Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Jun 2013
Should we use one-sided or two-sided P values in tests of significance?
'P' stands for the probability, ranging in value from 0 to 1, that results from a test of significance. It can also be regarded as the strength of evidence against the statistical null hypothesis (H₀). When H₀ is evaluated by statistical tests based on distributions such as t, normal or Chi-squared, P can be derived from one tail of the distribution (one-sided or one-tailed P), or it can be derived from both tails (two-sided or two-tailed P). ⋯ However, if H₁ is specific and, for example, states than the mean or proportion of Group A is greater than that of Group B, then a one-sided P maybe used. The form that H₁ will take if H₀ is rejected must be stipulated a priori, before the experiment is conducted. It is essential that authors state whether the P values resulting from their tests of significance are one- or two-sided.
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Clin. Exp. Pharmacol. Physiol. · May 2013
Lack of association between genetic polymorphisms of CYP3A4, CYP2C9 and CYP2C19 and antituberculosis drug-induced liver injury in a community-based Chinese population.
The precise pathogenic mechanism of antituberculosis (anti-TB) drug-induced liver injury (ATLI) is poorly understood. It may be associated with drug-metabolizing enzymes, such as cytochrome P450 (CYP) 3A4, CYP2C9 and CYP2C19. The aim of the present study was to explore the role of tagging single nucleotide polymorphisms (tSNPs) of CYP3A4, CYP2C9 and CYP2C19 in the risk of ATLI in a population-based anti-TB treatment cohort. ⋯ No significant differences were observed in genotypes or allele frequencies of the five tSNPs between the two groups and none of the CYP2C9 or CYP2C19 haplotypes was significantly associated with the development of ATLI. Based on the Chinese anti-TB treatment cohort, we did not find a significant association between the risk of ATLI and genetic polymorphisms of CYP3A4, CYP2C9 and CYP2C19. None of the haplotypes exhibited a significant association with the development of ATLI in a Chinese tuberculosis population.
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Clin. Exp. Pharmacol. Physiol. · Mar 2013
Randomized Controlled TrialEvaluation of the analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist, in human capsaicin-induced pain and hyperalgesia.
The aim of the present study was to investigate the effects of AZD1940, a novel peripherally acting cannabinoid CB(1) /CB(2) receptor agonist, on capsaicin-induced pain and hyperalgesia, as well as on biomarkers of cannabinoid central nervous system (CNS) effects. The present study was a randomized, double-blind, placebo-controlled, four-sequence, two-period, cross-over study in 44 male healthy volunteers aged 20-45 years. The effects of two single oral doses of AZD1940 (400 and 800 μg) were compared with placebo. ⋯ Dose-dependent mild-to-moderate CNS-related and gastrointestinal adverse events were reported following treatment with AZD1940. No evidence of analgesic efficacy was found for a peripherally acting CB(1)/CB(2) receptor agonist in the human capsaicin pain model. The emergence of mild dose-dependent CNS effects suggests that the dose range predicted from preclinical data had been attained.
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Clin. Exp. Pharmacol. Physiol. · Feb 2013
ReviewHaemodynamic influences on kidney oxygenation: clinical implications of integrative physiology.
Renal blood flow, local tissue perfusion and blood oxygen content are the major determinants of oxygen delivery to kidney tissue. Arterial pressure and segmental vascular resistance influence kidney oxygen consumption through effects on glomerular filtration rate and sodium reabsorption. Diffusive shunting of oxygen from arteries to veins in the cortex and from descending to ascending vasa recta in the medulla limits oxygen delivery to renal tissue. ⋯ This sequence of events appears to cause renal microcirculatory dysfunction, which may then be exacerbated by the inappropriate use of therapies common in peri-operative medicine, such as fluid resuscitation. The development of new ways to prevent and treat AKI requires an integrative approach that considers not just the molecular mechanisms underlying failure of filtration and tissue damage, but also the contribution of haemodynamic factors that determine kidney oxygenation. The development of bedside monitors allowing continuous surveillance of renal haemodynamics, oxygenation and function should facilitate better prevention, detection and treatment of AKI.
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Clin. Exp. Pharmacol. Physiol. · Jan 2013
Effects of epidermal growth factor receptor and phosphatase and tensin homologue gene expression on the inhibition of U87MG glioblastoma cell proliferation induced by protein kinase inhibitors.
The aim of the present study was to analyse the antiproliferative effects and mechanisms of action of protein kinase inhibitors (PKIs) in human glioblastoma multiforme (GBM) cells with different epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) status. The GBM cell models were established by transfection of plasmids carrying wild-type EGFR, mutated EGFRvIII or PTEN and clonal selection in U87MG cells. Phosphatidylinositol 3-kinase (PI3-K)/AKT pathway-focused gene profiles were examined by real-time polymerase chain reaction-based assays, protein expression was evaluated by western blotting and the antiproliferative effects of PKI treatment were determined by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay in GBM cells. ⋯ Concurrent inhibition of mTOR and ribosomal protein s6 activity may underlie the inhibition of GBM proliferation by PKI. In conclusion, overexpression of EGFR or EGFRvIII, accompanied by a loss of PTEN, contributed to the activation of multiple intracellular signalling pathways in GBM cells. Rigorous examination of biomarkers in tumour tissues before and after treatment may be necessary to determine the efficacy of PKI therapy in patients with GBM.