Biomedical subjects

A Morelli

Publications and source records attributed to A Morelli.

At least 127 records · Page 7Linked to original sources

PubMed1996

Isolated guinea pig gastric chief cells express tumour necrosis factor receptors coupled with the sphingomyelin pathway.

The tumour necrosis factor alpha (TNF), has been implicated in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy and Helicobacter pylori induced gastritis. Both conditions are characterised by high plasma pepsinogen concentrations, which are thought to reflect an increased rate of enzyme release by the pepsinogen secreting (chief) cells. The mechanisms responsible for this cell dysfunction are unknown. This study investigates whether chief cells express TNF receptors and, if so, whether their activation results in cell death. Immunohistochemical studies conducted with monoclonal antibodies (mAbs) directed against two TNF receptor associated proteins of 55 kDa (TNF-R1) and 75 kDa (TNF-R2) showed that TNF binding sites were expressed in approximately 100% gastric chief cells. Western blot analysis of whole chief cell lysates probed with the TNF-R1 and TNF-R2 mAbs gave two distinct bands of 55 and 75 kDa in the immunoprecipitate. Incubating chief cells with TNF caused concentration and time dependent cell death, which was prevented by pretreating the cells with anti-TNF receptor mAbs. Exposing the cells to TNF reduced sphingomyelin content by 25%. Sphingomyelinase (10(-6) to 10(-2) IU/ml) mimicked the effect of TNF in that it provoked a concentration and time dependent reduction in chief cell viability and increased pepsinogen release. In conclusion, gastric chief cells express two TNF receptors partially linked to the sphingomyelin pathway. TNF induced chief cell dysfunction might be responsible for the high plasma pepsinogen concentrations seen in patients with NSAID gastropathy or H pylori induced gastritis.

Animals↗

PubMed1996

Antigliadin antibodies in HIV-infected children.

Immunoglobulin A-antigliadin antibodies and total immunoglobulin A were assessed on serum samples from 52 children infected by Human Immunodeficiency Virus (HIV). Titers of antigliadin antibodies exceeding the normal range were found in 14 children (27%). No statistically significant difference was observed either between children with symptomatic or asymptomatic infection, or among children with different degrees of immunosuppression. Though total immunoglobulin A concentration increased with the progression of the disease, no significant correlation was found between antigliadin antibodies and total immunoglobulin A. Mean antigliadin titers showed no significant difference between children with or without chronic gastrointestinal complaints. These findings suggest that, although a raised immunoglobulin A-antigliadin activity is a common feature of children infected by HIV, this is not merely the consequence of elevated total immunoglobulin A concentration. Moreover, in these children a raised antigliadin antibody titer should not be regarded as a reliable marker either of disease progression or of intestinal mucosa damage.

Biomarkers↗

PubMed1996

Selective endoscopic retrograde cholangiography and preoperative bile duct stone removal in patients scheduled for laparoscopic cholecystectomy: a prospective study.

OBJECTIVES: Laparoscopic cholecystectomy (LC) has become the treatment of choice for patients with symptomatic cholelithiasis. About 10% of patients with symptomatic gallstones may bear associated common bile duct (CBD) stones. The preferred approach to these patients is the removal of CBD stones by endoscopic retrograde cholangiography (ERCP) before LC. However, ERCP before LC should be performed only in patients with suspected choledocholithiasis. The aims of this study were to: 1) generate an efficacious predictive model for selecting patients with suspected choledocholithiasis to submit to preoperative ERCP, and 2) test the safety of the endoscopic/laparoscopic procedure. METHODS: Historical, biochemical, and ultrasonographic data were collected prospectively. Receiver operating characteristics curve analysis was adopted for determining optimal biochemical and ultrasonographic cut-off values. Multivariate analysis using logistic regression with generation of the best model identifying independent predictors of CBD stones was also employed. RESULTS: The optimal model predicted a 95% probability of CBD stones in a patient who presented with elevated ALP (over 300 IU/L) and ALT (over 40 IU/L) levels and CBD dilation > 8 mm at ultrasonography. Endoscopic removal of CBD stones was achieved in 95% of patients, with minimal morbidity and no mortality. CONCLUSIONS: The identified independent predictors of CBD stones are highly efficient selectors of patients with choledocholithiasis. Moreover, endoscopic removal of CBD stones before LC is a safe and efficacious procedure.

Adolescent↗

PubMed1996

Effect of ursodeoxycholic acid on hypertransaminasaemia and bile acid composition in patients undergoing bone marrow transplantation--a double-blind randomized control study.

A double-blind randomized placebo controlled trial of ursodeoxycholic acid was performed in 31 patients undergoing T-cell depleted allogeneic or autologous bone marrow transplantation to determine the effectiveness of this hydrophilic bile acid in improving the increase in serum liver enzymes that generally accompanies this procedure. Neither group showed any significant difference in magnitude of the increases in serum transaminases and gamma-glutamyltranspeptidase following the conditioning regimen that included chemotherapy and total body irradiation. In the 6 months after transplantation, serum enzymes decreased in both groups, but were consistently higher in the placebo treated patients, indicating that ursodeoxycholic enhances normalization of liver. Faecal bile acid showed that following chemotherapy and irradiation in which intestinal bacteria are ablated, secondary bile acid formation was practically abolished and faeces contained mainly cholic and chenodeoxycholic acids. During bile acid treatment, ursodeoxycholic acid accounted for 31.3 +/- 10.9% of faecal bile acids compared with 4.0 +/- 2.1% in the basal period. Serum and urinary ursodeoxycholic acid concentrations (mean +/- SD, 13.3 +/- 6.9 mumol/L and 2.65 +/- 0.84 mumol/L, respectively) were significantly higher in patients receiving bile acid than in thos on placebo (mean +/- SD, 0.15 +/- 0.12 mumol/L and 0.29 +/- 0.35 mumol/L, respectively) thus confirming compliance.

Administration, Oral↗

PubMed1996

[Efficacy and tolerability of paroxetine in the treatment of the depressive phase of bipolar disorders].

Eighty patients aged between 20-65 years and suffering from bipolar disease according to DSM IV criteria, were treated with paroxetine for os at the single dosage of 20-40 mg/die. At regular intervals psychometric reagents were administered for the evaluation and the variations in the bipolar disease. Tolerability was excellent and side-effects mild, with a tendency to regress after the second week of therapy. The clinical assessment and the psychometric findings both suggest that paroxetina has a useful action on the bipolar disease.

Adult↗

PubMed1996

[Ovarian tumefactions: the advantages and limits of echo-guided needle aspiration. Our experience].

One-hundred-seventy-five patients with a probably benign ovarian cyst were submitted to transvaginal ultrasound-guided needle aspiration (TVUSGA) for diagnostic and therapeutic purpose. Recovery was obtained in 68% of serous cysts (130 patients). In 34 endometriotic cysts transvaginal ultrasound guided needle aspiration has been an important diagnostic tool and it made possible a better therapeutic approach. The cytologic examination of aspirated benign and malignant cyst fluid didn't give a satisfactory result every time. In conclusion, the transvaginal ultrasound guided needle aspiration has been a good tool in the treatment of serous cysts and a diagnostic aid for endometriotic pathology.

Biopsy, Needle↗

PubMed1996

[Comparison of two treatment models in type-II diabetic patients with poor metabolic control: Preformed combination of glibenclamide 2,5 mg + metformin 400 mg or mono-therapy with sulfonylurea at maximal doses? An evaluation at six months].

Both glibenclamide and metformin have been used alone or in association for many years. In the treatment of type 2 or non-insulin-dependent diabetes (NIDDM). Glibenclamide stimulates insulin release by pancreatic beta cells (pancreatic attachment point), while metformin acts at a peripheral level by increasing glucose absorption in muscular, fatty and hepatic tissues, thus considerably reducing insulin resistance (extra-pancreatic attachment point). The aim of this study was to evaluate the therapeutic efficacy of the pre-formed association of glibenclamide 2.5 mg+metformin 400 mg (treatment group 1) compared to treatment with glibenclamide 5 mg alone (treatment group 2) at almost double therapeutic doses compared to those contained in the association. A total of 40 NIDDM patients were examined (24 females and 16 males) with a mean age of 55.86 years, a mean duration of disease of 9.37 years, generally obese or overweight. From the final results of the study it was found that the associative therapy of glibenclamide 2.5 mg+metformin 400 mg was very advantageous, leading to a significant improvement in the glycometabolic control (HbA1c and fasting plasma glucose) compared to patients treated using single drug therapy who maintained almost stable control of the disease.

Blood Glucose↗

PubMed1995

RFLP analysis of human chromosome 11 region q13 in multiple symmetric lipomatosis and multiple endocrine neoplasia type 1-associated lipomas.

Six lipomas from patients affected by Multiple Symmetric Lipomatosis (MSL) and by Multiple Endocrine Neoplasia Type 1 (MEN 1) were analyzed for loss of heterozygosity on chromosome 11 region q12-13 using four RFLPs. Allelic loss for the D11S146 locus was found only in one visceral MEN 1-associated lipoma. Lipomas that exhibited a lack of allelic lesions were analyzed for an eventual abnormal amount or a defective function of the Gs protein by studying the Gs alpha subunit gene, codons 201 and 207, by PCR and TGGE techniques. All the samples were negative for activating mutations.

Alleles↗

PubMed1995

Lack of allelic loss at the multiple endocrine neoplasia type 1 (MEN-1) gene locus in a pancreatic ductal (non-endocrine) adenocarcinoma of a patient with the MEN-1 syndrome.

The gene responsible for multiple endocrine neoplasia type I (MEN-1) syndrome has been mapped to chromosome 11q13. It appears to function as a tumour-suppressor gene analogous to that for retinoblastoma and allelic losses involving the wild-type of the MEN-1 allele have been found in parathyroid and pancreatic endocrine tumours of MEN-1 patients. No genetic information has been provided so far on non-endocrine malignancies that may occur in MEN-1 patients. A case of exocrine pancreatic adenocarcinoma presenting as the terminal event in a woman with a long standing history of MEN-1 syndrome and multiple endocrine tumours of the pancreas was investigated for possible allelic losses at the MEN-1 gene locus using restriction fragment length polymorphisms (RFLPs) closely linked to the MEN-1 gene and polymerase chain reaction (PCR) for D11S533 locus. No allelic losses were found in tumour tissue with two informative RFLPs (D11S97, D11S146) or with PCR analysis. These findings suggest that the MEN-1 gene does not confer a predisposition to develop tumours other than those that typify the syndrome.

Adenocarcinoma↗

PubMed1995

Human colonic motility: physiological aspects.

From the point of view of its motor activity, the human colon is probably the least understood of the abdominal hollow viscera. This is due to several facts: a) its proximal portions are relatively inaccessible due to anatomical reasons; b) there is no reliable animal model due to the considerable anatomic-physiological differences among mammals. For instance, most deductions about human colonic motor activity have been drawn from experiences in cats and dogs, in which the colon displays a cecum which is almost atrophic, and the viscus is featureless and C-shaped, without the haustrations and the sharp angulations seen in man, c) the wide fluctuations of motility in the daily time course of the same individual makes the interpretation of many studies difficult, especially considering the fact that, until recently, most of the studies on human colonic motility have been conducted for relatively short (30-180 min) recording periods. Recently, however, techniques that allow recording from the proximal portions of the human colon have been developed, and prolonged (24 h or more) observations of myoelectrical and contractile events have been achieved, thus improving our knowledge of the normal physiologic properties of the viscus. These informations have furthermore been integrated and confirmed by scintigraphic techniques (less invasive), that allow the measurement of intracolonic flow activity. The purpose of the present paper is to review the physiological aspects of colonic motility in man, quoting animal studies where human ones are lacking. We will briefly introduce some basic concepts, then a more detailed description of the main topic will follow.

Animals↗

PubMed1995

L-arginine/nitric oxide pathway modulates gastric motility and gallbladder emptying induced by erythromycin and liquid meal in humans.

There is recent evidence that nitric oxide, a soluble gas produced from L-arginine, is released by the smooth muscle cells and neurons of the gastrointestinal tract where it exerts a myorelaxive action. However, little is known about the effects nitric oxide has on gastric and gallbladder motility during the inter- and postprandial phases in man. We therefore investigated the effects 200 mg/kg/hr L-arginine exerts on the gastric and gallbladder motility induced by 2 mg/kg erythromycin or a liquid meal in 21 subjects in a double-blind, placebo-controlled study. Gastric and gallbladder emptying were evaluated by sonography. Fasting antral motility was expressed as antral motility index (MI). In fasting subjects, L-arginine administration determined a threefold increase in plasma nitrite concentrations. Administration of erythromycin caused a significant rise in the antral MI, which was inhibited by L-arginine (P < 0.05). Ingestion of a liquid meal also significantly increased antral MI, but it returned to basal values 90 min after the end of the meal. Although L-arginine administration caused a significant reduction in the antral MI (P < 0.05), it did not inhibit gastric emptying. L-Arginine provoked an approximately 40% increase in basal gallbladder volume, completely blocked erythromycin-induced emptying, and partially, but significantly, prevented the emptying induced by a liquid meal (P < 0.01). Our study suggests that nitric oxide may be implicated in the physiological modulation of gastric and gallbladder motility during the inter- and postprandial phases in man.

Adult↗

PubMed1995

Severe gastric mucosal damage induced by NSAIDs in healthy subjects is associated with Helicobacter pylori infection and high levels of serum pepsinogens.

Helicobacter pylori infection and NSAIDs are considered the two most important exogenous factors in ulcer disease. The interrelation between the two factors is not, however, clear. Moreover, serum pepsinogen has been suggested as a risk marker for the development of NSAID-induced gastrointestinal lesions. Fifty-one healthy volunteers, enrolled in a prospective, double-blind study carried out to evaluate gastrointestinal side effects of meloxicam and piroxicam, were analyzed to determine whether: (1) the prevalence of H. pylori correlates with the occurrence and severity of NSAID-induced gastrointestinal lesions, and (2) serum pepsinogen A and C levels could be used as markers of NSAID-induced mucosal damage. Upper endoscopy was performed by the same investigator before and after 28 days of treatment with placebo, meloxicam (7.5 mg/day and 15 mg/day), or piroxicam (20 mg/day). NSAID-induced damage was graded separately for hemorrhages and erosion ulcers according to Lanza's scale. There were no statistically significant differences in the prevalence of H. pylori in subjects with and without NSAID-induced mucosal lesions. However, there was a positive association between H. pylori infection and the severity of mucosal damage: total mean endoscopic score was 2.9 +/- 0.3 in H. pylori-positive subjects versus 1.6 +/- 0.5 in H. pylori-negative subjects (P < 0.05). Pepsinogen A and C levels increased from 55.3 +/- 3 to 149.4 +/- 15 and from 6.3 +/- 0.5 to 11.5 +/- 2.2, respectively (P < 0.05) in subjects who developed severe endoscopic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Idiopathic megarectum in adults. An assessment of manometric and radiologic variables.

Outlet obstruction is thought to be one of the major factors responsible for idiopathic constipation. However, outlet obstruction itself may be due to several mechanisms. Among these, the presence of a megarectum is a leading one. Pathophysiological studies in adult patients with idiopathic megarectum are scarce. We studied by manometric and defecographic means 15 adult subjects with idiopathic megarectum and severe chronic constipation. Twenty-five healthy volunteers of both sexes acted as controls. Manometric variables showed significant differences between patients and controls with respect to internal anal sphincter pressure (P = 0.02), minimum relaxation volume (P < 0.001), defecatory sensory threshold (P < 0.001), mean rectal tolerable volume (P < 0.001), and rectal compliance (P < 0.001). An altered response to straining was observed in 46.6% of patients and in 12% of controls (P < 0.04); the ability to expel a 50-ml balloon per anum was 13.3% in patients and 100% in controls (P < 0.001). Although all patients opened the anorectal angle and had descent of the pelvic floor, thereby confirming an adequate expulsion effort, evacuation of contrast material appeared extremely difficult. In fact, no subject was able to expel more than 30% of the rectal contents during fluoroscopic screening. These results confirm previous hypotheses that idiopathic megarectum displays features of a neuropathic process as an underlying mechanism. Further studies are needed that also take into consideration the muscle tone component of the rectum in these patients.

Adolescent↗

PubMed1995

Genetic screening to identify the gene carrier in Italian and German kindreds affected by multiple endocrine neoplasia type 1 (MEN 1) syndrome.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominantly inherited disorder characterized by parathyroid hyperplasia, anterior pituitary adenomas and neoplasms of the endocrine cells of the gastroenteric tract. It has been established that also other tissues exhibit excessive proliferation associated to the MEN 1 syndrome: carcinoids (bronchial and intestinal), lipomas (visceral and cutaneous), thyroid adenomas and goiter, and adrenal gland cortex adenomas. The men 1 gene has been mapped by genetic studies to the long arm of human chromosome 11, region q12-13. Genetic analysis of families and tumoral deletion mapping made possible to narrow the men 1 region to a 5 cM interval on chromosome 11q12-13. Thirteen marker complexes (17 DNA probes) were found to be linked to the men 1 gene and they span a 14% meiotic recombination with the men 1 locus in the middle. We report a genetic study on 103 subjects from 7 collected MEN 1-kindreds, six Italian and one German, including 30 affected individuals. By linkage analysis to 9 DNA markers (10 DNA probes) of the chromosome region where the men 1 gene maps (11q12-13), we identified 10 mutant gene carriers. The predicted MEN 1 diagnosis was clinically confirmed for 2 of these identified carriers. A predictive accuracy of this genetic test can reach up to 99.5% when it is possible to exclude meiotic crossing-over between the analyzed DNA markers and the disease locus.

Adult↗

PubMed1995

Role of tumor necrosis factor alpha release and leukocyte margination in indomethacin-induced gastric injury in rats.

BACKGROUND/AIMS: Several studies have shown that polymorphonuclear neutrophil leukocyte (PMN) margination is an early and critical event in the pathogenesis of gastric mucosal injury caused by nonsteroidal anti-inflammatory drugs. Tumor necrosis factor (TNF) alpha is a proinflammatory cytokine that causes PMN margination by up-regulating expression of adhesion molecules on both PMN and endothelial cells. This study investigated whether substances that modulate TNF synthesis and release influence PMN margination and indomethacin-induced gastric damage. METHODS: Rats were treated with several doses of indomethacin alone or in association with substances known to increase (interleukin 2 and lipopolysaccharide) or inhibit (pentoxifylline, dexamethasone, granulocyte colony-stimulating factor [G-CSF]) TNF synthesis and release. RESULTS: Indomethacin administration caused dose-dependent damage and increased PMN margination and plasma TNF concentrations. Pretreatment with interleukin 2 and lipopolysaccharide significantly increased TNF release, PMN margination, and gastric mucosal damage, but administration of dexamethasone, pentoxifylline, and G-CSF provided almost total protection. The administration of G-CSF alone caused a significant increase in gastric PMN margination but protected against the indomethacin-induced gastropathy. CONCLUSIONS: Agents that regulate TNF synthesis and release influence gastric susceptibility to indomethacin by modulating PMN margination. G-CSF increased PMN infiltration but protected against the mucosal injury, suggesting that PMN margination alone is not sufficient to induce mucosal damage.

Animals↗

PubMed1995

Leukotrienes stimulate pepsinogen secretion from guinea pig gastric chief cells by a nitric oxide-dependent pathway.

BACKGROUND/AIMS: Leukotrienes (LTs) are involved in many inflammatory conditions including gastric damage induced by nonsteroidal anti-inflammatory drugs. Although LTs stimulate acid secretion, the effect they exert on pepsinogen secretion is unknown. The aim of this study was to investigate whether LTs stimulate pepsinogen secretion by isolated chief cells and to identify the intracellular messengers that mediate this action. METHODS: Isolated chief cells were incubated with concentrations of LTB4, LTC4, LTD4, or LTE4 ranging from 0.1 pmol/L to 10 mumol/L, and pepsinogen release, intracellular calcium and inositol(1,4,5)-trisphosphate (IP3) concentrations were measured. Nitric oxide generation was determined by the amount of citrulline generated during incubation. RESULTS: All four LTs caused a concentration-dependent stimulation of pepsinogen secretion with 50% effective concentration of 0.05-0.1 nmol/L and a dose-dependent increase in cytoplasmic free calcium and IP3 concentration. The LTB4 and LTD4 antagonists caused selective, concentration-dependent inhibition of LTB4- and LTD4-induced pepsinogen secretion, calcium mobilization, and IP3 generation. All four LTs increased NO generation, and the effect was inhibited by LTB4 and LTD4 antagonists and an NO synthase inhibitor NG-monomethyl-L-arginine and reversed by L-arginine. NG-monomethyl-L-arginine caused a 50%-60% reduction of LT-induced pepsinogen release. Each of the four LTs caused a fivefold increase in 5'-cyclic guanosine monophosphate. CONCLUSIONS: LTs are powerful stimulators of pepsinogen secretion in isolated chief cells and act via occupancy of specific cell-surface receptors.

Animals↗

PubMed1995

Nitric oxide modulates pepsinogen secretion induced by calcium-mediated agonist in guinea pig gastric chief cells.

BACKGROUND & AIMS: Nitric oxide, a putative cellular messenger synthesized from L-arginine, is a powerful modulator of gastric motility and secretions. The aim of this study was to investigate whether (1) guinea pig gastric chief cells express NO synthase, (2) NO modulates the pepsinogen secretion and guanosine 3',5'-cyclic monophosphate (cGMP) generation induced by calcium (Ca2+)-mediated agents, and (3) NO donors and cGMP analogues stimulate pepsinogen release. METHODS: Chief cells were prepared by sequential digestion with collagenase and Ca2+ chelation. NO generation was measured by determining the NO coproduct citrulline. RESULTS: NO synthase immunoreactivities were constitutively expressed in approximately 70% chief cells. Carbachol (10 mumol/L) caused a 4- 6-fold increase in pepsinogen release, citrulline generation, intracellular Ca2+ concentration ([Ca2+]i) and cGMP concentration. These effects were concentration dependently inhibited by NG-monomethyl-L-arginine (L-NMMA). As gastrin, cholecystokinin, thapsigargin, and Ca2+ ionophore increased NO generation, [Ca2+]i seemed to regulate NO synthase activity. [Ca2+]i chelator and calmodulin antagonist inhibited the carbachol-induced pepsinogen secretion and NO generation. Preincubating the cells with L-NMMA had no effect on carbachol-stimulated inositol triphosphate generation or [Ca2+]i or Ca(2+)-dependent adenosine triphosphatase levels. Nitrovasodilator agents and 8-bromo-cGMP stimulated pepsinogen release. CONCLUSIONS: Gastric chief cells express a Ca2+/calmodulin-dependent NO synthase. NO modulates the stimulatory effect of Ca(2+)-mediated agonists on pepsinogen release.

Animals↗

PubMed1995

Effect of some abdominal surgical operations on small bowel motility in humans: our experience.

Until recently, it was only possible to make inferences about small bowel motility from experimental animal models, but manometric techniques now allow prolonged recordings of small bowel motor activity in humans. We have studied the effect of abdominal surgery on motor behavior of the small intestine and here report our observations after various surgical procedures (total gastrectomy, Billroth I and II gastrectomy, ileoanal anastomosis). We discuss the data together with the experiences of others.

Adult↗