bluuebunny/crossref_metadata_2025 huggingface dataset:
Securitization and counter-securitization in Afghanistan
Authors: Stritzel Holger , Chang Sean C
Published: September 2015

This article confronts securitization theory with the war in Afghanistan and thus explores questions and dynamics of securitization in a specific communicative situation of military combat. The confrontation highlights not only less well researched questions of implementation, resistance, legitimacy and difficulties of establishing authority in securitizations, but it also inspires a conceptualization of counter-securitization within the theory. In Afghanistan sovereign power to control and realize a securitization at the implementation stage was significantly fragmented so that processes of securitization became more iterative and interactive, and acts of acceptance versus resistance with regard to securitizing moves were more complex than traditionally assumed by the theory. Reflecting on securitization theory, the article thus explores the case of Afghanistan through a conceptualization of its dynamics as a prolonged political game of moves and counter-moves marked by securitizing and counter-securitizing speech acts in which the communicative situation of war becomes visible as a process of strategic interactions in continuous sequences of action and reaction.
Families Living in Poverty
Authors: Swafford Melinda D. , Wingate Kim O. , Zagumny Lisa , Richey Dean
Published: September 2015

This study examined family-centeredness and experiences in early intervention from the perspectives of families living near or below the federal poverty level. Data were collected from 17 families (11 were single-parent families) across three early intervention service districts in Tennessee, as a subset of a larger investigation of the Pathways to Family Empowerment Project. Qualitative inquiry guided the investigation, and families participated in one-on-one interviews. Notable findings include families’ satisfaction with experiences in early intervention, how demographic variables influenced families’ experiences, families’ suggestions to improve practices, acknowledgment of effective practices, and families’ perceptions of their quality of life. Researchers found contradictions in that some families described specific practices as barriers to positive outcomes whereas other families described those same practices as effective. The study’s contributions are discussed in relation to developing comprehensive early intervention practices that meet families’ unique needs and are consistent with the goals of family-centeredness.
Empowering Pre-Adolescent Girls
Authors: Galeotti Stephanie
Published: September 2015

This research study examined the extent of long-term participation in Girls on the Run (GOTR), an experiential learning program for pre-adolescent girls, and its effect on healthy living and self-esteem. To explore these relationships, an exploratory, mixed-methods study was conducted, which involved open- and closed-ended surveys and interviews. Data collection took place in Seattle, Washington, with former Girls on the Run Puget Sound (GOTRPS) participants who now range in age from 8 to 20 years. Specifically, this study scrutinized the (a) long-term participation of the GOTR program, (b) self-perceptions and perceived behavioral changes as a result of GOTR, and (c) whether or not GOTR values were reinforced in the home. Even though the sample size was small, results concluded positive program impact on girls who participated either once (short-term) or repeatedly (long-term). Correlations on long-term participation revealed a positive and statistical significant correlation ( r = .350, p = .002).
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.
Disney’s pedagogies of pleasure and the eternal recurrence of whiteness
Authors: Sandlin Jennifer A , Maudlin Julie Garlen
Published: September 2015

In this article, we examine how Disney participates in an affective economy through an analysis of how it engages with pleasure, and ask questions about what Disney’s manufacturing and selling of pleasure does, pedagogically. We posit that Disney’s pedagogies of pleasure, which operate from the notion that escape is attainable via the pleasurable experiences offered at Disney parks, teach us how to be particular kinds of Disney subjects who escape into safe and controlled forms of pleasure – these escape fantasies offer a way for consumers to disavow the racism and white supremacy that characterize Western humanist and colonialist projects. Then, through a reading of Escape From Tomorrow, a recent surrealist horror film that explores the “dark side” of the “Happiest Place on Earth,” we analyze how pleasure and the false promise of escape from conflict are illustrated in the film. We take up Nietzsche’s concept of “eternal recurrence” to explore the inescapability of our own complicity in the perpetuation of white, heteropatriarchal narratives through our repetitive affective engagements with Disney. Finally, we explore how an acceptance of inescapability demands that we acknowledge how we are complicit in the perpetuation of white supremacy through our engagements with Disney’s pedagogies of pleasure. We argue that this acceptance is not a nihilistic trap that suggests only an unbearable despair but an active choice that holds productive potential for acknowledging and exposing the racist myths of Western humanism perpetuated through Disney’s pedagogies of pleasure.
On-site non-invasive condition assessment for cement mortar–lined metallic pipelines by time-domain fluid transient analysis
Authors: Gong Jinzhe , Stephens Mark L , Arbon Nicole S , Zecchin Aaron C , Lambert Martin F , Simpson Angus R
Published: September 2015

Pipeline condition assessment is essential for targeted and cost-effective maintenance of aging water transmission and distribution systems. This article proposes a technique for fast and non-invasive assessment of the wall condition of cement mortar–lined metallic pipelines using fluid transient pressure waves (water hammer waves). A step transient pressure wave can be generated by shutting off a side-discharge valve in a pressurised pipeline. The wave propagates along the pipe and reflections occur when it encounters sections of pipe with changes in wall thickness. The wave reflections can be measured by pressure transducers as they are indicative of the location and severity of the wall deterioration. A numerical analysis is conducted to obtain the relationship between the degree of change in wall thickness in a cement mortar–lined pipe and the size of the corresponding pressure wave reflection. As a result, look-up charts are generated for any specific cement mortar–lined pipeline to map this relationship. The wall thickness of a deteriorated or distinct section can be determined directly and quickly from the charts using the size of the reflected wave, thus facilitating on-site pipeline condition assessment. The validity of this time-domain pipeline condition assessment technique is verified by numerical simulations and a case study using the field data measured in a mild steel cement mortar–lined water main in South Australia. The condition of the pipe as assessed by the proposed technique is generally consistent with ultrasonic measurements.
Does Public Financing Affect Judicial Behavior? Evidence From the North Carolina Supreme Court
Authors: Hazelton Morgan L. W. , Montgomery Jacob M. , Nyhan Brendan
Published: September 2015

Many observers are concerned that campaign contributions could affect the decisions of elected judges. However, the empirical correlation between contributions and judicial decisions is consistent with two different explanations of judicial behavior: (a) money influences judges or (b) contributors choose to support candidates with a similar philosophical or legal perspective. In this article, we take advantage of North Carolina’s shift to a voluntary public finance system for state Supreme Court candidates to obtain more credible estimates of the contributions–behavior relationship. Applying a difference-in-differences research design, we provide evidence that justices who opted into public financing became relatively less favorable toward attorney donors. We also find partial support for our hypothesis that participating justices became more moderate in their voting patterns. Taken together, these findings suggest that public financing reduced responsiveness to donors among participating justices.
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.
A Never Ending Journey
Authors: Kozleski Elizabeth B. , Yu Ting , Satter Allyson L. , Francis Grace L. , Haines Shana J.
Published: September 2015

A team from Schoolwide Integrated Framework for Transformation (SWIFT), a federally funded technical assistance project focused on creating cascading, aligned systems for inclusive education, conducted a series of focus groups and interviews with school administrators, general and special educators, and related service providers in six schools across the United States. Six themes merged from the study that highlighted the importance of defining inclusive education as well as building the capacity of people to understand and implement the components of a system of inclusive education. These themes suggest that leadership for inclusive education requires attention to the structures and processes used to signal that inclusive education is an undergirding principle of practice. Equally important is the development of relationships among students, teachers, and families that cement the structures. Networking, planning and organizing, using time and space strategically, and connecting schools with their communities were all aspects of capacity building. In addition, data revealed the importance of paying attention to the context of inclusive education within schools and in their surrounding communities. Further, enthusiastic support from and communication with families emerged as an important theme.
Scientific Dishonesty
Authors: Hofmann Bjørn , Helgesson Gert , Juth Niklas , Holm Søren
Published: September 2015

As we need knowledge about the prevalence of scientific dishonesty, this study investigates the knowledge of, experiences with, and attitudes toward various forms of scientific dishonesty among PhD students at the main medical faculties in Sweden and Norway. An anonymous questionnaire was distributed to all post-graduate research students attending basic PhD courses at the medical faculties in Stockholm and Oslo during the fall 2014. The responding doctoral students reported to know about various forms of scientific dishonesty from the literature, in their department, and for some also through their own experience. Some forms of scientific misconduct were considered to be acceptable by a significant minority. There was a high level of willingness to report misconduct but little awareness of relevant policies for scientific conduct.
Witnessing distant and proximal suffering within a zone of danger: Lay moralities of media audiences in the Philippines
Authors: Ong Jonathan Corpus
Published: September 2015

Drawing on the anthropology of moralities, the phronetic turn in media ethics scholarship, and audience research in media studies, this article explores how media audiences in the global South are implicated in moral dilemmas of bearing witness. Central are the diverse audience practices of engaging with proximal suffering on one hand and distant suffering on the other, where sympathy with or denial strategies towards suffering others are shaped not only by audiences’ geographical distance to tragedy, but crucially by classed moralities that profoundly shape judgments to sufferers and the media that represent them. A synthesis of ethnographic audience research with middle-class and low-income populations in disaster-prone Philippines shows how middle-class moralities of respectability inform social denial to proximal suffering, while low-income people’s personal experiences of suffering lead to the instrumentalization of television narratives as symbolic resources to cope with their own suffering.
The Frequency of Frailty in Ambulatory Patients With Chronic Lung Diseases
Authors: Mittal Neha , Raj Rishi , Islam Ebtesam Attaya , Nugent Kenneth
Published: September 2015

Objectives: To determine the prevalence of frailty in patients with chronic lung diseases. Methods: We studied 120 patients with chronic lung disease using Fried’s criteria (gait speed, weight loss, exhaustion, grip strength, and physical activity). Results: The study population (56% women) had a mean age of 64 ± 13 years, mean body mass index of 31± 9 kg/m2, and a mean FEV1 (forced expiratory volume in 1 second) of 60% ± 25% of predicted. The average gait speed was 52.1 ± 14.3 m/min; 18% were frail, 64% prefrail, and 18% robust. Gait speed correlated with frailty status and decreased as frailty worsened (57 m/min in robust subjects and 41 m/min in frail subjects). Slow gait speeds (<60 m/min) had a 95% sensitivity and 34% specificity to predict frailty. Conclusions: Patients with chronic lung disease frequently meet Fried’s criteria for frailty. Gait speed can be used to screen these patients to determine if a more detailed evaluation is needed.
Computational modeling to predict the functions and impact of drug transporters
Authors: Matsson Pär , Bergström Christel A S
Published: September 2015

Transport 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

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.

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

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

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 < 3 and > 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

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 < 5 s, drug-loaded < 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

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

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

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.
Two novel lupane triterpenoids from Paullinia pinnata L. with fibroblast stimulatory activity
Authors: Annan Kofi , Houghton Peter J
Published: September 2015

Objectives

Novel lupane triterpenoids from Paullinia pinnata L., a Ghanaian plant traditionally used for wound healing, were examined for in-vitro fibroblast stimulatory activity using the 142BR cell line.

Methods

Bioactivity-guided isolation of the crude extract of P. pinnata L. was carried out in order to determine the nature of the compounds responsible for the stimulation of fibroblast proliferation.

Key findings

Two novel compounds were isolated and characterised, namely, 6β-(3′-methoxy-4′-hydroxybenzoyl)-lup-20(29)-ene-one (1) and 6β-(3′-methoxy-4′-hydroxybenzoyl)-lup-20(29)-ene-ol (2), together with three known compounds, friedelin (3), β-sitosterol (4) and β-sitosterol-3-d-glucoside (5). The methanol extract of the roots of P. pinnata caused a significant in-vitro increase (94%) in 142BR cell line proliferation at 20 µg/ml compared with the control.

Conclusions

Compounds 1 and 2, which were isolated from the active chloroform fraction, have not previously been reported and showed a dose-dependent increase in proliferation of 142BR cells up to 3 µm; compounds 3, 4 and 5 had no effect on the 142BR cell line at the concentrations tested.
Transdermal iontophoretic delivery of a novel series of dopamine agonists in vitro: physicochemical considerations
Authors: Ackaert Oliver W , De Graan Jeroen , Capancioni Romano , Dijkstra Durk , Danhof Meindert , Bouwstra Joke A
Published: September 2015

Objectives

The transdermal iontophoretic delivery of a novel series of 2- aminotetralins and chromanamine-based dopamine agonists was investigated in vitro.

Methods

Systematic structural modifications allowed us to investigate their effect on solubility in the donor phase and iontophoretic delivery across human skin. Transport profiles were analysed with nonlinear mixed effect modelling, utilizing an extension to an existing compartmental model. Furthermore, relationships between physicochemical properties and transport parameters were addressed.

Key findings

A solubility increase was observed: 5,6-di-OH-DPAT < 5-OH-MPAT < 5-OH-EPAT < 8-OH-DPAC. The structure significantly affected the iontophoretic delivery across human stratum corneum and dermatomed human skin with the highest flux for 5-OH-EPAT and 5-OH-MPAT. The extended model with two skin release constants (KR1, KR2) described more adequately iontophoretic transport profiles than the existing model with one release constant. The extended model suggested two parallel transport pathways during current application. Across human stratum corneum, the electrophoretic mobility, measured with capillary electrophoresis, showed a linear relationship with the electromigrative flux and the zero-order iontophoretic mass input into the skin (I0).

Conclusions

Combining transport parameters (I0, KR1 and KR2), predicted from physicochemical properties, with compartmental modelling provided a powerful tool to simulate iontophoretic transport profiles for screening potential candidates and designing experiments.
Surface tension and wettability in transdermal delivery: a study on the in-vitro permeation of haloperidol with cyclodextrin across human epidermis
Authors: Azarbayjani Anahita Fathi , Lin Haishu , Yap Chun Wei , Chan Yew Weng , Chan Sui Yung
Published: September 2015

Objectives

The aim of this work was to study the effect of surface tension and contact angle on the permeation of haloperidol across human skin using cyclodextrin derivatives.

Methods

Surface tension and contact angle of randomly methylated β-cyclodextrin (RM β-CD) and hydroxypropyl β-cyclodextrin (HP β-CD) solutions were measured. Haloperidol solubility and molecular modelling were carried out using the two cyclodextrin derivatives. In-vitro skin permeation was carried out using human skin models.

Key findings

The highest increase in drug solubility was observed when the drug was in solution with pH 5 when compared to non-ionised solution, resulting in a 128-fold increase in the intrinsic solubility of the drug. Surface tension measurements indicate a surface-active effect for RM β-CD and HP β-CD. Contact angle measurements showed that vehicles with higher skin wettability increased the contact of the drug with the skin surface and therefore resulted in higher drug permeation across human epidermis.

Conclusions

It is concluded that transdermal flux of a drug through the skin may be optimised by controlling surface tension, drug solubility and skin wettability.
Chitosan-coated antifungal formulations for nebulisation
Authors: Albasarah Yacoub Y , Somavarapu Satyanarayana , Stapleton Paul , Taylor Kevin M G
Published: September 2015

Objectives

The aim of this study was to produce and characterise amphotericin B (AmB) containing chitosan-coated liposomes, and to determine their delivery from an air-jet nebuliser.

Methods

Soya phosphatidylcholine : AmB (100 : 1) multilamellar vesicles were generated by dispersing ethanol-based proliposomes with 0.9% sodium chloride or different concentrations of chitosan chloride. These liposomes were compared with vesicles produced by the film hydration method and micelles. AmB loading, particle size, zeta potential and antifungal activity were determined for formulations, which were delivered into a two-stage impinger using a jet nebuliser.

Key findings

AmB incorporation was highest for liposomes produced from proliposomes and was greatest (approximately 80% loading) in chitosan-coated formulations. Following nebulisation, approximately 60% of the AmB was deposited in the lower stage of the two-stage impinger for liposomal formulations, for which the mean liposome size was reduced. Although AmB loading in deoxycholate micellar formulations was high (99%), a smaller dose of AmB was delivered to the lower stage of the two-stage impinger compared to chitosan-coated liposomes generated from proliposomes. Chitosan-coated and uncoated liposomes loaded with AmB had antifungal activities against Candida albicans and C. tropicalis similar to AmB deoxycholate micelles, with a minimum inhibitory concentration of 0.5 µg/ml.

Conclusions

This study has demonstrated that chitosan-coated liposomes, prepared by an ethanol-based proliposome method, are a promising carrier system for the delivery of AmB using an air-jet nebuliser, having a high drug-loading that is likely to be effectively delivered to the peripheral airways for the treatment of pulmonary fungal infections.
Investigation of solute permeation across hydrogels composed of poly(methyl vinyl ether-co-maleic acid) and poly(ethylene glycol)
Authors: Raj Singh Thakur Raghu , Woolfson A David , Donnelly Ryan F
Published: September 2015

Objectives

Swelling kinetics and solute permeation (theophylline, vitamin B12 and fluorescein sodium) of hydrogels composed of poly(methyl vinyl ether-co-maleic acid) (PMVE/MA) and poly(ethylene glycol) (PEG) are presented.

Methods

The effects of PMVE/MA and PEG 10 000 content on swelling behaviour (percentage swelling, the type of diffusion and swelling rate constant) were investigated in 0.1 m phosphate buffer. Network parameters, such as average molecular weight between crosslinks (Mc) and crosslink density, were evaluated.

Key findings

The percentage swelling and Mc of hydrogels increased with decrease in PMVE/MA content, where the water diffusion mechanism into the hydrogels was Class-II type. In contrast, increase in PMVE/MA content caused an increase in the crosslink density. Permeation of theophylline, vitamin B12 and fluorescein sodium, with increasing hydrodynamic radii, was studied through the equilibrium swollen hydrogels composed of PMVE/MA and PEG. In general, the permeability and diffusion coefficients of all three solutes decreased with increase in the PMVE/MA content. In addition, permeability and diffusion coefficient values increased with decreases in the hydrodynamic radii of the solute molecules.

Conclusions

The hydrogels have shown a change in swelling behaviour, crosslink density, Mc and solute permeation with change in PMVE/MA content, thus suggesting a potential application in controlled drug-delivery systems.
Enhancement of the intranasal delivery of insulin via a novel mucoadhesive Carbopol gel
Authors: El-Dakrouri Walaa Ahmed , Ibrahim Howida Kamal , Ghorab Mohamed Khaled , Ghorab Mahmoud Mohamed
Published: September 2015

Objectives

The objectives of this study were to develop an intranasal insulin gel using Carbopol homogenization rather than neutralization and to examine the effectiveness of the gel compared with a subcutaneous injection.

Methods

Four factors, namely the molecular weight of polyethylene glycol (PEG), the concentration of Carbopol, the temperature of preparation and the type of absorption enhancer, were evaluated for their effect on viscosity and in-vitro insulin release. Bioavailability of insulin from selected formulations was compared with an intranasal solution and subcutaneous injection in rabbits.

Key findings

Increasing the molecular weight of PEG and Carbopol concentration increased the gel viscosity and changed the release mechanism from diffusion to case II transport. Applying heat during preparation resulted in a lower viscosity gel and increased the in-vitro insulin release. Among the two enhancers studied, sodium deoxycholate resulted in a higher viscosity gel than Tween 80. In vivo, the intranasal gel showed a stronger and longer hypoglycaemic effect with 1.7- and 3.1-fold higher maximum decrease in blood glucose level and area above the curve, respectively, compared with the subcutaneous injection.

Conclusions

The homogenized Carbopol intranasal gel could be an efficient noninvasive way for insulin delivery but selection of gel components and method of preparation are critical for achieving the most desired effect.
The orally combined neuroprotective effects of sodium ferulate and borneol against transient global ischaemia in C57 BL/6J mice
Authors: Chen Xiao-hong , Lin Zhu-zhen , Liu An-min , Ye Jian-tao , Luo Yan , Luo Yu-yan , Mao Xue-xuan , Liu Pei-qing , Pi Rong-biao
Published: September 2015

Objectives

This study aimed to investigate the possible modification of the neuroprotective effect of sodium ferulate, when orally co-administered with borneol, in transient global cerebral ischaemia-induced functional, histological and cellular alterations in mice.

Methods

The bilateral common carotid artery occlusion was conducted in C57 BL/6J mice for 25 min. The mice were then subjected to a water maze test over an extended recovery period, followed by an assessment of neuronal loss in the CA1 region of the hippocampus (haematoxylin and eosin staining). The blood–brain barrier permeability (Evans blue tracing), brain oedema and oxidative stress were assayed and histological sections were also immunostained for gliofibrillar acid protein (GFAP) expression.

Key findings

The ischaemia reperfused mice were associated with long-lasting spatial learning deficits in the absence of other behavioural impairments and with neurodegeneration in the hippocampal CA1 region. However, the histological injuries were significantly attenuated by oral co-administration of sodium ferulate and borneol. Furthermore, combined treatment with sodium ferulate and borneol resulted in a significant reduction in brain oedema, GFAP-positive cells, malonaldialdehyde levels and blood–brain barrier permeability, but an increase in superoxide dismutase activity.

Conclusions

Borneol may have benefits for the neuroprotective effect of sodium ferulate against injury induced in the brain by ischaemia/reperfusion.
Systemic chemotherapy-induced microsatellite instability in the mononuclear cell fraction of women with breast cancer can be reproduced in vitro and abrogated by amifostine
Authors: Pinto Jorge L F , Fonseca Fernando L A , Marsicano Sarah R , Delgado Pamela O , Sant'Anna Aleksandra V L , Coelho Patrícia G , Maeda Patríca , Del Giglio Auro
Published: September 2015

Objectives

Microsatellite instability (MSI) induction by alkylating agent-based chemotherapy (ACHT) may underlie both tumor resistance to chemotherapy and secondary leukaemias in cancer patients. We investigated if ACHT could induce MSI in tumor-derived plasma-circulating DNA (pfDNA) and in normal peripheral blood mononuclear (PBMN) cells. We also evaluated if amifostine could interfere with this process in an in-vitro model.

Methods

MSI was determined in pfDNA, PBMN cells and urine cell-free DNA (ufDNA) of 33 breast cancer patients before and after ACHT. MCF-7 cells and PBMN from normal donors were exposed in vitro to melphalan, with or without amifostine.

Results

We observed at least one MSI event in PBMN cells, pfDNA or ufDNA of 87, 80 and 80% of patients, respectively. In vitro, melphalan induced MSI in both MCF-7 and normal PBMN cells. In PBMN cells, ACHT-induced MSI occurred together with a significant decrease in the expression of the DNA mismatch repair gene hMSH2. Amifostine decreased hMSH2 expression and also prevented MSI induction only in normal PBMN cells.

Conclusions

ACHT induced MSI in PBMN cells and in tumour-derived pfDNA. Because of its protective effect against ACHT induction of MSI in normal PBMN cells in vitro, amifostine may be a potential agent for preventing secondary leukaemias in patients exposed to ACHT.
Protection by apple peel polyphenols against indometacin-induced oxidative stress, mitochondrial damage and cytotoxicity in Caco-2 cells
Authors: Carrasco-Pozo Catalina , Gotteland Martin , Speisky Hernán
Published: September 2015

Objectives

Exposure of Caco-2 cells to indometacin can be a useful model to assess some of the cytotoxic events that appear to underlie the gastrointestinal lesions associated with the use of this anti-inflammatory agent. Using such a cellular model, we addressed here the cytoprotective potential of a recently standardized apple peel polyphenol extract, APPE.

Methods

We firstly characterized APPE in terms of its free radical scavenging and antioxidant properties, and subsequently investigated its potential to protect Caco-2 cells against the deleterious effects of indometacin on cellular oxidative status (redox state, malondialdehyde, glutathione (GSH) and oxidized glutathione (GSSG) levels), mitochondrial function (ATP and mitochondrial membrane potential) and cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) leakage). For comparative purposes, the free radical scavenging properties and reducing capacity of quercetin, epicatechin and rutin were also estimated.

Key findings

In the absence of APPE, indometacin induced mitochondrial perturbations (reducing ATP and the mitochondrial membrane potential), enhanced the oxidative status (decreasing the GSH/GSSG ratio and increasing dichlorofluorescein oxidation and malondialdehyde) and lowered the cell viability (decreasing MTT reduction and increasing LDH leakage). APPE, whether pre-added or co-incubated with indometacin, concentration-dependently prevented these mitochondrial, oxidative and cell viability alterations. Prompted by the recently recognized ability of indometacin to enhance the mitochondrial formation of reactive oxygen species, APPE was also characterized in terms of its free radical-scavenging capacity. APPE was found to actively scavenge O2·-, HO· and peroxyl radicals. Such free radical-scavenging activity of APPE suggests that its ability to protect mitochondria and prevent the oxidative and lytic damage induced by indometacin arises from its potent antioxidant capacity.

Conclusions

In Caco-2 cells APPE prevented mitochondrial oxidative and cell viability alterations induced by indometacin possibly through its ability to scavenge reactive oxygen species. These findings are of interest in view of the high prevalence of gastrointestinal side-effects associated with the use of conventional anti-inflammatory agents.
Cerebrospinal Fluid Biomarkers of Japanese Encephalitis
Authors: Sengupta Nabonita , Mukherjee Sriparna , Tripathi Piyush , Kumar Rashmi , Suryawanshi Amol Ratnakar , Basu Anirban
Published: September 2015

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Acute encephalitis syndrome (AES) is a group of central nervous system (CNS) disorders caused by a wide range of viruses, bacteria, fungi, chemicals and toxins. It is important to distinguish between various forms of infectious encephalitis with similar clinical manifestations in order to ensure specific and accurate diagnosis and development of subsequent therapeutic strategies. Cerebrospinal fluid (CSF) is in direct contact with the CNS and hence it is considered to be an excellent source for identifying biomarkers for various neurological disorders. With the recent advancement in proteomic methodologies, the field of biomarker research has received a remarkable boost.  The present study identifies potential biomarkers for JE using a proteomics based approach. The CSF proteomes from ten patients each with JE and Non-JE acute encephalitis were analyzed by 2D gel electrophoresis followed by mass spectrometry. Vitamin D-binding protein (DBP), fibrinogen gamma chain, fibrinogen beta chain, complement C4-B, complement C3 and cytoplasmic actin were found to be significantly elevated in case of JE indicating severe disruption of the blood brain barrier and DBP can be suggested to be an important diagnostic marker.