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Biomedical subjects

N Frisina

Publications and source records attributed to N Frisina.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cardiovascular effects of raloxifene hydrochloride.

Raloxifene hydrochloride binds to the estrogen receptor and shows tissue-selective effects; thus, it belongs to a class of drugs recently described as selective estrogen receptor modulators (SERMs). Tissue selectivity of raloxifene may be achieved through several mechanisms: the ligand structure, interaction of the ligand with different receptor subtypes in various tissues, and intracellular events after ligand binding. Raloxifene has estrogen-agonist effects on bone and lipids and estrogen antagonist effects on the breast and uterus. In addition to its well established effects on osteoporosis, recent preclinical and clinical findings suggest that raloxifene also possesses beneficial effects on the cardiovascular system. These findings indicated that raloxifene may have cardioprotective properties without an increased risk of cancer or other side effects. Raloxifene has been shown to reduce total and low-density lipoprotein cholesterol concentrations in plasma, an effect similar to that produced by estrogens. Unlike estrogens, however, raloxifene does not increase high-density lipoprotein cholesterol and triglyceride levels in plasma. Endothelium is thought to play an important role in the genesis of atherosclerosis. Several lines of evidence suggest that an intervention with endothelial function might influence the progression of coronary disease and the incidence of cardiovascular events. Raloxifene increases the nitric oxide/endothelin-1 ratio, and improves endothelium-dependent vasomotion in post-menopausal women to the same extent as estrogens. Furthermore, in two randomized trials on post-menopausal women raloxifene reduced homocysteine levels, another independent risk factor for the development of cardiovascular disease. Although estrogens remain the drugs of choice in the hormonal therapy of most postmenopausal women, raloxifene may represent and alternative in women who are at risk of coronary artery disease.

Animals↗
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↗
PubMed2001

Urinary excretion of aquaporin-2 water channel during pregnancy.

BACKGROUND: In healthy primiparas the total body water content increases by about 8 liters within the last trimester, with a consequent reduction in plasma arginine-vasopressin (AVP) levels. The aim of the present study was to investigate the effect of normal pregnancy on urinary excretion of AQP2, a vasopressin sensitive water channel. METHODS: Forty-five healthy pregnant primiparas (specify mean age and range) with a physiological single-fetus pregnancy were studied during weeks 12, 24 and 36 of pregnancy and then for 3 to 5 days postpartum. The control group consisted of 14 age-matched women in the early follicular phase of the menstrual cycle (day 5 or 6). The behavior of plasma AVP, ANP, oxytocin, urinary 6-keto-PGF1alpha (a metabolite of prostacyclin) and urinary AQP-2 excretion were evaluated in all subjects. RESULTS: Plasma ANP and oxytocin, and urinary AQP-2 and 6kPGF1alpha excretion increased during all three trimesters, with the highest peaks at the 36(th) week. In the postpartum period, these values markedly decreased. No statistically significant changes were found in plasma AVP levels throughout the study period. CONCLUSIONS: Our findings suggest that a non-AVP factor present in pregnancy plays a role in the control of the excretion of AQP-2 water channels.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma no concentrations, endothelin-1 levels, and endothelium-dependent vasodilation in postmenopausal women.

The endothelium is thought to play an important role in the genesis of atherosclerosis, and several lines of evidence suggest that the effect of an intervention on endothelial function might predict its involvement in coronary disease progression and in the rate of cardiovascular events. Estrogen has direct effects on the blood vessel wall, indicating that vascular endothelium may play a key role in the cardiovascular protective effects of hormone replacement therapy (HRT). Raloxifene relaxes coronary arteries in vitro by an estrogen receptor-dependent and NO-dependent mechanism, thus suggesting that this selective estrogen receptor modulator could also have beneficial effects on endothelial function. This study compared the effects of HRT and raloxifene on NO products, endothelin-1 plasma levels, and endothelium-dependent vasodilatation in postmenopausal women. Healthy postmenopausal women (n=90) were enrolled in a double-blind, randomized, placebo-controlled, 6-month trial. Women were randomly assigned to receive continuous HRT (1 mg 17beta-estradiol combined with 0.5 mg norethisterone acetate), raloxifene (60 mg/d), or placebo for 6 months. Flow-mediated endothelium-dependent vasodilation of the brachial artery, plasma NO concentrations, and endothelin levels were measured at baseline and after 6 months of therapy. The mean baseline level of NO breakdown products was 26.5+/-10.7 micromol/L and increased to 36.3+/-11.4 micromol/L after 6 months of treatment with raloxifene. The mean baseline plasma endothelin level was 17.3+/-8.9 pg/mL and decreased to 11.5+/-2.1 pg/mL after 6 months of treatment with the selective estrogen receptor modulator. The mean baseline ratio of NO (breakdown products) to endothelin was also significantly increased at the end of treatment with raloxifene. Postmenopausal women treated with HRT had similar changes in plasma nitrites/nitrates and endothelin levels as well as in the ratio of NO to endothelin. In contrast, these markers of endothelial function did not change in the placebo-treated women. Flow-mediated endothelium-dependent vasodilation of the brachial artery was 8.3+/-2.1% at baseline and increased to 12.3+/-2.1% after 6 months of treatment with raloxifene. HRT also caused a significant and similar increase in flow-mediated endothelium-dependent vasodilation. No change in flow-mediated vasodilation was observed in the participants treated with placebo. We conclude that raloxifene therapy and HRT influence endothelial function and improve flow-mediated endothelium-dependent vasodilation to a comparable extent in healthy postmenopausal women at least after a 6-month treatment period. However, further investigation is warranted to enhance our understanding of the mechanisms of the effect of raloxifene on vascular function and to determine whether its effect on endothelial function may contribute to the reduction in cardiovascular-related morbidity and mortality.

Aged↗
PubMed2001

Metabolic effects of dehydroepiandrosterone replacement therapy in postmenopausal women.

OBJECTIVE: To investigate whether long-term treatment with dehydroepiandrosterone (DHEA) in postmenopausal women can modify insulin sensitivity and plasma lipid profile. DESIGN AND METHODS: Twenty healthy postmenopausal women with serum dehydroepiandrosterone sulfate (DHEA-S) concentrations <2.5 micromol/l were enrolled and randomly assigned to two different treatment groups: group 1 were treated with micronized DHEA, 25 mg/day at 0800 h for 12 months; group 2 were treated with an identical placebo tablet. At the beginning and at the end of the study, plasma lipid profile, glucose tolerance (oral glucose tolerance test) and insulin sensitivity (euglycemic hyperinsulinemic clamp: M index) were assessed. RESULTS: After 12 months, the group treated with DHEA showed a considerable improvement of insulin sensitivity (M index +29.55%, P=0.01) and lipid pattern (high-density lipoprotein cholesterol +11.61%, P=0.03; low-density lipoprotein cholesterol -11.07%, P=0.04; triglycerides -19.60%, P=0.03), but glucose tolerance did not change. No modifications were observed in the placebo group. CONCLUSIONS: Long-term treatment with DHEA ameliorates some metabolic parameters that are linked to increased cardiovascular risk and, consequently, this seems to be an interesting therapeutic tool in the management of the postmenopausal syndrome.

Dehydroepiandrosterone↗
PubMed2000

Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation.

Erythropoietin prevents in vitro glutamate-induced neuronal death and could play a role in the central nervous system. We investigated the in vivo effects of recombinant human erythropoietin after intraperitoneal (i.p.; 25-100 U) or intracerebroventricular (i.c.v.; 0.25-25 U) administration on survival, brain malonildialdehyde (MDA) levels, brain edema, hippocampal neuronal death and brain nitric oxide (NO) synthesis after bilateral carotid occlusion (5 min), followed by reperfusion in the Mongolian gerbil. Peripheral posttreatment with recombinant human erythropoietin reduced postischemic MDA levels, brain edema and increased survival. Either peripheral or i.c.v. posttreatment with recombinant human erythropoietin significantly reduced hippocampal CA1 neuronal loss, observed 7 days after the ischemic event. Increase of nitrite and nitrate (as an index of NO formation) in the hippocampus, as observed after ischemia, was reduced in animals treated with recombinant human erythropoietin. These data suggest that in vivo recombinant human erythropoietin effects on brain ischemic injury could be due to inhibition of NO overproduction.

Aldehydes↗
PubMed2000

In vivo evidence that erythropoietin has a neuroprotective effect during subarachnoid hemorrhage.

To ascertain in vivo whether recombinant human erythropoietin has a neuroprotective effect on the cortex during subarachnoid hemorrhage, 56 rabbits were divided into the following groups: Group 1 control sham operated plus placebo (n=14; saline solution - NaCl 0.9%); Group 2 control sham operated plus recombinant human erythropoietin (n=14); Group 3 subarachnoid hemorrhage plus placebo (n=14); Group 4 subarachnoid hemorrhage plus recombinant human erythropoietin (n=14; intraperitoneal administration of recombinant human erythropoietin immediately after inducing subarachnoid hemorrhage). In none of the Groups 1 and 2 animals was subarachnoid hemorrhage induced. In Group 3 rabbits, an increase in locomotor activity (open field apparatus) was observed 24, 48 and 72 h after surgery, and the mortality rate was 42.9% within 72 h after surgery, and, no increase in locomotor activity was observed in Group 4 rabbits, which survived for at least 72 h. Our findings suggest that recombinant human erythropoietin may be of benefit in the treatment of subarachnoid hemorrhage.

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

Effects of lisinopril administration on blood bcl-2 concentrations in patients with immunoglobulin A nephropathy.

We evaluated blood concentrations of bcl-2, a proto-oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl-2 were higher in patients with proteinuria than in those without proteinuria. A 6-month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl-2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl-2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin-converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.

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↗
PubMed1999

Does captopril have a direct pro-apoptotic effect?

The beneficial effect of ACE inhibitors on cardiovascular remodelling from hypertension and ischemic disease may be due to the effect of these drugs on the proliferation/cell death balance. We therefore investigated the effect of the addition of captopril in vitro, on the onset of apoptosis in human vascular myocytes, by using a propidium iodide fluorescence analysis and a morphological analysis using the acridine orange technique. Captopril (0.23 mM) caused an increase in apoptotic phenomena that was more than 3. 5-fold than in controls both at the 24th (7.7 vs. 2%) and the 48th h (10.1 vs. 3.8%). The addition of propranolol strengthened the effect on apoptosis. The induction of apoptotic phenomena may be a mechanism by which ACE inhibitors affect cardiovascular remodelling and it might also explain the favorable effect these drugs have on diseases such as IgA nephropathy and diabetic nephropathy.

Adrenergic beta-Antagonists↗