bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teneurin C‐terminal associated peptide‐1 blocks the effects of corticotropin‐releasing factor on reinstatement of cocaine seeking and on cocaine‐induced behavioural sensitization
Authors: Kupferschmidt David A. , Lovejoy David A. , Rotzinger Susan , Erb Suzanne 
Published: September 2010

BACKGROUND AND PURPOSEThe stress‐related neuropeptide, corticotropin‐releasing factor (CRF), has become an important focus of studies of cocaine addiction, and in particular, the effects of stress on cocaine‐related behaviours. A recently discovered peptide system, the teneurin C‐terminal associated peptides (TCAP), has been implicated in the regulation of the stress response, via a CRF‐related mechanism. Here we have determined whether treatment with TCAP‐1, a synthetic analogue of TCAP, modulated two cocaine‐related behaviours induced by CRF: reinstatement of cocaine seeking, and expression of cocaine‐induced behavioural sensitization.EXPERIMENTAL APPROACHIn Experiment 1, rats trained to self‐administer cocaine were given acute or repeated (once daily for 5 days) i.c.v. injections of TCAP‐1 before tests for reinstatement in response to CRF (105 pmol, i.c.v.), intermittent footshock stress (0.9 mA), or cocaine (15 mg·kg−1, i.p.). In Experiment 2, rats pre‐exposed to cocaine (15–30 mg·kg−1, i.p.) or saline for 7 days were treated with TCAP‐1 (once daily for 5 days; i.c.v.) and subsequently tested for locomotor responses to CRF (105 pmol, i.c.v.) or cocaine (15 mg·kg−1, i.p.).KEY RESULTSFive day pre‐exposure with TCAP‐1 blocked CRF‐, but not footshock‐ or cocaine‐induced reinstatement of cocaine seeking; acute pretreatment with TCAP‐1 was without effect in all test conditions. Similarly, repeated TCAP‐1 pre‐exposure blocked the cocaine‐sensitized locomotor response to CRF, but not to cocaine.CONCLUSIONS AND IMPLICATIONSRepeated TCAP‐1 exposure induced robust and selective inhibition of cocaine‐related behavioural responses to CRF, suggesting that TCAP‐1 may normalize signalling within CRF systems dysregulated by cocaine exposure.
Thyroid hormone potentiates insulin  signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes
Authors: Lin Yi , Sun Zhongjie 
Published: September 2010

BACKGROUND AND PURPOSEThe thyroid hormone, triiodothyronine (T3) has many metabolic functions. Unexpectedly, exogenous T3 lowered blood glucose in db/db mice, a model of type 2 diabetes. Here, we have explored this finding and its possible mechanisms further.EXPERIMENTAL APPROACHdb/db and lean mice were treated with T3, the phosphoinositide 3‐ kinase (PI3‐kinase) inhibitor, LY294002, plus T3, or vehicles. Blood glucose, insulin sensitivity, levels and synthesis were measured. Effects of T3 on intracellular insulin signaling were analyzed in 3T3‐L1 pre‐adipocytes with Western blotting. Knock‐down of the thyroid hormone receptor α1 (TRα1) in 3T3‐L1 cells was achieved with an appropriate silencing RNA (siRNA).KEY RESULTSSingle injections of T3 (7 ng·g−1 i.p.) rapidly and markedly attenuated hyperglycemia. Treatment with T3 (14 ng·g−1·day−1, 18 days) dose‐dependently attenuated blood glucose and increased insulin sensitivity in db/db mice. Higher doses of T3 (28 ng·g−1·day−1) reversed insulin resistance in db/db mice. T3 also increased insulin levels in plasma and the neurogenic differentiation factor (an insulin synthesis transcription factor) and insulin storage in pancreatic islets in db/db mice. These anti‐diabetic effects of T3 were abolished by the PI3‐kinase inhibitor (LY294002). In 3T3‐L1 preadipocytes, T3 enhanced insulin‐induced tyrosine phosphorylation of insulin receptor substrate (IRS)‐1 and activation of PI3‐kinase, effects blocked by siRNA for TRα1.CONCLUSIONS AND IMPLICATIONST3 potentiated insulin signaling, improved insulin sensitivity, and increased insulin synthesis, which may contribute to its anti‐diabetic effects. These findings may provide new approaches to the treatment of type 2 diabetes.
Lubiprostone targets prostanoid EP4 receptors in ovine airways
Authors: Cuthbert AW 
Published: September 2010

BACKGROUND AND PURPOSE Lubiprostone, a prostaglandin E1 derivative, is reported to activate ClC‐2 chloride channels located in the apical membranes of a number of transporting epithelia. Lack of functioning CFTR chloride channels in epithelia is responsible for the genetic disease cystic fibrosis, therefore, surrogate channels that can operate independently of CFTR are of interest. This study explores the target receptor(s) for lubiprostone in airway epithelium.EXPERIMENTAL APPROACH All experiments were performed on the ventral tracheal epithelium of sheep. Epithelia were used to measure anion secretion from the apical surface as short circuit current or as fluid secretion from individual airway submucosal glands, using an optical method.KEY RESULTS The EP4 antagonists L‐161982 and GW627368 inhibited short circuit current responses to lubiprostone, while EP1,2&3 receptor antagonists were without effect. Similarly, lubiprostone induced secretion in airway submucosal glands was inhibited by L‐161982. L‐161982 effectively competed with lubiprostone with a Kd value of 0.058 µM, close to its value for binding to human EP4 receptors (0.024 µM). The selective EP4 agonist L‐902688 and lubiprostone behaved similarly with respect to EP4 receptor antagonists. Results of experiments with H89, a protein kinase A inhibitor, were consistent with lubiprostone acting through a Gs‐protein coupled EP4 receptor/cAMP cascade.CONCLUSIONS AND IMPLICATIONS Lubiprostone‐induced short‐circuit currents and submucosal gland secretions were inhibited by selective EP4 receptor antagonists. The results suggest EP4 receptor activation by lubiprostone triggers cAMP production necessary for CFTR activation and the secretory responses, a possibility precluded in CF tissues.
Rolandic epilepsy: An uncommon presentation with leg motor seizures
Authors: Fusco Lucia , Trivisano Marina , Specchio Nicola , Vigevano Federico 
Published: September 2010

SummaryRolandic epilepsy (RE) is the most common and one of the most benign epileptic syndromes of childhood. It is typically characterized by sleep‐related orofacial seizures, of brief duration, of variable frequency, in otherwise healthy children. Electroencephalography (EEG) shows typical centrotemporal spike and spike‐and‐wave complexes, often bilateral and asynchronous, activated by sleep. Therapy is often unnecessary and seizures spontaneously end at puberty. Apart from typical orofacial localization, arm or more diffuse clonic jerks are frequently described by parents. More rare and probably underestimated are sensorimotor seizure localized to one leg. When such seizures represent the only type of seizures in RE, the exact recognition of this benign epileptic syndrome appears difficult, leading to unnecessary investigation and therapy. We describe six children, among 230 with RE, who presented leg sensorimotor seizures as the mainly type of ictal manifestations.
Ictogenesis and symptomatogenesis of gelastic seizures in hypothalamic hamartomas: An ictal SPECT study
Authors: Kameyama Shigeki , Masuda Hiroshi , Murakami Hiroatsu 
Published: September 2010

SummaryPurpose: To topographically localize the ictogenic zone within hypothalamic hamartomas (HHs) and the symptomatogenic zone for gelastic seizure (GS), we analyzed data from both interictal and ictal single photon emission computed tomography (SPECT).Methods: Ictal SPECT was performed immediately after GS onset in 21 patients with HH (aged 2–36 years, mean 13.8 years) who underwent stereotactic radiofrequency thermocoagulation (SRT). SPECT data were statistically analyzed by means of subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM) and statistical parametric mapping (SPM). Topographic localization of ictal hyperperfusion areas was evaluated.Results: SISCOM obtained in 27 studies demonstrated ictal hyperperfusion in the HH interface zone in 16 studies of 13 patients (hot HH group). In these patients, HHs were significantly larger than those without hyperperfusion of HH in 11 studies of 8 patients (21.4 ± 10.3 vs. 12.3 ± 7.3 mm in diameter, p < 0.05,t‐test). In all patients and in the hot HH group, SPM group analysis of individual differences between interictal and ictal data revealed significantly (p < 0.001) hyperperfused areas in the ipsilateral hypothalamus, mediodorsal (MD) nucleus of the thalamus and putamen, bilateral pontine tegmentum, and contralateral inferior semilunar lobule of the cerebellum. There was no hyperperfusion in the mammillothalamocingulate pathway.Discussion: The present study confirmed that ictogenesis occurs in the HH interface zone, which should accordingly be the target for SRT. We suggest that a thalamopontocerebellar circuit plays an important role for stereotypical and automatic symptomatogenesis of GS and that the hypothalamus and MD nucleus of the thalamus are potentially involved in epileptic encephalopathy.
Neurocognitive effects of brivaracetam, levetiracetam, and lorazepam
Authors: Meador Kimford J. , Gevins Alan , Leese Philip T. , Otoul Christian , Loring David W. 
Published: September 2010

SummaryPurpose:  Brivaracetam (BRV) is a new anticonvulsant under development. Although BRV is an analog of levetiracetam (LEV), in addition to being an SV2A ligand, it also inhibits sodium channels in a voltage‐dependent manner. The cognitive effects of BRV are uncertain.Methods:  A randomized, double‐blind, placebo‐controlled, four‐way cross‐over design was employed in 16 healthy volunteers comparing acute dosing (i.e., two doses) of BRV 10 mg, LEV 500 mg, lorazepam (LZP) 2 mg, and placebo. The primary outcome was the summary score from the cognitive neurophysiologic test (CNT), which combines electrophysiologic and performance measures. Secondary outcomes included CNT cognitive and electrophysiologic subscores, traditional neuropsychological measures, and treatment‐emergent adverse events (TEAEs).Results:  Compared to BRV, LEV, and placebo, LZP adver‐sely affected the CNT summary score and the majority of CNT subscores and neuropsychological measures. In contrast, BRV did not differ from placebo or LEV on any measure. More TEAEs occurred with LZP compared to each of the other treatment conditions.Discussion:  The differential pattern of drug effects was consistent across multiple electrophysiologic, cognitive, and subjective measures. The profile of cognitive, subjective, and electrophysiologic effects for BRV was similar to the analog compound LEV and to placebo. The findings suggest that BRV should be tolerated well from a neuropsychological perspective, but additional studies are needed.
Sinus Node Injury as a Result of Superior Vena Cava Isolation during Catheter Ablation for Atrial Fibrillation and Atrial Flutter
Authors: CHEN GANG , DONG JIAN ZENG , LIU XING PENG , ZHANG XIN YONG , LONG DE YONG , SANG CAI HUA , NING MAN , TANG RI BO , JIANG CHEN XI , SHENG MA CHANG 
Published: September 2010

Background: The ectopic foci originating from superior vena cava (SVC) may act as triggers in the occurrence and perpetuation of atrial fibrillation (AF). Unfortunately, the SVC isolation may result in potential dysfunction of sinus node. Furthermore, little is known about the occurrence of sinus node injury complicated by the SVC isolation.
Methods:
Patients with AF or atypical atrial flutter experienced SVC isolation. The junctional rhythm or sinus arrest could be observed, if sinus node was injured. Atropin and dopamine administration ruled out the vagal irritation of sinus node, when junctional rhythm or sinus arrest occurred.
Results:
One hundred and thirty‐two patients who had no electrocardiogram signs of sinus node dysfunction before ablation experienced the SVC isolation. Six patients (three men, three women, mean age 62.5 ± 8.6 years) had sinus node injury (4.5%, 6/132): four patients had junctional rhythm and one male patient had junctional rhythm and sinus arrest simultaneously; another male patient required AAI mode permanent pacemaker implantation due to the persistent junctional rhythm after SVC isolation. The ablation sites of all six patients closed to the junction of right atrium and SVC during the ablation of anterolateral free wall of the SVC.
Conclusion:
Sinus node may be damaged due to the ablation sites closer to sinus node. The definition of the junction of right atrium and SVC is very important, the ablation sites of anterolateral free wall of the SVC should not be too close to the SVC orifice. (PACE 2011; 34:163–170)
Improvement in Right Ventricular Systolic Function after Cardiac Resynchronization Therapy Correlates with Left Ventricular Reverse Remodeling
Authors: AKSOY HAKAN , OKUTUCU SERCAN , AYTEMIR KUDRET , KAYA ERGUN BARIS , TULUMEN EROL , EVRANOS BANU , FATIHOGLU SEFIK GÖRKEM , KABAKCI GIRAY , TOKGOZOGLU LALE , OZKUTLU HILMI , OTO ALI 
Published: September 2010

Background: Cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function in heart failure (HF). However, the effects of CRT on right ventricular (RV) systolic function are not fully understood.
Objective: We aimed to determine echocardiographic correlates of improvement in RV systolic function after CRT.
Methods: Fifty‐four patients (61.9 ± 10.5 years; 43 men; LV ejection fraction 24.6 ± 4.0%; QRS duration > 120 ms) with HF were enrolled. Standard echocardiography, strain rate (SR), and tissue Doppler imaging were performed in all patients before and 6 months after CRT. Pulsed‐wave TDI‐derived systolic indices of RV included systolic (RVS) and isovolumic velocity (RVIVV) and isovolumic acceleration (RVIVA). Response to CRT was defined as decline in LV end‐systolic volume (LVESV) ≥ 10%.
Results: When indices of RV systolic function were assessed between responders and nonresponders, in responders (38 patients, 70.4%) RV end‐diastolic diameters (RVD1–3), mid‐RV strain, and mid‐RV SR improved significantly (P < 0.01, for all). RVS (10.77 ± 4.29 vs 12.62 ± 4.10 cm/sec, P = 0.005), RVIVV (14.71 ± 5.88 vs 18.52 ± 6.62 cm/sec, P < 0.001), and RVIVA (1.69 ± 0.70 vs 2.39 ± 0.77 m/sec2, P < 0.001) significantly increased among responders. There was no significant change in these parameters among nonresponders. Pearson's analyses revealed moderate positive correlations between reduction of LVESV and ΔRVIVV (r = 0.467, P = 0.001) and ΔRVIVA (r = 0.473, P = 0.001), respectively.
Conclusions: RV diameters and systolic indices after CRT improved only in the responder group. Improvement in RV systolic performance after CRT is correlated with the reduction of LVESV. (PACE 2011; 34:200–207)
Clinical Characteristics of Focal Atrial Tachycardias Arising from the Atrial Appendages during Childhood
Authors: SAKAGUCHI HEIMA , MIYAZAKI AYA , YAMAMOTO MASAKI , KUROSAKI KENICHI , OHUCHI HIDEO , SATOMI KAZUHIRO , SUYAMA KAZUHIRO , YAMADA OSAMU 
Published: September 2010

Background: Focal atrial tachycardias (ATs) arising from the atrial appendages (AAT) are uncommon in adults. On the other hand, we frequently encounter AATs during childhood. However, the topographic distribution and clinical characteristics of focal ATs during childhood have not yet been clearly revealed. The aim of this study was to investigate the clinical characteristics of AATs in childhood.
Methods: The study population consisted of 16 consecutive pediatric patients with focal AT enrolled between March 1991 and June 2009. A retrospective analysis was performed. The patients with focal AT were divided into two groups: the AAT group and other AT (OAT) group, in which the foci arose from other atrial sites.
Results: Fifty percent had AAT. The AAT patients consisted of more males (88% vs 25%; P < 0.05), were more often asymptomatic at the initial visit (75% vs 25%; P < 0.05), and more often presented with an incessant form of the AT (88% vs 25%; P < 0.05) than the OAT patients. Second‐degree atrioventricular block during slow ATs of <120 beats per minute were more often observed in the AAT patients (63% vs 13%; P < 0.05). The incidence of tachycardia‐mediated cardiomyopathy was 19% out of all our subjects and 38% of the AAT patients.
Conclusions: The AATs are the major source of focal ATs in pediatric patients that are typically incessant. These characteristics probably explain why a much higher percentage of the patients are presented with TMC. (PACE 2011; 34:177–184)
Cutaneous metastatic cholangiocarcinoma: a report of three cases and review of the literature
Authors: West Kelly L. , Selim Maria Angelica , Puri Puja K. 
Published: September 2010

Cutaneous metastasis from cholangiocarcinoma is an extremely rare event. Herein, we present three cases with review of the literature. Case 1 is that of a young female with scalp metastasis. Cases 2 and 3 involve cutaneous metastasis to the sites of prior biliary drains, one occurring in a young female with a history of multiple biliary surgeries and one in a male with a history of sclerosing cholangitis. Review of the literature shows that the presentation of cutaneous metastases from cholangiocarcinoma can vary in terms of anatomic location and clinical features. The pathological and immunohistochemical profile of metastatic cholangiocarcinoma can be non‐specific, and accurate diagnosis relies in part on clinical correlation. In summary, metastatic disease should always be included in the differential diagnosis of cutaneous lesions in patients with known malignancy.West KL, Selim MA, Puri PK. Cutaneous metastatic cholangiocarcinoma: a report of three cases and review of the literature.
Suppressive effect of the antimicrobial peptide LL‐37 on expression of IL‐6, IL‐8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts
Authors: Inomata Megumi , Into Takeshi , Murakami Yukitaka 
Published: September 2010

Inomata M, Into T, Murakami Y. Suppressive effect of the antimicrobial peptide LL‐37 on expression of IL‐6, IL‐8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts. Eur J Oral Sci 2010; 118: 574–581. © 2010 Eur J Oral Sci Porphyromonas gingivalis is a major periodontogenic bacterium and possesses immunostimulatory components, such as lipopolysaccharides (LPS) and fimbriae. The host antimicrobial peptide, LL‐37, suppresses proinflammatory responses of immune cells but its effect on human gingival fibroblasts (HGFs) is not known. In this study, we assessed the effect of LL‐37 on the proinflammatory responses of HGFs stimulated with P. gingivalis cells and their components. Live P. gingivalis cells did not induce proinflammatory responses of HGFs, and LL‐37 did not alter these responses. However, LL‐37 was able to suppress the killed P. gingivalis cell‐induced secretion of interleukin (IL)‐6 and IL‐8. LL‐37 also suppressed the expression of IL6, IL8, and CXCL10 genes that was induced by P. gingivalis components, including phenol–water extracts, lipid A, and fimbriae, and the induction of phosphorylation of p38 and extracellular signal‐regulated kinase (ERK) by P. gingivalis lipopolysaccharide (LPS). CAMP was found to be expressed in oral epithelial cells but not in HGFs, despite stimulation with P. gingivalis components. Therefore, LL‐37 can exert a suppressive effect on P. gingivalis‐induced proinflammatory responses of HGFs in a paracrine manner, suggesting that excess inflammatory responses to P. gingivalis in the gingival tissue are suppressed by LL‐37 in vivo.
Apoptotic and anti‐apoptotic factors in early human mandible development
Authors: Brakus Snjezana Mardesic , Govorko Danijela Kalibovic , Vukojevic Katarina , Jakus Ivana Alujevic , Carev Dominko , Petricevic Josko , Saraga‐Babic Mirna 
Published: September 2010

Mardesic Brakus S, Kalibovic Govorko D, Vukojevic K, Alujevic Jakus I, Carev D, Petricevic J, Saraga‐Babic M. Apoptotic and anti‐apoptotic factors in early human mandible development. Eur J Oral Sci 2010; 118: 537–546. © 2010 Eur J Oral Sci The regulators of apoptosis Bcl‐2, Bax, caspase‐3, p53, and Hsp70 were analyzed immunohistochemically in the developing human mandible of eight human conceptuses from weeks 5 to 10 of gestation. During this period, all proteins displayed an increased pattern of expression in the mandible ectomesenchyme and in newly formed bone, except for caspase‐3, which showed decreased expression in the ectomesenchyme, but appeared first in the ossification zone at the 7th wk of development. Simultaneously, the oral epithelium showed weak (p53) to strong (hsp70) expression of all proteins investigated, while in Meckel’s cartilage cells, bcl‐2 was expressed weakly and hsp70 was expressed moderately. Cells on the surface of the forming bone were predominantly bax positive, and only occasionally bcl‐2 positive. Only a few cells on the surface and inside the bony spicules co‐expressed bax and bcl‐2. Terminal deoxynucleotidyl transferase (TdT)‐mediated biotin–dUTP nick‐end labelling (TUNEL)‐positive cells were found to be apoptotic osteoblasts. The expression of all proteins investigated changed dynamically during early mandible development and the subsequent differentiation of Meckel’s cartilage and bone. While interactions between those factors might be associated with the survival of Meckel’s cartilage, in the ossification zone they might participate in the control of cell numbers, mineralization, and bone remodelling. Among many other factors, precise orchestration of pro‐ and anti‐apoptotic factors contributes to normal mandible development.
The impact of cyclooxygenase inhibition on duodenal motility and mucosal alkaline secretion in anaesthetized rats
Authors: Nylander O. 
Published: September 2010

AbstractAim: Non‐steroidal anti‐inflammatory drugs (NSAIDs) are effective in the treatment of various human diseases. However, these drugs also have serious adverse effects in the gastrointestinal tract. In the duodenum NSAIDs inhibit mucosal alkaline secretion (DMAS), an important protective mechanism against the acid emptied from the stomach in most species, including humans. Surprisingly, NSAIDs have been shown to stimulate DMAS in an anaesthetized rat model. The aim of this review was to summarize the effects of NSAIDs and selective cyclooxygenase‐2 (COX‐2) inhibition on duodenal function in the rat and provide an explanation for why these drugs stimulate DMAS. Included are new data examining the effect of α‐adrenergic drugs on duodenal motility and DMAS.Methods: Experiments were performed in anaesthetized rats. The proximal duodenum was perfused luminally with an isotonic NaCl solution. DMAS, motility, fluid flux and epithelial permeability were assessed in the absence and presence of various COX inhibitors.Results: COX inhibition induced duodenal motility, increased DMAS and augmented the sensitivity as well as the maximal response of the duodenal mucosa to lidocaine‐ or hypotonicity‐induced increases in mucosal permeability. Furthermore, the ability of the duodenum to absorb water and to adjust osmolality in response to luminal hypotonicity was improved in COX‐inhibited animals. These improvements are mediated predominately via inhibition of COX‐2.Conclusions: Inhibition of COX‐2 in rats with postoperative duodenal ileus induces muscle contractions, which in turn activate a nicotinic receptor‐dependent intramural reflex that stimulates duodenocytes to increase the activity of apical Cl−/HCO3−exchangers, resulting in a rise in DMAS.