Do External Auditors Perform A Corporate Governance Role? Evidence From Malaysia

Tumpuan pemilikan korporattelah mencipta konflik agensi antara pemilik-pemilik pengawalan dan pemegang saham minoriti di Malaysia. Concentration of corporate ownership has created agency conflicts between controlling owners and minority shareholders especially in emerging markets like Malaysia

Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI.

BACKGROUND:Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods. METHODS:Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5. RESULTS:SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p<0.01). Midazolam clearance correlated well with irinotecan clearance (r = 0.563 p<0.01). SN-38 AUC correlated well with Log10Nadir Absolute Neutrophil Count (ANC) (r = -0.397 p<0.05). Significant correlation was found between nadir ANC and formation rate constant of raltegravir glucuronide (r = 0.598, P<0.005), but not UGT1A1 genotype. CONCLUSION:Raltegravir glucuronide formation is a good predictor of nadir ANC, and can predict neutropenia in East Asian patients. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize irinotecan therapy. TRIAL REGISTRATION:Clinicaltrials.gov NCT00808184

[Zn(phen)(O,N,O)(H2O)] and [Zn(phen)(O,N)(H2O)] with O,N,O is 2,6-dipicolinate and N,O is L-threoninate: Synthesis, characterization, and biomedical properties

Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylatecontaining ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H 2O)]·H2O (1) and [Zn(phen)(L-Thr)(H 2O)Cl] ·2H2O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50 % inhibition of cell proliferation (IC50) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequenceselective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index. © SBIC 2012.Link_to_subscribed_fulltex

CONSORT Flow Diagram for trial.

<p>CONSORT Flow Diagram for trial.</p

Box-plot showing the association between the rate constant of formation of raltegravir glucuronide from raltegravir (K₂₃) and presence or absence of dose delay amongst the patients.

<p>Box-plot showing the association between the rate constant of formation of raltegravir glucuronide from raltegravir (K₂₃) and presence or absence of dose delay amongst the patients.</p

Box-plots showing the statistically insignificant associations between the nadir absolute neutrophil count and UGT1A1 genotypes.

<p>Box-plots showing the statistically insignificant associations between the nadir absolute neutrophil count and UGT1A1 genotypes.</p