bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antisense Vasopressin Oligonucleotides: Uptake, Turnover, Distribution, Toxicity and Behavioral Effects
Authors: Meeker Rick , LeGrand Gordon , Ramirez Julio , Smith Tracy , Shih Ying‐Hsien 
Published: September 2006

AbstractThe uptake, turnover, distribution, toxicity and behavioral effects of antisense vasopressin oligonucleotides were investigated to define how these compounds interact with neural tissue to inhibit translation of a target mRNA. Both phosphorothioate modified and unmodified oligonucleotides are rapidly taken up by mammalian neural tissue. Turnover of the unmodified oligonucleotide was found to be fast (t1/2 < 1 h) relative to the phosphorothioate modified oligonucleotide (t1/2= 12 h). The phosphorothioate vasopressin antisense oligonucleotide suppressed vasopressin synthesis in vitro at concentrations below the toxic threshold of approximately 5 μM. Intracranial injections of phosphorothioate antisense oligonucleotide into the region of the SON in vivo, resulted in a small decrease in vasopressin mRNA and a compensatory drinking response within the first 24 h, consistent with a deficit in vasopressin translation with kinetics similar to those observed in vitro. Water intake returned to normal by the second day indicating relatively rapid clearance of the oligonucleotide and minimal side effects. Although the mechanisms of accumulation and details of the molecular interactions are still unknown, our observation of preferential uptake and/or retention of oligonucleotide within a subset of neurons in vitro suggests some process of selective targeting. Thus, low concentrations of oligonucleotides targeted to the untranslated 5′ end of vasopressin mRNA can be effective for the acute and reversible control of vasopressin synthesis in mammalian CNS with relatively rapid onset of behavioral effects and minimal side effects.
Glutaminyl‐Cyclase Expression in the Bovine/Porcine Hypothalamus and Pituitary
Authors: Böckers Tobias M. , Kreutz Michael R. , Pohl Thomas 
Published: September 2006

AbstractThe expression of the glutaminyl cyclase (QC), an enzyme responsible for the post‐translational modification of N‐terminal pyroglutamyl residues of neuropeptide precursors, was examined in bovine/porcine hypothalamic and pituitary tissue by means of immunocytochemistry and in situ hybridization. In the anterior pituitary a distinct pattern of QC immunoreactivity and mRNA expression was found associated exclusively with somatotrophs. In corticotrophs of the pars intermedia QC expression was undetectable, whereas a small portion of putative pars tuberalis cells in the rostra1 part of the pars distalis were heavily labelled. The neurointermediate lobe was devoid of signals for QC mRNA, but showed significant QC‐immunoreactivity on secretory granules of axonal nerve endings. Also nuclei of the hypothalamus were found to be positive for QC‐immunoreactivity. Intense labelling was observed in the nucleus supraopticus and nucleus paraventricularis. Staining of the nucleus periventricularis was found to be moderate, whereas no labelling of perikarya in the nucleus arcuatus, the preoptic area and the nucleus suprachiasmaticus was detectable. Moreover, varicose fibers stained positive for QC‐immunoreactivity and could be identified in the main transport route from the hypothalamus to the pars neuronalis (tractus hypothalamo hypophysialis). These results suggest that the enzyme is transported via the same routes as its substrate/product to the median eminence or the neural lobe. Furthermore, the mapping of the cellular QC distribution reveals a strikingly distinctive expression pattern, that should be useful for the identification of yet undiscovered places of peptide synthesis and processing.
Contribution of the Ventral Subiculum to Inhibitory Regulation of the Hypothalamo‐Pituitary‐Adrenocortical Axis
Authors: Herman James P. , Cullinan William E. , Morano Maria Ines , Akil Huda , Watson Stanley J. 
Published: September 2006

AbstractAnatomical studies indicate that the ventral subiculum is in a prime position to mediate hippocampal inhibition of the hypothalamo‐pituitary‐adrenocortical (HPA) axis. The present study evaluated this hypothesis by assessing HPA function following ibotenic acid lesion of the ventral subiculum region. Rats with lesions of the ventral subiculum (vSUB) or ventral hippocampus (vHIPPO) did not show changes in basal corticosterone (CORT) secretion at either circadian peak or nadir time points when compared to sham‐lesion rats (SHAM) or unoperated controls. However, rats with vSUB lesions exhibited a prolonged glucocorticoid stress response relative to all other groups. Baseline CRH mRNA levels were significantly increased in the medial parvocellular paraventricular nucleus (PVN) of the vSUB group relative to controls. CRH mRNA differences were particularly pronounced at caudal levels of the nucleus, suggesting topographic organization of vSUB interactions with PVN neurons. Notably, the vHIPPO group, which received large lesions of ventral CA1, CA3 and dentate gyrus without significant subicular damage, showed no change in stress‐induced CORT secretion, suggesting that the ventral subiculum proper is principally responsible for ventral hippocampal actions on the HPA stress response. No differences in medial parvocellular PVN AVP mRNA expression were seen in either the vSUB or vHIPPO groups. The results indicate a specific inhibitory action of the ventral subiculum on HPA activation. The increase in CRH biosynthesis and stress‐induced CORT secretion in the absence of changes in baseline CORT secretion or AVP mRNA expression suggests that the inhibitory actions of ventral subicular neurons affect the response capacity of the HPA axis.
Morphological Evidence for a Galanin‐Opiate Interaction in the Rat Mediobasal Hypothalamus
Authors: Horvath Tamas L. , Kalra Satya P. , Naftolin Frederick , Leranth Csaba 
Published: September 2006

AbstractIt is well established that hypothalamic galanin‐ and β‐endorphin‐containing circuits play important roles in the neuroendocrine regulation of pituitary hormone secretion and sexual behaviors, as well as in feeding. Recent experimental evidence suggests that an opiate‐galanin interaction may be involved in these neuroendocrine responses. In particular, galanin and β‐endorphin have been shown to stimulate prolactin release from the pituitary, and concurrently, evoke feeding in the rat. The present study was designed to elucidate the morphological component underlying these responses in the hypothalamus. Sections of the mediobasal hypothalamus of colchicine‐pretreated female rats were double immunostained for galanin and β‐endorphin. A dark blue nickel ammonium sulfate‐intensified diaminobenzidine reaction was used to visualize galanin profiles, while b‐endorphin neurons were labeled with a light brown diaminobenzidine reaction. Light microscopy revealed putative connections between galanin boutons and β‐endorphin cells. Electron microscopic examination showed that galanin boutons form axo‐somatic and axo‐dendritic synaptic connections with β‐endorphin neurons. The vast majority (89.6%) of the β‐endorphin‐immunoreactive neurons were found to be contacted by galanin‐immunopositive fibers in the hypothalamus. To determine the origin of the galanin fibers innervating this region, the arcuate nuclei of additional rats were isolated unilaterally using a Halász‐knife. After a ten day survival period, immunostaining was carried out for galanin. The relative surface occupied by galanin immunoreactive profiles on the ipsi‐ and contralateral sides were compared using an image analyzer. This analysis revealed that deafferentation of the arcuate nucleus did not decrease the density of galanin immunoreactive profiles on the isolated side of the arcuate nucleus compared to the control side, thus, indicating that the galanin boutons contacting β‐endorphin cells are most probably of local origin.These studies support the proposal that galanin‐evoked prolactin secretion and feeding behavior may, in part, be mediated by enhanced β‐endorphin release and raises the possibility that a hypothalamic galanin‐β‐endorphin axis may operate in the control of other pituitary hormones.
The 24‐hour Rhythms in Plasma Growth Hormone, Prolactin and Thyroid Stimulating Hormone: Effect of Sleep Deprivation
Authors: Sadamatsu Miyuki , Kato Nobumasa , Iida Hideharu , Takahashi Saburo , Sakaue Kyoko , Takahashi Kiyohisa , Hashida Seiichi , Ishikawa Eiji 
Published: September 2006

AbstractTwenty‐four hour secretory rhythms of growth hormone (GH), prolactin (PRL) and thyroid stimulating hormone (TSH) were investigated in 9 normal adult men by means of serial blood sampling at 30 min intervals. The profiles of pituitary hormones were compared in 6 subjects between in normal nocturnal sleep condition and in delayed sleep condition. Plasma GH was measured with use of highly sensitive enzyme immunoassay (EIA) recently developed. Plasma TSH was also evaluated by highly sensitive time‐resolved fluorometric immunoassay (TR‐FIA). Time series analysis of plasma GH and PRL was performed by auto‐ and cross‐ correlation and spectral analysis.The detection limit of EIA for GH was 0.3 pg/ml and all plasma GH levels were within the detectable range of this EIA. Cross‐correlation and spectral analysis suggested the presence of approximately 2–3 h rhythmicity of plasma GH. Plasma PRL appeared to have some 24‐hour rhythmicity besides its sleep‐dependent component. Sleep deprivation caused marked elevation of plasma TSH during night time. It is suggested that there appears two mechanisms regulating GH secretion: one has a sleep‐independent and ultradian rhythm and another has a sleep‐dependent rhythm.
Daily Melatonin Injections Induce Cytological Changes in Pars Tuberalis‐Specific Cells Similar to Short Photoperiod
Authors: Böckers T. M. , Niklowitz P. , Bockmann J. , Fauteck J.‐D. , Wittkowski W. , Kreutz M. R. 
Published: September 2006

AbstractHypophyseal pars tuberalis (PT)‐specific cells are known to exhibit remarkable seasonal changes in morphology especially in photoperiodic animals like the Djungarian hamster Phodopus sungorus. Their high density of melatonin‐receptors leads to the supposition that fluctuations in circulating melatonin levels are a crucial factor for the morphological alterations induced by photoperiodic signals. To prove this hypothesis the nocturnal elevation of melatonin in long photoperiods was prolonged by late afternoon administration of melatonin. We investigated whether this treatment induces cytological changes usually observable under short photoperiod. Electron microscopy revealed that in contrast to hamsters maintained in long photoperiods PT‐specific cells of hamsters injected with melatonin or those kept in short photoperiods appear inactive, containing a relatively high number of secretory granules, sparse endoplasmatic reticulum, irregularly outlined and invaginated cell nuclei and a high amount of glycogen. Furthermore immunoreactivity for the common α‐chain of glycoprotein hormones and β‐TSH was significantly weaker in hamsters kept in short photoperiods or daily injected with melatonin than untreated or vehicle injected controls in long photoperiod. These results demonstrate that an exogenous prolongation of the elevated nocturnal melatonin levels causes a similar morphological appearance of PT‐specific cells as observed in short photoperiods. It is tempting to speculate that the melatonin signal is a direct ‘Zeitgeber’ for the transduction of photoperiodic information to the secretory activity in this cell type.
Evidence that Melatonin Acts in the Pituitary Gland through a Dopamine‐independent Mechanism to Mediate Effects of Daylength on the Secretion of Prolactin in the Ram
Authors: Lincoln G. A. , Clarke I. J. 
Published: September 2006

AbstractA previous study provided evidence that melatonin acts in the pituitary gland to mediate the effects of daylength on the secretion of prolactin in sheep. This was based on the observation that hypothalamo‐pituitary disconnected (HPD) Soay rams showed normal patterns in the changes in the peripheral blood concentrations of prolactin in response to alterations in photoperiod (10‐fold higher concentrations under long than short days), and in response to exogenous melatonin (rapid decline following the administration of a constant‐release implant of melatonin). The purpose of this study was to establish whether dopamine (DA) might be involved in mediating the effects of melatonin on the secretion of prolactin. Groups of HPD (n = 7) and control Soay rams (n = 8) were treated with vehicle (control, 2.0 ml 0.1 M tartaric acid/saline sc), bromocriptine (DA agonist, 0.06 mg/kg sc) or sulpiride (DA antagonist, 0.6 mg/kg sc), and the acute prolactin responses were measured over the next 4 h. Treatments were carried out under short days (8L:16D, low prolactin), long days (16L:8D, high prolactin), and under long days in the presence of a constant‐release implant of melatonin (low prolactin). The prolactin response to TRH (1.25μg/kg iv) was also measured. Bromocriptine caused a decrease in the plasma concentrations of prolactin in both HPD and control rams under short and long days. Sulpiride had no effect in the HPD rams on any occasion, but caused a very marked increase in the plasma concentrations of prolactin in the control rams under short days, long days, and under long days + melatonin. TRH caused an acute increase in the plasma concentrations of prolactin in the HPD rams under both long and short days although the responses were notably reduced compared with the controls especially under long days + melatonin. Overall, the inhibitory response to the DA agonist in HPD rams indicates the presence of DA D2 receptors linked to functional lactotrophs in the isolated pituitary gland. However, the total lack of a response to the DA antagonist indicates the absence of endogenous DA mechanisms regulating the secretion of prolactin in the HPD rams. The conclusion is that melatonin acts directly on the pituitary gland to mediate effects of photoperiod through a DA‐independent mechanism.
Effects of Chronic Octreotide Treatment on GH Secretory Dynamics and Tumor Growth in Rats Bearing an Ectopic Somatotroph (GC) Tumor
Authors: Mounier Françoise , Bluet‐Pajot Marie Thérèse , Viollet Cécile , Bertherat Jérôme , Timsit José , Tannenbaum Gloria S. , Epelbaum Jacques 
Published: September 2006

AbstractThe effects of octreotide, a long‐acting somatostatin agonist selective of the sstr2/sstr3/sstr5 receptor subtypes, on ectopic GH secretion and tumor growth were investigated in Wistar‐Furth female rats implanted with GH secreting (GC) cells which express mostly somatostatin receptors of the sstr1 and sstr2 subtypes. Octreotide dose dependently inhibited thymidine incorporation (−57%) and GH secretion (−41%) from GC cells in culture. In vivo, 6 weeks after GC cell implantation, plasma GH, IGF‐1 and insulin levels were highly elevated. Cluster analysis of GH secretory dynamics revealed that GH secretion was less pulsatile in GC‐implanted than in control animals. Furthermore, in GC‐implanted animals, passive immunization either with SRIH or GHRH antisera did not affect GH plasma levels. Three weeks after GC cell implantation, when tumors became palpable, octreotide (1 μg/h/kg BW) or saline was infused constantly for three weeks by osmotic minipumps. In octreotide treated rats, GH, IGF‐1 and insulin levels were not different from sham‐implanted animals and tumors weight were reduced by 80%. High affinity somatostatin binding sites were found in equivalent amounts on tumors from octreotide‐treated or saline‐treated animals. These findings indicate that GH secretion in GC‐rats is mainly derived from the tumors and independent of hypothalamic control and that octreotide reduces both GH secretion and tumor growth. We conclude that the GC‐implanted rat represents a good animal model to test the antisecretory and antitrophic properties of somatostatin analogs in vivo.
Sodium Pentobarbitone and the Suppression of Luteinizing Hormone Pulses in the Female Rat: the Role of Hypothermia
Authors: Strutton Paul H. , Coen Clive W. 
Published: October 2006

AbstractThe role of hypothermia in the suppression of pulsatile luteinizing hormone (LH) release by the barbiturate sodium pentobarbitone has been investigated in ovariectomized rats. Each animal was fitted with an intraperitoneal miniature radio transmitter to monitor core temperature and with an indwelling intravenous and intraperitoneal catheter. During the 6‐h sampling period the animal's core temperature was recorded automatically every 5 min and a 25 μl blood sample was obtained concurrently using an automated system. After the initial 3 h of sampling either the drug or the vehicle was administered via the intraperitoneal cannula from outside the cage, thus ensuring minimal disturbance to the animal. Administration of sodium pentobarbitone (40 mg/kg) at an ambient temperature of 21°C resulted in a significant hypothermia throughout the 3‐h post‐injection period. During this period there was a significant reduction in mean LH concentration, and in the frequency and amplitude of the LH pulses. When the drug was administered at an ambient temperature of 35°C there was no reduction in core temperature and no significant change in the LH pulse parameters. Vehicle treatment was without significant effect on core temperature or on the LH pulse parameters when administered at an ambient temperature of either 21°C or 35°C. These results indicate that the effects of this barbiturate on the pulsatile release of LH are secondary to the induced hypothermia and suggest that hypothermia per se may be able to disrupt LH pulses. It is therefore imperative to reassess the significance of previous studies that have implicated particular neurotransmitter systems in the control of LH pulses; unrecognized hypothermic effects of the treatments may have been the primary cause of the pulse suppression, rather than a direct involvement of the neurotransmitter in question in the regulation of LH releasing hormone. The neurophysiological process by which the hypothermic state may inhibit LH pulses remains to be determined.
Contrasting interactions between ethylene and abscisic acid in Rumex species differing in submergence tolerance
Authors: Benschop Joris J. , Jackson Michael B. , Gühl Kerstin , Vreeburg Robert A. M. , Croker Stephen J. , Peeters Anton J. M. , Voesenek Laurentius A. C. J. 
Published: September 2006

SummaryComplete submergence of flooding‐tolerant Rumex palustris plants strongly stimulates petiole elongation. This escape response is initiated by the accumulation of ethylene inside the submerged tissue. In contrast, petioles of flooding‐intolerant Rumex acetosa do not increase their elongation rate under water even though ethylene also accumulates when they are submerged. Abscisic acid (ABA) was found to be a negative regulator of enhanced petiole growth in both species. In R. palustris, accumulated ethylene stimulated elongation by inhibiting biosynthesis of ABA via a reduction of RpNCED expression and enhancing degradation of ABA to phaseic acid. Externally applied ABA inhibited petiole elongation and prevented the upregulation of gibberellin A1 normally found in submerged R. palustris. In R. acetosa submergence did not stimulate petiole elongation nor did it depress levels of ABA. However, if ABA concentrations in R. acetosa were first artificially reduced, submergence (but not ethylene) was then able to enhance petiole elongation strongly. This result suggests that in Rumex a decrease in ABA is a prerequisite for ethylene and other stimuli to promote elongation.
Extended coagulation profiles of healthy baboons and of baboons rejecting GT‐KO pig heart grafts
Authors: Ezzelarab Mohamed , Cortese‐Hassett Andrea , Cooper David K. C. , Yazer Mark H. 
Published: October 2006

Abstract:  Introduction:  Derangements of coagulation, e.g. thrombotic microangiopathy (TM) and disseminated intravascular coagulation (DIC), limit the success of pig‐to‐baboon organ transplantation. Studies have investigated the coagulation profile in baboons post‐xenotransplantation (XTx), but an extended coagulation profile of healthy baboons pre‐XTx has not been reported.Methods:  Blood was drawn from nine healthy male baboons (approximate age 5 yr, mean weight 15 kg) that had not undergone any prior surgical or therapeutic procedures. An extended coagulation profile, consisting of markers of thrombin activation, fibrinolysis, endothelial activation, the protein C pathway, and overall reactive state, was investigated by a reference coagulation laboratory, using tests for human plasma. The mean value ± SD was calculated for 18 parameters (analytes); values outside of the mean ± 2 SD were excluded. Three baboons subsequently underwent transplantation with hearts from GT‐KO pigs, and received either no therapy (B24603), CVF (B25003), or CVF + leflunomide (B24903), and their extended coagulation parameters were followed.Results:  For 14 of the 18 analytes, the human reference range reflected the coagulation status of healthy baboons. Exceptions included thrombin/antithrombin complex and fibrinopeptide A, which were elevated compared with the human reference range, while plasminogen activity was lower. The human assay failed to detect baboon plasminogen activator inhibitor‐1. Immediately after GT‐KO pig heart transplantation, the untreated B24603 demonstrated a coagulation profile consistent with its postoperative clinical status; DIC was not apparent, and the heart was electively excised within 2.5 h. In B25003 and B24903, that rejected their grafts on days 8 and 12, respectively, the coagulation profile showed evidence of DIC, particularly in B24903, which was clinically coagulopathic by this time.Conclusions:  (i) The human reference range of extended coagulation parameters forms a basis for studies in baboons, with a few exceptions. (ii) Antibody‐mediated rejection of GT‐KO pig hearts in baboons can be associated with laboratory and clinical evidence of DIC.
Yield improvement for manufacture of α1‐proteinase inhibitor
Authors: Zimmerman T. P. 
Published: September 2006

Background and Objectives  The aim of this study was to increase the yield of active α1‐proteinase inhibitor (α1‐PI) from Cohn fraction IV‐1 paste during the manufacture of this therapeutic protein and to investigate the molecular mechanism for this yield increase.Materials and Methods  Dissolution experiments with IV‐1 paste investigated the impact of different variables on the yield of α1‐PI activity. Solutions of IV‐1 paste prepared under different conditions were assayed for evidence of protease activity by Western blots of α1‐PI following SDS‐PAGE, by azocaseinolytic and amidolytic (S‐2288) assays, and by zymography, and for the extent of α1‐PI oligomerization by Western blots following nondenaturing PAGE.Results  Minor modification of the manufacturing process by combining dissolution of IV‐1 paste with the subsequent pH adjustment (to 9·25–9·50 with NaOH), achieved by addition of a standard concentration of NaOH to the 10‐mm Tris base dissolvent for IV‐1 paste, was found to give a highly reproducible 9·4 ± 0·9% increase in yield of active α1‐PI. Solutions of IV‐1 paste prepared with this combined dissolvent contained reduced amounts of low molecular weight fragments of α1‐PI, reduced protease activity, and reduced amounts of oligomers of α1‐PI. Addition of the protease inhibitor leupeptin to the 10‐mm Tris base dissolvent for IV‐1 paste also caused an increase in the yield of α1‐PI activity.Conclusions  Dissolution of IV‐1 paste in a more alkaline medium gave a significant increase in the yield of active α1‐PI. This yield increase was attributed to a reduction both in protease activity and in the extent of oligomerization of α1‐PI.
Diagnostik von Mykosen des Auges und seiner Adnexe
Authors: Behrens‐Baumann W. , Müller J. 
Published: September 2006

ZusammenfassungDas Spektrum der Mykosen des Auges und seiner Adnexe wird im klinischen Bild und im labordiagnostischen Vorgehen abgehandelt. Die einzelnen Lokalisationsformen unterscheiden sich in ihrer Symptomatik, in ihren Risikofaktoren und im Erregerspektrum.