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S Greco

Publications and source records attributed to S Greco.

At least 19 recordsLinked to original sources
PubMed2007

Effects of etanercept, a tumour necrosis factor-alpha antagonist, in an experimental model of periodontitis in rats.

BACKGROUND AND PURPOSE: Etanercept is a tumour necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate, for the first time, the therapeutic efficacy of in vivo inhibition of TNF-alpha in an experimental model of periodontitis. EXPERIMENTAL APPROACH: Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg-1, s.c., after placement of the ligature. KEY RESULTS: Periodontitis in rats resulted in an inflammatory process characterized by oedema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators, tissue damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg-1, s.c., after placement of the ligature) significantly reduced the degree of (1) periodontitis inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of nitrotyrosine and cytokines (eg TNF-alpha)) and (4) apoptosis (Bax and Bcl-2 expression). CONCLUSIONS AND IMPLICATIONS: Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury, events associated with periodontitis.

Animals↗
PubMed2006

Current evidence on diagnostic accuracy of commercially based nucleic acid amplification tests for the diagnosis of pulmonary tuberculosis.

BACKGROUND: Even though commercial nucleic acid amplification tests (NAATs) have become the most frequently used molecular tests for laboratory diagnosis of pulmonary tuberculosis (TB), published studies report variable estimates of their diagnostic accuracy. We analysed the accuracy of commercial NAATs for the diagnosis of pulmonary TB in smear positive and smear negative respiratory samples using culture as a reference standard. METHODS: English language studies reporting data sufficient for calculating sensitivity and specificity of commercial NAATs on smear positive and/or smear negative respiratory samples were included. Meta-regression was used to analyse associations with reference test quality, the prevalence of TB, sample and test type. Predictive values for different levels of pre-test probability were quantified using Bayes' approach. RESULTS: Sixty three journal articles published between 1995 and 2004 met the inclusion criteria. Pooled sensitivity and specificity were 0.96 and 0.85 among smear positive samples and 0.66 and 0.98 among smear negative samples. The number of culture media used as reference test, the inclusion of bronchial samples, and the TB prevalence were found to influence the reported accuracy. The test type had no effect on the diagnostic odds ratio but seemed to be correlated with sensitivity or specificity, probably via a threshold effect. CONCLUSIONS: Commercial NAATs can be confidently used to exclude TB in patients with smear positive samples in which environmental mycobacteria infection is suspected and to confirm TB in a proportion of smear negative cases. The methodological characteristics of primary studies have a considerable effect on the reported diagnostic accuracy.

Humans↗
PubMed2006

Protein kinase C (PKC)-delta/-epsilon mediate the PKC/Akt-dependent phosphorylation of extracellular signal-regulated kinases 1 and 2 in MCF-7 cells stimulated by bradykinin.

In this paper the signal transduction pathways evoked by bradykinin (BK) in MCF-7 breast cancer cells were investigated. BK activation of the B(2) receptor provoked: (a) the phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2); (b) the translocation from the cytosol to the membrane of the conventional protein kinase C-alpha (PKC-alpha) and novel PKC-delta and PKC-epsilon; (c) the phosphorylation of protein kinase B (PKB/ Akt); (d) the proliferation of MCF-7 cells. The BK-induced ERK1/2 phosphorylation was completely blocked by PD98059 (an inhibitor of the mitogen-activated protein kinase kinase (MAPKK or MEK)) and by LY294002 (an inhibitor of phosphoinositide 3-kinase (PI3K)), and was reduced by GF109203X (an inhibitor of both novel and conventional PKCs); Gö6976, a conventional PKCs inhibitor, did not have any effect. The BK-induced phosphorylation of PKB/Akt was blocked by LY294002 but not by PD98059. Furthermore, LY294002 inhibited the BK-provoked translocation of PKC-delta and PKC-epsilon suggesting that PI3K may be upstream to PKCs. Finally, the proliferative effects of BK were blocked by PD98059, GF109203X and LY294002. These observations demonstrate that BK acts as a proliferative agent in MCF-7 cells activating intracellular pathways involving novel PKC-delta/-epsilon, PKB/Akt and ERK1/2.

Analysis of Variance↗
PubMed2006

Cost determinants of tuberculosis management in a low-prevalence country.

SETTING: Division of respiratory medicine in a specialised infectious disease hospital in Rome, Italy. OBJECTIVE: Retrospective evaluation of tuberculosis (TB) care associated costs in an integrated in- and out-patient management programme. DESIGN: Review of the medical records of 92 human immunodeficiency virus negative TB cases admitted between September 2000 and May 2003. RESULTS: Length of in-hospital stay (45 +/- 35 days) was the major cost determinant, as hospitalisation accounted for almost 80% of the total costs of the case, with fixed bed-per-day charges amounting to 76% of hospital costs. Factors associated with higher costs were chest X-ray score, fever, sputum bacterial load and multidrug resistance (P < 0.05). Cure/treatment completion was achieved in 82% of patients entering the out-patient programme (63% of all cases). Homelessness, age and comorbidities were associated with unfavourable outcomes. CONCLUSIONS: A closely followed hospital-centred protocol carried out in a high-resource setting may produce acceptable cure/completion treatment rates. As a too high fraction of resources invested in TB control goes toward hospital costs, out-patient treatment strategies should be implemented.

Adult↗
PubMed2005

Bradykinin stimulates cell proliferation through an extracellular-regulated kinase 1 and 2-dependent mechanism in breast cancer cells in primary culture.

We have previously reported that bradykinin (BK) represents an influential mitogenic agent in normal breast glandular tissue. We here investigated the mitogenic effects and the signalling pathways of BK in primary cultured human epithelial breast cells obtained from a tumour and from the histologically proven non-malignant tissue adjacent to the tumour. BK provoked cell proliferation, increase in cytosolic calcium, activation of protein kinase C (PKC)-alpha, -beta, -delta, -epsilon and -eta and phosphorylation of the extracellular-regulated kinases 1 and 2 (ERK1/2). The following compounds blocked the proliferative effects of BK: Hyp3-BK, a B2 receptor subtype inhibitor; U73122, a phospholipase C-beta inhibitor; GF109203X, a protein kinase C (PKC) inhibitor; and PD98059, a mitogen-activated protein kinase kinase inhibitor. Gö6976, a Ca(2+)-dependent PKC inhibitor, did not have any effect. In conclusion, the mitogenic effects of BK are retained in peritumour and tumour cells; hence, it is likely that BK has an important role in cancer endorsement and progression.

Analysis of Variance↗
PubMed2004

Behaviour of the bowel wall during the first year after surgery is a strong predictor of symptomatic recurrence of Crohn's disease: a prospective study.

BACKGROUND: Recurrences after surgery for Crohn's disease are frequent and unpredictable. To date, there is little agreement as to which factors increase a patient risk of early recurrence. AIM: To assess whether the post-operative behaviour of diseased bowel walls, as determined by ultrasound, may be a useful predictor of relapse. METHODS: A total of 127 Crohn's disease patients were monitored after surgery by means of bowel ultrasound as well as by clinical and laboratory evaluations for a median follow-up of 41.0 months. Bowel wall thickness of diseased loops measured at ultrasound during follow-up was compared with the presurgery values. Multivariable survival analysis was performed to elucidate predictors of early post-operative recurrence. Receiver operating characteristic curves were also constructed taking into account bowel wall thickness for selecting Crohn's disease patients with high risk of clinical/surgical recurrence. RESULTS: The estimated 5 years survival probability of symptomatic Crohn's disease recurrence were 90% and 33%, respectively for unchanged/worsened bowel wall thickness vs. improved bowel wall thickness at 12 months from surgery. The hazard ratio for unchanged/worsened bowel wall thickness at 12 months was 8.9 (95% CI: 3.4-23.2). Receiver operating characteristic curve identified a bowel wall thickness > 6.0 mm at 12 months from surgery as directly associated with the risk of having a Crohn's disease recurrence (hazard ratio was 6.5, 95% CI: 2.8-15.4). CONCLUSIONS: Systematic ultrasound follow-up of diseased bowel walls after conservative surgery allows the early identification of patients at high risk of clinical/surgical recurrence.

Adolescent↗
PubMed2004

Mitogenic signalling by B2 bradykinin receptor in epithelial breast cells.

The kinin peptides are released during inflammation and are amongst the most potent known mediators of vasodilatation, pain, and oedema. A role in the modulation or induction of healthy breast tissue growth has been postulated for tissue kallikrein present in human milk. Moreover, tissue kallikrein was found in malignant human breast tissue and bradykinin (BK) stimulates the proliferation of immortalised breast cancer cells. Aim of the present article was to investigate whether BK also exerts mitogenic activity in normal breast epithelial cells and partially characterise the signalling machinery involved. Results show that BK increased up to 2-fold the 24 h proliferation of breast epithelial cells in primary culture, and that the BK B2 receptor (not B1) inhibitor alone fully blocked the BK response. Intracellular effects of B2 stimulation were the following: (a) the increase of free intracellular Ca(2+) concentration by a mechanism dependent upon the phospholipase C (PLC) activity; (b) the cytosol-to-membrane translocation of conventional (PKC)-alpha and -beta isozymes, novel PKC-delta, -epsilon, and -eta isozymes; (c) the phosphorylation of the extracellular-regulated kinase 1 and 2 (ERK1/2); and (d) the stimulation of the expression of c-Fos protein. EGF, a well known stimulator of cell proliferation, regulated the proliferative response in human epithelial breast cells to the same extent of BK. The effects of BK on proliferation, ERK1/2 phosphorylation, and c-Fos expression were abolished by GF109203X, which inhibits PKC-delta isozyme. Conversely, Gö6976, an inhibitor of PKC-alpha and -beta isozymes, and the 18-h treatment of cells with PMA, that led to the complete down-regulation of PKC-alpha, -beta, -epsilon, and -eta, but not of PKC-delta, did not have any effect, thereby indicating that the PKC-delta mediates the mitogenic signalling of BK. Phosphoinositide 3-kinase (PI3K), tyrosine kinase of the epidermal growth factor receptor (EGFR), and mitogen activated protein kinase kinases (MEK) inhibitors were also tested. The results suggest that EGFR, PI3K, and ERK are required for the proliferative effects of BK. In addition, the BK induced cytosol-to-membrane translocation of PKC-delta was blocked by PI3K inhibition, suggesting that PI3K is upstream to PKC-delta. In conclusion, BK has mitogenic actions in cultured human epithelial breast cells; the activation of PKC-delta through B2 receptor acts in concert with ERK and PI3K pathways to induce cell proliferation.

Bradykinin↗
PubMed2004

Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn's disease. A prospective comparison with conventional ultrasound, x ray studies, and ileocolonoscopy.

UNLABELLED: BACKGROUND/ AIM: Although ultrasound (US) has proved to be useful in intestinal diseases, barium enteroclysis (BE) remains the gold standard technique for assessing patients with small bowel Crohn's disease (CD). The ingestion of anechoic non-absorbable solutions has been recently proposed in order to distend intestinal loops and improve small bowel visualisation. The authors' aim was to evaluate the accuracy of oral contrast US in finding CD lesions, assessing their extent within the bowel, and detecting luminal complications, compared with BE and ileocolonoscopy. METHODS: 102 consecutive patients with proven CD, having undergone complete x ray and endoscopic evaluation, were enrolled in the study. Each US examination, before and after the ingestion of a polyethylene glycol (PEG) solution (500-800 ml), was performed independently by two sonographers unaware of the results of other diagnostic procedures. The accuracy of conventional and contrast enhanced US in detecting CD lesions and luminal complications, as well as the extent of bowel involvement, were determined. Interobserver agreement between sonographers with both US techniques was also estimated. RESULTS: After oral contrast, satisfactory distension of the intestinal lumen was obtained in all patients, with a mean time to reach the terminal ileum of 31.4 (SD 10.9) minutes. Overall sensitivity of conventional and oral contrast US in detecting CD lesions were 91.4% and 96.1%, respectively. The correlation coefficient between US and x ray extent of ileal disease was r1 = 0.83 (p<0.001) before and r2 = 0.94 (p<0.001) after PEG ingestion; r1 versus r2 p<0.01. Sensitivity in detecting strictures was 74% for conventional US and 89% for contrast US. Overall interobserver agreement for bowel wall thickness and disease location within the small bowel was already good before but significantly improved after PEG ingestion. CONCLUSIONS: Oral contrast bowel US is comparable with BE in defining anatomic location and extension of CD and superior to conventional US in detecting luminal complications, as well as reducing interobserver variability between sonographers. It may be therefore regarded as the first imaging procedure in the diagnostic work up and follow up of small intestine CD.

Adult↗
PubMed2003

Role of early ultrasound in detecting inflammatory intestinal disorders and identifying their anatomical location within the bowel.

BACKGROUND: Although bowel ultrasound is a widely accepted diagnostic tool in bowel diseases, its value as the primary imaging procedure in patients with symptoms/signs suggestive of inflammatory bowel disorders is still unclear. AIM: To investigate the accuracy of bowel ultrasound compared with barium X-ray studies, computed tomography, endoscopy and bowel surgery in the initial assessment of inflammatory bowel disorders. METHODS: Four hundred and eighty-seven patients hospitalized consecutively for symptoms or signs suggestive of a bowel disorder between December 1999 and March 2002 were initially enrolled in the study. All patients underwent bowel ultrasound as the first imaging procedure within 36 h of admission; radiographic evaluations, endoscopy and/or surgery were then performed as appropriate and the results of these investigations were used as the gold standard. RESULTS: Three hundred and thirty-six patients had pathological findings of the bowel detectable at ultrasound as the final diagnosis. The main organic disorders found were Crohn's disease (56%), ulcerative/indeterminate colitis (30%), bowel tumours (5%), appendicitis/diverticulitis (2%) and other inflammatory conditions (8%). The overall sensitivity and specificity of bowel ultrasound were 85% and 95%, respectively, whereas the positive and negative predictive values were 98% and 75%, respectively. Comparisons of ultrasound with X-ray or endoscopic results by disease localization showed that the diagnostic performance of ultrasound was higher for inflammatory conditions of the ileum and sigmoid/descending colon (sensitivity of 92% and 87%, respectively), whereas abnormalities localized in the rectum, duodenum and proximal jejunum were often missed by ultrasound. CONCLUSIONS: In expert hands, bowel ultrasound is highly predictive of inflammatory disease localized in the ileum or colon, and may well be used as the primary imaging method when Crohn's disease or ulcerative colitis is suspected on a clinical basis.

Adolescent↗
PubMed2003

Hospital use of acid-suppressive medications and its fall-out on prescribing in general practice: a 1-month survey.

BACKGROUND: Acid-suppressive medications are commonly used in hospitalized patients, but, to date, little is known about the overall use of these drugs in the hospital setting. AIM: To evaluate the appropriateness of acid-suppressive therapy in a large teaching hospital in northern Italy, and the fall-out of hospital prescription in general practice. METHODS: The use of antisecretory agents was monitored for 1 month in adult patients consecutively admitted to L. Sacco University Hospital by reviewing their clinical charts. The appropriateness of each prescription was reviewed jointly by two consultant gastroenterologists. RESULTS: A total of 46.8% of 799 hospitalized patients received acid-suppressive therapy. Ranitidine was the most frequently used drug (44.4%), followed by pantoprazole (31.8%) and omeprazole (23.0%). Stress ulcer prophylaxis and the prevention of non-steroidal anti-inflammatory drug-induced ulcer accounted for 60.4% of the indications for use. Overall, 68% of prescriptions were not appropriate as determined by consensus review; 56.4% of patients receiving unnecessary prophylactic treatment whilst in hospital were discharged on therapy, and 46% were still receiving the treatment 3 months later. CONCLUSIONS: Acid-suppressive agents are over-used in hospitalized patients. Most of the inappropriate hospital prescriptions are for ulcer prophylaxis in low-risk patients. This unnecessary use may also induce inappropriate drug consumption in general practice.

Antacids↗
PubMed2003

Angiotensin II AT1 receptor stimulates Na+ -K+ATPase activity through a pathway involving PKC-zeta in rat thyroid cells.

Angiotensin II (Ang II) receptor subtype 1, AT1, is expressed by the rat thyroid. A relationship between thyroid function and several components of the renin-angiotensin system has also been established, but the Ang II cellular effects in thyrocytes and its transduction signalling remain undefined. The aim of the present paper was to investigate the modulation of the activity of the Na(+)-K(+)ATPase by Ang II and its intracellular transduction pathway in PC-Cl3 cells, an established epithelial cell line derived from rat thyroid. Here we have demonstrated, by RT-PCR analysis, the expression of mRNA for the Ang II AT1 receptor in PC-Cl3 cells; mRNA for the Ang II AT2 receptor was not detected. Ang II was not able to affect the intracellular Ca(2+) concentration in fura-2-loaded cells, but it stimulated the translocation from the cytosol to the plasma membrane of atypical protein kinase C-zeta (PKC-zeta) and -iota (PKC-) isoforms with subsequent phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1 and 2). Translocated atypical PKCs displayed temporally different activations, the activation of PKC-zeta being the fastest. PC-Cl3 cells stimulated with increasing Ang II concentrations showed dose- and time-dependent activation of the Na(+)-K(+)ATPase activity, which paralleled the PKC-zeta translocation time course. Na(+)-K(+)ATPase activity modulation was dependent on PKC activation since the PKC antagonist staurosporine abolished the stimulatory effect of Ang II. The inhibition of the ERK kinases 1 and 2 (MEK1 and 2) by PD098059 (2'-amino-3'-methoxyflavone) failed to block the effect of Ang II on the Na(+)-K(+)ATPase activity. In conclusion, our results suggest that Ang II modulates Na(+)-K(+)ATPase activity in PC-Cl3 cells through the AT1 receptor via activation of atypical PKC-zeta while the Ang II-activated PKC- appears to have other as yet unknown functions.

Adenosine Triphosphate↗
PubMed2003

Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells.

Angiotensin II (Ang II) induces, through AT1, intracellular Ca(2+) increase in both normal and cancerous breast cells in primary culture (Greco et al., 2002 Cell Calcium 2:1-10). We here show that Ang II stimulated, in a dose-dependent manner, the 24 h-proliferation of breast cancer cells in primary culture, induced translocation of protein kinase C (PKC)-alpha, -beta1/2, and delta (but not -epsilon, -eta, -theta, -zeta, and -iota), and phosphorylated extracellular-regulated kinases 1 and 2 (ERK1/2). The proliferative effects of Ang II were blocked by the AT1 antagonist, losartan. Also epidermal growth factor (EGF) had mitogenic effects on serum-starved breast cancer cells since induced cell proliferation after 24 h and phosphorylation of ERK1/2. The Ang II-induced proliferation of breast cancer cells was reduced by (a) Gö6976, an inhibitor of conventional PKC-alpha and -beta1, (b) AG1478, an inhibitor of the tyrosine kinase of the EGF receptor (EGFR), and (c) downregulation of 1,2-diacylglycerol-sensitive PKCs achieved by phorbol 12-myristate 13-acetate (PMA). A complete inhibition of the Ang II-induced cell proliferation was achieved using the inhibitor of the mitogen activated protein kinase kinase (MAPKK or MEK), PD098059, or using Gö6976 together with AG1478. These results indicate that in human primary cultured breast cancer cells AT1 regulates mitogenic signaling pathways by two simultaneous mechanisms, one involving conventional PKCs and the other EGFR transactivation.

Angiotensin II↗
PubMed2003

Improving feasibility of posterior descending coronary artery flow recording by transthoracic Doppler echocardiography.

AIMS: Recording coronary arteries' flow by transthoracic Doppler echocardiography (TTDE) is a new task. Despite several studies concerning the left anterior descending artery (LAD) exist, the same for posterior descending coronary artery (PD) do not. Reported feasibility is not more than 76%. The aim of the study was to try to improve feasibility by using an additional two-dimensional view as a guide. METHODS AND RESULTS: PD flow recording was performed in 35 consecutive unselected patients under the guidance of the usual two-dimensional modified view [a two-chamber view (2-C)], and with a new four-chamber modified view (4-C). A semi-quantitative growing-quality score (from 0 to 3 points) to the trace was given. Contrast enhancement was used if PD was not visualized without it. The overall feasibility was 80%. A good or very good velocity signal (TTDE score > or = 2) was observed in 48% of patients without contrast enhancement. Time for first visualization of PD was short and significantly lower in 2-C than in 4-C (66 +/- 39 vs 90 +/- 70 s, respectively, P<0.05). CONCLUSIONS: TTDE recording of PD flow gained better feasibility being guided by two views. Maximal time for first visualization of PD was less than 3 min.

Adult↗
PubMed2003

[Cardiac evaluation for non-cardiac surgical patients].

There is no evidence that most of the clinical examinations we prescribe before any surgical operation may be useful to a prognostic evaluation of the patient. Recently, some authors showed that there was no postoperative difference between 2 groups of patients. The 1(st) group had performed many laboratory examinations, the 2(nd) group none at all. Both the surgical operations and the characteristics of the patients may foresee a high, intermediate or low risk. The major clinical complications may be foreseen through tested algorithms. Patients who are at risk of cardiac events should perform tests which may be invasive but may reveal a serious heart disease. In some cases, the patients should have to be submitted to heart surgery before their programmed intervention.

Anticoagulants↗
PubMed2003

Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis.

OBJECTIVE: As Mycobacterium tuberculosis isolation rates in tuberculous effusions are relatively low, several biochemical and immunological markers have been proposed to diagnose tuberculous pleurisy including adenosine deaminase (ADA) and interferon-gamma (IFN-gamma). Here we summarise the literature on ADA and IFN-gamma as predictors of tuberculous pleurisy. METHODS: After a systematic review of English language studies, we used summary receiver operating characteristic curve (SROC) analysis to determine the cumulative diagnostic accuracy of both markers and Bayes' theorem to calculate post-test probability of disease in settings with different prevalences of tuberculous pleurisy, assessed and reported the quality of primary studies. RESULTS: From 1978 to November 2000, studies containing sufficient data for the determination of both sensitivity and specificity were 31 on ADA, including 4738 patients, and 13 on IFN-gamma, including 1189 patients. SROC curve yielded a maximum joint sensitivity and specificity of 93% for ADA and 96% for IFN-gamma. In the setting of tuberculous effusion prevalence of 5%, 25% and 85%, post-test probability of a negative ADA test were 0.4%, 2.4% and 24%, and 0.22%, 1.2% and 17% for a negative IFN-gamma test. CONCLUSION: With the caveat that limitations in the design of the studies summarised here may distort estimates of test performance, ADA and IFN-gamma appear to be reasonably accurate at detecting TB pleurisy.

Adenosine Deaminase↗