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Biomedical subjects

A Sbarbati

Publications and source records attributed to A Sbarbati.

At least 19 recordsLinked to original sources

Allelochemical communication in vertebrates: kairomones, allomones and synomones.

Communication between different species by means of chemicals (allelomones) is widespread among prokaryotes, plants and invertebrates. This study reviews data suggesting that allelochemically mediated communication also exists among vertebrates. The work aims to provide a concise, interdisciplinary review of communication mediated by infochemicals, with a focus on interspecies and interkingdom signaling. A definition of infochemicals is given, with a brief review of the general principles of chemical communication in different kingdoms in nature. Findings are reported which suggest that interspecies chemical signaling is important for vertebrates also. It is proposed that the general laws of chemical ecology are valid for mammals too, and that the terms indicating the different types of allelomones (i.e. kairomone, allomone and synomone) might also be used in medicine. In particular, the microchemical environment at the airway and digestive interfaces are discussed from an infochemical point of view.

Animals↗

Structural and functional MRI following 4-aminopyridine-induced seizures: a comparative imaging and anatomical study.

Structural and functional MRI was used in conjunction with computerized electron microscopy morphometry to study changes 2 h, 24 h and 3 days after 4-aminopyridine-induced seizures lasting 2 h in rats. T2 (relaxation time) values showed changes throughout the cerebral cortex, hippocampus, amygdala and medial thalamus, with a different temporal progression, showing a complete recovery only after 3 days. Two hours after seizures, the apparent diffusion coefficient was decreased throughout the brain compared to control animals, and a further decrease was evident 24 h after seizures. This was followed by a complete recovery at 3 days post-seizures. Functional MRI was performed using regional cerebral blood volume (rCBV) maps. The rCBV was increased shortly after convulsions (2 h) in all structures investigated, with a significant return to baseline values in the parietal cortex and hippocampus, but not in the medial thalamic nuclei, 24 h after seizure onset. No rCBV alterations were detected 3 days after seizures. Electron microscopy of tissue samples of parietal neocortex and hippocampus revealed prominent astrocytic swelling 2 h post-convulsions which decreased thereafter gradually. In conclusion, this experiment reports for the first time structural and functional brain alterations, lasting several hours, in 4-aminopyridine-treated rats after seizure onset. MRI approach combined with histological and ultrastructural analysis provided a clarification of the mechanisms involved in the brain acute response to ictal activity.

4-Aminopyridine↗

The taste cell-related diffuse chemosensory system.

Elements expressing the molecular mechanisms of gustatory transduction have been described in several organs in the digestive and respiratory apparatuses. These taste cell-related elements are isolated cells, which are not grouped in buds, and they have been interpreted as chemoreceptors. Their presence in epithelia of endodermal origin suggests the existence of a diffuse chemosensory system (DCS) sharing common signaling mechanisms with the "classic" taste organs. The elements of this taste cell-related DCS display a site-related morphologic polymorphism, and in the past they have been indicated with various names (e.g., brush, tuft, caveolated, fibrillo-vesicular or solitary chemosensory cells). It may be that the taste cell-related DCS is like an iceberg: the taste buds are probably only the most visible portion, with most of the iceberg more caudally located in the form of solitary chemosensory cells or chemosensory clusters. Comparative anatomical studies in lower vertebrates suggest that this 'submerged' portion may represent the most phylogenetically ancient component of the system, which is probably involved in defensive or digestive mechanisms. In the taste buds, the presence of several cell subtypes and of a wide range of molecular mechanisms permits precise food analysis. The larger, 'submerged' portion of the iceberg is composed of a polymorphic population of isolated elements or cell clusters in which the molecular cascade of cell signaling needs to be explored in detail. The little data we have strongly suggests a close relationship with taste cells. Morphological and biochemical considerations suggest that the DCS is a potential new drug target. Modulation of the respiratory and digestive apparatuses through substances, which act on the molecular receptors of this chemoreceptive system, could be a new frontier in drug discovery.

Animals↗

A new fate for old cells: brush cells and related elements.

Over the past 50 years, hundreds of studies have described those cells that are characterized by a brush of rigid apical microvilli with long rootlets, and which are found in the digestive and respiratory apparatuses. These cells have been given names such as brush cells, tuft cells, fibrillovesicular cells, multivesicular cells and caveolated cells. More recently, it has been realized that all these elements may represent a single cell type, probably with a chemosensory role, even if other functions (e.g. secretory or absorptive) seem to be possible. Very recent developments have permitted a partial definition of the chemical code characterizing these elements, revealing the presence of molecules involved in chemoreceptorial cell signalling. A molecular cascade, similar to those characterizing the gustatory epithelium, seems to be present in these elements. These new data suggest that these elements can be considered solitary chemosensory cells with the presence of the apical 'brush' as an inconsistent feature. They seem to comprise a diffuse chemosensory system that covers large areas (probably the whole digestive and respiratory apparatuses) with analogies to chemosensory systems described in aquatic vertebrates.

Amphibians↗

Neurochemistry of the gustatory subgemmal plexus.

Nerve fibers present in the basal plexus of the vallate papilla of the rat tongue were analyzed using cytochemical, immunocytochemical and ultrastructural methods to investigate whether the subgemmal plexus is subdivided into neurochemical compartments and to provide a clear definition of the reciprocal spatial relationships between nitrergic, peptidergic and acetylesterase positive structures. Several neuronal fibers were detected under the chemoreceptorial epithelium. Some of these fibers were in contact with the taste buds and in some cases neuronal projections were also present between the buds or inside them; some others fibers were present below this layer but in a more peripheral area. Antibodies against CGRP, SP and CCK stained fibers just below the chemoreceptorial epithelium, whereas fibers more distally located were immunolabeled by anti VIP, NOS-1 and NF-200 antibodies. Some double staining experiments were conducted using confocal microscopy. Other sections were processed cytochemically for AChE and subsequently for NADPH-d in colocalization experiments. All the data obtained using these techniques confirmed the results obtained with single immunostaining, as did the ultrastructural results. In conclusion, the present work demonstrates that the subgemmal plexus is a bilayered structure, suggesting that the complex relationship between the two layers plays a pivotal role in taste and in the control of processes ancillary to taste, such as control of vascular or secretory mechanisms.

Acetylcholine↗

In vivo MRI in different models of experimental epilepsy.

In order to investigate epilepsy, that is one of the most common neurological disorders, in the last decades different animal models have been proposed. Prevention, diagnosis, treatment and basic knowledge have been improved by the mean of these models. Numerous animal models have been developed in epilepsy research, both for generalized and for simple/complex partial seizures. Animal models for generalized seizures include sensory (light, noise, movement, etc) or electrical stimulations and genetic models. Models for focal seizures include topical or systemic application of pro-convulsive compounds or electrical stimulation. Baboons, mice, rats, rabbits, and Fayoumi chicken have been extensively used in this regard. Since 1983, when magnetic resonance spectroscopy was used to evaluate for the first time in vivo alterations induced by status epilepticus in rabbit, an increasing interest for the neuroimaging perspective has led to new insights in the study of epileptic disorders. In the early 1990s experimental studies provided evidence for the feasibility of magnetic resonance imaging analysis and detection of tissue damage in kainic acid-induced epilepsy in rat. In the following years a wealth of data has been obtained by the mean of functional MRI and/or by diffusion-weighted images. The studies reported in the literature of the last decades indicate in vivo magnetic resonance of epilepsy model as valuable and extremely informative tool.

Animals↗

Magnetic resonance imaging of changes elicited by status epilepticus in the rat brain: diffusion-weighted and T2-weighted images, regional blood volume maps, and direct correlation with tissue and cell damage.

The rat brain was investigated with structural and functional magnetic resonance imaging (MRI) 12 h after the arrest of pilocarpine-induced status epilepticus lasting 4 h. Histopathological data, obtained immediately after MRI analysis, were correlated with the images through careful evaluation of tissue shrinkage. Diffusion-weighted and T2-weighted imaging showed changes throughout the cerebral cortex, hippocampus, amygdala, and medial thalamus. However, only T2-weighted imaging, based on rapid acquisition relaxation-enhanced sequences, revealed in the cortex inhomogeneous hyperintensity that was highest in a band corresponding to layer V. Regional cerebral blood volume (rCBV) maps were generated using T2*-weighted gradient-echo images and an ultrasmall superparamagnetic iron oxide contrast agent. In the cortex, rCBV peaked in superficial and deep bands exhibiting a distribution complementary to the highest T2-weighted intensity. Selective rCBV increase was also documented in the hippocampus and subcortical structures. In tissue sections, alterations indicative of marked edema were found with Nissl staining in areas corresponding to the highest T2-weighted intensity. Degenerating neurons, revealed by FluoroJadeB histochemistry, were instead concentrated in tissue exhibiting hyperperfusion in rCBV maps, such as hippocampal subfields and dentate gyrus, cortical layers II/III and VI, and medial thalamus. The data indicate that:(i) T2-weighted imaging provides a sensitive tool to investigate edematous brain alterations that follow sustained seizures; (ii) rCBV maps reveal regional hyperperfusion; (iii) rCBV peaks in tissue exhibiting marked neurodegeneration, which may not be selectively revealed by structural MRI. The findings provide an interpretation of the brain response to sustained seizures revealed in vivo by different strategies of MRI analysis.

Amygdala↗

Gluten sensitivity and 'normal' histology: is the intestinal mucosa really normal?

BACKGROUND: Early pathogenetic events of gluten intolerance may be overlooked in patients with serologic markers of celiac disease and normal intestinal mucosa by both conventional histology and immunohistochemistry. AIMS: To investigate if a submicroscopical damage of the absorptive cell surface was associated with developing gluten sensitivity. PATIENTS AND METHODS: Duodenal biopsies of seven subjects with positive anti-endomysial antibodies and normal histology underwent ultrastructural evaluation of the epithelial surface by means of both scanning and transmission electron microscopy. Specimens of intestinal mucosa of 14 children with non-celiac conditions were used as controls. RESULTS: In four patients, electron microscopy revealed alterations of the enterocyte brush border with a significant reduction of the height of microvilli. After several months, three of them had a second biopsy that eventually showed histological modifications suggestive of celiac disease. In the other three patients, no significant alteration of enterocyte ultrastructure was observed. One of them, rebiopsied after 12 months, still showed a normal duodenal histology. CONCLUSIONS: Gluten sensitivity can be associated with 'minimal' mucosal changes not detectable with conventional light microscopy. Such lesions, which primarily involve microvillous structure, may imply a reduction of intestinal absorptive surface already in the latent stage of the disease.

Adolescent↗

Solitary chemosensory cells in mammals?

In fish, solitary chemosensory cells (SCCs) occur in the oropharynx, gills and skin and have often been found in association with taste buds. Among amphibia, a diffuse chemosensory system has been described on the ventral skin of toads, and a structural resemblance of SCCs to taste bud cells has been reported in frogs. Putative solitary chemoreceptors have been described in mammals too, at specific sites in the digestive or respiratory apparatus. In newborn rodents, a specific set of SCCs (composed of elements positive for alpha-gustducin, a marker of chemosensory cells) is associated with the gustatory epithelium. In conclusion, the available data suggest that a SCC system is not restricted to fish but is present in amphibia and mammals as well. At our present level of knowledge, establishing a precise homology between different species is difficult. However, the data from mammals and amphibia fully confirm previous findings in fish, and the use of chemical markers to study the diffuse chemosensory systems of vertebrates seems promising.

Amphibians↗

Correlation MRI/ultrastructure in cerebral ischemic lesions: application to the interpretation of cortical layered areas.

The origin and fate of cortical ischemic lesions, showing a stratified appearance at in vivo MRI-examination, was studied on rats in which a focal brain ischemia was induced by occlusion of the middle cerebral artery. One week after ischemia induction, six rats were selected in which three layers of different intensity were visible in the lesioned cortex. Two animals were sacrificed and studied by histology and electron microscopy. The external hyperintense layer was composed of pial and lesioned nervous tissue, the intermediate of degenerating nervous tissue in which an accumulation of macrophages was found, the deepest of edematous nerve tissue without a marked accumulation of macrophages. The remaining rats underwent further MRI examinations showing that, in the lesioned areas, cerebral blood volume was 14-69% lower than the contralateral healthy cortex. At histological and ultrastructural examination, a large part of the lesion was occupied by enlarged pial tissue and marginal glia. A dilatation of the ventricular cavity and cystic structures were also visible. In three animals an increase of the transverse diameter of the caudo-putamen ipsilateral to the lesion was found. The study suggests that the layered appearance is mainly due to an accumulation of macrophages in the intermediate layer and that several processes contribute to the occlusion of the space created by the removal of the necrotic tissue in stratified ischemic lesions (i.e. expansion of the pial tissue, thickening of the marginal glia; expansion of the caudo-putamen, enlargement of the ventricular cavity and development of cystic structures).

Animals↗

Immunohistochemical investigation of the nitrergic system in the taste organ of the frog, Rana esculenta.

We have studied by immunocytochemistry, the taste discs of the frog, Rana esculenta, with the aim of providing morphological and neurochemical data on the nitrergic system and of assessing the eventual presence of intrinsic neurons associated with the gustatory organs. In taste discs, antibodies against neuronal nitric oxide synthase (nNOS) revealed a positive immunoreaction in the taste receptor cell bodies and processes. The basal cells were also stained. All the fungiform papillae contained intragemmal nerve fibers showing nNOS immunoreactivity; these fiber were mainly located in the basal plexus. Immunoreactive nerve fibers were also visible at the periphery of the papilla-contacting ciliate cells, which form a ring around the taste disc. In conclusion, the findings obtained in this study suggest that the occurrence of nNOS-immunoreactivity in basal cells, taste cells and nerves might reflect a role for nitric oxide in taste mechanisms of Amphibia. The results may also sustain the physiological implication of NO as a molecule involved in the local target function of maintaining the taste bud mucosal integrity and in regulating the blood flow to the epithelium.

Animals↗

The neuroprotective activity of the glycine receptor antagonist GV150526: an in vivo study by magnetic resonance imaging.

The neuroprotective activity of GV150526 (3-[2-(Phenylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid sodium salt), a selective glycine receptor antagonist of the NMDA receptor, has been evaluated by magnetic resonance imaging (MRI) in a rat model of middle cerebral artery occlusion. The aim of the work was to evaluate, using an in vivo method, whether GV150526 was able to reduce the extent of ischemic brain damage when administered both before and after (6 h) middle cerebral artery occlusion. GV150526 was administered at a dose of 3 mg/kg i.v. T2-weighted (T2W) and diffusion weighted (DW) images were acquired at 6, 24 and 144 h after the establishment of the cerebral ischemia. Substantial neuroprotection was demonstrated at all investigated time points when GV150526 was administered before the ischemic insult. The ischemic volume was reduced by 84% and 72%, compared to control values, when measured from T2W and DW images, acquired 24 h after middle cerebral artery occlusion. Administration of the same dose of GV150526, 6 h post-ischemia, also resulted in a significant (p < 0.05) neuroprotection. The ischemic volume was reduced by 48% from control values when measured from T2W images and by 45% when measured from DW images. No significant difference was found between volumes of brain ischemia obtained by either MRI or triphenyltetrazolium chloride staining. These data confirm the potential neuroprotective activity of the glycine receptor antagonist GV150526 when administered either before or up to 6 h after ischemia.

Animals↗

Polyunsaturated fatty acids mapping by (1)H MR-chemical shift imaging.

Parametric mapping of polyunsaturated fatty acids (PUFA) distribution in adipose tissues was obtained by (1)H chemical shift imaging (CSI). A matrix of spectra, acquired with a CSI sequence having two spatial and one spectroscopic dimension, was processed with ad hoc algorithms. The protocol was applied to phantoms containing different lipids in which the degree of polyunsaturation was determined by high-resolution nuclear magnetic resonance (NMR). High correlation (R(2) = 0.998) between degrees of polyunsaturation given by our protocol and that measured by high-resolution NMR was found. The thoracic region of rats was also examined. Parametric maps of the polyunsaturation degree were obtained for the brown adipose tissue and the white axillary fat: the first deposit was found more polyunsaturated than the second. Finally, in vivo mapping of the inguinal region of the rat was produced that allowed us to individuate PUFA-rich areas in adipose tissue. This work demonstrates the feasibility of PUFA imaging in vivo.

Adipose Tissue↗

In-vivo quantitative hydrolipidic map of perirenal adipose tissue by chemical shift imaging at 4.7 Tesla.

OBJECTIVE: In this work, chemical shift magnetic resonance imaging is used for in vivo quantitative evaluation of fat and water content in the perirenal white adipose tissue. DESIGN AND MEASUREMENTS: Experiments were carried out on female Sprague-Dawley rats with a 4.7 T magnet. Fat and water fractions were computed pixel-by-pixel from the chemical shift selective images with an algorithm of reconstruction that allowed parametric maps (called hydrolipidic maps) to be produced with a pixel size of 625 x 625 microm. RESULTS: Our findings indicate that, in the perirenal adipose tissue, the water content ranges between 15% and 20%, with slight differences between the ventral and dorsal portions, and between the left and right deposits. The mesenteric adipose tissue, observed for comparison, has a mean water content of 30%. CONCLUSION: The present work demonstrates that methods based on magnetic resonance imaging can be useful tools for non-invasive in vivo quantitative mapping of the hydrolipidic content of adipose tissues.

Adipose Tissue↗

Delayed muscle injuries in arterial insufficiency: contrast-enhanced MR imaging and 31P spectroscopy in rats.

PURPOSE: To evaluate whether the vascular system resulting from an arterial lesion shows differences in permeability to a tracer with respect to the normal vascular system and whether eventual differences are maintained for long periods. MATERIALS AND METHODS: Permanent ischemia was induced in rats with femoral arterial removal, and magnetic resonance (MR) imaging was performed after 1, 7, 14, and 90 days. Gadopentetate dimeglumine was injected, and the kinetics of its penetration in the leg were studied. Phosphorus 31 spectroscopy was performed to determine the bioenergetic characteristics of the gastrocnemius muscle at rest and stimulation. Ischemic muscles were then processed for electron microscopy. RESULTS: After ischemia induction, a hyperintense area that progressively decreased was present on T2-weighted images. Gadopentetate dimeglumine improved the signal intensity of the area. Three months after arterial occlusion, the contrast-enhanced images still showed microvessels highly permeable to the tracers. Spectroscopic data revealed that 3 months after arterial removal, the bioenergetic reserve of the gastrocnemius muscle was reduced, suggesting that the contrast-enhanced MR imaging-visible area is functionally relevant. Ultrastructural examination revealed persistent muscle damage and signs of chronic microangiopathy. CONCLUSION: After ischemia induction, the restitutio ad integrum is not complete, and delayed muscle injuries can result from arterial insufficiency.

Animals↗

A brief survey of the modifications in sensory-secretory organs of the neonatal rat tongue.

Recent data obtained on rats suggest that in the days immediately following birth several events take place in the circumvallate papillae of the oral cavity. A phylogenetically primitive system of solitary chemosensory cells develops and is rapidly replaced by taste buds. The lipase-secreting von Ebner gland, which is associated with taste organs, begins to develop by forming short tubules. The intrinsic nervous system of the gustatory organs rapidly completes its maturation showing fast proliferation of fibers and immunocytochemical maturation. Intraepithelial lipid accumulation is visible in the non-receptorial mucosa of the tongue, showing aspects which suggest an active lipid secretion. These data demonstrate that in the rat the structure of the sensory-secretory organs of the newborn's tongue shows a typical conformation with respect to the adult and rapidly changes its organization in the first week after the birth. At the present level of knowledge, it is difficult to link the anatomical structures to peculiar functional roles but the rather simple organization of the neonatal gustatory epithelium could be in relation to the dietary regimen. The data obtained in laboratory animals underline the necessity of studies on human newborns to update the anatomical knowledge of the oral chemoceptive system.

Animals↗

Regional cerebral blood volume mapping after ischemic lesions.

The possible persistence of a microvascular deficit at long time intervals after cerebral ischemia induction is not well established. In rats, we have generated in vivo maps of the regional cerebral blood volume (rCBV) at different time intervals after middle cerebral artery occlusion (MCAo) with the aim to evaluate the persistence of a rCBV deficit in the damaged area or in the surrounding regions. The rats were examined by magnetic resonance imaging (MRI) at different time intervals, starting from the first day until three months after ischemia and postmortem histological and ultrastructural correlation was obtained. All MRI experiments were carried out using an imager-spectrometer equipped with a 4.7 Tesla magnet. To produce the susceptibility-weighted rCBV images, a suspension of superparamagnetic iron oxide nanoparticles (AMI-25) was injected to the rat. In a control group (nonoperated or sham-operated rats), a symmetrical distribution of rCBV values was found between the two hemispheres (differences between left and right cortex below 8%). In the rats with MCAo an evident vascular asymmetry was found 24 h after ischemia (differences between left and right ranging from 22 and 77%) and reduced rCBV values were evident in the ischemic areas. In a time range following the 15th day most of the rats showed a complete recovery of the lesion while only four animals still had a small residual lesion, as probed by T2-weighted (T2W) images. In three of these four cases, the reduction of rCBV in the ipsilateral cortex with respect to the contralateral was greater than 20%. Correlation was found (Y > 0.8) between late rCBV measurement and the initial volume of the lesion (hyperintense region in T2W images). The postmortem measurements correlate much better with the rCBV data than with the T2W ones. In conclusion, the present work demonstrates that cortical lesions may result in a deficit of rCBV for long periods and that a mismatch between T2w and rCBV data can be present during the repair process.

Animals↗

Anti-atherosclerotic activity of the calcium antagonist lacidipine in cholesterol-fed hamsters.

We have investigated the activity of the calcium antagonist lacidipine in male hamsters fed an atherogenic diet containing 2% cholesterol and 5% butter. Animals were examined at 14, 20 and 24 weeks of treatment. At 14 weeks, in hamsters fed the atherogenic diet and without lacidipine treatment, there were significant increases in serum levels of total cholesterol, triglycerides and lipoproteins; these values were approximately similar at week 24. Lacidipine treatment at 0.3, 1.0 and 3.0 mg/kg/d did not affect levels of serum cholesterol, triglycerides and lipoproteins. At 24 weeks, in hyperlipidemic hamsters fed the atherogenic diet, the area of the fatty streak in the aortic arch covered a mean area of 375 +/- 145 micron2 x 100, which accounted for 2.7% of the total surface area of the aortic arch. In hamsters fed the atherogenic diet and treated with lacidipine at 0.3, 1.0 and 3.0 mg/kg, at 24 weeks, the surface area of the aortic arch lesion was significantly reduced by 41 to 71%. In the thoracic aorta at 24 weeks, in lacidipine-treated animals, both the incidence and degree of severity of the lesions was reduced, the area of the fatty streak being lowered by 78 to 97% in comparison with non-lacidipine-treated control animals. Ultrastructural examination demonstrated that the early changes in the aorta in hamsters fed the atherogenic diet involved the intima and smooth muscle cells; lacidipine treatment reduced the severity of the intimal lesions significantly. With SEM, lacidipine administration was seen to reduce endothelial irregularity and the presence of crater-like lesions. At TEM, treatment with lacidipine reduced the number of foam cells and the presence of liposomes in the subendothelium. This investigation demonstrates that in the hyperlipidemic hamster, lacidipine treatment decreases atheromatous lesions without lowering serum lipids. It is suggested that lacidipine influences the atherogenic process by an unusual mechanism which may be related to a combination of both the long-lasting calcium antagonism of the drug and significant antioxidant activity.

Animals↗