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Biomedical subjects

A Benedetti

Publications and source records attributed to A Benedetti.

At least 163 records · Page 9Linked to original sources

MgATP-dependent, glucose 6-phosphate-stimulated liver microsomal Ca2+ accumulation: difference between rough and smooth microsomes.

Some features of the MgATP-dependent Ca2+-accumulating capacity of rough as compared to smooth liver microsomal fraction were studied. Smooth microsomes accumulate somewhat higher amounts of Ca2+ than rough ones in the presence of MgATP. In the presence of glucose 6-phosphate, which markedly stimulates MgATP-dependent Ca2+ accumulation in both fractions, smooth microsomes exhibit a much higher Ca2+-accumulating capacity than rough ones. Possible reasons of the differences observed between the two fractions were investigated. Smooth microsomes exhibit a higher Ca2+-dependent ATPase activity, suggesting a higher Ca2+ inward transport into smooth vesicles. Also, following the inhibition of active Ca2+ transport by means of vanadate, smooth microsomes appear to release the Ca2+ previously accumulated--both in the absence (i.e., with MgATP only) and in the presence of glucose 6-phosphate--at a lower rate than rough ones. This indicates a lower passive backflux of Ca2+ accumulated in smooth vesicles. On the basis of these data, differences can be envisaged with respect to cellular Ca2+ handling by different domains of endoplasmic reticulum in the liver.

Adenosine Triphosphate↗

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↗

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↗

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↗

Computed tomography of epidural fibrosis after discectomy: a comparison between symptomatic and asymptomatic patients.

The evaluation of patients with symptoms recurrent after disc surgery is a difficult diagnostic problem. The most common causes are recurrent herniation and postoperative scarring; routine x-ray and myelographic differentiation between herniation and scarring is difficult or impossible. High resolution computed tomography (CT) has shown some results in the evaluation of postoperative patients, but the role of epidural fibrosis in failed back surgery syndrome (FBSS) is not clear. Some knowledge of the "normal" CT physiological healing and scarring after disc surgery is necessary. We scanned 20 asymptomatic operated patients and 20 patients with recurrent sciatic nerve pain after disc surgery who did not have bony stenosis, recurrent disc herniation, or other causes of FBSS. Our observations showed no important differences in the fibrosis demonstrated by CT between symptomatic and asymptomatic patients. The degree and type of fibrosis are not related to recurrent symptoms.

Adult↗

Stimulatory effect of glucose 6-phosphate on the non-mitochondrial Ca2+ uptake in permeabilized hepatocytes and Ca2+ release by inositol trisphosphate.

The relationships between Ca2+ transport and glucose-6-phosphatase activity, previously studied in isolated liver microsomes, were investigated in permeabilized hepatocytes in the presence of mitochondrial inhibitors. It was found that the addition of glucose 6-phosphate to the cells markedly stimulates the MgATP-dependent Ca2+ uptake. A progressive increase in the stimulation of Ca2+ uptake was seen with increasing amounts of glucose 6-phosphate up to 5 mM concentrations. Vanadate, when added in adequate concentrations (20-40 microM) to the hepatocytes inhibits both the glucose-6-phosphatase activity and the stimulation of Ca2+ uptake by glucose 6-phosphate, while not affecting the MgATP-dependent Ca2+ uptake. The addition of inositol 1,4,5-trisphosphate to permeabilized hepatocytes in which Ca2+ had been accumulated in the presence of MgATP and glucose 6-phosphate, results in a rapid release of Ca2+.

Animals↗

New technique for three-dimensional linear accelerator radiosurgery.

A new method for external stereotactic focal irradiation of three-dimensional irregular target volumes is proposed. In this method the target is irradiated by a linear accelerator set in various angular positions around the isocenter. During the irradiation the target is translated in a direction perpendicular to the beam. By controlling the velocity of the translation it is possible to modify the configuration of therapeutic isodoses so as to make them follow the borders of the target.

Brain Diseases↗

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↗

Linear accelerator radiosurgery of arteriovenous malformations.

Forty-five patients affected by cerebral arteriovenous malformations not suitable to open surgery have been treated by a radiosurgical technique employing a linear accelerator. One-year follow-up angiography is available for 10 cases. Therapeutic effect of focalized irradiation is presented.

Adolescent↗

Bromotrichloromethane-induced damage to bronchiolar Clara cells.

Administration of bromotrichloromethane (BrCCl3) to rats results in selective damage to bronchiolar non-ciliated Clara cells; ciliated bronchiolar cells and pneumocytes were unaffected. The cellular alterations begin very early (10 min) after poisoning. Lipid peroxidation, as measured by the malonic dialdehyde (MDA) content in the lung, is greatly increased 10 min after BrCCl3 administration. A histochemical technique to detect, in vitro, lipid peroxidation in frozen sections was used to demonstrate whether sufficient activation of BrCCl3 occurs in lung tissue. The positivity for the histochemical reaction was observed in bronchiolar epithelium in which cytochrome P450-dependent monooxygenase activity is predominantly located. The data obtained strongly support that BrCCl3 is highly metabolized in bronchiolar Clara cells.

Animals↗

Detection of 4-hydroxynonenal and other lipid peroxidation products in the liver of bromobenzene-poisoned mice.

Lipid peroxidation in cellular membranes leads to the formation of toxic aldehydes. One product provided with particular reactivity has been identified as 4-hydroxynonenal and thoroughly studied as one of the possible mediators of the cellular injury induced by pro-oxidants. In the present study we have searched for the presence of 4-hydroxynonenal and other lipid peroxidation products in the liver of bromobenzene-poisoned mice, since under this experimental condition the level of lipid peroxidation is much greater than in the case of CCl4 or BrCCl3 hepatotoxicity. 4-Hydroxynonenal was looked for in liver extracts as either free aldehyde or its 2,4-dinitrophenylhydrazone derivative. In both cases, by means of thin-layer chromatography (TLC) and high-pressure liquid chromatography, a well resolved peak corresponding to the respective standards (free aldehyde or 2,4-dinitrophenylhydrazone derivative) was obtained. Total carbonyls present in the liver of intoxicated animals were detected as 2,4-dinitrophenylhydrazone derivatives. The hydrazones were pre-separated by TLC into three fractions according to different polarity (polar, non-polar, fraction I, and non-polar, fraction II). The amounts of carbonyls present in each fraction were determined by ultraviolet-visible spectroscopy. 'Non-polar carbonyls, fraction II' were further fractionated by TLC. The fraction containing alkanals and alk-2-enals was analyzed by high-pressure liquid chromatography and several aldehydes were identified. In addition, protein bound carbonyls were determined in the liver of bromobenzene-treated mice. The biological implications of the finding of 4-hydroxynonenal and other carbonyls in vivo in an experimental model of hepatotoxicity are discussed.

Aldehydes↗

Studies on the mechanism of formation of 4-hydroxynonenal during microsomal lipid peroxidation.

The mechanism of the formation of 4-hydroxynonenal through the NADPH-linked microsomal lipid peroxidation was investigated. The results were as follows: 4-hydroxynonenal arises exclusively from arachidonic acid contained in the polar phospholipids, neither arachidonic acid of the neutral lipids nor linoleic acid of the polar or neutral lipids are substrates for 4-hydroxynonenal generation. This finding results from the estimation of the specific radioactivity of 4-hydroxynonenal produced by microsomes prelabelled in vivo with [U-14C]arachidonic acid. Phospholipid-bound 15-hydroperoxyarachidonic acid would have the structural requirements needed for 4-hydroxynonenal (CH3-(CH2)4-CH(OH)-CH=CH-CHO). Microsomes supplemented with 15-hydroperoxyarachidonic acid and NADPH, ADP/iron converted only minimal amounts (0.6 mol%) of 15-hydroperoxyarachidonic acid into 4-hydroxynonenal; similarly, 15-hydroperoxyarachidonic acid incubated at pH 7.4 in the presence of ascorbate/iron yielded only small amounts of 4-hydroxynonenal with a rate orders of magnitude below that observed with microsomes. Phospholipid-bound 15-hydroperoxyarachidonic acid is therefore not a likely intermediate in the reaction pathway leading to 4-hydroxynonenal. The rate of 4-hydroxynonenal formation is highest during the very initial phase of its formation and the onset does not show a lag phase, suggesting a transient intermediate predominantly formed during the early phase of microsomal lipid peroxidation. After 60 min of incubation, 204 nmol polyunsaturated fatty acids (20 nmol 18:2, 143 nmol 20:4, 41 nmol 22:6) were lost per mg microsomal protein and the incubation mixture contained 206 nmol lipid peroxides, 71.6 nmol malonic dialdehyde and 4.6 nmol 4-hydroxynonenal per mg protein. Under artificial conditions (pH 1.0, ascorbate/iron, 20 h of incubation) not comparable to the microsomal peroxidation system, 15-hydroperoxyarachidonic acid can be decomposed in good yields (15 mol%) into 4-hydroxynonenal. Autoxidation of arachidonic acid in the presence of ascorbate/iron gave after 25 h of incubation 2.8 mol% (pH 7.4) and 1.5 mol% (pH 1.0) 4-hydroxynonenal. The most remarkable difference between the non-enzymic system and the enzymic microsomal system is that the latter forms 4-hydroxynonenal at a much higher rate.

Aldehydes↗

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↗

Our experiences in early aneurysm operations: a preliminary report.

Twenty-seven patients affected by ruptured aneurysms and operated on within three days of the first haemorrhage, are presented. At operation 22 patients were graded I-II; a six months follow-up showed a 22% mortality rate. Five patients were graded III-IV at operation and none survived. The results of early operation in our series are examined and discussed. In our opinion it is necessary to know the results of other larger series in order to obtain a final evaluation of early operations on aneurysms.

Adult↗