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Biomedical subjects

M Moro

Publications and source records attributed to M Moro.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chondrocyte-biocompatibility of DegraPol-foam: in vitro evaluations.

Histological and biochemical investigations were carried out in order to evaluate the chondrocyte compatibility of a recently developed biodegradable polyesterurethane-foam (DegraPol-foam). Therefore, cell adhesion, cell growth, and the preservation of chondrocyte phenotype was measured in rat xyphoid chondrocytes seeded on DegraPol-foam. Chondrocytes, isolated from xyphoids of adult male rats, exhibited relatively high cell adhesion on DegraPol-foam (about 60% of that found on TCPS). Scanning electron microscopy (SEM) showed that chondrocytes grew on the surface and into the open cell pores of the foam. Morphologically, cells found on the surface of the foam exhibited a flat cell appearance and built a confluent cell multilayer. In contrast, the interior of the foam cells showed rounded morphology in cell aggregates and cell islets. In addition, chondrocytes proliferated on the DegraPol-foam (doubling-time of about 12.5 days) and preserved their phenotype for up to 14 days. Compared to freshly isolated chondrocytes, cells seeded on the foam produced high concentrations of collagen type II for up to 2 weeks: the ratio of type II/I collagen was 1.2-1.4 fold higher than the ratio found in freshly isolated cells. No significant difference was observed in chondroitin sulfate levels produced by freshly isolated cells and cells cultured on DegraPol-foam for up to 14 days. To sum up, our results indicate that DegraPol-foam is a compatible substrate for chondrocytes.

3T3 Cells↗
PubMed1998

Growing patterns of cavernous angioma in the fourth ventricle. Case report.

Cavernous malformations are vascular lesions that occur in all parts of the central nervous system but most commonly in the cerebral hemispheres; unusually they may be found along the midline (basal ganglia, pineal region or brain stem), into the ventricle possibly encroaching upon the fourth and third ventricle. We report a case of midline cavernomas of the IV ventricle, that grew to large size in-time, demonstrating the capacity for rapid expansion.

Aged↗
PubMed1998

[Diagnostic biopsy with paranasal sinus endoscopy].

Rigid endoscopy allows clear visualization of the nasal fossa and paranasal sinuses and permits biopsies to be obtained under direct vision from relatively inaccessible sites. In most cases the biopsy can be made using local anesthesia, but selected patients require general anesthesia. We report the results of 31 patients who underwent biopsy with rigid nasal endoscopy under general anesthesia. Of the 31 patients, a diagnostic biopsy was achieved in 30 (96.7%). We define a diagnostic biopsy as one which yielded a histopathological diagnosis that did not change as a result of clinical findings, examinations or further biopsies performed during follow-up. We recommend the use of endoscopic nasal biopsy of nasal and paranasal neoplasms as an easy, safe and reliable technique.

Adenocarcinoma↗
PubMed1997

Rapid purification and properties of human glycodelin (endometrial alpha2-globulin).

The method presented can easily produce milligram amounts of glycodelin from pregnancy endometrium, with a 19% yield. It involves anion-exchange chromatography, gel permeation and chromatofocusing; it results in one stainable band at Mr 28,000 after sodium dodecyl sulphate-polyacrylamide electrophoresis, as well as after immunoblot analysis, performed using an affinity-purified IgG fraction from an antiserum against glycodelin. In spite of this, the corresponding gel isoelectric focusing pattern gives four stainable bands with pI values between 4.55 and 5.2. Western immunoblot analysis of tissue extracts indicates the presence of glycodelin epitopes associated with materials heavier than the native protein. Circular dichroism spectra of the highly purified protein in water solutions indicate a large amount of beta-sheet conformation, whereas those obtained with different proportions of 2-propanol in water, show an increased proportion of alpha-helix conformation.

Anions↗
PubMed1997

Tumor cell targeting with antibody-avidin complexes and biotinylated tumor necrosis factor alpha.

Tumor pretargeting with biotinylated antibodies and avidin, followed by a delayed delivery of radioactive-labeled biotin, is currently used for in vivo diagnosis and therapy in cancer patients. Herein, we describe the use of a three-step antibody/avidin targeting approach to increase the local concentration and the persistence of biotinylated human tumor necrosis factor alpha (bio-TNF) on a mouse tumor. Mouse RMA lymphoma cells were transfected with the Thy 1.1 allele (RMA-Thy 1.1) to generate a unique tumor-associated antigen. In vitro pretargeting of RMA-Thy 1.1 cells with the biotinylated anti-Thy 1.1 monoclonal antibody 19E12 (bio-19E12) and NeutrAvidin increased the amount of bio-TNF that bound to the cell (10-20 times in comparison with non-pretargeted cells), as well as its half-life on the surface (>30 times). Furthermore, cell pretargeting reduced by more than 2 orders of magnitude the LD50 of bio-TNF in a cytolytic assay with actinomycin D. Finally, RMA-Thy 1.1 cells, pretreated in vitro with bio-TNF according to the three-step procedure and injected into syngeneic C57/BL6 mice, were less tumorigenic than controls. These results indicate that the three-step targeting approach markedly increases the amount and the persistence of bio-TNF on the cell surface and that cell-bound bio-TNF can trigger cytolytic effects in vitro and antitumor effects in vivo. Tumor pretargeting with biotinylated antibodies and avidin could be a novel strategy for increasing the therapeutic index of TNF.

Animals↗
PubMed1997

Changes in the structure of the agonistic behavior of mice produced by D-amphetamine.

The effects of three acute doses of D-amphetamine (0.25, 1.5 and 3 mg/kg) were studied in a model of isolation-induced aggression in male mice. An ethopharmacological analysis of the encounters was carried out, which studied the frequency, total and mean duration of different behavioral categories, including the temporal distribution of attacks and the duration of inter-attack intervals. The results show a reduction in the total and mean duration of the Attack category and an increase in motor activity manifested by longer durations, both total and mean, of Non Social Exploration and shorter Immobility. The temporal analysis of Attack revealed an increase in the number of very short (< 15 s) inter-attack intervals and a temporal redistribution of the attacks to later in the course of the social encounters. These results confirm for a complex behavior such as aggression, that D-amphetamine, even at low doses, favors a fragmentation and repetition of motor routines with a simultaneous reduction in the influence of environmental cues on the control of behavior.

Agonistic Behavior↗
PubMed1997

Glyceraldehyde 3-phosphate-induced DNA or protein modifications severely inhibit the protein/DNA interaction.

In this study, the effect of the reducing sugar glyceraldehyde 3-phosphate on protein/DNA interaction has been investigated. Treatment with glyceraldehyde 3-phosphate of oligonucleotides recognized by various transcription factors severely inhibits protein binding. The inhibitory effect is time and dose-dependent. Treatment with glyceraldehyde 3-phosphate of the homeodomain protein TTF-1 HD has also an inhibitory effect on the interaction with DNA, again in a time and dose-dependent manner. These "in vitro" effects could have "in vivo" counterparts and therefore contribute to molecular alterations observed either when intracellular protein are exposed to high doses of reducing sugars (i.e. in diabetes) or after a long time exposure (i.e. in Gzero-arrested cells during aging).

Animals↗
PubMed1997

Effects of repeated administration of d-amphetamine on agonistic behaviour of isolated male mice.

Insufficient research has been carried out on the effects of repeated treatments with psychostimulants on agonistic behaviour. These effects were studied in mice using different schedules of administration and employing a low dose of amphetamine (1.5 mg/kg) which did not produce significant motor disruptions. After two injections, with a 5-day interval between them, antiaggressive effects (decreases in attack and increases in avoidance/flight behaviour) were found, which were similar to those observed after acute administration, in addition to an increase in defence. With a higher number of injections but with shorter intervals (daily treatment) the effects diminished and even disappeared. Tolerance to the antiaggressive as well as to motor effects (digging and non-social exploration) was found after 7 daily injections. The appearance of avoidance, defensive and flight behaviours in this model supports the inclusion of agonistic behaviour in rodent models of psychoses and highlights the importance of analysing the effects of different characteristics of the repeated treatment.

Animals↗
PubMed1997

Endothelium-derived nitric oxide-dependent response to hypoxia in piglet intrapulmonary arteries.

The purpose of this study was to determine the involvement of eicosanoids and nitric oxide (NO) in the response to hypoxia in isolated intrapulmonary (third branch) arteries from 10- to 17-day-old piglets. We also compared the response to hypoxia in pulmonary arteries to pulmonary veins, mesenteric arteries and coronary arteries. Hypoxia was generated in vascular rings (under resting force or precontracted with 30 mM KCl) by switching the gas aerating the organ chambers from one composed of 21% O2-5% CO2-balance N2 (pO2 145 +/- 1.27 mm Hg) to a mixture of 5% CO2-balance N2 (pO2 33.87 +/- 0.24 mm Hg). In precontracted rings hypoxia produced a transient vasoconstriction (26 +/- 8% of the precontraction value) reaching a peak in 3-4 min, followed by a relaxation. A similar pattern of response was observed in pulmonary veins, coronary arteries and mesenteric arteries. The contractile phase was not present in endothelium-denuded arteries or after incubation with the NO synthase inhibitor L-NAME (10(-4) M) or the guanylate cyclase inhibitor methylene blue (10(-5) M). No changes in the hypoxia-induced vasoconstriction were observed after preincubation with the NO precursor L-arginine (10(-5) M), the lipoxygenase inhibitor meclofenamate (10(-5) M), the cyclooxygenase inhibitor AA 861 (10(-5) M), or the cytochrome P450 oxidase inhibitor SKF 525A (10(-5) M). These findings demonstrate that the contractile response to hypoxia in the isolated intrapulmonary porcine artery is caused by the loss of the inhibitory effects of endothelium-derived NO on the vascular tone. Eicosanoids do not appear to be involved in this response. Since the response to hypoxia in isolated rings is not specific to pulmonary vessels, any correlation between this response and hypoxic pulmonary vasoconstriction should be avoided.

Animals↗
PubMed1997

[Intraperitoneal single-dose toxicity studies of active metabolite, optical isomers, hydrolysis products and bi-product of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence, in mice].

NS-21, (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, is a new drug for the treatment of urinary frequency and incontinence. To evaluate acute toxicities of its related compounds including the optical isomers of NS-21 ((S)NS-21 and (R)NS-21), the active metabolite of NS-21 ((R/S)RCC-36), the optical isomers of (R/S)RCC-36 ((S)RCC-36 and (R)RCC-36), the hydrolysis products of NS-21 (RCC-32 and RCC-38) and the bi-product of NS-21 (RCC-66), single-dose intraperitoneal toxicity studies were conducted in ddY mice. The LD50 values of these compounds in male and female mice were as follows: 199 and 184 mg/kg for (S)NS-21, 261 and 240 mg/kg for (R)NS-21, 74 and 100-150 mg/kg for (R/S)RCC-36, 93 mg/kg for (S)RCC-36 in both sexes, 83 and 104 mg/kg for (R)RCC-36, higher than 510 mg/kg for RCC-32 in both sexes, 340-510 mg/kg for RCC-38 in both sexes, and 1000-2000 mg/kg for RCC-66 in both sexes, respectively. The clinical signs included decreased spontaneous locomotor activity, prone or lateral position, ataxic gait, clonic convulsion, hypopnea, hypothermia, pale skin, mydriasis, abdominal distention and unkempt fur for (S)NS-21, (R)NS-21, (R/S)RCC-36, (S)RCC-36 and (R)RCC-36, decreased spontaneous locomotor activity, prone position, ataxic gait, clonic convulsion, tail elevation and hypopnea for RCC-32 and RCC-38, and decreased spontaneous locomotor activity and unkempt fur for RCC-66. Body weight was decreased or its gain was suppressed for every compound examined. Pathological examination of the dead mice showed atrophy of the thymus and spleen, intestinal distention with the retention of dark red contents, white spots or white materials in the abdominal fatty tissue for (S)NS-21, (R)NS-21, (R/S)RCC-36, (S)RCC-36, (R)RCC-36 and RCC-66, but no treatment related change for RCC-32 and RCC-38. Adhesion between the abdominal organs was observed in survivors treated with (S)NS-21, (R)NS-21, (S)RCC-36, (R)RCC-36, RCC-32 and RCC-66.

Animals↗
PubMed1997

Dopamine infusion enhances the adrenocorticotropic hormone and cortisol response to metoclopramide in hyperprolactinemic patients but not in normal subjects.

Based on the facts that prolactin and adrenocorticotropic hormone (ACTH) each seem to influence the secretion of the other, that dopamine is the established inhibitory factor for prolactin secretion and negatively modulates ACTH release, and finally that alterations of the central dopaminergic tone have been postulated in tumorous hyperprolactinemia, we studied the effects of pharmacological manipulations of the dopaminergic system on ACTH and cortisol secretion in patients bearing a prolactinoma and in normal subjects. Twenty-seven patients with a prolactin-secreting pituitary tumor and 12 healthy controls were submitted to three tests: (a) 4-h saline infusion; (b) 10 mg metoclopramide (MTC) as an intravenous bolus after a 2-h saline infusion; and (c) 4-h dopamine infusion at the dose of 0.01 microgram/kg/min with a 10-mg intravenous bolus of MTC given at the second hour of dopamine infusion. Administration of MTC, compared to saline, caused a moderate (not significant) plasma ACTH increase, and a significant cortisol increase (p < 0.05), both in hyperprolactinemic and normal subjects, without statistically significant differences between the two group. When MTC was administered during dopamine infusion, the ACTH and cortisol elevation was significantly potentiated in prolactinoma patients while it was similar in magnitude to that recorded after MTC alone in control subjects. These findings support the concept of an inhibitory role exerted by dopamine and are compatible with a stimulatory influence exerted by prolactin on corticotropin-releasing hormone and ACTH secretion, and also favor the view of a reduced central dopaminergic tone in patients with tumorous hyperprolactinemia.

Adrenocorticotropic Hormone↗
PubMed1997

A functional screen for regulators of the c-Abl protein tyrosine kinase.

c-Abl protein tyrosine kinase activity is tightly regulated in vertebrate cells. Several mutations can activate Abl and convert it into an oncogene. In man, chromosomal translocations result in fusion proteins associated with chronic myelogenous leukemias and some acute lymphocytic leukemias. In viral forms of abl, gag sequences are fused to Abl portions resulting in a deletion of N-terminal sequences. To study c-Abl activity in a cellular environment likely to lack specific regulators, we have expressed human c-Abl in Schizosaccharomyces pombe in an inducible fashion. c-Abl causes growth arrest followed by death of the cells. Mutations in the SH2 domain or in the autophosphorylation site dramatically reduce the ability of Abl to confer the growth arrest phenotype and to phosphorylate endogenous proteins, suggesting a fundamental role of these structures in the activity of the enzyme. An SH3 domain deletion mutant of Abl is as active as c-Abl in yeast indicating that there is no intrinsic regulation of c-Abl occurring via the SH3 domain and suggesting that the inhibitory effect of the SH3 domain observed in cells of vertebrate origin is mediated by a factor that is absent in fission yeast. We have used this assay to functionally screen a human cDNA library for molecules able to counteract the lethal effect of c-Abl expression. We are currently in the process of characterising the isolated clones. We hope to identify among them the molecule(s) responsible for regulating c-Abl activity in human cells.

Animals↗
PubMed1996

Pulmonary versus systemic effects of vasodilator drugs: an in vitro study in isolated intrapulmonary and mesenteric arteries of neonatal piglets.

The ability of several vasodilators to inhibit the responses to noradrenaline and U46619 (a thromboxane A2 analog) in isolated pulmonary and mesenteric arteries of neonatal piglets was compared. In pulmonary arteries, acetylcholine produced endothelium-dependent relaxations (pIC50 = about 6.8) while, in mesenteric arteries, a relaxant (< or = 10(-7) M) or a contractile response (> or = 10(-6) M) was observed. Sodium nitroprusside produced relaxant effects in pulmonary and mesenteric arteries contracted by noradrenaline (pIC50 = 6.6 and 6.0, respectively) and U46619 (pIC50 = 5.4 and 6.7, respectively). ATP induced an endothelium-independent relaxation in pulmonary arteries (pIC50 = about 4) but in mesenteric arteries it produced weak relaxant effects. In resting mesenteric arteries, ATP induced a concentration-dependent contraction which was not observed in pulmonary arteries. Prostaglandin E1 induced a contractile effect whereas, at higher concentrations, a relaxant response was observed. The alpha-adrenoceptor antagonist tolazoline had no effect on arteries contracted by U46619 but relaxed arteries contracted by noradrenaline being slightly more potent in mesenteric than in pulmonary arteries (pIC50 = 5.1 and 4.8, respectively). Nifedipine (> 10(-7) M) relaxed both arteries, mesenteric being more sensitive than pulmonary arteries and noradrenaline more sensitive than U46619-induced contractions. In conclusion, differences in the relaxant effects for all vasodilators were found depending on the artery, the vasoconstrictor used or both. However, ATP was the only drug which, regardless of the concentration or vasoconstrictor used, produced greater relaxant effects in pulmonary than in mesenteric arteries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗