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Biomedical subjects

A Riva

Publications and source records attributed to A Riva.

At least 37 records · Page 2Linked to original sources
PubMed2002

Intralobular ducts of human major salivary glands contain leptin and its receptor.

Leptin, a 16-kDa hormone, plays an important role in the control of food intake and in energy homeostasis both in rodents and in man. Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode. In addition, a leptin receptor has been detected in taste cells of mouse circumvallate papillae and in rat intestinal epithelium. These data prompted us to carry out a detailed study of human salivary glands as potential leptin-producing organs. Biopsies of salivary glands (submandibular and parotid) obtained from male and female patients during surgery for different clinical indications were subjected to immunohistochemical study for the presence of leptin, its functional receptor, insulin and glucagon. The presence and cellular distribution of glucocorticoid receptor in leptin-secreting cells were also investigated. Double immunohistochemical staining (silver-gold intensification and avidin-biotin-peroxidase) was used for the visualization of glucocorticoid receptor and leptin labelling, respectively. The results show that intralobular duct cells of submandibular and parotid glands are immunoreactive for leptin, leptin receptor and glucagon but not for insulin. Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands.

Adult↗
PubMed2002

Relationship of fluid and mucin secretion to morphological changes in the perfused rat submandibular gland.

Transport of electrolytes/water and exocytosis are activated by elevation of the cytosolic Ca(2+) concentration and are potentiated by elevation of cytosolic cyclic AMP. To correlate mucin and fluid secretion with morphological changes, rat submandibular glands were vascularly perfused and the fluid secretion and N-acetylgalactosamine in the saliva were measured during stimulation with various concentrations of carbachol (CCh) and/or isoproterenol (ISP). Single stimulation with 1 microM CCh induced a transient increase of N-acetyl galactosamine followed by a decline to a low level during sustained stimulation. The overload of 1 microM ISP increased secretion of N-acetyl galactosamine to a higher sustained level of 40-50 microg/g-min. However, at 1 microM CCh, fluid secretion was maintained at the same level during stimulation and even overload of 1 microM ISP did not significantly affect its level, whereas addition of 0.5 microM ISP to the gland stimulated with 0.1 microM CCh increased fluid secretion. Morphological observation was carried out by HRSEM and TEM. Combination of CCh and ISP in different concentrations resulted in distinctive morphological changes which reflect fluid secretion and mucin secretion. The kinetics of ATP and creatine phosphate (PCr) were measured using P-31 NMR, which indicated that the potentiation of fluid secretion is limited under a higher level of CCh stimulation due to a limited energy supply.

Acetylgalactosamine↗
PubMed2002

Morphofunctional studies on human labial salivary glands.

In this study, the first experimental investigation carried out at the ultrastructural level on mucous cells of human salivary glands, we have examined by light microscopy (LM), transmission electron microscopy (TEM), high resolution scanning electron microscopy (HRSEM), the secretory response of labial glands stimulated in vitro by the beta-adrenergic agent, D,L isoproterenol, and by the muscarinic agent carbachol. For comparison we have used identical methods to study samples of mixed portions of human submandibular glands. Morphological findings obtained here on both submandibular and labial glands mucous cells demonstrate that mucous droplets are released solely by muscarinic stimulation, and that cytological events occurring during secretory discharge are similar to those described by others, using TEM, on stimulated mucous cells of rat sublingual glands. Despite the fact that human labial glands are said to have a prominent cholinergic innervation with scanty adrenergic nerves, the response of seromucous cells in these organs to stimulation with carbachol and with isoproterenol was similar to that observed by us, (using LM, TEM and HRSEM), in serous cells of human major salivary glands.

Adult↗
PubMed2002

SNPper: retrieval and analysis of human SNPs.

MOTIVATION: Single Nucleotide Polymorphisms (SNPs) are an increasingly important tool for the study of the human genome. SNPs can be used as markers to create high-density genetic maps, as causal candidates for diseases, or to reconstruct the history of our genome. SNP-based studies rely on the availability of large numbers of validated, high-frequency SNPs whose position on the chromosomes is known with precision. Although large collections of SNPs exist in public databases, researchers need tools to effectively retrieve and manipulate them. RESULTS: We describe the implementation and usage of SNPper, a web-based application to automate the tasks of extracting SNPs from public databases, analyzing them and exporting them in formats suitable for subsequent use. Our application is oriented toward the needs of candidate-gene, whole-genome and fine-mapping studies, and provides several flexible ways to present and export the data. The application has been publicly available for over a year, and has received positive user feedback and high usage levels.

Database Management Systems↗
PubMed2001

Phase II study of sequential administration of docetaxel followed by doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the feasibility and efficacy of a sequential administration of four cycles of docetaxel (100 mg/m(2) every 3 weeks) followed by four cycles of doxorubicin and cyclophosphamide (AC; 60/600 mg/m(2) every 3 weeks), with subsequent consolidation with docetaxel or AC, as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-eight patients received 443 cycles of chemotherapy (median, 11 cycles/patient; range, 1 to 13 cycles). A total of 267 cycles of docetaxel (60.3%) and 176 of AC (39.7%) were given. Consolidation therapy was given to 33 patients (29 with docetaxel). RESULTS: Grade 4 neutropenia was the most frequent toxicity (83% of patients). This was not cumulative and was rarely complicated by febrile neutropenia or severe infection. The nonhematologic safety profile was favorable: there were no grade 4 adverse events, and grade 3 episodes were infrequent. Docetaxel-specific toxicities were generally not severe. With a median cumulative doxorubicin dose of 397 mg/m(2) (range, 150 to 543 mg/m(2)), two incidences of unrelated congestive heart failure after further treatment with anthracyclines and two of asymptomatic left ventricular ejection fraction decrease were observed. Among the 42 assessable patients, five (12%) had complete and 25 (60%) had partial responses, for an overall response rate of 71% (95% confidence interval, 55% to 84%). Median duration of response was 53 weeks (range, 12 to 72 weeks), and median time to progression was 46 weeks (range, 3 of 72 weeks). With a median follow-up of 40.4 months, median survival was 32 months (range, 2 to 55 months). CONCLUSION: This docetaxel-based sequential schedule is safe and effective in first-line therapy for MBC, without incurring cumulative toxicity, and provides a feasible chemotherapeutic option in this clinical setting.

Adult↗
PubMed2001

Resistance to Fas-mediated apoptosis of human T-cell lines expressing human T-lymphotropic virus type-2 (HTLV-2) Tax protein.

The susceptibility to Fas-mediated apoptosis was evaluated in seven T-cell lines (two infected with HTLV-2, one with HTLV-1, and four HTLV-free) as well as in Jurkat cells transfected with a Tax-2 expressing vector. Fas-mediated apoptosis was significantly reduced in the HTLV-1- and HTLV-2-infected lines in comparison with the HTLV-free lines regardless of the surface expression of Fas antigen (which was no different in the infected and uninfected cells). Fas-mediated apoptosis was also significantly inhibited in Jurkat cells transfected with the Tax-2 expressing vector without any modification in Fas expression. There was significantly more antiapoptotic Bcl-x(L) mRNA and protein in the transfected than in the untransfected Jurkat T cells. In conclusion, our results suggest that HTLV-2 is capable of inhibiting Fas-mediated apoptosis by means of a mechanism involving the tax-2 gene and probably the expression of bcl-x(L) messenger and protein.

Antibodies↗
PubMed2001

Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer.

PURPOSE: This pilot phase II study investigated the efficacy and toxicity of docetaxel with doxorubicin and cyclophosphamide (TAC) as first-line chemotherapy for anthracycline-naive patients with metastatic breast cancer. PATIENTS AND METHODS: Fifty-four patients received a total of 359 courses consisting of docetaxel 75 mg/m2 given intravenously (IV) over 1 hour, preceded by IV doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 for a maximum of eight 3-week cycles. RESULTS: After an independent panel review, the overall objective response rate was 77% (complete response, 6%). Overall objective response rates in patients with visceral, bone, and liver involvement were 82%, 82%, and 80%, respectively. Median duration of response was 52 weeks, and median time to progression was 42 weeks. With a median follow-up of 32 months, the median survival had not yet been reached, whereas the 2-year survival was 57%. The main toxicities were hematologic (neutropenia grade 3/4 in 100% of patients and 95% of cycles; febrile neutropenia in 34% of patients and 9% of cycles). Documented grade 3 infection was seen in one patient (2%) in one cycle, and no toxic death was reported. Severe acute or chronic nonhematologic adverse events were infrequent, and docetaxel-specific toxicities (such as fluid retention and nail changes) were mild, with only one patient being discontinued for fluid retention. Congestive heart failure was seen in two patients (4%). CONCLUSION: TAC is an active and manageable regimen that has been chosen as the basis of five randomized phase III trials, including two pivotal studies comparing TAC to fluorouracil plus doxorubicin and cyclophosphamide in the metastatic and adjuvant treatment of breast cancer.

Adult↗
PubMed2001

Web-based telemedicine systems for home-care: technical issues and experiences.

The use of the Web for telemedicine applications seems nowadays a compulsory solution: the Web has become a standardized infrastructure for giving access to sophisticated telemedicine applications from virtually any machine and operating system. Such standardized communication platform guarantees accessibility and usability advantages to both customers and providers (patients and physicians). However, there are several issues that should be discussed in depth, with particular reference to all the applications related to the provision of care at distance, nowadays called telecare applications. In telecare applications the role of the patient becomes central, since he/she is actively involved in the process of managing care and treatments, and since he/she (or his/her families) is responsible for collecting some measurements and related information. In this paper we will discuss the general architectural and technical issues related to the development of Web-based systems for telecare applications, relying on the experience we gained within the telecare project T-IDDM (Telematic Management of Insulin Dependent Diabetes Mellitus), devoted to assist the management and home-monitoring of Type 1 Diabetes Mellitus patients.

Computer Security↗
PubMed2001

The personal internetworked notary and guardian.

In this paper, we propose a secure, distributed and scaleable infrastructure for a lifelong personal medical record system. We leverage on existing and widely available technologies, like the Web and public-key cryptography, to define an architecture that allows patients to exercise full control over their medical data. This is done without compromising patients' privacy and the ability of other interested parties (e.g. physicians, health-care institutions, public-health researchers) to access the data when appropriately authorized. The system organizes the information as a tree of encrypted plain-text XML files, in order to ensure platform independence and durability, and uses a role-based authorization scheme to assign access privileges. In addition to the basic architecture, we describe tools to populate the patient's record with data from hospital databases and the first testbed applications we are deploying.

Computer Security↗
PubMed2001

Phase I dose-finding and pharmacokinetic study of docetaxel and vinorelbine as first-line chemotherapy for metastatic breast cancer.

BACKGROUND AND PURPOSE: Anthracycline-containing regimens are widely used in advanced breast cancer. However, there is a need for new, non-anthracycline regimens that are active in patients for whom anthracyclines are contraindicated. The aim of this study was to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs) and recommended doses of docetaxel and vinorelbine as first-line chemotherapy in patients with metastatic breast cancer. The pharmacokinetics of both drugs was also evaluated. PATIENTS AND METHODS: Thirty-four women with first-line metastatic breast cancer were treated with docetaxel, 60-100 mg/m2 (day 1), and vinorelbine, 20-22.5 mg/m2 (days 1 and 5), repeated every three weeks and administered on an outpatient basis. RESULTS: Two MTDs were determined: MTD1 was defined at the dose level using docetaxel 75 mg/m2, and vinorelbine 22.5 mg/m2 DLT being a grade 3 stomatitis that was more related to the dose of vinorelbine than that of docetaxel. Therefore, the study continued with a fixed dose of vinorelbine, 20 mg/m2, and docetaxel 85-100 mg/m2. MTD2 was defined at the dose level combining docetaxel, 100 mg/m2, and vinorelbine, 20 mg/m2; DLTs were grade 3 stomatitis and severe asthenia. Fluid retention was observed in 41% of patients but was never severe or a reason for patient discontinuation. In comparison with historical experience, Daflon 500 did not seem to increase the efficacy of the three-day corticosteroid premedication by further reducing the incidence or severity of fluid retention. No significant neurotoxicity was observed and no patient discontinued the study due to this site effect. Activity was observed at all dose levels and at all metastatic sites, with an overall response rate of 71% (95% CI: 52.0%-85.8%). The median time to progression was 31.4 weeks (95% CI: 12-48 weeks) and median survival was 15.6 months (95% CI: 2.6-26.6 months). The pharmacokinetics of docetaxel and vinorelbine were not modified between day 1 and day 3 when the two drugs were combined with the day 1 administration schedule used in this study. CONCLUSION: The recommended doses for phase II studies are docetaxel, 75 mg/m2 (day 1), plus vinorelbine, 20 mg/m2 (days 1 and 5), repeated every three weeks. At these doses, the combination was found to be active and well tolerated.

Adult↗
PubMed2001

Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy.

This study was designed to assess the potential chemopreventive effect of the administration of a standardized soy extract, SOYSELECT, on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats. Three groups, 24 females each, were used. Animals were fed either a phytoestrogen-free diet alone (control) or the same diet supplemented with 0.35% or 0.7% of soy extract. Treatment started at weaning and continued to the end of the study (24 weeks after DMBA administration). At day 50 of age all animals received via oral gavage 80 mg/kg DMBA. Only tumors subsequently classified as adenocarcinomas were considered for data evaluation. In rats on the soy diet, mammary tumors took a longer period of time to develop as compared to control rats. However, at the end of the study, no relevant difference in tumor incidence and multiplicity was observed among the groups. The most significant changes were seen between control and soy-treated groups when tumor dimension and results from histopathologic examination were considered. The latter, in fact, showed a dose-dependent reduction in the percentage of poorly differentiated tumors in treated animals. This change was statistically significant in animals receiving 0.7% soy. In addition, assessment of estrogen and progesterone receptor (ERalpha, PR) levels, revealed a significant reduction in the percentage of ERalpha and PR positive tumors in animals receiving 0.7% dietary soy, when compared to controls. Interestingly, genistein and daidzein plasma levels determined at the end of the study were within the range of those detected in people consuming large amounts of soyfoods.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Effect of mono-dose intraperitoneal cecropins in experimental septic shock.

OBJECTIVE: To investigate the efficacy of three cecropins, cecropin A, cecropin B, and cecropin P1, in preventing lethality in a rat model of septic shock. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Rats were given an intraperitoneal injection of 2 x 10(10) colony forming units of Escherichia coli, with the exception of the uninfected control group (C0). Animals were randomized to receive, immediately after bacterial challenge, intraperitoneally isotonic sodium chloride solution (untreated control group C1), 1 mg/kg cecropin A (group 2), 1 mg/kg cecropin B (group 3), 1 mg/kg cecropin P1 (group 4), 20 mg/kg imipenem (group 5), or 60 mg/kg piperacillin (group 6). Each group included 15 animals. MEASUREMENTS AND MAIN RESULTS: We measured bacterial growth (quantitative agar culture) in abdominal exudate and plasma, endotoxin and tumor necrosis factor-alpha concentration in plasma, and mortality. Results were evaluated at 48 hrs after inoculation. Cecropins, piperacillin, and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. In addition, cecropin B significantly decreased the lethality compared with piperacillin treatment. Finally, only cecropins significantly reduced plasma endotoxin concentration. CONCLUSIONS: Mono-dose cecropin treatment prevents bacterial growth, endotoxemia, and mortality in rats with septic shock. Cecropin B was the most effective compound in reducing all variables measured.

Animals↗
PubMed2001

Taxane/anthracycline combinations: setting a new standard in breast cancer?

Among the novel chemotherapeutic drugs introduced in the 1990s, the taxanes have emerged as the most powerful compounds in breast cancer. Both compounds, paclitaxel and docetaxel, have been evaluated in metastatic settings before adjuvant trials proceeded. Docetaxel was shown in several phase III trials to be superior, particularly in terms of survival, for salvaging polychemotherapies after failure of prior chemotherapy, including that with anthracyclines. A benefit of docetaxel was also reported when compared with doxorubicin after failure of alkylating agents. In phase III trials paclitaxel was reported to be as efficacious over 24 hours as doxorubicin 60 mg/m(2), while paclitaxel was significantly inferior to doxorubicin 75 mg/m(2) over 3 hours and was close to CMF in another trial. The role of taxanes in combination with anthracyclines in first-line therapy of advanced breast cancer is emerging. Following several phase II studies, a phase III trial showed the significant superiority of docetaxel/doxorubicin (AT) versus doxorubicin/cyclophosphamide (AC) in terms of response and time to progression. In several phase II studies with paclitaxel (3 hours), anthracyclines in the metastatic setting showed high efficacy but produced cardiac toxicity related to a pharmacokinetic interaction between the two agents. This finding led to the implementation of metastatic strategies (phase III trials) aimed at avoiding the pharmacokinetic interaction, while the adjuvant strategies with paclitaxel focused primarily on the sequential approach (AC followed by paclitaxel). In contrast, adjuvant strategies with docetaxel/anthracycline-based programs were implemented following both sequential and combination approaches.

Anthracyclines↗
PubMed2001

The choice of adjuvant combination therapies with taxanes: rationale and issues addressed in ongoing studies.

The taxanes are emerging as the most powerful compounds in breast cancer. Both compounds, paclitaxel and docetaxel, have been evaluated in the metastatic setting before proceeding with adjuvant trials. Docetaxel was shown in phase III trials to be superior, in particular, in terms of time to progression and survival, to salvage polychemotherapies after failure of prior chemotherapy including anthracyclines. Also, after failure of alkylating agents, a benefit in favor of docetaxel was reported when compared to doxorubicin, whereas paclitaxel was reported to be either as efficacious or inferior to doxorubicin, while being comparable to cyclophosphamide/methotrexate/5-fluorouracil. The role of taxanes in combination with anthracyclines in first-line therapy of advanced breast cancer is still unclear although emerging. One phase III trial showed the significant superiority of doxorubicin/docetaxel (AT) versus doxorubicin/cyclophosphamide (AC) in terms of response and time to progression. Several phase II studies with paclitaxel (over 3 hours) and anthracyclines in the metastatic setting showed high efficacy, but they also showed cardiac toxicity related to a pharmacokinetic interaction between the 2 agents. This fact led to the implementation of metastatic strategies (several phase III trials) aimed at avoiding the pharmacokinetic interaction or specifically limiting the cardiac toxicity that resulted in contradictory results. Consequently, adjuvant strategies with paclitaxel focused mostly on the sequential approach (AC followed by paclitaxel). In contrast, adjuvant strategies with docetaxel/anthracycline-based programs were implemented following both sequential and combination approaches. Results of all of these trials in the adjuvant setting are eagerly awaited in order to establish the role of taxanes in adjuvant breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

A web-based tool to retrieve human genome polymorphisms from public databases.

Single Nucleotide Polymorphisms (SNPs) are the most important source of variation in our genome, and an invaluable tool in the hands of researchers who investigate genetic diseases. Databases of SNPs are growing at a very fast rate, and the ability to perform large-scale, high-resolution association studies is quickly becoming a reality. In this paper we describe SNPper, a web-based tool to search for SNPs in public databases. The system allows searching for all SNPs in a given set of genes (for candidate gene studies) or in a specified region of a chromosome. The information displayed for each gene or each SNP is fully annotated and linked to the leading bioinformatics web sites. The first release of SNPper is available on the web, and has received positive feedback from the genetic and bioinformatics community.

Databases, Genetic↗
PubMed2001

Developmental effects of lead acetate on the chick embryo metanephros.

The developmental effects of lead acetate were studied in the chick embryo metanephros, the third renal rudiment that acquires morphological characteristics of functioning kidney already during the prenatal life. Lead exposure was obtained by applying a lead acetate solution on the chick embryo chorioallantoic membrane at the days 9, 10 and 11 of incubation. Quantitative evaluation of the lead concentration assessed by furnace atomic absorption spectrophotometry at the days 14 and 21 of incubation demonstrated metal presence both in the chorioallantoic membrane (CAM) and in metanephros (MN). The lead concentration was higher in CAM than in MN; the metal amount was similar in the CAM of 14 and 21 day embryos, but significantly higher in the 14day embryo MN than in the 21 day embryo MN. Morphological observations on metanephros tissue of control and lead-treated embryos were performed under light, electron transmission and electron scanning microscopes. Peculiar attention was devoted to the expression of the junctional protein connexin 43, the major component of the gap junctions in the renal cells. The results indicated that lead treatment does not intervene in the general differentiation of the metanephric nephrons. The lead is reabsorbed by the proximal tubule cells that are engulfed by endocytotic vacuoles and metal deposits and show long term degenerative changes. Expression of Cx43 protein and ultrastructure of gap junctions between proximal tubule cells appeared to be unchanged. The morphological aspects of the MN corpuscles and tubules agree with the suggestion of a lead cytotoxic effect but do not corroborate, at least in this experimental model, the view of primary damage exerted by lead on the gap junctions of the renal epithelial cells.

Abnormalities, Drug-Induced↗