bluuebunny/crossref_metadata_2025 huggingface dataset:
Progesterone Treatment That either Blocks or Augments the Estradiol-Induced Gonadotropin-Releasing Hormone Surge Is Associated with Different Patterns of Hypothalamic Neural Activation
Authors: Richter Trevor A. , Robinson Jane E. , Evans Neil P.
Published: April 2003

Progesterone can either augment or inhibit the surge of gonadotropin-releasing hormone (GnRH) that drives the preovulatory luteinizing hormone (LH) surge. This study investigated the central mechanisms through which progesterone might achieve these divergent effects by examining the effects of exogenous steroids on the activation of GnRH neurons and non-GnRH-immunopositive cells in the preoptic area/anterior hypothalamus of steroid-treated ovariectomized ewes. Fos expression (an index of cellular activation) was examined during the estradiol-induced GnRH surge in ewes treated with progesterone using regimes that have been reported to either augment (progesterone pretreatment) or inhibit (progesterone treatment at the time of the surge-inducing estradiol increment) the GnRH surge. Control groups received either no progesterone pretreatment or no surge-inducing estradiol increment. Induction of an LH surge was associated with a significant (p < 0.0001) increase in the proportion of activated GnRH neurons, irrespective of whether ewes received progesterone pretreatment. However, the number of non-GnRH-immunopositive cells activated during the surge was significantly (p < 0.0001) increased in ewes that received the progesterone pretreatment. By contrast, the proportion of GnRH neurons and non-GnRH-immunopositive cells that expressed Fos was significantly (p < 0.0001) reduced in ewes in which the surge was inhibited by progesterone compared to ewes in which a surge was stimulated. These data indicate that (1) progesterone pretreatment increases the activation of non-GnRH cells during the estradiol-induced surge, but does not affect the proportion of GnRH neurons activated and (2) when administered concurrently with a surge-inducing estradiol increment, progesterone prevents the activation of GnRH neurons and non-GnRH cells that is normally associated with the estradiol-induced surge. Therefore, progesterone does not appear to augment the GnRH surge by increasing the proportion of GnRH neurons that are activated by estradiol, whereas inhibition of the GnRH surge involves prevention of the activation of GnRH neurons. Thus, the augmentation and inhibition of the GnRH surge by progesterone appear to be regulated via different effects on the GnRH neurosecretory system.
Protooncogene c-fos Involvement in the Molecular Mechanism of Rat Brain Sexual Differentiation
Authors: Giannakopoulou Margaret , Bozas Evangelos , Philippidis Helen , Stylianopoulou Fotini
Published: April 2003

Brain sexual differentiation is mediated through testosterone, which acts during the perinatal period in the form of both 5α-dihydrotestosterone and estradiol. In order to gain insight into the molecular mechanisms involved, we studied induction of c-fos, an index of functional neuronal activation, in the 2-day-old female rat brain after injection of a masculinizing dose of testosterone. Administration of testosterone resulted in induction of c-fos gene expression in the hypothalamus, as determined by Northern analysis. Following immunocytochemistry, we demonstrated an increase in the number of Fos-positive nuclei in the median and medial preoptic nucleus, the medial preoptic area extending to the lateral preoptic area, and the peri- and paraventricular area. In an effort to see whether testosterone acted as 5α-dihydrotestosterone or as estradiol, we injected either steroid and looked at fos induction. Estradiol mimicked the effect of testosterone, while 5α-dihydrotestosterone was without effect. Furthermore, injection of an estrogen receptor blocker, clomiphene, together with testosterone, abolished the testosterone-induced increase in Fos-positive nuclei, thus confirming the finding that testosterone induces c-fos by acting through estrogen receptors. Electrophoretic mobility shift assays showed that nuclear extracts from 2-day-old female hypothalamus contain a protein, most probably the estrogen receptor, which binds specifically to oligodeoxynucleotides with the sequence of either vitERE, the consensus estrogen-responsive element (ERE) found in the vittelogenin gene, or fosERE, the ERE found in the 3′-untranslated region of the mouse c-fos gene. This suggests that the effect of testosterone-derived estradiol on c-fos expression is a direct one, mediated by binding of estrogen receptors to an ERE in the c-fos gene-regulatory regions.
Nitric Oxide Mediates the Inhibitory Effect of Tumor Necrosis Factor-α on Prolactin Release
Authors: Theas Susana , De Laurentiis Andrea , Candolfi Marianela , López Silvia L. , Carrasco Andrés E. , Zaldivar Verónica , Seilicovich Adriana
Published: April 2003

Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that markedly affects neuroendocrine functions. This cytokine is expressed in the anterior pituitary where its receptors are also present. Nitric oxide (NO) is synthesized in gonadotropes and folliculo-stellate cells of the anterior pituitary. Since NO directly inhibits prolactin secretion, we investigated the involvement of NO in the inhibitory effect of TNF-α on prolactin release from anterior pituitary cells of female rats. The presence of L-NAME (1 mM), an inhibitor of NO synthase (NOS), in the incubation medium significantly blunted the inhibition of prolactin release produced by TNF-α (50 ng/ml). TNF-α increased nitrite release to the incubation medium. The activity of NOS as measured by [14C]citrulline production was significantly enhanced when anterior pituitary cells were incubated with TNF-α for 8 h or more. Also, TNF-α induced iNOS gene expression in anterior pituitary cells as assessed by reverse transcriptase-polymerase chain reaction. The current results indicate that NO is involved in the inhibitory effect of TNF-α on prolactin secretion and that TNF-α induces iNOS transcription and stimulates NO synthesis in anterior pituitary cells.
Stimulation of Porcine Pituitary Luteinizing Hormone Release by Galanin: Putative Auto/Paracrine Regulation
Authors: Elsaesser Folkmar
Published: April 2003

It has repeatedly been suggested that galanin acts within the anterior pituitary (AP) in an auto/paracrine manner to modulate luteinizing hormone (LH) release. Except for one recent report in the rat, evidence for this notion is absent. The purpose of this study was to investigate in the pig the effects of galanin on LH and growth hormone (GH) release and to evaluate putative local effects using various AP culture systems (monolayer, perifusion, reaggregates). Independent of age galanin dose dependently (0.05, 0.2, 1 µM) stimulated basal but not gonadotropin-releasing hormone (GnRH; ≧0.01 nM)-induced LH release. Neither basal nor GH-releasing hormone (GHRH)-stimulated GH release was affected at any age. Of 4 galanin receptor antagonists (0.2, 1 µM) tested C7 proved to have agonistic effects, whereas M40 and M15 (galantide) were ineffective in blocking galanin (0.2 µM)-induced LH secretion or affecting basal or GnRH-induced LH release. M32 [galanin (1–13) NPY (25–36) amide] inhibited (p ≤ 0.05) GnRH-induced LH release at doses of ≧2 µM, an effect which could be totally compensated by 1 µM galanin. However, the neuropeptide (NPY) antagonist BIBP 3226 (1 µM) partially overcame the effect of M32 (M32 is known to also bind to NPY receptors and NPY is inhibitory in the pig). In further studies using APs from preovulatory gilts a specific well-characterized galanin antiserum diluted 1:20 or 1:50 attenuated GnRH-induced LH release (p ≤ 0.05). However, an NPY antiserum (also affinity purified and at the same dilution) used as control unexpectedly inhibited GnRH (and galanin)-induced LH release as well, thus suggesting that attenuation of GnRH-induced LH release by galanin antiserum might be at least partly nonspecific. Furthermore 96-hour exposure of AP reaggregates to two types of porcine preprogalanin antisense oligodeoxynucleotides neither affected basal nor GnRH-induced LH release. In line with the failure to unequivocally prove paracrine effects of galanin, concentrations of galanin in AP cultures and AP culture medium were very low (≤2 pg galanin/105 AP cells). In conclusion the present study provides some evidence to ascribe a hypophysiotropic role to galanin in regulating LH but not GH secretion in the pig. The study also points to the critical role of appropriate controls when trying to prove auto/paracrine control mechanisms within the anterior pituitary. Our findings do not provide convincing evidence to support the notion that intrapituitary galanin is involved in the fine tuning of LH secretion, at least in the preovulatory pig.
Differential Interaction of Estrogen Receptor and Thyroid Hormone Receptor Isoforms on the Rat Oxytocin Receptor Promoter Leads to Differences in Transcriptional Regulation
Authors: Vasudevan Nandini , Davidkova Genoveva , Zhu Yuan-Shan , Koibuchi Noriyuki , Chin William W. , Pfaff Donald
Published: April 2003

Both the estrogen receptor (ER) and thyroid hormone receptor (TR) are members of the nuclear receptor superfamily. Two isoforms of the ER, α and β, exist. The TRα and β isoforms are products of two distinct genes that are further differentially spliced to give TRα1 and α2, TRβ1 and β2. The TRs have been shown to interfere with ER-mediated transcription from both the consensus estrogen response element (ERE) and the rat preproenkephalin (PPE) promoter, possibly by competing with ER binding to the ERE or by squelching coactivators essential for ER-mediated transcription. The rat oxytocin receptor (OTR) gene is thought to be involved in several facets of reproductive and affiliative behaviors. 17β-Estradiol-bound ERs upregulate the OTR gene in the ventromedial hypothalamus, a region critical for the induction of lordosis behavior in several species. We investigated the effects of the ligand-binding TR isoforms on the ER-mediated transcription from a physiological promoter of a behaviorally relevant gene such as the OTR. Only ERα could induce the OTR gene in two cell lines tested, the CV-1 and the SK-N-BE2C neuroblastoma cell lines. ERβ was incapable of inducing the gene in either cell line. ERα is therefore not equivalent to ERβ on this physiological promoter. Indeed, in the neural cell line, ERβ can inhibit ERα-mediated induction from the OTR promoter. While the TRα1 isoform inhibited ERα-mediated induction in the neural cell line, the TRβ1 isoform stimulated induction, thus demonstrating isoform specificity in the interaction. The use of a DNA-binding mutant, the TR P box mutant, showed that inhibition of ERα-mediated induction of the rat OTR gene promoter by the TRα1 isoform does not require DNA-binding ability. SRC-1 overexpression relieved TRα1-mediated inhibition in both cell lines, suggesting that squelching for coactivators is an important molecular mechanism in TRα-mediated inhibition. Such interactions between TR and ER isoforms on the rat OTR promoter provide a mechanism to achieve neuroendocrine integration.
Hypothalamic Gene Expression in Sheep for Cocaine- and Amphetamine-Regulated Transcript, Pro-Opiomelanocortin, Neuropeptide Y, Agouti-Related Peptide and Leptin Receptor and Responses to Negative Energy Balance
Authors: Adam Clare L. , Archer Zoe A. , Findlay Patricia A. , Thomas Louise , Marie Michel
Published: April 2003

Hypothalamic pathways involved in the regulation of energy balance have not been widely studied in ruminants to date. Here, we used in situ hybridisation to study the gene expression of a number of leptin-sensitive receptors and neuropeptides in the ovine hypothalamus. Gene expression was first localised for cocaine- and amphetamine-regulated transcript (CART) and agouti-related peptide (AGRP). We then examined in adult male castrated sheep the effects of acute negative energy balance induced by a 4-day fast on the amounts of these mRNAs and those for leptin receptor (OB-Rb), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC). CART mRNA was localised in the arcuate nucleus (ARC), paraventricular nucleus, median eminence and ventromedial hypothalamic nucleus, and extensive co-localisation with POMC mRNA was demonstrated in the ARC. AGRP mRNA was localised in the ARC. Fasting up-regulated gene expression for OB-Rb and for the orexigenic neuropeptides NPY and AGRP in the ARC. There was a trend towards down-regulation of gene expression for the anorexigenic neuropeptide CART and no effect on POMC in the ARC, although these results are inconclusive. The presence or absence of oestradiol-containing subcutaneous implants did not influence gene expression or the effects of fasting. The hypothalamic changes were consistent with responses to the observed reduction in circulation leptin and suggest that the peripheral feedback and central mechanisms for restoring the energy balance may be largely conserved across monogastric and ruminant species.
Clinical Effects of L-Threo-3,4-Dihydroxyphenylserine on Orthostatic Hypotension in Hemodialysis Patients
Authors: Akizawa Tadao , Koshikawa Shozo , Iida Nobutoshi , Marumo Fumiaki , Akiba Takashi , Kawaguchi Yoshindo , Imada Akio , Yamazaki Chikao , Suzuki Masashi , Tubakihara Yoshiharu
Published: April 2003

Orthostatic hypotension is one of the major factors interfering with everyday activities in hemodialysis patients, but there has been no effective agent for treating it. In order to clarify the clinical effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on orthostatic hypotension of hemodialysis patients, we conducted a randomized, double-blind comparative trial. 149 regular hemodialysis patients with orthostatic hypotension were randomly allocated to three groups and L-DOPS at doses of 400 mg, 200 mg or placebo was orally administrated to each group 30 min before starting every hemodialysis for 4 weeks. Changes of blood pressure (BP) in orthostatic hypotension immediately after completion of hemodialysis and symptoms related to orthostatic hypotension were compared between the three groups. In the 400-mg group, systolic and diastolic BP after standing increased significantly and the drop of mean BP after standing was also reduced compared with pretreatment levels. No such changes were observed in the placebo group. Fatiguability, malaise/weakness, dizziness and light-headed feeling, the interdialytic symptoms commonly observed in hemodialysis patients who developed orthostatic hypotension, were improved to a significant extent in the L-DOPS group compared with the placebo group. In particular, the improvement was more remarkable for the L-DOPS 400-mg group than the placebo group in patients with diabetic nephropathy, lower systolic BP after standing, and the long duration type of orthostatic hypotension. The incidence of adverse events was comparable between the three groups, and all recovered after discontinuation of L-DOPS or concomitantly administered drugs, or without any treatment. These findings indicate that L-DOPS taken before hemodialysis prevents orthostatic hypotension in patients undergoing hemodialysis, and is also effective for the interdialytic symptoms related to orthostatic hypotension.
The Product of Duration and Amount of Proteinuria (Proteinuria Index) Is a Possible Marker for Glomerular and Tubulointerstitial Damage in IgA Nephropathy
Authors: Eiro Masaaki , Katoh Tetsuo , Kuriki Minoru , Asano Kenichiro , Watanabe Kazuo , Watanabe Tsuyoshi
Published: April 2003

Background/Aims: IgA nephropathy (IgAN) is one of the major causes for chronic renal failure (CRF). Presence of massive proteinuria, hypertension, increased serum creatinine level and sclerotic histopathological changes of the glomerulus are known to be determinants for the progression of CRF. However, the relationships between duration of proteinuria/hematuria and histopathological changes, which may be correlated with the renal prognosis, have not been clarified. Methods: A cross-sectional, univariate analysis of clinical parameters on the four glomerular and three tubulointerstitial histopathological grades in 57 untreated biopsy-proven IgAN patients (M/F = 32/25) was performed. Results: The age at the time of renal biopsy (35.2 ± 13.0 years; mean ± SD), average duration of proteinuria (5.3 ± 5.8 years), mean urinary protein excretion (0.99 ± 1.22 g/day), serum creatinine (Cr 0.97 ± 0.28 mg/dl), Cr clearance (Ccr 75.5 ± 29.4 ml/min), and blood urea nitrogen (BUN 15.4 ± 3.9 mg/dl) were well correlated with both histopathological grades. The product of duration (years) and urinary protein excretion (g/day) at the time of renal biopsy was more significantly correlated with glomerular and tubulointerstitial histopathological grades and serum Cr. Conclusion: The natural course of IgAN is steadily progressive depending on the duration and amount of proteinuria. The product of these two factors (proteinuria index) may be a useful predictor for glomerular and interstitial histopathological changes and the fate of renal function in IgAN.
Angiotensin II Enhances Glomerular Expression of a Nonmuscle Myosin Heavy Chain, SMemb, with Extracellular Matrix Accumulation
Authors: Mise Naobumi , Kimura Kenjiro , Kurabayashi Masahiko , Nagai Ryozo , Okuda Toshihiro , Ohba Shigeyoshi , Suzuki Naoe , Miyashita Kazuhisa , Kamijo Atsuko , Tojo Akihiro , Goto Atsuo , Omata Masao
Published: April 2003

Background/Aims: We previously showed that the mesangial expression of nonmuscle-type myosin heavy chain, SMemb, was related to glomerular sclerosis. Although angiotensin II (AII) is known to promote the glomerular accumulation of extracellular matrix and sclerosis, the effect of AII on the mesangial expression of SMemb is unknown. Thus, we investigated the effect of AII on the mesangial expression of SMemb and synthesis of fibronectin. Methods: We continuously administered AII to Sprague-Dawley rats with subcutaneous osmotic minipumps for 14 days. Control animals received normal saline instead. The effects of oral administration of an AII type 1 (AT1) receptor antagonist, candesartan cilexetil, and a vasodilator, hydralazine, were also examined. Results: Semiquantitative immunohistochemical evaluation and Western blot analysis showed that AII significantly enhanced glomerular expression of SMemb (0.87 ± 0.33 vs. 0.40 ± 0.19 for immunohistochemical grading, p < 0.05; 2.55 ± 0.88 vs. 1.16 ± 0.75 for Western blot analysis, p < 0.05). Glomerular fibronectin was also increased in AII-administered rats (301.7 ± 206.8 ng/5 µg protein vs. 95.8 ± 81.3 ng/5 µg protein, p < 0.05). Candesartan cilexetil attenuated these effects. On the other hand, hydralazine did not change the glomerular expression of SMemb enhanced by AII administration. Conclusion: All induced a phenotypic alteration in mesangial cells, enhanced the mesangial expression of SMemb and stimulated the fibronectin synthesis. These results suggest that the mesangial expression of SMemb is related to glomerular matrix accumulation and that AII mediates both mesangial processes via AT1 receptors.
Prevalence of Essential Tremor: A Door-to-Door Survey in Bidasoa, Spain
Authors: Bergareche A. , De la Puente E. , López de Munain A. , Sarasqueta C. , De Arce A. , Poza J.J. , Martí-Massó J.F.
Published: April 2003

Objectives: To assess the prevalence of essential tremor (ET) in two Spanish populations (Irun and Hondarribia, Bidasoa region) and to compare the results with those of similar surveys. Methods: The survey included 2,000 participants aged 65 years or older in a door-to-door, two-phase design. ET was defined as postural or kinetic tremor of the head or limbs. Results: ET prevalence after age adjustment was 4.8% (95% confidence interval, 3.6–6.4). Prevalence increased significantly with age and there were no sex differences. Conclusions: The age-adjusted prevalence rate of ET in people 65 years old and older in Bidasoa, Spain, is close to those described in other studies using a similar design and suggest no geographical variation. ET prevalence increases with age and has a similar distribution in males and females.
Multiple Sclerosis and Ionizing Radiation
Authors: Axelson Olav , Landtblom Anne-Marie , Flodin Ulf
Published: April 2003

The etiology of multiple sclerosis (MS) may involve exposure to infectious, chemical or physical agents damaging the blood-brain barrier and an autoimmune reaction against myelin breakdown products. Here we report a pooled analysis of 174 MS cases and 815 population controls from two case-control studies with regard to such a potentially damaging exposure, namely X-ray examinations, radiological work and treatment with ionizing radiation. Exposure was assessed by questionnaires to the subjects. We obtained odds ratios of 4.4 (95% confidence interval, CI, 1.6–11.6) and 1.8 (95% CI 1.2–2.6) for radiological work and X-ray examinations, respectively; 5 cases, but no controls, in one of the studies had been treated with ionizing radiation. Our data and some other observations reported in the literature suggest a contributory role for ionizing radiation to the development of MS in some cases.
Exploring the Impact of Prevalence and Mortality on Incidence of Dementia in the Oldest Old: The Sensitivity of a Deterministic Approach
Authors: McGee M.A. , Brayne C.
Published: April 2003

Background: There has been considerable debate about whether dementia is an age-related or an aging-related phenomenon. When the evidence is restricted to prevalence data, the inferences are not sound because incidence, mortality and differential mortality are not taken into account. The aim of the paper is to demonstrate the use and sensitivity of a deterministic model based on the relationship between mortality, incidence and prevalence with the example of the chronic disease dementia. Design: The simple deterministic model used here allows the calculation of one component given the other three. The sensitivity of calculated incidence to individual and combined changes in mortality, differential mortality (as measured by the mortality odds ratio) and prevalence is examined using published data. Main Results: Calculated incidence continues to increase with age despite extreme but plausible changes in each of the other components. Calculated incidence declines amongst the oldest old only when the changes are combined. Conclusion: The deterministic model is shown to provide robust interrogation of the relationship between prevalence, incidence and survival. The effect incidence and survival have on the age-related and aging-related debate is illustrated. Only with extreme assumptions can the incidence of dementia be lessened. Clearly, more information on the oldest old is needed, but incidence studies of sufficient size at such great ages are problematic, and therefore there is a need to use flexible models for maximising the value of empirical data.
A Population-Based Study of Familial Central Nervous System Hemangioblastomas
Authors: Hemminki Kari , Li Xinjun , Collins V. Peter
Published: April 2003

We used the nationwide Swedish Family-Cancer Database to analyze the risk for central nervous system hemangioblastoma (HB) in offspring (0–61 years) of parents with cancer. Eighty-three offspring were identified, and the age at onset showed a bimodal distribution. The early-onset component peaked at 25–29 years, was associated with von Hippel-Lindau (VHL) disease and presented with HBs, renal cell carcinomas, pheochromocytomas and insulomas in the proband or other family members. Standardized incidence ratios (SIRs) were 600 for offspring HB by parental HB, and they were even high for the other VHL-related tumors. Second tumors were common in this early-onset group, and the types were as expected in VHL. The late-onset component peaked at 40–44 years, and it was twice as prevalent as the early-onset component. Because there was no evidence of familial risks, this is suggested to be a sporadic form of HB.
Akute Mastoiditis im Kindesalter
Authors: Mross C. , Klemm E.
Published: April 2003

Fragestellung: Die akute Mastoiditis hat in den letzten Jahren einen Wandel ihres Erscheinungsbildes erfahren. Diesem Gestaltswandel einerseits als auch den Morbiditätsschwankungen andererseits nachzugehen, war Ziel der vorliegenden Studie. Patienten: Retrospektiv wurden die Krankengeschichten von 84 Kindern eines regionalen Krankengutes ausgewertet, die zwischen 1979 und 1998 auf Grund einer akuten Mastoiditis stationär behandelt worden waren. Ergebnisse und Schlussfolgerungen: Unter Beachtung des Geburtenrückganges ab 1991 in den Neuen Bundesländern liess sich keine signifikante Änderung der Morbiditätsrate der akuten Mastoiditis nachweisen. Das Durchschnittsalter der Patienten lag bei 2,6 Jahren. Die klassischen Symptome, retroaurikuläre Rötung, Schmerz sowie abstehende Ohrmuschel, wurden nur bei 34 Kindern (40,5%) festgestellt. Präoperative Komplikationen traten als Fazialisparese, Abszessbildungen und septische Sinusthrombose bei 9 Kindern auf. Im intraoperativen Abstrich wurde in 56% Streptococcus pneumoniae gefunden. Therapeutisch erfolgte frühzeitig eine operative Intervention mit kombinierter Antibiotikagabe. Hier fanden vor allem Cephalosporine Anwendung.
TEOAE-Messungen zur Verlaufsbeurteilung akuter kochleovestibulärer Störungen: methodische Aspekte
Authors: Nölle Corinna , Wunder Michael , Ernst Arne
Published: April 2003

Ziel der vorliegenden Arbeit ist es, mit Hilfe von TEOAE-Messungen (TEOAE = transiently evoked otoacoustic emissions) bei ausgewählten otologischen Erkrankungen (Hörsturz und M. Ménière) Schlussfolgerungen zum Verlauf und gegebenenfalls zur Prognose dieser Erkrankungen unter besonderer Berücksichtigung der methodischen Auswertungsverfahren ziehen zu können. Es wurden bei 46 Patienten vor Therapiebeginn, nach 3 und 9 Tagen sowie nach 1 und 2 Monaten ein Reintonaudiogramm angefertigt und TEOAE-Messungen durchgeführt. Die wichtigsten TEOAE-Befunde waren die frühzeitige Zunahme der Amplitude vor einem Hörschwellenanstieg beim klassischen Morbus Ménière (Stadium I) sowie die frühzeitige Zunahme der Amplitude und der Reproduzierbarkeit beim kochleären M. Ménière (Stadium II). TEOAE-Parameter könnten somit Indikatorfunktion für die Erholung des Gehörs haben. Beim Hörsturz trifft dieses nicht zu, was eine wesentliche Ursache in der ungeklärten Ätiopathogenese der Erkrankung haben könnte. Die statistische Auswertung eines Patientenkollektives ermöglicht eine prognostische Aussage zur Hörschwellenentwicklung. Dabei wird deutlich, dass TEOAE-Resultate besonders bei der Verlaufsbeurteilung des M. Ménière gut dazu geeignet sein können, das Therapieregime zu überwachen (Monitoring) bzw. zu einer Modifikation der Behandlungsstrategie beizutragen.
Georg von Békésys Beziehungen zu Bern und der Schweiz
Authors: Aerni A. , Boschung U. , Häusler R.
Published: April 2003

Einer der wichtigsten Forscher auf dem Gebiet der Gehörphysiologie ist der Biophysiker Georg von Békésy (1899–1972), Nobelpreisträger von 1961. Der gebürtige Ungar war zu diesem Zeitpunkt an der Harvard University in Cambridge (Mass., USA) tätig und wechselte später an die University of Hawaii in Honolulu. Wenig bekannt ist die Tatsache, dass Békésy als Zwölfjähriger mit seinen Eltern in die Schweiz kam und hier während eines mehr als 10 Jahre dauernden Aufenthaltes das Gymnasium besuchte und an der Universität Bern Naturwissenschaften studierte. Ziel dieses Artikels ist es, Békésys frühe Beziehungen zur Schweiz darzustellen. Ebenfalls dokumentiert wird eine der ersten Ehrungen Békésys, nämlich die Verleihung der Ehrendoktorwürde durch die Medizinische Fakultät der Universität Bern 1959. In gekürzter Form wurde die Arbeit anlässlich der Feier zu Békésys 100. Geburtstag an der ‘International Békésy Centenary Conference on Hearing and Related Sciences’ im Sommer 1999 in Budapest vorgetragen.
Middle Ear Exotoxin and Endolymphatic Sac Response: An Immune Reaction?
Authors: Nordang Leif , Anniko Matti , Rask-Andersen Helge
Published: April 2003

Objectives: The endolymphatic sac (ES) is presumed to be involved in immune response in the inner ear. The ES has been shown to respond immunologically to an antigen instilled into the scala tympani. Pseudomonas aeruginosa exotoxin A (PaExoA) is known to pass the round window membrane and to cause cochlear functional impairment. Does the ES in the inner ear respond immunologically to exotoxin exposed in the middle ear? Methods: In the present study, the ES was examined morphologically after application of PaExoA in the middle ear of the rat. The ES changes were correlated with electrophysiological results using ABR measurements. Results: In 18 out of 32 exposed ES we found signs of inflammatory activity with raised numbers of intraluminal macrophages together with signs of epithelial alterations. There were also changes in character and stainability of the intraluminal glycoprotein conjugates. Conclusions: The ES changes may either be due to a direct exposure of toxin to the ES or possibly represent the expression of an augmented general response in the inner ear. These findings are similar to earlier descriptions of changes in the ES after experimental labyrinthitis. This is the first presentation showing altered ES activity following middle ear application of exotoxin.
Modulation of Neural Cell Membrane Conductance by the Herbal Anxiolytic and Antiepileptic Drug Aswal
Authors: Grunze H. , Langosch J. , von Loewenich C. , Walden J.
Published: April 2003

To evaluate the effects of aswal on ionic fluxes and neuronal excitation, we performed extracellular and whole cell patch clamp recordings on CA1 pyramidal neurons of guinea pigs and Long-Evans rats. Aswal (100– 250 mg/l) was administered systemically, and its effects on the rate of synchronized extracellular field potentials (EFP), membrane parameters, action potentials and postsynaptic potentials were recorded. The extracellular results obtained are consistent with calcium antagonistic properties. Intracellular recordings suggest that a direct sodium antagonistic effect as seen in many antiepileptic drugs plays no significant role. Further effects on ligand gated ion channels are discussed controversially. In summary, the cellular action of aswal appears heterogeneous with calcium antagonism playing a prominent role in counteracting excitation which may be a common feature in epilepsy and different psychiatric conditions as mood and anxiety disorder.
Adding Low-Dose Antidepressants to Interferon Alpha Treatment for Chronic Hepatitis C Improved Psychiatric Tolerability in a Patient with Schizoaffective Psychosis
Authors: Schäfer M. , Schmidt F. , Amann B. , Schlösser S. , Loeschke K. , Grunze H.
Published: April 2003

Treatment of chronic hepatitis C with interferon alpha (IFN-α) is relatively contraindicated in patients with psychiatric disorders because of possible severe psychiatric side effects. We report on a case of a female patient with a chronic schizoaffective psychosis, who was treated for 3 months with 3 × 3 mio IE IFN-α s.c./week because of a chronic hepatitis C (genotype 1b). Psychosis was stable with flupentixol monotherapy. After 2 months, she developed a severe depressive syndrome which lead to suicidal ideation. Until this time, she was without any antidepressive medication. Depressive symptoms disappeared after interferon therapy was stopped. Under prophylactic treatment with low-dose trimipramine (50 mg) or nefazodone (200 mg/day) therapy with IFN-α 3 × 3 mio IE/week was re-established after several months and again 2 years later adding ribavirin 1200 mg/day, a virustaticum. In contrast to the symptoms during monotherapy with IFN-α, during the time of both combination treatments, no psychiatric side effects occurred. While for ribavirin antidepressant effects are not known, we suppose that antidepressants may prevent changes in serotonergic or noradrenergic neurotransmission caused by IFN-α.
Topiramate Monotherapy in the Maintenance Treatment of Bipolar I Disorder:Effects on Mood, Weight and Ser um Lipids
Authors: Erfurth Andreas , Kuhn Gabriela
Published: April 2003

Topiramate is a newly developed anticonvulsant agent with possible mood-stabilizing properties. Little is known about the short- and long-term effects of topiramate monotherapy in bipolar disorder. We here present the case of a 60-year-old female bipolar patient who received topiramate alone as maintenance treatment after recovering from euphoric mania. During 7 months, she was free from new manic symptomatology and she was able to reduce her overweight by 16.5 kg. The patient who is known to have a strongly hyperthymic temperament described symptoms of fatigue and sedation and eventually discontinued topiramate monotherapy. When she presented again in our bipolar clinic, severe euphoric mania had developed. After hospitalization, she slowly responded to oral sodium valproate loading plus zotepine. Her weight increased again and so did her triglyceride serum levels. Topiramate treatment and discontinuation did not seem to affect cholesterol serum levels.
CSF Collection Time at Lumbar Puncture Is Influenced by Plasma Cholesterol and Triglycerides
Authors: Nordin Conny , Eklundh Thomas , Eriksson Mats , Sjöberg Stefan
Published: April 2003

It is a fairly well-known fact that the CSF collection time (tapping time) at lumbar puncture may influence CSF levels of monoamine compounds (e.g. the serotonin metabolite 5-hydroxyindoleacetic acid, 5-HIAA) and some neuropeptides. Since serum levels of cholesterol and triglycerides and low CSF levels of 5-HIAA have been linked to violent behaviour and impulsivity, we investigated retrospectively whether serum cholesterol and triglycerides affect CSF collection time. The series consists of 14 healthy males lumbar punctured at the L4–5 level. We found that both serum cholesterol and serum triglycerides influenced the CSF collection time for 12 ml of CSF (R = 0.77; p = 0.0067). There was no correlation between cholesterol in serum and CSF, nor between cholesterol in the CSF and collection time. However, we accidentally found a correlation between cholesterol in the CSF and age. The proposed hypothesis tries to explain why cholesterol- and triglyceride-rich lipoprotein particles modify the CSF collection time and influence endothelial function with a subsequent effect on CSF production and/or intraspinal pressure. Thus, it may be of interest to pay attention to serum cholesterol and triglycerides, their effect on CSF collection time and, in the next step, their putative impact on levels of various compounds in the CSF.
No Correlation between Aggression and Platelet 3H-Paroxetine Binding in Obsessive-Compulsive Disorder Patients
Authors: Marazziti Donatella , Conti Luciano , Pfanner Chiara , Presta Silvio , Rossi Alessandra , Gemignani Alfredo , Dell’Osso Liliana , Cassano Giovanni B.
Published: April 2003

Different findings suggest that the serotonin (5-HT) system may be involved in both the regulation of aggression and the pathophysiology of obsessive-compulsive disorder (OCD). Our study aimed to evaluate the aggressive features of a group of OCD patients and to explore possible correlations with a serotonergic marker, namely platelet 5-HT transporter. Psychopathological and biological patterns were compared with those of a group of healthy controls and those of patients with major depression. Twenty-one patients affected by OCD, 21 by depression and 21 healthy controls were included in the study. Aggressive features were measured by means of the Buss and Durkee Hostility Inventory (BDHI). The platelet 5-HT transporter was evaluated by means of the 3H-paroxetine binding parameters (maximum binding capacity, Bmax and dissociation constant, Kd). The OCD patients showed a total score on the BDHI not significantly different from that of healthy controls and lower than that of depressed patients. The factor profile was similar in the 3 groups, but higher in the depressed patients. The irritability, resentment, guilt, negativism and suspiciousness factors were significantly more pronounced in depressed patients. Some sex-related difference in single factors were also observed. The Bmax of 3H-paroxetine binding was lower in OCD patients than in depressives or healthy controls. OCD patients were more similar to healthy controls than to depressed patients with regard to aggressive features measured by means of the BDHI. This suggests that aggression in OCD is a complex phenomenon that probably requires specific instruments of evaluation.
A Possible Role of Apolipoprotein E Polymorphism in Predisposition to Higher Education
Authors: Hubacek Jaroslav A. , Pitha Jan , Škodová Zdena , Adámková Vera , Lánská Vera , Poledne Rudolf
Published: April 2003

A potential candidate gene that could contribute to the education process is the apolipoprotein E (apo E) gene that has been shown to correlate with memory function and memory decline. We measured apo E polymorphism in groups of probands with different levels of education selected from a population sample. In the group of probands with higher education (n = 82), 24.4% had the e4 allele, compared with 7.3% who had the e2 allele. A reverse association was found in the group that left school aged 15 (n = 36) – 8.3% had the e4 allele and 13.9% had the e2 allele. Eighty-seven percent of the probands with the allele e4 reached higher education, compared to only 54.5% with the allele e2. The difference between the groups is statistically significant (p = 0.039), and this may indicate some role for the apo E polymorphism in subjects` intelligence or ability to learn.
Neurotransmitter and Hormonal Background of Hostility in Anorexia nervosa
Authors: Brambilla Francesca , Bellodi Laura , Arancio Cinzia , Limonta Daniela , Ferrari Ettore , Solerte Bruno
Published: April 2003

Marked hostility toward relatives, therapists and friends is very frequently observed in anorexia nervosa (AN) as expression of outward-directed aggressiveness which interferes with the therapeutic programs of the patients. With the purpose to investigate this aspect of the disorder and its biological background, we studied in anorexics some neurotransmitter-hormonal secretions which are known to modulate aggressivity-hostility by measuring plasma concentrations of total (TT) and free testosterone (FT), total estrogens (TE), the TT/E and FT/TE ratios, and the serotonergic function by measuring basal prolactin (PRL) levels and responses to stimulation with the specific serotonin (5-HT)-releasing agent D-fenfluramine (D-Fen). In 13 women with AN, 5 of the restricted (AN-R) and 8 of the bingeing/purging type (AN-BP) in an active phase of the disease, and in 13 healthy controls matched for sex and age, we measured hostility by the SCL-90 scale (subscale items 11, 24, 63, 67, 74, 81). Basal TT, FT, TE, TT/TE, FT/TE, PRL values and PRL responses to D-Fen and to saline administration were measured radioimmunologically in AN patients and controls. Hostility was significantly higher in AN patients than in controls, TT, FT and TE concentrations were significantly lower in AN patients than in controls, TT/TE ratio was significantly higher in AN patients than in controls, and FT/TE ratio was not different in the two groups. In AN patients and controls, hostility correlated positively with TT and FT values. Basal PRL values and responses to D-Fen administration were significantly lower in anorexics than in controls, but they did not correlate with the degree of hostility in either patients or controls. In conclusion, hostility is higher than normal in anorexics, and its severity seems to be linked to the secretion of FT and not to the alterations in the 5-HT function.
Excess Tryptophan Hydroxylase 17 779C Allele in Surviving Cotwins of Monozygotic Twin Suicide Victims
Authors: Roy Alec , Rylander Gunnar , Forslund Kaj , Asberg Marie , Mazzanti Chiara M. , Goldman David , Nielsen David A.
Published: April 2003

Objective: To evaluate the relationship of the tryptophan hydroxylase (TPH) genotype to suicidality by the study of surviving monozygotic (MZ) cotwins of twins who committed suicide. Method: Twenty-four surviving Swedish MZ twins whose MZ cotwins had committed suicide were compared to 158 demographically sampled Swedish general population controls for TPH alleles. We also examined serotonin transporter alleles. Results: The living MZ cotwins of suicide victims had a significantly higher TPH 17 779C allele frequency than controls. No significant difference was observed for serotonin transporter alleles. Conclusion: These results, in a small sample, suggest the possibility that the 17 779C allele of the TPH gene may be associated with an increased risk of suicide. Further studies in larger samples are needed.
Effects of Strain, Behavior and Age on the Self-Administration of Ethanol, Nicotine, Cocaine and Morphine by Two Rat Strains
Authors: Todte Karsten , Tselis Nikolaos , Dadmarz Mitra , Golden Gregg , Ferraro Thomas , Berrettini Wade H. , Vogel Wolfgang H.
Published: April 2003

Two genetically different strains, Brown Norway rats (BNR) and Wistar Kyoto rats (WKR), with the latter showing higher emotionality and lower plasma stress catecholamine responses, were compared for their voluntary intake of ethanol, nicotine, cocaine and morphine. Younger BNR self-administered the same amounts of all 4 substances as did the younger WKR suggesting a similar genetic basis for all drugs at this age. Older BNR consumed less ethanol and nicotine but equal amounts of cocaine and morphine as compared to older WKR, and older BNR were more sensitive to the effects of ethanol than WKR suggesting a different genetic basis for different drugs at an older age. Forcing both strains to consume one of the drugs did not affect a subsequent voluntary consumption of ethanol and morphine but reduced nicotine intake in WKR and decreased cocaine intake in both strains suggesting that drug use is determined by individual preferences and not drug exposure per se. The behavioral characteristics of both strains coincide only with the self-administration of ethanol and nicotine supporting a possible genetic linkage between anxiety/stress and ethanol and nicotine use.
Association Study of the 5-HT6 Receptor Polymorphism (C267T) and Symptomatology and Antidepressant Response in Major Depressive Disorders
Authors: Wu Wei-Hsin , Huo Sheue-Jane , Cheng Chih-Ya , Hong Chen-Jee , Tsai Shih-Jen
Published: April 2003

The serotonergic neurotransmitter system has been implicated in the pathogenesis of major depressive disorder (MDD). Of the 14 human serotonin (5-HT) receptors, the 5-HT6 receptor may be a candidate for the study of MDD because of its relative abundance in certain limbic areas and its high affinity to several antidepressants. The present study tested the hypothesis that a 5-HT6 genetic polymorphism (C267T) is associated with the clinical manifestations of, and/or antidepressant response in, MDD. The Hamilton Depression Rating Scale was used to assess 57 MDD patients before antidepressant treatment, with 34 patients completing the 4-week treatment and evaluation. The results of the association study provide that the 5-HT6 C267T genetic variant does not play a major role in producing the clinical manifestations or antidepressant response for MDD patients. Further study with a functional 5-HT6 polymorphism is needed to explore the role of 5-HT6 in the pathogenesis of MDD.
Memory Failures, Dream Illusions and Mental Malfunction
Authors: Kavanau J. Lee
Published: April 2003

Dreams are widely believed to be produced as the brain’s memory circuits are reinforced during sleep by self-generated brain waves. Reinforcement maintains synaptic strengths in the ‘dedicated’ ranges that support circuit functions. Without these activations, turnover of molecules essential for synaptic function would lead to deleterious alterations in, and eventual loss of, memories. The pathological processes underlying many mental disorders appear to exert their deleterious influences by inducing abnormalities in brain waves, largely in slow waves of less than about 14 cycles/s. The pathologically altered slow waves, in turn, cause long-lasting weakening or dysfunction of synapses of affected circuits, frequently resulting in mental disorders and deviant sleep. These abnormalities can be remediated for varying periods by therapies that restore normal brain waves. With many trillions of synapses between billions of neurons in enormously complex circuits needing reinforcement during sleep, the process is susceptible to failures. As a result, some synapses ‘normally’ weaken or become dysfunctional, accumulating to the greatest extent in old memory circuits. Activation of resulting incompetent circuits during waking may lead to hallucinations and delusions; activation during sleep may lead to dreams with bizarre, incoherent or impossible contents.
Effects of Sertraline Treatment on Plasma Cortisol, Prolactin and Thyroid Hormones in Female Depressed Patients
Authors: Šagud Marina , Pivac Nela , Mück-Šeler Dorotea , Jakovljević Miro , Mihaljević-Peleš Alma , Koršić Mirko
Published: April 2003

The aim of the study was to evaluate the effects of 4 and 24 weeks of sertraline treatment (average dose 42.5 mg/day) on plasma hormone levels in 15 female patients with major depression. Baseline levels of triiodothyronine (T3) were lower, while cortisol, prolactin (PRL), thyroid-stimulating hormone (TSH), and thyroxin (T4) levels did not differ from the values in 16 female controls. There was a positive correlation between the scores on the Montgomery-Asperg Depression Rating Scale and baseline cortisol levels. Treatment with sertraline for 4 weeks increased plasma cortisol levels, while 24 weeks of sertraline treatment increased plasma T3 levels in depressed patients. Neither 4, nor 24 weeks of sertraline treatment affected PRL, T4 and TSH levels in depressed patients. The data show different and time-dependent effects of sertraline treatment on plasma cortisol, PRL and thyroid hormones in female depressed patients.
Effects of Acute Nicotine Administration on Cognitive Event-Related Potentials in Tacrine-Treated and Non-Treated Patients with Alzheimer’s Disease
Authors: Knott V. , Mohr E. , Mahoney C. , Engeland C. , Ilivitsky V.
Published: April 2003

Earlier studies of cognitive event-related brain potentials (ERPs) reporting diminished amplitudes and delayed latencies of the P300 potential in dementia of the Alzheimer type (DAT), together with independent findings of the P300- and performance-enhancing properties of nicotine in normal adults, stimulated this study to explore the single-dose effects of nicotine on auditory and visual P300s in DAT. Thirteen patients, 6 currently receiving treatment with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine; THA) and the remaining being medication free, were administered 2 mg of nicotine polacrilex under double-blind, randomized, placebo-controlled conditions. Prior to nicotine administration, THA-treated patients exhibited shorter auditory P300 latencies than non-treated patients. Acutely administered nicotine failed to alter auditory P300, but increased the amplitudes of visual P300s in both DAT patient groups. Neither THA treatment nor single-dose nicotine altered behavioural performance in the visual and auditory task paradigms. The results are discussed in relation to nicotinic cholinergic, attentional and cognitive processes in DAT.