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F Mosca

Publications and source records attributed to F Mosca.

At least 73 records · Page 4Linked to original sources
PubMed2000

Thoracoscopic splanchnicectomy for pain relief in unresectable pancreatic cancer.

HYPOTHESIS: Unilateral truncal thoracoscopic splanchnicectomy (TS) provides safe and effective treatment for pain relief in patients with unresectable pancreatic cancer. DESIGN: Before-and-after trial of 24 patients undergoing 25 TS procedures. SETTING: Surgical unit at a university teaching hospital. PATIENTS: A consecutive sample of 24 patients with severe pain due to unresectable (primary or recurrent) pancreatic cancer refractory to drug therapy and with a life expectancy of less than 6 months. INTERVENTION: The key point of the reported operation is intrathoracic carbon dioxide insufflation, which allows a more distal division of the greater splanchnic nerve and a 2-port technique. MAIN OUTCOME MEASURES: Pain and the effect of this symptom on quality of life were assessed before and after TS using a 10-point visual analog pain scale (VAS) and the Nottingham Health Profile questionnaire, respectively. RESULTS: Four TS procedures were technical failures because of pleural adhesions. One patient required a contralateral procedure 12 weeks after TS. Mean (+/- SD) preoperative VAS basal score was 7.4 +/- 1.7. Twenty-four hours after TS, it was reduced to 0.6 +/- 1.0. Significant reduction of VAS scores persisted over the first 3 months after TS (P<.001). Recurrence of pain of low intensity (mean VAS basal score, 4.2) was observed in 8 patients. Significant improvement (P<.001) in each area covered by the Nottingham Health Profile questionnaire was reported at 1 month after TS. CONCLUSION: Thoracoscopic splanchnicectomy offered substantial short-term relief of pain in patients with unresectable pancreatic cancer, and significantly ameliorated the quality of their residual life.

Aged↗
PubMed2000

Lymphokine release from human lymphomononuclear cells after co-culture with isolated pancreatic islets: effects of islet species, long-term culture, and monocyte-macrophage cell removal.

This study evaluated the release of Th1 and Th2 cytokines from human lymphomononuclear cells (LMC) in response to purified human (HI) or bovine (BI) islets, and the role of long-term (3-4 weeks) islet culture and removal of monocyte-macrophage cells. The results showed that HI and BI caused a similar increase of the release of gamma interferon (IFN), IL-2 and IL-6 from LMC, whereas BI had a more marked effect than HI on IL-10 release. Culturing the islets had possible positive effects (reduction of IFN and IL-2), but also potentially negative effects (increase of TNF). Removal of monocyte-macrophage cells determined a significant reduction of IL-6, IL-10 and TNF production in response to xeno-islets.

Animals↗
PubMed2000

Differential inhibition of hepatic and duodenal sulfation of (-)-salbutamol and minoxidil by mefenamic acid.

OBJECTIVE: The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. METHODS: Sulfotransferase activities were measured for 10 mM (-)-salbutamol and 5 mM minoxidil, and the concentration of 3'-phosphoadenosine-5'-phosphosulphate-[35S] was 0.4 microM. RESULTS: The IC50 estimates for (-)-salbutamol and minoxidil sulfation of mefenamic acid were 72 +/- 5.4 nM and 1.5 +/- 0.6 microM (liver), respectively, and 161 + 23 microM and 420 +/- 18 microM (duodenum), respectively. The figures for the liver were significantly lower (P < 0.0001) than those for the duodenum. The IC50 estimates for (-)-salbutamol sulfation of salicylic acid were 93 +/- 11 microM (liver) and 705 +/- 19 microM (duodenum, P < 0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. CONCLUSION: The IC50 estimates for (-)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (-)-salbutamol in vivo.

Adrenergic beta-Agonists↗
PubMed2000

Mycophenolic acid glucuronidation and its inhibition by non-steroidal anti-inflammatory drugs in human liver and kidney.

OBJECTIVE: The aims of this investigation were to study the glucuronidation of mycophenolic acid (MPA) in human liver and kidney and to search for a compound that inhibits MPA glucuronidation among the non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A sensitive and reproducible radiometric assay was developed to measure the rate of MPA glucuronidation in human liver and kidney microsomes. The assay employed uridine 5'-diphosphate-[U-14C]-glucuronic acid (UDPGA) and MPA-glucuronide was isolated by TLC. The final concentrations of UDPGA and MPA necessary were 1 mM (liver), and MPA concentration was 0.5 mM (kidney). The inhibition of MPA glucuronidation was studied with 18 NSAIDs and tacrolimus. RESULTS: Glucuronosyl transferase activity followed Michaelis-Menten kinetics and the Km (mean +/- SD; mM) was 0.31+/-0.06 (liver; n = 5) and 0.28+/-0.07 (kidney; n = 5; P = 0.555); the Vmax (mean SD; nmol/mg per minute) was 5.2+/-1.4 (liver; n = 5) and 10.5+/-1.2 (kidney; n = 5; P = 0.0005). The MPA glucuronidation rates (mean +/- SD; nmol/min/mg) were 3.3+/-0.9 (liver; n = 10) and 7.8+/-1.5 (kidney; n = 10; P = 0.0002). The rate of MPA glucuronidation ranged between 2.0 and 5.1 nmol/ mg per minute with a 2.5-fold variation (liver) and between 5.7 and 9.8 nmol/mg per minute with a 1.7-fold variation (kidney). The inhibition study was performed in liver and revealed that the percentage of control ranged from 8%+/-3% (niflumic acid) to 119%+/-16% (Ketoralac). The inhibition curves for MPA glucuronidation rate were determined with the four most effective inhibitors: niflumic acid, flufenamic acid, mefenamic acid and diflunisal. Their IC50 estimates (microM) were 8+/-1, 19+/-9, 63+/-8 and 109+/-15, respectively (liver), and 8+/-2, 13+/-2, 49+/-4 and 122+/-18, respectively (kidney). The IC50 estimate for niflumic acid was eightfold lower than the peak plasma levels after a single oral dose of 250 mg of this drug. CONCLUSION: The human liver and kidney are important sites of MPA glucuronidation. MPA glucuronidation was inhibited to various extents by different NSAIDs and the four most effective inhibitors were niflumic acid, flufenamic acid, mefenamic acid and diflunisal. These drugs have similar molecular structures consisting of two aromatic rings bearing a carboxylic group.

Aged↗
PubMed2000

Inhibition of human liver phenol sulfotransferase by nonsteroidal anti-inflammatory drugs.

OBJECTIVE: The aim of this investigation was to study the inhibition of 11 nonsteroidal anti-inflammatory drugs (NSAIDs) on the human liver phenol sulfotransferases (HL-PST) and catechol sulfotransferase (HL-CST). METHODS: The activities of HL-PST and HL-CST were measured with 4 microM 4-nitrophenol and 60 microM dopamine (the sulfate acceptors) and 0.4 microM 3'-phosphoadenosine-5'-phosphosulfate [35S] (the sulfate donor). Samples of liver were obtained from five patients, aged 55-79 years, undergoing clinically indicated hepatectomy. The inhibition curves were constructed with at least five concentrations of the inhibitor. RESULTS: With the exception of piroxicam, NSAIDs inhibited HL-PST, and the estimates of the inhibitory concentration for 50% of responses (IC50; microM) were: 0.02 (mefenamic acid), 3.7 (diflunisal), 5.4 (nimesulide), 9.5 (diclofenac), 30 (salicylic acid), 41 (ketoprofen), 74 (indomethacin), 159 (ibuprofen), 245 (ketoralac) and 473 (naproxen). With 4-nitrophenol as the variable substrate, the inhibition of salicylic acid on HL-PST was non-competitive and the Ki and Kies were 18 microM and 21 microM (n = 5; P = 0.548), respectively. HL-CST was less susceptible than HL-PST to inhibition by NSAIDs, with only five drugs inhibiting this enzyme. The IC50 estimates for these drugs (microM) were 76 (mefenamic acid), 79 (diflunisal), 103 (indomethacin), 609 (salicylic acid) and 753 (diclofenac). CONCLUSION: The comparison of the IC50 estimates of HL-PST with the therapeutic plasma concentrations of NSAIDs corrected for the plasma unbound fraction was consistent with the view that mefenamic acid and salicylic acid, when administered at therapeutic doses, should impair the hepatic sulfation of those compounds that are substrates of phenol sulfotransferase.

Aged↗
PubMed2000

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Journal Article↗
PubMed2000

Genetics of drug response to immunosuppressive treatment and prospects for personalized therapy.

The use of immunosuppressive agents in the treatment of transplant rejection and autoimmune disorders is gaining momentum, with significant improvements of both graft and patient survival. The individual response to drugs, however, is variable and unexpected toxicity, or impaired activity might be seen, as a result of molecular determinants that eventually dictate how the individual will respond to immunosuppressive agents. This review addresses a number of issues related to pharmacogenetics, and discusses how this approach might be used to improve the clinical efficacy and tolerability of therapeutic options for the management of organ transplantation and autoimmune disorders in the next decade.

Autoimmune Diseases↗
PubMed2000

Palliative treatment of malignant esophageal stenosis: the role of self-expanding stent endoscopic implantation.

Endoscopic tube implantations were carried out in 40 patients with malignant stenosis of the esophagus and gastric cardia using self-expanding metallic stents. The indications for endoscopic intubation were the advanced stage of the tumor in 27 cases and risk factors that made resection inadvisable in 13 cases. In three patients, it proved impossible to implant a stent endoscopically because we were not able to pass the guide wire through the stenosis, whereas correct stent placement was achieved in 37 cases. Functional results were good in 33 patients, but four patients did not show any improvement of symptoms. Complications occurred in nine patients (24.3%): two bleedings, three neoplastic obstructions, one food obstruction, and three distal dislodgements of the prosthesis were observed, but could be readily corrected. No deaths occurred. The median survival time was 151 days (range 25-545 days). This study suggests that endoscopic placement of metallic self-expanding stents is safe and is to be preferred to plastic stents for easier implantation and lower morbidity.

Aged↗
PubMed2000

Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver.

1. Resveratrol, a polyphenolic compound present in grape and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It has been shown that the compound is sulphated in human liver and the aims of the present investigation were to study resveratrol glucuronidation in human liver microsomes and to determine whether flavonoids inhibit resveratrol glucuronidation. 2. A simple and reproducible radiometric assay for resveratrol glucuronidation was developed. The assay employed uridine-5'-diphosphoglucuronic acid-[14C] and unlabelled resveratrol. Resveratrol-glucuronide was isolated by TLC. The intra- and interassays variabilities were 1 and 1.5%, respectively. 3. The rate of resveratrol glucuronidation was measured in 10 liver samples. The mean +/- SD and median of resveratrol glucuronidation rate were 0.69 +/- 0.34 and 0.80 nmol/min/mg, respectively. Resveratrol glucuronosyl transferase followed Michaelis-Menten kinetics and the Km and Vmax (mean +/- SD; n = 5) were 0.15 +/- 0.09 mM and 1.3 +/- 0.3 nmol/min/mg, respectively. The intrinsic clearance was 11 +/- 4 x 10(-3) ml/min.mg. 4. The flavonoid quercetin inhibited resveratrol glucuronidation and its IC50 (mean +/- SD; n = 3) was 10 +/- 1 microM. Myricetin, catechin, kaempferol, fisetin and apigenin (all at 20 microM) inhibited resveratrol glucuronidation and the percent of control ranged between 46% (catechin) to 72% (apigenin). 5. The present results show that resveratrol is glucuronated in the human liver. Glucuronidation may reduce the bioavailability of this compound however, flavonoids inhibit resveratrol glucuronidation and such an inhibition might improve the bioavailability of resveratrol.

Adult↗
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↗