bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes
Authors: Bébarová M. , Matejovič P. , Pásek M. , Ohlídalová D. , Jansová D. , Šimurdová M. , Šimurda J. 
Published: July 2010

AbstractAim: Even though alcohol intoxication is often linked to arrhythmias, data describing ethanol effect on cardiac ionic channels are rare. In addition, ethanol is used as a solvent of hydrophobic compounds in experimental studies. We investigated changes of the action potential (AP) configuration and main ionic membrane currents in rat cardiomyocytes under 20–1500 mmethanol.Methods: Experiments were performed on enzymatically isolated rat right ventricular myocytes using the whole cell patch‐clamp technique at room temperature.Results: Ethanol reversibly decelerated the upstroke velocity and decreased AP amplitude and duration at 0.2 and 3 Hz. The fast sodium currentINa,l‐type calcium currentICaand transient outward potassium currentItowere reversibly inhibited in a concentration‐dependent manner (50% inhibition at 446 ± 12, 553 ± 49 and 1954 ± 234 mm, respectively, with corresponding Hill coefficients 3.1 ± 0.3, 1.1 ± 0.2 and 0.9 ± 0.1). Suppression ofINaandICamagnitude was slightly voltage dependent. The effect onICaandItowas manifested mainly as an acceleration of their apparent inactivations with a decreased slow and fast time constant respectively. As a consequence of marked differences innH, sensitivity of the currents to ethanol at 10% inhibition decreases in the following order:ICa(75 mm, 3.5‰),Ito(170 mm, 7.8‰) andINa(220 mm, 10.1‰).Conclusion: Our results suggest a slight inhibition of all the currents at ethanol concentrations relevant to deep alcohol intoxication. The concentration dependence measured over a wide range may serve as a guideline when using ethanol as a solvent.
ORIGINAL ARTICLE: The bone‐anchored hearing aid in the rehabilitation of single‐sided deafness: experience with 58 patients
Authors: Martin T.P.C. , Lowther R. , Cooper H. , Holder R.L. , Irving R.M. , Reid A.P. , Proops D.W. 
Published: July 2010

Clin. Otolaryngol. 2010, 35, 284–290Objectives:  To assess the efficacy of the bone‐anchored hearing aid (BAHA) in the rehabilitation of single‐sided deafness (SSD).Study design:  Retrospective case–control series review.Setting:  Tertiary referral unit.Patients:  Fifty‐eight consecutive patients that had a bone‐anchored hearing aid for single‐sided deafness completed outcome questionnaires, building upon earlier audiological assessment of 19 patients. Single‐sided deafness controls (n = 49) were mainly acoustic neuroma patients. Main outcome measurements: speech discrimination testing in directional noise, speech and spatial qualities of hearing questionnaire and the Glasgow Benefit Inventory (GBI).Results:  The mean follow‐up time was 28.4 months. Five (13%) of the bone‐anchored hearing aid patients were non‐users because of lack of benefit. The audiometric testing confirmed that when noise was on the bone‐anchored hearing aid side speech perception was reduced but benefited when noise was on the side of the hearing ear. There was no difference between the Speech and Spatial Qualities of Hearing Scores in bone‐anchored hearing aid users and controls. In particular there was no difference in the spatial subscores. In the bone‐anchored hearing aid users the median Glasgow Benefit Inventory score was 11. If the non‐users are included then 13 (22%) patients had no or detrimental (negative) Benefit scores. No or negative benefit scores were more frequent in those deaf for <10 years. In open‐field questions, patients felt the bone‐anchored hearing aid was most useful in small groups or in ‘one‐to‐one’ conversation.Conclusions:  Bone‐anchored hearing aid rehabilitation for single‐sided deafness is less successful than for other indications, reflected here by relatively low median Glasgow Benefit Inventory scores. There was also no significant difference between controls and bone‐anchored hearing aid users in the Speech and Spatial Qualities of Hearing Questionnaire. Patients with a longer duration of deafness report greater subjective benefit than those more recently deafened, perhaps due to differing expectations.
Evaluation of the Role of the Pharmacological Inhibition of Staphylococcus aureus Multidrug Resistance Pumps and the Variable Levels of the Uptake of the Sensitizer in the Strain‐Dependent Response of Staphylococcus aureus to PPArg2‐Based Photodynamic Inactivation
Authors: Grinholc Mariusz , Zawacka‐Pankau Joanna , Gwizdek‐Wiśniewska Anna , Bielawski Krzysztof P. 
Published: July 2010

AbstractThe emergence of antibiotic resistance among pathogenic bacteria has caused an urgent need for the development of alternative therapeutics. One possibility is a combination of nontoxic photosensitizers (PS) and visible light, recognized as photodynamic therapy. Although it is known that Staphylococcus aureus is susceptible to photodynamic inactivation (PDI), the factors that determine the emerging variation among strains in the response to the treatment remain unclear. Some data indicate that cationic photosensitizing dyes such as phenothiaziniums which vary a lot in the chemical structure might target multidrug resistance pumps. In this study, we analyzed whether the uptake and activity of the multidrug resistance pumps might influence the previously observed variations among the clinical strains to protoporphyrin‐derived, amphipilic protoporphyrin diarginate‐mediated photodynamic treatment (12 J cm−2). Using a new set of four additionally selected methicillin‐resistant and methicillin‐susceptible clinical as well as ATCC S. aureus strains we confirmed that the bactericidal effect of the PDI is strain‐dependent as it ranged from 0 to 5 log10‐unit reduction in viable counts. However, neither the variable levels of the uptaken PS nor the pharmacological inhibition of NorA efflux pump explained such a phenomenon.
Characterization of the Effects of Aryl‐azido Compounds and UVA Irradiation on the Viral Proteins and Infectivity of Human Immunodeficiency Virus Type 1
Authors: Belanger Julie M. , Raviv Yossef , Viard Mathias , Jason de la Cruz Michael , Nagashima Kunio , Blumenthal Robert 
Published: July 2010

AbstractHydrophobic UV‐activatable compounds have been shown to partition into the hydrophobic region of biological membranes to selectively label transmembrane proteins, and to inactivate enveloped viruses. Here, we analyze various UV‐activatable azido‐ and iodo‐based hydrophobic compounds for their ability to inactivate a model‐enveloped virus, human immunodeficiency virus (HIV‐1 MN). Treatment of HIV‐1 with 1,5‐diazidonapthalene (DAN), 1‐iodo, 5‐azidonaphthalene (INA), 1‐azidonaphthalene (AzNAP) or 4,4′‐diazidobiphenyl (DABIPH) followed by UVA irradiation for 2 min resulted in complete viral inactivation, whereas treatment using analogous non–azido‐containing controls had no effect. Incorporation of an azido moiety within these hydrophobic compounds to promote photoinduced covalent reactions with proteins was found to be the primary mechanism of viral inactivation for this class of compounds. Prolonged UVA irradiation of the virus in the presence of these azido compounds resulted in further modifications of viral proteins, due to the generation of reactive oxygen species, leading to aggregation as visualized via Western blot analysis, providing additional viral modifications that may inhibit viral infectivity. Furthermore, inactivation using these compounds resulted in the preservation of surface antigenic structures (recognized by neutralizing antibodies b12, 2g12 and 4e10), which is favorable for the creation of vaccines from these inactivated virus preparations.
An Evaluation of Qualitative Indexes of Physical Habitat Applied to Agricultural Streams in Ten U.S. States1
Authors: Hughes Robert M. , Herlihy Alan T. , Kaufmann Philip R. 
Published: July 2010

Hughes, Robert M., Alan T. Herlihy, and Philip R. Kaufmann, 2010. An Evaluation of Qualitative Indexes of Physical Habitat Applied to Agricultural Streams in Ten U.S. States. Journal of the American Water Resources Association (JAWRA) 46(4): 792‐806. DOI: 10.1111/j.1752‐1688.2010.00455.xAbstract:  Assessment of stream physical habitat condition is important for evaluating stream quality globally. However, the diversity of metrics and methods for assessing physical habitat condition confounds comparisons among practitioners. We surveyed 51 previously sampled stream sites (0.0‐6.3 m wide) located in regions of row‐crop agriculture in Oregon, California, North Dakota, South Dakota, Nebraska, Iowa, Minnesota, Pennsylvania, Maryland, and West Virginia to evaluate the comparability of four indexes of physical habitat condition relative to each other. We also compared the indexes to previously calculated indexes of fish and macroinvertebrate condition. The physical habitat indexes included the Stream Visual Assessment Protocol Version 2 of the Natural Resources Conservation Service, the qualitative habitat evaluation index of the Ohio Environmental Protection Agency, the rapid bioassessment protocol of the United States Environmental Protection Agency (USEPA), and a qualitative physical habitat index based on USEPA quantitative physical habitat measurements. All four indexes were highly correlated with each other, but low‐to‐moderately correlated with biotic index scores for fish and macroinvertebrate assemblages. Moderately high correlations occurred between some macroinvertebrate biotic index scores and quantitative metrics. We conclude that additional research is needed to increase the predictive and diagnostic capabilities of qualitative physical habitat indexes.
Reciprocal insights into adaptation from agricultural and evolutionary studies in tomato
Authors: Moyle Leonie C. , Muir Christopher D. 
Published: July 2010

AbstractAlthough traditionally separated by different aims and methodologies, research on agricultural and evolutionary problems shares a common goal of understanding the mechanisms underlying functionally important traits. As such, research in both fields offers potential complementary and reciprocal insights. Here, we discuss adaptive stress responses (specifically to water stress) as an example of potentially fruitful research reciprocity, where agricultural research has clearly produced advances that could benefit evolutionary studies, while evolutionary studies offer approaches and insights underexplored in crop studies. We focus on research onSolanumspecies that include the domesticated tomato and its wild relatives. Integrated approaches to understanding ecological adaptation are particularly attractive in tomato and its wild relatives: many presumptively adaptive phenotypic differences characterize wild species, and the physiological and mechanistic basis of many relevant traits and environmental responses has already been examined in the context of cultivated tomato and some wild species. We highlight four specific instances where these reciprocal insights can be combined to better address questions that are fundamental both to agriculture and evolution.
Serum Levels of Advanced Glycation End Products (AGEs) are Independent Correlates of Insulin Resistance in Nondiabetic Subjects
Authors: Tahara Nobuhiro , Yamagishi Sho‐ichi , Matsui Takanori , Takeuchi Masayoshi , Nitta Yoshikazu , Kodama Norihiro , Mizoguchi Minori , Imaizumi Tsutomu 
Published: July 2010

SUMMARYBackground: Advanced glycation end products (AGEs) evoke oxidative stress generation and inflammatory reactions, thus being involved in vascular complications in diabetes. Since oxidative stress and inflammation impair insulin actions as well, it is conceivable that AGEs may play some role in insulin resistance. However, there is no clinical study to examine the relationship between serum levels of AGEs and insulin resistance. This study investigated whether serum AGE levels were independent correlates of insulin resistance in humans. Methods: Three hundred twenty‐two nondiabetic Japanese subjects (216 male and 106 female; mean age 61.5 ± 9.1 years) underwent a complete history and physical examination, determinations of blood chemistries, anthropometric and metabolic variables, including AGEs. Serum AGE levels were examined with an enzyme‐linked immunosorbent assay. Results: Mean serum AGE levels were 8.96 ± 2.57 U/mL. In univariate analysis, waist circumference, diastolic blood pressure (BP), mean BP, AGEs, low‐density lipoprotein (LDL) cholesterol, triglycerides, high‐density lipoprotein (HDL) cholesterol (inversely), hemoglobin A1c (GHb), creatinine clearance, uric acid, and high sensitivity C‐reactive protein were significantly associated with insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA‐IR) index. After performing multiple regression analysis, waist circumference (P < 0.001), GHb (P < 0.001), triglycerides (P < 0.001), and AGEs (P < 0.01) still remained significant independently. When age‐adjusted HOMA‐IR levels stratified by AGE tertiles were compared using ANCOVA, a significant trend was demonstrated in both males and females. Conclusion: The present study demonstrated for the first time that serum AGE levels were one of the independent correlates of HOMA‐IR index, thus suggesting that AGEs may play some pathological role in insulin resistance in humans.
Nutraceuticals in Diabetes and Metabolic Syndrome
Authors: Davì Giovanni , Santilli Francesca , Patrono Carlo 
Published: July 2010

SUMMARYMetabolic syndrome represents a clustering of risk factors related to an elevated risk of cardiovascular disease and type 2 diabetes. Occurrence of both metabolic syndrome and diabetes and their vascular complications share several pathogenetic features including subclinical, low‐grade inflammation, altered oxidative/antioxidant status, and persistent platelet activation. Despite the availability of multiple interventions to counteract these metabolic changes, including appropriate diet, regular exercise, weight control and drugs, epidemiological data are witnessing the growing trend of the problem, reflecting both the multifactorial nature of these diseases as well as the scarce compliance of patients to established strategies. Several nutraceuticals used in clinical practice have been shown to target the pathogenesis of diabetes mellitus, metabolic syndrome and their complications and to favorably modulate a number of biochemical and clinical endpoints. These compounds include antioxidant vitamins, such as vitamins C and E, flavonoids, vitamin D, conjugated linoleic acid, omega‐3 fatty acids, minerals such as chromium and magnesium, α‐lipoic acid, phytoestrogens, and dietary fibers. Several areas of concern exist regarding the use of dietary supplements and nutraceuticals in this setting, including product standardization, definition of optimal dosing regimen, potential side effects, drug interactions, and need for evidence‐based indications.
Lipid‐Altering Efficacy of Ezetimibe/Simvastatin 10/20 mg Compared to Rosuvastatin 10 mg in High‐Risk Patients with and without Type 2 Diabetes Mellitus Inadequately Controlled Despite Prior Statin Monotherapy
Authors: Vaverkova Helena , Farnier Michel , Averna Maurizio , Missault Luc , Viigimaa Margus , Dong Qian , Shah Arvind , Johnson‐Levonas Amy O. , Brudi Philippe 
Published: July 2010

SUMMARYAims: This post hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) or rosuvastatin 10 mg (ROSUVA) in uncontrolled high‐risk hypercholesterolemic patients with/without type 2 diabetes mellitus (T2DM) despite statin monotherapy. Methods: Patients (n = 618) at high risk for coronary vascular disease with elevated LDL‐C ≥100 and ≤190 mg/dL despite use of statins were randomized 1:1 to double‐blind EZE/SIMVA 10/20 mg or ROSUVA 10 mg for 6 weeks. Patients were classified as having T2DM based on ≥1 of the following: diagnosis of T2DM, antidiabetic medication, or FPG ≥126 mg/dL. This analysis evaluated percent changes from baseline in lipids among patients with (n = 182) and without T2DM (n = 434). Results: EZE/SIMVA was more effective than ROSUVA at lowering LDL‐C, TC, non‐HDL‐C, and apo B in the overall study population and within both subgroups. Numerically, greater between‐treatment reductions in LDL‐C, TC, non‐HDL‐C, and apo B were seen in patients with T2DM versus those without T2DM. A significant interaction (P= 0.015) was seen for LDL‐C indicating that patients with T2DM achieved larger between‐group reductions versus those without T2DM. Conclusions: Switching to EZE/SIMVA 10/20 mg versus ROSUVA 10 mg provided superior lipid reductions in patients with/without T2DM.
Effects of Cholinesterase Inhibitors in Parkinson's Disease Dementia: A Review of Clinical Data
Authors: van Laar Teus , De Deyn Peter Paul , Aarsland Dag , Barone Paolo , Galvin James E 
Published: July 2010

SUMMARYAims: Cognitive impairment and dementia are common features of Parkinson's disease (PD). Patients with Parkinson's disease dementia (PDD) often have significant cholinergic defects, which may be treated with cholinesterase inhibitors (ChEIs). The objective of this review was to consider available efficacy, tolerability, and safety data from studies of ChEIs in PDD. Discussions: A literature search resulted in the identification of 20 relevant publications. Of these, the treatment of PD patients with rivastigmine, donepezil, or galantamine was the focus of six, eleven, and two studies respectively, while one study reported use of both tacrine and donepezil. The majority of studies were small (<40 patients), with the exception of two large randomized controlled trials (RCTs) that are the main focus of this review. In the smaller studies, treatment benefits were reported on a range of outcome measures, though results were extremely variable. While the full results of a large RCT of donepezil in patients with PDD are not yet available, significant treatment differences were reported on the CIBIC‐plus at the highest treatment dose. A trend toward improvement was also observed in treated patients on the ADAS‐cog. The second large RCT found significant improvements in rivastigmine‐treated patients compared with placebo on both the ADAS‐cog (P < 0.001) and the ADCS‐CGIC (P < 0.007), as well as on all secondary efficacy outcomes. Consequently, rivastigmine is now widely approved for the symptomatic treatment of mild to moderate PDD. Conclusions: Taken together, these studies suggest that ChEIs are efficacious in the treatment of PDD.
The Combination of Interferon‐Beta and HMG‐CoA Reductase Inhibition in Multiple Sclerosis: Enthusiasm Lost too Soon?
Authors: Sellner Johann , Weber Martin S. , Vollmar Patrick , Mattle Heinrich P. , Hemmer Bernhard , Stüve Olaf 
Published: July 2010

SUMMARYRecent studies support the notion that statins, widely prescribed cholesterol‐lowering agents, may target key elements in the immunological cascade leading to inflammation and tissue damage in the pathogenesis of multiple sclerosis (MS). Compelling experimental and observational clinical studies highlighted the possibility that statins may also exert immunomodulatory synergy with approved MS drugs, resulting in several randomized clinical trials testing statins in combination with interferon‐beta (IFN‐β). Some data, however, suggest that this particular combination may not be clinically beneficial, and might actually have a negative effect on the disease course in some patients with MS. In this regard, a small North American trial indicated that atorvastatin administered in combination with IFN‐β may increase disease activity in relapsing‐remitting MS. Although other trials did not confirm this finding, the enthusiasm for studies with statins dwindled. This review aims to provide a comprehensive overview of the completed clinical trials and reports of the interim analyses evaluating the combination of IFN‐β and statins in MS. Moreover, we try to address the evident question whether usage of this combination routinely requires caution, since the number of IFN‐β‐treated MS patients receiving statins for lowering of cholesterol is expected to grow.
REVIEW: Oxytocin: Crossing the Bridge between Basic Science and Pharmacotherapy
Authors: Viero Cedric , Shibuya Izumi , Kitamura Naoki , Verkhratsky Alexei , Fujihara Hiroaki , Katoh Akiko , Ueta Yoichi , Zingg Hans H. , Chvatal Alexandr , Sykova Eva , Dayanithi Govindan 
Published: July 2010

SUMMARYIs oxytocin the hormone of happiness? Probably not. However, this small nine amino acid peptide is involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterus contraction, milk ejection, maternal behavior, osteoporosis, diabetes, cancer, social bonding, and stress, which makes oxytocin and its receptor potential candidates as targets for drug therapy. In this review, we address the issues of drug design and specificity and focus our discussion on recent findings on oxytocin and its heterotrimeric G protein‐coupled receptor OTR. In this regard, we will highlight the following topics: (i) the role of oxytocin in behavior and affectivity, (ii) the relationship between oxytocin and stress with emphasis on the hypothalamo–pituitary–adrenal axis, (iii) the involvement of oxytocin in pain regulation and nociception, (iv) the specific action mechanisms of oxytocin on intracellular Ca2+ in the hypothalamo neurohypophysial system (HNS) cell bodies, (v) newly generated transgenic rats tagged by a visible fluorescent protein to study the physiology of vasopressin and oxytocin, and (vi) the action of the neurohypophysial hormone outside the central nervous system, including the myometrium, heart and peripheral nervous system. As a short nine amino acid peptide, closely related to its partner peptide vasopressin, oxytocin appears to be ideal for the design of agonists and antagonists of its receptor. In addition, not only the hormone itself and its binding to OTR, but also its synthesis, storage and release can be endogenously and exogenously regulated to counteract pathophysiological states. Understanding the fundamental physiopharmacology of the effects of oxytocin is an important and necessary approach for developing a potential pharmacotherapy.