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Biomedical subjects

M Mancini

Publications and source records attributed to M Mancini.

At least 451 records · Page 25Linked to original sources
PubMedDate not supplied

Respiratory muscle overloading and dyspnoea during bronchoconstriction in asthma: protective effects of fenoterol.

Whether, and to what extent, beta 2-agonists protect against respiratory muscle overloading and breathlessness during bronchoconstriction remains to be defined in patients with asthma. In a double blind placebo-controlled study, 100 micrograms of fenoterol were administered to six stable asthmatics before a bronchial provocation test, performed by inhaling doubling concentrations of histamine from a Devilbiss 646 nebulizer. We recorded breathing pattern (tidal volume VT, inspiratory time TI, total time of the respiratory cycle TTOT), inspiratory capacity (IC), dynamic pleural pressure swing (Pplsw), total lung resistance (RL) and FEV1. VT was expressed both in actual values and as % of IC. Changes in VT (%IC) during histamine inhalation reflected changes in dynamic end-inspiratory lung volume (EILV). Pplsw was expressed as % of maximal (the most negative in sign) pleural pressure, obtained under control conditions during a sniff manoeuvre (Pplsn). Pplsw (%Pplsn) is an index of inspiratory muscle effort. The test ended when the concentration of histamine which caused a decrease in FEV1 of > or = 40% post-saline was reached. Dyspnoea rating was scored by a modified Borg scale. At the ultimate degree of bronchoconstriction (UDB) with histamine: (i) decrease in FEV1 was similar after placebo and fenoterol, while increase in RL was lower after fenoterol (P < 0.005); (ii) VT(%IC) increased less after fenoterol (P < 0.027); (iii) increases in Pplsw (%Pplsn) was lower after fenoterol (P < 0.001); (iv) delta Borg (from saline) was lower (P < 0.01) after fenoterol; (v) differences in delta Borg, from placebo to fenoterol, related to concurrent changes in VT(%IC) (r2 = 0.67). In conclusion, at UDB 100 micrograms of fenoterol produced a beneficial effect on the degree of inspiratory muscle loading and breathlessness, an effect greater than it would be expected from measuring FEV1 alone.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Flow cytometric measurement of mitochondrial mass and function: a novel method for assessing chemoresistance.

BACKGROUND: Chemotherapeutic agents induce apoptosis in cancer cells. Drugs failing to induce apoptosis are likely to have decreased clinical efficacy. We hypothesize that (1) chemotherapeutic agents induce mitochondrial changes and apoptosis through mechanisms associated with reactive oxidant species production; (2) the anti-apoptotic protein Bcl-2 prevents drug-induced mitochondrial changes, reactive oxygen species (ROS) production, and apoptosis; and (3) the assay of drug-induced mitochondrial changes can reflect drug-specific chemoresistance in a given cancer cell line. METHODS: A stable Bcl-2 transfectant of the Bcl-2 negative breast cancer cell line SKBr3 was created (SKBr3/Bcl2-2). Both SKBr3 and SKBr3/Bcl2-2 cells were treated with Herbimycin A (300 ng/mL) or vehicle (1% DMSO). Cell cycle changes were assessed by BRDU staining. Apoptosis was determined by electron microscopy, TUNEL (TdT-mediated dUTP-biotin nick end labeling) staining, and diphenylamine assay of DNA fragmentation. Changes in mitochondrial mass and transmembrane potential (deltapsi(m)) were assessed by flow cytometric assessment of JC-1 fluorescence. Reactive oxygen species production was measured by 2',7'-dichlorodihydrofluorescein diacetate (DCFH) fluorescence. RESULTS: Both SKBr3 and SKBr3/Bcl2-2 cells show cell cycle arrest after Herbimycin treatment. However, SKBr3 cells, but not SKBr3/Bcl2-2 cells, undergo apoptosis. Herbimycin-treated SKBr3 cells show increased mitochondrial mass (JC-1 green fluorescence), with no corresponding increase in deltapsi(m) (JC-1 red fluorescence). By contrast, Herbimycin-treated SKBr3/Bcl2-2 cells show no change in mitochondrial mass or deltapsi(m). Similarly, drug-treated SKBr3 cells, but not SKBr3/Bcl2-2 cells, demonstrate increased reactive oxygen species (ROS) production concomitant with the development of apoptosis. CONCLUSION: SKBr3 cells undergoing apoptosis demonstrate mitochondrial changes associated with ROS production. Bcl-2 transfection prevents these changes because it prevents apoptosis and induces chemoresistance to Herbimycin in SKBr3. Flow cytometric measurement of drug induced mitochondrial changes and ROS production may facilitate in vitro assessment of chemosensitivity or chemoresistance in breast cancer.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

The relationship between blood glucose concentration and beat-to-beat variation in asymptomatic subjects.

Very little is known about the presence of autonomic neuropathy in subjects with slight abnormalities of glucose metabolism. This study was carried out to investigate whether impaired glucose tolerance (IGT) is associated with abnormalities of beat-to-beat variation (BTBV). Sixty-two subjects, aged 40-59 years, with IGT (according to EASD criteria) and 124 normals, matched for age, sex and body mass index (BMI), were selected among the participants in a health examination survey and tested for BTBV. Among the possible factors influencing this test, sex did not shown any effect, while age and BMI were significantly and negatively correlated to BTBV in both groups. Glucose intolerance was not associated with any impairment of BTBV which was almost identical in the normal (15.8 +/- 6.3 beats/min) (mean +/- SD) and in the IGT group (16.7 +/- 7.0 beats/min). Similarly no significant difference was found in BTBV between subjects with constant IGT or normal results at OGTT, repeated on two occasions. All subjects were then stratified according to blood glucose values 2 h after an oral glucose load (after load): only those with blood glucose after load greater than 200 mg/dl displayed a significant decrease in BTBV (9.7 +/- 3.8 beats/min) compared to those found normal at the glucose tolerance test (p less than 0.025). They were also the only ones with an average HBa1 level significantly higher than in normal individuals (p less than 0.005). In conclusion, IGT is not associated with abnormalities of BTBV.

Adult↗