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Biomedical subjects

M Grandi

Publications and source records attributed to M Grandi.

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

Biological profile of FCE 24517, a novel benzoyl mustard analogue of distamycin A.

FCE 24157 (chemically (beta-[1-methyl-4-(1-methyl-4--[1-methyl-4-(4-N,N- bis(2-chloroethyl) amino-benzene-1-carboxy-amido) pyrrole-2-carboxiamido]pyrrole-2-carboxyamido)pyrrole-2-c arboxyamido]) propionamidine, hydrochloride) is a distamycin A (Dista A) derivative bearing a benzoyl mustard moiety instead of the formyl group at the N-terminal. Contrary to Dista A, FCE 24517 has been found to display potent cytotoxic activity on human and murine tumour cell lines. The compound maintains activity on melphalan (L-PAM)-resistant cells, whereas cross-resistance is observed on doxorubicin-(DX)-resistant cells. In vivo, FCE 24517 was found to possess evident antineoplastic activity on a series of murine transplanted solid tumours and human tumour xenografts. The following neoplasms were in fact found to be sensitive to FCE 24517 treatment: M14 human melanoma xenograft, N592 human small cell lung carcinoma, MTV murine mammary carcinoma, Colon 38 murine carcinoma, PO2 murine pancreatic carcinoma and M5076 murine reticulosarcoma. Lower effectiveness was observed against the murine P388 and Gross leukaemia, Lewis lung murine carcinoma, LoVo human colon carcinoma xenografts and A459 human lung adenocarcinoma. Against the murine L1210 leukaemia, FCE 24517 displayed a clear activity only when the tumour was transplanted i.p. and treatment was given i.p., whereas only marginal activity was seen against this leukaemia if transplanted i.v. and the drug was given i.v. As true also in vitro, FCE 24517 was effective against i.p. implanted L1210 leukaemia resistant to L-PAM. The mode(s) of action of this new compound is under active investigation.

Animals↗
PubMed1991

Influence of lipophilicity on cytotoxicity of anthracyclines in LoVo and LoVo/Dx human cell lines.

Quantitative structure-activity relationship studies aimed at improving drug activity profiles require the determination of the physicochemical properties possibly involved in biological action. The lipophilic character of selected anthracyclines has been measured by means of reverse-phase high performance liquid chromatography, selecting appropriate experimental conditions. The capacity coefficients at zero percentage of the organic phase (log K0), which are retention indexes, have been used as lipophilicity descriptors in a QSAR study, involving as biological data the cytotoxicity of anthracyclines in a doxorubicin-sensitive (LoVo) and in a doxorubicin-resistant (LoVo/Dx) human cell lines. The results obtained in these in vitro models indicate that lipophilicity plays a role in anthracycline activity, influencing drug availability at the site of action.

Antibiotics, Antineoplastic↗
PubMed1991

[Obesity: relationships with the endocrine system].

In this study we have examined the relationship between obesity and endocrine glands. We have underlined that obesity can be a symptom of some endocrine diseases and that, on the other side, only a few number of cases with excessive weight have a true endocrine pathogenesis. The endocrine implications of essential obesity, only detectable with appropriate dynamic tests, are sometimes expression of an altered peripheral metabolism. The more relevant hormonal data that we will examine in details are: increase of insulin plasma levels, altered hypothalamic neuroregulation with consequence on the gonadotropin secretion and values of prolactin, growth hormone and cortisol.

Endocrine Glands↗
PubMed1990

In vitro bone marrow purging of multidrug-resistant cells with a mouse monoclonal antibody directed against Mr 170,000 glycoprotein and a saporin-conjugated anti-mouse antibody.

Selective elimination of multidrug resistance-positive cells (LoVo/Dx) was obtained by using the monoclonal antibody MRK 16, which recognizes a surface epitope of the Mr 170,000 glycoprotein, and a sheep anti-mouse immunoglobulin antibody, conjugated to the ribosome-inactivating protein saporin 6. The killing was greatly decreased or even abolished by adding the monoclonal antibody at a 100-fold concentration. Both the MRK 16 and anti-mouse saporin 6 conjugate did not show any killing activity when they were used separately. In cell suspensions composed of 90% normal bone marrow cells and 10% multidrug resistance-positive cells, the monoclonal antibody MRK 16 followed by the anti-mouse immunotoxin caused the elimination of 99% multidrug resistance-positive cells, as revealed by immunofluorescence and immunocytochemistry as well as by a clonal assay. Human normal hematopoietic precursors (granulomonocytic colony-forming units, erythroid burst-forming units, and multipotent granulomonocytic, erythroid, and megakaryocytic-forming units) were not affected by the MRK 16 plus immunotoxin treatment. This technique might be suitable for ex vivo bone purging in an appropriate clinical setting, such as autologous bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1990

Effects of football on the pituitary-testicular axis (PTA): differences between professional and non-professional soccer players.

Basal levels of LH, FSH, PRL and T, as well as LH, FSH and PRL relative maximum responses (RMRs = peak values/basal values) to an iv bolus of GnRH (0.1 mg) plus TRH (0.2 mg) were evaluated in 7 professional soccer players (PSP) examined on 3 occasions: after a 30 days rest period and 14-15 h from the end of both a customary training session and a strenuous football match, performed at the end of a 3 months regular training program. In 5 out of the 7 PSP a semen analysis was carried out after each endocrine evaluation. The results were compared with those obtained in 10 non-professional soccer players (NPSP) subjected to a similar study protocol, and with the data from 10 healthy, sedentary men. Basal LH values in the rest period were significantly higher (P less than 0.05) in PSP than in control men, whereas LH RMR and sperm motility were significantly lower (P less than 0.02) in the former group. No significant differences in basal hormone concentration and in the RMRs to GnRH-TRH were observed between PSP and NPSP. The training session performed by the PSP after 3 months of regular training did not significantly affect the hormonal parameters. In contrast, the football match induced a significant increase in PRL basal levels (P less than 0.02 vs. controls) and a significant fall in PRL RMR (P less than 0.02 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Sex change in children with Morris syndrome].

Eleven boys with Morris syndrome underwent feminizing genitoplasty utilizing a segment of the sigmoid colon for neovaginal reconstruction. Bilateral orchiectomy was performed for cosmetic reasons and to prevent neoplasms. Patient follow-up ranging from 6 months to 13 years have demonstrated good results were obtained. No intra- or postoperative complications were observed. Patient psycho-social-sexual identification and satisfaction were achieved.

Adolescent↗
PubMed1989

Cellular and molecular pharmacology of 4'-epidoxorubicin in HeLa cells. Comparison with its parent drug, doxorubicin.

The effects on cellular DNA and cytotoxicity produced by doxorubicin (Dx) and its epimer 4'-epidoxorubicin (4'E-Dx) were investigated in cultured HeLa cells. 4'E-Dx was 2.3 times more cytotoxic than Dx after 1 h of treatment, but the two anthracyclines were equally cytotoxic on longer-term (24 h) drug exposure. The different kinetics of cell lethality were related to pharmacodynamic differences between the two drugs. In fact, cellular uptake and efflux rates of 4'E-Dx were faster than those of Dx on 1 h of drug exposure but similar after 24 h of treatment. 4'E-Dx caused more protein-concealed strand breaks in DNA (single and double) than did Dx, despite a lower potency for free-radical formation. The degree of strand breakage by 4'E-Dx was not a linear function of exposure time and, in fact, the rate of strand-break induction declined continuously with time. In contrast, Dx caused an almost linear increase in DNA single-strand breaks with time during 1 h of drug exposure; this was apparently due to its slower uptake. There was little repair of the DNA single-strand breaks produced by Dx upon postincubation for 5 h in a drug-free medium, whereas DNA lesions caused by 4'E-Dx were removed with a t1/2 of about 1.7 h. These findings underline the importance of the cellular pharmacokinetics of anthracyclines in relation to their cytotoxic and DNA-damaging effects.

DNA Damage↗
PubMed1989

The pituitary-testicular axis in non-professional soccer players.

In European countries, football is one of the most popular forms of physical exercise. However, the possibility that endocrine changes can arise in football players has not been investigated completely. Therefore, the aim of the present study was to evaluate the effects of a training program and the consequences of a football match on the pituitary-testicular axis in ten trained non-professional soccer players. Basal levels of LH, FSH, PRL and T, as well as LH, FSH and PRL responses to an iv bolus of GnRH (0.1 mg) plus TRH (0.2 mg), were measured in each subject. The endocrine evaluation was performed before the beginning of the seasonal training (after a 30 days rest period), and repeated on 2 consecutive days at the end of a 3 months regular training program, 14-15 h from the end of both a customary 3 h training session and a 90 min strenuous soccer match. In 5 out of the 10 athletes a semen analysis was performed after each endocrine evaluation. Ten age-matched, healthy, sedentary men served as a control group. Basal serum levels of LH (10.4 +/- 1.3 mIU/ml), FSH (8.7 +/- 1.1 mIU/ml), PRL (9.7 +/- 1.6 ng/ml) and T (6.3 +/- 0.9 ng/ml) measured in the soccer players before the beginning of the seasonal training were similar to those found in the control subjects (LH = 9.2 +/- 1.7 mIU/ml, FSH = 8.5 +/- 1.4 mIU/ml, PRL = 8.8 +/- 1.8 ng/ml, T = 6.4 +/- 1.1 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Not Available].

Explore the source record for details and available documents.

Equipment and Supplies↗
PubMed1988

Intracellular doxorubicin concentrations and drug-induced DNA damage in a human colon adenocarcinoma cell line and in a drug-resistant subline.

The mechanisms of resistance to doxorubicin (DX) were investigated using a human colon adenocarcinoma cell line (LoVo) and a subline approximately 30 times less sensitive to doxorubicin. LoVo and LoVo/DX were similar in terms of DNA and protein content, cell volume, duration of S phase and the generation time, and proportion of cycling cells. LoVo/DX showed cross-resistance to other anthracyclines, to vinca alkaloids, epipodophyllotoxin derivatives, 4'-(9-acridinylamino-methanesulfon-m-aniside) and actinomycin D. LoVo/DX was equally sensitive to melphalan and showed collateral sensitivity to cis-platinum and 1-beta-D-arabinofuranosylcytosine. On exposing LoVo and LoVo/DX to 1.25 and 40 micrograms/ml DX respectively, for 4 hr, similar DX intracellular concentrations were reached in the two cell lines. In these treatment conditions protein associated DNA-single strand breaks or DNA-double strand breaks, assessed by alkaline elution methods were only slightly less in LoVo/DX than in LoVo cells. In LoVo/DX cells, however, DNA breaks disappeared very quickly after drug removal whereas they persisted longer in LoVo cells. This persistance is probably related to the much slower DX efflux from LoVo than LoVo/DX. When verapamil was combined with DX it inhibited the rapid DX efflux from LoVo/DX and reversed the resistance in this cell line, but it had no significant activity on LoVo cells. Verapamil also increased DX-induced DNA-single strand breaks and DNA-double strand breaks in LoVo/DX cells, but not in LoVo cells.

Adenocarcinoma↗
PubMed1988

A new class of contrast agents for magnetic resonance imaging based on selective reduction of water-T2 by chemical exchange.

Compounds containing mobile protons can act as contrast agents by increasing the value of the term (1/12 - 1/11). The efficiency of this method is markedly pH- and field-dependent. There are many such compounds allowing a choice to be made based on the characteristics of the tissue or organ, magnetic field strength, and solution pH levels. The properties of some of these chemicals have been investigated at different magnetic field strength and solution pH levels. The authors report herein the properties of iopamidol a well-known x-ray contrast agent, and stress its potential effect as an MRI contrast agent. The influence on the T2 decrease of the chemical shift separation delta omega (in frequency units) between water and exchangeable proton of the contrast agent may be increased by adding suitable shift reagents which interact with basic sites close to the protons involved in the chemical exchange.

Animals↗
PubMed1987

Human tumor cell lines with pleiotropic drug resistance are efficiently killed by interleukin-2 activated killer cells and by activated monocytes.

Two human cell lines, the colon carcinoma Lovo and the transformed intestinal I-407, and their variants (Lovo/Dx and I-407/Dx), with pleiotropic resistance to cancer chemotherapeutic drugs, were examined for their susceptibility to human Interleukin-2-activated killer cells and to activated monocytes. These non-specific or broadly specific effector cells expressed cytotoxicity levels on pleiotropically resistant tumor cells comparable to those of the parental cell populations. This finding provides a rationale for immunological approaches designed to eradicate residual tumor cells surviving and resistant to cytotoxic chemotherapy.

Antineoplastic Agents↗
PubMed1987

Changes in mouse Leydig cell steroidogenesis following infrared and helium-neon laser irradiation.

The effects on mouse Leydig cell steroidogenesis of infrared (IR) laser rays, in the presence or absence of helium-neon (He-Ne) radiations, were investigated. Testosterone (T) production in response to luteinizing hormone (LH) by mouse Leydig cells exposed to IR (4.2 X 10(-3) J/cm2/min) plus He-Ne (8.0 X 10(-7) J/cm2/min) laser radiations was significantly higher than that by control Leydig cells. The Leydig cell responsiveness to LH (T delta %), as well as the secretion of cyclic AMP (cAMP) and androstenedione (A) in response to the highest dose of LH (0.5 mIU), were also significantly increased by the IR plus He-Ne irradiation. In contrast, the He-Ne irradiation (8.0 X 10(-7) J/cm2/min) in the absence of IR rays failed to affect T production by mouse Leydig cells. Similar results were obtained by adding to the He-Ne rays a low dose of IR radiation (3.4 X 10(-3) J/cm2/min), whereas higher doses of IR radiations (4.2 X 10(-3) and 5.1 X 10(-3) J/cm2/min) elicited a similar significant increase of T production by mouse interstitial cells.

Animals↗