bluuebunny/crossref_metadata_2025 huggingface dataset:
Rosiglitazone Inhibits Early Stage of Glucolipotoxicity-Induced Beta-Cell Apoptosis
Authors: Han Seung Jin , Kang Eun Seok , Hur Kyu Yeon , Kim Hae Jin , Kim So Hun , Yun Chae-Ok , Choi Sung-E , Ahn Chul Woo , Cha Bong Soo , Kang Yup , Lee Hyun Chul
Published: July 2008

Aim: We investigated whether rosiglitazone protects β-cells from glucolipotoxicity directly. Methods: INS-1 cells were incubated with 25 mM glucose and 0.5 mM palmitate in the absence or presence of 2.5 µM rosiglitazone. We evaluated caspase-3 expression and nuclear DAPI staining. An in vivo study was performed, in which 18-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with rosiglitazone (4 mg/kg/day, n = 6) and with placebo (n = 6) for 10 weeks. At 28 weeks of age, an oral glucose tolerance test, insulin sensitivity test, TUNEL assay and histologic examination were performed. Results: Rosiglitazone attenuated glucolipotoxicity-induced nuclear change and caspase-3 expression for 8 h after treatment, but this effect was not observed at 12 h in INS-1 cells. Rosiglitazone treatment decreased β-cell apoptosis, preserved β-cell mass and improved glucose tolerance in OLETF rats. Conclusion: The present in vitro findings suggest that rosiglitazone can inhibit the early stage of glucolipotoxicity-induced β-cell apoptosis. Our results suggest that the antidiabetic action of rosiglitazone is, at least in part, related to a direct effect on β-cells rather than simply an indirect effect of improving insulin sensitivity.
Expression of Bcl-2 Family Proteins in Thyrocytes from Young Patients with Immune and Nonimmune Thyroid Diseases
Authors: Bossowski A. , Czarnocka B. , Bardadin K. , Urban M. , Niedziela M. , Dadan J.
Published: July 2008

The Bcl-2 family proteins that control homeostasis of cells play an important role in apoptosis. This group consists of antiapoptotic (Bcl-2, Bcl-XL) and proapoptotic (Bcl-2 associated protein X, Bax; B-cell homologous antagonist/killer, Bak) molecules. In the thyroid, abnormal apoptotic activity may be involved in a variety of diseases such as autoimmune thyroid diseases. The aim of the current study was to estimate the expression of pro- and antiapoptotic proteins in thyroid tissues from young patients with Graves’ disease (GD), nontoxic nodular goiter and toxic nodular goiter using Western Blot and immunohistochemistry. Identification of the antiapoptotic Bcl-2 and Bcl-XL molecules in the thyrocytes revealed higher expression of both proteins in patients with GD (assessed as +++/++ and ++/+, respectively). In adolescents with toxic and nontoxic nodular goiter, this expression was lower (Bcl-2 ++/+ , ++/+; Bcl-XL +, +). The tissue material was additionally subjected to Western Blot analysis, which in GD patients showed the presence of Bcl-2 and Bcl-XL in one band p26 kDa. In patients with toxic and nontoxic nodular goiter, the intensity of expression for these two antiapoptotic proteins was lower (referred to band 26 kDa for Bcl-2 and Bcl-XL). Identification of the proapoptotic proteins Bax and Bak revealed their predominance in thyrocytes of GD patients (+, ++/+, respectively) as compared to patients with toxic and nontoxic nodular goiter (0/+, 0/+ for Bax and 0/+, 0/+ for Bak). In GD patients, Western Blot analysis showed Bax expression in one band 21 kDa and Bak in two bands p50, p24 kDa. In patients with nodular goiter, the degree of expression of both proapoptotic proteins was lower and referred to band 21 kDa for Bax (toxic and nontoxic goiter) and 24 kDa for Bak (toxic goiter only). Patients with GD showed a statistically significant correlation between Bcl-2 expression and antibodies against receptor for thyroid stimulating hormone (R = 0.47, p < 0.03); however, such a correlation was not observed in patients with nodular goiter. In conclusion, our findings suggest that the changes in the expression of regulatory proteins of the Bcl-2 family in the thyroid follicular cells indicate the involvement of apoptosis in the pathogenesis of GD.
Protein Carbonyls Damage the Water-Holding Capacity of the Stratum Corneum
Authors: Iwai I. , Hirao T.
Published: July 2008

Background: Acrolein is a degradation product of lipid peroxide as well as a well-known environmental pollutant. As a hallmark of oxidatively damaged protein, protein carbonyl, including acrolein-protein adduct, has been observed in the skin. However, the influence of protein carbonylation on the stratum corneum (SC) has not yet been clarified. Objectives: We explored the influence of oxidative protein modification, focusing on the major function of the SC, the water-holding capacity, by introducing experimental protein carbonylation. Methods: The level of carbonyls in the SC was evaluated by reaction with a labeled hydrazide. The water-holding capacities of the SC or keratin gels were evaluated by measurement of the surface conductance. The bound water (nonfreezing water) content in the SC was measured by the heat of fusion of frozen SC. Results: Acrolein caused protein carbonylation, decreased the water-holding capacity and the bound water of the porcine SC in vitro. The water-holding capacity of the keratin gels prepared from human SC was also decreased by acrolein in vitro. Water content in the human SC in vivo was decreased by sodium hypochlorite and accompanied by the increase in carbonyls. Conclusion: Exposure of SC to the oxidative environment damages the water-holding capacity of the SC through the modification of protein-water interaction.
Change in Skin Physiological Parameters in Space – Report on and Results of the First Study on Man
Authors: Tronnier H. , Wiebusch M. , Heinrich U.
Published: July 2008

Astronauts often show skin reactions in space. Systematic tests, e.g. with noninvasive skin physiological test methods, have not yet been done. In an interdisciplinary cooperation, a test series with skin physiological measurements was carried out before, during and after a long-term mission in the International Space Station. The hydration of the stratum corneum (Corneometer), transepidermal water loss (Tewameter), and the surface structure of the skin (SkinVisiometer) were measured. In order to record cutaneous states, the suction elasticity was measured (Cutometer), and an ultrasound measurement with 20 MHz (DermaScan) was also made. In addition, one measuring field of the two inner forearms was treated with a skin care emulsion. There were indications of a delayed epidermal proliferation of the cells, which would correspond to the clinical symptoms. Hydration and TEWL values are improved by respective skin care. On the cutaneous level, the elasticity measurements and the ultrasound picture showed results which correspond to a significant loss of elasticity of the skin. Further examinations are necessary to validate these preliminary results.
Performance of Fluorescence Methods, Radiographic Examination and ICDAS II on Occlusal Surfaces in vitro
Authors: Rodrigues J.A. , Hug I. , Diniz M.B. , Lussi A.
Published: July 2008

This study compared the performance of fluorescence-based methods, radiographic examination, and International Caries Detection and Assessment System (ICDAS) II on occlusal surfaces. One hundred and nineteen permanent human molars were assessed twice by 2 experienced dentists using the laser fluorescence (LF and LFpen) and fluorescence camera (FC) devices, ICDAS II and bitewing radiographs (BW). After measuring, the teeth were histologically prepared and assessed for caries extension. The sensitivities for dentine caries detection were 0.86 (FC), 0.78 (LFpen), 0.73 (ICDAS II), 0.51 (LF) and 0.34 (BW). The specificities were 0.97 (BW), 0.89 (LF), 0.65 (ICDAS II), 0.63 (FC) and 0.56 (LFpen). BW presented the highest values of likelihood ratio (LR)+ (12.47) and LR– (0.68). Rank correlations with histology were 0.53 (LF), 0.52 (LFpen), 0.41 (FC), 0.59 (ICDAS II) and 0.57 (BW). The area under the ROC curve varied from 0.72 to 0.83. Inter- and intraexaminer intraclass correlation values were respectively 0.90 and 0.85 (LF), 0.93 and 0.87 (LFpen) and 0.85 and 0.76 (FC). The ICDAS II ĸ values were 0.51 (interexaminer) and 0.61 (intraexaminer). The BW ĸ values were 0.50 (interexaminer) and 0.62 (intraexaminer). The Bland and Altman limits of agreement were 46.0 and 38.2 (LF), 55.6 and 40.0 (LFpen) and 1.12 and 0.80 (FC), for intra- and interexaminer reproducibilities. The posttest probability for dentine caries detection was high for BW and LF. In conclusion, LFpen, FC and ICDAS II presented better sensitivity and LF and BW better specificity. ICDAS II combined with BW showed the best performance and is the best combination for detecting caries on occlusal surfaces.
A Randomised, Observer-Blind, Clinical Study Investigating the Effect of Fluoridated Milk on Artificially Created Early Enamel Caries Using Transverse Microradiography
Authors: Nicol A.J. , Creanor S. , Hall A.F. , Macpherson L.M.D.
Published: July 2008

Much of the research regarding the efficacy of fluoridated milk was obtained prior to the routine use of fluoridated dentifrices. The aim was to investigate, in situ, the effect of fluoridated and non-fluoridated milk on mineral change in artificial caries lesions, with the additional use of fluoridated dentifrice. The roles of different milk fluoride concentrations, volumes and frequencies in mineral change were studied. In total, 29 edentulous subjects were recruited and tooth blocks, containing artificial caries lesions, were inserted into their full dentures at 4 areas (sites). Each subject followed 5 randomly ordered, 6-week beverage experiments: 0.5 mg of F in 200 ml of milk, 3 times per day; 1.5 mg of F in 200 ml of milk, once per day; 200 ml of milk, once per day; 200 ml of milk, 3 times per day, and no beverage (negative control). In addition, the subjects were allocated to 1 of 2 groups; experimental treatment only or treatment and dentifrice. Mineral change was measured with transverse microradiography. Statistical analysis was performed using 2-sample t tests and a general linear modelling procedure. For integrated mineral loss there was a statistically significant effect of group (p = 0.001), indicating fluoridated toothpaste significantly increased remineralisation. For lesion depth there was a statistically significant combined effect of ‘group and site’. ‘Experiment’ had no statistically significant influence on change in integrated mineral loss or lesion depth. The study demonstrated that the use of fluoridated dentifrice twice per day had a positive effect on the remineralisation of caries lesions. However, no additional significant effect of fluoridated milk was observed.
Bone Vibration-Induced Nystagmus Is Useful in Diagnosing Superior Semicircular Canal Dehiscence
Authors: Manzari Leonardo , Modugno Giovanni Carlo , Brandolini Cristina , Pirodda Antonio
Published: July 2008

Objective: To explore vestibular integrity by bone vibration-induced nystagmus (VIN) during bedside examination. Disease or dysfunction of vestibular end organs would reduce or eliminate their contribution to total eye movement response to VIN. Background: It is assumed that vibration of the mastoid (at a frequency of 100 Hz) stimulates all vestibular end organs (semicircular canals and otolith structures). Previous studies have described oculomotor responses to vestibular activation by vibratory stimulus. Stimulation of individual semicircular canals produces eye movement in the plane of the stimulated canal. Vibratory stimulation of otolith structures (utricular macula) produces changes in ocular torsional position. Superior semicircular canal dehiscence (SCD) is responsible for nontypical cochleovestibular symptoms. Diagnosis is difficult without resorting to imaging, high-resolution computed tomography (HRCT) being the only tool providing reliable assessment. To avoid unnecessary referral for expensive imaging, it would be useful to have a simple screening test to select cases for HRCT. Methods: Video eye movements were recorded in complete darkness in patients diagnosed with SCD. The eye movement responses to long-lasting unilateral vibratory stimulation applied to the mastoid surface were evaluated. Results: VIN evoked a response in all cases, mostly demonstrating excitation of the affected side. The pattern of vertical, torsional and horizontal eye velocity and eye position was evaluated with three-dimensional infrared video-oculography (50 Hz sampling). Conclusion: Analysis of VIN, recently proposed to study transmission of excitatory stimuli by bone conduction, may be appropriate for altered immittance caused by dehiscence. This promises to be an interesting new field of research.
Spiral Ganglion Outgrowth and Hearing Development in p75NTR-Deficient Mice
Authors: Brors Dominik , Hansen Stefan , Mlynski Robert , Volkenstein Stefan , Aletsee Christoph , Sendtner Michael , Ryan Allen F. , Dazert Stefan
Published: July 2008

To explore the role of nerve growth factor receptor p75NTR during the terminal neuronal development of the mammalian cochlea the onset of hearing and the in vitro response of spiral ganglion neurites to neurotrophin 3 (NT-3), which is known to play a critical role during neonatal inner ear development, were investigated in p75NTR-deficient mice (p75NTR–/–). Auditory-evoked brain stem response recordings from p75NTR–/– and wild-type (WT) littermates were measured from postnatal days (PD) 8 to 23. Additionally, spiral ganglion explants from p75NTR–/– and WT animals were dissected and cultured in an organotypic tissue culture system. In both groups, spiral ganglion neurite outgrowth was analyzed with and without NT-3 supplementation. No significant differences in the onset of hearing of mutant mice compared to the WT mice were detected, and both groups showed a similar development of hearing until PD 23. After stimulation with NT-3, neurite outgrowth was enhanced in both p75NTR–/– and WT mice. However, neurites from p75NTR–/– spiral ganglion explants were longer in both culture conditions. Moreover, NT-3 did not significantly enhance neurite number in p75NTR–/–, as it did in WT mice. P75NTR has a remarkable influence on spiral ganglion neurite growth behavior. However, p75NTR does not seem to be essential for the development of basic hearing function in the first 3 postnatal weeks.
Effects of Acetyl-DL-Leucine in Vestibular Patients: A Clinical Study following Neurotomy and Labyrinthectomy
Authors: Ferber-Viart C. , Dubreuil C. , Vidal P.P.
Published: July 2008

For 40 years, the amino acid acetyl-DL-leucine (or isoleucine – Tanganil®) has been used in clinical practice to reduce imbalance and autonomic manifestations associated with acute vertigo crises. In animal models, acetyl-DL-leucine accelerates vestibular compensation following unilateral labyrinthectomy, and has only minor effects on normal vestibular function. Our work in animal models suggested that acetyl-DL-leucine acted mainly on abnormally hyperpolarized and/or depolarized vestibular neurons by restoring their membrane potential towards a mean value of –65 to –60 mV. Acute vestibular disorders are associated with asymmetrical spontaneous activities of vestibular neurons, so this previous study suggested that acetyl-DL-leucine may reduce acute, vestibular-related imbalances in humans. To test this hypothesis, we investigated the efficacy of acetyl-DL-leucine during the acute stage following neurotomy or labyrinthectomy in patients undergoing surgery for unilateral vestibular acoustic neurinoma, or suffering from unilateral and intractable Ménière’s disease. By clinical testing of the vestibular function, patients were categorized according to the degree of compensation of the vestibular deafferentation prior to surgery. For patients who had achieved a close to perfect compensation before surgery, acetyl-DL-leucine had minor or no effect after surgery. For patients who displayed residual vestibular function before surgery, acetyl-DL-leucine eased the static vestibular syndromes, which followed neurotomy. Our findings tend to confirm the view that acetyl-DL-leucine mainly acts, in humans, on abnormally hyperpolarized and/or depolarized vestibular neurons by restoring their membrane potential towards normal values; this is consistent with findings in guinea pigs following unilateral labyrinthectomy. Moreover, it suggests that the degree of caloric paresis of the patients before neurotomy is useful both to predict the outcome of any acute vestibular syndrome following neurotomy and to assess the potential value of the administration of acetyl-DL-leucine to treat any such syndrome.
Increased Plasma S100A12 (EN-RAGE) Levels in Hemodialysis Patients with Atherosclerosis
Authors: Mori Yasukiyo , Kosaki Atsushi , Kishimoto Noriko , Kimura Tatsuji , Iida Kumiko , Fukui Masayoshi , Nakajima Fumitaka , Nagahara Masayuki , Urakami Masaya , Iwasaka Toshiji , Matsubara Hiroaki
Published: July 2008

Background: S100A12, also known as EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) is a ligand for RAGE, and has been proposed to contribute to the development of atherosclerosis. In this study, we examined the plasma S100A12 concentration in patients with ESRD and undergoing hemodialysis (HD) and evaluated the relation between S100A12 level and carotid intimal media thickness (IMT) by ultrasound. Methods: We measured plasma S100A12 concentration in 72 HD patients and 42 control subjects. IMT of the carotid artery was measured by high-resolution B-mode ultrasonography in 46 HD patients. Results: The mean plasma S100A12 level was 2.3-fold higher in HD patients than in control subjects (25.0 ± 2.32 vs. 10.7 ± 0.97 ng/ml, p < 0.001). Stepwise multiple regression analysis identified circulating white blood cell count as a positive independent determinant and total cholesterol and serum albumin levels as negative independent determinants of plasma S100A12 concentration. The maximum IMT was positively correlated with plasma S100A12 level. Stepwise multiple regression analysis also identified plasma S100A12 as a significant independent determinant of the maximum IMT. Conclusion: These findings suggest that S100A12 protein is involved in the acceleration of atherosclerosis in HD patients.
Usefulness of Segmental Bioimpedance Ratio to Determine Dry Body Weight in New Hemodialysis Patients: A Pilot Study
Authors: Park Jongha , Yang Won Seok , Kim Soon Bae , Park Su-Kil , Lee Sang Koo , Park Jung Sik , Chang Jai Won
Published: July 2008

Background: The ratio of bioimpedance in the right leg (rl-RBI) may be helpful in adjusting dry body weight (DBW) in new hemodialysis (HD) patients. Methods: rl-RBI was calculated as follows: rl-RBI = impedance at 50 kHz/impedance at 500 kHz, as measured by bioimpedance spectroscopy (BIS). Theoretically, rl-RBI is inversely related to extracellular water. A reference range of rl-RBI was obtained from 137 chronic but stable HD patients already achieving DBW. In 34 new HD patients (females:males = 16:18; age 49 ± 12 years), DBW(s) were stepwise adjusted under the guidance of rl-RBI by modifying the amount of ultrafiltration. Results: The target range of rl-RBI was defined as 1.106–1.150. rl-RBI before the first HD was 1.115 ± 0.027. At the study endpoint, when the target range of rl-RBI was achieved, pretibial pitting edema and pulmonary edema were resolved without any episode of muscle cramping or intradialytic hypotension. Along with an increase in rl-RBI, pre-HD blood pressure tended to decrease at systole (p = 0.072) and diastole (p = 0.005). The cardiothoracic ratio also decreased significantly (p = 0.004). Conclusion: The measurement of rl-RBI by BIS is worthy of further evaluation as an objective and applicable index for determining DBW in new HD patients.
Superior Endurance Performance in Aging Mountain Runners
Authors: Burtscher Martin , Förster Holger , Burtscher Johannes
Published: July 2008

Background: Oxygen uptake at the anaerobic threshold (VO2AT) is considered as the main determinant for endurance performance in humans. Endurance performance steeply decreases with aging but seems to be kept exceedingly high in elite mountain runners. Methods: To obtain the age- and gender-related upper limits of endurance performance in this sport, we analyzed the results of the World Masters Athletic Championships in Mountain Running 2007. Additionally, to investigate the relationship between the individual VO2AT values and running times, laboratory tests were performed in 10 mountain runners. Results: The World Championships race times of the first 5 finishers of the 5-year age groups did not differ significantly from 35 to 49 years. The corresponding mean (± SD) values of the VO2AT were 68.0 ± 1.7 ml/min/kg in males and 58.1 ± 1.9 ml/min/kg in females. In the following age groups up to 70+ there was a decrease in the VO2AT of 29.1% in males and 33.9% in females. Conclusion: Thus, at the beginning of the 3rd millennium, elite mountain runners demonstrate that VO2AT and probably also VO2max may be held at top levels in humans up to the age of 45–49 years in both sexes. Despite the following decrease, endurance capacity remains about 3.5-fold higher in elite mountain runners up to 70+ years when compared to their untrained peers.
Management of Neuroendocrine Tumors: A Meeting of Experts from Latin America
Authors: Costa F. , Domenichini E. , Garavito G. , Medrano R. , Mendez G. , O’Connor J. , Rojas W. , Torres S. , Younes R.N. , Delle Fave G. , Öberg K.
Published: July 2008

A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs.
Genetic Ablation of the
Bmpr2
Gene in Pulmonary Endothelium Is Sufficient to Predispose to Pulmonary Arterial Hypertension
Authors: Hong Kwon-Ho , Lee Young Jae , Lee Eunji , Park Sung Ok , Han Chul , Beppu Hideyuki , Li En , Raizada Mohan K. , Bloch Kenneth D. , Oh S. Paul
Published: July 2008

Background—

Pulmonary arterial hypertension (PAH) is a rare but fatal lung disease of diverse origins. PAH is now further subclassified as idiopathic PAH, familial PAH, and associated PAH varieties. Heterozygous mutations in
BMPR2
can be detected in 50% to 70% of patients with familial PAH and 10% to 40% of patients with idiopathic PAH. Although endothelial cells have been suspected as the cellular origin of PAH pathogenesis, no direct in vivo evidence has been clearly presented. The present study was designed to investigate whether endothelial
Bmpr2
deletion can predispose to PAH.

Methods and Results—

The
Bmpr2
gene was deleted in pulmonary endothelial cells using
Bmpr2
conditional knockout mice and a novel endothelial Cre transgenic mouse line. Wide ranges of right ventricular systolic pressure were observed in mice with heterozygous (21.7 to 44.1 mm Hg; median, 23.7 mm Hg) and homozygous (20.7 to 56.3 mm Hg; median, 27 mm Hg) conditional deletion of
Bmpr2
in pulmonary endothelial cells compared with control mice (19.9 to 26.7 mm Hg; median, 23 mm Hg) at 2 to 7 months of age. A subset of mice with right ventricular systolic pressure >30 mm Hg exhibited right ventricular hypertrophy and an increase in the number and wall thickness of muscularized distal pulmonary arteries. In the lungs of these mice with high right ventricular systolic pressure, the expression of proteins involved in the pathogenesis of PAH such as serotonin transporter and tenascin-C was elevated in distal arteries and had a high incidence of perivascular leukocyte infiltration and in situ thrombosis.

Conclusions—

Conditional heterozygous or homozygous
Bmpr2
deletion in pulmonary endothelial cells predisposes mice to develop PAH.
Reduced Atherosclerotic Lesions in P2Y1/Apolipoprotein E Double-Knockout Mice
Authors: Hechler Béatrice , Freund Monique , Ravanat Catherine , Magnenat Stéphanie , Cazenave Jean-Pierre , Gachet Christian
Published: July 2008

Background—The P2Y1receptor plays a key role in arterial thrombosis and is widely expressed in many cell types involved in atherosclerosis. The aim of this study was to evaluate its potential involvement in the development of atherosclerotic lesions.

Methods and Results—Apolipoprotein E–deficient (ApoE−/−) andP2Y1−/−/ApoE−/−mice were maintained on regular chow for 17 or 30 weeks before analysis of atherosclerotic lesions. At 17 weeks, lesions in the aortic sinus and entire aorta were smaller inP2Y1−/−/ApoE−/−compared with those inApoE−/−animals. At 30 weeks, the aortic sinus lesions inP2Y1−/−/ApoE−/−mice were still diminished in size and displayed reduced inflammation, reflected by decreased macrophage infiltration and diminished VCAM-1 immunostaining, compared with those inApoE−/−mice. They also had a lower smooth muscle cell content. Unexpectedly, bone marrow transplantation showed that the absence of the P2Y1receptor in blood cells only led to no significant modification of the lesion compared with controlApoE−/−reconstituted animals. Conversely, the absence of the P2Y1receptor except in blood cells resulted in a reduction in lesion size similar to that in controlP2Y1−/−/ApoE−/−reconstituted mice, pointing to a role of non–hematopoietic-derived P2Y1receptors, most likely the endothelial or smooth muscle cell P2Y1receptors. In addition, although this was not statistically significant, plasma cholesterol levels were consistently decreased inP2Y1−/−animals, suggesting that a modification of lipid metabolism could be responsible for the observed phenotype.

Conclusion—The P2Y1receptor contributes to atherosclerosis, primarily through its role in non–hematopoietic-derived cells.
Protein Kinase C-ε Induces Caveolin-Dependent Internalization of Vascular Adenosine 5′-Triphosphate–Sensitive K
+
Channels
Authors: Jiao Jundong , Garg Vivek , Yang Baofeng , Elton Terry S. , Hu Keli
Published: July 2008

Vascular ATP-sensitive K
+
(K
ATP
) channels are critical regulators of arterial tone and, thus, blood flow in response to local metabolic needs. They are important targets for clinically used drugs to treat hypertensive emergency and angina. It is known that protein kinase C (PKC) activation inhibits K
ATP
channels in vascular smooth muscles. However, the mechanism by which PKC inhibits the channel remains unknown. Here we report that caveolin-dependent internalization is involved in PKC-ε–mediated inhibition of vascular K
ATP
channels (Kir6.1 and SUR2B) by phorbol 12-myristate 13-acetate or angiotensin II in human embryonic kidney 293 cells and immortalized human saphenous vein vascular smooth muscle cells. We showed that Kir6.1 substantially overlapped with caveolin-1 at the cell surface. Cholesterol depletion with methyl-β-cyclodextrin significantly reduced, whereas overexpression of caveolin-1 largely enhanced, PKC-induced inhibition of Kir6.1/SUR2B currents. Importantly, we demonstrated that activation of PKC-ε caused internalization of K
ATP
channels, the effect that was blocked by depletion of cholesterol with methyl-β-cyclodextrin, expression of dominant-negative dynamin mutant K44E, or knockdown of caveolin-1 with small interfering RNA. Moreover, patch-clamp studies revealed that PKC-ε–mediated inhibition of the K
ATP
current induced by PMA or angiotensin II was reduced by a dynamin mutant, as well as small interfering RNA targeting caveolin-1. The reduction in the number of plasma membrane K
ATP
channels by PKC activation was further confirmed by cell surface biotinylation. These studies identify a novel mechanism by which the levels of vascular K
ATP
channels could be rapidly downregulated by internalization. This finding provides a novel mechanistic insight into how K
ATP
channels are regulated in vascular smooth muscle cells.
Aortic Root Diameter and Longitudinal Blood Pressure Tracking
Authors: Ingelsson Erik , Pencina Michael J. , Levy Daniel , Aragam Jayashri , Mitchell Gary F. , Benjamin Emelia J. , Vasan Ramachandran S.
Published: July 2008

Proximal aortic diameter, including aortic root (AoR) diameter, has been inversely related to pulse pressure in cross-sectional studies. So, investigators have hypothesized that a smaller AoR diameter may increase the risk of developing hypertension. Prospective studies are lacking to test this hypothesis. We measured AoR diameter in 3195 Framingham Study participants (mean age: 49 years; 57% women; 8460 person-examinations) free from hypertension and previous cardiovascular disease who underwent routine echocardiography. We related AoR to hypertension incidence and blood pressure (BP) progression (increment of ≥1 category, as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). On follow-up (median: 4 years), 1267 individuals (15%; 661 women) developed hypertension, and 2978 participants experienced BP progression (35%; 1588 women). In logistic regression models adjusted for age, sex, and height, AoR was positively associated with hypertension incidence (odds ratio: 1.15; 95% CI: 1.08 to 1.23) and BP progression (odds ratio: 1.09; 95% CI: 1.04 to 1.14) on follow-up. However, adjustment for other factors known to influence BP tracking (baseline systolic and diastolic BP, smoking, diabetes, and weight) rendered these relations statistically nonsignificant (odds ratio: 1.03; 95% CI: 0.96 to 1.11 for hypertension incidence; odds ratio: 1.03; 95% CI: 0.97 to 1.08 for BP progression). In our large community-based sample of nonhypertensive individuals, AoR diameter was not associated with hypertension incidence or BP progression prospectively after adjustment for potential confounders. Our prospective study does not support the notion that a smaller AoR predisposes to hypertension.
Linoleate-Rich High-Fat Diet Decreases Mortality in Hypertensive Heart Failure Rats Compared With Lard and Low-Fat Diets
Authors: Chicco Adam J. , Sparagna Genevieve C. , McCune Sylvia A. , Johnson Christopher A. , Murphy Robert C. , Bolden David A. , Rees Meredith L. , Gardner Ryan T. , Moore Russell L.
Published: July 2008

Recent studies indicate that high-fat diets may attenuate cardiac hypertrophy and contractile dysfunction in chronic hypertension. However, it is unclear whether consuming a high-fat diet improves prognosis in aged individuals with advanced hypertensive heart disease or the extent to which differences in its fatty acid composition modulate its effects in this setting. In this study, aged spontaneously hypertensive heart failure rats were administered a standard high-carbohydrate diet or high-fat diet (42% of kilocalories) supplemented with high-linoleate safflower oil or lard until death to determine their effects on disease progression and mortality. Both high-fat diets attenuated cardiac hypertrophy, left ventricular chamber dilation, and systolic dysfunction observed in rats consuming the high-carbohydrate diet. However, the lard diet significantly hastened heart failure mortality compared with the high-carbohydrate diet, whereas the linoleate diet significantly delayed mortality. Both high-fat diets elicited changes in the myocardial fatty acid profile, but neither had any effect on thromboxane excretion or blood pressure. The prosurvival effect of the linoleate diet was associated with a greater myocardial content and linoleate-enrichment of cardiolipin, an essential mitochondrial phospholipid known to be deficient in the failing heart. This study demonstrates that, despite having favorable effects on cardiac morphology and function in hypertension, a high-fat diet may accelerate or attenuate mortality in advanced hypertensive heart disease depending on its fatty acid composition. The precise mechanisms responsible for the divergent effects of the lard and linoleate-enriched diets merit further investigation but may involve diet-induced changes in the content and/or composition of cardiolipin in the heart.
Oxidized Low-Density Lipoprotein Cholesterol Is Associated With Decreases in Cardiac Function Independent of Vascular Alterations
Authors: Rietzschel Ernst R. , Langlois Michel , De Buyzere Marc L. , Segers Patrick , De Bacquer Dirk , Bekaert Sofie , Cooman Luc , Van Oostveldt Patrick , Verdonck Pascal , De Backer Guy G. , Gillebert Thierry C.
Published: July 2008

In contrast to the plethora of vasculopathies to which oxidized low-density lipoprotein cholesterol (ox-LDL) can be linked, there are no data linking ox-LDL to myocardial (dys)function in the community. We tested whether ox-LDL, a marker of oxidative stress, was linked to early cardiac structural and functional damage in the general population. The Asklepios Study is a random sample of 2524 male and female volunteers, comparable to the Belgian population between 35 and 55 years free from overt cardiovascular disease. Cardiac morphology, systolic, and early and late diastolic tissue Doppler mitral annulus velocities were recorded during an echocardiography, followed by a vascular examination (carotid and femoral arteries). Serum ox-LDL was measured by sandwich ELISA using the mAb-4E6 monoclonal antibody. Effects of ox-LDL were assessed after adjustment for age, gender, lipid fractions, blood pressure, heart rate, height, weight, glycemia, smoking, and drug treatment. Mean ox-LDL was 96.0±38.9 U/L. After adjustment, increasing ox-LDL levels were associated with a more spherical left ventricular cavity (minor/major axis dimensions;
P
<0.001) and decreasing diastolic (early diastolic tissue Doppler mitral annulus velocity;
P
<0.001, more pronounced in women) and systolic function (amplitude of systolic tissue Doppler mitral annulus velocity;
P
=0.008, more pronounced in men). These results remained unaffected when further adjustments were made for inflammatory markers, lifestyle, or vascular damage (atherosclerosis and arterial stiffening). These results are the first “proof of concept” that ox-LDL impacts cardiac structure and function at a community level, independent of classic risk factors, lifestyle, inflammation, and prevalent vascular damage. Our data suggest that ox-LDL is a risk marker for early ventricular remodelling. However, the effect size in the general population is small.
The Reception of Eighteenth-Century Women's Poetry by Two Male Authors, Yuan Mei (1716–98) and Zhang Xuecheng (1738–1801)
Authors: Schmidt J.D.
Published: July 2008

The eastward expansion of the Shansabanid sultanate of Ghur in the late twelfth century has usually been depicted as a confrontation between a unitary Muslim self and its Hindu ‘other’. The reification of heterogeneous and protean categories of belief implicit in this paradigm is particularly ill suited to represent the dynamic religious life of mediaeval Ghur. This was characterised by shifting patterns of royal patronage that reflect intense competition between the Karramiya, a popular pietistic sect, and the orthodox Sunni madhhabs. Drawing on Ghurid architectural and numismatic inscriptions, this article examines the ways in which contemporary doctrinal disputes inflected elite cultural production during the period. Based on the content and context of Qur™anic citations, it suggests that a rhetorical emphasis on idolatryand unbelief in Ghurid epigraphy was part of a contemporary intra-Sunni polemic, and notprimarily an address to those who were literally outside the fold of Islam. The deploymentof scripture in the service of sectarian rivalry has significant implications for the inter-pretation of Qur™anic epigraphy in Indo-Ghurid mosques such as the Quwwat al-Islam
Dynamic Volunteer's Dilemmas over a Finite Horizon
Authors: Otsubo Hironori , Rapoport Amnon
Published: July 2008

Volunteer's dilemmas that evolve over time are presented and modeled as noncooperative n-person games in extensive form with symmetric players, discrete time, finite horizon, and complete information. Volunteering is costly, thereby giving rise to free riding. Reflecting on the observation that in many naturally occurring social dilemmas it is beneficial to volunteer earlier than later, the model assumes that the payoff to the volunteer and the (higher) payoff to each of the nonvolunteers decrease monotonically over time. The authors construct symmetric and asymmetric subgame perfect equilibria to the game. An experimental study shows that financially motivated subjects who are rewarded contingent on their performance volunteer more readily when the cost of volunteering is relatively low; that they largely fail to coordinate on any of the asymmetric equilibria in which only a single subject volunteers immediately; that they volunteer, on average, earlier than predicted; and that they vary considerably from one another in their inclination to free ride.
Treatment Integrity of Literacy Interventions for Students With Emotional and/or Behavioral Disorders
Authors: Griffith Annette K. , Duppong Hurley Kristin , Hagaman Jessica L.
Published: July 2008

This review examines the treatment integrity data of literacy interventions for students with emotional and/or behavioral disorders (EBD). Forty-four studies published between 1977 and 2005 were examined. Findings indicate that studies focusing on literacy interventions for students with EBD included clear operational definitions and data on treatment integrity to a higher degree than have been found in other disciplines. However, neither were consistently reported and treatment integrity data were still only reported in just over half of the studies. Considerations for future research and reporting are discussed.
The Push-Pull Effects of the Information Technology Boom and Bust
Authors: Hotchkiss Julie L. , Pitts M. Melinda , Robertson John C.
Published: July 2008

This article examines the inflow and outflow of workers to different industries in Georgia during the information technology (IT) boom of the 1990s and the subsequent bust. Workers in the software and computer services industry were much more likely to have been absent from the Georgia workforce before the boom but were no more likely than workers from other industries to have exited Georgia's workforce during the bust. Consequently, Georgia likely experienced a net gain in worker human capital as a result of being an area of concentration of IT-producing activity during the IT boom.
Crime's Impact on the Survival Prospects of Young Urban Small Businesses
Authors: Bates Timothy , Robb Alicia
Published: July 2008

The authors investigate the empirical link between prevailing levels of crime and the viability of small businesses. Using confidential microdata from the U.S. Census Bureau's Characteristics of Business Owners Survey, they find, on balance, that young firms operating in high-crime niches in urban America appear not to be disadvantaged by crime. Crime's impact may certainly be harmful, with other factors being constant, but the crux of the findings is that other factors are not constant. Firms most negatively affected by crime do not appear to be less viable than otherwise identical firms reporting that crime has no effect on their businesses. High-crime niches may in fact be rational choices for some business owners, present and potential.
Cluster Regions
Authors: Reid Neil , Smith Bruce W. , Carroll Michael C.
Published: July 2008

One ongoing debate in the cluster literature concerns methods of delineating the spatial footprint of industrial clusters. Some cluster regions correspond to political boundaries. Researchers have also used qualitative methods and various quantitative techniques including location quotients and spatial statistics to demarcate clusters. A common weakness of most approaches is that researchers do not incorporate collaboration among cluster participants. In this article, the use of social network analysis (SNA) is illustrated. SNA is not proposed as an alternative to other methods of cluster mapping. Instead, the authors suggest that it complements other methods. Because SNA focuses on networks of social or interpersonal relationships, it provides a dimension that techniques focusing on economic relationships do not capture. One advantage of SNA is that it enables the identification of critical nonindustry actors, such as politicians, economic development practitioners, and academic researchers.
Case Methodology for Adult Learning
Authors: Tripathy Manas Ranjan
Published: July 2008

The emergence of case-based learning underscores the relevance of traditional learning discourses in professional education. Modern day cases are not stories of the past but tools of experiential learning, which evoke sharp critical thinking, analysis, interpretation and application. Opponents of the case method may assert that case studies lack in rigour and reliability and that they do not address the issues of generalizability, which can be effectively tackled by quantitative methods. Cases are not designed to present a right answer, which one can memorize in the hope that it can be applied to similar situations. The learning comes from actually participating in the search for solutions. This article explores the domain of case-based teaching as a learning tool and the underlying issues and challenges inherent to the design, analysis and pedagogy of case form. It also attempts to make a critical review of systemic issues related to theory and practices.
Recrafting Iucn—Asia Regional Organization
Authors: Qureshi Zafar Iqbal
Published: July 2008

The International Union for Conservation of Nature (IUCN)—Asia Regional Organization's rapid growth in various countries as well as within the region put pressure on the existing organization structure and its capacity to manage growth in an effective fashion. The Asia Regional Director (ARD) realized that the reorganization of the Region had become imperative in order to manage this rapid growth. She felt the need to seek outside assistance to generate options for the reorganization. Therefore two consultants were hired to analyze the current situation and propose some options. The consultants handed in their proposals in May 2002 for discussion at a meeting in Bangkok. This meeting led to the creation of three Task Forces to tackle the contentious issues surrounding Country Programmes, Regional Thematic Programmes and Corporate Services. ARD told the three Task Forces that she would like to implement the reorganization by December 2002.
Zareen and Majid Durrani
Authors: Haque Ehsan ul
Published: July 2008

This disguised case focuses on the challenges faced by a female entrepreneur, Zareen Durrani, in balancing her personal and professional life. Details about the family background, education and work experience of the two protagonists of the case, Zareen and her husband Majid Durrani, are provided to understand their goals and aspirations. Both are ambitious professionals and their work related ambitions create serious tensions in their personal lives. While the case deals with deeper, macro-level factors (such as socioeconomic, cultural and traditional forces) in shaping the positions and worldviews of the protagonists, an immediate and very real issue of their children coming down with chicken pox brings all the tensions to a head. Which parent should take significant time out will be determined partly by the participants’ own worldviews of the appropriate roles assigned to the two sexes by society. The case examines interesting ways to explore and debate socially designated roles in Pakistani society. Majid Durrani poses specialization of labour, contract violation and cost-benefit arguments to make his case while Zareen has her own set of fairly valid arguments. The case will expose participants to the various issues that women face in balancing home and work.
HIPAA's Preconsent: Impact on Study Validity
Authors: Rice Michael J. , Records Kathie
Published: July 2008

The Health Insurance Portability and Accountability Act (HIPAA) regulations added potential validity threats to clinical studies. The HIPAA regulations, using the principle of patient autonomy were designed to increase patient's control over the all health related information. The Department of Health and Human Services did not identify rules related to research regulations believing HIPAA regulations facilitate investigations through use of de-identified information. Yet, under HIPAA guidelines, health care agencies can not allow access because of the need to obtain a patient's prior permission to release raw data. The problem of how to conduct investigations in the face of the HIPAA “Privacy Rule” raises concerns for effects on subject recruitment and selection. This paper examines the impact of obtaining a HIPAA preconsent on subject recruitment, selection, and subject characteristics, and offers strategies for addressing the validity threats associated with the HIPAA regulations. J Am Psychiatr Nurses Assoc, 2008; 14(3), 225–230. DOI: 10.1177/1078390308319224
Private security, political economy and the policing of race
Authors: Kempa Michael , Singh Anne-Marie
Published: July 2008

In this article, we hypothesize that the punitive and disciplinary dimensions of the private security industry reflect and propagate a peculiar and practically alarming story about human security: that it is possible to pursue a form of individualized political peace nearly apart from broader projects for social and economic peace. We reflect upon the impacts for different `racial' groups of the continued currency of this story for human security. We probe these developing hypotheses through the empirical case of South Africa. Toward framing this form of analysis, we elaborate upon controversies concerning the combination of Foucauldian analyses with political economic and realist critical race approaches, to yield critical sociologies of political economy.
Valiant beggars and global vagabonds
Authors: Weber Leanne , Bowling Benjamin
Published: July 2008

Attempts by governments to control unwanted border crossings are a defining feature of late modernity; but the suppression of cross-border mobility is not new. In pre-industrial England the `masterless men' and `valiant beggars' were subjected to harsh measures designed to curtail their mobility. In this article, we observe that border control intensifies at times of tumultuous structural change when institutions capable of preserving the emerging economic and social order are largely absent. In a globally mobile society, we argue that `flawed consumers' and `suspect citizens' are the most likely to be earmarked for exclusion. This designation links historical conceptions of `the other' with the tropes of race, class and foreignness to underpin contemporary xeno-racism.
Difference, diversity and criminology
Authors: Hudson Barbara
Published: July 2008

This article argues that criminology has not moved sufficiently from the construction of a series of different `others', towards an epistemology of diversity. The emerging theory of cosmopolitanism is advocated as more consistent with the empirical realities of diversity and globalization than the identity/difference logic of modernity. Cosmopolitanism emphasizes the universality of rights because of humans' common possession of the earth, and proposes the grounding of justice on the need to respond to strangers without hostility. As well as this normative cosmopolitanism, methodological cosmopolitanism has been espoused in recent works by Ulrich Beck and Paul Gilroy. This methodological cosmopolitanism, it is argued, can yield valuable insights into diversity and its implications in single societies and in the globalized world.