Cytoprotective Effect of Tocotrienol-Rich Fraction and α-Tocopherol Vitamin E Isoforms Against Glutamate-Induced Cell Death in Neuronal Cells

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0140-0151 ◽  
Author(s):  
Thilaga Rati Selvaraju ◽  
Huzwah Khaza’ai ◽  
Sharmili Vidyadaran ◽  
Mohd Sokhini Abd Mutalib ◽  
Vasudevan Ramachandran ◽  
...  
Keyword(s):  
Vitamin E ◽  
Cell Viability ◽  
Neuronal Cells ◽  
Positive Control ◽  
Post Treatment ◽  
Mitochondrial Activity ◽  
Before And After ◽  
Pre Treatment ◽  
Tocotrienol Rich Fraction ◽  
Major Mediator

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.

scholarly journals Low frequency of pre-treatment and post-treatment haematological abnormalities in dogs with non-infectious meningoencephalitis treated with cytosine arabinoside and prednisolone

2019 ◽  
Vol 6 (1) ◽  
pp. e000315 ◽  
Author(s):  
Sarah Keegan ◽  
Jeremy H Rose ◽  
Zohra Khan ◽  
Francois-Xavier Liebel
Keyword(s):  
Cytosine Arabinoside ◽  
Standard Dose ◽  
Low Frequency ◽  
Post Treatment ◽  
Inclusion Criteria ◽  
Presumptive Diagnosis ◽  
Prednisolone Treatment ◽  
Before And After ◽  
Pre Treatment ◽  
The Uk

BackgroundCytosine arabinoside (CA) and prednisolone are drugs commonly used together in the management of canine non-infectious meningoencephalitis (NIME). The aim of this study was to report the haematological findings before and after CA and prednisolone treatment and identify any adverse haematological events in this clinical setting, following the veterinary cooperative oncology group established common terminology criteria for recording adverse events following administration of chemotherapy or biological antineoplastic therapy.ResultsWhile 48 patients with a presumptive diagnosis of NIME had pretreatment haematology results, only 12 patients met the inclusion criteria of also having post-treatment haematology results available for review after being treated with prednisolone and CA at a standard dose (200 mg/m2) in a single referral hospital in the UK. Forty-nine post-treatment haematology results were available for these 12 patients.ConclusionsFour adverse haematological events were identified in four patients. None of these events were convincingly attributable to CA administration.

OCT-Angiography as a reliable prognostic tool in laser-treated proliferative diabetic retinopathy: The RENOCTA Study

2020 ◽  
pp. 112067212096345
Author(s):  
Marco Lupidi ◽  
Ramkailash Gujar ◽  
Alessio Cerquaglia ◽  
Jay Chhablani ◽  
Daniela Fruttini ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Additional Treatment ◽  
Post Treatment ◽  
Vascular Perfusion ◽  
Significant Difference ◽  
Before And After ◽  
The Mean ◽  
Pre Treatment ◽  
Induced Changes

Purpose: To quantitatively assess retinal neovascularizations (RNVs) in proliferative diabetic retinopathy (PDR) before and after photocoagulative laser treatment (PLT) using Optical Coherence Tomography Angiography (OCT-A). Methods: Consecutive patients with PDR were examined with fluorescein angiography (FA) and OCT-A before and after PLT. Baseline and after-treatment FA images were quantitatively analyzed to assess both the RNVs area and leakage area. On OCT-A RNVs area, vascular perfusion density (VPD), vessel length density (VLD) and fractal dimension were computed. VPD of the full-retina OCT-A underneath the RNV was determined to evaluate potential laser-induced changes in vascular perfusion. Results: Fifteen eyes of 13 patients with PDR were enrolled. The mean area of the RNVs was 0.47 ± 0.50 mm2 in the baseline OCT-A and 0.32 ± 0.40 mm2 in the post-treatment assessment ( p = 0.0002). The mean RNV VPD of RNV was 2% ± 4% in pre-treatment and 1% ± 1% for the post-treatment ( p = 0.0001). The mean VLD of RNV was 7.26 ± 1.53 at baseline and 6.64 ± 1.65 in the post treatment ( p = 0.0002). A significant difference in terms of mean RNVs area and VPD reduction between eyes that needed additional treatment and those that did not (~40% vs ~20%; p < 0.05), was observed. Mean VPD of full-retinal thickness OCT-angiogram was 55% ± 10% for the pre-treatment and 53% ± 8% for the post treatment scan ( p = 0.02). Conclusion: The quantitative OCT-A assessment of laser-induced changes of RNVs can be a useful non-invasive approach for determining treatment efficacy. A reduction of RNVs area or VPD ⩾ 40% might reveal those eyes that won’t require additional treatment. Retinal perfusion impairment seemed to progress independently from the treatment.

Association of CD133 expression levels with the k-ras mutation status in rectal cancers before and after preoperative radiochemotherapy.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 400-400
Author(s):  
Thilo Sprenger ◽  
Jochen Gaedcke ◽  
Lena-Christin Conradi ◽  
Peter Jo ◽  
Klaus Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Rectal Cancer ◽  
Prognostic Marker ◽  
Tumor Regression ◽  
Post Treatment ◽  
Preoperative Radiochemotherapy ◽  
Cd133 Expression ◽  
Before And After ◽  
Rectal Cancers ◽  
Pre Treatment

400 Background: The role of the potential stem cell marker CD133 as a predictive or prognostic marker in multimodal rectal cancer treatment is currently under debate. While CD133 has been identified as a prognostic marker in rectal cancers after preoperative radiochemotherapy (RCT) it was recently characterized as a very unspecific feature for colorectal cancer stem cells. We therefore analyzed the association between CD133 expression and mutations in the proto-oncogenes K-Ras and PI3K in rectal cancer patients receiving neoadjuvant RCT. Methods: CD133 expression was evaluated immunhistochemically in pre-treatment biopsies and surgical specimens of 128 patients with locally advanced rectal cancers (cUICC II/III) treated with preoperative RCT within the phase-III German Rectal Cancer Trials. K-Ras mutations were analyzed by sequencing of exons 1, 2, and 3. PI3K mutations were detected by sequencing the p110α subunit (PIK3CA) and correlated with histopathologic parameters, tumor regression and survival. Results: CD133 expression was significantly associated with mutations in the K-Ras gene in both pre-treatment biopsies and post-treatment tumor specimens in uni- and multivariate analyses. However, no significant correlation was observed between CD133 and PI3K mutations. Post-treatment CD133 levels were correlated with neoadjuvant RCT (50.4 Gy/5-FU vs. 50.4 Gy/5-FU+Ox) and tumor regression grading. Anyway, there was no significant association between pre- and post-treatment CD133 expression and disease-free survival. Conclusions: CD133 expression levels are strongly associated with mutations in the K-Ras proto-oncogene in rectal cancers before and after preoperative RCT. Our results strengthen the hypothesis that CD133 is not a specific marker for colorectal stem cells but might be integrated in proliferation pathways like the ras-raf axis.

Peer Assessment Rating (PAR) scoring of cleft patients treated within a regional cleft centre in the United Kingdom

2021 ◽  
pp. 146531252110367
Author(s):  
Claire Furness ◽  
Helen Veeroo ◽  
Giles Kidner ◽  
Martyn T Cobourne
Keyword(s):  
Cleft Lip ◽  
Peer Assessment ◽  
Post Treatment ◽  
Percentage Change ◽  
Lower Percentage ◽  
Median Percentage ◽  
Hospital Units ◽  
Before And After ◽  
Pre Treatment ◽  
Peer Assessment Rating

Objective: To assess static occlusal outcomes for patients with cleft lip and/or palate (CLP) and cleft palate (CP) managed within a UK Regional Cleft Service and to compare with previously published Peer Assessment Rating (PAR) scores from a non-cleft population of patients treated within a UK consultant-led hospital service. Design: Retrospective multicentre study. Setting: Eight orthodontic hospital units within the Spires Cleft Service, UK. Participants: Patients born with CLP or CP between 1985 and 1995 treated within the service. Methods: Patients were assigned to groups by cleft type and whether they were treated by orthodontics only or a combination of orthodontics and orthognathic surgery. PAR was recorded before and after treatment from study models. Results: Data were collected for 171 patients included in the study. Median pre-treatment PAR was 42 and post-treatment 11. Median percentage change in PAR for all patients was 73%, although 12% of cleft patients had a PAR improvement that was worse or no different. Median change in PAR score was 71% for those treated with orthodontics only and 83% for those who had an osteotomy. Median PAR improvement for those treated with orthodontics only was 73% in the cleft lip group, 77% in the CP group, 66% in the unilateral CLP group and 53% in the bilateral CLP group. Median pre- and post-treatment PAR for the cleft group was higher and PAR reduction lower than those published for non-cleft patients. Conclusion: These data demonstrate high severity of malocclusion, complexity of orthodontic treatment and difficulty in achieving an ideal static occlusion for cleft patients. If PAR is to be used to assess orthodontic outcomes in cleft patients the findings of this study should be considered. A higher proportion of cases are likely to be classed as ‘worse or no different’, and a lower percentage change will be expected.

scholarly journals Changes in headache characteristics with oral appliance treatment for obstructive sleep apnea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji Woon Park ◽  
Sujay Mehta ◽  
Sandra Fastlicht ◽  
Alan A. Lowe ◽  
Fernanda R. Almeida
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Oxygen Saturation ◽  
Oral Appliance ◽  
Post Treatment ◽  
Mandibular Advancement ◽  
Headache Intensity ◽  
Obstructive Sleep ◽  
Before And After ◽  
Pre Treatment

AbstractChanges in headache characteristics in obstructive sleep apnea (OSA) patients following oral appliance treatment was investigated for the first time. Thirteen OSA patients with headaches treated with a mandibular advancement device were investigated. Level I polysomnography and Migraine Disability Assessment Questionnaire were completed before and after treatment. Various headache characteristics and concomitant conditions were analyzed. The patient was considered a headache responder when ≥ 30% reduction in headache frequency following treatment. Differences in headache and polysomnographic parameters were compared between headache responder groups. Eight patients (62%) were headache responders. Eleven patients (85%) before and 7 (54%) after treatment reported morning headaches. Significantly more patients had bilateral headache in the responder group before treatment (P = 0.035). The severest headache intensity (P = 0.018) at baseline showed a significant decrease in the headache responder group after treatment. The time spent in N2 (r = − 0.663, P = 0.014), REM sleep (r = 0.704, P = 0.007) and mean oxygen saturation (r = 0.566, P = 0.044) showed a significant correlation with post-treatment average headache intensity. Pre-treatment lower PLM index (r = − 0.632, P = 0.027) and higher mean oxygen saturation levels (r = 0.592, P = 0.043) were significantly correlated with higher post-treatment severest headache intensity. Treatment with an oral appliance is beneficial for many OSA patients with headaches. It should be considered as an alternative treatment in headache patients with mild to moderate OSA.

scholarly journals Post-azacitidine clone size predicts long-term clinical outcome of patients with myelodysplastic syndromes and related myeloid neoplasms

2021 ◽  
Author(s):  
Seishi Ogawa ◽  
Magnus Tobiasson ◽  
Shinya Sato ◽  
Elsa Bernard ◽  
Shigeki Ohtake ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcome ◽  
Clinical Response ◽  
Post Treatment ◽  
Clone Size ◽  
Myeloid Neoplasms ◽  
Mutational Profiling ◽  
Before And After ◽  
Pre Treatment ◽  
Next Generation Sequencing Ngs

Abstract Azacitidine is a mainstay of therapy for high-risk MDS and other myeloid neoplasms. A significant correlation between azacitidine response and clinical outcome suggests a potential role of mutational profiling based on next-generation sequencing (NGS) before and after therapy in evaluating response and predicting overall survival (OS), which however has not fully elucidated. Here through NGS-based mutational profiling of large cohorts (n=451) of azacitidine-treated patients with high-risk MDS and other myeloid neoplasms, we show significant roles of multi-hit TP53 and germline DDX41 mutations in pre-treatment samples and post-treatment clone size in the evaluation/prediction of azacitidine response and OS after azacitidine therapy, which outperformed the prediction based only on clinical response and IPSS-R score. Post-treatment clone size strongly correlated with clinical response with exception of large persistent mutations frequently affecting TET2 after achieving complete remission and those with DDX41 mutations, which poorly correlated with clinical response. Our results highlight the importance of evaluating mutations in both pre- and post-treatment samples in the assessment of response and the prediction of OS after azacitidine therapy.

scholarly journals Study the expression level of beta 2 microglobulin gene on hepatitis C patients before and after treatment with interferon

2012 ◽  
Vol 9 (3) ◽  
pp. 504-510 ◽  
Author(s):  
Baghdad Science Journal
Keyword(s):  
Hepatitis C ◽  
Treatment Group ◽  
Post Treatment ◽  
Expression Level ◽  
Fourth Decade ◽  
Before And After ◽  
Beta 2 ◽  
Pre Treatment ◽  
Beta 2 Microglobulin ◽  
Age Range

This study has been carried out to evaluate the expression level of beta 2 microglobulin gene on patients infected by hepatitis C virus before and after treatment with interferon. The study included 117 hepatitis C patients comprising as 63 pre-treated patients, the range of age was between 20-65 year with a mean age of 48.12 ± 16.1 and 54 post-treated patients with age range was between 23-63 year with the mean of 46.1 ± 18.1. Also it was found that more than half of patients were located within third and fourth decade i.e. 30-49 year, with a percentage of 52.4% and 55.6 % for pre-treatment and post-treatment patients respectively. Moreover , regarding both groups, males are more than females with the ratio of ( 3.2:1) among pre-treatment group and 2:1 among post-treatment group. Further , It has been found that the concentration of ?2 microglobulin was (3.425±0.943mg/L) among pre-treatment group and (1.860±0.723 mg/L) among post-treatment group with significant correlation (P=0.05). Besides that , in the present study ,It has been found the concentration of ?2 microglobulin was decrease after treatment from (3.425±0.943 mg/L) to (1.860±0.723mg/L) which was statistically significant (P=0.05) , Thus ?2 microglobulin can be used as a supporting marker of responsiveness to treatment with interferon in hepatitis C patients as well as indicator for monitoring the disease progression.

scholarly journals Assessment of the Antioxidant Potential of Hypoestes rosea Leaf in Lead-acetate-induced Albino Rats

2020 ◽  
pp. 45-55
Author(s):  
F. K. Uwikor ◽  
E. O. Nwachuku ◽  
F. Igwe ◽  
E. S. Bartimaeus
Keyword(s):  
Oxidative Stress ◽  
Lead Acetate ◽  
Positive Control ◽  
Post Treatment ◽  
Albino Rats ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Pre Treatment ◽  
The Impact ◽  
Dose Dependent

Hypoestes rosea has been used as a traditional medicine in the Niger delta for dysfunction of the endocrine system. However, there has been no known study on the effects of hypoestes rosea on oxidative stress. In this study we evaluated the effect of aqueous extract of Hypoestes rosea (AEHR) leaf on oxidative stress markers of lead acetate induced male and female albino rats at acute and sub-chronic stages in pre-treatment and post-treatment phases. Animals were divided into 17 groups of five each for both sexes in the treatment groups, while the positive control group had 10 animals in each sex. 8 groups were for the acute phase of the study for 21 days in each sex, while 8 were for 35 days for the sub chronic stage of the study. Negative Control (NC) group received rat feed only, Experimental (EC) group received 100 mg/kg bwt/day for 21 days at acute and 35 days for sub chronic.  Positive Control (PC) group received 60mg/kg b.wt per day of lead acetate for 35 days. The other 3 groups received 100 mgkg, 200 mg/kg and 300 mg/kg b. wt respectively for 14 and 28 days either as pre treatment or post treatment, for both sexes of the albino rats. Samples were taken at the end of the study period through the jugular vein under chloroform anaesthesia. Results showed lead acetate induced oxidative stress in the rats, evidenced by the significantly decreased (p < 0.05) Superoxide Dismutase (SOD) and Total Antioxidant Capacity (TAC) between the NC and PC groups. The plant in a dose dependent pattern was able to significantly (p < 0.05), reverse the effect of lead acetate in the Post and pre treatment phases. Our study also shows that dose dependent AEHR extract significantly reduced the impact of lead in oxidative stress markers. In conclusion, consumption of AEHR by albino rats could help protect against lead acetate induced oxidative stress.

scholarly journals Protective Effect of Alpha-Tocopherol Isomer from Vitamin E against the H2O2Induced Toxicity on Dental Pulp Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Fernanda da Silveira Vargas ◽  
Diana Gabriela Soares ◽  
Ana Paula Dias Ribeiro ◽  
Josimeri Hebling ◽  
Carlos Alberto De Souza Costa
Keyword(s):  
Vitamin E ◽  
Protective Effect ◽  
Cell Viability ◽  
Dental Pulp ◽  
Positive Control ◽  
Negative Control ◽  
Alpha Tocopherol ◽  
Dental Pulp Cells ◽  
Cell Protection ◽  
Pulp Cells

The aim of this study was to evaluate the protective effects of different concentrations of vitamin E alpha-tocopherol (α-T) isomer against the toxicity of hydrogen peroxide (H2O2) on dental pulp cells. The cells (MDPC-23) were seeded in 96-well plates for 72 hours, followed by treatment with 1, 3, 5, or 10 mMα-T for 60 minutes. They were then exposed or not to H2O2for 30 minutes. In positive and negative control groups, the cells were exposed to culture medium with or without H2O2(0.018%), respectively. Cell viability was evaluated by MTT assay (Kruskal-Wallis and Mann-Whitney tests;α=5%). Significant reduction of cell viability (58.5%) was observed in positive control compared with the negative control. Cells pretreated withα-T at 1, 3, 5, and 10 mM concentrations and exposed to H2O2had their viability decreased by 43%, 32%, 25%, and 27.5%, respectively. These values were significantly lower than those observed in the positive control, thereby showing a protective effect ofα-T against the H2O2toxicity. Overall, the vitamin Eα-T isomer protected the immortalized MDPC-23 pulp cells against the toxic effects of H2O2. The most effective cell protection was provided by 5 and 10 mM concentrations ofα-T.

FLT3 Inhibitors for the Treatment of Acute Myeloid Leukemia: An Evaluation of Efficacy of Target Inhibition and Relationship to Disease Progression

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4940-4940 ◽  
Author(s):  
Adam Cloe ◽  
Richard A. Larson ◽  
Jason X. Cheng
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Poor Prognosis ◽  
Post Treatment ◽  
Flt3 Inhibitors ◽  
Before And After ◽  
Pre Treatment ◽  
Acute Myeloid

Abstract Introduction FLT3 is a receptor tyrosine kinase that plays a role in hematopoietic stem/progenitor cell proliferation and survival and is frequently found to be mutated in patients with acute myeloid leukemia (AML). Mutations that lead to constitutive activation of FLT3 (such as internal tandem duplications of the juxtamembrane domain or point mutations involving the kinase domain) are associated with a poor prognosis. This poor prognosis is in part due to an increased relapse rate after allogeneic hematopoietic cell transplant (HCT). Several compounds that inhibit the activity of FLT3 in vitro, including ASP2215, midostaurin and quizartinib, are now being studied in clinical trials for the treatment of AML. Inhibition of the formation of phospho-FLT3 has been correlated with clinical anti-leukemia effects and remissions. Methods In this pilot study we use immunohistochemistry to measure the levels of activated FLT3 in bone marrow biopsies of patients prior to and during treatment inclinical trials at our institution to determine the efficacy of these FLT3 inhibitors and correlate it with patient outcomes. Results The different FLT3 compounds tested had a heterogenous effect on activated FLT3 levels. In some patients, ASP2215 caused a decrease in levels of activated FLT3 (indicated by brown nuclear staining), which corresponded to a decrease in leukemic blasts (Fig 1). Other patients, however, showed similar amounts of activated FLT3 both before and after treatment, which corresponded with no significant change in leukemic blasts. (Fig 2). Other FLT3 inhibitors also showed differences in their effects. Midostaurin reduced activated FLT3 levels, which correlated with a positive clinical response. In contrast, one patient receiving quizartinibshowed little to no decrease in activated FLT3 levels, despite remaining in clinical remission. This suggests that this FLT3 inhibitor may have alternative targets, such as the tyrosine kinases AXL or LTK. Conclusions The heterogeneity in the responses to ASP2215, midostaurin, and quizartinib suggests that there may be other targets for these compounds that are not currently accounted for in the clinical studies. Immunohistochemicalmeasurements of activated FLT3 in bone marrow sections before and after treatment with FLT3 inhibitors was not predictive for clinical response. Figure 1. Activated FLT3 levels in patient responsive to ASP2215; pre-treatment (A) and post-treatment (B) Figure 1. Activated FLT3 levels in patient responsive to ASP2215; pre-treatment (A) and post-treatment (B) Figure 2. Activated FLT3 levels in patient not responsive to ASP2215; pre-treatment (A) and post-treatment (B) Figure 2. Activated FLT3 levels in patient not responsive to ASP2215; pre-treatment (A) and post-treatment (B) Disclosures Larson: Pfizer: Consultancy; Ariad: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy.

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