Ahmet Bora Inceoglu

6.9 – Genetically Modified Baculoviruses for Pest Insect Control

Abstract Baculoviruses are insect pathogenic viruses that are used for pest insect control and as tools to produce recombinant proteins. Numerous studies show that both natural baculoviruses and genetically modified (GM) baculoviruses hold clear and substantial benefits for crop protection. Natural baculoviruses and potentially GM baculoviruses are particularly valuable under conditions where traditional chemical insecticides, have become ineffective, are economically prohibitive or have lost favor with the general public. The increased use of natural baculoviruses for pest insect control as well as GM baculoviruses for the production of pharmaceuticals may open doors to the use of GM baculoviruses for pest insect control. We review here the major approaches that are used to modify the baculovirus genome for improved efficacy as a biopesticide. The most common and successful of these approaches involve the insertion of a gene into the baculovirus genome that disrupts host insect feeding or is toxic to the host. GM baculoviruses remain a viable alternative to synthetic chemical pesticides and GM crops, we believe that baculoviruses should be utilized when alternative methods of pest insect control are required due to resistance, high cost of traditional insecticides, or changes in the regulatory environment and public opinion.

Inhibition of soluble epoxide hydrolase limits niacin-induced vasodilation in mice

Background: The use of niacin in the treatment of dyslipidemias is limited by the common side effect of cutaneous vasodilation, commonly termed flushing. Flushing is thought to be due to release of the vasodilatory prostanoids prostaglandin D2 (PGD2) and prostaglandin E2 from arachidonic acid metabolism through the cyclooxygenase pathway. Arachidonic acid is also metabolized by the cytochrome P450 system, which is regulated, in part, by the enzyme soluble epoxide hydrolase (sEH). Methods: These experiments used an established murine model in which ear tissue perfusion was measured by laser Doppler to test the hypothesis that inhibition of sEH would limit niacin-induced flushing. Results: Niacin-induced flushing was reduced from 506 ± 126% to 213 ± 39% in sEH knockout animals. Pharmacologic treatment with 3 structurally distinct sEH inhibitors similarly reduced flushing in a dose-dependent manner, with maximal reduction to 143% ± 15% of baseline flow using a concentration of 1 mg/kg TPAU (1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl) urea). Systemically administered PGD2 caused ear vasodilation, which was not changed by either pharmacologic sEH inhibition or sEH gene deletion. Conclusions: Inhibition of sEH markedly reduces niacin-induced flushing in this model without an apparent effect on the response to PGD2. sEH inhibition may be a new therapeutic approach to limit flushing in humans.