bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tropical Cyclogenesis Detection in the North Pacific Using the Deviation Angle Variance Technique
Authors: Wood Kimberly M. , Rodríguez-Herrera Oscar G. , Ritchie Elizabeth A. , Piñeros Miguel F. , Hernández Ivan Arias , Tyo J. Scott 
Published: September 2015

AbstractThe deviation angle variance technique (DAV-T) for genesis detection is applied in the western and eastern North Pacific basins. The DAV-T quantifies the axisymmetric organization of cloud clusters using infrared brightness temperature. Since axisymmetry is typically correlated with intensity, the technique can be used to identify relatively high levels of organization at early stages of storm life cycles associated with tropical cyclogenesis. In addition, the technique can be used to automatically track cloud clusters that exhibit signs of organization. In the western North Pacific, automated tracking results for the 2009–11 typhoon seasons show that for a false alarm rate of 25.6%, 96.8% of developing tropical cyclones are detected with a median time of 18.5 h before the cluster reaches an intensity of 30 knots (kt; 1 kt = 0.51 m s−1) in the Joint Typhoon Warning Center best track at a DAV threshold of 1750°2. In the eastern North Pacific, for a false alarm rate of 38.0%, the system detects 92.9% of developing tropical cyclones with a median time of 1.25 h before the cluster reaches an intensity of 30 kt in the National Hurricane Center best track during the 2009–11 hurricane seasons at a DAV threshold of 1650°2. A significant decrease in tracked nondeveloping clusters occurs when a second organization threshold is introduced, particularly in the western North Pacific.
Cortical oxygenation suggests increased effort during cognitive inhibition in ecstasy polydrug users
Authors: Roberts CA , Montgomery Catharine 
Published: September 2015

Background: It is understood that 3,4-methylenedioxymethamphetamine (ecstasy) causes serotonin dysfunction and deficits in executive functioning. When investigating executive function, functional neuroimaging allows the physiological changes underlying these deficits to be investigated. The present study investigated behavioural and brain indices of inhibition in ecstasy-polydrug users. Methods: Twenty ecstasy-polydrug users and 20 drug-naïve participants completed an inhibitory control task (Random Letter Generation (RLG)) while prefrontal haemodynamic response was assessed using functional near infrared spectroscopy (fNIRS). Results: There were no group differences on background measures including sleep quality and mood state. There were also no behavioural differences between the two groups. However, ecstasy-polydrug users displayed significant increases in oxygenated haemoglobin (oxy-Hb) from baseline compared to controls at several voxels relating to areas of the inferior right medial prefrontal cortex, as well the right and left dorsolateral prefrontal cortex. Regression analysis revealed that recency of ecstasy use was a significant predictor of oxy-Hb increase at two voxels over the right hemisphere after controlling for alcohol and cannabis use indices. Conclusion: Ecstasy-polydrug users show increased neuronal activation in the prefrontal cortex compared to non-users. This is taken to be compensatory activation/recruitment of additional resources to attain similar performance levels on the task, which may be reversible with prolonged abstinence.
Incidence of Stingers in Young Rugby Players
Authors: Kawasaki Takayuki , Ota Chihiro , Yoneda Takeshi , Maki Nobukazu , Urayama Shingo , Nagao Masashi , Nagayama Masataka , Kaketa Takefumi , Takazawa Yuji , Kaneko Kazuo 
Published: September 2015

Background: A stinger is a type of neurapraxia of the cervical roots or brachial plexus and represents a reversible peripheral nerve injury. The incidence of and major risk factors for stingers among young rugby players remain uninvestigated. Purpose: To investigate the incidence, symptoms, and intrinsic risk factors for stingers in elite rugby union teams of young players. Study Design: Descriptive epidemiology study. Methods: A total of 569 male rugby players, including 358 players from 7 high school teams and 211 players from 2 university teams, were investigated using self-administered preseason and postseason questionnaires. Results: The prevalence of a history of stingers was 33.9% (95% CI, 30.3-37.9), and 20.9% (119/569) of players experienced at least 1 episode of a stinger during the season (34.2 [95% CI, 26.2-42.1] events per 1000 player-hours of match exposure). The reinjury rate for stingers per season was 37.3% (95% CI, 30.4-44.2). Using the multivariate Poisson regression method, a history of stingers in the previous season and the grade and position of the player were found to be risk factors for stingers during the current season. The mean severity of injury was 2.9 days, with 79.3% (191/241) of the players not losing any time from playing after sustaining a stinger injury and 5.8% (14/241) of the players recovering within more than 14 days. The most frequent symptom was numbness in the unilateral upper extremity, and the most severe symptom was weakness of grasping (mean severity, 6 days). A logistic regression analysis indicated that a history of stingers in the previous season and an injury with more than 3 symptoms, especially motor weakness, were correlated with the severity of injury. Conclusion: Young rugby players with a history of stingers have a significantly high rate of repeat injuries. Although nearly 80% of the players experienced only minimal (0-1 day) time loss injuries, neurological deficits sometimes last beyond 1 month. A history of stingers was identified to be the strongest risk factor for injuries and for lasting symptoms. This information may be useful for planning the proper treatment for stingers in young rugby players.
Immunohistochemical Analysis of GDNF and Its Cognate Receptor GFRα-1 Protein Expression in Vitiliginous Skin Lesions
Authors: Adly Mohamed A. , Assaf Hanan A. , Abdel-Rady Shaima’a F. , Ahmed Nagwa Sayed , Hussein Mahmoud Rezk Abdelwahed 
Published: September 2015

Background: Vitiligo is an idiopathic skin disease, characterized by circumscribed white macules or patches on the skin due to loss of the functional melanocytes. Glial cell line–derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are distal members of the transforming growth factor-β superfamily. GDNF, produced by the basal cell keratinocytes, is involved in the migration and differentiation of the melanocytes from the neural crest to the epidermis. This study examines the hypothesis that expression of GDNF protein and its cognate receptor GFRα-1 protein is altered in vitiliginous skin. Patients and Methods: To test our hypothesis, we examined the expression patterns of these proteins in vitiliginous and corresponding healthy (control) skin biopsies (20 specimens each) using immunoperoxidase staining techniques. Results: We found variations between the vitiliginous skin and healthy skin. In healthy skin, the expression of GDNF and GFRα-1 proteins was strong (basal cell keratinocytes and melanocytes), moderate (spinous layer), and weak (granular cell layer). In contrast, weak expression of GDNF protein was observed in all epidermal layers of vitiliginous skin. GFRα-1 protein expression was strong (basal cell keratinocytes and melanocytes), moderate (spinous layer), and weak (granular cell layer). In both healthy skin and vitiliginous skin, the expression of GDNF and GFRα-1 proteins was strong in the adnexal structures. Conclusions: We report, for the first time, decreased expression of GDNF proteins in the epidermal keratinocytes of vitiliginous skin. Our findings suggest possible pathogenetic roles for these proteins in the development of vitiligo. The clinical ramifications of these observations mandate further investigations.
Influence of Iliac Vein Stent Implantation on the Contralateral Iliac Vein
Authors: Zhang Xicheng , Chen Zhaolei , Sun Yun , Xu Miao , Pan Guangrui 
Published: September 2015

Objectives: Stent implantation is frequently used to treat iliac vein occlusion. However, the recommended extension of the stent mesh into the inferior vena cava (IVC) may affect blood flow through the contralateral iliac vein. We analyzed the influence of iliac vein stent extension on contralateral iliac vein patency and neointima formation in a dog surgery model. Methods: Bare stents were implanted into the left iliac veins of 12 beagles with the proximal end covering the opening of the contralateral iliac vein. Blood flow was measured by color Doppler 4, 8, and 12 weeks postoperation. At each measurement point, a subgroup was killed, and the stents and veins were removed for pathological examination. Results: Stents were successfully implanted, and there was no immediate stent occlusion or iliac vein thrombus by color Doppler examinations. Contralateral blood flow was maintained with no obvious abnormalities for 12 weeks. Neointima formed and advanced toward the center of the stent, but small coverage of the contralateral iliac vein opening did not change significantly with time postoperation (9.33% ± 1.54% at 4 weeks, 10.65% ± 1.01% at 8 weeks, and 10.92% ± 1.30% at 12 weeks; P > .05). Scanning electron microscopy showed neointima covering the surface of stent wires at the opening of the contralateral iliac vein, which did increase with time: 63.58% ± 12.39% at 4 weeks, 97.13% ± 2.71% at 8 weeks ( P < .001 vs 4 weeks), and 99.63% ± 0.60% after 12 weeks ( P > .05 vs 8 weeks; P < .001 vs 4 weeks). The neointimal coverage rate of the meshes increased obviously with time. However, no neointima was found forming a mesh between stent wires. Conclusion: Although there was intimal hyperplasia on the rim of the bare stent in the IVC, expansion was limited and did not block the opening of the contralateral iliac vein. The stent had no obvious influence on blood backflow in the contralateral iliac vein.
Computational modeling to predict the functions and impact of drug transporters
Authors: Matsson Pär , Bergström Christel A S 
Published: September 2015

AbstractTransport proteins are important mediators of cellular drug influx and efflux and play crucial roles in drug distribution, disposition and clearance. Drug-drug interactions have increasingly been found to occur at the transporter level and, hence, computational tools for studying drug-transporter interactions have gained in interest. In this short review, we present the most important transport proteins for drug influx and efflux. Computational tools for predicting and understanding the substrate and inhibitor interactions with these membrane-bound proteins are discussed. We have primarily focused on ligand-based and structure-based modeling, for which the state-of-the-art and future challenges are also discussed.
Loperamide and P-glycoprotein inhibition: assessment of the clinical relevance
Authors: Vandenbossche Joris , Huisman Maarten , Xu Yimei , Sanderson-Bongiovanni Dawn , Soons Paul 
Published: September 2015

Abstract

Objectives
Loperamide is a peripherally acting μ opioid receptor agonist and an avid substrate for P-glycoprotein. This may give rise to drug–drug interactions and increased risk for central adverse effects. The objective of this study was to re-evaluate the predictability of non-clinical data using loperamide as a probe P-glycoprotein substrate. We searched the literature for papers containing data on drug–drug interactions of loperamide-containing products in humans. We also reviewed the internal worldwide safety database of Johnson & Johnson for spontaneous case reports suggestive of a central opioid effect after coadministration of loperamide with a P-glycoprotein inhibitor or substrate.

Key findings
Only one of the ten studies in our review supported the finding that inhibition of P-glycoprotein is associated with clinically relevant signs or symptoms of central nervous system (CNS) depression/opioid toxicity of loperamide. None of the 25 spontaneous case reports of interest were suggestive of signs or symptoms of CNS depression/opioid toxicity due to coadministration of loperamide and a P-glycoprotein inhibitor or substrate.

Summary
Based on a review of the literature and a cumulative review of the sponta-neous case reports, there is insufficient evidence that an interaction between loperamide and a P-glycoprotein inhibitor or substrate is associated with clinical symptoms of CNS depression/opioid toxicity when loperamide is taken at the recommended dose.
Surfactant systems for nasal zidovudine delivery: structural, rheological and mucoadhesive properties
Authors: Carvalho Flávia C , Barbi Mariana S , Sarmento Victor Hugo V , Chiavacci Leila A , Netto Flávia M , Gremião Maria P D 
Published: September 2015

Abstract

Objectives
Zidovudine is the antiretroviral drug most frequently used for the treatment of AIDS. Although its effectiveness is recognized, it undergoes extensive first-pass metabolism and exhibits poor oral bioavailability. The nasal route is an option for enhanced therapeutic efficacy and to reduce the extent of the first-pass effect. There are some mechanisms that limit intranasal absorption, such as mucociliary clearance, which rapidly removes the formulation from the nasal cavity. To improve the nasal residence time of zidovudine on the nasal mucosa, we aimed to develop a mucoadhesive surfactant system for zidovudine nasal administration.

Methods
Systems composed of PPG-5-CETETH-20 as surfactant, oleic acid and water were characterized by polarized light microscopy, small-angle X-ray scattering and rheological measurements. Mucoadhesion was investigated by phase behaviour studies, rheological synergism and mucoadhesive strength determination.

Key findings
Results indicate that the original formulations were microemulsions that displayed phase transition to a lamellar phase when brought into contact with aqueous nasal simulated mucus. The phase transition was accompanied by an increase in system elasticity and, irrespective of phase behaviour, all the systems showed a good mucoadhesive force. Thus, a viscous and mucoadhesive liquid crystalline matrix could be formed when the formulations were in contact with simulated mucus, which may prolong the residence time of zidovudine in the nasal cavity.

Conclusions
These findings indicate a potentially useful system for nasal administration of zidovudine.
Modification of gastric pH in the fasted dog
Authors: Polentarutti Britta , Albery Tamsin , Dressman Jennifer , Abrahamsson Bertil 
Published: September 2015

Abstract

Objectives
The aim was to compare the ability of pretreatments to consistently adjust gastric conditions to low or high pH in the fasted state in dogs.

Methods
Four male Labrador/Labrador-cross dogs weighing 25–35 kg were surgically equipped with a ventricle fistula cannula in the stomach and a jejunal nipple valve stoma. Dogs were fasted overnight before the experiments, with free access to water. The pH in the dogs' stomach was modified either orally with buffers (0.1 mol/l HCl-KCl, 0.05 mol/l glycine-HCl, 0.1 mol/l citrate or 0.1 mol/l BIS-TRIS) or intravenously with pharmacological agents (pentagastrin 4–6 μg/kg, ranitidine 50 mg or omeprazole 1 mg/kg). Intragastric pH was recorded continuously for 2 h with an electrode connected to an ambulatory pH meter. Chyme was collected simultaneously from the jejunal stoma as an approximate measure of gastric emptying.

Key findings
0.1 mol/l HCl-KCl buffer p.o. and 1 mg/kg omeprazole i.v. attained low and high gastric pH more reproducibly (11/11 and 6/7 experiments met target values of pH &lt; 3 and &gt; 4, respectively) and for a longer duration (average time exceeding target value 90 and 103 min, respectively) than the other buffers and pharmacological pretreatments. The starting pH did not alter the modifiers' capacity to increase or decrease the pH. However, the lag time before chyme appeared at the jejunal stoma appeared to be longer when the pH was low and shorter when the pH was high.

Conclusions
To achieve a consistently low gastric pH in fasting dogs, 0.1 mol/l HCl-KCl buffer should be administered orally, 15 min before the dosage form. To elevate the gastric pH reproducibly, omeprazole 1 mg/kg should be administered intravenously at least 90 min before oral administration of the dosage form.
Comparative investigations on different polymers for the preparation of fast-dissolving oral films
Authors: Garsuch Verena , Breitkreutz Jörg 
Published: September 2015

Abstract

Objectives
The aim was to compare different film-forming materials used for the preparation of fast-dissolving oral films.

Methods
Films were prepared with and without caffeine and caffeine citrate as model drugs. The disintegration/dissolution behaviour of films was investigated using the newly developed slide frame method and Petri dish method. Films were also characterised by dynamic vapour sorption.

Key findings
All films dissolved within 40 s. Drug-loaded films disintegrated more slowly than the equivalent drug-free formulations. Disintegration/dissolution was fastest with films made from the carboxymethyl cellulose C 30 PA 09 (drug-free &lt; 5 s, drug-loaded &lt; 10 s). Dissolution times for drug-loaded oral films made from C 30 PA 09 and HM 6 PA 2910 (hydroxypropyl methyl cellulose) differed significantly (α= 0.05). Dynamic vapour sorption studies revealed higher water absorption ratios for carboxymethyl cellulose films, and these were sticky and difficult to handle.

Conclusions
This case study showed that hydroxypropyl methyl cellulose was the most suitable film-forming material for drug-free and caffeine-loaded films, providing fast dissolution films that were not sticky and were easy to handle.
Molecularly imprinted polymers as drug delivery systems for the sustained release of glycyrrhizic acid
Authors: Cirillo Giuseppe , Parisi Ortensia Ilaria , Curcio Manuela , Puoci Francesco , Iemma Francesca , Spizzirri Umile Gianfranco , Picci Nevio 
Published: September 2015

Abstract

Objectives
The aim was to synthesize molecularly imprinted polymers (MIPs) with high recognition properties towards glycyrrhizic acid and to evaluate the performance of these materials to act as base excipients in glycyrrhizic acid sustained release in gastrointestinal simulating fluids.

Methods
MIPs were synthesized using methacrylic acid (MAA) as acidic, 2-(dimethylamino)ethyl methacrylate (DMAEMA) as basic, and 2-hydroxyethylmethacrylate (HEMA) as neutral functional monomers, while ethylene glycol dimethacrylate (EGDMA) was chosen as a crosslinking agent. The imprinting effect was evaluated by binding experiments using glycyrrhizic acid and glycyrrhetic acid (analogue molecule) solutions and in-vitro release studies were performed in gastrointestinal simulating fluids.

Key findings
Good recognition and selectivity properties were found in all the synthesized materials in both ethanol and ethanol–water mixture. The release from non-imprinted polymers was indeed higher at acidic pH, while a slower release was observed in MIPs' case, because of the presence of imprinted cavities in the polymeric structure. The stronger capacity of MAA to interact by hydrogen bonds with the template makes MAA-containing MIPs the most effective materials in both rebinding and release experiments.

Conclusions
The release tests confirm the applicability of imprinted polymer for glycyrrhizic acid sustained release in gastrointestinal simulating fluids.
In-situ absorption, protein binding and pharmacokinetic studies of S002-853, a novel antidiabetic and antidyslipidaemic flavone derivative in rats
Authors: Gautam Nagsen , Kushwaha Hari Narayan , Pratap Ram , Singh Shio Kumar 
Published: September 2015

Abstract

Objectives
The aim of the study was to investigate the in-situ absorption kinetics, plasma protein binding and pharmacokinetic characteristics of a novel synthetic flavone derivative, S002-853, which shows pronounced antidiabetic and antidyslipidaemic activity.

Methods
Quantification of S002-853 in plasma was performed by the LC-MS/MS method and in-situ sample analysis was carried out by the HPLC-UV method.

Key findings
The absorption rate constant was 0.274/h in a mild alkaline environment, which S002-853 experiences in the intestine following oral dose administration. Plasma protein binding was found to be 26.37 ± 2.58% at a concentration of 1 μg/ml. The pharmacokinetic parameters were determined in male rats after administration of a single 40 mg/kg oral dose and 10 mg/kg intravenous dose. The peak plasma concentration (Cmax) was found to be 60.93 ng/ml at 8 h after oral administration. Irregular concentration–time profiles with secondary peaks were observed after oral dose administration. The elimination half-life of the compound was 19.56 h and 16.30 h after oral and intravenous doses, respectively. Comparison of the AUC after oral and intravenous dosing of S002-853 indicates that only about 29.48% (bioavailability) of the oral dose reaches the systemic circulation.

Conclusions
In-situ study of S002-853 shows slow absorption from the gastrointestinal tract. S002-853 also shows low plasma protein binding. The pharmacokinetic parameters after oral and intravenous dose reveal low oral bioavailability and high mean residence time.
NaHS ameliorates diabetic vascular injury by correcting depressed connexin 43 and 40 in the vasculature in streptozotocin-injected rats
Authors: Zheng Yu-Fen , Dai De-Zai , Dai Yin 
Published: September 2015

Abstract

Objectives
Cardiovascular complication contributes an important role to morbidity and mortality in patients with diabetes. We hypothesized that these abnormalities are mainly mediated by oxidative stress, endothelial dysfunction and impaired intracellular communications. Thus, we examined vasoactivity and expression of connexin (Cx) 43 and 40, protein kinase C-ɛ (PKCɛ) and NADPH oxidase of the vasculature of thoracic aorta in streptozotocin (STZ)-injected rats, and whether NaHS could reverse these abnormalities compared with aminoguanidine.

Methods
Male Sprague–Dawley rats were administered with STZ (60 mg/kg, i.p.) to induce diabetes. Diabetic rats were divided into untreated and treated groups in the 5th–8th week and intervention with either NaHS (5 mg/kg daily, s.c.) or aminoguanidine (100 mg/kg daily, p.o.) was made.

Key findings
In rats with untreated diabetes, hyperglycaemia, increased activity of inducible nitric oxide (NO) synthase, increased NO, mild vascular spasm, reduced NO bioavailability and diminished vasorelaxation were found. These findings were accompanied by downregulated Cx43 and Cx40, and upregulated PKCɛ and NADPH oxidase subunits p22phox/p47phox/p67phox in the thoracic aorta. NaHS appears to be as effective as aminoguanidine in attenuating these abnormalities.

Conclusions
NaHS shows promise in relieving diabetic vascular abnormality by upregulating junctional connexin Cx40 and Cx43, via normalizing NADPH oxidase and PKCɛ in the vasculature.