Performance of a UV-A LED system for degradation of aflatoxins B1 and M1 in pure water: kinetics and cytotoxicity study

The efficacy of a UV-A light emitting diode system (LED) to reduce the concentrations of aflatoxin B1, aflatoxin M1 (AFB1, AFM1) in pure water was studied. This work investigates and reveals the kinetics and main mechanism(s) responsible for the destruction of aflatoxins in pure water and assesses the cytotoxicity in liver hepatocellular cells. Irradiation experiments were conducted using an LED system operating at 365 nm (monochromatic wave-length). Known concentrations of aflatoxins were spiked in water and irradiated at UV-A doses ranging from 0 to 1,200 mJ/cm2. The concentration of AFB1 and AFM1 was determined by HPLC with fluorescence detection. LC–MS/MS product ion scans were used to identify and semi-quantify degraded products of AFB1 and AFM1. It was observed that UV-A irradiation significantly reduced aflatoxins in pure water. In comparison to control, at dose of 1,200 mJ/cm2 UV-A irradiation reduced AFB1 and AFM1 concentrations by 70 ± 0.27 and 84 ± 1.95%, respectively. We hypothesize that the formation of reactive species initiated by UV-A light may have caused photolysis of AFB1 and AFM1 molecules in water. In cell culture studies, our results demonstrated that the increase of UV-A dosage decreased the aflatoxins-induced cytotoxicity in HepG2 cells, and no significant aflatoxin-induced cytotoxicity was observed at UV-A dose of 1,200 mJ/cm2. Further results from this study will be used to compare aflatoxins detoxification kinetics and mechanisms involved in liquid foods such as milk and vegetable oils

Impact of UV-C irradiation on the quality, safety, and cytotoxicity of cranberry-flavored water using a novel continuous flow UV system

The influence of short wavelength UV-C irradiation at 254 nm on microbial inactivation, anthocyanins stability, ascorbic acid, and cytotoxicity of formulated cranberry flavored water was studied. Escherichia coli ATCC 25922 and Salmonella enterica serovar Typhimurium ATCC 13311 were inactivated by more than 5 log10 at UV-C fluence of 21 mJ cm−2. At UV-C fluence of 40 mJ cm−2 the content of ascorbic acid was 82% of that in the untreated beverage. The concentrations of the anthocyanins (Cy3Ar, Cy3Ga, Pe3Ar, and Pe3Ga) were not significantly affected at the same treatment level. Cytotoxicity evaluation of the irradiated beverage on normal colon (CCD-18Co), colon cancer (HCT-116), and healthy mice liver (AML-12) cells showed that UV-C irradiation had no cytotoxic effects on all three cell lines. This research study suggests that UV-C treatment of formulated cranberry flavored water can achieve high levels of microbial inactivation without significantly decreasing the concentration of anthocyanins, ascorbic acid content or generating cytotoxic effects. These results suggest that UV-C irradiation can be an alternative to thermal pasteurization in producing high quality beverages

Hysteresis and Avalanches in the Random Anisotropy Ising Model

The behaviour of the Random Anisotropy Ising model at T=0 under local relaxation dynamics is studied. The model includes a dominant ferromagnetic interaction and assumes an infinite anisotropy at each site along local anisotropy axes which are randomly aligned. Two different random distributions of anisotropy axes have been studied. Both are characterized by a parameter that allows control of the degree of disorder in the system. By using numerical simulations we analyze the hysteresis loop properties and characterize the statistical distribution of avalanches occuring during the metastable evolution of the system driven by an external field. A disorder-induced critical point is found in which the hysteresis loop changes from displaying a typical ferromagnetic magnetization jump to a rather smooth loop exhibiting only tiny avalanches. The critical point is characterized by a set of critical exponents, which are consistent with the universal values proposed from the study of other simpler models.Comment: 40 pages, 21 figures, Accepted for publication in Phys. Rev.

Virologic Failure of Protease Inhibitor-Based Second-Line Antiretroviral Therapy without Resistance in a Large HIV Treatment Program in South Africa

Background: We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa. Methodology/ Principal Findings HIV-infected patients $\geq$15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged. Conclusions/ Significance: Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure

Role of Cytochrome P450 Enzymes in the Metabolic Activation of Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitors are a rapidly expanding class of molecular targeted therapies for the treatment of various types of cancer and other diseases. An increasing number of clinically important small molecule tyrosine kinase inhibitors have been shown to undergo cytochrome P450-mediated bioactivation to form chemically reactive, potentially toxic products. Metabolic activation of tyrosine kinase inhibitors is proposed to contribute to the development of serious adverse reactions, including idiosyncratic hepatotoxicity. This article will review recent findings and ongoing studies to elucidate the link between drug metabolism and tyrosine kinase inhibitor-associated hepatotoxicity

Ca2+-regulated Pool of Phosphatidylinositol-3-phosphate Produced by Phosphatidylinositol 3-Kinase C2α on Neurosecretory Vesicles

Phosphatidylinositol-3-phosphate [PtdIns(3)P] is a key player in early endosomal trafficking and is mainly produced by class III phosphatidylinositol 3-kinase (PI3K). In neurosecretory cells, class II PI3K-C2α and its lipid product PtdIns(3)P have recently been shown to play a critical role during neuroexocytosis, suggesting that two distinct pools of PtdIns(3)P might coexist in these cells. However, the precise characterization of this additional pool of PtdIns(3)P remains to be established. Using a selective PtdIns(3)P probe, we have identified a novel PtdIns(3)P-positive pool localized on secretory vesicles, sensitive to PI3K-C2α knockdown and relatively resistant to wortmannin treatment. In neurosecretory cells, stimulation of exocytosis promoted a transient albeit large increase in PtdIns(3)P production localized on secretory vesicles sensitive to PI3K-C2α knockdown and expression of PI3K-C2α catalytically inactive mutant. Using purified chromaffin granules, we found that PtdIns(3)P production is controlled by Ca2+. We confirmed that PtdIns(3)P production from recombinantly expressed PI3K-C2α is indeed regulated by Ca2+. We provide evidence that a dynamic pool of PtdIns(3)P synthesized by PI3K-C2α occurs on secretory vesicles in neurosecretory cells, demonstrating that the activity of a member of the PI3K family is regulated by Ca2+ in vitro and in living neurosecretory cells