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Biomedical subjects

E Fehér

Publications and source records attributed to E Fehér.

At least 19 recordsLinked to original sources

Neuroimmune link in the mucosa of chronic gastritis with Helicobacter pylori infection.

It is suggested that different neuropeptides regulate gastric mucosal integrity and participate in the development of chronic gastritis. The aim of this study was to examine the roles and changes of immunoreactive (IR) nerves and immunocompetent cells in human gastritis. Immunohistochemical, immunocytochemical, and confocal laser microscopic methods were used. All investigated nerve fibers were found in different quantities in the mucosa of both control and gastritis samples. The number of SP, NPY, and VIP IR nerve fibers increased significantly (P < 0.05) in gastritis. No IR immunocompetent cells (lymphocytes, plasma cells, mast cells) were found in the control, however, some showed NPY (16.8%) and SP (9.4%) immunoreactivity in chronic gastritis. The distance between nerve fibers and immunocompetent cells was 200 nm to 1 microm. In conclusion, the increased number of SP, NPY, and VIP IR nerves and IR immunocytes suggests that they participate in development of neurogenic inflammation, repairing processes of chronic gastritis.

Adult↗

Does chronic experimental head-down tilt alter intramural innervation density of limb blood vessels?

Earlier, substantial increases in the intramural sympathetic innervation density of rat hind-limb blood vessels were found after 2 weeks of experimental orthostasis with tubular 45 degrees head-up tilt cages. In the present study, we presumed that chronic head-down tilting induces opposite changes in the innervation density. Tilted rats were kept 45 degrees head-down in long tubular cages for either 2 or 4 weeks (HDT2, HDT4), and the control animals were maintained in horizontal tilt cages for the same period (HOR2, HOR4). Segments of the saphenous and brachial veins and arteries were used for quantitative electron microscopic examinations. Intramural innervation density was defined by nerve terminal density (NTD) and synaptic microvesicle count (SVC) within the vascular adventitia. Neither HDT2 nor HDT4 resulted in a decrease of NTD or SVC of the saphenous and brachial veins or arteries; instead, a tendency to increase was observed in some cases. Thus in contrast to the large increases we found earlier in hind-limb vascular innervation density after 2 weeks of head-up tilting, head-down tilting of the same duration-or even twice as long-did not decrease the adventitial innervation density in our model. We assume that the quasi-free locomotor exercise the tilted animals in the long tubular cages were allowed may counteract a possible suppressive effect of chronic head-down tilt on hind-limb vascular innervation density.

Animals↗

Morphological basis of sensory neuropathy and neuroimmunomodulation in minor salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: A predominance of sensory neuropathy was earlier described in Sjögren's syndrome (SS), which might precede the presence of sicca symptoms. The mechanism of sensory neuropathy in SS is unknown. Therefore, the aim of this study was to determine the quantitative changes of the different neuropeptide containing nerve terminals and the immunocompetent cells in labial salivary glands of primary SS. DESIGN: Immunohisto- and immunocytochemical methods were used for the detection of immunoreactive (IR) elements and the data were compared with the healthy controls. RESULTS: All of the investigated IR nerve fibres were found in different quantity and localisation in both of control and SS glands. The density of them was changed variously in SS. The number of the substance P (SP), neuropeptide Y (NPY) (P < 0.05), galanin (GAL) IR nerve terminals was decreased, however, the number of vasoactive intestinal polypeptide (VIP) and tyrosine beta-hydroxylase (TH) IR nerve fibres (P < 0.05) was increased compared to the control. There were no IR immunocompetent cells in the control materials, however, a large number of them showed IR for SP (46.2%) and NPY (34.4%) in the SS. The IR was demonstrated mainly in the mast cells, plasma cells and some of the lymphocytes. CONCLUSIONS: These neuropeptides might have a role in the sensory neuropathy; they might activate nociceptive and sympathetic pathways. Some neuropeptides (SP, NPY) are endogenous in the immune system and produced in certain conditions, e.g. inflammation and chronic autoimmune disorders such as SS, so they might participate in the neuroimmunomodulation and contribute to the atrophy, apoptosis and necrosis.

Adult↗

[Osteomalacia with fatal outcome in an elderly patient].

HISTORY AND ADMISSION FINDINGS: A 63-year-old woman was admitted with diffuse bone pain, chest deformity and orthopnea. She had previous prolonged periods of bed rest and decreased sunlight exposure after several bone fractures. INVESTIGATIONS: Laboratory tests showed hypocalcemia, hypophosphatemia with secondary hyperparathyroidism. The 25-hydroxy-D-vitamin level was too low for measurement. Radiological investigations raised the possibility of metabolic bone disease with secondary fracture. (99m)Tc-MDP bone scintigraphy demonstrated pathological isotope accumulation in places typical for osteomalacia. The histological investigation of the bone showed a thickening of the osteoid substance. DIAGNOSIS, TREATMENT AND COURSE: Osteomalacia was diagnosed. Two weeks of administering of daily 3000 I.U. vitamin D and 1500 mg calcium normalised the serum level of calcium and phosphate. Because of orthopnea and bone pain the patient stayed in the bed, and had to be given her nadroparin calcium. After six weeks heart and respiratory failure occurred. The patient died from a subtotal pulmonary embolism, which was a consequence of a deep vein thrombosis of the leg. CONCLUSION: In elderly people chronic and serious vitamin D deficiency can cause a life-threatening condition which can be prevented by vitamin D and calcium administration.

Bone and Bones↗

Mapping genes affecting flowering time and frost resistance on chromosome 5B of wheat.

Two populations of single chromosome recombinant lines were used to map genes controlling flowering time on chromosome 5B of wheat, and one of the populations was also used to map a new frost resistance gene. Genetic maps were developed, mainly using microsatellite markers, and QTL analysis was applied to phenotypic data on the performance of each population collected from growth-room tests of flowering time and frost tolerance. Using a recombinant substitution-line mapping population derived from a cross between the substitution-line 'Chinese Spring' ('Cheyenne' 5B) and 'Chinese Spring' (CS), the gene Vrn-B1, affecting vernalization response, an earliness per se locus, Eps-5BL1, and a gene, Fr-B1, affecting frost resistance, were mapped. Using a 'Hobbit Sib' ('Chinese Spring' 5BL) x 'Hobbit Sib' recombinant substitution line mapping population, an earliness per se locus, Eps-5BL2 was mapped. The Vrn-B1 locus was mapped on the distal portion of the long arm of chromosome 5B, to a region syntenous with the segments of chromosomes 5A and 5D containing Vrn-A1 and Vrn-D1 loci, respectively. The two Eps-5BL loci were mapped close to the centromere with a 16-cM distance from each other, one in agreement with the position of a homoeologous locus previously mapped on chromosome 5H of barley, and suggested by the response of 'Chinese Spring' deletion lines. The Fr-B1 gene was mapped on the long arm of chromosome 5B, 40 cM from the centromeric marker. Previous comparative mapping data with rice chromosome 9 would suggest that this gene could be orthologous to the other Fr genes mapped previously by us on chromosomes 5A or 5D of wheat, although in a more proximal position. This study completes the mapping of these homoeoallelic series of vernalization requirement genes and frost resistance genes on the chromosomes of the homoeologous group 5 in wheat.

Acclimatization↗

Role of the activation of the nuclear enzyme poly(ADP-ribose) polymerase in the pathogenesis of periodontitis.

We have investigated the role of the activation of nuclear poly(ADP-ribose) polymerase (PARP) enzyme, a mediator of downstream nitric oxide toxicity, using a combined approach of pharmacological inhibition and genetic disruption in a ligature-induced-periodontitis model in rats and mice. Immunohistochemical analysis revealed significantly increased poly(ADP-ribose) nuclear staining (indicative of PARP activation) in the subepithelial connective tissue of the ligated side compared with the non-ligated side. Ligation-induced periodontitis resulted in marked plasma extravasation in the gingivomucosal tissue and led to alveolar bone destruction compared with the non-ligated side, as measured by the Evans blue technique and by videomicroscopy, respectively. PARP inhibition with PJ34, as well as genetic PARP-1 deficiency, significantly reduced the extravasation and the alveolar bone resorption of the ligated side compared with controls. Thus, PARP activation contributes to the development of periodontal injury. Inhibition of PARP may represent a novel host response modulatory approach for the therapy of periodontitis.

Alveolar Bone Loss↗

Effects of black radish root (Raphanus sativus L. var niger) on the colon mucosa in rats fed a fat rich diet.

The effect of black radish root (Raphanus sativus L. var niger) was studied on the structure and redox state of the colon mucosa in fat-rich diet fed rats. The epithelial lining disrupted, the number of enterocytes and the goblet cells reduced and inflammatory cells were observed in rats fed with a fat-rich diet. After treatment with granules from black radish root all of the histopathological changes and parameters of the redox state caused by the fat-rich diet were improved. The structure of the epithelial cells was similar to the controls, the number of goblet cells increased and no inflammation was observed.

Animals↗

Nitric oxide synthase immunoreactivity of interstitial cells of Cajal in experimental colitis.

OBJECTIVE: There is functional and morphological evidence that interstitial cells of Cajal (ICC) may play a role in nitric oxide (NO) dependent signal transduction. However, little is known about the nitric oxide synthase (NOS) containing ICC during inflammation. MATERIALS AND METHODS: Immunocytochemical methods were used for the ultrastructural localization of NOS1-containing ICC in the wall of the colon of rats in experimental colitis. RESULTS: Large numbers of NOS immunoreactive (IR) nerve terminals were found in very close vicinity to smooth muscle cells as well as to blood vessels. IR nerves were found in close relationship with the ICC. The gap between the NOS IR nerve fibers and the membrane of smooth muscle cells and of ICC was 20-250 nm. In experimental colitis the number of NOS IR nerve fibers slightly decreased, however, large numbers (24%) of the ICC became IR for NOS. In the noninflamed area and in the controls, all these cells were immunonegative for NOS. CONCLUSIONS: Our light- and ultrastructural study suggests that some of the ICC can also synthesize NO, at least during inflammation. Therefore the change in the number and structure of ICC could play an important role in the pathogenesis of a variety of motility disorders.

Animals↗

Evidence for the expression of cyclooxygenase-2 enzyme in periodontitis.

We investigated the role of the inducible isoform of cyclooxygenase (COX-2) in a rat model of periodontitis using a selective COX-2 inhibitor NS-398. Periodontitis was produced by a silk ligature placed around the lower left 1st molar. Animals were treated with NS-398 (3 mg kg(-1) i.p., 2 times per day for 7 days) or vehicle. At Day 8, the gingivomucosal tissues encircling the mandibular 1st molars were removed on both sides for COX-2 immunohistochemistry, measurement of plasma extravasation by the Evans blue technique, and alveolar bone loss by videomicroscopy. Immunohistochemical analysis revealed numerous strongly COX-2-positive cells in the subepithelial tissues in the ligated side and only a few COX-2-reactive cells in the contralateral (control) side. Ligation significantly increased Evans blue extravasation in the gingivomucosal tissue and alveolar bone destruction compared to the control side. NS-398 treatment significantly reduced the plasma extravasation and alveolar bone resorption of the ligated side compared to vehicle administration. The present results suggest that COX-2 is induced by periodontitis, and plays an important role in gingival inflammation and alveolar bone destruction. In a previous study (Br J Pharmacol 1998;123:353-60) we found the expression of the inducible isoform of nitric oxide synthase in this model. Therefore, based on our own data and the literature, we propose that selective inhibition of these inducible enzymes might be a basis for adjunctive therapy, or new therapeutic approaches in periodontitis.

Animals↗

Electronmicroscopical localization of nitric oxide synthase-containing nerve elements in cat pylorus.

Intrinsic nitric oxide synthase (NOS)-containing nerve cells and fibers were studied in the wall of the pylorus of cat at the ultrastructural level using ABC immunocytochemistry. Large numbers of NOS immunoreactive (IR) nerve cell bodies were observed in the myenteric and in the submucous plexuses, and few in the tunica propria mucosa. The NOS IR nerve fibers were most abundant in the inner circular muscle layer and in the tunica mucosa. They were found in very close vicinity to the smooth muscle cells of the inner circular muscular layer as well as to the blood vessels and the epithelial lining. The gap between the NOS IR nerve fibers and the membrane of the target cells was 20 to 250nm. Apparent synaptic contacts were observed between the IR nerve fibers and unlabelled nerve processes and other non IR nerve cell body. It is confirmed that NO might influence smooth muscle cell activity, regulate blood flow and modulate the function of the epithelial cells. Our ultrastructural study suggested that some of the NOS containing neurons belong to the intrinsic interneurons and have a regulatory effect on other intrinsic nerve elements involved in local neuronal reflexes.

Animals↗

Influence of long-term experimental orthostatic body position on innervation density in extremity vessels.

The aim of this study was to quantitate the density of nerve terminals as well as their synaptic vesicle population in the adventitia of saphenous (SV and SA) and brachial veins and arteries (BV and BA) obtained from rats maintained in a horizontal control or a tilted position. Adult animals were kept individually in tube-like cages in a 45 degrees head-up position. After 2 wk, both tilted and control animals were anesthetized, and the whole body was perfused with fixative solution at physiological pressure. Vessels segments were then excised for electron microscopy and immunohistochemistry. The nerve terminal density (NTD) of SA was 8.20 +/- 1.46 nerve terminals/100 microm(2) cross section of adventitia and that of SV was 4.53 +/- 0.61 nerve terminals/100 microm(2) cross section of adventitia in control rats. Tilting caused a significant increase in NTD of both SA (70%) and SV (52%). The synaptic microvesicle density (SyVD) was larger in SA than SV in control rats (30.48 +/- 4.41 vs. 13.38 +/- 2.61 synaptic vesicles/10 terminal sections), but tilting resulted in more pronounced changes in SyVD of SV (95%) than SA (54%). No significant changes in NTD and SyVD of BA were found after tilt (-3.6% relative to 4.99 +/- 0.33 compared with 0.4% relative to 24.89 +/- 3.7, respectively). Whereas NTD of BV exhibited a tendency to increase (3.73 +/- 0.86 vs. 2.31 +/- 0.29 nerve terminals/100 microm(2) cross section of adventitia), SyVD did not change significantly (18.96 +/- 2.74 vs. 22.85 +/- 3.17 synaptic vesicles/10 terminal sections). A large number of nerve terminals of all vessels were tyrosine hydroxylase immunoreactive (containing norepinephrine). These findings support the hypothesis that long-term gravitational load causes adaptive morphological and functional remodeling of sympathetic innervation in blood vessels of the extremities.

Animals↗

Neuroimmune interactions in experimental colitis. An immunoelectron microscopic study.

With its abundance of neurons and immunocytes, the gut is a potentially important site for the study of the interaction between the nervous and immune systems. In this electron microscopic study we have investigated the distribution of substance P (SP)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (IR) nerve terminals and the immunocytes during experimental colitis in the rat. A mild colitis was induced by a luminal enema containing trinitrobenzene sulfonic acid. The most severe inflammation was detected after 2 days and the density and the distribution of the SP- and VIP-IR nerve terminals as well as the immunocompetent cells were studied at that time. Many SP- and VIP-IR nerve terminals were observed in a very close situation to the inflammatory cells. The number of VIP-IR nerve terminals slightly increased in the inflamed area. The gap between the axolemma of the nerve terminals and immunocytes was 20-200 nm. Some lymphocytes and plasma cells were also IR for SP in the inflamed area, whereas no IR immunocytes were observed in the control and in noninflamed area from the same animal. The very close apposition of the SP- and VIP-IR nerve terminals to the inflammatory cells as well as the presence of SP-IR immunocytes in inflamed area support the suggestion that bidirectional neuroimmunomodulation exists in the colon.

Animals↗

Enzyme- and immunohistochemical localization of nitric oxide synthase in nerves of the porcine pancreas.

The distribution of nitric oxide synthase (NOS) in neuronal and non-neuronal porcine pancreatic tissues was examined using nicotinamide adenine dinucleotide hydrogen phosphate diaphorase (NADPHd) enzymehistochemistry and neuronal type NOS immunohistochemistry. NOS-containing perikarya were regularly discernible in the pancreatic ganglia, whereas positive thin nerve fibers appeared within nerve bundles of the interlobular spaces and as thin varicose fibers in the vicinity of pancreatic blood vessels. Vascular endothelium showed intense staining for NADPHd and most of the islet cells were NOS immunoreactive. The above morphological findings indicate that nitrergic innervation of the porcine pancreas is very similar to that of the pancreata of other mammalian species and suggest that nitric oxide of both neuronal and extraneuronal origin may regulate blood flow and secretion of the porcine pancreas.

Animals↗

Immunocytochemical localisation of neuropeptide-containing nerve fibres in human labial glands.

Different neuropeptide-containing nerve fibers (vasoactive intestinal polypeptide, substance P, neuropeptide Y) and nitric oxide synthase (NOS) positive nerve fibers were investigated to clarify their role in the function of human labial glands using immunohisto- and immunocytochemical techniques. The distribution pattern of all immunoreactive nerve fibers was similar both in the control and in the Sjögren's syndrome specimens. A large number of thin varicose vasoactive intestinal polypeptide and NOS positive nerve fibers were seen around or in close contact with the acini. Some of the immunoreactive nerve fibers were associated with the salivary ducts and blood vessels. Substance P and neuropeptide Y immunoreactive nerve fibers were located mainly around the blood vessels. Immunocytochemistry demonstrated that some of the positive nerve fibers were in direct contact with the acini, blood vessels and with the lymphocytes. The gap between the membranes of immunoreactive nerve terminals and the target cells was 40 to 200 nm. The number of the nerve terminals in Sjögren's syndrome specimens was decreased and some degenerated axons were also found. These results suggest that these neuropeptides and nitric oxide might act as a neurotransmitter in the regulation of secretion and blood flow in the labial glands. These fibers might also alter the neuroimmunological processes, because the investigated neuropeptides are known to be immunoregulators.

Axons↗

Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat.

1. Excessive production of nitric oxide (NO), and the generation of peroxynitrite have been implicated in various proinflammatory conditions. In the present study, using mercaptoethylguanidine (MEG), a selective inhibitor of iNOS and a peroxynitrite scavenger, we investigated the role of iNOS and peroxynitrite in a rat model of periodontitis. 2. Periodontitis was produced in rat by a ligature of 2/0 braided silk placed around the cervix of the lower left 1st molar. Animals were then divided into two groups: one group of rats was treated with MEG (30 mg kg(-1), i.p., 4 times per day for 8 days), animals in the other group received vehicle. At day 8, the gingivomucosal tissue encircling the mandibular 1st molars was removed on both sides from ligated and sham operated animals for inducible nitric oxide synthase (iNOS) activity assay and for immunocytochemistry with anti-iNOS serum. Plasma extravasation was measured with the Evans blue technique. Alveolar bone loss was measured with a videomicroscopy. 3. Ligation caused a significant, more than 3 fold increase in the gingival iNOS activity, whereas it did not affect iNOS activity on the contralateral side, when compared to sham-operated animals. Immunohistochemical analysis revealed iNOS-positive macrophages, lymphocytes and PMNs in the connective tissue and immunoreactive layers of epithelium on side of the ligature, and only a few iNOS reactive connective tissue cells on the contralateral side [corrected]. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. 4. The present results demonstrated that ligature-induced periodontitis increases local NO production and that MEG treatment protects against the associated extravasation and bone destruction. Based on the present data, we propose that enhanced formation of NO and peroxynitrite plays a significant role in the pathogenesis of periodontitis.

Animals↗

[Immunocytochemical demonstration of nitric acid synthase in rat pancreatic tissue].

To investigate the age-related alterations of pancreatic distribution of nitric oxide synthase in rats, we applied light microscopic immunocytochemistry. Tissue samples were obtained from the pancreata of 5-day-old rat newborns and 120-day-old adult rats and processed for immunocytochemistry using anti neuronal nitric oxide synthase primary serum with the avidin-biotin-streptavidin complex method. Nitric oxide synthase immunopositive intrinsic nerve cells and perivascular/periacinar nerve fibers could be seen in both the newborn and the adult rat pancreas. In addition to the labelled neuronal structures we detected some immunoreactive acinar cells in the newborns, while the neonatal ductal epithelium and the islet cells were immunonegative. Strong staining for nitric oxide synthase was observed in the adult ductal epithelial cells and moderate positivity was displayed by the adult islet cells. The localization of nitric oxide shows age-related changes mainly in the non-neuronal structures of the rat pancreas: these findings could form the morphological base of pancreatic dysfunctions in the aged.

Animals↗