Breast density in NF1 women: a retrospective study.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in the NF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population. Mammograms from 98 NF1 women affected by NF1, and enrolled onto our monocentric BC screening program, were compared with those from 300 healthy subjects to verify differences in breast density. Mammograms were independently reviewed and scored by a radiologist and using a Computer-Aided Detection (CAD) software. The comparison of breast density between NF1 patients and controls was performed through Chi-squared test and with multivariable ordinal logistic models adjusted for age, body mass index (BMI), number of pregnancies, and menopausal status.breast density was influenced by BMI and menopausal status in both NF1 patients and healthy subjects. No difference in breast density was observed between NF1 patients and the healthy female population, even after considering the potential confounding factors.Although NF1 and a highly fibroglandular breast are known risk factors of BC, in this study, NF1 patients were shown to have comparable breast density to healthy subjects. The presence of pathogenic variants in the NF1 gene does not influence the breast density value.

Features of microvessel density (MVD) and angiogenesis inhibitors in therapeutic approach of hepatocellular carcinoma (HCC).

OBJECTIVE: The curative hepatocellular carcinoma (HCC) therapy was traditionally based on surgical or loco-regional ablation approach. However, HCC is a solid tumor characterized by a highest level of vascularization; therefore, angiogenesis inhibitor could play a pivotal role in the pharmacological therapeutic approach. Despite the low number of approved drugs, a wide range of multi-kinase and MET inhibitor is currently being evaluated in phase II and III study. In this review, we described all the drugs that have shown efficacy in recently and ongoing trials. Moreover, the immunotherapy represents a recent challenge in the HCC treatment. The strategy based on the production of multi-epitope, multi-HLA peptide vaccine naturally processed and presented on primary tumor tissues of HCC patients. A further upgrade of cancer vaccine could be represented by the combination of metronomic chemotherapy and checkpoint inhibitors.

Steroids and growth factors in oral squamous cell carcinoma: useful source of dental-derived stem cells to develop a steroidogenic model in new clinical strategies.

OBJECTIVE: Head and neck region is involved in a high percentage of malignant lesions, and oral squamous cell carcinoma (OSCC) is undoubtedly the most frequently found, accounting for over 90% of malignant tumors. Hormone receptor overexpression, like Estrogen Receptor (ER), Progesterone Receptor (PR) and Endothelial Growth Factor Receptor (EGFR), and signaling have been related to the pathogenesis of OSCC. For metastasis of OSCC, Cancer Stem Cells (CSCs) undergo epithelial to mesenchymal transition (EMT) under the influence of growth factors, cytokines, and regulation of cadherins from the tumor's microenvironment. In this context, the stem cells may become a potential therapeutic target for OSCC through modulation of cytokines and RAS pathway, which is involved in intracell signal transduction. The objective of this study was to suggest an experimental steroidogenic model for OSCC in translational research. PATIENTS AND METHODS: Dental-derived Stem Cells (D-dSCs) have been obtained from apical papilla tissue that surrounds the developing tooth of healthy donors and cultured in vitro. The cells have been exposed to different concentrations of Estradiol (E2 - 10 nM and 40 nM) in order to verify their response. The number of cells and cell viability has been evaluated up to 96 hours of treatment. RESULTS: The results showed that cell growth was increased under estradiol treatments compared with cells maintained without estradiol. Moreover, no significant difference in cell death levels was detected among treatments. CONCLUSIONS: This work underlines as D-dSCs could represent a useful steroidogenic model for the development of the target and gene therapies in OSCC.

Diagnostic application of a capture based NGS test for the concurrent detection of variants in sequence and copy number as well as LOH.

Whole exome sequencing (WES) has made the identification of causative SNVs/InDels associated with rare Mendelian conditions increasingly accessible. Incorporation of softwares allowing CNVs detection into the WES bioinformatics pipelines may increase the diagnostic yield. However, no standard protocols for this analysis are so far available and CNVs in non-coding regions are totally missed by WES, in spite of their possible role in the regulation of the flanking genes expression. So, in a number of cases the diagnostic workflow contemplates an initial investigation by genomic arrays followed, in the negative cases, by WES. The opposite workflow may also be applied, according to the familial segregation of the disease. We show preliminary results for a diagnostic application of a single next generation sequencing panel permitting the concurrent detection of LOH and variations in sequences and copy number. This approach allowed us to highlight compound heterozygosity for a CNV and a sequence variant in a number of cases, the duplication of a non-coding region responsible for sex reversal, and a whole-chromosome isodisomy causing reduction to homozygosity for a WFS1 variant. Moreover, the panel enabled us to detect deletions, duplications, and amplifications with sensitivity comparable to that of the most widely used array-CGH platforms.

Antibacterial effect of silver nanoparticles in Pseudomonas aeruginosa.

Pseudomonas aeruginosa has great intrinsic antimicrobial resistance limiting the number of effective antibiotics. Thus, other antimicrobial agents such as silver nanoparticles (AgNPs) are considered potential agents to help manage and prevent infections. AgNPs can be used in several applications against bacteria resistant to common antibiotics or even multi-resistant bacteria such as P. aeruginosa. This study assessed the antimicrobial activity of commercial 10 nm AgNPs on two hospital strains of P. aeruginosa resistant to a large number of antibiotics and a reference strain from a culture collection. All strains were susceptible to 5 µg/mL nanoparticles solution. Reference strains INCQS 0230 and P.a.1 were sensitive to AgNPs at concentrations of 1.25 and 0.156 µg/mL, respectively; however, this was not observed for hospital strain P.a.2, which was more resistant to all antibiotics and AgNPs tested. Cytotoxicity evaluation indicated that AgNPs, up to a concentration of 2.5 µg/mL, are very safe for all cell lines tested. At 5.0 µg/mL, AgNPs had a discrete cytotoxic effect on tumor cells HeLa and HepG2. Results showed the potential of using AgNPs as an alternative to conventional antimicrobial agents that are currently used, and a perspective for application of nanosilver with antibiotics to enhance antimicrobial activity.

Antibacterial effect of silver nanoparticles in Pseudomonas aeruginosa

Pseudomonas aeruginosa has great intrinsic antimicrobial resistance limiting the number of effective antibiotics. Thus, other antimicrobial agents such as silver nanoparticles (AgNPs) are considered potential agents to help manage and prevent infections. AgNPs can be used in several applications against bacteria resistant to common antibiotics or even multiresistant bacteria such as P. aeruginosa. This study assessed the antimicrobial activity of commercial 10 nm AgNPs on two hospital strains of P. aeruginosa resistant to a large number of antibiotics and a reference strain from a culture collection. All strains were susceptible to 5 mu g/mL nanoparticles solution. Reference strains INCQS 0230 and P.a.1 were sensitive to AgNPs at concentrations of 1.25 and 0.156 mu g/mL, respectively; however, this was not observed for hospital strain P.a.2, which was more resistant to all antibiotics and AgNPs tested. Cytotoxicity evaluation indicated that AgNPs, up to a concentration of 2.5 mu g/mL, are very safe for all cell lines tested. At 5.0 mu g/mL, AgNPs had a discrete cytotoxic effect on tumor cells HeLa and HepG2. Results showed the potential of using AgNPs as an alternative to conventional antimicrobial agents that are currently used, and a perspective for application of nanosilver with antibiotics to enhance antimicrobial activity.

Relationship between primary headache and nutrition: a questionnaire about dietary habits of patients with headache.

The role of food associated with the headache has been the subject of scientific research since 1900, especially for migraine patients. A substantial proportion of patients (ranging from 12 to 60 %) report that their migraine attacks may be precipitated by dietary elements, certain eating habits (fasting) and abuse (caffeine and alcoholic beverages abuse and withdrawal). The biological mechanism by means of triggers in general and food in particular precipitate migraine attacks remains obscure. Based on the data in the literature, we performed an osservational study searching for possible correlations between nutrition and primary headaches. We enrolled 50 consecutive patients from the Headache Center of the Neurology Department of Hospital "Cardinal Massaia" of Asti and submitted them a 14-item questionnaire for the assessment of relationship between primary headache and food. Our preliminary data, although the follow up is still in progress, show that there are strong associations between the onset of the headache and dietary habits. It will be necessary to analyze a larger sample in order to draw more precise conclusions on this topic.

Effects of chronic administration of ß-blockers on airway responsiveness in a murine model of heart failure.

Lung function abnormalities, both at rest and during exercise, are frequently observed in patients with chronic heart failure (HF), also in absence of respiratory disease. It has been documented that, in HF, chronic adrenergic stimulation down-regulates ß-adrenoceptors (ß-ARs) and modifies airway relaxant responses. This study was designed to investigate in an animal model of HF whether a treatment with a ß-AR blocker, metoprolol, could modify the altered airway hyperresponsiveness. In rats, randomly assigned to 3 experimental groups sham-operated rats (SH), rats with HF induced by left anterior descending coronaric occlusion (HF n = 10), and rats treated with metoprolol 100 mg/kg/die (MET = 10), HF was evaluated after 10 weeks and resulted in increases in plasma norepinephrine and epinephrine and left ventricular end diastolic pressure. ß2-ARs and G-protein-ßAR2-kinase (GRK2) mRNA levels were determined by real time reverse transcriptase PCR. Carbachol-precontracted isolated tracheal rings were used to functionally assess airway smooth muscle relaxation. In pulmonary tissues, ß2-AR mRNA level was significantly decreased in HF groups (-48.73 ± 5.18%, P < 0.01); in the same groups the GRK2 mRNA-levels were significantly enhanced (+222.50 ± 6.13%, P < 0.001); in lung deriving from MET groups the levels of mRNA were significantly increased (+339.86 ± 11.26%, P < 0.001), while the GRK2 mRNA-levels unchanged (-59.02 ± 3.97%, P < 0.001), when compared to SH groups. Relaxation of tracheal strips in response to salbutamol was significantly reduced in HF groups; in tracheal rings, deriving from MET groups, the relaxant effects of salbutamol were significantly enhanced (SH, Emax: 34.87 ± 2.98%, pD2: 7.45 ± 0.27; HF, Emax: 34.87 ± 2.98%, pD2: 7.45 ± 0.27; MET, Emax: 85.43 ± 6.80%, pD2: 6.95 ± 0.59, P < 0.001). In HF, the down-regulation of pulmonary ß-ARs results in a significant attenuation of airway relaxation. These effects have been reversed by a treatment with metoprolol, suggesting a potential role of ß-AR blockers in the treatment of patients suffering from HF and chronic obstructive airway diseases.

Adiponectin elevation by telmisartan ameliorates ischaemic myocardium in Zucker diabetic fatty rats with metabolic syndrome.

AIM: This study investigated whether telmisartan, a selective angiotensin type 1 (AT1) receptor antagonist and gamma peroxisome proliferator-activated receptor (PPAR-γ) partial agonist, reduces myocardial ischaemia/reperfusion (I/R) injury in an experimental model of metabolic syndrome. METHODS: Zucker Diabetic Fatty (ZDF) rats were treated for 3 weeks with telmisartan at doses of 2, 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25-min occlusion of the left descending coronary artery followed by 2-h reperfusion (I/R). RESULTS: Telmisartan reduced the extension of the infarct size in a dose-dependent fashion and decreased the levels of plasma troponin I, a specific marker of myocardial damage. Telmisartan also caused a dose-dependent increase in adiponectin both in plasma and cardiac tissue of infarcted ZDF rats. These levels were minimally increased (p < 0.05 vs. vehicle) by telmisartan 7 mg/kg/day and reached the maximum values with the highest dose of 12 mg/kg/day (p < 0.01 vs. vehicle). In contrast, within the infarcted tissue telmisartan decreased the expression of markers of inflammation such as the transcription factor NF-κB, the toll-like receptors TLR2 and TLR4 as well as TNF-α cytokine. Nitrosative stress was maximal in vehicle-treated infarcted hearts as evidenced by increased expression of iNOS, which was almost abolished after treatement with telmisartan. CONCLUSIONS: Treatment of ZDF rats for 3 weeks with telmisartan, a dual angiotensin II receptor antagonist and partial PPAR-γ receptor agonist, resulted in a significant reduction of myocardial damage induced by I/R and was associated with increased adiponectin and a decrease in inflammatory markers.

Cardiorespiratory effects of change in posture after spinal anesthesia with hyperbaric bupivacaine.

Spinal anesthesia is a special regional anesthetic technique that is applied in lower limb orthopedic and other surgical procedures made below the transverse umbilical line, which is able to produce a neuraxial central block. The patient's position, together with the baricity of the drug solution injected, is a variable that can affect the success of anaesthesia. According to clinical practice, lateral decubitus or the sitting position are to be maintained for a period ranging from 15 to 20 minutes to avoid any possible motion of the injected solution that could cause side effects due to anesthetic being distributed up to thoracic segments. We describe a case of cardiovascular and respiratory effects occurred approximately 65 min after spinal anesthesia with 7 mg of 1% hyperbaric bupivacaine in a patient during change in posture from mild anti-Trendelemburg to supine decubitus. These findings show that a change in posture after spinal anaesthesia with hyperbaric bupivacaine can affect the safety of this anesthesia technique, also after a longer period of time than is usually recommended to avoid the spread of anaesthetic drug.

Regional surveillance of emergency-department visits for outpatient adverse drug events.

AIMS: To determine the (1) incidence of adverse drug events (ADEs) in 10 emergency department (EDs) of general hospitals in the Regione Campania (southern Italy), (2) rate of ADE-related hospital admissions, (3) drug classes most frequently involved, and (4) the types of ADEs and their frequency. METHODS: We performed a cohort study of all patients attending the EDs. This study was carried out in two observational periods of 10 days each in 10 EDs. Demographic, clinical, and pharmacological data about all patients admitted to EDs were collected by trained and qualified monitors. Records related to ADEs were analyzed and validated by a specific scientific committee. RESULTS: Of 7,861 ED visits, 96 were ADE-related. The incidence of hospitalization was higher in patients who had taken medication than in patients with a negative drug history (24.9 vs. 16.4%). ADEs were significantly more frequent in women. Patients aged between 60 and 69 years and between 30 and 39 years were significantly more likely to experience an ADE. Serious ADEs were identified in 20 ED visits (20.8% of total sample). Antibiotics, NSAIDs, and agents acting on the renin-angiotensin system were the drugs most often involved in ADEs. In multivariate analyses, the adjusted odds ratio was 3.4 (95% CI: 1.07-2.84) for patients taking NSAIDs, 4.78 (95% CI: 2.26-10.12) for those taking beta(2)-adrenergic-receptor agonists, and 6.20 (95%CI: 2.74-14.06) for those taking beta-lactam antibiotics. CONCLUSION: This study shows that ADEs are an important problem in industrialized countries. Moreover, it shows that ADEs affect hospital admission rates and reinforces the importance of drug-induced disease as a public health problem.

Blood-borne cells involved in arterial repair upon experimental incision injury.

We had previously shown that microscopically detectable infiltration of dendritic cells and expression of Hsp47 in tissue lysates occur during repair upon experimental arterial injury. We have further analysed here the cell types involved in the repair process by histology, electron microscopy and immunofluorescence. Rat carotid arteries were subjected to brief crushing and full thickness incision and were analysed up to 21 d thereafter. Adhesion and activation of platelets occurred 3 h after surgery. A neointima had formed 7 d after surgery, where immature cells entered from the lumen and gave rise to cells rich in organelles of the secretory pathway and endowed with bundles of phalloidin-binding microfilaments. Alpha smooth muscle-positive, secretory and contractile smooth muscle cells were found in the neointima 14 and 21 d after injury. Seven to 21 d after surgery, endothelial cells appeared immature and the newly formed tissue contained MHC-II positive, CD43 positive dendritic cells which clustered with lymphocytes, a few macrophages containing apoptotic remnants and cells labelled for Hsp47. Thin elastic fibrils appeared in the neointima 21 d after injury. The results suggest that the response to acute arterial incision injury is mediated by blood borne cells which differentiate along multiple pathways; the process evolves without reaching stabilization within the observed time lapse; the secretion of extracellular matrix is marked by the expression of Hsp47; and the constant presence of dendritic cells clustered with lymphocytes makes these cells candidate to a pivotal role in the tissue response to injury.

Antibiotic prophylaxis in surgery: an observational prospective study conducted in a large teaching hospital in Naples.

This was a 9-month observational prospective study conducted in two steps to evaluate surgical prophylaxis procedures used by surgeons in several departments of the Second University of Naples (SUN). In step 1 (4 months), we collected and analyzed data on surgical interventions and antibiotic prophylaxis. Surgeons were informed of the analysis outcome and were given an antibiotic prophylaxis protocol based on international guidelines. In step 2 (5 months), we collected data on surgical interventions and antibiotic prophylaxis, and compared them with step 1 data. The analysis of 354 forms (step 1) showed that third-generation cephalosporins were the preferred prophylactic antibiotics. The analysis of 369 forms (step 2) showed that ceftriaxone and ampicillin were the most frequently used antibiotics. Surgeons did not comply with guidelines for antibiotic prophylaxis as regards type of antibiotic and treatment duration but implementation of antibiotic prophylaxis protocols resulted in more appropriate and better timing of antibiotic prophylaxis.

Granuloma telangectásico post-circuncisión / Telangectasic granuloma secondary to circumcision

Paciente de 5 años, con antecedente de Hemofilia por déficit de factor VIII, que fue sometido en febrero del 2002 a una circuncisión, con la debida administración de Factor VIII preoperatorio, cirugía que evolucionó sin incidentes hemorragíparos. El paciente permaneció asintomático hasta tres meses del postoperatorio, donde presentó una lesión hemangiomatosa alrededor del meato uretral, solevantada, indolora, que no alteraba la micción y que creció rápidamente. Una evaluación dermatológica diagnosticó un granuloma telangectásico o piógeno, secundario probablemente al traumatismo quirúrgico, aplicándole corticoides tópico. La respuesta fue inmediata, presentando una importante remisión de la lesión glandular. Este granuloma telangectásico está definido como un nódulo de tipo vascular, a menudo en el sitio de un trauma. Son escasos los casos publicados en niños sometidos a una circuncisión. No tendría relación con la presencia de hemofilia.

Effects of docosahexaenoic acid on [Ca(2+)](i) increase induced by doxorubicin in ventricular rat cardiomyocytes.

The clinical use of doxorubicin (DXR) is limited by cardiotoxicity partially due to interference with intracellular Ca(2+) homeostasis and involving the activation of the sarcoplasmic reticulum (SR) Ca(2+) release channels. It is known that docosahexaenoic acid (DHA) is able to potentiate the sensitivity of cancer cells to DXR. The aim of our study was to further evaluate the effects of DHA on [Ca(2+)](i) overload induced by DXR in adult rat ventricular cardiomyocytes in order to verify if DHA interferes with DXR-induced cardiotoxicity too. [Ca(2+)](i) was measured by microfluorimetry. Our data demonstrated that 100 microM DXR induced a statistically significant [Ca(2+)](i)-increase in cardiomyocytes perfused with CaCl(2) Krebs solution (from 135.7 +/- 15 nM to 560.2 +/- 49 nM, n = 9, p < 0.01) and with Ca(2+)-free Krebs solution (from 89.3 +/- 15 nM to 551.1 +/- 35 nM, n = 9, p < 0.01). Treatment with 10 microM DHA for 20 min significantly suppressed DXR [Ca(2+)](i)- increase in cells perfused with CaCl(2) Krebs solution (142.3 +/- 12 nM, n = 9, p < 0.01) and in Ca(2+)-free procedures (100.4 +/- 12 nM, n = 9, p < 0.01). Caffeine 10 mM significantly increased [Ca(2+)](i) in cardiomyocytes perfused with CaCl(2) Krebs solution (from 135.7 +/- 15 nM to 979.2 +/- 17.8 nM, n = 9, p < 0.01) and with Ca(2+)-free Krebs solution (from 89.3 +/- 15 nM to 891.1 +/- 30 nM, n = 9, p < 0.01). Treatment with 10 microM DHA for 20 min suppressed caffeine [Ca(2+)](i)-increase in cardiomyocytes perfused with CaCl(2) Krebs solution (174.2 +/- 28 nM, n = 9, p < 0.01) and in Ca(2+)-free procedures (161.9 +/- 34 nM, n = 9, p < 0.01). In conclusion, our results suggest that DHA is able to prevent acute modifications of calcium homeostasis induced by DXR probably interfering with SR Ca(2+) release channels.

Effects of docosahexaenoic acid on calcium pathway in adult rat cardiomyocytes.

In this study we examined the effect of polyunsaturated fatty acids (PUFAs), in particular of docosahexaenoic acid (DHA), on calcium homeostasis in isolated adult rat cardiomyocytes exposed to KCl, ET-1 and anoxia. Free [Ca(2+)](i) in rat cardiomyocytes was 135.7 +/- 0.5 nM. Exposure to 50 mM KCl or 100 nM ET-1 resulted in a rise in free [Ca(2+)](i) in freshly isolated cells (465.4 +/- 15.6 nM and 311.3 +/- 12.6 nM, respectively) and in cultured cells (450.8 +/- 14.8 nM and 323.5 +/- 14.8 nM respectively). An acute treatment (20 minutes) with 10 microM DHA significantly reduced the KCl- and ET-1-induced [Ca(2+)](i) increase (300.9 +/- 18.1 nM and 232.08 +/- 11.8 nM, respectively). This reduction was greater after chronic treatment with DHA (72 h; 257.7 +/- 13.08 nM and 192.18 +/- 9.8 nM, respectively). Rat cardiomyocytes exposed to a 20 minute superfusion with anoxic solution, obtained by replacing O(2) with N(2) in gas mixture, showed a massive increase in cytosolic calcium (1200.2 +/- 50.2 nM). Longer exposure to anoxia induced hypercontraction and later death of rat cardiomyocytes. Preincubation with DHA reduced the anoxic effect on [Ca(2+)](i) (498.4 +/- 7.3 nM in acute and 200.2 +/- 12.2 nM in chronic treatment). In anoxic conditions 50 mM KCl and 100 nM ET-1 produced extreme and unmeasurable increases of [Ca(2+)](i.) Preincubation for 20 minutes with DHA reduced this phenomenon (856.1 +/- 20.3 nM and 782.3 +/- 7.6 nM, respectively). This reduction is more evident after a chronic treatment with DHA (257.7 +/- 10.6 nM and 232.2 +/- 12.5 nM, respectively). We conclude that in rat cardiomyocytes KCl, ET-1 and anoxia interfered with intracellular calcium concentrations by either modifying calcium levels or impairing calcium homeostasis. Acute, and especially chronic, DHA administration markedly reduced the damage induced by calcium overload in those cells.

Self-prescribed laxative use: a drug-utilization review.

This study was conducted to determine the reasons for the choice of self-prescribed laxatives and to acquire information on how they were used and tolerated. From November 1999 to February 2000, 70 pharmacies, uniformly located throughout the Campania region of southern Italy, distributed a questionnaire to purchasers of over-the-counter laxatives. The average age of the (mostly female) respondents was 45.9 years; 23.8% were elderly. Among the 7324 individuals who completed the survey, 77.6% selected an oral product; 22.4% preferred rectal administration. A physician influenced the choice of a laxative in 37.7% of the cases, a pharmacist in 20.5%; other suggestions came from relatives (14%), acquaintances (12.1%), advertisements (11.7%), and miscellaneous sources (4%). Only 59.8% of respondents used these drugs correctly, and 58.2% consulted a physician or pharmacist because of constipation. Adverse effects, mainly gastrointestinal symptoms, occurred in 6.1% of those surveyed. The long-term use or abuse of laxatives can cause serious medical consequences, as well as mask diseases, delaying diagnosis and appropriate treatment. Physicians, pharmacists, and other health-care personnel should counsel patients on the proper use of these easily available, ubiquitous drugs.

Effects of nebivolol on human platelet aggregation.

It has been documented that beta-adrenergic antagonists can influence platelet aggregation by a mechanism independent of their ability to antagonize beta-adrenoceptors. Nebivolol, a selective beta1-adrenergic receptor antagonist with additional hemodynamic effects, is able to vasodilate human forearm vasculature by acting on the L-arginine/nitric oxide pathway. Constitutive nitric oxide synthase is present also in human platelets, resulting in the formation of nitric oxide, an endogenous inhibitor of platelet aggregation. The aim of this study was to investigate the effects of nebivolol on platelet aggregation and in particular to determine the involvement of the platelet L-arginine/nitric oxide pathway. Propranolol, a nonselective beta-adrenergic antagonist, and carvedilol, a beta-blocker with vasodilating properties, were compared with nebivolol on platelet activity. Plasma from healthy male subjects was used. Platelet aggregation was achieved with adenosine diphosphate (ADP) (3 microM) and collagen (1 microg/ml), using the Born turbidimetric method to measure platelet aggregation. Our results showed that nebivolol, propranolol, and carvedilol all had an inhibitory effect on both ADP- and collagen-induced platelet aggregation. Nebivolol exhibited the greatest inhibition effect on platelet aggregation. The mechanism responsible for the inhibitory effect of nebivolol appeared to involve a nitric oxide-dependent pathway. Indeed, L-arginine augmented the inhibitory effects of nebivolol on platelet aggregation induced by collagen and ADP. Furthermore, the inhibitory effect of nebivolol on platelet aggregation was reduced in the presence of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). In conclusion, we have demonstrated in this study that nebivolol's mechanism of platelet aggregation inhibition differs from that of other beta-adrenergic antagonists by being partially dependent on nitric oxide production.