Hans Joachim Lehmler

..The review of the synthesis of these two classes of fluorinated compounds includes a review of their industrial synthesis and the synthesis of relevant degradation products...

..Therefore, for biomedical applications, the use of a partially fluorinated tail may offer advantages over simple hydrocarbon systems because, in addition to the chain length, the position and degree of fluorination can be adjusted...

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..Overall, the complex phase behavior most likely results from the head-tail mismatch of the nicotinates and the geometric packing constraints in the two-component lipid bilayer...

..Although more fundamental studies of the underlying anti-inflammatory mechanisms are needed, respiratory treatment modalities involving PFCs hold great clinical promise...

..Overall, changes in chiral signatures are powerful, but currently underutilized tools for studies of environmental and biological processes of PCBs...

..These direct PFOS-DPPC interactions are one possible mechanism by which PFOS may contribute to adverse effects, for example neonatal mortality, in laboratory studies and possibly in humans...

..However, their mixing behavior is far from ideal, thus suggesting the presence of domains or lipid aggregates with high acid concentrations which may (adversely) impact the function of biological mono- and bilayers...

..To overcome this obstacle, several approaches, such as dispersions, prodrugs, solubilizing agents and (micro)emulsions, are under investigation to develop homogeneous PFC-drug mixtures suitable for intrapulmonary administration...

..Thus, PFOB may be a novel and biocompatible vehicle for the delivery of lipophilic prodrugs of nicotinic acid and other drugs directly to the lung of laboratory animals and humans...

..meta/para) of unknown PCB sulfate metabolites isolated from environmental or laboratory samples...

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..The greater the number of chlorines on the (hydro-)quinone (oxygenated) ring, the higher the steady-state level of the resulting semiquinone radical at near neutral pH...

..g., gel versus liquid-crystalline phase) of the lipid assembly...

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..Overall, this study does not support the hypothesis that metabolism by CYP2B enzymes is responsible for the enrichment of (+)-PCB 136 in mice...

..To aid with future quantitative structure activity relationship studies, the structures of two 2,2,2-trichloroethyl-protected PCB sulfates were verified by X-ray diffraction...

..Therefore, the choice of administration route may well have implications for the enantioselective disposition of PCB 136 and other chiral substances...

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..Overall, this study demonstrates the biotransformation of N-EtFOSE to PFOS in rats that is accompanied by N-EtFOSE-induced alterations in antioxidant enzyme activity...

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..In summary, PFBS disrupted different model lipid assemblies, indicating potential for PFBS to be a human toxicant. However, the effects of PFBS are not as pronounced as those seen with longer chain PFAAs...

..This alteration in specificity of rSULT1A1 for certain OH-PCBs suggests that conditions of oxidative stress may significantly alter the sulfation of some OH-PCBs in the rat...

..This is the first evidence of enantioselectivity of chiral PCBs in whole plants, and suggests that poplars can enantioselectively biotransform at least one chiral PCB...

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..The methylated derivatives of two OH-PCB 136 metabolites showed an enantiomeric enrichment in liver tissue, whereas PCB 136 itself was near racemic...

..e., gel versus liquid phase) of the membrane. DLS experiments are also consistent with partial liposome solubilization at PFOA/lipid molar ratios>1, which suggests the formation of mixed PFOA-lipid micelles...

..However, the major mammalian metabolite, 4'OH-CB79 was not detected in any of the samples. The results suggest that the hydroxylated metabolic pathway of CB77 is via an epoxide intermediate in poplar...

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..These findings suggest that it is important to determine the isomer composition of PFOS samples used in both environmental and toxicological studies...

..Hydrocarbon and fluorocarbon alkyl β-d-xylopyranosides with intermediate chain length displayed some toxicity at millimolar concentrations due to apoptosis...

..Overall, this study demonstrates for the first time that chiral PCBs, such as PCB 91, 95, 132, and 149, are enantioselectively metabolized to OH-PCBs by cytochrome P450 enzymes...

..The dihedral angle of PCB 77 is 43.94(6) degrees, which is slightly larger than calculated or experimental dihedral angles of biphenyl derivatives in solution but smaller than experimental dihedral angles in the gas phase...

..Together, the differences in the toxicokinetics of PCB atropisomers point toward enantioselective biotransformation processes as the origin of PCB's enantiomeric enrichment in mammals and, possibly, humans...

..Our discovery that chlorinated quinones undergo a rapid, nonenzymatic dechlorination upon reaction with GSH opens a different view on mechanisms of metabolism and the toxicity of this class of compounds...

..Our results demonstrate a PCB-induced increase in cellular levels of ROS causing DNA damage, resulting in cell killing...

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..Selective uptake and elimination led to accumulation of a distinct congener spectrum in tissue. Minimal evidence of toxicity was observed...

..Comparable results were obtained with an established analysis method for PCBs, OH-PCBs and MeSO(2)-PCBs...

..4 h half-life. This study demonstrates rapid metabolism of CB11 and elimination of 4-OH-CB11 and suggests that the metabolite is not retained in the body but is susceptible to further biotransformation...

..The dihedral angles between the benzene rings in the two mol-ecules are 37.8 (2) and 35.0 (2)°...

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..Results suggested that OH-PCB3s were the substrates of sulfotransferases which catalyzed the formation of PCB3 sulfates in the metabolic pathway of PCB3...

..18 ± 2.16 μg/mL. This is the first report that sulfated metabolites of PCBs are formed in vivo. These findings suggest a prospective approach for exposure assessment of LC-PCBs by analysis of phase II metabolites in urine...

..These five OH-CB3s clearly showed the complete metabolism profile from CB3 to monohydroxylated CB3. More importantly, it's the first report and confirmation of 2OH-CB3 and 3OH-CB3 (new metabolites of CB3) in a living organism...

..Our data also point to futile redox cycling as being one mechanism by which oxygenated PCBs can lead to the formation of reactive oxygen species, but this is most efficient in the presence of SOD...

..The few other known structures of compounds with both (CF(2))(n) and (CH(2))(m) regions show evidence of the same conflict...

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..Finally, the data suggest that the metabolic pathway be via epoxide intermediates...

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..This approach offers the advantage of high selectivity and moderate to good yields compared to conventional methods such as the Cadogan reaction and allows the use of less toxic starting materials...

..The miscibility apparently decreases with increasing chain length of the carboxylic acids (C15>C17>C19)...

..The varying degree of CO2 induced expansion is attributed to the solvation of the "CO2-philic" fluorinated tail and is interpreted from interfacial behavior of HFOPC, HFDoMePC, and HFDePC at the CO2-water interface...

..These results suggest that catecholic cytotoxicity can be attributed to mitochondrial toxicity and oxidative stress. Semiquinone or benzoquinone species were also important in the cytotoxicity of catecholic metabolites...

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..The inhibition of GJIC by OH-PCBs represents a novel mode of action of both the lower chlorinated and the persisting high molecular weight OH-PCBs...

..These findings indicate that PCBs can interfere with TH signaling in the fetal brain by direct actions on the fetus rather than by producing maternal hypothyroidism...

..This effect was not seen in nonselection groups. We conclude that, under the conditions and time courses of these experiments, several PCBs have initiating activity in male Fischer 344 rats...

..Experiments are underway to determine their in vivo significance...

..5). However, a stronger relationship for the surface area and surface volume of the molecule was observed (r(2) >or= 0.5). This study explains in part why some PCB metabolites persist in the body...

..Inhibition of glucuronosyltransferase by low concentrations of OH-PCBs has not been reported before and may have important consequences for the bioavailability, bioaccumulation, and toxicity of other phenolic environmental contaminants...

..PCB-77, but not PCB-153, increased hepatic NF-kappaB activity. In conclusion, dietary vitamin E supplementation does not protect against the induction of altered hepatic focal lesions by PCBs...

..These findings demonstrate an interaction between potentially toxic hydroxylated metabolites of PCBs and polycyclic aromatic hydrocarbons, which could result in reduced clearance by sulfonation...

..Differences in the induction of cytochrome P-450 1A and 2B subfamilies reflected the homologue composition of the respective mixtures and predict a different toxicity profile for Chlorofen than for Aroclor 1254...

..The effects of Se on altered hepatic foci do not correlate with its effects on GPx and TrxR...

..Although liver has a greater glucuronidation capacity than proximal intestine, the properties of intestinal UGTs in channel catfish enable them to efficiently glucuronidate low concentrations of OH-PCBs...

..But the data overall indicate that Kupffer cells likely do not contribute to the tumor promoting activities of PCB-77 and PCB-153...

..Thus, the interactions of OHPCBs with human SULT2A1 represent both a potential route of metabolism and a possible source of interference with sulfation reactions catalyzed by this enzyme...

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..Detection limits as low as 1 x 10(-6) mol L(-1) were obtained for various dihydroxylated PCBs...

..Our results revealed that neither the accumulative PCB 28 nor the more readily metabolisable PCB 101 was an efficacious tumor promoter in the livers of female rats...

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..We infer that: (1) metabolism of PCB3 does not protect against endocrine disruption and (2) the estrogenic effect of these compounds is due to stimulation of aromatase activity...

..It is suggested that molecules that crystallize with Z' > 1 are good candidates for solid-state compound formation...

..Taken together, these data indicate that the absence of the NF-kappaB p50 subunit inhibits the promoting activity of PCB-153 and alters the proliferative and apoptotic changes in mouse liver in the response to PCBs...

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..The long term career goal is to establish Dr. Lehmler as an investigator with independent research status and funding. ..

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