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Biomedical subjects

F Orlandi

Publications and source records attributed to F Orlandi.

At least 91 records · Page 5Linked to original sources
PubMed1988

Preferential distribution of apoptotic bodies in acinar zone 3 of normal human and rat liver.

The aim of the present investigation was to study the number and acinar distribution of apoptotic bodies in normal liver as an approach to a better understanding of cell kinetics in the hepatic parenchyma. The material included 20 normal human needle liver biopsies and 20 normal male Sprague-Dawley rats. For each liver sample, the following parameters were measured: number of apoptotic bodies in the lobule, topographical localization, and distance from terminal hepatic veins (THV), i.e., the row of hepatocytes concerned, H1 being the closest to the THV. The results were strikingly similar in human and in animal material, showing that apoptotic bodies are rare in the normal liver and, when present, are always observed in zone 3, next to the THV. In fact, the first two rows of hepatocytes (H1 and H2) contained 80% of the apoptotic bodies in human liver, and 95% in rat liver. These data show that apoptotic bodies are not randomly dispersed in normal liver tissue but show a preferential acinar distribution. In addition, the vast majority of apoptotic bodies are located in the row of liver cells immediately adjacent to the THV. If apoptosis is indeed an expression of physiological cell renewal or 'programmed cell death', these findings support the concept of an aging gradient of liver cells, with zone 3 containing older hepatocytes.

Adult↗
PubMed1988

Subcellular changes and apoptosis induced by ethanol in rat liver.

The livers of rats given ethanol for 5 weeks showed marked structural alterations of hepatocytes of acinar zone 3 including mitochondrial pleomorphism, increased smooth endoplasmic reticulum and deposition of small (less than 0.5 micron) lipid droplets. In addition, apoptotic bodies involving altered parenchymal cells were frequently observed, together with prominent mononuclear infiltrates adjacent to the terminal hepatic veins. It is suggested that 'age' of liver cells may play a role in the preferential perivenular localization of early ethanol-induced liver damage.

Animals↗
PubMed1988

A quantitative evaluation of apoptotic bodies in rat liver.

The aim of the present study was to determine if data on the number and acinar distribution of apoptotic bodies (AB) in normal liver could help in the understanding of cell kinetics in the liver, and the mechanism of early ethanol-induced liver damage. Normal male Sprague-Dawley rats were studied. They had free access to Purina chow and drinking water. Ethanol-treated rats received the drug at increasing concentration in drinking water for 5 weeks. The following parameters were measured: number of AB in the lobule, topographical localization, distance from terminal hepatic veins (THV), i.e. row of hepatocytes concerned, H1 being the closest to the THV. The results show that AB are rare in the normal liver and are always observed in zone 3, next to the THV. Of 149 THV examined, 56 showed one associated AB, exceptionally two. 74% of the AB were confined to the first row of hepatocytes (H1), 21% to H2, 4% to H3, and 1% to H4. In ethanol-treated rats the mean number of AB was 2 or 3 for each THV. 42% were found in H1, 32% in H2, 15% in H3, 7% in H4, and 4% in H5. The data show that AB are not randomly dispersed in normal liver but show a preferential acinar distribution. In addition, most AB are located in the row of liver cells immediately adjacent to the THV. If apoptosis is indeed an expression of physiological cell renewal, these findings support the concept that zone 3 contains older hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The effect of famotidine, a new H2 receptor antagonist, on antipyrine clearance in healthy volunteers.

The salivary clearance of Antipyrine (15 mg/kg p.o.) has been measured in nine healthy volunteers (5 males, 4 females) before and after 7 days treatment with Famotidine (40 mg/day at bedtime). Samples of saliva were collected twenty four hours after each dose of Antipyrine. The post-treatment sample was taken 12 hours after the last dose of Famotidine. The clearance of Antipyrine was measured by Gas-Liquid Chromatography using the simplified formula proposed by Dossing et al. (1982). After treatment with Famotidine, a slight but significant (p less than 0.01) increase of Antipyrine clearance was observed in eight out of the nine subjects, suggesting some interference of Famotidine with Antipyrine metabolism.

Adult↗
PubMed1987

Modification of lipid composition of erythrocyte membranes in chronic alcoholism.

The lipid composition and microviscosity of erythrocyte membranes have been studied in chronic alcoholics with macrocytosis and minimal liver dysfunction. The findings have been compared with those obtained in subjects with macrocytosis not related to ethanol abuse. In all instances, macrocytosis was accompanied by an increased microviscosity of erythrocyte membranes, together with an increase of the cholesterol/phospholipid and of saturated/unsaturated fatty acids ratio. Both microviscosity and saturated/unsaturated ratio were significantly higher in alcoholics compared to subjects with macrocytosis not related to ethanol abuse. These findings confirm that altered lipid composition and fluidity of erythrocyte membrane may be observed in chronic alcoholics with minimal liver dysfunction, possibly due to the "stabilising" properties of ethanol - among a number of drugs- on biological membranes.

Adult↗
PubMed1987

Shifted distribution of cation-related cyst types in post-menopausal patients with gross cystic disease of the breast.

Gross cystic disease of the breast (GCD) is rarely seen after the menopause. Recent work has shown that by measuring electrolytes in the breast cyst fluid (BCF) it is possible to identify two principal classes of cyst, designated Type 1 (K+/Na+ greater than 1.5) and Type 2 (K+/Na+ less than 0.66). A smaller, intermediate class (Type 3) also appears to exist. We measured K+, Na+ and dehydroepiandrosterone sulphate (DHA-S) in 38 BCF samples aspirated from 33 women with GCD who had undergone spontaneous menopause at least 1 yr previously. Statistically significant correlations were found between DHA-S and cations (positive in relation to K+, P less than 0.001; negative in relation to Na+, P less than 0.001). The distribution of cyst types was shifted with respect to that characteristic of cases that occur at an earlier age: whereas Type 1 cysts predominate in menstruating women, Type 2 cysts proved more numerous in the post-menopausal subjects. The difference was statistically validated (P less than 0.001). The results seem to indicate a sharp reduction in high K+, high DHA-S cysts after the menopause, which may be paralleled by a decrease in the associated apocrine metaplasia. In view of the major biochemical differences between Type 1 and Type 2 cysts and of the suggested differences as regards cancer risk, classification of post-menopausal patients with GCD by cyst type is critical prior to any clinical trial or follow-up.

Adult↗
PubMed1987

A morphological study of the early stages of hepatic fibrosis induced by low doses of dimethylnitrosamine in the rat.

Hepatic fibrosis has been induced in rats by low doses of dimethylnitrosamine (DMN) and special attention has been paid to early morphological events. DMN (10 microliter/kg body wt., i.p.) was given 3 days a week for 3 weeks to Sprague-Dawley rats. Liver samples were taken on days 7, 14, 21, 28 and 35 and examined by light and electron microscopy. Hemorrhagic necrosis, mainly centrolobular, was evident on day 7, with disruption of the sinusoidal lining, and widening or disappearance of the spaces of Disse invaded by erythrocytes and lymphocytes. Large granular lymphocytes similar to pit cells were also present in close contact with hepatocytes. At day 14, fibrotic septa were associated with cells bearing 'transitional' features between those of lipocytes, myofibroblasts and fibroblasts. Hepatocytes showed foci of increased smooth endoplasmic reticulum, and altered sinusoidal and canalicular membranes. At day 21, all animals showed nodularity of the parenchyma, with evidence of micronodular cirrhosis associated with ascites in two animals. At day 35 (19 days after cessation of treatment) there was little residual inflammation, but well-defined micronodules were still present in all animals. This shows that, in the rat, 3-week treatment with a low dose of DMN produces micronodular cirrhosis following diffuse hemorrhagic necrosis without steatosis. The response of the animals was uniform and reproducible. Lesions of the sinusoidal wall and of membranes of liver cells associated with the inflammatory reaction appeared prominent.

Animals↗
PubMed1986

Effect of chronic ethanol abuse on the physico-chemical properties of erythrocyte membranes in man.

Chronic alcoholics (greater than 150 g/day) showing minor serum and histological changes have been studied, compared to healthy non alcoholic subjects, and the following parameters have been considered: S. (Serum)cholesterol (CH), S.phospholipids (PH), S.folate level, and mean corpuscular volume (MCV). Erythrocyte ghosts have been studied for CH and PH content and membrane fluidity using diphenylhexatriene as a probe. All alcoholics showed decreased fluidity of red cell membrane with increased CH/PH ratio, even in patients showing normal MCV or minimal alterations of functional tests, suggesting that changes in red cell membrane fluidity represent an early sign of ethanol abuse. These likely reflect the diffuse interaction of ethanol with biological membranes. The administration of N5-Methyltetrahydrofolate produced an increase of membrane fluidity over the 3 weeks considered, associated with modest changes of MCV. The latter were delayed with respect to changes in fluidity. If changes of red cell membrane fluidity are a sensitive index of alcohol abuse, they could be a useful marker for detection and follow-up of chronic alcoholism.

Adult↗
PubMed1986

Cations and dehydroepiandrosterone-sulfate in cyst fluid of pre- and menopausal patients with gross cystic disease of the breast. Evidence for the existence of subpopulations of cysts.

Cations (K+ and Na+) content was evaluated in 444 breast cyst fluid (BCF) specimens, aspirated from 391 patients with gross cystic disease of the breast (GCD), a benign form admittedly at major risk of cancer. In 306/444 BCF, dehydroepiandrosterone-sulfate (DHA-S) content was also evaluated. A positive correlation (P less than 0.001) was observed between log K+ vs. log DHA-S whereas a negative correlation was found between log Na+ and log DHA-S (P less than 0.001). Cysts were subdivided in three types according to their cationic concentration: most were of type I (K+/Na+ greater than 1.5) and type II (K+/Na+ less than 0.66) whereas only 10% was of the type III (intermediate). No statistical difference in subtype distribution was apparent when considering patients aspirated in the follicular vs. luteal phase of the menstrual cycle; on the contrary, a significant difference (P less than 0.001) was found between menstruating vs. menopausal patients (type I = 54.8% vs. 32.2%; type II = 34.5% vs. 58.1%, respectively). Ninety-four BCF samples were aspirated simultaneously in 41 patients bearing multiple cysts: the same cationic subtype was present in 29/41 patients. Our data confirm and extend previous observations, and provide conclusive evidence that breast macrocysts can be divided on the basis of their electrolyte composition into different types. Accordingly, the composition of BCF should always be assessed for prospective studies on GCD and breast cancer risk.

Adult↗
PubMed1986

The fate of electron opaque tracers (horseradish peroxidase and lanthanum chloride) during valproic acid-induced choleresis.

Horseradish peroxidase (HRP) and lanthanum chloride (LaCl3) are useful tools for, respectively, the study of vesicular transport through the hepatocyte and the study of the permeability of junctional complexes. These tracers have been used to detect the changes associated with the choleresis independent of bile acids induced by valproic acid (VPA) in rats. The animals were given a single dose of VPA (600 mg/kg, ip). HRP (100 mg/kg) or 5 mM LaCl3 were given intraportally after 1 h, when bile flow had increased twofold. The excretion of HRP in bile was measured colorimetrically up to 2 h after HRP. Ultrastructural morphometry was conducted on liver of intact rats taken from 1 to 40 min after HRP. The volume density (VD) of HRP-containing vesicles and of HRP-containing multivesicular bodies (MVB) was counted. In VPA-treated rats, HRP appeared in bile with a peak showing at 5 min against 20 min in controls, but the total amount of HRP excreted was less than in controls. The intrahepatocytic vesicular transport of HRP was also modified, showing a peak at 3 min in VPA-treated rats compared to 10 min in controls, together with a decreased VD of pericanalicular vesicles. This was accompanied by an increase of HRP-containing MVB, already evident at 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[Radiologic aspects of the surface mucosa of the duodenal bulb. Correlation with the endoscopic and histological aspects].

Double contrast barium meal, endoscopy and histology of the duodenal bulb were blindly compared in 47 consecutive patients. The agreement in the judgement of normality of the mucosal surface between radiology and endoscopy was 78%. The agreement in the diagnosis of presence or absence of nodularity and thickened folds was respectively 91% and 87%. The findings of nodularity correspond to duodenitis with pyloric metaplasia or to heterotopic gastric mucosa, while the thickened folds correspond to duodenitis with pyloric metaplasia, Brunner's hyperplasia, lymphatic nodular hyperplasia or cystic glandular dilatation. The diagnostic errors in the radiological examinations in respect to endoscopy is quite important in the case of erosions.

Adult↗
PubMed1985

The effects of H2 receptor antagonists on hepatic microsomal drug metabolism and fine morphology of rat liver.

The study is concerned with the effects of cimetidine (C), ranitidine (R) and oxmetidine (O) on rat liver cells, in order to compare the effects of increasing amounts of the drugs on various metabolic pathways and on hepatocyte morphology, and their relationship with the drug structure, namely the presence of an imidazole or furan ring. In vitro, an inhibition of ethylmorphine N-demethylase (E-DM) (60%) and of aniline hydroxylase (A-OH) (20%) was observed when either C or R were added at a concentration higher than 0.5 mM to microsomes from untreated rats. Microsomes from phenobarbital or 3-methylcholanthrene-pretreated animals showed a 30 to 40% inhibition of E-DM (mixed type inhibition). In vivo, administration of a single dose (475 microM/kg) of R was followed by an inhibition of E-DM activity, significantly less pronounced (p less than 0.05) than following an equimolar amount of C, whereas O did not alter the enzymatic activity. The amount of cytochrome P-450 and the activities of NADPH cytochrome c reductase and of A-OH were substantially unaffected. No changes of smooth endoplasmic reticulum or of other liver cell organelles were observed by electron microscopy. These findings demonstrate that both in vivo and in vitro E-DM appears as the more sensitive among the pathways considered. Moreover the data support the view that the mere presence of the imidazole ring does not account for the inhibitory effect of H2 antagonists.

Animals↗
PubMed1985

Diagnostic value of the fibrosis of the terminal hepatic venule in fatty liver and chronic hepatitis due to ethanol or other aetiology.

The frequency of fibrosis of the terminal hepatic venule (FTHV) has been investigated by two observers unaware of the patient's history, in needle biopsy specimens showing normal histology (n = 23), alcoholic steatosis (n = 23), steatosis in diabetes or overweight (n = 26), alcoholic hepatitis (n = 21), or virus-related chronic active hepatitis (n = 44). FTHV was coded following a scale from 0 to 3 of severity. Minimal (grade 1) FTHV was seen in most venules of biopsies with a normal histological pattern, and was considered a normal feature. Grade 2 of FTHV was absent in the group showing normal histology but was evident in 17.4%-39.7% of the venules observed in the other groups without attaining diagnostic relevance. The percentage rate of severe (grade 3) FTHV was 0.0, 4.9, 6.6, 18.7 and 2.9 in the respective groups as delineated above. In alcoholic hepatitis, severe FTHV therefore showed a higher frequency than in virus-related chronic hepatitis (p less than 0.001), with high values of sensitivity (0.75), specificity (0.93), and predictivity (0.84 positive, 0.98 negative) for ethanol aetiology. The ethanol-related diagnostic value of FTHV however, was low in steatosis.

Diagnosis, Differential↗
PubMed1985

Prolactin and thyrotropin response to thyrotropin-releasing hormone in premenopausal women with fibrocystic disease of the breast.

Plasma PRL, TSH, total and free T4, total and free T3, and 17 beta-estradiol were evaluated in 29 premenopausal women with well-documented fibrocystic disease of the breast and in 29 healthy matched controls. Plasma PRL and TSH dynamics after acute TRH injection (200 micrograms i.v.) were also determined. All hormonal measurements were performed in the follicular phase of the menstrual cycle. Neither patients nor controls showed any thyroid function impairment. Basal plasma levels of the examined hormones were in the normal range in both groups. When considering data pertinent to PRL and TSH secretory patterns after TRH stimulation, no difference was recorded between patients and controls for TSH secretion, evaluated in terms of maximum peak, net (delta) and percent (delta %) increase above the baseline level and integrated area of response. On the contrary, the response of PRL was significantly higher in patients than controls (maximum peak at 20 min, mean +/- SE, 119.9 +/- 14.1 vs. 60.8 +/- 5.5 ng/ml, p less than 0.001; integrated area of response, 5,725 +/- 908 vs. 3,243 +/- 266 ng/ml/120 min, p less than 0.01). The results are compatible with the view that, in most patients with fibrocystic disease of the breast, there are abnormalities in the control of PRL secretion, which lead to enhanced release of the hormone after stimulation. In such cases the control of TSH appears to be operating normally.

Adult↗
PubMed1985

In vivo and in vitro inhibition of hepatic microsomal drug metabolism by ketoconazole.

Ketoconazole (KC), a broad spectrum antifungal drug, has been recognized recently as a cause of hepatic injury. The mechanism of the adverse reaction remains unclear: a metabolic idiosincrasy has been suggested. However as a substituted imidazole, KC might be expected to interfere with the hepatic microsomal mixed function oxidases. Ethylmorphine N-demethylase (E-DM) and aniline hydroxylase (A-OH) activities were determined in rat liver microsomes in the presence of increasing amounts of KC. Both were inhibited in an exponential fashion. The E-DM inhibition was almost complete at concentrations greater than 250 microM and was of the mixed type. A much weaker effect was observed for A-OH. A significant inhibition of E-DM was also observed when KC was administered in vivo to rats either orally for 7 days at the dose of 100 mg/kg/day (P less than 0.02) or intraperitoneally for 4 days at the dose of 50 or 100 mg/kg day (P less than 0.01 or P less than 0.001 respectively). A-OH activity was significantly reduced (P less than 0.01) only after ip administration of 100 mg/kg/day of the drug for 4 days. Neither the amount of cytochrome P-450 nor NADPH cytochrome c reductase activity were affected at the doses considered. These data show that KC interferes with hepatic oxidative drug metabolism and suggest that this mechanism might be involved in the unwanted side effects of therapy with KC.

Administration, Oral↗
PubMed1984

Changes induced in human liver by long-term anticonvulsant therapy. Functional and ultrastructural data.

The study reports functional and morphological findings in eight male subjects undergoing anticonvulsant therapy for periods from 20 days up to 15 years. All subjects showed an increased activity of the hepatic microsomal NADPH cytochrome c reductase and an increased amount of smooth membranes in hepatocytes. The enzymatic activity was higher in the first years of treatment. Quantitative ultrastructural analysis showed that a twofold increase of the smooth membranes of hepatocytes had already been reached after 20 days of therapy, with a modest additional increase occurring thereafter. Both enzymatic and structural changes appear to be related to therapy. In addition, abnormal lipofuscin-related cytoplasmic formations were present in the hepatocytes of five subjects. Such formations are thought to represent an accumulation of abnormal degradation products, possibly related to an interaction of the drug(s) metabolites with cellular components.

Adult↗
PubMed1984

Comparative effects of cimetidine on biliary lipid secretion in fasted and fed rats.

The effect of cimetidine on biliary lipid secretion has been investigated in fasted and fed rats with biliary drainage for 4 h after a single intraperitoneal administration at a dose of 120 mg/kg body weight. Bile flow, bile acids, cholesterol and phospholipids in bile have been determined. In intact rats similarly treated, serum bile acids, cholesterol and phospholipids have been determined. Biochemical and morphological studies have been conducted on the liver tissue in both experiments. Bile flow and bile acid secretion were not affected by cimetidine in fasted rats, but, 15 min after administration of the drug, fed rats showed an increase of the molar percentage of cholic acid together with a decrease of deoxycholic acid, a decreased secretion of cholesterol and an increased secretion of phospholipids. The values of these biliary lipids were in the range observed in fasted animals, so that the drug appeared to 'mimic' the effect of fasting. These findings could be related to altered vascular properties of the gastro-intestinal wall induced by cimetidine, leading to interference with intestinal postprandial hyperaemia and capillary permeability, so that there appears to be a conversion of bile composition from a digestive to an interdigestive pattern.

Animals↗