We tested several classes of antioxidant manganese compounds for radioprotective effects using human lymphoblastoid cells: six porphyrins, three salens and two cyclic polyamines. Radioprotection was evaluated by seven assays: XTT; Annexin V and propidium iodide flow cytometry analysis; γ-H2AX immunofluorescence; the neutral comet assay; dichlorofluorescein and dihydroethidium staining; resazurin and colony survival assay. Two compounds were most effective in protecting wildtype, and A-T cells, against radiation-induced damage: MnMx-2-PyP-Calbio (a mixture of differently N-methylated MnT-2-PyP+ from Calbiochem) and MnTnHex-2-PyP. MnTnHex-2-PyP protected WT cells against radiation-induced apoptosis by 58% (p=0.04) in WT by XTT and 39% (p=0.01) in A-T by Annexin V and propidium iodide staining. MnTnHex-2-PyP protected WT cells against DNA damage by 57% (p=0.005) by Gamma H2AX immunofluorescence and by 30% (p<0.01) by neutral comet assay. MnTnHex-2-PyP is more lipophilic than MnMx-2-PyP-Calbio and is also >10-fold more SOD-active; consequently it is >50-fold more potent as a radioprotectant, as supported by six of the tests employed in this study. Thus, lipophilicity and antioxidant potency correlated with the magnitude of the beneficial radioprotectant effects observed. Our results identify a new class of porphyrinic radioprotectants for the general and radiosensitive populations and may also provide a new option for treating A-T patients.

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These data suggest that an increased local anesthetic requirement for epidural labor analgesia is associated with more intense pain related to dystocia. Women in early, clinically normal labor but who later develop dystocia require more local anesthetic and, by inference, are experiencing more severe pain than women who deliver vaginally. This association should be considered when studying the relation between the method of labor analgesia and the course of labor.