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Andrea Rinaldi

Publications and source records attributed to Andrea Rinaldi.

At least 19 recordsLinked to original sources
PubMed2005

Effect of successful hypertension control by manidipine or lisinopril on albuminuria and left ventricular mass in diabetic hypertensive patients with microalbuminuria.

OBJECTIVE: The aim of this open-labelled, randomised, parallel-group study was to evaluate the effect of long-term monotherapy with manidipine or lisinopril on albumin excretion rate (AER) and left ventricular mass index (LVMI) in hypertensive patients with type-2 diabetes and microalbuminuria. METHODS: After a 4-week wash-out period, 174 patients with essential hypertension [diastolic blood pressure (DBP) >80 mmHg and <100 mmHg], type-2 diabetes and microalbuminuria were randomised to manidipine 10 mg o.d. or lisinopril 10 mg o.d.; after 8 weeks, the dose was doubled in non-responders (DBP >80 mmHg); after 3 months, treatment was discontinued in the non-responder patients and in those complaining of side effects; the remaining 121 patients continued their therapy with manidipine or lisinopril, and 99 completed the 2-year study. At the end of the wash-out period, of the titration period and after 6, 12, 18 and 24 months of treatment, BP was measured, AER, creatinine clearance, glycosylated haemoglobin (HbA1c) and body mass index (BMI) were evaluated and an echocardiographic evaluation was performed. RESULTS: The 99 patients who completed the study were statistically analysed according to a per-protocol evaluation. Manidipine and lisinopril significantly reduced systolic blood pressure (SBP) and DBP levels (at 24 months, --22.3/15.5 mmHg, P<0.001 versus baseline and --21.4/15.7 mmHg, P<0.01 versus baseline, respectively). Both drugs provided a significant decrease in AER, but it was significantly more pronounced with lisinopril (at 24 weeks, --37.2 mg/24 h, P<0.001 versus baseline) than with manidipine (--29.9 mg/24 h, P<0.05 versus baseline) and became evident earlier in the lisinopril group (after 3 months versus 6 months of treatment). Manidipine produced a greater reduction of LVMI than lisinopril (--14.9 g/m(2) versus --10.8 g/m(2) at 24 months). The effect was more pronounced in patients with left ventricular hypertrophy at baseline (--19.8 g/m(2) versus --12.8 g/m(2), P<0.05). CONCLUSION: These data suggest that, despite similar BP lowering, non-haemodynamic factors play an important role in the pharmacological reduction of AER and LVMI in diabetic hypertensive patients.

Aged↗
PubMed2005

Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells.

Toll-like receptors (TLRs) sense microbial products and initiate adaptive immune responses by activating dendritic cells (DCs). As pathogens may contain several TLR agonists, we sought to determine whether different TLRs cooperate in DC activation. In human and mouse DCs, TLR3 and TLR4 potently acted in synergy with TLR7, TLR8 and TLR9 in the induction of a selected set of genes. Synergic TLR stimulation increased production of interleukins 12 and 23 and increased the Delta-4/Jagged-1 ratio, leading to DCs with enhanced and sustained T helper type 1-polarizing capacity. Global gene transcriptional analysis showed that TLR synergy 'boosted' only approximately 1% of the transcripts induced by single TLR agonists. These results identify a 'combinatorial code' by which DCs discriminate pathogens and suggest new strategies for promoting T helper type 1 responses.

Animals↗
PubMed2005

Effect of telmisartan/hydrochlorothiazide combination versus nifedipine GITS on ambulatory blood pressure and sympathetic activation.

BACKGROUND: This study compares the effects of telmisartan hydrochlorothiazide (HCTZ) combination versus nifedipine GITS on ambulatory blood pressure (BP) and sympathetic activity, in patients with mild-to-moderate hypertension. METHODS: One hundred twenty-four outpatients with sitting diastolic BP > or =95 mmHg and <110 mm Hg were randomized to telmisartan 80 mg/HCTZ 12.5 mg daily (n = 62) or nifedipine GITS 60 mg daily (n = 62) for 12 weeks, according to a prospective, open-label, blind end point, parallel-group design. At the end of a 2-week washout period and after 12 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed, clinic BP and heart rate were measured, and plasma norepinephrine and cardiovascular responses to mental stress induced by the color word test were assessed. RESULTS: Both treatments reduced ambulatory and clinic BP. However, the drug combination had an antihypertensive efficacy significantly greater than nifedipine GITS, as shown by the 24-h (P < .001), daytime (P < .001), and night-time (P < .01) ambulatory BP monitoring values, as well as by the clinic BP at trough (P < .05). The trough-to-peak ratio was similar, but the smoothness index was significantly higher with the combination for both systolic and diastolic BP (P < .05). A significant increase in plasma norepinephrine levels in resting conditions was observed with nifedipine GITS (+20%) but not with telmisartan/HCTZ combination. The color word test produced a greater increase in plasma norepinephrine and heart rate values in the patients treated with nifedipine GITS than in those treated with the combination. CONCLUSIONS: These results suggest that the telmisartan 80 mg/HCTZ 12.5 mg combination provided a more sustained and homogeneous BP control than nifedipine GITS 60 mg, without producing sympathetic activation.

Adult↗
PubMed2005

The newt in us.

Explore the source record for details and available documents.

Animals↗
PubMed2005

Effect of manidipine as compared to atenolol on platelet aggregation in elderly patients with isolated systolic hypertension and type II diabetes mellitus.

This study was done to evaluate the effect of treatment with manidipine as compared with atenolol on thrombin-mediated platelet aggregation in elderly patients with isolated systolic hypertension and type II diabetes mellitus. After a 2-week washout placebo period, 60 elderly patients (aged 65-80 years) with isolated systolic hypertension (SBP > 140 mm Hg and DBP < 90 mm Hg) were randomly assigned to manidipine 10 mg or atenolol 50 mg 6-week treatment according to a double-blind, crossover design. Thirty patients had a concomitant well-controlled type 2 diabetes mellitus (HbA1c < or = 6.5%). At the end of the washout and of each treatment period, blood pressure (BP) (by mercury sphygmomanometer) and platelet aggregation (by Born-type aggregometer) were evaluated. Blood samples were collected using sodium citrate as anticoagulant, and platelet aggregation was induced by 2 different concentrations of ADP and collagen. Manidipine and atenolol produced a significant BP reduction in both diabetic and nondiabetic patients, with no difference between treatments. Despite the similar BP effect, in diabetic patients manidipine produced a significant reduction in platelet aggregation induced by both doses of either ADP or collagen. In nondiabetic hypertensives, manidipine inhibited platelet aggregation only at the highest doses of both inducers. The difference in the platelet inhibitory effect of manidipine between diabetic and nondiabetic subjects was statistically significant (P < 0.05) at both inducer concentrations. No changes in platelet aggregation were observed in the atenolol group. These data indicate that, unlike atenolol, manidipine inhibits platelet aggregation in elderly hypertensive patients, expecially in those with associated type II diabetes mellitus. The clinical impact of this positive effect in terms of prevention of cardiovascular complications in these high-risk patients remains to be clarified.

Aged↗
PubMed2004

Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.

OBJECTIVE: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients. METHODS: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP > or =95 mmHg and < or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.) treatment with valsartan 160 mg ( n=73) or enalapril 20 mg ( n=71) for 16 weeks. The patients were examined every 4 weeks during the study, with pre-dose BP (standard mercury sphygmomanometer, Korotkoff I and V) and heart rate (pulse palpation) being recorded at each visit. Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests (verbal fluency, the Boston naming test, word list memory, word list recall and word list recognition). RESULTS: Both valsartan and enalapril had a clear antihypertensive effect, but the former led to a slightly greater reduction in SBP/DBP at 16 weeks (18.6+/-4.6/13.7+/-4.0 mmHg vs 15.6+/-5.1/10.9+/-3.9 mmHg; P<0.01). Enalapril did not induce any significant changes in any of the cognitive function test scores; valsartan significantly increased the word list memory score (+11.8%; P<0.05 vs baseline and P<0.01 vs enalapril) and the word list recall score (+18.7%; P<0.05 vs baseline and P<0.01 vs enalapril), but not those of the other tests. CONCLUSION: These findings indicate that, in elderly hypertensive patients, 16 weeks of treatment with valsartan 160 mg o.d. is more effective than enalapril 20 mg o.d. in reducing BP, and (unlike enalapril) improves some of the components of cognitive function, particularly episodic memory.

Aged↗
PubMed2004

Effect of valsartan and atenolol on sexual behavior in hypertensive postmenopausal women.

BACKGROUND: The aim of this study was to evaluate the effect of valsartan compared with atenolol on sexual behavior in hypertensive postmenopausal women. METHODS: A total of 120 postmenopausal women, aged 51 to 55 years, with mild to moderate hypertension (diastolic blood pressure [DBP] >/=95 and </=105 mm Hg) were enrolled. After a 4-week placebo period they were randomized to treatment with valsartan 80 mg (n = 60) or atenolol 50 mg (n = 60) once daily for 16 weeks, according to a parallel arm design. After 4 weeks of treatment the nonresponder patients (DBP >90 mm Hg) were given a double dose of each drug. Patients were checked at the end of the placebo period and every 4 weeks thereafter. At each visit, sitting blood pressure (BP) was measured by mercury sphygmomanometer (Korotkoff I and V). At baseline and after 16 weeks of treatment, patients were given a questionnaire that comprised 10 self-evaluations of various aspects of sexual desire, orgasmic response, and coital activity. The questions were presented in the form of a visual analog scale. RESULTS: Both drugs significantly lowered BP without any difference between the two treatments. In the valsartan-treated women, the scores for three of the items related to libido significantly improved: sexual desire (+38%, P <.01), changes in behavior (+45%, P <.001), and sexual fantasies (+51%, P <.001) In contrast, in the atenolol-treated group the scores for the items "sexual desire" and "sexual fantasies" significantly worsened (-18%, P <.01 and -23%, P <.001, respectively). CONCLUSIONS: These results suggest that in postmenopausal, sexually active hypertensive women, valsartan treatment improved sexual function at least in some respects, whereas atenolol worsened it. This may be relevant for quality of life in these patients and their compliance with antihypertensive therapy.

Adrenergic beta-Antagonists↗
PubMed2004

Effect of amlodipine-atorvastatin combination on fibrinolysis in hypertensive hypercholesterolemic patients with insulin resistance.

BACKGROUND: The aim of this study was to evaluate the effect of the amlodipine-atorvastatin combination on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) activity in hypercholesterolemic, hypertensive patients with insulin resistance. METHODS: The study population included 45 patients, aged 41 to 70 years, with mild to moderate essential hypertension (diastolic blood pressure [BP] > or = 95 and < or = 105 mm Hg), hypercholesterolemia (total cholesterol > 200 and < 350 mg/dL), and insulin resistance (HOMA index > 2.5) After a 4-week wash-out period, they were randomized to amlodipine (5 mg) or atorvastatin (20 mg) or their combination at the same oral dosage for 12 weeks in three cross-over periods each separated by a 4-week placebo period (3 by 3 latin square design). At the end of the placebo wash-out and of each treatment period, office BP, total cholesterol, PAI-1, and t-PA activity were evaluated. RESULTS: The amlodipine-atorvastatin combination, in addition to the expected hypocholesterolemic effect, produced: 1) a greater decrease in PAI-1 activity (-10.2 U/mL, P <.01 v placebo) and an even greater increase in t-PA activity (+0.26 U/mL, P <.01 v placebo) than amlodipine (-0.5 U/mL for PAI-1, P = not significant; +0.17 U/mL for t-PA, P <.01 v placebo) and atorvastatin alone (respectively, -9.9 U/mL, P <.01 v placebo and +0.08 U/mL, P <.05 v placebo); and 2) a greater systolic BP/diastolic BP mean reduction (-22/17 mm Hg, P <.005 v placebo) than amlodipine (-18/14 mm Hg, P <.01 v placebo) and atorvastatin alone (-2.8/3.8 mm Hg, P <.05 v placebo only for diastolic BP). CONCLUSIONS: The positive effect on fibrinolytic balance and BP control observed suggests that in hypertensive, hypercholesterolemic patients with impaired fibrinolysis, the combination of amlodipine and atorvastatin could be the treatment of choice.

Adult↗
PubMed2004

Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down's syndrome, revealing PRAME as a specific discriminating marker.

Transient myeloproliferative disorder (TMD) is a unique, spontaneously regressing neoplasia specific to Down's syndrome (DS), affecting up to 10% of DS neonates. In 20-30% of cases, it reoccurs as progressive acute megakaryoblastic leukaemia (AMKL) at 2-4 years of age. The TMD and AMKL blasts are morphologically and immuno-phenotypically identical, and have the same acquired mutations in GATA1. We performed transcript profiling of nine TMD patients comparing them with seven AMKL patients using Affymetrix HG-U133A microarrays. Similar overall transcript profiles were observed between the two conditions, which were only separable by supervised clustering. Taqman analysis on 10 TMD and 10 AMKL RNA samples verified the expression of selected differing genes, with statistical significance (P < 0.05) by Student's t-test. The Taqman differences were also reproduced on TMD and AMKL blasts sorted by a fluorescence-activated cell sorter. Among the significant differences, CDKN2C, the effector of GATA1-mediated cell cycle arrest, was increased in AMKL but not TMD, despite the similar level of GATA1. In contrast, MYCN (neuroblastoma-derived oncogene) was expressed in TMD at a significantly greater level than in AMKL. MYCN has not previously been described in leukaemogenesis. Finally, the tumour antigen PRAME was identified as a specific marker for AMKL blasts, with no expression in TMD. This study provides markers discriminating TMD from AMKL-M7 in DS. These markers have the potential as predictive, diagnostic and therapeutic targets. In addition, the study provides further clues into the pathomechanisms discerning self-regressive from the progressive phenotype.

Acute Disease↗
PubMed2004

Imatinib mesylate (STI571) interference with growth of neuroectodermal tumour cell lines does not critically involve c-Kit inhibition.

A therapeutic role of STI571 (imatinib mesylate) has been anticipated in patients with c-Kit positive neuroectodermal tumors. We examined the efficacy of STI571 to inhibit expansion of c-Kit positive neuroectodermal tumor cell lines in vitro and in a mouse model inoculated with ES (Ewing sarcoma) derived tumor cells, and investigated the molecular mechanism of STI571 action. Eleven tumor lines of ES, PNET (primitive neuroectodermal tumors) and NB (neuroblastoma) were assayed in the presence of 1, 5, 10, 15, 20 or 30 micro M STI571 for 24, 48, 72 h and 7 days. The mechanism of STI571 action was investigated using a microphysiometer cytosensor that determines cellular metabolic rates in the presence of STI571. c-Kit and global protein phosphorylation was assayed by immunoprecipitation and a direct enzyme-linked immunoadsorbent assay after 72 h of 10 micro M STI571. Apoptosis was investigated by propidium iodide (PI), Annexin V staining and by enzymatic activity of caspase-3. Moreover, apoptotic gene expression was investigated using microarray technology. In nude mice, tumor volume and histology were analyzed in STI571 treated and untreated mice, and apoptotic gene expression analysis was performed on tumor masses. A decrease in cell proliferation and increase of cell apoptosis was caused by STI571 in a concentration- and time-dependent manner. Cytosensor microphysiometer and immunoprecipitation experiments demonstrated a time- and concentration-dependent decrease of cellular metabolic activity and global protein dephosphorylation after STI571 exposure. The inhibition by STI571 appeared at least to some extent independent of c-Kit inhibition since cells remained sensitive to SCF stimulation. Tumor volume was significantly reduced in STI571-treated mice compared to tumors from control inoculated non-treated mice. The apoptosis pathway in response to STI571 appeared not to be dependent on caspase activation, while gene expression profiles suggested accumulation of reactive oxygen species (ROS) resulting in cell death after exposure to STI571. The results point to the potential relevance of STI157 for neuroectodermal tumor therapy in view of its inhibitory effect on tumor cell growth, in spite of the observation that the inhibition of the c-Kit signaling pathway is not critically involved.

Animals↗
PubMed2003

Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder.

Transient myeloid disorder is a unique self-regressing neoplasia specific to Down's syndrome. The transcription factor GATA1 is needed for normal growth and maturation of erythroid cells and megakaryocytes. Mutations in GATA1 have been reported in acute megakaryoblastic leukaemia in Down's syndrome. We aimed to investigate changes in GATA1 in patients with Down's syndrome and either transient myeloid disorder (n=10) or acute megakaryoblastic leukaemia (n=6). We recorded mutations eliminating exon 2 from GATA1 in all patients with transient myeloid disorder (age 0-24 days) and in all with acute megakaryoblastic leukaemia (age 14-38 months). The range of mutations did not differ between patients with each disorder. Patients with transient myeloid disorder with mutations in GATA1 can regress spontaneously to complete remission, and mutations do not necessarily predict later acute megakaryoblastic leukaemia.

Child, Preschool↗
PubMed2003

Differential effects of lercanidipine and nifedipine GITS on plasma norepinephrine in chronic treatment of hypertension.

This study aimed to compare the effects of two long-acting dihydropyridine calcium channel blockers (CCBs) with different pharmacologic properties, lercanidipine and nifedipine Gastro-Intestinal Therapeutic System (GITS), in the chronic treatment of essential hypertension. After a 4-week placebo run-in period, 60 patients of both sexes were randomly treated with lercanidipine 10 to 20 mg or nifedipine GITS 30 to 60 mg taken orally for 48 weeks, according to a double-blind, parallel group design. For the first 4 weeks of treatment, the lowest dose of each drug was used, followed by higher doses if diastolic blood pressure (BP) was >90 mm Hg. At the end of the placebo period and after 4, 8, 12, 24, and 48 weeks of active treatment BP, heart rate (HR), and plasma norepinephrine (NE) levels were assessed. Lercanidipine and nifedipine GITS similarly reduced BP values after 48 weeks (-21.7/15.9 mm Hg and -20.7/14.6 mm Hg, respectively, both P <.001 v placebo), with no change in HR. Despite the similar lack of effect on HR, the two drugs displayed different influences on plasma NE, which was significantly increased by nifedipine GITS (+56 pg/mL, P <.05 v placebo) but not by lercanidipine. These findings suggest that 1) sympathetic activation occurs during chronic therapy with nifedipine GITS but not with lercanidipine, which might be related to the different pharmacologic characteristics of the two CCBs at the doses evaluated; and 2) nifedipine GITS seems to activate peripheral but not cardiac sympathetic nerves, consistent with differing regulation of cardiac and peripheral sympathetic activity.

Adult↗
PubMed2002

Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men.

OBJECTIVE: To compare the effects of valsartan and atenolol on sexual activity and plasma testosterone in newly diagnosed, previously untreated, essential hypertensive male subjects. METHODS: One hundred and ten hypertensive men, aged 40-49 years, homogeneous for marital status and without any previous sexual dysfunction were randomly treated with valsartan 80 mg daily (o.d.) or atenolol 50 mg o.d. for 16 weeks according to a double-blind, parallel-arm study design. After 8 weeks the dose was doubled in the non-responders (diastolic blood pressure > 90 mmHg). Clinical evaluation was performed after 8 weeks and 16 weeks of treatment and included blood pressure and plasma testosterone measurements and the compilation of a questionnaire about sexual activity (sexual intercourse episodes/month). RESULTS: Despite similar blood pressure lowering, atenolol significantly reduced sexual activity (from 6.0 sexual intercourse episodes/month to 4.2 sexual intercourse episodes/month, P < 0.01 vs placebo), whereas valsartan increased it, although not significantly (from 5.8 sexual intercourse episodes/month to 7.4 sexual intercourse episodes/month, P = 0.058), compared with placebo, but significantly compared with the atenolol group ( P < 0.05). Testosterone was reduced by atenolol (from 18.2 nmol/l to 13.8 nmol/l, P < 0.01 vs baseline) but was not affected by valsartan (from 17.6 nmol/l to 18.3 nmol/l). CONCLUSIONS: These results suggest that atenolol induces a worsening of sexual activity and a reduction of testosterone, whereas valsartan does not worsen sexual activity and does not change testosterone levels.

Adult↗
PubMed2002

Sexual activity and plasma testosterone levels in hypertensive males.

The aim of this study was to compare sexual activity and plasma testosterone levels of hypertensive men with those of healthy normotensive controls. We investigated 110 newly diagnosed, never treated hypertensive (blood pressure [BP] > or = 140/95 mm Hg) men and 110 healthy normotensive (diastolic BP <90 mm Hg) men. All of them were aged 40 to 49 years, married, without any previous sexual dysfunction, nondiabetic, nonobese (body mass index <28 kg/m2), nonsmoking, and not taking any drug. All subjects were evaluated in the morning after an overnight fast. Clinical evaluation included BP, body weight, and height measurements, determination of testosterone, and an interview about sexual activity, assessed as number of sexual intercourse episodes per month. Hypertensive men presented a 25% reduction in sexual activity as compared to normotensive men (5.9 +/- 2.6 v 7.9 +/- 2.5 sexual intercourse episodes per month, respectively, P < .01) and a 12% reduction in testosterone levels (510.6 +/- 151.9 ng/dL v 578.6 +/- 146.8 ng/dL, P < .01). In both normotensive and hypertensive men Pearson's correlation analysis showed a significant positive correlation between testosterone levels and sexual activity and a significant negative correlation between testosterone and age and between testosterone and BP values. Multiple regression analysis confirmed a significant inverse relationship between testosterone and age in normotensive men, whereas only a nonsignificant trend was found in the hypertensive ones. In addition, a significant inverse correlation between testosterone and BP levels was confirmed in hypertensive men limited to systolic BP, whereas a nonsignificant trend was observed in the normotensive controls. In conclusion, these findings suggest a relationship between essential hypertension and impaired testosterone levels in men. The elucidation of the nature of such a relationship and its physiologic and clinical significance needs further investigation.

Adult↗