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Biomedical subjects

G Palasciano

Publications and source records attributed to G Palasciano.

At least 19 recordsLinked to original sources
PubMed2006

Indomethacin enhances bile salt detergent activity: relevance for NSAIDs-induced gastrointestinal mucosal injury.

Gastroduodenal toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) is partly independent from cyclooxygenase inhibition, possibly related to increased intermixed micellar-vesicular (nonphospholipid-associated) bile salt concentrations thought to be responsible for bile salt cytotoxicity. We evaluated the effects of indomethacin on bile salt cytotoxicity with complementary in vitro and ex vivo systems. In the erythrocyte model, indomethacin alone did not induce hemolysis. In contrast, indomethacin enhanced and phospholipids decreased hemolysis induced by hydrophobic taurodeoxycholate (TDC). Hydrophilic tauroursodeoxycholate (TUDC) enhanced rather than decreased TDC-induced hemolysis in the presence of indomethacin. Indomethacin did not affect intermixed micellar-vesicular bile salt concentrations or compositions. Indomethacin also increased TDC-induced lactate dehydrogenase release in CaCo-2 cells and bile salt-induced rat colonic mucosal injury, and prevented potential protective effects of TUDC in these systems. Our data show that indomethacin enhances bile salt-induced cytotoxicity without affecting intermixed micellar-vesicular bile salt concentrations or compositions. These findings may be relevant for gastroduodenal injury during NSAID therapy.

Animals↗
PubMed2006

Gallstone disease: Symptoms and diagnosis of gallbladder stones.

The clinical aspects and the diagnostic features of gallstone disease are described. The natural history of silent gallstones is overviewed, and the risk of developing symptoms and complications is also discussed. The importance of colicky pain as a specific gallstone symptom is highlighted, and the role of both laboratory tests and diagnostic investigations for differential diagnosis is discussed. Finally, we describe the diagnostic features of gallbladder stone disease, including indications, sensitivity, specificity, and limitations of different test investigations under special circumstances.

Abdomen↗
PubMed2005

Indomethacin-induced ileitis is associated with tensiometric, vascular and oxidative changes in the experimental rat model.

BACKGROUND: Indomethacin-induced enteritis is a model of inflammatory bowel disease. MATERIALS AND METHODS: To further characterize this model, rats received two injections of indomethacin (7.5 mg kg(-1)) 24 h apart and histological damage of intestinal mucosa, oxidative stress, alterations of intestinal motility and mesenteric vascular bed (MVB) reactivity were investigated after 5 days. RESULTS: The results show that indomethacin caused several histological and functional changes at the ileal level. In particular, response to carbachol as well as the nonadrenergic-noncholinergic inhibitory response to electrical field stimulation (EFS) was lower in the treated than control rats. Moreover, nitric oxide (NO)-component of the inhibitory response was higher in the treated than control rats. Mesenteric vessels preparations from the treated rats showed increased noradrenaline (NA)-induced perfusion pressure, whereas relaxant responses to acetylcholine, although not significantly reduced in the treated rats, had a higher nitrergic component. This finding suggests that vascular dysfunction may contribute to chronic inflammation. Indomethacin injection also determined acute and severe oxidative stress in ileum mucosa. CONCLUSIONS: In conclusion, our study contributes to further characterize the rat model of indomethacin-induced enteritis and suggests that it is suitable for drug screening in rats, as this model can be obtained in a very short period and is simple and reproducible.

Acetylcholine↗
PubMed2005

Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease.

BACKGROUND: Since 1990 our group has been using extracorporeal circulation to ozonate blood by an original method, known as extracorporeal blood oxygenation and ozonation (EBOO), with the aim of amplifying the results observed with ozone autohemotherapy. OBJECTIVE: To verify the hypothesis that EBOO improves the skin lesions typical of peripheral artery disease (PAD) patients. METHODS: Twenty-eight patients with PAD were randomized to receive EBOO or intravenous prostacyclin in a controlled clinical trial. The primary efficacy parameters were regression of skin lesions and pain,and improvement in quality of life and vascularisation. RESULTS: Patients treated with EBOO showed highly significant regression of skin lesions with respect to patients treated with prostacyclin. Other parameters that were significantly different in the two groups of patients were pain,pruritus, heavy legs and well-being. No significant differences in vascularisation of the lower limbs before and after treatment were found in either group. No side effects or complications were recorded during the 210 EBOO treatments. CONCLUSION: EBOO was much more effective than prostacyclin for treating skin lesions in PAD patients and also had a positive effect on patient general condition without any apparent change in arterial circulation. This suggests other mechanisms of action of EBOO.

Aged↗
PubMed2003

Pathways of cholesterol crystallization in model bile and native bile.

Hypersecretion of hepatic cholesterol, chronic supersaturation of bile with cholesterol and rapid precipitation of cholesterol crystals in the gallbladder from cholesterol-enriched vesicles represent the primum movens in cholesterol gallstone formation. Physical-chemical factors and pathways leading to cholesterol crystallization can be investigated in artificial model biles and ex vivo in fresh human bile. Depending on modulatory factors (i.e., lipid concentration, bile salt or phospholipid species, humidity, mucins, etc.), cholesterol can precipitate in several forms (i.e., monohydrate, anhydrous) and habits (i.e., plate-like, needle-like, intermediate arcs, filaments, tubules, spirals). Careful analysis of biliary cholesterol crystals includes biochemical analysis of precipitated crystals, polarizing quantitative light microscopy, and turbidimetric methods. In this paper, recent concepts on cholesterol crystallization in artificial model biles as well as in human bile will be reviewed.

Bile↗
PubMed2003

Measurements of gallbladder motor function by ultrasonography: towards standardization.

As real-time ultrasonography is a cheap, noninvasive, relatively easy, validated and reproducible technique, it can be repeated over time to document time-related changes of gallbladder motor function. Ultimately, functional ultrasonography estimates gallbladder shape and volume in fasting state and in response to a test meal (liquid or mixed solid-liquid, provided there is sufficient fat content) or exogenous stimulus (e.g., i.v. cholecystokinin or ceruletide). Although functional ultrasonography of the gallbladder has been mainly used for research purposes in specific referral centres, its simplicity makes such a technique appealing in the clinical setting to assess gallbladder motor function in both health and disease. Indications include the study of healthy subjects and of patients during pathophysiologically relevant conditions; in particular when subjects are at risk for gallbladder stasis and gallstone disease or during gallstone disease when a decision concerning medical dissolution therapy is required.

Cholecystolithiasis↗
PubMed2003

Sphingomyelin protects against apoptosis and hyperproliferation induced by deoxycholate: potential implications for colon cancer.

High fecal deoxycholate levels may promote colonic cancer. Phospholipids protect against bile salt-induced cytotoxicity. We therefore aimed to examine whether the dietary phospholipid sphingomyelin could decrease hyperproliferation induced by deoxycholate. In CaCo2 cells, hyperproliferation (by bromodeoxyuridine assay), phosphorylation state of cellular proteins, and apoptosis with concomitant caspase-3 activity were evaluated after incubation with 50-500 microM deoxycholate, with or without sphingomyelin. At 2 and 4 hr of incubation, deoxycholate induced dose-dependent apoptosis, with concomitant caspase-3 activation. At 16 hr, apoptosis had decreased markedly, but there was dose-dependent hyperproliferation (with changed phosphorylation status of cellular proteins) at this time point. Sphingomyelin dose-dependently reduced deoxycholate-induced apoptosis and hyperproliferation. In conclusion, sphingomyelin reduces deoxycholate-induced hyperproliferation and apoptosis. These findings may have implications for colonic cancer prevention by dietary modification.

Apoptosis↗
PubMed2003

Adaptation of subcellular glutathione detoxification system to stress conditions in choline-deficient diet induced rat fatty liver.

The response of fatty liver to stress conditions (t-butyl hydroperoxide [t-BH] or 36 h of fasting) was investigated by assessing intracellular glutathione (GSH) compartmentation and redox status, GSH peroxidase (GSH-Px) and reductase (GSSG-Rx) activities, lipid peroxidation (TBARs) and serum ALT levels in rats on a choline-deficient diet. Baseline cytosolic GSH was similar between fatty and normal livers, while the mitochondrial GSH content was significantly lower in fatty livers. With the except of cytosolic GSH-Px activity, steatosis was associated with significantly higher GSH-related enzymes activities. Liver TBARs and serum ALT levels were also higher. Administration of t-BH significantly decreased the concentration of cytosolic GSH, increased GSSG levels in all the compartments, and increased TBARs levels in cytosol and mitochondria and serum ALT; all these alterations were more marked in rats with fatty liver. Fasting decreased the concentration of GSH in all the compartments both in normal and fatty livers, increased GSSG, TBARs and ALT levels, and decreased by 50% the activities of GSH-related enzymes. Administration of diethylmaleimide (DEM) resulted in cytosolic and microsomal GSH pool depletion. Administration of t-BH to DEM-treated rats further affected cytosolic GSH and enhanced ALT levels, whereas the application of fasting to GSH depleted rats mainly altered the mitochondrial GSH system, especially in fatty livers. This study shows that fatty livers have a weak compensation of hepatic GSH regulation, which fails under stress conditions, thus increasing the fatty liver's susceptibility to oxidative damage. Differences emerge among subcellular compartments which point to differential adaptation of these organelles to fatty degeneration.

Alanine Transaminase↗
PubMed2003

Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: an in vitro study.

BACKGROUND: In rodents, interleukins administration induces intestinal changes similar to those found in inflammatory bowel disease. We investigated the effects of in vivo subchronic treatment with IL-1 beta and IL-6 on rat colonic mucosa and circular smooth muscle. MATERIALS AND METHOD: We evaluated transmucosal electrical parameters (Ussing chambers) and early changes of in vitro direct contractility induced by carbachol and tachykinins. Alterations in excitatory and inhibitory neurotransmission were studied with electrical field stimulation (EFS). RESULTS: Treatment with interleukins induces inflammation proved by fever, early signs of colonic histological damage and changes in mucosal ion transport. Concentration response-curve to carbachol was significantly lower in treated rats (P<0.02) with significant difference in Emax between control (1.67+/-0.17 g) and treated preparations (1.20+/-0.13 g) (P<0.05). Concentration response-curve to NK2 agonist was significantly lower in the treated rats (P<0.005) with a significant difference in Emax between the control (0.26+/-0.04 g) and treated preparations (0.12+/-0.02 g) (P<0.02). None of the drugs used induces changes in EC50. The contractile reflex response to electrically induced distension was significantly higher in the treated rats and more reduced after administration of atropine. Adding NK2 receptor antagonist resulted in a further reduction being observed in the treated and control rats (P=NS). Relaxation by EFS on cholinergic tone was not different between treatments, although pretreatment with L-NNA resulted in greater relaxation in the treated (-21.7%) than in the control rats (-14.8%). CONCLUSION: Early inflammation induced by a subchronic treatment with ILs causes changes in mucosal ionic transport parameters, a reduction in the direct contractile response, and an alteration in the neurotransmission (by an enhancing cholinergic component) that may affect the physiological pattern of colonic motility and the sensory reflex.

Animals↗
PubMed2003

Structural and oxidative modifications of erythrocyte ghosts in patients with primary biliary cirrhosis: relation with the disease stage and effect of bile acid treatment.

BACKGROUND: Erythrocyte membrane modifications in patients with cholestasis are supposed to reflect those of hepatocytes. METHODS: Erythrocyte membrane composition (cholesterol, phospholipids, fatty acids, protein sulphydrils and carbonyls) was assessed and related to the stage of liver disease in patients with primary biliary cirrhosis before and after 1 year of ursodeoxycholate treatment. RESULTS: Compared with controls, patients showed lower levels of protein sulphydrils (28.9 +/- 7.1 vs. 65.6 +/- 1.8 nmol mg(-1) prot) and accumulation of carbonyls (4.7 +/- 1.7 vs. 1.4 +/- 0.1 nmol mg(-1) prot). Phosphatidylethanolamine level was lower in stage III-IV cirrhosis while phosphatidylcholine and cholesterol levels were higher; as a consequence the phosphatidylcholine/sphingomyelin ratio was higher than in controls (4.25 +/- 0.55 in the I-II stage and 2.89 +/- 0.44 in the stage III-IV vs. 1.61 +/- 0.30). These changes were particularly evident in patients with more advanced stages of liver disease. Protein sulphydrils and carbonyls, phosphatidylethanolamine and cholesterol levels correlated (P<0.05) with the histological stage of the liver disease, serum and membrane cholesterol levels were significantly related (r=0.66, P<0.05). One year of ursodeoxycholate administration was accompanied by major changes of the membrane lipid composition, partial reversal of protein oxidation, and improvement of serum parameters. CONCLUSIONS: This study indicates that major alterations in protein status and lipid composition occur in erythrocyte membrane of patients with primary biliary cirrhosis. These changes were more pronounced in patients with advanced liver disease. Ursodeoxycholate was able to revert in part serum and erythrocyte alterations, especially in patients with early stages of liver disease.

Adult↗
PubMed2002

Hereditary hemorrhagic teleangiectasia (Rendu-Osler-Weber disease).

Rendu-Osler-Weber disease, or hereditary hemorrhagic telangiectasia (HHT), is an autosomal dominant disorder with incomplete penetrance, characterized by vascular anomalies which may virtually develop in many organs. The prevalence varies and may range from 1/3,500 to 1/5,000 in specific regions. Two chromosal sites have been at least identified: in HHT1, mutations at chromosome 9 alter the protein endoglin and in HHT2, mutations at chromosome 12 alter the protein activine or ALK-1. Clinical manifestations include recurrent epistaxis, mucocutaneous telangiectases that bleed easily, and larger arteriovenous malformations in parenchymatous organs. Epistaxis is the first symptom, occurring in the vast majority of affected persons. The lung is the most common site for arteriovenous malformations. Brain abscess, transient ischemic attack and ischemic stroke occur exclusively in patients with pulmonary arteriovenous malformations and right-to-left shunt, which facilitates the passage of emboli into the cerebral circulation. Transcatheter embolotherapy with detachable balloons or stainless-steel coils has been used in order to occlude such malformations and to prevent such complications. At present a genetic diagnosis is possible in only a few families. The clinical diagnosis is based on 4 criteria: family history, epistaxis, mucocutaneous telangiectases and arteriovenous malformations. The diagnosis will be definite if 3 criteria are present, suspected if 2 criteria are present, unlikely if fewer than 2 criteria are present. In conclusion, the authors examine clinical features of 28 HHT patients observed in the HHT University Centre of Bari from September 2000 to May 2001.

Angiography↗
PubMed2001

Mitochondrial oxidative damage and myocardial fibrosis in rats chronically intoxicated with moderate doses of ethanol.

Mitochondrial oxidative balance and myocardial fibrosis were investigated in pair-fed rats received ethanol (3%) or saccharose in drinking water for 8 weeks. The concentrations of glutathione, malondialdehyde, protein carbonyls and sulfhydrils were determined. The presence and distribution of fibronectin were detected by immunohistochemistry. The myocardial concentrations of reduced glutathione and protein sulfhydrils were lower in ethanol treated rats. The oxidised/reduced glutathione ratio, the levels of malondialdehyde and protein carbonyls were higher in ethanol-treated rats. The mitochondrial amount of proteins, glutathione and protein sulfhydrils were lower in ethanol treated rats, whereas the content of protein carbonyls and malondialdehyde were higher. Accumulation of fibronectin was detected at subepicardial and subendocardial districts in ethanol-treated rats, with moderate degree of fibrosis in 20% of the cases. In conclusion, moderate ethanol consumption is associated with oxidative damage to heart mitochondria and fibronectin deposition. These oxidative and ultrastuctural changes may be assumed as basic alterations in the development of alcoholic cardiomyopathy.

Administration, Oral↗
PubMed2001

Changes of gallbladder and gastric dynamics in patients with acute hepatitis A.

Transient alterations of gallbladder morphology and dynamics have been reported in patients with during acute hepatitis A. The presence of dyspepsia also suggests involvement of gastric motility. During a 60-day follow-up, we investigated gallbladder and gastric motility in relation to dyspepsia in acute viral hepatitis A patients. Twenty patients were assessed at referral (day 0) and at days 7, 21, 42 and 60 and compared with 20 healthy volunteers. Gallbladder morphology and motility and gastric motility were assessed in the fasting and postprandial period by functional ultrasonography using a liquid test meal. Dyspeptic symptoms were scored. At day 0, fasting gallbladder volume was 5.9 +/- 1.3 mL, 32.6 +/- 4.6 mL, and 21.5 +/- 1.9 mL (mean +/- SE) in patients with gallbladder sludge (n = 7), without sludge (n = 13) and controls, respectively (P < 0.05 in sludge vs. no sludge and controls; P < 0.05 in no sludge vs. controls, ANOVA). Small fasting gallbladder volume in patients with sludge increased and sludge disappeared within 7 days. At day 0, patients with sludge also had increased thickness of fasting gallbladder wall and increased serum transaminase levels compared with patients without sludge and controls. Gallbladder contraction was similar in patients and controls. However, patients had delayed gastric emptying, which positively correlated with dyspepsia score. Gallbladder morphological changes observed in the acute phase of hepatitis A are transient and are associated with hepatocellular damage. Gastric emptying is delayed during the first week of disease and is associated with dyspeptic symptoms.

Acute Disease↗
PubMed2001

Haemodynamic effects of propranolol, octreotide and their combination during fasting and post-prandial splanchnic hyperaemia in patients with cirrhosis.

BACKGROUND/AIMS: This double-blind study was designed to evaluate the haemodynamic effect of two drugs, propranolol and octreotide, and their combination in patients with cirrhosis. METHODS: Fifteen patients with cirrhosis were randomly assigned to two groups receiving either octreotide subcutaneously at 100 microg ('octreotide' group, n = 9) or propranolol orally at 40 mg followed by a subcutaneous dose of octreotide (100 microg) after 1 h ('propranolol + octreotide' group, n = 6); then, after 30 min, a standard meal was administered to both groups. The hepatic vein pressure gradient by hepatic vein catheterization, portal and superior mesenteric artery blood flow velocity, superior mesenteric artery pulsatility index by the echo-Doppler duplex system were recorded at baseline, 1 h after propranolol in the 'propranolol + octreotide' group, and in both groups 30 min after octreotide and 30 min after meal. RESULTS: At fast, propranolol was more active in decreasing portal pressure (from 16 +/- 2.2 to 12.7 +/- 3.8 mmHg, -20%, P < 0.05) as compared to octreotide (from 18.6 +/- 4.8 to 16.6 +/- 4.3 mmHg, -11%, P < 0.05). Conversely, octreotide was more active on the mean blood flow velocity of superior mesenteric artery (from 22.8 +/- 5 to 19 +/- 4.5 cm/ s, -17%; P< 0.05). Octreotide administration in patients receiving beta-blockers showed, also, a trend to increase the mesenteric vascular resistances (pulsatility index from 3.14 +/- 0.69 to 3.68 +/- 1.29, +17%, not significant (NS)) which had not been affected by previous treatment with propranolol. After the meal, a reduction of the expected hyperaemic response occurred in both groups. CONCLUSIONS: The combined acute haemodynamic effect of this association suggests the possible combination of these two drugs in critical situations, such as variceal bleeding in patients receiving beta-blockers. The simultaneous use of echo-Doppler and hepatic vein catheterization permitted us a more complete analysis of the acute haemodynamic events.

Adrenergic beta-Antagonists↗
PubMed2001

Cholesterol crystallization in model biles: effects of bile salt and phospholipid species composition.

Cholesterol in human bile is solubilized in micelles by (relatively hydrophobic) bile salts and phosphatidylcholine (unsaturated acyl chains at sn-2 position). Hydrophilic tauroursodeoxycholate, dipalmitoyl phosphatidylcholine, and sphingomyelin all decrease cholesterol crystal-containing zones in the equilibrium ternary phase diagram (van Erpecum, K. J., and M. C. Carey. 1997. Biochim. Biophys. Acta. 1345: 269-282) and thus could be valuable in gallstone prevention. We have now compared crystallization in cholesterol-supersaturated model systems (3.6 g/dl, 37 degrees C) composed of various bile salts as well as egg yolk phosphatidylcholine (unsaturated acyl chains at sn-2 position), dipalmitoyl phosphatidylcholine, or sphingomyelin throughout the phase diagram. At low phospholipid contents [left two-phase (micelle plus crystal-containing) zone], tauroursodeoxycholate, dipalmitoyl phosphatidylcholine, and sphingomyelin all enhanced crystallization. At pathophysiologically relevant intermediate phospholipid contents [central three-phase (micelle plus vesicle plus crystal-containing) zone], tauroursodeoxycholate inhibited, but dipalmitoyl phosphatidylcholine and sphingomyelin enhanced, crystallization. Also, during 10 days of incubation, there was a strong decrease in vesicular cholesterol contents and vesicular cholesterol-to-phospholipid ratios (approximately 1 on day 10), coinciding with a strong increase in crystal mass. At high phospholipid contents [right two-phase (micelle plus vesicle-containing) zone], vesicles were always unsaturated and crystallization did not occur. Strategies aiming to increase amounts of hydrophilic bile salts may be preferable to increasing saturated phospholipids in bile, because the latter may enhance crystallization.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Standards for diagnosis of gastrointestinal motility disorders. Section: ultrasonography. A position statement from the Gruppo Italiano di Studio Motilità Apparato Digerente.

Ultrasonography is a non-invasive, relatively easy, validated and reproducible technique. We assessed the usefulness of functional ultrasonography to study disorders of gastro-oesophageal tract, gallbladder and pancreatic duct. Oesophagus Oesophagus and the gastro-oesophageal junction can be visualized in children up to 5 years old. Ultrasonography shows 100% sensitivity and 87.5% specificity compared to ambulatory pH-metry for gastro-oesophageal reflux disease diagnosis. Stomach Ultrasonography can be used to estimate whole gastric volume, antral area or diameters, antro-pyloric volume, transpyloric flow in fasting state and in response to test meal. Gallbladder Ultrasonography is reliable to estimate volume in fasting state and in response to test meal or exogenous stimulus. For both stomach and gallbladder, indications might include the study of healthy subjects and of pathophysiologically relevant conditions such as dysmotility-like dyspepsia, suspicion of delayed gastric emptying, diabetes mellitus, gallstone disease and effect of drugs either delaying or accelerating motility. Common bile duct Ultrasonography can be used to estimate interprandial and postprandial common bile duct diameter in patients with clinical suspicion of common bile duct obstruction in fasting state and in response to test meal or exogenous stimuli. Although functional ultrasonography is used mainly for research purposes, its simplicity makes it appealing for clinical use to assess gastrointestinal motility in health and disease.

Gastrointestinal Diseases↗
PubMed2000

Review article: in vitro studies of gall-bladder smooth muscle function. Relevance in cholesterol gallstone disease.

The interplay between contraction and relaxation in the gall-bladder muscularis leads to appropriate gall-bladder emptying and refilling during fasting and in the postprandial state in vivo. Several studies in both human and animal models have focused on cellular and molecular events in the gall-bladder wall in health and disease in vitro. Principal methods to study gall-bladder smooth muscle function include receptor binding studies (at the level of plasmamembranes or histological sections), phase contrast microscopy (at the level of isolated smooth muscle cells), and tensiometry (at the level of smooth muscle strips or the whole gall-bladder). At a very early stage, cholesterol gallstone disease is characterized by exposure of the gall-bladder wall to excess of biliary cholesterol and the cytotoxic effect of the bile salt deoxycholate. On a long-term basis, a form of gall-bladder leiomyopathy develops with defects involving the mechanisms of signal transduction at the level of plasmamembranes. The end-stage result is pathological contraction and/or relaxation of smooth musculature, impaired gall-bladder motility and gall-bladder stasis, all key factors in the pathogenesis of biliary cholesterol crystallization and gallstones.

Bile Acids and Salts↗