bluuebunny/crossref_metadata_2025_split huggingface dataset:
New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer
Authors: Cang Shundong , Ma Yuehua , Liu Delong 
Published: June 2009

AbstractDNA methylation and histone acetylation are two well known epigenetic chromatin modifications. Epigenetic agents leading to DNA hypomethylation and histone hyperacetylation have been approved for treatment of hematological disorders. The first histone deacetylase inhibitor, vorinostat, has been licensed for cutaneous T cell lymphoma treatment. More than 11 new epigenetic agents are in various stages of clinical development for therapy of multiple cancer types. In this review we summarize novel histone deacetylase inhibitors and new regimens from clinical trials for epigenetic therapy of cancer.
Impaired glucose transporter-1 degradation and increased glucose transport and oxidative stress in response to high glucose in chondrocytes from osteoarthritic versus normal human cartilage
Authors: Rosa Susana C , Gonçalves Juliana , Judas Fernando , Mobasheri Ali , Lopes Celeste , Mendes Alexandrina F 
Published: June 2009

Abstract
Introduction
Disorders that affect glucose metabolism, namely diabetes mellitus (DM), may favor the development and/or progression of osteoarthritis (OA). Thus far, little is known regarding the ability of chondrocytes to adjust to variations in the extracellular glucose concentration, resulting from hypoglycemia and hyperglycemia episodes, and so, to avoid deleterious effects resulting from deprivation or intracellular accumulation of glucose. The aim of this study was to compare the ability of normal and OA chondrocytes to regulate their glucose transport capacity in conditions of insufficient or excessive extracellular glucose and to identify the mechanisms involved and eventual deleterious consequences, namely the production of reactive oxygen species (ROS).

Methods
Chondrocytes, isolated from normal and OA human cartilage, were maintained in high-density monolayer cultures, in media without or with 10 or 30 mM glucose. Glucose transport was measured as the uptake of 2-deoxy-D-glucose (2-DG). Glucose transporter-1 (GLUT-1) mRNA and protein content were evaluated by real-time RT-PCR and western blot, respectively. ROS production was measured with 2',7'-dichlorodihydrofluorescein diacetate.

Results
Basal and IL-1β-induced 2-DG uptake, including the affinity (1.066 ± 0.284 and 1.49 ± 0.59 mM) and maximal velocity (0.27 ± 0.08 and 0.33 ± 0.08 nmol/μg protein/hour), and GLUT-1 content were identical in normal and OA chondrocytes. Glucose deprivation increased 2-DG uptake and GLUT-1 protein both in normal and OA chondrocytes. Exposure to high glucose (30 mM) for 18 or 48 hours decreased those parameters in normal but not in OA chondrocytes. GLUT-1 mRNA levels were unaffected by high glucose, either in normal or OA chondrocytes. The high glucose-induced reduction in GLUT-1 protein in normal chondrocytes was reversed by treatment with a lysosome inhibitor. High glucose induced ROS production, which lasted significantly longer in OA than in normal chondrocytes.

Conclusions
Normal human chondrocytes adjust to variations in the extracellular glucose concentration by modulating GLUT-1 synthesis and degradation which involves the lysosome pathway. Although capable of adjusting to glucose deprivation, OA chondrocytes exposed to high glucose were unable downregulate GLUT-1, accumulating more glucose and producing more ROS. Impaired GLUT-1 downregulation may constitute an important pathogenic mechanism by which conditions characterized by hyperglycemia, like DM, can promote degenerative changes in chondrocytes that can facilitate the progression of OA.
Evaluation of arthroscopy and macroscopic scoring
Authors: af Klint Erik , Catrina Anca I , Matt Peter , Neregråd Petra , Lampa Jon , Ulfgren Ann-Kristin , Klareskog Lars , Lindblad Staffan 
Published: June 2009

Abstract
Introduction
Arthroscopy is a minimally invasive technique for retrieving synovial biopsies in rheumatology during the past 20 years. Vital for its use is continual evaluation of its safety and efficacy. Important for sampling is the fact of intraarticular variation for synovial markers. For microscopic measurements scoring systems have been developed and validated, but for macroscopic evaluations there is a need for further comprehensive description and validation of equivalent scoring systems.

Methods
We studied the complication rate and yield of arthroscopies performed at our clinic between 1998 and 2005. We also created and evaluated a macroscopic score set of instructions for synovitis.

Results
Of 408 procedures, we had two major and one minor complication; two haemarthrosis and one wound infection, respectively. Pain was most often not a problem, but 12 procedures had to be prematurely ended due to pain. Yield of biopsies adequate for histology were 83% over all, 94% for knee joints and 34% for smaller joints. Video printer photographs of synovium taken during arthroscopy were jointly and individually reviewed by seven raters in several settings, and intra and inter rater variation was calculated. A macroscopic synovial scoring system for arthroscopy was created (Macro-score), based upon hypertrophy, vascularity and global synovitis. These written instructions were evaluated by five control-raters, and when evaluated individual parameters were without greater intra or inter rater variability, indicating that the score is reliable and easy to use.

Conclusions
In our hands rheumatologic arthroscopy is a safe method with very few complications. For knee joints it is a reliable method to retrieve representative tissue in clinical longitudinal studies. We also created an easy to use macroscopic score, that needs to be validated against other methodologies. We hope it will be of value in further developing international standards in this area.
Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma
Authors: Motzer Robert J. , Hutson Thomas E. , Tomczak Piotr , Michaelson M. Dror , Bukowski Ronald M. , Oudard Stéphane , Negrier Sylvie , Szczylik Cezary , Pili Roberto , Bjarnason Georg A. , Garcia-del-Muro Xavier , Sosman Jeffrey A. , Solska Ewa , Wilding George , Thompson John A. , Kim Sindy T. , Chen Isan , Huang Xin , Figlin Robert A. 
Published: June 2009

Purpose A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-α) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. Patients and Methods Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-α 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up. Results Median overall survival was greater in the sunitinib group than in the IFN-α group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-α group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor–signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-α (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-α (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%). Conclusion Sunitinib demonstrates longer overall survival compared with IFN-α plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy.
Ischaemia-modified albumin elevation after percutaneous coronary intervention reflects albumin concentration rather than ischaemia
Authors: Demir H , Topkaya B Ç , Erbay A R , Doğan M , Yücel D 
Published: June 2009

Background Percutaneous coronary intervention (PCI) is accepted as a model of myocardial ischaemia in studies of ischaemia markers, especially of ischaemia-modified albumin (IMA). However, there is concern that IMA levels may reflect changes in albumin concentrations rather than myocardial ischaemia also during PCI. Methods Twenty-one consecutive patients (17 men and 4 women) undergoing single-vessel percutaneous coronary angioplasty were enrolled in the study. IMA and albumin levels were measured together with myoglobin, creatine kinase 2 and cardiac troponin I, before (Group 1), immediately after (Group 2) and 6 h after (Group 3) the procedure of PCI. Results The IMA levels of Group 2 were significantly higher than those of Group 1 and Group 3 ( P < 0.05 for both). However, correction of IMA by multiplying with the (individual albumin concentration of the patient/median albumin concentration of Group 1) ratio gave no statistical differences between the groups ( P > 0.05). There were strong negative correlations between IMA levels and albumin concentrations within individual groups ( r = −0.757, P < 0.001; r = −0.712, P < 0.001; and r = −0.705, P < 0.001 for Group 1, Group 2 and Group 3, respectively). Conclusion The results confirm the close dependency of IMA results on albumin concentrations. Therefore, IMA results reflect albumin concentrations rather than myocardial ischaemia also in PCI. This situation and lack of standard reference materials for the albumin cobalt binding assay can lessen the diagnostic performance of IMA.
Circulating levels of cobalt and chromium from metal-on-metal hip replacement are associated with CD8+ T-cell lymphopenia
Authors: Hart A. J. , Skinner J. A. , Winship P. , Faria N. , Kulinskaya E. , Webster D. , Muirhead-Allwood S. , Aldam C. H. , Anwar H. , Powell J. J. 
Published: May 2009

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders. Laboratory-defined T-cell lymphopenia was present in13 patients (15%) (CD8+ lymphopenia) and 11 patients (13%) (CD3+ lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8+ lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.
The Anatomical Graduated Component total knee replacement
Authors: Ritter M. A. 
Published: May 2009

The long-term success of total knee replacement is multifactorial, including factors relating to the patient, the operation and the implant. The purpose of this study was to examine the 20-year survival of the cemented Anatomical Graduated Component (AGC) total knee replacement. Between 1983 and 2004, 7760 of these were carried out at our institution. Of these, 6726 knees which received the non-modular metal-backed tibial component with compression-moulded polyethylene and had a minimum two-year follow-up were available for study. In all, 36 knees were followed over 20 years with a survival of the tibial and femoral components together of 97.8% (95% confidence interval (CI) 0.9851 to 0.9677), with no implants being revised for polyethylene wear or osteolysis. Age > 70 was associated with increased survival (99.6%, 95% CI 99.0 to 99.8) (p < 0.0001) but pre-operative valgus alignment reduced survival (95.1%, 95% CI 90.0 to 97.6) (p = 0.0056). Age < 55 (p = 0.129), pre-operative varus alignment (p = 0.707), osteonecrosis (p = 0.06), rheumatoid arthritis (p = 0.247), and gender (p = 0.666) were not statistically associated with failure. We attribute the success of the AGC implant to its relatively unconstrained articular geometry and the durability of a non-modular metal-backed tibial component with compression moulded polyethylene.
A comparative study of two methods of surgical treatment for painful neuroma
Authors: Balcin H. , Erba P. , Wettstein R. , Schaefer D. J. , Pierer G. , Kalbermatten D. F. 
Published: May 2009

Painful neuromas may follow traumatic nerve injury. We carried out a double-blind controlled trial in which patients with a painful neuroma of the lower limb (n = 20) were randomly assigned to treatment by resection of the neuroma and translocation of the proximal nerve stump into either muscle tissue or an adjacent subcutaneous vein. Translocation into a vein led to reduced intensity of pain as assessed by visual analogue scale (5.8 (sd 2.7) vs 3.8 (sd 2.4); p < 0.01), and improved sensory, affective and evaluative dimensions of pain as assessed by the McGill pain score (33 (sd 18) vs 14 (sd 12); p < 0.01). This was associated with an increased level of activity (p < 0.01) and improved function (p < 0.01).Transposition of the nerve stump into an adjacent vein should be preferred to relocation into muscle.
The Ccr4-Pop2-NOT mRNA Deadenylase Contributes to Septin Organization in Saccharomyces cerevisiae
Authors: Traven Ana , Beilharz Traude H , Lo Tricia L , Lueder Franziska , Preiss Thomas , Heierhorst Jörg 
Published: June 2009

Abstract
In yeast, assembly of the septins at the cell cortex is required for a series of key cell cycle events: bud-site selection, the morphogenesis and mitotic exit checkpoints, and cytokinesis. Here we establish that the Ccr4-Pop2-NOT mRNA deadenylase contributes to septin organization. mRNAs encoding regulators of septin assembly (Ccd42, Cdc24, Rga1, Rga2, Bem3, Gin4, Cla4, and Elm1) presented with short poly(A) tails at steady state in wild-type (wt) cells, suggesting their translation could be restricted by deadenylation. Deadenylation of septin regulators was dependent on the major cellular mRNA deadenylase Ccr4-Pop2-NOT, whereas the alternative deadenylase Pan2 played a minor role. Consistent with deadenylation of septin regulators being important for function, deletion of deadenylase subunits CCR4 or POP2, but not PAN2, resulted in septin morphology defects (e.g., ectopic bud-localized septin rings), particularly upon activation of the Cdc28-inhibitory kinase Swe1. Aberrant septin staining was also observed in the deadenylase-dead ccr4-1 mutant, demonstrating the deadenylase activity of Ccr4-Pop2 is required. Moreover, ccr4Δ, pop2Δ, and ccr4-1 mutants showed aberrant cell morphology previously observed in septin assembly mutants and exhibited genetic interactions with mutations that compromise septin assembly (shs1Δ, cla4Δ, elm1Δ, and gin4Δ). Mutations in the Not subunits of Ccr4-Pop2-NOT, which are thought to predominantly function in transcriptional control, also resulted in septin organization defects. Therefore, both mRNA deadenylase and transcriptional functions of Ccr4-Pop2-NOT contribute to septin organization in yeast.
The Effect of Doxycycline Hyclate, Chlorhexidine Gluconate, and Minocycline Hydrochloride on Osteoblastic Proliferation and Differentiation In Vitro
Authors: Almazin Salah M. , Dziak Rosemary , Andreana Sebastiano , Ciancio Sebastian G. 
Published: June 2009

Background: The purpose of this study was to determine the effect of the active substance of three types of local delivery systems, doxycycline hyclate 10% (DOXY), chlorhexidine gluconate, 2.5 mg (CHX), and minocycline hydrochloride, 1 mg (MINO), on osteoblastic cell proliferation and differentiation.Methods: There were four groups: control osteoblastic cells (OB) alone, OB + DOXY, OB + CHX, and OB + MINO. Trypan blue and MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assays were used to test osteoblastic cell viability. Cell differentiation was tested by measuring alkaline phosphatase levels. Osteoblast morphology was investigated by light and scanning electron microscopy.Results: At a concentration of 0.5 mg/ml, the Trypan blue test showed that DOXY, MINO, and CHX had significant toxicity effects on osteoblast cells compared to the control group, with a mean cell viability of 84%, 74%, and 51%, respectively (P <0.05). The MTT test showed that the control and DOXY groups were statistically significantly different (P <0.05) compared to CHX and MINO groups. The DOXY group showed a significantly higher alkaline phosphatase activity (∼56%) than the control and MINO groups, and it was nearly 178% higher than the CHX group (P <0.05). The morphology of the osteoblasts seemed to be slightly altered when they were incubated with DOXY; however, with MINO, they appeared rounded with minimal attachment. In the CHX group, the osteoblasts assumed a shape of a very thin filopodia with a volcano‐like nucleus.Conclusions: At a concentration of 0.5 mg/ml, CHX and, to a lesser extent, MINO had a cytotoxic effect on osteoblast proliferation in vitro. However, DOXY seemed to enhance maturation and differentiation rather than proliferation. In addition to DOXY's beneficial effect as an adjunctive therapy to mechanical debridement in the treatment of periodontal disease, it may have an effect on periodontal regeneration.
Uptake of Metronidazole by Human Gingival Fibroblasts
Authors: Yu Liqiang , Liu Hongchen , E Lingling , Wu Xia , Wang Dongsheng 
Published: June 2009

Background: Metronidazole is an important antimicrobial agent for the therapeutic management of periodontal diseases and dentoalveolar infections. As in other tissues, the metronidazole concentration in gingival crevicular fluid is about equal to the plasma level. Thus, we hypothesized that metronidazole is not actively transported into human gingival fibroblasts.Methods: Using high performance liquid chromatography, the influences of extracellular metronidazole concentrations, temperature, pH, and inhibitors of transporters on the uptake of metronidazole by cultured human gingival fibroblasts were tested.Results: Metronidazole was taken up rapidly by fibroblasts; the intracellular metronidazole concentration reached the extracellular level in 3 minutes at 37°C and in 2 minutes at 4°C. The uptake of metronidazole by human gingival fibroblasts was not saturable, and the intracellular metronidazole concentrations increased linearly with the extracellular level. Temperature and pH had no significant influence on the uptake of metronidazole by fibroblasts. Probenecid and adenine had no influence on the uptake of metronidazole by fibroblasts. These findings indicate that metronidazole uptake does not involve a transporter. Metronidazole bound rapidly to human gingival fibroblasts, but the cell‐associated drug declined progressively until it reached a stable plateau in 15 minutes.Conclusions: Metronidazole rapidly entered human gingival fibroblasts via simple diffusion. Metronidazole easily reached the minimal inhibitory concentration in fibroblasts and gingiva. Given the fact that intracellular concentrations of metronidazole in other tissues and cells are also close to the plasma level, we speculate that metronidazole enters other tissues and cells via simple diffusion.
Periodontal Wound Healing With and Without Platelet‐Rich Plasma: Histologic Observations and Assessment of Flap Tensile Strength
Authors: Powell Charles A. , Bannister Sharon R. , Mackey Scott A. , Maller Steven C. , McDonnell Howard T. , Deas David E. 
Published: June 2009

Background: Platelet‐rich plasma (PRP) has been promoted as a surgical adjunct to enhance hard and soft tissue wound healing. Although anecdotally reported to be of value, the results of controlled studies examining the added effects of PRP on surgical procedures have been mixed. The purpose of this study was to test the effect of PRP on flap strength at various post‐surgical time points in a minipig animal model.Methods: Twelve Yucatan minipigs provided four sites per animal. PRP was prepared from each animal at the time of surgery. Following reflection of a mucoperiosteal flap in each quadrant, subgingival plaque and calculus were removed. Each surgical site was irrigated with sterile saline; prior to suturing, one randomly selected test quadrant in each arch was treated with PRP. Four animals were euthanized at day 14, and two animals were euthanized at 2, 7, 10, and 28 days. The flap strength in each quadrant was tested by attaching to a loop of 3‐0 silk suture through the tissue; the force required to separate the flap from the tooth/bone interface was recorded for each site. A separate portion of each flap site was prepared for descriptive histologic examination, including inflammation, hemorrhage, and new bone growth.Results: Flap strength was significantly less on day 2 compared to later time points, and there were no significant differences between the test and control groups. No histologic differences in healing between test and control sites were seen at any time point.Conclusions: PRP did not seem to contribute to greater flap strength at any post‐surgical time point, nor was it associated with any histologic differences in wound healing in this Yucatan minipig model. The time points chosen for observation post‐surgery, as well as the variability in the PRP platelet count, may have contributed to the lack of positive findings in this study.
Fractional Newtonian mechanics
Authors: Baleanu Dumitru , Golmankhaneh Alireza , Nigmatullin Raoul , Golmankhaneh Ali 
Published: May 2009

Abstract
In the present paper, we have introduced the generalized Newtonian law and fractional Langevin equation. We have derived potentials corresponding to different kinds of forces involving both the right and the left fractional derivatives. Illustrative examples have worked out to explain the formalism.