Mepivacaine: a closer look at its properties and current utility.

The use of mepivacaine in dentistry has remained strong since its introduction in the 1960s. It has retained its place as a valuable local anesthetic, either as a primary agent or as an alternative to lidocaine or articaine. Mepivacaine is commonly used in medically compromised patients--for whom elevations in blood pressure or heart rate are not advisable--in a formulation with a vasoconstrictor, or in pediatric populations in a formulation without a vasoconstrictor. Pharmacologically, these are the 2 groups most susceptible to side effects and toxicity, thus mepivacaine is commonly indicated. Most often the decision to use mepivacaine is based on its vasoconstrictor effect or lack thereof (depending on the formulation). However, the pharmacokinetics of mepivacaine are not well understood or assumed to be similar to that of other local anesthetics. It is important to understand the unique pharmacologic characteristics of mepivacaine in order to minimize the potential for inadvertent toxicity.

Hepatocellular proliferation in response to agonists of peroxisome proliferator-activated receptor alpha: a role for Kupffer cells?

BACKGROUND: It has been proposed that PPARalpha agonists stimulate Kupffer cells in rodents which in turn, release mitogenic factors leading to hepatic hyperplasia, and eventually cancer. However, Kupffer cells do not express PPARalpha receptors, and PPARalpha agonists stimulate hepatocellular proliferation in both TNFalpha- and TNFalpha receptor-null mice, casting doubt on the involvement of Kupffer cells in the mitogenic response to PPARalpha agonists. This study was therefore designed to investigate whether the PPARalpha agonist PFOA and the Kupffer cell inhibitor methylpalmitate produce opposing effects on hepatocellular proliferation and Kupffer cell activity in vivo, in a manner that would implicate these cells in the mitogenic effects of PPARalpha agonists. METHODS: Male Sprague-Dawley rats were treated intravenously via the tail vein with methylpalmitate 24 hrs prior to perfluorooctanoic acid (PFOA), and were sacrificed 24 hrs later, one hr after an intraperitoneal injection of bromodeoxyuridine (BrdU). Sera were analyzed for TNFalpha and IL-1beta. Liver sections were stained immunohistochemically and quantified for BrdU incorporated into DNA. RESULTS: Data show that PFOA remarkably stimulated hepatocellular proliferation in the absence of significant changes in the serum levels of either TNFalpha or IL-1beta. In addition, methylpalmitate did not alter the levels of these mitogens in PFOA-treated animals, despite the fact that it significantly blocked the hepatocellular proliferative effect of PFOA. Correlation between hepatocellular proliferation and serum levels of TNFalpha or IL-1beta was extremely poor. CONCLUSION: It is unlikely that mechanisms involving Kupffer cells play an eminent role in the hepatic hyperplasia, and consequently hepatocarcinogenicity attributed to PPARalpha agonists. This conclusion is based on the above mentioned published data and the current findings showing animals treated with PFOA alone or in combination with methylpalmitate to have similar levels of serum TNFalpha and IL-1beta, which are reliable indicators of Kupffer cell activity, despite a remarkable difference in hepatocellular proliferation.

Genotoxicity assessment of oxirane-based dental monomers in mammalian cells.

The potential use of oxirane (epoxy) monomers in dental composite development raises the concern to test their genetic safety. Oxiranes can interact with DNA resulting in DNA damage, mutations, and possibly carcinogenesis. Our objective was to evaluate DNA damage and cell-cycle disruption in mammalian cells after exposure to epoxy monomers. The experimental oxiranes were Araldite trade mark GY 281, Cyracure trade mark UVR 6105 and 1,3-dioxane-2,2'-1,3-dioxane-5',4'-bicyclo[4.1.0] heptane (DECHE-TOSU). L929 fibroblast cells were incubated with the monomer for 7 and 24 h at 37 degrees C/5% CO(2). After incubation, cells were subjected to DNA damage alkaline unwinding assay and flow cytometry cell-cycle analysis. Lack of DNA damage and cell-cycle effects were observed with DECHE-TOSU. Exposure to subtoxic doses of Araldite trade mark GY 281 or Cyracure trade mark UVR 6105 caused DNA damage and cell cycle disruption. A significant (p < 0.01) effect for Araldite trade mark GY 281 was observed with cell populations in G1 and G2/M when compared to DMSO solvent control. Similar comparisons revealed significant differences in G2/M cell cycle population after 24-h exposure to 100 microM Cyracure trade mark UVR 6105. For comparison, BISGMA was evaluated to produce DNA damage but without cell-cycle effects suggesting DNA repair mechanisms were effective. Our findings with DECHE-TOSU, Araldite trade mark GY 281 and Cyracure trade mark UVR 6105 indicated cell-cycle disruption followed DNA damage.