Biomedical subjects

M Piccoli

Publications and source records attributed to M Piccoli.

At least 19 recordsLinked to original sources

PubMed2006

A hand-carried cardiac ultrasound device in the outpatient cardiology clinic reduces the need for standard echocardiography.

OBJECTIVE: To assess the potential value and cost-effectiveness of a hand-carried ultrasound (HCU) device in an outpatient cardiology clinic. METHODS: 222 consecutive patients were prospectively enrolled in the study. When standard echocardiography (SE) was specifically indicated on the basis of clinical history, electrocardiogram and physical examination, the same cardiologist (level-2 or level-3 trained) immediately performed an HCU examination. The cardiologist then reassessed the clinical situation to confirm or cancel the SE request according to the information provided by HCU. The SE examination was performed by a sonographer and examined in a blinded fashion by a cardiologist expert in echocardiography. Findings from the two examinations were compared. RESULTS: HCU was performed in 108/222 patients, and a definite diagnosis was established in 34 of them (31%), making SE examination potentially avoidable. In the 74 patients with inconclusive HCU results and for whom SE was still indicated, the decision was mainly dictated by the lack of spectral Doppler modality in the HCU system. The overall agreement between HCU and SE for diagnosis of normal/abnormal echocardiograms was 73% (kappa = 0.4). On the basis of the potentially avoided SE examinations and the obviated need for a second cardiac consultation, a total cost saving of euro2142 per 100 patients referred for echocardiography was estimated. CONCLUSIONS: The use of a simple HCU device in the outpatient cardiology clinic allowed reliable diagnosis in one third of the patients referred for echocardiography, which translates into cost and time saving benefits.

Ambulatory Care↗

PubMed2006

Rosiglitazone modifies the adipogenic potential of human muscle satellite cells.

AIMS/HYPOTHESIS: Satellite cells are responsible for postnatal skeletal muscle regeneration. It has been demonstrated that mouse satellite cells behave as multipotent stem cells. We studied the differentiation capacities of human satellite cells and evaluated the effect of the insulin sensitiser rosiglitazone, a well known peroxisome proliferative activated receptor gamma (PPARG) agonist, on their adipogenic conversion. SUBJECTS, MATERIALS AND METHODS: We obtained human satellite cells from human muscle biopsies of healthy subjects by single-fibre isolation and cultured them under myogenic, osteogenic and adipogenic conditions. Moreover, we compared the morphological features and the adipose-specific gene expression profiling, as assessed by quantitative PCR, between adipocytes differentiated from human satellite cells and those obtained from the stromal vascular fraction of human visceral fat. RESULTS: We proved by morphological analysis, mRNA expression and immunohistochemistry that human satellite cells are able to differentiate into myotubes, adipocytes and osteocytes. The addition of rosiglitazone to the adipogenic medium strongly activated PPARG expression and enhanced adipogenesis in human satellite cells, but did not in itself trigger the complete adipogenic programme. Moreover, we observed a decrease in wingless-type MMTV integration site family member 10B and an upregulation of growth differentiation factor 8 expression, both being independent of PPARG activation. CONCLUSIONS/INTERPRETATION: Human satellite cells possess a clear adipogenic potential that could explain the presence of mature adipocytes within skeletal muscle in pathological conditions such as obesity, type 2 diabetes and ageing-related sarcopenia. Rosiglitazone treatment, while enhancing adipogenesis, induces a more favourable pattern of adipocytokine expression in satellite-derived fat cells. This could partially counteract the worsening effect of intermuscular adipose tissue depots on muscle insulin sensitivity.

Adipogenesis↗

PubMed2006

Aetiology of preterm labour: bacterial vaginosis.

Bacterial vaginosis (BV) is a common condition characterised by a polymicrobial disorder, with an overgrowth of several anaerobic or facultative bacteria and with a reduction or absence of lactobacillus colonisation. The prevalence of BV ranges from 4 to 64%, depending on the racial, geographic and clinical characteristics of the study population. In asymptomatic women, the prevalence varies from 12 to 25%, and similar percentages are observed in pregnant women. Although BV is associated with several adverse outcomes, such as upper genital tract infections, pelvic inflammatory disease, endometritis, preterm birth and low birthweight, many basic questions regarding the pathogenesis of BV remain unanswered. Mucosal immune system activation may represent a critical determinant of adverse consequences associated with BV. An unequal risk for BV acquisition and\or recurrence could derive from different mucosal immune host abilities and\or capability of invading microbes to produce factors that inactivate the local immune response. BV is associated with a two-fold increased risk of preterm birth, with the greatest risk when BV is present before 16 weeks of gestation (odds ratio = 7.55). This may indicate a critical period during early gestation when BV-related organisms can gain access to the upper genital tract and set the stage for spontaneous preterm labour later in gestation. The results of treatment trials for pregnant women with BV have been heterogeneous, with anywhere from an 80% reduction to a two-fold increase in preterm birth among women who received treatment. For this reason, in current clinical practice significant controversy surrounds determining not only who and when to screen but also who and how to treat. Recent evidence shows that individual genetic backgrounds can affect chemokine production. This is an interesting area for future research and could lead to trials of treatment only for women genetically predisposed to preterm birth.

Female↗

PubMed2005

Video laparoscopic surgery: is out-of-hospital thromboprophylaxis necessary?

Despite widespread use of laparoscopic procedures, no adequate data are available to support specific recommendations for venous thromboprophylaxis in patients undergoing laparoscopic surgery. This prospective, randomized trial is the first to be designed to evaluate a regimen of out-of-hospital thromboprophylaxis after laparoscopic surgery. Consecutive patients admitted for laparoscopic surgery were considered for the study. The thromboprophylaxis regimen used for each patient was based on a risk score. Possible thromboprophylactic measures included elastic stockings and pre- and postoperative Dalteparin or early ambulation. At discharge, patients were randomly allocated either to continue Dalteparin for 1 week, or to receive no further prophylaxis. Patients judged to be at low risk were not randomized. Compression ultrasound of the leg veins was performed in all patients 4 weeks after hospital discharge. Fifty-three patients, all with acute appendicitis, were judged to be at low risk of deep vein thrombosis and were not included in the randomized study. The remaining 209 patients fell into two groups: 104 patients received postdischarge Dalteparin and 105 patients did not. The incidence of deep vein thrombosis was 0% (0 of 104) vs. 0.95% (one of 105), respectively (P = 1.00). The risk of postdischarge venous thromboembolism is low in patients undergoing laparoscopic surgery who receive in-hospital thromboprophylaxis. Given this low risk, a clinical trial powered to determine if extending prophylaxis in such patients reduces the risk of clinically apparent deep vein thrombosis would be unfeasibly large.

Adult↗

PubMed2004

Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death.

Herein, we provide the first evidence on the capsaicin (CPS) receptor vanilloid receptor type-1 (VR1) by rat thymocytes, and its involvement in CPS-induced apoptosis. VR1 mRNA was identified by quantitative RT-PCR in CD5(+) thymocytes. By immunofluorescence and flow cytometry, we found that a substantial portion of CD5+ thymocytes, namely CD4+ and double negative (DN) cell subsets, express VR1 that was present on plasma membrane on discrete spots. By Western blot, VR1 protein was identified as a single band of 95 kDa. We also described that CPS could trigger two distinct pathways of thymocyte death, namely apoptosis and necrosis depending on the dose of CPS exposure. CPS-induced apoptosis involved intracellular free calcium (Ca2+) influx, phosphatidylserine exposure, mitochondrial permeability transmembrane pore (PTP) opening and mitochondrial transmembrane potential (Delta Psi m) dissipation leading to cytochrome c release, activation of caspase-9 and -3 and oligonucleosomal DNA fragmentation. VR1 was functionally implicated in these events as they were completely abrogated by the VR1 antagonist, capsazepine (CPZ). Finally, we demonstrated that VR1 expression on distinct thymocytes was associated with the selective ability of CPS to trigger DNA fragmentation in VR1+ CD4+ and DN thymocytes. Overall, our results suggest that the expression of VR1 on thymocytes may function as a sensor of harmful stimuli present in the thymic environment.

Animals↗

PubMed2004

Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma.

BACKGROUND: A study was undertaken to analyse the potential prognostic value of the immunohistochemical expression of cyclooxygenase-2 (COX-2) and p27 in 29 malignant mesotheliomas already screened for the expression of p21 and p53. METHODS: Immunohistochemistry was used to determine the expression of COX-2 and p27. The correlation with survival of these factors and of p21 and p53 expression was assessed by univariate and multivariate analyses. RESULTS: A positive statistically significant correlation was found between p27 and p21 expression (p<0.0001), but there was a negative correlation between COX-2 expression and both p27 (p = 0.001) and p21 (p<0.0001). No statistically significant correlation was recorded between p53 and all the other immunohistochemical parameters. Univariate analysis showed that overall survival was strongly influenced by p21, p27, and COX-2 expression, but multivariate Cox regression analysis showed that the only immunohistochemical parameter to influence overall survival of patients with mesothelioma was COX-2. CONCLUSIONS: These findings suggest that COX-2 expression may be a useful prognostic parameter for mesothelioma.

Cell Cycle Proteins↗

PubMed2001

Ubiquitination and degradation of Syk and ZAP-70 protein tyrosine kinases in human NK cells upon CD16 engagement.

Syk and ZAP-70 nonreceptor protein tyrosine kinases (PTKs) are essential elements in several cascades coupling immune receptors to intracellular responses. The critical role of these kinases in promoting the propagation of intracellular signaling requires a tight regulation of their activity, thus the existence of a negative feedback loop regulating their expression can be hypothesized. Herein, we have investigated whether ubiquitin-dependent proteolysis could be a mechanism responsible for controlling the fate of Syk and ZAP-70 after their immunoreceptor-induced activation. We found that both Syk and ZAP-70 become ubiquitinated in response to aggregation of the low affinity Fc receptor for IgG (CD16) on human natural killer cells. We confirmed the identity of the major in vivo ubiquitinated kinase species by performing an in vitro ubiquitination assay. In addition, we found that after CD16 stimulation, ubiquitinated forms of Syk and ZAP-70 associate with the receptor complex. After CD16 engagement, we also observed a decrease in the stability of Syk and ZAP-70 PTKs that is counteracted by pretreatment with either proteasome or lysosomal inhibitors. Moreover, in the presence of the proteasome inhibitor, epoxomicin, we observed an accumulation of ubiquitinated forms of both kinases. Our findings provide evidence of ligand-induced ubiquitination of nonreceptor PTKs belonging to the Syk family and propose the ubiquitin-dependent proteasome-mediated degradation pathway as a mechanism for attenuating the propagation of intracellular signaling initiated by immune receptor engagement.

Cells, Cultured↗

PubMed2001

The adaptor protein shc is involved in the negative regulation of NK cell-mediated cytotoxicity.

The activation of protein tyrosine kinase(s) (PTK) is a critical event required for the development of NK cell-mediated cytotoxicity. Here we demonstrate that the adaptor protein shc undergoes tyrosine phosphorylation during the generation of antibody-dependent cellular cytotoxicity (ADCC) and natural killing. In addition, we report that, upon direct or antibody-dependent target cell interaction, shc coprecipitates with the Src homology 2 (SH2)-containing inositol phosphatase, SHIP. To gain information on the functional role of shc in NK cytotoxicity, we overexpressed wild-type or dominant negative shc constructs in the human NKL cell line. Our findings show a consistent shc-mediated down-regulation of ADCC and natural killing. Such functional effect correlates with a perturbation of the phosphoinositide (PI) metabolism by means of a shc-mediated negative regulation of inositol 1,4,5 triphosphate (IP3) generation and intracellular calcium flux upon CD16 ligation. Furthermore, our data show that dominant-negative shc-mediated perturbation of shc/SHIP interaction leads to inhibition of ligand-dependent SHIP recruitment to CD16 zeta chain. We suggest that shc plays a role of negative adaptor by modulating SHIP recruitment to activation receptors involved in the generation of NK cytotoxic function.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Involvement of alpha(v)beta3 integrin-like receptor and glycosaminoglycans in Candida albicans germ tube adhesion to vitronectin and to a human endothelial cell line.

The present study was undertaken to investigate the expression of alpha(v)beta3 and alpha(v)beta5 integrin-like vitronectin receptors (VNRs) on Candida albicans germ tube and their involvement in its adhesion to vitronectin (VN) and human endothelial cells. By immunofluorescence and FACS analysis, several monoclonal antibodies directed against human alpha(v) or beta3 integrin subunit or alpha(v)beta3 and alpha(v)beta5 heterodimers, positively stained C. albicans germ tubes. C. albicans germ tubes specifically adhered (45-50%) to VN and this adhesion was markedly inhibited by RGD-, but not RGE-containing peptides. Adhesion of C. albicans germ tubes to VN was strongly inhibited by anti-alphav, anti-beta3 or anti-alpha(v)beta3, but not by alpha(v)beta5 monoclonal antibody. C. albicans germ tube adhesion to VN was also inhibited by glycosaminoglycans (GAGs) such as heparin or chondroitin sulphate. Finally, we show that C. albicans germ tubes adhere to the human EA.hy 926 endothelial cell line. This adhesion is markedly blocked by anti-beta3 monoclonal antibody, GRGDSP peptide or heparin, and is completely abolished by their combination. Overall these results indicate that C. albicans germ tube adherence to VN and to a human endothelial cell line is mediated by alpha(v)beta3, but not by alpha(v)beta5-like integrin, and depends on GAGs which may act by regulating alpha(v)beta3 integrin-like/VN adhesive interaction.

Adhesiveness↗

PubMed2001

Efficacy of maintenance therapy with topical boric acid in comparison with oral itraconazole in the treatment of recurrent vulvovaginal candidiasis.

OBJECTIVE: Our purpose was to examine the efficacy of a topical long-term treatment with boric acid versus an oral long-term treatment (itraconazole) in the cure and prevention of recurrent vulvovaginal candidiasis. STUDY DESIGN: A prospective, nonrandomized study of patients affected by recurrent vulvovaginal candidiasis was undertaken. In 3 years we recruited 22 consecutive patients who underwent therapy with itraconazole (group 1) or boric acid (group 2). Women were followed up for 1 year, with clinic and microbiologic controls after 1, 3, 6, and 12 months after the first visit. RESULTS: During the treatment, the positive culture results (15.1% vs 12.1%) and the signs and symptoms (33.3% vs. 24.2%) were similar within the 2 groups, with no significant statistical difference. With the withdrawal, after 6 months relapses were common in the 2 groups (54.5%). CONCLUSIONS: Boric acid seems to be a valid and promising therapy both in the cure of the vaginal infection and in the prevention of relapses of recurrent vulvovaginal candidiasis, but its efficacy ends with the suspension of the therapy.

Adult↗

PubMed2001

[Perioperative nursing: identification of the nursing diagnosis of risk for infection based on the Levine's conceptual model].

The pre-operative visit consists in the first phase in the systematization of perioperative nursing care. This study aimed at identifying, during the pre-operative visit and more frequently, a nursing diagnosis of clients submitted to general surgery. The selected theoretical framework was Levine's conceptual model based on the four conservation principles, which are: energy conservation, structural integrity conservation, personal integrity conservation and social integrity conservation. In order to reach the proposed objective, an instrument was previously elaborated and validated for data collection. The sample consisted of 30 patients, males and females, who had been submitted to general surgery. The nursing diagnosis Infection Risk obtained 100% of frequency during the pre-operative visits to surgery patients. As to related factors that were identified, we point out: the site of invasion by organisms after the surgery and invasive procedures. Thus, the identification of this diagnosis can help nurses with the planning and implementation of preventive and infection control care, especially if risk factors are identified in the preoperative period.

Adult↗

PubMed2001

Modifications in cardiovascular functional parameters with aging.

BACKGROUND: The constant rise in the number of old people involves a great interest towards the aging of the cardiovascular system. Many authors have studied age-adjusted limits to echocardiographic and functional parameters. The aim of this study is to evaluate some functional parameters so as to define the cardiovascular modifications of the aging heart. METHODS: We have studied 66 patients, 32 of mean age 71+/-4 years (Group 1) and 34 with mean age 33+/-6 years (Group 2), without cardiovascular diseases, through basal echocardiography and exercise test. RESULTS: In comparison to group 2, in group 1 we have observed at rest normal ventricular dimensions with increase of the thickness (SIV 11.2+/-0.4 vs 9+0.6, p=0.01; PP 10.6+/-0.6 vs 9.2+0.4, p=0.01), of the left atrium (41.2+/-1.08 vs 36.2+1.3, p=0.05), and of the aortic root (33.2+/-1.3 vs, 30.8+0.9, p=0.05), altered diastolic function (E/A 0.7+/-0.14 vs 1.9+/-0.7, p=0.01), with normal systolic indexes. At 100 Watts workload there was an age-related increase in end-diastolic volume (142+/-10.6 vs 127+/-4.3, p=0.01) and an age related decrease in heart rate (HR 100 W 148+/-10.7 vs 169+/-10.9, p=0.05). CONCLUSIONS: In the heart of an elderly subject therefore there are morphological modifications that in the absence of organic pathologies can support the metabolic demands of the organism and adapt to the physiological modifications of the elderly subject.

Adaptation, Physiological↗

PubMed2000

Impairment of rat thymocyte differentiation and functions by neonatal capsaicin treatment is associated with induction of apoptosis.

The direct and indirect interaction between the nervous system and its transmitters with the immune system was evaluated in the rat by using the neurotoxin capsaicin (Caps). In the present study we investigated the effect of Caps administration to neonatal rats on thymocyte subpopulation distribution and functions at different times after treatment. Caps treatment results in a marked reduction of thymus weight and cellularity. As shown by immunofluorescence and FACS analysis, profound depletion of double negative (DN), double positive (DP), and single positive (SP) CD4(+) cells was already evident at day 7 after treatment and persisted until day 28. Reduced numbers of SP CD8(+) cells were observed only at later time points. Analysis of TCR phenotype indicates that CD5(+) TCR gamma/delta(+) are particularly sensitive to neonatal Caps treatment. Caps-induced thymocyte depletion was associated with reduced proliferation in response to T cell mitogens. Moreover, in situ TUNEL reaction and agarose gel electrophoresis indicate that neonatal Caps treatment induces apoptosis of thymus cells. Morphological analysis reveals the presence of apoptotic cells in the subcapsular thymus cortical region. Overall our results suggest that Caps when administered at birth, profoundly affects T cell differentiation, likely through its ability to activate apoptotic cell death program.

Animals↗

PubMed2000

Cutting edge: functional role for proline-rich tyrosine kinase 2 in NK cell-mediated natural cytotoxicity.

Protein tyrosine kinase activation is one of the first biochemical events in the signaling pathway leading to activation of NK cell cytolytic machinery. Here we investigated whether proline-rich tyrosine kinase 2 (Pyk2), the nonreceptor protein tyrosine kinase belonging to the focal adhesion kinase family, could play a role in NK cell-mediated cytotoxicity. Our results demonstrate that binding of NK cells to sensitive target cells or ligation of beta2 integrins results in a rapid induction of Pyk2 phosphorylation and activation. By contrast, no detectable Pyk2 tyrosine phosphorylation is found upon CD16 stimulation mediated by either mAb or interaction with Ab-coated P815 cells. A functional role for Pyk2 in natural but not Ab-mediated cytotoxicity was demonstrated by the use of recombinant vaccinia viruses encoding the kinase dead mutant of Pyk2. Finally, we provide evidence that Pyk2 is involved in the beta2 integrin-triggered extracellular signal-regulated kinase activation, supporting the hypothesis that Pyk2 plays a role in the natural cytotoxicity by controlling extracellular signal-regulated kinase activation.

Antibody-Dependent Cell Cytotoxicity↗

PubMed2000

CD69-triggered ERK activation and functions are negatively regulated by CD94 / NKG2-A inhibitory receptor.

CD69 represents a functional triggering molecule on activated NK and T cells, capable of inducing cytotoxic activity and costimulating cytokine production. It belongs to the C-lectin type superfamily, and its gene maps in the NK gene complex, close to other genes coding for NK receptors. CD94 / NKG2-A complex is the inhibitory receptor for the non classical MHC class I molecule HLA-E on human NK cells. To investigate CD69-initiated signal transduction pathways, and to evaluate CD94 / NKG2-A interference on CD69 triggering ability, we have generated transfectants expressing both receptors in the RBL cell line. Here we report that CD69 engagement leads to the activation of extracellular signal-regulated kinase (ERK) enzymes belonging to the MAPK family, and that this event is required for CD69-mediated cell degranulation. Moreover, we show that the co-engagement of CD94 / NKG2-A inhibitory receptor effectively suppresses both CD69-triggered cell degranulation in RBL transfectants, through the inhibition of ERK activation, and CD69-induced cytotoxicity in human NK cells. Thus, here we provide new information on the molecular mechanisms initiated by CD69 activation receptor, and show that CD69-initiated signaling pathways and functional activity are negatively regulated by CD94 / NKG2-A inhibitory complex.

Animals↗

PubMed2000

RAC1/P38 MAPK signaling pathway controls beta1 integrin-induced interleukin-8 production in human natural killer cells.

The MAP kinase (MAPK) p38 plays a key role in regulating inflammatory responses. Here, we demonstrate that beta1 integrin ligation on human NK cells results in the activation of the p38 MAPK signaling pathway, which is required for integrin-triggered IL-8 production. In addition, we identified some of the upstream events accompanying the beta1 integrin-mediated p38 MAPK activation, namely, the activation of the Rac guanine nucleotide exchange factor (GEF) p95 Vav, the small G protein Rac1, and the cytoplasmic kinases Pak1 and MKK3. Finally, we provide direct evidence that p95 Vav and Rac control the activation of p38 MAPK triggered by beta1 integrins.

Cells, Cultured↗

PubMed2000

[Myocardial ischemia after administration de sildenafil: description of a case and review of the literature].

Erectile dysfunction is a common condition in middle-aged and older men and frequently occurs in association with various chronic illnesses, particularly cardiovascular diseases. As there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient's cardiovascular status before initiating any treatment for erectile dysfunction. This is particularly relevant for men with decreased exercise tolerance as a result of their ischemic heart disease. We examined 2 patients with no history of cardiovascular disease suffering from myocardial ischemia after sildenafil administration. The literature about a correlation between sildenafil and coronary artery disease is reviewed.

Electrocardiography↗

PubMed2000

[Gynecologic infections in adolescence].

BACKGROUND: Adolescence in the age bracket with the highest incidence of sexually transmitted diseases (STDs). An observational study was performed in symptomatic patients attending our Outpatient Clinic for STDs in order to evaluate the diffusion of genital infections in the adolescent population and the different epidemiological distribution compared to adults. METHODS: The incidence of these infections was compared in two groups of patients attending the clinic between April 1995 and April 1999. The first consisted of 54 teenagers (13-19 years-old) and the second, used as a control, consisted of 917 women of child-bearing age (20-40 years). All patients underwent clinical examinations and microbiological tests of vaginal secretions (bacterioscopic test on coloured plates using the Gram method, cold tests, cultural assay of bacteria and fungi, assay for (Chlamydia trachomatis, Mycoplasma spp., Neisseria gonorrhoeae, Herpes simplex virus). RESULTS: The most common genital infection in teenagers was candidosis (35% vs 23.9%), followed by bacterial vaginosis (31.9% vs 25.8%) and mixed flora vaginitis (25.9% vs 22.6%). HSV was found in 1.8% of adolescents (vs 0.6%), in selected cases, Chlamydia and Mycoplasma were present in 16.6% (vs 1.1%) and 50% (vs 28%) of teenagers respectively. CONCLUSIONS: All genital infections were more frequent in the study population of adolescents compared to the control group. The adolescent population should be the target of a serious and systematic programme of prevention in order to ward off the sequelae of early and often irresponsible sexual activity.

Adolescent↗