Τρίτη 6 Φεβρουαρίου 2018
A single channel sleep-spindle detector based on multivariate classification of EEG epochs: MUSSDET
Source:Journal of Neuroscience Methods, Volume 297
Author(s): Daniel Lachner-Piza, Nino Epitashvili, Andreas Schulze-Bonhage, Thomas Stieglitz, Julia Jacobs, Matthias Dümpelmann
BackgroundStudies on sleep-spindles are typically based on visual-marks performed by experts, however this process is time consuming and presents a low inter-expert agreement, causing the data to be limited in quantity and prone to bias. An automatic detector would tackle these issues by generating large amounts of objectively marked data.New MethodOur goal was to develop a sensitive, precise and robust sleep-spindle detection method. Emphasis has been placed on achieving a consistent performance across heterogeneous recordings and without the need for further parameter fine tuning. The developed detector runs on a single channel and is based on multivariate classification using a support vector machine. Scalp-electroencephalogram recordings were segmented into epochs which were then characterized by a selection of relevant and non-redundant features. The training and validation data came from the Medical Center-University of Freiburg, the test data consisted of 27 records coming from 2 public databases.ResultsUsing a sample based assessment, 53% sensitivity, 37% precision and 96% specificity was achieved on the DREAMS database. On the MASS database, 77% sensitivity, 46% precision and 96% specificity was achieved. The developed detector performed favorably when compared to previous detectors. The classification of normalized EEG epochs in a multidimensional space, as well as the use of a validation set, allowed to objectively define a single detection threshold for all databases and participants.ConclusionsThe use of the developed tool will allow increasing the data-size and statistical significance of research studies on the role of sleep-spindles.
http://ift.tt/2E7z9Lo
Intracranial rat glioma model for tumor resection and local treatment
Source:Journal of Neuroscience Methods
Author(s): Zhiqun Wu, Makoto Nakamura, Joachim K. Krauss, Kerstin Schwabe, Nadine John
BackgroundAlthough tumor resection is among the most important prognostic factors, high grade gliomas regrow in most cases. Also, resection of glial tumors in eloquent brain regions is not or only partially possible. Despite these severe restraints, however, only a few in-vivo models have been established to investigate tumor recurrence and local treatment. Here we characterize the intracranial BT4Ca rat glioma as a model for these aspects.New MethodBT4Ca cells were stereotaxically implanted into the frontal cortex of BDIX rats. Rats were than allocated to (1) a control group, which received no further treatment; (2) a catheter group, where a catheter was implanted for repeated microinjection of vehicle every 3rd day as catheter-control; (3) a resection group, where the tumor was microsurgically removed eight days after cell injection. Postoperatively, survival time, weight and general health condition were scored and the tumor size was histologically assessed.ResultsInjection of BT4Ca cells induced fast-growing tumors with a mean survival time of 16 days in the control and catheter groups. Resection significantly prolonged survival time whereby the tumor regrew in all rats. Tumor size was similar between all groups.Comparison with Existing Method(s)We here present a robust and reliable intracranial rat glioma model, which is suitable to simulate tumor recurrence after surgical resection and local treatment. Importantly, this model does not require advanced imaging or elaborate surgical techniques.ConclusionsThe intracranial BT4Ca glioma model appears to be a feasible tool to investigate tumor recurrence after resection and to test local treatment.
http://ift.tt/2EMn5jz
Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids
Abstract
Derivatives of hydrocortisone, such as mometasone furoate, a (2′) furoate-17 ester with chlorine substitutions at positions 9 and 21, have been designed to improve efficacy and reduce the incidence of adverse effects. An extensive literature search of MEDLINE, Embase and other databases was conducted to review the safety and efficacy of various formulations of topical mometasone furoate. Mometasone furoate exhibits high potency with greater anti-inflammatory activity and a longer duration of action than betamethasone. In clinical trials, mometasone furoate shows comparable or significantly better efficacy, depending on the comparator, in all indications studied in both adults and children. It is well tolerated with only transient, mild to moderate local adverse effects. It is characterised by low systemic availability due to its high lipophilicity, low percutaneous absorption and rapid hepatic biotransformation, and consequently has no significant effect on the hypothalamic-pituitary-adrenal axis. The molecular biotransformation of mometasone furoate in the skin results in a lower affinity with dermal cells than epidermal cells, which contributes to its low atrophogenicity. Sensitisation to mometasone furoate is low. Overall, mometasone furoate is a highly efficacious potent corticosteroid with a low risk of both local and systemic adverse effects.
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Editorial Board
Publication date: February 2018
Source:Pathology - Research and Practice, Volume 214, Issue 2
http://ift.tt/2nJ4Kgl
Editorial Board
Publication date: January 2018
Source:Pathology - Research and Practice, Volume 214, Issue 1
http://ift.tt/2nSVVzR
De Novo Designed Proteins for Colloidal Stabilization and Improvement of Cellular Uptake
Publication date: 2 February 2018
Source:Biophysical Journal, Volume 114, Issue 3, Supplement 1
Author(s): Tingting Zheng, Felipe Perona Martínez, Ingeborg Maria Storm, Wolf Rombouts, Joris Sprakel, Renko de Vries, Romana Schirhagl
http://ift.tt/2nJ4dLn
Randomized investigator-blinded comparative study of moisturizer containing 4-t-butylcyclohexanol and licochalcone A versus 0.02% triamcinolone acetonide cream in facial dermatitis
Summary
Background
Facial dermatitis can result from various conditions, some of which are of a chronic and relapsing nature. The use of topical corticosteroid therapy may lead to additional adverse effects.
Objective
To compare the efficacy of moisturizer containing 4-t-butylcyclohexanol, which acts as a sensitivity regulator, and licochalcone A, an anti-inflammatory agent from the licorice plant Glycyrrhiza inflata, with that of 0.02% triamcinolone acetonide (TA) for the treatment of facial dermatitis.
Methods
This was a randomized, prospective, investigator-blinded study. Eighty participants with mild to moderate facial dermatitis were randomly treated with either the test facial moisturizer or 0.02% TA twice daily for the first 2 weeks. For the subsequent 2 weeks, all patients used only the test moisturizer. Clinical assessment by investigators, bioengineering measurements, patients' subjective evaluation, and clinical photography were performed at baseline, week 2, and week 4.
Results
Both treatments showed a statistically significant improvement with regard to physician clinical assessment, skin hydration, transepidermal water loss, and patient-assessed visual analog scale after 2 and 4 weeks of treatment compared with baseline. The test facial moisturizer produced better skin hydration than TCS. The improvement in TEWL after 4 weeks of using the test moisturizer was comparable with 2-week treatment with 0.02% TA cream. However, subjective evaluation by patients indicated that TA more rapidly improved sensation sensitivity.
Conclusion
The test facial moisturizer was slower than 0.02% TA in improving facial dermatitis, but showed greater benefit in erythema control and skin hydration.
http://ift.tt/2C3YOTu
Is Action Execution Part of the Decision-Making Process? An Investigation of the Embodied Choice Hypothesis.
Author: Aczel, Balazs; Szollosi, Aba; Palfi, Bence; Szaszi, Barnabas; Kieslich, Pascal J.
DOI: 10.1037/xlm0000484
Publication Date: POST AUTHOR CORRECTIONS, 5 February 2018
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Ginseng phytochemicals as therapeutics in oncology: Recent perspectives
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Fatima Majeed, Fozia Zahur Malik, Zaheer Ahmed, Asma Afreen, Muhammad Naveed Afzal, Nauman Khalid
During the last few decades, cancer has mushroomed as a major health issue; and almost all drugs used for its therapy are very toxic with lethal side effects. Complementary and alternative medicines gain popularity among health professionals in recent era owing to its preventive mechanism against side effect chemotherapeutic drugs. Efforts are focused by scientists to isolate compounds from medicinal plant that have chemotherapeutic attributes; and ability to neutralize the side effects of chemotherapy. Ginseng is an oriental medicinal recipe from Araliceae family and Panax species. The chemotherapeutic effect of ginsenoside is resultant of its appetites, anti-proliferative, anti-angiogenic, anti-inflammatory and anti-oxidant properties. The anticancer effect of ginseng is proven in various types of cancer, including; breast, lung, liver, colon and skin cancer. It increases the mitochondrial accumulation of apoptosis protein and downregulate the expression of anti-apoptotic protein. It also aids in the reduction of alopecia, fatigue and nausea, the known side effects of chemotherapeutic drugs. The aim of the present review is to provide the brief review of the recent researches related to mechanism of action of ginseng in different types of cancer as complementary and alternative medicine on different body organs.
Graphical abstract
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MicroRNA-204 protects H9C2 cells against hypoxia/reoxygenation-induced injury through regulating SIRT1-mediated autophagy
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Ruixia Qiu, Wen Li, Yunhai Liu
Ischemia/reperfusion (I/R) injury is a main cause of acute myocardial infarction, and the pathogenesis of I/R injury is still not definitely confirmed. In the present study, we aimed to explore the roles of miR-204 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury in vitro. The H9C2 cells were subjected to hypoxia for 12 h followed by reoxygenation for another 24 h, and we found that miR-204 was significantly down-regulated after H/R treatment. Transfection of miR-204 mimics attenuated the H/R-induced impaired cell viability and increased apoptosis rates. Furthermore, SIRT1 was identified as a direct target of miR-204, and its expression is negatively regulated by miR-204. Forced expression of SIRT1 could partly rescue the effects of miR-204 on H/R-induced apoptosis and autophagy. Taken together, our study first revealed that overexpression of miR-204 has a protective effect against myocardial I/R injury.
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Long non-coding RNA ENST01108 promotes carcinogenesis of glioma by acting as a molecular sponge to modulate miR-489
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Dawei Xu, Ruihua Liu, Lei Meng, Yi Zhang, Guangjian Lu, Pengju Ma
Gliomas are the most common primary malignant tumor in the adult central nervous system with poor prognosis. Exploring novel biomarkers and elucidating underlying molecular mechanisms to provide effective therapeutic methods is in an urgent need. Long noncoding RNAs (lncRNAs) is involved in various human diseases including cancer. However, studies on lncRNAs and gliomas are limited. In this study, we explored the expression patterns of lncRNAs in 4 pairs of glioma samples and adjacent normal tissues via microarray and chose the most up-regulated lncRNA ENST01108 (ENST01108) to further verify its oncogenic role in glioma. Clinical data suggest that ENST01108 is closely associated with the malignant status in glioma. In vitro experiment demonstrated that overexpression of ENST01108 promoted glioma cell proliferation, migration, invasion, EMT process and survival, while knockdown of ENST01108 has an opposite effect, indicating that ENST01108 serves as an oncogenic property in glioma carcinogenesis. Further, we identified miR-489 as a direct target of ENST01108 and ENST01108 negatively regulate miR-489 by act as a sponge. SIK1 is verified as the direct target of miR-489 and it is negatively regulated by miR-489. ENST01108 also positively regulate SIKI and it promotes SIKI expression by suppressing miR-489. Taken together, the reciprocal repression of ENST011081 and miR-489 may be served as potential targets for cancer therapeutics in glioma.
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Polyphenol-enriched extract of Rosa rugosa Thunb regulates lipid metabolism in diabetic rats by activation of AMPK pathway
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Liu Liu, Mireguli Yasen, Dan Tang, Jianping Ye, Haji Akber Aisa, Xuelei Xin
This study was designed to investigate the mechanism of polyphenol-enriched extract of Rosa rugosa Thunb (RPE) in the control of dyslipidemia in diabetic rats. RPE was tested at three dosages (37.5 mg/kg, 75 mg/kg and 150 mg/kg) in the rat dyslipidemia model established with high fat diet feeding in combination with STZ injection (30 mg/kg). The RPE effect was evaluated after 4 weeks of treatment. In the RPE-treated rats, hepatic total cholesterol (TC) and triglyceride (TG) were significantly reduced, lipoprotein lipase (LPL) and liver lipase (HL) were significantly increased. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were decreased in the serum. Those effects of RPE were observed primarily at the mediate and high dosages. Expression of FGF21 was increased in the liver tissue and hepatic cell line 1c1c7 by RPE. The signals of p-AMPK, p-ACC, ACC, p-SIRT, and PGC-1α were significantly induced in the liver by RPE. The results suggest that RPE may improve hepatic steatosis and liver function by induction of AMPK signaling activity in the control of dyslipidemia.
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Ghrelin attenuates ultraviolet B radiation-induced impairment in capacities of epidermal stem cells
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Yue-hui Wang, Cheng-kuan Sun, Xiang-lan Li, Yan Huang, Jing Sun
Persistent exposure to solar ultraviolet radiation (UVR) causes continuous damages to skin, including progressive impairment of epidermal stem cells (ESCs) capacities. Ghrelin is the only known endogenous orexigenic hormone, which has displayed its various pharmacological functions. In the current study, we found that the specific receptor of ghrelin, growth hormone secretagogue receptor (GHS-R), is expressed in ESCs. Interestingly, GHS-R expression is significantly upregulated in response to ultraviolet B (UVB) radiation. We also found that ghrelin treatment prevented UVB radiation-induced reduction in cell viability and the release of lactate dehydrogenase (LDH). Additionally, ghrelin reduced UVB radiation-induced generation of reactive oxygen species (ROS) and restored the intracellular level of reduced glutathione (GSH). UVB radiation significantly suppressed the expressions of integrin β1 and Krt19, the two major ESC markers, which were restored by ghrelin. Notably, knockdown of GHS-R abolished the effects of ghrelin on the expressions of integrin β1 and Krt19, suggesting the involvement of GHS-R. Also, we found that ghrelin treatment inhibited UVB radiation- induced reduction of Wnt1, Wnt3a, Myc, and cyclin D1 at both the mRNA levels and the protein levels. Taken together, our findings identify a novel function of ghrelin on maintaining the capacities of ESCs against UVB radiation.
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Therapeutic efficacy of osthole against dinitrobenzene sulphonic acid induced-colitis in rats
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Hanan Khairy, Hanan Saleh, Abeer M. Badr, Mohamed-Assem S. Marie
Several mediators were associated with the pathogenesis of inflammatory bowel disease such as oxidative stress through the production of reactive oxygen metabolites, neutrophils infiltration and release of pro-inflammatory cytokines. This study was designed to investigate the therapeutic efficacy of osthole against dinitrobenzene sulfonic acid (DNBS) induced-colitis in rats through its anti-oxidant and anti-inflammatory properties. Colitis was induced in rats by single intracolonic instillation of (250 μl DNBS-25 mg/rat). Then 4 days later, rats were received oral administration of either (osthole 50 mg/kg), (sulfasalazine 500 mg/kg) or both in combination for 7 consecutive days. Body weight, some hematological parameters, colonic malondialdehyde (MDA) and myeloperoxidase activity (MPO), antioxidant parameters, colon injury and mucosa architectures were assessed. T helper (Th1)-related cytokines [Tumor necrosis factor alpha (TNF-α) and interferon-gamma (INF-γ)], Th2-relarted cytokines (interleukin-4 [IL-4 and IL-10], and Th-17 related cytokines [IL-17] were determined by ELISA. Osthole significantly improved the loss in body weight. That was accompanied with a remarkable amelioration of the disruption of the colonic architecture as well as a significant improvement in the antioxidant defense system. A reduction in MPO and MDA was observed in flamed colon. Treatment with either osthole or combination therapy showed suppressive activities on pro-inflammatory Th2-related cytokines and upregulation of anti-inflammatory Th2-related cytokines The results of this study suggest that osthole exert beneficial therapeutic effect in experimental colitis and improved the efficacy of the synthetized drugs such as sulfasalazine. Therefore, osthole may have a valuable sound in the treatment of inflammatory bowel disease.
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Icariside II attenuates myocardial fibrosis by inhibiting nuclear factor-κB and the TGF-β1/Smad2 signalling pathway in spontaneously hypertensive rats
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Shu Fu, Ye-Li Li, Yu-Ting Wu, Yun Yue, Zhi-Qiang Qian, Dan-Li Yang
Studies have demonstrated that icariin plays important roles in preventing hypertension and improving myocardial hypertrophy, inflammatory and infiltration. Icariside (ICS II) is the main metabolite of icariin, which has anti-inflammatory and anti-oxidant activities and protects against ischaemic brain injury. Whether ICS II improves myocardial fibrosis in spontaneously hypertensive rats (SHRs) and the related mechanism remain unknown. Some studies have suggested that TGF-β and the nuclear factor κB signalling pathway play a key role in the progression of myocardial fibrosis. Therefore, in the current study, we aimed to evaluate the effects of ICS II on induced myocardial fibrosis in SHRs and explore the mechanism underlying this activity. The SHRs were treated with ICS II (4, 8, and 16 mg/kg) via daily gavage for 12 weeks. Left ventricular function was detected using the Vevo2100 system, and the collagen area was measured by Masson staining. The results indicated that ICS II markedly improved left ventricular function and decreased the left ventricular myocardial collagen area compared with the SHR group. To further investigate the mechanism underlying this activity, we measured the protein expression of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), Smad2, inhibitory κB (IκB), and nuclear factor κB (NF-κB) p65 by Western blot. The results showed that ICS II inhibited NF-κB p65 expression and the TGF-β1/Smad2 signalling pathways. In conclusion, the present results suggest that ICS II suppresses myocardial fibrosis in SHRs, and this effect might be at least partially mediated through suppression of NF-kB signalling and the TGF-β1/Smad2 signalling pathway.
http://ift.tt/2BKTKaH
miR-145 overexpression triggers alteration of the whole transcriptome and inhibits breast cancer development
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Peng Ye, Yu Shi, Nairui An, Qian Zhou, Juan Guo, Xinghua Long
Cumulative evidence has associated microRNA (miRNA) with cancer development, and among those miRNAs, miR-145 has been identified as an anti-oncomiRNA. However, the comprehensive mechanisms of action of miR-145 in breast cancer development have not yet been fully elucidated. Herein, we performed next-generation sequencing to detect the expression profiles of the transcriptome and conducted cellular function experiments after miR-145 overexpression. The results verified the inhibitory effects of miR-145 on breast cancer cell proliferation, colony formation, migration and invasion. Sequencing data revealed that miR-145 triggered the alteration of the whole transcriptome and further led to regulation of the competing endogenous RNA (ceRNA) network. Our study also identified a list of 49 target mRNAs of miR-145 and specific non-coding RNAs, which could be utilized as potential breast cancer biomarkers. This study might serve as a significant platform for further research on miR-145 along with the ceRNA network in breast cancer.
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Annona muricata Linn. leaf as a source of antioxidant compounds with in vitro antidiabetic and inhibitory potential against α-amylase, α-glucosidase, lipase, non-enzymatic glycation and lipid peroxidation
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Allisson Benatti Justino, Natália Carnevalli Miranda, Rodrigo Rodrigues Franco, Mário Machado Martins, Neide Maria da Silva, Foued Salmen Espindola
Annona muricata leaves are used in traditional medicine to manage diabetes mellitus and its complications. The aim of this study was to evaluate the potential in vitro antidiabetic properties of Annona muricata leaf by identifying its main phytochemical constituents and characterizing the phenolic-enriched fractions for their in vitro antioxidant capacity and inhibitory activities against glycoside and lipid hydrolases, advanced glycation end-product formation and lipid peroxidation. Ethanol extract of A. muricata leaf was subjected to a liquid-liquid partitioning and its fractions were used in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant (DPPH, ORAC, FRAP and Fe2+-ascorbate-induced lipid peroxidation assays) and anti-glycation (BSA-fructose, BSA-methylglyoxal and arginine-methylglyoxal models) capacities. In addition, identification of the main bioactive compounds of A. muricata leaf by HPLC-ESI-MS/MS analysis was carried out. Ethyl acetate (EtOAc) and n-butanol (BuOH) fractions showed, respectively, antioxidant properties (ORAC 3964 ± 53 and 2707 ± 519 μmol trolox eq g−1, FRAP 705 ± 35 and 289 ± 18 μmol trolox eq g−1, and DPPH IC50 4.3 ± 0.7 and 9.3 ± 0.8 μg mL−1) and capacity to reduce liver lipid peroxidation (p < .01). Also, EtOAc and BuOH, respectively, inhibited glycation in BSA-fructose (IC50 45.7 ± 13.5 and 61.9 ± 18.2 μg mL−1), BSA-methylglyoxal (IC50 166.1 ± 21.6 and 413.2 ± 49.5 μg mL−1) and arginine-methylglyoxal (IC50 437.9 ± 89.0 and 1191.0 ± 199.0 μg mL−1) assays, α-amylase (IC50 9.2 ± 2.3 and 6.1 ± 1.6 μg mL−1), α-glucosidase (IC50 413.1 ± 121.1 and 817.4 ± 87.9 μg mL−1) and lipase (IC50 74.2 ± 30.1 and 120.3 ± 50.5 μg.mL−1), and presented lower cytotoxicity, when compared to the other fractions and crude extract. Various biomolecules known as potent antioxidants were identified in these fractions, such as chlorogenic and caffeic acids, procyanidins B2 and C1, (epi)catechin, quercetin, quercetin-hexosides and kaempferol. This study presents new biological activities not yet described for A. muricata, which contributes to the understanding of the potential effectiveness in the use of the A. muricata leaf, especially its polyphenols-enriched fractions, for the management of diabetes mellitus and its complications.
Graphical abstract
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Ginsenoside Rb2 promotes glucose metabolism and attenuates fat accumulation via AKT-dependent mechanisms
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Shanshan Dai, Yilian Hong, Jing Xu, Yi Lin, Qiya Si, Xuejiang Gu
Ginsenosides, the major active constituents of ginseng, have been demonstrated possess anti-diabetic, anti-inflammatory effects. Ginsenoside Rb2 (Rb2) is the most abundant saponin in Panax ginseng, this study investigates the role of Rb2 in the anti-hyperglycemic mechanism of insulin-sensitive cell lines 3T3-L1 adipocytes as well as high fat diet-induced obesity mice. Glucose uptake of 3T3-L1 adipocytes was measured. The insulin signaling cascade, including insulin AKT, insulin receptor (IR) beta-subunit, IR substrate (IRS) -1, phosphatidylinositol 3-kinase (PI3K) were also examined. TNF-α-treated 3T3-L1 adipocytes were used as an insulin resistant model in which p-AKT, c-Jun NH2-terminal kinase (JNK), MAPK, and nuclear factor (NF) -κB signaling cascades were examined. As an in vivo study, C57BL/6J mice were fed with a high-fat diet for 9 weeks, with or without Rb2 supplementation. Then we investigated the effects of Rb2 on glycometabolism in these high fat diet-induced obesity mice. Our results demonstrate Rb2 increases glucose uptake in 3T3-L1 adipocytes, independent of insulin receptor β-subunit (IRβ) and principally through the insulin receptor substrate (IRS)-1-phosphatidylinositol 3-kinase (PI3K)-AKT/PKB pathway. Rb2 inhibited TNF-α-induced activation of MAPK and nuclear factor (NF)-κB signaling pathway as well as the expression of inflammatory factors. In high fat diet-induced obesity mice, Rb2 attenuated fat mass and regulated insulin resistance. In mouse adipose tissue, Rb2 phosphorylation of AKT was correlated with glycometabolism. Furthermore, Rb2 attenuates insulin resistance in 3T3-L1 adipocytes, reduces fat mass, and improves insulin sensitivity in high fat diet-obesity mice.
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LncRNA Uc.173 is a key molecule for the regulation of lead-induced renal tubular epithelial cell apoptosis
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Jiabi Qin, Huacheng Ning, Yao Zhou, Yue Hu, Bo Huang, Yue Wu, Ruixue Huang
Transcribed ultra-conserved region (T-UCR) transcripts are a novel class of long non-coding RNAs (lncRNAs) transcribed from ultra-conserved region which is highly conserved in human, rat, and mouse genome. LncRNA UC.173 has been found significantly down-regulated in lead-exposed population and lead-exposed animal mode, and had an inhibitory effect on lead-induced nerve cell apoptosis. We supposed that lncRNA UC.173 had an inhibitory effect on lead-induced renal tubular epithelial cell apoptosis. Thus, the aim of our study was to explore the function of lncRNA UC.173 in lead-exposed renal tubular epithelial cells. In our results, lead exposure inhibited renal tubular epithelial cells viability and promoted cell apoptosis and apoptosis-associated genes expression, but no effect on cell-cycle distribution. Lead exposure inhibited the expression of lncRNA UC.173 in renal tubular epithelial cells, and the inhibition effect was time-dependent and concentration-dependent. Up-regulation of lncRNA UC.173 had no effect on renal tubular epithelial cell viability, cell cycle and apoptosis, but significantly rescued lead-induced inhibition of renal tubular epithelial cell viability and suppressed lead-induced cell apoptosis. In summary, our experiments suggest that lncRNA UC.173 is certainly involved in the regulation of lead-induced renal tubular epithelial cell apoptosis, which may supply a new strategy to minimize lead-induced nephrotoxicity.
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Tumor suppressive ZBTB4 inhibits cell growth by regulating cell cycle progression and apoptosis in Ewing sarcoma
Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Yongxin Yu, Ruguo Shang, Yunzhou Chen, Jiehua Li, Zhichao Liang, Jianwei Hu, Kai Liu, Chao Chen
Increasing studies identify that zinc finger and BTB domain containing 4 (ZBTB4) functions as a tumor suppressor in human cancer. Underexpression of ZBTB4 is correlated with poor survival of breast cancer patients. However, the expression of ZBTB4 and its possible function remain unknown in Ewing sarcoma (ES). To clarify these issues, we investigated the expression difference between ES and normal tissues based on Gene Expression Omnibus (GEO) data from R2: Genomics Analysis and Visualization Platform (http://r2.amc.nl). GEO data (GSE68776) indicated that the expression of ZBTB4 in ES tissues was prominently lower compare to normal tissues. Our data further confirmed the underexpression of ZBTB4 in ES tissues. GEO data (GSE63157 and GSE17679) demonstrated that ZBTB4 underexpression predicted a obvious shorter overall survival and event-free survival of ES patients. Interestingly, the expression of ZBTB4 was inversely correlated with proliferation makers Ki-67 and proliferating cell nuclear antigen (PCNA) in ES tissues. In vitro, ZBTB4 overexpression inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in SK-ES-1 and RD-ES cells. Moreover, ZBTB4 restoration suppressed the tumor growth of ES in mice. An inversely correlation between ZBTB4 and Survivin expression was observed in ES tissues. ZBTB4 overexpression reduced Survivin abundance in ES cells. Notably, Survivin restoration reversed the regulatory effect of ZBTB4 on ES cell proliferation, cell cycle progression and apoptosis. To conclude, our data indicated that ZBTB4 exhibited a tumor suppressive role in ES possibly by reducing Survivin expression. ZBTB4/Survivin axis might serve as a therapeutic target for ES.
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Trends of incidence, mortality, and survival of multiple myeloma in Switzerland between 1994 and 2013
Source:Cancer Epidemiology, Volume 53
Author(s): Martin Andres, Anita Feller, Volker Arndt
BackgroundTreatment of multiple myeloma has changed considerably over the last two decades with remarkable reduction in mortality rates in clinical trials and in population-based studies. Since health care systems and patient management differ between countries, population-based data from cancer registries with high coverage may provide further insight into real-life achievements and unmet needs. We report on the first population-based nation-wide study of incidence, mortality and survival of multiple myeloma in Switzerland covering the era of autologous stem cell transplantation and the first proteasome inhibitors and immunomodulatory drugs.MethodsWe performed a retrospective registry study with data from the National Institute for Cancer Epidemiology and Registration (NICER) database in Switzerland from 1994 to 2013.ResultsWe identified 5770 patients with multiple myeloma. Incidence has increased from 419 new cases per year in 1994–1998 to 557 new cases per year in 2009–2013 while the age-adjusted incidence rate remained stable at 4.7–5.0 per 100′000 person-years. Five- and 10-year relative survival increased from 32.6% (95%CI 29.3–36.0) and 17.8% (95%CI 14.9–21.0) in 1994–1998 to 46.4% (95%CI 43.3–49.3) and 25.0% (95%CI 21.9–28.3) in 2009–2013.ConclusionThe increase in incidence can be attributed to demographic changes. There is a trend to longer relative survival in all age groups with substantial increase in myeloma patients aged less than 75 years and only minimal changes in older persons.
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Esophageal cancer male to female incidence ratios in Africa: A systematic review and meta-analysis of geographic, time and age trends
Source:Cancer Epidemiology, Volume 53
Author(s): Daniel R.S. Middleton, Liacine Bouaoun, Rachel Hanisch, Freddie Bray, Charles Dzamalala, Steady Chasimpha, Diana Menya, Charles Gombé Mbalawa, Guy N'Da, Mathewos A. Woldegeorgis, Ramou Njie, Moussa Koulibaly, Nathan Buziba, Josefo Ferro, Hassan Nouhou, Femi Ogunbiyi, Henry R. Wabinga, Eric Chokunonga, Margaret Z. Borok, Anne R. Korir, Amos O. Mwasamwaja, Blandina T. Mmbaga, Joachim Schüz, Valerie A. McCormack
Esophageal squamous cell carcinoma (ESCC) remains the predominant histological subtype of esophageal cancer (EC) in many transitioning countries, with an enigmatic and geographically distinct etiology, and consistently elevated incidence rates in many Eastern and Southern African countries. To gain epidemiological insights into ESCC patterns across the continent, we conducted a systematic review and meta-analysis of male-to-female (M:F) sex ratios of EC age-standardised (world) incidence rates in Africa according to geography, time and age at diagnosis. Data from 197 populations in 36 countries were included in the analysis, based on data from cancer registries included in IARC's Cancer Incidence in Five Continents, Cancer in Africa and Cancer in Sub-Saharan Africa reports, alongside a systematic search of peer-reviewed literature. A consistent male excess in incidence rates overall (1.7; 95% CI: 1.4, 2.0), and in the high-risk Eastern (1.6; 95% CI: 1.4, 1.8) and Southern (1.8; 95% CI: 1.5, 2.0) African regions was observed. Within the latter two regions, there was a male excess evident in 30–39 year olds that was not observed in low-risk regions. Despite possible referral biases affecting the interpretability of the M:F ratios in place and time, the high degree of heterogeneity in ESCC incidence implies a large fraction of the disease is preventable, and directs research enquiries to elucidate early-age exposures among young men in Africa.
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Development and validation of a prognostic index for survival in non-small cell lung cancer: Results from a Tunisian cohort study
Source:Cancer Epidemiology, Volume 53
Author(s): Ghassen Soussi, Nissaf Ben Alaya, Nawel Chaouch, Hajer Racil
IntroductionDespite the continuous efforts made with the TNM system, the issue of heterogeneity of prognosis within the stages of non-small cell lung cancer (NSCLC) could not be resolved. Our aim was to identify prognostic factors and develop an index to predict NSCLC survival with greater accuracy.MethodsWe conducted a survival study over 5 years on patients with NSCLC. Kaplan–Meier analysis followed by Cox regression modelling were used. Prognostic indices were derived, using either an additive or a multiplicative pattern, and were compared by their receiver operating characteristics (ROC) curves. We then proceeded to a risk stratification and validation of the index on the derivation cohort.ResultsTwo hundred and sixty-two NSCLC patients were included. Two models were constructed, using the following nine variables as prognostic factors: age, performance status, haemoglobin level, leucocyte count, calcium, lactate dehydrogenase, alkaline phosphatase levels, histological type and TNM stage. Four prognostic indices were derived, and the best one was picked and validated on a population of five risk groups. The higher the risk group, the shorter the survival.ConclusionsThis novel and simple prognostic tool could predict survival more accurately in patients with NSCLC.
http://ift.tt/2nPaLY5
Brainstem Injury in Pediatric Patients With Posterior Fossa Tumors Treated With Proton Beam Therapy and Associated Dosimetric Factors
Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Michelle S. Gentile, Beow Y. Yeap, Harald Paganetti, Claire P. Goebel, Dillon E. Gaudet, Sara L. Gallotto, Elizabeth A. Weyman, Michael L. Morgan, Shannon M. MacDonald, Drosoula Giantsoudi, Judith Adams, Nancy J. Tarbell, Hanne Kooy, Torunn I. Yock
PurposeProton radiation therapy is commonly used in young children with brain tumors for its potential to reduce late effects. However, some proton series report higher rates of brainstem injury (0%-16%) than most photon series (2.2%-8.6%). We report the incidence of brainstem injury and a risk factor analysis in pediatric patients with posterior fossa primary tumors treated with proton radiation therapy at our institution.Methods and MaterialsThe study included 216 consecutive patients treated between 2000 and 2015. Dosimetry was available for all but 4 patients. Grade 2 to 5 late brainstem toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.ResultsThe histologies include medulloblastoma (n=154, 71.3%), ependymoma (n=56, 25.9%), and atypical teratoid rhabdoid tumor (n=6, 2.8%). The median age at irradiation was 6.6 years (range, 0.5-23.1 years); median dose, 54 gray relative biological effectiveness (Gy RBE) (range, 46.8-59.4 Gy RBE); and median follow-up period, 4.2 years (range, 0.1-15.3 years) among 198 survivors. Of the patients, 83.3% received chemotherapy; 70.4% achieved gross total resection. The crude rate of injury was 2.3% in all patients, 1.9% in those with medulloblastoma, 3.6% in those with ependymoma, and 0% in those with atypical teratoid rhabdoid tumor. The 5-year cumulative incidence of injury was 2.0% (95% confidence interval, 0.7%-4.8%). The median brainstem dose (minimum dose received by 50% of brainstem) in the whole cohort was 53.6 Gy RBE (range, 16.5-56.8 Gy RBE); maximum point dose within the brainstem (Dmax), 55.2 Gy RBE (range, 48.4-60.5 Gy RBE); and mean dose, 50.4 Gy RBE (range, 21.1-56.7 Gy RBE). In the 5 patients with injury, the median minimum dose received by 50% of the brainstem was 54.6 Gy RBE (range, 50.2-55.1 Gy RBE); Dmax, 56.2 Gy RBE (range, 55.0-57.1 Gy RBE); mean dose, 51.3 Gy RBE (range, 45.4-54.4 Gy RBE); and median volume of the brainstem receiving ≥55 Gy RBE (V55), 27.4% (range, 0%-59.4%). Of the 5 patients with injury, 4 had a brainstem Dmax in the highest quartile (≥55.8 Gy RBE, P = .016) and a V55 in the highest tertile (>6.0%) of the cohort distribution (P = .047). Of the 5 patients with injury, 3 were aged >6 years (age range, 4.1-22.8 years), and 4 of 5 patients received chemotherapy and achieved gross total resection.ConclusionsThe incidence of injury in pediatric patients with posterior fossa tumors is consistent with previous reports in the photon setting. Our data suggest that when Dmax and V55 are kept <55.8 Gy RBE and ≤6.0%, respectively, the 5-year rate of radiation brainstem injury would be <2%.
http://ift.tt/2FQfr76
In Reply to Daisne et al
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Jean-Emmanuel Bibault, Philippe Giraud, Magali Morelle, Lionel Perrier, Marius Huguet
http://ift.tt/2EKLeXU
Stereotactic Radiosurgery for Resected Brain Metastases: New Evidence Supports a Practice Shift, but Questions Remain
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Giuseppe Minniti, Scott G. Soltys, Lia M. Halasz, John C. Breneman, Michael Chan, Nadia N. Laack, John P. Kirkpatrick
http://ift.tt/2E7Wtsc
Radiation Oncology in Egypt: A Model for Africa
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Mohamed S. Zaghloul, Mai K. Bishr
http://ift.tt/2En5jFV
Secondary Acute Leukemia in Sarcoma Patients: A Population-Based Study
Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Nina N. Sanford, Allison M. Martin, Andrew M. Brunner, Gregory M. Cote, Edwin Choy, Thomas F. DeLaney, Ayal A. Aizer, Yen-Lin Chen
PurposeTo compare rates of secondary acute leukemia between sarcoma patients and the general population, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry, and to examine whether various patient, tumor, and treatment factors were associated with development of a secondary acute leukemia.Methods and MaterialsPatients with a primary diagnosis of connective tissue malignancy between 1973 and 2008 in the SEER database were included. Multivariable competing risk analysis was used to determine risk factors associated with subsequent development of acute leukemia. Using observed-to-expected ratios, we compared incidence rates of secondary acute leukemia between sarcoma patients and the general population.ResultsA total of 72,945 patients were identified, with median follow-up of 131 months. On multivariable competing risk analysis, factors associated with increased risk of secondary acute leukemia included receipt of radiation therapy (hazard ratio [HR] 1.67, P=.02), distant disease (HR 2.67, P=.004), male gender (HR 1.53, P=.03), year of diagnosis (HR 0.98, P=.049), and Ewing sarcoma histology (HR 9.95, P < .0001) and osteosarcoma histology (HR 5.06, P=.0001). The observed-to-expected ratio for development of a secondary acute leukemia was 3.67 (95% confidence interval [CI] 1.95-6.28), 3.41 (95% CI 2.73-4.20), and 1.6 (95% CI 1.38-8.19) for acute lymphocytic leukemia, acute myeloid leukemia, and acute monocytic leukemia, respectively. The 10-year cumulative incidence of secondary acute leukemia for patients who did and did receive radiation therapy was 0.3% versus 0.1% (P=.02).ConclusionsPatients treated for sarcoma, in particular those with Ewing sarcoma and osteosarcoma histology, seem to have a higher incidence of secondary acute leukemia as compared with the general population. Treatment factors including radiation therapy and chemotherapy seem to play a role in this increased risk, although the absolute incidence nevertheless remains very small.
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Seymour H. Levitt, MD, 1928-2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Luther W. Brady
http://ift.tt/2E7GAC2
Involved-Site Radiation to Maximize Control
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Parag Sanghvi
http://ift.tt/2E37Xx9
Issue Highlights
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
http://ift.tt/2Erc5dK
Watch and Wait, Salvage Later
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Avyakta Kallam, James O. Armitage
http://ift.tt/2En5jpp
Development of a Radiation Oncology Resident Continuity Clinic to Improve Clinical Competency and Patient Compliance
Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Stella K. Yoo, Shelly X. Bian, Eugene Lin, Sukhjeet S. Batth, Lydia W. Ng, Jacob Andrade, Patrick A. Williams, Anthony H. Pham, Omar M. Ragab, Naomi R. Schechter, Eric L. Chang, Richard L.S. Jennelle
http://ift.tt/2EmTnE5
Complex DNA Damage Induced by High Linear Energy Transfer Alpha-Particles and Protons Triggers a Specific Cellular DNA Damage Response
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Rachel J. Carter, Catherine M. Nickson, James M. Thompson, Andrzej Kacperek, Mark A. Hill, Jason L. Parsons
PurposeTo investigate the precise mechanism of recognition and processing of ionizing radiation (IR)-induced complex DNA damage (CDD), where two or more DNA lesions are in close proximity, in cellular DNA which is packaged with histones to form chromatin.Methods and MaterialsHeLa and oropharyngeal squamous cell carcinoma (UMSCC74A and UMSCC6) cells were irradiated with high linear energy transfer (LET) α-particles or protons, versus low-LET protons and X rays. At various time points after irradiation, site-specific histone post-translational modifications were analyzed by quantitative Western blotting; DNA damage and repair were measured by different versions of the comet assay; and cell survival was determined using clonogenic assays.ResultsSite-specific histone post-translational modifications after low- and high-LET radiation, particularly proton irradiation, were screened, aiming to identify those responsive to CDD. We demonstrate that histone H2B ubiquitylated on lysine 120 (H2Bub) is specifically induced several hours after irradiation in response to high-LET α-particles and protons but not by low-LET protons or X rays/γ-radiation. This is associated with increased levels of CDD, which contributes to decreased cell survival. We further discovered that modulation of H2Bub is under the control of two E3 ubiquitin ligases, MSL2 and RNF20/RNF40 complex, whose depletion leads to defective processing and further persistence of CDD, and to additional decreased cell survival after irradiation.ConclusionThis study demonstrates that the signaling and repair of CDD, particularly induced by high-LET IR is co-ordinated through the specific induction of H2Bub catalyzed by MSL2 and RNF20/40, a mechanism that contributes significantly to cell survival after irradiation.
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Utilizing 10-Year Results From the American Board of Radiology Clinical Examination to Identify Areas for Programmatic Improvement
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Robert B. Den, Marlene Folino, Adam P. Dicker
http://ift.tt/2E7v9dT
In Reply to Leddy
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Nishant K. Shah, Brad Zehr, Ankit Agarwal, Apar Gupta, Ariel E. Hirsch
http://ift.tt/2E9OMC8
In Reply to Overgaard et al
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): William A. Stokes, Sana D. Karam
http://ift.tt/2EnZloh
Radiation Safety for Pregnant Workers at a Proton Facility
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Genevieve Maquilan, Marc R. Bussière, Joseph McCormack, Tara Medich, Andrzej Niemierko, Helen A. Shih
PurposeTo quantify radiation exposure of radiation therapy technologists (RTTs) in a proton treatment facility in comparison with a photon therapy facility, to inform and establish these specialized occupational safety guidelines.Methods and MaterialsTwo groups of RTTs, consisting of 12 full-time passive scattering proton RTTs and 18 full-time conventional photon RTTs, wore an additional dosimetry badge at the waist for a period of 14 weeks. The 2 groups of RTTs were given identical instructions on the proper use of the badges. To compare exposures between passive scatter and scanning beam systems, exposure rates from activated equipment in both systems were measured.ResultsOver the 14-week period, the mean and standard deviation background-corrected dose for the passively scattered proton RTTs was 39.9 ± 5.4 mrem. The mean and standard deviation background-corrected dose for the conventional photon RTTs was similar at 39.9 ± 9.0 mrem (P = .6). Exposure rates were lower in equipment activated in a scanning beam system in comparison with those from a passive scatter system.ConclusionsRadiation dose to passively scattered proton and photon radiation therapy technologists was similar when measured with a dosimeter worn at the waist over a period of 14 weeks. On the basis of these data, the departmental policy permits pregnant radiation workers to work in proton treatment areas, and the policy for pregnant workers does not differ between proton and photon radiation workers or between passive scatter and scanning beam systems. All employees are encouraged to limit time near and proximity to activated equipment.
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Editorial Board
Source:Behavioural Brain Research, Volume 342
http://ift.tt/2EoDehz
Comparison of dosimetric parameters derived from whole organ and wall contours for bladder and rectum in cervical cancer patients treated with intracavitary and interstitial brachytherapy
Source:Radiotherapy and Oncology
Author(s): Rachel Gerber, Alexandra Rink, Jennifer Croke, Jette Borg, Akbar Beiki-Ardakani, Anthony Fyles, Michael Milosevic, Jason Xie, Harald Keller, Kathy Han
For volumes up to 2 cm3 of the bladder and possibly up to 5 cm3 of the rectum, doses computed from the whole organ were good estimates of the doses in the wall in cervix brachytherapy, and there were no significant differences between patients treated with or without interstitial needles.
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Unique electrophysiological and impedance signatures between encapsulation types: An analysis of biological Utah array failure and benefit of a biomimetic coating in a rat model
Source:Biomaterials, Volume 161
Author(s): Patrick A. Cody, James R. Eles, Carl F. Lagenaur, Takashi D.Y. Kozai, X.Tracy Cui
Intracortical microelectrode arrays, especially the Utah array, remain the most common choice for obtaining high dimensional recordings of spiking neural activity for brain computer interface and basic neuroscience research. Despite the widespread use and established design, mechanical, material and biological challenges persist that contribute to a steady decline in recording performance (as evidenced by both diminished signal amplitude and recorded cell population over time) or outright array failure. Device implantation injury causes acute cell death and activation of inflammatory microglia and astrocytes that leads to a chronic neurodegeneration and inflammatory glial aggregation around the electrode shanks and often times fibrous tissue growth above the pia along the bed of the array within the meninges. This multifaceted deleterious cascade can result in substantial variability in performance even under the same experimental conditions. We track both impedance signatures and electrophysiological performance of 4 × 4 floating microelectrode Utah arrays implanted in the primary monocular visual cortex (V1m) of Long-Evans rats over a 12-week period. We employ a repeatable visual stimulation method to compare signal-to-noise ratio as well as single- and multi-unit yield from weekly recordings. To explain signal variability with biological response, we compare arrays categorized as either Type 1, partial fibrous encapsulation, or Type 2, complete fibrous encapsulation and demonstrate performance and impedance signatures unique to encapsulation type. We additionally assess benefits of a biomolecule coating intended to minimize distance to recordable units and observe a temporary improvement on multi-unit recording yield and single-unit amplitude.
http://ift.tt/2BLpOLu
Lower fluidity of supported lipid bilayers promotes neuronal differentiation of neural stem cells by enhancing focal adhesion formation
Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Wangping Hao, Jie Han, Yun Chu, Lei Huang, Jie Sun, Yan Zhuang, Xiaoran Li, Hongwei Ma, Yanyan Chen, Jianwu Dai
Extensive studies have been performed to understand how the mechanical properties of a stem cell's microenvironment influence its behaviors. Supported lipid bilayers (SLBs), a well-known biomimetic platform, have been used to mimic the dynamic characteristics of the extracellular matrix (ECM) because of their fluidity. However, the effect of the fluidity of SLBs on stem cell fate is unknown. We constructed SLBs with different fluidities to explore the influence of fluidity on the differentiation of neural stem cells (NSCs). The results showed that the behavior of NSCs was highly dependent on the fluidity of SLBs. Low fluidity resulted in enhanced focal adhesion formation, a dense network of stress fibers, stretched and elongated cellular morphology and increased neuronal differentiation, while high fluidity led to less focal adhesion formation, immature stress fibers, round cellular morphology and more astrocyte differentiation. Mechanistic studies revealed that low fluidity may have enhanced focal adhesion formation, which activated FAK-MEK/ERK signaling pathways and ultimately promoted neuronal differentiation of NSCs. This work provides a strategy for manipulating the dynamic matrix surface for the development of culture substrates and tissue-engineered scaffolds, which may aid the understanding of how the dynamic ECM influences stem cell behaviors as well as improve the efficacy of stem cell applications.
Graphical abstract
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Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation
Source:Biomaterials, Volume 161
Author(s): Hong Ji Yan, Tommaso Casalini, Gry Hulsart-Billström, Shujiang Wang, Oommen P. Oommen, Matteo Salvalaglio, Sune Larsson, Jöns Hilborn, Oommen P. Varghese
Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.
http://ift.tt/2BKCIJR
Exogenous ROS-induced cell sheet transfer based on hematoporphyrin-polyketone film via a one-step process
Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Min-Ah Koo, Mi Hee Lee, Byeong-Ju Kwon, Gyeung Mi Seon, Min Sung Kim, Dohyun Kim, Ki Chang Nam, Jong-Chul Park
To date, most of invasive cell sheet harvesting methods have used culture surface property variations, such as wettability, pH, electricity, and magnetism, to induce cell detachment. These methods that rely on surface property changes are effective when cell detachment prior to application is necessary, but of limited use when used for cell sheet transfer to target regions. The study reports a new reactive oxygen species (ROS)-induced strategy based on hematoporphyrin-incorporated polyketone film (Hp-PK film) to transfer cell sheets directly to target areas without an intermediate harvesting process. After green LED (510 nm) irradiation, production of exogenous ROS from the Hp-PK films induces cell sheet detachment and transfer. The study suggests that ROS-induced cell detachment property of the Hp-PK film is closely related to conformational changes of extracellular matrix (ECM) proteins. Also, this strategy with the Hp-PK film can be applied by regulating production rate of exogenous ROS in various types of cells, including fibroblasts, mesenchymal stem cells and keratinocytes. In conclusion, ROS-induced method using the Hp-PK film can be used for one-step cell sheet transplantation and has potential in biomedical applications.
Graphical abstract
http://ift.tt/2Ben34m
Harnessing macrophage-mediated degradation of gelatin microspheres for spatiotemporal control of BMP2 release
Source:Biomaterials, Volume 161
Author(s): Ramkumar T. Annamalai, Paul A. Turner, William F. Carson, Benjamin Levi, Steven Kunkel, Jan P. Stegemann
Biomaterials-based approaches to harnessing the immune and inflammatory responses to potentiate wound healing hold important promise. Bone fracture healing is characterized by an acute inflammatory phase, followed by a transition to a regenerative and repair phase. In this study, we developed genipin-crosslinked gelatin microspheres designed to be preferentially degraded by inflammatory (M1) macrophages. Highly crosslinked (>90%) microspheres allowed efficient incorporation of bioactive bone morphogenetic protein 2 (BMP2), a potent stimulator of osteogenesis in progenitor cells, via electrostatic interactions. Release of BMP2 was directly correlated with degradation of the gelatin matrix. Exposure of microspheres to polarized murine macrophages showed that degradation was significantly higher in the presence of M1 macrophages, relative to alternatively activated (M2) macrophages and unpolarized controls. Microsphere degradation in the presence of non-inflammatory cells resulted in very low degradation rates. The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs) by macrophages were consistent with the observed phenotype-dependent degradation rates. Indirect co-culture of BMP2-loaded microspheres and macrophages with isolated adipose-derived mesenchymal stem cells (MSC) showed that M1 macrophages produced the strongest osteogenic response, comparable to direct supplementation of the culture medium with BMP2. Controlled release systems that are synchronized with the inflammatory response have the potential to provide better spatiotemporal control of growth factor delivery and therefore may improve the outcomes of recalcitrant wounds.
http://ift.tt/2BN0R2q
Dual non-viral gene delivery from microparticles within 3D high-density stem cell constructs for enhanced bone tissue engineering
Source:Biomaterials, Volume 161
Author(s): Alexandra McMillan, Minh Khanh Nguyen, Tomas Gonzalez-Fernandez, Peilin Ge, Xiaohua Yu, William L. Murphy, Daniel J. Kelly, Eben Alsberg
High-density mesenchymal stem cell (MSC) aggregates can be guided to form bone-like tissue via endochondral ossification in vitro when culture media is supplemented with proteins, such as growth factors (GFs), to first guide the formation of a cartilage template, followed by culture with hypertrophic factors. Recent reports have recapitulated these results through the controlled spatiotemporal delivery of chondrogenic transforming growth factor-β1 (TGF-β1) and chondrogenic and osteogenic bone morphogenetic protein-2 (BMP-2) from microparticles embedded within human MSC aggregates to avoid diffusion limitations and the lengthy, costly in vitro culture necessary with repeat exogenous supplementation. However, since GFs have limited stability, localized gene delivery is a promising alternative to the use of proteins. Here, mineral-coated hydroxyapatite microparticles (MCM) capable of localized delivery of Lipofectamine-plasmid DNA (pDNA) nanocomplexes encoding for TGF-β1 (pTGF-β1) and BMP-2 (pBMP-2) were incorporated, alone or in combination, within MSC aggregates from three healthy porcine donors to induce sustained production of these transgenes. Three donor populations were investigated in this work due to the noted MSC donor-to-donor variability in differentiation capacity documented in the literature. Delivery of pBMP-2 within Donor 1 aggregates promoted chondrogenesis at week 2, followed by an enhanced osteogenic phenotype at week 4. Donor 2 and 3 aggregates did not promote robust glycosaminoglycan (GAG) production at week 2, but by week 4, Donor 2 aggregates with pTGF-β1/pBMP-2 and Donor 3 aggregates with both unloaded MCM and pBMP-2 enhanced osteogenesis compared to controls. These results demonstrate the ability to promote osteogenesis in stem cell aggregates through controlled, non-viral gene delivery within the cell masses. These findings also indicate the need to screen donor MSC regenerative potential in response to gene transfer prior to clinical application. Taken together, this work demonstrates a promising gene therapy approach to control stem cell fate in biomimetic 3D condensations for treatment of bone defects.
http://ift.tt/2BcoDDM
A self-delivery membrane system for enhanced anti-tumor therapy
Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Wen-Xiu Qiu, Ming-Kang Zhang, Li-Han Liu, Fan Gao, Lu Zhang, Shi-Ying Li, Bo-Ru Xie, Chi Zhang, Jun Feng, Xian-Zheng Zhang
Nowadays, cell membrane targeting therapy has drawn much attention for its high anti-tumor effect by avoiding the cellular barriers. In this study, therapeutic agent conjugated chimeric peptide (Cp) was anchored in cracked cancer cell membranes (CCCM) to construct a self-delivery membrane system (M-Cp), which could relize precise cell membrane targeting therapy. It was found that compared with Cp, M-Cp could target to the cancer cell membrane with longer retention time, which is very crucial for in vivo applications. And the superior cell membrane targeting ability was attributed to the specific proteins (focal adhesion proteins, focal adhesion kinase, RHO family proteins, and integrin) on the CCCM surface. Importantly, the M-Cp could promote tumor-specific immune response, which further enhanced anti-tumor effect when combined with therapeutic agents in M-Cp. What's more, this self-delivery membrane system could be used as a template for cell membrane targeting therapy by changing the therapeutic agents as well as the CCCM, and this strategy would open a new window for various cell membrane targeting therapy.
Graphical abstract
http://ift.tt/2BN0RPY
Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis
Source:Biomaterials, Volume 161
Author(s): Xin Cui, Renee-Tyler Tan Morales, Weiyi Qian, Haoyu Wang, Jean-Pierre Gagner, Igor Dolgalev, Dimitris Placantonakis, David Zagzag, Luisa Cimmino, Matija Snuderl, Raymond H.W. Lam, Weiqiang Chen
Glioblastoma (GBM) is the most lethal primary adult brain tumor and its pathology is hallmarked by distorted neovascularization, diffuse tumor-associated macrophage infiltration, and potent immunosuppression. Reconstituting organotypic tumor angiogenesis models with biomimetic cell heterogeneity and interactions, pro-/anti-inflammatory milieu and extracellular matrix (ECM) mechanics is critical for preclinical anti-angiogenic therapeutic screening. However, current in vitro systems do not accurately mirror in vivo human brain tumor microenvironment. Here, we engineered a three-dimensional (3D), microfluidic angiogenesis model with controllable and biomimetic immunosuppressive conditions, immune-vascular and cell-matrix interactions. We demonstrate in vitro, GL261 and CT-2A GBM-like tumors steer macrophage polarization towards a M2-like phenotype for fostering an immunosuppressive and proangiogenic niche, which is consistent with human brain tumors. We distinguished that GBM and M2-like immunosuppressive macrophages promote angiogenesis, while M1-like pro-inflammatory macrophages suppress angiogenesis, which we coin "inflammation-driven angiogenesis." We observed soluble immunosuppressive cytokines, predominantly TGF-β1, and surface integrin (αvβ3) endothelial-macrophage interactions are required in inflammation-driven angiogenesis. We demonstrated tuning cell-adhesion receptors using an integrin (αvβ3)-specific collagen hydrogel regulated inflammation-driven angiogenesis through Src-PI3K-YAP signaling, highlighting the importance of altered cell-ECM interactions in inflammation. To validate the preclinical applications of our 3D organoid model and mechanistic findings of inflammation-driven angiogenesis, we screened a novel dual integrin (αvβ3) and cytokine receptor (TGFβ-R1) blockade that suppresses GBM tumor neovascularization by simultaneously targeting macrophage-associated immunosuppression, endothelial-macrophage interactions, and altered ECM. Hence, we provide an interactive and controllable GBM tumor microenvironment and highlight the importance of macrophage-associated immunosuppression in GBM angiogenesis, paving a new direction of screening novel anti-angiogenic therapies.
http://ift.tt/2BejECw
Inhibition of tumor-promoting stroma to enforce subsequently targeting AT1R on tumor cells by pathological inspired micelles
Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Yun Zhu, Lijuan Wen, Shihong Shao, Yanan Tan, Tingting Meng, Xiqin Yang, Yupeng Liu, Xuan Liu, Hong Yuan, Fuqiang Hu
Cancer associated fibroblasts (CAFs) are the most abundant, genetically stable stroma cells and localize near blood vessels within "finger-like" collagen-rich stroma, which lead to restrained drug transport in dense stroma instead of tumor cells inside tumor mass, especially for targeting micelles. Meanwhile, the bioactive cytokines secreted by stroma cells result in microenvironment mediated drug resistance (TMDR). Hence, a biologically inspired Telmisartan (Tel) grafting glycolipid micelles (Tel-CSOSA) are constructed, which can sequentially target angiotensin II type I receptor (AT1R) overexpressed on both CAFs and tumor cells. More Tel-CSOSA are demonstrated to specifically accumulate in tumor site compared to CSOSA. In addition, the retention of Tel-CSOSA is primarily prolonged around tumor vessel in virtue of CAFs targeting and the stroma barrier. In contrast, the elimination of "finger-like" ECM resulting from CAFs apoptosis by Tel-CSOSA/DOX contributes to a more uniform and deeper penetration post-administration, which can enforce subsequently tumor cells targeting. Meanwhile, cytokines are decreased along with CAFs apoptosis so that tumor cells are more vulnerable to chemotherapeutics. Collectively, this strategy of sequentially targeting CAFs and tumor cells could synergistically increase antitumor therapy with reversed TMDR.
Graphical abstract
http://ift.tt/2BK6xKL
Lipophilic indocarbocyanine conjugates for efficient incorporation of enzymes, antibodies and small molecules into biological membranes
Source:Biomaterials, Volume 161
Author(s): Weston J. Smith, Huy Tran, James I. Griffin, Jessica Jones, Vivian P. Vu, Lizanne Nilewski, Nathan Gianneschi, Dmitri Simberg
Decoration of cell membranes with biomolecules, targeting ligands and imaging agents is an emerging strategy to improve functionality of cell-based therapies. Compared to covalent chemistry or genetic expression on the cell surface, lipid painting (i.e., incorporation of lipid-conjugated molecules into the cell bilayer) is a fast, non-damaging and less expensive approach. Previous studies demonstrated excellent incorporation and retention of distearyl indocarbocyanine dye DiI in membranes of cells in vitro and in vivo. In order to exploit the membrane stability of DiI, we synthesized an amino-DiI derivative, to which we subsequently conjugated an antibody (cetuximab), an enzyme (superoxide dismutase), and a small molecule (DyLight 800). Red blood cells have long been used as drug delivery vehicles so they were utilized as a model to study the incorporation of DiI conjugates in the plasma membrane. All the DiI constructs demonstrated fast and efficient ex vivo incorporation in the membrane of mouse RBCs, resulting in millions of exogenous molecules per RBC. Following an intravenous injection into mice, the molecules were detected on circulating RBCs for several days. DiI anchored molecules showed longer residence time in blood and significantly higher area under the curve (AUC) compared to free non-conjugated molecules. Thus, cetuximab, SOD and DyLight painted on RBC showed 5.5-fold, 6.5-fold and 78-fold increase in the AUC, respectively, compared to the non-modified molecules. Lipophilic indocarbocyanine anchors are a promising technology for incorporation of biomolecules and small molecules into biological membranes for in vivo applications.
http://ift.tt/2BeaLJb
High-density lipoprotein-mimicking nanodiscs carrying peptide for enhanced therapeutic angiogenesis in diabetic hindlimb ischemia
Source:Biomaterials, Volume 161
Author(s): Hyun-Ji Park, Rui Kuai, Eun Je Jeon, Yoojin Seo, Youngmee Jung, James J. Moon, Anna Schwendeman, Seung-Woo Cho
Therapeutic strategies using endogenous stem cell mobilizer can provide effective cell-free therapy for addressing various ischemic diseases. In particular, substance P (SP) exhibited therapeutic regeneration by facilitating mobilization of endogenous stem cells from bone marrow to the injured sites. However, its therapeutic effect has been limited due to short half-life and rapid degradation of administered SP peptides in vivo. Here we sought to develop high-density lipoprotein (HDL)-mimicking nanodiscs conjugated with SP (HDL-SP) in order to increase the in vivo half-life, bone marrow targeting, and therapeutic efficacy of SP for the treatment of diabetic peripheral ischemia. Conjugation of SP onto HDL nanodisc led to remarkable ∼3215- and ∼1060-fold increase in the ex vivo and in vivo half-lives of SP, respectively. Accordingly, HDL-SP nanodiscs improved retention of SP in bone marrow after systemic administration, leading to efficient mobilization of stem cells from bone marrow into blood circulation and reduction of systemic inflammation. Consequently, nanodisc based SP peptide delivery promoted blood vessel formation, blood perfusion recovery and markedly improved limb salvage in diabetic hindlimb ischemia model relative to administration of free SP without nanodisc modification. Therefore, HDL-SP nanodisc can provide a novel strategy for the treatment of diabetic ischemia and HDL nanodisc modification could be potentially useful for the extension of plasma circulation of other labile peptides.
http://ift.tt/2BHn9m4
Protecting neurons from cerebral ischemia/reperfusion injury via nanoparticle-mediated delivery of an siRNA to inhibit microglial neurotoxicity
Source:Biomaterials, Volume 161
Author(s): Ye Wang, Shi-Yong Li, Song Shen, Jun Wang
Complement component C3 (C3) plays a central role in microglial neurotoxicity following cerebral ischemia/reperfusion (I/R) injury. In this study, we focused on the role of nanoparticles loaded with C3 siRNA (NPsiC3) in inhibiting microglial neurotoxicity after brain (I/R) injury. NPsiC3 inhibited the hypoxia/re-oxygenation-induced increase in C3 expression in microglia in vitro. Importantly, treatment with NPsiC3 decreased C3b deposition on neurons and reduced microglia-mediated neuronal damage under hypoxia/re-oxygen conditions. Nanoparticles could effectively deliver C3-siRNA from the blood into ischemic penumbra across the blood-brain barrier (BBB) and significantly decrease C3 expression in microglia and ischemic brain tissue, while reducing the number of infiltrating inflammatory cells and the concentration of pro-inflammatory factors in the penumbra. Furthermore, NPsiC3 also prevented neuronal apoptosis, reduced the volume of the ischemic zone, and substantially improved functional recovery after I/R injury. Therefore, the NPsiC3-induced inhibition of microglial neurotoxicity represents a novel therapeutic strategy for treating brain I/R injury.
http://ift.tt/2BfyCbJ
Improved magnetic regulation of delivery profiles from ferrogels
Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Stephen Kennedy, Charles Roco, Alizée Déléris, Patrizia Spoerri, Christine Cezar, James Weaver, Herman Vandenburgh, David Mooney
While providing the ability to magnetically enhance delivery rates, ferrogels have not been able to produce the various types of regulated delivery profiles likely needed to direct complex biological processes. For example, magnetically triggered release after prolonged periods of payload retention have not been demonstrated and little has been accomplished towards remotely controlling release rate through alterations in the magnetic signal. Also, strategies do not exist for magnetically coordinating multi-drug sequences. The purpose of this study was to develop these capabilities through improved ferrogel design and investigating how alterations in the magnetic signal impact release characteristics. Results show that delivery rate can be remotely regulated using the frequency of magnetic stimulation. When using an optimized biphasic ferrogel design, stimulation at optimized frequencies enabled magnetically triggered deliveries after a delay of 5 days that were 690- to 1950-fold higher than unstimulated baseline values. Also, a sequence of two payloads was produced by allowing one payload to initially diffuse out of the ferrogel, followed by magnetically triggered release of a different payload on day 5. Finally, it was demonstrated that two payloads could be sequentially triggered for release by first stimulating at a frequency tuned to preferentially release one payload (after 24 h), followed by stimulation at a different frequency tuned to preferentially release the other payload (After 4 days). The strategies developed here may expand the utility of ferrogels in clinical scenarios where the timing and sequence of biological events can be tuned to optimize therapeutic outcome.
Graphical abstract
http://ift.tt/2BIFBuO
Self-indicating, fully active pharmaceutical ingredients nanoparticles (FAPIN) for multimodal imaging guided trimodality cancer therapy
Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Xiangdong Xue, Yee Huang, Xinshuai Wang, Zhongling Wang, Randy P. Carney, Xiaocen Li, Ye Yuan, Yixuan He, Tzu-yin Lin, Yuanpei Li
Conventional drug delivery systems contain substantial amounts of excipients such as polymers and lipids, typically with low drug loading capacity and lack of intrinsic traceability and multifunctionality. Here, we report fully active pharmaceutical ingredient nanoparticles (FAPIN) which were self-assembled by minimal materials, but seamlessly orchestrated versatile theranostic functionalities including: i) self-delivery: no additional carriers were required, all components in the formulation are active pharmaceutical ingredients; ii) self-indicating: no additional imaging tags were needed. The nanoparticle itself was composed of 100% imaging agents, so that the stability, drug release, subcellular dispositions, biodistribution and therapeutic efficacy of FAPINs can be readily visualized by ample imaging capacities, including energy transfer relay dominated, dual-color fluorogenic property, near-infrared fluorescence imaging and magnetic resonance imaging; and iii) highly effective trimodality cancer therapy, encompassing photodynamic-, photothermal- and chemo-therapies. FAPINs were fabricated with very simple material (a photosensitizer-drug conjugate), unusually achieved ∼10 times better in vitro antitumor activity than their free counterparts, and were remarkably efficacious in patient-derived xenograft (PDX) glioblastoma multiforme animal models. Only two doses of FAPINs enabled complete ablation of highly-malignant PDX tumors in 50% of the mice.
Graphical abstract
http://ift.tt/2Bfse4h
Lysosomal deposition of copper oxide nanoparticles triggers HUVEC cells death
Source:Biomaterials, Volume 161
Author(s): Jun Zhang, Zhen Zou, Bin Wang, Ge Xu, Qiong Wu, Yuchan Zhang, Zhiyi Yuan, Xi Yang, Chao Yu
The increasing use of copper oxide nanoparticles (CuONPs) has led to major concerns regarding both the predominant physicochemical properties and the potential toxic effects on the environment and human health. The objective of this study is to explore the possible mechanisms underlying the toxicity of CuONPs in vascular endothelial cells. We found that CuONPs induced the cell death in human umbilical vein endothelial cells (HUVECs) through a caspase-independent pathway. Our results also demonstrated that CuONPs were prevalently deposited within lysosomes. The lysosomal deposition of CuONPs led to lysosomal dysfunction, resulting in the impairment of autophagic flux and the accumulation of undegraded autophagosomes. Nevertheless, blockage of the lysosomal deposition of CuONPs could significantly attenuate HUVEC cell death. Interestingly, we found that the inhibition of lysosomal deposition of CuONPs reduced the release of Cu ions, which has been considered as the crucial factor for the toxicity of CuONPs. In summary, our results indicate that the lysosomal deposition of CuONPs (along with the enhanced release of Cu ions form CuONPs) triggers CuONPs-induced HUVEC cell death. Our findings provide an insight into the mechanism of toxicity to the cardiovascular system induced by toxic metal oxide nanoparticles exposure.
http://ift.tt/2BIFCyS
Editorial Board
Source:Medical Hypotheses, Volume 111
http://ift.tt/2ELiNcx
Identification of functional groups of Opuntia ficus-indica involved in coagulation process after its active part extraction
Abstract
Opuntia ficus-indica that belongs to the Cactaceae family and is a member of Opuntia kind has received increasing research interest for wastewater treatment by flocculation. The objectives of this study were (i) to provide more information regarding the active constituents of Opuntia spp. and (ii) to improve the extracting and using conditions of the flocculant molecules for water treatment. A classic approach by jar test experiments was used with raw and extracted material by solubilization and precipitation. The surface properties of solid material were characterized by FTIR, SEM, zeta potential measurement, and surface titration. The splitting based on the solubility of the material with pH and the titration of functional groups completed the method. The optimal pH value for a coagulation–flocculation process using cactus solid material (CSM) was 10.0 and a processing rate of 35 mg L−1. The alkaline pH of flocculation suggests an adsorption mechanism with bridging effect between particles by water-soluble extracted molecules. To validate this mechanism, an extraction water was carried out at pH = 10 (optimum of flocculation) and the solution was acidified (pH = 7) to allow precipitation of so considered active flocculant molecules. The strong flocculant property of this extract was verified, and titration of this solution showed at least one specific pKa of 9.0 ± 0.6. This pKa corresponds to phenol groups, which could be assigned to lignin and tannin.
http://ift.tt/2E4XuRX
Microwave-assisted extraction and dyeing of chemical and bio-mordanted cotton fabric using harmal seeds as a source of natural dye
Abstract
The revival of cultural heritage in a form of natural colorants for textile dyeing is gaining popularity due to their soothing nature and bright shades. The present study was conducted to explore the coloring potential of harmala (Peganum harmala) seeds and to improve color strength of dye using microwave radiations followed by a mordanting process. The results showed that harmala plant seeds could be an excellent source of natural dyes for cotton dyeing if the irradiated acidified methanolic extract (RE, 4 min) is used to dye un-irradiated fabric (NRC) at 85 °C for 45 min using a dye bath of pH 9.0 having salt concentration of 7 g/100 mL. Alum (1%) as pre-mordants and iron (7%) as post-mordants have improved the color strength in chemical mordanting more than other mordants employed. The bio-mordants employed reveal that 10% of acacia as pre-bio-mordants and 7% of acacia as post-bio-mordants are effective amounts to obtain high color strength. Suggested ISO standards for colorfastness illustrate that bio-mordanting has given more excellent rating as compared to chemical mordants. It is concluded that harmala seeds have a great potential to act as a source of natural colorant for cotton dyeing under the influence of microwave radiation.
http://ift.tt/2Eoy70R
Levels and distribution of cobalt and nickel in the aquatic macrophytes found in Skadar Lake, Montenegro
Abstract
Macrophytes react to changes in the quality of the environment in which they live (water/sediment), and they are good bioindicators of surface water conditions. In the present study, the content of the metals cobalt (Co) and nickel (Ni) was determined in the sediment, the water, and different organs of macrophytes from six localities around Lake Skadar, across four different seasons of year. The aquatic macrophytes that have been used as bioindicator species in this study are Phragmites australis (an emerged species), Ceratophyllum demersum (a submerged species), and Lemna minor (a floating species). The aim of this study was to determine the distribution of metals in macrophyte tissues and also to discover the degree of bioaccumulation of the investigated metals, depending both on the location and on the season. The content of Co and Ni in the examined parts of the macrophytes was in the range of 0.04–8.78 and 0.30–28.5 ppm, respectively. The greatest content of the investigated metal in the organs of P. australis and C. demersum was recorded at the beginning of and during the growing season. Greater concentrations of metals in the tissue of L. minor were observed at the end of the growing season.
http://ift.tt/2E9F16A
Using laboratory-generated biosolids to evaluate the microbial ecotoxicity of triclosan in a simulated land application scenario
Abstract
Land application accounts for approximately 50% of wastewater solids disposal in the USA. Yet, little is known regarding the ecological impacts of many non-regulated chemicals found in biosolids. In most previous studies aimed at assessing ecological impacts, a model biosolid is generated by spiking high concentrations of the target chemical into a soil or biosolid. This approach does not account for the interaction of the chemical of interest with the solids throughout the biosolids production process (a.k.a., aging) which may impact the bioavailability and, thus, ultimate toxicity of the chemical. In the present study, using a lab-scale wastewater and digestion treatment system, we generated biosolids which contained aged triclosan and compared ecological impacts to that of spiked biosolids. Ecotoxicity was assessed based on functional and community structure changes to soil denitrifiers, microorganisms critical to nitrogen cycling. A decrease in denitrifier abundance and diversity was observed in the aged biosolids at concentrations of 17.9 ± 1.93 μg/kg while decreases in activity were observed at 26.9 ± 4.6 μg/kg. In the spiked biosolids treatment, lower denitrifier abundance, diversity, and activity were observed at triclosan (TCS) concentrations of 68.6 ± 26.9 μg/kg. This difference suggests a need to better understand TCS bioavailability dynamics.
http://ift.tt/2Em6XYx
Bow hunter's syndrome in a patient with a right hypoplastic vertebral artery and a dynamically compressible left vertebral artery
David Z Cai, Ryan P Roach, John P Weaver, Gerald T McGillicuddy, Zachary M Mansell, Jonathan P Eskander, Mark S Eskander
Asian Journal of Neurosurgery 2018 13(1):133-135
This is a case report of a 48-year-old man with multiple transient ischemic attacks and a known hypoplastic right vertebral artery (VA) who presented after a syncopal event while turning his head to the left. The objective of this study is to demonstrate the necessity of proper diagnosis and management of cerebrovascular pathology including imaging and surgical intervention in patients with known anatomical anomalies. This study was conducted at Massachusetts, United States of America. Our patient's history was significant for a hypoplastic right VA and a stenotic segment of the right VA at the C3–C4 junction. There was also degeneration of the C3–C4 facet on the left, with osteophyte formation compressing the VA, and a fusion of the C2–C3 segment. Imaging demonstrated obliteration of the left VA flow with head rotation to the left and subsequent reconstitution of flow in the neutral position. After consultation, the patient decided to proceed with surgical management with an anterior cervical discectomy and fusion at the level of C3–C4. Symptoms of vertebrobasilar insufficiency including syncopal episodes resolved after treatment. VA anomalies, although uncommon, are important to understand. Our patient presented with an anomalous right VA, as well as severe degenerative changes to the C2/C3 vertebrae that contributed to the development of Bow Hunter's syndrome. It is essential that proper monitoring and follow-up has to be carried out in patients with abnormal cerebral vasculature to minimize the occurrence of Bow Hunter's syndrome.
http://ift.tt/2nPt92T
Asian Journal of Neurosurgery 2018 13(1):133-135
This is a case report of a 48-year-old man with multiple transient ischemic attacks and a known hypoplastic right vertebral artery (VA) who presented after a syncopal event while turning his head to the left. The objective of this study is to demonstrate the necessity of proper diagnosis and management of cerebrovascular pathology including imaging and surgical intervention in patients with known anatomical anomalies. This study was conducted at Massachusetts, United States of America. Our patient's history was significant for a hypoplastic right VA and a stenotic segment of the right VA at the C3–C4 junction. There was also degeneration of the C3–C4 facet on the left, with osteophyte formation compressing the VA, and a fusion of the C2–C3 segment. Imaging demonstrated obliteration of the left VA flow with head rotation to the left and subsequent reconstitution of flow in the neutral position. After consultation, the patient decided to proceed with surgical management with an anterior cervical discectomy and fusion at the level of C3–C4. Symptoms of vertebrobasilar insufficiency including syncopal episodes resolved after treatment. VA anomalies, although uncommon, are important to understand. Our patient presented with an anomalous right VA, as well as severe degenerative changes to the C2/C3 vertebrae that contributed to the development of Bow Hunter's syndrome. It is essential that proper monitoring and follow-up has to be carried out in patients with abnormal cerebral vasculature to minimize the occurrence of Bow Hunter's syndrome.
http://ift.tt/2nPt92T
Direct cerebral revascularization: Extracranial-intracranial bypass
Sengottuvel Thanapal, Shyam Duvuru, Treepob Sae-Ngow, Yoko Kato, Katsumi Takizawa
Asian Journal of Neurosurgery 2018 13(1):9-17
In 1967, the first extracranial to intracranial (EC-IC) arterial anastomosis was performed. Since that time, EC-IC bypass surgery has become a widely accepted surgical treatment for patients with IC stenotic or occlusive atherosclerotic lesions. This article will discuss the history, indications, types, surgical methods, and complications of the EC-IC bypass.
http://ift.tt/2nJDX3n
Asian Journal of Neurosurgery 2018 13(1):9-17
In 1967, the first extracranial to intracranial (EC-IC) arterial anastomosis was performed. Since that time, EC-IC bypass surgery has become a widely accepted surgical treatment for patients with IC stenotic or occlusive atherosclerotic lesions. This article will discuss the history, indications, types, surgical methods, and complications of the EC-IC bypass.
http://ift.tt/2nJDX3n
Unusual case of cerebellopontine angle epidermoid causing cerebellar atrophy
Rajasekharan Rajeev, Kamble Jayaprakash Harsha, Jain George Panattil
Asian Journal of Neurosurgery 2018 13(1):195-196
http://ift.tt/2nNw4cv
Asian Journal of Neurosurgery 2018 13(1):195-196
http://ift.tt/2nNw4cv
Is mechanical ventilation mandatory for the management of severe head injury? outcome in 53 medically managed severe head injury patients, without ventilatory support: A prospective study
Ponraj Kamatchi Sundaram, Pankaj Arora, Jinendrakumar Ramalingam, Jorson D'Costa
Asian Journal of Neurosurgery 2018 13(1):18-22
Background: Severe head injury (SHI) is a major cause of mortality and morbidity across the world. The current paradigm of management of SHI involves admission in Intensive Care Unit (ICU), mechanical ventilation (MV), and intracranial pressure (ICP) monitoring. Such resources are expensive and often unavailable in the developing world. Objective: MV or ICP monitoring was unavailable for our patients due to the scarcity of resources. Hence, other alternatives were considered to prevent secondary brain injury due to hypoxia. This study assessed the outcome after SHI when managed with an early tracheostomy (ET). Methods: This prospective observational study over 13 months included all medically managed SHI patients without MV or ICP monitoring. The Glasgow outcome scale (GOS) was assessed at discharge and compared with published historical data reported after treatment in an ICU environment. Results: Our study included 53 unoperated patients with SHI among 1862 patients with traumatic brain injury. Overall mortality was 24.5% (13/53) and compared favorably with reported mortality of 25%–40% reported from centers using intensive management. At discharge, the favorable outcome with a GOS of 4 or 5 was seen in 39.6% (21/53). Conclusion: With ET, the results of management of SHI in our patients were comparable to results reported after MV in an ICU environment. Hence, ET is a cost-effective alternative when resources are scarce. MV should be used if hypoxia persists after tracheostomy. Although MV effectively prevents hypoxia, it has complications. We conclude that although MV was unavailable for our patients, they did not have the complications associated with it.
http://ift.tt/2E82Vjd
Asian Journal of Neurosurgery 2018 13(1):18-22
Background: Severe head injury (SHI) is a major cause of mortality and morbidity across the world. The current paradigm of management of SHI involves admission in Intensive Care Unit (ICU), mechanical ventilation (MV), and intracranial pressure (ICP) monitoring. Such resources are expensive and often unavailable in the developing world. Objective: MV or ICP monitoring was unavailable for our patients due to the scarcity of resources. Hence, other alternatives were considered to prevent secondary brain injury due to hypoxia. This study assessed the outcome after SHI when managed with an early tracheostomy (ET). Methods: This prospective observational study over 13 months included all medically managed SHI patients without MV or ICP monitoring. The Glasgow outcome scale (GOS) was assessed at discharge and compared with published historical data reported after treatment in an ICU environment. Results: Our study included 53 unoperated patients with SHI among 1862 patients with traumatic brain injury. Overall mortality was 24.5% (13/53) and compared favorably with reported mortality of 25%–40% reported from centers using intensive management. At discharge, the favorable outcome with a GOS of 4 or 5 was seen in 39.6% (21/53). Conclusion: With ET, the results of management of SHI in our patients were comparable to results reported after MV in an ICU environment. Hence, ET is a cost-effective alternative when resources are scarce. MV should be used if hypoxia persists after tracheostomy. Although MV effectively prevents hypoxia, it has complications. We conclude that although MV was unavailable for our patients, they did not have the complications associated with it.
http://ift.tt/2E82Vjd
Combined retrosigmoid-paramedian supracerebellar transtentorial approach as an alternative to classical transtemporal approaches: A technical note
Tamer Altay, Cem Akkurt
Asian Journal of Neurosurgery 2018 13(1):161-164
Epidermoid tumors are rare benign neoplasms. They commonly occur in the parasellar region and the cerebellopontine angle but may sometimes present in the so-called petroclival region, or beyond the boundaries of this location. For those that are localized in multiple compartments, staged surgeries, extensive transtemporal approaches, or somewhat limited extended middle fossa approach are generally performed. Although a good resection can be achieved by these approaches, they carry relatively high morbidity and mortality. We report a case of epidermoid tumor with infra- and supratentorial extensions, and propose a combined retrosigmoid-paramedian supracerebellar transtentorial approach as an alternative to classical transtemporal approaches.
http://ift.tt/2Em38Tb
Asian Journal of Neurosurgery 2018 13(1):161-164
Epidermoid tumors are rare benign neoplasms. They commonly occur in the parasellar region and the cerebellopontine angle but may sometimes present in the so-called petroclival region, or beyond the boundaries of this location. For those that are localized in multiple compartments, staged surgeries, extensive transtemporal approaches, or somewhat limited extended middle fossa approach are generally performed. Although a good resection can be achieved by these approaches, they carry relatively high morbidity and mortality. We report a case of epidermoid tumor with infra- and supratentorial extensions, and propose a combined retrosigmoid-paramedian supracerebellar transtentorial approach as an alternative to classical transtemporal approaches.
http://ift.tt/2Em38Tb
Cerebral contusion: An investigation of etiology, risk factors, related diagnoses, and the surgical management at a major government hospital in Cambodia
Louise Vera Hilmer, Kee Bum Park, Iv Vycheth, Michael Wirsching
Asian Journal of Neurosurgery 2018 13(1):23-30
Introduction: Cerebral contusions are a common type of injury among the Cambodian population, mostly due to road traffic accidents. This article aims to assess various aspects around brain contusion focusing on the condition at admission, residing province, mechanism and time of injury, age and sex distribution with differing helmet wearing, and alcohol consumption patterns. Hospitalization-related data such as treatment and outcome were analyzed. Methods: This was a retrospective analysis of 406 cases who have been admitted during the period between May 2013 and May 2016. Results: Two hundred and ninety-five (75.51%) of the patients came from rural areas, 312 (76.84%) were male (mean age 31.17 ± 12.90 years for males and 38.5 ± 16.29 years for females). The average hospital stay amounted to 10.51 ± 6.67 days. One hundred and eight two cases (52.29%) happened between 4.00 and 11.00 p.m. Three hundred and nineteen (79%) of the injured patients were motorcycle drivers and 18% pedestrians. Male patients had an alcohol involvement in 135 (49.45%) (females in 5 [6.25%]) cases and 26 (10%) wore a helmet (females in 5 [6.25%]). Surgery was performed in 82 cases, specifically craniotomy and craniectomy +/− elevation of a depressed skull fracture. Two hundred and ninety-six (73.09%) patients showed related second diagnosis, mostly subdural hematoma in 96 (32.43%) and epidural hematoma in 63 (21.28%) cases. Fifty patients (13.16%) had a Glasgow Coma Scale of 3–8. 92 (24.21%) of 9–12 and 238 (62.63%) of 13–15 on admission. Most of the patients were discharged with an improved status 324 (91.52%) according to the Glasgow Outcome Scale 4 or 5. Conclusion: The severity and resulting neurologic impairment of cerebral contusions show the importance of more in-depth research and prevention programs.
http://ift.tt/2E82N3d
Asian Journal of Neurosurgery 2018 13(1):23-30
Introduction: Cerebral contusions are a common type of injury among the Cambodian population, mostly due to road traffic accidents. This article aims to assess various aspects around brain contusion focusing on the condition at admission, residing province, mechanism and time of injury, age and sex distribution with differing helmet wearing, and alcohol consumption patterns. Hospitalization-related data such as treatment and outcome were analyzed. Methods: This was a retrospective analysis of 406 cases who have been admitted during the period between May 2013 and May 2016. Results: Two hundred and ninety-five (75.51%) of the patients came from rural areas, 312 (76.84%) were male (mean age 31.17 ± 12.90 years for males and 38.5 ± 16.29 years for females). The average hospital stay amounted to 10.51 ± 6.67 days. One hundred and eight two cases (52.29%) happened between 4.00 and 11.00 p.m. Three hundred and nineteen (79%) of the injured patients were motorcycle drivers and 18% pedestrians. Male patients had an alcohol involvement in 135 (49.45%) (females in 5 [6.25%]) cases and 26 (10%) wore a helmet (females in 5 [6.25%]). Surgery was performed in 82 cases, specifically craniotomy and craniectomy +/− elevation of a depressed skull fracture. Two hundred and ninety-six (73.09%) patients showed related second diagnosis, mostly subdural hematoma in 96 (32.43%) and epidural hematoma in 63 (21.28%) cases. Fifty patients (13.16%) had a Glasgow Coma Scale of 3–8. 92 (24.21%) of 9–12 and 238 (62.63%) of 13–15 on admission. Most of the patients were discharged with an improved status 324 (91.52%) according to the Glasgow Outcome Scale 4 or 5. Conclusion: The severity and resulting neurologic impairment of cerebral contusions show the importance of more in-depth research and prevention programs.
http://ift.tt/2E82N3d
Use of detachable coils without the need of a double marker microcatheter: Technical note
Akiyo Sadato, Motoharu Hayakawa, Kazuhide Adachi, Yoko Kato, Yuichi Hirose
Asian Journal of Neurosurgery 2018 13(1):119-122
When using detachable coils for cerebral aneurysm embolization, it is necessary to place a microcatheter with radiopaque markers at 2 sites (tip and 3 cm proximal from the tip) in most cases. Detachable coils that can be positioned independently from the proximal marker may facilitate new applications utilizing their characteristics. Herein, we report 2 cases that were treated with new applications. Detachable coils that function to electrically detect the moment they come out of the microcatheter were used. In one patient with a large aneurysm with an irregular shape, coil embolization was applied by advancing the catheter more than 3 cm from the aneurysm neck to the caudally protruded compartment near the proximal end of the neck, which was difficult to reach with the coil. In the other patient with cerebral arteriovenous malformation (AVM), microcatheters for AVM without a proximal marker were used for coil embolization before Onyx injection: Coil embolization was applied through one microcatheter to a site more proximal than the tip of the other microcatheter, followed by Onyx injection through the distal catheter, by which the nidus was continuously penetrated from the initiation of injection, obtaining an effect similar to that of the plug and push technique. Through the use of detachable coils, which are not dependent on the visibility of the proximal marker, the limitation of catheter positioning is reduced and the applicable types of catheter increase, which may facilitate to enable its use for new clinical indications.
http://ift.tt/2EoZ988
Asian Journal of Neurosurgery 2018 13(1):119-122
When using detachable coils for cerebral aneurysm embolization, it is necessary to place a microcatheter with radiopaque markers at 2 sites (tip and 3 cm proximal from the tip) in most cases. Detachable coils that can be positioned independently from the proximal marker may facilitate new applications utilizing their characteristics. Herein, we report 2 cases that were treated with new applications. Detachable coils that function to electrically detect the moment they come out of the microcatheter were used. In one patient with a large aneurysm with an irregular shape, coil embolization was applied by advancing the catheter more than 3 cm from the aneurysm neck to the caudally protruded compartment near the proximal end of the neck, which was difficult to reach with the coil. In the other patient with cerebral arteriovenous malformation (AVM), microcatheters for AVM without a proximal marker were used for coil embolization before Onyx injection: Coil embolization was applied through one microcatheter to a site more proximal than the tip of the other microcatheter, followed by Onyx injection through the distal catheter, by which the nidus was continuously penetrated from the initiation of injection, obtaining an effect similar to that of the plug and push technique. Through the use of detachable coils, which are not dependent on the visibility of the proximal marker, the limitation of catheter positioning is reduced and the applicable types of catheter increase, which may facilitate to enable its use for new clinical indications.
http://ift.tt/2EoZ988
The effect of hand exercise on reducing the symptoms in hemodialysis patients with carpal tunnel syndrome
Seher Unver, Neriman Akyolcu
Asian Journal of Neurosurgery 2018 13(1):31-36
Context: Carpal tunnel syndrome (CTS) is one of the most common peripheral neuropathies, and there is no consensus on the preferred method of treatment. Aims: The aim of this study is to determine the effects of hand exercise performed with a ball on symptoms and to evaluate the results in hemodialysis (HD) patients with CTS. Settings and Design: This study was conducted in patients with HD who were treated in dialysis centers and state hospitals in Turkey between 2011 and 2012. Subjects and Methods: This study included 19 patients (28 hands) that were diagnosed as CTS. For exercise treatment, a hand and finger exercise ball that consists of two parts: a foam body and flexible rubber cords was used. Patients placed their fingers through each cord, squeezed it for 1 s, and then opened their fingers against the cord for 1 s. Patients repeated this exercise for 30 s to 1 min/day. Statistical Analysis Used: The McNemar, Friedman ANOVA, and the Wilcoxon test with a Bonferroni correction were used on SPSS 20.0 software package program. P < 0.05 was considered statistically significant. Results: Results showed that recovery was performed from physical examination results, grip strength, and Boston questionnaire scores. About 21.4% of patients' electrophysiological results were negative at the end of the 1st month and 32.1% of them at the end of the 3rd month. Conclusion: Due to the slowed progress of CTS and detection of slight improvement in evaluation parameters, this self-applicable and practical exercise can be used as an alternative treatment of mild CTS in patients with HD.
http://ift.tt/2E6qskm
Asian Journal of Neurosurgery 2018 13(1):31-36
Context: Carpal tunnel syndrome (CTS) is one of the most common peripheral neuropathies, and there is no consensus on the preferred method of treatment. Aims: The aim of this study is to determine the effects of hand exercise performed with a ball on symptoms and to evaluate the results in hemodialysis (HD) patients with CTS. Settings and Design: This study was conducted in patients with HD who were treated in dialysis centers and state hospitals in Turkey between 2011 and 2012. Subjects and Methods: This study included 19 patients (28 hands) that were diagnosed as CTS. For exercise treatment, a hand and finger exercise ball that consists of two parts: a foam body and flexible rubber cords was used. Patients placed their fingers through each cord, squeezed it for 1 s, and then opened their fingers against the cord for 1 s. Patients repeated this exercise for 30 s to 1 min/day. Statistical Analysis Used: The McNemar, Friedman ANOVA, and the Wilcoxon test with a Bonferroni correction were used on SPSS 20.0 software package program. P < 0.05 was considered statistically significant. Results: Results showed that recovery was performed from physical examination results, grip strength, and Boston questionnaire scores. About 21.4% of patients' electrophysiological results were negative at the end of the 1st month and 32.1% of them at the end of the 3rd month. Conclusion: Due to the slowed progress of CTS and detection of slight improvement in evaluation parameters, this self-applicable and practical exercise can be used as an alternative treatment of mild CTS in patients with HD.
http://ift.tt/2E6qskm
Case of an intracranial malignant peripheral nerve sheath tumor in the setting of pacer-dependent heart block
Jonathan Chica, Isaac Yepes, S Shelby Burks, Ricardo Komotar, Roger Carrillo
Asian Journal of Neurosurgery 2018 13(1):147-149
Intracranial malignant peripheral nerve sheath tumors (MPNSTs) are an extremely rare entity with only a handful of cases reported in the literature. MPNSTs typically occur in the extremities and the trunk. The treatment algorithm includes, when possible, gross-total resection as these tumors are extremely aggressive. When these tumors occur intracranially, they are termed malignant intracerebral nerve sheath tumors. The diagnosis hinges on immunohistochemistry and pathological features and often the diagnosis can be delayed for this reason. In this setting, it is critical to utilize intraoperative navigation, thus necessitating the use of fine-cut magnetic resonance imaging (MRI). This report presents a patient who presented with symptoms of obstructive hydrocephalus secondary to an intracranial mass. The patient underwent a full and extensive metastatic workup that was ultimately negative. To complicate things, the patient was fully pacemaker dependent. In this report, we review the literature surrounding this type of tumor, along with a detailed presentation of the case mentioned including the difficulties of cardiac pacing in the setting of MRI.
http://ift.tt/2ElW1dw
Asian Journal of Neurosurgery 2018 13(1):147-149
Intracranial malignant peripheral nerve sheath tumors (MPNSTs) are an extremely rare entity with only a handful of cases reported in the literature. MPNSTs typically occur in the extremities and the trunk. The treatment algorithm includes, when possible, gross-total resection as these tumors are extremely aggressive. When these tumors occur intracranially, they are termed malignant intracerebral nerve sheath tumors. The diagnosis hinges on immunohistochemistry and pathological features and often the diagnosis can be delayed for this reason. In this setting, it is critical to utilize intraoperative navigation, thus necessitating the use of fine-cut magnetic resonance imaging (MRI). This report presents a patient who presented with symptoms of obstructive hydrocephalus secondary to an intracranial mass. The patient underwent a full and extensive metastatic workup that was ultimately negative. To complicate things, the patient was fully pacemaker dependent. In this report, we review the literature surrounding this type of tumor, along with a detailed presentation of the case mentioned including the difficulties of cardiac pacing in the setting of MRI.
http://ift.tt/2ElW1dw
Etanercept prevents histopathological damage after spinal cord injury in rats
Askin Esen Hasturk, Cagdas Baran, Erdal Resit Yilmaz, Murat Arikan, Guray Togral, Nazli Hayirli, Berrin Imge Erguder, Oya Evirgen
Asian Journal of Neurosurgery 2018 13(1):37-45
Background: The aim of our study is to assess the neuroprotective effects of the tumor necrosis factor alpha (TNF-α) inhibitor etanercept (ETA) on histopathological and biochemical changes following spinal cord injury (SCI). Patients and Methods: Fifty-four male Wistar albino rats were randomly assigned into three main groups: The sham, trauma, and ETA group (n = 18 per group). Each of these groups was further divided into three subgroups (n = 6 per subgroup) based on the different tissue sampling times postinjury: 1 h, 6 h, and 24 h. Clip compression model was used for SCI. Rats in the ETA group were treated with 5 mg/kg of ETA immediately after the clip was removed. After 1, 6, and 24 h, the spinal cord was totally removed between the levels T8–T10. Sample tissue was immediately harvested and fixed for histopathological and electron microscopic examination and were analyzed for TNF-α, interleukin-1β (IL-1β), superoxide dismutase (SOD), adenosine deaminase, catalase (CAT), and malondialdehyde levels in both the tissue and serum. Results: The serum and tissue levels of cytokines and enzymes were seen to change after SCI between hyperacute, acute, and subacute stages. Treatment with ETA selectively inhibited TNF-α, and IL-1β expression together with increased levels of antioxidative enzymes (SOD, CAT). Conclusion: Early administration of ETA after SCI may remarkably attenuate neuronal injury by decreasing tissue and serum TNF-α and IL-1β levels, while increasing antioxidative enzymes such as SOD and CAT in subacute and acute stages, respectively.
http://ift.tt/2E9ahmr
Asian Journal of Neurosurgery 2018 13(1):37-45
Background: The aim of our study is to assess the neuroprotective effects of the tumor necrosis factor alpha (TNF-α) inhibitor etanercept (ETA) on histopathological and biochemical changes following spinal cord injury (SCI). Patients and Methods: Fifty-four male Wistar albino rats were randomly assigned into three main groups: The sham, trauma, and ETA group (n = 18 per group). Each of these groups was further divided into three subgroups (n = 6 per subgroup) based on the different tissue sampling times postinjury: 1 h, 6 h, and 24 h. Clip compression model was used for SCI. Rats in the ETA group were treated with 5 mg/kg of ETA immediately after the clip was removed. After 1, 6, and 24 h, the spinal cord was totally removed between the levels T8–T10. Sample tissue was immediately harvested and fixed for histopathological and electron microscopic examination and were analyzed for TNF-α, interleukin-1β (IL-1β), superoxide dismutase (SOD), adenosine deaminase, catalase (CAT), and malondialdehyde levels in both the tissue and serum. Results: The serum and tissue levels of cytokines and enzymes were seen to change after SCI between hyperacute, acute, and subacute stages. Treatment with ETA selectively inhibited TNF-α, and IL-1β expression together with increased levels of antioxidative enzymes (SOD, CAT). Conclusion: Early administration of ETA after SCI may remarkably attenuate neuronal injury by decreasing tissue and serum TNF-α and IL-1β levels, while increasing antioxidative enzymes such as SOD and CAT in subacute and acute stages, respectively.
http://ift.tt/2E9ahmr
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