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G D'Agostino

Publications and source records attributed to G D'Agostino.

At least 19 recordsLinked to original sources
PubMed2006

Potentiometric sensor for atrazine based on a molecular imprinted membrane.

A molecular imprinted polymer (MIP) membrane for atrazine, not containing macropores, was synthesized and implemented in a potentiometric sensor. It is expected to work like a solid ISE (where the specific carrier are the imprinted sites) the specific carrier being the imprinted site. The active ion is the protonated atrazine, positively charged. To form this species the determination is carried out in acidic solution at pH lower than 1.8, in which atrazine is prevalently monoprotonated. At these conditions the membrane potential increases with atrazine concentration over a wide concentration range (3 x 10(-5) to 1 x 10(-3)M). The slope of the function E versus logc is about 25 mV/decade, showing that the atrazine form sorbed on MIP is the biprotonated one. The detection limit is determined by the relatively high concentration of atrazine released by the membrane in the sample solution at the considered conditions. It seems to be independent of the atrazine concentration in the internal solution of the sensor, but it depends on the acidity of the solution. The response time is less than 10s and the sensor can be used for more than 2 months without any divergence.

Atrazine↗
PubMed2006

[Open radiofrequency liver resection: technical details].

AIM: Radiofrequency (RF) for the treatment of hepatic neoplasms can be performed through percutaneous, laparoscopic or open surgery. The aim of this study was to point out the details of the role of open RF (ORF). METHODS: Between November 2002 and November 2003, we performed 13 ORFs. Seven patients had an association with chronic liver cirrhosis. With the aid of intraoperative single, internally cooled needle RF, 12 liver resections were performed (7 subsegmentectomies, 3 segmentectomies, 1 left lateral lobectomy, and 1 right lobectomy). In 1 case RF was applied directly to the tumor lesion. In all cases ultrasonography (US) was performed intraoperatively, other lesions were found in 7.7% of the cases. RF energy was applied along the margins of the tumor to create < > before resection with a scalpel. RESULTS: Average operating time for ORF alone was 74.4 minutes (range 30-115 minutes). Mean intraoperative blood loss during the procedure was 104 mL (range 25-250 mL), and blood transfusions were required in 3 patients. Mean hospital stay was 7.9 days (range 6-10 days). Only minor complications were found, and no mortality was observed. No liver recurrence was detected during mean follow-up of 6 months. CONCLUSIONS: This technique is suitable for patients who are at risk of bleeding because it offers a new method for transfusion-free resection, reducing postoperative complications and shorter long-term survival. Adequate follow-up is necessary to judge its true efficacy, in terms of recurrence and survival.

Aged↗
PubMed2005

Aluminium speciation in natural water by sorption on a complexing resin.

Very stable aluminium complexes may be present in natural waters, which can be detected only using appropriate methods. One of them is the resin titration based on the sorption of aluminium on a strongly sorbing resin, Chelex 100. It was here used to detect strong aluminium complexes, and to characterize them by determining their concentration, and the corresponding stability constant. High and low salinity waters were sampled in different sites in the North of Italy. In all the samples aluminium complexes with high stability constant, up to 10(17.4) M(-1) in the less acidic solution, were detected. The stability constant depends mainly on the solution acidity, increasing with increasing pH up to 7. The concentration of the ligands responsible for the strong complexation is similar to that of aluminium (from 0.5 to 1.5 microM), or somewhat lower in the case of estuarine and sea waters. A small fraction of aluminium (from 0% to 2%) in freshwaters, higher in estuarine and sea waters (14% and 10%, respectively), is present in weakly bound forms which could also be the hydrolysis products. The conditional constants of the strong complexes were determined for the different samples examined. They were found to be slightly lower in the case of the high salinity waters, in which a value of 10(16.1) M(-1) at pH 7.5 was obtained. This is probably due to the higher ionic strength in marine water, which strongly influences the complexation of trivalent metal ions, as seen for example also in the hydrolysis. It could be deduced that similar substances, but at different concentration, would be responsible for the aluminium complexation in the sea and freshwaters here examined. They could be natural organics like fulvic substances, or better some particular complexing sites in this substances with very high affinity for aluminium.

Journal Article↗
PubMed2004

Phase II study of pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients. May a new treatment schedule improve toxicity profile?

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) has shown promising activity in the treatment of recurrent ovarian cancer but skin toxicity remains the dose-limiting toxicity of the drug. The aim of this study was to investigate whether a different treatment schedule may improve the toxicity profile, especially in terms of dermatological and mucosal toxicity. METHODS: It is an open-label phase II study in a population of heavily pretreated ovarian cancer patients. PLD was administered at the dose of 35 mg/m2 q21 until disease progression or unacceptable toxicity. RESULTS: Thirty-seven heavily pretreated (median number of previous chemotherapy regimens 2, range 1-6) ovarian cancer patients were enrolled. All patients received at least two courses of chemotherapy and all were evaluated for response. No one showed complete response, while five partial responses (13.5%), 16 stabilizations of disease (48.6%) and 14 progressions of disease (37.8%) were observed. The median time to response was 12 weeks (range 8-16). The median duration of response was 22.8 weeks (range 4-68), the median duration of stabilization of disease was 17.6 weeks (range 4-28). Palmar plantar erythrodysesthesia (PPE) occurred in 8 patients (21.6%) and was of grade 3 in one patient (2.8%). Grade 1 stomatitis occurred in 3 patients (8.1%). Grade 3-4 neutropenia occurred in only 4 patients (10.8%). CONCLUSIONS: PLD at the dose of 35 mg/m2 q21 seems to translate into an acceptable skin toxicity profile with a response rate comparable to others obtained with a standard schedule.

Adult↗
PubMed2003

Phase II study of liposomal doxorubicin and gemcitabine in the salvage treatment of ovarian cancer.

In total, 70 patients were enrolled into this phase II study, to evaluate the activity of the pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) combination in recurrent ovarian cancer patients. PLD, 30 mg m(-2), was administered on day 1 by 60' i.v. infusion, followed by GEM, 1000 mg m(-2), given by 30' i.v. on days 1 and 8; cycles were repeated every 21 days. In all, 67 patients are so far evaluable for response. Seven complete responses (10.4%, 95% CI: 3.1-17.7), 16 partial responses (23.9%, 95% CI: 13.7-34.1), 26 disease stabilisations (38.8%, 95% CI: 27.1-50.5) and 18 progressions (26.9%, 95% CI: 16.3-37.5) have been registered. Within the resistant population (n=36), the response rate was 25% (95% CI: 10.9-39.1). Within the group of platinum-sensitive patients (n=31), the response rate was 45.2% (95% CI: 27.7-62.7). A total of 443 courses are evaluable for toxicity. Grade 3-4 hematological toxicity was registered in 30 patients (42.8%), mainly represented by neutropenia (35.6%); palmar-plantar erythrodysesthesia affected 24 patients (34.2%), but it was of grade 3 in only seven of them (10%).

Adult↗
PubMed2002

Presence and passage dependent loss of biochemical M3 muscarinic receptor function in human detrusor cultured smooth muscle cells.

PURPOSE: We explored morphological and biochemical aspects of human detrusor cells in culture as a tool for investigating the physiological mechanisms underlying bladder function and disturbances. MATERIALS AND METHODS: Primary cultures of smooth muscle cells were derived from human bladder specimens of patients with an average age of 70 years undergoing cystectomy. Cultured cells were investigated by morphological, immunocytochemical and Western blot analysis. The alpha-actin content as well as the presence of muscarinic M2 and M3 receptors was determined in cell lysates and in fresh tissue homogenate for comparison. The functional response to muscarinic stimulation was assessed by measuring IP3 production induced by 1 mM. carbachol. RESULTS: Cultured smooth muscle cells showed a characteristic spindle-shaped morphology at early passages. Similarly immunocytochemical and Western blot analysis revealed an alpha-actin cell content that was unmodified up to passage 3. Conversely this marker protein sharply decreased during further passages. M3 muscarinic receptor was present in cultured cells and fresh tissue homogenates, whereas the M2 subtype was evident only in homogenates. Carbachol produced a time dependent increase in IP3 cell content, reaching maximal production after 20 minutes of exposure. This response was passage sensitive. CONCLUSIONS: Cultured human detrusor smooth muscle cells maintain their morphological and biochemical characteristics up to passage 3. With this caveat such cells can be an appropriate tool for investigating the molecular pathways underlying cholinergic activation in normal physiological and pathological bladders, and accordingly for detecting putative targets for pharmacological intervention.

Actins↗
PubMed2001

Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo.

Type I interferons (IFN-I) are rapidly induced following infection and play a key role in nonspecific inhibition of virus replication. Here we have investigated the effects of IFN-I on the generation of antigen-specific antibody responses. The data show that IFN-I potently enhance the primary antibody response to a soluble protein, stimulating the production of all subclasses of IgG, and induce long-lived antibody production and immunological memory. In addition, endogenous production of IFN-I was shown to be essential for the adjuvant activity of CFA. Finally, IFN-I enhanced the antibody response and induced isotype switching when dendritic cells were the only cell type responding to IFN-I. The data reveal the potent adjuvant activity of IFN-I and their important role in linking innate and adaptive immunity.

Adjuvants, Immunologic↗
PubMed2001

Tachykinin-dependent and -independent components of peristalsis in the guinea pig isolated distal colon.

BACKGROUND & AIMS: In the intestine, tachykinins regulate motility by participating in neuromuscular and neuro-neuronal transmission. The aim of this study was to test the hypothesis that colonic propulsion is regulated by an interplay between tachykinergic and cholinergic transmission. METHODS: Propulsion was elicited by intraluminal distention of a thin rubber balloon, which traveled from the oral to the anal end of guinea pig isolated distal colon segments. The overall contribution of endogenous tachykinins to colonic propulsion was examined by blocking NK1, NK2, and NK3 receptors simultaneously. RESULTS: NK2-receptor blockade by MEN 11420 inhibited propulsion, whereas blockade of NK(1) by SR 140333 or of NK3 receptors by SR 142801 had minor effects on motility. Blockade of muscarinic or nicotinic receptors by hyoscine or hexamethonium decelerated peristalsis up to propulsion arrest. In the presence of partial muscarinic receptor blockade, the NK1-receptor antagonist SR 140333 and the NK2-receptor antagonist MEN 11420 markedly inhibited propulsion. Propulsion was also inhibited by the NK3-receptor antagonist SR 142801 in the presence of partial nicotinic receptor blockade. The simultaneous administration of the 3 tachykinin antagonists inhibited propulsion by 50%. CONCLUSIONS: This study demonstrates the existence of an interplay between tachykinergic and cholinergic pathways during peristalsis and the importance of endogenous tachykinins acting at multiple receptor sites in the control of colonic propulsion.

Animals↗
PubMed2001

Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer.

24 patients were enrolled into a phase I-II study conducted to determine the maximum tolerated doses of topotecan-gemcitabine in sequential combination and the response rate in platinum/paclitaxel resistant ovarian cancer patients. A total of 83 courses are evaluable, with a median number of three cycles administered per patients (range 2-7). Topotecan was administered on days 1-5 by 30 min i.v. infusion immediately after gemcitabine given by 30 min i.v. on days 1 and 3; cycles were repeated every 28 days. The starting doses were topotecan 0.7 mg/m(2) and gemcitabine 200 mg/m(2). Following dose levels were 08/400; 0.9/600; 0.9/800 for topotecan and gemcitabine, respectively. The maximum tolerated dose (MTD) was reached at dose level 3, the dose-limiting toxicity being represented by febrile neutropenia and thrombocytopenia. After the MTD was reached, granulocyte-colony-stimulating factor was administered in 27% of cycles. Mild and manageable was non hematological toxicity. All patients are so far evaluable for response. Among them 2 complete responses (8.3%; 95% CI: 2.6-19), 1 partial response (4.2%; 95% CI: 3.8-12), 9 no change (37.5%; 95% CI: 18-56.8) and 12 progressions (50%; 95% CI: 30-70) have been registered. Based on these data, there is no evidence that combining topotecan and gemcitabine is better than using either of the two drugs used separately.

Adult↗
PubMed2001

Nuclear changes in pathogen-infected tomato roots.

We have investigated nuclear changes induced in tomato (Lycopersicon esculentum) plant roots by two different pathogens, a phytoplasma of the stolbur group and the soil-borne fungus Phytophthora nicotianae var. parasitica, using light and electron microscopy as well as flow cytometry. Our results show that both pathogens strongly influenced nuclear structure, causing pyknosis and chromatolysis, and induced variations in proportion of nuclear populations with different DNA content, increasing the 2C and decreasing the 4C nuclear populations. These latter results suggest a block of the endoreduplication process in the presynthetic phase of the host cell cycle. Moreover, in pathogen-infected roots, nuclei of the same DNA content were less fluorescent, and therefore had a lower DNA content, compared to those of controls, as confirmed by morphological analyses. Our findings suggest that different stimuli may evoke similar nuclear changes, and confirm the usefulness of flow cytometry as a tool to recognize the stress conditions related to the presence of a pathogen.

Animals↗
PubMed2000

Tachykinin NK(2) receptors facilitate acetylcholine release from guinea-pig isolated trachea.

The release of newly synthesised [3H]acetylcholine was evoked by electrical field stimulation (5 Hz, 600 pulses) of epithelium-deprived guinea-pig trachea strips after sensory neuropeptides depletion with 3 microM capsaicin. The selective tachykinin NK(2) receptor agonist [betaAla(8)]neurokinin A-(4-10) increased in a concentration-dependent manner the electrically-induced release of [3H]acetylcholine. The facilitatory effect was antagonised by the selective non-peptide tachykinin NK(2) receptor antagonist, SR 48968 (apparent pK(B) 8.9). The tachykinin NK(1) and NK(3) receptor agonists substance P methyl ester and senktide (both 10 and 100 nM), respectively, did not affect the evoked release of [3H]acetylcholine. It is concluded that the cholinergic nerves of guinea-pig trachea are endowed with prejunctional facilitatory tachykinin receptors of the NK(2) subtype.

Acetylcholine↗
PubMed2000

The interaction of antidepressant drugs with enteric 5-HT7 receptors.

In this study the functional interaction of the antidepressant drugs amitriptyline, mianserin, maprotiline, imipramine, fluoxetine and the putative antidepressant drug flibanserin has been studied on 5-HT7-mediated responses to 5-carboxamidotryptamine (5-CT) in the guinea-pig ileum. 5-CT induced a concentration-dependent inhibition of the contractile response to substance P (100 nM). Except for fluoxetine and flibanserin, all the antidepressants antagonized by different degrees the 5-CT inhibitory response with the following rank affinity order: mianserin > maprotiline > imipramine > amitriptyline. Mianserin was the only antidepressant to show a profile of competitive antagonism at 5-HT7 receptors in a tenfold range of concentrations (0.1-1 microM), with an affinity (pA2) value of 8.1 +/- 0.6. The antagonism of the other antidepressants was not concentration-dependent (amitriptyline) or was associated with slight or moderate reduction of the maximal 5-CT response (imipramine or maprotiline). The apparent affinity (pKB) values were: amitriptyline, 7.0 +/- 0.2; maprotiline, 7.3 +/- 0.6; imipramine, 7.2 +/- 0.4. Our results show that various antidepressant drugs belonging to different chemical classes behave as antagonists at enteric 5-HT7 receptors through competitive or allosteric mechanisms. This evidence extends our previous findings demonstrating the interaction of antidepressants with other 5-HT receptors, namely 5-HT3 and 5-HT4 receptors.

Animals↗
PubMed2000

Role of agonist-dependent receptor internalization in the regulation of mu opioid receptors.

Organotypic cultures and ileal neuromuscular preparations were used to determine (i) whether endogenous release of opioids by electrical stimulation induces mu receptor endocytosis, and (ii) whether and under which conditions ligand-induced mu receptor endocytosis influences the responsiveness of neurons expressing native mu receptors. In longitudinal muscle-myenteric plexus preparations, electrical stimulation at 20 Hz induced a prominent endocytosis of mu receptors in enteric neurons, indicating endogenous release of opioids. A similar massive endocytosis was triggered by exogenous application of the mu receptor agonist, [D-Ala(2),MePhe(4), Gly-ol(5)] enkephalin, whereas exogenous application of morphine was ineffective. [D-Ala(2),MePhe(4),Gly-ol(5)] enkephalin and morphine induced a concentration-dependent inhibition of neurogenic cholinergic twitch contractions to electrical stimulation at 0.1 Hz. beta-Chlornaltrexamine shifted to the right the inhibitory curve of both agonists with a concentration-dependent reduction of the maximum agonist response, which is consistent with the existence of spare mu opioid receptors. Under these conditions, the induction of mu receptor endocytosis by exogenously applied [D-Ala(2), MePhe(4),Gly-ol(5)] enkephalin diminished the inhibitory effect of this agonist on twitch contractions and tritiated acetylcholine release. In contrast, there was no reduction of the inhibitory effect of morphine, which failed to induce mu receptor endocytosis, on neurogenic cholinergic response. These results provide the first evidence for the occurrence of mu receptor endocytosis in neurons by endogenously released opioids and show that agonist-dependent mu receptor endocytosis could serve as a mechanism to regulate mu opioid receptor responsiveness to ligand stimulation when the opioid receptor reserve is reduced.

Acetylcholine↗
PubMed2000

Prejunctional muscarinic inhibitory control of acetylcholine release in the human isolated detrusor: involvement of the M4 receptor subtype.

1. Experiments were carried out in human detrusor strips to characterize muscarinic receptor subtypes involved in the prejunctional regulation of acetylcholine (ACh) release from cholinergic nerve terminals, and in the postjunctional smooth muscle contractile response. 2. In detrusor strips preincubated with [3H]-choline, electrical field stimulation (600 pulses) delivered in six trains at 10 Hz produced a tritium outflow and a contractile response. In the presence of 10 microM paraoxon (to prevent ACh degradation) the tritium outflow was characterized by HPLC analysis as [3H]-ACh (76%) and [3H]-choline (24%). 3. Electrically-evoked [3H]-ACh release was abolished by tetrodotoxin (TTX: 300 nM) and unaffected by hexamethonium (10 microM), indicating a postganglionic event. It was reduced by physostigmine (100 nM) and the muscarinic receptor agonist, muscarone (10 nM-1 microM), and enhanced by atropine (0.1-100 nM). These findings indicate the presence of a muscarinic negative feedback mechanism controlling ACh release. 4. The effects of various subtype-preferring muscarinic receptor antagonists were evaluated on [3H]-ACh release and muscle contraction. The rank potency (-log EC50) orders at pre- and postjunctional level were: atropine > or = 4-diphenyl-acetoxy-N-piperidine (4-DAMP) > mamba toxin 3 (MT-3) > tripitramine > para-fluorohexahydrosiladiphenidol (pF-HHSiD) > or = methoctramine > or = pirenzepine > tripinamide, and atropine > or = 4-DAMP > pF-HHSiD >> pirenzepine = tripitramine > tripinamide > methoctramine >> MT-3, respectively. 5. The comparison of pre- and post-junctional potencies and the relationship analysis with the affinity constants at human cloned muscarinic receptor subtypes indicates that the muscarinic autoreceptor inhibiting ACh release in human detrusor is an M4 receptor, while the receptor involved in muscular contraction belongs to the M3 subtype.

Acetylcholine↗
PubMed2000

Type I consensus interferon (CIFN) gene transfer into human melanoma cells up-regulates p53 and enhances cisplatin-induced apoptosis: implications for new therapeutic strategies with IFN-alpha.

In this study, we describe the effects produced by the retroviral transduction of human type I consensus IFN (CIFN) coding sequence into the 8863 and 1B6 human melanoma cell lines, derived from a metastatic and a primary human melanoma, respectively. Melanoma cell lines producing approximately 103 IU/ml of IFN were obtained. Interestingly, cisplatin treatment of IFN-producing 8863 and 1B6 melanoma cells resulted in a three- to four-fold increase in the percentage of apoptotic cells with respect to similarly treated parental or control-transduced cell cultures. A similar effect, although less intense, was caused by cultivation of parental melanoma cells in the presence of exogenous CIFN. The increased susceptibility of the IFN-producing melanoma cell lines to cisplatin-induced apoptosis was associated with an IFN-dependent accumulation of p53, which also correlated with a decrease in Bcl-2 expression. Addition of exogenous CIFN to parental melanoma cells resulted in similar although weaker modulations of p53 and Bcl-2 expression. Cisplatin administration to nude mice bearing 3-day-old IFN-producing 8863 tumors resulted in complete tumor regression, while only a partial tumor inhibition was observed upon cisplatin treatment of mice bearing parental or control-transduced 8863 tumors. Starting the cisplatin treatment 7 days after tumor cell injection still resulted in a stronger inhibition of tumor growth in the mice bearing IFN-producing 8863 tumors as compared with parental tumor-bearing mice. A comparable therapeutic effect was obtained after repeated peritumoral administration of 103 IU of exogenous CIFN and cisplatin treatment. Interestingly, a spontaneous tumor regression was observed in nude mice injected with IFN-producing 1B6 cells, in contrast to the progressive tumor growth occurring in mice receiving a similar inoculum of the parental or control-transduced 1B6 melanoma cells. Repeated peritumoral administration of 103 IU of exogenous CIFN to mice bearing parental 1B6 tumors caused only a transient inhibition of tumor growth. These results indicate that type I IFN gene transfer is an effective approach for suppressing the tumorigenic phenotype of human melanoma cells and for increasing the efficacy of anticancer drugs. These observations, together with our previous findings showing the importance of IFN-alpha-T cell interactions in the generation of an antitumor response in mouse models, underline the interest of using type I IFN in gene therapy strategies for the treatment of human melanoma.

Animals↗
PubMed2000

Cerebellar agenesis in a suicide.

A case of a suicidal death associated with autopsy findings of right cerebellar and vermian agenesis is described. A review of the literature points out the various recurrence of agenesis, symptoms, and the likelihood of motor deficits. The singular coexistence of only behavioral and intellectual deficiency with suicidal inclination in an adult man with partial cerebellar agenesis is discussed.

Adult↗
PubMed2000

[Hemorrhoidectomy in muco-hemorrhoidal prolapse using mechanical stapler].

BACKGROUND: The treatment of hemorrhoids has changed throughout the latter years. In selected cases hemorrhoidectomy with circular stapler, in personal opinion, is the best surgical technique. The goal of the present study is to evaluate the therapeutic results of hemorrhoidectomy by means of the above technique in 150 consecutive cases. METHODS: From March 1997 to November 1999, 150 patients were surgically treated, 84 women and 66 men with a median age of 57 years. 130 patients had III degree, thus with a reducible prolapse, 10 IV degree and 10 patients with II degree hemorrhoids resistant to ambulatory banding and/or sclerotherapy. Every patient was operated with the circular stapler in Day Surgery regimen, and the patients were discharged after 24 hours. RESULTS: Eight immediate hemorrhages were seen, four of which were surgically treated; 10 patients had urinary retention which required an urinary catheter. Healing was complete in the 15-20th day. The follow-up after one month was performed on 140 patients, at 3 months and at one year, on 100 patients. No suture stenosis and no recurrences of the hemorrhoid prolapse were observed. Follow-up after 6, 12 and 24 months on 100 patients was also considered in order to evaluate the results after surgery and late complications or sequelae. Fifteen patients were reevaluated after one and two months with anorectal manometry which did not demonstrate important alterations of the continence. CONCLUSIONS: The advantages of this technique is to carry out a radical surgical procedure in a single event, by means of a rapid and mini-invasive technique, with an earlier physical recovery, with the absence of medication in the postoperative period, and an early social and working reestablishment.

Adult↗