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Biomedical subjects

A Riva

Publications and source records attributed to A Riva.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Vascular graft infection by Staphylococcus epidermidis: efficacy of various perioperative prophylaxis protocols in an animal model].

A rat model was used to investigate the efficacy of levofloxacin, cefazolin and teicoplanin in the prevention of vascular prosthetic graft infection. Graft infections were established in the subcutaneous tissue of 300 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis (10 mg/kg), two contaminated groups with intraperitoneal cefazolin prophylaxis (30 mg/kg), two contaminated groups with intraperitoneal teicoplanin prophylaxis (10 mg/kg) and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or te- icoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture. The efficacy of levofloxacin against the methicillin- susceptible strain did not differ from that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The levofloxacin-rifampin combination proved to be similarly effective to the rifampin-teicoplanin combination and more effective than the rifampin-cefazolin combination against both strains. The rifampin-levofloxacin combination may be useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis because it takes advantage of the good anti-staphylococcal activity of both drugs.

Animals↗
PubMed2000

Phase I and pharmacokinetic study of docetaxel and irinotecan in patients with advanced solid tumors.

PURPOSE: We conducted a phase I and pharmacokinetic study of docetaxel in combination with irinotecan to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the dose at which at least 50% of the patients experienced a DLT during the first cycle, and to evaluate the safety and pharmacokinetic profiles in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with only one prior chemotherapy treatment (without taxanes or topoisomerase I inhibitors) for advanced disease were included in the study. Docetaxel was administered as a 1-hour IV infusion after premedication with corticosteroids followed immediately by irinotecan as a 90-minute IV infusion, every 3 weeks. No hematologic growth factors were allowed. RESULTS: Forty patients were entered through the following seven dose levels (docetaxel/irinotecan): 40/140 mg/m(2), 50/175 mg/m(2), 60/210 mg/m(2), 60/250 mg/m(2), 60/275 mg/m(2), 60/300 mg/m(2), and 70/250 mg/m(2). Two hundred cycles were administered. Two MTDs were determined, 70/250 mg/m(2) and 60/300 mg/m(2); the DLTs were febrile neutropenia and diarrhea. Neutropenia was the main hematologic toxicity, with 85% of patients experiencing grade 4 neutropenia. Grade 3/4 nonhematologic toxicities in patients included late diarrhea (7.5%), asthenia (15.0%), febrile neutropenia (22.5%), infection (7.5%), and nausea (5.0%). Pharmacokinetics of both docetaxel and irinotecan were not modified with the administration schedule of this study. CONCLUSION: The recommended dose of docetaxel in combination with irinotecan is 60/275 mg/m(2), respectively. At this dose level, the safety profile is manageable. The activity of this combination should be evaluated in phase II studies in different tumor types.

Adult↗
PubMed2000

IDN5109, a taxane with oral bioavailability and potent antitumor activity.

IDN5109 is a new taxane, derived from 14beta-hydroxy-10-deacetylbaccatin III, selected for its lack of cross-resistance in tumor cell lines expressing the multidrug resistant phenotype. Because, unlike paclitaxel, IDN5109 is a poor substrate for P-glycoprotein, we hypothesized that IDN5109 given p.o. could improve bioavailability compared with paclitaxel. Here, we studied the p.o. and i.v. pharmacokinetics of IDN5109 together with its antitumor activity. Using a high-performance liquid chromatography method, the bioavailability of IDN5109 was determined to be 48% after oral delivery. IDN5109 given p.o. was highly active against the two human ovarian carcinoma xenografts 1A9 and HOC18 (90-100% tumor regressions) and showed significant activity on the paclitaxel-resistant MNB-PTX1 xenograft (10% tumor regressions). The p.o. administration was as active as the i.v. route at doses reflecting the pharmacokinetic data. IDN5109 is the first taxane with good oral bioavailability and potent antitumor activity and represents a potential candidate for clinical investigation.

Administration, Oral↗
PubMed2000

In vitro evaluation of newly developed chalcone analogues in human cancer cells.

PURPOSE: Among flavonoids, chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. We studied a panel of newly developed chalcone analogues (S1-S10) using MDA-MB 231 and MCF-7 ADRr breast cancer cells and the T-leukemic Jurkat cell line. Quercetin was used as the reference compound. METHODS: Antiproliferative activity was evaluated by cell counts performed after 72 h of exposure to the drugs. DNA analysis and redox activity were evaluated using flow cytometry. Apoptosis was assessed by morphological analysis, using YOYO-1 as DNA dye; p-glycoprotein function was ascertained by quantitating the efflux of rhodamine 123. RESULTS: All cells were sensitive to chalcone analogues yielding IC50 in micromolar concentrations with the following order regardless of the multidrug resistance (MDR) status: S1 > S2 > quercetin. S1 and S2, the most active compounds, were selected to evaluate their effect on the cell cycle, apoptosis, redox activity, and modulation of the p-glycoprotein function. No significant perturbation in cell cycle was seen with concentration up to 1 microM after 24 h. After 72 h a slight increase in G2/M block and DNA fragmentation occurred at 10 microM. Morphological analysis of apoptosis showed that chalcone analogues induced apoptosis to a higher extent than quercetin. Redox analysis demonstrated that all substances were able to increase intracellular thiol levels, which returned to baseline value after 24 h for all drugs except quercetin. Production of reactive oxygen species was essentially unaffected by all compounds. Finally, in MDR-positive MCF-7 ADRr cells chalcone analogues were unable to modulate p-glycoprotein function while quercetin was able to. CONCLUSIONS: Newly developed S1 and S2 chalcones have a different but higher antitumor activity than quercetin and could be considered as potential new anticancer drugs.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Anti-tumour activity of a panel of taxanes toward a cellular model of human cervical cancer.

Using a model of human cervical cancer (ME-180 cells), the anti-tumour activity of paclitaxel was compared to that of docetaxel and IDN5109, a newly developed taxane. The growth inhibition effect of taxanes was assessed after 3 days of exposure. DNA analysis, the taxane-dependent modulation of the expression of the alpha and beta subunits of tubulin and DNA fragmentation were assessed by flow cytometry. The presence of apoptosis was confirmed by morphological analysis using a laser scan cytometer. For the evaluation of "in vivo" anti-tumour activity, taxanes were administered to nude mice intravenously once daily, according to a q3/4d x 4 schedule. Docetaxel, IDN5109 and paclitaxel obtained "in vitro" IC(50) values of 0.86, 1.4 and 2.4 nM, respectively. DNA analysis demonstrated a transient block at the G(2)/M phase of the cell cycle only after 12 h of culture in the presence of taxanes and an increase of nuclear fragmentation suggestive for apoptosis after additional 12 and 60 h of exposure. Morphological analysis confirmed the presence of apoptosis. Taxanes induced a down-modulation of the alpha subunit of tubulin in the G(0/1) phase of the cell cycle, and an overexpression of the beta subunit in the G(2)/M phase. A strong anti-tumour activity was obtained "in vivo" for nude mice xenografted using ME-180 cells (T/C=0% for all drugs). These data indicate that the three taxanes are strongly active both "in vitro" and "in vivo" toward ME-180 cells. Clinical studies are now needed to ascertain if the higher anti-tumour activity observed "in vitro" using docetaxel and IDN5109 yields a better clinical response in advanced cervical carcinoma with respect to paclitaxel.

Animals↗
PubMed2000

A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer.

BACKGROUND AND PURPOSE: Docetaxel is an active agent in the treatment of metastatic breast cancer. We evaluated the feasibility of docetaxel-based sequential and combination regimens as adjuvant therapies for patients with node-positive breast cancer. PATIENTS AND METHODS: Three consecutive groups of patients with node-positive breast cancer or locally-advanced disease, aged < or = 70 years, received one of the following regimens: a) sequential A-->T-->CMF: doxorubicin 75 mg/m2 q 3 weeks x 3, followed by docetaxel 100 mg/m2 q 3 weeks x 3, followed by i.v. CMF days 1 + 8 q 4 weeks x 3; b) sequential accelerated A-->T-->CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks x 4, followed by CMF x 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CMF. RESULTS: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients receiving the sequential accelerated therapy (23% during A-->T), due principally to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated patients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been reported. CONCLUSIONS: The accelerated sequential A-->T-->CMF treatment is not feasible due to an excess of skin toxicity. The sequential non accelerated and the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.

Adult↗
PubMed2000

Environmental and serological evidence for the presence of toxocariasis in the urban area of Ancona, Italy.

To evaluate the Toxocara spp. eggs environmental contamination of the soil of the urban or suburban area Ancona (Italy), 22 public playgrounds were selected and several cores of soil were taken from any selected areas. To study the Toxocara seroprevalence in the inhabitants of Ancona, blood samples were collected from selected groups of individuals. One hundred and sixty-three blood samples were tested using an enzyme linked immunosorbent assay (ELISA) technique (Lofarma Lab, Milan, Italy) for the detection of IgG-specific antibodies to T. canis excretory-secretory antigens. Toxocara spp. eggs were found in the soil samples from 14 (63.6%) playgrounds. Toxocara seroprevalence was detected in blood specimens from six (8.1%) out of 74 symptomatic individuals and from one (1.1%) out of 89 asymptomatic controls. Among symptomatic individuals, the association between Toxocara seroprevalence and eosinophilia resulted statistically significant (p = 0.029). The high environmental contamination frequency found make necessary to prompt preventive public health measures, such as control of stray animals, treatment of infected pets and hygiene education of the population.

Adolescent↗
PubMed2000

Efficacy of rifampin-levofloxacin as a prophylactic agent in preventing Staphylococcus epidermidis graft infection.

OBJECTIVES: To investigate the efficacy of levofloxacin in the prevention of vascular prosthetic graft infection in a rat model. METHODS: Graft infections were established in the subcutaneous tissue of 225 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis, two contaminated groups with intraperitoneal cefazolin prophylaxis, two contaminated groups with intraperitoneal teicoplanin prophylaxis and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or teicoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture. RESULTS: The efficacy of levofloxacin against the methicillin-susceptible strain was not different to that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The combination levofloxacin-rifampin demonstrated to be similarly effective to the combination rifampin-teicoplanin and more effective than the combination rifampin-cefazolin against both strains. CONCLUSIONS: Rifampin-levofloxacin combination seems useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis.

Animals↗
PubMed2000

Interferon-alpha2b reduces phosphorylation and activity of MEK and ERK through a Ras/Raf-independent mechanism.

Interferon (IFN)-alpha affects the growth, differentiation and function of various cell types by transducing regulatory signals through the Janus tyrosine kinase/signal transducers of activation and transcription (Jak/STAT) pathway. The signalling pathways employing the mitogen-activated ERK-activating kinase (MEK) and the extracellular-regulated kinase (ERK) are critical in growth factors signalling. Engagement of the receptors, and subsequent stimulation of Ras and Raf, initiates a phosphorylative cascade leading to activation of several proteins among which MEK and ERK play a central role in routing signals critical in controlling cell development, activation and proliferation. We demonstrate here that 24-48 h following treatment of transformed T- and monocytoid cell lines with recombinant human IFN-alpha2b both the phosphorylation and activity of MEK1 and its substrates ERK1/2 were reduced. In contrast, the activities of the upstream molecules Ras and Raf-1 were not affected. No effect on MEK/ERK activity was observed upon short-term exposure (1-30 min) to IFN. The anti-proliferative effect of IFN-alpha was increased by the addition in the culture medium of a specific inhibitor of MEK, namely PD98059. In conclusion, our results indicate that IFN-alpha regulates the activity of the MEK/ERK pathway and consequently modulates cellular proliferation through a Ras/Raf-independent mechanism. Targeting the MEK/ERK pathway may strengthen the IFN-mediated anti-cancer effect.

Antineoplastic Agents↗
PubMed2000

Antitumour activity of novel taxanes that act at the same time as cytotoxic agents and P-glycoprotein inhibitors.

Taxanes antitumour agents such as paclitaxel and docetaxel represent a successful family of chemotherapeutic drugs. Unfortunately, acquired and innate resistance represents a clinical problem for these drugs. We investigated, on a panel of 7 human cancer cell lines, the growth inhibition effect of 3 newly developed taxanes (SB-T-1213, SB-T-1250 and SB-T-101187) with modification at the C10 and C3' positions of the taxane framework. These positions have been previously characterized as critical to make taxanes highly active against cells overexpressing the efflux pump P-glycoprotein (P-gp). Paclitaxel and docetaxel were used as reference compounds. Results unambiguously indicate the exceptional activity of the novel taxanes toward P-gp positive cells (up to >400 fold higher potency than that of paclitaxel). SB-T-1213 and SB-T-1250 are also substantially more active than the reference compounds against P-gp negative cells. To better understand the mechanisms underlying the enhanced activity of the newly developed taxanes, we performed cell cycle and apoptosis analysis. This study demonstrates that the striking growth inhibition effect exhibited by the novel taxanes is ascribed to their increased ability in inducing apoptosis and G(2)/M cell cycle block. SB-T-1213 and SB-T-1250 are also more active than reference compounds in inducing intracellular accumulation of the beta-tubulin subunits. Finally, it is revealed that these novel taxanes have ability to inhibit the function of the P-gp efflux pump on the basis of the Rhodamine 123 assay. These findings strongly suggest that SB-T-1213, SB-T-1250 and SB-T-101187 represent a new tool to overcome innate or acquired P-gp mediated taxane-resistance.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

A high resolution sem study of human minor salivary glands.

By SEM we have investigated the human minor salivary glands using the NaOH method for the visualization of endpieces and myoepithelial cells, and the osmium maceration technique that reveals membranous intracellular structures. With the former method all minor glands, including the posterior deep (Ebner's) lingual glands, consist of tubules sometimes dilated into alveoli, while true acini of the kind observed in human major salivary glands, are absent. Tubules of the posterior deep lingual gland exhibit stellate myoepitelial cells that leave a substantial part of the secretory cells uncovered. The latter cells, at variance with serous cells of major glands, do not show basal folds. In contrast, tubules of the other minor glands, like the mucous ones of major glands, are covered almost completely by band-like myoepithelial cells. The osmium maceration method clearly demonstrates that posterior deep lingual glands are serous in character and that all the other minor glands, together with the predominant mucous cells, possess a variable number of seromucous cells that, despite variations among individuals, increase in order from palatine and posterior superficial lingual (Weber's), to minor sublingual, labial, anterior lingual (Blandin and Nuhn's), and buccal glands.

Humans↗
PubMed2000

Cell biology of human salivary secretion.

We treated surgical specimens of human parotid and submandibular glands in vitro to manipulate the receptor-signaling cascade pharmacologically and analyzed cellular responses by light microscopy on epoxy embedded sections. Treatment of specimens with the b-agonist, isoproterenol, and with the second messenger analog, dibutyryl cyclic AMP, stimulated serous acinar cells to engage in exocytosis and degranulation. The muscarinic agonist, carbachol, and the calcium ionophore, A23187, on the other hand, elicited formation of "vacuoles" in the cytoplasm of serous acinar cells. Taking previous in vivo human and animal studies into account, these changes are suggested as the morphological expression of enzyme release and fluid secretion, respectively. Specimens obtained from patients over 70 years old exhibited poor response even though their morphological appearance remained intact. Aged salivary glands are thus suggested to experience a decline in their secretory activity at the cellular level, probably by impairment of the signaling processes downstream to the receptor activation and second messenger production.

Adrenergic beta-Agonists↗
PubMed2000

Relationship between amylase and fluid secretion in the isolated perfused whole parotid gland of the rat.

Whole gland perfusion technique was applied to rat parotid glands to assess whether amylase affects fluid secretion. Control perfusion without any secretagogue evoked no spontaneous secretion. Carbachol (CCh 1 microM) induced both amylase and fluid secretion with distinctive kinetics. Fluid secretion occurred constantly at 40-120 microliter/g-min (average plateau was 60 microliter/g-min), whereas amylase secretion exhibited an initial peak (10 mg maltose/30 s per g wet w. of the gland), followed by a rapid decrease to reach a plateau level of 1 mg maltose/30 s later than 1.5-2 min. Isoproterenol (Isop 1 microM) alone did not induce fluid secretion although it evoked amylase secretion as measured in isolated perfused acini. Addition of Isop during CCh stimulation evoked a rapid and large rise in amylase secretion to 15 mg maltose/30 s accompanied by the increase in oxygen consumption. However, the fluid secretion exhibited a rather gradual decrease. These findings suggest that control of salivary fluid secretion is independent of the amylase secretion system induced by CCh and/or Isop. Morphological observations carried out by HR SEM and TEM revealed exocytotic profiles following Isop stimulation. CCh stimulation alone seldom showed -exocytotic profiles, suggesting a low incidence of amylase secretion during copious fluid secretion. Combined stimulation of CCh and Isop induced both vacuolation and exocytosis along intercellular canaliculi. During washout of secretagogues, lysosomal digestion of excess membrane took place.

Amylases↗
PubMed2000

Efficacy of polycationic peptides in preventing vascular graft infection due to Staphylococcus epidermidis.

A rat model was used to investigate the efficacy of two polycationic peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides. The in vitro activity of the peptides was compared with those of vancomycin and teicoplanin by MIC determination and time-kill study. Moreover, the efficacy of collagen-sealed peptide-soaked Dacron was evaluated in a rat model of graft infection. Graft infections were established in the dorsal subcutaneous tissue of 120 adult male Wistar rats. The in vivo study included a control group, one contaminated group that did not receive any antibiotic prophylaxis and four contaminated groups that received an antibiotic-soaked graft. Experiments demonstrated that the activities of buforin II and ranalexin were greater than those of vancomycin and teicoplanin. Particularly, rats with buforin II-coated Dacron grafts showed no evidence of staphylococcal infection while, for the rats with ranalexin-, vancomycin- and teicoplanin-coated Dacron grafts, the quantitative graft cultures demonstrated bacterial growth (1.9 x 10(2) +/- 0.6 x 10(2) cfu/mL, 6. 2 x 103 +/- 1.9 x 10(3) cfu/mL and 5.1 x 10(4) +/- 4.8 x 10(3) cfu/mL, respectively). The study demonstrated that the use of peptide-soaked Dacron graft can result in significant bacterial growth inhibition and indicates that these compounds may be potentially useful in prosthetic surgery.

Animals↗
PubMed2000

Mupirocin prophylaxis against methicillin-susceptible, methicillin-resistant, or vancomycin-intermediate Staphylococcus epidermidis vascular-graft infection.

A rat model was used to investigate the efficacy of mupirocin in the prevention of vascular prosthetic graft infection due to Staphylococcus epidermidis strains with different susceptibility patterns (methicillin susceptible, methicillin resistant, and with intermediate resistance to vancomycin). The effect of mupirocin-soaked Dacron was compared to that of perioperative intraperitoneal prophylaxis with vancomycin. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses (1 cm(2)) followed by topical inoculation with 5 x 10(7) CFU of one staphylococcal strain. The study included a control group (no graft contamination), three contaminated groups that did not receive any antibiotic prophylaxis, three contaminated groups that received mupirocin-soaked grafts, three contaminated groups in which perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg of body weight) was administered, and three contaminated groups that received mupirocin-soaked grafts and perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Data analysis showed the efficacy of mupirocin against all three strains, with growth of the strains in treated rats significantly different than that in the untreated control. In addition, mupirocin was more effective than vancomycin against the strain with intermediate susceptibility to the glycopeptide. Finally, the combination of mupirocin and vancomycin produced complete suppression of the growth of all of the strains.

Aminoglycosides↗
PubMed2000

Polycationic peptides as prophylactic agents against methicillin-susceptible or methicillin-resistant Staphylococcus epidermidis vascular graft infection.

Several polycationic peptides isolated from animals, plants, and bacterial species possess a broad spectrum of antimicrobial activity. A rat model was used to investigate the efficacies of two peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infections. The effect of peptide-soaked collagen-sealed Dacron was compared to that of rifampin-soaked collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible rifampin-susceptible Staphylococcus epidermidis and methicillin-resistant rifampin-susceptible S. epidermidis. Graft infections were established in the back subcutaneous tissue of 240 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses, followed by topical inoculation with 2 x 10(7) CFU of S. epidermidis. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups to which perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg of body weight) was administered, six contaminated groups that received a peptide- or rifampin-soaked graft, and six contaminated groups that received a peptide- or rifampin-soaked graft and perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Overall, the efficacies of the polycationic peptides against the methicillin-susceptible and methicillin-resistant strains were not significantly different from that of rifampin. Nevertheless, the combinations of ranalexin- and buforin II-coated grafts with cefazolin treatment demonstrated efficacies significantly higher than that of the combination of rifampin-coated grafts and cefazolin treatment against the methicillin-resistant strain.

Animals↗