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Biomedical subjects

M Senatore

Publications and source records attributed to M Senatore.

At least 19 recordsLinked to original sources
PubMed2001

Effects of homocysteine on proliferation, necrosis, and apoptosis of vascular smooth muscle cells in culture and influence of folic acid.

BACKGROUND: It is known that hyperhomocysteinemia is associated with an increased risk of vascular disease, yet little is known about the pathogenic mechanisms underlying the action of homocysteine (Hcy) itself. METHODS: We evaluated the effects of Hcy on cell proliferation, apoptosis, and necrosis in smooth muscle cells (SMCs) cultured for 24 h with different amounts of Hcy. The percentage of apoptotic and necrotic cells from the culture was evaluated using two different techniques: annexin V-FITC and propidium iodide (PI) fluorescence and apoptosis TUNEL assay. RESULTS: The addition of 10 microM/l of Hcy to the medium was followed by a significant increase in cell proliferation and death, through apoptosis and necrosis, respectively. Notwithstanding this apparent balance, a significant increase was found in the total number of cells present in Hcy-treated culture, thus demonstrating a positive dose-dependent correlation with Hcy concentrations in the culture medium. The addition of folic acid to the culture medium significantly reduced both Hcy concentrations in media and the effects of Hcy on the proliferation/apoptosis/necrosis balance of cells in culture. The percentages for apoptotic cells and for cells with a necrotic morphology continued to increase as Hcy concentrations increased, although the absolute values were lower in the culture treated than in that not treated with folic acid. CONCLUSIONS: In the presence of folic acid, at increasing concentrations of Hcy, the total number of cells in culture showed increases far less relevant with respect to the control. Also the percentage of apoptotic cells to that of cells with a necrotic morphology, although conserving the tendency to increase to growth of the concentrations of Hcy, have shown absolute values that were lower in the folic acid-treated cultures.

Apoptosis↗
PubMed2001

Cell proliferation/cell death balance in renal cell cultures after exposure to a static magnetic field.

The effect of a static magnetic field (MF) of 0.5 mT of intensity on the cell proliferation/cell death balance was investigated in renal cells (VERO) and cortical astrocyte cultures from rats. Magnetic stimulation was delivered by magnetic disks at known intensities. The percentage of apoptotic and necrotic cells was evaluated using flow cytometry and morphological analysis following Hoechst chromatin staining. An index of cell proliferation was determined using sulfonated tetrazolium (WST-1). Control cultures were prepared without exposure to MFs. After 2, 4 and 6 days of exposure to a MF, we observed a gradual decrease in apoptosis and proliferation and a gradual increase in cells with a necrotic morphology with respect to the control group. In astrocyte cultures, over a 6-day exposure period. A gradual increase was observed in apoptotic, proliferating, and necrotic cells. Our findings suggest that the effect of exposure to MFs varies, depending on the cell type; MFs may also have a nephropathogenic effect.

Animals↗
PubMed2000

Cardiovascular remodeling, apoptosis, and drugs.

Apoptosis, a form of programmed cell death, mediates the controlled deletion of so-called "unwanted" cells. This review deals with the key features of this cell death program, showing that apoptosis is regulated by factors extrinsic and intrinsic to the dying cell. The elucidation of the possible interactions between these factors may be of major interest in preventing the progression to cardiovascular remodeling in patients with hypertensive disease. New pathways of research are emerging for drugs, such as beta-blockers, ACE inhibitors, the calcium-antagonists, and the receptor antagonist of angiotensin II, all of which have beneficial effects on cardiovascular remodeling. This may be due to the direct effect of these drugs on the cell proliferation/apoptosis balance.

Adrenergic beta-Antagonists↗
PubMed2000

Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are established drugs for the treatment of hypercholesterolemia, but several studies have shown that benefits obtained with these drugs are not causally related only to regression of cholesterol lowering. Moreover, in experimental models of progressive renal disease, statins have reduced the extent of glomerulosclerosis. This study evaluated the antiproteinuric effect of a daily dose of 40 mg fluvastatin for 6 months in moderately proteinuric patients with immunoglobulin A nephropathy, stable renal function, and no indicators of poor long-term prognosis. The effects of therapy were evaluated on the basis of 24-hour proteinuria (total proteinuria and albuminuria), albuminemia, creatinine clearance, cholesterol, and triglyceride values. Renal function remained stable in all patients. A significant decrease in proteinuria was observed after 6 months of therapy and persisted for all the observations. An increase in serum albumin was observed after 6 months of therapy. This study suggests that there is an antiproteinuric effect of HMG-CoA reductase inhibitors in moderately proteinuric patients with immunoglobulin A nephropathy.

Adult↗
PubMed2000

Water immersion increases urinary excretion of aquaporin-2 in healthy humans.

Many previous studies have shown that aquaporin-2 (AQP2), the vasopressin-regulated water channel, is excreted in the urine and that the excretion increases in response to vasopressin. Moreover, recently a close correlation between AQP2 excretion in urine and kidney AQP2 expression has been demonstrated, showing that urinary excretion of AQP2 is a reliable indicator for AQP-2 function. As head-out water immersion causes an expansion in the central vascular volume equal to that induced by 2 liters of saline, without modifying plasma composition, we used immersion in water to evaluate if the response to acute expansion of the central vascular volume could involve vasporessin (AVP) and AQP2. In healthy subjects, concentrations of plasma atrial natriuretic factor (ANF) and AVP, and urinary AQP2 were measured during a 2-hour immersion period. In all subjects, immersion caused a prompt and marked increase in immunoreactive ANF (23.0 +/- 2.12 pg/ml at second hour vs. 2.17 +/- 0.42 pg/ml at baseline) and in urinary excretion of AQP2 (23.9 +/- 2. 69 pmol/mg creatinine at second hour vs. 4.42 +/- 0.14 pmol/mg creatinine at baseline), while a significant decrease was found in plasma AVP. Recovery was associated with a prompt return to pre-study levels. These findings demonstrate that heat-out water immersion stimulates urinary excretion of AQP2 in absence of an increase in plasma AVP.

Adult↗
PubMed1999

Pro-apoptotic effect of fluvastatin on human smooth muscle cells.

The antiatherosclerotic effect of statins has been attributed to their hypocholesterolemic action. We therefore evaluated the effect, in vitro, of the addition of the serum of patients taking fluvastatin on human smooth muscle cells in order to ascertain the effect of the drug on cell proliferation and apoptosis. We found that the addition of serum from patients treated with fluvastatin for 6 days caused a significant reduction in cell proliferation, increased cell apoptosis and reduced the B cell leukemia-2 (bcl-2) concentration. It is concluded that the induction of apoptosis by statins could be a supplementary mechanism in the prevention of atherosclerotic lesions in humans.

Adult↗
PubMed1999

Reduced bcl-2 concentrations in hypertensive patients after lisinopril or nifedipine administration.

In 30 patients with essential hypertension and 30 healthy control subjects, we evaluated blood concentrations of B cell leukemia-2 (bcl-2), a protooncogene that can reduce apoptosis. Bcl-2 concentrations were higher in hypertensive than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood bcl-2 concentrations, in both hypertensive and normotensive subjects. Treatment of hypertensive patients with hypotensive drugs caused a reduction in bcl-2 concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of bcl-2 are increased in patients with hypertension, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing bcl-2 concentrations, with potentially beneficial effects on vascular modifications in patients with hypertension.

Administration, Oral↗
PubMed1990

Response to intermediate and standard doses of IFN-beta in hairy-cell leukaemia.

Thirteen hairy-cell leukaemia patients were treated with IFN-beta (6 X 10(6) IU/m2) for 7 days, alternate weeks, for three cycles. IFN-beta was then continued at the same dose twice a week for 24 weeks. Treatment was discontinued in 2 non-responders and 2 partial responders (1 haem PR, 1 path PR) because of complications unrelated to IFN. The objective response in the nine patients who completed therapy was 66% (1 CR, 3 path PR and 2 haem PR); 2 patients achieved MR. Responses lasted from 5 to 45+ months. Four newly diagnosed patients and 3 in relapse after discontinuation of IFN-beta therapy (6 X 10(6) IU/m2), were treated with a lower dose of IFN-beta (2 X 10(6) IU/m2). The objective response to this dose was 57% (3 path PR, 1 haem PR). Another patient obtained MR. No patient has relapsed 6-12 months after therapy discontinuation. IFN-beta was well tolerated, especially at the lower dose and no chronic toxicity was observed. Therefore IFN-beta may be suggested as an alternative treatment for HCL.

Adult↗
PubMed1990

Electrophysiological and neuropsychological functions in patients treated with interferon-beta.

The neurotoxicity of interferon-beta (IFN-beta) was assessed by performing electrophysiological examinations and neuropsychological tests on 22 patients with malignant hematological diseases before, during, and after IFN-beta treatment. IFN-beta (6 x 10(6) IU/m2) was infused i.v. for 6 h daily for 7 days on alternate weeks for a total of three cycles (induction therapy) and was then continued at the same dose, twice a week, for an additional 24 weeks (maintenance therapy). Twenty-one of the 22 patients were evaluable. There were no significant changes in EEGs, visual evoked potentials, sensory conduction central time or motor nerve conduction velocity of two long nerves in the 15-19 patients studied before and after induction therapy, nor in the 6-8 patients investigated at the end of maintenance therapy. Neuropsychological monitoring failed to disclose any IFN-induced deterioration in 21 patients tested before and at the end of induction therapy or in the 10 patients who were also studied at the end of maintenance therapy. Despite certain limitations in the patient follow-up, the results underline the good general tolerance of IFN-beta.

Adult↗
PubMed1989

Modulation of NK activity by thymic hormones: in vitro effects of thymostimulin.

Plastic-adherent depleted or not depleted peripheral mononuclear blood cells (PMBC) from healthy donors showed enhanced lytic activity against 51Cr-labelled K562 target cells when exposed to thymostimulin (TS), 1 microgram ml-1, for 3 h, washed and incubated in TS-free medium before testing for natural killer (NK) cytotoxicity. No modification of NK cell activity was seen when effector cells were treated with placebo (splenic extract). The NK boosting activity of TS was lost when effector cells were treated for 3 h immediately before the performance of the cytotoxic test or when this thymic extract was added directly to the mixture of effector and target cells during the lytic phase of 51Cr release assay.

Cell Survival↗
PubMed1989

A phase I study of human natural interferon-beta in cancer patients.

In this phase I study 15 patients with metastatic tumors were given interferon (IFN)-beta by i.v. bolus injections. Twelve individual doses of 1, 2, 3.3, 5, 7, 9, 12, 16, 21, 27, 35, and 46 x 10(6) IU were administered every other day. The single maximal tolerated dose ranged from 9 to 46 x 10(6) IU. Eight patients tolerated the dose of 46 x 10(6) IU without side effects. Disturbances of cardiac rhythm were observed, but were closely related temporally to severe chills and appeared to be the consequence of adrenergic stimulation associated with this side-effect. In addition, no significant variations in the left ventricular function as assessed by nuclear stethoscope were observed. Neurotoxicity was not a major side-effect. The toxicity of IFN-beta given as scheduled in this study was significant, but acceptable.

Adult↗
PubMed1988

A randomized trial to evaluate the immunorestorative properties of thymostimulin in patients with Hodgkin's disease in complete remission.

A total of 19 Hodgkin's disease (HD) patients (12 male, 7 female) aged 26-67 years, who had been in complete unmaintained remission for 6 months or more when the study was initiated, were randomly given 50 mg thymostimulin (TS) i.m. daily (G1) or every other day (G2) for 35 days. A third group (G3) was not treated. Then TS, at the same dose was administered twice a week for the following 22 weeks in patients both initially receiving loading or intermittent TS treatment. When compared with age- and sex-matched controls, as a group, the patients' circulating OKT3+, OKT4+, OKT11+ and E-AETR+ cells were depressed (P less than 0.001 for both proportions and absolute numbers), whereas their OKT8+ cell population was not. Following 5 weeks of daily TS administration, the proportions and numbers of all T cell fractions significantly increased in G1 patients (P less than 0.03 for all the comparisons tested), while following intermittent TS treatment (G2) only the proportions of OKT3+ and OKT11+ cells (P less than 0.03), but not of other T cell fractions, significantly increased. In addition, no significant changes in the absolute numbers of T cell fractions were observed in this group of patients. Furthermore, no spontaneous variations in the T cell pool size occurred in untreated patients. TS maintenance therapy did not produce any further improvement in the size of overall T cells and T cell subsets but sustained percentage and absolute numbers of these cells during administration and the absolute number of T cells even after discontinuation of therapy. The TS-induced improvement in the T cell pool was not associated with any change in the size of circulating non-T lymphocytes and monocytes. In vitro phytohemagglutinin-induced interleukin-2 (IL-2) and gamma-interferon (IFN-gamma) synthesis was assessed in 11 patients (3 G1, 4 G2, and 4 G3). Although it was not statistically significant, a rise in IL-2 and IFN-gamma production was observed in TS-treated patients, but not in untreated controls. TS failed to exert any effect on the serum circulating levels of neopterin, type I and II IFN, beta-2 microglobulin (B2-M) and immunoglobulins (Ig). TS can thus improve defective T cell frequences and numbers and may modulate IL-2 and IFN-gamma production.

Adjuvants, Immunologic↗
PubMed1988

Biochemical host response to interferon-beta.

To assess influence of host response to interferon-beta (IFN-beta), on biochemical parameters, beta 2-microglobulin (beta 2-M) and neopterin were evaluated in 15 and 12 patients respectively before and 24 h after 1-46 X 10(6) IU intravenously (i.v.) IFN-beta given every other day. In 4 additional patients, both molecules were determined before and after 24, 48, 72, and 96 h of weekly IFN-beta injections. Serum beta2-M levels significantly increased 24 h after IFN-beta administration in the overall group of 15 patients treated with the alternate day schedule (p = 0.003) as well as in the group of patients treated with the weekly schedule (p = 0.00003). Maximum induction of beta 2-M was observed 24 h after a single weekly IFN-beta injection, but the levels of this protein 72 h after still remained significantly higher than baseline values (p = 0.001). This demonstrates the progressive accumulation of beta 2-M in the circulation produced by the continuous IFN administration. Nevertheless, in patients treated with both IFN treatment schedules, a clear correlation between the increments of beta 2-M and the IFN-beta doses was observed (p = 0.00002 and p = 0.0016 for the alternate day and the weekly schedule respectively). Furthermore the under curve area (AUC) of 48 h beta 2-M levels after IFN administration significantly rose (p less than 0.05) with increasing IFN doses in 4/6 patients. In spite of the accumulation of beta 2-M in the circulation, the overall serum values of this protein 24 h after each successive IFN-injection, in the 15 patients receiving the alternate-day treatment, were significantly higher than before the immediate preceding dose both in patients with initially normal and those with initially high base levels (p = 0.00055 and p = 0.011, respectively). As with beta 2-M, neopterin levels significantly rose during IFN treatment (p less than 0.05) in the group of patients as a whole. After single weekly IFN-beta injections, maximum induction of neopterin was observed 24 h after administration, then the levels of this molecule slowly declined towards the baseline levels, but 96 h after, its levels were still significantly elevated (p less than 0.00001). Neopterin induction was not related to IFN-beta doses, but the levels of this molecule both before and after IFN administration were correlated with an increase in the number of IFN injections (p = 0.0006 and p = 0.0009, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗