bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of 308 nm excimer laser on segmental vitiligo: a retrospective study of 80 patients with segmental vitiligo
Authors: Do Jeong Eun , Shin Jae Yong , Kim Do‐Young , Hann Seung‐Kyung , Oh Sang Ho
Published: May 2011

Background: Segmental vitiligo (SV), which frequently accompanies poliosis, indicating a poor prognosis that is likely resistant to treatments.

Objectives: In this study, we performed a retrospective analysis to evaluate the treatment response to 308 nm excimer laser in SV patients.

Methods: A retrospective chart and photographic review was performed on 80 SV patients who had been treated with 308 nm excimer laser for >3 months.

Results: Eighty patients with SV (mean age: 24.0 years ± 15.3, males: 50%) were included in this study. The mean grade of repigmentation was 2.3 after 20.6 months of mean treatment duration; 23.8% of 80 patients showed grade 4, 20% showed grade 3, and 56.2% showed grade 1–2 repigmentation. However, none of them achieved complete repigmentation with excimer laser. The degree of repigmentation was positively correlated with treatment duration (r=0.315, P=0.004) and cumulative ultraviolet (UV) dosage (r=0.366, P=0.001), whereas it was negatively correlated with disease duration (r=−0.265, P=0.017).

Conclusion: This study suggests that SV has a better repigmentation response when excimer laser is used at earlier stages of the disease and long‐term use and high cumulative UV energy of the excimer laser elicit better responses. Additional treatments like surgical procedures in addition to excimer laser should be considered for complete repigmentation.
Effect of sealer coating on mechanical and physical properties of permanent soft lining materials
Authors: Dayrell Andreza , Takahashi Jessica , Valverde Guilherme , Consani Rafael , Ambrosano Glaucia , Mesquita Marcelo
Published: May 2011

doi: 10.1111/j.1741‐2358.2011.00487.x
 
Effect of sealer coating on mechanical and physical properties of permanent soft lining materials

Objective:  To evaluate the long‐term effects of sealer coating on tensile bond strength and surface roughness of soft liners.

Background:  Failure of the bond between resilient liners and denture base significantly compromise the dentures’ longevity. In addition, surface roughness contributes to bacterial adherence on prosthetic materials, increasing the risk of oral infections.

Methods:  Specimens were manufactured from four reliners [Mucopren Soft (MS), Dentuflex (DF); Soft Comfort Denso (SC) and Ufi Gel SC (USC)], distributed into 10 groups (n = 10), according to material and coating treatment. Tensile bond strength was performed after one year of ageing, while surface roughness was evaluated at 0, 1, 3, 6 and 12 ageing months. Bond strength data were submitted to two‐way anova and Tukey‐HSD tests, while roughness data were submitted to mixed model analysis for repeated measurements (p ≤ 0.05).

Results:  MS and DF without sealer coating presented the highest tensile bond strength. After coating, DF and SC presented increased tensile bond strength. No surface roughness difference was observed in the non‐coated groups over time, acrylic‐based reliners presented higher roughness. Among coated groups, only SC presented increased surface roughness. Acrylic‐based materials presented reduced roughness at three months.

Conclusion:  Surface coating was effective for acrylic reliners in maintaining their initial properties. However, sealer coating should be re‐applied every 3 months.
How to remain nonfolded and pliable: the linkers in modular α‐amylases as a case study
Authors: Feller Georges , Dehareng Dominique , Lage Jean‐Luc Da
Published: May 2011

The primary structure of linkers in a new class of modular α‐amylases constitutes a paradigm of the structural basis that allows a polypeptide to remain nonfolded, extended and pliable. Unfolding is mediated through a depletion of hydrophobic residues and an enrichment of hydrophilic residues, amongst which Ser and Thr are over‐represented. An extended and flexible conformation is promoted by the sequential arrangement of Pro and Gly, which are the most abundant residues in these linkers. This is complemented by charge repulsion, charge clustering and disulfide‐bridged loops. Molecular dynamics simulations suggest the existence of conformational transitions resulting from a transient and localized hydrophobic collapse, arising from the peculiar composition of the linkers. Accordingly, these linkers should not be regarded as fully disordered, but rather as possessing various discrete structural patterns allowing them to fulfill their biological function as a free energy reservoir for concerted motions between structured domains.
Salicylic Acid and its Function in Plant ImmunityF
Authors: An Chuanfu , Mou Zhonglin
Published: May 2011

Zhonglin Mou (Corresponding author)

The small phenolic compound salicylic acid (SA) plays an important regulatory role in multiple physiological processes including plant immune response. Significant progress has been made during the past two decades in understanding the SA‐mediated defense signaling network. Characterization of a number of genes functioning in SA biosynthesis, conjugation, accumulation, signaling, and crosstalk with other hormones such as jasmonic acid, ethylene, abscisic acid, auxin, gibberellic acid, cytokinin, brassinosteroid, and peptide hormones has sketched the finely tuned immune response network. Full understanding of the mechanism of plant immunity will need to take advantage of fast developing genomics tools and bioinformatics techniques. However, elucidating genetic components involved in these pathways by conventional genetics, biochemistry, and molecular biology approaches will continue to be a major task of the community. High‐throughput method for SA quantification holds the potential for isolating additional mutants related to SA‐mediated defense signaling.
PECTIN‐BASED EDIBLE COATING FOR SHELF‐LIFE EXTENSION OF ATAULFO MANGO
Authors: MOALEMIYAN MITRA , RAMASWAMY HOSAHALLI S. , MAFTOONAZAD NEDA
Published: May 2011

Mango is a commercial but highly perishable fruit, and therefore, a longer shelf life is necessary for its successful marketing and consumer satisfaction. This study aims at evaluating the effects of edible coating, based on pectin, on the quality and shelf‐life extension of mangoes. The coating formulations included different combinations of pectin, beeswax, sorbitol and monoglyceride. The fruits were coated and stored at room temperature along with uncoated controls. Samples tested were evaluated periodically for quality parameters, which included visual observation, weight loss, respiration rate, color, firmness, pH, soluble solids (SS), titrable acidity and extent of decay. The coated‐fruits reduced the rate of color development, texture softening, weight loss, CO2 evolution and acid production (only pH and SS increased) compared with the control. The shelf life of control sample was less than a week, whereas the coated fruits remained good for over 2 weeks, thereby offering a significant advantage.

PRACTICAL APPLICATIONS

The study evaluates the use of pectin‐based edible coating for extending the shelf life of mango. The formulation is a blend of hydrophilic and hydrophobic groups to provide controlled respiration and water vapor permeability. The properties of pectin films have been highlighted in a previous paper, and several applications based on the coating have been demonstrated. The present study demonstrates that modifications to the formulation were necessary in order to successfully apply it to mango. Mango is a popular commercial product with high heritability. Simple edible coatings that can help to improve the shelf life and marketability of the product will be of significant interest in the marketing of mango products.
Black‐spot poison ivy: A rare phenomenon
Authors: Paniagua Carmen T. , Bean Ashley S.
Published: May 2011

Purpose: To provide an overview of the clinical presentation, diagnosis, management, and treatment with advanced practice nursing implications of black‐spot poison ivy phenomenon.

Data sources: Case presentation and comprehensive literature review on black‐spot poison ivy.

Conclusions: Black‐spot poison ivy is a rare phenomenon and usually poses a diagnostic challenge. It usually presents after exposure to a higher concentration of uroshiol on Toxicodendron plants. Patients present with black‐spot deposits on the epidermis with underlying poison ivy dermatitis. The black deposits cannot be washed off the skin and are followed by itchy blisters. They eventually peel off and the skin heals without scarring.

Implications for practice: An understanding of the pathophysiology, clinical presentation, treatment, and management of this rare phenomenon is important for the nurse practitioner (NP) to be able to make an accurate diagnosis and initiate appropriate treatment without delay. The NP's recognition and differentiation of it from other skin disorders including melanoma is paramount.
Shin Buddhist Women in America
Authors: Ama Michihiro
Published: May 2011

This article introduces the position of Shin Buddhist women in the United States. It explores how they have negotiated within and without their organizations on local, regional, national and transnational levels.
Statistical Machine Translation: A Guide for Linguists and Translators
Authors: Hearne Mary , Way Andy
Published: May 2011

This paper presents an overview of Statistical Machine Translation (SMT), which is currently the dominant approach in Machine Translation (MT) research. In Way and Hearne (2011), we describe how central linguists and translators are to the MT process, so that SMT developers and researchers may better understand how to include these groups in continuing to advance the state‐of‐the‐art. If these constituencies are to make an impact in the field of MT, they need to know how their input is used by SMT systems. Accordingly, our objective in this paper is to present the basic principles underpinning SMT in a way that linguists and translators will find accessible and useful.
A Sociological Alternative to the Psychiatric Conceptualization of Mental Suffering
Authors: Smith Dena T.
Published: May 2011

Uncovering both the structural causes and experiences of suffering is a central sociological endeavor. Sociologists study many different kinds of suffering; after all, strife is experienced both physically and emotionally, because of internal factors such as illness, due to external factors such as trauma, and as a result of economic, political or natural environments. In this paper, I address one form of suffering: mental suffering. In particular, I describe the medicalization of mental suffering in biological psychiatry, which focuses on the genetic factors of illness and equates mental suffering with mental illness. The psychiatric concept of mental illness highlights the continuing, crucial role for sociology in both understanding the experience and identifying the structural roots of suffering. Since the dominant conceptualization of mental suffering is as a medical concept, it is vital for sociology to offer alternative explanations and contribute to a multidimensional analysis. The roots of mental suffering are much more than biological; social comparison, social inequality, and other social stressors are equally important etiological considerations. Therefore, a true understanding of mental suffering requires multiple perspectives, and sociological constructs guard against a total medicalization of mental suffering.
African‐American Women and Suicide: A Review and Critique of the Literature
Authors: Spates Kamesha
Published: May 2011

This paper reviews the literature on African‐American women’s suicide rates. This topic is often neglected due to African‐American women’s low rates of suicide occurrence. This review seeks to answer the call for increased scientific inquiry on matters related to African‐American women and suicide. The author begins by identifying complex dynamics surrounding African‐American women’s unique social position in order to establish a better understanding of how socio‐cultural influences are addressed in the literature in relation to the suicide paradox. Both theoretical and empirical studies are thoroughly assessed in order to identify the risk and protective factors exclusive to African‐American women. The literature concludes that a history of mental disorders, particularly depression, a history of physical and emotional abuse, and a history of alcohol and substance abuse have all proven significant in increasing the risk of suicidal behavior among African‐American women. Untreated depression continues to be the leading cause of suicide among African‐American women. Contrarily, the literature identifies religious/spiritual beliefs, strong social ties, low rates of suicide acceptability, and unique coping strategies developed as a result of longstanding oppressive conditions as primary reasons for African‐American women’s exceptionally low suicide rates.
Habitat requirements of the endangered beetle Boros schneideri (Panzer, 1796) (Coleoptera: Boridae)
Authors: BLAŽYTĖ‐ČEREŠKIENĖ LAIMA , KARALIUS VIDMANTAS
Published: May 2011

Abstract.  1. To further knowledge regarding habitat requirements of the threatened species Boros schneideri, a total of 1522 dead standing Scots pine (Pinus sylvestris) were checked for the presence of B. schneideri larvae. For the 245 trees inhabited by larvae (16% of all examined trees), tree characteristics and occupancy patterns were measured.

2. As most of the investigated forests were 40–80 years old and were dominated by comparatively thin dead trees (5–20 cm diameter at breast height), B. schneideri larvae were mainly found under the bark of trees with a diameter in the range of 10–20 cm. However, the probability of a tree being inhabited by B. schneideri increased progressively with tree diameter and forest age.

3. Most of the trees with B. schneideri (79%) were in medium‐dense and sparse‐growth pine forests where the canopy cover was 60–80%. The presence of Norway spruce (Picea abies) in Scots pine forests was an important factor affecting the probability of trees being inhabited by B. schneideri. Only 6% of trees inhabited by B. schneideri were found in mixed Scots pine‐Norway spruce forests, where the shadowing was higher than 80%.

4. All dead trees inhabited by B. schneideri had loose and at least slightly fragmented bark. A bark area of 0.08 m2 was found to be sufficient for the survival of B. schneideri. The critical bark thickness for B. schneideri larvae was 5 mm.

5. The data obtained are important for the optimisation of conservation measures implemented during forest management operations.
Treatment of Oral Squamous Cell Carcinoma with Accelerated Radiation Therapy and Concomitant Carboplatin in Cats
Authors: Fidel J. , Lyons J. , Tripp C. , Houston R. , Wheeler B. , Ruiz A.
Published: May 2011

Background:Feline oral squamous cell carcinoma (SCC) carries a very poor prognosis with traditional treatments.

Hypothesis/Objectives:To examine the effectiveness of adding carboplatin to a previously published accelerated radiation protocol in the treatments of oral SCC in cats.

Animals:Thirty‐one cases of oral SCC in cats. Tumor sites included lingual (n = 9), mandible (n = 10), maxilla (n = 7), tonsil (n = 4), and cheek (n = 1).

Methods:Prospective trial using a planned radiation protocol consisting of 14 fractions of 3.5 Gy given within a 9‐day period with the addition of carboplatin given at 90–100 mg/m2on day 1 and day 4.5. Treatments were twice daily with a 6‐hour delay between treatments. All cats presenting with oral SCC without evidence of distant metastasis were eligible.

Results:Median survival for all cats was 163 days (range 53–770 days) with a mean of 319 ± 53 days with significant predictors of survival being site (P= .004) and whether there was a complete response at 30 days (P= .001). Cats with tumors of tonsil origin or cheek responded best to therapy and were long‐term survivors with a mean survival of 724 days and the median had not been reached because of continued survival of 4 cats.

Conclusions and Clinical Importance:This protocol offers an aggressive yet tolerable treatment of oral SCC in cats that might offer improved survival as compared with previously reported treatments. The long‐term survival of cats with tonsillar SCC has not been reported previously.
Selective Saber Rattling by Iraqi Politicians
Authors: Tures John A. , Beaver Kim S.
Published: May 2011

Former Prime Minister Iyad Allawi stunned the Iraqi and American political establishment with his comeback success in Iraq's 2010 election. Speculation immediately began to focus on how his coalition could have won the most seats, focusing on disaffection with the status quo. But the answer could come from a tactic Allawi has repeatedly used: tying his domestic political opponents to countries that Iraq has clashed with in the past, to reignite old hatreds and fears. This article investigates, not only how Allawi and even his rivals have adopted such a strategy, but also how our current understanding of the diversionary theory of conflict needs to be modified to see how politicians in other places play this wag the dog game.
Libya and the International System: Retracing the Aftermath of the Lockerbie Bombing
Authors: Stottlemyre Steven
Published: May 2011

The defining moment of Libya's relationship with the United States during the last decade of the 20th century was the 1991 implication of Libya and its government by the United States and United Kingdom in the 1988 bombing of Pan American Flight 103 over Lockerbie, Scotland. The controversial decision of the United Nations Security Council to employ sanctions against Libya after its refusal to surrender two bombing suspects to the United States and United Kingdom was largely ignored by European countries with interests in Libya, and led to the eventual open opposition to sanctions by many of Libya's African neighbors. Libya was quickly found guilty in the U.S. and UK courts of public opinion; however the common assumption that Libya's refusal reflected its indignation toward the West is problematic, and does not take into account historical factors that pushed Libya away from compliance, nor the lengths to which Libya attempted to sidestep those factors in order to respect international law. This article places Libya's reaction to the destruction of Flight 103 into the context of its recent relationship with the United States, and argues that despite the tainted U.S. public perception of Libya and its leader, the aftermath of the destruction of Flight 103 no longer plays an important role in shaping United States–Libya relations.
Synergistic virulence of Porphyromonas gingivalis and Treponema denticola in a murine periodontitis model
Authors: Orth R.K‐H. , O’Brien‐Simpson N.M. , Dashper S.G. , Reynolds E.C.
Published: May 2011

Chronic periodontitis is characterized by the destruction of the tissues supporting the teeth and has been associated with the presence of a subgingival polymicrobial biofilm containing Porphyromonas gingivalis and Treponema denticola. We have investigated the potential synergistic virulence of P. gingivalis and T. denticola using a murine experimental model of periodontitis. An inoculation regime of four intra‐oral doses of 1 × 1010P. gingivalis cells induced significant periodontal bone loss compared with loss in sham‐inoculated mice, whereas doses of 1 × 109 cells or lower did not induce bone loss. Inoculation with T. denticola with up to eight doses of 1 × 1010 cells failed to induce bone loss in this model. However, four doses of a co‐inoculum of a 1 : 1 ratio of P. gingivalis and T. denticola at 5 × 108 or 1 × 109 total bacterial cells induced the same level of bone loss as four doses of 1 × 1010P. gingivalis cells. Co‐inoculation induced strong P. gingivalis‐specific T‐cell proliferative and interferon‐γ‐dominant cytokine responses, and induced a strong T. denticola‐specific interferon‐γ dominant cytokine response. Only at the higher co‐inoculum dose of 1 × 1010 total cells was a T. denticola‐specific T‐cell proliferative response observed. These data show that P. gingivalis and T. denticola act synergistically to stimulate the host immune response and to induce alveolar bone loss in a murine experimental periodontitis model.
Vasorelaxant and hypotensive effects of the extract and the isolated flavonoid rutin obtained from Polygala paniculata L.
Authors: da Rocha Lapa Fernanda , Soares Kelly Cristina , Rattmann Yanna Dantas , Crestani Sandra , Missau Fabiana Cristina , Pizzolatti Moacir Geraldo , Marques Maria Consuelo Andrade , Rieck Lia , Santos Adair Roberto Soares
Published: May 2011

Objectives

This study aimed to investigate the in-vitro and in-vivo cardiovascular effects of the crude hydroalcoholic extract from Polygala paniculata (HEPP) in rats.

Methods

The procedures were performed on aortic rings and on normotensive anaesthetized rats.

Key findings

When tested in endothelium-intact aorta rings, HEPP (30–1000 µg/ml) produced a significant non-concentration-dependent relaxing effect (∼40%), which was completely prevented by incubation with L-NAME (nitric oxide synthase inhibitor), ODQ (soluble guanylate cyclase inhibitor) and partially inhibited by tetraethylammonium (TEA; a non-selective potassium channel blocker) and charybdotoxin (a large- and intermediate-conductance calcium-activated potassium channel blocker). In contrast, atropine (a muscarinic receptor antagonist) or pyrilamine(a histamine H1 receptor antagonist) had no effect. Furthermore, oral administration of HEPP (30–300 mg/kg) in anaesthetized rats caused a dose-dependent and sustained hypotensive action. This effect was unchanged by atropine or TEA, but was strongly reduced in rats continuously infused with L-NAME or methylene blue. Moreover, rutin (1–3 mg/kg) administered by an intravenous route also caused a dose-dependent hypotensive effect in rats.

Conclusions

Our results demonstrated that the extract obtained from P. paniculata induces potent hypotensive and vasorelaxant effects that are dependent on the nitric oxide/guanylate cyclase pathway. These effects could be related, at least in part, to the rutin contents in this extract.
Possible mechanism of the antidepressant effect of 3,6′-disinapoyl sucrose from Polygala tenuifolia Willd
Authors: Hu Yuan , Liu Ming , Liu Ping , Guo Dai-Hong , Wei Ri-Bao , Rahman Khalid
Published: May 2011

Objective

The present study was designed to observe the effects of 3,6′-disinapoyl sucrose (DISS), an active oligosaccharide ester component obtained from the roots of Polygala tenuifolia Willd., on behavioral and biochemical aspects of depression induced by chronic mild stress (CMS) in rats. It is the first exploration of the possible association between DISS's antidepressant-like effects and biochemical markers of depression, and involved measuring monoamine oxidase (MAO) activity, cortisol levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels.

Methods

Rats were exposed to stressor once daily for consecutive 5 weeks. DISS and a positive control drug, fluoxetine, were administered via gastric intubation to once daily for consecutive 3 weeks from the third week.

Key findings

The results showed that rats subjected to CMS exhibit a reduction in sucrose intake. Conversely, brain MAO-A and MAO-B activity, plasma cortisol levels, and MDA levels were increased, while SOD activity was decreased following CMS exposures. DISS significantly inhibited MAO-A and MAO-B activity and blocked plasma elevated cortisol level, an indicator of the hypothalamic–pituitary–adrenal (HPA) axis. In addition, DISS increases SOD activity, inhibits lipid peroxidation, and lessens production of MDA.

Conclusion

These results suggest that DISS may possess potent and rapid antidepressant properties, which are mediated via MAO, the HPA axis and oxidative systems. These antidepressant actions make DISS a potentially valuable drug for the treatment of depression.
A novel tri-layered buccal mucoadhesive patch for drug delivery: assessment of nicotine delivery
Authors: Rao Shasha , Song Yunmei , Peddie Frank , Evans Allan M
Published: May 2011

Objectives

The aim of this study was to assess the potential of a novel delivery device for administering drugs that suffer from a high degree of first-pass metabolism.

Methods

A tri-layered buccal mucoadhesive patch, comprising a medicated dry tablet adhered to a mucoadhesive film, was prepared and characterized by its physicochemical properties and mucoadhesive strength. Nicotine was used as a model drug for the characterization of drug release and drug permeation. The influence of different adsorbents on the release of nicotine base from the patches was evaluated in vitro. Different molecular forms of nicotine (base and complex salt) were evaluated for their effect on release performance and permeation in vitro.

Key findings

Results demonstrated acceptable physicochemical and mucoadhesive properties for the tri-layered patch. Rapid release of nicotine was observed when nicotine base was incorporated with calcium sulfate dihydrate as the adsorbent. Patches incorporating nicotine base showed distinct advantages over those containing nicotine polacrilex, in terms of drug release (complete drug release achieved at 30 vs 60 min) and transmucosal permeation (37.28 ± 4.25 vs 2.87 ± 0.26% of the dose permeating through mucosa within 120 min).

Conclusions

The novel tri-layered patch can effectively adhere to, and deliver an active ingredient through the buccal mucosa, confirming its potential for buccal mucoadhesive drug delivery.
Development of effervescent tablets containing benznidazole complexed with cyclodextrin
Authors: Maximiano Flávia Pires , Costa Guilherme Hideki Yoshizane , de Sá Barreto Lívia Cristina Lira , Bahia Maria Terezinha , Cunha-Filho Marcílio S S
Published: May 2011

Objectives

Benznidazole (BNZ), the primary chemotherapy agent used to treat Chagas disease, has poor aqueous solubility, which results in low bioavailability. The purpose of this work was to develop stable effervescent tablets using an inclusion complex of BNZ with cyclodextrin (CD).

Method

In the first phase, different CDs were evaluated according to their ability to improve the aqueous solubility of BNZ. Then, inclusion complexes of BNZ in the solid state were produced by the kneading method and the complexes were evaluated using several physical–chemical assays. Finally, effervescent tablets were prepared according to a complete 32 factorial design. The effects of the concentration of CD and effervescent mixture on the dissolution rate and physical stability of tablets were evaluated.

Key findings

Hydroxypropyl-β-cyclodextrin produced the greatest improvement in the aqueous solubility of BNZ, almost 20-times greater than the water system. Solid systems produced with BNZ and CD showed physical–chemical interactions and increased the drug dissolution rate, suggesting the formation of a true solid inclusion complex. Moreover, the effervescent matrix of the tablets was effective in improving the dissolution behaviour of BNZ complexed with CD.

Conclusions

Effervescent tablets produced using an inclusion complex of BNZ with CD suggest a possible improvement in the bioavailability of BNZ, and this could represent a relevant advance in Chagas therapy.
Effect of bile on the oral absorption of halofantrine in polyethylene glycol 400 and polysorbate 80 formulations dosed to bile duct cannulated rats
Authors: Tønsberg Henrik , Holm René , Mu Huiling , Boll Jette Bisgaard , Jacobsen Jette , Müllertz Anette
Published: May 2011

Objectives

The aim of this study was to examine the effects of bile on the oral absorption of the poorly water-soluble compound, halofantrine, when administered to rats in vehicles consisting of the co-solvent polyethylene glycol 400 (PEG 400) alone or in mixtures with the surfactant polysorbate 80 (PS 80) (95 : 5; 85 : 15; 75 : 25 PEG 400 : PS 80).

Methods

Halofantrine (17.5 mg/kg) was administered to bile duct cannulated (BDC) and sham-operated rats in a fixed vehicle volume of 5 ml/kg.

Key findings

The bioavailability of halofantrine was significantly lower in BDC rats when dosed with 0–5% PS 80 in PEG 400 compared with BDC rats dosed with >15% PS 80. Increasing the concentration of PS 80 to 15–100% eliminated this difference. A possible explanation for the lower bioavailability of halofantrine in BDC rats when dosed in pure PEG 400 could be the dilution of the vehicle by intestinal fluids, decreased transit time and precipitation in the gastrointestinal tract upon dilution of PEG 400.

Conclusions

The addition of PS 80 to the formulation increased its solubilising power upon dilution and may have inhibited precipitation and substituted the absence of bile above a certain level. Adjusting the level of surfactant in drug formulations could therefore be used to minimise variability in the bioavailability from co-solvent systems based upon differences in bile concentration between individuals.
Influence of atorvastatin on fractional and subfractional composition of serum lipoproteins and MMP activity in mice with Triton WR 1339-induced lipaemia
Authors: Korolenko Tatyana A , Cherkanova Marina S , Tuzikov Fedor V , Johnston Thomas P , Tuzikova Natalia A , Loginova Viktoriya M , Kaledin Vassilij I
Published: May 2011

Objectives

The effects of atorvastatin on the atherogenic and anti-atherogenic lipoprotein-cholesterol (C-LP) and lipoprotein-triglyceride (TG-LP) fractions and subfractions at the early stage of murine acute hyperlipidaemia, and its pleiotropic anti-inflammatory effects via the activity of matrix metalloproteinases (MMPs) were studied.

Methods

Atorvastatin (75 mg/kg) was administered to ICR mice with acute lipaemia induced by a single injection of Triton WR 1339 (500 mg/kg). A novel small-angle X-ray scattering (SAXS) method was used for the determination of the fractional and subfractional composition of C-LP and TG-LP.

Key finding

In Triton WR 1339-treated mice, there was a drastic increase in the atherogenic low-density C-LP (C-LDL) fraction, intermediate density lipoprotein-cholesterol (C-IDL) subfraction, and very low-density C-LP (C-VLDL) fractions (C-VLDL3–5 subfraction). Additionally, there was an increase in the C-HDL3 subfraction. Treatment of lipaemia with atorvastatin resulted in the normalization of the atherogenic C-LDL fraction and the C-IDL subfraction. A decrease in C-VLDL (C-VLDL3–5 subfraction), total cholesterol and, especially, triglyceride (TG) concentrations was also demonstrated. Similar results were obtained with the TG-LP fractions and subfractions. Additionally, atorvastatin treatment resulted in an increase in the serum and liver MMP activity.

Conclusion

High-dose atorvastatin therapy exerts its rapid lipid-lowering and pleiotropic effect(s) in the early stages of acute lipaemia induced with Triton WR-1339.
Investigation into drug release from colon-specific azoreductase-activated steroid prodrugs using in-vitro models
Authors: Ruiz Juan F Marquez , Kedziora Kinga , Windle Henry , Kelleher Dermot P , Gilmer John F
Published: May 2011

Objectives

The aim of this study was to investigate drug release from a double steroid prodrug, OPN501, which incorporates a phenylpropionate linker, and its phenylacetate analogue. The prodrugs, which were designed to deliver prednisolone to the colon for the treatment of inflammatory bowel disease, are based on a novel design that requires sequential azoreductase activity and cyclization of an amino ester to trigger drug release. We sought to explain the divergent effects of the two compounds in anti-inflammatory models and to justify the selection of OPN-501 for clinical development.

Methods

The compounds were incubated in mouse colonic contents (10%) fermented in brain heart infusion under anaerobic conditions. The disappearance of the prodrugs and release of prednisolone was monitored by HPLC. We then developed a method for assessment of prodrug activation using suspensions of Clostridium perfringens, an anaerobe from the human colon. The cyclization of the compounds was studied in various media, assessing the influence of pH and bulk solvent polarity on cyclization rate using HPLC and NMR.

Key findings

The prodrugs were activated via multiple pathways releasing prednisolone in mouse colonic ferment. The compounds released prednisolone by reduction–cyclization in C perfringens suspension. The active OPN-501 generated a stoichiometric amount of prednisolone following azoreductase activation, whereas its analogue did not. The pH rate profile for the cyclization of the amino intermediates of the two compounds revealed significant differences in rate at pH values relevant to the inflamed colon, which explain in part the different amounts of drug produced.

Conclusions

The steroid prodrug OPN-501 has optimal drug release characteristics for colon targeting because of a kinetic advantage of a six-membered ring formation in the aminolysis reactions of anilides. The results are relevant to the development of OPN-501 but also to cyclization strategies in prodrug design especially for colon targeting.
Three- and Seven-Point Optimally Weighted Recursive Median Filters for Gas Turbine Diagnostics
Authors: Guruprakash V. N. , Ganguli Ranjan
Published: May 2011

Measured health signals incorporate significant details about any malfunction in a gas turbine. The attenuation of noise and removal of outliers from these health signals while preserving important features is an important problem in gas turbine diagnostics. The measured health signals are a time series of sensor measurements such as the low rotor speed, high rotor speed, fuel flow, and exhaust gas temperature in a gas turbine. In this article, a comparative study is done by varying the window length of acausal and unsymmetrical weighted recursive median filters and numerical results for error minimization are obtained. It is found that optimal filters exist, which can be used for engines where data are available slowly (three-point filter) and rapidly (seven-point filter). These smoothing filters are proposed as preprocessors of measurement delta signals before subjecting them to fault detection and isolation algorithms.
Modified-Roll Profile Correction for a Gear Shaping Cutter Made by the Lengthwise-Reciprocating Grinding Process
Authors: Huang Chin-Lung , Fong Zhang-Hua
Published: May 2011

The tooth profile error of a gear shaping cutter made by the lengthwise-reciprocating grinding process (LRGP) is usually corrected by modifying the grinding wheel profile. However, such grinding wheel modification cannot eliminate the twisting profile error along the face of the shaping cutter. A kinematic modified roll motion for generating a shaping cutter is proposed to minimize such twisted profile errors even after cutter resharpening. The tooth profile errors of the work gears generated by the shaping cutter with various resharpening depths are represented as a novel topographic error map. Based on the error map and its sensitivity matrix, the roll ratio between the shaping cutter and the grinding wheel stroke is modified to reduce the twisted profile error as illustrated by the numerical examples. Combining this modified roll motion modification and the grinding wheel profile correction, the high accuracy resharpening depth of the LRGP helical shaping cutter is increased.
Dropwise Condensation Modeling Suitable for Superhydrophobic Surfaces
Authors: Kim Sunwoo , Kim Kwang J.
Published: May 2011

A mathematical model is developed to represent and predict the dropwise condensation phenomenon on nonwetting surfaces having hydrophobic or superhydrophobic (contact angle greater than 150 deg) features. The model is established by synthesizing the heat transfer through a single droplet with the drop size distribution. The single droplet heat transfer is analyzed as a combination of the vapor-liquid interfacial resistance, the resistance due to the conduction through the drop itself, the resistance from the coating layer, and the resistance due to the curvature of the drop. A population balance model is adapted to develop a drop distribution function for the small drops that grow by direct condensation. Drop size distribution for large drops that grow mainly by coalescence is obtained from a well-known empirical equation. The evidence obtained suggests that both the single droplet heat transfer and drop distribution are significantly affected by the contact angle. More specifically, the model results indicate that a high drop-contact angle leads to enhancing condensation heat transfer. Intense hydrophobicity, which produces high contact angles, causes a reduction in the size of drops on the verge of falling due to gravity, thus allowing space for more small drops. The simulation results are compared with experimental data, which were previously reported.
Subcooled Boiling of PF-5060 Dielectric Liquid on Microporous Surfaces
Authors: El-Genk Mohamed S. , Ali Amir F.
Published: May 2011

Presented are the results of experiments that investigated nucleate boiling of PF-5060 on microporous Cu surface layers at saturation and 10 K, 20 K, and 30 K subcooling. The three microporous layers, electrochemically deposited on 10×10 mm2 Cu substrates and investigated herein, are ∼139 μm, 171 μm, and 220 μm thick. The critical heat flux increases linearly with increased subcooling, ΔTsub, at an average rate of 4.5%/K. For the 171 μm thick, Cu microporous surface, saturation boiling CHF of 27.8 W/cm2 increases to 63.25 W/cm2 at ΔTsub=30 K, while the saturation hMNB of 13.5 W/cm2 K decreases slightly to 12.7 W/cm2 K at ΔTsub=30 K. The values of the surface superheat, ΔTsat, at hMNB and CHF increase from 2.0 K and 2.16 K at saturation to 4.2 and 6.42 K at 30 K subcooling.
Solid-Liquid Two-Phase Flow Measurement Using an Electromagnetically Induced Signal Measurement Method
Authors: Yamaguchi Hiroshi , Niu Xiao-Dong , Nagaoka Shogo , De Vuyst Florian
Published: May 2011

An electromagnetically induced signal measurement method is presented to measure solid-liquid two-phase flows in the present study. The method is validated by comparing visualization results for three flow patterns of “pseudo-homogenous flow,” “heterogeneous flow” and “heterogeneous and sliding-bed flow.” The present method has demonstrated a promising capability of measuring concentration and velocity of solid particles simultaneously with good accuracy.
Regeneration Waves
Authors: VanHook Annalisa M.
Published: May 2011

Mathematical modeling identifies a robust mechanism for coordinating regeneration across a large tissue.
Comparison of the Efficacy and Safety of Oritavancin Front-Loaded Dosing Regimens to Daily Dosing: an Analysis of the SIMPLIFI Trial
Authors: Dunbar Lala M. , Milata Joe , McClure Ty , Wasilewski Margaret M. ,   the SIMPLIFI Study Team
Published: May 2011

Oritavancin is a novel lipoglycopeptide with demonstrated effectiveness against complicated skin and skin structure infections (cSSSI) caused by Gram-positive pathogens, including those caused by methicillin-resistant
Staphylococcus aureus
(MRSA). The pharmacokinetic and pharmacodynamic profile of oritavancin is favorable for single or infrequent dosing. A phase 2, multicenter, randomized, double-blind, parallel, active-comparator study (ClinicalTrials.gov identifier, NCT00514527) of single and infrequent dosing of intravenous (i.v.) oritavancin for the treatment of cSSSI caused by Gram-positive pathogens (wound infections, major abscess, and cellulitis) was undertaken to evaluate the noninferiority of front-loaded dosing regimens compared to a daily-dosing regimen. A total of 302 patients ≥18 years of age were randomized equally to one of three oritavancin treatment groups, receiving either a daily dose (200 mg) administered for 3 to 7 days, a single dose (1,200 mg), or an infrequent dose (800-mg dose, with the option for an additional 400 mg on day 5). The primary efficacy was defined as a clinical response in clinically evaluable (CE) patients assessed at days 21 to 29 (test of cure [TOC]). The cure rates in the CE population were 72.4% (55/76) in the daily-dose group, 81.5% (66/81) in the 1,200-mg-single-dose group, and 77.5% (55/71) in the infrequent-dose group. In patients with MRSA at baseline, the cure rates were 78.3% (18/23), 73.0% (27/37), and 87.0% (20/23) in the daily-, 1,200-mg-single-, and infrequent-dose groups, respectively; however, the study was not powered to assess outcomes in the MRSA subpopulation, and given the heterogeneity of the types of infection and the small sample size, these do not suggest any true differences in efficacy rates for these pathogens. The frequencies of adverse events were similar among treatment groups. The results of this study show that single- and infrequent-dosing schedules of oritavancin were as efficacious as daily administration and had a similar safety profile in treating cSSSI caused by Gram-positive pathogens, including MRSA.
Antimicrobial Resistance in Urinary Tract Pathogens in Canada from 2007 to 2009: CANWARD Surveillance Study
Authors: Karlowsky James A. , Lagacé-Wiens Philippe R. S. , Simner Patricia J. , DeCorby Melanie R. , Adam Heather J. , Walkty Andrew , Hoban Daryl J. , Zhanel George G.
Published: May 2011

From January 2007 to December 2009, an annual Canadian national surveillance study (CANWARD) tested 2,943 urinary culture pathogens for antimicrobial susceptibilities according to Clinical and Laboratory Standards Institute guidelines. The most frequently isolated urinary pathogens were as follows (number of isolates, percentage of all isolates):
Escherichia coli
(1,581, 54%), enterococci (410, 14%),
Klebsiella pneumoniae
(274, 9%),
Proteus mirabilis
(122, 4%),
Pseudomonas aeruginosa
(100, 3%), and
Staphylococcus aureus
(80, 3%). The rates of susceptibility to trimethoprim-sulfamethoxazole (SXT) were 78, 86, 84, and 93%, respectively, for
E. coli
,
K. pneumoniae
,
P. mirabilis
, and
S. aureus
. The rates of susceptibility to nitrofurantoin were 96, 97, 33, and 100%, respectively, for
E. coli
, enterococci,
K. pneumoniae
, and
S. aureus
. The rates of susceptibility to ciprofloxacin were 81, 40, 86, 81, 66, and 41%, respectively, for
E. coli
, enterococci,
K. pneumoniae
,
P. mirabilis
,
P. aeruginosa
, and
S. aureus
. Statistical analysis of resistance rates (resistant plus intermediate isolates) by year for
E. coli
over the 3-year study period demonstrated that increased resistance rates occurred only for amoxicillin-clavulanate (from 1.8 to 6.6%;
P
< 0.001) and for SXT (from 18.6 to 24.3%;
P
= 0.02). For isolates of
E. coli
, in a multivariate logistic regression model, hospital location was independently associated with resistance to ciprofloxacin (
P
= 0.026) with higher rates of resistance observed in inpatient areas (medical, surgical, and intensive care unit wards). Increased age was also associated with resistance to ciprofloxacin (
P
< 0.001) and with resistance to two or more commonly prescribed oral agents (amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and SXT) (
P
= 0.005). We conclude that frequently prescribed empirical agents for urinary tract infections, such as SXT and ciprofloxacin, demonstrate lowered
in vitro
susceptibilities when tested against recent clinical isolates.
Five-Minute Exposure to Caspofungin Results in Prolonged Postantifungal Effects and Eliminates the Paradoxical Growth of Candida albicans
Authors: Shields Ryan K. , Nguyen M. Hong , Press Ellen G. , Clancy Cornelius J.
Published: May 2011

We studied the impact of brief caspofungin exposures on postantifungal effects (PAFEs) and paradoxical effects for five
Candida albicans
isolates. In time-kill studies, caspofungin at 4× and 16× the MIC resulted in significant killing of all isolates. Caspofungin at 8 μg/ml resulted in lower levels of killing, and paradoxical effects were evident with 4 isolates. Caspofungin exposures of 5 to 60 min caused prolonged, concentration-dependent killing that approached or exceeded the results seen with time-kill experiments and eliminated paradoxical growth.
Fate of Mutation Rate Depends on
agr
Locus Expression during Oxacillin-Mediated Heterogeneous-Homogeneous Selection in Methicillin-Resistant Staphylococcus aureus Clinical Strains
Authors: Plata Konrad B. , Rosato Roberto R. , Rosato Adriana E.
Published: May 2011

Methicillin-resistant
Staphylococcus aureus
(MRSA) strains are characterized by a heterogeneous expression of resistance. We have previously shown in clinical oxacillin-susceptible,
mecA-
positive MRSA strains that selection from a very heterogeneous (HeR) to highly homogeneous (HoR) resistant phenotype was mediated by acquisition of mutations through an oxacillin-induced SOS response. In the present study, we used a spotted DNA microarray to evaluate differential gene expression during HeR-HoR selection and found increased expression of the
agr
two-component regulatory system. We hypothesized that increased expression of
agr
represents a mechanistically relevant component of this process. We demonstrated that inactivation of
agr
during the HeR-HoR selection process results in a significant increase in mutation rate; these effects were reversed by complementing the
agr
mutant. Furthermore, we found that extemporal ectopic expression of
agr
and, more specifically, RNAII in
agr
-null mutant HeR cells suppressed mutation frequency and the capacity of these cells to undergo the HeR-HoR selection. These findings sustain the concept that increased expression of
agr
during HeR-HoR selection plays a critical role in regulating the β-lactam-induced increased mutation rate in very heterogeneous MRSA strains. Moreover, they indicate that a temporally controlled increase in
agr
expression is required to tightly modulate SOS-mediated mutation rates, which then allows for full expression of oxacillin homogeneous resistance in very heterogeneous clinical MRSA strains.
The Antibiotic Dehydrophos Is Converted to a Toxic Pyruvate Analog by Peptide Bond Cleavage in Salmonella enterica
Authors: Circello Benjamin T. , Miller Charles G. , Lee Jin-Hee , van der Donk Wilfred A. , Metcalf William W.
Published: May 2011

The metabolic processing of dehydrophos, a broad-spectrum peptide antibiotic containing an unusual vinyl-phosphonate moiety, was examined by using a panel of
Salmonella enterica
mutants deficient in peptide uptake and catabolism. Dehydrophos bioactivity is lost in
opp
tpp
double mutants, demonstrating a requirement for uptake via nonspecific oligopeptide permeases. Dehydrophos bioactivity is also abolished in a quadruple
Salmonella
mutant lacking the genes encoding peptidases A, B, D, and N, showing that hydrolysis of the peptide bond is required for activity.
31
P nuclear magnetic resonance spectroscopy was used to assess the fate of dehydrophos following
in vitro
digestion of the antibiotic with purified PepA. The results suggest that the initial product of peptidase processing is 1-aminovinyl-phosphonate
O
-methyl ester. This phosphonate analogue of dehydroalanine undergoes rearrangement to the more stable imine, followed by spontaneous hydrolysis to yield
O
-methyl-acetylphosphonate, a structural analogue of pyruvate. This compound is a known inhibitor of pyruvate dehydrogenase and pyruvate oxidase and is probably the active species responsible for dehydrophos bioactivity.