Reducing radiation dose for multi-phase contrast-enhanced dual energy renal CT: pilot study evaluating prior iterative reconstruction

Abdominal Radiology - Prior iterative reconstruction (PIR) uses spatial information from one phase of enhancement to reduce image noise in other phases. We sought to determine if PIR could reduce...     

Selective inhibition of histone deacetylase 6 alters the composition of circulating blood cells in a lethal septic model

Background

Phagocytes, especially monocytes, macrophages, and dendritic cells, play a pivotal role in the innate and adaptive immune responses during sepsis. We have shown that inhibition of histone deacetylase 6 improves survival and increases bacterial clearance in a mouse model of cecal ligation and puncture (CLP). The aim of this study was to determine whether this effect was associated with changes in the number and composition of different blood cell types in the circulation.

Methods

C57BL/6J mice were subjected to CLP, and 1 h later given an intraperitoneal injection of either Tubastatin A dissolved in dimethyl sulfoxide, or dimethyl sulfoxide only. Sham-operated animals were treated in an identical fashion but not subjected to CLP. Forty-eight hours later, peripheral blood was obtained via cardiac puncture and analyzed using a HemaTrue veterinary hematology analyzer.

Results

Tubastatin A administration increased the number of circulating monocytes in the sham-operated and the CLP animals. In comparison with the sham, CLP animals displayed an increase in the granulocyte percentage in white blood cells and decrease in the lymphocyte number and percentage, with a resultant increase in the granulocyte-to-lymphocyte ratio. Treatment of CLP animals with Tubastatin A decreased the granulocyte percentage and restored the lymphocyte number and percentage, which decreased the granulocyte-to-lymphocyte ratio. In the sham animals, Tubastatin A increased red blood cell number, hematocrit, and hemoglobin. This effect was not seen in CLP animals.

Conclusions

Tubastatin A treatment has significant impact on the composition of circulating blood cells. It increases the number of circulating monocytes and the red blood cell mass in sham-operated animals. In the CLP animals, it increases the monocyte count, decreases the percentage of granulocytes, restores the lymphocyte population, and decreases the granulocyte-to-lymphocyte ratio. These results may explain why Tubastatin A treatment improves survival in the septic models.     

Valproic acid for the treatment of hemorrhagic shock: a dose-optimization study

Background

Valproic acid (VPA) has been shown to improve survival in animal models of hemorrhagic shock at a dose of 300 mg/kg. Our aim was to identify the ideal dose through dose-escalation, split-dosing, and dose de-escalation regimens.

Materials and methods

Rats were subjected to sublethal 40% hemorrhage and treated with vehicle or VPA (dose of 300, 400, or 450 mg/kg) after 30 min of shock. Acetylated histones and activated proteins from the PI3K–Akt–GSK-3β survival pathway at different time points were quantified by Western blot analysis. In a similar model, a VPA dose of 200 mg/kg followed 2 h later by another dose of 100 mg/kg was administered. Finally, animals were subjected to a lethal 50% hemorrhage and VPA was administered in a dose de-escalation manner (starting at dose of 300 mg/kg) until a significant drop in percent survival was observed.

Results

Larger doses of VPA resulted in greater acetylation of histone 3 and increased activation of PI3K pathway proteins. Dose-dependent differences were significant in histone acetylation but not in the activation of the survival pathway proteins. Split-dose administration of VPA resulted in similar results to a single full dose. Survival was as follows: 87.5% with 300 and 250 mg/kg of VPA, 50% with 200 mg/kg of VPA, and 14% with vehicle-treated animals.

Conclusions

Although higher doses of VPA result in greater histone acetylation and activation of prosurvival protein signaling, doses as low as 250 mg/kg of VPA confer the same survival advantage in lethal hemorrhagic shock. Also, VPA can be given in a split-dose fashion without a reduction in its cytoprotective effectiveness.     

Triterpenoids from<Emphasis Type="Italic">Schisandra henryi</Emphasis> with cytotoxic effect on leukemia and hela cells<Emphasis Type="Italic">in vitro</Emphasis>

Four known lanostane triterpenoids, schiprolactone A (1), schisanlactone B (2), nigranoic acid (3) and schisandronic acid (4) were isolated from the stems of Schisandra henryi for the first time. Their structures were characterized by IR, MS and NMR techniques. Compounds 1, 2 and 4 showed moderate cytotoxic activity against Leukemia cells in vitro. Cytotoxic activity of compounds 1-4 showed IC50 of 0.0097, 0.01, 0.097 and 0.0099 micromol/mL respectively toward Leukemia cells and IC50 of 0.097, 0.1, 0.097 and 0.099 micromol/mL toward Hela cells respectively. It is the first report that these compounds possess cytotoxic activity on Leukemia and Hela cells.     

Compliance with evidence-based guidelines for computed tomography of children with head and abdominal trauma

Introduction

Recently, two large prospective clinical trials developed and validated prediction rules for children at very low risk for clinically important traumatic brain injuries (ciTBI) or abdominal injury for whom CT is unnecessary. Specific criteria/guidelines were identified which if met would obviate the need for CT scanning. The purpose of this study was to assess compliance at a level one pediatric center with these guidelines as a tool for quality improvement.

Naringin does not alter caffeine pharmacokinetics, energy expenditure, or cardiovascular haemodynamics in humans following caffeine consumption

1. Naringin, a grapefruit constituent interacts with many medications including caffeine, a popular weight loss supplement. The purpose of the current study was to identify changes in caffeine pharmacokinetics, resting energy expenditure (REE), oxygen consumption (VO(2)) and respiratory exchange ratio (RER) after an acute dosage of caffeine and naringin. 2. Using a double-blinded, counterbalanced design, REE, VO(2), and RER were measured before and systematically for 8 h after a single dosage of caffeine (CAF, 200 mg) with and without naringin (100 mg (CN100) or 200 mg (CN200)) in 10 apparently healthy individuals. A standardized meal was provided following 240-minute measurements (400 kcals; 35 g carbohydrate; 27 g protein; 7 g fat). 3. Caffeine, CN100, CN200 did not alter VO(2) or VO(2) area under the curve (137 301 +/- 8318, 139 729 +/- 9300, 134 297 +/- 8318, mL/480 min). Resting energy expenditure (k/cals) was 10.0 +/- 1.4% higher with CAF versus CN200 (6.0 +/- 1.4%) and CN100 (6 +/- 1.5%) at 240 min (P = 0.07) which was then negated following a standardized meal. Percent change in RER from pre to 240 min and pre to 480 min was not different between the CAF, CN100, or CN200 (-0.2 +/- 1.7%, 1.7 +/- 1.7%, -2.8 +/- 1.9%). 4. Although caffeine alone suggests a trend of increased REE, the results of the present study indicate that concurrent consumption of caffeine with naringin in acute dosages does not affect RER, VO(2), and prevents the increase of REE in adult humans. The results suggest that the interaction of grapefruit juice and caffeine may be due to constituents of grapefruit juice other than naringin or in addition to naringin.     

Compounds with DNA cleaving activity from Kadsura ananosma

Two DNA cleavage agents, meso-dihydroguaiaretic acid (1) and isobavachalcone (2) together with the known alpha-ylangene, beta-sitosterol, daucosterol, pentacosane, hexacosanic acid and cerotic acid 1-monoglyceride were isolated from the stem barks of Kadsura ananosma Kerr for the first time. Compounds 1 and 2 showed relaxation of supercoiled DNA to nicked DNA. 1 represented a new structural type of DNA cleavage agent, while 2 was reported to show DNA strand-scission activity for the first time. 1 also showed significant cytotoxic effect on Hela and Leukemia cells in vitro.     

Open versus endoscopic component separation: a cost comparison

Background  

The components separation technique (CST) is performed through an open or endoscopic approach. It is unclear whether the costs associated with the endoscopic instruments outweigh any clinical benefit derived from their use and the avoidance of lipocutaneous flaps. This study aimed to compare the direct costs associated with each approach.