In this study, a novel electrochemical aptamer sensor for detecting ochratoxin A (OTA) was constructed. First, a gold-copper alloy film was prepared via electrochemical deposition, and copper was selectively dissolved in constant potential mode for obtaining the nano-porous gold modified screen-printed carbon electrodes (NPG/SPCE). Then, 2-mercaptoethylamine was dropped on the NPG/SPCE surface and Au-S covalent bonds were formed for immobilizing the metal. Glutaraldehyde as cross-linking agent was added, which resulted in immobilization and attachment of PAMAM to the 2-mercaptoethylamine through the dehydration condensation reaction. During the preparation process, the nano-porous gold and PAMAM-modified layers were characterized by SEM, XRD, and IR spectroscopy, respectively. The characterization results showed that the nano-porous gold and PAMAM composite films were successfully modified. Finally, the OTA aptamer was cross-linked with PAMAM by glutaraldehyde to complete construction of the Apt/PAMAM/NPG/SPCE sensor. The electrochemical performance of this sensor was tested in ochratoxin A solutions with the DPV method. The results showed that the sensor\'s reproducibility, stability, and specificity were good. The spiked recoveries in red wine ranged from 99.65%∼101.6%, with a linear range of 0.5 ng/mL∼20 ng/mL and a minimum detection limit of 0.141 ng/mL. Thus, the novel biosensor may provide a promising tool for the trace detection of OTA.

OBJECTIVE: We have undertaken this study to investigate the feasibility of topical application of the radioprotective compound WR-2721 to the buccal mucosa.
METHODS: Saliva samples were collected from 5 volunteers and were reconstituted in 3 amifostine solutions. Measurements of amifostine and WR-1065 contents were performed at 6 different time points. Young-adult guinea pigs were topically administered amifostine 50 and 100 mg to each buccal mucosa. At 0, 15 and 30 min after application, the blood samples obtained from the heart and the buccal tissues were prepared for the analysis of amifostine and WR-1065.
RESULTS: There was no significant difference between the 3 concentrations of amifostine in saliva in vitro at any of the 6 study time points (p > 0.05). No WR-1065 was detected in saliva. In the guinea pigs from groups A and B, there were significant differences in concentrations of amifostine and WR-1065 in the tissues between the 0-min and 15-min subgroups and between the 0-min and 30-min subgroups (p < 0.05). The concentrations of amifostine and WR-1065 from the 15-min and 30-min subgroups did not differ statistically (p > 0.05).
CONCLUSIONS: It is feasible to administer topical amifostine (WR-2721) to mucosa to prevent radiation-induced oral mucositis, and systemic absorption is negligible. Relatively high concentrations of amifostine in human saliva in vitro were maintained, although some inconsistent changes are observed.

OBJECTIVE: Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect. We hypothesized that amifostine would permit escalation of whole-liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy.
METHODS: We conducted a radiation dose-escalation trial for patients with diffuse, intrahepatic cancer treated with whole-liver radiation and intravenous amifostine. Radiation dose was assigned using the time-to-event continual reassessment method. A companion pharmacokinetic study was performed.
RESULTS: Twenty-three patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared with our previously treated patients, amifostine increased liver tolerance by 3.3 ± 1.1 Gy (p = 0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 μM with an elimination half-life of 1.5 h; these levels are consistent with radioprotective effects of amifostine in patients.
CONCLUSIONS: These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer.

BACKGROUND: Ionizing radiation (IR) initiates intracellular oxidative stress through enhanced formation of reactive oxygen species (ROS) that attack DNA leading to cell death. Because of the diversity of IR applied in medicine, agriculture, industry, and the growing threats of global terrorism, the acquisition of radioprotectors is an urgent need for the nation. However, the applicability of radioprotectors currently under investigation is limited due to their inherent toxicity.
OBJECTIVE: This study investigated the effect of a standardized North American ginseng extract (NAGE, total ginsenoside content: 11.7%) on DNA damage in human lymphocytes at 90 minutes postirradiation.
METHODS: With the application of NAGE (250-1000 microg mL(-1)) at 90 minutes postirradiation (1 and 2 Gy), DNA damage in lymphocytes obtained from 40 healthy individuals was evaluated by cytokinesis-block micronucleus assay. Similar experiments were also performed in lymphocytes treated with WR-1065 (1 mmol/L or 3 mmol/L). In addition, before and after irradiation, lymphocytes obtained from 10 individuals were measured for their total antioxidant capacity (TAC) and the reactive oxygen species (ROS).
RESULTS: The significant effect of NAGE against (137)Cs-induced micronuclei (MN) in lymphocytes is concentration dependent. NAGE (750 microg mL(-1)) reduced MN yield by 50.7% after 1 Gy and 35.9% after 2 Gy exposures, respectively; these results were comparable to that of WR-1065. Furthermore, we also found that NAGE reduces MN yield and ROS but increases TAC in lymphocytes.
CONCLUSIONS: Our results suggest that NAGE is a relatively nontoxic natural compound that holds radioprotective potential in human lymphocytes even when applied at 90 minutes postirradiation. One of the radioprotective mechanisms may be mediated through the scavenging of free radicals and enhancement of the intracellular TAC.

It is now generally accepted that both the structure and function of a number of specific transcriptional factors, including p53, are subject to redox regulation in cells in which these factors are expressed. The present chapter describes methods for the analysis of redox changes in the structure of p53 and the effect of redox modulation on binding of p53 to a DNA consensus sequence. In addition, methods are described for studying the effect of redox perturbations of cells on the functioning of p53 in the cell cycle and in apoptosis. By studying the effect ofredox agents on p53, we have concluded that p53 is subject to structural redox modulation and that this modulation affects the functional ability of the protein to bind to DNA, to cause cell cycle arrest, and to trigger apoptosis.

The effect of the amoxicilline as a possible cisplatin-action protector on pBR322 DNA has been visually studied by atomic force microscopy in comparison with the modifications caused by the controversed cisplatin protector amifostine. Incubation of amoxicilline with the plasmid DNA showed aggregation and compaction of DNA. Cisplatin incubated in the same conditions with DNA produced kinks and super-coiling of the circular form. In the case of previous treatment of DNA with amoxicilline, the characteristic effect of cisplatin is only partially observed. The amoxicilline seemed to control the action of cisplatin on DNA. The initial effect of dephosphorylated amifostine (WR-1065) when this protector was incubated with the plasmid was also the formation of aggregates and the compaction of DNA. However, addition of cisplatin successively after 1 and 2 h showed the characteristic modification caused by cisplatin but only in a decreasing percentage of molecules of DNA. Both molecules, amoxicilline and WR-1065 seem to control the strong direct action of cisplatin on DNA. This effect can justify the role as protecting agent of amifostine on side effects caused by cisplatin and can open new possibilities to other agents like amoxicilline.

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