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Biomedical subjects

A Andreoni

Publications and source records attributed to A Andreoni.

At least 19 recordsLinked to original sources
PubMed1996

Kinetic transport analysis of daunorubicin by LoVo and LoVo/DX cells.

We describe a fluorometric technique for the measurement of transport parameters of fluorescent drugs through cellular membranes. Unlike other procedures, this method gives an accurate measure of drug accumulated in the cells and measures the fraction of free and bound drug in the cell. The kinetic parameters of transport through cellular membranes are determined using a simple three-compartment model combined with fluorescence measurements performed on the extracellular medium and on Triton-permeabilized cells during daunorubicin incorporation. With this technique we found that LoVo cells have a greater daunorubicin uptake, a similar input rate constant and a lower output rate constant than the drug-resistant LoVo/DX cells.

Antibiotics, Antineoplastic↗
PubMed1995

Involvement of brain catecholamines and acetylcholine in growth hormone hypersecretory states. Pathophysiological, diagnostic and therapeutic implications.

Secretion of growth hormone (GH) is excessive in acromegaly, but also in a number of other pathological states such as anorexia nervosa, insulin-dependent diabetes mellitus (IDDM), liver cirrhosis, depression, renal failure and GH-insensitivity syndrome. Abnormalities in the neuroendocrine control of GH secretion and/or a state of insensitivity to GH contribute to hypersecretion of GH in these states, with the possible exception of acromegaly, which appears to be a primary pituitary disease. GH hypersecretion may also occur in neonates or adolescents with tall stature, thus reflecting particular physiological or paraphysiological conditions. In the cohort of brain neurotransmitters, catecholamines and acetylcholine reportedly play a major role in the control of neurosecretory GH-releasing hormone (GHRH) and somatostatin (SS)-producing neurons, and hence GH secretion. Activation of alpha 2-adrenoceptors or of muscarinic cholinergic receptors in the hypothalamus stimulates GH release, probably through stimulation of GHRH and inhibition of SS release, respectively. Activation of dopamine receptors likewise stimulates GH release, while activation of beta-receptors inhibits GH release through stimulation of hypothalamic SS function. This review discusses the involvement of brain catecholamines and acetylcholine in GH hypersecretory states, including anorexia nervosa, acromegaly, IDDM, liver cirrhosis, depression, renal failure and GH insensitivity syndrome, with a view to providing a fuller understanding of their pathophysiology and, whenever possible, diagnostic and therapeutic implications.

Acetylcholine↗
PubMed1994

Fluorochromes with long-lived fluorescence as potential labels for pulsed laser immunocytofluorometry: photophysical characterization of pyrene derivatives.

An apparatus for laser-induced time-resolved fluorescence measurements, in conjunction with pyrene derivatives endowed with long-lived excited singlet states, was employed for immunocytofluorometric measurements. N-(1-pyrene)maleimide, 1-pyrenesulfonyl chloride and 1-pyreneisothiocyanate were conjugated with immunoglobulin, antimouse-IgG, and the fluorescence decays of both free and conjugated forms were investigated. Bi-exponential decays were obtained in all cases with time constants of the short-lived component in the range 3-4.7 ns and the long-lived one in the range 20-55 ns. Only the spectral distribution of the two components is essentially affected upon conjugation. The persistence of the long-lived component, well above the lifetime of autofluorescence, and of the antibody specificity, as shown by immunodiffusion tests, upon conjugation indicates that this technique could be advantageously adopted in immunocytofluorometry.

Animals↗
PubMed1994

Fluorometric determination of the kinetics of anthracyclines uptake by cells.

Fluorometric measurements on extracellular medium are shown to allow kinetic parameters of in vitro anthracycline uptake by cells to be calculated. The method provides influx and efflux rates, as well as the time dependence of both influx and efflux. It is applied to a normal thyroid epithelial cell line (FRTL-5) and a cell line (MPTK-6) derived from the lung metastases of a thyroid carcinoma exposed to daunorubicin at concentrations within the range of 250 to 1000 ng/ml. The results show that the number of cells influences the dependence of the kinetics upon the extracellular drug concentration and that the MPTK-6 cells are endowed with very efficient efflux mechanisms.

Animals↗
PubMed1994

Laser photosensitization of cells by hypericin.

Administering a light dose of 90 J/cm2 at 599 nm during incubation with hypericin to a highly differentiated normal epithelial cell line (FRTL-5), derived from Fisher rat thyroid, and to a neoplastic cell line (MPTK-6), derived from the lung metastases of a thyroid carcinoma induced in Fisher rats, produces cell kill at drug doses 1000 times lower than those necessary to cause the same mortality in the dark. The photocytocidal activity of this polycyclic quinone drug on neoplastic cells is superior to that of antitumor anthraquinone drugs, such as daunomycin and mitoxanthrone, and to the photosensitized antiviral activity previously reported for hypericin.

Animals↗
PubMed1994

Corticotrophin-releasing hormone does not inhibit growth hormone-releasing hormone-induced release of growth hormone in control subjects but is effective in patients with eating disorders.

Previous studies have shown that corticotrophin-releasing hormone (CRH) inhibits GH secretion in response to GH-releasing hormone (GHRH) in normal women and men, and animal studies suggest that this effect is mediated by an increased release of somatostatin from the hypothalamus. It has been reported that there are abnormalities in the neuroendocrine regulation of the hypothalamo-pituitary-somatotrophic axis and the hypothalamo-pituitary-adrenocortical axis in patients with eating disorders. The present study therefore investigated the ability of CRH to inhibit the GH response to GHRH in eight young women with anorexia nervosa (AN) and in seven young women with eating disorders which were not otherwise specified (NOS). We also compared the effect of CRH in the patients with the response it caused in ten control women. In contrast to a previous report, combined i.v. administration of 50 micrograms human CRH (hCRH) and 50 micrograms GHRH(1-29) caused a GH response in control women which was higher, although not significantly so, than that induced by GHRH alone (area under the curve (AUC) 988.5 +/- 506.0 compared with 1568.4 +/- 795.6 (S.E.M.) ng/ml per 120 min for GHRH alone and GHRH plus hCRH respectively). Conversely, the administration of hCRH given together with GHRH markedly inhibited the GH response induced by the latter in both AN patients (AUC 2253.0 +/- 385.7 compared with 1224.4 +/- 265.7 ng/ml per 120 min for GHRH and GHRH plus hCRH respectively; P < 0.005 and NOS patients (AUC 2827.4 +/- 281.1 compared with 308.5 +/- 183.4 ng/ml per 120 min for GHRH and GHRH plus hCRH respectively; P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Enhanced response to daunomycin of normal, tumor and metastatic cell lines via drug photoactivation.

We have compared the cytotoxicity of daunomycin in vitro to highly differentiated normal epithelial cells (Fisher rat thyroid cells, FRTL-5) and to two neoplastic cell lines, a thyroid carcinoma (TK-6) and its lung metastasis (MPTK-6). Whereas the cell lines are equally sensitive to the drug in the dark, if irradiated during incubation with daunomycin (86 J/cm2 at 488 nm), they become more and differently sensitive. Namely, the drug doses producing 50% mortality decrease by factors of about 22, 28 and 16 for FRTL-5, TK-6 and MPTK-6 cell lines, respectively. This result correlates with differences in drug uptake and resistance observed in the normal and neoplastic cell lines.

Animals↗
PubMed1992

Excited singlet state properties of anthracenedione photosensitizers.

The absorption, fluorescence and S1 state kinetics of anthracycline antitumour drugs (e.g. daunomycin, adriamycin) and several imino- and/or amino-substituted derivatives are investigated. The study, which includes all anthracyclines which possess photocytocidal activity, is extended to the disubstituted aminoanthracenedione, mitoxantrone, a red-light-absorbing antitumour drug whose activity, both in vitro and in vivo, is enhanced by photoactivation. The S1 state of the anthracycline imino and amino derivatives, in aqueous buffer at pH 7.4, is characterized by bi-exponential decay kinetics which indicates the presence of two ground state populations differing in the extent of hydrogen bonding. The ammonium group of the sugar moiety of anthracyclines contributes to the quenching of the S1 state population through a prototropic mechanism.

Antibiotics, Antineoplastic↗
PubMed1991

B16 melanoma response in vivo to photochemotherapy with mitoxantrone and red light.

The cytocidal activity of light-activated mitoxantrone in mice bearing B16 melanoma was investigated. Mice inoculated with 10(6) tumor cells on day 0 were i.p. injected with 1 mg/kg body weight of mitoxantrone on days 1, 5 and 9 and exposed to 108 J/cm2 of suitably filtered red light from a halogen lamp on days 2, 6 and 10. The treatment significantly prolonged the median survival time compared to both therapy with mitoxantrone and with red light alone.

Animals↗
PubMed1991

Blockade of cholinergic muscarinic receptors by pirenzepine and GHRH-induced GH secretion in the acute and recovery phase of anorexia nervosa and atypical eating disorders.

In view of the important role played by the cholinergic system in the neural regulation of growth hormone (GH) secretion, the ability of pirenzepine, a selective antagonist of muscarinic cholinergic receptors, to blunt the GH response to GH-releasing hormone (GHRH) was studied in adolescent females with anorexia nervosa in the acute (AN-AP) five AN-AP patients, administration of GHRH 1-40 (1 microgram/kg IV) evoked a significantly higher GH response than in controls at established intervals, whereas in eight AN-RP and seven AED patients it was higher than in controls at only one (150-min) and two (150-min, 180-min) time intervals, respectively. In the AN-AP patients, pretreatment with pirenzepine (0.6 mg/kg IV) only partially blocked the GH response to GHRH, whereas in the same AN-AP patients tested during recovery, and in AN-RP and AED patients, the drug completely suppressed the GH response to GHRH, as it did in controls. In view of pirenzepine's mechanism of action, these findings are best explained by the existence in the hypothalamus of AN-AP patients of a cholinergic hypertone and/or a diminished somatostatinergic function. Evaluation of the clinical and hormonal characteristics of the anorectic patients studied would indicate that factors other than undernutrition and its biological consequences, which subside in the recovery stage of the disease and are not present in AED patients, contribute to the anomalous GH response pattern of AN-AP patients.

Adolescent↗
PubMed1991

Enhancement of antitumor drug cytotoxicity via laser photoactivation.

We investigate the efficacy of daunomycin, some imino- and amino-substituted daunomycin analogues and the disubstituted aminoanthracenedione, mitoxantrone, in photosensitizing short-term cell kill upon irradiation in the long wavelength visible range, during incubation of Fisher rat thyroid cells with the drugs. While all compounds exhibit similar cytocidal effects on our cell line, in the absence of irradiation, administering 86 J/cm2 at wavelengths either coincident or close to drug absorption peaks causes greater enhancement in cell mortality for the 4-demethoxydaunomycin analogues than either the parent drug or its 5-imino-derivative. A lower enhancement is observed with mitoxantrone. In particular, C50 doses (i.e. concentrations that would kill 50% cells) as low as approximately 10(-9) M are found for both 6- and 11-amino 4-demethoxydaunomycin, compared with the values obtained in the absence of light, which are 2.59 x 10(-4) and 0.43 x 10(-4) M, respectively. Our previous studies of the photophysical and photochemical properties of the excited states of these drugs, and ESR and spin trapping studies of photosensitized generation of singlet oxygen, which were extended in this work to include mitoxantrone, indicate that the cytocidal effects proceed via type I rather than type II mechanisms.

Animals↗
PubMed1991

Photocytotoxicity of anthracyclines upon laser excitation in their long-wavelength absorption bands.

Newly synthesized daunomycin derivatives with red-shifted absorption compared to the parent molecule are shown to be able to photosensitize cells in vitro upon excitation with either argon or argon-pumped dye laser. Administering 86 J/cm2 total fluence (1 h irradiation) to Fisher rat thyroid cells during 2 h incubation with either daunomycin (excitation wavelength: 488 nm) or 5-iminodaunomycin (595 nm) produced cell killing at doses (about 2.7 X 10(-7) M for 50% cell survival) which were not toxic if administered in the dark. Greater photocytotoxicity (about 7 X 10(-8) M for 50% cell survival) was obtained with 4-demethoxydaunomycin as well as with its 6- and 11-amino derivatives (514 nm) while no cell killing as a result of photosensitization was observed for either Adriamycin or its 4'-iodo derivative. Our results suggest that the photosensitizing efficacy correlates with the absence of the methoxy group in the anthraquinone chromophore but is rather independent of the occurrence of triplet-mediated photoreactions. Finally, the fact that the imino- or amino-substituted 4-demethoxy compounds exhibit red-shifted absorption spectra compared to the parent molecule might be exploited for in vivo applications of the photoactivated cytotoxicity reported in this work.

Animals↗
PubMed1990

Failure of glucose infusion to suppress the exaggerated GH response to GHRH in patients with anorexia nervosa.

The growth hormone (GH) response to GH-releasing hormone (GHRH) is characteristically exaggerated in anorexia nervosa (AN). Hyperglycemia suppresses the GH response to GHRH in normal subjects. To test whether this inhibitory action of hyperglycemia is preserved in AN, we performed a GHRH (GHRH 1-40, 1 micrograms/kg) test under basal conditions (saline infusion) and during steady-state hyperglycemia (200 mg/dl, induced by the intravenous administration of 8 mg/min.kg of glucose) in 6 adolescent girls with acute-stage AN (as diagnosed by psychopathological, hormonal, and nutritional criteria) and in 5 age-matched female controls. In control subjects, GHRH stimulated GH release during saline, but not glucose, infusion. In the anorectic patients, the GH response to GHRH was exaggerated during both saline infusion (2.97 +/- 0.79 versus 0.52 +/- 0.22 micrograms.120 min.ml-1, p less than 0.02) and under hyperglycemic conditions (4.61 +/- 0.56 versus 0.33 +/- 0.10, p less than 0.001). We conclude that the inhibitory action of hyperglycemia on GHRH-induced GH release is lost in the acute phase of AN.

Acute Disease↗
PubMed1990

Quantitative measurements of porphyrin pigments in tissues via photoacoustic spectroscopy.

We investigated the possibility of using photoacoustic spectroscopy as an analytical technique for the quantitative measurement of injected porphyrins in tissues. Samples of liver excised from treated (i.e., injected 24 h in advance with 100 mg/kg Photofrin II) mice and control mice were lyophilized and reduced to powder; then, about 16-mg powder samples were compacted to equal volumes inside the photoacoustic cell. Amplitude and phase spectra were measured in the range 280-760 nm. From these data we computed the photoacoustic absorbance spectra; they were suitably normalized in order to account for differences in hemoglobin concentration among the livers of different mice. The absorbance difference spectra (treated minus control) were computed in the region of wavelengths above 450 nm, where porphyrins and hemoglobin exhibit major differences. Finally, by estimating the value of the thermal diffusion length of the powdered sample and those of the extinction coefficients of the most relevant Photofrin II components in the spectral region considered, we were able to evaluate the local drug concentration and determined a value (260 micrograms/g of wet tissue) that is in the range expected for the dose of Photofrin II injected.

Acoustics↗