Schwannoma of the nasal septum: a case report with review of the literature

Schwannomas are neurogenic neoplasms rarely found in the sinonasal tract, where localization to the nasal septum is exceedingly rare (only 11 cases have been described in the western literature). We report the case of a 29-year-old white male with a schwannoma completely filling the left nasal fossa and arising from the bony part of the septum. A computer tomography (CT) scan and a biopsy suggestive of benign schwannoma were obtained before the lesion was removed by a degloving approach. The preoperative diagnosis of nasal septum schwannoma was confirmed. The patient is asymptomatic and without endoscopic evidence of recurrence 7 years after surgery. A review of the literature with particular emphasis on the clinical presentation, histological features, differential diagnosis and therapeutic options for such a rare lesion is included. Received: 11 June 1999 / Accepted: 10 February 2000     

Synthetic Evolution of a Supramolecular Harpooning Mechanism to Immobilize Vesicles at Antifouling Interfaces

The immobilization of vesicles has been conceptualized as a method to functionalize biointerfaces. However, the preservation of their integrity post immobilization remains a considerable challenge. Interfacial interactions can cause vesicle rupture upon close surface contact and non-specific protein adsorption impairing surface functions. To date, immobilization of vesicles has relied solely on either entrapment or prior modification of vesicles, both of which require laborious preparation and limit their applications. This work develops a bioinspired strategy to pin vesicles without prior modification while preserving their intact shape. This work introduces antifouling diblock copolymers and ultrathin surface-attached hydrogels containing a brush-like interface consisting of a bottle brush copolymer of N-(2-hydroxypropyl) methacrylamide (HPMA) and N-(3-methacrylamidopropyl)-N,N-dimethyldodecan-1-aminiumiodide (C12+). The presence of positive charges generates an attractive force that pulls vesicles toward the surface. At the surface, the amphiphilic properties of the combs facilitate their insertion into the membrane, mimicking the harpooning mechanism observed in antimicrobial peptides. Importantly, the antifouling poly(HPMA) backdrop serves to safeguard the vesicles by preventing deformation and breakage. Using a combination of thermodynamic analysis, surface plasmon resonance, and confocal laser scanning microscopy, this work demonstrates the efficiency of this biomimetic system to capture vesicles while maintaining an antifouling interface necessary for bioapplications.     

Modulation of electrically evoked [3H]-noradrenaline release from cultured chick sympathetic neurons

In the present study we attempted a comprehensive characterization of modulation of noradrenaline release from chick sympathetic neurons. To this purpose sympathetic neurons derived from chick lumbosacral paravertebral ganglia and kept in culture for 7 days were loaded with 0.05 mol/l [³H]-noradrenaline and subjected to electrical field stimulation (36 pulses/3 Hz). Since the released transmitter was partially recaptured, superfusion was usually performed in the presence of (+)-oxaprotiline, an inhibitor of noradrenaline re-uptake. [³H]-Noradrenaline was released in a manner which was dependent on extracellular Ca²⁺ and sensitive to tetrodotoxin (TTX). -Conotoxin (-CTX; 100 nmol/l) abolished [³H]-noradrenaline release indicating that influx through -CTX-sensitive Ca²⁺-channels was essential for transmitter release. 1,4-dihydro-2,6-dimethyl-5-nitro4-[2-(trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester ((±)Bay K 8644) and 4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3-nitro-5-pyridinecarboxylic acid isopropyl ester ((±)-202-791), agonists at L-type voltage sensitive Ca²⁺-channels (VSCCs), increased noradrenaline release and induced, in addition, an overflow of tritium which was Ca²⁺-dependent and prevented by the presence of TTX. The L-type VSCC antagonists (–)-202-791 and (+)-4-(4-benzofurazanyl)-1,4-dihydro2,6-dimethyl-3,5-pyridinedicar boxylic acid methyl, isopropyl ester ((+)-PN 200–110) diminished [³H]-noradrenaline release. These data suggest that L-type VSCCs, probably located on the cell body of the neuron, play an additional role in modulation of release. The full ₂-adrenoceptor agonists 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline ( UK-14,304) and noradrenaline significantly inhibited noradrenaline release, whereas clonidine, a partial a2-agonist, produced only a slight inhibition even at 10 mol/l. The facilitation of noradrenaline release observed in the presence of the ₂-adrenoceptor antagonist rauwolscine was very low in comparison to that obtained with brain slices and isolated smooth muscle tissues. These results corroborate the observation that noradrenaline release from chick sympathetic neurons is regulated by an ₂-adrenoceptor which needs further subtype characterization. The experiments were mostly performed at 25°C, since a rise in temperature to 37°C increased the resting outflow, but not the evoked overflow of tritium, approximately 4-fold. In the presence of pargyline to block monoamine oxidase, however, the temperature-dependent enhancement was diminshed and the release showed properties comparable to those observed at 25°C (with respect to TTX-sensitivity, Ca²⁺ dependence and modulation via ₂-adrenoceptors). In addition to the ₂-adrenoceptors, we detected inhibitory -adrenoceptors, opioid and receptors, and P₂ purinoceptors as well as facilitatory prostaglandin (PG) E receptors. No indication was found for a functional relevance of 5-hydroxytryptamine (5-HT), opioid , PGD, adenosine A₁ or glutamate receptors. In conclusion, electrically evoked noradrenaline release from cultured chick sympathetic neurons shows the properties of action-potential-induced transmitter release and is bidirectionally regulated by various substances. Therefore, sympathetic neurons in culture offer the possibility to investigate directly the mechanisms bringing about receptor-coupled modulation of transmitter release.Abbreviations ATP adenosine 5-triphosphate - Bay K 8644 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester - DAGO (d-Ala²,N-methyl-Phe⁴,Gly-ol⁵)-enkephalin - DPDPE (d-Pen ^2,5)-enkephalin - 5-HT 5-hydroxytryptamine - -CTX -conotoxin - KRBB modified Krebs-Ringer bicarbonate buffer - NMDA N-methyl-d-aspartic acid - PG prostaglandin - PN 200-110 4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxy lic acid methyl, isopropyl ester - R-PIA R(–)-N⁶-(2-phenyl-isopropyl)-adenosine - TTX tetrodotoxin - U-50,488H trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzene acetamide - UK-14,304 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline - VSCC voltage sensitive Ca²⁺-channel - 202-791 4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3-nitro-5-pyridinecarboxylic acid isopropyl ester Correspondence to: C. Allgaier at the above address     

Ontogeny of serine hydroxymethyltransferase isoenzymes in fetal sheep liver, kidney, and placenta

Serine is an amino acid that is not transported from the placenta to the ovine fetus. Thus, fetal plasma serine levels may be controlled by flux through their relevant biosynthetic pathways. This study was designed to determine, in fetal sheep tissues, the ontogeny of the three key enzymes in the biosynthetic pathway for serine, the cytosolic (c) and mitochondrial (m) isoforms of serine hydroxymethyltransferase (SHMT), phosphoglycerate dehydrogenase (PGD), and phosphoserine aminotransferase (PSAT). PGD and PSAT activity did not vary during gestation in either liver (PSAT, 9.4 +/- 1.3 nmol/min/mg cytosolic protein; and PGD, 76 +/- 10 mU/mg protein) or placenta (PGD, 8.0 +/- 3.6 mU/mg protein). In the liver, cSHMT activity was low early in gestation (0.6 +/- 0.5 nmol/min/mg protein at 45 days), rose in the last one-third of gestation, and peaked in the newborn period (25 +/- 3 nmol/min/mg protein at 1 week of age). Hepatic cSHMT RNA levels parallel the activity pattern. Mitochondrial SHMT was stable throughout gestation and with low constant mSHMT RNA levels. In contrast, the kidney and placenta had high mSHMT and steady low cSHMT activity throughout gestation. These data support the possible role of SHMT in the fetal control of plasma serine levels. While cSHMT may contribute to fetal hepatic serine production, its activity pattern does not support a primary role in the control of fetal hepatic serine biosynthesis. In the placenta, mSHMT may be important for glycine production from serine.     

Activation of A(1) adenosine or mGlu3 metabotropic glutamate receptors enhances the release of nerve growth factor and S-100beta protein from cultured astrocytes.

Pharmacological activation of A(1) adenosine receptor with 2-chloro-N6-cyclopentyladenosine (CCPA) or mGlu3 metabotropic glutamate receptors with (2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl)glycine (DCG-IV) or aminopyrrolidine-2R, 4R-dicarboxylate (2R,4R-APDC) enhanced the release of nerve growth factor (NGF) or S-100beta protein from rat cultured astrocytes. Stimulation of release by CCPA and DCG-IV or 2R,4R-APDC was inhibited by the A(1) adenosine receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine and by the mGlu2/3 receptor antagonist (2S,1'S, 2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-4), respectively. Time-course studies revealed a profound difference between the release of S-100beta protein and the release of NGF in response to extracellular signals. Stimulation of S-100beta protein exhibited rapid kinetics, peaking after 1 h of drug treatment, whereas the enhancement of NGF release was much slower, requiring at least 6 h of A(1) adenosine or mGlu3 receptor activation. In addition, stimulation of NGF but not S-100beta release was substantially reduced in cultures treated with the protein synthesis inhibitor cycloheximide. In addition, a 6-8 h treatment of cultured astrocytes with A(1) or mGlu3 receptor agonists increased the levels of both NGF mRNA and NGF-like immunoreactive proteins, including NGF prohormone. We conclude that activation of A(1) adenosine or mGlu3 receptors produces pleiotropic effects in astrocytes, stimulating the synthesis and/or the release of protein factors. Astrocytes may therefore become targets for drugs that stimulate the local production of neurotrophic factors in the CNS, and this may provide the basis for a novel therapeutic strategy in chronic neurodegenerative disorders.     

A psychometric-genetic study of schizotypal disorder

This study aimed to clarify the structure and the etiological constituents of schizotypal disorder (SPD) by directly interviewing pairs of twins. A latent class analysis was applied to each individual's outcome for specified SPD items, such that each subject's phenotype could be redefined in terms of individual probabilities of class membership. Intraclass correlations were then calculated for each twin pair, and a standard univariate twin model applied. The best latent class analysis solution encompassed a model with four latent classes (three latent classes of SPD subjects, one of non-SPD). The intraclass correlations revealed a moderate to high heritability for two out of three SPD classes and for the modal class (a class composed of subjects that possessed a conditional probability of belonging to any of the SPD classes). Model fittings revealed considerable variation in the extent to which the different classes of SPD were influenced by additive genetic constituents or non-genetic factors. Although these data confirm the importance of genetic contributors in determining liability to SPD and the schizophrenia spectrum, they indicate that there is a relationship between psychometric multidimensionality and etiological heterogeneity in SPD.     

Structured diagnostic assessment and depot fluphenazine treatment of multiple suicide attempters in the emergency department

The aim of this study was to compare the efficacy of two doses of monthly intramuscular (i.m.) injections of fluphenazine decanoate in reducing self-harm behaviours in outpatients with histories of multiple suicide attempts. Fifty-eight patients who presented to a psychiatric emergency service after an attempted suicide and who had histories of multiple suicide attempts, were randomized to receive monthly i.m. injections of fluphenazine decanoate. Thirty patients received monthly 12.5 mg ('low' dose), and 28 patients received monthly 1.5 mg ('ultra low' dose) under double-blind conditions. DSM-III-R diagnoses were obtained on all patients using the Structured Clinical Interview for DSM-III-R-Patient Version (SCID-P) and SCID for DSM-III-R Personality Disorders (SCID-II). Outcomes were assessed by the Parasuicide History Inventory and the Abnormal Involuntary Movement Scale, collected monthly for 6 months. Patients had an average of six current Axis I and 2.6 Axis II diagnoses, with borderline personality (85%) and alcohol dependence (58%) occurring most frequently in the sample. Both the low dose and ultra-low dose groups showed a marked reduction in self-harm behaviours. For 'serious' self-harm behaviours, there was a trend for a greater effect of the low dose over the ultra-low dose group, however, the differences did not reach statistical significance. A survival analysis indicated that the presence of 'acute' stressors at baseline and female sex were risk factors for continuing (post-randomization) 'serious' self-harm behaviours, while younger age and the absence of concurrent general medical conditions were risk factors for all self-harm behaviours.     

Tachykinin receptors mediate atropine-resistant rat duodenal reflex contractions in vivo

The study aimed to establish the possible role of tachykinins as mediators of atropine-resistant reflex contractions evoked by balloon distension in the proximal duodenum of urethane-anesthetized, guanethidine (34 mol/kg s.c.)-pretreated rats. Distension of the balloon with a small amount (0.2–0.3 ml) of saline induced the appearance of phasic rhythmic contractions (about 11 mmHg in amplitude) which were promptly suppressed by either atropine (3 mol/kg i.v.) or hexamethonium (28 mol/kg i.v.). Despite the continuous i.v. infusion of atropine (2 mol/h), low-amplitude rhythmic phasic contractions recovered, which were promptly suppressed by hexamethonium, to indicate the involvement of an atropine-resistant excitatory reflex. The amplitude of these atropine-resistant contractions was increased to about 4–5 mmHg by further distension of the balloon (0.4–0.6 ml) : under these conditions, the atropine-resistant contractions undergo a progressive fading. The fading was prevented by i.v. administration of the nitric oxide (NO) synthase inhibitor, L-nitroarginine methyl ester (L-NAME, 55 mol/h), to provide a suitable baseline (amplitude of contractions was 7–8 mmHg) for studying the effect of tachykinin receptor antagonists.I.v. administration of the selective tachykinin NK₂ receptor antagonists, MEN 10,627 (10–100 nmol/kg) and SR 48968 (100–300 nmol/kg) or of the selective NK₁ antagonist SR 140333 (100 nmol/kg), at doses which do not affect the duodenal contractions induced by acetylcholine (5.5 µmol/kg i.v.), produced a prompt and long lasting suppression of the atropine-resistant reflex duodenal contractions produced by balloon distension in urethane-anesthetized rats, whilst SR 48965 (300 nmol/kg), the enantiomer of SR 48968 devoid of NK₂ receptor blocking activity, was without effect.I.v. administration of the selective NK_i receptor agonists [Sar⁹] substance P sulfone and septide or of the NK₂ receptor selective agonist, Ala⁸] neurokinin A(4–10) produced dose-dependent contractions of the duodenum. SR 140333 (100 nmol/kg i.v.) selectively antagonized the duodenal contractions produced by [Sar⁹] substance P sulfone and septide without affecting those produced by [Ala⁸] neurokinin A(4–10). On the other hand, MEN 10,627 (30–100 nmol/kg i.v.) and SR 48968 (100–300 nmol/kg i.v.) but not SR 48965 (300 nmol/kg i.v.) antagonized, at a comparable extent, duodenal contractions induced by both the selective NK₂ and NK₁ receptor agonists.We conclude that endogenous tachykinins are involved in mediating atropine-resistant reflex contractions evoked by distension of the rat duodenum in vivo: both NK₁ and NK₂ receptors are activated by endogenous ligands to produce NANC contractions of rat duodenum in vivo. However, the contractile response to i.v. administered NK₁ receptor agonists, [Sar⁹] substance P sulfone and septide, may involve the release of mediators producing smooth muscle contraction via NK₂ receptors.