Antioxidant Networks In vivo

Oxygen interacts with cells and can form highly reactive compounds in vivo known as reactive oxygen species (ROS). High levels of ROS can lead to cellular damage, oxidative stress, heart diseases and cancer. Known substances that are capable of halting the physiological process of oxidation in tissue are called antioxidants.This review covers developments in the field of antioxidant chemistry including interactions between antioxidants and ROS, topics about sources and natural occurrences, classification of antioxidants and a discussion of possible mechanisms. We also summarize examples of oxidative stress biomarkers.

Enantioselective liquid chromatography–mass spectrometry assay for the determination of ifosfamide and identification of the N-dechloroethylated metabolites of ifosfamide in human plasma

A sensitive and specific liquid chromatography-mass spectrometry (LC-MS) method has been developed and validated for the enantioselective determination of ifosfamide [(R)-IF and (S)-IF] in human plasma and for the detection of the N-dechloroethylated metabolites of IF, 2-N-dechloroethylifosfamide [(R)-2-DCl-IF and (S)-2-DCl-IF] and 3-N-dechloroethylifosfamide [(R)-3-DCl-IF and (S)-3-DCl-IF]. IF, 2-DCl-IF and 3-DCl-IF were extracted from plasma using solid-phase extraction and resolved by liquid chromatography on a column containing a Chirabiotic T chiral stationary phase. The enantioselective separations were achieved using a mobile phase composed of 2-propanol:methanol (60:40 v/v) and a flow rate of 0.5 ml/min. The observed enantioselectivities (α) for IF, 2-DCl-IF and 3-DCl-IF were 1.20, 1.17 and 1.20, respectively. The calibration curve was linear in the concentration range of 37.50-4800 ng/ml for each ifosfamide enantiomer (r2 > 0.997). The lower limit of detection (LLOD) was 5.00 ng/ml. The inter- and intra-day precision ranged from 3.63 to 15.8 % relative standard deviation (RSD) and 10.1 to 14.3 % RSD, respectively, and the accuracy ranged from 89.2 to 101.5 % of the nominal values. The method was applied to the analysis of plasma samples obtained from a cancer patient who received 3.75 g/m2/d dose of (R,S)-ifosfamide as a 96-h continuous infusion

19F MRI of 3-D CEM cells to study the effects of tocopherols and tocotrienols

Oximetry of the human T-Lymphoblastoid (CEM) cells was measured using 19F magnetic resonance imaging (19F MRI). The cells were treated with the analogues of vitamin E, \u3b1-, \u3b3-, \u3b4-tocopherols and corresponding tocotrienols, ex vivo in three-dimensional (3D) cell culture. The study showed that 19F MRI allows to measure the effect of the analogues due to changes of oxygenation, which were detected using MRI. Hexafluorobenzene was used as a 19F MRI probe sensitive to oxygen concentrations. After 72 h of treatment in HFBR with \u3b1-, \u3b3-, \u3b4-tocopherols the oxygen concentration was 19.9 \ub1 0.8%, 19.3 \ub1 1.4%, 16 \ub1 3.5%, respectively. The oxygen concentration in cells treated with \u3b1-, \u3b3-, \u3b4-tocotrienols was found to be 14 \ub1 1.5%, 10 \ub1 1.2% and 8.8 \ub1 1.1%, respectively whereas for the control cells it was 22.1 \ub1 1%. The results show that \u3b4-tocopherol and \u3b4-tocotrienol are the most effective treatments in CEM cells among all the tested analogues.Peer reviewed: YesNRC publication: Ye

Effects of perineural administration of ropivacaine combined with perineural or intravenous administration of dexmedetomidine for sciatic and saphenous nerve blocks in dogs.

peer reviewedOBJECTIVE: To evaluate the effects of using ropivacaine combined with dexmedetomidine for sciatic and saphenous nerve blocks in dogs. ANIMALS: 7 healthy adult Beagles. PROCEDURES: In phase 1, dogs received each of the following 3 treatments in random order: perineural sciatic and saphenous nerve injections of 0.5% ropivacaine (0.4 mL/kg) mixed with saline (0.9% NaCl) solution (0.04 mL/kg; DEX0PN), 0.5% ropivacaine mixed with dexmedetomidine (1 μg/kg; DEX1PN), and 0.5% ropivacaine mixed with dexmedetomidine (2 μg/kg; DEX2PN). In phase 2, dogs received perineural sciatic and saphenous nerve injections of 0.5% ropivacaine and an IV injection of diluted dexmedetomidine (1 μg/kg; DEX1IV). For perineural injections, the dose was divided equally between the 2 sites. Duration of sensory blockade was evaluated, and plasma dexmedetomidine concentrations were measured. RESULTS: Duration of sensory blockade was significantly longer with DEX1PN and DEX2PN, compared with DEX0PN; DEX1IV did not prolong duration of sensory blockade, compared with DEX0PN. Peak plasma dexmedetomidine concentrations were reached after 15 minutes with DEX1PN (mean ± SD, 348 ± 200 pg/mL) and after 30 minutes DEX2PN (816 ± 607 pg/mL), and bioavailability was 54 ± 40% and 73 ± 43%, respectively. The highest plasma dexmedetomidine concentration was measured with DEX1IV (1,032 ± 415 pg/mL) 5 minutes after injection. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that perineural injection of 0.5% ropivacaine in combination with dexmedetomidine (1 μg/kg) for locoregional anesthesia in dogs seemed to balance the benefit of prolonging sensory nerve blockade while minimizing adverse effects