Biomedical subjects

M Ceruti

Publications and source records attributed to M Ceruti.

At least 37 records · Page 2Linked to original sources

PubMed1994

[Bacterial vaginosis. Prevention of recurrence].

Bacterial vaginosis (BV) is the main cause of vaginitis. The condition is characterised by an abundant and odorous vaginal loss, but more than half the patients with demonstrable signs of BV do not report symptoms at all. Gardnerella vaginalis (Gv) is often associated with BV, but it is not the sole factor responsible, as is shown by the fact that it can be isolated in the vagina of women withBV. In 1992 and 1993, 2630 patients, 1460 of them gynaecological and 1170 obstetric, were admitted to the Obstetrics and Gynaecology Clinic of Parma University. Amsel criteria were adopted for diagnosing BV. Cases of BV were treated with 5 mg/die 2% clindamycin vaginal cream for 7 days. In the event of recurrences, 250 mg tablets of metronidazol were added: 8 tablets in 4 administrations in a single day, treatment also being extended to the partner. Patients admitted in 1993 received a protocol of hygienic and behavioural standards, stress being laid on prophylaxisa measures even after the end of therapy. BV proved to be present in 12.3% of cases, of whom only half were symptomatic. The situation was practically stationary if the 2 years are considered separately. Recurrences of symptomatic bacterial vaginosis were 15% in the absence of protocol application and 8.3% after the protocol. Recurrences were less frequent in the asymptomatic forms. Compared to the total number od cases of BV, recurrences were significantly low (12.1% p < 0.001).

Female↗

PubMed1994

Fetal distress: role of cardiotocography.

The FHR monitoring in 320 patients with fetal distress were randomly analyzed and revised over 16 years. The aim of our study, in so long a period, was to evaluate the role of cardiotocography in order to preserve the fetus from irreversible damage. The results show a progressive improvement of neonatal outcome, due to the development of the experience with this method, and to the improvement in interpretative criteria. However, cardiotocography showed its limits, and the moment has come to seek new integrative methods to associate cardiotocography with a continuous monitoring of the fetal status.

Adult↗

PubMed1994

Methods of contraception and rates of genital infections.

Bacterial vaginosis, trichomoniasis and candidiasis are the most common genital infection. The aim of this study was to evaluate the various methods of contraception with regard to the prevalence of bacterial vaginosis and vulvo-vaginitis over a period of four years. We also evaluated in the same period the rates of trichomoniasis, candidiasis, bacterial vaginosis and vulvo-vaginitis between users and non users of contraceptional methods and the relationship between ages of patients and types of contraceptives. Finally we considered the change of contraceptive use with regard to age among two different periods. The IUD users showed a significant increase of B.V., T.v. and other bacteria and a decrease of the negatives compared to OC users. Barrier contraceptive users had a reduction (0.01 > p > 0.001) of B.V. and an increase (p < 0.001) of the negatives compared to IUD users. OC users had a significant (p < 0.05) increase in candidiasis, B.V. together with a reduction of the negatives compared to non users group. IUD users had a significant (p < 0.001) increase of B.V. and vulvo-vaginitis from other bacteria, and the reduction of the negatives. Teenagers use OC much more than adults, but less IUD (p < 0.001). The use of OC has increased and the use of IUD decreased among adults (p < 0.001). The barrier methods were seen to be statistically reduced.

Adult↗

PubMed1994

2,3,4,5-tetrahydroxy-5-(4-hydroxyphenyl)valeric acid: a new cleavable monofunctional reagent for monoclonal antibody labeling.

The synthesis and preliminary biological assays of a new monofunctional reagent to reversible derivatize monoclonal antibodies is described. This compound, comprising a 1,4-polyiol moiety, is cleavable by means of sodium periodate in mild conditions; moreover it also contains a phenolic residue suitable for 125I labelling and a carboxylic group for reaction with epsilon-lysyl amino group of antibodies. These features are suitable to study the monoclonal antibodies cell-internalization process and antigen expression on cell surface. The 125I labelled reagent has been coupled to the monoclonal antibody AR-3, an IgG1 directed toward the CAR-3 antigen widely expressed on human ovarian and colorectal adenocarcinomas. The cleavage capability is tested in different conditions both on reagent and on derivatized MAb. Cell labelling experiments are performed both on target and untarget cell lines.

Antibodies, Monoclonal↗

PubMed1993

Differential inhibition of fungal oxidosqualene cyclase by 6E and 6Z isomers of 2,3-epoxy-10-aza-10,11-dihydrosqualene.

Inhibitory properties of 6E (compound 1) and 6Z (compound 2) isomers of 2,3-epoxy-10-aza-10,11-dihydrosqualene against oxidosqualene-lanosterol cyclase were assayed on microsomes and whole cells of Saccharomyces cerevisiae and Candida albicans. Only the 6E isomer (compound 1), bearing a correct substrate-like configuration, strongly inhibited the enzyme both in microsomes and cell cultures. The difference between compounds 1 and 2 (which had an unfavorable geometry) was especially evident when measuring [14C]acetate incorporation into non-saponifiable lipids extracted from treated cells. While isomer Z was totally ineffective at up to 30 microM, in cells treated with 5 microM isomer E, labelled oxidosqualene, the level of which was negligible in the control, rose to over 60% of the non-saponifiable lipids.

Candida albicans↗

PubMed1993

Toxin-targeted design for anticancer therapy. I: Synthesis and biological evaluation of new thioimidate heterobifunctional reagents.

In an effort to obtain a more potent and specific immunotoxin for cancer therapy, we designed a series of heterobifunctional linkers characterized by a thioimidate group linked to a S-acetyl thiol (4, 5) or substituted aryldithio group (6-10). These ligands were synthesized by a Pinner-type process from the corresponding nitrile derivatives obtained by thiol-disulphide exchange reaction, reaction with substituted benzene-sulphenyl chloride, or other known procedures. To check the reagent of choice for immunoconjugate preparation, we studied thioldisulphide exchange kinetics between the intermediate nitrile derivatives and cysteine. Among the tested aryldithio derivatives (6-10), we selected ethyl 3-(4-carboxamido-phenyldithio)propionthioimidate (CDPT, 9) for further studies. By analyzing the rate of incorporation of the linkers 4, 5, and 9 in a model immunoglobulin G protein, we found similar results with CDPT 9 and ethyl S-acetyl 3-mercaptopropionthioimidate ester hydrochloride (AMPT, 5) because both reagents showed a linear correlation between the number of introduced thiol groups and factors such as time and protein and reagent concentrations. Comparison of the two acetylthio-derivative ligands 4 and 5 showed that AMPT 5 was more stable toward deacetylation than ethyl S-acetyl 2-mercaptopropionthioimidate ester hydrochloride (AMAT, 4). By comparing the kinetic and biological parameters of seven new thioimidate linkers, we found that two of these (CDPT and AMPT) could be superior ligands for protein-protein conjugation. They offer advantages over the commercially available compounds, such as minimal perturbation of the protein structure, controlled reactivity, and good stability.

Animals↗

PubMed1993

Toxin-targeted design for anticancer therapy. II: Preparation and biological comparison of different chemically linked gelonin-antibody conjugates.

To obtain more potent immunotoxins for anticancer therapy a gelonin-AR3 antibody immunoconjugate was prepared with different new linkers and coupling procedures. The gelonin was derivatized with the heterobifunctional thioimidate linkers ethyl-acetyl-3-mercaptopropionthioimidate (AMPT) and 3-(4-carboxamidophenyldithio)propionthioimidate (CDPT), and with the succinimidyl type reagents N-succinimidyl-3-(4-carboxamidophenyldithio)propionate (SCDP) and N-succinimidyl-S-acetyl thiolacetate (SATA). The biological activity of gelonin modified with different linkers (AMPT, CDPT, SCDP, SATA) was determined by a rabbit reticulocyte assay. We found that AMPT was the molecule of choice to derivatize the toxin, confirming the preferability of thioimidate linkers. The monoclonal antibody Mab was derivatized with CDPT and SCDP. Then the following immunoconjugates were prepared with different procedures: Mab-CDPT with gelonin-AMPT; Mab-CDPT with gelonin-CDPT; Mab-SCDP with gelonin-SATA. To verify whether selection of the most suitable coupling procedure could affect the antitumoral activity of the gelonin-AR3 immunoconjugate, the three immunotoxins were tested on target HT-29 human colon carcinoma cells versus nontarget MeWo cells. The gelonin immunoconjugate linked via the AMPT-CDPT thioimidate reagents showed highest antitumoral activity as well as best selectivity for the target cells.

Animals↗

PubMed1993

[Vaginitis and vaginosis. Comparison of two periods].

Vaginitis is the most frequent gynecological disease. It is characterized by objective and subjective signs of inflammation and differs from bacterial vaginosis (BV) which is an abnormal condition of the vaginal ecosystem caused by the excessive growth of aerobic and anaerobic flora normally present in the vagina with an increased risk of pelvic inflammatory disease (PID). The authors report the results of a study carried out at the Centre for Gynecological Infections at the Clinic of Obstetrics and Gynecology of the University of Parma. 828 patients were enrolled in the study during the period 1985-86 and 1559 patients during the two-year period 1991-92. The aim of the study was to evaluate variations in epidemiological data for vaginitis and bacterial vaginosis in the two periods examined. No significant changes were observed (p > 0.05) with regard to the prevalence of Ca, Tv and BV forms. On the other hand, there was a significant reduction (p < 0.001) in the forms sustained by other microorganisms (above all, streptococcus and enterobacteria) between the first and second periods with a parallel increase in the number of negative cases. The analysis of the age distribution of vaginitis and BV showed a reduction of other microorganisms and an increase in negative vaginal swabs in adults (> 20 years old).

Adult↗

PubMed1993

In vitro metabolism of 1,3-dioxane, 1,3-oxathiolane, and 1,3-dithiane derivatives of theophylline: a structure-metabolism correlation study.

Correlation between structure and metabolism was studied within a series of cyclic acetal and thioacetal theophylline derivatives. All the compounds showed marked regioselectivity in in vitro metabolism, the metabolites arising only from 7-cycloalkyl side chain transformation. The 1,3-dioxane derivative, besides N-dealkylation to theophylline, underwent enzymatic ring cleavage, through the oxidation of the acetal carbon and subsequent rearrangement. Thus the acetal group was converted enzymatically to an ester. A similar transformation, catalyzed by cytochrome P450-dependent monooxygenases, was previously found for the 1,3-dioxolane ring of doxophylline. The cyclic thioacetal derivatives (i.e. 1,3-oxathiolane and 1,3-dithiane) were not cleaved during oxidative metabolism. The metabolites arise only from the oxidation of the sulfur atom, the major nucleophilic center in the molecule. No N-dealkylation to theophylline was observed. Enzymatic sulfoxidation proceeded diastereoselectively in both the 1,3-oxathiolane and 1,3-dithiane rings, the trans isomers being the major ones with a ratio trans: cis 75:25 and 60:40 respectively. The sulfoxides were stable to hydrolysis and were not further metabolized. Neither disulfoxides nor sulfones were detected in the incubations.

Animals↗

PubMed1993

A new 'solid phase' procedure to synthesize immunotoxins (antibody-ribosome inactivating protein conjugates).

A method to produce immunotoxins (conjugates comprising of a monoclonal antibody and toxin) using ribosome inactivating protein anchored on an affinity gel derivatized with triazinic dye is described. The adsorbed toxins were activated with 2-imino-thiolane and then conjugated to monoclonal antibody activated by SPDP. The "heterogeneous phase" system offered several advantages, reducing the usually required purification steps and opening a way to automatize the conjugation procedure.

Antibodies, Monoclonal↗

PubMed1992

2,3-Epoxy-10-aza-10,11-dihydrosqualene, a high-energy intermediate analogue inhibitor of 2,3-oxidosqualene cyclase.

2,3-Epoxy-10-aza-10,11-dihydrosqualene, a high-energy intermediate analogue inhibitor of 2,3-oxidosqualene (SO) cyclase was obtained by total synthesis. This involved the preparation of three main building blocks: (1) C17 squalenoid N-methylamine, (2) 3-(diphenylphosphinoyl)propanal, and (3) 5,6-epoxy-6-methylheptan-2-one. The final stages of the reconstruction of the 6E double bond were obtained by a Wittig-Horner reaction which was modified for poorly reactive systems. This compound was designed to mimic the C-8 carbonium ion formed during SO cyclization. Its inhibitory activity on various SO cyclases was evaluated and compared with the 6 Z isomer which has an unfavorable geometry. Only isomer 6 E, the carbocation analogue, was active on SO cyclases from rat liver, pig liver, S. cerevisiae, and C. albicans microsomes, with an I50 varying from 3 to 5 microM. Both E and Z isomers were inactive on squalene epoxidase at the higher concentrations tested.

Animals↗

PubMed1992

Characterization and partial purification of squalene-2,3-oxide cyclase from Saccharomyces cerevisiae.

The membrane nature of squalene oxide cyclase from Saccharomyces cerevisiae was investigated by comparing properties of the enzyme recovered from both microsomes and the soluble fraction of the yeast homogenate. The "apparent soluble" form and microsomal form of the enzyme were both stimulated by the presence of mammalian soluble cytoplasm and corresponded to one another in response to detergents Triton X-100 and Triton X-114. The observed strong dependence of the enzyme activity on the presence of detergents and the behavior of the enzyme after Triton X-114 phase separation were peculiar to a lipophilic membrane-bound enzyme. A study of the conditions required to extract the enzyme from microsomes confirmed the lipophilic character of the enzyme. Microsomes, exposed to ipotonic conditions to remove peripheral membrane proteins, retained most of the enzyme activity within the integral protein fraction. Quantitative dissociation of the enzyme from membranes occurred only if microsomes were treated with detergents (Triton X-100 or octylglucoside) at concentrations which alter membrane integrity. The squalene oxide cyclase was purified 140 times from yeast microsomes by (a) removal of peripheral proteins, (b) extraction of the enzyme from the integral protein fraction with octylglucoside, and (c) separation of the solubilized proteins by DEAE Bio-Gel A chromatography. Removal of the peripheral proteins seemed to be a key step necessary for obtaining high yields.

Detergents↗

PubMed1990

22,23-Epoxy-2-aza-2,3-dihydrosqualene derivatives: potent new inhibitors of squalene 2,3-oxide-lanosterol cyclase.

Two new azasqualenoid derivatives, bearing a 22,23 epoxidic function, were synthesized, to obtain more efficient, competitive inhibitors of the enzyme squalene 2,3-oxide-lanosterol cyclase (EC 5.4.99.7). The activities of 22,23-epoxy-2-aza-2,3-dihydrosqualene 4 and of its N-oxide derivative 5 were studied using rat and pig liver microsomal preparations and compared with a pig liver partially purified squalene 2,3-oxide-lanosterol cyclase. The activities of compounds 4 and 5 were compared in the different enzymatic preparations with the activities of 2-aza-2,3-dihydrosqualene 2 and of 2-aza-2,3-dihydrosqualene N-oxide 3 previously studied only with rat liver microsomes. Using a solubilized, partially purified squalene 2,3-oxide cyclase, all the compounds exhibited a non-competitive type of inhibition. As the previously suggested mechanism of inhibition does not account for this kinetic behaviour, a new hypothesis is suggested.

Animals↗

PubMed1989

In vitro metabolism of azasqualene derivatives and their effects on aminopyrine N-demethylase activity in rat liver microsomes.

The metabolism of squalene dimethylamine (I), a potent inhibitor of 2,3-oxidosqualene (SO) cyclase, and of sixteen other squalene derivatives was investigated in rat liver microsomes. N-oxidation was the only metabolic pathway observed, squalene dimethylamine N-oxide being the only metabolite isolated from incubation of I. The azasqualane and quaternary ammonium derivatives did not form N-oxides during their metabolism. The inhibition of aminopyrine N-demethylase activity was also studied and the IC50, for compound I, which shows weak competitive inhibition, was determined. At 1 mM concentration the other squalene derivatives showed a range of inhibition activity possibly due to their different lipophilicity.

Aminopyrine N-Demethylase↗

PubMed1988

Inhibition of sterol biosynthesis in Saccharomyces cerevisiae by N,N-diethylazasqualene and derivatives.

The ability of some azasqualene derivatives to inhibit yeast cell growth was compared with their inhibition activity on squalene-2,3-oxide cyclase (EC 5.4.99.7) both in living cells and in microsome preparations. Among the compounds tested, N,N-diethylazasqualene showed the best correlation between the activity on squalene-2,3-oxide cyclase and its inhibition of yeast growth. The N-oxide derivative, N,N-diethylazasqualene N-oxide, which was as active as the amine in microsomes, was much less active in living cells, probably because it could not easily penetrate the cell wall. Kinetic analysis of the inhibitory activity of compounds on squalene-2,3-oxide cyclase revealed a sharp difference between N,N-diethylazasqualene and its N-oxide; the former showed a non-competitive-type inhibition, whereas the latter behaved as a competitive inhibitor.

Aza Compounds↗

PubMed1986

The squalene-2,3-epoxide cyclase as a model for the development of new drugs.

The 2,3-oxido squalene (SO) cyclases represent a group of enzymes which convert SO into polycyclic triterpenoids such as lanosterol, cycloartenol, cucurbitadienol and beta-amyrin. Taking into account the postulated model of the enzymatic cyclization of SO, we have investigated the possibility of designing compounds that would be selective and potent inhibitors of SO cyclases. Due to the fundamental role of sterols in animal, higher plant and fungal tissues, these inhibitors might behave as very selective (ipocholesterolemic, antifungal or phytotoxic) drugs. Our first approach was the synthesis and biological evaluation of 2-aza-2,3-dihydrosqualene and its derivatives which, being protonated at physiological pH, would present some similarities to the C-2 carbon ion generated by the opening of the oxirane ring of SO. Microsomes from different sources (germinated pea cotyledons, maize seedlings, rat liver and yeasts) were utilized to determine the inhibition values (I50: concentration of inhibitor producing 50% inhibition at a given substrate concentration). From the results obtained so far we conclude that 2-aza-2-dihydrosqualene and its derivatives strongly inhibited the cyclases, the site of the enzyme responsible for binding to the inhibitor is quite sensitive to the steric hindrance, and the degree of the inhibitory activity is greater in higher plants than in rat liver or fungi.

Animals↗

PubMed1986

In vitro activity of alpha, beta, gamma human interferons and Aspergillus terreus mycotoxins on cell proliferation.

The in vitro effect of different doses of alpha, beta and gamma human interferons and their interaction on the proliferation rate of human erythroleukemic cell line (K-562) and other cell lines has been evaluated. The results show that the stronger activity is exerted by beta HIF in comparison with alpha HIF. The action is selective and species-specific. beta HIF never elicited an "enhancing" effect on cell proliferation; on the contrary this phenomenon has been observed to occur with alpha and gamma HIF. In our cell system, the interaction between beta and gamma HIF gave a synergistic effect; on the contrary, no interaction has been observed to take place when beta HIF and directly cytotoxic mycotoxins extracted from A. terreus are associated.

Cell Division↗

PubMed1984

[Cesarean section: incidence, indications and early maternal morbidity (comparison of 2 periods: 1970-1972 and 1980-1982)].

In this study the authors compared cesarean section rate and post-operative maternal morbidity occurred during the period 1970-72 with the period 1980-82. The data showed an increased cesarean section rate from 8% to 24% but no difference about number of maternal post-operative complications and fever. Particularly post-operative maternal morbidity in emergency cesarean section fold down till to reach the already low morbidity found in elective cesarean section, besides febrile urinary tract infections are reduced in period 1980-82. No reduction was instead noted in post-cesarean endometrities and bronchopulmonary complications.

Cesarean Section↗