Enrica Cecchi - Academia.edu (original) (raw)

Papers by Enrica Cecchi

Clinical Pharmacology & Therapeutics, 1995

To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742... more To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742 hospitalized patients taking nitrates were studied during their hospital stay. Those patients with admission serum creatinine levels from 97 to 133 mumol/L and > 133 mumol/L were compared with patients with creatinine levels < 97 mumol/L. Gender, body mass index, comorbidity, cognitive status, new intake of nitrates, number of daily administrations, and daily dosage, as well as intake of angiotensin converting enzyme inhibitors, calcium antagonists, diuretics and nonsteroidal anti-inflammatory drugs were examined as possible confounders. Fifty-six patients had headaches that had a causal link with intake of nitrates. Compared with the lowest creatinine group, after adjustment for potential confounding variables, the odds ratios and 95% confidence interval (95% CI) for headache caused by nitrates associated with increasing serum creatinine levels were 0.6 (95% CI, 0.3 to 1.1) and 0.2 (95% CI, 0.0 to 1.2), respectively (p for trend = 0.013). Increasing age was inversely associated with headache (odds ratio for 10-year increase, 0.6 [95% CI, 0.5 to 0.7]). Serum creatinine and age were independently and inversely associated with headache caused by nitrates.

Pharmacological Research, 2000

Calcium channel blockers and ACE-inhibitors are among the most common drugs prescribed for the in... more Calcium channel blockers and ACE-inhibitors are among the most common drugs prescribed for the initial treatment of hypertension. While their ability to control surrogate outcomes, such as blood pressure and left ventricular hypertrophy, is proven, there is limited evidence of their prevention of major cardiovascular events, including mortality. The aim of our work was to assess the use of these drugs in Italy in comparison with beta-blockers and diuretics. We examined the consumption of the four main antihyperten-Ž sive classes of drugs beta-blockers, diuretics, calcium channel blockers and ACE-. Ž inhibitors . In-hospitalization data from the GIFA Gruppo Italiano di Farmacoepidemiolo-. gia nell'Anziano database were used. During the period from 1988 to 1995, the most Ž . frequently prescribed antihypertensive drugs were calcium channel blockers 47% followed Ž . Ž . Ž . by diuretics 37% , ACE-inhibitors 33% and beta-blockers 5.5% . Changes over time in the use of these drugs were analysed: ACE-inhibitors had the greatest increase in use over time. Calcium channel blockers, ACE-inhibitors and beta-blockers were usually prescribed Ž . to the youngest patients aged -65 years , while diuretics to the oldest. Calcium channel blockers were prescribed to 60% of patients with myocardial infarction and to 55% of those with congestive heart failure. In conclusion, our study demonstrates that the Italian physicians very often prescribe drugs like calcium channel blockers and ACE-inhibitors.

Emergency Medicine Australasia, 2004

A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and... more A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and fainting. A blood analysis revealed high levels of serum amylase and lipase, confirming a diagnosis of acute pancreatitis. The history showed that the patient had self-administered a single dose of pegylated interferon alfa-2b and ribavirin daily for 7 days for chronic hepatitis C. The medications were stopped and his condition gradually improved. In agreement with the literature and the Naranjo algorythm result, pegylated interferon alfa-2b is associated with acute pancreatitis. Identification of a few signs and symptoms is the first 'signal' in preventing a serious drug-induced adverse event.

British Journal of Pharmacology, 1993

1 In Fura-2 preloaded human platelets, the increase in cytosolic calcium induced by a-thrombin wa... more 1 In Fura-2 preloaded human platelets, the increase in cytosolic calcium induced by a-thrombin was reduced by some L-and D-arginine ester compounds the IC50 (#uM) values of which were 7.4 for TAEE, 56.9 for BAEE, 77.6 for TAME, 560 for T(d)AME, 656.3 for L-ArgOMe and 2206.7 for D-ArgOMe.

Gastroenterology, Jan 7, 1993

Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at leas... more Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at least in part, on intrinsic platelet abnormalities. The aim of this study was to evaluate the activating and inhibitory pathways of platelet signal transduction in cirrhotic patients. Twelve cirrhotic patients and 12 control subjects participated in this study. Measurements were performed on washed platelets. Thrombin-stimulated inositol 1,4,5-trisphosphate production was reduced fivefold, and the increase in cytosolic calcium concentration was significantly lower in platelets from cirrhotic patients following stimulation with thrombin, platelet activating factor, or U-46619. In addition, the activity of the platelet Na+/H+ antiporter, evaluated after an acid load, was significantly lower in platelets from cirrhotic patients (0.90 +/- 0.19 vs. 1.37 +/- 0.16 delta pHi/min, P = 0.07). Cirrhotic patients also showed a significantly increased basal intraplatelet content of both 5'-cyclic adenosine monophosphate (cAMP) (2724 +/- 330 vs. 1561 +/- 258 fmol/10(8) platelets, P < 0.05) and 5'-cyclic guanosine monophosphate (cGMP) (217 +/- 18 vs. 159 +/- 29 fmol/10(8) platelets, P < 0.05). Our results indicate that in platelets from cirrhotic patients, defective early signal transduction is associated with an increase in platelet cAMP and cGMP, thus revealing new mechanisms contributing to the defective platelet function in this disease.

Gastroenterology, 1993

Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at leas... more Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at least in part, on intrinsic platelet abnormalities. The aim of this study was to evaluate the activating and inhibitory pathways of platelet signal transduction in cirrhotic patients. Twelve cirrhotic patients and 12 control subjects participated in this study. Measurements were performed on washed platelets. Thrombin-stimulated inositol 1,4,5-trisphosphate production was reduced fivefold, and the increase in cytosolic calcium concentration was significantly lower in platelets from cirrhotic patients following stimulation with thrombin, platelet activating factor, or U-46619. In addition, the activity of the platelet Na+/H+ antiporter, evaluated after an acid load, was significantly lower in platelets from cirrhotic patients (0.90 +/- 0.19 vs. 1.37 +/- 0.16 delta pHi/min, P = 0.07). Cirrhotic patients also showed a significantly increased basal intraplatelet content of both 5'-cyclic ade...

Clinical Pharmacology & Therapeutics, 1995

To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742... more To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742 hospitalized patients taking nitrates were studied during their hospital stay. Those patients with admission serum creatinine levels from 97 to 133 mumol/L and > 133 mumol/L were compared with patients with creatinine levels < 97 mumol/L. Gender, body mass index, comorbidity, cognitive status, new intake of nitrates, number of daily administrations, and daily dosage, as well as intake of angiotensin converting enzyme inhibitors, calcium antagonists, diuretics and nonsteroidal anti-inflammatory drugs were examined as possible confounders. Fifty-six patients had headaches that had a causal link with intake of nitrates. Compared with the lowest creatinine group, after adjustment for potential confounding variables, the odds ratios and 95% confidence interval (95% CI) for headache caused by nitrates associated with increasing serum creatinine levels were 0.6 (95% CI, 0.3 to 1.1) and 0.2 (95% CI, 0.0 to 1.2), respectively (p for trend = 0.013). Increasing age was inversely associated with headache (odds ratio for 10-year increase, 0.6 [95% CI, 0.5 to 0.7]). Serum creatinine and age were independently and inversely associated with headache caused by nitrates.

Journal of Clinical Pharmacy and Therapeutics, 2009

We report a case of increase in serum tumour markers CA 125 and CA 19AE9 induced by cyclic combin... more We report a case of increase in serum tumour markers CA 125 and CA 19AE9 induced by cyclic combined hormone replacement therapy (HRT). A 52-year-old Caucasian post-menopausal woman presented with a slight enlargement of the right ovary and uterine fibromyomatosis. She was taking HRT for 4 years in a cyclic combined regimen of 2 mg oestradiol with 1 mg cyproterone acetate. The serum tumour markers occasionally measured were in normal range except CA 19AE9 (997 U ⁄ mL; normal values 0AE0-37) and CA 125 (85 U ⁄ mL; normal values 0AE0-35). However, on one occasion, the CA 19AE9 and CA 125 were high and then showed persistently high values (1005 and 81AE3 U ⁄ mL, respectively). Radiodiagnostic investigations excluded any malignancies and a hysteroscopy showed endometrial thickening. After discontinuation of HRT, CA 125 levels returned to normal after 1 month, whereas CA 19AE9 took 6 months to do so. Four months after the beginning subsequent therapy with over-thecounter phyto-oestrogens a new serum test showed an increase in CA 19AE9 but CA 125 remained within the normal range. Phyto-oestrogen therapy was then interrupted and 1 month later CA 19AE9 returned to normal. In this case, cyclic HRT was the probable cause of CA 19AE9 and CA 125 increase. Positive dechallenge and subsequent CA 19AE9 increase after phyto-oestrogen intake seem to confirm the role of oestrogens as the cause of the endometrial thickening through hormonal imbalance. Increased CA 19AE9 and CA 125 levels in benign gynaecological conditions may be a source of misdiagnosis of malignant disease.

European Journal of Nutrition, 2005

■ Summary Background Plasma accumulation of asymmetric dimethyl arginine (ADMA), is considered as... more ■ Summary Background Plasma accumulation of asymmetric dimethyl arginine (ADMA), is considered as a risk factor for endothelial dysfunction and a strong predictor for coronary heart diseases. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) increasing

European Journal of Integrative Medicine, 2012

European Journal of Clinical Pharmacology, 2008

Background More than 380,000 angiographic procedures are performed every year in Italian hospital... more Background More than 380,000 angiographic procedures are performed every year in Italian hospitals, with an increase rate of 8% per year. Although contrast media (CM) are considered relatively safe, adverse drug reactions (ADRs) remain an important issue.

Cardiovascular Drugs and Therapy, 1995

We studied the interaction between the synthetic prostacyclin analog iloprost and the aggregating... more We studied the interaction between the synthetic prostacyclin analog iloprost and the aggregating agent athrombin by measuring the internal calcium ion concentration ([Ca2+]i) of human fura-2-1oaded platelets. Iloprost (0.003-100 }xg/l) did not modify the resting calcium level; when added 2 minutes before exposure of the platelets to a submaximally active concentration of c~-thrombin (10 U/l), iloprost dose-dependently antagonized the increase in [Ca2+]i. To evaluate if iloprost retained this antagonistic effect even after a prolonged contact, which is well known to cause a "desensitization" phenomenon, platelets were preincubated with iloprost (35 pLg/l) for 3 hours. After washout, the effect of newly added iloprost (0.01-100 p~g/l) on the oLthrombin-induced increase in [Ca2+]i was tested. Iloprost was still able to antagonize the increase in [Ca2+]i induced by c~-thrombin in "desensitized" platelets; however, the doseinhibitory response curve was significantly shifted to the right when compared with that obtained in control platelets (i.e., platelets preincubated for 3 hours with iloprost's solvent), and the resulting IC50 was significantly higher: 1.78 versus 0.2 Ixg/l (p < 0.001). Since the maximal inhibitory effect of iloprost could also be reached under these experimental conditions, we conclude that iloprost retains its ability to antagonize the increase in [Ca2+]i induced by ~thrombin in desensitized platelets.

British Journal of Pharmacology, 2000

1 While the expression and/or activity of endothelial nitric oxide synthase (eNOS) has been chara... more 1 While the expression and/or activity of endothelial nitric oxide synthase (eNOS) has been characterized in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rat (WKY) hearts, in coronary endothelial cells (ECs) from both strains, the eect of NO on intracellular calcium concentration ([Ca 2+ ] i ) is still unknown. 2 Coronary microvascular ECs were isolated from SHR and WKY and characterized. Immunocytochemistry and Western blot analysis showed that eNOS was similarly expressed in ECs from both strains. 3 Measuring [Ca 2+ ] i by imaging analysis of fura-2-loaded cells, we demonstrated that a-thrombin (37180 U l 71 ) induced a superimposable dose-dependent calcium transient in ECs from both strains. 4 In WKY ECs, S-nitroso-N-acetyl-DL-penicillamine (SNAP) dose-dependently (10 ± 100 mM) and 0.1 mM atrial natriuretic factor (ANF) reduced the maximum and the decay time of a-thrombininduced calcium transient. The inhibitory eects of SNAP and ANF were prevented by blocking cyclic GMP-dependent protein kinase. Non selective eNOS inhibitors prolonged the decay time of athrombin-induced calcium transient, while the selective inducible NOS inhibitor 1400 W was ineective. SNAP (100 mM) and 0.1 mM ANF increased cyclic GMP content up to 22.9 and 42.3 fold respectively. 5 In SHR ECs, a-thrombin-induced calcium transient was not modi®ed by SNAP, ANF or eNOS inhibition. SNAP (100 mM) and 0.1 mM ANF increased cyclic GMP content up to 9.3 and 51 fold respectively. 6 In WKY ECs, SNAP dose-dependently (10 ± 100 mM) reduced also bradykinin-induced calcium transient, while in SHR ECs was ineective. 7 We concluded that in SHR ECs, the cyclic GMP-dependent regulation of calcium transient is lost.

British Journal of Pharmacology, 1998

1 The eect of the NSAIDs indomethacin, indoprofen, diclofenac and acetylsalicylic acid on the inc... more 1 The eect of the NSAIDs indomethacin, indoprofen, diclofenac and acetylsalicylic acid on the increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) induced by nitric oxide-donor agents was tested in human whole platelets and in platelet crude homogenate. 2 In whole platelets, indomethacin reduced the increase in cyclic GMP induced by the nitric oxidedonors (NO-donors) sodium nitroprusside (NaNP) and S-nitroso-N-acetylpenicillamine (SNAP) in a dose-dependent way, its IC 50 being 13.7 mM and 15.8 mM, respectively. 3 Of the other cyclooxygenase inhibitors tested, only indoprofen reduced the increase in cyclic GMP induced by both NO-donors in a dose-dependent way (IC 50 =32.7 mM, NaNP and 25.0 mM, SNAP), while acetylsalicylic acid (up to 1000 mM) and diclofenac (up to 100 mM) were ineective. 4 However, in platelet crude homogenate neither indomethacin nor indoprofen reduced the cyclic GMP production. 5 Indomethacin (10 mM), indoprofen (30 mM), diclofenac (100 mM) and acetylsalicylic acid (1000 mM) showed a comparable ecacy in inhibiting platelet thromboxane B 2 (TXB 2 ) production, suggesting that the inhibitory eect of indomethacin and indoprofen on the increase in cyclic GMP induced by both NO-donors was not mediated by inhibition of cyclooxygenase. 6 In vitro, the NSAIDs analysed did not interfere with nitrite production of SNAP. 7 The unhomogeneous behaviour of NSAIDs on the increase in cyclic GMP induced by NO-donors in whole platelets may contribute to the dierent pharmacological and toxicological characteristics of the drugs, providing new knowledge on the eect of indomethacin and indoprofen.

To explore pregnant women's use, attitudes, knowledge and beliefs of complementary and alternativ... more To explore pregnant women's use, attitudes, knowledge and beliefs of complementary and alternative drugs (CADs) defined as products manufactured from herbs or with a natural origin. A preliminary survey was conducted among 172 pregnant women in their third trimester of pregnancy, consecutively recruited in two obstetrical settings; 15 women were randomly selected to compute a test-to-retest analysis. Response rate was 87.2%. Test-to-retest analysis showed a questionnaire's reproducibility exceeding a K-value of 0.7 for all items. Mean age was 32.4 AE 0.4 years; most women were nulliparae (62.7%). The majority of subjects (68%) declared to have used one or more CADs during their lifetime; 48% of pregnant women reported taking at least one CAD previously and during the current pregnancy. Women's habitual use of CADs meant they were at higher risk of taking CADs also during pregnancy (adjusted odds ratio = 10.8; 95% confidence interval: 4.7-25.0). Moreover, 59.1% of the subjects were unable to correctly identify the type of CADs they were using. The majority of women resorted to gynecologists as the primary information source for CADs during pregnancy, while they mainly referred to herbalists when not pregnant. Habitual use of CADs seems to be a strong predictor for their ingestion also during pregnancy; in addition most subjects were unable to correctly identify the products they were taking. In the light of the scanty data concerning the safety of CADs during pregnancy, these preliminary results confirm the need to investigate thoroughly the situation of pregnant women and CADs consumption.

Drugs & Aging, 2005

Several studies have raised concerns over a possible reduction in the beneficial effects of ACE i... more Several studies have raised concerns over a possible reduction in the beneficial effects of ACE inhibitors on mortality in people also taking aspirin (acetylsalicylic acid). We performed this study to determine whether there is a reduction in the beneficial effects of ACE inhibitors on mortality in elderly people with heart failure also taking aspirin. 822 patients discharged from hospital wards with a diagnosis of heart failure participated in the GIFA (Italian Group of Pharmacoepidemiology in the Elderly) study. We analysed the characteristics of the participants according to the type of therapy prescribed (no ACE inhibitor/no aspirin, ACE inhibitor/no aspirin, no ACE inhibitor/aspirin and ACE inhibitor/aspirin). We calculated the hazard ratios (HRs) for dying associated with each of these treatments, and calculated the synergy index to identify any negative interaction between ACE inhibitor and aspirin. The mean age of study participants was 79 +/- 7.3 (SD) years. Of the 629 (76.5%) patients discharged on ACE inhibitor and/or aspirin therapy, 31.0% were taking both drugs. Compared with no therapy with ACE inhibitor or aspirin, the HR for death was 0.65 (95% CI 0.31, 1.36) for aspirin users, 0.45 (95% CI 0.27, 0.74) for ACE inhibitor users and 0.37 (95% CI 0.19, 0.70) for ACE inhibitor/aspirin users. The synergy index was 0.98 (95% CI 0.34, 2.80), suggesting no interaction between the drugs. Our data do not support the existence of a negative interaction between ACE inhibitors and aspirin in elderly patients with heart failure.

Clinical Pharmacology & Therapeutics, 1995

To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742... more To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742 hospitalized patients taking nitrates were studied during their hospital stay. Those patients with admission serum creatinine levels from 97 to 133 mumol/L and &amp;amp;gt; 133 mumol/L were compared with patients with creatinine levels &amp;amp;lt; 97 mumol/L. Gender, body mass index, comorbidity, cognitive status, new intake of nitrates, number of daily administrations, and daily dosage, as well as intake of angiotensin converting enzyme inhibitors, calcium antagonists, diuretics and nonsteroidal anti-inflammatory drugs were examined as possible confounders. Fifty-six patients had headaches that had a causal link with intake of nitrates. Compared with the lowest creatinine group, after adjustment for potential confounding variables, the odds ratios and 95% confidence interval (95% CI) for headache caused by nitrates associated with increasing serum creatinine levels were 0.6 (95% CI, 0.3 to 1.1) and 0.2 (95% CI, 0.0 to 1.2), respectively (p for trend = 0.013). Increasing age was inversely associated with headache (odds ratio for 10-year increase, 0.6 [95% CI, 0.5 to 0.7]). Serum creatinine and age were independently and inversely associated with headache caused by nitrates.

Pharmacological Research, 2000

Calcium channel blockers and ACE-inhibitors are among the most common drugs prescribed for the in... more Calcium channel blockers and ACE-inhibitors are among the most common drugs prescribed for the initial treatment of hypertension. While their ability to control surrogate outcomes, such as blood pressure and left ventricular hypertrophy, is proven, there is limited evidence of their prevention of major cardiovascular events, including mortality. The aim of our work was to assess the use of these drugs in Italy in comparison with beta-blockers and diuretics. We examined the consumption of the four main antihyperten-Ž sive classes of drugs beta-blockers, diuretics, calcium channel blockers and ACE-. Ž inhibitors . In-hospitalization data from the GIFA Gruppo Italiano di Farmacoepidemiolo-. gia nell'Anziano database were used. During the period from 1988 to 1995, the most Ž . frequently prescribed antihypertensive drugs were calcium channel blockers 47% followed Ž . Ž . Ž . by diuretics 37% , ACE-inhibitors 33% and beta-blockers 5.5% . Changes over time in the use of these drugs were analysed: ACE-inhibitors had the greatest increase in use over time. Calcium channel blockers, ACE-inhibitors and beta-blockers were usually prescribed Ž . to the youngest patients aged -65 years , while diuretics to the oldest. Calcium channel blockers were prescribed to 60% of patients with myocardial infarction and to 55% of those with congestive heart failure. In conclusion, our study demonstrates that the Italian physicians very often prescribe drugs like calcium channel blockers and ACE-inhibitors.

Emergency Medicine Australasia, 2004

A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and... more A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and fainting. A blood analysis revealed high levels of serum amylase and lipase, confirming a diagnosis of acute pancreatitis. The history showed that the patient had self-administered a single dose of pegylated interferon alfa-2b and ribavirin daily for 7 days for chronic hepatitis C. The medications were stopped and his condition gradually improved. In agreement with the literature and the Naranjo algorythm result, pegylated interferon alfa-2b is associated with acute pancreatitis. Identification of a few signs and symptoms is the first &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;signal&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; in preventing a serious drug-induced adverse event.

British Journal of Pharmacology, 1993

1 In Fura-2 preloaded human platelets, the increase in cytosolic calcium induced by a-thrombin wa... more 1 In Fura-2 preloaded human platelets, the increase in cytosolic calcium induced by a-thrombin was reduced by some L-and D-arginine ester compounds the IC50 (#uM) values of which were 7.4 for TAEE, 56.9 for BAEE, 77.6 for TAME, 560 for T(d)AME, 656.3 for L-ArgOMe and 2206.7 for D-ArgOMe.

Gastroenterology, Jan 7, 1993

Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at leas... more Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at least in part, on intrinsic platelet abnormalities. The aim of this study was to evaluate the activating and inhibitory pathways of platelet signal transduction in cirrhotic patients. Twelve cirrhotic patients and 12 control subjects participated in this study. Measurements were performed on washed platelets. Thrombin-stimulated inositol 1,4,5-trisphosphate production was reduced fivefold, and the increase in cytosolic calcium concentration was significantly lower in platelets from cirrhotic patients following stimulation with thrombin, platelet activating factor, or U-46619. In addition, the activity of the platelet Na+/H+ antiporter, evaluated after an acid load, was significantly lower in platelets from cirrhotic patients (0.90 +/- 0.19 vs. 1.37 +/- 0.16 delta pHi/min, P = 0.07). Cirrhotic patients also showed a significantly increased basal intraplatelet content of both 5&amp;amp;#39;-cyclic adenosine monophosphate (cAMP) (2724 +/- 330 vs. 1561 +/- 258 fmol/10(8) platelets, P &amp;amp;lt; 0.05) and 5&amp;amp;#39;-cyclic guanosine monophosphate (cGMP) (217 +/- 18 vs. 159 +/- 29 fmol/10(8) platelets, P &amp;amp;lt; 0.05). Our results indicate that in platelets from cirrhotic patients, defective early signal transduction is associated with an increase in platelet cAMP and cGMP, thus revealing new mechanisms contributing to the defective platelet function in this disease.

Gastroenterology, 1993

Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at leas... more Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at least in part, on intrinsic platelet abnormalities. The aim of this study was to evaluate the activating and inhibitory pathways of platelet signal transduction in cirrhotic patients. Twelve cirrhotic patients and 12 control subjects participated in this study. Measurements were performed on washed platelets. Thrombin-stimulated inositol 1,4,5-trisphosphate production was reduced fivefold, and the increase in cytosolic calcium concentration was significantly lower in platelets from cirrhotic patients following stimulation with thrombin, platelet activating factor, or U-46619. In addition, the activity of the platelet Na+/H+ antiporter, evaluated after an acid load, was significantly lower in platelets from cirrhotic patients (0.90 +/- 0.19 vs. 1.37 +/- 0.16 delta pHi/min, P = 0.07). Cirrhotic patients also showed a significantly increased basal intraplatelet content of both 5'-cyclic ade...

Clinical Pharmacology & Therapeutics, 1995

To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742... more To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742 hospitalized patients taking nitrates were studied during their hospital stay. Those patients with admission serum creatinine levels from 97 to 133 mumol/L and &amp;amp;gt; 133 mumol/L were compared with patients with creatinine levels &amp;amp;lt; 97 mumol/L. Gender, body mass index, comorbidity, cognitive status, new intake of nitrates, number of daily administrations, and daily dosage, as well as intake of angiotensin converting enzyme inhibitors, calcium antagonists, diuretics and nonsteroidal anti-inflammatory drugs were examined as possible confounders. Fifty-six patients had headaches that had a causal link with intake of nitrates. Compared with the lowest creatinine group, after adjustment for potential confounding variables, the odds ratios and 95% confidence interval (95% CI) for headache caused by nitrates associated with increasing serum creatinine levels were 0.6 (95% CI, 0.3 to 1.1) and 0.2 (95% CI, 0.0 to 1.2), respectively (p for trend = 0.013). Increasing age was inversely associated with headache (odds ratio for 10-year increase, 0.6 [95% CI, 0.5 to 0.7]). Serum creatinine and age were independently and inversely associated with headache caused by nitrates.

Journal of Clinical Pharmacy and Therapeutics, 2009

We report a case of increase in serum tumour markers CA 125 and CA 19AE9 induced by cyclic combin... more We report a case of increase in serum tumour markers CA 125 and CA 19AE9 induced by cyclic combined hormone replacement therapy (HRT). A 52-year-old Caucasian post-menopausal woman presented with a slight enlargement of the right ovary and uterine fibromyomatosis. She was taking HRT for 4 years in a cyclic combined regimen of 2 mg oestradiol with 1 mg cyproterone acetate. The serum tumour markers occasionally measured were in normal range except CA 19AE9 (997 U ⁄ mL; normal values 0AE0-37) and CA 125 (85 U ⁄ mL; normal values 0AE0-35). However, on one occasion, the CA 19AE9 and CA 125 were high and then showed persistently high values (1005 and 81AE3 U ⁄ mL, respectively). Radiodiagnostic investigations excluded any malignancies and a hysteroscopy showed endometrial thickening. After discontinuation of HRT, CA 125 levels returned to normal after 1 month, whereas CA 19AE9 took 6 months to do so. Four months after the beginning subsequent therapy with over-thecounter phyto-oestrogens a new serum test showed an increase in CA 19AE9 but CA 125 remained within the normal range. Phyto-oestrogen therapy was then interrupted and 1 month later CA 19AE9 returned to normal. In this case, cyclic HRT was the probable cause of CA 19AE9 and CA 125 increase. Positive dechallenge and subsequent CA 19AE9 increase after phyto-oestrogen intake seem to confirm the role of oestrogens as the cause of the endometrial thickening through hormonal imbalance. Increased CA 19AE9 and CA 125 levels in benign gynaecological conditions may be a source of misdiagnosis of malignant disease.

European Journal of Nutrition, 2005

■ Summary Background Plasma accumulation of asymmetric dimethyl arginine (ADMA), is considered as... more ■ Summary Background Plasma accumulation of asymmetric dimethyl arginine (ADMA), is considered as a risk factor for endothelial dysfunction and a strong predictor for coronary heart diseases. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) increasing

European Journal of Integrative Medicine, 2012

European Journal of Clinical Pharmacology, 2008

Background More than 380,000 angiographic procedures are performed every year in Italian hospital... more Background More than 380,000 angiographic procedures are performed every year in Italian hospitals, with an increase rate of 8% per year. Although contrast media (CM) are considered relatively safe, adverse drug reactions (ADRs) remain an important issue.

Cardiovascular Drugs and Therapy, 1995

We studied the interaction between the synthetic prostacyclin analog iloprost and the aggregating... more We studied the interaction between the synthetic prostacyclin analog iloprost and the aggregating agent athrombin by measuring the internal calcium ion concentration ([Ca2+]i) of human fura-2-1oaded platelets. Iloprost (0.003-100 }xg/l) did not modify the resting calcium level; when added 2 minutes before exposure of the platelets to a submaximally active concentration of c~-thrombin (10 U/l), iloprost dose-dependently antagonized the increase in [Ca2+]i. To evaluate if iloprost retained this antagonistic effect even after a prolonged contact, which is well known to cause a "desensitization" phenomenon, platelets were preincubated with iloprost (35 pLg/l) for 3 hours. After washout, the effect of newly added iloprost (0.01-100 p~g/l) on the oLthrombin-induced increase in [Ca2+]i was tested. Iloprost was still able to antagonize the increase in [Ca2+]i induced by c~-thrombin in "desensitized" platelets; however, the doseinhibitory response curve was significantly shifted to the right when compared with that obtained in control platelets (i.e., platelets preincubated for 3 hours with iloprost's solvent), and the resulting IC50 was significantly higher: 1.78 versus 0.2 Ixg/l (p < 0.001). Since the maximal inhibitory effect of iloprost could also be reached under these experimental conditions, we conclude that iloprost retains its ability to antagonize the increase in [Ca2+]i induced by ~thrombin in desensitized platelets.

British Journal of Pharmacology, 2000

1 While the expression and/or activity of endothelial nitric oxide synthase (eNOS) has been chara... more 1 While the expression and/or activity of endothelial nitric oxide synthase (eNOS) has been characterized in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rat (WKY) hearts, in coronary endothelial cells (ECs) from both strains, the eect of NO on intracellular calcium concentration ([Ca 2+ ] i ) is still unknown. 2 Coronary microvascular ECs were isolated from SHR and WKY and characterized. Immunocytochemistry and Western blot analysis showed that eNOS was similarly expressed in ECs from both strains. 3 Measuring [Ca 2+ ] i by imaging analysis of fura-2-loaded cells, we demonstrated that a-thrombin (37180 U l 71 ) induced a superimposable dose-dependent calcium transient in ECs from both strains. 4 In WKY ECs, S-nitroso-N-acetyl-DL-penicillamine (SNAP) dose-dependently (10 ± 100 mM) and 0.1 mM atrial natriuretic factor (ANF) reduced the maximum and the decay time of a-thrombininduced calcium transient. The inhibitory eects of SNAP and ANF were prevented by blocking cyclic GMP-dependent protein kinase. Non selective eNOS inhibitors prolonged the decay time of athrombin-induced calcium transient, while the selective inducible NOS inhibitor 1400 W was ineective. SNAP (100 mM) and 0.1 mM ANF increased cyclic GMP content up to 22.9 and 42.3 fold respectively. 5 In SHR ECs, a-thrombin-induced calcium transient was not modi®ed by SNAP, ANF or eNOS inhibition. SNAP (100 mM) and 0.1 mM ANF increased cyclic GMP content up to 9.3 and 51 fold respectively. 6 In WKY ECs, SNAP dose-dependently (10 ± 100 mM) reduced also bradykinin-induced calcium transient, while in SHR ECs was ineective. 7 We concluded that in SHR ECs, the cyclic GMP-dependent regulation of calcium transient is lost.

British Journal of Pharmacology, 1998

1 The eect of the NSAIDs indomethacin, indoprofen, diclofenac and acetylsalicylic acid on the inc... more 1 The eect of the NSAIDs indomethacin, indoprofen, diclofenac and acetylsalicylic acid on the increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) induced by nitric oxide-donor agents was tested in human whole platelets and in platelet crude homogenate. 2 In whole platelets, indomethacin reduced the increase in cyclic GMP induced by the nitric oxidedonors (NO-donors) sodium nitroprusside (NaNP) and S-nitroso-N-acetylpenicillamine (SNAP) in a dose-dependent way, its IC 50 being 13.7 mM and 15.8 mM, respectively. 3 Of the other cyclooxygenase inhibitors tested, only indoprofen reduced the increase in cyclic GMP induced by both NO-donors in a dose-dependent way (IC 50 =32.7 mM, NaNP and 25.0 mM, SNAP), while acetylsalicylic acid (up to 1000 mM) and diclofenac (up to 100 mM) were ineective. 4 However, in platelet crude homogenate neither indomethacin nor indoprofen reduced the cyclic GMP production. 5 Indomethacin (10 mM), indoprofen (30 mM), diclofenac (100 mM) and acetylsalicylic acid (1000 mM) showed a comparable ecacy in inhibiting platelet thromboxane B 2 (TXB 2 ) production, suggesting that the inhibitory eect of indomethacin and indoprofen on the increase in cyclic GMP induced by both NO-donors was not mediated by inhibition of cyclooxygenase. 6 In vitro, the NSAIDs analysed did not interfere with nitrite production of SNAP. 7 The unhomogeneous behaviour of NSAIDs on the increase in cyclic GMP induced by NO-donors in whole platelets may contribute to the dierent pharmacological and toxicological characteristics of the drugs, providing new knowledge on the eect of indomethacin and indoprofen.

To explore pregnant women's use, attitudes, knowledge and beliefs of complementary and alternativ... more To explore pregnant women's use, attitudes, knowledge and beliefs of complementary and alternative drugs (CADs) defined as products manufactured from herbs or with a natural origin. A preliminary survey was conducted among 172 pregnant women in their third trimester of pregnancy, consecutively recruited in two obstetrical settings; 15 women were randomly selected to compute a test-to-retest analysis. Response rate was 87.2%. Test-to-retest analysis showed a questionnaire's reproducibility exceeding a K-value of 0.7 for all items. Mean age was 32.4 AE 0.4 years; most women were nulliparae (62.7%). The majority of subjects (68%) declared to have used one or more CADs during their lifetime; 48% of pregnant women reported taking at least one CAD previously and during the current pregnancy. Women's habitual use of CADs meant they were at higher risk of taking CADs also during pregnancy (adjusted odds ratio = 10.8; 95% confidence interval: 4.7-25.0). Moreover, 59.1% of the subjects were unable to correctly identify the type of CADs they were using. The majority of women resorted to gynecologists as the primary information source for CADs during pregnancy, while they mainly referred to herbalists when not pregnant. Habitual use of CADs seems to be a strong predictor for their ingestion also during pregnancy; in addition most subjects were unable to correctly identify the products they were taking. In the light of the scanty data concerning the safety of CADs during pregnancy, these preliminary results confirm the need to investigate thoroughly the situation of pregnant women and CADs consumption.

Drugs & Aging, 2005

Several studies have raised concerns over a possible reduction in the beneficial effects of ACE i... more Several studies have raised concerns over a possible reduction in the beneficial effects of ACE inhibitors on mortality in people also taking aspirin (acetylsalicylic acid). We performed this study to determine whether there is a reduction in the beneficial effects of ACE inhibitors on mortality in elderly people with heart failure also taking aspirin. 822 patients discharged from hospital wards with a diagnosis of heart failure participated in the GIFA (Italian Group of Pharmacoepidemiology in the Elderly) study. We analysed the characteristics of the participants according to the type of therapy prescribed (no ACE inhibitor/no aspirin, ACE inhibitor/no aspirin, no ACE inhibitor/aspirin and ACE inhibitor/aspirin). We calculated the hazard ratios (HRs) for dying associated with each of these treatments, and calculated the synergy index to identify any negative interaction between ACE inhibitor and aspirin. The mean age of study participants was 79 +/- 7.3 (SD) years. Of the 629 (76.5%) patients discharged on ACE inhibitor and/or aspirin therapy, 31.0% were taking both drugs. Compared with no therapy with ACE inhibitor or aspirin, the HR for death was 0.65 (95% CI 0.31, 1.36) for aspirin users, 0.45 (95% CI 0.27, 0.74) for ACE inhibitor users and 0.37 (95% CI 0.19, 0.70) for ACE inhibitor/aspirin users. The synergy index was 0.98 (95% CI 0.34, 2.80), suggesting no interaction between the drugs. Our data do not support the existence of a negative interaction between ACE inhibitors and aspirin in elderly patients with heart failure.