bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flavokawain B induces apoptosis of human oral adenoid cystic cancer ACC-2 cells via up-regulation of Bim and down-regulation of Bcl-2 expression
Authors: Zhao Xi , Chao Yong-Lie , Wan Qian-Bing , Chen Xin-Min , Su Peng , Sun Jian , Tang Yaxiong 
Published: November 2011

Novel effective drugs are still urgently needed in the prevention and treatment of oral adenoid cystic carcinoma (ACC). In this study, we have assessed the antitumor potential and molecular mechanisms of flavokawain B (FKB) as a kava chalcone on the ACC-2 cell line in vitro. The results demonstrated that FKB could significantly inhibit the cell proliferation of ACC-2 in a dose-dependent manner that was associated with induced apoptosis and cell cycle G2-M arrest, and the half maximal inhibitory concentration (IC50) of flavokawain-B treatment for 48 h was estimated to be 4.69 ± 0.43 µmol/L. Mechanistically, FKB could induce the release of cytochrome c from mitochondria into the cytosol, and activate the cleavage of caspase-3 and, eventually, the poly(ADP-ribose) polymerase (PARP), in a dose-dependent manner, leading to marked apoptotic effect of ACC-2 cells. The apoptotic action of FKB was associated with the increased expression of proapoptotic proteins: Bim, Bax, Bak and a decreased expression of antiapoptotic Bcl-2. Among them, Bim expression was significantly induced by FKB, and knockdown of Bim expression by short-hairpin RNAs attenuated the inhibitory effect induced by FKB on ACC-2 cells. These results suggest Bim may be one of the potential transcriptional targets, and suggests the potential usefulness of FKB for the prevention and treatment of ACC.
Effect of captopril and the bradykinin–PKC pathway on ROS production in type 1 diabetic rats
Authors: Rodrigues de Araujo Glaucy , Granato de Faria Karine , Lima Wanderson Geraldo , Pádua Bruno da Cruz , Rossoni Joamyr Victor , Souza Aline Arlindo , Chianca-Júnior Deoclecio , Silva Marcelo Eustáquio , Pedrosa Maria Lucia , Chaves Miriam Martins , Costa Daniela Caldeira 
Published: November 2011

The aim of this study was to investigate the possible effects of captopril as a promoter in modulating the oxidant–antioxidant balance in rats with type 1 diabetes, and the influence of protein kinase C (PKC) pathways in the production of reactive oxygen species (ROS) induced by bradykinin in type 1 diabetic rats. This study evaluated the redox status in both the cardiac tissue and at the cellular level (neutrophils). Two concentrations of captopril were utilized: (i) 5 mg·(kg body mass)–1, which was considered a therapeutic dose; and (ii) 10 mg·(kg body mass)–1. Body mass, plasma glucose, and serum insulin were evaluated. To investigate the redox status of the cardiac tissue, we analyzed lipid peroxidation, concentration of carbonylated protein, catalase activity, and the concentration of glutathione. For a more accurate assessment of the possible antioxidant effect of captopril, we also analyzed ROS in neutrophils (in vivo), and ROS production induced by bradykinin and the influence of the PKC pathway in this production (in vitro). Our data show that the hearts of diabetic animals have increased oxidative damage, exemplified by the increased concentration of carbonylated protein and thiobarbituric acid reactive substances (TBARS). However, animals treated with captopril at both concentrations showed lower concentrations of carbonylated protein compared with untreated diabetic animals. We found an increase of catalase activity in the heart of diabetic rats, which was reversed by captopril treatment at both of the dosages tested. Our data showed that captopril was able to reduce ROS production in the neutrophils of diabetic rats at a dose of 10 mg captopril·(kg body mass)–1. However, the antioxidant effect of captopril is independent of bradykinin. Diabetes induces oxidative stress, and these results suggest that captopril has an antioxidant effect and can modulate the production of ROS in circulating neutrophils.
Platelet soluble CD40L and matrix metalloproteinase 9 activity are proinflammatory mediators in Behçet disease patients
Authors: López-Longo Francisco J. , Arias-Salgado Elena G. , Martín Mónica , Jiménez-Yuste Víctor , de la Rúa Ana , Bello Ihosvany , Álvarez María T. , Butta Nora V. 
Published: November 2011

SummaryPlatelets are the major source of plasma-soluble CD40L (sCD40L), an important inflammatory mediator. This study explored the impact of platelet-derived sCD40L on Behçet disease (BD), an autoinflammatory vasculitis. We also searched for influences by platelet matrix metalloproteinases (MMP) –2 and MMP-9, implicated in several inflammatory diseases, on CD40L shedding from platelet membrane. Platelet activation were studied by flow cytometry and aggregometry, surface expression of CD40L and platelet-leukocyte aggregates by flow cytometry, sCD40L by ELISA, cellular CD40L and CD40 levels by Western blot and MMPs activity by gelatin zymography. The effect of sCD40L on MMP9 expression was studied in cultured MEG-01 cells. Plasma and platelet-released sCD40L levels were higher in BD patients. No differences in platelet activation and in platelet-leukocyte aggregates formation were observed between BD patients and controls. Plasma and platelet MMP-9 levels were increased in BD patients, whereas there was no difference in platelet MMP-2 activity. Since a correlation between plasma sCD40L and platelet MMP-9 activity was observed, we studied the influence of sCD40L on MMP-9 levels in the megakaryoblastic cell line MEG-01. Treatment of MEG-01 cells with recombinant sCD40L increased MMP-9 but did not change MMP-2 levels. In conclusion, sCD40L release from platelets was mediated by MMP-9, and MMP-9 expression was in turn upregulated by sCD40L in the MEG-01 cell line. We conclude that platelets and megakaryocytes might participate in a positive feedback loop occurring between sCD40L and MMP-9 which would contribute to the proinflammatory state observed in BD.
The Creating an Optimal Warfarin Nomogram (CROWN) Study
Authors: Perlstein Todd S. , Goldhaber Samuel Z. , Nelson Kerrie , Joshi Victoria , Morgan T. , Lesko Lawrence J. , Lee Joo-Yeon , Gobburu Jogarao , Schoenfeld David , Kucherlapati Raju , Freeman Mason , Creager Mark 
Published: November 2011

SummaryA significant proportion of warfarin dose variability is explained by variation in the genotypes of the cytochrome P450 CYP2C9 and the vitamin K epoxide reductase complex, VKORC1, enzymes that influence warfarin metabolism and sensitivity, respectively. We sought to develop an optimal pharmacogenetic warfarin dosing algorithm that incorporated clinical and genetic information. We enroled patients initiating warfarin therapy. Genotyping was performed of the VKORC1, –1639G>A, the CYP2C9*2, 430C>T, and the CYP2C9*3, 1075C>A genotypes. The initial warfarin dosing algorithm (Algorithm A) was based upon established clinical practice and published warfarin pharmacogenetic information. Subsequent dosing algorithms (Algorithms B and Algorithm C) were derived from pharmacokinetic / pharmacodynamic (PK/PD) modelling of warfarin dose, international normalised ratio (INR), clinical and genetic factors from patients treated by the preceding algorithm(s). The primary outcome was the time in the therapeutic range, considered an INR of 1.8 to 3.2. A total of 344 subjects are included in the study analyses. The mean percentage time within the therapeutic range for each subject increased progressively from Algorithm A to Algorithm C from 58.9 (22.0), to 59.7 (23.0), to 65.8 (16.9) percent (p = 0.04). Improvement also occurred in most secondary endpoints, which included the per-patient percentage of INRs outside of the therapeutic range (p = 0.004), the time to the first therapeutic INR (p = 0.07), and the time to achieve stable therapeutic anticoagulation (p < 0.001). In conclusion, warfarin pharmacogenetic dosing can be optimised in real time utilising observed PK/PD information in an adaptive fashion.Clinical Trial Registration: ClinicalTrials.gov (NCT00401414)
Effects of two different intensities of aerobic exercise on elderly people with mild cognitive impairment: a randomized pilot study
Authors: Varela Silvia , Ayán Carlos , Cancela José M , Martín Vicente 
Published: November 2011

Objective: To evaluate the effect of different intensities of aerobic exercise on elderly people with mild cognitive impairment. Design: A randomized trial. Setting: Residential care homes for elderly people. Subjects: Forty-eight patients were included in the study. Interventions: The patients were randomized in three groups. Group A performed aerobic exercise at 40% of heart rate reserve, group B did the same at 60% and group C carried out recreational activities. The duration of the study was three months. Main measures: Cognitive level and functional ability were assessed by means of the Mini Mental State Examination and the Timed Up and Go test before the intervention, at the end of it and three months later as a follow-up. Results: After completion of the aerobic training programme, the patients’ Mini Mental State Examination scores improved marginally (group A from 19.8 ± 5.1 to 20.6 ± 7.3; group B from 20.8 ± 4.6 to 21 ± 5.4). A similar trend was observed for the Timed Up and Go test scores (group A from 18.8 ± 5.3 to 18.5 ± 5 seconds; group B from 15.4 ± 4.2 to 14.3 ± 5.1 seconds). However, no statistically significant differences were found at any time during the evaluation regarding cognitive level and functional autonomy among the three groups. Conclusion: In this pilot study, intensity does not seem to be a determining factor when aerobic exercise is performed by people with mild cognitive impairment.
Incidence of migraine and tension-type headache in three different populations at risk within the German DMKG headache study
Authors: Khil Laura , Pfaffenrath Volker , Straube Andreas , Evers Stefan , Berger Klaus 
Published: November 2011

Background: Unlike the prevalence, the incidence of headache disorders has attracted only little attention in epidemiological research. Different definitions of the ‘population at risk’ among the few published migraine and tension-type headache incidence studies limit their comparability and warrant further research. Therefore, we analysed data from the German Migraine and Headache Society (DMKG). Methods: Incidences were assessed in the general population in Germany via standardized headache questions using the International Classification of Headache Disorders, 2nd Edition (ICHD-2). The population was drawn from a 5-year age-group- stratified and gender-stratified random sample from the population register. Results: Of the 1312 baseline participants examined between 2003 and 2004, 1122 (85.5%) participated in the follow-up in 2006 and were the basis for three different populations at risk. We found that the three populations differed in size, age, gender and incidence estimate. The total sample incidence of migraine ranged between 0% and 3.3% and of tension-type headache between 5.3% and 9.2% depending on the definition of ‘at risk’. Conclusion: We concluded that one significant problem in headache incidence estimation is the definition of ‘at risk’, limiting comparability. Thus, this study supports the need for a common definition for prospective headache incidence estimations.
Characteristics of acute posttraumatic headache following mild head injury
Authors: Lieba-Samal Doris , Platzer Patrick , Seidel Stefan , Klaschterka Petra , Knopf Astrid , Wöber Christian 
Published: November 2011

Background: To examine the prevalence and characteristics of acute posttraumatic headache (APTH) attributed to mild head injury within a prospective, observational study design. Methods: We recruited 100 patients with acute mild head injury as defined in the International Classification of Headache Disorders, 2nd Edition (ICHD-2) presenting to the department of trauma surgery at the Medical University of Vienna. Patients underwent a detailed telephone interview between days 7 and 10 and between days 90 and 100 after the injury. Results: The prevalence of APTH was 66%. APTH had occurred within 24 hours after the trauma in 78% and lasted for a median of 3.0 days. Headache was unilateral in 45%. Aggravation by physical activity, nausea and photo-/phonophobia was present in 49%, 42% and 55%, respectively. The prevalence of APTH was related to conditions of chronic pain (excluding headache), pre-existing episodic headache, number of posttraumatic symptoms, anxiety and depression. At follow-up at 90–100 days, posttraumatic headache had abated in all patients. Conclusions: APTH attributed to mild head injury is a common but self-limiting condition frequently showing migrainous features. Participants with chronic pain other than headache, pre-existing headache and affective disorders are at higher risk of developing APTH. None of the patients developed chronic posttraumatic headache.
Characteristics of migraine visual aura in Southern Brazil and Northern USA
Authors: Queiroz Luiz Paulo , Friedman Deborah Isa , Rapoport Alan Mark , Purdy R Allan 
Published: November 2011

Background: Migraine aura, made up of one or more neurological symptoms arising from the cortex or brainstem, is a complex neurological phenomenon. Visual aura is the most frequent aura manifestation. Studying the subjective components of visual aura makes it possible to identify common characteristics. Objective: To thoroughly describe the characteristics of migraine visual aura in patients with migraine with aura. Methods: We performed a retrospective, descriptive study of the visual aura of 122 migraine patients collected at two headache clinics in the Americas. This study was designed to determine the characteristics of a typical visual aura. Results: The most common features of the visual aura in our study are that it occurs before the headache with a gap of less than 30 minutes, lasts 5 to 30 minutes, has a gradual onset, usually begins peripherally, is unilateral, and shimmers. Furthermore, the location of typical visual aura in the visual field has no fixed relationship to headache laterality, is slightly more often without color, and is often described as small bright dots and zigzag lines. Blurred vision, not typically considered to be an aura phenomenon of cortical origin, is in fact the most frequently reported visual symptom. Conclusions: Migraine visual aura is heterogeneous and pleomorphic, and some of our findings run contrary to common beliefs.
Neuromodulation of the posterolateral hypothalamus for the treatment of chronic refractory cluster headache: Experience in five patients with a modified anatomical target
Authors: Seijo F , Saiz A , Lozano B , Santamarta E , Alvarez-Vega M , Seijo E , Fernández de León R , Fernández-González F , Pascual J 
Published: November 2011

Introduction: Deep brain stimulation (DBS) of the posterior hypothalamus has been found to be effective in the treatment of refractory chronic cluster headache (CCH). Methods: We report the long-term outcomes of five patients with refractory CCH on whom stimulation of a modified target of approximately 3 mm in radius, which included the posterolateral hypothalamus, the fasciculus mammillotegmentalis, the fasciculus mammillothalamicus and the fasciculus medialis telencephali, was performed. The stereotaxic coordinates were 4 mm from the third ventricle wall, 2 mm from behind the mid-intercommissural point and 5 mm from under the intercommissural line. Results: All patients became pain-free for 1–2 weeks after the procedure, but then needed an average of 54 days to optimize stimulation parameters. After a mean follow-up of 33 months, two remain pain-free, two have an excellent response (>90% decrease in attack frequency) and in one the attacks have been reduced by half. There were no serious adverse events. Permanent myosis and euphoria/well-being feeling were seen in three patients. Other adverse events, such as diplopia, dizziness, global headache of cervical dystonia, were seen transiently related to an increase in stimulation parameters. Attacks reappeared transiently in two patients as a result of cable rupture and when the stimulator was disconnected. Conclusions: Our results supports the efficacy of DBS in very refractory CCH with a slightly modified hypothalamic target conceived to avoid the lateral ventricle wall so as to extend the stimulated brain area and to decrease the morbidity of potential haemorrhagic complications.
A Prospective Evaluation of the Landing Error Scoring System (LESS) as a Screening Tool for Anterior Cruciate Ligament Injury Risk
Authors: Smith Helen C. , Johnson Robert J. , Shultz Sandra J. , Tourville Timothy , Holterman Leigh Ann , Slauterbeck James , Vacek Pamela M. , Beynnon Bruce D. 
Published: November 2011

Background: Anterior cruciate ligament (ACL) injuries are immediately disabling, costly, take a significant amount of time to rehabilitate, and are associated with an increased risk of developing posttraumatic osteoarthritis of the knee. Specific multiplanar movement patterns of the lower extremity, such as those associated with the drop vertical jump (DVJ) test, have been shown to be associated with an increased risk of suffering noncontact ACL injuries. The Landing Error Scoring System (LESS) has been developed as a tool that can be applied to identify individuals who display at-risk movement patterns during the DVJ. Hypothesis: An increase in LESS score is associated with an increased risk of noncontact ACL injury. Study Design: Case-control study; Level of evidence, 3. Methods: Over a 3-year interval, 5047 high school and college participants performed preseason DVJ tests that were recorded using commercial video cameras. All participants were followed for ACL injury during their sports season, and video data from injured participants and matched controls were then assessed with the LESS. Conditional logistic regression analysis was used to examine the association between LESS score and ACL injury risk in all participants as well as subgroups of female, male, high school, and college participants. Results: There was no relationship between the risk of suffering ACL injury and LESS score whether measured as a continuous or a categorical variable. This was the case for all participants combined (odds ratio, 1.04 per unit increase in LESS score; 95% confidence interval, 0.80-1.35) as well as within each subgroup (odds ratio range, 0.99-1.14). Conclusion: The LESS did not predict ACL injury in our cohort of high school and college athletes.
Some considerations of classification for high dimension low-sample size data
Authors: Zhang Lingsong , Lin Xihong 
Published: November 2011

Abstarct We review in this article several classification methods, especially for high-dimensional and low-sample size data. We discuss several desirable properties for classifiers in such settings, including predictability, consistency, generality, stability, robustness and sparsity. Specifically, a good classifier should have a small prediction error (predictability); converge to the Bayes-rule classifier asymptotically (consistency); be stable when adding/removing an observation (generality); be stable for different data sets of the same kind (stochastic stability); be stable when there are a small number of contaminated observations (robustness); and have a small number of variables in the classifier (interpretability or sparsity). Several simulation examples and real applications are used to illustrate the usefulness of the existing popular classifiers and compare their performance.
Regulation of MMP-3 expression and secretion by the chemokine eotaxin-1 in human chondrocytes
Authors: Chao Pin-Zhir , Hsieh Ming-Shium , Cheng Chao-Wen , Lin Yung-Feng , Chen Chien-Ho 
Published: November 2011

AbstractBackgroundOsteoarthritis (OA) is characterized by the degradation of articular cartilage, marked by the breakdown of matrix proteins. Studies demonstrated the involvement of chemokines in this process, and some may potentially serve as diagnostic markers and therapeutic targets; however, the underlying signal transductions are not well understood.MethodsWe investigated the effects of the CC chemokine eotaxin-1 (CCL11) on the matrix metalloproteinase (MMP) expression and secretion in the human chondrocyte cell line SW1353 and primary chondrocytes.ResultsEotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Inhibitors of extracellular signal-regulated kinase (ERK) and p38 kinase were able to repress eotaxin-1-induced MMP-3 expression. On the contrary, Rp-adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP receptors, and H-89, a protein kinase A (PKA) inhibitor, markedly enhanced eotaxin-1-induced MMP-3 expression. These results suggest that MMP-3 expression is specifically mediated by the G protein-coupled eotaxin-1 receptor activities. Interestingly, little amount of MMP-3 protein was detected in the cell lysates of eotaxin-1-treated SW1353 cells, and most of MMP-3 protein was in the culture media. Furthermore we found that the eotaxin-1-dependent MMP-3 protein secretion was regulated by phospholipase C (PLC)-protein kinase C (PKC) cascade and c-Jun N-terminal kinase (JNK)/mitogen-activated protein (MAP) kinase pathways. These data indicate a specific regulation of MMP-3 secretion also by eotaxin-1 receptor activities.ConclusionsEotaxin-1 not only induces MMP-3 gene expression but also promotes MMP-3 protein secretion through G protein-coupled eotaxin-1 receptor activities. Chemokines, such as eotaxin-1, could be a potential candidate in the diagnosis and treatment of arthritis.
High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy
Authors: Stewart Larissa R , Hall April L , Kang Sung-Hae L , Shaw Chad A , Beaudet Arthur L 
Published: November 2011

AbstractBackgroundMany copy number variants (CNVs) are documented to be associated with neuropsychiatric disorders, including intellectual disability, autism, epilepsy, schizophrenia, and bipolar disorder. Chromosomal deletions of 1q21.1, 3q29, 15q13.3, 22q11.2, andNRXN1and duplications of 15q11-q13 (maternal), 16p11, and 16p13.3 have the strongest association with schizophrenia. We hypothesized that cases with both schizophrenia and epilepsy would have a higher frequency of disease-associated CNVs and would represent an enriched sample for detection of other mutations associated with schizophrenia.MethodsWe used array comparative genomic hybridization (CGH) to analyze 235 individuals with both schizophrenia and epilepsy, 80 with bipolar disorder and epilepsy, and 191 controls.ResultsWe detected 10 schizophrenia plus epilepsy cases in 235 (4.3%) with the above mentioned CNVs compared to 0 in 191 controls (p = 0.003). Other likely pathological findings in schizophrenia plus epilepsy cases included 1 deletion 16p13 and 1 duplication 7q11.23 for a total of 12/235 (5.1%) while a possibly pathogenic duplication of 22q11.2 was found in one control for a total of 1 in 191 (0.5%) controls (p = 0.008). The rate of abnormality in the schizophrenia plus epilepsy of 10/235 for the more definite CNVs compares to a rate of 75/7336 for these same CNVs in a series of unselected schizophrenia cases (p = 0.0004).ConclusionWe found a statistically significant increase in the frequency of CNVs known or likely to be associated with schizophrenia in individuals with both schizophrenia and epilepsy compared to controls. We found an overall 5.1% detection rate of likely pathological findings which is the highest frequency of such findings in a series of schizophrenia patients to date. This evidence suggests that the frequency of disease-associated CNVs in patients with both schizophrenia and epilepsy is significantly higher than for unselected schizophrenia.