[Territorial organization of a surveillance system for the patient at risk of sudden death].
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Death, Sudden↗
Biomedical subjects
R Tongiani
Publications and source records attributed to R Tongiani.
Metyrapone modulation of tyrosine aminotransferase induction by dexamethasone in cultured hepatocytes.
Metyrapone, an inhibitor of cytochrome P-450-dependent monooxygenases, enhanced the induction of tyrosine aminotransferase by dexamethasone in primary cultures of hepatocytes, while it had no effect on the basal level of the enzyme activity in the absence of the hormone. The amplification of the hormonal induction of tyrosine aminotransferase activity was strictly correlated with the concentration and with the inhibitory action of the compound on cytochrome P-450. The phenomenon occurred even at the maximally effective concentrations of dexamethasone, thus showing that metyrapone is a 'Glucocorticoid Potency Amplifier'. The dexamethasone activity amplification by metyrapone could be the consequence of a modulation of the glucocorticoid biotransformations due to the cytochrome P-450 inhibitor.
7-Alkoxycoumarin O-Dealkylase↗
Gamma-glutamyltransferase induction by dexamethasone in cytochrome P-450-depleted rat liver.
The effects of the cytochrome P-450 depletion by cobaltic protoporphyrin IX on the postnatal glucocorticoid-inducibility of the membrane-bound enzyme gamma-glutamyltransferase have been assessed in the rat liver. Dexamethasone-induced gamma-glutamyltransferase activity in 14-, 28- and 77-day-old rats was high, weak and absent, respectively, and inversely correlated with the physiological cytochrome P-450 activity. In the liver acinus, the enzyme was reexpressed by the zone 1 and zone 2 hepatocytes in suckling rats, substantially only by the zone 1-hepatocytes in just weaned rats. Following cytochrome P-450 depletion, gamma-glutamyltransferase induction by dexamethasone was more rapid, more intense and more extended in the liver acinus, occurring also in the zone 3 hepatocytes in suckling rats, in the zone 2 and a few zone 3 hepatocytes in just weaned rats. Further, the enzyme induction occurred also in adult rats in the zone 1 and in some zone 2 cells. This shows that cytochrome P-450 modulates the extent of hepatic gamma-glutamyltransferase induction by dexamethasone in postnatal rat-hepatocytes. The phenomenon may be consequent on hormone biotransformation changes caused by the cytochrome P-450 depletion.
7-Alkoxycoumarin O-Dealkylase↗
Dexamethasone induction of gamma-glutamyl transferase in primary cultures of hepatocytes is enhanced by metyrapone.
Metyrapone, a cytochrome P-450 inhibitor, reduces by about 3,000 times the dexamethasone concentration required to cause a maximal induction of gamma-glutamyltransferase in adult rat hepatocyte cultures, in itself having no inducing activity. Metyrapone effect decreases as dexamethasone concentration approaches the optimally inducing one. Metyrapone action on low DEX concentrations is dose-dependent while inhibiting 7-ethoxycoumarin O-deethylation by 20% to 75%. At the same doses, metyrapone amplifies also the effects of all the hormonal concentrations inducing tyrosine aminotransferase. These phenomena may be triggered by a modulation of the glucocorticoid biotransformation effective at both transcriptional and translational levels.
7-Alkoxycoumarin O-Dealkylase↗
Gamma-glutamyltransferase induction by glucocorticoids in rat liver: age-dependence, time-dependence, dose-dependence, and intralobular distribution.
Postnatal responsiveness of rat-liver gamma-glutamyltransferase (GGT) to glucocorticoids (GC) has been defined by investigating: age-dependence, time-dependence, hormonal dose-dependence, and lag-time of the enzyme re-expression; half-life of the induced enzyme activity; dynamics of the enzyme reappearance in the liver tissue. Hydrocortisone-acetate (HC) or dexamethasone (DEX) were administered to the animals starting 1, 2, 3, 4, or 5 d before killing, at the doses of 25 micrograms or 1 microgram/(g b. w. x d), respectively. In 14 d old rats, after a lag-time of about 20 h (DEX) or 30 h (HC), GGT activity progressively increased up to 38 and 31 times the control value, respectively, at 5th d; the enzyme re-expression was linearly hormone dose-dependent; half-life of the induced enzyme activity was about 36 h. In 21 d old rats, GGT re-induction behaved as in 14 d old animals, except that the induced activity was about half that of each correspondent treatment. In 28 d old rats, a very low but significant GGT activity was re-expressed only after hormonal treatments longer than 48 h. In 35 and 77 d old rats, significant GGT activity was never re-induced. GGT was re-expressed in liver parenchyma, with a defined space-course. In 14 d old rats, GGT reappeared first in periportal areas, then in acinar zone 1, finally in acinar zone 2. While the animals were ageing, GGT re-expression occurred to lesser and lesser extents in liver tissues, because of a progressive space-restriction from acinar zones 1 and 2 to zone 1 and finally, in 35 d old rats, to periportal areas. In adults, GGT was re-expressed only by rare hepatocytes in periportal spaces. Acinar zone-3 hepatocytes did never re-express GGT, irrespectively of the animal age. Thus, 2 rat hepatocyte populations could be distinguished (1 responsive, the other unresponsive to GC for GGT re-expression), the relative proportion of which changes in favour of the unresponsive one while the animal ages. Hepatic GGT re-induction by GC, occurring after a long lag-time, does not follow the typical model of hormonal induction. Previous permissive cell changes seem to be required. Hepatocyte-GGT re-expression by GC appears to be inversely correlated with the differentiation level and the cytochrome P-450 amount (activity) of the cell as limiting factors for the triggering of the enzyme induction.
Aging↗
Cytological and quantitative cytochemical changes in the hepatocyte population of newborn rats following hydrocortisone administration.
Changes have been assessed in cytological and quantitative cytochemical parameters of the hepatocyte population of newborn rats under glucocorticoid stimulation. Administration of hydrocortisone-acetate at the dose of 25 micrograms/g b.w./d during the 2nd week of postnatal life, caused: 1. an increase of the liver weight and of average dry mass, protein content, and volume of the hepatocytes; 2. a decrease of the number of hepatocytes per mg of liver tissue; 3. a reduction of the mitotic activity in liver parenchyma; 4. a gain in number of hepatocytes per liver lower than under normal conditions; 5. an increase of frequency of binuclear cells; 6. an increase of DNA-Feulgen per hepatocyte nucleus; 7. an increase per cell, greater than the mean protein increase per cell, in activity of arylhydrocarbonmonooxygenase and 7-ethoxycoumarin 0-deethylase, 2 enzymes dependent on cytochrome P-450. Induction of arylhydrocarbonmonooxygenase activity was prevalent in centrolobule. All the examined parameters, except that of DNA-Feulgen per nucleus and that of mitotic activity, changed strictly correlated with the duration of hormonal treatment. The values of a number of hepatocyte parameters (particularly: mean cell dry mass and volume, frequency of binuclear cells, enzymic activity) detected in the 12 d old rats after a 5 d long hormonal pretreatment, were in the range of those of animals 1 to 2 weeks older.
Animals↗
Changes in protein sulfur groups in hepatocytes of newborn rats under glucocorticoid stimulation.
A daily administration of hydrocortisone-acetate (25 micrograms/g b.w.) increased both dry mass and protein content of the hepatocytes of newborn rats by 84% and 89% respectively, after 5-day-treatment. The increase correlated with the duration of hormonal treatment. As an average per cell, the total reactive protein sulfur increased up to 127%. This increase depends on a major increment of thiols (+179%) and on a minor increment of disulfides (+18%). Within the thiols, the fast reactive ones exhibited the most pronounced increment (+214%). Per protein unit, the total reactive sulfur increased, after a 1 day lag period, by up to +20%. Thiols showed a 47%-increment due to increase of fast reactive thiols (+70%) more than of slow reactive thiols (+20%). On the contrary, disulfides decreased (-37%). Consequently, the protein thiol/disulfide ratio shifted from 2.14 in control hepatocytes to 4.98 (+133%) in hormone-stimulated hepatocytes. Both the increase of the thiol content, and the shift of the SH/SS-equilibrium of the cellular proteins, correlated with a concomitant increase of enzymic activities such as gamma-glutamyltranspeptidase, glutathione reductase, glutathione peroxidase, glutathione S-transferase and 7-ethoxycoumarin O-deethylase.
Age Factors↗
Gamma-glutamyltranspeptidase induction by cortisol in liver parenchyma of unweaned rats.
In contrast to many differentiated hepatic functions developing after birth, very little is known about in vivo glucocorticoid influences on postnatal expression of fetal liver enzymes, such as GGT. This study showed that cortisol markedly induces liver GGT activity in unweaned rats, but has no effect after weaning. Enzyme induction was dose- and time-dependent and occurred in parenchymal cells, progressing with time from zone 1 to zone 2 of the liver acinus. Zone-3 hepatocytes were unresponsive even after a 5-day treatment. Lag-times for GGT induction in zones 1 and 2 of the liver acinus were 1 to 2 days and 2 to 3 days, respectively. From this, a permissive cell change, determined by the hormone administration itself, seems required for the hepatocyte GGT induction by cortisol in pre-weaning rats.
Animals↗
Circadian rhythm of dry mass and weight-class-pattern of the rat hepatocytes--effects of light-dark and feeding regimens.
1. Dry weight has been determined of individual hepatocytes isolated from rats kept at natural or at reversed daily light-dark cycle, and from rats under time-restricted feeding. Behaviours of liver weight, mitotic activity and binuclearity frequency of the hepatocytes and serum corticosterone have been also investigated. 2. At natural light-dark cycle, liver weight, hepatocyte mitotic activity, and serum corticosterone were higher during the day than during the night. In accordance, dry weight and class number of the hepatocytes were both higher by day than by night. 3. By reversal of the light-dark cycle, circadian rhythms of liver weight, hepatocyte mitotic activity and serum corticosterone underwent a reversal. In accordance, circadian rhythm also reversed of both dry mass of the hepatocytes, which became heavier by night than by day, and pattern of the hepatocyte weight-classes, which became sharper, more discrete and more numerous by night, less defined and lower in number by day. 4. Feeding restriction to early morning or to late afternoon did not affect substantially the circadian rhythms of the parameters examined. 5. Binuclear cell frequency did never differ significantly at midnight with respect to midday, irrespectively to the experimental condition. 6. Regulation of the circadian rhythm of both weight-class pattern and dry mass of the hepatocytes appears to be mainly acted by the light-dark regimen likely via modulation of the plasma glucocorticoids (corticosterone) concentration, and increase/decrease of which causes a decrease/increase of the total solid content of hepatocytes, with redistribution of cells in the weight-classes. 7. Feeding rhythm and time elapsed from food intake mainly influence definition of the individual weight-classes and weight range of the hepatocytes.
Animals↗
Microinterferometric characterization of cells isolated from primary hepatomata and from allografts of hepatomata by 4-dimethylaminoazobenzene.
Distribution of individual cells according to their solid protoplasmic content has been determined in cell populations isolated from two primary hepatomata by 4-dimethylaminoazobenzene (DAB) and from subcutaneous allografts of two others DAB hepatomata carried for years as transplant lines in rats. In nodular (neoplastic) tissue of the primary hepatomata, the cells maintained the typical distribution of the mammalian hepatocytes in a weight class pattern, but (i) the number of cell clases was reduced due to disappearance of the heavier cells and (ii) the frequency of the light cells was markedly increased with respect to the findings in anodular (non-neoplastic) liver tissue. In the allografts the great majority of the cells had a small content in solids and were normally grouped in one class. It is suggested that a delay in the cell differentiation may be responsible of this change.
Animals↗
A quantitative cytochemical study of isolated epithelial cells of the hamster cheek pouch.
1. Dissociation of the hamster cheek pouch epithelium by a method combining trypsin attack and EDTA exposure, yielded a mixture f highly viable isolated cells (basal, spinous, and granular cells). 2. Such heterogeneous cell population was reproducibly separated into 4 fractions by pycnic sedimentation: in order of increasing density, Fraction I and Fraction II predominantly contained cells of the basal layer (93% and 76%, respectively), Fraction III basal, spinous and granular cells in equivalent concentration, Fraction IV mainly granular cells (69%). Horny squamae sedimented at the bottom of the tube. 3. Individual cells of the whole population and those of the population fractions separated by density gradient, were analyzed and charcterized as regards morphology, viability, volume, dry mass, density and DNA synthesizing ability. 4. A positive correlation was found between morphology, dry mass and density of the cells, showing that differentiation occurs by increments in mass and density. The weights of the basal, spinous and granular cells were distributed within ranges well defined and scantily overlapping, and were positively correlated with cell differentiation. Also cell density increased with differentiation degree. On the contrary, volume distribution of the various types of cells showed differences of minor importance, indicating for an increase of solids concentration in the more differentiated cells. 5. DNA synthesis took place only in basal cells, the density of which was generally very low.
Animals↗
Dry weight, triglycerides content and glucose-6-phosphatase activity of hepatocytes separated by sedimentation.
1) Isolated rat-hepatocytes were subfractionated by isopycnic or velocity sedimentation, and dry mass, triglycerides content and Glucose-6-Phosphatase activity of different subpopulations were determined. 2) Distribution of the cell dry masses and dry mass per average cell were substantially similar in all the fractions separated by isopycnic sedimentation. Velocity sedimentation allowed a satisfactory separation of cells of different dry mass. 3) Triglycerides content and Glucose-6-Phosphatase activity of cells of the different fractions obtained by isopycnic sedimentation showed no statistically significant difference. Subpopulations fractionated by velocity sedimentation differed in both triglycerides content and Glucose-6-Phosphatase activity, which were substantially parallel to the cell dry mass.
Animals↗
Effects of phalloidin and alpha-amanitin on the total solid content of isolated hepatocytes.
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Amanitins↗
Effects of dibenzothioline and silymarin on the dry weight of isolated hepatocytes of rats acutely poisoned with phalloidin and alpha-amanitin.
The protective action of dibenzothioline and silymarin in the acute intoxication by phalloidin and alpha-amanitin has been studied on the basis of their ability to attenuate changes in dry mass distribution and class-pattern of the hepatocytes, as evaluated by microinterferometry. Protective agents were given to male rats 30 min before toxin, and the animals were sacrificed 3.0 h later. Both dibenzothioline and silymarin markedly counteract the toxic action of phalloidin and alpha-amanitin on the hepatocyte population, as revealed by a substantial prevention (a) of the striking displacement of hepatocytes in the intervals among the classes as regards phalloidin poisoning, and (b) of the number decrease of hepatocyte classes due to disappearance of the heaviest ones, of the shift of hepatocytes to the lighter classes, of the appearance of very light cells, of the displacement of hepatocytes into the class intervals and of the decrease in nuclear dry mass as regards alpha-amanitin. It is suggested that dibenzothioline and silymarin exert their protective action by a non-specific stabilization of the cell membrane.
Amanitins↗
[Effect of silymarin on the total dry mass of hepatocytes inacute poisoning by phalloidin and alpha-amanitine (author's transl)].
The effects of silymarin on the total dry mass and class pattern of rat hepatocytes have been studied during acute poisoning by phalloidin and alpha-amanitine. Phalloidin (2/5 of the LD50) after 3 h causes a marked change in the hepatocyte class pattern due to a displacement of a high percentage of cells in the intervals among classes, while the cell dry mass increases slightly. alpha-Amanitine (1/4 or 1/2 of the LD50) after 3 h causes a decrease in the number of classes of hepatocytes due to a disappearance of the heavier ones, a displacement of cells in the intervals among classes, an appearance of very light cells, and a decrease by about 25% in the mean dry mass of the hepatocytes. Silymarin, administered 30 min before poisoning, prevents all the changes due to 2/5 of the LD50 of phalloidin and to 1/4 of the LD50 of alpha-amanitine, and strongly reduces the effects of 1/2 of the LD50 of alpha-amanitine. The effects of alpha-amanitine and phalloidin and the protective action of silymarin on the dry mass and class pattern of hepatocytes are discussed.
Amanitins↗
[Interference of rifampicin on liver cytology].
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Animals↗
Hepatocyte population dynamics during hydrocortisone and thioacetamide treatment.
The orderly organization in a number of discrete classes of weight persists in the hepatocytes during acute and chronic poisoning with thioacetamide and during a prolonged treatment with hydrocortisone, though many striking cytological and structural changes occur in the liver. The number of hepatocyte classes decreases under hydrocortisone treatment and during acute and chronic thioacetamide poisoning, and increases during recovery after acute thioacetamide poisoning and during the late phases of chronic thioacetamide poisoning. This is due to decrements and increments in dry mass of the hepatocytes, which occur by steps, through repeated losses and additions of a constant amount of solids substantially corresponding to the class period. Such a mechanism is similar to that acting in the hepatocyte atrophy due to starvation and in the hepatocyte enlargement occurring during postnatal development. Therefore, the increment and the decrement in dry mass by defined steps takes place in the hepatocytes in both physiological and pathological conditions.
Acetamides↗
Separation of the hepatocyte weight classes by gradient centrifugation [proceedings].
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Animals↗