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Biomedical subjects

S Milani

Publications and source records attributed to S Milani.

At least 19 recordsLinked to original sources
PubMed2006

An induction dose of epoetin alpha of 40 000 IU daily for three consecutive days increases and maintains hemoglobin levels in anemic cancer patients undergoing chemotherapy.

BACKGROUND: This pilot study was conducted to evaluate the feasibility, activity, and safety of an induction dose of epoetin alpha in cancer patients with moderate or severe anemia who were receiving chemotherapy. PATIENTS AND METHODS: Thirty patients with solid tumors and hemoglobin (Hb) levels <11.0 g/dl were enrolled. Patients received single s.c. injections of epoetin alpha, 40 000 IU for three consecutive days, and were then observed for the following 30 days. The primary efficacy variable was the response rate (Hb increase > or=1 g/dl) at day 15. Secondary efficacy variables included the proportion of patients given blood transfusions between baseline and the end of study, the duration of response (Hb level > or=1 g/dl), and ability to maintain the planned chemotherapy dose (dose intensity). RESULTS: At day 15, 23 of 30 (77%) patients had achieved increases in Hb levels of at least 1 g/dl. The mean Hb increase in responders was 2.0 g/dl [95% confidence interval (CI) = 1.7-2.3 g/dl]. The Hb increase was 2.3 +/- 0.7 g/dl in responders with baseline Hb levels <9.5 g/dl (median Hb value), and 1.7 +/- 0.6 g/dl in those with higher Hb levels (P = 0.012). The median duration of response was 6.1 weeks (95% CI = 1.6-10.6 weeks). Hematologic parameters were not significantly changed in nonresponders. Multivariate analysis detected no significant differences in Hb increase at day 15 on the basis of age, sex, weight, baseline Hb levels, type or stage of tumor, or treatment with platinum-based chemotherapy. No serious adverse event related to epoetin alpha treatment was observed. CONCLUSIONS: We conclude that a higher initial dosing of epoetin alpha appears to be an efficient schedule for treating anemia in cancer patients undergoing chemotherapy, conferring higher response rates than those seen with standard doses. Further evaluation of these and other epoetin alpha dosage regimens is warranted.

Adult↗
PubMed2006

Postnatal weight increase and growth velocity of very low birthweight infants.

BACKGROUND: Only a few studies have dealt with postnatal growth velocity of very low birthweight (VLBW) infants. OBJECTIVE: To analyse weight growth kinetics of VLBW infants from birth to over 2 years of age. PATIENTS: A total of 262 VLBW infants were selected; inaccurate estimate of gestational age, major congenital anomalies, necrotising enterocolitis, death, and loss to follow up within the first year were the exclusion criteria. METHODS: Body weight was recorded daily up to 28 days or up to discontinuation of parenteral nutrition, weekly up to discharge, then at 1, 3, 6, 9, 12, 18, and 24 months of corrected age. Individual growth profiles were fitted with a seven constant, exponential-logistic function suitable for modelling weight loss and weight recovery, two peaks, and the subsequent slow decrease in growth velocity. RESULTS: After a postnatal weight loss, all infants showed a late neonatal peak of growth velocity between the 7th and 21st weeks; most also experienced an early neonatal peak between the 2nd and 6th week. VLBW infants who were small for gestational age and those with major morbidities grew less than reference VLBW infants who were the appropriate size for gestational age without major morbidities: at 2 years of age, the difference in weight was about 860 g. The more severe growth impairment seen in VLBW infants with major morbidities is almost entirely due to the reduced height of the late neonatal peak of velocity. CONCLUSIONS: The growth model presented here should be a useful tool for evaluating to what extent different pathological conditions or nutritional and medical care protocols affect growth kinetics.

Aging↗
PubMed2006

Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study.

BACKGROUND: Recent studies suggest a role of n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) as peroxisome proliferator-activated receptor-alpha ligands in improving non-alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking. AIM: To evaluate the efficacy of prolonged PUFA supplementation in patients with NAFLD. METHODS: Fifty-six patients with NAFLD were enrolled. Among the overall eligible patients, 42 assumed n-3 PUFA 1-g capsule daily for 12 months, whereas 14 refused the treatment and were analysed as controls. All patients underwent haematochemical and ultrasound follow-up. RESULTS: Polyunsaturated fatty acid supplementation significantly decreased serum aspartate transaminase (P = 0.003), alanine transaminase (P = 0.002), gamma-glutamyl transpeptidase (P = 0.03), triglycerides (P = 0.02) and fasting glucose (P = 0.02) in comparison with controls. Circulating arachidonate and n-6/n-3 fatty acid ratio was reduced (P = 0.0002, and P = 0.0001 respectively) in treated patients. Moreover, ultrasonography demonstrated improvement of liver echotexture after PUFA (P = 0.0001), and increase of Doppler perfusion index (P = 0.001), whereas no significant changes occurred in controls. CONCLUSIONS: Supplementation with n-3 PUFA improves biochemical, ultrasonographic and haemodynamic features of liver steatosis. Our study supports the efficacy of n-3 PUFA as a new therapeutic approach in the treatment of NAFLD.

Adult↗
PubMed2005

Ternary CdSxSe 1-x deposited on Ag(111) by ECALE: synthesis and characterization.

Morphology and electronic properties of CdS, CdSe, and the ternary compounds of formula CdSxSe(1-x) deposited on Ag(111) by ECALE have been characterized as a function of the composition. The number of the attainable x values is limited by the necessity of using well-defined CdS/CdSe deposition sequences. However, the quantitative analysis carried out by XPS and electrochemical stripping experiments indicates that the ECALE method has a good control on composition. The AFM images together with the electrochemical characterization indicate both two-dimensional and three-dimensional growth contributions. The photospectra recorded at CdS film electrodes in liquid junction with an alkaline (poly)sulfide electrolyte show good efficiency of photoconversion and band gap typical of the single crystal. Lower photoconversion efficiency and the presence of subband gap response are observed for CdSe; a possible reason is some crystalline disorder due to lower control of the layer-by-layer deposition in the case of Se. The dependence of band gap on composition of ternary CdSxSe(1-x) ECALE films is monotonic and in agreement with literature data reported for bulk materials.

Journal Article↗
PubMed2004

Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPARgamma independent mechanisms.

BACKGROUND/AIMS: Thiazolidinediones (TZD) are a new class of oral antidiabetic drugs that have been shown to inhibit growth of some epithelial cancer cells. Although TZD were found to be ligands for peroxisome proliferators activated receptor gamma (PPARgamma) the mechanism by which TZD exert their anticancer effect is currently unclear. Furthermore, the effect of TZD on local motility and metastatic potential of cancer cells is unknown. The authors analysed the effects of two TZD, rosiglitazone and pioglitazone, on invasiveness of human pancreatic carcinoma cell lines in order to evaluate the potential therapeutic use of these drugs in pancreatic adenocarcinoma. METHODS: Expression of PPARgamma in human pancreatic adenocarcinomas and pancreatic carcinoma cell lines was measured by reverse transcription polymerase chain reaction and confirmed by western blot analysis. PPARgamma activity was evaluated by transient reporter gene assay. Invasion assay was performed in modified Boyden chambers. Gelatinolytic and fibrinolytic activity were evaluated by gel zymography. RESULTS: TZD inhibited pancreatic cancer cells' invasiveness, affecting gelatinolytic and fibrinolytic activity with a mechanism independent of PPARgamma activation and involving MMP-2 and PAI-1 expression. CONCLUSION: TZD treatment in pancreatic cancer cells has potent inhibitory effects on growth and invasiveness suggesting that these drugs may have application for prevention and treatment of pancreatic cancer in humans.

Adenocarcinoma↗
PubMed2003

Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial.

BACKGROUND: To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen. PATIENTS AND METHODS: Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease. RESULTS: Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation. CONCLUSIONS: The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients.

Age Factors↗
PubMed2002

Italian cross-sectional growth charts for height, weight and BMI (6-20 y).

OBJECTIVE: To trace growth charts for height, weight and body mass index (BMI) that apply to the whole Italian population. Different charts were drawn for central-north and south Italy since children in central-north regions are known to be taller and leaner. DESIGN: Cross-sectional study. SETTING: A sample of schoolchildren covering 16 of the 20 Italian regions, with data collected between 1994 and 2000. SUBJECTS: A total of 27 421 girls and 27 374 boys, aged 6-20 y. METHODS: Height and weight were measured using portable Harpenden stadiometers and properly calibrated scales, respectively. SIEDP references are presented both as centiles and as LMS curves for the calculation of standard deviation scores. According to International Obesity Task Force, SIEDP charts for BMI include the limits for overweight and obesity, ie the centiles having, at 18 y of age, the value of 25 and 30 kg/m(2), respectively. RESULTS: The comparison between SIEDP and Tanner et al's charts for height, still in use among most Italian paediatricians, shows that before puberty Italian children are 2-4 cm taller than their English peers. Because of these differences, Tanner's charts fail to detect, when applied to Italian children, 50-90% of short children aged 6-11 y, ie with stature below the 3rd centile of their reference population. Rolland-Cachera et al's centiles for BMI are lower than those of SIEDP standards, mainly during adolescence (up to 6.6 kg/m(2) for the 97th centile), and apply poorly to Italian children. The prevalence of overweight is 27 (boys) and 19% (girls) in south Italy vs 17 (boys) and 10% (girls) in central-north Italy. CONCLUSIONS: These references intend to supply Italian paediatricians with a tool that avoids the use of outdated or inadequate charts, and thus should be suitable for monitoring their patients' growth. SPONSORSHIP: Italian Society for Pediatric Endocrinology and Diabetes (SIEDP).

Adolescent↗
PubMed2002

A phase II study of cisplatin and vinorelbine in patients with metastatic breast cancer.

BACKGROUND: To evaluate the efficacy and safety of the combination of cisplatin and vinorelbine in metastatic breast cancer. PATIENTS AND METHODS: Cisplatin (80 mg/m(2) day 1) and vinorelbine (25 mg/m(2) days 1 and 8) were administrated every 3 weeks to 52 patients (mean age 57 years; range 35-75 years) with metastatic breast cancer. Thirty-two patients were previously untreated for metastatic disease. Treatment was repeated for a maximum of six cycles. RESULTS: Objective responses were obtained in 27 patients (52.9%; complete response 9.8%). The response rate was similar in pretreated and untreated patients (50% and 54.7%, respectively; P = 0.7). ECOG performance status was good (grade 0 or 1) in 55.7% of patients at baseline assessment and in 90.3% at the end of treatment (P = 0.0001). Median time to progression was 8.5 months (8.5 months in first-line and 8.7 months in second-line patients). Median survival was 16.6 months (21.2 months in first-line and 16.1 months in second-line patients). Grade 3/4 toxicity included neutropenia (44% in first-line, 60% in second-line patients), nausea (17.3%), anemia (17%), asthenia (3.8%) and thrombocytopenia (1.9%). There were no cases of febrile neutropenia or treatment-related deaths. Alopecia did not develop in any of the patients. CONCLUSIONS: Cisplatin plus vinorelbine is active and tolerable in metastatic breast cancer, in untreated and pretreated patients.

Adult↗
PubMed2001

Role of growth factors and their receptors in gastric ulcer healing.

The repair of gastric ulcers requires the reconstitution of epithelial structures and the underlying connective tissue, including vessels and muscle layers. Several growth factors have been implicated in this process, since they are able to regulate important cell functions, such as cell proliferation, migration, differentiation, secretion, and degradation of extracellular matrix, all of which are essential during tissue healing. Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), hepatocyte growth factor (HGF), and trefoil factors (TFFs) are mainly involved in the reconstitution of the epithelial structures. Platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta) play a major role in the reconstitution of connective tissue, including vessels and smooth muscle cells, and provide the extracellular matrix substrate for cell migration and differentiation. The expression of these growth factors and their receptors is increased during ulcer healing and, in some cases, intracellular signaling related to receptor binding and transduction has been demonstrated. EGF, TGF-alpha and TFFs are normally present either in the gastric juice or in the mucosa, and may exert their effects immediately after damage, before newly synthesized EGF and TFFs are released from the ulcer margin. The inhibition of their effects by neutralizing antibodies may result in delayed ulcer healing, while the administration of recombinant or natural analogues may improve ulcer repair. In this review, we will summarize the basic molecular characteristics of some of these growth factors, and will discuss available evidence supporting their role in the ulcer repair process.

Animals↗
PubMed2001

Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen alpha1(I) and TIMP-1.

BACKGROUND/AIMS: Silymarin reduces hepatic collagen accumulation by 35% in rats with secondary biliary cirrhosis. The aim of the present study was to explore its antifibrotic mechanism. METHODS: Thirty female adult Wistar rats were allocated to (1) bile duct occlusion, (2) bile duct occlusion and oral silymarin at 50 mg/kg per day, and (3) sham operation and oral silymarin at 50 mg/kg per day. Steady-state mRNA levels for procollagen alpha1(I), tissue inhibitor of metalloproteinases-1 (TIMP-1), and transforming growth factor (TGF) beta1 were determined by multi-probe ribonuclease protection assay. RESULTS: After 6 weeks of bile duct occlusion, liver collagen content was increased 12-fold, when compared with the sham-operated controls. These animals displayed 17-, 6.5- and 16-fold higher transcript levels for procollagen alpha1(I), TIMP-1 and TGFbeta1 (P < 0.01). Silymarin downregulated elevated procollagen alpha1(I), TIMP-1 and TGFbeta1 mRNA levels by 40-60% (P < 0.01). These lowered hepatic profibrogenic transcript levels correlated with decreased serum levels of the aminoterminal propeptide of procollagen type III. CONCLUSIONS: Silymarin suppresses expression of profibrogenic procollagen alpha1(I) and TIMP-1 most likely via downregulation of TGFbeta1 mRNA in rats with biliary fibrosis. The serum procollagen type III propeptide level mirrors profibrogenic mRNA expression in the liver.

Animals↗
PubMed2001

Transforming growth factor beta-1 stimulates invasivity of hepatic stellate cells by engagement of the cell-associated fibrinolytic system.

The activation of hepatic stellate cells (HSC) during liver fibrogenesis has been shown to be mediated by paracrine and autocrine loops involving transforming growth factor-beta1 (TGF-beta1) as the main fibrogenic mediator secreted by activated macrophages, endothelial cells and liberated by disintegrated platelets. The cell-associated plasminogen activation system regulates extracellular matrix (ECM) catabolism and cell movement. We have studied whether TGF-beta1 could modulate the plasminogen activation system in human HSC and the role of such protease system in the activity of TGF-beta1 on HSC. Urokinase plasminogen activator receptors (u-PAR), u-PA and plasminogen activator inhibitor type 1 (PAI-1) were determined by immunoassay and RNase protection assay. Cell migration, evaluated either as chemotaxis or as chemoinvasion, was studied in Boyden chambers after addition of TGF-beta1, and inhibition with anti-u-PA and anti-u-PAR antagonists [antibodies against u-PA and u-PAR and antisense oligonucleotides (aODN) against u-PAR mRNA]. We have shown that TGF-beta1 is not mitogenic for HSC, while it is a powerful motogen either in chemotaxis or chemoinvasion assays. TGF-beta1 up-regulates the synthesis and expression of PAI-1, as well as u-PAR expression and exposure at the cell membrane, while it does not affect u-PA levels. TGF-beta1-dependent chemoinvasion of reconstituted basement membrane exploits the cell-associated plasminogen activation system, since it is blocked by monoclonal antibodies against u-PA and against various u-PAR domains, as well as by anti-u-PAR aODN. We have also observed a cumulative effect of TGF-beta1, b-FGF and PDGF in the invasion assay of HSC: in the presence of low amounts of TGF-beta1 the chemoinvasive activity of PDGF and bFGF is dramatically increased. Also this cooperation requires u-PAR and is inhibited by monoclonal antibodies against u-PAR domains I, II and III.

Animals↗
PubMed2000

Collagen type I synthesized by pancreatic periacinar stellate cells (PSC) co-localizes with lipid peroxidation-derived aldehydes in chronic alcoholic pancreatitis.

Chronic alcoholic pancreatitis (CAP) is characterized by progressive pancreatic fibrosis and loss of the acinar cell mass, but the pathogenesis of pancreatic fibrosis in the human is poorly understood. It has been recently suggested that lipid peroxidation-derived aldehydes such as 4-hydroxynonenal (HNE) are involved in tissue damage and fibrosis in other organs. The aim of this study was to evaluate the role of oxidative stress in the development of alcohol-induced pancreatic fibrosis in humans, and to assess the contribution of pancreatic periacinar stellate cells (PSC) in the in vivo synthesis of extracellular matrix components during CAP. Lipid peroxidation was evaluated in tissue specimens obtained from patients with CAP who underwent surgical procedures, by immunohistochemistry using a monoclonal antibody directed against HNE-protein adducts. Immunohistochemical determination of collagen type I, alpha-smooth muscle actin (alpha-SMA), and the beta subunit of human platelet-derived growth factor (PDGF-Rbeta) was also performed. In addition, the tissue mRNA expression of procollagen I, PDGF-Rbeta, and transforming growth factor-beta1 (TGF-beta1) was evaluated by in situ hybridization. In CAP, increased formation of HNE-protein adducts was evident in acinar cells adjacent to the interlobular connective tissue that stained positively for collagen type I. HNE staining was absent in normal pancreas. Several non-parenchymal periacinar cells (PSC) underlay the HNE-stained acinar cells. Those PSC stained positively for alpha-SMA and PDGF-Rbeta and showed active synthesis of procollagen type I by in situ expression of the specific mRNAs. The pattern of expression of PDGF-Rbeta mRNA reflected that observed in immunostaining, showing increased amounts of transcripts in PSC. TGF-beta1 mRNA expression was increased in CAP, but transcripts were found in several cell types including PSC, acinar, and ductal cells. These results indicate that significant lipid peroxidation phenomena occur in CAP and that they are associated with active synthesis of collagen by PSC.

Actins↗
PubMed2000

Lack of nitric oxide- and guanosine 3':5'-cyclic monophosphate-dependent regulation of alpha-thrombin-induced calcium transient in endothelial cells of spontaneously hypertensive rat hearts.

While the expression and/or activity of endothelial nitric oxide synthase (eNOS) has been characterized in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rat (WKY) hearts, in coronary endothelial cells (ECs) from both strains, the effect of NO on intracellular calcium concentration ([Ca(2+)](i)) is still unknown. Coronary microvascular ECs were isolated from SHR and WKY and characterized. Immunocytochemistry and Western blot analysis showed that eNOS was similarly expressed in ECs from both strains. Measuring [Ca(2+)](i) by imaging analysis of fura-2-loaded cells, we demonstrated that alpha-thrombin (3-180 U l(-1)) induced a superimposable dose-dependent calcium transient in ECs from both strains. In WKY ECs, S-nitroso-N-acetyl-DL-penicillamine (SNAP) dose-dependently (10 - 100 microM) and 0.1 microM atrial natriuretic factor (ANF) reduced the maximum and the decay time of alpha-thrombin-induced calcium transient. The inhibitory effects of SNAP and ANF were prevented by blocking cyclic GMP-dependent protein kinase. Non selective eNOS inhibitors prolonged the decay time of alpha-thrombin-induced calcium transient, while the selective inducible NOS inhibitor 1400 W was ineffective. SNAP (100 microM) and 0.1 microM ANF increased cyclic GMP content up to 22.9 and 42.3 fold respectively. In SHR ECs, alpha-thrombin-induced calcium transient was not modified by SNAP, ANF or eNOS inhibition. SNAP (100 microM) and 0.1 microM ANF increased cyclic GMP content up to 9. 3 and 51 fold respectively. In WKY ECs, SNAP dose-dependently (10 - 100 microM) reduced also bradykinin-induced calcium transient, while in SHR ECs was ineffective. We concluded that in SHR ECs, the cyclic GMP-dependent regulation of calcium transient is lost.

Animals↗