bluuebunny/crossref_metadata_2025 huggingface dataset:
GABAB Receptors in Anterior Pituitary Cells
Authors: Lux-Lantos Victoria , Becú-Villalobos Damasia , Bianchi María , Rey-Roldán Estela , Chamson-Reig Astrid , Pignataro Omar , Libertun Carlos
Published: April 2003

The activation of pituitary GABAB receptors by the specific agonist baclofen inhibits pituitary hormone secretion in vitro. Here we studied the mechanism of action of GABAB receptors in rat adenohypophysis. Anterior pituitary cells were obtained by trypsinization and were either plated for hormonal studies and cAMP determination or incubated in FURA 2AM for calcium measurements. Baclofen (BACL: 1·10–5 M) significantly inhibited basal and thyrotropic releasing hormone (TRH)-stimulated (1·10–7 M) PRL secretion in anterior pituitary cells from proestrous rats. In the presence of pertussis toxin (PTX: 150 ng/ml, 20 h), which leads to the uncoupling of the Gi/o-protein from the receptor, both effects of BACL were abolished while the effect of dopamine (DA: 1·10–8 M), used as an inhibitory control, was reduced from 70 to 25%. PTX also reversed BACL-induced inhibition of gonadotropin-releasing hormone (GnRH)-elicited luteinizing hormone (LH) secretion in anterior pituitary cells from 15-day-old female rats. In addition, though working in a pituitary mixed cell population, in which only some cell types possess GABAB receptors, BACL (1·10–5 M) attenuated the forskolin-induced (0.5 µM) increase in cAMP. This effect was prevented by co-incubation with the antagonist 2 hydroxysaclofen and by preincubation with PTX. BACL (5· 10–5 M) and DA (5·10–7 M) inhibited basal intracellular calcium concentrations ([Ca2+]i) in pituitary cells and the effect of the latter was significantly stronger. The effect of BACL on [Ca2+]i was abolished after preincubation with PTX. In the presence of the potassium channel blocking agents barium (200 µM and 1 mM) and tetraethylammonium (10 mM), BACL was still able to inhibit [Ca2+]i. Blockade of voltage-sensitive calcium channels (VSCC) with either verapamil (5·10–6 M) or nifedipine (1·10–6 M) completely abolished the effect of BACL on [Ca2+]i. In the presence of 12.5 mM potassium concentration baclofen significantly inhibited [Ca2+]i. In conclusion, our results describe the negative coupling of adenohypophyseal GABAB receptors to VSCC through PTX-sensitive G-proteins. These characteristics suggest a resemblance of these receptors to the typical presynaptic GABAB sites described in the central nervous system.
Sensitivity to a Neurosteroid Is Increased during Addition of Progestagen to Postmenopausal Hormone Replacement Therapy
Authors: Wihlbäck Anna-Carin , Sundström-Poromaa Inger , Nyberg Sigrid , Bäckström Torbjörn
Published: April 2003

The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during different hormonal settings of postmenopausal hormone replacement therapy (HRT). Twenty-seven postmenopausal women with climacteric symptoms were administered HRT in a randomized, double-blinded, placebo-controlled crossover study. The women received 2 mg estradiol (E2) continuously during four 28-day cycles and 10 mg medroxyprogesterone acetate (MPA), 1 mg norethisterone acetate (NETA) or placebo sequentially for the last 14 days in each cycle. The pharmacodynamic response to pregnanolone was assessed before treatment and during the last week of each treatment, by comparing the effects of intravenous pregnanolone (3α-hydroxy-5β-pregnan-20-one) on saccadic eye velocity (SEV), saccade deceleration, saccade latency and self-rated sedation. Throughout the study daily symptom rating scales were kept. During the progesta gen phase of the treatment cycles, negative mood symptoms and physical symptoms were increased, whereas positive mood symptoms were decreased. Compared to pretretreatment conditions, E2 alone did not change the responsiveness to pregnanolone. During progestagen addition to E2, the responsiveness to pregnanolone was increased. The sedation response increased compared to pretreatment conditions during both E2 + MPA and E2 + NETA treatment. Compared to E2 treatment alone, addition of MPA increased the postpregnanolone effect on saccade deceleration, whereas the SEV response to pregnanolone was increased during E2 + NETA treatment. It is concluded that pregnanolone sensitivity increases together with deterioration in mood symptoms during addition of progestagen to HRT.
Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors
Authors: Vázquez-Martínez Rafael , Malagón María M. , Castaño Justo P. , Tonon Marie Christine , Vaudry Hubert , Gracia-Navarro Francisco
Published: April 2003

The melanotrope population of the frog intermediate lobe consists of two subtypes of cells, referred to as high-(HD) and low-density (LD) melanotrope cells, which differ markedly in their basal morphofunctional features as well as their in vitro response to hypothalamic factors, such as the stimulator thyrotropin-releasing hormone (TRH) and the inhibitor dopamine. In this study, we have investigated whether other major hypothalamic regulators of the release of α-melanocyte-stimulating hormone (α-MSH), such as γ-aminobutyric acid (GABA) and neuropeptide Y (NPY), also differentially regulate frog melanotrope subpopulations. Our results show that in LD cells, both factors markedly inhibited proopiomelanocortin (POMC) mRNA accumulation and α-MSH secretion. In contrast, the secretory and biosynthetic activity of HD cells was not modified by GABA. NPY inhibited POMC transcript accumulation and tended to reduce α-MSH secretion in HD cells, yet these effects were less pronounced than those evoked in LD cells. In addition, GABA and NPY inhibited the KCl-induced rise in cytosolic free calcium levels in both subpopulations. Taken together, these results further indicate that frog melanotrope subpopulations are differentially regulated by the hypothalamus and strongly suggest that the intensity of such regulation is directly related to the activity of the cell subset. Thus, the LD subpopulation represents a highly responsive cell subset which is regulated by multiple neuroendocrine factors (TRH, dopamine, GABA and NPY), whereas the hormone storage HD subpopulation shows a moderate response to single stimulatory (TRH) and inhibitory (NPY) inputs.
A Reassessment of Leptin’s Role in Triggering the Onset of Puberty in the Rat and Mouse
Authors: Cheung Clement C. , Thornton Janice E. , Nurani Shafeena D. , Clifton Donald K. , Steiner Robert A.
Published: April 2003

Leptin is an adipocyte-derived hormone that has been implicated to serve as a metabolic signal to the reproductive axis. The role of leptin in pubertal maturation, however, has been a much-debated topic. We have previously reported that leptin serves as a permissive signal to the onset of puberty in the female rat. In an attempt to further understand the mechanics of leptin during pubertal maturation in rodent species, we had three experimental objectives: first, to describe the temporal relationship of leptin with development in the male and female rat; second, to seek evidence for an increase in responsiveness of the neuroendocrine axis to leptin by assessing for possible changes in leptin receptor expression during pubertal developmental in the female rat; and, third, to reevaluate the possible role of leptin as a permissive signal to the onset of puberty in the mouse. We found that serum leptin levels remain relatively constant during the prepubertal and postpubertal stages of both sexes. In addition, we could not detect any significant developmental changes in leptin receptor gene expression in the hypothalamus of the female rat. Lastly, we corroborated our findings in the female rat that leptin reversed the delay in pubertal maturation secondary to food restriction but did not advance the onset of puberty in female mice. Together, these results suggest that leptin is not a metabolic trigger for the onset of puberty in the rodent; instead, leptin is one of several permissive factors, whose presence may be necessary but alone is not sufficient to initiate sexual maturation in these species.
Estrogen and Laryngeal Synaptic Strength in Xenopus laevis: Opposite Effects of Acute and Chronic Exposure
Authors: Wu Kwok Hang , Tobias Martha L. , Kelley Darcy B.
Published: April 2003

Synaptic transmission at the vocal synapse, the laryngeal neuromuscular junction, of Xenopus laevis has been shown to be regulated by long-term changes in circulating estrogen. In females, high levels of circulating estrogen also accompany gonadotropin-induced ovulation and oviposition and the switch from sexually unreceptive to receptive states, including changes in vocal behaviors (ticking to rapping). Here we examine the effects of gonadotropin injection on laryngeal synaptic strength and call type. Gonadotropin acutely reduced quantal content values of laryngeal synapses in intact, adult females; the lowest values were attained by 12 h post-injection. Estrogen and progesterone levels increased following human chorionic gonadotropin (hCG) injection; the time course was similar to, but negatively correlated with, changes in synaptic strength. In ovariectomized frogs, exogenous estrogen, but not progesterone or hCG, mimicked the acute effects of hCG in weakening laryngeal synapses of intact frogs. hCG injection suppressed ticking and sometimes induced rapping. Females could tick with either strong or weakened laryngeal synapses while rapping was only produced during the weakening action of hCG. The normally strong synapses of females may enable vocal production even when laryngeal synapses are weakened by hormones that induce ovulation. In contrast to the acute effect of estrogen on weakening laryngeal synapses, juveniles required more than 2 weeks of estrogen treatment to strengthen laryngeal synapses while at least 4 weeks postovariectomy were required to weaken synapses in adult females. We conclude that acute (hours) increases in circulating levels of estrogen weaken synapses while chronic (weeks) increases strengthen laryngeal synapses.
The Circadian Clock, Light/Dark Cycle and Melatonin Are Differentially Involved in the Expression of Daily and Photoperiodic Variations in mt1 Melatonin Receptors in the Siberian and Syrian Hamsters
Authors: Schuster Carole , Gauer François , Malan André , Recio Joaquim , Pévet Paul , Masson-Pévet Mireille
Published: April 2003

Mechanisms underlying the daily and photoperiodic variations in mt1 melatonin receptors were investigated in the pars tuberalis (PT) and suprachiasmatic nuclei (SCN) of Siberian and Syrian hamsters. Whatever its daily profile, melatonin receptor density was strongly increased in both structures and species after constant light exposure or pinealectomy, and decreased after a single melatonin injection, indicating melatonin involvement in the daily regulation of the receptor protein. This was confirmed by a strong inverse correlation between melatonin binding capacity and plasma melatonin concentration. In contrast, regulation of mt1 mRNA appeared more complex. The circadian clock, the light/dark cycle and melatonin are all implicated in mt1 gene daily fluctuations, but the extent of their involvement depends upon the structure and the species studied. The photoperiodic decrease in melatonin receptor density observed in short photoperiod (PT of the two hamster species and Syrian hamster SCN) seems to be the consequence of a long-term mt1 gene repression induced by the lengthening of the melatonin peak. Altogether, these results show that during daily variations, mt1 melatonin receptor mRNA and protein are differentially regulated, while at the photoperiodic level, the mt1 protein status depends on mRNA transcription.
Dual Effect of Melatonin on Gonadotropin-Releasing-Hormone-Induced Ca2+ Signaling in Neonatal Rat Gonadotropes
Authors: Zemkova Hana , Vanecek Jiri
Published: April 2003

In neonatal rat gonadotropes, melatonin inhibits gonadotropin-releasing-hormone (GnRH)-stimulated increase in intracellular Ca2+ concentration ([Ca2+]i); in cells transfected with the Mel1a melatonin receptor, however, melatonin has been shown to potentiate agonist-stimulated [Ca2+]i increase. To elucidate this discrepancy, we investigated the effects of melatonin in neonatal gonadotropes over a wide range of melatonin concentrations. Nystatin perforated patch recording of Ca2+-dependent potassium currents was used to monitor GnRH-induced [Ca2+]i changes. In 32% of cells, increasing melatonin concentrations in the range of 1 pM to 100 nM prolonged the latency of, and inhibited GnRH (10 nM)-stimulated [Ca2+]i increases in a concentration-dependent manner. In the remaining 68% of cells, the Ca2+ increase elicited by exposure to 10 nM GnRH was also inhibited by picomolar concentrations of melatonin, but at nanomolar concentrations the inhibitory effect disappeared and melatonin was only able to prolong the latency of the response. This dual effect of melatonin however was not observed in cells stimulated with lower (2 nM) GnRH concentrations; in that case, melatonin was inhibitory at all concentrations tested with an IC50 of about 30 pM. In contrast, application of nanomolar concentrations of melatonin resulted in potentiation of the GnRH-induced Ca2+ increase in a small population of gonadotropes which did not respond by inhibition or prolonged latency. These results indicate that in neonatal gonadotropes, melatonin has both inhibitory and potentiating effects on GnRH-stimulated [Ca2+]i increases. Ranges of concentrations needed to produce either effect suggest that two distinct G proteins may be involved, as already observed in transfected cells.
Hypothalamic Targets for Prolactin: Assessment of c-Fos Induction in Tyrosine Hydroxylase- and Proopiomelanocortin-Containing Neurones in the Rat Arcuate Nucleus following Acute Central Prolactin Administration
Authors: Cave Belinda J. , Wakerley Jon B. , Luckman Simon M. , Tortonese Domingo J.
Published: April 2003

Prolactin (PRL) has been implicated in central actions including those that result in its own regulation and/or the suppression of gonadotropin secretion. It is not clear, however, which neuronal systems may mediate the central effects of PRL. Here, using dual immunohistochemistry for c-Fos and either tyrosine hydroxylase (TH) or proopiomelanocortin (POMC), we have assessed neuronal activation, following centrally administered PRL, within two neuronal networks that have been shown to participate in the inhibitory regulation of reproductive function. Male rats received one intracerebroventricular injection of either PRL (5 µg) or saline (vehicle control) 5 days after cannulae were inserted into the lateral ventricles. Ninety minutes after treatment, animals were perfused with 4% paraformaldehyde, the brains were removed and 30-µm frozen sections were cut throughout the entire hypothalamic region. Parallel sets of sections were processed for both c-Fos immunoreactivity (ir) and either TH-ir or POMC-ir. PRL increased the mean number of c-Fos-ir neurons within the rostral arcuate nucleus (9.3 ± 2.0 vs. 5.0 ± 1.2 cells/section, for PRL and control rats, respectively; p < 0.05). Within the TH-ir neurones, PRL induced a significant increase in c-Fos in the dorsomedial portion of the mid-arcuate nucleus (p < 0.05). In contrast, there was no significant increase in the expression of c-Fos within the POMC neurones of the arcuate nucleus. PRL also induced c-Fos expression in the supraoptic nucleus (SON) (11.7 ± 3.2 vs. 3.0 ± 1.4 cells/section for PRL and control rats, respectively; p < 0.05), but not in the medial preoptic nucleus, ventromedial nucleus or the dorsomedial nucleus, areas reported to either contain gonadotropin-releasing hormone neurones or express PRL receptors. The results from this study show immediate early gene activation within both the arcuate nucleus and the SON of the hypothalamus following acute PRL administration. While the role of PRL-responsive neurones in the SON remains to be elucidated, these findings support the notion that the central actions of PRL could be mediated via the TH neurones of the dorsomedial arcuate nucleus and/or by a population of neurones in the rostral arcuate nucleus that contain neither TH nor POMC.
Forced Swimming Differentially Affects Male and Female Brain Corticosteroid Receptors
Authors: Karandrea Despoina , Kittas Christos , Kitraki Efthimia
Published: April 2003

Corticosteroid receptors are key mediators of the neuroendocrine response to stress. Previously, we have determined the effects of restraint stress on the regulation of corticosteroid receptor genes in the brain and pituitary of male and female rats. Significant gender- and regional-specific regulation of receptor mRNAs was observed. To further investigate the stressor specificity in the same context, we have determined glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) mRNAs following exposure to swimming stress paradigms applied alone, or in combination with restraint stress. Our data revealed stressor-specific alterations in GR or MR mRNA levels, which were more pronounced in males, the gender most affected by swimming stress. No alterations in GR or MR mRNA levels were detected in the female hippocampus and hypothalamus upon exposure to swimming paradigms, while in males the same stressors down-regulated GR mRNA in the hippocampus (chronic exposure) and up-regulated both genes in the hypothalamus (acute exposure). In the frontal cortex, acute swimming stress caused a reciprocal change in GR mRNA levels in the two sexes. The above difference is not due to circulating ovarian steroids, since ovariectomy did not change the female pattern of GR gene expression following acute stress. Our results further showed a hypothalamic-pituitary-adrenal axis facilitation to a novel superimposed stressor expressed at the level of limbic corticosteroid receptors: When chronically restrained rats of both sexes were exposed to acute swimming stress, a reduced GR/MR mRNA ratio, implying reduced feedback axis sensitivity, was detected in both the hippocampus and the hypothalamus. In conclusion, our work provides additional evidence on stressor, gender and region specificity in the regulation of brain corticosteroid receptors.
Leptin Immunoreactivity Is Localized to Neurons in Rat Brain
Authors: Ur Ehud , Wilkinson Diane A. , Morash Barbara A. , Wilkinson Michael
Published: April 2003

Leptin is secreted from adipocytes and is thought to enter the brain to regulate and coordinate metabolism, feeding behaviour, energy balance and reproduction. It is now clear that there are many additional sites of leptin production, including human placenta, ovary, stomach, skeletal muscle, mammary gland, pituitary gland and brain. In the present work, we employed double-label immunofluorescent histochemistry to establish the neuronal localization of leptin immunoreactivity (IR). To accomplish this, we used the neuron-specific marker NeuN to label cells in the arcuate nucleus (ARC), piriform cortex and hippocampus. In the supraoptic nucleus (SON) and paraventricular nucleus (PVN), we used antisera to oxytocin and vasopressin as neuronal markers. Double labelling revealed leptin IR in neurons of the ARC and piriform cortex. Leptin IR was confined to the nucleus and to distinct perinuclear sites. In contrast, neurons in the CA 2/CA 3 region of the hippocampus showed little nuclear staining. Leptin IR was clustered around the nucleus in these cells. Neurons of the dentate gyrus exhibited both nuclear and perinuclear localization of leptin IR. In the SON/PVN, most oxytocin- and vasopressin-IR neurons also contained leptin IR, often in perinuclear sites. In conclusion, the neuronal, perinuclear localization of leptin IR in rat brain corresponds closely to that of leptin receptor (OB-R) IR, which has also been detected intracellularly. Our observation of leptin IR associated with cell nuclei suggests the existence of an OB-R distinct from the well-described membrane forms.
The Presence and Prognostic Importance of Glomerular Macrophage Infiltration in Renal Allografts
Authors: Özdemir B. Handan , Demirhan Beyhan , Güngen Yücel
Published: April 2003

Aim: The purpose of this study was to analyze the role of intraglomerular macrophage infiltration in human renal allografts by examining biopsies from kidney grafts that were dysfunctional after transplantation. Methods: Eighty-three patients (58 men, 25 women) of a mean age of 30.2 ± 1.4 years were evaluated. In all cases, biopsy specimens were examined for the presence of macrophage infiltration in the glomeruli. The infiltration of these cells was evaluated immunohistochemically using monoclonal antibody CD68, which labels macrophage cytoplasm. 10 renal allograft biopsies with normal histopathology were used as control group. The CD68-positive macrophages in all glomeruli were counted and the glomerular macrophage index (GMI) was calculated. Results: Of the 83 patients, 40 showed acute rejection (AR), 33 showed chronic rejection (CR) and 10 showed cyclosporin A (CsA) toxicity. Only the biopsies of 28 patients stained positive for CD68 in the glomeruli. Neither patients with CsA toxicity nor controls showed intraglomerular macrophages. The CD68-positive group consisted of 7/33 CR and 21/40 AR patients. We observed intraglomerular macrophages in only 6 of the 20 AR cases that responded to steroid therapy (mean GMI 0.3 ± 0.1) and in 15 of the 20 steroid-resistant AR cases (mean GMI 1.7 ± 1.2; p < 0.01). The outcome of grafts that contained intraglomerular macrophages was significantly worse than the outcomes of other grafts noticed during the follow-up. Conclusion: We conclude that the presence of glomerular macrophages can be considered a marker for rejection and is a valuable additional criterion of rejection in the histological examination of renal allograft biopsies. The presence of intraglomerular macrophages indicates that the outcome of the graft will be significantly worse than that of grafts without intraglomerular macrophage infiltration.
Exogenous Nitric Oxide Inhibits VCAM-1 Expression in Human Peritoneal Mesothelial Cells
Authors: Lee Sang Koo , Kim Ji Hoon , Yang Won Seok , Kim Soon Bae , Park Su-Kil , Park Jung Sik
Published: April 2003

Leukocyte adhesion to mesothelium is an important step during peritonitis, which is mediated by adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1). We investigated the effect of exogenous nitric oxide (NO) on VCAM-1 expression in cultured human peritoneal mesothelial cells and its signal transduction pathway. Mesothelial cells were exposed to tumor necrosis factor-α (TNF-α) in the presence or absence of NO donors, 3-morpholino-sydnonimine (SIN-1) and nitroprusside (NP). VCAM-1 mRNA and protein expression were measured by Northern blot analysis and flow cytometry. Nuclear factor-ĸB (NF-ĸB) binding activity was determined by electrophoretic mobility shift assay. Both SIN-1 and NP inhibited the TNF-α induced VCAM-1 mRNA expression in a dose dependent manner (0.25–2 mM). SIN-1 also suppressed the cell surface expression of VCAM-1 molecule. Furthermore, SIN-1 and NP inhibited the VCAM-1 mRNA expression induced by interleukin-1β or lipopolysaccharide as well. NF-ĸB inhibitor, PDTC dose dependently inhibited the TNF-α induced VCAM-1 mRNA expression. SIN-1 inhibited the TNF-α- induced NF-ĸB binding activity. Analogue of cGMP (8-bromo-cGMP) had no significant effect on TNF-α-induced VCAM-1 mRNA expression and guanylate cyclase inhibitor (ODQ) also had no significant influence on the inhibitory effect of SIN-1. These results suggest that exogenous NO inhibits VCAM-1 expression via suppression of NF-ĸB through a cGMP-independent pathway.
Socioeconomic Differences in the Incidence, Mortality and Prognosis of Intracerebral Hemorrhage in Finnish Adult Population
Authors: Jakovljević Dimitrije , Sarti Cinzia , Sivenius Juhani , Torppa Jorma , Mähönen Markku , Immonen-Räihä Pirjo , Kaarsalo Esko , Alhainen Kari , Tuomilehto Jaakko , Puska Pekka , Salomaa Veikko
Published: April 2003

We examined the association of socioeconomic status (SES) with the incidence, mortality and case fatality of intracerebral hemorrhage (ICH). During 1982–1992, 909 ICH events were registered among persons aged 25–74 years. Taxable income was used as an indicator of SES. It was stratified into three categories: low, middle and high. The age-standardized incidence and mortality of ICH were significantly higher in the low- than in the high-income group in both genders. Among men aged 25–59 years, the adjusted odds ratio (OR) of ICH death within 1 year after the onset of the event was twice as high in the low-income group as in the high-income group (OR = 2.12, 95% confidence interval 1.02–4.40). In conclusion, marked socioeconomic differences were found in the incidence and mortality of ICH, in particular among working aged men.
Multiple Sclerosis and Dental Amalgam: Case-Control Study in Ferrara, Italy
Authors: Casetta Ilaria , Invernizzi Matteo , Granieri Enrico
Published: April 2003

Dental amalgam fillings containing mercury have been suggested as a possible risk factor for multiple sclerosis (MS). In the context of a wider program of investigation into environmental risk factors and MS, we conducted a case-control comparison to investigate the alleged association between MS, dental caries, and amalgam fillings. We included 132 MS patients with onset during the last 16 years and 423 controls, matched to cases for sex, age and residence. Data were collected by a personal interview conducted by trained doctors. Cases and controls gave informed consent. Although we report a trend toward a higher number of dental fillings in cases than controls, odds ratios for subjects with exposures of different duration and with different numbers of amalgam fillings were not statistically significant. This case-control study failed to demonstrate an association between either the number of dental amalgam fillings or the duration of exposure to mercury amalgam and MS.
Dandy-Walker Syndrome: Incidence in a Defined Population of Tabuk, Saudi Arabia
Authors: Ohaegbulam Samuel C. , Afifi Hesham
Published: April 2003

Dandy-Walker syndrome (DWS) is characterized by cystic dilatation of the 4th ventricle and absence of the cerebellar vermis. There may also be posterior fossa enlargement, hydrocephalus, hypoplastic cerebellar hemispheres and other malformations within and outside the central nervous system (CNS). The condition is uncommon, and the incidence is unknown. We studied the incidence of DWS in a defined Saudi Arabian population of military personnel and their dependants. We identified all patients diagnosed with DWS during an 11-year period (1989–1999) from a cohort of 45,274 live births. The incidence of DWS was 1.0 per 100,000 live births per year. The incidence by sex per 100,000 live births per year was 1.24 for males and 0.78 for females. DWS formed 3.5% of our cases of infantile hydrocephalus.
Human T Cell Lymphotropic Virus Type 1-Associated Myelopathy in São Paulo, Brazil
Authors: Milagres Antonio C.P. , Jorge Maria Lúcia S.G. , Marchiori Paulo E. , Segurado Aluisio A.C.
Published: April 2003

We report epidemiologic and clinical features of human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis in a Brazilian cohort of 86 patients from a university hospital. Cerebrospinal fluid (CSF) abnormalities and magnetic resonance imaging (MRI) findings were correlated with neurologic signs and symptoms. The patients’ mean age at disease onset was 43.2 years and the female to male ratio 1.5:1. Risk factors for retroviral exposure included blood transfusions, sexual transmission and intravenous drug use. Neurologic manifestations consisted mostly of spastic paraparesis, of gradual and asymmetric onset, with increased deep-tendon reflexes. Disability was associated with disease duration. CSF findings included mild mononuclear pleocytosis and elevated protein levels. MRI showed hemispheric areas of high signal intensity in 32.7% and spinal cord atrophy in 5.6% of cases, particularly in patients with longer duration of disease. A high frequency of past blood transfusion (32.6%) suggests that blood-borne infection was an important means of HTLV infection before implementation of screening of blood donors in Brazil.
Regional Variations in the Transport of Interleukin-1α across the Blood-Brain Barrier in ICR and Aging SAMP8 Mice
Authors: Moinuddin Asif , Morley John E. , Banks William A.
Published: April 2003

Objectives: The blood-brain barrier (BBB) transports blood-borne interleukin-1α (IL-1) into the brain by a saturable process. Here, we determined whether all regions of the brain could transport IL-1 and whether transport differed between ICR and SAMP8 mice, a strain which overexpresses amyloid beta protein (Aβ) with aging. Methods: We used multiple-time regression analysis to measure the unidirectional influx rate (transport rate) of radioactively labeled IL-1 for 10 brain regions in young (2 months old) ICR mice and in young and aged (17 months old) SAMP8 mice. We also used radioactively labeled sucrose and albumin to determine whether the BBB was disrupted in aged SAMP8 mice. Results: In young ICR mice, eight of the 10 brain regions transported IL-1, with the pons-medulla having the fastest transport rate (0.584 ± 0.163 µl/g·min), but no statistically significant differences occurred among regions. In SAMP8 mice, only four regions transported IL-1. In young SAMP8 mice, the pons-medulla transported IL-1 faster than any other region (0.642 ± 0.197 µl/g·min), a rate that was significantly different (p < 0.01) from each of the other regions. Aged SAMP8 mice had a similar regional transport pattern to young SAMP8 mice, but there were no statistically significant differences among the four transporting regions. Sucrose and albumin spaces were not increased in aged SAMP8 mice, demonstrating an intact BBB. Conclusions: The smaller number of regions transporting IL-1 in SAMP8 mice as compared to ICR mice demonstrates a genetic influence on transport which could alter the ability of blood-borne IL-1 to directly affect brain functions. No evidence of BBB disruption was found in the aged SAMP8 mice from this colony.
Qualitätsmanagement in der Therapie des chronischen Tinnitus
Authors: Goebel G. , Hiller W.
Published: April 2003

Fragestellung: In den letzten Jahren hat die Bedeutung psychologischer Diagnostik und Therapie bei der Behandlung chronischer Ohrgeräusche erheblich zugenommen. Im Gegensatz zum Schmerzbereich existieren weltweit nur etwa neun relevante Messinstrumente zur Erfassung des Tinnitusschweregrades. Hierzu gehört der seit 1988 im internationalen Kontext mit Hallams Tinnitus Questionnaire entwickelte und von deutschsprachigen wissenschaftlichen HNO-Gremien akzeptierte «Tinnitus-Fragebogen» (TF) von Goebel und Hiller. Material und Methode: In diesem Beitrag werden in Form einer aktuellen Bestandesaufnahme die Instrumente mit Hinweisen auf qualitative Merkmale der einzelnen Verfahren miteinander verglichen und kritisch diskutiert: Entwicklungen der Items und deren Selektion, Realibilität, faktorielle Stabilität, kriterienbezogene Validität, Veränderungssensitivität, Zusammenhänge mit tinnitusübergreifenden psychischen Beschwerdebereichen und Persönlichkeitsmerkmalen, Objektivität, Praktikabilität, wissenschaftliche Akzeptanz usw. Des Weiteren werden kursorisch die im deutschen Sprachraum bereits gemachten Erfahrungen mit dem TF bei Evaluationsstudien vorgestellt: Plazebobehandlungen, Kurz- und Langzeitwartegruppen (bis 8 Monate), Counseling in HNO-Ambulatorien und psychologischen Einrichtungen, Langzeittherapie mit Masker und Hörgerät, Tinnitus-Retraining-Therapie (bis 2 Jahre), Relaxationsverfahren, Musikkassetten (6 Monate), ambulante Tinnitus-Bewältigungs-Gruppentherapien, stationäre multimodale Verhaltenstherapien, Spontanverlauf unterschiedlicher Tinnitusschweregrade, Katamnesestudien (bis 2 Jahre) usw. Ergebnisse und Schlussfolgerung: Es zeigt sich, dass der TF im Vergleich zu den bisher bekannten Instrumenten zu den am besten evaluierten Verfahren gerechnet werden kann. Seine semantisch und linguistisch mit der englischen Version übereinstimmenden Aussagen erlauben vergleichende transkulturelle Untersuchungen. Die hohe Akzeptanz des TF erweist sich als Vorteil bei der Evaluation unterschiedlicher Interventionen und deren Effektivitätsbeurteilung.
Periodic Motor Impairments in a Case of 48-Hour Bipolar Ultrarapid Cycling before and under Treatment with Valproate
Authors: Tigges Peter , Juckel Georg , Schröter Andreas , Möller Hans-Juergen , Hegerl Ulrich
Published: April 2003

Motor impairments of psychiatric patients can be assessed with digital recordings of handwriting tasks. The investigation of patients with bipolar affective disorders differentiates intraindividual changes related to the patient’s fluctuating affective states. An unmedicated 67-year-old male with 48-hour bipolar ultrarapid cycling was investigated during 8 consecutive days of ultrarapid cycling and 4 weeks later, after remission under treatment with valproate. The handwriting skills of the patient followed the same rhythmic changes of the psychopathology in the first part of the study and a steady pattern in the second phase, after remission. Therefore, it can be assumed that the handwriting skills reflect a state marker of the disease. Poorer handwriting skills on the manic days, as compared to the depressive ones, support the hypothesis of a low arousal in manic patients.
No Association between Tryptophan Hydroxylase Gene Polymorphism and Alzheimer’s Disease
Authors: Wang Ying-Chieh , Tsai Shih-Jen , Liu Tsung-Yun , Liu Hsiu-Chih , Hong Chen-Jee
Published: April 2003

Serotonergic dysfunction is implicated in Alzheimer’s disease (AD) on the basis of studies of serotonin and its metabolite in postmortem specimens and CSF. There were also reports on association of a tryptophan hydroxylase (TPH) intron 7 variant and CSF 5-hydroxyindoleacetic acid concentrations. These suggested TPH might be a candidate to study for possible involvement in AD. Using a case-control association approach, we studied the TPH polymorphism in 150 subjects with AD and 100 controls. There were no significant differences in genotype or allele frequencies between controls and AD patients. The negative findings suggested that this TPH polymorphism has no major effect on the development of AD. However, the genetic variation of the TPH gene related to the symptomatology of AD deserves further investigation.
Maintenance Electroconvulsive Therapy in Affective and Schizoaffective Disorder
Authors: Swoboda E. , Conca A. , König P. , Waanders R. , Hansen M.
Published: April 2003

Twenty-one patients (13 depressives and 8 schizoaffectives) who underwent maintenance electroconvulsive therapy (M-ECT) were compared with controls who received maintenance pharmacotherapy alone. Measures of effectiveness and safety of maintenance treatment were prospectively obtained during a 1-year follow-up. Survival analysis demonstrated a significantly better outcome defined by time to rehospitalization for all patients of the M-ECT group. Regarding the subgroups, depressives of the M-ECT group had markedly decreased rehospitalization rates cmpared to depressive controls. Furthermore, M-ECT in depressives resulted in a significant reduction in hospitalization rates and duration during follow-up. In schizoaffective patients, a significant difference in survival time was found in favor of the M-ECT group. In both groups, schizoaffectives had a markedly poorer outcome compared to depressive subjects. Our results indicate that in selected patients M-ECT, at least in combination with supporting medication, may be an efficient and safe alternative to pharmacological continuation or maintenance therapy alone.
Effect of the Repeated Administration of (±)-3,4-Methylenedioxymethamphetamine on the Behavioral Response of Rats to the 5-HT1A Receptor Agonist (±)-8-Hydroxy-(di-n-Propylamino)Tetralin
Authors: Granoff Martin I. , Ashby Jr. Charles R.
Published: April 2003

In this study, we examined the effect of the subcutaneous administration (twice daily for 4 consecutive days) of 3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg) or saline (1 ml/kg) on the response of rats to the behavioral effects of the 5-HT1A agonist (±)-8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT) 30 days after the last saline or MDMA treatment. The reciprocal forepaw treading elicited by the 0.25-mg/kg dose of 8-OH-DPAT was significantly lower in animals pretreated with MDMA compared to vehicle-treated animals. However, there were no significant differences between the MDMA- and vehicle-treated animals in flat body posture, locomotor activity and rectal temperature measured after the systemic administration of 8-OH-DPAT. Overall, our results suggest that the depletion of 5-HT levels by the repeated administration of MDMA does not produce a supersensitivity of central 5-HT1A receptors in the rat as determined via our approach.
Evidence for an Association between Polymorphism in the Serotonin-2A Receptor Variant (102T/C) and Increment of N100Am plitude in Schizophrenics Treated with Clozapine
Authors: Yu Younger W.-Y. , Tsai Shih-Jen , Yang Kuan-Hung , Lin Ching-Hua , Chen Ming-Chao , Hong Chen-Jee
Published: April 2003

Using event-related potentials (ERPs), a reduction in the auditory N100, N200 and P300 amplitude has been found in schizophrenic patients and may represent some pathophysiological deficit. Therefore, we investigated whether the genetic variant of the serotonin-2A receptor is associated with ERP change after clozapine treatment in schizophrenic patients. Ninety-nine schizophrenic patients were included in the study. The results demonstrated that patients with 102C/C genotype have higher N100 amplitude than other patients after clozapine treatment. Our findings suggested that serotonin-2A receptor polymorphism may relate to clozapine response in schizophrenic patients. An objective and reliable tool like ERPs to assess patients’ treatment response may afford more consistent results in pharmacogenetic studies.
Differential Effects of Emotional Content on Event-Related Potentials in Word Recognition Memory
Authors: Dietrich Detlef E. , Waller Christiane , Johannes Sönke , Wieringa Bernardina M. , Emrich Hinderk M. , Münte Thomas F.
Published: April 2003

The aim of this study was to delineate the influence of the emotional content of stimuli to be remembered on the recognition performance of normal subjects by means of the event-related potential (ERP) technique. When words are presented repeatedly, brain responses to repeated and recognized items are characterized by a more positive waveform, referred to as ‘old/new effect’. Words judged for their emotional connotation (‘negative’, ‘positive’ and ‘neutral’) were presented successively on a video monitor to subjects, who had the task to indicate whether a given word occurred for the first (‘new’) or second (‘old’) time within the list by pressing one of two buttons. For each word category, the ERPs of the old words were more positive compared to those of the new items from about 250 ms after stimulus. The old/new effect was significantly enhanced for the negative and positive items compared to the neutral stimuli between 450 and 650 ms after stimulus pointing to a significant influence of the emotional content of words on verbal memory processes. This paradigm appears to be feasible to investigate interactions of emotion and cognition in psychiatric patients.
Neurodevelopmental Schizophrenia: Obstetric Complications, Birth Weight, Premorbid Social Withdrawal and Learning Disabilities
Authors: Willinger Ulrike , Heiden Angela M. , Meszaros Kurt , Formann Anton K. , Aschauer Harald N.
Published: April 2003

Neurodevelopmental schizophrenia seems to be caused by impaired cerebral development and is supposed to be associated with obstetric complications (OCs), poor premorbid adjustment, schizotypal or schizoid personality traits and negative symptoms. In the present study, 36 schizophrenic and schizoaffective patients and their same-sex, healthy siblings were recruited. They were diagnosed according to DSM-III-R, using structured psychiatric interviews and a consensus of 2 psychiatrists. Information on OCs, birth weight, premorbid social and learning functioning was obtained from their mothers. The main results show significant differences in OCs, birth weight, premorbid social and learning functioning between patients and their same-sex, healthy siblings. Using multivariate analyses, both premorbid variables were again identified to discriminate well between affected and unaffected siblings. Our findings seem to confirm the concept of schizophrenia as a neurodevelopmental process.
Dopaminergic Lateralisation in the Forebrain: Relations to Behavioural Asymmetries and Anxiety in Male Wistar Rats
Authors: Thiel C.M. , Schwarting R.K.W.
Published: April 2003

Neurochemical lateralisation has been demonstrated in dopaminergic systems in the rat brain, and it has been suggested that such lateralisation might contribute to asymmetric and emotional behaviour. Here, we investigated dopaminergic brain lateralisation in relation to spontaneous and drug-induced behavioural asymmetries, and to emotional behaviour in a sample of 24 male Wistar rats. Asymmetric behaviour was measured in the open field in the undrugged state and after a systemic challenge with the muscarinic receptor antagonist scopolamine (0.5 mg/kg). Emotional behaviour was measured in the elevated plus-maze. Dopaminergic lateralisation was assessed by means of a post-mortem analysis of tissue dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) content. We found higher DOPAC/DA ratios in the neostriatum, ventral striatum, frontal cortex and amygdala of the right hemisphere. In the open field, the complete sample of rats did not show a left/right asymmetry in spontaneous behaviour, whereas systemic scopolamine induced a left-sided preference in thigmotactic scanning. A correlational analysis yielded individual relationships between behaviour and post-mortem neurochemistry, since lateralisation of DOPAC/DA ratios in favour of the right ventral striatum was related to right-side thigmotaxis. Furthermore, a right dopaminergic lateralisation in the frontal cortex was associated with lower anxiety. The study indicates that asymmetries in ventral striatal dopamine might contribute to side preferences in thigmotactic scanning while frontal dopaminergic lateralisation might influence emotional processing.
Dexamethasone Blocking Effects on Mu- and Delta-Opioid-Induced Seizures Involves Kappa-Opioid Activity in the Rabbit
Authors: Di Giannuario Amalia , Pieretti S. , Sagratella S. , Loizzo A.
Published: April 2003

Previous data indicate that intracerebroventricular administration of agonists for µ- and δ-opioid receptors induces limbic seizures in rats, but no data are reported in rabbits. We found that the µ- and δ-opioid peptides [D-Ala2-N,Me-Phe4-Gly5-ol]enkephalin (DAMGO), β-endorphin and deltorphin II, induced EEG non-convulsive hippocampal seizures, and changes in hippocampal background EEG, physical parameters and overt behaviour after central administration. Dexamethasone pre-treatment prevented DAMGO-, deltorphin II- and β-endorphin-induced seizures as well as changes in background EEG, physical parameters and overt behaviour induced by µ-opioid agonists. Dexamethasone antagonism on opioid action was blocked by pre-treatment with a protein synthesis inhibitor, cycloheximide or by the ĸ-opioid antagonist nor-binaltorphimine. Our data suggest that dexamethasone influences opioid actions at µ- and δ-receptors via a protein synthesis mechanism involving ĸ-opioid receptors.
Contingent Negative Variation and Personality in Depression
Authors: Hansenne Michel , Ansseau Marc
Published: April 2003

Contingent negative variation (CNV) has been applied in depression with controversial results. A major source for these controversial results could result from the diversity of depressed patients included in the different studies. Supporting this assumption, impulsivity, blunted affect and suicidal behavior significantly influence CNV amplitude. However, no data are available on the possible influences of personality of depressed patients on CNV. Since personality is related to CNV in normal subjects, the aim of the present study was to investigate the relationship between CNV and personality as assessed by the Temperament and Character Inventory (TCI) in 52 depressed patients. A group of 76 healthy volunteers was included in the study. Among depressed patients, the main results of the study shows that CNV amplitude is positively correlated with self-transcendence dimension. In healthy volunteers, results show that CNV amplitude is negatively correlated with novelty seeking and persistence dimensions. The other dimensions are not related to CNV amplitude either in depressed patients or in healthy volunteers. The findings among depressed subjects suggest that lower CNV amplitude may be associated with psychotic traits (high self-transcendence scores), and those observed in healthy subjects are consistent with previous studies and support energetical models of slow potentials. However, the preliminary nature of the present results with respect to the weak statistical significance should be underlined.
Season of Birth Variations in the Temperament and Character Inventory of Personality in a General Population
Authors: Chotai Jayanti , Forsgren Thomas , Nilsson Lars-Göran , Adolfsson Rolf
Published: April 2003

Background: Since several studies show season of birth variations in morbidity, suicidal behavior and CSF (cerebrospinal fluid) monoamine metabolites, we investigated season of birth variations in personality in the population. Methods: We analyzed by multiple logistic regressions the Temperament and Character Inventory (TCI) for 2,130 individuals taking part in the Betula prospective random cohort study of Umeå, Sweden. Results: The personality dimensions were correlated significantly with age and gender. We stratified the data according to age, gender and the season of TCI measurement. By the median split in each stratum, a high-value group and a low-value group were obtained for each of the personality dimensions. Those born during February to April were significantly more likely than those born during October to January to have high NS (novelty seeking) among women, particularly the subscale NS2 (impulsiveness vs. reflection), and to have high PS (persistence) among men. Temperament profiles also showed season of birth variations. Conclusions: We discuss the associations in the literature between personality and the monoamines serotonin and dopamine, and suggest that our results are compatible with a hypothesis of season of birth variation in the monoamine turnover. The personality traits are likely to be influenced by several genetic and environmental factors, one of them being the season of birth.
The Influence of Personality on Nicotine Craving: A Hierarchical Multivariate Statistical Prediction Model
Authors: Reuter Martin , Netter Petra
Published: April 2003

The present study proposes a hierarchical multivariate statistical prediction model which enables to determine the most prominent variables (physiological, biochemical and personality factors) related to nicotine craving and dopaminergic activation. Based on animal studies reporting a reduction of the rewarding effects of psychotropic drugs after blockade or destruction of the mesolimbic dopamine (DA) system, changes in nicotine craving after pharmacological manipulation by means of a DA agonist (lisuride 0.2 mg) and a DA antagonist (fluphenazine 2 mg) were assessed in 36 healthy male heavy smokers. The major aim was the development of a multivariate prediction model which is applicable in samples lacking variance homogeneity or the prerequisite of a multivariate normal distribution. The model proposed is a combination of multivariate parametric and nonparametric methods taking advantage of their individual merits. Especially personality variables, such as sensation seeking, impulsivity, and neuroticism showed to be important predictors of craving in this responder approach.