bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenergic and Cholinergic Regulation of in vitro Melatonin Release during Ontogeny in the Pineal Gland of Long Evans Rats
Authors: Wagner Gabriela , Brandstätter Roland , Hermann Anton 
Published: April 2003

Melatonin, produced by the pineal gland, plays an important role in a great variety of neuroendocrine functions. The rhythmic release of melatonin by the mammalian pineal gland is regulated by norepinephrine (NE) acting via α- and β-adrenergic receptors utilizing distinct signal transduction pathways. Acetylcholine has been demonstrated to exert various effects in the mammalian pineal gland, including an inhibitory action on the NE-induced stimulation of melatonin production. However, data obtained by different laboratories on the interaction of adrenergic receptors are not consistent and whether muscarinic and/or nicotinic receptors participate in the various effects of acetylcholine is still contradictory. To investigate noradrenergic as well as cholinergic mechanisms during ontogeny, we have investigated in vitro melatonin release from isolated pineal glands of Long Evans rats of different ages. NE as well as the β-adrenergic receptor agonist isoproterenol (ISO) significantly elevated the melatonin release in pineal glands from postnatal week 2 on. In pineal glands originating from 2- to 4-week-old rats, simultaneous activation of α- and β-adrenergic receptors by ISO and the α-adrenergic receptor agonist methoxamine (MET) or NE resulted in significantly weaker stimulation of melatonin production than β-receptor activation alone. Acetylcholine evoked a significant increase in melatonin release in pineal glands from 2- to 4-week-old rats. In pineal glands from 8- to 20-week-old animals, ISO, ISO + MET or NE stimulated pineal melatonin release to comparable maxima, whereas acetylcholine was without effect. Our data indicate (1) that the adrenergic stimulation of pineal melatonin production in Long Evans rats is dominated by a β-adrenergic mechanism, (2) that additional α-adrenergic receptor activation is inhibitory and (3) dependent on the developmental status of the animal, and (4) that acetylcholine acting via muscarinic receptors has the capacity to stimulate melatonin release during early ontogeny. These data suggest that the melatonin-generating system of the pineal gland of Long Evans rats undergoes substantial functional changes during early postnatal development, including adrenergic as well as cholinergic mechanisms.
Serotonin Inhibits Luteinizing Hormone Release via 5-HT1A Receptors in the Zona incerta of Ovariectomised, Anaesthetised Rats Primed with Steroids
Authors: Siddiqui Arif , Kotecha Krishna , Salicioni Ana-Maria , Kalia Veena , Murray Joanne F. , Wilson Catherine A. 
Published: April 2003

The zona incerta (ZI), an area in the dorsal hypothalamus, contains neuronal systems that appear to control gonadotropin release. Previous findings show that there is an inverse relationship between serotonin (5-HT) activity in the ZI and plasma luteinizing hormone (LH) levels, indicating that the 5-HT system in this area has an inhibitory effect on LH release. Employing anaesthetised, ovariectomised rats primed with 5 µg oestradiol benzoate followed at 48 h by 0.5 mg progesterone, we have shown that 2 µg/side 5-HT in the ZI inhibits the LH surge that normally occurs 4 h after the progesterone treatment. This effect was mimicked by 2 µg/side 8-OH-DPAT, a 5-HT1A agonist, but not by DOI, a 5-HT2 agonist, BMY7378, a presynaptic 5-HT1A agonist or MCPP, a 2B &#38; 2C agonist. The inhibitory effect of 5-HT and 8-OH-DPAT was prevented by pretreatment, 1 h before, with either 2 mg/kg i.p. WAY100135, a 5-HT1A antagonist or 0.25 mg/kg i.p. ritanserin, a 5-HT2 antagonist. These results indicate that 5-HT in the ZI exerts its inhibitory effect on LH release via 5-HT1A receptors but that another 5-HT subtype may also be involved.
Responsiveness of Irradiated Rat Anterior Pituitary Cells to Hypothalamic Releasing Hormones Is Restored by Treatment with Growth Hormone
Authors: Chiarenza Andrea , Lempereur Laurence , Palmucci Tullio , Cantarella Giuseppina , Amico-Roxas Matilde , Goffin Vincent , Murabito Paolo , Magro Gaetano , Bernardini Renato 
Published: April 2003

Hypopituitarism is a common sequela of irradiation in cancer patients. Here we report that recombinant human growth hormone (r-hGH) prevents cell death and restores secretory capacity of irradiated rat pituitary cells in vitro. Dispersed rat pituitary cells from male Sprague-Dawley rats, irradiated with a 9-Gy sublethal dose, were incubated with r-hGH before, after, or before and after irradiation. Treatment with GH resulted in increased cell survival, which reached its maximum at the concentration of 5 n<i>M</i>, with an EC<sub>50</sub> of 3.5 n<i>M</i>. Protective effects of GH on pituitary cells were more pronounced in cultures treated before and after irradiation. Similarly, beneficial effects of GH were observed on the secretory capacity of surviving cells. In fact, irradiated pituitary cells treated with GH secreted substantial amounts of GH, luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone and adrenocorticotropic hormone in response to specific releasing hormones. Such effects of GH were prevented in the presence of the specific GH receptor antagonists B2036 and G120K. Our results show that r-hGH exerts a specific protective effect on irradiated rat pituitary cells and suggest possible use of GH as an adjuvant agent for prevention of postirradiation hypopituitarism.
Estrogen Modulates α<sub>1</sub>/β-Adrenoceptor- Induced Signaling and Melatonin Production in Female Rat Pinealocytes
Authors: Hernández-Díaz Francisco J. , Sánchez Juan J. , Abreu Pedro , López-Coviella Ignacio , Tabares Lucía , Prieto Luis , Alonso Rafael 
Published: April 2003

Nocturnal rise in pineal melatonin output is due to the night-induced acceleration of noradrenergic transmission and α<sub>1</sub>- and β-adrenoceptor activation. In addition, in female animals, cyclic oscillations in circulating levels of sex steroid hormones are accompanied by changes in the rate of pineal melatonin secretion. To investigate whether estrogen directly affects pineal adrenoceptor responsiveness, pinealocytes from 21-day-old ovariectomized rats were exposed to physiological concentrations of 17β-estradiol (17β-E<sub>2</sub>) and treated with noradrenergic agonists. Direct exposure to 17β-E<sub>2</sub> reduced α<sub>1</sub>/β-adrenoceptor-induced stimulation of melatonin synthesis and release. This effect was mediated by an estrogen-dependent inhibition of both β-adrenoceptor-induced accumulation of cAMP and α<sub>1</sub>-adrenoceptor-induced phosphoinositide hydrolysis. Furthermore, estrogen reduced transient Ca<sup>2+</sup> signals elicited in single pinealocytes by α<sub>1</sub>-adrenoceptor activation or by potassium-induced depolarization. In the case of β-adrenoceptor responsiveness, neither forskolin- nor cholera toxin-induced accumulation of cAMP were affected by previous exposure to 17β-E<sub>2</sub>. This indicates that estrogen effects must be exerted upstream from adenylylcyclase activation, and independent of modifications in G protein expression, therefore suggesting changes in either adrenoceptor expression or receptor-effector coupling mechanisms. Since estrogen effects upon adrenoceptor responsiveness in pineal cells was not mimicked by 17β-E<sub>2</sub> coupled to bovine serum albumin and showed a latency of 48 h, this effect could be compatible with a genomic action mechanism. This is also consistent with the presence of two estrogen receptor proteins, α- and β-subtypes, in female rat pinealocytes under the present experimental conditions.
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 <i>L</i>-NAME (1 m<i>M</i>), 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 [<sup>14</sup>C]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.
Clinical Effects of <i>L</i>-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 <i>L</i>-threo-3,4-dihydroxyphenylserine (<i>L</i>-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 <i>L</i>-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 <i>L</i>-DOPS group compared with the placebo group. In particular, the improvement was more remarkable for the <i>L</i>-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 <i>L</i>-DOPS or concomitantly administered drugs, or without any treatment. These findings indicate that <i>L</i>-DOPS taken before hemodialysis prevents orthostatic hypotension in patients undergoing hemodialysis, and is also effective for the interdialytic symptoms related to orthostatic hypotension.
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

<i>Background/Aims: </i>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. <i>Methods:</i> 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. <i>Results: </i>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. <i>Conclusion: </i>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.
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.
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 L<sub>4–5</sub> 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.
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.
Dynamic Magnetic Resonance Imaging of the Levator palpebrae superioris Muscle
Authors: Ettl Armin , Daxer Albert , Priglinger Siegfried , Kramer Josef , Koornneef Leo 
Published: April 2003

The relationship between upper lid elevation (h) and shortening (s) of the levator palpebrae superioris muscle (LPS) has an influence on the dose-response relationship in ptosis surgery. In order to investigate the relationship between upper lid elevation and shortening of the LPS, parasagittal T<sub>1</sub>-weighted MR images of the orbit were obtained in healthy subjects with the eye in down- and upgaze. The position of the upper lid margin and the length of the LPS were measured in the images in down- and upgaze and the amount of h and s was determined. For a mean (± SD) vertical upper lid elevation of 15 ± 1 mm, the mean (± SD) shortening of the LPS muscle was 21 ± 3 mm (n = 4). The mean ratio of h:s was calculated to be 1:1.4, which means that the levator muscle must contract by 1.4 cm in order to achieve a lid elevation of 1 cm. Therefore, the force of the LPS which is necessary to lift the upper eyelid can be smaller than the lid-closing force. This strongly suggests a physiological mechanism which reduces the muscle force necessary for lifting the upper eyelid.
Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress
Authors: Andersson Madeleine , Sjöstrand Johan , Petersen Anne , Karlsson Jan-Olof 
Published: April 2003

The purpose of this study was to examine changes in calcium-dependent proteolytic activity in the lens epithelium from whole rabbit lenses exposed to long-term oxidative stress at near physiological levels. Rabbit lenses, incubated in 50 µ<i>M</i> H<sub>2</sub>O<sub>2</sub> for 1 or 24 h, were checked for clarity and morphological changes in the epithelium. Proteolytic activity was measured in the epithelium using a fluorogenic synthetic substrate; N-succinyl-Leu-Tyr-7-amino-4-methylcoumarin, both in the presence and the absence of calcium (1 m<i>M</i> Ca<sup>2+</sup> and 5 m<i>M</i> EDTA respectively). The effect on transparency and morphology of the epithelium following a 1-hour incubation in 100 µ<i>M</i> H<sub>2</sub>O<sub>2</sub> was also studied. Lenses incubated in 50 µ<i>M</i> H<sub>2</sub>O<sub>2</sub> were clear even after 24 h. After a 1-hour incubation in 50 µ<i>M</i> H<sub>2</sub>O<sub>2</sub> the epithelium of the exposed lens appeared normal. However, after 24 h the epithelium cells appeared swollen and microscopical examination showed extensive intracellular and subepithelial vacuolization. Incubation in 100 µ<i>M</i> H<sub>2</sub>O<sub>2</sub> for 1 h caused loss of transparency; vacuole formation, globulization of the superficial lens fibers and death of the epithelial cells. There was a 55% increase in calcium-dependent proteolytic activity after 1 h in 50 µ<i>M</i> H<sub>2</sub>O<sub>2</sub>, implying a role for the calcium-activated protease calpain in oxidatively induced cataract.
Regulatory Effects of Soluble Growth Factors on Choriocapillaris Endothelial Growth and Survival
Authors: Liu Xipu , Ye Xiaodan , Yanoff Myron , Li Weiye 
Published: April 2003

The effects of soluble growth factors on regulating the survival and growth of choriocapillaris endothelial (CCE) cells were investigated in vitro. CCE cells were cultured in a serum-free medium in the presence or absence of various soluble growth factors. Cell growth and cell viability were assessed by counting viable cells. Results showed that acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) significantly stimulated CCE growth in a dose-dependent manner. Platelet-derived growth factor BB (PDGF, 0.4–10 ng/ml), insulin-like growth factor (IGF, 0.4–10 ng/ml) or insulin (0.4–10 µg/ml) alone did not affect the growth of CCE cells. In the presence of insulin (10 µg/ml), however, PDGF stimulated CCE growth in a dose-dependent manner. By contrast, transforming growth factor β1 (TGF-β1) induced CCE death in the absence of other growth factors and inhibited the CCE growth induced by aFGF, bFGF or VEGF. When CCE cells had been cultured in media containing aFGF, bFGF, VEGF or the combination of PDGF and insulin for 48 h, withdrawal of aFGF, bFGF or VEGF, but not PDGF, from the media resulted in CCE death. The CCE death induced by either an introduction of TGF-β1 or withdrawal of aFGF, bFGF or VEGF was defined as apoptosis based on morphologic characteristics (condensation and fragmentation of nuclei, shrinkage of cells in size) and DNA fragmentation in multiples of approximately 180 base pairs. Phorbol 12-myristate 13-acetate (PMA, 2 or 5 n<i>M</i>) protected CCE cells against apoptosis induced by the introduction of TGF-β1 and withdrawal of aFGF, bFGF or VEGF, while H7 (50 µ<i>M</i>), but not HA1004 (50 µ<i>M</i>), abrogated the protective effect of PMA on CCE apoptosis. However, cycloheximide (0.1 µ<i>M</i>), a protein synthesis inhibitor, was only effective to protect CCE cells from apoptosis induced by aFGF, bFGF or VEGF withdrawal, but not that induced by the introduction of TGF-β1. Moreover, cycloheximide and a low concentration of PMA (2 n<i>M</i>) showed an additive effect on protecting CCE cells from apoptosis as the result of a growth factor withdrawal. These data may suggest that some growth factors, such as aFGF, bFGF, VEGF and TGF-β1, play a more critical role than the others, such as PDGF and IGF, in the regulation of CCE growth and survival. CCE apoptosis as a result of withdrawal of a survival factor or of receiving a death factor such as TGF-β1 may involve different mechanisms, which merits further study.