Impact of constitution of the terthiophene-vinylene conjugated side chain on the optical and photovoltaic properties of two-dimensional polythiophenes.

The effects of the spatial arrangement of the conjugated side chains of two-dimensional polymers on their optical, electrochemical, molecular-packing, and photovoltaic characteristics were investigated. Accordingly, novel polythiophenes with horizontally (PBTTTV-h) and vertically (PBTTTV-v) grafted terthiophene­vinylene (TTV) conjugated side chains were synthesized that display two and one UV-vis peaks, respectively; the difference is due to the different constitutions of the conjugated side-chains. Because the spatial arrangement affects the molecular self-assembly, PBTTTV-h shows stronger crystallinity than PBTTTV-v, which enhances the charge mobility in devices. Moreover, PBTTTV-h has a lower HOMO energy level (−5.49 eV) than PBTTTV-v (−5.40 eV). Bulk heterojunction solar cells fabricated from PBTTTV-h/PC71BM and PBTTTV-v/PC71BM exhibit power conversion efficiencies of 4.75% and 4.00%, respectively, and Voc values of 800 and 730 mV, respectively, under AM1.5G illumination (100 mW cm(−2)). Thus, the architecture of the TTV conjugated side chains affects the optical, electrochemical, and photovoltaic properties; this study provides more ideas for improving 2-D conjugated polymers for semiconductor devices.

α-Lipoic acid prevents mild portal endotoxaemia-induced hepatic inflammation and ß cell dysfunction.

BACKGROUND: This study was undertaken to evaluate the preventive effect of α-lipoic acid (LA) on chronic mild portal endotoxaemia-mediated subacute hepatic inflammation and pancreatic ß cell dysfunction in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned into four groups: those with intraportal vehicle (saline) or low-dose lipopolysaccharide (LPS) (0·42 ng/kg/min) infusion, combined with oral administration of vehicle or LA, a potent antioxidant (60 mg/kg/day) for 4 weeks. The hyperglycaemic clamp and euglycaemic clamp techniques were used to access the glucose-stimulated insulin secretion and systemic insulin sensitivity in vivo. RESULTS: Body weight, fasting plasma glucose and insulin were not different among groups. In rats with chronic intraportal LPS infusion, plasma C-reactive protein, amylase, superoxide levels, the contents of thiobarbituric acid-reactive substance, tumour necrosis factor α and interleukin 6 in liver and pancreas and also the gene expression of Toll-like receptor 4 in liver were significantly increased as compared with those with LA cotreatment. The histopathological examination showed that inflammatory changes were clearly visible in liver and pancreatic islets of LPS-infused rats and rarely observed in those cotreated with LA. In addition, low-dose intraportal LPS infusion also significantly impaired glucose-stimulated insulin secretion but not affect the systemic insulin sensitivity and metabolic clearance rate of insulin. LA administration markedly reversed LPS-induced ß cell dysfunction. CONCLUSIONS: α-Lipoic acid cotreatment could significantly prevent mild portal endotoxaemia-induced chronic hepatic inflammation and impaired pancreatic insulin secretion in absence of changing systemic insulin resistance.

Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics.

BACKGROUND: Concurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for treatment of abdominal malignancy. Nonetheless, the interactions between radiation and 5-FU remain unclear. We evaluated the influence of abdominal irradiation on the pharmacokinetics of 5-FU in rats. METHODS: The radiation dose distributions of cholangiocarcinoma patients were determined for the low dose areas, which are generously deposited around the intrahepatic target volume. Then, corresponding single-fraction radiation was delivered to the whole abdomen of Sprague-Dawley rats from a linear accelerator after computerized tomography-based planning. 5-FU at 100 mg/kg was intravenously infused 24 hours after radiation. A high-performance liquid chromatography system equipped with a UV detector was used to measure 5-FU in the blood. Ultrafiltration was used to measure protein-unbound 5-FU. RESULTS: Radiation at 2 Gy, simulating the daily human treatment dose, reduced the area under the plasma concentration vs. time curve (AUC) of 5-FU by 31.7% compared to non-irradiated controls. This was accompanied by a reduction in mean residence time and incremental total plasma clearance values, and volume of distribution at steady state. Intriguingly, low dose radiation at 0.5 Gy, representing a dose deposited in the generous, off-target area in clinical practice, resulted in a similar pharmacokinetic profile, with a 21.4% reduction in the AUC. This effect was independent of protein binding capacity. CONCLUSIONS: Abdominal irradiation appears to significantly modulate the systemic pharmacokinetics of 5-FU at both the dose level for target treatment and off-target areas. This unexpected and unwanted influence is worthy of further investigation and might need to be considered in clinical practice.

Effect of cyclosporin A on the brain regional distribution of doxorubicin in rats.

Doxorubicin (DOX) is an anthracycline antibiotic that possesses broad-spectrum antineoplastic activity, and is one of the most important anticancer agents. The purpose of this study was to investigate the effects of cyclosporine A (CsA) on the brain regional distribution of DOX and its liposome DOX formulation (Lipo-Dox). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to measure DOX in rat plasma and in various brain regions (cerebral cortex, hippocampus, striatum, midbrain, cerebellum, and the rest of brain). Good linearity was achieved over the 5-5000ng/mL range, with coefficients of correlation greater than 0.995. The limit of quantification for doxorubicin was 5ng/mL. This study was divided into the following four groups: DOX alone, DOX+CsA, Lipo-Dox alone and Lipo-Dox+CsA. After administering DOX (5mg/kg, i.v.) alone and DOX+CsA (10mg/kg, i.v.), it was undetectable in various brain regions. When the same dose of Lipo-Dox (5mg/kg, i.v.) and Lipo-Dox+CsA (10mg/kg, i.v.) were given individually, the plasma level and the brain regional level of DOX were much greater than those of DOX given alone. These results indicate that Lipo-Dox prolongs the DOX level in plasma and enhances brain distribution of DOX. The disposition of DOX might be regulated by P-glycoprotein.

Insights into the Morphological Instability of Bulk Heterojunction PTB7-Th/PCBM Solar Cells upon High-Temperature Aging.

The impact of the morphological stability of the donor/acceptor mixture under thermal stress on the photovoltaic properties of bulk heterojunction (BHJ) solar cells based on the poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b;4,5-b']-dithiophene-2,6-diyl-alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4-b]-thiophene)-2-carboxylate-2,6-diyl]/phenyl-C61-butyric acid methyl ester (PTB7-Th/PC61BM) blend is extensively investigated. Both optical microscopy and transmission electron microscopy micrographs show that long-term high-temperature aging stimulates the formation of microscale clusters, the size of which, however, is about 1 order of magnitude smaller than those observed in thermally annealed poly(3-hexylthiophene)/PC61BM composite film. The multilength-scale evolution of the morphology of PTB7-Th/PC61BM film from the scattering profiles of grazing incidence small-angle and wide-angle X-ray scattering indicates the PC61BM molecules spatially confine the self-organization of polymer chains into large domains during cast drying and upon thermal activation. Moreover, some PC61BM molecules accumulate into ∼30-40 nm clusters, the number of which increases with heating time. Therefore, the hole mobility in the active layer decays much more rapidly than the electron mobility, leading to unbalanced charge transport and degraded cell performance. Importantly, the three-component blend that is formed by replacing a small amount of PC61BM in the active layer with the bis-adduct of PC61BM (bis-PC61BM) exhibits robust morphology against thermal stress. Accordingly, the PTB7-Th/PC61BM:bis-PC61BM (8 wt %) device has an extremely stable power conversion efficiency.

Measurement and pharmacokinetic study of plumbagin in a conscious freely moving rat using liquid chromatography/tandem mass spectrometry.

The aim of the present study is to develop an automated blood sampling (ABS) method coupled to a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method to evaluate the oral bioavailability of plumbagin in a conscious freely moving rat. Plumbagin, an herbal ingredient, was isolated from Plumbago zeylanica L. The separation was performed using a reversed phase C18 (150mmx4.6mm I.D.; 5microm) column and was eluted with the mobile phase of water-acetonitrile (40:60, v/v) at a flow-rate of 0.8ml/min. Multiple reaction monitoring (MRM) was used to monitor the transition of the deprotonated molecule m/z 187 [MH](-) to the product ion m/z 159 [MHCO](-) for the plumbagin analysis. The calibration curve was linear over the concentration range of 10-2000ng/ml with a coefficient estimation of 0.995. The intra- and inter-day variations (% relative standard deviation; RSD and % bias) of the assay for rat plasma samples were less than 17%. The limit of detection and the limit of quantification were 5 and 10ng/ml, respectively. Recovery of plumbagin from the rat plasma was about 80%. This LC-MS/MS method has been validated to study the pharmacokinetics of plumbagin in rats. The oral bioavailability (AUC(PO)/Dose(PO))/(AUC(IV)/Dose(IV)) of plumbagin was about 38.7+/-5%.

Bioavailability of salvianolic acid B in conscious and freely moving rats.

Salvianolic acid B is an herbal ingredient isolated from Salvia miltiorrhiza. The aim of this study was to apply an automated blood sampling system coupled to a simple liquid chromatographic system to determine the bioavailability of salvianolic acid B in stress-free rats. The plasma sample (25 microl) was vortex-mixed with 50 microl of internal standard solution (chloramphenicol 10 microg/ml in acetonitrile) to achieve protein precipitation. Salvianolic acid B in the rat plasma was separated using a reversed-phase C18 column (250 mm x 4.6 mm, 5 microm) with a mobile phase of acetonitrile-methanol-20mM NaH(2)PO(4) (adjusted to pH 3.5 with H(3)PO(4)) (20:10:70 v/v/v) containing 0.1mM 1-octanesulfonic acid, and the flow-rate of 1 ml/min. The UV detection wavelength was 286 nm. The concentration-response relationship from the present method indicated linearity over a concentration range of 0.5-200 microg/ml. Intra- and inter-assay precision and accuracy of salvianolic acid B fell well within the predefined limits of acceptability (<15%). The plasma sample of salvianolic acid B was further identified by LC-MS/MS in the negative ion mode using mass transition m/z 358.2 to the product ion m/z 196.9. After salvianolic acid B (100mg/kg, i.v.; 500 mg/kg, p.o.) was given in conscious and freely moving rats, the AUC were 5030+/-565 and 582+/-222 min microg/ml for intravenous (100 mg/kg) and oral (500 mg/kg) doses, respectively. The oral bioavailability of salvianolic acid B in freely moving rats was calculated to be 2.3%.

Determination and identification of plumbagin from the roots of Plumbago zeylanica L. by liquid chromatography with tandem mass spectrometry.

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is an herbal ingredient which is isolated from the root of Plumbago zeylanica L. This herb is a semi-climbing subshrub distributed in thickets or grassland at low elevations of Taiwan. The crushed roots of P. zeylanica L. were ground from lumps to powder and boiled with H2O, 50% EtOH, or 95% EtOH. Chromatographic separation of plumbagin from the herb was carried out using a ZORBAX Extend-C18 column (150 x 4.6 mm I.D.; 5 microm) that was eluted with the mobile phase of water-methanol (10:90, v/v). Multiple reaction monitoring (MRM) was used to monitor the transition of the deprotonated molecule m/z 187 [M-H]- to the product ion m/z 159 [M-H-CO]- for plumbagin analysis. The limit of quantification was determined to and accuracy of 1 ng/ml. Furthermore, the mass fractions of plumbagin in P. zeylanica L. for H2O, 50% EtOH and 95% EtOH were 0.24 +/- 0.04, 3.92 +/- 0.87 and 13.4 +/- 1.59 g/kg, respectively. These results present a reliable liquid chromatography coupled with tandem mass spectrometric (LC-MS/MS) method for the determination of plumbagin form herbal medicines.

[60]Fulleropyrrolidines bearing π-conjugated moiety for polymer solar cells: contribution of the chromophoric substituent on C60 to the photocurrent.

Two fullerene-terthiophene dyads without hexyl chains (3T-C60) and with hexyl chains (3TH-C60) on the terthiophene substituent are synthesized by 1,3-dipolar cycloaddition of corresponding azomethine ylides to C60. The cyclic voltammetry studies indicate no apparent electronic communication between the terthiophene pendent group and the fulleropyrrolidine core in the ground state. However, a significant florescence quenching is observed for 3T-C60 and 3TH-C60, compared to their fluorescent terthiophene (3T) and 3TH precursors, respectively, suggesting the occurrence of strong intramolecular electron/energy transfers in the photoexcited state. Furthermore, these new fulleropyrrolidine derivatives are applied as electron acceptors to fabricate poly(3-hexylthiophene) (P3HT) based bulk heterojunction solar cells. The incident photon-to-current efficiency (IPCE) value of the P3HT/3T-C60 device is significantly higher than that of the P3HT/PCBM cell in wavelengths of 350-420 nm. This finding provides direct evidence for the contribution of 3T excitons to the photocurrent. Replacing 3T-C60 with 3TH-C60 effectively improves the morphology of the photoactive layer and widens the window of optimal D/A ratios, raising the power conversion efficiency (PCE) from 2.14% to 2.54%. Importantly, these devices exhibit superior stability of PCE against high-temperature aging.

Impact of liver diseases on the development of type 2 diabetes mellitus.

The prevalence of type 2 diabetes mellitus (T2DM) is higher in patients who have liver diseases such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease and cirrhosis. It is suggested that there is a pathogenic link between the presence of T2DM and the severity of liver injury. However, evidence related to the impact of hepatic inflammation on the development of T2DM has not yet emerged. This article provides an overview of the evidence for an increased prevalence of diabetes in a range of liver diseases, the impact of liver diseases on insulin resistance and ß cell dysfunction, and the potential mechanisms whereby coexistent liver diseases exacerbate the development of T2DM.

Matrix metalloproteinase-8 mediates the unfavorable systemic impact of local irradiation on pharmacokinetics of anti-cancer drug 5-Fluorouracil.

Concurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for cancer treatment. However, the interactions between radiation and 5-FU remain unclear. Here, we evaluated the influence of local irradiation on the pharmacokinetics of 5-FU in rats. The single-fraction radiation was delivered to the whole pelvic fields of Sprague-Dawley rats after computerized tomography-based planning. 5-FU at 100 mg/kg was prescribed 24 hours after radiation. A high-performance liquid chromatography system was used to measure 5-FU in the blood. Matrix metalloproteinase-8 (MMP-8) inhibitor I was administered to examine whether or not RT modulation of 5-FU pharmacokinetic parameters could be blocked. Compared with sham-irradiated controls, whole pelvic irradiation reduced the area under the concentration versus time curve (AUC) of 5-FU in plasma and, in contrast, increased in bile with a radiation dose-dependent manner. Based on protein array analysis, the amount of plasma MMP-8 was increased by whole pelvic irradiation (2.8-fold by 0.5 Gy and 5.3-fold by 2 Gy) in comparison with controls. Pretreatment with MMP-8 inhibitor reversed the effect of irradiation on AUC of 5-FU in plasma. Our findings first indicate that local irradiation modulate the systemic pharmacokinetics of 5-FU through stimulating the release of MMP-8. The pharmacokinetics of 5-FU during concurrent chemoradiaiton therapy should be rechecked and the optimal 5-FU dose should be reevaluated, and adjusted if necessary, during CCRT.