Surface functionalization-specific binding of coagulation factors by zinc oxide nanoparticles delays coagulation time and reduces thrombin generation potential in vitro.

Zinc oxide nanoparticles (ZnO NPs) have many biomedical applications such as chemotherapy agents, vaccine adjuvants, and biosensors but its hemocompatibility is still poorly understood, especially in the event of direct contact of NPs with blood components. Here, we investigated the impact of size and surface functional groups on the platelet homeostasis. ZnO NPs were synthesized in two different sizes (20 and 100 nm) and with three different functional surface groups (pristine, citrate, and L-serine).

Evaluation of radioisotopic and non-radioisotopic versions of local lymph node assays for subcategorization of skin sensitizers compliant to UN GHS rev 4.

Recently UN GHS has introduced the sub-categorization of skin sensitizers for which ECt (concentration estimated to induce stimulation index above threshold) of the murine local lymph node assay (LLNA) is used as criteria. Non-radioisotopic variants of LLNA, LLNA: DA, LLNA: BrdU-ELISA, LNCC and LLNA: BrdU-FCM were developed yet their utilities for potency sub-categorization are not established. Here we assessed the agreement of LLNA variants with LLNA or human data in potency sub-categorization for 22 reference substances of OECD TG429.

Comparison of BALB/c and CBA/J mice for the local lymph node assay using bromodeoxyuridine with flow cytometry (LLNA: BrdU-FCM).

The local lymph node assay using 5-bromo-2-deoxyuridine (BrdU) with flow cytometry (LLNA: BrdU-FCM) is a modified LLNA that is used to identify skin sensitizers by counting BrdU-incorporated lymph node cells (LNCs) with flow cytometry. Unlike other LLNA methods (OECD TG 429, 442A and 442B) in which the CBA/J mouse strain is used, LLNA: BrdU-FCM was originally designed to be compatible with BALB/c, a mouse strain that is more widely used in many countries. To justify the substitution of CBA/J for BALB/c, the equivalence of the test results between two strains shall be established prior to the official implementation of LLNA: BrdU-FCM.

Performance standard-based validation study for local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method.

Local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method (LLNA: BrdU-FCM) is a modified non-radioisotopic technique with the additional advantages of accommodating multiple endpoints with the introduction of FCM, and refinement and reduction of animal use by using a sophisticated prescreening scheme. Reliability and accuracy of the LLNA: BrdU-FCM was determined according to OECD Test Guideline (TG) No. 429 (Skin Sensitization: Local Lymph Node Assay) performance standards (PS), with the participation of four laboratories.

Distinguishing between genotoxic and non-genotoxic hepatocarcinogens by gene expression profiling and bioinformatic pathway analysis.

A rapid and sensitive method to determine the characteristics of carcinogens is needed. In this study, we used a microarray-based genomics approach, with a short-term in vivo model, in combination with insights from statistical and mechanistic analyses to determine the characteristics of carcinogens. Carcinogens were evaluated based on the different mechanisms involved in the responses to genotoxic carcinogens and non-genotoxic carcinogens.

Stouffer's test in a large scale simultaneous hypothesis testing.

In microarray data analysis, we are often required to combine several dependent partial test results. To overcome this, many suggestions have been made in previous literature; Tippett's test and Fisher's omnibus test are most popular. Both tests have known null distributions when the partial tests are independent.

B cell increases and ex vivo IL-2 production as secondary endpoints for the detection of sensitizers in non-radioisotopic local lymph node assay using flow cytometry.

Non-radioisotopic local lymph node assay (LLNA) using 5-bromo-2'-deoxyuridine (BrdU) with flow cytometry (FCM) is gaining attention since it is free from the regulatory issues in traditional LLNA (tLLNA) accompanying in vivo uses of radioisotope, (3)H-thymidine. However, there is also concern over compromised performance of non-radioisotopic LLNA, raising needs for additional endpoints to improve the accuracy. With the full 22 reference substances enlisted in OECD Test Guideline No.