bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma
Authors: Susa Michiro , Iyer Arun K , Ryu Keinosuke , Hornicek Francis J , Mankin Henry , Amiji Mansoor M , Duan Zhenfeng 
Published: November 2009

Abstract

Background
Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the efficacy.

Methods
Doxorubicin was loaded onto a lipid-modified dextran based polymeric nano-system. The effect of various concentrations of doxorubicin alone or nanoparticle loaded doxorubicin on KHOS, KHOSR2, U-2OS, and U-2OSR2 cells was analyzed. Effects on drug retention, immunofluorescence, Pgp expression, and induction of apoptosis were also analyzed.

Results
Dextran nanoparticles loaded with doxorubicin had a curative effect on multidrug resistant osteosarcoma cell lines by increasing the amount of drug accumulation in the nucleus via Pgp independent pathway. Nanoparticles loaded with doxorubicin also showed increased apoptosis in osteosarcoma cells as compared with doxorubicin alone.

Conclusion
Lipid-modified dextran nanoparticles loaded with doxorubicin showed pronounced anti-proliferative effects against osteosarcoma cell lines. These findings may lead to new treatment options for MDR osteosarcoma.
Functional activation of proline-rich tyrosine kinase2 (PYK2) in peripheral blood mononuclear cells from patients with systemic lupus erythematosus
Authors: Wang Meiying , Sun Hongsheng , Zhang Wei , Zhang Yuanchao 
Published: November 2009

AbstractBackgroundSystemic lupus erythematosus (SLE) is a representative systemic autoimmune disease characterized by activated T cells and polyclonally activated B cells that produce autoantibodies. Activation of autoreactive T and B cells plays a pivotal role in the pathogenesis of this disease. A role of focal adhesion kinase (FAK) in the pathogenesis has been suggested. Proline-rich tyrosine kinase2 (PYK2) is structurally related to FAK, however, the functional activation of PYK2 in SLE remains unclear. In the present study, we showed that PYK2 is significantly increased and activated in peripheral blood mononuclear cells (PBMCs) of patients with SLE. In addition, we showed the involvement of PYK2 proteins in the up-regulation of CD40L and CTLA4 expression and PBMC proliferation.MethodsFreshly isolated PBMCs from 48 SLE patients, 32 patients with rheumatoid arthritis(RA) and 24 healthy individuals were analyzed for the expression and activation of PYK2 by western-blotting and immunocytochemistry. The other isolated PBMCs from patients with this condition were cultured and stimulated with PMA or TyrA9, and then the expression of costimulatory molecules CD40L and CTLA4 was evaluated using flow cytometry, PBMCs proliferation was determined with [3H]-thymidine incorporation (CPM).ResultsCompared with RA patients and healthy donors, PBMCs from SLE patients expressed more of both the total PYK2 protein and its activated/phosphorylated form. The increase of activated PYK2 protein in SLE PBMCs was correlated with the complication of nephritis and inversly associated the level of serum complements. In active SLE patients, activation of PYK2 in PBMCs is accompanying the increased cell proliferation and the induced expression of costimulatory molecules CD40L and CTLA4.ConclusionOur findings indicate that phosphorylated PYK2 in SLE PBMCs may induce the expression of CD40L and CTLA4, and subsequently the cell proliferation. PYK2 signaling enhances the autoreactive lymphocyte activation and plays an important role in the pathogenesis of SLE.
Pretreatment organ function in patients with advanced head and neck cancer: clinical outcome measures and patients' views
Authors: van der Molen Lisette , van Rossum Maya A , Ackerstaff Annemieke H , Smeele Ludi E , Rasch Coen RN , Hilgers Frans JM 
Published: November 2009

Abstract

Background
Aim of this study is to thoroughly assess pretreatment organ function in advanced head and neck cancer through various clinical outcome measures and patients' views.

Methods
A comprehensive, multidimensional assessment was used, that included quality of life, swallowing, mouth opening, and weight changes. Fifty-five patients with stage III-IV disease were entered in this study prior to organ preserving (chemoradiation) treatment.

Results
All patients showed pretreatment abnormalities or problems, identified by one or more of the outcome measures. Most frequent problems concerned swallowing, pain, and weight loss. Interestingly, clinical outcome measures and patients' perception did no always concur. E.g. videofluoroscopy identified aspiration and laryngeal penetration in 18% of the patients, whereas only 7 patients (13%) perceived this as problematic; only 2 out of 7 patients with objective trismus actually perceived trismus.

Conclusion
The assessment identified several problems already pre-treatment, in this patient population. A thorough assessment of both clinical measures and patients' views appears to be necessary to gain insight in all (perceived) pre-existing functional and quality of life problems.
Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells
Authors: Izuta Hiroshi , Shimazawa Masamitsu , Tsuruma Kazuhiro , Araki Yoko , Mishima Satoshi , Hara Hideaki 
Published: November 2009

Abstract

Background
Vascular endothelial growth factor (VEGF) is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ), bee pollen, and Chinese red propolis] from the honeybee, Apis mellifera, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs).

Methods
In an in vitro tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE)]. To clarify the mechanism of in vitro angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE.

Results
RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced in vitro tube formation in the descending order: CAPE > Chinese red propolis >> bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation.

Conclusion
Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases.
Experiences, attitudes and barriers towards research amongst junior faculty of Pakistani medical universities
Authors: Sabzwari Saniya , Kauser Samreen , Khuwaja Ali Khan 
Published: November 2009

Abstract

Background
The developing world has had limited quality research and in Pakistan, research is still in its infancy. We conducted a study to assess the proportion of junior faculty involved in research to highlight their attitude towards research, and identify the factors associated with their research involvement.

Methods
A cross-sectional study was conducted in four medical universities/teaching hospitals in Pakistan, representing private and public sectors. A pre-tested, self-administered questionnaire was used to collect information from 176 junior faculty members of studied universities/hospitals. Logistic regression analysis was used to identify factors related to attitudes and barriers in research among those currently involved in research with those who were not.

Results
Overall, 41.5% of study subjects were currently involved in research. A highly significant factor associated with current research involvement was research training during the post-graduate period (p < 0.001). Other factors associated with current involvement in research were male gender, working in the public sector and previous involvement in research. Overall, a large majority (85.2%) of doctors considered research helpful in their profession and had a positive attitude towards research; nevertheless this positive attitude was more frequently reported by doctors who were currently involved in research compared to those who were not (OR = 4.69; 95% CI = 1.54-14.26). Similarly, a large proportion (83.5%) of doctors considered research difficult to conduct; higher by doctors who were not presently involved in research (OR = 2.74; 95% CI = 1.20-6.22)

Conclusion
Less than half of the study participants were currently involved in research. Research output may improve if identified barriers are rectified. Further studies are recommended in this area.
Is flow cytometry better in counting malaria pigment-containing leukocytes compared to microscopy?
Authors: Hänscheid Thomas , Frita Rosangela , Längin Matthias , Kremsner Peter G , Grobusch Martin P 
Published: November 2009

Abstract

Background
Detection of malaria pigment (or haemozoin; Hz)-containing leukocytes may have prognostic relevance in malaria; however, studies reported conflicting results, with microscopic counts suggestive of being inaccurate and imprecise.

Methods
Numbers of Hz-containing leukocytes from a malaria patient obtained with a flow cytometer counting 50.000 gated events were compared with thin film microscopy as applied under field conditions.

Results
Flow cytometry identified 5.8% Hz-containing monocytes and 1.8% Hz-containing neutrophils. The microscopic examination yielded 10% and 13% of Hz-containing monocytes, as well as 0% and 0.5% of Hz-containing neutrophils for observers one and two, respectively.

Conclusion
Novel, robust and affordable cytometric methods should be evaluated in the field as they may assist in utilizing Hz-containing cells as clinically useful parameter.
Radiation biology of mosquitoes
Authors: Helinski Michelle EH , Parker Andrew G , Knols Bart GJ 
Published: November 2009

AbstractThere is currently renewed interest in assessing the feasibility of the sterile insect technique (SIT) to control African malaria vectors in designated areas. The SIT relies on the sterilization of males before mass release, with sterilization currently being achieved through the use of ionizing radiation. This paper reviews previous work on radiation sterilization ofAnophelesmosquitoes. In general, the pupal stage was irradiated due to ease of handling compared to the adult stage. The dose-response curve between the induced sterility and log (dose) was shown to be sigmoid, and there was a marked species difference in radiation sensitivity. Mating competitiveness studies have generally been performed under laboratory conditions. The competitiveness of males irradiated at high doses was relatively poor, but with increasing ratios of sterile males, egg hatch could be lowered effectively. Males irradiated as pupae had a lower competitiveness compared to males irradiated as adults, but the use of partially-sterilizing doses has not been studied extensively. Methods to reduce somatic damage during the irradiation process as well as the use of other agents or techniques to induce sterility are discussed. It is concluded that the optimal radiation dose chosen for insects that are to be released during an SIT programme should ensure a balance between induced sterility of males and their field competitiveness, with competitiveness being determined under (semi-) field conditions. Self-contained60Co research irradiators remain the most practical irradiators but these are likely to be replaced in the future by a new generation of high output X ray irradiators.
Endothelial cells influence the osteogenic potential of bone marrow stromal cells
Authors: Xue Ying , Xing Zhe , Hellem Sølve , Arvidson Kristina , Mustafa Kamal 
Published: November 2009

Abstract

Background
Improved understanding of the interactions between bone cells and endothelial cells involved in osteogenesis should aid the development of new strategies for bone tissue engineering. The aim of the present study was to determine whether direct communication between bone marrow stromal cells (MSC) and human umbilical vein endothelial cells (EC) could influence the osteogenic potential of MSC in osteogenic factor-free medium.

Methods
After adding EC to MSC in a direct-contact system, cell viability and morphology were investigated with the WST assay and immnostaining. The effects on osteogenic differentiation of adding EC to MSC was systematically tested by the using Superarray assay and results were confirmed with real-time PCR.

Results
Five days after the addition of EC to MSC in a ratio of 1:5 (EC/MSC) significant increases in cell proliferation and cellular bridges between the two cell types were detected, as well as increased mRNA expression of alkaline phosphatase (ALP). This effect was greater than that seen with addition of osteogenic factors such as dexamethasone, ascorbic acid and β-glycerophosphate to the culture medium. The expression of transcription factor Runx2 was enhanced in MSC incubated with osteogenic stimulatory medium, but was not influenced by induction with EC. The expression of Collagen type I was not influenced by EC but the cells grown in the osteogenic factor-free medium exhibited higher expression than those cultured with osteogenic stimulatory medium.

Conclusion
These results show that co-culturing of EC and MSC for 5 days influences osteogenic differentiation of MSC, an effect that might be independent of Runx2, and enhances the production of ALP by MSC.
Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors
Authors: Kohler Corina , Radpour Ramin , Barekati Zeinab , Asadollahi Reza , Bitzer Johannes , Wight Edward , Bürki Nicole , Diesch Claude , Holzgreve Wolfgang , Zhong Xiao Yan 
Published: November 2009

Abstract

Background
With the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA) seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been found in several cancer types and might have a diagnostic value.

Methods
Using multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic) curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters.

Results
While the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P < 0.001) and the healthy control group (P < 0.001), the level of ccf mtDNA was found to be significantly lower in the two tumor-groups (benign: P < 0.001; malignant: P = 0.022). The level of ccf nDNA was also associated with tumor-size (<2 cm vs. >2 cm<5 cm; 2250 vs. 6658; Mann-Whitney-U-Test: P = 0.034). Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P < 0.001) and between the tumor group and the healthy controls using ccf mtDNA as marker (cut-off: 463282 GE/ml; sensitivity: 53%; specificity: 87%; P < 0.001).

Conclusion
Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.
Influence of involvement of anterior leaflet versus posterior leaflet on residual regurgitation as assessed by transesophageal echocardiography in patients undergoing valve repair for mitral regurgitation due to mitral valve prolapse
Authors: Sulcaj Laureta , Rizza Antonio , Glauber Mattia , Trianni Giuseppe , Palmieri Cataldo , Ravani Marcello , Dibra Alban , Maffei Stefano , Berti Sergio 
Published: November 2009

Abstract

Background
Repair of anterior leaflet prolapse is technically more challenging and this might influence outcomes as compared to the repair of posterior leaflet prolapse in patients undergoing surgical correction of mitral regurgitation. We investigated the association of anterior leaflet prolapse with minor residual mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) who underwent valve repair.

Methods
Eligible for this study were consecutive patients with severe MR due to MVP, who underwent mitral valve repair with residual MR by postpump transesophageal echocardiography ≤2+ during a 20-month period at Pasquinucci Hospital, Massa. Patients undergoing other cardiovascular surgical interventions were excluded. Two groups were defined according to the involvement of mitral valve leaflets: group 1, consisting of patients with anterior leaflet prolapse (isolated or not); and group 2, consisting of patients with isolated posterior leaflet prolapse.

Results
A total of 70 patients (18 in group 1 and 52 in group 2) were analyzed. Patients in group 2 were younger than those in group 1, but the difference was not significant (P = 0.052). There were no significant differences between the 2 study groups with respect to other variables. The proportion of patients with residual MR 1+/2+ was higher in group 1 than in group 2 (61.1% vs. 32.7%, respectively; P = 0.034). In a logistic regression model, anterior leaflet prolapse was an independent predictor of residual MR 1+/2+ (odds ratio, 4.0; 95% confidence interval, 1.14 to 14.04; P = 0.03).

Conclusion
In our study population, patients with anterior leaflet prolapse had a higher proportion of residual MR 1+/2+ as compared to those with posterior leaflet prolapse after repair of mitral valve.
The New Jersey Institute of Technology Robot-Assisted Virtual Rehabilitation (NJIT-RAVR) system for children with cerebral palsy: a feasibility study
Authors: Qiu Qinyin , Ramirez Diego A , Saleh Soha , Fluet Gerard G , Parikh Heta D , Kelly Donna , Adamovich Sergei V 
Published: November 2009

Abstract

Background
We hypothesize that the integration of virtual reality (VR) with robot assisted rehabilitation could be successful if applied to children with hemiparetic CP. The combined benefits of increased attention provided by VR and the larger training stimulus afforded by adaptive robotics may increase the beneficial effects of these two approaches synergistically. This paper will describe the NJIT-RAVR system, which combines adaptive robotics with complex VR simulations for the rehabilitation of upper extremity impairments and function in children with CP and examine the feasibility of this system in the context of a two subject training study.

Methods
The NJIT-RAVR system consists of the Haptic Master, a 6 degrees of freedom, admittance controlled robot and a suite of rehabilitation simulations that provide adaptive algorithms for the Haptic Master, allowing the user to interact with rich virtual environments. Two children, a ten year old boy and a seven year old girl, both with spastic hemiplegia secondary to Cerebral Palsy were recruited from the outpatient center of a comprehensive pediatric rehabilitation facility. Subjects performed a battery of clinical testing and kinematic measurements of reaching collected by the NJIT-RAVR system. Subjects trained with the NJIT-RAVR System for one hour, 3 days a week for three weeks. The subjects played a combination of four or five simulations depending on their therapeutic goals, tolerances and preferences. Games were modified to increase difficulty in order to challenge the subjects as their performance improved. The testing battery was repeated following the training period.

Results
Both participants completed 9 hours of training in 3 weeks. No untoward events occurred and no adverse responses to treatment or complaints of cyber sickness were reported. One participant showed improvements in overall performance on the functional aspects of the testing battery. The second subject made improvements in upper extremity active range of motion and in kinematic measures of reaching movements.

Conclusion
We feel that this study establishes the feasibility of integrating robotics and rich virtual environments to address functional limitations and decreased motor performance in children with mild to moderate cerebral palsy.
Does neuroinflammation fan the flame in neurodegenerative diseases?
Authors: Frank-Cannon Tamy C , Alto Laura T , McAlpine Fiona E , Tansey Malú G 
Published: November 2009

Abstract
While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), tauopathies, and age-related macular degeneration (ARMD), are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the pathophysiology of several neurodegenerative diseases.