Coenzyme Q in pregnant women and rats with intrahepatic cholestasis.

BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy is a high-risk liver disease given the eventual deleterious consequences that may occur in the foetus. It is accepted that the abnormal accumulation of hydrophobic bile acids in maternal serum are responsible for the disease development. Hydrophobic bile acids induce oxidative stress and apoptosis leading to the damage of the hepatic parenchyma and eventually extrahepatic tissues. As coenzyme Q (CoQ) is considered an early marker of oxidative stress in this study, we sought to assess CoQ levels, bile acid profile and oxidative stress status in intrahepatic cholestasis. METHODS: CoQ, vitamin E and malondialdehyde were measured in plasma and/or tissues by HPLC-UV method whereas serum bile acids by capillary electrophoresis in rats with ethinyl estradiol-induced cholestasis and women with pregnancy cholestasis. RESULTS: CoQ and vitamin E plasma levels were diminished in both rats and women with intrahepatic cholestasis. Furthermore, reduced CoQ was also found in muscle and brain of cholestatic rats but no changes were observed in heart or liver. In addition, a positive correlation between CoQ and ursodeoxycholic/lithocholic acid ratio was found in intrahepatic cholestasis suggesting that increased plasma lithocholic acid may be intimately related to CoQ depletion in blood and tissues. CONCLUSION: Significant CoQ and vitamin E depletion occur in both animals and humans with intrahepatic cholestasis likely as the result of increased hydrophobic bile acids known to produce significant oxidative stress. Present findings further suggest that antioxidant supplementation complementary to traditional treatment may improve cholestasis outcome.

Diffusion Coefficients of Variable-Size Amphiphilic Additives in a Glass-Forming Polyethylene Matrix.

Diffusion of additives in polymers is an important issue in the plastics industry since migratory-type molecules are widely used to tune the properties of polymeric composites. Predicting the diffusional behavior of new additives can minimize the need for repetitive experiments. This work presents molecular dynamics simulations at the microsecond time scale and uses the MARTINI force field to estimate self-diffusion coefficients, D, of six monounsaturated amides and their analogs carboxylic acids in polyethylene matrices (PE, MW = 5600 Da). The results are strongly influenced by the glass-forming properties of the PE matrix, which we characterize by three distinct temperatures. The metastability region (T < 325 K), the glass transition temperature (Tg = 256-260 K), and the end of the transition (T ≅ 200 K). Self-diffusion mechanisms are inferred from the results of the dependence of D on the molecular mass of the additive, observing a Rouse-like behavior at high temperatures and deviations from it within the metastability region of the matrix. Interestingly, D values are nonsensitive to the nature of the considered polar head for additives of similar size. The temperature-dependent behavior of D follows, at fixed additive size, a linear Arrhenius pattern at high temperatures and a super Arrhenius trend at lower temperatures, which is well represented with a power law equation as predicted by the Mode Coupling Theory (MCT). We offer a conceptual explanation for the observed super-Arrhenius behavior. This explanation draws on Truhlar and Kohen's interpretation of the available energies at both the initial and the transition states along the diffusion pathway. The matrix's mobility significantly affects solute self-diffusion, yielding equal activation enthalpies for the Arrhenius region or the same power law parameters for the super-Arrhenius regime. Finally, we establish a one-to-one time-equivalence of the self-diffusion processes between CG and all-atom systems for the largest additives and the PE matrix in the high-temperature regime.

Novel approach over template molecule elimination in molecularly imprinted polymers by using heat activated persulfate.

This study proposes a new alternative for template removal from molecularly imprinted polymers by heat activated persulfate. It is known that trace amounts of template molecule remains in the polymer network after extraction by current methodologies leading to bleeding and incomplete removal of template which could compromise final determination of target analytes especially in trace analysis. A previously developed molecularly imprinted polymer specially designed for Coenzyme Q10 (CoQ10) extraction was employed as a model to test this template elimination approach. This polymer is based on methacrylic acid and ethylene glycol dimethylacrylate as monomers and Coenzyme Q0 as template. This coenzyme has the same quinone group as the CoQ10. Selectivity was analyzed comparing the recovery of CoQ10 and ubichromenol, a CoQ10 related substance. Chemical degradation using heat-activated persulfate allows the elimination of the template molecule with a high level of efficiency, being a simple and ecological methodology, yielding a polymer that exhibits comparable selectivity and imprinting effect with respect to traditional extraction methods.

Lithocholic acid as a biomarker of intrahepatic cholestasis of pregnancy during ursodeoxycholic acid treatment.

BACKGROUND: The diagnosis and treatment of intrahepatic cholestasis of pregnancy (ICP) has important implications on fetal health. The biochemical parameter commonly used in the diagnosis of ICP is the determination of the concentration of total serum bile acids (TSBA). However, bile acid profile, especially lithocholic acid (LCA) analysis is a more sensitive and specific biomarker for differential diagnosis of this pathology and also could be an alternative to evaluate the efficiency of ursodeoxycholic acid (UDCA) for ICP treatment. METHODS: Serum bile acid (SBA) profiles including LCA determination, were studied in 28 ICP patients using a capillary electrophoresis method. The effects of UDCA treatment on bile acid profile, were analysed in 23 out of 28 ICP patients and the two samples obtained before and 15 days after treatment were compared. Two samples taken as controls were also obtained from each of five patients without therapy. RESULTS: A dramatic decrease in LCA concentrations and maintenance of TSBA concentrations were found in all patients after UDCA therapy, whereas SBA profiles together with LCA values did not change in patients without therapy. CONCLUSION: We propose LCA as an alternative biomarker and a more sensitive parameter than TSBA to evaluate the effectiveness of UDCA treatment, at least in ICP patients from Argentina.

Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis.

An abrupt increase in metastatic growth as a consequence of the removal of primary tumors suggests that the concomitant resistance (CR) phenomenon might occur in human cancer. CR occurs in murine tumors and ROS-damaged phenylalanine, meta-tyrosine (m-Tyr), was proposed as the serum anti-tumor factor primarily responsible for CR. Herein, we demonstrate for the first time that CR happens in different experimental human solid tumors (prostate, lung anaplastic, and nasopharyngeal carcinoma). Moreover, m-Tyr was detected in the serum of mice bearing prostate cancer (PCa) xenografts. Primary tumor growth was inhibited in animals injected with m-Tyr. Further, the CR phenomenon was reversed when secondary implants were injected into mice with phenylalanine (Phe), a protective amino acid highly present in primary tumors. PCa cells exposed to m-Tyr in vitro showed reduced cell viability, downregulated NFκB/STAT3/Notch axis, and induced autophagy; effects reversed by Phe. Strikingly, m-Tyr administration also impaired both, spontaneous metastasis derived from murine mammary carcinomas (4T1, C7HI, and LMM3) and PCa experimental metastases. Altogether, our findings propose m-Tyr delivery as a novel approach to boost the therapeutic efficacy of the current treatment for metastasis preventing the escape from tumor dormancy.