Search PubMed⌕ Search

Biomedical subjects

R Mazzanti

Publications and source records attributed to R Mazzanti.

At least 37 records · Page 2Linked to original sources
PubMed1994

Bile acid inhibition of P-glycoprotein-mediated transport in multidrug-resistant cells and rat liver canalicular membrane vesicles.

To study the effect of bile acids on P-glycoprotein-mediated drug transport, we performed experiments using multidrug resistant cells and rat canalicular membrane vesicles. Cellular accumulation and efflux of rhodamine 123 were measured in drug-resistant cells by means of computerized quantitative image analysis and fluorescence microscopy. ATP-dependent [3H]daunomycin transport was studied by means of rapid filtration in canalicular membrane vesicles prepared from normal rats. Doxorubicin-sensitive (PSI-2) and -resistant (PN1A) 3T3 cells and human-derived hepatocellular carcinoma doxorubicin-sensitive and -resistant cells were used. Taurochenodeoxycholate and glycochenodeoxycholate, taurolithocholate and ursodeoxycholate (50 to 200 mumol/L) inhibited rhodamine 123 and [3H]daunomycin transport in multidrug-resistant cells and canalicular membrane vesicles, respectively, whereas taurocholate, taurodeoxycholate and tauroursodeoxycholate did not. Primary and secondary unconjugated bile acids had no effect. These results reveal that taurolithocholate, taurochenodeoxycholate and glycochenodeoxycholate and ursodeoxycholate inhibit P-glycoprotein-mediated drug transport function in multidrug resistant cell lines and in canalicular membrane vesicles. These results suggest possible interaction between P-glycoprotein function and bile acids in cholestasis and after treatment of patients with ursodeoxycholic or chenodeoxycholic acid.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Long-term ambulatory enterogastric reflux monitoring. Validation of a new fiberoptic technique.

A new technique for the long-term ambulatory detection of enterogastric and nonacid gastroesophageal reflux has been conceived, developed, and validated. It is based on the use of a fiberoptic sensor that utilizes the optical properties of bile. In vitro studies have shown good precision, good stability, sensitivity of 2.5 mumol/liter bilirubin concentration, as well as a useful working range of 2.5-100 mumol/liter bilirubin concentration. In vivo studies have been performed in 29 subjects. Simultaneous gastric aspirations have allowed a comparison of fiberoptic system measurements both with spectrophotometric analysis and bile acid concentrations of corresponding gastric juice samples. Linear correlations were shown between fiberoptic assessment and both spectrophotometric and bile acid concentration findings (P < 0.01). Simultaneous assessment of reflux with the fiberoptic system and cholescintigraphy has shown a 92.9% concordance as regards the presence or absence of reflux. Present results imply that the fiberoptic system is an important tool for the understanding of the clinical relevance of enterogastric and nonacid gastroesophageal reflux.

Adult↗
PubMed1993

Reflux-related gastric mucosal injury is associated with increased mucosal histamine content in humans.

BACKGROUND: Experimental studies in the dog and the rat have shown histamine involvement in reflux-related gastric mucosal injury. However, no definite demonstrations of a link between reflux-related gastric mucosal injury and mast cell mediators exist in humans. METHODS: The relationships between reflux, gastric mucosal histamine content, and gastric histology were assessed in partially gastrectomized subjects presumptively with high (11 Billroth II subjects) and low reflux levels (9 total biliary diversion subjects), respectively. Findings were compared with those in a control group consisting of 8 endoscopically and histologically proven normal subjects. RESULTS: Bile acid quantity and concentration in the gastric aspirates were significantly greater in Billroth II subjects than in total biliary diversion subjects. Significantly higher cumulative scores for foveolar hyperplasia, mucosal edema, capillary dilatation and congestion, and smooth muscle fibers in the lamina propria were found in Billroth II subjects than in total biliary diversion subjects. Mucosal histamine content as well as mast cell density and degranulation differed significantly between Billroth II and the other two groups. CONCLUSIONS: These results represent the first demonstration in humans of an association between mast cell mediators and chemical gastric mucosal injury.

Adult↗
PubMed1993

[The pathogenetic mechanisms of intrahepatic cholestasis].

The present review firstly gives some details regarding nosological approach to the cholestatic syndrome. In addition, different steps are considered, identifying 12 possible metabolic defects responsible for determining a cholestatic syndrome either in man or in experimental conditions. Eleven defects out of these 12 steps should be considered related to the structure and function of the hepatocyte, whereas the twelfth one, which comprises 3 different sub-groups, is based on a mechanical obstructive mechanism, localized exclusively into the liver parenchyma, thus resembling the other ones included in the chapter of intrahepatic cholestasis.

Bile↗
PubMed1992

Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells.

We have previously shown that efflux of cytotoxic drugs from multidrug resistant (MDR) cell lines can be quantitated at the single cell level using a sensitive fluorescence microscopy technique. Based on the structure of compounds which inhibited the efflux of Rhodamine-123 (Rho-123) using this methodology, we hypothesized that the antiemetic, antihistaminic agent benzquinamide (BZQ) would interfere with P-glycoprotein (P-gp) mediated drug transport and potentiate the effects of anticancer agents in MDR cell lines. We show that BZQ interferes with P-gp mediated drug efflux and increases drug accumulation in MDR cells using Rho-123 as a fluorescent probe. BZQ increases the cytotoxicity of chemotherapeutic agents to both human and hamster MDR cell lines in vitro. A slight increase in cytotoxicity to chemotherapeutic agents is also observed in the parental cell lines with BZQ. BZQ increases [3H]daunorubicin accumulation and inhibits the binding of [125I]iodoaryl azidoprazosin to the P-gp in MDR cells. BZQ is a new agent to increase the cytotoxic effects of anticancer agents in MDR cells and may ultimately prove useful as an adjunct in cancer chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Acute phase proteins in alcoholics with or without liver injury.

Acute phase proteins behaviour has been examined in chronic alcoholics to verify the hypothesis that chronic alcohol consumption stimulates the hepatic synthesis of acute phase proteins. Certain acute phase proteins were studied in two groups of alcoholics, one with and one without liver damage, and in a third group of healthy volunteers. The results show that the acute phase proteins were similar in the two groups of alcoholics, but differed when compared to the control group. The authors have concluded from these results, that chronic alcohol consumption causes a serum increase of: mucoproteins (p less than 0.001), alpha 1 acid glycoprotein (p less than 0.05), haptoglobin (p less than 0.05) and fibrinogen (p less than 0.02). Such increases are independent from the existence of liver damage.

Acute-Phase Proteins↗
PubMed1991

Gastric cell proliferation kinetics and bile reflux after partial gastrectomy.

Thirty-four randomized, partially gastrectomized subjects (12 with a Billroth II, 11 with a Billroth I, and 11 with a total biliary diversion reconstruction) were studied in order to assess the relationships between bile reflux, gastric histology, and cell proliferation kinetics. Bile acid quantity and concentration in the gastric aspirates progressively decreased from Billroth II to Billroth I to total biliary diversion (after which reflux was almost absent). Perianastomotic mucosa in Billroth II subjects showed the greatest degree of foveolar hyperplasia, and this decreased markedly with increasing distance from the anastomosis. Hyperplastic changes were less evident in Billroth I, and virtually absent in total biliary diversion subjects. The overall foveolar hyperplasia-like behavior of cell kinetic parameters (total pit cell number, labeled pit cell number, and labeling index) was shown. Moreover, subjects with mean bile acid concentration greater than 150 mumol/L had both a greater prevalence of foveolar hyperplasia and greater values of cell kinetic parameters than those with mean bile acid concentration less than or equal to 150 mumol/L. A superficialization of the proliferative compartment was also evident in the former group. These results show a close relationship between postgastrectomy bile reflux, foveolar hyperplasia, and cell kinetic parameters. Histologic and cell kinetic findings are probably the expression of gastric adaptation to chronic bile reflux exposure. Moreover, the type and entity of cell kinetic involvement and its relationship to foveolar hyperplasia and reflux may suggest new "tools" in post-gastrectomy surveillance and help to clarify patterns of gastric carcinogenesis.

Bile Reflux↗
PubMed1990

Structure and function of P-glycoprotein in the normal liver and intestine.

Multidrug resistance (MDR) genes encode a family of membrane glycoproteins of approximately 170 kD (P-glycoproteins). In man and mouse, the MDR 1 (mdr 1) genes confer resistance to relatively hydrophobic cationic anti-cancer drugs (i.e., vinblastin, adriamycin). Anti-cancer drug sensitivity is restored by addition of other drugs (i.e., verapamil, reserpine) which are also P-glycoprotein substrates. Transfection of MDR 1 genes produces the resistance phenotype and overexpression of P-glycoprotein. Parenchymal cells in several normal tissues express P-glycoprotein in the secretory domain of the plasma membrane (i.e., bile canaliculus of hepatocytes, brush border of proximal tubular, and small intestinal cells). Studies using plasma membrane vesicles of different sidedness derived from the bile canaliculus and small intestinal brush border permit characterization of P-glycoprotein as a unidirectional, temperature dependent, saturable, ATP-dependent transporter which is competitively inhibited by various anti-cancer drugs and other compounds. Transport studies using single cell fluorescence microscopy with image analysis confirm observations in vesicles. No natural substrate has been identified. Structural studies indicate that the requirements for substrates are molecular weight of 350 to 100, hydrophobicity, two planar rings, and a weak cationic charge. Alternative mechanisms of transport function are considered. The identity of P-glycoproteins in normal rat and human tissues has not been established. Antibody reactions suggest that they may belong to the MDR 2 or 3 class. Studies using everted gut sacs suggest that inhibition of P-glycoprotein may facilitate accumulation of anti-cancer drugs in the tissue.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Hepatic lipid peroxidation and aldehyde dehydrogenase activity in alcoholic and non alcoholic liver disease.

It has been suggested that lipid peroxidation plays a role in the pathogenesis of chronic alcoholic liver disease (CALD). However, whether or not CALD differs from chronic non alcoholic liver disease (CLD) in lipid peroxidation, is still questionable. Thirty-eight patients affected by CALD and CLD who were matched for age, sex, nutrition and liver function tests (LFTs) and 17 controls (C) took part in this study. The following tests were performed: serum and liver malondialdehyde (MDA) determination by the TBA test, liver total glutathione (GSH) estimate, mitochondrial (ALDH2) and cytosolic (ALDH1) aldehyde dehydrogenase activity determinations. Patients who showed signs of malnutrition were excluded from this study. Serum and hepatic TBA-reactive substances resulted in a slight increase in chronic liver patients compared to controls but did not show any difference between CALD and CLD groups. Liver total glutathione did not show any change. Hepatic ALDH2 activity was significantly (P less than 0.01) higher in CALD than in CLD and control patients whereas ALDH1 did not show any difference. These results suggest that the increased lipid peroxidation in CALD and in CLD is probably secondary to liver damage rather than being the pathogenic factor.

Adult↗
PubMed1989

Acute and chronic exposure to ethanol and the electrophysiology of the brush border membrane of rat small intestine.

In this study we have investigated the effects of (a) chronic ethanol intake on glucose and galactose absorption across the rat jejunum in vivo and on the potential difference across the isolated brush border membrane (Vm) and (b) acute exposure to ethanol (4% or 8%) and acetaldehyde (0.25%) on changes in Vm associated with Na(+)-dependent galactose absorption across the jejunum and ileum. Chronic ethanol intake was associated with hyperpolarization of Vm and an enhanced galactose but not glucose transport. Acute ethanol and acetaldehyde were without effect on Vm whether or not galactose was present. We conclude that while a greater electrochemical gradient across the brush border membrane is a likely explanation for the stimulation of galactose absorption induced by ethanol feeding, factors other than changes in Vm are responsible for the inhibitory effects of acute ethanol.

Acetaldehyde↗
PubMed1988

Short-term effects of bile diversion on postgastrectomy gastric histology.

Twelve partially gastrectomized subjects who have consecutively undergone total biliary diversion for severe bilious vomiting were studied before and after operation in order to assess the effects of surgery on gastric histology and enterogastric reflux. Before and six months after operation, the following protocol was performed: (1) blood examinations including serum basal gastrin; (2) endoscopy with multiple gastric biopsies; and (3) quantitation of bile acids in the gastric aspirate. Of the preoperative symptoms, bilious vomiting and heartburn completely disappeared postoperatively in all the subjects. Fasting bile reflux was significantly reduced (bile reflux was annulled in six and considerably lowered in the remaining six subjects), and erythema of the gastric mucosa completely disappeared in all the subjects after diversion. Among histological findings, while a significant regression of foveolar hyperplasia was found both in the perianastomotic area and in the body of gastric remnant, none of the other aspects identifiable in postgastrectomy gastric mucosa (chronic gastritis changes included) were affected by diversion. These results show that biliary diversion is effective in correcting reflux, bilious vomiting, erythema, and foveolar hyperplasia of the gastric mucosa and confirm the suggested relationship between bile reflux and gastric foveolar hyperplasia.

Adult↗
PubMed1988

Billroth I versus Billroth II partial gastrectomy in the treatment of gastric ulcer.

Short- and long-term results of B-I and B-II reconstructions were compared in order to assess which anastomosis is to be recommended after partial gastrectomy for gastric ulcer. All the patients (287) electively operated for gastric ulcer 10-20 years ago were considered for the study. Operative mortality did not significantly differ, while duration of post-operative time before discharge and post-operative morbidity were significantly lower after B-I. Long-term percentage probability of survival was higher after B-I than after B-II (87.0 and 63.7 after 19 years, respectively), while quality of life was similar in the two groups. In the 64 subjects (26 B-I and 38 B-II) who underwent the study protocol, fasting bile reflux appeared more abundant and bile acid concentration greater after B-II than after B-I. While bacteria and nitrite concentrations did not differ in the two groups, bile acid pattern differed in a greater deoxycholic acid percentage concentration in the B-II group. In spite of an increased deoxycholic acid concentration and therefore a probably more lithogenic bile, gallstones were shown in 23.11% and 39.41% of the B-I and the B-II subjects, respectively, without significant differences. In conclusion, when partial gastrectomy is indicated for gastric ulcer, B-I reconstruction seems preferable to B-II because of its lower post-operative mobility, less evident entero-gastric reflux and histological consequences, less evident bile acid pattern changes from normal, and an apparently longer life-expectancy after discharge.

Adult↗
PubMed1987

Gastric histology and fasting bile reflux after partial gastrectomy.

Forty-four randomized, partially gastrectomized subjects were studied to assess whether gastric histologic findings after partial gastrectomy were related to reflux. Gastric biopsy specimens (12) were taken at different distances from the anastomosis. Histologic findings were as follows: (a) hyperplastic changes of the foveolar epithelium and (b) loss of the chief and parietal gland cells with atrophy of gastric glands (chronic atrophic gastritis). Hyperplastic changes typical of the perianastomotic area gradually decreased with increasing distance from the anastomosis. Hyperplastic changes showed a greater prevalence in Billroth II than in Billroth I subjects (100% vs. 29.4%). No significant association was found between histologic findings and symptoms. Hourly bile acid quantity (fasting bile reflux) and concentration were determined in the gastric aspirates. Bile reflux was greater after Billroth II than after Billroth I (fasting bile reflux median values: 30.5 vs. 0.18 mumol/h, respectively). The same was true for bile acid concentration (mean bile acid concentration median values: 624.9 vs. 17.5 mumol/L, respectively). Moreover, Billroth I subjects with hyperplasia had a greater quantity and concentration of reflux than those without hyperplasia (fasting bile reflux and mean bile acid concentration median values: 2.6 vs. 0.8 mumol/h and 4.7 vs. 2.7 mumol/L, respectively). These findings show that bile reflux is correlated with hyperplastic changes of the foveolar epithelium, but prevalence and severity of atrophic gastritis were not related to reflux. Therefore, although we failed to show any relationship between chronic atrophic gastritis and reflux, foveolar hyperplasia was shown to be reflux related.

Bile Reflux↗
PubMed1987

Effect of chronic ethanol ingestion on enterocyte turnover in rat small intestine.

Whether chronic ethanol ingestion significantly damages the small intestine remains controversial. To clarify this we have analysed the morphology of the small intestinal epithelium and quantified its renewal in chronically ethanol fed rats. Twenty adult male rats were pair fed for 28 days a nutritionally adequate liquid diet containing either ethanol as 36% of total calories or an isocaloric diet in which fat substituted for ethanol. Crypt cell production rate was determined in the jejunum and ileum by the metaphase arrest method. Weight gain and small intestinal morphology were similar in ethanol fed and control rats, but enterocyte turnover was significantly reduced in the jejunum (p less than 0.05) and ileum (p less than 0.01) of the ethanol fed rats. This effect of ethanol on the small intestine is probably systemic rather than local, because the changes in jejunum and ileum were similar, and it may contribute to the development of malnutrition in chronic alcoholics.

Animals↗
PubMed1987

Effect of chronic ethanol intake on lactase activity and active galactose absorption in rat small intestine.

The effects of feeding a nutritionally adequate liquid diet containing 5% ethanol to rats over a four week period on intestinal lactase activity and the kinetics of jejunal galactose absorption in vivo have been determined. Both lactase activity and the maximum capacity for active, saturable galactose absorption (Jmax) were increased significantly after chronic ethanol ingestion. In contrast, uptake of the sugar via the phlorhizin-insensitive (passive) route was unaffected by ethanol. Our results imply the presence of an increased maturity of the enterocyte population on the villus surface in response to ethanol. The relevance of this work to uptake studies in alcoholics is briefly discussed.

Animals↗