bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoid Effects on the Diurnal Rhythm of Circulating Leptin Levels
Authors: Nishiyama Mitsuru , Makino Shinya , Suemaru Shuso , Nanamiya Wakako , Asaba Koichi , Kaneda Tadafumi , Mimoto Tomoko , Nishioka Tatsuya , Takao Toshihiro , Hashimoto Kozo 
Published: April 2003

It is known that circulating leptin shows diurnal variation with a nocturnal rise; however, the mechanisms generating this rhythm have not been fully elucidated. Glucocorticoids are a potent stimulator of leptin secretion, and there is a reciprocal relationship between circulating leptin and glucocorticoid levels. We hypothesized that glucocorticoids could modulate the diurnal rhythm of circulating leptin. We therefore explored the diurnal variation of leptin under situations in which subjects showed no or some shift of glucocorticoid diurnal rhythm, such as prednisolone-administered humans, and adrenalectomized and corticosterone-replaced (ADX+B) rats. The peak level of plasma cortisol immunoreactivity was shifted from early morning to noon by prednisolone administration. The nocturnal increment of plasma leptin in prednisolone-administered patients (71.2 ± 14.2% from 08:00 h value) was significantly greater than that in normal volunteers (12.2 ± 7.5% from 08:00 h value), but the timing of nadir and the peak of plasma leptin was not shifted. In normal rats, the plasma concentration of leptin showed the diurnal rhythm with the bottom at 16:00 h and the top between midnight and early morning. The amplitude of leptin diurnal rhythm was significantly reduced in ADX+B rats (08:00 h: 3.0 ± 0.2, 16:00 h: 2.7 ± 0.2, 00:00 h; 3.7 ± 0.2 ng/ml) compared with sham operated rats (08:00 h: 3.0 ± 0.2, 16:00 h 2.2 ± 0.2, 00:00 h: 4.7 ± 0.4 ng/ml); but ADX+B rats still retained similar timing of nadir and the peak of plasma leptin as observed in sham rats. These results indicate that glucocorticoids enhance the amplitude of leptin diurnal rhythm, and are consistent with previous findings showing that glucocorticoids increase leptin secretion. Glucocorticoids appear to play modulatory, but not essential roles in generating leptin diurnal rhythm.
Evaluation of Cutaneous Modifications in Seventy-Seven Growth Hormone-Deficient Children
Authors: Conte Françoise , Diridollou Stéphane , Jouret Béatrice , Turlier Virginie , Charveron Marie , Gall Yvon , Rochiccioli Pierre , Bieth Eric , Tauber Maïthé 
Published: April 2003

Cutaneous parameters such as dermal thickness, stiffness, elasticity, skin surface lipid and hydration were evaluated using noninvasive methods in 77 growth hormone-deficient (GHD) children before replacement therapy and in 70 non-GHD children. We showed that in GHD children, dermis was <i>thinner</i> (0.70 ± 0.10 vs. 0.80 ± 0.10 mm, p < 0.0001 for prepubertal children and 0.81 ± 0.10 vs. 0.94 ± 0.11 mm, p < 0.0001 for pubertal children), <i>stiffer</i> (178.5 ± 57.3 vs. 113.09 ± 37 kPa, p < 0.0001 for prepubertal children and 172.5 ± 61.7 vs. 117.3 ± 42.5 kPa for pubertal children, p < 0.001) and <i>less elastic</i> (0.44 ± 0.09 vs. 0.39 ± 0.06 (nonelasticity index), p < 0.01 for prepubertal children and 0.39 ± 0.05 vs. 0.33 ± 0.04, p < 0.001 for pubertal children) compared to controls. Fourteen GHD children were re-evaluated after 1 year of GH treatment: dermal thickness and skin stiffness were significantly improved (p < 0.001 and p < 0.05 respectively) while elasticity was not modified. During the same period, 11 controls did not show any significant cutaneous modification. IGF-1 values, but not IGFBP-3 values, correlated positively with dermal thickness in GHD children, before and after 1 year of GH treatment. To conclude, GHD children exhibited specific cutaneous modifications. In a subset of GHD children, we showed that these modifications were influenced by GH treatment. More extensive studies are needed to see if these changes correlated with other GH effects.
Neonatal Leukemoid Reaction and Early Development of Bronchopulmonary Dysplasia in a Very Low-Birth-Weight Infant
Authors: Zanardo Vincenzo , Magarotto Mariella , Rosolen Angelo 
Published: April 2003

The factors controlling the recruitment of inflammatory cells and the activation of the cytokine cascade in low-birth-weight premature infants have been implicated in the sequence of multiorgan inflammatory diseases, including the chronic lung disease of prematurity, bronchopulmonary dysplasia. This article describes a 982-gram, 25 (+2 days) weeks’ gestation male infant, who had a leukemoid reaction throughout the first week of life, followed by early development of bronchopulmonary dysplasia.
Signalling Pathways Activated by 5-HT<sub>1B</sub>/5-HT<sub>1D</sub> Receptors in Native Smooth Muscle and Primary Cultures of Rabbit Renal Artery Smooth Muscle Cells
Authors: Hinton J.M. , Hill P.B. , Jeremy J.Y. , Garland C.J. 
Published: April 2003

The potential of primary cultures of rabbit renal artery vascular smooth muscle cells (VSMCs) was assessed as a means to investigate the signalling pathways linked to 5-hydroxytryptamine (5-HT) 5-HT<sub>1B</sub>/5-HT<sub>1D</sub> receptors in native arteries. In renal artery segments denuded of endothelium, incubated with ketanserin and prazosin (each 1 µ<i>M</i>), and prestimulated with 20 m<i>M</i> K<sup>+</sup> Krebs buffer, 5-HT and CP 93,129, a 5-HT<sub>1B</sub> receptor agonist, evoked concentration-dependent contractions. GR 127935, a 5-HT<sub>1B</sub>/5-HT<sub>1D</sub> receptor antagonist, significantly antagonised 5-HT-evoked contractions at nanomolar concentrations. Reverse transcription polymerase chain reaction (RT-PCR) of mRNA from smooth muscle cells from the isolated renal artery and from primary cultures of VSMCs from the same artery expressed mRNA transcripts for the 5-HT<sub>1B</sub> receptor and the 5-HT<sub>1D</sub> receptor in both preparations. The sequence of the PCR fragments corresponded to the known sequence for these receptors. Application of 5-HT evoked a concentration-dependent, pertussis toxin (PTx)-sensitive reduction in cyclic AMP in both cultured cells and intact artery (cyclic AMP concentration reduced by 65.53 ± 3.33 and 52.65 ± 5.34% from basal with 10 µ<i>M</i> 5-HT, respectively). The effect of 10 µ<i>M</i> 5-HT on cAMP was increased in the presence of 20 m<i>M</i> K<sup>+</sup> (reduced by 82.50 ± 2.50 and 87.54 ± 3.97%, respectively). In intact arteries, contraction through 5-HT<sub>1B</sub>/5-HT<sub>1D</sub> receptors was significantly attenuated by inhibitors of phosphatidylinositol 3-kinase (wortmannin) and activated mitogen-activated protein kinase (MAPK), MEK (U01296). In the cultured VSMCs, activated MAPK was identified by immunocytochemistry and immunoblotting after stimulation with 5-HT, but only if 20 m<i>M</i> K<sup>+</sup> was present at the onset of stimulation. These data provide the first direct evidence that 5-HT<sub>1B</sub>/5-HT<sub>1B</sub> receptors are linked to the activation of MAPK and indicate that primary cultures of renal VSMCs could provide a model system to study further the signalling pathways linked to these receptors.
Diadenosine Polyphosphates Are Largely Ineffective as Agonists at Natively Expressed P2Y<sub>1</sub> and P2Y<sub>2</sub> Receptors on Cultured Human Saphenous Vein Endothelial Cells
Authors: Conant Alan R. , Fisher Michael J. , McLennan Alexander G. , Simpson Alec W.M. 
Published: April 2003

The diadenosine polyphosphates are a group of long-lasting compounds, released into the bloodstream by platelet degranulation. They mediate endothelium-dependent vasodilatation in several animal vascular systems via P2Y receptors coupled to increases in cytoplasmic calcium ([Ca<sup>2+</sup>]<sub>c</sub>). However, there is little evidence of diadenosine-mediated vasodilatation in the human vasculature, and a direct interaction with natively expressed P2Y receptors on human endothelium has not been demonstrated. We have therefore studied the effects of diadenosines on primary cultures of human saphenous vein endothelial cells (HSVECs) and related this to the expression of P2Y receptors. HSVECs were loaded with the calcium-sensitive dye fura-2, and nucleotide-stimulated [Ca<sup>2+</sup>]<sub>c</sub> responses were recorded. HSVECs responded to 10 µ<i>M</i> UTP, ATP and 2-methylthio-ATP but not to UDP. Consistent with the recorded [Ca<sup>2+</sup>]<sub>c</sub> responses, RT-PCR analysis of HSVEC RNA amplified specific products for the P2Y<sub>1</sub> and P2Y<sub>2</sub> receptors but not the P2Y<sub>4</sub> and P2Y<sub>6</sub> receptors. HSVECs responded to Ap<sub>3</sub>A with a rise in [Ca<sup>2+</sup>]<sub>c</sub>, but none of the other diadenosines tested elicited a response. Therefore natively expressed human P2Y<sub>1</sub> and P2Y<sub>2</sub> receptors are insensitive to diadenosine polyphosphates with the exception of Ap<sub>3</sub>A. We would therefore predict that the diadenosine polyphosphates have only a limited vasodilatory role in human saphenous veins.
Evaluation of β-Galactosidase Activity in Tissue in the Presence of Blood
Authors: Pelisek Jaroslav , Armeanu Sorin , Nikol Sigrid 
Published: April 2003

The reporter gene for β-galactosidase is frequently used to determine the efficiency of gene transfer in arteries. However, blood is often present in arterial explants and may compromise the results by the presence of hemoglobin. The light absorption of hemoglobin is similar to the absorption of several colorimetric products of the commonly used β-galactosidase substrates, including <i>o</i>-nitrophenyl-β-<i>D</i>-galactopyranoside (ONPG) and chlorophenol red galactopyranoside (CPRG). This may result in false-positive measurements of β-galactosidase enzyme activity. The aim of this investigation was to determine the most appropriate method for quantification of β-galactosidase activity in the presence of blood. Colorimetric substrates (ONPG, CPRG) or the chemiluminescent Galacton-Plus substrate were used, and light absorption was measured at different concentrations of erythrocyte extract. Among the β-galactosidase substrates tested, CPRG was the most appropriate, allowing detection of enzyme activity at concentrations as low as 0.05 mU, independent of blood contamination. Addition of reducer stabilized enzyme activity for at least 5 h. Endogenous β-galactosidase activity was evaluated and used to correct results. CPRG substrate, in combination with the reducer agent mercaptoethanol, was found to be the optimal reagent for quantifying β-galactosidase activity in the presence of blood after nonviral in vivo reporter gene transfection, even with a relatively low transfer efficiency.
A Prospective Randomized Study Comparing Nifedipine versus Ritodrine for the Suppression of Preterm Labour
Authors: Al-Qattan Fawzia , Omu Alexander E. , Labeeb Najwa 
Published: April 2003

Nifedipine is a dihydropyridine and a calcium channel blocker during the second phase of the action potential of uterine smooth muscle cells, and ritodrine is a β-sympathomimetic. <i>Objective of Study: </i>To compare the efficacy and side-effects of oral nifedipine to ritodrine in the inhibition of preterm labour. <i>Methodology: </i>Sixty parturients admitted to the Maternity Hospital with preterm labour who fulfilled the inclusion criteria were randomized into two equal therapy groups: (a) oral nifedipine (n = 30) and (b) intravenous ritodrine (n = 30). During the period, the parturients were under continuous monitoring of fetal well-being, maternal uterine contractions, blood pressure, and pulse and respiratory rates. Both groups were given dexamethasone and followed up through delivery and the early neonatal period. <i>Results: </i>The incidence of preterm deliveries during the study period was 6.5%. Ritodrine had a quicker onset of inhibition of uterine contractions, especially between 20 and 40 min after initiation of tocolytic therapy (p < 0.04). Labour was delayed on the average for 40 h in the nifedipine group compared to 24 h in the ritodrine group (p < 0.05). Eighteen patients (60%) in the nifedipine group had cessation for more than 48 h compared to 7 (30.4%) in the ritodrine group (p < 0.05). Nifedipine inhibited uterine contractions for more than 7 days in more patients than ritodrine (13 versus 5, p < 0.05). Ten patients in the nifedipine group went beyond 36 weeks of gestation compared to 4 in the ritodrine group (p < 0.03). In 5 (17.9%) of the ritodrine group compared to none in the nifedipine group, treatment was abandoned because of severe side-effects of nausea (11 versus 2, p < 0.01) and palpitations (16 versus 3, p < 0.004). There were no significant differences in the Apgar scores and neonatal morbidity. More infants in the ritodrine group (17, 73.9%) than in the nifedipine group (14, 46.1%, p < 0.05) were admitted to the neonatal unit. <i>Conclusion: </i>Nifedipine is recommended for aborting preterm contractions because it has fewer side-effects, superior efficacy and greater ease of administration than intravenous ritodrine.
Quantitation and Regulation of Pyroglutamyl Peptidase II Messenger RNA Levels in Rat Tissues and GH3 Cells
Authors: Lin Jun , Wilk Sherwin 
Published: April 2003

The distribution of the mRNA of the specific thyrotropin-releasing-hormone (TRH)-degrading enzyme pyroglutamyl peptidase II (EC 3.4.19.6) in rat tissues and brain regions and its regulation in rat tissues and in GH3 cells was studied by a reliable and quantitative solution hybridization ribonuclease protection assay. The distribution of pyroglutamyl peptidase II mRNA levels was uneven with the highest level of mRNA found in brain. Within brain the distribution of pyroglutamyl peptidase II mRNA was heterogeneous. A single dose of T<sub>3</sub> markedly increased the level of pyroglutamyl peptidase II mRNA in the pituitary (p < 0.01) and in the liver (p < 0.05). In GH3 cells, exposure to T<sub>3</sub> at concentrations from 10<sup>–10</sup> to 10<sup>–6</sup><i>M</i> for time periods of 2–24 h, did not change pyroglutamyl peptidase II mRNA levels. Acute administration of TRH to rats had no effect on pyroglutamyl peptidase II mRNA levels. By contrast, TRH down-regulated pyroglutamyl peptidase II mRNA in GH3 cells. A similar effect was produced in GH3 cells by activators of protein kinase C. These studies reveal fundamental differences in the mechanism of regulation of pyroglutamyl peptidase II mRNA in pituitary and in GH3 cells. Elevation of pyroglutamyl peptidase II mRNA in liver by T<sub>3</sub> suggests that this organ is the source of the enzyme in serum.
Absence of an Inhibitory Vasopressinergic Tone on LH Release in Pubertal Male Rhesus Macaques
Authors: Lado-Abeal Joaquin , Norman Reid L. 
Published: April 2003

During puberty, primates begin to secrete LH, and presumably GnRH, at night and then eventually throughout the day as they mature. We examined the role of vasopressin, a putative inhibitor of the GnRH pulse generator, on LH secretion in pubertal male macaques both during the day when the GnRH pulse generator was not active and during the night when pulsatile LH secretion was observed. As has been found in other primates, LH and testosterone levels were low during the day and elevated at night. A potent vasopressin receptor antagonist (VPa) was administered during the middle 5 h of a 15-hour daytime or nighttime blood collection period to determine the effects on LH, testosterone and cortisol secretion. Both during the day and night, cortisol secretion was elevated during VPa infusion, suggesting that this V1a receptor antagonist has agonist activity on the V1b receptor in the pituitary involved in vasopressin-stimulated corticotropin release. Mean LH levels during VPa infusion were not different from the control period for that group during the day when LH secretion was absent. Mean LH levels were significantly higher (p < 0.05) than pre-VPa LH levels at night when pulsatile LH secretion was observed. However, LH levels at night during VPa were not higher than levels in untreated animals at the same time. The results of these studies demonstrate that LH and testosterone profiles are similar to those observed in human males during the pubertal transition and suggest that the absence of daytime gonadotropin release during puberty is not due to inhibitory vasopressinergic tone on the GnRH pulse generator.
Evidence for a Leptin-Neuropeptide Y Axis for the Regulation of Growth Hormone Secretion in the Rat
Authors: Vuagnat Béatrice A.M. , Pierroz Dominique D. , Lalaoui Meriem , Englaro Piera , Pralong François P. , Blum Werner F. , Aubert Michel L. 
Published: April 2003

The obese gene (OB) product, leptin, has been shown to exert control on metabolic processes such as food intake and body weight homeostasis, possibly through a neuropeptide Y (NPY) neurotransmission. More recently, leptin has been shown to control several neuroendocrine axes, modulating pituitary hormone secretions in function of metabolic conditions. Since in the rat growth hormone (GH) secretion is dependent upon prevailing metabolic conditions, and NPY has been shown to be implicated in the feedback mechanisms of this hormone, we reasoned that leptin could also exert control over GH secretion and we examined this hypothesis in male rats submitted to a 3-day fast. Circulating leptin concentrations measured by RIA abruptly fell to low values after 24 h of fasting and remained low thereafter. Upon refeeding, leptin secretion regularly increased. As shown by others, pulsatile GH secretion had disappeared after 3 days of fasting. Centrally administered leptin (10 µg/day, i.c.v. infusion initiated at the beginning of the fasting period) totally prevented the disappearance of pulsatile GH secretion. No leak of centrally administered leptin to the general circulation was observed. Infusing the same amount of leptin intracerebroventricularly to rats receiving ad libitum feeding produced a severe reduction in food intake but maintained a normal GH secretory pattern. In contrast, pair-fed rats, submitted to the same food restriction, exhibited a marked reduction in GH secretion. Hypothalamic NPY gene expression, estimated by Northern blot analysis, was significantly increased in fasting rats, and decreased in leptin-treated, fasting rats. In rats receiving ad libitum feeding, leptin treatment reduced NPY gene expression, consistent with the observed reduction in food intake, whereas pair-fed animals logically exhibited increased NPY gene expression. In both situations with reduced feeding, normal GH secretion was seen in leptin-treated animals exhibiting low NPY gene expression, whereas decreased or abolished GH secretion was seen in animals not receiving leptin and exhibiting increased NPY mRNA levels. Interestingly, despite maintenance of normal GH secretion in leptin-treated, fasting rats, plasma IGF-I levels were low, as in vehicle-treated rats. Indeed, hepatic gene expression for both GH receptor and IGF-I was markedly reduced by fasting, and no correction was seen with leptin treatment. In summary, the regulation of GH secretion, at least the changes linked with malnutrition, appears to be dependent upon a leptin signal, perceived centrally, possibly related to circulating levels of this new hormone. The present data suggest that leptin can rescue normal pulsatile GH secretion by preventing the documented inhibitory action of NPY on GH secretion.
Role of Glucocorticoids in the Modulation of Corticotropin-Releasing Hormone mRNA Level by the Endogenous Benzodiazepine Receptor Ligand Octadecaneuropeptide in Rat Brain
Authors: Givalois Laurent , Li Songyun , Pelletier Georges 
Published: April 2003

We have recently demonstrated that the endozepine octadecaneuropeptide (ODN) exerts an inhibitory influence on corticotropin-releasing hormone (CRH) mRNA expression. The effect is mediated by GABA<sub>A</sub> receptors and is reversed by adrenalectomy. In order to investigate the involvement of peripheral steroids and more particularly of glucocorticoids in the ODN modulation of CRH mRNA expression, we have evaluated, in adrenalectomized and castrated male rats (ADX/CX), the effect of dexamethasone (DEX) pretreatment on CRH mRNA expression induced by central injection of ODN. Variations in the CRH mRNA expression in the hypothalamic paraventricular nucleus have been studied using quantitative in situ hybridization. The intracerebroventricular injection of ODN (4 µg/kg), as previously reported, induced a significant inhibition of CRH mRNA expression in sham-operated rats (–33%). This inhibition was reversed in ADX/CX male rats (+65% vs. sham vehicle-injected rats and +20% vs. ADX/CX vehicle-injected rats). Pretreatment with DEX (5 mg/kg) during 4 days induced in ADX/CX rats a decrease of 22% (vs. ADX/CX vehicle-injected rats) in the CRH mRNA signal, which became comparable to that observed in sham vehicle-injected rats. Pretreatment of ADX/CX animals with DEX prevented the ODN-induced increase in CRH mRNA expression, inducing rather a 16 and 30% inhibition when compared to vehicle- and ODN-injected ADX/CX rats, respectively. Moreover the CRH mRNA levels observed in ODN-injected ADC/CX rats were higher than those observed in sham vehicle- and sham ODN-injected rats (+16% vs. sham vehicle-injected rats and +63% vs. sham ODN-injected rats). These results indicate that dexamethasone treatment in ADX/CX rats can restore mRNA levels to those observed in sham-operated animals but not the inhibiting effect induced by ODN. Together with previous findings, these results suggest that adrenal and/or gonadal factor(s) other than glucocorticoids are involved in ODN modulation of the HPA axis.
Effects of Amylin and Salmon Calcitonin on β-Endorphin-Induced Growth Hormone and Prolactin Secretion in the Rat
Authors: Pagani Francesca , Netti Carmela , Guidobono Francesca , Lattuada Norma , Ticozzi Chiara , Sibilia Valeria 
Published: April 2003

In this study we examined the possible interplay of amylin (AMY) and salmon calcitonin (sCT) in the central control of growth hormone (GH) and prolactin (PRL) secretion in male rats. For this purpose we first compared effects of central intracerebroventricular (i.c.v.) admininstration of various doses of AMY (2.5–2,500 ng/rat) and sCT (2.2–220 ng/rat) on β-endorphin (β-END, 0.5 µg/rat)-induced GH and PRL secretion. AMY and sCT dose-dependently inhibited β-END-induced GH secretion, whereas only sCT was able to inhibit β-END-induced PRL secretion. To examine whether the GH inhibitory effect of AMY was due to the possible cross-reactivity of AMY and sCT on the same receptors in the CNS, we pretreated some rats with the AMY antagonist (AMY<sub>8–37</sub>, 2.5 µg/rat, i.c.v.). AMY<sub>8–37</sub> significantly enhanced the GH-stimulatory action of β-END. AMY<sub>8–37</sub>, administered prior to AMY and sCT, significantly removed the inhibitory effect of both AMY and sCT on β-END-induced GH release, suggesting that both peptides mediate their response on GH through a common receptor. In vitro competition binding studies on rat hypothalamic membranes have shown that both AMY and sCT compete with [<sup>125</sup>I]rAMY binding with half inhibition (IC<sub>50</sub>) values of 3.6 × 10<sup>–11</sup> and 1.6 × 10<sup>–10</sup> <i>M</i>, respectively. Binding of [<sup>125</sup>I]sCT was inhibited by sCT with an IC<sub>50</sub> of 1.09 × 10<sup>–10</sup><i>M</i> and to a lesser extent by AMY with an IC<sub>50</sub> of 1.3 × 10<sup>–6</sup> <i>M</i>. Thus it is possible that the two peptides recognize a common hypothalamic receptor but with different affinities (sCT > AMY). Overall these data indicate that AMY behaves as a mimic of sCT in the central control of GH secretion. The failure of AMY, at variance with sCT, to modify the PRL-releasing activity of β-END indicates that different receptor subtypes for sCT are involved in the endocrine effects of sCT and only those mediating the modulatory action of GH respond to AMY.