bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of apoptosis by the ginsenoside Rh2 by internalization of lipid rafts and caveolae and inactivation of Akt
Authors: Park E‐K , Lee EJ , Lee S‐H , Koo KH , Sung JY , Hwang EH , Park JH , Kim C‐W , Jeong K‐C , Park B‐K , Kim Y‐N 
Published: March 2010

Background and purpose:  Lipid rafts and caveolae are membrane microdomains with important roles in cell survival signalling involving the Akt pathway. Cholesterol is important for the structure and function of these microdomains. The ginsenoside Rh2 exhibits anti‐tumour activity. Because Rh2 is structurally similar to cholesterol, we investigated the possibility that Rh2 exerted its anti‐tumour effect by modulating rafts and caveolae.Experimental approach:  A431 cells (human epidermoid carcinoma cell line) were treated with Rh2 and the effects on cell apoptosis, raft localization and Akt activation measured. We also examined the effects of over‐expression of Akt and active‐Akt on Rh2‐induced cell death.Key results:  Rh2 induced apoptosis concentration‐ and time‐dependently. Rh2 reduced the levels of rafts and caveolae in the plasma membrane and increased their internalization. Furthermore, Akt activity was decreased and consequently, Akt‐dependent phosphorylation of Bad, a pro‐survival protein, was decreased whereas the pro‐apoptotic proteins, Bim and Bax, were increased upon Rh2 treatment. Unlike microdomain internalization induce by cholesterol depletion, Rh2‐mediated internalization of rafts and caveolae was not reversed by cholesterol addition. Also, cholesterol addition did not restore Akt activation or rescue cells from Rh2‐induced cell death. Rh2‐induced cell death was attenuated in MDA‐MB‐231 cells over‐expressing either wild‐type or dominant‐active Akt.Conclusions and implications:  Rh2 induced internalization of rafts and caveolae, leading to Akt inactivation, and ultimately apoptosis. Because elevated levels of membrane rafts and caveolae, and Akt activation have been correlated with cancer development, internalization of these microdomains by Rh2 could potentially be used as an anti‐cancer therapy.
Endocannabinoid modulation of hyperaemia evoked by physiologically relevant stimuli in the rat primary somatosensory cortex
Authors: Ho W‐SV , Patel S , Thompson JR , Roberts CJ , Stuhr KL , Hillard CJ 
Published: March 2010

Background and purpose: In vitrostudies demonstrate that cannabinoid CB1receptors subserve activity‐dependent suppression of inhibition in the neocortex. To examine this mechanismin vivo, we assessed the effects of local changes in CB1receptor activity on somatosensory cortex neuronal activation by whisker movement in rats.Experimental approach: Laser Doppler flowmetry and c‐Fos immunohistochemistry were used to measure changes in local blood flow and neuronal activation, respectively. All drugs were applied directly to the cranium above the whisker barrel fields of the primary somatosensory cortex.Key results: The CB1receptor agonist WIN55212‐2 potentiated the hyperaemia induced by whisker movement and this potentiation was occluded by bicuculline. The CB1receptor antagonists, rimonabant and AM251, inhibited hyperaemic responses to whisker movement; indicating that activation of endogenous CB1receptors increased during whisker movement. Whisker movement‐induced expression of c‐Fos protein in neurons of the whisker barrel cortex was inhibited by rimonabant. Movement of the whiskers increased the 2‐arachidonoylglycerol content in the contralateral, compared to the ipsilateral, sensory cortex.Conclusions and implications: These results support the hypothesis that endocannabinoid signalling is recruited during physiologically relevant activation of the sensory cortex. These data support the hypothesis that the primary effect of CB1receptor activation within the activated whisker barrel cortex is to inhibit GABA release, resulting in disinhibition of neuronal activation. These studies provide physiological data involving endocannabinoid signalling in activity‐dependent regulation of neuronal activation and provide a mechanistic basis for the effects of cannabis use on sensory processing in humans.This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Changes in Salivary Prostaglandin Levels During Menstrual Migraine With Associated Dysmenorrhea
Authors: Durham Paul L. , Vause Carrie V. , Derosier Frederick , McDonald Susan , Cady Roger , Martin Vincent 
Published: March 2010

(Headache 2010;50:844‐851)Objective.— To measure prostaglandin levels in the saliva of individuals during menstrual migraine associated with dysmenorrhea (MMaD) and in response to treatment with a single tablet combination of sumatriptan succinate and naproxen sodium.Background.— Prostaglandins are thought to play a role in MMaD as elevated serum prostaglandin levels have been reported during attacks of menstrual migraine and are increased in the menstrual fluid of women with dysmenorrhea. While triptans are the primary line of migraine treatment, nonsteriodal anti‐inflammatory drugs are the most commonly prescribed therapy for dysmenorrhea symptoms. Data from recent clinical studies have provided evidence that treatment with a single tablet combination of sumatriptan and naproxen sodium is an effective abortive therapy for attacks of MMaD.Methods.— Women diagnosed with MMaD were treated with a sumatriptan succinate and naproxen sodium single tablet combination or placebo at time of migraine attack. Saliva samples were collected at time of attack as well as 2 and 4 hours after treatment. PGD2, PGE2, PGF2, PGI2, and TXA2 levels were determined by enzyme‐linked immunosorbent assay.Results.— Elevated levels of PGD2, PGF2, and TXA2 at 2 and 4 hours and PGE2 at 4 hours were found in saliva obtained from placebo subjects when compared with onset of attack levels. However, in subjects treated with a single tablet combination of sumatriptan and naproxen sodium, the levels of PGD2, PGF2, and PGE2 were not elevated at either time point while TXA2 levels were still elevated at 4 hours.Conclusions.— Data from this pilot study provide evidence that saliva levels of several prostaglandins increase during attacks of MMaD and that treatment with a single tablet combination of sumatriptan and naproxen sodium prevents elevation of prostaglandin levels.
Comparison of Kinematic Variables in Defining Lameness Caused by Naturally Occurring Rupture of the Cranial Cruciate Ligament in Dogs
Authors: Sanchez‐Bustinduy Maitane , de Medeiros Magda Alves , Radke Heidi , Langley‐Hobbs Sorrel , McKinley Trevelyan , Jeffery Nick 
Published: March 2010

Objective:To (1) discover kinematic variables that differ between dogs with cranial cruciate ligament rupture (CCLR) and control dogs and (2) to identify suitable outcome variables for longitudinal studies on the effects of surgical interventions for CCLR in dogs.Study Design:In vivo case–control comparison.Animals:Dogs with unilateral CCLR (n=16), and no other detectable neurologic or orthopedic disease and 10 dogs without CCLR, neurologic, or orthopedic disease.Methods:Kinematic data was collected from dogs as they walked at constant speed on a treadmill, using an infrared camera system and adhesive reflective markers applied to the pelvic limbs. Data on 5 selected variables was extracted and comparisons made between paired pelvic limbs in both CCLR and control dogs and between control and CCLR dogs.Results:Comparisons in CCLR dogs revealed significant differences between affected and unaffected limbs for many examined variables; the largest differences were in paw velocity and stifle angular velocity. There were highly significant differences between CCLR and control dogs when examining paired limb ratios for 4 of the variables, the largest differences were in stride length and paw velocity.Conclusions:Kinematic analysis provides straightforward and objective methods for defining the lameness associated with CCLR in dogs. Paw velocity and stride length were most notably reliable and not susceptible to systematic alterations in stifle joint dynamics that might be associated with specific surgical procedures.Clinical Relevance:This study identifies several variables that can provide the objective measurements essential to evaluate the efficacy of surgical interventions for CCLR in dogs.
The Effect of Uniaxial Cyclic Tensile Load on Gene Expression in Canine Cranial Cruciate Ligamentocytes
Authors: Breshears Lee A. , Cook James L. , Stoker Aaron M. , Fox Derek B. , Luther Jill K. 
Published: March 2010

Objective:To determine the effects of uniaxial cyclic tensile load amplitude and duration on gene expression in cranial cruciate ligamentocytes cultured in monolayer.Study Design:In vitro experimental study.Animals:Adult dogs (n=9) weighing 20–35 kg.Methods:Cranial cruciate ligaments (CCL, n=18) were aseptically collected, diced, digested using clostridial collagenase, and primary monolayer cultures were established. CCL cells were seeded at a concentration of 3 × 105 cells/mL onto a specialized collagen membrane. After 24 hours to allow attachment, ligamentocytes were subjected to 0%, 4%, or 8% uniaxial strain for 24 or 48 hours using a sinusoidal strain profile at 0.5 Hz. At the end of each time point, the ligamentocytes were harvested and analyzed for collagen 1 (COL1), collagen 3 (COL3), and matrix metalloproteinase‐3 (MMP‐3) gene expression using reverse transcriptase real‐time polymerase chain reaction.Results:Approximately 33% of CCL processed for this study yielded viable cell cultures compared with 100% of the medial collateral ligaments processed. For CCL cells under uniaxial strain, gene expression for COL1 was variable, but higher strains and longer time in culture resulted in increased COL1 expression. There were no significant differences found for COL3 at any time point or between strain regimens. In general, MMP‐3 gene expression was increased early in tissue culture and at higher strains.Conclusions:COL1 and MMP‐3 gene expression can be influenced by amplitude and duration of strain on CCL cells in monolayer culture.Clinical Relevance:These data have implications for modeling and understanding canine cruciate ligament pathophysiology. In particular, MMP‐3 could serve as a potential preventative or therapeutic target in cruciate disease.
Ablation of Ligament of Marshall Attenuates Atrial Vulnerability to Fibrillation Induced by Inferior Left Atrial Fat Pad Stimulation in Dogs
Authors: LIU XINGPENG , YAN QIAN , LI HUI , TIAN YING , SU JING , TANG RIBO , LU CHUNSHAN , DONG JIANZENG , MA CHANGSHENG 
Published: March 2010

Ligament of Marshall and Atrial Fibrillation Induction. Background: The role of ligament of Marshall (LOM) in the mechanism of “vagal” atrial fibrillation (AF) is still unknown.
Objective:
To investigate the impact of LOM ablation on atrial vulnerability to AF induced by inferior left atrial fat pad (ILAFP) stimulation in dogs.
Methods:
AF inducibility and atrial effective refractory period (ERP) were elevated before and after LOM ablation in 8 of 14 dogs (the ablation group). Same protocol but without LOM ablation was conducted in the remaining 6 dogs (the control group). The activation patterns of LOM and left pulmonary veins (LPVs) during sustained AF were analyzed. The distribution of epicardial cholinergic nerve fibers between LOM and ILAFP was investigated in the control group.
Results:
Ablation of LOM significantly attenuated AF inducibility (87.5% vs 33.3%, P < 0.001) and prolonged ERPs of the structures in contiguity with LOM (P < 0.05) in the ablation group. In contrast, there was no significant change in ERPs and AF inducibility in the control group. During sustained AF, fractionated atrial electrograms were more common in the LOM area than the LPVs (84% vs 18% of the analyzed episodes, P < 0.001). In 46.7% of the episodes with identifiable LOM spikes, atrial potentials, and LOM spikes were related in 2:1 or 3:2 pattern during the intermittent organized activity. Acetylcholinesterase staining revealed a close cholinergic nerved relationship between LOM and ILAFP.
Conclusions:
LOM plays a critical role in maintaining AF induced by stimulation of ILAFP. Ablation of LOM can markedly attenuate AF inducibility in this model. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1024‐1030, September 2010)
Area Under the Real‐Time Contact Force Curve (Force–Time Integral) Predicts Radiofrequency Lesion Size in an In Vitro Contractile Model
Authors: SHAH DIPEN C. , LAMBERT HENDRIK , NAKAGAWA HIROSHI , LANGENKAMP ARNE , AEBY NICOLAS , LEO GIOVANNI 
Published: March 2010

FTI Predicts RF Lesion Size in Contractile Model. Introduction: Electrode tissue contact, radiofrequency (RF) power and duration are major determinants of RF lesion size. Since contact forces (CF) vary in the beating heart, we evaluated contact force–time integral (FTI) as a predictor of lesion size at constant RF power in a contractile bench model simulating the beating heart.
Methods and Results:
An open‐tip irrigated catheter was attached to a movable mount incorporating a dynamic force sensor allowing closed loop control to achieve desired force variations between the catheter tip and bovine skeletal muscle placed on a ground plate. RF energy (20 and 40 W for 60 seconds, 17 cc/min irrigation) was delivered during (1) constant contact (C) at 20 g, (2) variable contact (V) with a 20 g peak and 10 g nadir, and (3) intermittent contact (I) with a 20 g peak and 0 g nadir with loss of contact. V and I protocols were performed at 50 and 100 catheter movements/min and 2 systole:diastole time ratios (50:50 and 30:70). The area under the CF curve was calculated as the FTI. Measured FTI was highest in C, intermediate during V and lowest during I and correlated linearly with lesion volume (P < 0.0001 for 20 and 40 W). Lesion volume was highest in group C, intermediate in V and lowest in group I (P < 0.05 for C vs V, V vs I, and C vs I).
Conclusions:
Lesion size correlates linearly with measured contact FTI. Constant contact produces the largest and intermittent contact the smallest lesions despite constant RF power and identical peak contact forces. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1038‐1043, September 2010)
Dialysis patients treated with Epoetin alfa show improved anemia symptoms: A new analysis of the Canadian Erythropoietin Study Group trial
Authors: KEOWN Paul A. , CHURCHILL David N. , POULIN‐COSTELLO Melanie , LEI Lei , GANTOTTI Sandeep , AGODOA Irene , GITLIN Matthew , GANDRA Shravanthi R. , MAYNE Tracy J. 
Published: March 2010

AbstractThe health‐related quality of life (HRQOL) claims in the current Epoetin alfa label are based on the reanalyses of the exercise and physical function data from the Canadian Erythropoietin Study Group trial. The reanalysis was done to comply with the Food and Drug Administration's requirement of using statistical methods that are currently standard in evaluating clinical trial data. Presented here are HRQOL results associated with anemia. The Canadian Erythropoietin Study Group trial was a multicenter, double blind, randomized, placebo‐controlled trial evaluating the effects of Epoetin alfa on HRQOL in anemic hemodialysis patients. A total of 118 patients who were 18–75 years old, on hemodialysis for >3 months, who had a hemoglobin <9.0 g/dL, and did not have coronary artery disease or diabetes mellitus, were randomized to either receive placebo (n=40), or receive intravenous Epoetin alfa to achieve a target hemoglobin of 9.5–11.0 g/dL (n=40) or a target of 11.5–13.0 g/dL (n=38). Patients were followed for 6 months. The two Epoetin alfa‐treatment groups were combined for all analyses performed. This post hoc analysis was conducted using an intent‐to‐treat repeated measures mixed model analysis of variance using Bonferroni's multiplicity correction. The Epoetin alfa‐treated group showed a statistically significant improvement in the Kidney Disease Questionnaire symptom of fatigue in comparison with placebo. Additionally, the change in hemoglobin at 2 months was correlated with change in fatigue, energy, shortness of breath, and weakness, but had minimal effect on depression. These analyses confirm previously reported results, which indicate that treating hemodialysis patients with an erythropoiesis‐stimulating agent improves HRQOL.
Impact of coronary artery calcification in hemodialysis patients: Risk factors and associations with prognosis
Authors: OHTAKE Takayasu , ISHIOKA Kunihiro , HONDA Kenjiro , OKA Machiko , MAESATO Kyoko , MANO Tsutomu , IKEE Ryota , MORIYA Hidekazu , HIDAKA Sumi , KOBAYASHI Shuzo 
Published: March 2010

AbstractThe risk factors of coronary artery calcification (CAC) and the impact of CAC on cardiovascular events, cardiovascular deaths, and all‐cause deaths in hemodialysis (HD) patients have not been fully elucidated. We examined the CAC score (CACS) in 74 HD patients using electron‐beam computed tomography. Fifty‐six patients underwent a second electron‐beam computed tomography after a 15‐month interval to evaluate CAC progression. We evaluated (1) the risk factors for CAC and its progression and (2) the impact of CAC on the prognosis. In the cross‐sectional study, HD vintage and high‐sensitive C‐reactive protein (hsCRP) were the independent risk factors for CAC. In the prospective cohort study, delta CACS (progression of CAC) was significantly correlated with hsCRP, fibrinogen, and serum calcium level in the univariate analysis. Stepwise multiple regression analysis revealed that only hsCRP was the independent risk factor for CAC progression in HD patients. Kaplan‐Meier survival analysis revealed that cardiovascular events (P<0.0001), cardiovascular deaths (P=0.039), and all‐cause deaths (P=0.026) were significantly associated with CACS. In conclusion, CAC had significantly progressed in HD patients during the 15‐month observation period. Microinflammation was the only independent risk factor for CAC progression in HD patients. The advanced CAC was a significant prognostic factor in HD patients, i.e., which was strongly associated with future cardiovascular events, cardiovascular deaths, and all‐cause deaths.
Association of serum alkaline phosphatase and bone mineral density in maintenance hemodialysis patients
Authors: PARK Jong Chan , KOVESDY Csaba P. , DUONG Uyen , STREJA Elani , RAMBOD Mehdi , NISSENSON Allen R. , SPRAGUE Stuart M. , KALANTAR‐ZADEH Kamyar 
Published: March 2010

AbstractRecent studies indicate that serum alkaline phosphatase (AlkPhos), a surrogate of high turnover bone disease, is associated with coronary artery calcification and death risk in maintenance hemodialysis (MHD) patients. The association between AlkPhos and bone mineral density (BMD) is not well studied. We studied the association between AlkPhos and dual‐energy X‐ray absorptiometry‐assessed BMD in a group of MHD patients in Southern California. In 154 MHD patients, aged 55.3 ± 13.6 years, including 42% women, 38% Hispanics, 42% African Americans, and 55% diabetics, the mean serum AlkPhos was 121 ± 63 U/L (median: 101, Q25–75: 81–141); 36% had AlkPhos≥120 U/L and 50% had a total T‐score≤−1. Whereas the total BMD did not correlate with age (r=0.01, P=0.99) or body mass index (r=0.10, P=0.22), it correlated negatively with AlkPhos (r=−0.25, P=0.002), including after multivariate adjustment (r=−0.24, P=0.003). The proportion of patients with a high coronary artery calcification score>400 was incrementally higher across worsening BMD tertiles (P trend=0.04). The BMD was significantly worse in MHD patients with serum AlkPhos≥120 U/L compared with <120 U/L (1.01 ± 0.016 vs. 1.08 ± 0.013 g/cm2, respectively, P<0.001). The multivariate adjusted odds ratio of AlkPhos≥120 U/L for having a total T‐score<−1.0 was 2.3 (1.1–4.8, P=0.037). Among routine clinical and biochemical markers, serum AlkPhos≥120 U/L was a better predictor of total T‐score≤−1 in MHD patients. An association exists between higher serum AlkPhos and worse dual‐energy X‐ray absorptiometry‐assessed BMD in MHD patients. Given these findings, studies are indicated to examine whether interventions that lower serum AlkPhos improve BMD in MHD patients.
Regression of brown tumor of the maxilla in a patient with secondary hyperparathyroidism after a parathyroidectomy
Authors: NABI Zahid , ALGAILANI Mohammed , ABDELSALAM Mohammed , ASAAD Lina , ALBAQUMI Mamdouh 
Published: March 2010

AbstractBrown tumors or osteoclastomas are erosive bony lesions arising as a complication of hyperparathyroidism. In patients with end‐stage renal disease, brown tumors are uncommon skeletal manifestations that are usually seen in severe forms of secondary hyperparathyroidism. Initial treatment involves the correction of hyperparathyroidism, which usually leads to regression of the tumors. We report a case of brown tumors of the maxilla in a 24‐year‐old female referred to us by a local hospital, where she had been on regular hemodialysis for >10 years. After a complete biochemical and radiological workup, she underwent a total parathyroidectomy, which subsequently resulted in significant regression of her tumor.
Bone augmentation after soft‐tissue expansion using hydrogel expanders: effects on microcirculation and osseointegration
Authors: Von See Constantin , Gellrich Nils‐Claudius , Jachmann Ulrike , Laschke Matthias W. , Bormann Kai‐Hendrik , Rücker Martin 
Published: March 2010

AbstractObjectives: The success of bone augmentation, for example of the alveolar ridge, might be endangered by dehiscence of the soft tissue that covers the augmented bone. Soft‐tissue coverage can be achieved without tension through pre‐augmentation tissue expansion with hydrogel expanders. We used a periosteal chamber to study the influence of tissue expansion on microcirculation and osseointegration in an in vivo animal model.Material and methods: Sixteen isogeneic Lewis rats were randomised into two groups. Additional eight animals served as donors of isogeneic bone grafts (Group 3, n=8). The bone grafts were harvested and implanted into Group 1 animals (n=8) (without tissue expansion) and Group 2 animals (after tissue expansion). In Group 2 (n=8), hydrogel expanders were inserted subperiosteally at the site to be augmented for 21 days. We used intravital microscopy to monitor microcirculation in vivo for 19 days after implantation. Specimens from both groups were evaluated histologically.Results: During the entire study period, functional microvessel density in the region above the augmentation material was significantly higher after previous tissue expansion (P>0.05). Both groups showed physiological microcirculation around the augmentation material. Histology revealed bone osseointegration of the bone graft in the group with tissue expansion and the presence of connective and granulation tissue in the group without tissue expansion.Conclusions: Pre‐augmentation soft‐tissue expansion with hydrogel expanders leads to higher functional microvessel density in the tissue above the augmentation material and thus, to more rapid osseointegration. The use of hydrogel expanders appears to increase the probability of success, especially of pre‐implant bone augmentation. To cite this article:
von See C, Gellrich N‐C, Jachmann U, Laschke MW, Bormann KH, Rücker M. Bone augmentation after soft‐tissue expansion using hydrogel expanders: effects on microcirculation and osseointegration. Clin. Oral Impl. Res. 21, 2010; 842–847 doi: 10.1111/j.1600‐0501.2009.01847.x