bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of the islet nitric oxide system with L‐arginine‐induced secretion of insulin and glucagon in mice
Authors: Åkesson Björn , Mosén Henrik , Panagiotidis Georgios , Lundquist Ingmar 
Published: July 2012

Several recent in vitro studies have suggested that production of nitric oxide (NO) from the islet NO system may have an important regulatory influence on the secretion of insulin and glucagon. In the present paper we have investigated, mainly with an in vivo approach, the influence and specificity of the NO synthase (NOS) blocker NG‐nitro‐L‐arginine methyl ester (L‐NAME) on L‐arginine‐induced secretion of insulin and glucagon.
In freely fed mice, L‐NAME pretreatment (1.2 mmol kg−1) influenced the dynamics of insulin and glucagon release following an equimolar dose of L‐arginine, the specific substrate for NOS activity, in that the NOS inhibitor enhanced the insulin response but suppressed the glucagon responses. This was reflected in a large decrease in the plasma glucose levels of the L‐NAME pretreated animals.
L‐NAME pretreatment did not influence the insulin and glucagon secretory responses to the L‐arginine‐enantiomer D‐arginine, which cannot serve as a substrate for NOS activity.
Replacing L‐NAME pretreatment by pretreatment with D‐arginine or L‐arginine itself, which both carry the same cationic charge and are devoid of NOS inhibitory properties, did not mimic the effects of L‐NAME on L‐arginine‐induced hormone release.
Fasting the animals for 24 h totally abolished the L‐NAME‐induced potentiation of L‐arginine stimulated insulin release suggesting that the sensitivity of the β‐cell secretory machinery to NO‐production is greatly changed in the fasting state. However, the L‐NAME‐induced suppression of L‐arginine stimulated glucagon release was unaffected by starvation.
In isolated islets from freely fed mice, L‐arginine (5 mM) stimulated insulin release was greatly enhanced and glucagon release markedly suppressed by the presence of the NOS inhibitor L‐NAME in the incubation medium. These effects were abolished in isolated islets taken from 24 h fasted mice.
Our present results, which showed that the NOS inhibitor L‐NAME markedly enhances insulin release but suppresses glucagon release induced by L‐arginine in the intact animal, give strong support to our previous hypothesis that the islet NO system is a negative modulator of insulin secretion and a positive modulator of glucagon secretion. Additionally, we observed that the importance of the β‐cell NO‐production for secretory mechanisms, as evaluated by the effect of L‐NAME on L‐arginine‐induced insulin release, was greatly changed after starvation, an effect less prominent with regard to glucagon release.
Stereoselective recognition of the enantiomers of phenglutarimide and of six related compounds by four muscarinic receptor subtypes
Authors: Waelbroeck M. , Lazareno S. , Pfaff O. , Friebe T. , Tastenoy M. , Mutschler E. , Lambrecht G. 
Published: July 2012

We have compared the binding properties of the enantiomers of phenglutarimide (1) and of six related compounds to M1 receptors in NB‐OK‐1 cells, M2 receptors in rat heart, M3 receptors in rat pancreas and the M4 receptors of rat striatum, with their functional (antimuscarinic) properties in rabbit vas deferens (Mj/M4‐like), guinea‐pig atria (M2) and guinea‐pig ileum (M3) receptors. The binding properties of the enantiomers of three of the compounds were also measured on cloned human ml‐m4 receptors expressed by CHO cells, using [3H]‐N‐methylscopolamine ([3H]‐NMS) as radioligand.
The high affinity enantiomers behaved as competitive antagonists in binding and pharmacological studies. (S)‐phenglutarimide (pKiM1 = 9.0/9.3) and (R)‐thienglutarimide (pKiM1 = 8.6/9.2) recognized selectively the native M1 > M4 > M3 > M2 receptors in tissues as well as the respective cloned receptors.
The pA2 values at the inhibitory heteroreceptors in the rabbit vas deferens, and at the guinea‐pig atria and ileum for the seven more potent enantiomers were compatible with the previous classification of these receptors as M1/M4‐like, M2 and M3, respectively.
Replacement of the phenyl by a thienyl ring or of the diethylamino by a piperidino group in the phenglutarimide molecule did not affect markedly the potencies of the high affinity enantiomer. In contrast, replacement of the phenyl by a cyclohexyl ring decreased 20 fold the active enantiomers potency. Methylation of the piperidine‐2,6‐dione nitrogen also reduced markedly the eutomers' affinities, more on the M1 than on the other subtypes.
The selectivity profiles (recognition of four receptor subtypes) of six of the seven less active enantiomers were different from the corresponding more active enantiomers selectivity profiles, suggesting that the preparations used in this study were pure. However, we cannot not exclude the hypothesis that the batch of (S)‐thienglutarimide used in this study was contaminated by less than 0.02% of the eutomer.
In contrast with the eutomer binding site, replacement of the phenyl ring by a thienyl or cyclohexyl ring did not affect binding of the low affinity enantiomers to the muscarinic receptor or the [3H]‐NMS‐receptor complex. The replacement of the diethylamino group by a piperidine ring, and N‐methylation of the piperidine‐2,6 dione moiety increased slightly these enantiomers' potencies.
The muscarinic receptors were extremely stereoselective, and had up to 20 000 fold lower affinity for the less active enantiomers. However, the stereochemical requirements of the muscarinic receptor subtypes were different for the enantiomers of compounds 1–7, being most stringent at M1 receptors.
The weaker enantiomers behaved as competitive antagonists in pharmacological studies, at least in the concentration‐range investigated.
Influence of authentic nitric oxide on basal cytosolic [Ca2+] and Ca2+ release from internal stores in human platelets
Authors: Sang Kim‐Hanh Le Quan , Lantoine Frédérique , Devynck Marie‐Aude 
Published: July 2012

Nitric oxide (NO) donors inhibit platelet function and Ca2+ mobilization evoked by different agonists. This led us to investigate the direct effects of authentic NO on basal cytosolic Ca2+ concentration ([Ca2+]i) and on Ca2+ mobilization induced by thrombin or by two inhibitors of intracellular Ca2+‐ATPases, thapsigargin and 2,5‐di‐(t‐butyl)‐l,4‐benzohydroquinone (t‐BuBHQ).
Cytosolic Ca2+ concentration was evaluated with Fura‐2, in the absence of Ca2+ influx. Addition of 5 μm NO increased by 48% the basal cytosolic [Ca2+] of resting human platelets whereas a lower concentration (0.1 μm) did not induce significant modifications. This NO‐induced Ca2+ increase was inversely correlated with the basal level of cytosolic [Ca2+].
NO pretreatment for 30 to 120 s decreased by 42 to 57% the transient [Ca2+]i peak evoked by 0.10 u ml−1 thrombin and strongly attenuated the initial rate of [Ca2+]i rise induced by 1 μm thapsigargin or by 20 μm t‐BuBHQ. The two components of the thapsigargin response, the Ca2+ release due to inhibition of Ca2+ pumps and the thromboxane A2‐dependent self‐amplification mechanism, were inhibited by NO. The observation that a subsequent stimulation was still capable of eliciting Ca2+ release suggests the presence of NO‐insensitive Ca2+ stores.
These findings indicate that nitric oxide can modulate basal cytosolic [Ca2+] in unstimulated human platelets and decrease the Ca2+ mobilization from NO‐sensitive internal stores evoked by stimulation of receptors or by Ca2+‐ATPase inhibitors. This underlines the important role of nitric oxide in the modulation of platelet Ca2+ handling.
Endothelin‐1‐induced contraction in isolated aortae from normotensive and DOCA‐salt hypertensive rats: effect of magnesium
Authors: Laurant Pascal , Berthelot Alain 
Published: July 2012

The contractile responses to endothelin‐1 and the effect on these of various magnesium concentrations, were studied in isolated aortic rings from normotensive Sprague‐Dawley rats and deoxycorticosterone acetate‐salt (DOCA‐salt) hypertensive rats.
Contractions induced by endothelin‐1 were smaller in endothelium‐denuded aortae from DOCA‐salt hypertensive rats than in those from normotensive rats. The absence of calcium in the medium attenuated endothelin‐1‐induced contractions of aortae from both normotensive and DOCA‐salt rats, but the contraction was greater in aortae from DOCA‐salt hypertensive rats. Ryanodine (which inhibits the release of intracellular calcium) inhibited endothelin‐1‐induced contractions in aortae from DOCA‐salt hypertensive rats to a greater extent than in aortae from normotensive rats.
A high extracellular magnesium concentration (4.8 mM) attenuated endothelin‐1‐induced contractions in tissues from DOCA‐salt hypertensive rats but not in tissues from normotensive rats. In the absence of calcium, a high concentration of magnesium attenuated endothelin‐1‐induced contraction in aortae from both normotensive and hypertensive rats. In the presence of ryanodine, a high concentration of magnesium did not modify the contraction in preparations from either strain.
Absence of magnesium attenuated endothelin‐1‐induced contractions in aortae from both normotensive and DOCA‐salt hypertensive rats. In the absence of calcium, removal of magnesium totally inhibited endothelin‐1‐induced contraction in tissues from normotensive rats but had no effect in those from hypertensive rats. In the presence of ryanodine, the lack of magnesium inhibited endothelin‐1‐induced contractions in aortae from DOCA‐salt hypertensive rats but increased the sensitivity to endothelin‐1 of aortae from normotensive rats.
The presence of endothelium did not modify the effect of high magnesium on endothelin‐1‐induced contractions in aortae from normotensive and DOCA‐salt hypertensive rats. Conversely, the attenuating effect of magnesium removal on endothelin‐1‐induced contractions did not occur when endothelium was present.
In conclusion, endothelin‐1‐induced contraction was blunted in aortae from DOCA‐salt hypertensive rats. The blunted response was related to altered calcium utilization during contraction. Changes in extracellular magnesium concentration differentially alter endothelin‐1‐induced contraction in aortae from normotensive and hypertensive rats, possibly by interfering with calcium utilization during contraction. Magnesium may be required for the contractile response to endothelin‐1 and increasing magnesium may limit the vascular effects of endothelin‐1 in blood vessels from DOCA‐salt hypertensive rats.
Differential regulation of 5‐hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats
Authors: Tao Rui , Ma Zhiyuan , Auerbach Sidney B. 
Published: July 2012

Extracellular 5‐hydroxytryptamine (5‐HT) was determined in dorsal raphe nucleus (DRN), median raphe nucleus (MRN) and nucleus accumbens by use of microdialysis in unanaesthetized rats.
Infusion of the γ‐aminobutyric acid (GABA)A receptor agonist muscimol into DRN and MRN resulted in decreased 5‐HT in DRN and MRN, respectively. Muscimol infusion into nucleus accumbens had no effect on 5‐HT.
Infusion of the GABAA receptor antgonist bicuculline into DRN resulted in increased DRN and nucleus accumbens 5‐HT. Bicuculline infusion into MRN had no effect on 5‐HT. This suggests that endogenous GABA had a tonic, GABAA receptor‐mediated inhibitory effect on 5‐HT in DRN, but not in MRN.
Infusion of the GABAB receptor agonist baclofen into DRN produced a decrease in DRN 5‐HT. Baclofen infusion into nucleus accumbens resulted in decreased nucleus accumbens 5‐HT. This suggests that GABAB receptors are present in the area of cell bodies and terminals of 5‐hydroxytryptaminergic neurones.
Infusion of the GABAB receptor antagonists phaclofen and 2‐hydroxysaclofen had no effect on midbrain raphe and forebrain 5‐HT. This suggests that GABAB receptors did not contribute to tonic inhibition of 5‐HT release.
In conclusion, 5‐HT release is physiologically regulated by distinct subtypes of GABA receptors in presynaptic and postsynaptic sites.
Role of chondroitin 4‐sulphate as a receptor for polycation induced human platelet aggregation
Authors: Donato José L. , Marcondes Sisi , Antunes Edson , Nogueira Marie D. , Nader Helena B. , Dietrich Carl P. , Rendu Francine , de Nucci Gilberto 
Published: July 2012

Proteoglycans provide negatively charged sites on the surface of platelets, leukocytes and endothelial cells. Since chondroitin 4‐sulphate is the main proteoglycan present on the platelet surface, the role of this molecule in mediating the activation of human platelets by polylysine was studied.
Platelets were desensitized with phorbol 12‐myristate 13‐acetate (PMA, 10 nM) 5 min before the addition of polylysine to platelet‐rich plasma (PRP). Changes in the intracellular Ca2+ concentration were measured in fura2‐am (2 μm) loaded platelets and protein phosphorylation was assessed by autoradiography of the electrophoretic profile obtained from [32P]‐phosphate labelled platelets. The release of dense granule contents was measured in [14C]‐5‐hydroxytryptamine loaded platelets and the synthesis of thromboxane (TXA2) was assessed by radioimmunoassay. Surface chondroitin 4‐sulphate proteoglycan was degraded by incubating platelets with different concentrations of chondroitinase AC (3 min, 37°C). The amount of chondroitin 4‐sulphate remaining in the platelets was then quantified after proteolysis and agarose gel electrophoresis.
The addition of PMA to PRP before polylysine inhibited the aggregation by 88 ± 18% (n = 3). Staurosporine (1 μm, 5 min) prevented the PMA‐induced inhibition. Chondroitinase AC (4 pu ml−1 to 400 μu ml−1, 3 min) abolished the polylysine‐induced aggregation in PRP but caused only a discrete inhibition of ADP‐induced aggregation. The concentration of chrondroitin 4‐sulphate in PRP (0.96 ± 0.2 μg/108 platelets, n = 3) and in washed platelets (WP; 0.35 ± 0.1 μg/108 platelets, n = 3) was significantly reduced following incubation with chondroitinase AC (PRP = 0.63 ± 0.1 μg/108 platelets and WP = 0.08 ± 0.06 μg/108 platelets).
Washed platelets had a significantly lower concentration of chondroitin 4‐sulphate than platelets in PRP. The addition of polylysine to WP induced a rapid increase in light transmission which was not accompanied by TXA2 synthesis or the release of dense granule contents. This effect was not inhibited by sodium nitroprusside (SNP), iloprost, EDTA or the peptide RGDS. This event was accompanied by the discrete phosphorylation of plekstrin and myosin light chain, which were inhibited by staurosporine (10 μm, 10 min). The hydrolysis of platelet surface chondroitin 4‐sulphate strongly reduced the polylysine‐induced phosphorylation.
Our results indicate that polylysine activates platelets through a specific receptor which could be the proteoglycan chondroitin 4‐sulphate present on the platelet membrane.
Effect of dexamethasone and endogenous corticosterone on airway hyperresponsiveness and eosinophilia in the mouse
Authors: De Bie J.J. , Hessel E.M. , Van Ark I. , Van Esch B. , Hofman G. , Nijkamp F.P. , Van Oosterhout A.J.M. 
Published: July 2012

Mice were sensitized by 7 intraperitoneal injections of ovalbumin without adjuvant (10 μg in 0.5 ml of sterile saline) on alternate days and after 3 weeks exposed to either ovalbumin (2 mg ml−1 in sterile saline) or saline aerosol for 5 min on 8 consecutive days. One day before the first challenge, animals were injected intraperitoneally on a daily basis with vehicle (0.25 ml sterile saline), dexamethasone (0.5 mg kg−1) or metyrapone (30 mg kg−1).
In vehicle‐treated ovalbumin‐sensitized animals ovalbumin challenge induced a significant increase of airway responsiveness to metacholine both in vitro (27%, P < 0.05) and in vivo (40%, P < 0.05) compared to saline‐challenged mice. Virtually no eosinophils could be detected after saline challenge, whereas the numbers of eosinophils were significantly increased (P < 0.01) at both 3 and 24 h after the last ovalbumin challenge (5.48 ± 3.8 × 103 and 9.13 ± 1.7 × 103 cells, respectively). Furthermore, a significant increase in ovalbumin‐specific immunoglobulin E level (583 ± 103 units ml−1, P < 0.05) was observed after ovalbumin challenge compared to saline challenge (201 ± 38 units ml−1).
Plasma corticosterone level was significantly reduced (−92%, P < 0.001) after treatment with metyrapone. Treatment with metyrapone significantly increased eosinophil infiltration (17.4 ± 9.93 × 103 and 18.7 ± 2.57 × 103 cells, P < 0.05 at 3 h and 24 h, respectively) and potentiated airway hyperresponsiveness to methacholine compared to vehicle‐treated ovalbumin‐challenged animals. Dexamethasone inhibited both in vitro and in vivo hyperresponsiveness as well as antigen‐induced infiltration of eosinophils (0, P < 0.05 and 0.7 ± 0.33 × 103 cells, P < 0.05 at 3 h and 24 h, respectively). Metyrapone as well as dexamethasone did not affect the increase in ovalbumin‐specific immunoglobulin E levels after ovalbumin challenge (565 ± 70 units/ml−1; P < 0.05; 552 ± 48 units ml−1, P < 0.05 respectively).
From these data it can be concluded that exogenously applied corticosteroids can inhibit eosinophil infiltration as well as airway hyperresponsiveness. Vise versa, endogenously produced corticosteroids play a down‐regulating role on the induction of both eosinophil infiltration and airway hyperresponsiveness.
Psychological Distress and Depression in Patients with Chronic Kidney Disease
Authors: Zalai Dora , Szeifert Lilla , Novak Marta 
Published: July 2012

AbstractDepressive disorders are 1.5–4 times more prevalent in medically ill patients than in the general population. Mood disorders can be regarded as the final common pathway developing from the interaction among multiple pathophysiological, psychological, and socioeconomic stressors that chronic illness imposes on the individual. Symptoms of clinical depression affect approximately 25% patients on hemodialysis and can be associated with low quality of life and increased mortality. The epidemiology of depressive disorders is less well studied in the renal transplant population. However, depression is a risk factor for poor outcomes, such as graft failure and death after renal transplantation. A high prevalence of severe psychological distress in patients with advanced CKD and its impact on CKD outcomes call for screening and intervention integrated in routine renal care. Preliminary data indicate that some of the selective serotonin reuptake inhibitor agents and time‐limited, manualized, structured psychotherapies can be safe and effective for treating depression in this population.
The Other‐Race Effect in a Longitudinal Sample of 3‐, 6‐ and 9‐Month‐Old Infants: Evidence of a Training Effect
Authors: Spangler Sibylle M. , Schwarzer Gudrun , Freitag Claudia , Vierhaus Marc , Teubert Manuel , Fassbender Ina , Lohaus Arnold , Kolling Thorsten , Graf Frauke , Goertz Claudia , Knopf Monika , Lamm Bettina , Keller Heidi 
Published: July 2012

We investigated the development of the other‐race effect “ORE” in a longitudinal sample of 3‐, 6‐, and 9‐month‐oldCaucasian infants. Previous research using cross‐sectional samples has shown an unstableOREat 3 months, an increase at 6 months and full development at 9 months. In Experiment 1, we tested whether 9‐month‐olds showed theOREwithCaucasian andAfrican faces. As expected, the 9‐month‐olds discriminated faces within their own ethnicity (Caucasian) but not within the unfamiliar ethnicity (African). In months. In Experiment 2, we longitudinally tested infants at 3, 6, and 9 months by presenting either theCaucasian or theAfrican faces used in Experiment 1. In contrast to previous cross‐sectional studies and Experiment 1, we found that infants discriminated between all stimuli. Hence, we did not find theOREin this longitudinal study even at 9 months. We assume that the infants in our longitudinal study showed noOREbecause of previous repetitive exposure to African faces at 3 and 6 months. We argue that only a few presentations of faces from other ethnic categories sufficiently slow the development of theORE.
Pubertal Timing as a Potential Mediator of Adoption Effects on Problem Behaviors
Authors: Brooker Rebecca J. , Berenbaum Sheri A. , Bricker Josh , Corley Robin P. , Wadsworth Sally A. 
Published: July 2012

Adopted children show more problem behaviors than nonadopted children. Given that internationally adopted individuals show earlier puberty than nonadopted individuals, and early puberty is associated with problem behaviors in nonadopted youth, we analyzed data from adopted domestic adoptees to determine whether problem behaviors could be explained by differences in pubertal timing. Relative to nonadopted controls (n = 153), domestically adopted girls (n = 121) had earlier menarche, earlier sexual initiation, and more conduct disorder symptoms. Age at menarche partially mediated the relation of adoptive status to sexual initiation, but not to conduct disorder symptoms. Extending findings from international adoptees, results show that domestic adoption is also linked to earlier puberty, and suggest early puberty as one mechanism linking adoption to problematic outcomes.
Comparative Evaluation of Conventional and Transvaginal Laparoscopic Ovariohysterectomy in Dogs
Authors: Bakhtiari Jalal , Khalaj Ali Reza , Aminlou Elham , Niasari‐Naslaji Amir 
Published: July 2012

ObjectiveTo evaluate the feasibility and safety of a transvaginal approach for laparoscopic ovariohysterectomy (OVH) in dogs and to compare it with conventional laparoscopic OVH.Study DesignProspective study.AnimalsAdult healthy female mixed breed dogs (n = 24).MethodsDogs (weighing 14–17 kg) were anesthetized and positioned in dorsal recumbency for ovariohysterectomy. Dogs were prepared for either conventional (n = 12) or transvaginal (n = 12) laparoscopic OVH. For conventional laparoscopic OVH, 3 midline abdominal portals were used and for the transvaginal approach, 2 midline abdominal portals and one vaginal portal were used. The transected ovarian pedicles, broad ligament, and uterus were removed through the umbilical region in the conventional method and through the vagina in the transvaginal method. Mean surgical time, intraoperative and postoperative complications, clinical and hematologic findings, and wound complications were compared.ResultsOVH was successfully performed without complications using both methods. Mean ± SD surgical times were similar between conventional (34.2 ± 4.03 min) and transvaginal (37.0 ± 3.56 min) methods. No significant differences, hematologic and clinical variables, were found between groups. The vaginal port could limit surgical maneuvers ergonomically during manipulation of the uterine body.ConclusionsTransvaginal approach for laparoscopic OVH is a feasible technique with the advantage of requiring one less abdominal portal.
Weighty subjects: The biopolitics of the U.S. war on fat
Authors: Greenhalgh Susan 
Published: July 2012

ABSTRACTThe United States has declared a war on fat. I examine this campaign as a biopolitical field of science and governance that has emerged to manage the “obesity epidemic” by remaking overweight and obese subjects into thin, fit, proper Americans. Drawing on research in Southern California, I examine the impact of the campaign on the bodies, selves, and lives of the heavyset young people who are its main targets. At least in this corner of the country, I argue, the war on fat, far from alleviating the problem of fatness, is creating a new fat problem by expanding the number of weight‐obsessed, self‐identified “abnormal”“fat subjects,” who may not be technically obese but whose desperate efforts to lower their weight endanger their health and bring intense socioemotional suffering. These developments have implications for larger issues of social suffering and social justice.