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Biomedical subjects

F Innocenti

Publications and source records attributed to F Innocenti.

At least 37 records · Page 2Linked to original sources
PubMed1995

Inhibitory effect of the somatostatin analogue SMS 201-995 and cytokines on the proliferation of human colon adenocarcinoma cell lines.

The activity of the synthetic somatostatin analogue SMS 201-995 was investigated in vitro on the growth of SW480 and SW620 human colon adenocarcinoma cell lines. The inhibition of cell proliferation was significant in SW480 cells (-19.6 +/- 1.4% at SMS 201-995 10-9 M, P < 0.05), but not in SW620 cells (-5.5 +/- 0.8% at SMS 201-995 10-8 M) as compared to untreated cultures. Moreover, SMS 201-995 10-8 M decreased the mitogenic effect of epidermal growth factor (EGF) on the SW480 cell line (-26.6 +/- 3.4% vs. cells exposed to EGF 10 ng ml-1 alone, P < 0.05). The effect of combining SMS 201-995 plus the cytokines interleukin-2 (IL-2) or gamma-interferon (gamma-IFN) on SW480 and SW620 cancer cell growth was also evaluated. The treatment produced a synergistic antiproliferative effect against SW620 cells as compared to untreated cultures, with growth inhibition being -20.2 +/- 1.2 and -19.3 +/- 1.3%, at SMS 201-995 10-8 M plus IL-2 or gamma-IFN 100 IU ml-1, respectively, but did not increase the activity of SMS 201-995 against the SW480 cells. In conclusion, the effect of SMS 201-995 on colon cancer cell growth can be enhanced by its combination with cytokines in SW620 but not in SW480 colon adenocarcinoma cells.

Adenocarcinoma↗
PubMed1995

Plasma and tissue disposition of paclitaxel (taxol) after intraperitoneal administration in mice.

The pharmacokinetics of single intraperitoneal doses of paclitaxel (18 and 36 mg/kg) in mice were investigated in the present study. The analysis of drug concentrations by HPLC indicated that the plasma Cmax (13.0 +/- 3.1 and 25.7 +/- 2.8 micrograms/ml, respectively) were reached at the 2nd hr. The values of CL were low (0.06 and 0.1 ml/min, respectively), and t1/2 beta values of 3.0 and 3.7 hr were found, after 18 and 36 mg/kg, respectively. The highest tissue concentrations were observed in the liver (50.2 +/- 3.1 and 92.0 +/- 9.5 micrograms/g respectively), followed by the pancreas (39.3 +/- 9.9 micrograms/g) and the ovary (53.4 +/- 5.6 micrograms/g) after 18 and 36 mg/kg, respectively. In the case of the colic tissue, paclitaxel Cmax were 14.4 +/- 0.8 and 32.8 +/- 3.5 micrograms/g at the 3rd hr, respectively, with sustained drug levels still detectable 24 hr after treatment. Paclitaxel Cmax values of 12.7 +/- 3.0 and 53.4 +/- 5.6 micrograms/g were detected in the ovary after 18 and 36 mg/kg, respectively. The overall results provide evidence that, after intraperitoneal administration, paclitaxel concentrates in peritoneal organs; however, the intraperitoneal route does not prevent systemic drug exposure, allowing high and sustained levels of paclitaxel also in several extraperitoneal tissues.

Animals↗
PubMed1994

Indications of reduced pulmonary function in type 1 (insulin-dependent) diabetes mellitus.

Abnormalities of pulmonary function tests have been described in type 1 (insulin-dependent) diabetes mellitus (IDDM). To better characterise such abnormalities and to verify whether these latter are associated with the presence of diabetic microvascular disease we compared 23 non-smoking patients who had IDDM with 24 non-smoking healthy control subjects strictly matched for sex, age, and body mass index. Compared with controls, diabetic patients had a reduced forced vital capacity (FVC) (87.5 +/- 13.1% vs. 96.4 +/- 13.6% of the predicted; P = 0.03) and forced expiratory volume in 1 s (FEV1) (90.5 +/- 17.7% vs. 101.2 +/- 13.2% of the predicted; P = 0.02). While within the group of patients the presence of retinopathy and autonomic neuropathy were not associated with modifications of pulmonary function tests, those with altered urinary albumin excretion rate (AER > or = 20 micrograms/min; range 21-589) (n = 7) had a significantly lower pulmonary diffusion capacity (DLCO) than the 16 normoalbuminuric subjects (62.6 +/- 7.2% vs. 88.7 +/- 20.1% of the predicted; P = 0.01). Moreover, in the group of patients, DLCO was inversely related with AER (r = -0.43; P = 0.04). In conclusion, IDDM is characterised by reduced FVC and FEV1, while a significant decrease in DLCO may be considered as selectively associated with renal disease.

Adult↗
PubMed1994

Dissociation between in vitro cytotoxicity and in vivo cardiotoxicity of two new anthracyclines: 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin and 4'-deoxy-4'-iodo-doxorubicin.

The purpose of this study was to examine the cytotoxicity and cardiotoxicity of new doxorubicin (DXR) derivatives, 3'-deamino-3'-(2-methoxy-4- morpholinyl)DXR (MRA-MT), and 4'-deoxy-4'-iodo-doxorubicin (IDXR), comparing them to doxorubicin (DXR). Both anthracycline derivatives were approximately 1.5- to 9-fold more active than DXR in inhibiting the colony-formation ability of DU145, HOS, and A2780 human cancer cell lines. Anesthetized rats given a single intravenous (i.v.) dose of DXR 10 mg/kg showed significant changes in both ECG (S alpha T segment and QRS complex widening) and hemodynamic parameters (impairment in systemic arterial dP/dtmax systolic and diastolic blood pressure), whereas animals that received MRA-MT (0.1 and 0.3 mg/kg) had no significant signs of acute cardiotoxicity. In this case the animals treated with IDXR 1.2 mg/kg showed alterations in the ECG as the animals treated with DXR. In the chronic cardiotoxicity study, some animals received MRA-MT (0.03 mg/kg i.v. once a week for 3 weeks) and others IDXR (4 mg/kg once a week for 3 weeks). They did not show any alteration in ECG and cardiac histological picture. By contrast, DXR (3 mg/kg i.v. once a week for 3 weeks) induced a severe cardiomyopathy, characterized by progressive widening of S alpha T segment, increase in T wave, and histological damage consisting of vacuolations and loss of myofibrils. These results suggest that MRA-MT and IDXR are more active in vitro and markedly less cardiotoxic in vivo than DXR.

Analysis of Variance↗
PubMed1993

In vitro phencyclidine-induced inhibition of lymphocyte proliferation: prevention by cell activation.

The proliferative response of phytohemagglutinin (PHA)- and interleukin 2 (IL-2)-activated murine splenocytes was studied in the presence of phencyclidine (PCP), a potent psychotomimetic drug of abuse. PCP inhibited [3H]-thymidine incorporation in lymphocytes treated with PHA or IL-2. This inhibitory action was dependent upon the drug doses and the time of incubation with the cultures. There was no significant inhibitory activity of PCP when it was added 24 hrs or 48 hrs after mitogenic stimuli. Parallel, a lower inhibitory effect was observed when IL-2 or PHA were simultaneously present in the incubation medium. Moreover, the pretreatment for 18 hrs with IL-2 completely counteracted PCP-induced depression of PHA-stimulated lymphocytes. We suggest that PCP affects some pathway that regulates the activation of resting T cells rather than affecting already cycling cells.

Animals↗
PubMed1991

Thymosin alpha 1 potentiates interleukin 2-induced cytotoxic activity in mice.

We have investigated the effects of interleukin 2 (IL-2) on cytotoxic activity of spleen lymphocytes, from normal and cyclophosphamide (200 mg/kg) or B-16 melanoma suppressed mice, after in vitro or in vivo pretreatment with thymosin alpha 1 (TA1). The results of this study indicate that pretreatment in vitro (100 ng/ml for 1 hr) or in vivo (200 micrograms/kg/day for 4 days) with thymosin alpha 1 (TA1), significantly increased the IL-2 (from 100 to 500 U/ml) in vitro induced cytotoxic activity of spleen lymphocytes, collected from both normal and cyclophosphamide and tumor-suppressed animals, against both YAC-1 (NK sensitive) and MBL-2 (NK resistant) cell lines. The potential use in combination of these two different biological response modifiers, useful in enhancing the immunological responses to IL-2 of lymphocytes, may provide a novel model of immunotherapeutic intervention in cancer.

Animals↗
PubMed1989

Serum digoxin and beta-methyldigoxin in elderly patients on hospital admission: correlation with home compliance and clinical variables.

Serum digoxin and beta-methyldigoxin (BMD) were measured in 165 elderly patients (age greater than 60 years) admitted to hospital, of whom 109 had been treated at home with digoxin and 56 with BMD. The mean BMD level was significantly lower than that of digoxin (1.1 vs. 1.4 ng/ml). Creatinine clearance and daily dose were the variables most strongly associated with digoxin level, and the prescribed dose and serum albumin were the best predictors of the BMD concentration. Compliance was assessed by a compliance index (CI), namely the ratio of the measured glycoside concentration, corrected for creatinine clearance, over the expected steady-state dose, calculated from a hospitalized reference group. Compliant individuals in both treatment groups, i.e. those with a CI greater than the median value, were characterized by a lower daily dose and dosage frequency. Toxicity, whether clinical or electrocardiographic, was present in 9% of the patients and was associated only with a significantly higher mean serum level of the drug.

Aged↗
PubMed1989

Morphometry of peptide-containing nerves in gut muscle layers: a quantitative approach to the study of autonomic neuro-muscular junctions.

A method for the quantitative assessment of peptide-containing nerves in the gastrointestinal muscle layers is described. Tissue samples are sectioned obliquely, at 45 degrees, in the plane bisecting the long axes of longitudinal and circular muscle fibres, and peptide-containing nerve fascicles are revealed by immunofluorescence. Cross-sectioned fascicles are counted (number/area of muscle) and their length density per volume of muscle layer is calculated. The composition of immunostained nerve fascicles is also assessed, by counting peptide-containing fibres in each, while peptide transmitter co-distributions are studied in parallel using adjacent tissue sections. Thus, the approach described provides a means for the delineation of both quantitative tissue distribution and composition of autonomic neuro-muscular junctions in the gastro-intestinal tract.

Animals↗
PubMed1989

Microalbuminuria and casual and ambulatory blood pressure monitoring in normotensives and in patients with borderline and mild essential hypertension.

Several reports suggest that urinary albumin excretion may be elevated in patients with essential hypertension and that this index may be a good predictor for cardiovascular complications. The aim of this study was to compare 24-hour urinary albumin excretion in a group of normotensives, borderline, and untreated mild hypertertensives and to assess, in a subgroup of them, the possible relations between microalbuminuria and arterial blood pressure. Fifteen normotensives, 16 borderline, and 19 mild hypertensive patients were studied. Slightly but significantly higher values of microalbuminuria were observed in the mild hypertensives compared to the other two groups. In 21 borderline and mild hypertensive patients 24-hour microalbuminuria was related to casual blood pressure and noninvasive ambulatory blood pressure monitoring. A significant correlation was found between microalbuminuria and average day-time diastolic blood pressure. Our data suggest that albumin excretion is slightly increased in mild arterial essential hypertension; the direct association between microalbuminuria and arterial diastolic blood pressure during daily activities seems to confirm a pathophysiological link between transcapillary protein escape and arterial blood pressure that warrants further studies.

Adult↗
PubMed1981

[Glycosylated hemoglobins and the oral glucose tolerance test in evaluation of glucose tolerance].

We performed OGTT and glycosylated hemoglobin (HbA1) determinations in 62 subjects. In those with IGT we noticed significantly increased average levels of HbA1 in comparison to normal or borderline ones, but 65.3% of the subjects with abnormal OGTT according to Fajans and Conn's criteria and 83.3% of those scored as borderline, had normal HbA1. This latter group showed a positive significant correlation with sum and peak of plasma glucose concentrations at 60 and 120 min during the test. Our opinion is that the mutual presence of abnormal OGTT and of increased HbA1 levels allows a reliable diagnosis of IGT, and the presence of normal HbA1 must induce us to suspect a false IGT diagnosis. 18 normal subjects showed, moreover, a remarkable HbA1 increase 30 days after the glucose load, with a return to basal levels after 40 days, while in 8 subjects with IGT, HbA1 remained constantly unmodified after 30 and 40 days. This is probably a consequence of a difference in daily glycemic profile between individuals with normal glucose tolerance and others with a reduced one.

Adult↗
PubMed1980

Thermal decomposition of ibuproxam.

The thermal behavior of ibuproxam was studied at several temperatures, and the degradation products were separated by column chromatography and ethereal extractions. The resulting products were ibuprofen [2-(4-isobutylphenyl)propionic acid], 1-(4-isobutylphenyl)-ethylamine, 4-isobutylacetophenone, and 4-isobutylacetophenone oxime. The compounds were identified by IR, UV, and NMR spectroscopy and elemental analyses. 4-Isobutylacetophenone was treated with hydroxylamine to give 4-isobutylacetophenone oxime.

Anti-Inflammatory Agents↗