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Showing papers by "Marche Polytechnic University published in 2000"


Journal ArticleDOI
TL;DR: Her-2-neu expression appears to increase with progression to androgen independence, and therapeutic targeting of this tyrosine kinase in prostate cancer may be warranted.
Abstract: Background: Human prostate cancers are initially androgen dependent but ultimately become androgen independent. Overexpression of the Her-2-neu receptor tyrosine kinase has been associated with the progression to androgen independence in prostate cancer cells. We examined the expression of Her-2-neu in normal and cancerous prostate tissues to assess its role in the progression to androgen independence. Methods: Prostate cancer tissue sections were obtained from 67 patients treated by surgery alone (UNT tumors), 34 patients treated with total androgen ablation therapy before surgery (TAA tumors), and 18 patients in whom total androgen ablation therapy failed and who developed bone metastases (androgen-independent [AI] disease). The sections were immunostained for Her-2-neu, androgen receptor (AR), prostate-specific antigen (PSA), and Ki-67 (a marker of cell proliferation) protein expression. Messenger RNA (mRNA) levels and gene amplification of Her-2-neu were examined by RNA in situ hybridization and fluorescent in situ hybridization(FISH), respectively, in a subset of 27 tumors (nine UNT, 11 TAA, and seven AI). All statistical tests were two-sided. Results: Her-2-neu protein expression was statistically significantly higher in TAA tumors than in UNT tumors with the use of two different scoring methods (P = .008 and P = .002). The proportion of Her-2-neu-positive tumors increased from the UNT group (17 of 67) to the TAA group (20 of 34) to the AI group (14 of 18) (P<.001). When compared with UNT tumors, tumor cell proliferation was higher in AI tumors (P =.014) and lower in TAA tumors (P<.001). All tumors expressed AR and PSA proteins. Although Her-2-neu mRNA expression was high in TAA and AI tumors, no Her-2-neu gene amplification was detected by FISH in any of the tumor types. Conclusions: Her-2-neu expression appears to increase with progression to androgen independence. Thus, therapeutic targeting of this tyrosine kinase in prostate cancer may be warranted.

381 citations


Journal ArticleDOI
TL;DR: The results suggest that leptin and leptin-R could have a role in the invasive processes of the extravillous cytotrophoblastic cells by modulating the expression of MMPs and provide a foundation for studying pathological conditions characterized by insufficient or excessive trophoblast invasion.
Abstract: Leptin is a circulating hormone which plays an important role in the regulation of energy balance, haemopoiesis and reproduction. Leptin and its receptor (leptin-R) are localized in human placental tissue but their function is not known. In this study we have investigated the expression of leptin and leptin-R in the human placenta with particular attention to extravillous cytotrophoblastic cell islands and cell columns which play a pivotal role in trophoblast invasion and placental growth. We demonstrate that leptin-R immunoreactivity shows a strong expression in the distal extravillous cytotrophoblastic cells of cell columns invading the basal plate, whereas leptin expression is homogeneously expressed in all the cellular components of cell columns. Since the invasive ability of the distally located extravillous cytotrophoblast of cell columns is known to be regulated by a variety of proteases and some extracellular matrix molecules, we tested the influence of leptin on the in-vitro production of matrix metalloproteinase (MMP)-2, MMP-9 and fetal fibronectin (fFN) by cytotrophoblastic cells. We demonstrate that leptin increases, in a dose-dependent manner, the secretion of immunoreactive MMP-2 and fFN and enhances the activity of MMP-9 in cultured cytotrophoblastic cells. Our results suggest that leptin and leptin-R could have a role in the invasive processes of the extravillous cytotrophoblastic cells by modulating the expression of MMPs. In addition, these results provide a foundation for studying pathological conditions characterized by insufficient or excessive trophoblast invasion.

223 citations


Journal ArticleDOI
TL;DR: In patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniae antibodies level, which lends support to the hypothesis that inflammation plays a role in the pathogenesis of Atherosclerosis in these patients.
Abstract: OBJECTIVE To investigate the relationship between inflammatory processes and atherosclerosis in uraemic patients on chronic dialysis. DESIGN A cross-sectional study in 138 dialysis patients (92 on haemodialysis and 46 on continuous ambulatory peritoneal dialysis). METHODS Serum C-reactive protein (CRP), IgG anti-Chlamydia pneumoniae antibodies, lipoprotein (a), fibrinogen and plasma homocysteine as well as the intima-media thickness and the number of atherosclerotic plaques of the carotid arteries (by Echo-Colour-Doppler) were measured in each patient RESULTS One hundred and eight patients had at least one plaque and 26 had more than six plaques. Serum CRP was above the upper limit of the normal range (5 mg/I) in 85 of 138 patients (62%). IgG anti-Chlamydia pneumoniae antibodies were detectable in 64% of patients (high level in 24%, intermediate in 33% and low in 7%) and undetectable in the remaining 36% of patients. In a multiple regression model age (beta=0.35), serum CRP (beta=0.23), plasma homocysteine (beta=0.19), duration of dialysis (beta=0.19) and pulse pressure (beta=0.18) were independent predictors of intima-media thickness (R=0.54, P < 0.0001). Similarly, age (beta=0.33), serum CRP (beta=0.29), plasma homocysteine (beta=0.20) and serum albumin (beta=-0.18) were independent correlates of the number of atherosclerotic plaques (R = 0.55, P < 0.0001 ). Furthermore, in smokers, the interaction serum CRP-IgG anti-Chlamydia pneumoniae antibodies was the stronger independent predictor (beta=0.43, P=0.0001) of the number of atherosclerotic plaques while no such relationship (P=0.73) was found in non-smokers. CONCLUSIONS In patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniae antibodies level. These data lend support to the hypothesis that inflammation plays a role in the pathogenesis of atherosclerosis in these patients.

220 citations


Journal Article
TL;DR: VEGF may be used in a clinical setting to identify patients at high risk for relapse who may benefit from adjuvant treatment including new therapeutic strategies such as monoclonal antibody neutralizing VEGF.
Abstract: The usefulness of chemotherapy in patients with stage II disease continues to be debated. Biological prognostic factors may allow further insight into the optimal treatment strategy for patients with node-negative disease. Vascular endothelial growth factor (VEGF) seems to be essential for angiogenesis and for the growth of colorectal cancer. Recently, it was shown able to predict disease recurrence in patients with stage II colon cancer. Specimens of surgically resected colon cancer were immunostained for VEGF. Consecutive patients referred to the study institutions were considered eligible for this study. The main inclusion criteria were stage II tumor, sufficient tumor material, and adequate follow-up information. Analysis was performed on 121 patients. The recurrence rate in the patients with VEGF-positive tumors was 50% (18 of 36 patients), which was significantly higher than that observed in patients with VEGF-negative tumors [11.7% (10 of 85 patients); P = 0.001]. Also the degree of VEGF immunoreactivity was significantly higher in 28 relapsing patients compared with 93 disease-free patients (mean VEGF score, 2.84 ± 0.38 versus 0.66 ± 0.17; P = 0.0001). VEGF may be used in a clinical setting to identify patients at high risk for relapse who may benefit from adjuvant treatment including new therapeutic strategies such as monoclonal antibody neutralizing VEGF.

204 citations


Journal ArticleDOI
TL;DR: The results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.
Abstract: Background and objective The European Lacidipine Study of Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multi-national interventional trial to determine the effect of four-year treatment using the calcium antagonist lacidipine versus the beta-blocker atenolol on the progression of carotid atherosclerosis in 2259 asymptomatic hypertensive patients. B-mode ultrasound is used to measure the primary and secondary endpoints including the mean maximum intima-media thickness (IMT) of the carotid bifurcations and the common carotid arteries (CBM(max)), the mean maximum IMT of 12 standard carotid sites (M(max)) and the overall maximum IMT (T(max)). This paper reports the cross-sectional reproducibility of ultrasound measurements at baseline. Method To evaluate measurement reliability, each patient is scanned twice at baseline and again at four annual visits, with 80% of the replicate scans performed by the same sonographer and 20% by a different sonographer; 50% of the replicate scans are read by the same reader and the other 50% by different readers. Results The overall coefficient of reliability (R) was 0.859 for CBM(max), 0.872 for M(max) and 0.794 for T(max). The reliability for CBM(max) was stable during the 1 3/4-year baseline period (R = 0.848 to 0.953) and was uniform among the 23 field centres (R = 0.798 to 0.926). Intra- and inter-reader reliability were 0.915 and 0.872 respectively, and intra-sonographer reliability was 0.866. Conclusion The results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.

171 citations


Journal ArticleDOI
TL;DR: It is concluded that polymorphisms in HSD11B2 and decreased 11-HSD2 activity are associated with sensitivity to sodium loading, but a functional explanation for these associations remains to be elucidated.
Abstract: Mutations in the HSD11B2 gene encoding the kidney (11-HSD2) isozyme of 11beta-hydroxysteroid dehydrogenase cause apparent mineralocorticoid excess, a form of familial hypertension. Because the hypertension associated with AME is of the salt-sensitive type, it seemed possible that decreases in 11-HSD2 activity might be associated with salt sensitivity. To examine this, Italians with mild hypertension underwent a protocol consisting of a rapid intravenous saline infusion and subsequent furosemide diuresis. To determine whether there were genetic associations between HSD11B2 and salt sensitivity, 198 Italians were genotyped for a CA repeat polymorphism (11 alleles) in the first intron. Increased differences in mean arterial pressure between the sodium loaded and depleted states were correlated with shorter CA repeat length (R=0.214, P=0. 0025). The effect behaved as a recessive trait. This suggested that decreased HSD11B2 expression was associated with shorter CA repeat length. Furthermore, activity of renal 11-HSD2 as measured by an increase in the ratio of urinary-free cortisol/urinary-free cortisone was lower in 33 salt-sensitive subjects (urinary-free cortisol/urinary-free cortisone 0.89+/-0.04 [mean+/-SE]) compared with 34 salt-resistant subjects (0.71+/-0.04, P<0.001). However, when minigenes containing either 14 or 23 CA repeats were transfected into rabbit or human kidney cortical collecting duct cells, the construct with 14 repeats was instead expressed at levels 50% higher than those of the construct with 23 repeats, as determined by reverse transcription-polymerase chain reaction. We conclude that polymorphisms in HSD11B2 and decreased 11-HSD2 activity are associated with sensitivity to sodium loading, but a functional explanation for these associations remains to be elucidated.

134 citations


Journal ArticleDOI
TL;DR: This survey revealed the existence of a gap between the physicians' perception of tolerability and the real experience of patients, a clear need for greater tolerability of treatments, and a need for an enhancement of patient-physician communication.
Abstract: ObjectiveTo collect statistically significant information on patterns of antihypertensive therapy in medical practice, with particular attention to the drugs used in the pharmacological management of hypertensive patients and the reasons for the limited achievement of therapeutic goals during treatm

110 citations



Journal ArticleDOI
TL;DR: Fructose feeding induces hypertension in normal- or high-salt fed animals and it is associated with an increased expression of the AT1 receptor in adipose tissue, suggesting that AT1 receptors might play a role in the pathophysiology of metabolic and hemodynamic abnormalities induced by fructose feeding.
Abstract: ObjectiveFructose feeding induces hypertension, insulin-resistance and hypertriglyceridemia in Sprague-Dawley rats. The mechanisms of fructose-induced hypertension are as yet unknown. Here we investigate the effects of fructose feeding and of varying salt intake on blood pressure, glucose tolerance,

79 citations


Journal ArticleDOI
TL;DR: In this paper, a theoretical model of the market for used machines was developed and the authors analyzed data on United States (U.S.) exports of metalworking machine tools by country of destination, classifying machines according to their vintage and their technological characteristics.
Abstract: When countries import production machinery, they must choose between new and used equipment. This article looks at that choice in the presence of labor-saving technical progress and complementarity between technologies and skills within the firm. It develops a theoretical model of the market for used machines. It then analyzes data on United States (U.S.) exports of metalworking machine tools by country of destination, classifying machines according to their vintage and their technological characteristics. The data show that the share of used equipment imported is higher if the importing country has a lower level of development, as measured by income per capita. Econometric estimation of the determinants of this share shows that it also is higher the greater is the technological change embodied in the machine or the greater is the change in the skills required to run the machine efficiently. These results indicate that technological factors and skill constraints may be as important as factor prices in determining the choice of technique in developing countries. The policy recommendation emerging from this work avoid constraints on imports of used equipment is similar to that in the existing literature. But the reasoning is different. Instead of emphasizing inappropriate capital-labor ratios for low-wage countries, the results indicate that investment in advanced technologies is effective only if importing countries have the skills to use them.

45 citations


Journal ArticleDOI
TL;DR: This review discusses how such approaches are being developed through the identification of novel biochemical and molecular targets to meet the challenges imposed by the scientific research in medical mycology.
Abstract: With the increasing number of immunocompromised hosts and advances in medical technology there has been a concomitant rise in the number of cases of invasive fungal infections. Novel approaches for the discovery of new antifungal targets and their inhibitors will be needed. In this review we discuss how such approaches are being developed through the identification of novel biochemical and molecular targets to meet the challenges imposed by the scientific research in medical mycology.

Journal ArticleDOI
TL;DR: In this article, the authors exploit the presence of bankruptcy risk in a theoretical framework a la Greenwald-Stiglitz (Delli Gatti, Gallegati and Palestrini, 2000) to model an endogenous flow of exiting firms.
Abstract: In macroeconomic models with financial constraints (see, for instance, Greenwald and Stiglitz, 1993; Bernanke, Gertler and Gilchrist,1998; Kiyotaki and Moore,1997) firms' supply decisions depend upon the degree of financial robustness/fragility, which is identifed and measured in different ways. In the theoretical framework put forward by Greenwald and Stiglitz (GS hereafter), for example, financial fragility is due to the presence of bankruptcy risk. GS implicitly assume, however, that the number of firms is constant. In this paper we abandon the one-to-one replacement assumption and allow for an unconstrained turnover of firms. In particular we exploit the presence of bankruptcy risk in a theoretical framework a la Greenwald-Stiglitz (Delli Gatti, Gallegati and Palestrini, 2000) to model an endogenous flow of exiting firms. As to the flow of entrants, we assume that it is influenced by current macroeconomic conditions (summarized by the number of surviving, non-bankrupt firms) and by stochastic factors. This entry-exit pattern of industrial dynamics will affect the evolution of the distribution of firms according to the degree of financial robustness/fragility which in turn will affect aggregate outcomes. In our opinion, in fact, firms' heterogeneity plays a crucial role in determining the macroeconomic performance.

Journal Article
TL;DR: In the great majority of patients, positivity for these pollens was associated with positivity to the better recognized group of pollen allergens, although in some cases they were the primary pathogenic agent.
Abstract: Epidemiological studies on the pollens responsible for allergic diseases throughout Italy are lacking. Routine diagnostic panels consist prevalently of grass, Parietaria, weeds, birch, olive and mugwort. Considering the great variety of Italian geographical areas and the observation of the growing allergological importance of new botanical species (e.g., ambrosia), a survey on pollen species considered "minor" was necessary. A panel of "emerging" pollens (birch, hazelnut, alder, hornbeam, cypress, ragweed) and a routine panel were used to skin prick test 2,934 consecutive outpatients with respiratory pathology of suspected allergic origin, in 21 centers across Italy. A specific questionnaire was compiled. It was found that 20.1% of patients did not react to allergens tested, 28.2% were positive for at least one emerging pollen and 51.7% did not react to emerging pollens but tested positive for at least one allergen from the routine panel. The prevalence of single pollen species was related to geographical areas. Ragweed pollen was shown to provoke asthma much more frequently than other pollens. Hitherto scarcely considered pollens play a considerable role in causing allergic diseases in Italy. In the great majority of patients, positivity for these pollens was associated with positivity to the better recognized group of pollen allergens, although in some cases they were the primary pathogenic agent. We suggest that these more recently considered allergens be included in routine diagnostic panels.

Journal ArticleDOI
TL;DR: Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex, an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients.
Abstract: We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. Patients had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs) after a long-term experience with nucleoside reverse transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. One patient exhibited a 69S [VG] insert that has not been previously phenotypically characterized. This HIV-1 isolate had high levels of resistance to all NRTIs except stavudine. MddNR is an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various NRTI combinations were the common background in the patients with the 69 insert. The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed in several other European countries (3.4%-6.5%). These data suggest that patients failed by NRTI regimens should be analyzed for the presence of both patterns of MddNR.

Journal Article
TL;DR: The incidences of MACE and target vessel failure after six months follow-up were lower than that seen in other studies, and target lesion revascularization rates were low.
Abstract: The purpose of this registry was to document the safety and efficacy of elective deployment of the NIROYAL stent (Boston Scientific SCIMED, Maple Grove, Minnesota) in coronary arteries. This was a prospective, multi-center international registry. NIROYAL stents (9, 16, 25 and 32 mm-long) were manually crimped onto coronary balloons and deployed in de novo or restenotic lesions in 165 male and female patients with angina pectoris and a reference vessel diameter of 2.0-4.5 mm. Stent deployment was successful in 98.8% of the lesions. Mean percent diameter stenosis decreased from 83.5+/-10.8% to 2.7+/- 6.2% after intervention. The interventional procedure of the treatment site was successful in 97.6% of patients. At six-month clinical follow-up, 88.5% had event-free survival [i.e., did not experience a major adverse cardiac event (MACE)] and 95.2% had no anginal symptoms. Furthermore, 87.3% of the patients were free of target vessel failure (defined as a composite of acute procedural failure, target vessel revascularization, myocardial infarction or death at six months). Only three MACE were observed within the first 30 days after stent implantation. A low left ventricular ejection fraction and the percentage stenosis pre-procedure were identified as statistically significant (p<0.05) predictive factors for MACE. The incidences of MACE and target vessel failure after six months follow-up were lower than that seen in other studies, and target lesion revascularization rates were low.

Journal Article
TL;DR: The rapid test reproducibly identified patients in the upper and lower parts of the distribution of salt sensitivity, suggesting that the evaluation of the blood pressure response to saline infusion, upon careful standardization of dietary NaCl intake, may represent an alternative to the completion of the whole test for the screening of the salt-sensitivity.
Abstract: BACKGROUND: This multicenter trial in essential hypertensive patients (n=94) is aimed i) to evaluate the distribution of blood pressure salt-sensitivity by a rapid volume expansion/contraction protocol over three days; ii) to investigate the within-patient reproducibility and to identify predictors of the response to the test; iii) to compare this response with the response to dietary NaCl restriction. METHODS: The study design included: 1) screening for salt-sensitivity by the rapid test; 2) a controlled trial of dietary salt restriction; 3) repetition of the rapid test in a subgroup of patients. RESULTS: The mean BP response to the rapid test fitted a Gaussian curve. In multivariate regression analysis, controlling for the effect of potential confounders, the blood pressure increment during the intravenous saline infusion was the best independent predictor of the response to the test (r=0.713) with minor contributions by the 24-h urinary sodium excretion before the test and by baseline fasting serum insulin. These three variables together explained 61% of the overall variability of the response. The Spearman rank correlation coefficient between the BP response to the rapid test and the response to the dietary protocol was 0.21, p=0.05. Upon repetition of the rapid test, the correlation coefficient between the responses observed on the two occasions was 0.60 (n=19, p<0.01); there were no patients misclassified across the extreme tertiles of the distribution of salt-sensitivity. CONCLUSION: We conclude that the rapid test reproducibly identified patients in the upper and lower parts of the distribution of salt sensitivity. The analysis of possible predictors of the response to the test suggested that the evaluation of the blood pressure response to saline infusion, upon careful standardization of dietary NaCl intake, may represent an alternative to the completion of the whole test for the screening of the salt-sensitivity.

Journal ArticleDOI
TL;DR: In this article, the authors report tests of hypotheses that a variety of interest rates and other measures from financial markets in countries belonging to the European Monetary Union (EMU) were converging prior to the introduction of the euro in January 1999.
Abstract: This paper reports tests of hypotheses that a variety of interest rates and other measures from financial markets in countries belonging to the European Monetary Union (EMU) were converging prior to the introduction of the euro in January 1999. We expected to find convergence because of i) removal of national barriers to flows of funds, ii) explicit and market-driven harmonization of regulation and supervisory standards, iii) coordinated macroeconomic policies, iv) privatization of state enterprises, and v) fiscal redistribution of resources. The first series of tests (sigma-tests) are that standard deviations and/or coefficients of variation of cross-sections of national measures are diminishing over time, relative to a group of non-EMU countries. Evidence of convergence was found for inflation rates, short- and long-term nominal interest rates, and ex post real short-term rates, but not for real per capita GDP. The second series concerned levels and trends in interbank claims and noninterest income at banks. These measures are believed to be larger and growing more rapidly when banks are attempting to escape binding national regulations. Interbank claims were larger at EMU banks than at banks in other countries, but had no interpretable trends. The ratios of noninterest income to total bank income and assets were found to have positive trends. The third series of tests used a statistical cost accounting model estimated for twelve countries to examine whether marginal costs of liabilities and revenues from assets were tending toward equality, as might be expected in an efficient unified economy. Within the EMU, significant differences across six major countries were observed for 1994, 1995, and 1996, but not in 1997 or 1998. Convergence seemed to be being achieved.

Journal ArticleDOI
16 Jun 2000-AIDS
TL;DR: The data substantiate the reliability of the novel strategy for a fast (5 day) quantitative evaluation of HIV-1 phenotype to PI, and indicate that this method may contribute to the understanding of mechanisms of virus resistance to PI.
Abstract: OBJECTIVE To develop and optimize a fast and quantitative recombinant strategy for evaluating the HIV-1 phenotype to protease inhibitors (PI). DESIGN AND METHODS A non-replicative HIV-1 molecular vector (designated pdelta prodelta env) capable of expressing exogenous HIV-1 protease-encoding sequences was developed in this study. The HIV-1 protease sequences were amplified from either viral isolates or plasma samples (both from 21 HIV-1-infected individuals, 19 of whom were failing different anti-HIV-1 combination treatments) and cloned in the pdelta prodelta env backbone. The HIV-1 recombinant phenotype to PI was determined directly after transfection of viral chimeric clones by measuring protease activity and calculating a percentage sensitivity index (SI%; the ratio between the results from each clone and those from a PI-sensitive reference strain). RESULTS The SI% values obtained from the recombinant clones paralleled the IC50 results of the viral isolates and documented different degrees of resistance and cross-resistance to PI, compatible, with few exceptions, with the respective genotype. Interestingly, an inverse correlation between SI% values and the presence of primary mutations for resistance to PI (P = 0.0038 and P = 0.0414, for indinavir and ritonavir, respectively) and a difference in SI% between samples harbouring an increasing number of mutations (indinavir, P = 0.022; ritonavir, P = 0.0466) were observed. CONCLUSION The data substantiate the reliability of the novel strategy for a fast (5 day) quantitative evaluation of HIV-1 phenotype to PI, and indicate that this method may contribute to the understanding of mechanisms of virus resistance to PI.

Book ChapterDOI
TL;DR: Finally, a summary of the main characteristics of the CDB8 molecule are outlined in figure 7.
Abstract: Finally, a summary of the main characteristics of the CDB8 molecule are outlined in figure 7

Journal ArticleDOI
TL;DR: Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events) and Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses.
Abstract: ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), w...

Journal ArticleDOI
TL;DR: The 1CMM and 2CMM showed a substantial equivalence in detecting a severe reduction in insulin sensitivity and impaired glucose effectiveness in hypertensive patients compared with normal.
Abstract: A standard intravenous glucose tolerance test (IVGTT) was performed in 10 nondiabetic patients with essential hypertension (H group) and 9 normotensive control subjects (N group) A 2-compartment minimal model (2CMM) of glucose kinetics was applied to estimate indexes of glucose effectiveness, S2G and insulin sensitivity, S2I, by means of a maximum a posteriori (MAP) bayesian estimation technique These estimates were contrasted to the S1G and S1I indexes provided by the classic minimal model (1CMM) In both the N group and the H group, the 2CMM underestimated the glucose effectiveness and overestimated the insulin sensitivity In the H group, S2G was, on average, 63% of S1G (P > 05) and S2I was 137% of S1I (P > 05) In the N group S2G was 67% of S1G (P > 05) and S2I was 134% of S1I (P > 05) The 2CMM detected a reduction of approximately 40% (P > 05) and approximately 48% (P > 05) in S2G and S2I estimates, respectively, from the N group to the H group Despite its reduced complexity, the 1CMM also detected a reduction of approximately 35% (P < 05) and approximately 49% (P < 05) in the S1G and in S1I indexes, respectively Thus, the 1CMM and 2CMM showed a substantial equivalence in detecting a severe reduction in insulin sensitivity and impaired glucose effectiveness in hypertensive patients compared with normal

Journal Article
TL;DR: Reperfusion following a short period of acute ischemia such as in PTCA does not constitute an oxidative event detectable through a common marker of lipid peroxidation nor does it alter the concentration of lipophilic antioxidants.
Abstract: BACKGROUND Percutaneous transluminal coronary angioplasty (PTCA) constitutes a clinical model of reperfusion following a short period of ischemia connected to balloon inflation during the procedure. During the procedure some ischemic damage and oxidative injury related to free radical attack might occur. In the present study we investigated the extent of ischemic damage and some biochemical indexes of reperfusion damage in patients undergoing PTCA. METHODS Twenty-five patients who underwent PTCA because of angiographically detected occlusion of the coronary artery were enrolled. Balloon inflation lasted from 30 to 60 s. ECG changes were monitored throughout the procedure and blood samples were taken from the coronary artery and coronary sinus before balloon inflation, and again from coronary sinus at the peak of ischemia, 2 and 10 min after reperfusion. RESULTS During PTCA procedure angina pectoris appeared in 62.7% of patients, whereas ST-segment elevation was present in 87% of patients, regressing completely after balloon deflation. Plasma malonyldialdehyde, an index of lipid peroxidation, did not change; coenzyme Q10 (in its oxidized and reduced forms), vitamin E and beta-carotene were also unchanged. Total antioxidant capacity and uric acid decreased upon reperfusion. CONCLUSIONS Myocardial ischemia occurring during balloon inflation is brief and regresses completely after balloon deflation. Reperfusion following a short period of acute ischemia such as in PTCA does not constitute an oxidative event detectable through a common marker of lipid peroxidation nor does it alter the concentration of lipophilic antioxidants. It only lowers hydrosoluble antioxidants therefore representing a mild oxidative insult.

Journal ArticleDOI
TL;DR: In this article, the effect of thermal treatment on mechanical properties of the thixocast 319 alloy has been studied and the results showed that T5 aging treatment gives satisfactory results for elongation because the ductility values are comparable with the results from T6, while the UTS values are slightly lower.
Abstract: Among cast aluminum alloys, 319 ranks as one of the commercially important alloys used in automotive applications, on account of its excellent casting characteristics and good mechanical properties. It has become one of the candidates for shaping the aluminum alloys in the semisolid state or thixocasting. Semisolid bars have been heat treated in T4, T5 and T6 conditions and the microstructural evolution followed by optical and scanning electron microscopy. Hardness measurements have been performed on aged samples to follow the precipitation process. After aging, samples were prepared for tensile test at room temperature and the effect of thermal treatment on mechanical properties has been studied. Hardness measurements revealed a delay in precipitation starting in T5 with respect to T6 due to the lack of supersaturation. T5 aging treatment gives satisfactory results for elongation because the ductility values are comparable with the results from T6, while the UTS values are slightly lower. The thixocast 319 alloy has definitively good mechanical properties compared to the 319 alloy produces by other casting techniques.

Journal ArticleDOI
TL;DR: In this article, the authors investigated the hot working behavior of a 2618 aluminium alloy in torsion at temperatures ranging from 200 to 500°C and the peak flow stress was related to temperature and strain rate by means of the conventional constitutive equations normally used for high temperature deformation of metals.
Abstract: The hot working behaviour of a 2618 aluminium alloy was investigated in torsion at temperatures ranging from 200 to 500°C. The peak flow stress was related to temperature and strain rate by means of the conventional constitutive equations normally used for high temperature deformation of metals. On the basis of a preliminary investigation on the heat treatment response of the alloy, a subsequent study on the warm working of the material in the solution treated condition was carried out. Comparison between the results obtained at temperatures of 200 and 300°C indicated that deformation of the solution treated alloy resulted in an increase flow stress and in a reduced ductility.


Journal ArticleDOI
TL;DR: In this article, the heat treatment response and the microstructure of a 6082 aluminum alloy produced by thixoforming were investigated, which was characterised by globular dendrites separated by a low volume fraction of "liquid" (i.e. of eutectic).
Abstract: The heat treatment response and the microstructure of a 6082 aluminum alloy produced by thixoforming were investigated. The initial microstructure was characterised by globular dendrites separated by a low volume fraction of "liquid" (i.e. of eutectic). The heat-treatment response was investigated by testing the alloy in the form of thixoformed bars. The analysis of the hardness variation with ageing time and the electrical conductivity measurements suggested that the hardening of the alloy reflected the presence of coherent zones or semi-coherent precipitates at low temperature (160 °C) and the precipitation of equilibrium phases at high temperature (210 °C). These preliminary studies were partially repeated on samples obtained by sectioning a large component of more complex shape. The small fraction of liquid available at the thixoforming temperature was found to result in the formation of voids and hot-cracks in some locations of the component. The heat-treatment response was quite similar to that observed by testing thixoformed bars, even if the microstructure, and consequently the initial value of the hardness, was substantially less homogeneous in the component.



Journal Article
TL;DR: The study showed that in Brescia county the deficiency is more common than expected and that evaluation of liver and vessels might be as useful as lung function tests, and beneficial effect on local system has been observed.
Abstract: In a longitudinal clinical study, two hundred subjects have been evaluated in order to identify alpha 1-antitrypsin deficiency patients. According to their serum alpha 1-antitrypsin levels, they have been divided into three groups: 25 patients with severe deficiency (with both pathological alleles--ZZ, SZ or Z and rare deficiency allele--and, if clinically suggested, to be treated with augmentation therapy), 92 patients with intermediate deficiency (with one pathological allele, to be followed up in order to evaluate the risk to develop deficiency related disease) and 63 healthy subjects (normal alleles MM). They performed lung function test (including cardiopulmonary exercise test and methacholine bronchial challenge) chest X-ray and high resolution computed tomography, blood tests. Severe deficiency patients also performed perfusional lung scan to detect early disorders of blood flow, evaluation of arterial blood gases and liver echotomography. Expiratory flow limitation, the prevalence of vascular disease, the amount of urine elastin products and correlations between the amount of nitric oxide exhaled and bronchial hyperresponsiveness have been also investigated. The study showed that in Brescia county the deficiency is more common than expected and that evaluation of liver and vessels might be as useful as lung function tests. In addition, beneficial effect on local system has been observed. The longitudinal study might permit to detect early organ damage and to eliminate additive risk factors.

Journal ArticleDOI
TL;DR: In this article, the authors investigate whether comovements in some selected time series are common to various countries and periods of time, by comparing the various cyclical phases of the business cycle in 17 European countries.
Abstract: The goal of the paper consists in investigating if comovements in some selected time series are common to various countries and periods of time. To do so, we use 18 economic time series (GDP and demand components, employment and wages, money and prices, interest rates and stock prices) between 1960: I - 1998: IV for 17 European countries. We found "regularity" in terms of comovements and periodicity with respect to the GDP, in slightly most of the series. In particular, consumption and investment among the aggregate demand components, employment and productivity, and, to a lesser degree, the consumers' and GDP price indexes, their inflation rates and the stock market index, are stable across countries, while the "exogenous" component of the national income series, the monetary variables, the interest rates and the nominal wage level are not. Cyclical movements of some series certainly are policy and institutional specific, as previous studies argued. Moreover, we investigated if GDP-comovements are roboust within each single country, by comparing the various cyclical phases. As regards the cycle-specific approach, we found that only the real series are stable: prices, interest rates and wages are very irregular. Since our finding shows that prices, interest rates and the costs of the factors behave not uniformly, a most cautious approach to the analysis of the business cycle should be taken. Our results puzzle the "one-sided" impulse-propagation approach to fluctuations. The main message which emerges from this paper is that business cycles are not all alike, but some characteristics are very roboust.