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Biomedical subjects

E Gaudio

Publications and source records attributed to E Gaudio.

At least 37 records · Page 2Linked to original sources

Hepatic microcirculation as a morpho-functional basis for the metabolic zonation in normal and pathological rat liver.

The hepatic microcirculation is well known as a fundamental component of the liver structure, deeply involved in the zonal organization of the acinar structure. In cirrhosis, the microvascular tree shows dramatic changes that would heavily influence the development of the disease. When the cirrhosis becomes evident the result is a progressive organ failure, also in presence of only moderately decreased hepatocyte volume. The aim of this research was to compare the role of microcirculation of the hepatic zonation in normal and cirrhotic livers. Cirrhosis was experimentally induced in 36 rats following a controlled intragastric CCl4 administration. Cirrhotic and control normal livers were processed for routine light microscopy, histoenzimology, and scanning electron microscopy vascular corrosion cast. Control livers showed normal hepatic structure and microvascularization; enzymatic activities were constantly and normally distributed. In CCl4-treated animals LM showed a characteristic micronodular cirrhosis in all livers. Vascular corrosion casts under the scanning electron microscope displayed a progressive reduction of the distance between pre- and post-sinusoidal vessels and the presence of newly formed perinodular plexus. The histoenzymatic analysis demonstrated the loss of zonation in the cirrhotic parenchyma. Moreover, the sinusoid/hepatocyte ratio was significantly reduced, because of the presence of two or more hepatocyte thick laminae during the scarring development. The altered microcirculation in cirrhosis also changed the normal acinous metabolic gradient. The histoenzymatic study revealed a zonal rearrangement of the cirrhotic liver metabolic activity, that leads to a progressive hepatic failure. These data confirm the fundamental importance of the normal relationship between the hepatocyte laminae and the sinusoids for the preservation of a normal zonation which represents the basis for a normal liver function.

Animals↗

Effect of taurohyodeoxycholic acid, a hydrophilic bile salt, on bile salt and biliary lipid secretion in the rat.

Taurohyodeoxycholic acid is a natural 6 alpha-hydroxylated bile acid with an apparent hydrophilicity intermediate between those of tauroursodeoxycholic and taurocholic acids. We investigated in the rat the hepatobiliary metabolism, choleretic properties, and biliary maximum secretory rate (SRmax) of taurohyodeoxycholic in comparison with these two bile salts. Each compound was infused intravenously, at a rate increased in a stepwise manner from 100 to 300 nmol/min/100 g body wt, in bile salt-depleted bile fistula rats. The three bile salts appeared rapidly starting with the infusion and increased to represent more than 95% of the total bile salts. No apparent biliary metabolites were formed. All the bile salts caused a dose-dependent increase in bile flow and biliary lipid output. The absolute increase in bile flow was lower in rats infused with taurohyodeoxycholic acid, yet the volume of bile formed per nanomole of secreted bile salt was 13.8 nl for taurohyodeoxycholic, 6.4 nl for tauroursodeoxycholic acid, and 10.9 nl for taurocholic. The SRmax values were 1080, 3240, and 960 nmol/min/100 g, respectively. At all infusion rates, taurohyodeoxycholic acid caused a greater (P < 0.001) secretion of biliary lecithin compared to the other bile salts. There were no significant differences in the biliary secretion of cholesterol and proteins. Electron microscopy showed the recruitment of vesicles and lamellar bodies around and within bile canaliculi. In conclusion, taurohyodeoxycholic promotes a biliary lecithin secretion greater than expected from physicochemical predictions, representing a novel secretory property with potential pharmacological relevance.

Animals↗

Scanning electron microscopy of collagen fiber orientation in the bone lamellar system in non-decalcified human samples.

Previous studies on collagen fiber orientation have led to different interpretations and theories about the fiber arrangement in the lamellar compact bone. The purpose of this investigation was to provide new and more in-depth data on fiber arrangement in the lamellar bone system in order to explain the orientation of the fiber bundles. This was carried out by applying a simple method of preparation which permitted observation of non-decalcified samples. A previously isolated Haversian system was subjected to slow bending up to reaching the fracture point. Hence, the fracture surface was observed by SEM. The same samples were also observed by polarized light microscopy. A significant alternation of fiber orientation in the adjacent lamellae was observed. Different domains of differently oriented fibers were present within the same lamella; conjugating fibers connecting adjacent lamellae were also shown. This method avoided most of the artifacts due to chemical treatment of bone samples. The results can be easily interpreted by means of the same criteria applied in mechanics for the studying of composite materials.

Adult↗

5HT2-receptors and serotonin release: their role in human platelet aggregation.

Involvement of 5HT2 receptors in human platelet aggregation was assessed by studying the effect of ADP, epinephrine and thrombin on 3H-5HT release from platelets. The release experiments were made with a perfusion method to preserve any compound, released or formed by platelet, from interacting with platelet itself. In these conditions, aggregation does not occur, as confirmed by Scanning Electron Microscopy. These release experiments showed that the platelet activation by such agents is coupled with 5-HT release. The aggregation experiments, made on different aliquots of the same platelet-rich plasma (PRP), showed that the released 5-HT, interacting with its own receptors on platelet activated surface, determines aggregation. In fact, although it is known that 5-HT added to PRP was only able to induce a moderate platelet aggregation, the 5-HT2 antagonist ketanserin counteracted the aggregation induced by ADP, epinephrine and thrombin. These results suggest that a 5HT2 antagonist could be therapeutically important in those pathological states in which serotonin, released by activated platelets, may increase aggregation.

Adenosine Diphosphate↗

Zinc supplementation in experimental liver cirrhosis: a morphological, structural and ultrastructural study.

Zinc treatment in liver cirrhosis is known to prevent a number of clinical symptoms. Previous studies have also indicated that Zn has a protective effect on the development of the clinical, biochemical and morphological manifestations of hepatic injury if administered simultaneously with the noxious agent. In this study, the protective effects of zinc treatment against the development of liver cirrhosis have been tested in cirrhotic rats treated by intragastric administration of CCl4. The development of morphological lesions has been investigated by means of standardized and comparable techniques, LM, TEM, SEM, microvascular casts and measurements of liver collagen content by colorimetric determination in paraffin embedded sections. LM and EM observations showed typical morphological features of cirrhosis in all CCl4 treated rats. In the same group of animals, the microvascular casts showed the development of the typical 'perinodular' branching and the various anastomoses of pre and post-sinusoidal vessels. Colorimetric evaluation has shown a significant increase in collagen content after CCl4 treatment. Qualitative and quantitative data of livers of CCl4 treated rats supplemented or not with zinc were significantly similar. In conclusion, zinc treatment influences biochemical parameters, but not the morphology of liver cirrhosis.

Animals↗

A scanning electron microscopic study of liver microcirculation disarrangement in experimental rat cirrhosis.

Hepatic microcirculation has been related to liver function in several studies. The principle of this relationship lies in the sequential distribution of blood from the feeding vessels of the hepatic acinus to the central vein. This study was undertaken to investigate the progressive changes at different sites of the liver microvascular bed in the developing cirrhosis, both by light microscopy and scanning electron microscopy of corrosion casts. Experimental cirrhosis was induced with intragastric carbon tetrachloride. The most important vascular changes progressively observed are the reduction of the distance between the pre- and postsinusoidal vessels, the presence of newly formed shunting vessels bypassing the sinusoids and, finally, the development of a perinodular vascular plexus composed of pre- and postsinusoidal vessels. Newly formed vessels grow through preformed tissue septa. These vascular modifications make any zonal gradient hardly possible. The loss of the zonal gradient of perfusion could highly modify liver function, along with the structural changes of hepatic laminae. Hepatocyte regeneration cannot recover the original vascular relationships: this makes the morphological and functional destructuralization of cirrhotic liver irreversible.

Animals↗

Cytoprotective drugs in the prevention of ethanol-induced experimental gastric mucosal damage: a morphological study.

Various so-called "cytoprotective" agents (sucralfate, carbenoxolone, 16,16-dimethyl-PGE2, sulglycotide and Maalox TC) have been tested on rats, with the aim of quantifying their capability to prevent ethanol-induced gastric mucosal damage. Rats fasted for 48 hours received 1 ml of 80% ethanol by oral gavage, after prior oral treatment with placebo or one of the above-mentioned drugs u.i.d. for 5 consecutive days. Six hours after ethanol administration, the animals were sacrificed and the stomach was removed and processed for computerized macroscopic assessment of the damaged surface and for structural (light microscopy) and ultrastructural (scanning and transmission electron microscopy) studies. The results obtained demonstrate that ethanol injury caused extensive mucosal necrosis of the glandular region of the stomach, an event that was effectively reduced in rats treated with 16,16-dm-PGE2, carbenoxolone or sulglycotide. These drugs appeared to preserve the mucosa, with morphology comparable to that of normal noninjured rats - in contrast to the other drugs investigated. These data confirm the cytoprotective properties of sulglycotide in particular, which was the most potent agent for preventing the development of ethanol-induced acute lesions of the gastric mucosa.

16,16-Dimethylprostaglandin E2↗

Microcirculation of the extrahepatic biliary tree: a scanning electron microscopy study of corrosion casts.

The microvascular arrangement of the extrahepatic biliary tree of the rat was studied by light microscopy (LM) and scanning electron microscopy (SEM) of vascular corrosion casts. The plexus that encircles the lumen of the common bile duct, observed by LM, showed a network of vessels of different diameter situated under the epithelium in the lamina propria. Parallel SEM observations of the same structure demonstrated the presence of 2 main vascular layers: an outer arterial and venous layer, corresponding to the larger vessels seen by LM, and a richer inner capillary layer just under the epithelium. On the luminal part of the corrosion casts, there were many round avascular empty pits that corresponded to the presence of small acinar glands distributed along the epithelium of the common bile duct. The rich subepithelial capillary network present in the rat, an animal without a gallbladder, may play an important role in the reabsorption of water and solutes from bile. Moreover, in pathological conditions (e.g. portal hypertension), liver blood flow may take a preferential collateral route through the intrahepatic peribiliary plexus into the relatively large diameter vessels of the extrahepatic peribiliary plexus because of the continuity of the 2 plexi.

Animals↗

Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis.

Zinc deficiency is common in cirrhosis and may be involved in the alteration of ammonia metabolism. Rats with carbon tetrachloride-induced cirrhosis have high plasma ammonia and low serum and tissue zinc levels. We used this model to examine the effects of oral zinc supplementation on activities of plasma ammonia and liver ornithine transcarbamylase (a key enzyme in the urea cycle). These parameters were examined in two consecutive experiments. Each experiment included two groups of rats treated with carbon tetrachloride; one group received zinc in the drinking water during the induction of cirrhosis, and another served as a control group. Regardless of zinc supplementation, all carbon tetrachloride-treated rats exhibited similar micronodular cirrhosis, with similar histological appearance and liver function impairment. Cirrhotic rats without zinc supplementation showed high plasma ammonia and low serum and hepatic zinc levels and reduced liver ornithine transcarbamylase activity. Serum, hepatic zinc and liver ornithine transcarbamylase activity increased significantly in the zinc-supplemented group, and these rats' plasma ammonia levels became normal. Plasma ammonia level was significantly inversely correlated with liver ornithine transcarbamylase activity and positively correlated with serum and hepatic zinc content. Our results suggest that zinc deficiency may modify hepatic ornithine transcarbamylase activity and, therefore, ammonia disposal.

Administration, Oral↗

Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis.

Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1[14C]palmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls. These findings show a profound derangment of lysophosphatidylcholine handling and processing in the cirrhotic liver, which is of potential pathogenetic significance.

1-Acylglycerophosphocholine O-Acyltransferase↗

Intrinsic innervation of the rat knee joint articular capsule and ligaments.

In spite of the practical importance of having a detailed knowledge of knee joint innervation to understand the pathophysiologic aspects, little information is now available concerning the density and pattern of the nerve fibres which are distributed to it. The present study has been designed to investigate the density and distribution of nerve fibres and receptor corpuscles in the knee joint articular capsule, cruciate and collateral ligaments in the rat, using the acetylcholinesterase (AChE) histochemical in toto staining technique. The investigation was performed on male Wistar rats of 3 months of age, some of which had been treated with capsaicin to deplete their afferent 'C' fibres of their content of neuropeptides. AChE-positive nerve fibres and different types of receptor corpuscle endings were found within articular capsule and ligaments. The highest density of AChE-positive nerve fibres was noticeable in the fibular collateral ligament followed by the tibial collateral ligament, the posterior cruciate ligament, the anterior cruciate ligament and the articular capsule. In the articular capsule the number of type I endings was higher than in the ligaments. The opposite is true for the other type of receptor corpuscles found as well as for nerve endings. Capsaicin treatment significantly reduced the density of AChE-positive nerve fibres in knee joint ligaments but did not affect nerve fibres in the articular capsule. Moreover, it caused the disappearance of some kind of receptor corpuscles within the collateral and cruciate ligaments. The above data collectively suggest that the AChE in toto staining technique may represent a good method for investigating joint innervation and that a significant percentage of nerve fibres supplying knee joint ligaments is represented by C fibre afferents.

Acetylcholinesterase↗

Microcirculation of the extra-ocular muscles of rats. A scanning electron-microscopic corrosion cast study.

Specific researches, employing corrosion casts, were performed on different skeletal muscles, but not on extra-ocular muscles (EOMs). The microvascular bed of EOMs was studied by the corrosion cast technique in the rat. Two histologically and physiologically different layers were present in the EOMs. On the whole, the capillary pattern of EOMs was less dense than in the other skeletal muscles. The EOM orbital layer turned out to have a higher number of transverse anastomoses and tuning-fork divisions than the global layer had. These different microcirculatory patterns can be related with the physiological function and the anatomical situation of the EOMs.

Animals↗

Improvement of estradiol 17 beta-D-glucuronide cholestasis by intravenous administration of dimethylethanolamine in the rat.

The intravenous administration of dimethylethanolamine in the rat promotes a selective enrichment of liver membranes with polyunsaturated phosphatidylcholines. The effect of dimethylethanolamine pretreatment on cholestasis induced by estradiol 17 beta-D-glucuronide, a potent cholestatic agent, was assessed in this study. Dimethylethanolamine, dissolved in sodium-taurocholate was infused intravenously (0.3 mg/kg/min) for 15 hr. One group of control rats (estradiol 17 beta-D-glucuronide controls) received the bile salt only. An estradiol 17 beta-D-glucuronide bolus was then injected intravenously (10.4 mg/kg) into dimethylethanolamine-pretreated and estradiol 17 beta-D-control rats, and its effect on bile flow and biliary lipid secretion was compared for 3 hr. The estradiol 17 beta-D-glucuronide inhibitory effect on bile flow and biliary lipid secretion was significantly antagonized by dimethylethanolamine pretreatment. The maximum inhibition of bile flow was found 30 min after estradiol 17 beta-D-glucuronide administration, when it decreased from 3.5 +/- 0.4 microliters/min/100 gm (basal) to 0.9 +/- 0.3 microliters/min/100 gm in estradiol 17 beta-D-glucuronide controls, whereas in dimethylethanolamine-pretreated rats this decreased only from 3.2 +/- 0.4 (basal) to 2.3 +/- 0.4 microliters/min/100 gm. Bile flow and the biliary secretion of cholesterol, phosphatidylcholine and bile salts were significantly higher in the dimethylethanolamine-pretreated rats than in estradiol 17 beta-D-glucuronide controls (p less than 0.02) during the cholestatic phase. The inhibitory effect of estradiol 17 beta-D-glucuronide on bile flow was associated with a marked decrease of membrane fluidity (p less than 0.001) assessed by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy and with a cholesterol enrichment of microsomes, sinusoidal and canalicular liver plasma membranes and inhibition of sinusoidal Na+,K(+)-ATPase activity (p less than 0.05). These membrane alterations persisted 180 min after estradiol 17 beta-D-glucuronide administration despite complete normalization of bile flow. Dimethylethanolamine pretreatment significantly counteracted the reduction of membrane fluidity (p less than 0.001), the cholesterol enrichment and the inhibition of Na+,K(+)-ATPase (p less than 0.05) promoted by estradiol 17 beta-D-glucuronide administration in all membrane subfractions 30 and 180 min after administration. In addition, dimethylethanolamine-pretreated rats had more polyunsaturated fatty acids in membrane phosphatidylcholine with respect to the control groups. Dilatation of canaliculi and loss of microvilli were evident in estradiol 17 beta-D-glucuronide controls 180 min after estradiol 17 beta-D-glucuronide administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The hepatic microcirculation in experimental cirrhosis. A scanning electron microscopy study of microcorrosion casts.

The experimental model of liver cirrhosis induced by intragastric administration of CCl4 reproduces not only the histological picture of the postnecrotic cirrhosis but also its pathophysiological features. Corrosion casts of livers affected by CCl4-induced cirrhosis show the loss of the lobular pattern. Once the cirrhosis has completely developed, the whole microvascular bed appears to be composed of groups of sinusoid nodules of diameters varying between 0.3 and 1.5 mm.. Pre- and post-sinusoidal vessels and anastomoses between the former and the latter are mainly located at the perinodular spaces. This microvascular situation modifies the normal perfusion gradient within the parenchyma. Nevertheless, it can allow a still viable function.

Animals↗

Augmentation of bone repair by pulsed elf magnetic fields in rats.

Tibial osteotomies in rats were exposed for 2, 3, 5 and 8 weeks to a pulsed extremely low frequency magnetic field. The shape of the pulse was a double halfwave (50 Hz, 70 G). The rate of bone healing was evaluated by light and electron microscopy. An increase of bone healing was found in rats treated with magnetic fields persisting throughout the tested time. The accelerated healing process produced a sequence of morphological appearances identical to those of a normal fracture callus being the enhancement of osteogenesis produced by an acceleration of preliminary ossification.

Animals↗

A scanning electron microscopy morphometric study of the rabbit peritoneal surface.

Rabbit peritoneum was studied by SEM to obtain information and statistically meaningful morphometric data of different sites of visceral and parietal peritoneum and to verify the existence of "stomata." Samples were fixed by intraperitoneal infusion of glutaraldehyde, and were photographed by SEM under standard conditions. Morphometric data were obtained by Kontron MOP Videoplan. Variable cell surface patterns were present even within limited areas; however, "stomata" were not observed. The heterogeneity of data obtained can be related to the dynamism of mesothelial cell activity and to the different motilities of the underlying organs.

Animals↗

A three-dimensional study of the morphology and topography of pericytes in the microvascular bed of skeletal muscle.

Digested tissue specimens and corrosion casts of rat soleus and tibialis anterior muscles were employed for this Scanning Electron Microscopy (SEM) study. The shape, morphology, and position of pericytes were compared to corresponding imprints on the cast surfaces. Pericytes, observed in digested tissue specimens, showed a typical morphological pattern: a central body with two primary processes that run along the capillary in opposite directions. From these primary processes, secondary ones arise and often encircle the vessel almost completely. On the surface of corrosion casts, roundish imprints were found in the microvascular tree at the same level where digested tissue specimens showed the presence of pericyte bodies. Along and around the cast surface, shallow grooves reproduced the course of the primary and secondary processes. The peculiar tridimensional arrangement of pericytes at the level of capillary bifurcations underlines their role in red cell flow regulation. However, if the mechanical linkage of the pericytes to the endothelium and their contractability is taken into account, additional roles of these perivascular cells may be hypothesized.

Animals↗

[Action of an anti-inflammatory agent on the nasal mucosa].

The histological integrity of the nasal mucosa assures full efficacy of the respiratory, conditioning and defense functions. Together with ciliated and goblet cells, the respiratory epithelium not only carries out mucociliary clearance but it is also responsible for correct assembly of secretory IgA, the foundation of the mucosal defense system. The secretory component stabilizing the immunoglobulin molecule is indeed, an epithelial glycoprotein which begins to fail when the mucous trophism is altered through inflammatory processes of various natures. The efficacy of an anti-inflammatory drug (tiaprofenic acid) can thus be proven not only because the respiratory and mucociliary transport functions are normalized but, histologically speaking, through an accumulation of IgA in the epithelial cells and nasal secretions as well. In the present experiment the effect of tiaprofenic acid on the local production of antibodies appears prompt and long lasting. On the contrary, respiratory function and mucocillary transport are more deeply affected by structural alterations of the epithelium, most likely because the histological integrity-demonstrated by the increase of IgA in the secretion and accumulation of the secretory component in the epithelium-is the starting point for a perfect coordination according to fixed biological rhythms of all nasal functions.

Adult↗