bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of cardiac overexpression of type 6 adenylyl cyclase affects on the response to chronic pressure overload
Authors: Guellich Aziz , Gao Shumin , Hong Chull , Yan Lin , Wagner Thomas E. , Dhar Sunil K. , Ghaleh Bijan , Hittinger Luc , Iwatsubo Kosaku , Ishikawa Yoshihiro , Vatner Stephen F. , Vatner Dorothy E.
Published: June 2010

Adenylyl cyclase (AC) type 5 (AC5) and AC type 6 (AC6) are the two major AC isoforms in the heart. Cardiac overexpression of AC6 has been shown to be protective in response to several interventions. In this investigation, we examined the effects of chronic pressure overload in AC6 transgenic (TG) mice. In the absence of any stress, AC6 TG mice exhibited enhanced contractile function compared with their wild-type (WT) littermates, i.e., increased ( P < 0.05) left ventricular (LV) ejection fraction (EF) (75 ± 0.9 vs. 71 ± 0.5%) and LV dP/d t (7,850 ± 526 vs. 6,374 ± 315 mmHg/s). Forskolin (25 μg·kg−1·min−1for 5 min) increased LVEF more ( P < 0.05) in AC6 TG mice (14.8 ± 1.0%) than in WT mice (7.7 ± 1.0%). Also, isoproterenol (0.04 μg·kg−1·min−1for 5 min) increased LVEF more ( P < 0.05) in AC6 TG mice (18.0 ± 1.2%) than in WT mice (11.6 ± 2.1%). Pressure overload, induced by 4 wk of transverse aortic constriction (TAC), increased the LV weight-to-body weight ratio and myocyte cross-sectional area similarly in both groups, but reduced LVEF more in AC6 TG mice (22%) compared with WT mice (9%), despite the higher starting level of LVEF in AC6 TG mice. LV systolic wall stress increased more in AC6 TG mice than in WT mice, which could be responsible for the reduced LVEF in AC6 TG mice with chronic pressure overload. In addition, LV dP/d t was no longer elevated in AC6 TG mice after TAC compared with WT mice. LV end-diastolic diameter was also greater ( P < 0.05) in AC6 TG mice (3.8 ± 0.07 mm) than in WT mice (3.6 ± 0.05 mm) after TAC. Thus, in contrast to other interventions previously reported to be salutary with cardiac AC6 overpression, the response to chronic pressure overload was not; actually, AC6 TG mice fared worse than WT mice. The mechanism may be due to the increased LV systolic wall stress in AC6 TG mice with chronic pressure overload.
Wave intensity analysis of right ventricular and pulmonary vascular contributions to higher pulmonary than aortic blood pressure in fetal lambs
Authors: Smolich Joseph J. , Mynard Jonathan P. , Penny Daniel J.
Published: June 2010

Although fetal pulmonary trunk (PT) blood pressure may exceed aortic trunk (AoT) pressure, the specific mechanism(s) underlying this pressure difference remain undefined. To evaluate the potential role of ventricular and vascular factors in the generation of a fetal PT-AoT pressure difference, nine anesthetized late-gestation fetal sheep were instrumented with PT and AoT micromanometer catheters to measure high-fidelity pressure and transit-time flow probes to obtain blood velocity. The PT-AoT instantaneous pressure difference (IPDPT-AoT) was calculated from PT and AoT pressure profiles. PT and AoT wave intensity (WI) was derived from the product of the appropriate pressure and velocity rates of change. While diastolic pressures were near identical, systolic PT pressure exceeded AoT pressure ( P < 0.001), with a maximal IPDPT-AoT of 6.5 ± 2.5 mmHg. The comparison of IPDPT-AoT with wave-related PT and AoT pressure changes indicated that 1) a greater pressure-generating effect of the PT forward-running compression wave arising from impulsive right ventricular contraction in early and midsystole accounted for 2.3 ± 2.3 mmHg (35%) of the maximal IPDPT-AoT and 2) a larger pressure-generating effect of a large midsystolic backward-running compression wave transmitted into the PT from the pulmonary vasculature contributed 4.0 ± 1.5 mmHg (∼60%) of the maximal IPDPT-AoT. These results indicate that the higher PT than AoT blood pressure observed in fetal lambs is a systolic phenomenon principally related to the combination of a relatively higher level of right ventricular pump function manifest in early and midsystole and a pressure-increasing energy wave arising from the fetal pulmonary vasculature in midsystole.
Angiotensin-(1–12) requires angiotensin converting enzyme and AT1receptors for cardiovascular actions within the solitary tract nucleus
Authors: Arnold Amy C. , Isa Katsunori , Shaltout Hossam A. , Nautiyal Manisha , Ferrario Carlos M. , Chappell Mark C. , Diz Debra I.
Published: June 2010

The novel peptide, angiotensin (ANG)-(1–12), elicits a systemic pressor response and vasoconstriction. These effects are blocked by ANG converting enzyme (ACE) inhibitors or AT1receptor antagonists, suggesting a role as an ANG II precursor. However, ANG-(1–12) can serve as a substrate for either ANG II or ANG-(1–7) formation, depending on the local tissue enzymes. Although levels of ANG-(1–12) are higher than ANG I or ANG II in brain, the role and processing of this peptide for autonomic control of heart rate (HR) has yet to be considered. Thus we examined the effects of nucleus tractus solitarii (NTS) microinjection of ANG-(1–12) on baroreflex sensitivity for control of HR, resting arterial pressure (AP) and HR, and indexes of sympathovagal balance in urethane/chloralose anesthetized Sprague-Dawley rats. NTS injection of ANG-(1–12) (144 fmol/120 nl) significantly impaired the evoked baroreflex sensitivity to increases in AP [ n = 7; 1.06 ± 0.06 baseline vs. 0.44 ± 0.07 ms/mmHg after ANG-(1–12)], reduced the vagal component of spontaneous baroreflex sensitivity and HR variability, and elicited a transient depressor response ( P < 0.05). NTS pretreatment with an AT1receptor antagonist or ACE inhibitor prevented ANG-(1–12)-mediated autonomic and depressor responses. ANG-(1–12) immunostaining was observed in cells within the NTS of Sprague-Dawley rats, providing a potential intracellular source for the peptide. However, acute NTS injection of an ANG-(1–12) antibody did not alter resting baroreflex sensitivity, AP, or HR in these animals. Collectively, these findings suggest that exogenous ANG-(1–12) is processed to ANG II for cardiovascular actions at AT1receptors within the NTS. The lack of acute endogenous ANG-(1–12) tone for cardiovascular regulation in Sprague-Dawley rats contrasts with chronic immunoneutralization in hypertensive rats, suggesting that ANG-(1–12) may be activated only under hypertensive conditions.
Previous gestational diabetes impairs long-term endothelial function in a mouse model of complicated pregnancy
Authors: Stanley Joanna L. , Sankaralingam Sowndramalingam , Baker Philip N. , Davidge Sandra T.
Published: June 2010

Women who develop gestational diabetes mellitis (GDM) display endothelial dysfunction up to 1 yr after pregnancy, despite a return to normoglycemia. It is unknown whether this dysfunction was preexisting or whether GDM pregnancy leads to long-term endothelial dysfunction. A mouse model that spontaneously develops GDM ( Leprdb/+) was used to determine whether the endothelial dysfunction that develops during GDM is evident in later life. Heterozygous and wild-type (WT) controls were allowed to litter once, then age to 9–10 mo, and were compared with virgin controls. Vascular function of small mesenteric arteries was assessed using wire myography. Concentration response curves to the thromboxane A2mimetic U46619 and the endothelium-dependent vasodilator methacholine were constructed. Superoxide production and peroxynitrite formation was also measured. Mice with previous GDM displayed blood glucose concentrations similar to previously pregnant WT mice (8.0 ± 0.1 vs. 7.1 ± 0.3 mmol/l, P > 0.05). Arteries from mice with previous GDM displayed increased sensitivity to U46619 (EC505.2 ± 0.7 vs. 45.2 ± 1.0 nmol/l, P < 0.01) and impaired endothelium-dependent relaxation compared with WT controls (29 ± 8 vs. 58 ± 16 percent relaxation, P < 0.05). This was associated with increased superoxide production (93.3 ± 2.3 vs. 64.6 ± 1.6 mean fluorescence intensity, P < 0.001) and increased peroxynitrite formation (173.5 ± 11.0 vs. 57.4 ± 16.2 mean fluorescence intensity, P < 0.01) compared with virgin controls. In summary, endothelial dysfunction was evident in mice with previous GDM compared with previously healthy pregnant mice or virgin controls. These data suggest that GDM affects endothelial function and may contribute to an increased risk of cardiovascular disease.
Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates
Authors: Bello Nicholas T. , Kemm Matthew H. , Ofeldt Erica M. , Moran Timothy H.
Published: June 2010

Glucagon-like peptide-1 (GLP-1) and amylin mediate the feedback control of eating by seemingly separate, but overlapping mechanisms. This study examined the effects of combined doses of the GLP-1 agonist, exendin-4 (Ex-4), and the amylin analog, salmon calcitonin (sCT), on food intake and meal patterns in adult male rhesus monkeys. Monkeys received intramuscular injections of Ex-4 (0, 0.1, 0.32, or 0.56 μg/kg), sCT (0, 0.1, or 0.32 μg/kg), or combinations thereof before a 6-h daily access to food. Dose combinations produced reductions in food intake that were significantly greater than those produced by the individual doses. Surface plots of the hourly intake indicated a synergistic interaction at lower doses of Ex-4 and sCT during the first 4 h of feeding and additive effects at hours 5 and 6. Meal pattern analysis revealed the combinational doses reduced average meal size and meal frequency by additive interactions, whereas infra-additive effects were apparent at lower doses for first meal size. Combinational doses were further characterized by administration of repeated daily injections of 0.56 μg/kg Ex-4 + 0.32 μg/kg sCT for 5 days. This resulted in sustained reductions in daily food intake (>70% from saline baseline) for 5 days with residual reductions (∼48% from saline baseline) persisting on day 1 following the injections. In contrast, when pair-fed an identical amount of daily food, there was a compensatory food intake increase on day 1 following the pair-feeding (∼132% of saline baseline). Such data suggest Ex-4 and sCT interact in an overall additive fashion to reduce food intake and further the understanding of how GLP-1 and amylin agonist combinations influence feeding behavior.
Angiotensin II mediates epithelial-to-mesenchymal transformation in tubular cells by ANG 1–7/MAS-1-dependent pathways
Authors: Burns W. C. , Velkoska E. , Dean R. , Burrell L. M. , Thomas M. C.
Published: June 2010

Epithelial-to-mesenchymal transformation (EMT) of tubular cells into a myofibroblastic phenotype is an important mediator of renal scarring in chronic nephropathy. This study examines the role of the renin-angiotensin system (RAS) in this process. NRK-52E cells were exposed to angiotensin (ANG) II and ANG 1–7 in the presence or absence of inhibitors and agonists of RAS signaling. EMT was assessed at 3 days by expression of α-smooth muscle actin (α-SMA) and E-cadherin and the induction of a myofibroblastic phenotype. Expression of fibrogenic growth factors and matrix proteins was assessed by RT-PCR and immunofluorescence microscopy. To confirm findings in vivo, rats were also infused with ANG 1–7 (24 μg·kg−1·h−1) or saline via an osmotic minipump for 10 days, and renal fibrogenesis was then assessed. Treatment of NRK-52E cells with ANG II induced characteristic changes of EMT. Selective blockade of the AT1receptor or the AT2receptor failed to inhibit ANG II-induced EMT. However, blockade of the ANG 1–7 receptor, Mas-1, was able to prevent ANG II-dependent EMT. To confirm these findings, both ANG 1–7 and the selective Mas receptor agonist, AVE-0991, were able to induce NRK-52E cells in a dose-dependent manner. Exposing cells to recombinant ACE2 was also able to induce EMT. In addition, an infusion of ANG 1–7 induced the tubular expression of α-SMA and the expression of matrix proteins in the kidney. ANG II is a potent stimulus for EMT, but not through conventional pathways. This study points to the possible limitations of conventional RAS blockade, which not only fails to antagonize this pathway, but also may enhance it via augmenting the synthesis of ANG 1–7.
Membrane blebbing as an assessment of functional rescue of dysferlin-deficient human myotubes via nonsense suppression
Authors: Wang Bingjing , Yang Zhaohui , Brisson Becky K. , Feng Huisheng , Zhang Zhiqian , Welch Ellen M. , Peltz Stuart W. , Barton Elisabeth R. , Brown Robert H. , Sweeney H. Lee
Published: June 2010

Mutations that result in the loss of the protein dysferlin result in defective muscle membrane repair and cause either a form of limb girdle muscular dystrophy (type 2B) or Miyoshi myopathy. Most patients are compound heterozygotes, often carrying one allele with a nonsense mutation. Using dysferlin-deficient mouse and human myocytes, we demonstrated that membrane blebbing in skeletal muscle myotubes in response to hypotonic shock requires dysferlin. Based on this, we developed an in vitro assay to assess rescue of dysferlin function in skeletal muscle myotubes. This blebbing assay may be useful for drug discovery/validation for dysferlin deficiency. With this assay, we demonstrate that the nonsense suppression drug, ataluren (PTC124), is able to induce read-through of the premature stop codon in a patient with a R1905X mutation in dysferlin and produce sufficient functional dysferlin (∼15% of normal levels) to rescue myotube membrane blebbing. Thus ataluren is a potential therapeutic for dysferlin-deficient patients harboring nonsense mutations.
Facilitation of Corticostriatal Plasticity by the Amygdala Requires Ca2+-Induced Ca2+Release in the Ventral Striatum
Authors: Popescu Andrei T. , Saghyan Aleksandr A. , Nagy Frank Z. , Paré Denis
Published: June 2010

Motor learning and habit formation are thought to depend on corticostriatal synaptic plasticity. Moreover, basolateral amygdala (BLA) activity facilitates consolidation of striatal-dependent memories. Accordingly, BLA stimulation in vitro facilitates long-term potentiation (LTP) induction at corticostriatal synapses onto medium spiny neurons (MSNs). Although these effects were found to depend on N-methyl-d-aspartate (NMDA) receptor activation at BLA synapses and consequent Ca2+influx, it is unclear how this event can facilitate LTP at cortical synapses, even when the two inputs are not coactivated. Here, we aimed to shed light on this question, using whole cell recordings of MSNs in vitro. We first tested whether BLA inputs end at more proximal dendritic sites than cortical inputs. In this scenario, BLA synapses would experience stronger spike-related depolarizations and be in a strategic position to control the spread of second messengers. However, comparison of compound excitatory postsynaptic potentials and single-axon excitatory postsynaptic currents revealed that BLA and cortical synapses are intermingled. Next, we examined the sensitivity of cortical and BLA NMDA responses to ifenprodil because NR2A-containing NMDA receptors have faster kinetics than those containing NR2B subunits. However, the two inputs did not differ in this respect. Last, reasoning that propagating waves of Ca2+-induced Ca2+release (CICR) could bridge temporal gaps between the two inputs, we tested the effects of CICR inhibitors on the BLA facilitation of corticostriatal LTP induction. Pharmacological interference with CICR blocked corticostriatal LTP induction. Thus our results are consistent with the notion that NMDA-dependent Ca2+influx at BLA synapses initiates propagating waves of CICR, thereby biasing active corticostriatal inputs toward synaptic potentiation.
Regulation of Cellular Calcium in Vestibular Supporting Cells by Otopetrin 1
Authors: Kim Euysoo , Hyrc Krzysztof L. , Speck Judith , Lundberg Yunxia W. , Salles Felipe T. , Kachar Bechara , Goldberg Mark P. , Warchol Mark E. , Ornitz David M.
Published: June 2010

Otopetrin 1 (OTOP1) is a multitransmembrane domain protein, which is essential for mineralization of otoconia, the calcium carbonate biominerals required for vestibular function, and the normal sensation of gravity. The mechanism driving mineralization of otoconia is poorly understood, but it has been proposed that supporting cells and a mechanism to maintain high concentrations of calcium are critical. Using Otop1 knockout mice and a utricular epithelial organ culture system, we show that OTOP1 is expressed at the apex of supporting cells and functions to increase cytosolic calcium in response to purinergic agonists, such as adenosine 5′-triphosphate (ATP). This is achieved by blocking mobilization of calcium from intracellular stores in an extracellular calcium-dependent manner and by mediating influx of extracellular calcium. These data support a model in which OTOP1 acts as a sensor of the extracellular calcium concentration near supporting cells and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization.
The Effect of Land Cover Change on Soil Properties around Kibale National Park in South Western Uganda
Authors: Majaliwa J. G. M. , Twongyirwe R. , Nyenje R. , Oluka M. , Ongom B. , Sirike J. , Mfitumukiza D. , Azanga E. , Natumanya R. , Mwerera R. , Barasa B.
Published: June 2010

The change from natural forest cover to tea and Eucalyptus is rampant in protected areas of western Uganda. The objectives were; to examine the trend in land-use /cover change and determine the effect of these changes on the physico-chemical properties of soils around Kibale National Park. The trend in land use/cover change was assessed by analyzing a series of landsat images. Focused group discussions and key informant interviews were used for land-use/cover reconstruction. Three major land uses were included; woodlot (Eucalyptus grandis; 5 years old) ), tea (57 years old) and natural forest used as a control. Each of these land-uses were selected at two different North facing landscape positions and were replicated three times. A total of 36 composite soil samples were taken at 0–15 and 15–30 cm depth from natural forest, Tea plantation and eucalyptus on three ridges. Results showed that small scale farming, tea and eucalyptus plantation and built up area have increased over time, to the expense of woodlot and forest cover. Tea and Eucalyptus have induced changes in: exchangeable Mg and Ca, available P, SOM, pH, and bulk density of sub soil (P<.05). Landscape positions within land use also significantly influenced most soil properties (P<.05). Similar findings were observed by Wang et al. (2006) in commercial tea plantations in China that received nitrogen fertilizers.
Rhizoma coptidisInhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFκB-Dependent Pathway
Authors: Remppis Andrew , Bea Florian , Greten Henry Johannes , Buttler Annette , Wang Hongjie , Zhou Qianxing , Preusch Michael R. , Enk Ronny , Ehehalt Robert , Katus Hugo , Blessing Erwin
Published: June 2010

Introduction. The Chinese extractRhizoma coptidisis well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood.Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with eitherRhizoma coptidisextract or berberine. Activation of AP-1 and NFκB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants.Results. Incubation withRhizoma coptidisand berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP)-1 production in RAW cells. Activation of the transcription factors AP-1 and NFκB was inhibited byRhizoma coptidisin a dose- and time-dependent fashion.Conclusions. Rhizoma coptidisextract inhibits LPS-induced MCP-1/CCL2 productionin vitrovia an AP-1 and NFκB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine.
Exercised-Induced Coronary Spasm in Near Normal Coronary Arteries
Authors: Franzen Damian , Benzing Thomas
Published: June 2010

In contrast to effort-induced symptoms in obstructive coronary disease, spasm in normal coronary arteries is characterized by angina at rest. We describe a 44-year-old patient with minor coronary plaques and pure exercised-induced coronary spasm. The case questions the differential pathogenic considerations of variant of the variant as opposed to Prinzmetal's variant angina.
Recent Advancements in Cytotoxic T Lymphocyte Generation Methods Using Carbohydrate-Coated Liposomes
Authors: Ikehara Yuzuru , Yamanaka Masahiro , Yamaguchi Takashi
Published: June 2010

Both tumor-specificCD4+andCD8+T cells have been identified, and the latter is known as a major effector of adaptive antitumor immune responses. Optimal antitumor immune responses are considered to require the concomitant activation of bothCD8+andCD4+T cells and the additional selective activation ofCD4+T cells with helper, but not regulatory function. As optimal antitumor immune responses are generated by the concomitant activation of both T cell types, it is necessary for vaccine methods involving cytotoxic T-lymphocytes (CTLs) generation to possess a mechanism whereby antigen presenting cells can present administrated exogenous antigens on not only Major histocompatibility complex (MHC) class II, but also MHC class I molecules.
Structural Health Monitoring of Precast Concrete Box Girders Using Selected Vibration-Based Damage Detection Methods
Authors: Zhou Zhengjie , Wegner Leon D. , Sparling Bruce F.
Published: June 2010

Precast, prestressed concrete box girders are commonly used as superstructure components for short and medium span bridges. Their configuration and typical side-by-side placement make large portions of these elements inaccessible for visual inspection or the application of nondestructive testing techniques. This paper demonstrates that vibration-based damage detection (VBDD) is an effective alternative for monitoring their structural health. A box girder removed from a dismantled bridge was used to evaluate the ability of five different VBDD algorithms to detect and localize low levels of spalling damage, with a focus on using a small number of sensors and only the fundamental mode of vibration. All methods were capable of detecting and localizing damage to a region within approximately 1.6 times the longitudinal spacing between as few as six uniformly distributed accelerometers. Strain gauges configured to measure curvature were also effective, but tended to be susceptible to large errors in near support damage cases. Finite element analyses demonstrated that increasing the number of sensor locations leads to a proportional increase in localization accuracy, while the use of additional modes provides little advantage and can sometimes lead to a deterioration in the performance of the VBDD techniques.
Benign Fibrous Histiocytoma of the Buccal Mucosa: Case Report and Literature Review
Authors: Giovani Paraskevi , Patrikidou Anna , Ntomouchtsis Aris , Meditskou Soultana , Thuau Henri , Vahtsevanos Kostas
Published: June 2010

Benign fibrous histiocytoma is an interesting and challenging entity even in its most usual, cutaneous presentation. Noncutaneous presentation is extremely limited, even more so for the mucosa of the head and neck area. We herein report such a case, describing the clinical characteristics of the lesion, complete diagnostic evaluation, management, and follow-up. Diagnostic histopathological challenges are specifically illustrated. A complete review of the relevant literature is also included.
Chitin Fiber and Chitosan 3D Composite Rods
Authors: Wang Zhengke , Hu Qiaoling , Cai Lei
Published: June 2010

Chitin fiber (CHF) and chitosan (CS) 3D composite rods with layer-by-layer structure were constructed by in situ precipitation method. CHF could not be dissolved in acetic acid aqueous solution, but CS could be dissolved due to the different deacetylation degree (D.D) between CHF and CS. CHF with undulate surfaces could be observed using SEM to demonstrate that the sufficiently rough surfaces and edges of the fiber could enhance the mechanical combining stress between fiber and matrix. XRD indicated that the crystallinity of CHF/CS composites decreased and CS crystal plane d-spacing of CHF/CS composites became larger than that of pure CS rod. TG analysis showed that mixing a little amount of CHF could enhance thermal stability of CS rod, but when the content of CHF was higher than the optimum amount, its thermal stability decreased. When 0.5% CHF was added into CS matrix, the bending strength and bending modulus of the composite rods arrived at 114.2 MPa and 5.2 GPa, respectively, increased by 23.6% and 26.8% compared with pure CS rods, indicating that CHF/CS composite rods could be a better candidate for bone fracture internal fixation.
The S100B/RAGE Axis in Alzheimer's Disease
Authors: Leclerc Estelle , Sturchler Emmanuel , Vetter Stefan W.
Published: June 2010

Increasing evidence suggests that the small EF-hand calcium-binding protein S100B plays an important role in Alzheimer's disease. Among other evidences are the increased levels of both S100B and its receptor, the Receptor for Advanced Glycation Endproducts (RAGEs) in the AD diseased brain. The regulation of RAGE signaling by S100B is complex and probably involves other ligands including the amyloid beta peptide (A), the Advanced Glycation Endproducts (AGEs), or transtheyretin. In this paper we discuss the current literature regarding the role of S100B/RAGE activation in Alzheimer's disease.
Effects of Sitagliptin Treatment on Dysmetabolism, Inflammation, and Oxidative Stress in an Animal Model of Type 2 Diabetes (ZDF Rat)
Authors: Ferreira Liliana , Teixeira-de-Lemos Edite , Pinto Filipa , Parada Belmiro , Mega Cristina , Vala Helena , Pinto Rui , Garrido Patrícia , Sereno José , Fernandes Rosa , Santos Paulo , Velada Isabel , Melo Andreia , Nunes Sara , Teixeira Frederico , Reis Flávio
Published: June 2010

The purpose of this paper is to evaluate the chronic effect of sitagliptin on metabolic profile, inflammation, and redox status in the Zucker Diabetic Fatty (ZDF) rat, an animal model of obese type 2 diabetes. Diabetic and obese ZDF (fa/fa) rats and their controls (ZDF +/+) were treated during 6 weeks with vehicle (control) and sitagliptin (10 mg/kg/bw). Glucose, HbA1c, insulin, Total-c, TGs, IL-1β, TNF-α, CRPhs, and adiponectin were assessed in serum and MDA and TAS in serum, pancreas, and heart. Pancreatic histology was also evaluated. Sitagliptin in diabetic rats promoted a decrease in glucose, HbA1c, Total-c, and TGs accompanied by a partial prevention of insulinopenia, together, with a decrease in CRPhsand IL-1β. Sitagliptin also showed a positive impact on lipid peroxidation and hypertension prevention. In conclusion, chronic sitagliptin treatment corrected the glycaemic dysmetabolism, hypertriglyceridaemia, inflammation, and hypertension, reduced the severity of the histopathological lesions of pancreatic endocrine and exocrine tissues, together with a favourable redox status, which might be a further advantage in the management of diabetes and its proatherogenic comorbidities.
Humidity-Dependent Bacterial Cells Functional Morphometry Investigations Using Atomic Force Microscope
Authors: Nikiyan Hike , Vasilchenko Alexey , Deryabin Dmitry
Published: June 2010

The effect of a relative humidity (RH) in a range of 93–65% on morphological and elastic properties ofBacillus cereusandEscherichia colicells was evaluated using atomic force microscopy. It is shown that gradual dehumidification of bacteria environment has no significant effect on cell dimensional features and considerably decreases them only at 65% RH. The increasing of the bacteria cell wall roughness and elasticity occurs at the same time. Observed changes indicate that morphological properties ofB. cereusare rather stable in wide range of relative humidity, whereasE. coliare more sensitive to drying, significantly increasing roughness and stiffness parameters at RH 84% RH. It is discussed the dependence of the response features on differences in cell wall structure of gram-positive and gram-negative bacterial cells.
Evaluation of the WRF Double‐Moment 6‐Class Microphysics Scheme for Precipitating Convection
Authors: Hong Song-You , Lim Kyo-Sun Sunny , Lee Yong-Hee , Ha Jong-Chul , Kim Hyung-Woo , Ham Sook-Jeong , Dudhia Jimy
Published: June 2010

This study demonstrates the characteristics of the Weather Research and Forecasting (WRF) Double‐Moment 6‐Class (WDM6) Microphysics scheme for representing precipitating moist convection in 3D platforms, relative to the WSM6 scheme that has been widely used in the WRF community. For a case study of convective system over the Great Plains, the WDM6 scheme improves the evolutionary features such as the bow‐type echo in the leading edge of the squall line. We also found that the WRF with WDM6 scheme removes spurious oceanic rainfall that is a systematic defect resulting from the use of the WSM6 scheme alone. The simulated summer monsoon rainfall in East Asia is improved by weakening (strengthening) light (heavy) precipitation activity. These changes can be explained by the fact that the WDM6 scheme has a wider range in cloud and rain number concentrations than does the WSM6 scheme.
Antioxidant, Antimicrobial Activity and Toxicity Test ofPilea microphylla
Authors: Modarresi Chahardehi Amir , Ibrahim Darah , Fariza Sulaiman Shaida
Published: June 2010

A total of 9 plant extracts were tested, using two different kinds of extracting methods to evaluate the antioxidant and antimicrobial activities fromPilea microphylla(Urticaceae family) and including toxicity test. Antioxidant activity were tested by using DPPH free radical scavenging, also total phenolic contents and total flavonoid contents were determined. Toxicity assay carried out by using brine shrimps. Methanol extract of method I (ME I) showed the highest antioxidant activity at69.51±1.03. Chloroform extract of method I (CE I) showed the highest total phenolic contents at72.10±0.71and chloroform extract of method II (CE II) showed the highest total flavonoid contents at60.14±0.33. The antimicrobial activity ofPilea microphyllaextract was tested in vitro by using disc diffusion method and minimum inhibitory concentration (MIC). ThePilea microphyllaextract showed antibacterial activity against some Gram negative and positive bacteria. The extracts did not exhibit antifungal and antiyeast activity. The hexane extract of method I (HE I) was not toxic against brine shrimp (LC50 value was 3880 μg/ml). Therefore, the extracts could be suitable as antimicrobial and antioxidative agents in food industry.
Endoscopic Management of Drain Inclusion in the Gastric Pouch after Gastrojejunal Leakage after Laparoscopic Roux-en-Y Gastric Bypass for the Treatment of Morbid Obesity (LRYGBP)
Authors: Vilallonga Ramon , Fort José Manuel , Gonzalez Oscar , Baena Juan Antonio , Lecube Albert , Salord Josè , Armengol Carrasco Manel , Armengol-Miró Josep Ramon
Published: June 2010

Background. Drain inclusion inside the gastric pouch is rare and can represent an important source of morbidity and mortality associated with laparocopic Roux-en-Y gastric bypass (LRYGBP). These leaks can become chronic and challenging. Surgical options are often unsuccessful. We present the endoscopic management of four patients with drain inclusion.
Patients. All four obese morbidly patients underwent LRYGBP and presented a gastro-jejunal fistula after acute anastomotic leakage. During follow-up endoscopy the drain was found inside the gastric pouch. It was moved into the abdominal cavity. Fistula debit reduced significantly and closed. Results. Gastric leak closure in less than 24 hours was achieved in all, with complete resolution of symptoms. These patients benefited exclusively from endoscopic treatment. Conclusions. Endoscopy is useful and technically feasible in chronic fistulas. This procedure is a less invasive alternative to traditional surgical revision. Other therapeutic strategies can be used such as clips and fibrin glue. Drains should not be placed in contact with the anastomosis or stapled lines. Drain inclusion must be suspected when fistula debit suddenly arises. If so, endoscopy is indicated for diagnostic accuracy. Under endoscopy vision, the drain is gently removed from the gastric reservoir leading to sudden and complete resolution of the fistula.
Advanced Nanomaterials in Multimodal Imaging: Design, Functionalization, and Biomedical Applications
Authors: Liu Zhe , Kiessling Fabian , Gätjens Jessica
Published: June 2010

The biomedical applications of nanoparticles in molecular imaging, drug delivery, and therapy give rise to the term “nanomedicine” and have led to ever‐growing developments in the past decades. New generation of imaging probes (or contrast agents) and state of the art of various strategies for efficient multimodal molecular imaging have drawn much attention and led to successful preclinical uses. In this context, we intend to elucidate the fundamentals and review recent advances as well as to provide an outlook perspective in these fields.
Computer Simulation Tests of Feedback Error Learning Controller with IDM and ISM for Functional Electrical Stimulation in Wrist Joint Control
Authors: Watanabe Takashi , Sugi Yoshihiro
Published: June 2010

Feedforward controller would be useful for hybrid Functional Electrical Stimulation (FES) system using powered orthotic devices. In this paper, Feedback Error Learning (FEL) controller for FES (FEL-FES controller) was examined using an inverse statics model (ISM) with an inverse dynamics model (IDM) to realize a feedforward FES controller. For FES application, the ISM was tested in learning off line using training data obtained by PID control of very slow movements. Computer simulation tests in controlling wrist joint movements showed that the ISM performed properly in positioning task and that IDM learning was improved by using the ISM showing increase of output power ratio of the feedforward controller. The simple ISM learning method and the FEL-FES controller using the ISM would be useful in controlling the musculoskeletal system that has nonlinear characteristics to electrical stimulation and therefore is expected to be useful in applying to hybrid FES system using powered orthotic device.
Studies of the Antiproliferative Activity of Ruthenium (II) Cyclopentadienyl‐Derived Complexes with Nitrogen Coordinated Ligands
Authors: Moreno Virtudes , Lorenzo Julia , Aviles Francesc X. , Garcia M. Helena , Ribeiro João P. , Morais Tânia S. , Florindo Pedro , Robalo M. Paula
Published: June 2010

Four cationic ruthenium(II) complexes with the formula , with L = 5‐phenyl‐1H‐tetrazole (TzH) 1, imidazole (ImH) 2, benzo[1,2‐b;4,3‐b′] dithio‐phen‐2‐carbonitrile (Bzt) 3, and [5‐(2‐thiophen‐2‐yl)‐vinyl]‐thiophene‐2‐carbonitrile] (Tvt) 4 were prepared and characterized in view to evaluate their potentialities as antitumor agents. Studies by Circular Dichroism indicated changes in the secondary structure of ct‐DNA. Changes in the tertiary structure of pBR322 plasmid DNA were also observed in gel electrophoresis experiment and the images obtained by atomic force microscopy (AFM) suggest strong interaction with pBR322 plasmid DNA; the observed decreasing of the viscosity with time indicates that the complexes do not intercalate between DNA base pairs. Compounds 1, 2, and 3 showed much higher cytotoxicity than the cisplatin against human leukaemia cancer cells (HL‐60 cells).
New Strategies in Colorectal Cancer: Biomarkers of Response to Epidermal Growth Factor Receptor Monoclonal Antibodies and Potential Therapeutic Targets in Phosphoinositide 3-Kinase and Mitogen-Activated Protein Kinase Pathways
Authors: Dasari Arvind , Messersmith Wells A.
Published: June 2010

Initial experience with the epidermal growth factor receptor monoclonal antibodies (EGFR MoAb) in unselected patients with metastatic colorectal cancer (mCRC) showed that most of the treated patients did not derive therapeutic benefit. This outcome has driven the search for biomarkers for this population. Recent advances have further shown the heterogeneous nature of this disease with multiple interlinked pathways being implicated. Two such pathways downstream to the EGFR, mitogen-activated protein kinase (MAPK) and (phosphoinositide 3-kinase) PI3K, have gained increasing attention and become targets for development of novel biomarkers and therapeutic agents. Here, we highlight recent progress. Clin Cancer Res; 16(15); 3811–8. ©2010 AACR.
Hypothesis: Kisspeptin Mediates Male Hypogonadism in Obesity and Type 2 Diabetes
Authors: George Jyothis T. , Millar Robert P. , Anderson Richard A.
Published: June 2010

Hypogonadism occurs commonly in men with type 2 diabetes (T2DM) and severe obesity. Current evidence points to a decreased secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus and thereby decreased secretion of gonadotropins from the pituitary gland as a central feature of the pathophysiology in these men. Hyperglycaemia, inflammation, leptin and oestrogen-related feedback have been proposed to make aetiological contributions to the hypogonadotropic hypogonadism of T2DM. However, the neuroendocrine signals that link these factors with modulation of GnRH neurons have yet to be identified. Kisspeptins play a central role in the modulation of GnRH secretion and, thus, downstream regulation of gonadotropins and testosterone secretion in men. Inactivating mutations of the kisspeptin receptor have been shown to cause hypogonadotropic hypogonadism in man, whilst an activating mutation is associated with precocious puberty. Data from studies in experimental animals link kisspeptin expression with individual factors known to regulate GnRH secretion, including hyperglycaemia, inflammation, leptin and oestrogen. We therefore hypothesise that decreased endogenous kisspeptin secretion is the common central pathway that links metabolic and endocrine factors in the pathology of testosterone deficiency seen in men with obesity and T2DM. We propose that the kisspeptin system plays a central role in integrating a range of metabolic inputs, thus constituting the link between energy status with the hypothalamic-pituitary-gonadal axis, and put forward potential clinical studies to test the hypothesis.
Effect on Cell Surface Markers following Allergen-Induced Desensitization of Human Whole-Blood Basophils
Authors: Lund Gitte , Jacobi Henrik , Stahl Skov Per , Holm Jens , Lund Kaare
Published: June 2010

Background: Allergen-specific immunotherapy (SIT) leads to reduced symptoms upon allergen exposure through as yet unresolved mechanisms. Desensitization of basophils to specific allergens during the updosing phase of injection immunotherapy may contribute to the clinical effect of SIT. Here we report a protocol for efficient in vitro allergen-mediated desensitization of basophils in whole blood and the effect of desensitization on the expression of basophil activation markers (CD203c and CD63) as well as histamine release in response to allergen challenge. Methods: Whole blood from grass pollen-allergic subjects was incubated with Phleum pratense extract by stepwise increase of the allergen concentration in the culture from well below to well above the allergen threshold concentration for activation of basophils. Desensitization was determined by measuring the expression of the basophil activation markers CD63 and CD203c by FACS following challenge with high allergen concentrations. Results: The basophil desensitization protocol reported here affected both the expression of the cell-surface markers and the levels of histamine release. Following the stepwise desensitization procedure the whole-blood basophils were not activated when challenged with more than 10-fold increased allergen concentration. Conclusion: We have established a protocol for basophil desensitization. By mimicking the updosing phase of immunotherapy we raised the allergen threshold for basophil activation and obtained efficient desensitization for all donors. We showed that conditions leading to desensitization affect histamine release and expression of different basophil markers alike.
Extraction of Old Pacemaker or Cardioverter-Defibrillator Leads by Laser Sheath Versus Femoral Approach
Authors: Bordachar Pierre , Defaye Pascal , Peyrouse Eric , Boveda Serge , Mokrani Bilel , Marquié Christelle , Barandon Laurent , Fossaert Emilie Marcant , Garrigue Stephane , Reuter Sylvain , Laborderie Julien , Marijon Eloi , Deharo Jean-Claude , Jacon Peggy , Kacet Salem , Ploux Sylvain , Deplagne Antoine , Haissaguerre Michel , Clementy Jacques , Ritter Philippe , Klug Didier
Published: June 2010

Background—

Some operators routinely extract chronically implanted transvenous leads from a femoral, whereas others prefer a superior approach. This prospective study compared the safety and effectiveness of laser sheaths versus femoral snare extractions.

Methods and Results—

The single-center study comprised 101 patients referred for unequivocal indications to extract ≥1 transvenous lead(s). Patients were >4 years of age and were randomly assigned to extractions with a laser sheath (group 1: n=50) versus a snare via femoral approach (group 2: n=51). The multicenter study comprised 358 patients who underwent extraction of old transvenous leads using laser sheaths (n=218, group 3) in 3 centers and from a femoral approach (n=138, group 4) in 3 other centers. In the single-center study, the success and complications rates were similar in groups 1 and 2. No patient died of a periprocedural complication. The procedural duration (51±22 versus 86±51 minutes) and duration of total fluoroscopic exposure (7±7 versus 21±17 minutes) were significantly shorter (each
P
<0.01) in group I than in group 2. In the multicenter study, we observed 2 procedure-associated deaths in group 3 versus 1 in group 4. Major procedural complications were observed in 3% of patients in group 3, versus 3% in group 4 (
P
=NS). The rates of complete, partial, and unsuccessful extractions were similar in groups 3 and 4.

Conclusions—

Old transvenous leads were extracted with similar success and complication rates by the femoral and laser approaches. However, the femoral approach was associated with longer procedures and a longer duration of fluoroscopic exposure.
Inhibition of Small-Conductance Ca
2+
-Activated K
+
Channels Terminates and Protects Against Atrial Fibrillation
Authors: Diness Jonas Goldin , Sørensen Ulrik S. , Nissen Jakob Dahl , Al-Shahib Baha , Jespersen Thomas , Grunnet Morten , Hansen Rie Schultz
Published: June 2010

Background—

Recently, evidence has emerged that small-conductance Ca
2+
-activated K
+
(SK) channels are predominantly expressed in the atria in a number of species including human. In rat, guinea pig, and rabbit ex vivo and in vivo models of atrial fibrillation (AF), we used 3 different SK channel inhibitors, UCL1684,
N
-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA), and NS8593, to assess the hypothesis that pharmacological inhibition of SK channels is antiarrhythmic.

Methods and Results—

In isolated, perfused guinea pig hearts, AF could be induced in all control hearts (n=7) with a combination of 1 μmol/L acetylcholine combined with electric stimulation. Pretreatment with 3 μmol/L NS8593, which had no effect on QT interval, prolonged the atrial effective refractory period by 37.1±7.7% (
P
<0.001) and prevented acetylcholine-induced AF (
P
<0.001, n=7). After AF induction, perfusion with NS8593 (10 μmol/L), UCL1684 (1 μmol/L), or ICA (1 μmol/L) terminated AF in all hearts, comparable to 10 μmol/L amiodarone. In isolated, perfused rat hearts, AF was induced with electric stimulation; 10 μmol/L NS8593 terminated AF and prevented reinduction of AF in all hearts (n=6,
P
<0.001). In all hearts, AF could be reinduced after washing. In isolated, perfused rabbit hearts, AF was induced with 10 μmol/L acetylcholine and burst pacing; 10 μmol/L NS8593 terminated AF and prevented reinduction of AF in all hearts (n=6,
P
<0.001). After washing, AF could be reinduced in 75% of the hearts (n=4,
P
=0.06). In an in vivo rat model of acute AF induced by burst pacing, injection of 5 mg/kg of either NS8593 or amiodarone shortened AF duration significantly to (23.2±20.0%,
P
<0.001, n=5, and 26.2±17.9%,
P
<0.001, n=5, respectively) as compared with injection of vehicle (96.3±33.2%, n=5).

Conclusions—

Inhibition of SK channels prolongs atrial effective refractory period without affecting QT interval and prevents and terminates AF ex vivo and in vivo, thus offering a promising new therapeutic opportunity in the treatment of AF.
The Effect of Viewing a Self-Avatar on Distance Judgments in an HMD-Based Virtual Environment
Authors: Mohler Betty J , Creem-Regehr Sarah H , Thompson William B , Bülthoff Heinrich H
Published: June 2010

Few HMD-based virtual environment systems display a rendering of the user's own body. Subjectively, this often leads to a sense of disembodiment in the virtual world. We explore the effect of being able to see one's own body in such systems on an objective measure of the accuracy of one form of space perception. Using an action-based response measure, we found that participants who explored near space while seeing a fully-articulated and tracked visual representation of themselves subsequently made more accurate judgments of absolute egocentric distance to locations ranging from 4 m to 6 m away from where they were standing than did participants who saw no avatar. A nonanimated avatar also improved distance judgments, but by a lesser amount. Participants who viewed either animated or static avatars positioned 3 m in front of their own position made subsequent distance judgments with similar accuracy to the participants who viewed the equivalent animated or static avatar positioned at their own location. We discuss the implications of these results on theories of embodied perception in virtual environments.
Value Creation of Mobile Services Through Presence: Designing Mobile Information and Entertainment Applications with Presence in Mind
Authors: Lee Kwan Min , Yates David , Clark Joseph , Sawy Omar El
Published: June 2010

The inherent challenges and opportunities of mobile services design have recently led designers to embrace the theory of presence, as evidenced by recent white papers. However, our research finds that presence is a much richer theoretical construct than these studies suggest. Building on this viewpoint and drawing on prior communication research, we more fully explore the application of three types of presence—physical presence, social presence, and self-presence—to mobile services design and to the corresponding opportunities for value creation. We present a series of design challenges for mobility and identify opportunities for overcoming these challenges by incorporating presence. The implications of designing with presence are (1) a greater awareness of and response to the users' needs and behaviors; (2) strategies for design that leverage this awareness; and (3) methods for integrating unique features of mobile devices based on user-driven and environment-driven factors rather than technology-driven factors. Our research suggests the development of middle-range theories of presence for specific application domains such as mobility that combine theoretical aspects of presence theory with the real-world design factors of mobile services. Numerous real-world examples illustrate both the complete nature of presence and its application to mobile services.
The Jaina Cult of Relic Stūpas
Authors: Flügel Peter
Published: June 2010

This article gives an overview of recent findings on the thriving cult of bone relic stūpas in contemporary Jaina culture. Although Jaina doctrine rejects the worship of material objects, fieldwork in India on the hitherto unstudied current Jaina mortuary rituals furnished clear evidence for the ubiquity of bone relic stūpas and relic veneration across the Jaina sectarian spectrum. The article discusses a representative case and assesses the significance of the overall findings for the history of religions. It also offers a new theoretical explanation of the power of relics.