bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pectin-cysteine conjugate: synthesis and in-vitro evaluation of its potential for drug delivery
Authors: Majzoob Sayeh , Atyabi Fatemeh , Dorkoosh Farid , Kafedjiiski Krum , Loretz Brigitta , Bernkop-Schnürch Andreas 
Published: December 2006

Abstract
This study was aimed at improving certain properties of pectin by introduction of thiol moieties on the polymer. Thiolated pectin was synthesized by covalent attachment of cysteine. Pectin-cysteine conjugate was evaluated for its ability to be degraded by pectinolytic enzyme. The toxicity profile of the thiolated polymer in Caco-2-cells, its permeation enhancing effect and its mucoadhesive and swelling properties were studied. Moreover insulin-loaded hydrogel beads of the new polymer were examined for their stability in simulated gastrointestinal conditions and their drug release profile. The new polymer displayed 892.27 ± 68.68 μmol thiol groups immobilized per g polymer, and proved to have retained its biodegradability, upon addition of Pectinex Ultra SPL in-vitro, determined by viscosity measurements and titration method. Pectin-cysteine showed no severe toxicity in Caco-2 cells, as tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Moreover, the synthesized polymer exhibited a relative permeation enhancement ratio of 1.61 for sodium fluorescein, compared to unmodified pectin. Pectin-cysteine conjugate exhibited approximately 5-fold increased in in-vitro adhesion duration and significantly improved cohesive properties. Zinc pectin-cysteine beads showed improved stability in simulated gastrointestinal media; however, insulin release from these beads followed the same profile as unmodified zinc pectinate beads. Due to favourable safety and biodegradability profile, and improved cohesive and permeation-enhancing properties, pectin-cysteine might be a promising excipient in various transmucosal drug delivery systems.
Optimization of tamsulosin hydrochloride controlled release pellets coated with Surelease and neutralized HPMCP
Authors: Kim Min-Soo , Kim Jeong-Soo , Lee Sibeum , Jun Seoung Wook , Park Jeong-Sook , Woo Jong-Soo , Hwang Sung-Joo 
Published: December 2006

Abstract
This study was to optimize the coating level in the development of controlled release pellets coated with Surelease and neutralized hydroxypropyl methylcellulose phthalate (HPMCP) by a computer optimization technique based on a response surface methodology utilizing polynomial equation. A full factorial 32 design was used for the optimization procedure with coating level (X1) and HPMCP content (X2) as the independent variables. The drug release percent at 2, 3 and 5 h were the target responses, which were restricted to 12–39% (Y1), 44–70% (Y2) and 70–100% (Y3), respectively. The quadratic model was well fitted to the data, and the resulting equation was used to predict the responses in the optimal region. It was shown that the optimized coating formulation was achieved at the ratio of 3:1 (Surelease: neutralized HPMCP) with 20% coating level. The optimized formulation showed release profiles and responses, which were close to predicted responses. Therefore, a full factorial 32 design and optimization technique can be successfully used in the development of optimized coating formulations based on Surelease and neutralized HPMCP to achieve a controlled release drug delivery system containing tamsulosin hydrochloride.
Blockade of scavenger receptor class B type I raises high density lipoprotein cholesterol levels but exacerbates atherosclerotic lesion formation in apolipoprotein E deficient mice
Authors: Kitayama Ken , Nishizawa Tomohiro , Abe Koji , Wakabayashi Kenji , Oda Tomiichiro , Inaba Toshimori , Amemiya Yoshiya 
Published: December 2006

Abstract
Recent accumulating evidence supports the concept that raising high-density lipoprotein (HDL) may represent an additional therapeutic target for prevention of cardiovascular disease. Scavenger receptor class B type I plays a critical role in plasma HDL cholesterol concentration and structure. This study investigated the effect of scavenger receptor class B type I blockade by a synthetic scavenger receptor class B type I blocker on plasma lipids and atherosclerosis lesion formation in apolipoprotein E (apoE)-deficient mice. N-[4-(4-tert-Butoxycarbonylpiperazin-1-yl)phenyl]-(2-chloro-5-nitrophenyl)carboxamide (R-138329), a novel scavenger receptor class B type I blocker, was identified by screening with a half-maximal inhibitory potency (IC50 value) of around 1 μM in scavenger receptor class B type I-expressing COS-1 cells. Male apoE-deficient mice were fed a chow diet with or without R-138329 (0.01-0.10%, approximately 10–100 mg kg−1, n = 9 or 10) for 12 weeks. Compared with control, treatment with R-138329 at 0.10% caused significant (P &lt; 0.05) increases in plasma HDL cholesterol levels, and decreases in non-HDL cholesterol and triglyceride levels. Furthermore, R-138329 at 0.01% significantly increased the extent of atherosclerotic lesion formation in the aorta by 98% (P &lt; 0.05), while favourable changes in plasma lipid parameters were achieved. The results of quantitative analysis of atherosclerosis lesion areas were: control, 102691 ±22871 μm2 (n = 10); R-138329 0.01%, 119792 ± 30842 μm2 (n = 9); R-138329 0.03%, 141346 ± 21934 μm2 (n = 10); and R-138329 0.10% 203732 ± 36326 μm2 (n = 10). To clarify the mechanistic basis underlying this preferential deterioration, we examined the potential impact on closely related cellular functions. Further studies revealed that the active metabolite of R-138329 inhibited scavenger receptor class B type I-mediated cholesterol efflux. This study demonstrates for the first time pharmacological blockade of scavenger receptor class B type I in apoE-deficient mice. Blockade of scavenger receptor class B type I deteriorates atherosclerotic lesion formation in apoE-deficient mice even though it favourably affects plasma lipid parameters such as raising HDL cholesterol and decreasing non-HDL cholesterol. These results provide new insights for pharmaceutical industry research and development issues.
Changes in hepatic gene expression associated with the hypocholesterolaemic activity of royal jelly
Authors: Kamakura Masaki , Moriyama Tatsuya , Sakaki Toshiyuki 
Published: December 2006

Abstract
Royal jelly (RJ) has various pharmacological actions, including hypolipidaemic, hypocholesterolaemic and anti-atherosclerotic effects, in experimental animals but the molecular mechanisms involved remain unclear. Here, we investigated changes in the expression of lipid metabolism-associated genes in the liver of RJ-treated mice by means of a DNA microarray technique to obtain clues to the mechanism of the hypocholesterolaemic action of RJ. We compared the hepatic gene expression profiles in three groups of mice fed a diet containing 5% RJ, a diet containing 5% RJ stored at 40°C for 7 days (40-7d RJ) or a control diet which provided the same total energy as the other diets. RJ decreased gene expression of squalene epoxidase (SQLE), which is a key enzyme in cholesterol biosynthesis, and sterol regulatory element-binding protein (SREB)-1, which may be a transcriptional factor of SQLE. It increased gene expression of low-density lipoprotein receptor (LDLR), which is involved in cholesterol incorporation in liver. Thus, the hypocholesterolaemic action of RJ appears to be associated with a decrease of SQLE and an increase of LDLR in mice.
Synthesis of Unsymmetrically and Highly Substituted Thiophenes Utilizing Regioselective Ring-expansion of gem-Dichlorocyclopropyl Ketones with Lawesson’s Reagent
Authors: Nagano Takao , Kimoto Hiroki , Nakatsuji Hidefumi , Motoyoshiya Jiro , Aoyama Hiromu , Tanabe Yoo , Nishii Yoshinori 
Published: December 2006

Abstract
Ring-expansion of aryl gem-dichlorocyclopropyl ketones 1 using Lawesson’s reagent afforded unsymmetrically and highly substituted 5-chloro and 3-chlorothiophenes 2 and 3 with excellent regioselectivity. The Suzuki–Miyaura coupling of 2 and 3 with PhB(OH)2 was successfully performed to give 2-aryl-3-methyl-5-phenylthiophenes 4 and 2-aryl-3-methyl-4,5-diphenylthiophenes 5, respectively.
Short-Term Hemostatic Safety of Strontium Ranelate Treatment in Elderly Women with Osteoporosis
Authors: Halil Meltem , Cankurtaran Mustafa , Yavuz Burcu Balam , Ulger Zekeriya , Piskinpasa Serhan , Gedik Arzu , Haznedaroglu Ibrahim Celalettin , Kirazli Serafettin , Ariogul Servet 
Published: December 2006

Background: Strontium ranelate offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal osteoporosis. However, there are some data revealing an association between strontium ranelate treatment and increased incidence of venous thromboembolism (VTE), suggesting possible adverse prothrombotic effects of the drug. Objective: To assess the effect of strontium ranelate treatment on primary hemostasis, secondary hemostasis, and the natural anticoagulant defense system, together with prothrombotic markers, in elderly women with osteoporosis. Methods: This study was designed in a prospective manner. Thirty-five elderly women diagnosed with osteoporosis were included. During a 2 month treatment period, participants received strontium ranelate 2 g. Platelet Function Analyzer-100 (PFA-100) in vitro bleeding time was performed to depict primary hemostasis. Secondary hemostatic parameters including prothrombin time, international normalized ratio, activated partial thromboplastin time, anti-cardiolipine immunoglobulin (Ig) M and IgG, antiphospholipid IgM and IgG, protein C, protein S, anti-thrombin III, lupus anticoagulant, fibrinogen, thrombin, activated protein C resistance, and plasma levels of d-dimer were assessed. These parameters were tested before and after 2 month treatment with strontium ranelate. Results: Mean ± SD age of the patients was 72.82 ± 5.69 years. After 60 days of treatment, there was no statistically significant prolongation in PFA-100 in vitro bleeding time and no statistically significant change in the critical hemostatic parameters in patients receiving strontium ranelate that led to discontinuation of the treatment. None of the subjects developed clinical VTE during the 2 month period of strontium ranelate treatment. Conclusions: The hemostatic safety of strontium ranelate in the elderly population with osteoporosis was shown over 2 months of treatment; however, its long-term hemostatic safety should be evaluated further.
Memory for curvature of objects: Haptic touch vs. vision
Authors: Ittyerah Miriam , Marks Lawrence E. 
Published: December 2006

The present study examined the role of vision and haptics in memory for stimulus objects that vary along the dimension of curvature. Experiment 1 measured haptic‐haptic (T‐T) and haptic‐visual (T‐V) discrimination of curvature in a short‐term memory paradigm, using 30‐second retention intervals containing five different interpolated tasks. Results showed poorest performance when the interpolated tasks required spatial processing or movement, thereby suggesting that haptic information about shape is encoded in a spatial‐motor representation. Experiment 2 compared visual‐visual (V‐V) and visual‐haptic (V‐T) short‐term memory, again using 30‐second delay intervals.The results of the ANOVA failed to show a significant effect of intervening activity. Intra‐modal visual performance and cross‐modal performance were similar. Comparing the four modality conditions (inter‐modal V‐T, T‐V; intra‐modal V‐V, T‐T, by combining the data of Experiments 1 and 2), in a global analysis, showed a reliable interaction between intervening activity and experiment (modality). Although there appears to be a general tendency for spatial and movement activities to exert the most deleterious effects overall, the patterns are not identical when the initial stimulus is encoded haptically (Experiment 1) and visually (Experiment 2).
Delayed Development of Paget's Disease in Offspring Inheriting SQSTM1 Mutations
Authors: Bolland Mark J , Tong Pak Cheung , Naot Dorit , Callon Karen E , Wattie Diana J , Gamble Greg D , Cundy Tim 
Published: December 2006

Abstract
Familial Paget's disease is associated with mutations in SQSTM1. We compared the age at diagnosis and severity of Paget's disease in parents with SQSTM1 mutations to their offspring who inherited a mutation. At any given age, the offspring were less likely to be diagnosed with Paget's disease and had less severe disease than their parents.
Introduction: Mutations in sequestosome 1 (SQSTM1) occur in 25–50% of cases of familial Paget's disease and are thought to be disease-causing. We sought to determine whether there are differences in age at diagnosis and severity of disease in parents and their offspring who share the same genetic predisposition to Paget's disease.
Materials and Methods: Eighty-four offspring from 10 families (29 index patients with Paget's disease) with mutations in SQSTM1 were approached, and 58 agreed to participate. The ubiquitin-binding domain region of SQSTM1 was sequenced, and the presence or absence of the known mutation was established. The presence of Paget's disease in offspring who had inherited an SQSTM1 mutation was determined by bone scintigraphy and measurement of serum alkaline phosphatase (ALP).
Results: Twenty-three of 58 offspring had inherited a germline mutation in SQSTM1. The mean ALP was 77 U/liter in offspring with mutations and 72 U/liter in those without mutations (p = 0.84). Scintiscans from four offspring (mean age, 45 years; mean ALP, 139 U/liter; mean skeletal involvement, 6%) showed evidence of Paget's disease but were normal in the other 19 (mean age, 44 years; mean ALP, 64 U/liter). In comparison, in the 15 parents of the 23 offspring, the mean age of diagnosis was 48 years, the mean ALP was 850 U/liter, and the mean skeletal involvement was 30%. There was a 63% reduction in the risk of being diagnosed with Paget's disease at a comparable age in the offspring compared with the parents (p = 0.028).
Conclusions: Only 17% of offspring inheriting an SQSTM1 mutation had evidence of Paget's disease on scintigraphy, and this was diagnosed at a later age and was less extensive than in their affected parents. SQSTM1 thus shows incomplete penetrance. The data are consistent with the hypothesis that an environmental factor is important in the pathogenesis and clinical phenotype of familial Paget's disease and that exposure to this factor may be falling.
Is a School-Based Physical Activity Intervention Effective for Increasing Tibial Bone Strength in Boys and Girls?
Authors: Macdonald Heather M , Kontulainen Saija A , Khan Karim M , McKay Heather A 
Published: December 2006

Abstract
This 16-month randomized, controlled school-based study compared change in tibial bone strength between 281 boys and girls participating in a daily program of physical activity (Action Schools! BC) and 129 same-sex controls. The simple, pragmatic intervention increased distal tibia bone strength in prepubertal boys; it had no effect in early pubertal boys or pre or early pubertal girls.
Introduction: Numerous school-based exercise interventions have proven effective for enhancing BMC, but none have used pQCT to evaluate the effects of increased loading on bone strength during growth. Thus, our aim was to determine whether a daily program of physical activity, Action Schools! BC (AS! BC) would improve tibial bone strength in boys and girls who were pre- (Tanner stage 1) or early pubertal (Tanner stage 2 or 3) at baseline.
Materials and Methods: Ten schools were randomized to intervention (INT, 7 schools) or control (CON, 3 schools). The bone-loading component of AS! BC included a daily jumping program (Bounce at the Bell) plus 15 minutes/day of classroom physical activity in addition to regular physical education. We used pQCT to compare 16-month change in bone strength index (BSI, mg2/mm4) at the distal tibia (8% site) and polar strength strain index (SSIp, mm3) at the tibial midshaft (50% site) in 281 boys and girls participating in AS! BC and 129 same-sex controls. We used a linear mixed effects model to analyze our data.
Results: Children were 10.2 ± 0.6 years at baseline. Intervention boys tended to have a greater increase in BSI (+774.6 mg2/mm4; 95% CI: 672.7, 876.4) than CON boys (+650.9 mg2/mm4; 95% CI: 496.4, 805.4), but the difference was only significant in prepubertal boys (p = 0.03 for group × maturity interaction). Intervention boys also tended to have a greater increase in SSIp (+198.6 mm3; 95% CI: 182.9, 214.3) than CON boys (+177.1 mm3; 95% CI: 153.5, 200.7). Change in BSI and SSIp was similar between CON and INT girls.
Conclusions: Our findings suggest that a simple, pragmatic program of daily activity enhances bone strength at the distal tibia in prepubertal boys. The precise exercise prescription needed to elicit a similar response in more mature boys or in girls might be best addressed in a dose–response trial.
Enhanced Bone Regeneration Associated With Decreased Apoptosis in Mice With Partial HIF-1α Deficiency
Authors: Komatsu David E , Bosch-Marce Marta , Semenza Gregg L , Hadjiargyrou Michael 
Published: December 2006

Abstract
HIF-1α activates genes under hypoxia and was hypothesized to regulate bone regeneration. Surprisingly, HIF-1α+/− fracture calluses are larger, stronger, and stiffer than HIF-1α+/+ calluses because of decreased apoptosis. These data identify apoptosis inhibition as a means to enhance bone regeneration.
Introduction: Bone regeneration subsequent to fracture involves the synergistic activation of multiple signaling pathways. Localized hypoxia after fracture activates hypoxia-inducible factor 1α (HIF-1α), leading to increased expression of HIF-1 target genes. We therefore hypothesized that HIF-1α is a key regulator of bone regeneration.
Materials and Methods: Fixed femoral fractures were generated in mice with partial HIF-1α deficiency (HIF-1α+/−) and wildtype littermates (HIF-1α+/+). Fracture calluses and intact contralateral femurs from postfracture days (PFDs) 21 and 28 (N = 5–10) were subjected to μCT evaluation and four-point bending to assess morphometric and mechanical properties. Molecular analyses were carried out on PFD 7, 10, and 14 samples (N = 3) to determine differential gene expression at both mRNA and protein levels. Finally, TUNEL staining was performed on PFD 14 samples (N = 2) to elucidate differential apoptosis.
Results: Surprisingly, fracture calluses from HIF-1α+/− mice exhibited greater mineralization and were larger, stronger, and stiffer. Microarray analyses focused on hypoxia-induced genes revealed differential expression (between genotypes) of several genes associated with the apoptotic pathway. Real-time PCR confirmed these results, showing higher expression of proapoptotic protein phosphatase 2a (PP2A) and lower expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL2) in HIF-1α+/+ calluses. Subsequent TUNEL staining showed that HIF-1α+/+ calluses contained larger numbers of TUNEL+ chondrocytes and osteoblasts than HIF-1α+/− calluses.
Conclusions: We conclude that partial HIF-1α deficiency results in decreased chondrocytic and osteoblastic apoptosis, thereby allowing the development of larger, stiffer calluses and enhancing bone regeneration. Furthermore, apoptosis inhibition may be a promising target for developing new treatments to accelerate bone regeneration.
That Can't Be Right! What Causes Pragmatic Language Impairment Following Right Hemisphere Damage?
Authors: Martin Ingerith , McDonald Skye 
Published: December 2006

AbstractRight hemisphere damage (RHD) following unilateral stroke is often associated with impairment of pragmatic language, specifically, the ability to comprehend inferences that arise from language used in context. Three kinds of cognitive deficits have been proposed to explain the pragmatic deficits in RHD individuals, impaired Theory of Mind (TOM), weak central coherence (CC), and impaired executive function (EF). This study aims to evaluate the explanatory ability of these theories in relation to the comprehension of nonliteral (ironic) jokes versus literal lies. Twenty-one RHD patients and 21 age-matched controls were assessed on tasks tapping TOM, CC processing and general inference ability (EF) and the comprehension of irony. Second-order TOM and EF were found to play a significant role. However, neither construct, either in isolation or combined, completely explained the poor performance of RHD patients on this task compared to control participants.
Analysing Conversational Discourse After Traumatic Brain Injury: Isn't It About Time?
Authors: Turkstra Lyn S. , Brehm Sarah E. , Montgomery Erwin B. 
Published: December 2006

AbstractMost studies of conversational discourse in traumatic brain injury (TBI) have used summary measures averaged over time. These measures have yielded useful aggregate data but do not capture the temporal dynamics of interpersonal interactions. To fully characterise the conversational discourse of individuals with TBI, it may be useful to consider individuals and behaviours as systems changing over time. In this article, we review dynamic systems approaches that have been used to study conversational interactions, and present data to illustrate their potential utility in characterising the conversational discourse of individuals with TBI.
Visions of Salome: The Femme Fatale in American Popular Songs before 1920
Authors: HAMBERLIN LARRY 
Published: December 2006

AbstractThis article documents representations of Salome, an archetypal exotic femme fatale, in American popular songs of the early twentieth century. The production of Salome songs began shortly after the sensational 1907 U.S. premiere of Richard Strauss's Salome at New York's Metropolitan Opera. Vaudeville performers, beginning with the Met's own prima ballerina, capitalized on the ensuing fad for Salome dances, which the New York Times called “Salomania.” Relevant songs and dances figured in musical comedies and revues until some time after the return of Strauss's opera to the New York stage, in the 1909 Manhattan Opera Company production with Mary Garden in the title role. Through the next decade, musical, lyrical, and illustrative tropes that originated in the Salome songs became disassociated from the figure of Salome, gradually merging into “oriental fox-trots” and exotic romance songs. The topical humor of the Salome songs suggests that American audiences were skeptical of the allure of orientalist fantasy, then at its height in Europe, and that an unwillingness to grant artistic legitimacy to Salome's religious-themed eroticism is an important marker of the American reception of works such as Strauss's.