Clinically Approved Iron Chelators Influence Zebrafish Mortality,Hatching Morphology and Cardiac Function

Iron chelation therapy using iron (III) specific chelators such as desferrioxamine (DFO, Desferal), deferasirox (Exjade or ICL-670), and deferiprone (Ferriprox or L1) are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos. In this study, we took advantage of the rapid development and transparency of the zebrafish embryo, Danio rerio to assess and compare the toxicity of iron chelators. All three iron chelators described above were delivered to zebrafish embryos by direct soaking and their effects on mortality, hatching and developmental morphology were monitored for 96 hpf. To determine whether toxicity was specific to embryos, we examined the effects of chelator exposure via intra peritoneal injection on the cardiac function and gene expression in adult zebrafish. Chelators varied significantly in their effects on embryo mortality, hatching and morphology. While none of the embryos or adults exposed to DFO were negatively affected, ICL -treated embryos and adults differed significantly from controls, and L1 exerted toxic effects in embryos alone. ICL-670 significantly increased the mortality of embryos treated with doses of 0.25 mM or higher and also affected embryo morphology, causing curvature of larvae treated with concentrations above 0.5 mM. ICL-670 exposure (10 µL of 0.1 mM injection) also significantly increased the heart rate and cardiac output of adult zebrafish. While L1 exposure did not cause toxicity in adults, it did cause morphological defects in embryos at 0.5 mM. This study provides first evidence on iron chelator toxicity in early development and will help to guide our approach on better understanding the mechanism of iron chelator toxicity.     

Inhibition of amyloid fibrillation of lysozyme by indole derivatives--possible mechanism of action

Amyloid aggregation of polypeptides is related to a growing number of pathologic states known as amyloid disorders. There is a great deal of interest in developing small molecule inhibitors of the amyloidogenic processes. In the present article, the inhibitory effects of some indole derivatives on amyloid fibrillation of hen egg white lysozyme (HEWL) are reported. Acidic pH and high temperatures were used to drive HEWL towards amyloid formation. A variety of techniques, ranging from thioflavin T fluorescence and Congo red absorbance assays to far-UV CD and transmission electron microscopy, were employed to characterize the HEWL fibrillation process. Among the indole derivatives tested, indole 3-acetic acid, indole 3-carbinol and tryptophol had the most inhibitory effects on amyloid formation, indole and indole 3-propionic acid gave some inhibition, and indole aldehyde and tryptophan showed no significant inhibition. Although indoles did not protect the HEWL native state from conformational changes, they were effective in diminishing HEWL amyloid fibril formation, delaying both the nucleation and elongation phases. Disaggregation of previously formed HEWL amyloid fibrils was also enhanced by indole 3-acetic acid. Various medium conditions, such as the presence of different anions and alcoholic cosolvents, were explored to gain an insight into possible mechanisms. These observations, taken together, suggest that the indole ring is likely to play the main role in inhibition and that the side chain hydroxyl group may contribute positively, in contrast to the side chain carbonyl and intervening methylene groups.     

Design of Localized Surface Plasmon Resonance (LSPR) Biosensor for Immunodiagnostic of E. coli O157:H7 Using Gold Nanoparticles Conjugated to the Chicken Antibody

E. coli O157:H7 is one of the most important pathogens in food-borne diseases and is the main cause of the pseudo pandemic development of hemorrhagic colitis and hemolytic uremic syndrome. Also E. coli O157:H7 is the most common serotype of Shiga-toxin-producing E. coli. Traditional methods for detecting E. coli O157:H7 are expensive, time-consuming, and less sensitive. A method with high sensitivity and high-resolution optical detection is utilizes the LSPR property of spherical gold nanoparticles (GNP). In this work, we constructed a novel nano-bio probe to detect E. coli O157:H7 by synthesizing citrate gold nanoparticle conjugated (non-covalent bond) with specific chicken anti-E. coli O157:H7 antibody (IgY) by changing the pH of the nanoparticles’ environment. UV-visible and DLS methods were used to confirm the bonding between the antibody and nanoparticles and the LSPR sensitivity of the nano-bio probe was evaluated by ELISA method. We could optically detect this bacterium in less than 2 h by measuring the LSPR band λ max shifts of GNPs. The sensitivity of this novel biosensor was determined by about 10 CFU/ml, using the LSPR property of spherical gold nanoparticles. So that, the LSPR λ max red shifted from 530 to 543 nm in presence of 10 CFU bacterium. In conclusion, this nano biosensor can be used to detect this important pathogen among the clinical specimens.

     

Has vitamin E any shreds of evidence in cisplatin‐induced toxicity

Cisplatin is one of the highly consumed and effective antitumor agents whose clinical application is accompanied by nephrotoxicity adverse reaction. Also, other complications such as ototoxicity and hepatotoxicity are a matter of concern. Today, it is suggested that cisplatin‐associated toxicities are mainly induced by free radicals production, which will result in oxidative organ injury. The evidence is growing over the protective effects of antioxidants on cisplatin‐induced adverse reactions especially nephrotoxicity. The possible protective effects of vitamin E and its derivative in cisplatin‐induced nephrotoxicity and ototoxicity are reviewed here at the light of pertinent results from basic and clinical research. Administration of vitamin E alone or in combination with other antioxidant agents could cause amelioration in oxidative stress biomarkers such as decreasing the level of malondialdehyde, reducing serum urea and creatinine, and also enhancing the activities of renal antioxidant enzymes including renal catalase, glutathione‐S‐transferase, and superoxide dismutase. Although the data from most of the studies are in favors of protective effects of vitamin E against cisplatin‐induced toxicity, more clinical trials are needed to clarify the clinical importance of vitamin E administration as an antioxidant during cisplatin therapy in cancer condition.     

Association of MexAB-OprM with intrinsic resistance ofPseudomonas aeruginosa to aminoglycosides

MexAB-OprM is known to pump out mostly lipophilic and amphiphilic drugs. But in low-ionic-strength medium, nutrient broth (NB), this pump has been shown to contribute to hydrophilic antibiotic (aminoglycosides) resistance, via active efflux. The association of the MexAB-OprM efflux system to aminoglycosides resistance inPseudomonas aeruginosa were assessed using a drug susceptibility test carried out in NB, in presence and absence of protonophore, carbonyl cyanide m-chlorophenyl hydrazone (CCCP) by 23 multidrug resistant strains were selected from 104 clinical isolates ofP. aeruginosa. Active efflux was assessed using EtBr accumulation assays. PCR was used to identify themexAB-oprM and MexAB-OprM-dependent efflux of aminoglycosides and the results were confirmed by continuous fluorescence assay. A multidrug resistant mutant ofmexAB-oprM, derivative of PAO1, was selected by ciprofloxacin and subjected to the same analysis as described above for the clinical isolates. In this study, CCCP reduced the level of MICs in at least 1 dilution. Ethidium bromide accumulation assays confirmed the presence of efflux mechanism in all clinical isolates and PCR demonstrated that 17% of our isolates had themexAB-oprM operon. Results of aminoglycosides accumulation showed, in addition to amphiphilic antibiotics in NB medium, MexAB-OprM extrudes aminoglycosides (hydrophilic) drugs.     

Intersession Consistency of Single-Trial Classification of the Prefrontal Response to Mental Arithmetic and the No-Control State by NIRS

Near-infrared spectroscopy (NIRS) has been recently investigated for use in noninvasive brain-computer interface (BCI) technologies. Previous studies have demonstrated the ability to classify patterns of neural activation associated with different mental tasks (e.g., mental arithmetic) using NIRS signals. Though these studies represent an important step towards the realization of an NIRS-BCI, there is a paucity of literature regarding the consistency of these responses, and the ability to classify them on a single-trial basis, over multiple sessions. This is important when moving out of an experimental context toward a practical system, where performance must be maintained over longer periods. When considering response consistency across sessions, two questions arise: 1) can the hemodynamic response to the activation task be distinguished from a baseline (or other task) condition, consistently across sessions, and if so, 2) are the spatiotemporal characteristics of the response which best distinguish it from the baseline (or other task) condition consistent across sessions. The answers will have implications for the viability of an NIRS-BCI system, and the design strategies (especially in terms of classifier training protocols) adopted. In this study, we investigated the consistency of classification of a mental arithmetic task and a no-control condition over five experimental sessions. Mixed model linear regression on intrasession classification accuracies indicate that the task and baseline states remain differentiable across multiple sessions, with no significant decrease in accuracy (p = 0.67). Intersession analysis, however, revealed inconsistencies in spatiotemporal response characteristics. Based on these results, we investigated several different practical classifier training protocols, including scenarios in which the training and test data come from 1) different sessions, 2) the same session, and 3) a combination of both. Results indicate that when selecting optimal classifier training protocols for NIRS-BCI, a compromise between accuracy and convenience (e.g., in terms of duration/frequency of training data collection) must be considered.     

A new species of Myrmozercon Berlese (Acari,Mesostigmata, Laelapidae) associated?with?ant?from?Iran

This paper report on a new species of mites of the genus Myrmozercon associated with ant in Iran – Myrmozercon cyrusi Ghafarian and Joharchi sp. n. was collected associated of the Monomorium sp. in Kenevist Rural District in the Central District of Mashhad County, Khorasan Razavi Province, Iran. This new species is described and illustrations provided. Myrmozercon ovatum Karawajew, 1909 is suspected to be a junior synonym of Myrmozercon brevipes Berlese, 1902 and host-specificity and host range of Myrmozercon are also reviewed.     

Automated Detection of Actinic Keratoses in Clinical Photographs

Background

Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions.

Objective

The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible.

Methods

Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist’s assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group.

Results

The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist’s intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group.

Conclusions

The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53.1% on the arms.This suggests that image analysis is a feasible avenue of investigation for overcoming variability in clinical assessment. Future studies should focus on more sophisticated features to improve sensitivity for actinic keratoses without erythema and limit false positives associated with the anatomical structures on the face.     

Coenzyme Q10 protects isolated human blood cells from TiO2 nanoparticles induced oxidative/antioxidative imbalance,hemolysis, cytotoxicity,DNA damage and mitochondrial impairment

Molecular Biology Reports - TiO2 NPs have been investigated for their toxic potential and studies have reported their toxicity is due to generation of oxidative stress. In the present study, we...