- Clinical presentation, diagnosis, and survival in cholangiocarcinoma: A prospective study. [Journal Article]
- AJArab J Gastroenterol 2016 Nov 30
- CONCLUSIONS: The diagnosis of CCA is difficult and often delayed. The outcome is generally poor.
- Heme oxygenase-1 metabolite biliverdin, not iron, inhibits porcine reproductive and respiratory syndrome virus replication. [Journal Article]
- FRFree Radic Biol Med 2016 Nov 28; 102:149-161
- Porcinereproductiveandrespiratorysyndromevirus (PRRSV) causes significant economic losses to the pork industry worldwide. Previously, we demonstrated that heme oxygenase-1 (HO-1) interferes with PRRS...
Porcinereproductiveandrespiratorysyndromevirus (PRRSV) causes significant economic losses to the pork industry worldwide. Previously, we demonstrated that heme oxygenase-1 (HO-1) interferes with PRRSV replication. To elucidate the mechanisms involved, here we assess whether the HO-1 downstream metabolites biliverdin (BV) and/or iron mediate the HO-1 antiviral effect. We demonstrate a BV concentration-dependent suppression of PRRSV replication and show that virions are not directly inactivated by BV. Additionally, BV or N-acetyl cysteine (NAC) significantly reduced reactive oxygen species (ROS) in PRRSV-infected MARC-145 cells; however, because NAC did not reduce viral load, the BV antiviral effect is independent of decreased ROS levels. Moreover, a secondary metabolite of BV, bilirubin (BR), specifically mediates this anti-PRRSV activity via a nitric oxide (NO)-dependent cGMP/PKG signaling pathway. While increased iron via addition of FeCl3 did not interfere with PRRSV replication, iron depletion by deferoxamine (DFO) after cobalt-protoporphyrin IX induction of HO-1 did not restore PRRSV replication. Collectively, our findings identify a HO-1-BV/BR-NO-cGMP/PKG cascade as a novel pathway underlying the host cell antiviral effect. These results provide a unique insight into the molecular mechanisms underlying the antiviral effects of the stress-responsive protein HO-1 during PRRSV infection.
- A novel liquid chromatography tandem mass spectrometry method for the estimation of bilirubin glucuronides and its application to in vitro enzyme assays. [Journal Article]
- DMDrug Metab Lett 2016 Nov 24
- Bilirubin is a toxic waste product of metabolism, eliminated mainly through UGT1A1 mediated conjugation to mono- and di-glucuronides. Due to the potentially low Km value of bilirubin glucuronidation,...
Bilirubin is a toxic waste product of metabolism, eliminated mainly through UGT1A1 mediated conjugation to mono- and di-glucuronides. Due to the potentially low Km value of bilirubin glucuronidation, the quantitative sensitivity obtained with most UV/visible light detection methods are not sufficient to accurately calculate UGT1A1 enzyme kinetics and inhibition properties of new chemical entities at low bilirubin concentrations. In addition, bilirubin, as well as its metabolites, are unstable during sample preparation and bioanalysis. To address these issues, a robust LC-MS/MS method was developed to measure low levels of bilirubin glucuronides accurately from in vitro incubations, as well as stabilizing the analytes during sample preparation and analysis. The metabolites were quantified using a qualitative/quantitative approach utilizing UV to MS correction, thereby eliminating the need for synthetic standards. The method was sensitive enough to quantify mono- and di-glucuronides as low as 3 nM from in vitro incubations, and kinetic data was determined for total glucuronide formation. The Km and Vmax values for total bilirubin glucuronide formations were determined to be 0.05 ± 0.01µM and 181.9 ± 5.3 pmol/min/mg-protein, respectively, in human recombinant UGT1A1, and 0.23 ± 0.05 µM and 875 ± 45 pmol/min/mg protein in human liver microsomes (HLM). In summary, for the first time we have reported a LC-MS/MS based method for quantitation of bilirubin and its glucuronides from in vitro incubations.
- Factors associated with Short and Long Term Liver Graft Survival in the United Kingdom: Development of a UK Donor Liver Index. [Journal Article]
- TTransplantation 2016 Dec 01
- CONCLUSIONS: The DLI is an index of liver quality which enables analysis of the changing trends in liver quality and centre behaviour. DLI1 enables identification of factors affecting shorter term survival, and perhaps identifies a cohort of livers that may benefit from novel preservation technologies.
- Positive regulation of biochemical parameters by tea polyphenol encapsulated solid lipid nanoparticles at in vitro and in vivo conditions. [Journal Article]
- INIET Nanobiotechnol 2016; 10(6):419-424
- Tea polyphenols (TPPs) comprise preventive and therapeutic potentials against cancer, cardiovascular and neurological disorders. Chemical instability of TPP which leads to low bioavailability is the ...
Tea polyphenols (TPPs) comprise preventive and therapeutic potentials against cancer, cardiovascular and neurological disorders. Chemical instability of TPP which leads to low bioavailability is the major constrain to its use as therapeutic agent. The authors prepared TPP encapsulated solid lipid nanoparticles (TPP-SLNs) to increase its stability and bioefficacy. Comparison of Fourier transformed infrared spectra of unloaded SLN, free TPP and TPP-SLN indicated encapsulation of TPP. Sustained release of TPP from TP-SLN was observed. TPP-SLN showed prolonged free radical scavenging activity compared with free TPP indicating protection of TPP. TPP-SLN showed activation of Caspases-9 and -3 cascades in breast cancer cell line (Michigan cancer foundation (MCF)-7) at in vitro conditions. Biochemical parameters were altered in Ehrlich ascetic carcinoma (EAC) cell bearing mice compared with normal (uninduced) mice which were ameliorated significantly by oral feeding of TPP-SLN. Oral administration (pre- and post-treated) of TPP-SLN in EAC bearing mice resulted in significant increase of plasma haemoglobin, glucose, superoxide dismutase and catalase when compared with EAC bearing control mice. Other biochemical parameters (cholesterol, bilirubin, triglyceride, urea, total protein, alanine aminotransferase, alkaline phosphatase and aspertate transaminase were significantly decreased on oral administration (pre- and post-treated) of TPP-SLN in EAC bearing mice.
- Pancreatic metastases from ocular malignant melanoma: the use of endoscopic ultrasound-guided fine-needle aspiration to establish a definitive cytologic diagnosis: a case report. [Journal Article]
- JMJ Med Case Rep 2016 Dec 01; 10(1):332
- CONCLUSIONS: To the best of our knowledge, this is a very rare presentation of an ocular malignant melanoma with an isolated pancreatic metastasis causing symptomatic biliary obstruction. Endoscopic ultrasound-guided fine-needle aspiration has proven to be the best method to diagnose solid pancreatic lesions. In this particular case, cytology was essential in confirming the diagnosis and guiding the most adequate therapy, which was a pancreatic resection, ocular exenteration of the melanoma, followed by adjuvant chemotherapy.
- Circulating cell-free DNA, telomere length and bilirubin in the Vienna Active Ageing Study: exploratory analysis of a randomized, controlled trial. [Journal Article]
- SRSci Rep 2016 Dec 01; 6:38084
- Telomere length (TL) in blood cells is widely used in human studies as a molecular marker of ageing. Circulating cell-free DNA (cfDNA) as well as unconjugated bilirubin (UCB) are dynamic blood consti...
Telomere length (TL) in blood cells is widely used in human studies as a molecular marker of ageing. Circulating cell-free DNA (cfDNA) as well as unconjugated bilirubin (UCB) are dynamic blood constituents whose involvement