bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of nicotinic responses of bovine adrenal chromaffin cells by the protein kinase C inhibitor, Ro 31–8220
Authors: Marley Philip D. , Thomson Kerrie A.
Published: July 2012

The effects of the protein kinase C inhibitor, Ro 31–8220, on the responses of cultured bovine adrenal chromaffin cells to nicotine, phorbol 12,13‐dibutyrate (PDBu) and K+ have been investigated.

Tyrosine hydroxylase activity was measured in situ in intact cells by measuring 14CO2 evolved following the hydroxylation and rapid decarboxylation of [14C]‐tyrosine offered to the cells. Secretion of endogenous adrenaline and noradrenaline was measured by use of h.p.1.c. with electrochemical detection. Cyclic AMP levels were measured in cell extracts by RIA.

Ro 31–8220 produced a concentration‐dependent inhibition of 300 nM PDBu‐stimulated tyrosine hydroxylase activity with an IC50 of < 2 μm and complete inhibition at 10 μm. It had no effect on the responses to forskolin.

Ro 31–8220 produced a concentration‐dependent inhibition of 5 μm nicotine‐stimulated tyrosine hydroxylase activity, adrenaline and noradrenaline secretion and cellular cyclic AMP levels, with an IC50 of about 3 μm and complete inhibition by 10 μm. At concentrations up to 10 μm, Ro 31–8220 had little or no effect on the corresponding responses to 50 mM K+.

A structural analogue of Ro 31–8220, bisindolylmaleimide V, that lacks activity as a protein kinase C inhibitor, had no effect up to 10 μm on PDBu‐stimulated tyrosine hydroxylase activity or on nicotine‐stimulated cyclic AMP levels or noradrenaline secretion and only marginal inhibitory effects on nicotine‐stimulated tyrosine hydroxylase activity and adrenaline secretion.

A structurally related protein kinase C inhibitor, bisindolylmaleimide I, inhibited PDBu‐stimulated tyrosine hydroxylase activity with an IC50 of < 1 μm and complete inhibition by 3 μm, but had essentially no effect on nicotine stimulated tyrosine hydroxylase activity or catecholamine secretion.

The results suggest that Ro 31–8220 is not only a protein kinase C inhibitor but is also a potent inhibitor of nicotinic receptor responses in adrenal chromaffin cells by a mechanism unrelated to protein kinase C inhibition. The results are consistent with Ro 31–8220 being a nicotinic receptor antagonist.
P2x‐purinoceptors of myenteric neurones from the guinea‐pig ileum and their unusual pharmacological properties
Authors: Barajas‐López Carlos , Huizinga Jan D. , Collins Stephen M. , Gerzanich Vladimir , Espinosa‐Luna Rosa , Peres Andrea L.
Published: July 2012

Whole‐cell and outside‐out patch clamp recordings were used to characterize the physiological and pharmacological properties of the P2x‐purinoceptors of myenteric neurones from the guinea‐pig ileum.

Adenosine 5′‐triphosphate (ATP) and analogues (1–3000μm) evoked a rapid inward current in > 90% of all recorded neurones. The reversal potential of this current was dependent on the extracellular sodium concentration, at +14 ± 1.9, 0 ± 1.6 and −12 ± 1 mV for 166, 83 and 42 mM of sodium, respectively. The fast activation and inactivation of this current occurred even when guanosine 5′‐triphosphate (GTP) was omitted from the pipette solution or substituted with an equimolar concentration of guanosine 5′‐o‐[2‐thiotriphosphate] (GTP‐γ‐S). Single channel currents were observed when these outside‐out membrane patches were exposed to ATP (10–30 μm). These channels have a unitary conductance of about 17 picosiemens.

The rank‐order of potency of the agonists used to induce the whole‐cell currents was: ATP‐γ‐S = ATP = 2‐methylthio‐ATP (2‐Me‐S‐ATP) > > α,β‐methylene ATP = β,γ‐methylene ATP; adenosine and uridine 5′‐triphosphate (UTP) (up to 1 mM) were inactive.

Pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) (1–30μm) antagonized the effects of ATP (1 mM) with an IC50 of 4 μm. α,β‐Methylene ATP (100 μm) did not affect the ATP (30 μm)‐induced current. Cibacron Blue 3GA increased the ATP activated cationic current whereas Basilen Blue E‐3G had a very weak antagonistic effect (IC50 μ 3 mM). Suramin potentiated the currents induced by ATP through a mechanism that was independent of its inhibitory effect on ectonucleotidase activity, as suramin also potentiated the effect of α,β‐methylene ATP (an ATP analogue that is resistant to nucleotidases).

In conclusion, the myenteric P2x‐purinoceptor shares some properties with other purinoceptors in particular with the P2times4‐ and P2X6‐purinoceptors. This receptor has also some unusual pharmacological properties suggesting that myenteric neurones express a novel subtype of P2x‐purinoceptors. The properties of this receptor, however, might be a result of the combination of two or more of the homomeric purinoceptors so far characterized.
Effects of competitive and noncompetitive antagonists of the N‐methyl‐D‐aspartate receptor on the analgesic action of δ1‐ and δ2‐opioid receptor agonists in mice
Authors: Bhargava Hemendra N. , Zhao Guo‐Min
Published: July 2012

The effects of MK‐801, a noncompetitive antagonist of the N‐methyl‐D‐aspartate (NMDA) receptor and LY 235959, a competitive antagonist of the NMDA receptor on the analgesic actions of [D‐Pen2, D‐Pen5]enkephalin (DPDPE) and [D‐Ala2, Glu4] deltorphin II (deltorphin II), the putative δ1‐ and δ2‐opioid receptor agonists, respectively, were determined in the male Swiss‐Webster mice.

Intracerebroventricular administration of DPDPE or deltorphin II produced analgesia. MK‐801 administered intraperitoneally 10 min before the injection of DPDPE or deltorphin II, dose‐dependently antagonized the analgesic actions of both drugs.

LY 235959 also dose‐dependently antagonized the analgesic actions of DPDPE and deltorphin II.

The effects of MK‐801 and LY 235959 on the binding of [3H]‐DPDPE to mouse brain membranes were also determined. Neither of the NMDA receptor antagonists had any effect on the binding of [3H]‐DPDPE.

It is concluded that competitive and noncompetitive antagonists of the NMDA receptor antagonize the analgesic action of δ1‐ and δ2‐opioid receptor agonists and that such effects are not mediated via a direct interaction with brain δ‐opioid receptors.
Nociceptin receptor coupling to a potassium conductance in rat locus coeruleus neurones in vitro
Authors: Connor Mark , Vaughan Christopher W. , Chieng Billy , Christie Macdonald J.
Published: July 2012

In this study we have examined the effects of nociceptin, an endogenous ligand for the opioid‐like receptor ORL1, on the membrane properties of rat locus coeruleus (LC) neurones in vitro, using intracellular and whole cell patch clamp recording.

When locus coeruleus neurones were voltage clamped to −60 mV, application of nociceptin caused an outward current in all cells examined (n = 49), with an EC50 of 90 nM. Neither the potency nor the maximal effect of nociceptin was altered in the presence of the peptidase inhibitors, bestatin (20 μm) or thiorphan (2 μm).

The outward currents caused by nociceptin in 2.5 mM extracellular K+ reversed polarity at −123 mV, more negative than the predicted K+ reversal potential of −105 mV. Increasing extracellular K+ to 6.5 mM resulted in a shift of the reversal potential of +25 mV, a shift consistent with a K+ conductance. The conductance activated by nociceptin showed mild inward rectification.

Application of a high concentration of nociceptin (3 μm) occluded the current produced by simultaneous application of high concentrations of Met‐enkephalin (10 μm), (3 μm) somatostatin and UK 14304 (3 μm), indicating that nociceptin activated the same conductance as μ‐opioid and somatostatin receptors and α2‐adrenoceptors.

The actions of nociceptin were weakly antagonized by the opioid antagonist, naloxone, with pKb′s estimated from 2 cells of −4.23 and −4.33. The μ‐opioid antagonist, CTAP (D‐Phe‐Cys‐Tyr‐D‐Trp‐Arg‐Pen‐Thr‐NH2, 1 μm), the opioid antagonist, nalorphine (30 μm), or the somatostatin antagonist, CPP (cyclo(7‐aminoheptanoyl‐Phe‐D‐Tip‐Lys‐Thr[Bzl]) 3 μm) did not affect the nociceptin‐induced current.

Dynorphin A (3 μm), another putative endogenous ligand for ORL1, caused a robust outward current in locus coeruleus neurones that was, however, completely antagonized by moderate concentrations of naloxone (300 nM‐1 μm).

Continuous application of nociceptin (3 μm) resulted in a decrease of the outward current to a steady level of 70% of the maximum response with a t1/2 of 120s. Desensitization was largely homologous because simultaneous application of Met‐enkephalin (30 μm) during the desensitized period of the nociceptin response resulted in an outward current that was 92% of control responses to Met‐enkephalin in the same cells. Conversely, continuous application of Met‐enkephalin (30 μm) resulted in a decrease of Met‐enkephalin current to a steady level that was 54% of the initial current. During this desensitized period application of nociceptin (3 μm) resulted in a current that was 78% of the control responses to nociceptin in the same cells.

Thus nociceptin potently activates an inwardly rectifying K+ conductance in locus coeruleus neurones, with a pharmacological profile consistent with activation of the ORL1 receptor. Dynorphin A does not appear to be a ligand for ORL1 in rat locus coeruleus neurones.
Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats
Authors: Blandina P. , Giorgetti M. , Bartolini L. , Cecchi M. , Timmerman H. , Leurs R. , Pepeu G. , Giovannini M.G.
Published: July 2012

The effects of histamine and agents acting at histamine receptors on spontaneous and 100 mM K+‐evoked release of acetylcholine, measured by microdialysis from the cortex of freely moving rats, and on cognitive tests are described.

Local administration of histamine (0.1–100 μm) failed to affect spontaneous but inhibited 100 mM K+‐stimulated release of acetylcholine up to about 50%. The H3 receptor agonists (R)‐α‐methylhistamine (RAMH) (0.1–10 μm), imetit (0.01–10 μm) and immepip (0.01–10 μm) mimicked the effect of histamine.

Neither 2‐thiazolylethylamine (TEA), an agonist showing some selectivity for H1 receptors, nor the H2 receptor agonist, dimaprit, modified 100 mM K+‐evoked release of acetylcholine.

The inhibitory effect of 100 μm histamine was completely prevented by the highly selective histamine H3 receptor antagonist, clobenpropit but was resistant to antagonism by triprolidine and cimetidine, antagonists at histamine H1 and H2 but not H3 receptors.

The H3 receptor‐induced inhibition of K+‐evoked release of acetylcholine was fully sensitive to tetrodotoxin (TTX).

The effects of intraperitoneal (i.p.) injection of imetit (5 mg kg−1) and RAMH (5 mg kg−1) were tested on acetylcholine release and short term memory paradigms. Both drugs reduced 100 mM K+‐evoked release of cortical acetylcholine, and impaired object recognition and a passive avoidance response.

These observations provide the first evidence of a regulatory role of histamine H3 receptors on cortical acetylcholine release in vivo. Moreover, they suggest a role for histamine in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.
A New Transcutaneous Bidirectional Communication for Monitoring Implanted Artificial Heart Using the Human Body as a Conductive Medium
Authors: Okamoto Eiji , Kato Yoshikuni , Seino Kazuyuki , Miura Hidekazu , Shiraishi Yasuyuki , Yambe Tomoyuki , Mitamura Yoshinori
Published: July 2012

A transcutaneous communication system (TCS) is a key technology for monitoring and controlling artificial hearts and other artificial organs in the body. In this study, we developed a new TCS that uses the human body as a conductive medium. Direct data exchange provides a higher level of communication security compared to that of wireless methods without physical constraints such as an external wire. The external and internal units of the new TCS each consist mainly of a data transmitter and a data receiver. The data transmitter has an amplitude shift keying (ASK) modulator (carrier frequencies: 4 and 10 MHz) and an electrode. The ASK‐modulated data current is led into the body through the electrode, and it flows back to the energy source through the body, the data receiver, and the earth ground that includes all conductors and dielectrics in the environment that are in close proximity to the patient. Performance of the TCS was evaluated by a communication test on the surface of the human body and in an animal experiment using a goat. The TCS was able to transmit data concurrently for 4 weeks between everywhere on the surface of the body and everywhere inside the body under full‐duplex communication at a transmission rate of 115 kbps. The power consumption of each TCS unit was 125 mW with an ASK‐modulated current of 7 mA (root‐mean‐square). While further study is required to secure its safety, the newly developed TCS has promise to be a next‐generation transcutaneous communication device.
Quality of life in young adults who underwent resective surgery for epilepsy in childhood
Authors: Elliott Irene , Kadis Darren S. , Lach Lucyna , Olds Janet , McCleary Lynn , Whiting Sharon , Snyder Thomas , Smith Mary Lou
Published: July 2012

Purpose:  This study investigated quality of life (QOL) in young adults who had undergone epilepsy surgery before the age of 16 years. The contribution to QOL of seizure status in the prior year, sex, number of antiepileptic drugs, and mood were evaluated.

Methods:  Sixty‐nine young adults who had undergone surgery were subdivided into those who were seizure‐free in the past year (n = 38) and those who had seizures (n = 31) in that time. A nonsurgical comparison group of young adults (n = 29) with childhood‐onset medically intractable epilepsy was also studied. All groups completed measures of QOL and mood.

Key Findings:  After accounting for mood, sex, and number of antiepileptic drugs, the seizure‐free group reported better cognitive and physical function and overall QOL, experienced less seizure worry, and had better self‐perception. Mood was the most consistently predictive covariate, and was independently predictive of many aspects of QOL.

Significance:  Seizure freedom associated with surgery in childhood is associated with improved QOL in certain domains. Findings highlight the importance of mood in determining self‐perception of QOL.
Steady‐state plasma and cerebrospinal fluid pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine in healthy volunteers
Authors: Nunes Teresa , Rocha José Francisco , Falcão Amílcar , Almeida Luis , Soares‐da‐Silva Patrício
Published: July 2012

Purpose:  To evaluate the pharmacokinetics and tolerability of once‐daily eslicarbazepine acetate (ESL) and twice‐daily oxcarbazepine (OXC) and their metabolites in cerebrospinal fluid (CSF) and plasma following repeated oral administration.

Methods:  Single‐center, open‐label, randomized, parallel‐group study in healthy volunteers. Volunteers in ESL group (n = 7) received 600 mg on days 1–3 and 1,200 mg on days 4–9, once daily. Volunteers in the OXC group (n = 7) received 300 mg on days 1–3 and 600 mg on days 4–9, twice daily. Plasma and CSF sampling was performed following the last dose.

Key Findings:  Eslicarbazepine was the major drug entity in plasma and CSF, accounting for, respectively, 93.84% and 91.96% of total exposure in the ESL group and 78.06% and 76.42% in the OXC group. The extent of exposure to drug entities R‐licarbazepine and oxcarbazepine was approximately four‐fold higher with OXC as compared with ESL. There was relatively little fluctuation from peak‐to‐trough (ratio) in the CSF for both eslicarbazepine (ESL = 1.5; OXC = 1.2) and R‐licarbazepine (ESL = 1.2; OXC = 1.2). In contrast, oxcarbazepine showed larger differences between peak and trough (ESL = 3.1; OXC = 6.4). A total of 84 and 24 treatment‐emergent adverse events (TEAEs) were reported with OXC and ESL, respectively.

Significance:  In comparison to OXC, administration of ESL resulted in more eslicarbazepine, less R‐licarbazepine, and less oxcarbazepine in plasma and CSF, which may correlate with the tolerability profile reported with ESL. The smaller peak‐to‐trough fluctuation of eslicarbazepine in CSF (a measure of sustained delivery to the brain) than in plasma supports once‐daily dosing of ESL.
Decreased viability and absence‐like epilepsy in mice lacking or deficient in the GABAA receptor α1 subunit
Authors: Arain Fazal M. , Boyd Kelli L. , Gallagher Martin J.
Published: July 2012

Autosomal dominant mutations S326fs328X and A322D in the GABAA receptor α1 subunit are associated with human absence epilepsy and juvenile myoclonic epilepsy, respectively. Because these mutations substantially reduce α1 subunit protein expression in vitro, it was hypothesized that they produce epilepsy by causing α1 subunit haploinsufficiency. However, in a mixed background strain of mice, α1 subunit deletion does not reduce viability or cause visually apparent seizures; the effects of α1 subunit deletion on electroencephalography (EEG) waveforms were not investigated. Here, we determined the effects of α1 subunit loss on viability, EEG spike‐wave discharges and seizures in congenic C57BL/6J and DBA/2J mice. Deletion of α1 subunit caused strain‐ and sex‐dependent reductions in viability. Heterozygous mice experienced EEG discharges and absence‐like seizures within both background strains, and exhibited a sex‐dependent effect on the discharges and viability in the C57BL/6J strain. These findings suggest that α1 subunit haploinsufficiency can produce epilepsy and may be a major mechanism by which the S326fs328X and A322D mutations cause these epilepsy syndromes.
Pricing Mortality Securities With Correlated Mortality Indexes
Authors: Lin Yijia , Liu Sheen , Yu Jifeng
Published: July 2012

ABSTRACT

This article proposes a stochastic model, which captures mortality correlations across countries and common mortality shocks, for analyzing catastrophe mortality contingent claims. To estimate our model, we apply particle filtering, a general technique that has wide applications in non‐Gaussian and multivariate jump‐diffusion models and models with nonanalytic observation equations. In addition, we illustrate how to price mortality securities with normalized multivariate exponential titling based on the estimated mortality correlations and jump parameters. Our results show the significance of modeling mortality correlations and transient jumps in mortality security pricing.
Uncertainty about Government Policy and Stock Prices
Authors: PÁSTOR L̆UBOS̆ , VERONESI PIETRO
Published: July 2012

We analyze how changes in government policy affect stock prices. Our general equilibrium model features uncertainty about government policy and a government whose decisions have both economic and noneconomic motives. The model makes numerous empirical predictions. Stock prices should fall at the announcement of a policy change, on average. The price decline should be large if uncertainty about government policy is large, and also if the policy change is preceded by a short or shallow economic downturn. Policy changes should increase volatilities and correlations among stocks. The jump risk premium associated with policy decisions should be positive, on average.
Why Are U.S. Stocks More Volatile?
Authors: BARTRAM SÖHNKE M. , BROWN GREGORY , STULZ RENÉ M.
Published: July 2012

U.S. stocks are more volatile than stocks of similar foreign firms. A firm's stock return volatility can be higher for reasons that contribute positively (good volatility) or negatively (bad volatility) to shareholder wealth and economic growth. We find that the volatility of U.S. firms is higher mostly because of good volatility. Specifically, stock volatility is higher in the United States because it increases with investor protection, stock market development, new patents, and firm‐level investment in R&D. Each of these factors is related to better growth opportunities for firms and better ability to take advantage of these opportunities.
Mutual Fund Tax Clienteles
Authors: SIALM CLEMENS , STARKS LAURA
Published: July 2012

Mutual funds are held by investors in taxable and tax‐qualified retirement accounts. We investigate whether the characteristics, investment strategies, and performance of mutual funds held by these diverse tax clienteles differ. Examining both mutual fund distributions and mutual fund holdings, we find that funds held primarily by taxable investors choose investment strategies that result in lower tax burdens than funds held primarily in tax‐qualified accounts. Despite these differences, we find no evidence that any investment constraints that may arise from these tax‐efficient investment strategies result in performance differences between funds held by different tax clienteles.
Are Overconfident CEOs Better Innovators?
Authors: HIRSHLEIFER DAVID , LOW ANGIE , TEOH SIEW HONG
Published: July 2012

Previous empirical work on adverse consequences of CEO overconfidence raises the question of why firms hire overconfident managers. Theoretical research suggests a reason: overconfidence can benefit shareholders by increasing investment in risky projects. Using options‐ and press‐based proxies for CEO overconfidence, we find that over the 1993–2003 period, firms with overconfident CEOs have greater return volatility, invest more in innovation, obtain more patents and patent citations, and achieve greater innovative success for given research and development expenditures. However, overconfident managers achieve greater innovation only in innovative industries. Our findings suggest that overconfidence helps CEOs exploit innovative growth opportunities.
Value of Dynamic Substrate Mapping to Identify the Critical Diastolic Pathway in Postoperative Ventricular Reentrant Tachycardias After Surgical Repair of Tetralogy of Fallot
Authors: SCHNEIDER HEIKE E. , SCHILL MANFRED , KRIEBEL THOMAS , PAUL THOMAS
Published: July 2012

Characterization of the Critical Isthmus in VT in TOF. Introduction: The complexity of postoperative ventricular reentrant tachycardias may limit success of catheter ablation. The objective of this analysis was to compare the usefulness of dynamic substrate mapping (DSM) versus color‐coded isopotential mapping of the noncontact mapping system for the identification of the critical diastolic pathway of postoperative ventricular reentrant tachycardias (VT) after surgical repair of tetralogy of Fallot (TOF).

Methods:
Postoperative VT had been studied applying isopotential maps with the noncontact mapping system EnSite in 7 patients, and radiofrequency current lesion lines had been applied across the shortest isthmus to target during sinus rhythm. Data of the noncontact mapping system were reanalyzed applying the DSM algorithm. For DSM, a 2‐Hz filter and color settings between 0 mV and 50% of peak negative voltage (PNV) with autofocus turned off were used. DSM was initially applied over the QRS complex duration during sinus rhythm. Abnormal myocardium was defined as <35–40% of PNV. DSM was subsequently applied to ventricular diastole during the final 33% of VT cycle length. Areas with >70% of PNV within this time frame were to identify the critical diastolic pathway.

Results:
Applying DSM, the critical diastolic pathway of the VT was identified in all 7 patients that corresponded to the regions targeted for ablation.

Conclusion:
By focusing the time reference to electrical diastole, when the VT wavefront is moving through the low‐voltage area, the region of greatest relative voltage could be highlighted, which corresponded to the diastolic pathway. (J Cardiovasc Electrophysiol, Vol. 23, pp. 930‐937, September 2012)
Physical activity and self‐reported symptoms of insomnia, restless legs syndrome, and depression: The comprehensive dialysis study
Authors: Anand Shuchi , Johansen Kirsten L. , Grimes Barbara , Kaysen George A. , Dalrymple Lorien S. , Kutner Nancy G. , Chertow Glenn M.
Published: July 2012

Symptoms of sleep and mood disturbances are common among patients on dialysis and are associated with significant decrements in survival and health‐related quality of life. We used data from the Comprehensive Dialysis Study (CDS) to examine the association of self‐reported physical activity with self‐reported symptoms of insomnia, restless legs syndrome (RLS), and depression in patients new to dialysis. The CDS collected data on physical activity, functional status, and health‐related quality of life from 1678 patients on either peritoneal (n = 169) or hemodialysis (n = 1509). The Human Activity Profile was used to measure self‐reported physical activity. Symptoms were elicited in the following manner: insomnia using three questions designed to capture difficulty in initiating or maintaining sleep, RLS using three questions based on the National Institutes of Health workshop, and depression using the two‐item Patient Health Questionnaire. We obtained data on symptoms of insomnia and depression for 1636, and on symptoms of RLS for 1622 (>98%) patients. Of these, 863 (53%) reported one of three insomnia symptoms as occurring at a persistent frequency. Symptoms of RLS and depression occurred in 477 (29%) and 451 (28%) of patients, respectively. The Adjusted Activity Score of the Human Activity Profile was inversely correlated with all three conditions in models adjusting for demographics, comorbid conditions, and laboratory variables. Sleep and mood disturbances were commonly reported in our large, diverse cohort of patients new to dialysis. Patients who reported lower levels of physical activity were more likely to report symptoms of insomnia, RLS, and depression.
Contact allergy to local anaesthetics–value of patch testing with a caine mix in the baseline series
Authors: Brinca Ana , Cabral Rita , Gonçalo Margarida
Published: July 2012

Background Contact allergy to local anaesthetics is relatively common. Patch testing with benzocaine in the European baseline series is recommended for diagnosis, even though a caine mix has been previously suggested to be superior.

Objectives To assess the frequency and patterns of contact allergy to local anaesthetics by using a caine mix (benzocaine, tetracaine, and cinchocaine) in the baseline series, and evaluate its efficiency as compared with benzocaine alone.

Methods We reviewed the results of 2736 patch tests performed between 2000 and 2010, identifying patients with positive reactions to caine mix or to one of seven local anaesthetics.

Results One hundred and twelve patients (4.1%) had at least one allergic reaction to local anaesthetics; 86 were tested with all seven local anaesthetics, resulting in 71 reactions in 53 patients. Cinchocaine gave the most reactions (50.7%); these occurred as a single reaction in 83.3% of patients, mostly with current or past relevance (97%). Benzocaine represented 22.5% of reactions, many of which were non‐relevant (44%) or resulting from cross‐reactions with para‐compounds.

Conclusions Almost 70% of allergic reactions to local anaesthetics would have been missed if benzocaine had been used as a screening allergen. This study supports a recommendation to replace benzocaine with a caine mix containing cinchocaine in the baseline patch test series.
Comparison of CCL28, interleukin‐8, interleukin‐1β and tumor necrosis factor‐alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis
Authors: Ertugrul A. S. , Sahin H. , Dikilitas A. , Alpaslan N. , Bozoglan A.
Published: July 2012

Background and Objective:  Cytokines produced by various cells are strong local mediators of inflammation. Mucosa‐associated epithelial chemokine (CCL28), interleukin‐8 (IL‐8), interleukin‐1beta (IL‐1β) and tumor necrosis factor‐alpha (TNF‐α) are major cytokines that play important roles in the periodontal inflammatory process. In this study we aimed to compare the levels of CCL28, IL‐8, IL‐1β and TNF‐α in the gingival crevicular fluid of both periodontally healthy subjects and in subjects diagnosed with gingivitis, chronic periodontitis and generalized aggressive periodontitis.

Material and Methods:  A total of 84 subjects participated in the study: 21 subjects had gingivitis, 21 subjects had chronic periodontitis, 21 subjects had generalized aggressive periodontitis and 21 were periodontally healthy. The levels of CCL28, IL‐8, IL‐1β and TNF‐α were analyzed using enzyme‐linked immune sorbent assay (ELISA).

Results:  The total levels of CCL28 and IL‐8 in the gingival crevicular fluid of the generalized aggressive periodontitis group (324.74 ± 42.62 pg/30 s, 487.62 ± 49.21 pg/30 s) were significantly higher than those of the chronic periodontitis group (268.81 ± 28.64 pg/30 s, 423.65 ± 35.24 pg/30 s), the gingivitis group (146.35 ± 17.46 pg/30 s, 310.24 ± 48.20 pg/30 s) and the periodontally healthy group (92.46 ± 22.04 pg/30 s, 148.41 ± 24.64 pg/30 s). Similarly, the total levels of IL‐1β and TNF‐α in the generalized aggressive periodontitis group (110.23 ± 9.20 pg/30 s, 1284.46 ± 86.32 pg/30 s) were significantly higher than those in the chronic periodontitis group (423.65 ± 35.24 pg/30 s, 82.64 ± 9.12 pg/30 s), the gingivitis group (52.10 ± 7.15 pg/30 s, 824.24 ± 44.68 pg/30 s) and the periodontally healthy group (36.44 ± 8.86 pg/30 s, 628.26 ± 34.61 pg/30 s).

Conclusion:  CCL28, IL‐8, IL‐1β and TNF‐α may play key roles in the host response to inflammation in periodontal diseases. As the severity of periodontal diseases increases, destruction of periodontal tissues also increases. Inflammation is one among many factors that trigger periodontal tissue destruction. Identification of the mediators that influence the development and progression of inflammation in periodontal diseases may be very important in understanding the prognoses of periodontal diseases.
Upper‐body kinematics in team‐handball throw, tennis serve, and volleyball spike
Authors: Wagner H. , Pfusterschmied J. , Tilp M. , Landlinger J. , von Duvillard S. P. , Müller E.
Published: July 2012

Overarm movements are essential skills in many different sport games; however, the adaptations to different sports are not well understood. The aim of the study was to analyze upper‐body kinematics in the team‐handball throw, tennis serve, and volleyball spike, and to calculate differences in the proximal‐to‐distal sequencing and joint movements. Three‐dimensional kinematic data were analyzed via the Vicon motion capturing system. The subjects (elite players) were instructed to perform a team‐handball jump throw, tennis serve, and volleyball spike with a maximal ball velocity and to hit a specific target. Significant differences (P < 0.05) between the three overarm movements were found in 17 of 24 variables. The order of the proximal‐to‐distal sequencing was equal in the three analyzed overarm movements. Equal order of the proximal‐to‐distal sequencing and similar angles in the acceleration phase suggest there is a general motor pattern in overarm movements. However, overarm movements appear to be modifiable in situations such as for throwing or hitting a ball with or without a racket, and due to differences at takeoff (with one or two legs).
Closeness and separation in neonatal intensive care
Authors: Flacking Renée , Lehtonen Liisa , Thomson Gill , Axelin Anna , Ahlqvist Sari , Moran Victoria Hall , Ewald Uwe , Dykes Fiona ,   the SCENE group
Published: July 2012

In this paper, we highlight the need for acknowledging the importance and impact of both physical and emotional closeness between the preterm infant and parent in the neonatal intensive care unit. Physical closeness refers to being spatially close and emotional closeness to parental feelings of being emotionally connected to the infant (experiencing feelings of love, warmth and affection). Through consideration of the literature in this area, we outline some of the reasons why physical closeness and emotional closeness are crucial to the physical, emotional and social well‐being of both the infant and the parent. These include positive effects on infant brain development, parent psychological well‐being and on the parent–infant relationship. The influence of the neonatal unit environment and culture on physical and emotional closeness is also discussed.

Conclusions:  Culturally sensitive care practices, procedures and the physical environment need to be considered to facilitate parent–infant closeness, such as through early and prolonged skin‐to‐skin contact, family‐centred care, increased visiting hours, family rooms and optimization of the space on the units. Further research is required to explore factors that facilitate both physical and emotional closeness to ensure that parent–infant closeness is a priority within neonatal care.
Food preservative potential of gassericin A‐containing concentrate prepared from cheese whey culture supernatant of Lactobacillus gasseri LA39
Authors: NAKAMURA Kiyoshi , ARAKAWA Kensuke , KAWAI Yasushi , YASUTA Narimi , CHUJO Takahiro , WATANABE Masamichi , IIOKA Hiroyuki , TANIOKA Masashi , NISHIMURA Junko , KITAZAWA Haruki , TSURUMI Koichi , SAITO Tadao
Published: July 2012

Gassericin A (GA) is a circular bacteriocin produced by Lactobacillus gasseri LA39. In this study, GA‐containing concentrate was prepared using a cross‐flow membrane filtration device (30 kDa cut‐off) from the culture supernatant of Lb. gasseri LA39 cultivated in a cheese whey‐based food‐grade medium. The bacteriocin activity titer in the concentrate was 16 times as high as that of the culture supernatant and was completely maintained through each incubation at 4°C for 3 months, 37°C for 2 months, 60°C for 5 h, and 100°C for 30 min. The GA‐containing concentrate was used with glycine powder to make custard creams, and then four representative strains of custard cream spoilage bacteria (Bacillus cereus, Lactococcus lactis subsp. lactis, Achromobacter denitrificans and Pseudomonas fluorescens) were individually inoculated at c. 103 colony forming units/g in the custard creams. Throughout 30 days of incubation at 30°C, all of the inoculated bacteria were completely inhibited by the combination of 5% (w/w) of the GA‐containing concentrate and 0.5% (w/w) glycine. This is the first highly practical application of GA to foods as a biopreservative, and the concentration method and the bacteriocin concentrate would contribute to biopreservation of several foods.
The effects of dietary hesperidin supplementation on lamb performance and meat characteristics
Authors: SIMITZIS Panagiotis E. , ILIAS‐DIMOPOULOS Vagelis , CHARISMIADOU Maria A. , BINIARI Eugenia E. , DELIGEORGIS Stelios G.
Published: July 2012

An experiment was conducted to examine the effects of supplementing feed with hesperidin or α‐tocopheryl acetate on lambs' growth performance, carcass and meat characteristics. Sixteen male lambs were randomly assigned to four groups. One of the groups served as control and was given a basal diet, whereas the other three groups were given the same diet further supplemented with hesperidin at 1500 mg/kg, or hesperidin at 3000 mg/kg, or α‐tocopheryl acetate at 200 mg/kg. At the end of the experiment, lambs were fasted, weighed and slaughtered. After overnight chilling, samples of Longissimus thoracis muscle were taken and were used for meat quality evaluation. No significant differences were observed in final body weight, body weight gain and organ weights among the four groups. pH, color, water‐holding capacity, shear force values and intramuscular fat concentration of Longissimus thoracis muscle were also not significantly influenced by the dietary treatments. Measurement of lipid oxidation values showed that hesperidin supplementation positively influenced meat antioxidant properties during refrigerated storage.
Dual‐specificity MAP kinase phosphatases (MKPs)
Authors: Caunt Christopher J. , Keyse Stephen M.
Published: July 2012

Dual‐specificity MAP kinase phosphatases (MKPs) provide a complex negative regulatory network that acts to shape the duration, magnitude and spatiotemporal profile of MAP kinase activities in response to both physiological and pathological stimuli. Individual MKPs may exhibit either exquisite specificity towards a single mitogen‐activated protein kinase (MAPK) isoform or be able to regulate multiple MAPK pathways in a single cell or tissue. They can act as negative feedback regulators of MAPK activity, but can also provide mechanisms of crosstalk between distinct MAPK pathways and between MAPK signalling and other intracellular signalling modules. In this review, we explore the current state of knowledge with respect to the regulation of MKP expression levels and activities, the mechanisms by which individual MKPs recognize and interact with different MAPK isoforms and their role in the spatiotemporal regulation of MAPK signalling.
IPASS: A Study on the Tolerability and Effectiveness of Injectable Testosterone Undecanoate for the Treatment of Male Hypogonadism in a Worldwide Sample of 1,438 Men
Authors: Zitzmann Michael , Mattern Andreas , Hanisch Jens , Gooren Louis , Jones Hugh , Maggi Mario
Published: July 2012

Introduction

Morbidity/mortality is higher in men with below-normal serum testosterone. Restoring testosterone to normal is beneficial.

Aim

Assessment of safety and effectiveness of injectable long-acting testosterone undecanoate (TU) in hypogonadal men in daily clinical practice.

Methods

An international, multicenter, one-arm, prospective observational study in 23 countries.

Main Outcome Measures

Parameters of erectile function, libido, vigor/vitality, mood, and ability to concentrate assessed by physician interview using items and five-point Likert scales. Physical and circulatory parameters as well as hematocrit, prostate-specific antigen (PSA) levels, glucose control, and lipid profiles.

IPASS

An International, multicenter, Post-Authorisation (after authorized use in respective country) Surveillance Study on long-acting-intramuscular TU conducted at 155 centers in 23 countries in Europe, Asia, Latin America, and Australia. Patients received up to five TU injections during 9–12 months.

Results

Of the 1,493 hypogonadal men enrolled, 1,438 (aged 49.2 ± 13.9 years) having received 6,333 injections were analyzed. Scores of mental and psychosexual functions (libido, vigor, overall mood, and ability to concentrate) improved markedly, while mean waist circumference decreased from 100 to 96 cm. Blood pressure and lipid parameters were altered in a favorable and significant manner. After four TU injection intervals, the percentage of patients with “low” or “very low” levels of sexual desire/libido decreased from 64% at baseline to 10%; moderate, severe, or extremely severe erectile dysfunction decreased from 67% to 19%. At the last observation, 89% of patients were “satisfied” or “very satisfied” with TU therapy. Adverse events and adverse drug reactions (ADRs) occurred in 12% and 6% of patients, respectively, mostly mild to moderate. The most common ADRs were increase in hematocrit, increase in PSA, and injection site pain (all <1%). No case of prostate cancer was observed.

Conclusion

In this largest worldwide sample of hypogonadal men, injectable long-acting TU was effective and well tolerated.
Observations on torquaratorid acorn worms (Hemichordata, Enteropneusta) from the North Atlantic with descriptions of a new genus and three new species
Authors: Priede Imants G. , Osborn Karen J. , Gebruk Andrey V. , Jones Dan , Shale David , Rogacheva Antonina , Holland Nicholas D.
Published: July 2012

Enteropneusts in the family Torquaratoridae were imaged using still and video cameras in the deep North Atlantic and then collected by remotely operated vehicles. From this material, we describe Yoda purpurata n. gen, n. sp., Tergivelum cinnabarinum n. sp., and Allapasus isidis n. sp. Individuals of the first two species were browsing completely exposed on the sea floor, whereas the specimen of the last species was encountered floating ~1 m above the sea floor. Living specimens of Y. purpurata were 12–19 cm long and had a dark reddish‐purple proboscis, collar, and genital wings (folded dorsally over the anterior region of the trunk). Members of this species were hermaphrodites (the first ever discovered in the phylum Hemichordata), with numerous separate testes and ovaries in the genital wings. Living specimens of T. cinnabarinum were 12–26 cm long and had a cinnabar‐colored proboscis, collar, and back veils (arising from the anterior region of the trunk); sexes were separate, and body shape and internal morphology closely resemble those of its brown congener, T. baldwinae, from the eastern Pacific. The only specimen of A. isidis collected was a male 13 cm long and pale yellow when alive. Its body shape was proportionally shorter and broader than that of its orange congener, A. aurantiacus, from the eastern Pacific, but the internal anatomy of the two species is virtually identical. [Correction made after online publication August 21, 2012 to correct species name in preceding sentence.]
The Need for Sector‐Specific Materiality and Sustainability Reporting Standards
Authors: Eccles Robert G. , Krzus Michael P. , Rogers Jean , Serafeim George
Published: July 2012

The market continues to show growing interest in how well companies are performing across a broad range of environmental, social, and governance (ESG) dimensions. Partly as a result, the companies themselves are paying more attention to these performance dimensions, how they contribute to financial performance, and how to evaluate tradeoffs that arise.

One of the greatest challenges facing both investors and companies in using ESG performance information is the absence of standards. Another challenge is knowing which of the many ESG dimensions are most material for a company in terms of creating value for shareholders and stakeholders over the long term. The authors argue that materiality and reporting standards must be developed on a sector‐by‐sector basis, and that failure to do so will result in inconsistent and even misleading disclosures.

The authors illustrate this with the case of climate change. The SEC has already issued interpretive guidance on climate change disclosures, making it quite clear that existing regulations require companies to report on material effects of climate change, from both an upside and downside perspective. Based on an analysis of 10K filings in six industries, the authors show that, even within a given industry, there is substantial variation in reporting among companies that ranges from no disclosure, to boilerplate disclosure, industry‐specific interpretation, and the use of quantitative metrics. After providing further detail on this by looking at the airline and utilities industries, the authors conclude by offering a methodology for defining material ESG issues on a sector‐by‐sector basis that could provide the basis for developing key performance indicators.
Sleep-Disordered Breathing in Acute Ischemic Stroke and Transient Ischemic Attack: Effects on Short- and Long-Term Outcome and Efficacy of Treatment with Continuous Positive Airways Pressure – Rationale and Design of the SAS Care Study
Authors: Cereda Carlo W. , Petrini Liliane , Azzola Andrea , Ciccone Alfonso , Fischer Urs , Gallino Augusto , Györik Sandor , Gugger Matthias , Mattis Johannes , Lavie Lena , Limoni Costanzo , Nobili Lino , Manconi Mauro , Ott Sebastian , Pons Marco , Bassetti Claudio L.
Published: July 2012

Objectives

Sleep-disordered breathing represents a risk factor for cardiovascular morbidity and mortality and negatively affects short-term and long-term outcome after an ischemic stroke or transient ischemic attack. The effect of continuous positive airways pressure in patients with sleep-disordered breathing and acute cerebrovascular event is poorly known. The SAS CARE 1 study assesses the effects of sleep-disordered breathing on clinical evolution, vascular functions, and markers within the first three-months after an acute cerebrovascular event. The SAS CARE 2 assesses the effect of continuous positive airways pressure on clinical evolution, cardiovascular events, and mortality as well as vascular functions and markers at 12 and 24 months after acute cerebrovascular event.

Methods

SAS CARE 1 is an open, observational multicenter study in patients with acute cerebrovascular event acutely admitted in a stroke unit: a sample of 200 acute cerebrovascular event patients will be included. Vascular functions and markers (blood pressure, heart rate variability, endothelial function by peripheral arterial tonometry and specific humoral factors) will be assessed in the acute phase and at three-months follow-up. SAS CARE 2 will include a sample of patients with acute cerebrovascular event in the previous 60–90 days. After baseline assessments, the patients will be classified according to their apnea hypopnea index in four arms: non-sleep-disordered breathing patients (apnea hypopnea index <10), patients with central sleep-disordered breathing, sleepy patients with obstructive apnea hypopnea index ≥20, which will receive continuous positive airways pressure treatment, nonsleepy patients with obstructive sleep-disordered breathing (apnea hypopnea index ≥20), which will be randomized to receive continuous positive airways pressure treatment or not.

Conclusions

The SAS CARE study will improve our understanding of the clinical sleep-disordered breathing in patients with acute cerebrovascular event and the feasibility/efficacy of continuous positive airways pressure treatment in selected patients with acute cerebrovascular event and sleep-disordered breathing.
Comprehensive Stroke Units: A Review of Comparative Evidence and Experience
Authors: Chan Daniel K. Y. , Cordato Dennis , O'Rourke Fintan , Chan Daniel L , Pollack Michael , Middleton Sandy , Levi Chris
Published: July 2012

Background

Stroke unit care offers significant benefits in survival and dependency when compared to general medical ward. Most stroke units are either acute or rehabilitation, but comprehensive (combined acute and rehabilitation) model (comprehensive stroke unit) is less common.

Aim

To examine different levels of evidence of comprehensive stroke unit compared to other organized inpatient stroke care and share local experience of comprehensive stroke units.

Methods

Cochrane Library and Medline (1980 to December 2010) review of English language articles comparing stroke units to alternative forms of stroke care delivery, different types of stroke unit models, and differences in processes of care within different stroke unit models. Different levels of comparative evidence of comprehensive stroke units to other models of stroke units are collected.

Results

There are no randomized controlled trials directly comparing comprehensive stroke units to other stroke unit models (either acute or rehabilitation). Comprehensive stroke units are associated with reduced length of stay and greatest reduction in combined death and dependency in a meta-analysis study when compared to other stroke unit models. Comprehensive stroke units also have better length of stay and functional outcome when compared to acute or rehabilitation stroke unit models in a cross-sectional study, and better length of stay in a ‘before-and-after’ comparative study. Components of stroke unit care that improve outcome are multifactorial and most probably include early mobilization. A comprehensive stroke unit model has been successfully implemented in metropolitan and rural hospital settings.

Conclusions

Comprehensive stroke units are associated with reductions in length of stay and combined death and dependency and improved functional outcomes compared to other stroke unit models. A comprehensive stroke unit model is worth considering as the preferred model of stroke unit care in the planning and delivery of metropolitan and rural stroke services.