scholarly journals PROBING THE IMPACT OF GAMMA-IRRADIATION ON THE METABOLIC STATE OF NEURAL STEM AND PRECURSOR CELLS USING DUAL-WAVELENGTH INTRINSIC SIGNAL TWO-PHOTON EXCITED FLUORESCENCE

2011 ◽  
Vol 04 (03) ◽  
pp. 289-300 ◽  
Author(s):  
TATIANA B. KRASIEVA ◽  
ERICH GIEDZINSKI ◽  
KATHERINE TRAN ◽  
MARY LAN ◽  
CHARLES L. LIMOLI ◽  
...  
Keyword(s):  
Gamma Irradiation ◽  
Fluorescence Intensity ◽  
Low Dose ◽  
Cellular Proliferation ◽  
Precursor Cells ◽  
High Dose ◽  
Excitation Spectra ◽  
Metabolic State ◽  
Two Photon ◽  
The Impact

Two-photon excited fluorescence (TPEF) spectroscopy and imaging were used to investigate the effects of gamma-irradiation on neural stem and precursor cells (NSPCs). While the observed signal from reduced nicotinamide adenine dinucleotide (NADH) was localized to the mitochondria, the signal typically associated with oxidized flavoproteins (Fp) was distributed diffusely throughout the cell. The measured TPEF emission and excitation spectra were similar to the established spectra of NAD(P)H and Fp. Fp fluorescence intensity was markedly increased by addition of the electron transport chain (ETC) modulator menadione to the medium, along with a concomitant decrease in the NAD(P)H signal. Three-dimensional (3D) neurospheres were imaged to obtain the cellular metabolic index (CMI), calculated as the ratio of Fp to NAD(P)H fluorescence intensity. Radiation effects were found to differ between low-dose (≤ 50 cGy) and high-dose (≥ 50 cGy) exposures. Low-dose irradiation caused a marked drop in CMI values accompanied by increased cellular proliferation. At higher doses, both NAD(P)H and Fp signals increased, leading to an overall elevation in CMI values. These findings underscore the complex relationship between radiation dose, metabolic state, and proliferation status in NSPCs and highlight the ability of TPEF spectroscopy and imaging to characterize metabolism in 3D spheroids.

The impact of low-dose versus high-dose antibiotic prophylaxis regimens on surgical site infection rates after cesarean delivery

2019 ◽  
Vol 301 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Mauricio La Rosa ◽  
Chasey Omere ◽  
Tiffany Redfern ◽  
Mahmoud Abdelwahab ◽  
Nicholas Spencer ◽  
...  
Keyword(s):  
Surgical Site Infection ◽  
Antibiotic Prophylaxis ◽  
Cesarean Delivery ◽  
Low Dose ◽  
High Dose ◽  
Site Infection ◽  
Infection Rates ◽  
The Impact

scholarly journals CD8+-T-Cell Response to Secreted and Nonsecreted Antigens Delivered by Recombinant Listeria monocytogenes during Secondary Infection

2002 ◽  
Vol 70 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Amy R. Tvinnereim ◽  
Sara E. Hamilton ◽  
John T. Harty
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
T Cell ◽  
Cell Response ◽  
Low Dose ◽  
Recombinant Antigen ◽  
T Cell Response ◽  
Vector System ◽  
High Dose ◽  
The Impact

ABSTRACT Understanding how existing antivector immunity impacts live vaccine delivery systems is critical when the same vector system may be used to deliver different antigens. We addressed the impact of antivector immunity, elicited by immunization with attenuated actA-deficient Listeria monocytogenes, on the CD8+-T-cell response to a well-characterized lymphocytic choriomeningitis virus epitope, NP118-126, delivered by infection with recombinant L. monocytogenes. Challenges of immune mice with actA-deficient and with wild-type recombinant L. monocytogenes generated similar numbers of CD8+ T cells specific for the NP118-126 epitope. High-dose immunization with actA-deficient L. monocytogenes resulted in substantial numbers of CD8+ T cells specific for the L. monocytogenes LLO91-99 epitope in the effector and memory stages of the T-cell response. Challenge of these immune mice with recombinant L. monocytogenes resulted in rapid control of the infection and decreased CD8+-T-cell responses against both the secreted and nonsecreted form of the recombinant antigen compared to the response of naïve mice. In contrast, mice immunized with a low dose of actA-deficient L. monocytogenes had ∼10-fold fewer effector and memory T cells specific for LLO91-99 and a substantially higher CD8+-T-cell response against the recombinant antigen after challenge with recombinant L. monocytogenes. Although mice immunized with low-dose actA-deficient L. monocytogenes had a substantial recall response to LLO91-99, which reached the same levels by 5 to 7 days postchallenge as that in high-dose-immunized mice, they exhibited decreased ability to control L. monocytogenes replication. Thus, the level of antivector immunity impacts the control of infection and efficiency of priming responses against new antigens introduced with the same vector.

Do adjuvants add to the efficacy and tolerance of bowel preparations? A meta-analysis of randomized trials

Endoscopy ◽  
2017 ◽  
Vol 50 (02) ◽  
pp. 159-176 ◽  
Author(s):  
Sophie Restellini ◽  
Omar Kherad ◽  
Charles Menard ◽  
Myriam Martel ◽  
Alan Barkun
Keyword(s):  
Randomized Trials ◽  
Low Dose ◽  
Meta Analysis ◽  
High Dose ◽  
Detection Rates ◽  
Adenoma Detection ◽  
Adenoma Detection Rates ◽  
Split Dosing ◽  
Bowel Preparations ◽  
The Impact

Abstract Background and study aims Recommendations on adjuvant use with bowel preparations remain disparate. We performed a meta-analysis determining the clinical impact of adding an adjuvant to polyethylene glycol (PEG), sodium phosphate, picosulfate (PICO), or oral sulfate solutions (OSS)-based regimens. Methods Systematic searches were made of MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials from January 1980 to April 2016 that assessed preparations with or without adjuvants, given in split and non-split dosing, and PEG high- (> 3 L) or low-dose (≤ 2 L) regimens. Bowel cleansing efficacy was the primary outcome. Secondary outcomes included patient willingness to repeat the procedure, and polyp and adenoma detection rates. Results Of 3093 citations, 77 trials fulfilled the inclusion criteria. Overall, addition of an adjuvant compared with no adjuvant, irrespective of the type of preparation and mode of administration, yielded improvements in bowel cleanliness (odds ratio [OR] 1.23 [1.01 – 1.51]) without greater willingness to repeat (OR 1.40 [0.91 – 2.15]). Adjuvants combined with high-dose PEG significantly improved colon cleansing (OR 1.96 [1.32 – 2.94]). The odds for achieving adequate preparation with low-dose PEG with an adjuvant were not different to high-dose PEG alone (OR 0.95 [0.73 – 1.22]), but yielded improved tolerance (OR 3.22 [1.85 – 5.55]). However, split high-dose PEG yielded superior cleanliness to low-dose PEG with adjuvants (OR 2.53 [1.25 – 5.13]). No differences were noted for OSS and PICO comparisons, or for any products regarding polyp or adenoma detection rates. Conclusions Critical heterogeneity precludes firm conclusion on the impact of adjuvants with existing bowel preparations. Additional research is required to better characterize the methods of administration and resulting roles of adjuvants in an era of split-dosing.

scholarly journals Metabolic Imaging Using Two-Photon Excited NADH Intensity and Fluorescence Lifetime Imaging

2012 ◽  
Vol 18 (4) ◽  
pp. 761-770 ◽  
Author(s):  
Jorge Vergen ◽  
Clifford Hecht ◽  
Lyandysha V. Zholudeva ◽  
Meg M. Marquardt ◽  
Richard Hallworth ◽  
...  
Keyword(s):  
Fluorescence Lifetime ◽  
Fluorescence Intensity ◽  
Organ Of Corti ◽  
Metabolic Imaging ◽  
Fluorescence Lifetime Imaging ◽  
Metabolic State ◽  
Intact Mouse ◽  
Two Photon ◽  
Lifetime Imaging ◽  
Reduced Nicotinamide Adenine Dinucleotide

AbstractMetabolism and mitochondrial dysfunction are known to be involved in many different disease states. We have employed two-photon fluorescence imaging of intrinsic mitochondrial reduced nicotinamide adenine dinucleotide (NADH) to quantify the metabolic state of several cultured cell lines, multicell tumor spheroids, and the intact mouse organ of Corti. Historically, fluorescence intensity has commonly been used as an indicator of the NADH concentration in cells and tissues. More recently, fluorescence lifetime imaging has revealed that changes in metabolism produce not only changes in fluorescence intensity, but also significant changes in the lifetimes and concentrations of free and enzyme-bound pools of NADH. Since NADH binding changes with metabolic state, this approach presents a new opportunity to track the cellular metabolic state.

scholarly journals 411: The impact of low dose versus high dose antibiotic prophylaxis regimens on surgical site infection rates after cesarean delivery

2017 ◽  
Vol 216 (1) ◽  
pp. S244-S245
Author(s):  
Mauricio La Rosa ◽  
Chasey Omere ◽  
Tiffany Redfurn ◽  
Mahmoud Abdelwahab ◽  
Nicholas Spencer ◽  
...  
Keyword(s):  
Surgical Site Infection ◽  
Antibiotic Prophylaxis ◽  
Cesarean Delivery ◽  
Low Dose ◽  
High Dose ◽  
Site Infection ◽  
Infection Rates ◽  
The Impact

scholarly journals Selective regulation of cellular and secreted multimeric adiponectin by antidiabetic therapies in humans

2009 ◽  
Vol 297 (3) ◽  
pp. E767-E773 ◽  
Author(s):  
Susan A. Phillips ◽  
Jacqueline Kung ◽  
Theodore P. Ciaraldi ◽  
Charles Choe ◽  
Louis Christiansen ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Low Dose ◽  
Whole Body ◽  
Serum Adiponectin ◽  
High Dose ◽  
Hmw Adiponectin ◽  
Dose Combination ◽  
Cell Expression ◽  
The Impact

Adiponectin, an insulin-sensitizing factor secreted from adipose tissue, is decreased in individuals with type 2 diabetes (T2D) and increased in response to thiazolidinedione (TZD) therapy. Changes in its secretion and assembly into higher-order forms affect insulin sensitivity. To determine the relative potency of TZDs on intra-adipocyte multimerization and secretion of adiponectin, we assessed the impact of in vivo low- or high-dose rosiglitazone treatment alone or combined with metformin in subjects with T2D. T2D subjects received high-dose rosiglitazone (8 mg/day), high-dose metformin (2,000 mg/day), or low-dose combination rosiglitazone-metformin therapy (4 mg + 1,000 mg/day) for 4 mo. All subjects were then switched to high-dose rosiglitazone-metformin combination therapy (8 mg + 2,000 mg/day) for another 4 mo. Low-dose rosiglitazone increased serum adiponectin, whereas the high dose increased both adipocyte content and serum adiponectin levels. TZDs selectively increased the percentage of circulating adiponectin in the potent, high-molecular-weight (HMW) form. No TZD effects were evident on multimer distribution in the cell. Expression of the chaperone protein ERp44, which retains adiponectin within the cell, was decreased by TZD treatment. No changes occurred in Ero1-Lα expression. Metformin had no effect on any of these measures. Increases in adiponectin correlated with improvements in insulin sensitivity. In vivo, TZDs have apparent dose-dependent effects on cellular and secreted adiponectin. TZD-mediated improvements in whole body insulin sensitivity are associated with increases in circulating but not cellular levels of the HMW adiponectin multimer. Finally, TZDs promote the selective secretion of HMW adiponectin, potentially, in part, through decreasing the expression of the adiponectin-retaining protein ERp44.

scholarly journals 334. Impact of Overall Dexamethasone Exposure on Development of Invasive Pulmonary Aspergillosis in Hospitalized Patients with COVID-19

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S272-S272
Author(s):  
Erik Skoglund ◽  
Amy Kum ◽  
Allison Mac ◽  
Mark Nguyen
Keyword(s):  
Low Dose ◽  
Opportunistic Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
High Dose ◽  
Pulmonary Aspergillosis ◽  
European Organization ◽  
Eortc Criteria ◽  
Dexamethasone Therapy ◽  
Expanded Criteria ◽  
The Impact

Abstract Background Abbreviated courses of corticosteroids, such as dexamethasone, have demonstrated significant improvements in clinical outcomes among patients infected with COVID-19, although chronic corticosteroid use can predispose patients to opportunistic infections. The RECOVERY trial investigators showed reduced 28-day mortality among patients treated with 6 mg/day dexamethasone for up to 10 days, however in clinical practice the dosage and duration of dexamethasone therapy can vary widely based on severity of disease and provider discretion. Upon observing an anecdotal increase in the number of patients presenting with potential invasive aspergillosis during the third wave of COVID-19, we sought to evaluate the impact of overall dexamethasone exposure on the development of invasive pulmonary aspergillosis. Methods Patients presenting to our institution from Dec. 2020 – Jan. 2021 with positive PCR for SARS-CoV-2 were screened for dexamethasone therapy. Assignment of high vs low dose dexamethasone groups were retrospectively made based on overall dexamethasone exposure. Low dose dexamethasone assignment was restricted to a total exposure of no more than 78 mg during a patient’s hospitalization. Adjudication of invasive pulmonary aspergillosis was made based on criteria that included host factors, radiologic findings, clinical factors, and mycological evidence. Results Dexamethasone therapy was provided to 202 patients admitted to the hospital with COVID-19. Invasive pulmonary aspergillosis was determined to be probable in n=7 patients based on European Organization for Research and Treatment of Cancer (EORTC) criteria, and in n=13 patients based on expanded criteria. Patients in the low dose dexamethasone group were less likely to be diagnosed with probable IPA based on EORTC criteria (n=0, 0% on low dose vs. n=7, 11% on high dose) as well as expanded criteria (n=9, 5% on low dose vs. n=11, 17% on high dose), p< 0.001. Conclusion Patients hospitalized with COVID-19 receiving high-dose dexamethasone may be at a higher risk of opportunistic infections such as invasive pulmonary aspergillosis compared to patients who receive low-dose dexamethasone therapy. Further investigation is needed to obtain higher certainty of IPA diagnosis. Disclosures All Authors: No reported disclosures

scholarly journals Evaluation of anti-ulcer activity of 4-hydrooxy benzalydehide against NSAIDs induced ulcers in rats

2021 ◽  
Vol 9 (5) ◽  
pp. 1412
Author(s):  
Rupali V. Jadhav ◽  
V. K. Redasani ◽  
Shankar B. Kalbhare ◽  
Karishma Yadav ◽  
Aryan Langeh ◽  
...  
Keyword(s):  
Low Dose ◽  
Positive Control ◽  
Gastric Volume ◽  
Control Group ◽  
High Dose ◽  
Antiulcer Activity ◽  
Ulcer Index ◽  
Pylorus Ligation ◽  
The Impact ◽  
Intermediate Dose

Background: The aim of this study was to evaluate antiulcer activity of 4-hydroxybenzaldehyde against NSAIDs induced ulcer in rats based differences in its morphology, distance with other external landmarks and also to sigmoid and transverse sinuses.Methods: The antiulcer activity of 4-HBD was evaluated using pylorus ligation-aspirin induced ulcer method. Animals of this models were treated with 4-HBD (50mg/kg, 100mg/kg and 150mg/kg).Results: It has been observed that 4-HBD at low dose (50mg/kg), intermediate dose (100mg/kg) and high dose (150mg/kg) showed significant increase in pH, significant decrease in gastric volume, significant decrease in ulcer index and significant decrease in total acidity.Conclusions: The impact of 4-HBD therapy with intermediate (100mg/kg, p.o.) dose was observed to be similar with the positive control group.  

scholarly journals Impact of treatment dose on patient outcomes after Interdisciplinary Multimodal Pain Therapy

2021 ◽  
Author(s):  
Philipp Baumbach ◽  
Maria Richter ◽  
Johannes Schneider ◽  
Ulrich Christian Smolenski ◽  
Thomas Weiss ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Pain Therapy ◽  
Low Dose ◽  
High Dose ◽  
Multimodal Pain Therapy ◽  
Average Pain Intensity ◽  
Average Pain ◽  
Interdisciplinary Multimodal Pain Therapy ◽  
The Impact

Abstract Objectives The impact of duration and intensity on outcomes after Interdisciplinary Multimodal Pain Therapy (IMPT) is poorly researched. The aim of this study was to compare the effects of low dose (LD, avg. 25 hours) and high dose IMPT (HD, avg. 110 hours).Methods Patients completed pain-related questionnaires at the beginning (T1), at the end of therapy (T2) and at 3-month follow-up (T3) and were matched according to age, sex, presence of back-pain and pain-related disability at T1, resulting in 32 patients per group. Primary endpoint was the difference in pain-related disability and average pain intensity at T3 between both groups. In addition, early treatment effects and group differences at T2 were analyzed.Results Both groups showed significant improvements in pain-related disability and average pain intensity between T1 and T2. These positive effects persisted in the HD group until the 3-month follow-up, whereas outcomes in the LD group patients deteriorated and were significantly poorer compared to HD at T3.Discussion Within a widely comparable therapeutic setting, high-dose IMPT was associated with longer lasting improvements compared to low-dose IMPT in chronic pain patients, indicating that the “dose” of therapy is a relevant factor for clinical outcomes and should be further investigated.

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