bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attenuation of Luteinizing Hormone Surges in Neuropeptide Y Knockout Mice
Authors: Xu Ming , Hill Jennifer W. , Levine Jon E. 
Published: April 2003

To clarify the role of neuropeptide Y (NPY) in the regulation of the reproductive axis, these experiments evaluated the extent to which reproductive hormone secretions may be compromised in the absence of NPY expression. In NPY knockout (NPY-KO) and wild-type (WT) mice, hormone secretions were analyzed under conditions of basal release, following ovariectomy (OVX), in proestrus, after estrogen treatments which induce gonadotropin surges and after injection of gonadotropin-releasing hormone (GnRH). Radioimmunoassays of serum from metestrous females revealed that basal luteinizing hormone (LH), follicular-stimulating hormone (FSH), estrogen and progesterone levels, as well as hypothalamic GnRH tissue concentrations, were not different between the two genotypes. The LH and FSH levels and GnRH tissue concentrations were likewise similar in WT and NPY-KO mice 5 and 10 days following OVX. Significant differences in LH levels were observed however when animals were exposed to pheromone stimulation (male mouse urine) to induce preovulatory LH surges. In proestrous animals, mean LH levels at 18.30–19.00 h were reduced by about 66% in NPY-KO versus WT mice (4.33 ± 1.12 ng/ml in the WT mice vs. 1.47 ± 0.42 ng/ml in the NPY-KO mice, p = 0.028). Despite diminishment of LH surges in NPY-KO mice, corpora lutea were equally abundant in the ovaries of NPY-KO and WT mice. In an additional experiment, a surge-inducing regimen of estradiol-17-β (E<sub>2</sub>) and estradiol benzoate (E<sub>2</sub>B) was administered to OVX animals. The LH surges in the NPY-KO animals treated in this manner were again diminished by approximately 50% compared to corresponding values in WT animals (WT mice 7.33 ± 0.97 ng/ml, NPY-KO mice 3.58 ± 0.74 ng/ml; p = 0.0063). To assess the contribution of altered pituitary responsiveness to the diminishment of LH surges, LH responses to a GnRH challenge (200 ng/kg subcutaneously) were determined; NPY-KO animals exhibited LH responses that were significantly reduced compared to values in WT mice (WT mice 4.88 ± 0.56 ng/ml, NPY-KO mice 3.00 ± 0.41 ng/ml; p = 0.013). Taken together, these observations do not support the idea that NPY plays a major role in the regulation of basal gonadotropin secretion or in mediating negative feedback actions of gonadal hormones. They demonstrate however that preovulatory NPY release is required for normal amplification of the LH surge that occurs on proestrus. Involvement of NPY in the generation of normal LH surges is partially mediated by the ability of the peptide to prime the anterior pituitary gland to GnRH stimulation.
In vivo and in vitro Effects of Ghrelin/Motilin-Related Peptide on Growth Hormone Secretion in the Rat
Authors: Tolle Virginie , Zizzari Philippe , Tomasetto Catherine , Rio Marie-Christine , Epelbaum Jacques , Bluet-Pajot Marie-Thérèse 
Published: April 2003

Ghrelin (Ghr), a 28 amino acid gastric peptide with an n-octanoylation on Ser 3, has recently been identified as an endogenous ligand of the growth hormone secretagogue (GHS) receptor. A cDNA was also isolated from a mouse stomach library encoding a protein named prepromotilin-related peptide (ppMTLRP) which shares sequence similarities with prepromotilin. Mouse and rat ppMTLRP sequences (rGhr) are identical and show 89% identity with human ghrelin (hGhr). By analogy with promotilin, cleavage of proMTLRP into an 18 amino acid endogenous processed peptide can be assumed on the basis of a conserved dibasic motif in position 9–10 of its sequence. In the present work, we compared the GH-releasing activity of rGhr28/MTLRP and of hGhr28/MTRLP with that of a shorter form of the peptide, hGhr18. A short peptide devoid of Ser-3 n-octanoylation hGhr18[–] was also tested. Addition of rGhr28, hGhr28 and hGhr18 stimulated GH release to the same extent from superfused pituitaries. The effect was dose dependent in a 10<sup>–8</sup> to 10<sup>–6</sup><i>M</i> concentration range. In contrast, hGhr 18[–] was inactive. In freely moving animals, both rGhr28 and hGhr28 (10 µg, i.v.) stimulated GH release, whereas the same dose of hGhr18 or of hGhr18[–] was ineffective. After rGhr28, GH plasma levels increased as early as 5 min after injection and returned to basal values within 40–60 min. Expressed as percent stimulation, administration of rGhr28 was equally effective when injected during troughs or peaks of GH. Plasma concentrations of prolactin, adrenocorticotropin and leptin were not modified. Spontaneous GH secretory episodes were no longer observed within 3 h of rGhr28 treatment, but repeated administration of the secretagogue at 3- to 4-hour intervals resulted in a similar GH response. Activation of somatostatin (SRIH) release by ether stress did not blunt the GH response to rGhr28. This suggests that the secretagogue acts in part by inhibiting endogenous SRIH, as further substantiated by the ability of rGhr28 (10<sup>–6</sup><i>M</i>), to decrease the amplitude of 25 m<i>M</i> K<sup>+</sup>-induced SRIH release from perifused hypothalami. In conclusion, (1) n-octanoylation of Ghrs and the shorter form hGhr18 is essential for the direct pituitary GH-releasing effect of this new family of endogenous GHSs; (2) only the longer forms are active in vivo and (3) inhibition of SRIH release appears involved in the mechanism of Ghr action.
Immortalized Gonadotropin-Releasing Hormone Neurons (GT1-7 Cells) Exhibit Synchronous Bursts of Action Potentials
Authors: Funabashi Toshiya , Suyama Kumiko , Uemura Tsuguo , Hirose Makiko , Hirahara Fumiki , Kimura Fukuko 
Published: April 2003

Although it has been assumed that synchronized firing of gonadotropin-releasing hormone (GnRH) neurons is necessary for pulsatile GnRH secretion, there is no clear evidence for this. In the present study we simultaneously recorded spontaneous action potentials from multiple cells. Immortalized GnRH neurons (GT1-7 cells) were cultured on a multi-electrode dish (MED) and action potentials recorded by an extracellular recording method. One to two weeks after the beginning of culture, spontaneous action potentials appeared, exhibiting bursts composed of 5–10 action potentials. Burst activity was intermittent and periodic with mean burst intervals of 13.3 s. Furthermore, burst activity was recorded almost simultaneously from several micro-electrodes, suggesting that electrical activities of GT1-7 cells were synchronized with each other. Periodic bursts were completely and reversibly blocked by 1–5 µ<i>M</i> tetrodotoxin, indicating that voltage-dependent Na<sup>+</sup> channels are involved in their generation. γ-Aminobutyric acid (GABA) given at a 10-µ<i>M</i> concentration shortened inter-burst intervals, whereas 10 µ<i>M</i> bicuculline lengthened them. Finally, the gap junctional blockers n-octyl alcohol (1 m<i>M</i>) and carbenoxolone (100 µ<i>M</i>) reversibly blocked periodic burst activity. The present study provides direct evidence that the electrical activity of GT1-7 cells exhibits synchronous and periodic bursts composed of action potentials. In addition, endogenous GABA is involved in GT1-7 cells in determining burst frequency. Although the precise mechanism of synchronized burst activities needs to be clarified, gap junctional communications among GT1-7 cells are at least partially involved.
Appetite-Suppressing Effects of Urotensin I and Corticotropin-Releasing Hormone in Goldfish <i>(Carassius auratus)</i>
Authors: Bernier Nicholas J. , Peter Richard E. 
Published: April 2003

Fish urotensin I (UI), a member of the corticotropin-releasing hormone (CRH) family of peptides, is a potent inhibitor of food intake in mammals, yet the role of UI in the control of food intake in fish is not known. Therefore, to determine the acute effects of UI on appetite relative to those of CRH, goldfish were given intracerebroventricular (i.c.v.) injections of carp/goldfish UI and rat/human CRH (0.2–200 ng/g) and food intake was assessed for a 2-hour period after the injection. UI and CRH both suppressed food intake in a dose-related manner and UI (ED<sub>50</sub> = 3.8 ng/g) was significantly more potent than CRH (ED<sub>50</sub> = 43.1 ng/g). Pretreatment with the CRH receptor antagonist, α-helical CRH<sub>(9–41)</sub>, reversed the reduction in food intake induced by i.c.v. UI and CRH. To assess whether endogenous UI and CRH modulate fish appetite, goldfish were given intraperitoneal implants of the glucocorticoid receptor antagonist, RU-486 (50 and 100 µg/g), or the cortisol synthesis inhibitor, metyrapone (100 and 200 µg/g), and food intake was monitored over the following 72 h. Fish treated with either RU-486 or metyrapone were characterized by a sustained and dose-dependent reduction in food intake. Pretreatment with i.c.v. implants of α-helical CRH<sub>(9–41)</sub> partially reversed the appetite-suppressing effects of RU-486 and metyrapone. In a parallel experiment, the effects of RU-486 (100 µg/g) and metyrapone (200 µg/g) intraperitoneal implants on brain UI and CRH gene expression were assessed. Relative to sham-implanted controls, fish treated with RU-486 or metyrapone had elevated UI mRNA levels in the hypothalamus and CRH mRNA levels in the telencephalon-preoptic brain region. Together, these results suggest that UI is a potent anorectic peptide in the brain of goldfish and that endogenous CRH-related peptides can play a physiological role in the control of fish appetite.
Differential Inhibition of Growth Hormone Secretion by Analogs Selective for Somatostatin Receptor Subtypes 2 and 5 in Human Growth-Hormone-Secreting Adenoma Cells in vitro
Authors: Tulipano Giovanni , Bonfanti Carlo , Milani Gabriella , Billeci Bruno , Bollati Angelo , Cozzi Renato , Maira Giulio , Murphy William A. , Poiesi Claudio , Turazzi Sergio , Giustina Andrea 
Published: April 2003

Somatostatin (SRIH), a cyclic tetradecapeptide hormone originally isolated from mammalian hypothalamus, is a potent suppressor of pituitary growth hormone (GH) secretion. SRIH acts through a family of G-protein-coupled membrane receptors containing seven transmembrane domains. Five genes encoding distinct SRIH receptor (SSTR) subtypes have so far been cloned in human and other species and termed SSTR1–5. In human somatotrophe pituitary adenomas GH secretion is controlled by both SSTR2 and SSTR5. However, in clinical practice only somatostatin analogs selective for SSTR2 (octreotide and lanreotide) are available. This may explain why clinical and in vitro responses to these analogs in acromegaly are only partial. In this study, we investigated the inhibitory effect of two new SRIH analogs with high selectivity for SSTR2 (NC-4-28B) and SSTR5 (BIM-23268) and compared it to that of native somatostatin (SRIH-14) on a large number of GH-secreting adenomas obtained by transphenoidal neurosurgery. Tissues from 16 adenomas were enzymatically dispersed and plated in 24-well dishes at 50,000 cells/well. After 3 days, groups of three wells were incubated for 4 h with medium alone, SRIH-14 or analogs NC-4-28B or BIM-23268, at the concentrations of 0.01, 0.1 and 1 µ<i>M</i>. Our results show that 9 out of 16 adenomas were responsive (GH suppression: 20–40% vs. control, p < 0.05) to SRIH. In this group only 4 adenomas showed similar responses to both selective analogs, with 2 nonresponders (expression of other SRIH receptor subtypes) and 2 responders (concomitant expression of SSTR2 and SSTR5) to both analogs. GH release was selectively inhibited by NC-4-28B in 3 adenomas and by BIM-23268 in the remaining 2 adenomas, suggesting predominant expression of SSTR2 and SSTR5, respectively. SRIH failed to inhibit GH release in 7 adenomas (43%). Interestingly, in that group a better inhibitory effect was obtained with BIM-23268 (5 out of 7 adenomas) than with NC-4-28B, suggesting expression of a few SSTR5 receptors only, or of both SSTR2 and SSTR5, respectively. We conclude that the availability of somatostatin analogs selective for SSTR5 will enhance the treatment potency and spectrum in acromegaly.
Effects of Haloperidol Pretreatment on the Smoking-Induced EEG/Mood Activation Response Profile
Authors: Walker Darlene , Mahoney Colleen , Ilivitsky Vadim , Knott Verner J. 
Published: April 2003

This study examined the role of dopamine in modulating the CNS response to cigarette smoking. In a randomized, double-blind, repeated-measures design, quantitative electroencephalographic (EEG) changes and self-reports induced by the smoking of a single cigarette were assessed in 16 smokers following pretreatment with placebo and a dopamine antagonist, haloperidol (2 mg). Following placebo pretreatment, absolute (µV) and relative (%) amplitudes in slow-frequency bands (δ, &#920;, α<sub>1</sub>) were reduced and absolute and relative amplitudes in fast-frequency bands (α<sub>2</sub>, β) were increased following cigarette smoking as compared to sham smoking. Haloperidol pretreatment inhibited the smoking-induced increase in absolute β frequency. Self-ratings indicated that cigarette smoking induced increases in alertness, contentedness and calmness but not euphoria, and reduced cigarette cravings as compared to the sham smoking conditions. Smoking-induced, α<sub>2</sub> increments were associated with increases in alertness and decreases in euphoria while β increments were associated with increased calmness. Smoking-related self-ratings of mood and cigarette acceptability were not altered by haloperidol, but subjects were less content overall in the haloperidol condition as compared to placebo. Discussion of these results focuses on transmitter systems and their relationship to neuro-electric and behavioural activities associated with the smoking habit.
Multimodal Electroneurophysiological Studies of Systemic Lupus erythematosus
Authors: Khedr Eman M. , Khedr Tayseer , Farweez Hassan M. , Abdella Gamal , El Beih Esam A.S. 
Published: April 2003

The purpose of this study was to obtain electrophysiological documentation of possible involvement of central and peripheral nervous system (CNS and PNS) in systemic lupus erythematosus (SLE) patients even in the absence of neurological manifestations. The study included 30 consecutive patients with SLE and 25 age- and sex-matched volunteers as a control group. They were subjected to neurological and rheumatological tests and an extensive battery of neurophysiological tests, besides Wechsler adult intelligence scale. Overt neurological manifestations were observed in 14 patients (46.7%). Neurophysiological data revealed that 25 patients (83%) had at least 2 abnormal tests; 11 (68.8%) patients of the asymptomatic group and 14 patients (100%) of the symptomatic group with no significant differences between them. Seventeen patients (56.7%) had evidence of PNS dysfunction either in nerves (46.7%) or muscles (10%); 7 of them in the asymptomatic group. Twenty-four patients (80%) had evidence of CNS dysfunction. Twenty-two patients (73%) had abnormalities recorded on electroencephalography; 9 patients in the asymptomatic group and 13 patients in the symptomatic group. Eleven patients (37%) had abnormal values of P100 of visual evoked potential; 5 patients in the asymptomatic group and 6 in the symptomatic group. Eight patients (26.7%) had abnormal latency of wave I of brain stem response; 3 of them in the asymptomatic group. Abnormal prolongation of the P300 component of event-related potentials was recorded in 2 patients (12.5%) of the asymptomatic group, while low IQ was observed in 8 patients of each group. Neurophysiological abnormalities are fairly common in SLE patients whether symptomatic or asymptomatic. The use of such tests favors a true incidence of nervous system involvement, more accurate diagnosis, and may lead to better clinical care before the development of debilitating CNS and PNS changes.
Intraspinal Pressure Influences CSF Disposition of Tryptophan and 5-HIAA
Authors: Eklundh Thomas , Nordin Conny 
Published: April 2003

Cerebrospinal fluid (CSF) concentrations of monoamine compounds are influenced by factors such as age, gender, height, body weight, tapping time, and atmospheric pressure. We have now examined the role of intraspinal pressure. Thirteen male volunteers underwent lumbar puncture in the right decubitus position without preceding strict bed rest. The intraspinal pressure was recorded, and monoamine precursors, transmitters, and metabolites were analyzed in two consecutively collected CSF fractions. Tryptophan in 12 ml of CSF and the 5-hydroxyindoleacetic acid concentration ratio [fraction II (7–12 ml CSF)/fraction I (0–6 ml CSF)] correlated with the intraspinal pressure. Hypothetically, the intraspinal pressure may be a confounding factor for a correct interpretation of CSF tryptophan and 5-hydroxyindoleacetic acid concentrations, and this is an issue that has to be addressed in future CSF studies.
Morning and Evening Plasma Melatonin and Dexamethasone Suppression Test in Patients with Nonseasonal Major Depressive Disorder from Northern Greece (Latitude 40–41.5°)
Authors: Fountoulakis K.N. , Karamouzis M. , Iacovides A. , Nimatoudis J. , Diakogiannis J. , Kaprinis G. , Demitriadou A. , Bech P. 
Published: April 2003

<i>Introduction:</i> The present study aimed to search for correlations between melatonin (MT) levels and the dexamethasone suppression test (DST) and clinical variables. <i>Methods:</i> Fifty depressed patients aged 21–60 years took part in the study. The Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and the International Personality Disorders Examination were used for diagnosis. Psychometric assessment included the Hamilton Depression Rating Scale, the Hamilton Anxiety Scale, the General Assessment of Funtioning Scale, the Newcastle scales and the Diagnostic Melancholia Scale. The DST and 9.00 and 23.00 h MT values were assessed. Statistical analysis included Student’s t test, Pearson product moment correlation coefficient and forward stepwise multiple linear regression analysis. <i>Results:</i> Melancholic patients had lower 23.00 h MT values in comparison to the rest of the patients and the atypical and ‘undifferentiated’ patients. <i>Conclusion:</i> The current study shows that low MT values were closely related to melancholic depression. Distinct quality of mood, psychomotor agitation or retardation and anorexia or weight loss seemed to be responsible for this relationship.
Pharmacological Mechanism of Topical Lodoxamide Treatment in Vernal Keratoconjunctivitis: A Flow-Cytometric Study
Authors: Murat Avunduk Avni , Cihat Avunduk Mustafa , Dayanır Volkan , Tekelioglu Yavuz , Selim Dayioglu Yavuz 
Published: April 2003

The aim of this study was to investigate the possible effect of lodoxamide 0.1% ophthalmic solution (LOS) on tear T lymphocytes, especially Th2 (T helper 2 subgroup of helper T lymphocytes), in the tear specimens of patients with vernal keratoconjunctivitis (VKC) and to explore the mechanism of the anti-allergic effect of this drug. Twenty-eight active VKC patients were randomly divided into two groups each containing 14 patients. We obtained tear samples from all patients at the beginning of the study. LOS was prescribed to the study group (group A), but the controls (group B) received placebo over the course of 6 weeks. Tear samples were also collected from all patients following a 6-week course of treatment with either LOS or placebo. The percentages of Th1, Th2 and Th cells in the tear samples were measured by using a flow-cytometric technique and the results were compared to each other by using Wilcoxon matched-pairs signed-rank and Mann-Whitney U tests. We found that LOS treatment decreased the percentages of Th2 and Th cells in the tears of group A patients, while placebo had no effect on these values. Th1 cell count in the tears of both groups of patients did not show any significant change between the pre- and posttreatment stages. Our data suggest that LOS exerts, at least, some part of its anti-allergic effect via decreasing the Th2 cell number in the tears of VKC patients.
Pattern Electroretinogram Elicited by a Dartboard Pattern
Authors: Yoshii Masaru , Yanashima Kenji , Nakata Yasuhiko , Nozawa Fukumi , Okisaka Shigekuni 
Published: April 2003

The receptive field size of retinal ganglion cells is closely related to their eccentricity from the fovea. To elicit larger pattern-reversal electroretinograms (P-ERGs), it may be useful to stimulate the retina with patterns having elements that parallel this change in receptive field size. We describe a dartboard pattern consisting of reversal elements that enlarge gradually from the central to the peripheral stimulus field. The utility of the dartboard pattern for eliciting P-ERG was investigated by comparing it with the conventional uniform checkerboard pattern, but with the other stimulus parameters remaining unchanged (96% contrast, 35.9 cd/m<sup>2</sup> mean luminance, 3.3 rev/s temporal frequency, 15° circular field). The dartboard pattern produced a significantly larger P50 amplitude than did the checkerboard pattern, while no difference in peak latency was found when 54 min of arc was used as a standard check size for the checkerboard pattern. The dartboard pattern for eliciting P-ERG should prove clinically useful.
Cell Growth Inhibition and DNA Incorporation of Mitomycin C in Cell Culture
Authors: Takahashi Nobuo , Murayama Teiichirou , Oda Madoka , Miyakoshi Minoru 
Published: April 2003

The present study was performed to clarify the effects of a 4-min exposure of mitomycin C (MMC) on cell growth, the cell cycle and MMC dose incorporated into DNA, using Chang’s cultured human conjunctival cells. A low dose of MMC ranging from 0.00025 to 0.004% showed dose-dependent cytotoxicity when cell growth was active. Fifty percent cell viability was found when cells were treated with 0.001% MMC. A flow cytometer showed that 0.001% MMC inhibited the DNA synthetic phase. After 0.04% MMC was exposed to 3 ×10<sup>6</sup> cells and immediately rinsed, DNA was isolated to measure the dose of MMC detected from DNA. The total amount of DNA was 7 µg from which 3 µg of MMC was detected by high performance liquid chromatography. The above results revealed that the lowest concentration of MMC which caused 50% cell viability and cell cycle inhibition was 0.001% and that MMC was rapidly incorporated into DNA.
Scanning Electron Microscopy after Cryofracture of Normal and Ischemic Rat Retinas
Authors: Ménérath Jean Marc , Droy-Lefaix Marie-Thérèse , Doly Michel 
Published: April 2003

The authors described the use of scanning electron microscopy after cryofracture to analyze rat retinas after experimental ischemia-reperfusion sequence. In Sprague-Dawley albino rats, intraocular hypertony by cannulation of anterior chamber was performed for 1 h on one eye. The other eye served as control. After 48 h of reperfusion, retinas were dissected. They were frozen and fractured before ultrastructural analysis by a scanning electron microscope. In the ischemic eyes the thickness of the photoreceptors layer was reduced, through internal disorganization resulting in misalignment of rods. There was swelling of the outer segments, a loss of adhesion between segments and superficial necrosis. Scanning electron microscopy after cryofracture permitted an analysis of the external morphology of retinal cells and intercellular components, especially the outer layers.