, whereas in the PF they correlated with the luteal period of the menstrual cycle and with progesterone concentrations. No relevant changes in IR MET-ENK were detected in the FF or in the PF in relation to the phase of the menstrual cycle. In postmenopausal women, the concentrations of the two IR opioid peptides were undetectable in both fluids.

Adult↗

Chemical modifications of the aliphatic bridge of ansamycins. 3. Synthesis and activity of 21-epi-rifamycin S.

Rifamycins inhibit bacterial DNA-dependent RNA polymerase through the formation of non-covalent bonds by the oxygenated groups at C(1), C(8), C(21), and C(23). These must be unhindered and underivatized, with the antibiotic in a proper overall molecular conformation. The present study shows that contrary to previous conclusions the availability of the hydroxyl group at C(21) is not as important as that of the other three groups. In support of this is the observation that 21-epi-rifamycin S is partially active, both on the isolated DNA-dependent RNA polymerase and on some Gram-positive bacterial strains.

Anti-Bacterial Agents↗

A study of structure-activity relationships in 4-deoxypyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV derivatives by electron spectroscopy for chemical analysis and 1H NMR.

A new class of rifamycins, 4-deoxypyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV derivatives, has been synthesized. They are potent antibacterial agents and are not absorbed at the gastrointestinal level and can therefore probably be used as antibacterial intestinal disinfectants. From the present X-ray, electron spectroscopy for chemical analysis, and 1H NMR study, it appears that this peculiar pharmacokinetic behavior is mainly to be attributed to the fact that the pyridoimidazo system exists in these compounds in a mesomeric betaine form, bearing one positively and one negatively charged nitrogen. If it is assumed that rifamycins are generally absorbed by passive diffusion, the presence of the two oppositely charged nitrogens, together with the presence of the phenolic hydroxyls, means that these molecules are ionized at all pH values encountered along the gastrointestinal tract, which thus prevents their absorption. These molecules also display a strong tendency to self-associate both in solution and in the solid state, and the increase in molecular size may also play a role in preventing their absorption.

Magnetic Resonance Spectroscopy↗

The synthesis of 4-deoxypyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV derivatives.

Two series of new semisynthetic rifamycin SV derivatives have been prepared. One of them bears a quaternary ammonium salt at C3 (1-5), and the other a pyridoimidazo system condensed at C3 and C4 (6-11). While compounds 1-5 had poor antibacterial activity in vitro, compounds 6-11 were found to be highly active in vitro but poorly absorbed in vivo. They could thus have potential as agents in the therapy of intestinal infections. The synthesis and the 1H NMR structure determination of these new compounds are reported.

Magnetic Resonance Spectroscopy↗

X-ray crystal structure of 4-deoxy-3'-bromopyrido[1',2'-1,2]imidazo[5,4-c]rifamycin S.

This paper reports the determination of the X-ray molecular structure of 4-deoxy-3'-bromopyrido[1',2'-1,2]imidazo[5,4-c]rifamycin S, carried out in order to unequivocally define the general structure of a new series of rifamycin SV derivatives, which are potent antibacterial agents, and are not absorbed at the gastroenteric level. They have been prepared by Alfa Farmaceutici, Bologna, by condensing 2-aminopyridine derivatives to 3-bromorifamycin S. The solid state X-ray study has confirmed the structure proposed on the basis of 1H NMR studies in solution. It has also shown that the newly formed pyridoimidazo system is in a mesomeric betaine form, the pyrido nitrogen being positively charged and the imidazo nitrogen being negatively charged. This feature is believed responsible for the pharmacokinetic behavior of these new drugs, one of which, denoted either as rifamycin L 105 or rifaximin, is actually under clinical trial as a topical intestinal disinfectant.

Magnetic Resonance Spectroscopy↗

1H n.m.r. of the DNA-dependent RNA polymerase from Escherichia coli.

The (1)H n.m.r. study of the DNA-dependent RNA polymerase from Escherichia coli has revealed that the holoenzyme (betabeta'alpha(2)sigma) displays two mobile regions: one, observable also in the core enzyme (betabeta'alpha(2)), is characterized by basic amino acids and its appearance and form depend on ionic strength; the other, specific to the holoenzyme, is characterized by threonine residues and its appearance does not depend on ionic strength.

Apoenzymes↗

Vaginal agenesis (mayer - rokitansky - küster - hauser syndrome): recent etiopathogenetical and anatomical views.

Congenital absence of uterus and vagina is a picture known as Mayer-Rokitansky-Küster-Hauser syndrome. Six cases are reported and particular attention is devoted to the anatomical pictures, which can be found in typical or atypical form. Discussion on the etiopathogenetical problems, supporting Hauser's hypothesis of an inhibition of the müllerian ducts development by MIF production, allows to consider it as the slightest form of female pseudoermaphroditism. Moreover the terms used to delineate this condition, like "müllerian aplasia", "müllerian ducts aplasia", "müllerian ducts agenesis" and "uterovaginal agenesis" may be misleading and the term of "müllerian dysgenesis syndrome" is proposed.

Fallopian Tubes↗

Structure-activity relationships in the ansamycins. Molecular structure and activity of 3-carbomethoxy rifamycin S.

The X-ray and NMR structural study of 3-carbomethoxy rifamycin S5 was undertaken in order to determine whether its low antimicrobial activity was related to a conformation of the molecule which was unfavorable for interaction with bacterial DNA-dependent RNA polymerase. However, the molecule assumes a conformation similar to that of the active rifamycins. Indeed the compound was found to be active on the isolated enzyme, so that its low activity on whole bacteria has to be attributed to factors affecting its penetration through the bacterial cell wall.

Anti-Bacterial Agents↗

Camptomelic syndrome. A rare type of congenital dwarfism associated with skeletal and other abnormalities.

Three cases of the rare camptomelic syndrome are presented observed within fourteen months at the Mangiagalli University Clinic, Milan. The radiographic appearances and clinical characteristics are described, and compared with the thirty five cases in the literature. The differential diagnosis is discussed and the possibility of diagnosing this malformation prenatally is suggested.

Abnormalities, Multiple↗