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41.
Involvement of nitric oxide synthase in the physiology and pathophysiology of facial nerve function and dysfunction 总被引:1,自引:0,他引:1
O. Michel Alexander Hess Martin Krolzig Eberhard Stennert Klaus Addick Wilhelm Bloch 《European archives of oto-rhino-laryngology》2000,257(4):188-192
To date few reports have discussed the presence and function of nitric oxide (NO) in structures of the facial nerve. We performed
nicotinamide adenine dinucleotide phosphate (NADPH-d)-diaphorase-histochemistry and immunohistochemistry on the intratemporal
portion of the facial nerve, including the geniculate ganglion, of guinea pigs using specific antibodies to the three known
isoforms of NO synthase and soluble guanylyl-cyclase (sGC). Normal facial nerves were compared to those treated intratympanically
with bacterial lipopolysaccharides (LPS) and tumor necrosis factor-α (TNF-α). Both constitutive NOS isoforms and sGC could
be detected in the bipolar ganglion cells of normal animals, while the inducible isoform (iNOS or NOS II) was not found. Endothelial
NOS (NOS III) and sGC were present in blood vessels and were predominantly found in the perineurial sheath and less in the
endoneurium. sGC could be detected in all fibers in a cross section of the facial nerve. LPS and TNF treatment led to the
detection of iNOS in the perikaryia of the geniculate ganglion and the perineural sheath. These findings imply that NO may
be involved in neurotransmission at least in the visceroafferent system. NO regulates vascular tone of nutrient blood vessels
in the perineural sheath and endoneurium. The presence of sGC indicates that NO acts via its second messenger cGMP. NOS II
expression may be a contributing factor to facial nerve palsy via two different mechanisms: NOS II-generated NO may lead to
an overstimulation of the visceroefferent nerve fibers and motor fibers of the facial nerve. Dysregulation in facial nerve
blood vessels could lead to edema and elevated pressure on the nerve within its osseous canal.
Received: 13 April 1999 / Accepted: 12 August 1999 相似文献
42.
E. Schlicker M. Kathmann M. Detzner H. J. Exner M. Göthert 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(1):34-41
The effects of 2-adrenoceptor agonists (dexmedetomidine, oxymetazoline), alone or in combination with various -adrenoceptor subtype-selective antagonists (CH-38083, idazoxan, WB4101, BRL44408, ARC-239, prazosin), on noradrenaline- and isoprenaline-induced lipolysis were investigated in human isolated abdominal subcutaneous fat cells. The rank order of potency of antagonists in preventing dexmedetomidine- and oxymetazoline-evoked suppression of isoprenaline-induced lipolysis was (pA2-values): CH-38083 (7.69 and 7.48) idazoxan (7.5 and 7.41) > BRL 44408 (7.23 and 7.19) WB 4101 (7.13 and 7.12) > prazosin (5.18 and 5.17) > ARC-239 (4.72, 4.9). While CH-38083 and idazoxan, non-subtype selective 2-adrenoceptor antagonists and BRL44408, a selective a2A-adrenoceptor antagonist as well as WB4101 potentiated the lipolytic effect of noradrenaline, ARC-239, the selective 2B-adrenoceptor antagonist failed to affect it. In addition since the 2A-adrenoceptor selective agonist, oxymetazoline concentration dependently inhibited the lipolytic effect of isoprenaline, and WB4101 and BRL44408 (a2A-adrenoceptor antagonists) antagonised the effect of oxymetazoline in a competitive manner, it is concluded that the a2A-adrenoceptor subtype is involved in antilipolysis. In addition, functional evidence was obtained that there is an interaction between 2A- and -adrenoceptors located on the cell surface of adipocytes, through which locally released noradrenaline and/or circulating circulating adrenaline influence lipolysis.On leave from Institute of Medical Pharmacology, University of Pisa, Via Roma 55, I-5626 Pisa, Italy
Correspondence to: E. S. Vizi at the above address 相似文献
43.
E. Schlicker H. Pertz H. Bitschnau K. Purand M. Kathmann S. Elz W. Schunack 《Inflammation research》1995,44(7):296-300
We determined the affinity and/or potency of the novel H3 receptor antagonist iodoproxyfan at
2 and 5-HT3 receptors. Iodoproxyfan and rauwolscine (a reference
2 ligand) (i) monophasically displaced3H-rauwolscine binding to rat brain cortex membranes (pKi 6.79 and 8.59); (ii) facilitated the electrically evoked tritium overflow from superfused mouse brain cortex slices preincubated with3H-noradrenaline (pEC50 6.46 and 7.91) and (iii) produced rightward shifts of the concentration-response curve (CRC) of (unlabelled) noradrenaline for its inhibitory effect on the evoked overflow (pA2 6.65 and 7.88). In the guinea-pig ileum, iodoproxyfan 6.3µmol/l failed to evoke a contraction by itself but depressed the maximum of the CRC of 5-hydroxytryptamine (pD2 5.24). Tropisetron (a reference 5-HT3 antagonist) produced rightward shifts of the CRC of 5-hydroxytryptamine (pA2 7.84). In conclusion, the affinity/potency of iodoproxyfan at H3 receptors (range 8.3-9.7 [1]) exceeds that at
2 receptors by at least 1.5 log units and that at 5-HT3 receptors by at least 3 log units. 相似文献
44.
Hans Juha Exner Eberhard Schlicker 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(1):46-52
Mouse or rat brain cortex slices were preincubated with 3H-noradrenaline and superfused with physiological salt solution containing desipramine. We studied the effects of prostaglandin E2 (PGE2), prostaglandin D2 (PGD2) and related drugs on the electrically evoked (50 mA, 2 ms, 0.3 Hz) tritium overflow.PGE2 inhibited the electrically evoked tritium overflow from mouse brain cortex slices; the maximum effect of PGE2 (79010) was attenuated by the 2-adrenoceptor agonist talipexole (to 52010) and enhanced by the 2-adrenoceptor antagonist rauwolscine (to 92%). Rauwolscine was added to the superfusion medium in all subsequent experiments. The effect of PGE2 was readily reversible upon withdrawal from the medium and remained constant upon prolonged exposure of the tissue to the prostanoid. Studies with EP receptor agonists, mimicking the inhibitory effect of PGE2, showed the following potencies (pIC50): sulprostone (8.22); misoprostol (8.00); PGE2 (7.74); PGEZ (7.61); iloprost (5.86). The concentration-response curve of PGE2 was marginally shifted to the right by the EP1 receptor antagonist AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid; apparent pA2 3.97) and by the TP receptor antagonist vapiprost (4.50). AH 6809, by itself, did not affect the evoked overflow whereas vapiprost increased it. PGD2 inhibited the evoked overflow at high concentrations (pIC50 4.90); this effect was not altered by the DP receptor antagonist BW A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2hydroxyethylamino)hydantoin), which, by itself, did not affect the evoked overflow. Indometacin slightly increased the evoked overflow and tended to increase the inhibitory effect of PGE2. PGE2 inhibited the electrically evoked tritium overflow also in rat brain cortex slices. The maximum effect (obtained in the presence of rauwolscine) was 61%; the pIC30 value was 7.67.The present study suggests that PGE2 inhibits noradrenaline release from mouse brain cortex via EP3 receptors and that its maximum effect is more marked in the mouse than in the rat. The inhibitory effect of PGD2 (in the mouse brain) does not involve DP receptors and may also be related to EP3 receptors. The EP3 receptors interact with a2-adrenoceptors and may be activated by endogenous prostanoids. 相似文献
45.
B. Malinowska C. Leschke S. Elz W. Schunack E. Schlicker 《Inflammation research》1993,38(3-4):C257-C259
The effect of the newly synthetized H1 agonists 2-(3-trifluoromethylphenyl)histamine (2-TFMPH) and 2-(3-bromophenyl)histamine (2-BPH) and of the reference compound 2-(2-thiazolyl)ethylamine (2-TEA) on diastolic blood pressure and heart rate was studied in pithed and vagotomized rats. 2-TFMPH and 2-BPH were at least equipotent with 2-TEA in producinga dimethindene-sensitive, short-lasting vasodepressor response. At the highest dose, 2-TFMPH and 2-BPH produced an additional small vasopressor response, which was followed by a long-lasting vasodepressor effect not counteracted by dimethindene and ranitidine 2-TEA, at the highest dose, induced an additional vasopressor response abolished by prazosin plus rauwolscine. Basal heart rate was increased by 2-TEA (in a desipramine-sensitive manner) but not affected by 2-TFMPH or 2-BPH. In conclusion, 2-TFMPH and 2-BPH are potent H1 agonists, devoid of an indirect sympathomimetic effect; at high doses, they produce a vasodepressor response not mediated via histamine receptors.Recipient of a fellowship provided by the Alexander von Humboldt-Stiftung (Bonn, Germany) 相似文献
46.
47.
G. J. Molderings G. Weißenborn E. Schlicker J. Likungu M. Göthert 《Naunyn-Schmiedeberg's archives of pharmacology》1992,346(1):46-50
Summary The human saphenous vein was used to examine whether presynaptic histamine receptors can modulate noradrenaline release and, if so, to determine their pharmacological characteristics. Strips of this blood vessel were incubated with [3H]noradrenaline and subsequently superfused with physiological salt solution containing desipramine and corticosterone. Electrically (2 Hz) evoked 3H overflow was inhibited by histamine and the H3 receptor agonist R-(–)--methylhistamine. Histamine-induced inhibition of electrically evoked tritium overflow was not affected by 2-adrenoceptor blockade by rauwolscine. S-(+)--methylhistamine (up to 10 mol/l) as well as the histamine H1 and H2 receptor agonists 2-(2-thiazolyl)ethylamine (up to 3 mol/l) and dimaprit (up to 30 mol/l), respectively, were ineffective. The selective histamine H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine. The histamine H2 and H1 receptor antagonists ranitidine and pheniramine, respectively, did not affect the histamine-induced inhibition of evoked tritium overflow. The present results are compatible with the suggestion that the sympathetic nerves of the human saphenous vein are endowed with inhibitory presynaptic histamine receptors of the H3 class.
Send offprint requests to M. Gothert at the above address 相似文献
48.
Pesheva P Probstmeier R Spiess E Schachner M 《The European journal of neuroscience》1991,3(4):356-365
J1-160 and J1-180 are developmentally late appearing J1 extracellular matrix glycoproteins derived from oligodendrocytes. They prevent adhesion of neurons (but not of astrocytes or fibroblasts) when offered as a substrate in mixture with laminin (Pesheva et al., J. Cell Biol., 109, 1765 - 1778, 1989). In the present study we have examined the influence of divalent cations on the inhibitory substrate properties of J1-160/180 glycoproteins towards adhesion of neurons. By metal chelate affinity chromatography, we show that J1-180, but not J1-160, binds Ca2+, while both J1 components are capable of binding Zn2+ and other divalent metal ions. Divalent cation binding was observed by gel filtration, aggregation assays with coated latex beads and electron microscopic examination to elicit aggregation of the molecules. Divalent cation binding also affects their non-permissive substrate properties towards neurons from early postnatal mouse cerebellum. Without divalent cations, J1-160 and J1-180 are inhibitory for substrate adhesion of neurons independently of the adhesive substrate present (laminin or poly-l-lysine). This effect is neutralized when J1-180 is preincubated with Ca2+ or Zn2+ prior to coating as substrate. In contrast, preincubation with Ca2+ ions does not affect the inhibitory substrate properties of J1-160 under these conditions. These observations show that J1-160/180 molecules may undergo self-aggregation in a divalent cation-dependent mechanism, which correlates with the neutralization of their inhibitory effect on neuronal adhesion. The aggregation state of the molecules may thus influence the process of myelination by a homophilic binding mechanism and determine the effectiveness of neurite extension during central nervous system development and under traumatic conditions in the adult. 相似文献
49.
The interaction of phenylbutazone with the enantiomers and racemic [
3
H]phenprocoumon was studied in male inbred Wistar-Lewis rats following a single i.v. dose of the three forms of phenprocoumon and chronic oral treatment with phenylbutazone (average plasma concentration of about 60 g/ml). Phenylbutazone augmented the anticoagulant effect of R(+), S(–), and R, S (±) phenprocoumon to a similar extent. The free fraction of drug in the plasma of the enantiomers and racemic phenprocoumon increased in the presence of phenylbutazone. However, the rate of elimination of total drug from plasma and liver and the distribution between liver and plasma of all three forms of phenprocoumon remained nearly unaffected by phenylbutazone. Thus there is no evidence for a stereoselective drug interaction between phenprocoumon and phenyl-butazone. For racemic [
3
H]phenprocoumon it was possible to follow the kinetics of free drug in plasma and liver along with the time course of anticoagulant activity. In these studies, free drug concentrations in plasma and liver increased during treatment with phenylbutazone, but the elimination rate constant of free racemic phenprocoumon in plasma and liver remained essentially unchanged. Phenylbutazone markedly decreased the volume of distribution referenced to free drug and the clearance of free phenprocoumon (i.e., intrinsic metabolic clearance). Whereas the total (bound and unbound) drug concentration-effect relationship in plasma and liver was shifted to the left in rats treated with phenylbutazone, such shift was not seen in the free drug concentration-response relationship. In conclusion, the increase in the free concentration of phenprocoumon in plasma and liver and the concomitant decrease in the clearance of free drug are the mechanisms responsible for the marked and sustained enhancement of the anticoagulant effect which follows treatment with phenbutazone.This work was supported by the Deutsche Forschungsgemeinschaft. 相似文献
50.
Laurence Moureau-Zabotto Laurence Thomas Binh N'Guyen Bui Christine Chevreau Eberhard Stockle Pierre Martel Paul Bonneviale Bernard Marques Jean-Marie Coindre Guy Kantor Tomohiro Matsuda Martine Delannes 《Radiotherapy and oncology》2004,73(3):313-319
PURPOSE: To analyze the management and clinical outcome of patients treated for a first isolated local recurrence of soft tissue sarcomas (trunk or extremities) and to identify prognosis factors. METHODS AND MATERIAL: Between 1980 and 1999, 83 adult patients were included in the study. Mean age was 61 years. Mean tumor size was 6 cm. Most sarcomas were located in extremities (n=74), were deep (n=60), and proximal (n=53); 30 involved nerves or vessels. Histologic subtypes were mainly grade 2 (42%) or 3 (36%) histiocytofibrosarcomas (49%) and liposarcomas (20%). Surgical treatment of recurrences consisted in wide excision (29 cases), marginal resection (43 cases), 5 patients requiring amputation. Final results were R0 (n=33), R1 (n=47) or R2 (n=3) resection. Besides surgery, 6 patients received neo-adjuvant and 7 others adjuvant chemotherapy. Twenty three patients received post-operative external beam radiotherapy (EBRT) (mean dose 55 Gy) and 26 interstitial 192Ir low dose rate brachytherapy (BCT) (mean dose 45 Gy for BCT alone, 22 Gy when associated with EBRT), 19 patients being re-irradiated. RESULTS: Mean follow up was 13 years. Thirty-seven (45%) patients relapsed, 62% of whom presenting an isolated local recurrence. Nineteen patients developed distant metastases. Multivariate analysis showed only tumor depth (P=0.05) and re-resection for primary R1 resection (P=0.018) being independent prognosis factors for tumor control, radiotherapy (EBRT and/or BCT) being significant in univariate analysis (P=0.05). Overall survival rate was 73%, 54%, and 47% at, respectively, 3.5 and 10 years, and was 65%, 35% and 32% after a further local recurrence. Multivariate analysis showed trunk (P=0.0001) or inferior extremity locations (P=0.023), symptomatic (P=0.001), high grade (P=0.01), deep (P=0.01) tumors, and the occurrence of a further local failure (P=0.004) as unfavorable characteristics for overall survival. CONCLUSIONS: A first isolated local recurrence of STS increases mainly the risk of a subsequent local relapse. Quality of local treatment is decisive. When a conservative treatment is feasible, it should combine surgical resection and radiotherapy, BCT being the best suited in previously irradiated patients. Efforts have to be pursued to increase quality of the treatment of primary tumors, at best performed in centers that have expertise in this field. 相似文献