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Kailash Gupta

Publications and source records attributed to Kailash Gupta.

4 recordsLinked to original sources
PubMed2005

Ensuring quality of in vitro alternative test methods: issues and answers.

Many in vitro and ex vivo methods have been developed or are under development to reduce or replace animal usage in toxicity tests. Consistent with the goal of obtaining scientifically sound test data for hazard and risk assessment of chemicals, changes are being made in current policies and procedures to facilitate the acceptance of data developed using these methods. National and international organizations are developing policies and standards for scientific practice to assure quality in implementation of in vitro methods. Consensus is developing in the scientific community for the quality control measures needed for in vitro methods; including appropriate controls, data reporting elements, and benchmarks to be identified in test guidelines so that the potential risks of chemicals can be reviewed and reliably assessed. Additional guidance to the OECD's Good Laboratory Practice principles [Organization for Economic Cooperation and Development (. Advisory Document of the Working Group on Good Laboratory Practice: The Application of the Principles of GLP to in vitro Studies. OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring Number 14 (ENV/JM/MONO(2004)26). Paris, France] will help to ensure that in vitro tests used for regulatory purposes are reproducible, credible, and acceptable. Generic test guidelines incorporating performance standards are being written to allow acceptance of proprietary test methods by regulatory agencies and to provide assurance that any in vitro system performs over time in a manner that is consistent with the test system as it was originally validated.

Animal Testing Alternatives↗
PubMed2004

Interaction of mannose-binding lectin with HIV type 1 is sufficient for virus opsonization but not neutralization.

Mannose-binding lectin (MBL), a microbe-recognition protein in serum, binds to high mannose glycans on HIV-1 gp120 and has been reported to neutralize the cell line-adapted strain HIV(IIIB). Because HIV primary isolates (PI) are generally more resistant to neutralization by antibodies and considering that PI are produced in primary cells that could alter the number of high mannose glycans on HIV relative to cell lines, we assessed the ability to MBL to neutralize HIV PI. MBL at concentrations up to 50 microg/ml mediated relatively little neutralization (<20%) of HIV PI infection of peripheral blood mononuclear cells (PBMCs). MBL-neutralizing activity was slightly higher for cell line-adapted HIV infection of the H9 T cell line (up to 64% at 50 microg/ml). However, this effect was specific for H9 cells since MBL did not neutralize cell line-adapted virus infection of PBMCs, HIV PI infection of the GHOST cell line, or VSV pseudotyped with HIV gp160 from cell line-derived virus or PI. In contrast to its low activity in neutralization assays, MBL efficiently bound infectious HIV PI and opsonized HIV PI for uptake by monocytic cells. These results show that both PI and cell line-adapted HIV, despite binding of MBL, are relatively resistant to neutralization by levels of MBL normally present in serum. However, binding and opsonization of HIV by MBL may alter virus trafficking and viral-antigen presentation during HIV infection.

Cell Line↗
PubMed2002

Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

Animal Testing Alternatives↗