bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of active immunization against GnRH‐I on the reproductive function in cat
Authors: Jiang Shudong , Hong Meizhen , Su Shiping , Song Min , Tian Yuan , Cui Pei , Song Shuang , Wang Yaoyao , Li Fubao , Fang Fugui 
Published: January 2015

AbstractThis study was designed to explore the effect of active immunization against maltose binding protein‐gonadotropin releasing hormone I hexamer (MBP‐GnRH‐I6) on the reproductive function in cats. Each immunized cat was administered twice intramuscularly in the neck at 16 and 20 weeks old. The concentrations of the testosterone and estradiol and the level of anti‐GnRH‐I antibody in the serum were measured by radioimmunoassay and ELISA, respectively. The results showed that the weight and size of testicles and ovaries, and the concentrations of serum testosterone and estradiol in the immunized animals were lower than those of the control cats (P < 0.05), but that the levels of anti‐GnRH‐I antibody were significant higher compared to control animals (P < 0.05). Testicular tissues from the immunized male cats showed that seminiferous tubules were depauperate with the lumen relatively empty and that the differentiation of spermatogonia was not obvious. Tissues from the immunized female cats showed that the ovaries had many primordial follicles and primary follicles, but no secondary follicle was observed. These results showed active immunization against MBP–GnRH‐I6 could make the gonads atrophy and reduce the concentrations of gonadal hormones, which suggested that MBP‐GnRH‐I6 was a very effective immunogen in the cat.
Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study
Authors: Gacci Mauro , Sebastianelli Arcangelo , Salvi Matteo , De Nunzio Cosimo , Tubaro Andrea , Vignozzi Linda , Corona Giovanni , McVary Kevin T. , Kaplan Steven A. , Maggi Mario , Carini Marco , Serni Sergio 
Published: January 2015

ObjectiveTo evaluate the impact of components of metabolic syndrome (MetS) on urinary outcomes after surgery for severe lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), as central obesity can be associated with the development of BPE and with the worsening of LUTS.Patients and MethodsA multicentre prospective study was conducted including 378 consecutive men surgically treated for large BPE with simple open prostatectomy (OP) or transurethral resection of the prostate (TURP), between January 2012 and October 2013. LUTS were measured by the International Prostate Symptom Score (IPSS), immediately before surgery and at 6–12 months postoperatively. MetS was defined according the USA National Cholesterol Education Program‐Adult Treatment Panel III.ResultsThe improvement of total and storage IPSS postoperatively was related to diastolic blood pressure and waist circumference (WC). A WC of >102 cm was associated with a higher risk of an incomplete recovery of both total IPSS (odds ratio [OR] 0.343, P = 0.001) and storage IPSS (OR 0.208, P < 0.001), as compared with a WC of <102 cm. The main limitations were: (i) population selected from a tertiary centre, (ii) Use exclusively of IPSS questionnaire, and (iii) No inclusion of further data.ConclusionsIncreased WC is associated with persistent postoperative urinary symptoms after surgical treatment of BPE. Obese men have a higher risk of persistent storage LUTS after TURP or OP.
A novel urodynamic model for lower urinary tract assessment in awake rats
Authors: Schneider Marc P. , Hughes Francis M. , Engmann Anne K. , Purves J. Todd , Kasper Hansjörg , Tedaldi Marco , Spruill Laura S. , Gullo Miriam , Schwab Martin E. , Kessler Thomas M. 
Published: January 2015

ObjectivesTo develop a urodynamic model incorporating external urethral sphincter (EUS) electromyography (EMG) in awake rats.Materials and MethodsBladder catheters and EUS EMG electrodes were implanted in female Sprague Dawley rats. Assessments were performed in awake, lightly restrained rats on postoperative day 12–14. Measurements were repeated in the same rat on day 16 under urethane anaesthesia. Urodynamics and EUS EMG were performed simultaneously. In addition, serum creatinine and bladder histology was assessed.ResultsNo significant differences in urodynamic parameters were found between bladder catheter only vs bladder catheter and EUS EMG electrode groups. Urethane anaesthesia evoked prominent changes in both urodynamic parameters and EUS EMG. Serum creatinine was within the normal limits in all rats. Bladder weight and bladder wall thickness were significantly increased in both the bladder catheter only and the bladder catheter and EUS EMG group compared with controls.ConclusionsOur novel urodynamic model allows repetitive measurements of both bladder and EUS function at different time points in the same rat under fully awake conditions and opens promising avenues to investigate lower urinary tract dysfunction in a translational approach.
In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin
Authors: Devader C , Khayachi A , Veyssière J , Moha ou Maati H , Roulot M , Moreno S , Borsotto M , Martin S , Heurteaux C , Mazella J 
Published: January 2015

Background and PurposeWe have described a novel antidepressant peptide, spadin, that acts by blocking the TWIK‐related‐potassium channel, type 1 (TREK‐1). Here, we examined possible mechanisms of action of spadin at both molecular and cellular levels.Experimental ApproachesEffects of spadin were measured in primary cultures of neurons or tissues from mice injected i.v. with spadin. Western blots, qPCR, histochemical and electrophysiological techniques were used.Key ResultsIn vitro, spadin increased neuronal membrane potential and activated both the MAPK and PI3K signalling pathways, in a time‐ and concentration‐dependent manner. The latter pathway was involved in the protective effect of spadin against staurosporine‐induced apoptosis. Also, spadin enhanced both mRNA expression and protein of two markers of synaptogenesis, the post‐synaptic density protein of 95 kDalton (PSD‐95) and synapsin. We confirmed these effects on synaptogenesis by the observation that spadin treatment significantly increased the proportion of mature spines in cortical neurons. Finally, in vivo injections of spadin led to a rapid increase in both mRNA expression and protein level of brain‐derived neurotrophic factor (BDNF) in the hippocampus, confirming the antidepressant action of the peptide. We argue for a new role of spadin in synaptogenesis as both PSD‐95 and synapsin mRNA expression and protein levels were further enhanced in the hippocampus, following treatment in vivo with the peptide.Conclusions and ImplicationsThese findings provide new mechanisms of action for the rapidly acting antidepressant peptide spadin by stimulating expression of BDNF and synaptic proteins, both in vitro and in vivo.
The anti‐inflammatory mediator palmitoylethanolamide enhances the levels of 2‐arachidonoyl‐glycerol and potentiates its actions at TRPV1 cation channels
Authors: Petrosino Stefania , Schiano Moriello Aniello , Cerrato Santiago , Fusco Mariella , Puigdemont Anna , De Petrocellis Luciano , Di Marzo Vincenzo 
Published: January 2015

Background and PurposePalmitoylethanolamide (PEA) is an endogenous congener of anandamide and potentiates its actions at cannabinoid CB1 and CB2 receptors, and at transient receptor potential vanilloid type‐1 (TRPV1) channels. The other endocannabinoid, 2‐arachidonoylglycerol (2‐AG), was recently suggested to act as a TRPV1 channel agonist. We investigated if PEA enhanced levels of 2‐AG in vitro or in vivo and 2‐AG activity at TRPV1 channels.Experimental ApproachEndogenous lipid levels were measured by LC‐MS in (i) human keratinocytes incubated with PEA (10–20 μM, 40 min, 6 and 24 h, 37°C); (ii) the blood of spontaneously Ascaris suum hypersensitive beagle dogs given a single oral dose of ultramicronized PEA (30 mg·kg−1, 1, 2, 4 and 8 h from administration); (iii) the blood of healthy volunteers given a single oral dose of micronized PEA (300 mg, 2, 4 and 6 h from administration). Effects of 2‐AG at TRPV1 channels were assessed by measuring intracellular Ca2+ in HEK‐293 cells over‐expressing human TRPV1 channels.Key ResultsPEA elevated 2‐AG levels in keratinocytes (∼3‐fold) and in human and canine plasma (∼2 and ∼20‐fold respectively). 2‐AG dose‐dependently raised intracellular Ca2+ in HEK‐293‐TRPV1 cells in a TRPV1‐dependent manner and desensitized the cells to capsaicin. PEA only slightly enhanced 2‐AG activation of TRPV1 channels, but significantly increased 2‐AG‐induced TRPV1 desensitization to capsaicin (IC50 from 0.75 ± 0.04 to 0.45 ± 0.02 μM, with PEA 2 μM).Conclusions and ImplicationsThese observations may explain why several effects of PEA are attenuated by cannabinoid receptor or TRPV1 channel antagonists.Linked ArticlesThis article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc
Effects of the novel BK (KCa1.1) channel opener GoSlo‐SR‐5‐130 are dependent on the presence of BKβ subunits
Authors: Large R J , Kshatri A , Webb T I , Roy S , Akande A , Bradley E , Sergeant G P , Thornbury K D , McHale N G , Hollywood M A 
Published: January 2015

Background and PurposeGoSlo‐SR compounds are efficacious BK (KCa1.1) channel openers, but little is known about their mechanism of action or effect on bladder contractility. We examined the effects of two closely related compounds on BK currents and bladder contractions.Experimental ApproachA combination of electrophysiology, molecular biology and synthetic chemistry was used to examine the effects of two novel channel agonists on BK channels from bladder smooth muscle cells and in HEK cells expressing BKα alone or in combination with either β1 or β4 subunits.Key ResultsGoSlo‐SR‐5‐6 shifted the voltage required for half maximal activation (V1/2) of BK channels approximately −100 mV, irrespective of the presence of regulatory β subunits. The deaminated derivative, GoSlo‐SR‐5‐130, also shifted the activation V1/2 in smooth muscle cells by approximately −100 mV; however, this was reduced by ∼80% in HEK cells expressing only BKα subunits. When β1 or β4 subunits were co‐expressed with BKα, efficacy was restored. GoSlo‐SR‐5‐130 caused a concentration‐dependent reduction in spontaneous bladder contraction amplitude and this was abolished by iberiotoxin, consistent with an effect on BK channels.Conclusions and ImplicationsGoSlo‐SR‐5‐130 required β1 or β4 subunits to mediate its full effects, whereas GoSlo‐SR‐5‐6 worked equally well in the absence or presence of β subunits. GoSlo‐SR‐5‐130 inhibited spontaneous bladder contractions by activating BK channels. The novel BK channel opener, GoSlo‐SR‐5‐130, is approximately fivefold more efficacious on BK channels with regulatory β subunits and may be a useful scaffold in the development of drugs to treat diseases such as overactive bladder.
The long‐acting β2‐adrenoceptor agonist, indacaterol, enhances glucocorticoid receptor‐mediated transcription in human airway epithelial cells in a gene‐ and agonist‐dependent manner
Authors: Joshi T , Johnson M , Newton R , Giembycz M A 
Published: January 2015

Background and PurposeInhaled glucocorticoid (ICS)/long‐acting β2‐adrenoceptor agonist (LABA) combination therapy is a recommended treatment option for patients with moderate/severe asthma in whom adequate control cannot be achieved by an ICS alone. Previously, we discovered that LABAs can augment dexamethasone‐inducible gene expression and proposed that this effect may explain how these two drugs interact to deliver superior clinical benefit. Herein, we extended that observation by analysing, pharmacodynamically, the effect of the LABA, indacaterol, on glucocorticoid receptor (GR)‐mediated gene transcription induced by seven ligands with intrinsic activity values that span the spectrum of full agonism to antagonism.Experimental ApproachBEAS‐2B human airway epithelial cells stably transfected with a 2× glucocorticoid response element luciferase reporter were used to model gene transcription together with an analysis of several glucocorticoid‐inducible genes.Key ResultsIndacaterol augmented glucocorticoid‐induced reporter activation in a manner that was positively related to the intrinsic activity of the GR agonist. This effect was demonstrated by an increase in response maxima without a change in GR agonist affinity or efficacy. Indacaterol also enhanced glucocorticoid‐inducible gene expression. However, the magnitude of this effect was dependent on both the GR agonist and the gene of interest.Conclusions and ImplicationsThese data suggest that indacaterol activates a molecular rheostat, which increases the transcriptional competency of GR in an agonist‐ and gene‐dependent manner without apparently changing the relationship between fractional GR occupancy and response. These findings provide a platform to rationally design ICS/LABA combination therapy that is based on the generation of agonist‐dependent gene expression profiles in target and off‐target tissues.
Regulation of μ and δ opioid receptor functions: involvement of cyclin‐dependent kinase 5
Authors: Beaudry H , Mercier‐Blais A‐A , Delaygue C , Lavoie C , Parent J‐L , Neugebauer W , Gendron L 
Published: January 2015

Background and PurposePhosphorylation of δ opioid receptors (DOP receptors) by cyclin‐dependent kinase 5 (CDK5) was shown to regulate the trafficking of this receptor. Therefore, we aimed to determine the role of CDK5 in regulating DOP receptors in rats treated with morphine or with complete Freund's adjuvant (CFA). As μ (MOP) and DOP receptors are known to be co‐regulated, we also sought to determine if CDK5‐mediated regulation of DOP receptors also affects MOP receptor functions.Experimental ApproachThe role of CDK5 in regulating opioid receptors in CFA‐ and morphine‐treated rats was studied using roscovitine as a CDK inhibitor and a cell‐penetrant peptide mimicking the second intracellular loop of DOP receptors (C11‐DOPri2). Opioid receptor functions were assessed in vivo in a series of behavioural experiments and correlated by measuring ERK1/2 activity in dorsal root ganglia homogenates.Key ResultsChronic roscovitine treatment reduced the antinociceptive and antihyperalgesic effects of deltorphin II (Dlt II) in morphine‐ and CFA‐treated rats respectively. Repeated administrations of C11‐DOPri2 also robustly decreased Dlt II‐induced analgesia. Interestingly, DAMGO‐induced analgesia was significantly increased by roscovitine and C11‐DOPri2. Concomitantly, in roscovitine‐treated rats the Dlt II‐induced ERK1/2 activation was decreased, whereas the DAMGO‐induced ERK1/2 activation was increased. An acute roscovitine treatment had no effect on Dlt II‐ or DAMGO‐induced analgesia.Conclusions and ImplicationsTogether, our results demonstrate that CDK5 is a key player in the regulation of DOP receptors in morphine‐ and CFA‐treated rats and that the regulation of DOP receptors by CDK5 is sufficient to modulate MOP receptor functions through an indirect process.
Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests
Authors: Tokumoto S. , Hamamoto Y. , Fujimoto K. , Yamaguchi E. , Okamura E. , Honjo S. , Ikeda H. , Wada Y. , Hamasaki A. , Koshiyama H. 
Published: January 2015

AbstractAimTo investigate the relationship between plasma betatrophin concentrations and insulin secretion capacity in people with Type 2 diabetes.MethodsGlucagon stimulation tests (1 mg) were performed in 70 people with Type 2 diabetes after an overnight fast. Plasma betatrophin concentrations were measured using an enzyme‐linked immunosorbent assay. Insulin secretion capacity was evaluated by measuring increments of C‐peptide concentration in response to glucagon stimulation, and creatinine clearance was determined by comparing creatinine concentrations in serum and 24‐h urine samples.ResultsPlasma betatrophin concentrations were positively correlated with duration of Type 2 diabetes (r = 0.34, P = 0.003), and negatively correlated with increments of C‐peptide concentration (r = 0.37, P = 0.001) and creatinine clearance (r = 0.37, P = 0.001). The correlation with increments of C‐peptide concentration remained significant after adjustment for age and duration of Type 2 diabetes (r = 0.25, P = 0.037). Multivariate analysis identified age and increments of C‐peptide concentration as independent factors associated with plasma betatrophin levels.ConclusionPlasma betatrophin levels inversely correlate with insulin secretion capacity, suggesting that betatrophin levels are regulated by insulin secretion capacity in humans.
Is iatrogenic sleep disturbance worth the effort in Type 1 diabetes?
Authors: Barnard K. D. , Oliver N. , Adolfsson P. , Aldred C. , Kerr D. 
Published: January 2015

What's new?

Chronic sleep disturbance is common for people with Type 1 diabetes.

Fear of nocturnal hypoglycaemia is causing frequent nocturnal blood glucose testing causing impaired sleep.

New strategies for the prevention of nocturnal hypoglycaemia need to be devised and tested.

The consequences of chronic sleep disturbance for people living with diabetes and their families needs to be appreciated by their clinical advisors.
Latent autoimmune diabetes of the adult: current knowledge and uncertainty
Authors: Laugesen E. , Østergaard J. A. , Leslie R. D. G. ,   the Danish Diabetes Academy Workshop and Workshop Speakers
Published: January 2015

AbstractPatients with adult‐onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)‐associated genetic risk and fewer diabetes‐associated autoantibodies compared with patients with childhood‐onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non‐insulin‐requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult‐onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood‐onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult‐onset diabetes for diabetes‐associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes.
Mass spectrometry evaluation of the hepcidin‐25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients
Authors: Karlsson Torbjörn 
Published: January 2015

AbstractIn this study, mass spectrometry was used to evaluate the hepcidin‐25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients using the absence of stainable bone marrow iron as the gold standard criterion for iron deficiency (ID). In addition, correlation coefficients for hepcidin‐25 vs. haematimetric and biochemical iron parameters, and C‐reactive protein (CRP) were determined. The optimal cut‐off for hepcidin‐25 was 31.5 ng/mL corresponding to a sensitivity and specificity of 82% and 95%, respectively, for ID. For ferritin, a sensitivity and specificity of 70% and 100%, respectively, correspond to an optimal cut‐off of 41.5 μg/L. Receiver operating characteristics curve analysis revealed that mass spectrometry analysis of hepcidin‐25 does not appear to be superior to ferritin in the diagnosis of ID in elderly anaemic patients with concurrent inflammation. Hepcidin‐25 shows a strong positive correlation with ferritin, and also correlates positively with CRP, in this patient population.
Hepcidin‐25 vs. conventional clinical biomarkers in the diagnosis of functional iron deficiency
Authors: Enko Dietmar , Wagner Helga , Kriegshäuser Gernot , Kimbacher Christine , Stolba Robert , Worf Elfriede , Halwachs‐Baumann Gabriele 
Published: January 2015

AbstractObjectivesAs hepcidin‐25 is considered as a key regulator of human iron homoeostasis, this study aimed to compare this parameter with conventional biomarkers and diagnostic tools of iron deficiency (ID).MethodsIn total, 233 hospitalised adult patients, who underwent routine blood testing for ID, were included. All subjects were investigated for hepcidin‐25, reticulocyte haemoglobin content (CHr), soluble transferrin receptor (sTfR)/log ferritin ratio (i.e. Thomas plot), sTfR, ferritin, transferrin saturation (TSAT), C‐reactive protein (CRP) and for complete blood cell count. Functional ID was defined as a CHr < 28 pg. Separate logistic regression models were calculated with all potential biomarkers to evaluate and compare the predictive performance with respect to functional ID in patients without (CRP ≤ 0.5 mg/dL) and with (CRP > 0.5 mg/dL) acute‐phase reaction, respectively.ResultsOne hundred seventeen patients with CRP > 0.5 mg/dL showed a distinctly higher hepcidin‐25 median value [35.60 (range: 4.27–80.03) ng/mL] as compared to 116 patients with CRP ≤ 0.5 mg/dL [18.55 (range: 3.77–73.01) ng/mL]. With respect to functional ID, sTfR/log ferritin ratio and sTfR were of better positive predictive value (PPV) (sTfR/log ferritin ratio: 58.33% and 70.83%; sTfR: 60.00% and 60.00%) than when compared to hepcidin‐25 (PPV: 37.74% and 42.86%) and ferritin (PPV: 27.54% and 46.15%) in both subgroups.ConclusionsThe sTfR/log ferritin ratio, as well as sTfR, were better predictors of functional ID in patients with and without acute‐phase reaction as compared to hepcidin‐25 and ferritin.
Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome
Authors: Therkildsen C. , Ladelund S. , Rambech E. , Persson A. , Petersen A. , Nilbert M. 
Published: January 2015

Background and purposeBrain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome.MethodsThe national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life‐time risk for brain tumors in Lynch syndrome, and the mismatch repair (MMR) status in all tumors available was evaluated.ResultsPrimary brain tumors developed in 41/288 families at a median age of 41.5 (range 2–73) years. Biallelic MMR gene mutations were linked to brain tumor development in childhood. The risk of brain tumors was significantly higher (2.5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6. Glioblastomas predominated (56%), followed by astrocytomas (22%) and oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of which showed MMR defects. None of these tumors showed immunohistochemical staining suggestive of the IDH1 R132H mutation.ConclusionIn Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects.