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Biomedical subjects

A Saria

Publications and source records attributed to A Saria.

At least 55 records · Page 3Linked to original sources
PubMed1995

Mesencephalic grafts increase preprotachykinin-A mRNA expression in striatal grafts in an in oculo co-graft model.

In oculo transplantation provides a powerful tool to study development and gene expression of isolated brain regions. In this study we grafted striatal and mesencephalic brain tissue to the anterior eye chamber and allowed it to survive for 2 and 6 weeks. Striatal or mesencephalic pieces were either grafted alone (single grafts) or together in close connection (co-grafts). As a control normal adult untreated rats were analyzed at the striatal and hippocampal level. Using non-radioactive in situ hybridization with digoxigenin-labeled riboprobes we detected preprotachykinin-A mRNA, a neuropeptide marker for striatal neurons. We report that adult normal rats show a strong expression of preprotachykinin-A mRNA in the striatum, medial habenula and piriform cortex, verifying the specificity of the method. Mesencephalic in oculo grafts did not reveal any staining for preprotachykinin-A mRNA. In single striatal grafts only a very weak expression of preprotachykinin-A mRNA was found at both time points investigated. Co-grafts grown for 2 weeks were not different from single striatal grafts, however, when striatum was grown together with ventral mesencephalon for 6 weeks the level of preprotachykinin-A mRNA was strong and near normal adult levels. We conclude that the mesencephalic dopaminergic innervation to the striatum might be a potent stimulus to neurons expressing preprotachykinin-A mRNA.

Animals↗
PubMed1995

Evidence for a high density of secretoneurin-like immunoreactivity in the extended amygdala of the rat.

Secretoneurin is a novel 33-amino-acid neuropeptide produced by endoproteolytic processing from secretogranin II, which is a member of the chromogranin/secretogranin family. In this immunocytochemical study, we compared the distribution pattern of secretoneurin immunoreactivity with that of tyrosine hydroxylase, calbindin, substance P, and Leu-enkephalin in adjacent sections of rat forebrain. Secretoneurin appeared mainly in varicosities and fibers. Only a few cell bodies were stained. In the nucleus accumbens, a partial overlap of secretoneurin-immunoreactive patches with enkephalin-immunopositive areas was found. Secretoneurin displayed low to moderate levels of immunoreaction in calbindin-rich as well as in calbindin-immunonegative areas of the caudate-putamen. In the globus pallidus, entopeduncular nucleus, and substantia nigra, secretoneurin immunoreactivity was oriented ventromedially preferentially in woolly fibers. The dense immunostaining in the medial nucleus accumbens was directly continuous with dense secretoneurin immunoreactivity in the bed nucleus of the stria terminalis. Two strongly secretoneurin-immunopositive bands, one in the sublenticular portion and a smaller one along the posterior limb of the anterior commissure, interconnected the highly secretoneurin-immunopositive centromedial amygdala with the bed nucleus of the stria terminalis. Thus, the distribution pattern of secretoneurin immunoreactivity provides a marker of the extended amygdala that forms a continuum between the centromedial amygdala and the bed nucleus of the stria terminalis.

Amygdala↗
PubMed1995

Distribution of GABAA receptor alpha 1 subunit-like immunoreactivity in comparison with that of enkephalin and substance P in the rat forebrain.

The gamma-aminobutyric acid-A receptor consists of several subunits. In this immunohistochemical study we investigated the regional distribution of the alpha 1 subunit with an antibody directed against a specific amino acid sequence (1-9) of the (1-9) of the alpha 1 subunit. We compared the distribution pattern of the alpha 1 subunit-like immunoreactivity with that of substance P- and enkephalin-like immunoreactivities in adjacent sections of the rat forebrain. alpha 1 subunit-like immunoreactivity appeared in the form of varicosities and fibers. A band-like terminal staining pattern (woolly fibers) that has been shown by others for substance P- and enkephalin-like immunoreactivity is also observed for alpha 1 subunit-like immunoreactivity. In contrast to substance P and enkephalin, numerous alpha 1 subunit-like immunoreactive perikarya were found. The highest density of alpha 1 subunit-like immunoreactive fibers and perikarya was found in the pallidal areas and the substantia nigra pars reticulata whereas the nucleus accumbens and the caudate putamen displayed a low density. alpha 1 subunit-like immunoreactive neurons resembled typical pallidal neurons. Some of these neurons were pericellularly stained with enkephalin-like immunoreactive varicosities in the dorsal pallidum. The distribution pattern of alpha 1 subunit-like immunoreactivity reflects a partial overlap with the substance P and enkephalin system although a differential distribution to each of these peptides was observed for cell bodies, fibers, and axon terminals.

Animals↗
PubMed1995

Effects of haloperidol, clozapine and citalopram on messenger RNA levels of chromogranins A and B and secretogranin II in various regions of rat brain.

We have measured the messenger RNA levels of chromogranins A and B and secretogranin II in various brain regions of rats subchronically treated with various antipsychotic drugs. Since, as shown previously, the messenger RNA levels of these peptides are increased when neurons are stimulated, we hoped to identify by this approach those nuclei which are subchronically influenced by these drugs. The drugs chosen were the neuroleptic halperidol, a blocker of dopamine receptors, the atypical antipsychotic clozapine, which in addition to blocking dopamine receptors also blocks those for serotonin, and citalopram, a specific serotonin reuptake inhibitor. In agreement with previous data on neuropeptide messenger RNAs, we found in the dorsolateral striatum an increase of the secretogranin II messenger RNA levels after haloperidol and a much smaller one after clozapine. In the nucleus accumbens and in the bed nucleus of the stria terminalis, both compounds had a comparable positive effect. These differential effects can be attributed to a different action of these drugs on dopamine receptor subtypes. In the zona incerta, clozapine decreased the secretogranin II and chromogranin A message, whereas in the dorsal raphe it led to an increase. On the other hand, citalopram induced exactly the opposite effects in these two brain regions. This phenomenon can be explained by the differential interaction of these drugs with serotonergic mechanisms. Additional, relatively small changes of the mRNAs were seen in several other brain regions. These results establish that changes in the mRNA levels of the chromogranins are good indicators for the effect of drugs on certain brain nuclei. The concomitant action of haloperidol and clozapine on the limbic regions, i.e. the nucleus accumbens and the bed nucleus of the stria terminalis, points to these brain regions for the antipsychotic action of these two neuroleptics.

Animals↗
PubMed1995

[Treatment of nonspecific hyper-reflectory rhinopathy (vasomotor rhinitis) with capsaicin].

Apart from adrenergic and cholinergic neurones, peptidergic neurones are involved in the autonomic control of nasal mucosa. Their transmitter substances are peptides, so-called "neuropeptides". It is assumed that they are released from peptidergic neurones in the nasal mucosa after irritation of receptors by unspecific stimuli, and are responsible for the symptoms of hyperreactive rhinopathy. Repeated topical application of Capsaicin (8-methyl-N-vanillyl-6-nonenamide) leads to a selective degeneration of peptidergic neurones and desensitisation of its receptors in the nasal mucosa. 123 patients who were suffering from hyperreactive rhinopathy were treated in a prospective study by repeated topical applications of capsaicin solutions in increasing concentrations. A symptom score demonstrated an improvement of the predominating symptoms (nasal congestion, hypersecretion, sneezing) by 62% to 72%. A reduction of unpleasant side effects following application (epiphora, itching, sneezing, mucosal oedema) indicating a desensitising effect could be documented by a symptom score and by active anterior rhinomanometry. Immunohistochemical investigations of nasal mucosa biopsies revealed no reduction of peptidergic neurones within the nasal mucosa, so that a blockage of receptors seems to be responsible for the positive effects. The treatment of hyperreactive rhinopathy with capsaicin or related substances seems to be a promising new way in the treatment of hyperreactive rhinopathy. Further investigations have to prove the site of effect and mechanism of activity of the substance, such as the best modality of application.

Administration, Intranasal↗
PubMed1994

Human and rat primary C-fibre afferents store and release secretoneurin, a novel neuropeptide.

Secretoneurin is a recently discovered neuropeptide derived from secretogranin II (SgII). Since this peptide could be detected in the dorsal horn of the spinal cord we studied whether it is localized in and released from primary afferent neurons. Secretoneurin was investigated with immunocytochemistry and radioimmunoassay in spinal cord, dorsal root ganglia and peripheral organs. SgII mRNA was determined in dorsal root ganglia. Normal rats and rats pre-treated neonatally with capsaicin to destroy selectively polymodal nociceptive (C-) fibres were used. Slices of dorsal spinal cord were perfused in vitro for release experiments. Immunocytochemistry showed a distinct distribution of secretoneurin-immunoreactivity (IR) in the spinal cord and, lower brainstem. A particularly high density of fibres was found in lamina I and outer lamina II of the caudal trigeminal nucleus and of the spinal cord. This distribution was qualitatively identical in rat and human post-mortem tissue. Numerous small diameter and some large dorsal root ganglia neurons were found to contain SgII mRNA. Capsaicin treatment led to a marked depletion of secretoneurin-IR in the substantia gelatinosa, but not in other immunopositive areas of the spinal cord and to a substantial loss of small (< 25 microns) SgII-mRNA-containing dorsal root ganglia neurons. Radioimmunoassay revealed a significant decrease of secretoneurin-IR in the dorsal spinal cord, the trachea, heart and urinary bladder of capsaicin-treated rats. Perfusion of spinal cord slices with capsaicin as well as with 60 mM potassium led to a release of secretoneurin-IR. In conclusion, secretoneurin is a neuropeptide which is stored in and released from capsaicin-sensitive, primary afferent (C-fibre) neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Distribution of secretoneurin immunoreactivity in the spinal cord and lower brainstem in comparison with that of substance P and calcitonin gene-related peptide.

Secretoneurin is a peptide of 33 amino acids generated in brain by proteolytic processing of secretogranin II. The distribution of this newly characterized peptide was investigated by means of immunocytochemistry and in situ hybridization in the spinal cord and lower brainstem of the rat. The staining pattern of secretoneurin immunoreactivity (IR) was compared to that of substance P (SP) and calcitonin gene-related peptide (CGRP) in adjacent sections. A high density of secretoneurin-IR fibers and terminals was found in lamina I and outer lamina II of the caudal trigeminal nucleus and of the spinal cord at all levels, around the central canal, and in the sympathetic and parasympathetic areas of the lateral cell columns. The ventral horn displayed a low to moderate density of secretoneurin-IR. The highest number of secretogranin II mRNA-containing cells was found in lamina II of the dorsal horn and in neurons of the dorsal root ganglia. In the white matter, secretoneurin-IR was most prominent in the dorsolateral part of the lateral funiculus and in the tract of Lissauer. The distributions of secretoneurin-IR and SP-IR were strikingly similar. CGRP-IR and secretoneurin-IR overlapped in the outer laminae of the dorsal horn, in the lateral cell column, and probably in some motoneurons. This study establishes that, like SP and CGRP, secretoneurin is a peptide highly concentrated in the terminal field of primary afferents and in sympathetic and parasympathetic areas. Thus secretoneurin might be involved in the modulation of afferent transmission.

Animals↗
PubMed1994

Release of secretoneurin and noradrenaline from hypothalamic slices and its differential inhibition by calcium channel blockers.

Secretoneurin is a newly discovered peptide found in high concentrations in brain. We have studied the release of secretoneurin and noradrenaline from superfused hypothalamic slices from rat brain. Both electrical stimulation and potassium induced depolarisation released secretoneurin and noradrenaline from these slices in a calcium-dependent manner. Electrical stimulation caused a preferential release of noradrenaline when compared to the secretion elicited by high potassium. The time course of secretoneurin release was more protracted than that of noradrenaline. The calcium channel blocker omega-conotoxin inhibited only the electrically induced release of noradrenaline, whereas nifedipine inhibited only that of secretoneurin. These results establish that secretoneurin is secreted from neurons. Inhibition of this release by nifedipine is consistent with the concept that secretion from large dense core vesicles occurs at sites different from that of small vesicles and depends on calcium influx via L-type calcium channels.

Animals↗
PubMed1994

EEG alterations in patients treated with clozapine in relation to plasma levels.

It is well known that psychotropic drugs can induce EEG alterations. Dose dependence seems established; however, there are no data concerning the impact of plasma levels. The authors investigated the influence of clozapine plasma levels on the frequency of EEG alterations. Data from 29 inpatients (18 male, 11 female, 31.7 +/- 10.2 years) receiving clozapine in a dose range between 25 and 600 mg were collected prospectively. There was no psychotropic or anticholinergic comedication. All patients had normal EEGs before taking clozapine. Fifteen patients showed pathological changes (group 2) and 14 no changes (group 1). Discriminant analysis showed that EEG changes are dependent on plasma levels (P = 0.0009, plasma levels in group 1 mean 81.6 ng/ml, +/- SD 64.6, in group 2 235.7 ng/ml, +/- 169.8). A total of 72.4% of the patients were correctly classified as having either pathological EEG changes or none by this analysis. Variables such as dose, age, sex, weight and duration of treatment were not statistically relevant. It can therefore be suggested that clozapine plasma levels are a valid indicator for the appearance of electrophysiological reactions.

Adult↗
PubMed1994

Molecular characterization of immunoreactivities of peptides derived from chromogranin A (GE-25) and from secretogranin II (secretoneurin) in human and bovine cerebrospinal fluid.

Chromogranin A and secretogranin II are members of the so-called chromogranins, the acidic proteins stored in neuroendocrine large dense-core vesicles. We characterized chromogranin A and secretogranin II immunoreactivities in cerebrospinal fluid by radioimmunoassays using synthetic peptides derived from these components (GE-25 for chromogranin A and secretoneurin for secretogranin II). In lumbar cerebrospinal fluid, high levels (more than 1000 fmol/ml) of these two components were found, whereas in ventricular cerebrospinal fluid the secretoneurin levels were relatively low. The cerebrospinal fluid/serum ratio for secretoneurin was close to 170. High-performance liquid chromatography revealed that in both cerebrospinal fluid and extracts from human brain secretoneurin was the predominant immunoreactive component. In cerebrospinal fluid chromogranin A immunoreactivity was present as intermediate-sized peptides with little intact chromogranin A and free GE-25 peptide. In human brain samples smaller peptides including GE-25 were more predominant. Analogous findings for secretoneurin and chromogranin A were obtained for bovine brain samples. We can conclude that chromogranins are present in cerebrospinal fluid in concentrations much higher than those of classical neuropeptides also stored in large dense-core vesicles. Therefore, their degree of proteolytic processing can be analysed with small samples of cerebrospinal fluid. A possible disturbance of proteolytic processing in large dense-core vesicles in various pathological conditions can now be discovered.

Adult↗
PubMed1994

Distribution of secretoneurin-like immunoreactivity in comparison with that of substance P in the human brain stem.

Secretoneurin is a peptide of 33 amino acids generated in the brain by proteolytic processing of secretogranin II which is a member of the chromogranin/secretogranin family. The distribution of this newly characterized peptide was investigated by immunocytochemistry in the human brain stem. The staining pattern of secretoneurin-like immunoreactivity was compared with that of substance P in adjacent sections. Secretoneurin-like immunoreactivity appeared mainly in dot- and fiber-like structures with densities varying from low to very high. Only a low number of secretoneurin-immunoreactive perikarya was found. Pericellular staining of both secretoneurin-immunopositive and immunonegative cells was frequently observed in the area of the central gray, in the reticular formation and in the solitary nuclear complex. The medial part of the substantia nigra pars reticulata, the nucleus interpeduncularis, the area of the central gray, the raphe complex and the inferior olive displayed a high density of secretoneurin-like immunoreactivity. Furthermore, a very prominent staining was found in the medial, dorsal and gelatinous subnuclei of the solitary tract and the dorsal motor nucleus of vagus. The substantia gelatinosa of the caudal trigeminal nucleus and spinal cord were also very strongly secretoneurin-immunopositive. The staining patterns of secretoneurin- and substance P-like immunoreactivities were to a certain extent overlapping in several areas. The highest degree of coincidence was found in the substantia gelatinosa. This study demonstrated that secretoneurin is distinctly distributed in the human brain stem. Its distributional pattern indicates a role particularly in the modulation of afferent pain transmission and in the regulation of autonomic functions.

Adult↗
PubMed1994

Different concentrations of vasoactive intestinal polypeptide in aqueous humor of patients with proliferative vitreoretinopathy and cataract patients.

The pathophysiological events leading to cellular proliferation in proliferative vitreoretinopathy are largely unknown. An involvement of neuropeptides in that disease has recently been discussed, as substance P was found to be highly enriched in the intraocular fluid of patients with proliferative vitreoretinopathy. In the present study, aqueous humor was analyzed for another neuropeptide, vasoactive intestinal polypeptide. Radioimmunoassay revealed significantly increased levels of that polypeptide in the aqueous humor of patients with proliferative vitreoretinopathy as compared with cataract patients who served as controls. As vasoactive intestinal polypeptide contributes to the environment of the retinal pigment epithelial cell layer and induces proliferation of these cells in vitro, this peptide may be involved in the pathogenetic mechanisms leading to cellular proliferation in proliferative vitreoretinopathy.

Aqueous Humor↗
PubMed1994

Clozapine-induced transient white blood count disorders.

BACKGROUND: The aim of the study was to shed more light on the incidence and course of clozapine-induced transient white blood count (WBC) disorders. METHOD: In an analysis of our clozapine drug monitoring program, we evaluated the data of 68 patients receiving clozapine for the first time. Incidence rates were calculated by actuarial life table analysis. The potential influence of sex, age, dose, and plasma level was evaluated using discriminant analysis. RESULTS: Two patients developed progressive neutropenia, leading to agranulocytosis in one case. We also found the following transient hematologic dysfunctions: neutropenia (22.0%), eosinophilia (61.7%), and leukocytosis (40.9%). One patient showed chronic leukocytosis. Additionally, minor changes in the number of lymphocytes, monocytes, and basophilic granulocytes were detected in the study population. CONCLUSION: Hematologic side effects are frequently induced by the atypical antipsychotic clozapine. Next to agranulocytosis, a progressive and potentially lethal hematologic adverse effect, most of the WBC disorders are transient and appear to be harmless.

Actuarial Analysis↗
PubMed1994

[Autonomic and peptidergic innervation of the human larynx].

Autonomic and peptidergic innervation of the human larynx (vocal cords, ventricular folds, epiglottis, subglottic region and recurrent nerves) was studied by application of single and double immunocytochemistry and radioimmunoassay. In all tissues investigated, immunoreactivities for a variety of regulatory peptides were detected and included vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), helospectin, neuropeptide Y (NPY), C-flanking peptide of NPY (C-PON), calcitonin gene-related peptide (CGRP), substance P and neurokinin A. In the recurrent nerves, only a few peptide-immunoreactive nerve fibers were found. The laryngeal region of the epiglottis and the subglottic region showed characteristic corpuscular nerves containing substance P and CGRP running underneath and within the epithelium.

Adult↗
PubMed1993

Distribution of secretoneurin-like immunoreactivity in comparison with substance P- and enkephalin-like immunoreactivities in various human forebrain regions.

The distribution of secretoneurin-like immunoreactivity, a peptide derived from secretogranin II, was studied by means of immunocytochemistry and compared to the pattern of staining for substance P- and enkephalin-like immunoreactivities in the human basal forebrain, with special reference to the basal ganglia. Secretoneurin-like immunoreactivity was characterized by gel filtration and reversed-phase high pressure liquid chromatography analysis. Chromatographic analysis revealed a single peak for secretoneurin-like immunoreactivity. No secretoneurin-immunopositive forms of high molecular weight were found. Secretoneurin-like immunoreactivity appeared mainly in dot- and fibre-like structures. In addition, a band-like terminal staining (woolly fibres) that has been shown by others for substance P- and enkephalin-like immunoreactivities, was also observed for secretoneurin-like immunoreactivity. Medium-sized cells were found arranged in clusters or singly within the caudate and putamen. In the basal ganglia, a high density of secretoneurin-like immunoreactivity was found in the internal segment of the globus pallidus, the ventral pallidum and in the pars reticulata of the substantia nigra. In these areas the immunostaining appeared mainly as woolly fibres. The bed nucleus of the stria terminalis and medial amygdala displayed a high density of fine beaded secretoneurin-like immunoreactive fibres, sometimes forming pericellular contacts. The nucelus basalis of Meynert was highly innervated by secretoneurin-like immunoreactive fibres, mainly in the form of woolly fibres. In general, a large overlap was found between secretoneurin- and substance P-like immunoreactivity in all examined areas of the basal ganglia. In the bed nucelus of the stria terminalis and medial amygdala secretoneurin-like immunoreactivity was distributed very similarly to enkephalin-like immunoreactivity. These data provide evidence that in different subsets of neurons and neuronal pathways secretoneurin-like immunoreactivity coexists with substance P- and enkephalin-like immunoreactivity in several areas of the human brain.

Adult↗
PubMed1993

Intranigral injection of selective neurokinin-1 and neurokinin-3 but not neurokinin-2 receptor agonists biphasically modulate striatal dopamine metabolism but not striatal preprotachykinin-A mRNA in the rat.

Tachykinins are highly concentrated in striatum and substantia nigra. Intranigral injection of selective neurokinin-1 and neurokinin-3 but not neurokinin-2 receptor agonists significantly decreased striatal dopamine metabolism at early time points (1 and 5 min) but increased dopamine metabolism at late time points (60 and 180 min). This probably modified striatal dopamine release, was, however, not able to influence striatal preprotachykinin-A gene expression. The data suggest that tachykinins modulate nigro-striatal dopamine neurons via neurokinin-1 and neurokinin-3 receptors and the modified dopamine stimulus is not strong enough to influence striatal tachykinin neurons.

3,4-Dihydroxyphenylacetic Acid↗