Blood alcohol levels after prolonged histamine-2-receptor antagonist treatment.
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Duodenal Ulcer↗
Biomedical subjects
C Surrenti
Publications and source records attributed to C Surrenti.
Undulin RNA and protein expression in normal and fibrotic human liver.
We have analyzed the distribution, gene expression and cellular origin of undulin, a large extracellular matrix glycoprotein associated with mature collagen fibrils, in human liver by immunohistochemistry, Northern-blot analysis and in situ hybridization. In normal liver, undulin was distributed as densely packed fibers in portal tract stroma, and as fine fibers along sinusoids, and around central veins. Undulin ribonucleic acid expression was low in normal liver, and confined to mesenchymal cells of portal tract stroma, vessel walls and perisinusoidal space. In fibrotic liver, undulin deposition and gene expression were enhanced in fibrotic stroma and areas of fibrogenesis identified by the presence of active septa and inflammatory infiltrate. Undulin gene expression in fibrotic liver was exclusively localized in mesenchymal cells that could be identified by staining for vimentin, and partially for alpha-smooth muscle actin as (myo)fibroblasts, and possibly fat-storing cells. These data suggest that undulin is a constituent of the hepatic extracellular matrix of normal human liver, and that it participates in the rearrangement of connective tissue occurring in hepatic fibrosis.
Adolescent↗
Acetaldehyde regulates the gene expression of matrix-metalloproteinase-1 and -2 in human fat-storing cells.
Altered degradation of extracellular matrix has been implicated in the pathogenesis of hepatic fibrosis. We studied the effect of acetaldehyde (AcCHO) on gene expression of matrix-metalloproteinase (MMP)-1 (fibroblast type- interstitial collagenase) and MMP-2 (72 kDa gelatinase-type IV collagenase) in comparison with the AcCHO effect on collagen type I and IV synthesis in cultures of fat-storing cells (FSC) isolated from normal human livers. Cultured human FSC expressed single mRNA transcripts (2.7 and 3.2 kb) specific for MMP-1 and MMP-2, respectively. AcCHO inhibited MMP-1 mRNA levels, whereas it stimulated collagen type I mRNA and protein expression. Opposite AcCHO effects were evident on MMP-2 mRNA and collagen IV synthesis, being MMP-2 up-regulated and collagen IV down-regulated. These data suggest that regulation of MMP-1 and MMP-2 genes by AcCHO may contribute to disruption of the normal basement membrane and its replacement with fibrillar collagens in the early stages of alcoholic liver fibrosis.
Acetaldehyde↗
Capsaicin-like effect of resiniferatoxin in the rat stomach.
Neurochemical and functional studies were performed to investigate and to compare the effects of resiniferatoxin and capsaicin in the rat stomach. Neonatal administration of resiniferatoxin (0.6-1.6 mumol/kg subcutaneously (s.c.)) produced a marked decrease in gastric calcitonin gene-related peptide-like immunoreactivity in both secretory and non-secretory region of the stomach. Almost complete depletion of the peptide was determined by neonatal administration of capsaicin (164 mumol/kg s.c.). Vasoactive intestinal polypeptide-like immunoreactivity was concomitantly unaffected by resiniferatoxin or capsaicin, thus showing the selectivity of action of the neurotoxins on gastric afferent fibers. Oral administration of an equimolar dose (0.3 nmol/kg) of resiniferatoxin or capsaicin together with 50% ethanol reduced at a similar extent gastric haemorrhagic lesions produced by the mucosal barrier-breaker agent. These findings provide evidence that resiniferatoxin and capsaicin may act on a common neuronal target in the rat stomach and that the acute exciting (protective) effect is of the same magnitude.
Administration, Oral↗
Influence of capsaicin-sensitive afferent fibers on acetic acid-induced chronic gastric ulcers in rats.
Accumulating evidence indicates that capsaicin-sensitive afferent fibers play a pivotal role in acute gastroprotection. However, whether they also influence healing of chronic gastric ulcers is still unknown. The effects of ablation of sensory neurons on acetic acid-induced chronic gastric ulcers in rats were investigated at morphologic and biochemical levels by computerized imaging analysis of the ulcerated area, histologic examination, and neuropeptide determination. Afferent nerve ablation, as a result of treating rats with a neurotoxic dose of capsaicin (50 + 50 mg/kg subcutaneously over 2 days), produced a significant increase in the ulcer area at 1 and 2 weeks after acetic acid injection. The delay in ulcer healing was associated with a marked and persistent decrease in tissue calcitonin gene-related peptide-like immunoreactivity, whereas gastric vasoactive intestinal polypeptide was unaffected by capsaicin pretreatment. Histologically, as compared with control rats, capsaicin-desensitized animals only differed in a slight increase in the inflammatory infiltrate during the early phase of ulcer formation. These findings suggest that capsaicin-sensitive afferent fibers may play a role in the healing of chronic experimental gastric ulcers in rats, but the underlying mechanisms remain to be elucidated and deserve further investigation.
Acetates↗
Acetaldehyde induces c-fos and c-jun proto-oncogenes in fat-storing cell cultures through protein kinase C activation.
Hepatic fibrosis is an important morphological feature of alcohol-induced liver injury. We previously reported that acetaldehyde stimulates collagen I and fibronectin gene transcription in rat fat-storing cell (FSC) culture. We here evaluated whether acetaldehyde increases Col I and FN gene transcription through the induction of c-fos and c-jun proto-oncogenes and studied the possible role played by protein kinase C (PKC) and c-AMP. FSCs, isolated from rat liver on a Nycodenz density gradient, were exposed to acetaldehyde for 1/2, 1, 3, 6, 12, 24 hr and for 10, 20, 30, 45, 60, 90 min in the experiments for jun and fos expression, respectively. Acetaldehyde produced a rapid and transient induction of fos mRNA (undetectable at t = 0, peak at t = 45 and still evident at t = 90). Jun mRNA was weakly expressed in unstimulated FSCs; acetaldehyde induced a prolonged activation of jun expression up to 24 hr with a peak at 3 hr. To study the role of PKC were repeated the experiments in the presence of Staurosporine and H-7. These inhibitors of PKC activity blocked the stimulatory effect of acetaldehyde on fos and jun mRNA expression. Furthermore, they abolished the stimulatory effect of acetaldehyde on collagen I and fibronectin gene expression by FSCs. Acetaldehyde increased the cell membrane PKC activity in FSC cultures in a dose-dependent way. Intracellular cAMP levels were not significantly modified by acetaldehyde in the first 30 min of incubation. We conclude that acetaldehyde increases procollagen I and fibronectin gene transcription in FSCs, possibly through c-fos and c-jun expression, and that PKC may play a regulatory role in this chain of events.
Acetaldehyde↗
Prolonged bedtime treatment with H2-receptor antagonists (ranitidine and famotidine) does not affect blood alcohol levels after ethanol ingestion in male patients with duodenal ulcer.
OBJECTIVE: To verify whether a prolonged (therapeutic) treatment with ranitidine or famotidine may affect blood alcohol concentrations (BAC) in patients with duodenal ulcer (DU). METHODS: Sixteen male patients with DU were studied. Subjects with Helicobacter pylori-associated DU did not enter the study. Patients randomly received either 300 mg ranitidine (n = 8) or 40 mg famotidine (n = 8) at bedtime for 2 months. They had a standard lunch (1:00 PM), and 0.3 g/kg of alcohol was given 15 min after the meal. BAC were measured by head-space gas chromatography up to 150 min. RESULTS: The rate of GFPM was checked in all patients before they entered the study; we found it to be 53%, by comparing the area under the curve (AUC) of BAC after either intravenous or oral (po) administration of 0.3 g/kg ethanol. Ranitidine did not significantly modify either the mean AUCpo (5.8 +/- 1.8 vs. 6.2 +/- 1.4 mM/h, before vs. after treatment) or the peak BAC (4.6 +/- 1.1 vs. 5.3 +/- 1.7 mM) after 2 months of treatment. Famotidine failed to affect BAC in the second group of patients (AUCpo 5.0 +/- 1.4 vs. 5.6 +/- 1.7 mM/h, peak BAC 4.0 +/- 1.7 vs. 4.3 +/- 1.8 mM; before vs. after treatment). CONCLUSIONS: These findings suggest that, in males with DU, prolonged treatment with ranitidine or famotidine had no effect on BAC after administration of a small dose of postprandial alcohol.
Adult↗
Localization of epidermal growth factor/transforming growth factor-alpha receptor in the human gastric mucosa. An immunohistochemical and in situ hybridization study.
Current evidence indicates that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) play a pivotal role in the maintenance of gastric mucosal integrity, via binding to a common cell-surface receptor (EGF/TGF-alpha receptor). We examined the distribution and cellular sites of synthesis of EGF/TGF-alpha receptor in normal human gastric mucosa by immunohistochemical and in situ hybridization techniques. Intense EGF/TGF-alpha receptor immunoreactivity was observed in the basal cytoplasm and along basolateral membranes of mucus neck cells, foveolar columnar cells, and surface epithelial cells facing the gastric lumen. Parietal cells and mucus-secreting pyloric gland cells displayed a distinct basolateral immunostaining, whereas the luminal membrane was unstained. Immunoreactivity was also noted in spindle-shaped cells of the lamina propria and in smooth muscle cells of the muscularis mucosae and muscularis propria. In situ hybridization revealed EGF/TGF-alpha receptor RNA transcripts in all cell types displaying positive immunoreaction. These results suggest a physiological role for EGF/TGF-alpha in the regulation of multiple gastric functions. The receptor distribution at the luminal aspect of the gastric mucosa provides the anatomical basis for a possible interaction of gastric juice EGF (or TGF-alpha) with cells of the mucosal surface, whereas the expression of EGF/TGF-alpha receptor in cells which are not in direct contact with the gastric lumen is consistent with blood-mediated or paracrine/autocrine mechanisms of EGF/TGF-alpha action on these cells.
Adult↗
Regulation of extracellular matrix synthesis by transforming growth factor beta 1 in human fat-storing cells.
BACKGROUND: Fat storing cells (FSC) are nonparenchymal liver cells generally considered the major source of the hepatic extracellular matrix (ECM). Transforming growth factor beta 1 (TGF-beta 1) is a potent regulator of ECM synthesis in various cell types. In this study, the effect of TGF-beta 1 on procollagen types I, III, IV, laminin (Lam), and fibronectin (FN) synthesis in cultured human FSCs was analyzed. METHODS: FSCs were isolated from wedge sections of normal human livers. Morphological studies were performed by immunofluorescence and electron microscopy. ECM components in human FSC cultures were measured by an enzyme-linked immunosorbent assay. The expression of messenger RNA (mRNA) was evaluated by Northern blot and in situ hybridization. RESULTS: Cultured human FSCs displayed numerous fat droplets in the perinuclear zone, and immunoreactivity for vimentin and alpha-smooth muscle actin. A weak nonfibrillar staining was observed by using a polyclonal antidesmin antibody. TGF-beta 1 induced a dose-dependent increase of procollagen I, III, and FN accumulation in human FSC cultures, whereas procollagen IV and Lam production was not affected. Furthermore, TGF-beta 1 increased the expression of alpha 1 (I), alpha 1 (III) procollagen, FN and TGF-beta 1 mRNA in human FSC cultures. CONCLUSIONS: These data indicate that TGF-beta 1 is able to increase the synthesis of procollagen I, III, and FN in cultured human FSCs. Moreover, TGF-beta 1 can induce its own mRNA in the same cells.
Adipose Tissue↗
Colonic vasoactive intestinal polypeptide in ulcerative colitis.
Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide which is localised in both the central and peripheral nervous system. In the human colon VIP is found in all layers and the highest concentrations have been found in the myenteric plexus. It is known that VIP has various effects on intestinal functions: i) it is a potent stimulant of mucosal water and electrolyte secretion; ii) it is involved in the peristaltic reflex; and iii) plays an inhibitory role on immune cell function. Based on these biological effects it has been hypothesized that the intestinal mucosal immune system and inflammation may be influenced by alterations in the tissue concentrations of VIP. Some authors have demonstrated no changes in the VIP colonic content of patients with ulcerative colitis, whereas others have demonstrated a reduction. Our results, using specific radioimmunoassay, showed that there is a significant decrease of VIP in both rectal and colonic mucosa of patients with ulcerative colitis as compared to controls. The VIP decrease is selective since substance P and calcitonin gene-related peptide were unchanged in the mucosal tissue of ulcerative colitis patients and furthermore the VIP alteration is correlated to the degree of mucosal inflammation. These findings suggest that the reduction of VIP mucosal content, even if it represents a non-specific event, could influence local inflammatory response and the activity of the disease.
Colitis, Ulcerative↗
Ursodeoxycholic acid for symptomatic primary biliary cirrhosis. Preliminary analysis of a double-blind multicenter trial. Italian Multicenter Group for the Study of UDCA in PBC.
The administration of ursodeoxycholic acid, a hydrophilic bile acid not hepatotoxic to humans, has been suggested for treatment of primary biliary cirrhosis to improve cholestasis and reduce hepatocellular damage. Efficacy of treatment has been studied mainly in patients with asymptomatic or early-stage disease. In January 1988, to establish the efficacy and safety of ursodeoxycholic acid in a population with more severe disease, we started a multicenter, double-blind, placebo-controlled trial in patients with symptomatic disease, that is, with pruritus or serum bilirubin exceeding 2 mg/dl. Forty-four patients were assigned to ursodeoxycholic acid, 500 mg daily (corresponding to about 8.7 mg/kg body weight in these patients), and 44 to a placebo. As planned at the beginning of the study, a preliminary analysis was performed when all patients had been followed for at least 6 months (33 patients up to 12 months). Pruritus, self-evaluated by the patients, and cholestyramine consumption, as recorded in a diary, decreased significantly (p < 0.01) in both groups. In patients who initially had abnormal levels, serum bilirubin decreased significantly (p < 0.05) in the ursodeoxycholic acid group compared to placebo. After 6 months the following were also significantly better in the ursodeoxycholic acid than in the placebo group: a composite weighted biochemical index taking into account the changes in serum bilirubin, alkaline phosphatase, gamma-GT and AST (p < 0.001); serum prealbumin (p < 0.05); IgG (p < 0.01) and IgM (p < 0.01) levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Bilirubin↗
Acetaldehyde-protein adducts, but not lactate and pyruvate, stimulate gene transcription of collagen and fibronectin in hepatic fat-storing cells.
Hepatic fibrosis is an important morphological feature of alcohol-induced liver injury. We previously reported that acetaldehyde, but not ethanol can stimulate type I collagen and fibronectin synthesis in cultures of rat fat-storing cells (FSC) by increasing transcription of the specific genes. The effect of lactate and pyruvate was studied on collagen I, III, fibronectin accumulation by cultured rat FSCs and it was investigated whether acetaldehyde could increase procollagen I and fibronectin gene transcription through the formation of protein adducts. Lactate and pyruvate (5, 15 and 25 mmol/l) did not significantly affect collagen I, III and fibronectin production by cultured FSCs. Pyridoxal-phosphate and p-hydroxymecuribenzoate (inhibitors of acetaldehyde-protein adduct formation) blocked the stimulatory effect of acetaldehyde on procollagen I and fibronectin gene transcription. These data suggest that ethanol may act as a liver fibrogenic factor through acetaldehyde, its immediate metabolite, whereas lactate does not seem to play a role. Acetaldehyde might stimulate gene transcription of extracellular matrix components by liver FSCs through the formation of adducts with proteins.
Acetaldehyde↗
Pharmacokinetics of azithromycin in patients with impaired hepatic function.
The pharmacokinetics of azithromycin were determined over a 192-h period following oral administration of a single 500-mg dose to six healthy volunteers and to 16 cirrhotic patients (ten class A and six class B; Pugh's classification). Plasma and urinary levels were determined by microbiological assay. The mean Cmax, obtained 2-3 h after administration, was 0.29 mg/L in volunteers, and 0.39 and 0.51 mg/L in class A and class B cirrhosis, respectively. The elimination half-life was 53.5 h in control subjects, and 60.6 and 68.1 h in class A and class B cirrhotic patients, respectively. The mean residence time was significantly higher in class B patients, but AUC, Vd, Cltot and Clr values appeared to be similar in all groups. The mean urinary recovery of azithromycin at 192 h varied from 11-15.7%, and did not differ significantly among groups. These results demonstrate that azithromycin pharmacokinetics do not differ consistently in patients with mild or moderate hepatic impairment in comparison with healthy volunteers. Therefore, no dosage modifications of azithromycin seem to be required for patients with class A or B liver cirrhosis.
Adult↗
Gastric lesions induced by concentrated ethanol are associated with a decrease in gastric calcitonin gene-related peptide-like immunoreactivity in rats.
Gastric calcitonin gene-related peptide-like immunoreactivity (CGRP-li) was decreased in the gastric corpus of rats treated with 75% or 96% ethanol but not with 50% ethanol. The extent of gastric lesions was related to the increasing concentrations of ethanol (50-96%). CGRP-li decrease was evident already at 5 min after the 96% ethanol challenge, whereas a peptide recovery resulted 10 days after, concomitant with the healing of gastric lesions. Ethanol (96%) produced a significant decrease of CGRP-li in the whole thickness of the gastric corpus but not in the mucosal layers of the same area, indicating that the muscular layer of the gastric corpus is the zone involved in this phenomenon. Pretreatment with the selective sensory neurotoxin capsaicin induced a gastric CGRP-li decrease in the corpus and forestomach. Ethanol (96%) did not further decrease gastric corpus CGRP-li in capsaicin-pretreated rats. These findings suggest that 96% ethanol induced a decrease of CGRP-li deriving from a capsaicin-sensitive pool and that CGRP may play a role in gastric ulcer pathogenesis of haemorrhagic lesions induced by concentrated ethanol.
Analysis of Variance↗
Neuroendocrine regulation of gastrointestinal motility. Normal and abnormal physiology.
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Animals↗
Piezoelectric extracorporeal shock wave lithotripsy in 93 patients with gallstones.
Ninety-three patients with gallstones were selected for extracorporeal shock wave lithotripsy (ESWL) with a piezoelectric device (EDAP LT-OI) to verify the efficacy and safety of this technique. Neuroleptoanalgesia with intravenous diazepam and phentanyl was performed in almost all patients. The treatment was combined with adjuvant litholytic therapy using oral ursodeoxycholic acid. Follow-up period was nine months. Piezoelectric ESWL was able to disintegrate radiolucent gallstones in 97.9% of cases. By the ninth month 68 patients (73.1%) were stone-free. Best results were obtained with single stones smaller than 20 mm. After ESWL, surgical cholecystectomy was necessary in 2.1% of cases. This study confirms the efficacy and safety of piezoelectric extracorporeal shock wave lithotripsy combined with ursodeoxycholic acid adjuvant therapy for selected cases of gallstone disease.
Cholelithiasis↗
Sialoadenectomy selectively increases rat gastric CGRP. Interaction with capsaicin-sensitive afferents.
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Afferent Pathways↗
Cysteamine induced-duodenal ulcers are associated with a selective depletion in gastric and duodenal calcitonin gene-related peptide-like immunoreactivity in rats.
We have measured the endogenous levels of gastric and duodenal calcitonin gene-related peptide (CGRP)-, neurokinin A (NKA)-, galanin-vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-like immunoreactivity (li) in relation to cysteamine-induced gastric lesions and duodenal ulcers in rats. CGRP-li but not NKA-, galanin-, VIP- or NPY-li was decreased in gastric and duodenal samples following a single ulcerogenic dose of cysteamine (900 mg/kg p.o.). Temporal relationships of this phenomenon showed that CGRP-li was selectively decreased (stomach 45%, duodenum 68% as compared to controls, respectively after 24 h) concomitantly to the formation of acute gastric lesions and duodenal ulcers. Animals bearing healed ulcers 12 days after cysteamine, had gastroduodenal CGRP-li similar to control values. Pretreatment with the selective sensory neurotoxin capsaicin decreased gastroduodenal CGRP-li but not NKA-, galanin-, VIP- or NPY-li, showing that CGRP might be considered a marker of the afferent innervation of the gastroduodenal tract. The residual gastroduodenal CGRP-li levels in capsaicin-pretreated animals were not decreased by cysteamine administration, indicating that the effect of cysteamine is restricted to a peptide pool of primary afferent origin. Duodenal CGRP-li is selectively decreased by the duodenal ulcerogen cysteamine during the acute phase of ulcers formation and might be among the local mediators which afford protection against the ulcerogenic stimuli.
Animals↗