PubMed Health⌕ Search

Biomedical subjects

F Mosca

Publications and source records attributed to F Mosca.

At least 163 records · Page 9Linked to original sources
PubMed2000

Fenamates and the potent inhibition of human liver phenol sulphotransferase.

1. The inhibition of the human liver phenol sulphotransferase (HL-PST) and catechol sulphotransferase (HL-CST) by five fenamates has been studied and the activities of HL-PST and HL-CST were measured with 4-nitrophenol and dopamine as substrates, respectively. 2. The IC50 for inhibition of HL-PST were 0.02 microM (mefenamic acid); 0.12 microM (tolfenamic acid); 0.28 microM (niflumic acid); 0.87 microM (meclofenamic acid) and 1.50 microM (flufenamic acid). 3. HL-CST was less susceptible than HL-PST to the inhibition by fenamates and the IC50 for HL-CST were 36 microM (tolfenamic acid); 70 microM (flufenamic acid); 76 microM (mefenamic acid); 180 microM (niflumic acid) and 185 microM (meclofenamic acid). 4. The ratios of the IC50 for HL-CST:HL-PST were drug-dependent and ranged from 47 (flufenamic acid) to 3800 (mefenamic acid). Mefenamic acid is a relatively potent and selective inhibitor of HL-PST. 5. The IC50 for HL-PST obtained with mefenamic acid was three orders of magnitude lower than the peak plasma concentration of this drug after an oral dose of 0.5 g. Accordingly, mefenamic acid should impair sulphation in vivo.

Arylsulfotransferase↗
PubMed2000

Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum.

1. Resveratrol, a polyphenolic compound present in grapes and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It is present in the diet, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim was to study the sulphation of resveratrol in the human liver and duodenum. 2. A simple and reproducible radiometric assay for resveratrol sulphation was developed. It employed 3'-phosphoadenosine-5'-phosphosulphate-[35S] as the sulphate donor and the rates of resveratrol sulphation (mean +/- SD, pmol/min/mg cytosolic protein) were 90 +/- 21 (liver, n = 10) and 74 +/- 60 (duodenum, n = 10, p = 0.082). 3. Resveratrol sulphotransferase followed Michaelis-Menten kinetics and Km (mean +/- SD; microM) was 0.63 +/- 0.03 (liver, n = 5) and 0.50 +/- 0.26 (duodenum, n = 5, p = 0.39) and Vmax (mean +/- SD, pmol/min/mg cytosolic protein) were 125 +/- 31 (liver, n = 5) and 129 +/- 85 (duodenum, n = 5, p = 0.62). 4. Resveratrol sulphation was inhibited by the flavonoid quercetin, by mefenamic acid and salicylic acid, two commonly used non-steroidal anti-inflammatory drugs. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. The potent inhibition of resveratrol sulphation by quercetin, a flavonoid present in wine, fruits and vegetables, suggests that compounds present in the diet may inhibit the sulphation of resveratrol, thus improving its bioavailability.

Adult↗
PubMed2000

Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids.

1. Resveratrol, a polyphenolic compound present in grape and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. Resveratrol is sulphated, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim of this study was to see whether natural flavonoids present in wine, fruits and vegetables inhibit the sulphation of resveratrol in the human liver and duodenum. 2. In the liver, IC50 for the inhibition of resveratrol sulphation was 12+/-2 pM (quercetin), 1.0+/-0.04 microM (fisetin), 1.4+/-0.1 microM (myricetin), 2.2+/-0.1 microM (kaempferol) and 2.8+/-0.2 microM (apigenin). Similarly, in the duodenum, IC50 was 15+/-2 pM (quercetin), 1.3+/-0.1 microM (apigenin), 1.3+/-0.5 microM (fisetin), 2.3+/-0.1 microM (kaempferol) and 2.5+/-0.3 microM (myricetin). 3. The type of inhibition of quercetin on resveratrol sulphation was studied in three liver samples and was determined to be non-competitive and mixed in nature. Km (mean+/-SD; microM) was 0.23+/-0.07 (control), 0.40+/-0.08 (5 pM quercetin) and 0.56+/-0.09 (10 pM quercetin). Vmax (mean+/-SD; pmol min(-1) x mg(-1)) was 99+/-11 (control), 73+/-15 (5 pM quercetin) and 57 +/- 10 (10 pM quercetin). Kj and Kies estimates (mean+/-SD) were 3.7+/-1.8 pM and 12.1+/-1.7 pM respectively (p = 0.010). 4. Chrysin was a substrate for the sulphotransferase(s) and an assay was developed for measuring the chrysin sulphation rate in human liver. The enzyme followed Michaelis-Menten kinetics and Km and Vmax (mean+/-SD) measured in four livers were 0.29+/-0.07 microM and 43.1+/-1.9 pmol x min(-1) x mg(-1) respectively. 5. Catechin was neither an inhibitor of resveratrol sulphation nor a substrate of sulphotransferase. 6. These results are consistent with the view that many, but not all, flavonoids inhibit the hepatic and duodenal sulphation of resveratrol, and such inhibition might improve the bioavailability of this compound.

Aged↗
PubMed2000

Long-acting depot lanreotide in the treatment of patients with advanced neuroendocrine tumors.

Long-acting depot forms of somatostatin analogs administered by intramuscular injections are now available for the treatment of neuroendocrine tumors (NETs). In the present study, we investigated the efficacy and tolerability of a slow-release form of lanreotide in patients with advanced NETs. From July 1996 to January 1999, 25 patients with advanced NETs (12 carcinoids, 13 endocrine pancreatic tumors) were enrolled in the study. Thirteen patients were pretreated with subcutaneous octreotide, chemotherapy, or hepatic metastasis alcoholization. All the patients had measurable disease. Seventeen patients were symptomatic and 20 patients had elevated serum and/or urine markers. Octreotide scintigraphy was positive in 23 of 25 patients. Lanreotide was administered as intramuscular injections at the dose of 30 mg every 2 weeks until there was objective, biochemical, or symptomatic tumor progression. Objective partial responses (PRs) were documented in 2 patients (8%), whereas 10 patients (40%) had tumor stabilization. The PRs were observed in patients with midgut carcinoids, of whom one was pretreated with subcutaneous octreotide. The response duration was 21+ and 24+ months in responding patients; the median duration of disease stabilization was 8.5 months (range, 4-21+). The overall biochemical response rate was 42%, including 2 complete responses (CRs) (10.5%) and 6 PRs (31.5%); all biochemical responses were observed mostly in patients with carcinoid tumors; the duration of response was 18+ and 30+ months for CRs; the median duration of biochemical response was 7 months (range, 4-18+) for PRs. The overall symptomatic response rate was 70% with a median duration of 7.5, 18, and 18+ months for diarrhea, abdominal pain, and flushing, respectively. Median duration of lanreotide treatment was 10 months (range, 2-30+). No significant side effects were reported. Depot lanreotide 30 mg shows significant efficacy in terms of objective response rate and in biochemical and symptomatic control, in pretreated patients as well as nonpretreated patients with advanced NETs. Tolerability is good, with good patient compliance.

Abdominal Pain↗
PubMed2000

Cancer immunomodulation by carbohydrate ligands for the lymphocyte receptor NKR-P1.

Natural killer (NK) and T cells express a superfamily of proteins with structural features of C-type lectins. Recombinantly prepared soluble form of rat NKR-P1 (CD161) recognized carbohydrate GalNac and GlcNac moieties. Ganglioside GM2 and heparin related-IS oligosaccharides representing the high affinity ligands for this receptor, increased the sensitivity of targets for killing by the rat effectors isolated from blood and spleen in vitro. Based on these results, we investigated in vivo the possible therapeutic effect of GM2 and IS carried by liposomes during induced rat colorectal carcinogenesis. The reduction of cancer incidence versus the controls (50% vs 88.88%), approached the 5-fluorouracil treatment (41.66%).

Animals↗
PubMed2000

[Stenotic endometriosis of the sigmoid. Apropos a case].

The authors report a rare case of stenotic sigmoid endometriosis which presented with constipation and dysmenorrhea in a 48-year-old woman without past gynecological history. There were no typical radiological and endoscopic findings and only pathological examination revealed endometriosis. The patient did well after sigmoid resection and bilateral salpingo-oophorectomy and has had no further complaints. The authors stress the rare location of the disease and review the literature about etiopathogenetic hypotheses and pathological features. The diagnostic value of clinical examination, barium enema and colonoscopy is low as endometriosis rarely involves the mucosa. This case led the authors to discuss about diagnostic difficulties, differential diagnosis and therapeutic options.

Colon, Sigmoid↗
PubMed2000

[Malignant schwannoma of the small intestine: a report of 2 cases].

The authors report two cases of small bowel malignant schwannoma. It is an extremely rare disease and it is often difficult to diagnose malignancy. Histologic differentiation from other stromal tumors may require electron microscopy, although the preparation of immunohistochemical reactions now allows to identify forms which were previously diagnosed in different terms to be precisely classified. Diagnosis is often late and no preoperative test enables a correct clinical diagnosis to be made. The primary treatment is surgical and the resection is the only real therapy. Radiotherapy and chemotherapy are ineffective. Close postoperative observation is recommended because of the tendency to recurrence and metastasis.

Aged↗
PubMed2000

[Ablation therapy with gentamycin in the treatment of Meniere's disease].

Historically the therapy for untreatable Ménière's disease (Md) has been surgery: conservative (cochleosacculotomy and decompression or sacco-endolymphatic shunt) or radical (labyrinthectomy and vestibular neurectomy). A valid alternative to surgery is the use of ototoxic drugs such as aminoglycoside antibiotics based on the assumption that some of the drugs exert greater ototoxicity vs. the posterior labyrinth. The purpose of the present study was to verify a severe protocol for the intratympanic administration of gentamicin sulfate in the treatment of Md unresponsive to medical treatment. A total of 29 patients were recruited for the study, all suffering from monolateral Md with reduced or normal (i.e. not absent) vestibular reflectivity on the side involved. The protocol called for audiovestibular testing prior to the treatment cycle and then 7 days after the administration of each individual dose. The same treatment scheme was used in all patients: a weekly intratympanic injection of gentamicin, 16 mg/per dose, for a maximum of 2 or 3 treatments. Of these cases, 20 have been followed up for 2 or more years and these are described in the present study. The follow-up called for suspending treatment and then repeating the audiovestibular tests every six months. Equilibrium was fully controlled in 70% of the patients while control was substantial in 30%. Audiometry showed that the auditory threshold remained unchanged in 60% of the cases while it worsened in 20% and, surprisingly, improved in the remaining 20%. In two cases deafness arose after the second treatment. The vestibular tests showed an uncompensated areflexia on the treated side after the therapeutic cycle although, in all cases, this had been compensated by the time of observation at 24 months. Symptoms of deafness remained unchanged. In conclusion, with respect to other more invasive treatments, chemical labyrinthectomy is simpler to perform and has fewer side effects while producing analogous clinical results.

Adult↗
PubMed2000

[Cerebral oxygenation and near-infrared rays spectrophotometry].

Near infrared spectroscopy (NIRS) is a new technique which allows non invasive bedside monitoring of cerebral oxygenation and hemodynamics by measuring relative changes in cerebral oxy- and deoxyhaemoglobin and cytochrome aa3. We have applied this technique to evaluate the possible effects on cerebral oxygenation and hemodynamics of clinical procedures usually performed on preterm infants:--endotracheal suctioning, and we have demonstrated that the magnitude and the duration of the negative effects of open system are significantly reduced using closed endotracheal suctioning system;--withdrawal and infusion through umbilical vein and artery cause significant changes in cerebral hemodynamics: these effects are significantly reduced after administration of ibuprofen;--treatment of patent ductus arteriosus with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability compared to indomethacin and ibuprofen administration also does not affect cerebral vasoreactivity to arterial carbon dioxide tension;--administration of different types and doses of natural surfactant causes different changes in cerebral hemodynamics and these effects seem to be dose-related. Therefore NIRS is an useful device to investigate cerebral oxygenation state of preterm infants and new possibilities could derive from the introduction of a new NIRS method which allows to measure the tissue oxygenation index.

Blood Transfusion↗
PubMed1999

Regulation of Bcl-2 protein expression during oxidative stress in neuronal and in endothelial cells.

The relationship between oxidative stress and Bcl-2 expression was investigated in two different experimental models of oxidative stress. Acute oxidative stress was assessed by measuring, with fluorescence microscopy and cytofluorimetry, the increase in fluorescence of the oxidation-sensitive probe dihydrorhodamine 123, both in retinal rod receptor cells exposed to bright light (0.32 mW/cm(2) for 15 minutes) and in human endothelial cells treated with the immunosuppressant cyclosporin A (200 microM for 21 h). In both cell types, acute oxidative stress reduced Bcl-2 expression and also caused a significant increase in the level of nucleosomes. Interestingly, chronic treatment with clinical concentrations of cyclosporin A (0.5-2.5 microM for 8 days) led to a significant increase in Bcl-2 expression, while nucleosomes were similar to control level. This suggests that up-regulation of Bcl-2 protein by low levels of oxidants may represent a critical factor in cellular adaptation to drug toxicity.

Endothelium, Vascular↗
PubMed1999

The biguanide compound metformin prevents desensitization of human pancreatic islets induced by high glucose.

Pancreatic islet desensitization by high glucose concentrations is a temporary and reversible state of beta-cell refractoriness to glucose (and possibly other secretagogues), due to repeated or prolonged pre-exposure to increased glucose concentrations. We evaluated whether the oral antidiabetic agent metformin affects this phenomenon in isolated, human pancreatic islets, and whether the possible effects of the biguanide are influenced by the presence of a sulphonylurea, glyburide. Islets prepared from five human pancreases were incubated for 24 h in M199 culture medium containing either 5.5 or 22.2 mmol/l glucose, with or without a therapeutic concentration (2.4 microg/ml) of metformin. Then, the islets were challenged with either 3.3 mmol/l glucose, 16.7 mmol/l glucose, or 3.3 mmol/l glucose + 10 mmol/l arginine, and insulin release was measured. After incubation in the absence of metformin, the human islets exposed to 22.2 mmol/l glucose showed no significant increase in insulin release when challenged with 16.7 mmol/l glucose (confirming that hyperglycemia desensitizes pancreatic beta-cells). In the presence of metformin, the islets fully maintained the ability to significantly increase their insulin release in response to glucose, even when previously exposed to 22.2 mmol/l glucose. No major effect on arginine-induced insulin release was observed, whatever the culture conditions. The protective action of metformin was observed also when glyburide was present in the incubation medium, whereas the sulphonylurea alone did not affect insulin release from the islets previously exposed to high glucose concentrations. These in vitro results suggest that metformin can prevent the desensitization of human pancreatic islets induced by prolonged exposure to increased glucose concentrations.

Adolescent↗
PubMed1999

Laparoscopy and laparoscopic ultrasonography for staging pancreatic cancer: critical appraisal.

A pilot study was designed to elucidate the role of staging laparoscopy for determining resectability in patients with pancreatic cancer. The additional value of laparoscopic contact ultrasonography (LCU) was also evaluated with specific regard to its ability to detect hepatic metastases and assess vascular infiltration of the portomesenteric trunk. A consecutive sample of 50 patients referred for operation of a suspected pancreatic cancer were submitted to preoperative contrast-enhanced high-resolution computed tomography (CT) and staging laparoscopy combined with LCU at a university hospital. For those progressing to exploratory laparotomy, the intraoperative findings relating to tumor diffusion and vascular infiltration were compared to CT, laparoscopic, and LCU data. Analytical description of the laparoscopic findings is given. Row data of predicted versus observed vascular infiltration were tabulated for CT and LCU. The sensitivity, specificity, and overall accuracy of each diagnostic test were calculated for comparative analysis. Laparoscopy alone prevented unnecessary laparotomy in 20% of cases. A complete procedure could not be achieved in 28% of patients. Three false-negative staging results occurred. LCU identified small (benign) hepatic nodules not seen by CT in 8% of patients. Sensitivity, specificity, and overall accuracy for assessing vascular infiltration were 82%, 53%, and 69% for CT and 94%, 80%, and 87% for LCU. Laparoscopy was confirmed to be safe and effective for staging pancreatic cancer. Because of its unique capabilities to detect even small peritoneal tumor deposits a quick exploration immediately before laparotomy is advised in all patients. The additional benefit of a more extensive procedure is not supported by our results. Although LCU appears to define the vascular involvement more accurately than conventional CT, the limitation of getting clinically useful ultrasound data in all the patients suggests its adoption in only a selected population.

Adult↗
PubMed1999

Safety of adrenal vein ligation during endoscopic adrenalectomy: a technical note.

Endoscopic adrenalectomy has been recommended for the treatment of several benign adrenal diseases. The safety of this procedure largely depends on a careful surgical dissection and appropriate hemostatic technique. An established slipknotting technique was employed to control the main adrenal vein in a consecutive series of 14 patients undergoing endoscopic adrenalectomy. The operative steps to ligate the adrenal pedicle are described. A Medline search also was conducted to identify all reported bleeding episodes associated with this procedure. All attempted ligatures of the main adrenal vein were completed successfully by the described technique, and none of our patients required perioperative blood transfusion. Twenty-eight episodes of bleeding collected from the literature were analyzed. Hemorrhagic accidents related to dislodgement of clips were documented at least in three patients. The cause of bleeding was unspecified in 10 patients. Extracorporeal ligation of the main adrenal vein is feasible, safe, and advisable to prevent the occurrence of hemorrhage during endoscopic adrenalectomy.

Adrenal Glands↗
PubMed1999

The contribution of Na+/H+ exchange to postreperfusion injury and recovery of transplanted kidney.

Acute kidney injury soon after reperfusion seems to anticipate short- and long-term graft prognosis. Sodium-hydrogen exchanger (NHE) is involved in several steps of kidney graft function recovery, such as the restoration of intracellular pH, acute postreperfusion inflammation, and tubular epithelium repair and proliferation. We studied 20 first kidney transplantations by measuring the erythrocyte NHE of both recipient and donor as well as recipient serum and urine indices of renal structural and functional integrity every day since grafting. Heightened exchange activity in the donor-recipient couple resulted, which was associated to a prompt graft recovery together with a short stay for the donor in the intensive care unit, brief cold ischemia time, and a nonatherogenic lipoprotein profile for the recipient. Additional positive prognostic indices were time-zero diuresis and urinary excretion rates of N-acetyl-beta-D-glucosaminidase (NAG) and albumin. Over the one-year follow-up period, a long post-transplantation hospital stay was associated with a significantly increased risk of rejection, and the urinary alanine-aminopeptide (AAP) excretion rate was confirmed as a useful criterion for evaluating the clinical course of kidney graft.

Acetylglucosaminidase↗
PubMed1999

Microsatellite instability and mismatch repair gene inactivation in sporadic pancreatic and colon tumours.

Genomic instability has been proposed as a new mechanism of carcinogenesis involved in hereditary non-polyposis colorectal cancer (HNPCC) and in a large number of sporadic cancers like pancreatic and colon tumours. Mutations in human mismatch repair genes have been found in HNPCC patients, but their involvement in sporadic cancer has not been clarified yet. In this study we screened 21 pancreatic and 23 colorectal sporadic cancers for microsatellite instability by ten and six different microsatellite markers respectively. Microsatellite alterations were observed at one or more loci in 66.6% (14/21) of pancreatic cancers and in 26% (6/23) colon tumours, but all the pancreatic and half of the colon samples showed a low rate of microsatellite instability. All the unstable samples were further analysed for mutations in the hMLH1 and hMSH2 genes and for hypermethylation of the hMLH1 promoter region. Alterations in the hMLH1 gene were found only in colorectal tumours with a large presence of microsatellite instability. None of the pancreatic tumours showed any alteration in the two genes analysed. Our results demonstrate that microsatellite instability is unlikely to play a role in the tumorigenesis of sporadic pancreatic cancers and confirm the presence of mismatch repair gene alterations only in sporadic colon tumours with a highly unstable phenotype.

Adaptor Proteins, Signal Transducing↗
PubMed1999

p53 overexpression in lymph node metastases predicts clinical outcome in ductal pancreatic cancer.

In this study, we evaluated the prognostic significance of both p53 overexpression and proliferating activity in 133 primary ductal pancreatic carcinomas and in their regional synchronous lymph node metastases by immunohistochemistry, by using DO7 and MIB1 monoclonal antibodies, respectively. Tumor samples and lymph nodes were obtained from formalin-fixed, paraffin-embedded archival material of patients operated on between 1976 and 1996. Patients had a well-documented clinical history and were given accurate follow-up. p53 accumulation was observed in 77 (54%) of 133 primary tumors and in 22 (44%) of 50 patients with nodal metastases. The p53 overexpression was directly related to proliferating activity (p = 0.01) in the primary tumors. A significant direct correlation was present between the p53 expression in the primary tumor and in nodal metastases (p = 0.01); the same occurred for proliferating activity by MIB1 (p = 0.002). The patients' overall survival was affected by the presence of nodal (p = 0.02) and distant (p = 0.0001) metastases. The p53 immunoreactivity in nodal metastases was associated with a statistically significant decrease in the postoperative survival period (p = 0.005). Multivariate analysis confirmed these results, and the only two parameters that maintained statistical significance were M1 status (p = 0.0006) and p53 overexpression in nodal metastases (p = 0.01).

Adenocarcinoma↗
PubMed1999

Standard Kausch-Whipple pancreatoduodenectomy.

Despite the increasing number of clinical trials in pancreatic cancer there are no widely accepted definitions of different types of resection for pancreatic cancer. An agreed definition of the standard Kausch-Whipple pancreatoduodenectomy was derived by a group of international experts at a meeting in Castelfranco Veneto, Italy, in May 1998. The lymph node groups to be removed en bloc with the pancreatoduodenectomy and described using the Japanese Pancreas Society classification were as follows: 13a and 13b; 17a and 17b; 12b1, 12b2 and 12c; and 14a and 14b. Limited segmental major venous resection and adjacent organ resection, if required, may be included as part of a standard pancreatoduodenectomy. The pylorus-preserving procedure also may be included as part of standard resection, but not for tumours of the anterior-superior part of the head of the pancreas. Wider adoption of the definition of standard Kausch-Whipple resection will enable a more objective comparative analysis of the radicality of resection between institutions and permit a more coherant analysis on the type of surgery undertaken in multicentre adjuvant studies.

Combined Modality Therapy↗