bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion
Authors: Ertracht Offir , Liani Esti , Bachner‐Hinenzon Noa , Bar‐Am Orit , Frolov Luba , Ovcharenko Elena , Awad Huda , Blum Shany , Barac Yaron , Amit Tamar , Adam Dan , Youdim Moussa , Binah Ofer 
Published: February 2011

BACKGROUND AND PURPOSEBecause myocardial infarction is a major cause of morbidity and mortality worldwide, protecting the heart from the ischaemia and reperfusion (I/R) damage is the focus of intense research. Based on our in vitro findings showing that TVP1022 (the S‐enantiomer of rasagiline, an anti‐Parkinsonian drug) possesses cardioprotective effects, in the present study we investigated the hypothesis that TVP1022 can attenuate myocardial damage in an I/R model in rats.EXPERIMENTAL APPROACHThe model consisted of 30‐min occlusion of the left anterior descending artery followed by 4 or 24 h reperfusion. In addition, we investigated the possible mechanisms of cardioprotection in H9c2 cells and neonatal rat ventricular myocytes (NRVM) exposed to oxidative stress induced by H2O2.KEY RESULTSTVP1022 (20 and 40 mg·kg−1) administered 5 min before reperfusion followed by an additional dose 4 h after reperfusion reduced the infarct size and attenuated the decline in ventricular function. TVP1022 also attenuated I/R‐induced deterioration in cardiac mitochondrial integrity evaluated by mitochondrial swelling capacity. In vitro, using H9c2 cells and NRVM, TVP1022 attenuated both serum free‐ and H2O2‐induced damage, preserved mitochondrial membrane potential and Bcl‐2 levels, inhibited mitochondrial cytochrome c release and the increase in cleaved caspase 9 and 3 levels, and enhanced the phosphorylation of protein kinase C and glycogen synthase kinase‐3β.CONCLUSIONS AND IMPLICATIONSTVP1022 provided cardioprotection in a model of myocardial infarction, and therefore should be considered as a novel adjunctive therapy for attenuating myocardial damage resulting from I/R injuries.
Symptom‐relieving and neuroprotective effects of the phytocannabinoid Δ9‐THCV in animal models of Parkinson's disease
Authors: García C , Palomo‐Garo C , García‐Arencibia M , Ramos JA , Pertwee RG , Fernández‐Ruiz J 
Published: February 2011

BACKGROUND AND PURPOSE Previous findings have indicated that a cannabinoid, such as Δ9‐THCV, which has antioxidant properties and the ability to activate CB2 receptors but to block CB1, might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson's disease (PD).EXPERIMENTAL APPROACH The ability of Δ9‐THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6‐hydroxydopamine and in mice lesioned with lipopolysaccharide (LPS).KEY RESULTS Acute administration of Δ9‐THCV attenuated the motor inhibition caused by 6‐hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Δ9‐THCV attenuated the loss of tyrosine hydroxylase–positive neurones caused by 6‐hydroxydopamine in the substantia nigra, through an effect related to its antioxidant properties (it was reproduced by cannabidiol ‐enriched botanical extract). In addition, CB2 receptor–deficient mice responded to 6‐hydroxydopamine in a similar manner to wild‐type animals, and CB2 receptors were poorly up‐regulated in the rat substantia nigra in response to 6‐hydroxydopamine. By contrast, the substantia nigra of mice that had been injected with LPS exhibited a greater up‐regulation of CB2 receptors. In these animals, Δ9‐THCV also caused preservation of tyrosine hydroxylase–positive neurones. This effect probably involved CB2 receptors as it was also elicited by the selective CB2 receptor agonist, HU‐308, and CB2 receptor–deficient mice were more vulnerable to LPS lesions.CONCLUSIONS AND IMPLICATIONS Given its antioxidant properties and its ability to activate CB2 but to block CB1 receptors, Δ9‐THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
The dual neuroprotective–neurotoxic profile of cannabinoid drugs
Authors: Sarne Yosef , Asaf Fadi , Fishbein Miriam , Gafni Mikhal , Keren Ora 
Published: February 2011

Extensive in vitro and in vivo studies have shown that cannabinoid drugs have neuroprotective properties and suggested that the endocannabinoid system may be involved in endogenous neuroprotective mechanisms. On the other hand, neurotoxic effects of cannabinoids in vitro and in vivo were also described. Several possible explanations for these dual, opposite effects of cannabinoids on cellular fate were suggested, and it is conceivable that various factors may determine the final outcome of the cannabinoid effect in vivo. In the current review, we focus on one of the possible reasons for the dual neuroprotective/neurotoxic effects of cannabinoids in vivo, namely, the opposite effects of low versus high doses of cannabinoids. While many studies reported neuroprotective effects of the conventional doses of cannabinoids in various experimental models for acute brain injuries, we have shown that a single administration of an extremely low dose of Δ9‐tetrahydrocannabinol (THC) (3–4 orders of magnitude lower than the conventional doses) to mice induced long‐lasting mild cognitive deficits that affected various aspects of memory and learning. These findings led to the idea that this low dose of THC, which induces minor damage to the brain, may activate preconditioning and/or postconditioning mechanisms and thus will protect the brain from more severe insults. Indeed, our recent findings support this assumption and show that a pre‐ or a postconditioning treatment with extremely low doses of THC, several days before or after brain injury, provides effective long‐term cognitive neuroprotection. The future therapeutical potential of these findings is discussed.LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Do Clinical Outcomes in Chronic Hemodialysis Depend on the Choice of a Dialyzer?
Authors: Ward Richard A. 
Published: February 2011

AbstractNephrologists are presented with a range of choices when selecting a dialyzer for chronic hemodialysis. Dialyzers differ in the material, structure, permeability and surface area of their membrane, and how the dialyzer is sterilized. Opinions vary regarding the impact of dialyzer characteristics on patient outcomes and which, if any, of these properties to take into account when choosing a dialyzer can be confusing. In the general dialysis population, there is no compelling evidence that the choice of a membrane material from among those materials currently in clinical use has a significant impact on morbidity or mortality (although there are rare patients who will react adversely to a given dialysis membrane). Similarly, most dialyzers are capable of adequately removing small solutes, such as urea, provided they are used with an appropriate blood flow rate and treatment time to ensure delivery of a single‐pool Kt/Vurea of at least 1.25 for men and 1.65 for women. However, in some dialysis patient subpopulations, the results of randomized clinical trials suggest that use of dialyzer containing high‐flux membranes confers an outcome advantage. The extent to which this advantage is realized might also depend on how the dialyzer is used, with application in convective therapies such as hemodiafiltration being superior to diffusive therapies such as hemodialysis. This possibility is currently the subject of several large clinical trials.
Assessment of Voluntary Ethanol Consumption and the Effects of a Melanocortin (MC) Receptor Agonist on Ethanol Intake in Mutant C57BL/6J Mice Lacking the MC‐4 Receptor
Authors: Navarro Montserrat , Lerma‐Cabrera Jose M. , Carvajal Francisca , Lowery Emily G. , Cubero Inmaculada , Thiele Todd E. 
Published: February 2011

Background:  The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor proopiomelanocortin (POMC). Recent evidence shows that chronic exposure to ethanol significantly blunts central MC peptide immunoreactivity and MC receptor (MCR) agonists protect against high ethanol intake characteristic of C57BL/6J mice. Here, we assessed the role of the MC‐4 receptor (MC4R) in voluntary ethanol intake and in modulating the effects of the nonselective MCR agonist melanotan‐II (MTII) on ethanol consumption.Methods:  To assess the role of the MC4R, MC4R knockout (Mc4r−/−) and littermate wild‐type (Mc4r+/+) mice on a C57BL/6J background were used. Voluntary ethanol (3, 5, 8, 10, 15, and 20%, v/v) and water intake were assessed using standard two‐bottle procedures. In separate experiments, Mc4r−/− and Mc4r+/+ mice were given intracerebroventricular (i.c.v.) infusion of MTII (0, 0.5, or 1.0 μg/1 μl) or intraperitoneal (i.p.) injection of MTII (0 or 5 mg/kg/5 ml). The effects of MTII (0 or 0.5 μg/1 μl, i.c.v.) on 10% sucrose and 0.15% saccharin intake were assessed in C57BL/6J mice.Results:  Mc4r−/− mice showed normal consumption of ethanol over all concentrations tested. I.c.v. infusion of MTII significantly reduced ethanol drinking in Mc4r+/+ mice, but failed to influence ethanol intake in Mc4r−/− mice. When administered in an i.p. injection, MTII significantly reduced ethanol drinking in both Mc4r−/− and Mc4r+/+ mice. MTII attenuated consumption of caloric (ethanol, sucrose, and food) and noncaloric (saccharin) reinforcers.Conclusions:  When given centrally, the MCR agonist MTII reduced ethanol drinking by signaling through the MC4R. On the other hand, MTII‐induced reduction of ethanol drinking did not require the MC4R when administered peripherally. Together, the present observations show that the MC4R is necessary for the central actions of MCR agonists on ethanol drinking and that MTII blunts the consumption natural reinforcers, regardless of caloric content, in addition to ethanol.
Ethanol Influences on Bax Translocation, Mitochondrial Membrane Potential, and Reactive Oxygen Species Generation Are Modulated by Vitamin E and Brain‐Derived Neurotrophic Factor
Authors: Heaton Marieta B. , Paiva Michael , Siler‐Marsiglio Kendra 
Published: February 2011

Background:  This study investigated ethanol influences on intracellular events that predispose developing neurons toward apoptosis and the capacity of the antioxidant α‐tocopherol (vitamin E) and the neurotrophin brain‐derived neurotrophic factor (BDNF) to modulate these effects. Assessments were made of the following: (i) ethanol‐induced translocation of the pro‐apoptotic Bax protein to the mitochondrial membrane, a key upstream event in the initiation of apoptotic cell death; (ii) disruption of the mitochondrial membrane potential (MMP) as a result of ethanol exposure, an important process in triggering the apoptotic cascade; and (iii) generation of damaging reactive oxygen species (ROS) as a function of ethanol exposure.Methods:  These interactions were investigated in cultured postnatal day 8 neonatal rat cerebellar granule cells, a population vulnerable to developmental ethanol exposure in vivo and in vitro. Bax mitochondrial translocation was analyzed via subcellular fractionation followed by Western blot, and mitochondrial membrane integrity was determined using the lipophilic dye, JC‐1, that exhibits potential‐dependent accumulation in the mitochondrial membrane as a function of the MMP.Results:  Brief ethanol exposure in these preparations precipitated Bax translocation, but both vitamin E and BDNF reduced this effect to control levels. Ethanol treatment also resulted in a disturbance of the MMP, and this effect was blunted by the antioxidant and the neurotrophin. ROS generation was enhanced by a short ethanol exposure in these cells, but the production of these harmful free radicals was diminished to control levels by cotreatment with either vitamin E or BDNF.Conclusions:  These results indicate that both antioxidants and neurotrophic factors have the potential to ameliorate ethanol neurotoxicity and suggest possible interventions that could be implemented in preventing or lessening the severity of the damaging effects of ethanol in the developing central nervous system seen in the fetal alcohol syndrome (FAS).
Early alveolar bone grafting has a negative effect on maxillary dental arch dimensions of pre‐school children with complete unilateral cleft lip and palate
Authors: Fudalej P , Janiszewska‐Olszowska J , Wedrychowska‐Szulc B , Katsaros C 
Published: February 2011

To cite this article:
Fudalej P, Janiszewska‐Olszowska J, Wedrychowska‐Szulc B, Katsaros C:  Early alveolar bone grafting has a negative effect on maxillary dental arch dimensions of pre‐school children with complete unilateral cleft lip and palate  Orthod Craniofac Res 2011;14:51–57Structured AbstractAuthors –  Fudalej P, Janiszewska‐Olszowska J, Wedrychowska‐Szulc B, Katsaros C.Objective –  To evaluate maxillary dental arch dimensions in pre‐school children with a complete unilateral cleft lip and palate (CUCLP) after early alveolar bone grafting.Material and Methods –  Intercanine and intermolar widths, length of dental arch and mesiopalatal inclination of both maxillary segments were measured directly on the dental casts of 42 children (27 boys and 15 girls; mean age = 5.2 years, SD 0.5; Early‐grafted group), 30 children (18 boys and 12 girls; mean age = 5.8 years, SD 0.8; Non‐grafted group), and 40 children (25 boys and 15 girls, mean age = 5.8, SD 0.4; non‐cleft Control group). Children from Early‐grafted and Non‐grafted groups had a CUCLP repaired with a one‐stage closure of the entire cleft. An alveolar bone grafting was performed in the Early‐grafted group between 2 and 4 years (mean = 2.4, SD 0.6). A one‐way anova model with post hoc Tukey’s multiple comparison procedures were used to identify intergroup differences.Results –  The mesiopalatal inclination of the lesser segment in the Early‐grafted group was decreased in comparison with the Non‐grafted and Control groups. The intercanine width had a tendency to be reduced in the Early‐grafted group relative to Non‐grafted group.Conclusions –  Early bone grafting results in a larger collapse of the lesser segment than bone grafting carried out between 9 and 12 years of age.
Painless aortic dissection presenting with acute ischaemic stroke and multiple organ failure
Authors: Demircan Ahmet , Aksay Ersin , Ergin Mehmet , Bildik Fikret , Keles Ayfer , Aygencel Gullbin 
Published: February 2011

AbstractAcute aortic dissection is an uncommon, life‐threatening catastrophe, and early diagnosis is essential for the best chance of survival. Although acute onset of severe chest or back pain is the most common presenting symptom, some patients might present with atypical symptoms and findings such as acute stroke and mesenteric ischaemia related to the involving arterial segment. Establishing the diagnosis of aortic dissection can be difficult in the presence of atypical symptoms, especially in the absence of pain. Here, we report a case of acute, painless aortic dissection presenting with multiple organ failure and neurological deficits suggesting acute ischaemic stroke.
Regulatory Impact Assessment: How political and organizational forces influence its diffusion in a developing country
Authors: Peci Alketa , Sobral Filipe 
Published: February 2011

AbstractRegulatory Impact Assessments (RIAs) are being diffused progressively throughout the world following the recommendations of international organizations. Research has shown that the diffusion of RIA has not produced convergence in actual practices, particularly in developing countries, due to political forces at work in domestic contexts or the available organizational capacities. The Organisation for Economic Co‐operation and Development (OECD) has recently recommended that the Brazilian federal government adopt RIA. This article evaluates how contextual variables, specifically political and organizational ones, influence RIA adoption in Brazil. It is based on field research consisting of semi‐structured interviews with the main stakeholders of the Brazilian regulatory framework. The research explored RIA concept familiarity among stakeholders, the bureaucratic context, the policy process, pivotal stakeholders' standpoints in adopting RIA, and available organizational capacities. Contrary to previous studies in developing countries, the research reveals that strong organizational capacities are not a sufficient factor for successful diffusion of RIA, because political variables can influence divergence among agencies in future RIA practices.
Objective evidence for the efficacy of surgical management of the deviated septum as a treatment for chronic nasal obstruction: a systematic review
Authors: Moore M. , Eccles R. 
Published: February 2011

Clin. Otolaryngol. 2011, 36, 106–113Background:  Nasal septal surgery is a common procedure, but there are concerns that the benefits of this surgery are mainly cosmetic.Objective of review:  The primary aim is to identify any functional benefits of septal surgery and provide any evidence of a change in patency of the nasal airway, as assessed by objective methods such as rhinomanometry, acoustic rhinometry and peak nasal inspiratory flow.Type of review:  Systematic review.Search strategy:  A systematic search of the available literature was performed, using Pubmed, Medline (1950–November 2010), Embase (1947–November 2010) and the Cochrane Controlled Trials Register. Papers written in English that objectively compared pre‐ and post‐surgical treatment of nasal obstruction in adults because of septal deviation were reviewed. Objective measurements of rhinomanometry, acoustic rhinometry and nasal peak inspiratory flow were specified within the search. Searches were restricted to surgery on the nasal septum, which included septoplasty, submucous resection and septal (deviation) corrective surgery.Results:  Seven studies (460 participants) involving rhinomanometry, six studies (182 participants) with acoustic rhinometry and one study (22 participants) using nasal peak inspiratory flow were included in the review. All the studies reported an objective improvement in nasal patency after septal surgery. Mean unilateral nasal resistance (data from six studies) decreased from preoperative 1.19 Pa/cm3/s to postoperative 0.39 Pa/cm3/s, mean minimum cross‐sectional area (data from five studies) increased from preoperative 0.45 cm2 to postoperative 0.61 cm2, median peak nasal inspiratory flow (data from one study) increased by 35 L/min after surgery.Conclusions:  There is sufficient evidence in the literature to conclude that septal surgery improves objective measures of nasal patency and that improved nasal airflow may have beneficial effects for the patient.
How evolutionary principles improve the understanding of human health and disease
Authors: Gluckman Peter D. , Low Felicia M. , Buklijas Tatjana , Hanson Mark A. , Beedle Alan S. 
Published: February 2011

AbstractAn appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved. We consider these evolutionary principles in conjunction with population genetics and describe several pathways by which evolutionary processes can affect disease risk. These perspectives provide a more cohesive framework for gaining insights into the determinants of health and disease. Coupled with complementary insights offered by advances in genomic, epigenetic, and developmental biology research, evolutionary perspectives offer an important addition to understanding disease. Further, there are a number of aspects of evolutionary medicine that can add considerably to studies in other domains of contemporary evolutionary studies.
Evolution and behavioural responses to human‐induced rapid environmental change
Authors: Sih Andrew , Ferrari Maud C. O. , Harris David J. 
Published: February 2011

AbstractAlmost all organisms live in environments that have been altered, to some degree, by human activities. Because behaviour mediates interactions between an individual and its environment, the ability of organisms to behave appropriately under these new conditions is crucial for determining their immediate success or failure in these modified environments. While hundreds of species are suffering dramatically from these environmental changes, others, such as urbanized and pest species, are doing better than ever. Our goal is to provide insights into explaining such variation. We first summarize the responses of some species to novel situations, including novel risks and resources, habitat loss/fragmentation, pollutants and climate change. Using a sensory ecology approach, we present a mechanistic framework for predicting variation in behavioural responses to environmental change, drawing from models of decision‐making processes and an understanding of the selective background against which they evolved. Where immediate behavioural responses are inadequate, learning or evolutionary adaptation may prove useful, although these mechanisms are also constrained by evolutionary history. Although predicting the responses of species to environmental change is difficult, we highlight the need for a better understanding of the role of evolutionary history in shaping individuals’ responses to their environment and provide suggestion for future work.
Incorporating evolutionary principles into environmental management and policy
Authors: Lankau Richard , Jørgensen Peter Søgaard , Harris David J. , Sih Andrew 
Published: February 2011

AbstractAs policymakers and managers work to mitigate the effects of rapid anthropogenic environmental changes, they need to consider organisms’ responses. In light of recent evidence that evolution can be quite rapid, this now includes evolutionary responses. Evolutionary principles have a long history in conservation biology, and the necessary next step for the field is to consider ways in which conservation policy makers and managers can proactively manipulate evolutionary processes to achieve their goals. In this review, we aim to illustrate the potential conservation benefits of an increased understanding of evolutionary history and prescriptive manipulation of three basic evolutionary factors: selection, variation, and gene flow. For each, we review and propose ways that policy makers and managers can use evolutionary thinking to preserve threatened species, combat pest species, or reduce undesirable evolutionary changes. Such evolution‐based management has potential to be a highly efficient and consistent way to create greater ecological resilience to widespread, rapid, and multifaceted environmental change.