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Both the topical application and infusion administration resulted in a significantly higher concentration of steroids in perilymph than intracardial injection. The level of steroids in the perilymph reached a peak at 1-2 h after dosing, and this was maintained at a relatively high level for several hours. The intracardial injection with steroids yielded very low perilymph levels at all sampling times after administration.

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Objective: This study aimed to investigate the correlation of L-asparaginase (L-asp) activity, anti-L-asp antibody, asparagine and glutamine levels with the risks of adverse events (AEs), especially anaphylaxis, in pediatric acute lymphoblastic leukemia (ALL) patients who underwent polyethylene glycol-conjugated L-asp (PEG-asp)-contained treatment. Methods: Plasma samples were collected from 91 pediatric ALL patients who underwent PEG-asp-contained treatment on the 7th day after drug administration. Plasma L-asp activity, anti-L-asp antibody level, asparagine level and glutamine level were detected. Meanwhile, AEs related to PEG-asp administration were recorded. Results: AEs occurred in 13 (14.3%) patients, among which 7 (7.7%) patients had anaphylaxis, while another 6 patients had non-anaphylaxis AEs (including 4 (4.4%) patients who had acute pancreatitis, 1 (1.1%) patient who had abdominal pain and diarrhea, as well as 1 (1.1%) patient who had nausea and vomiting). L-asp activity was decreased, while asparagine and glutamine levels were increased in patients with AEs compared to patients without AEs, and ROC curves showed that they were correlated with higher AEs risk. Notably, further analyses revealed that L-asp activity, anti-L-asp antibody, asparagine and glutamine levels were highly correlated with anaphylaxis risk, but they were not associated with the risk of non-anaphylactic AEs. Conclusion: The measurement of L-asp activity, anti-L-asp antibody level, asparagine level and glutamine level might assist the prevention of anaphylaxis-related AEs in pediatric ALL patients who underwent PEG-asp-contained treatment.

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Natalizumab (Tysabri®, Biogen-Idec Inc., NAT), a humanized anti-α4 integrin monoclonal antibody, binds in both α4β1 (Very Late Antigen 4, VLA-4) and α4β7 (lymphocytes Peyer's patch adhesion molecule 1, LPAM-1) integrins, is approved for the treatment of Multiple sclerosis (MS) and Crohn's disease (CD). NAT has been well tolerated in pivotal trials. Progressive multifocal leukoencephalopathy (PML) is an uncommon but serious complications resulting from NAT treatment. It is not confirmed that higher NAT concentration increases the risk of PML. NAT can pass placental barrier before delivery and into breast milk. As MS is a disease that affects young women most, a proper risk-benefit analysis of NAT therapy in lactating women are still needed. Genome sequence variations in drug target proteins, drug-metabolizing enzymes, and drug transporters may alter the pharmacokinetics (PK) and pharmacodynamics (PD) properties of drugs and cause variable drug responses in individual patients. Pharmacogenomics research of NAT in MS or CD therapies are currently yielding an abundance of potential SNPs and markers of various outcomes of drug response. Gln-152, Lys-201, and Lys-256 are the three important point mutation on the α4 residues that NAT binds to. Syndecan-1 gene is a potential candidate gene for personalized approach for NAT use in MS. However, the relationship between single nucleotide polymorphisms (SNPs) and NAT treatment are still not clear. Antibodies against NAT can also result in a low serum NAT concentration and causing a loss of efficacy of NAT. This review highlights the detailed PK and PD information of NAT, and PK and PD information in Asian population, with the pharmacogenomics properties of NAT.

BackgroundThe aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL).MethodsA case–control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) of MTHFR genotypes were used to assess the associations of these polymorphisms with childhood ALL susceptibility.ResultsNo significant differences were observed for frequencies of the 677CC, 677CT and 677TT genotypes between patients and controls. Frequencies of the 1298AA, 1298 AC and 1298CC genotypes between the two groups were significantly different. The risk of ALL with the 1298C allele carriers (AC + CC) was elevated by 1.1 times compared with the AA genotype [OR = 2.100; 95% CI (1.149; 3.837); P = 0.015].ConclusionsThe MTHFR A1298C polymorphism is associated with susceptibility to childhood ALL in the Chinese population.

Background: Up to date, the efficacy and safety of warfarin treatment in atrial fibrillation patients receiving hemodialysis remain controversial. So we performed this meta-analysis to try to offer recommendations regarding warfarin management in this population.Methods: We searched Pubmed, Embase, and Cochrane library and reviewed relevant reference lists from 1980 to March 2018. Studies were included if they described the risks of mortality, stroke, and bleeding events with or without warfarin in atrial fibrillation patients receiving hemodialysis.Results: Overall, the use of warfarin was not associated with mortality (OR = 0.95, 95%CI = 0.89–1.02), stroke (OR = 1.06, 95% CI = 0.87–1.30) and ischemic stroke (OR = 0.85, 95% CI = 0.68–1.05), but its use could increase the risks of hemorrhagic stroke (OR = 1.34, 95% CI = 1.13–1.59) and major bleeding (OR = 1.24, 95% CI = 1.14, 1.35). In subgroup analyses, when analyses were mainly restricted to atrial fibrillation patients who were undergoing hemodialysis and taking other anticoagulation agents, warfarin therapy didn't reduce the risks for mortality (OR = 0.98, 95% CI = 0.68–1.42) and ischemic stroke (OR = 1.03, 95% CI = 0.89–1.19), but significantly increased the risks of stroke (OR:1.14, 95% CI = 1.01–1.29) and bleeding events such as hemorrhagic stroke (OR = 1.42, 95% CI = 1.14–1.77) and major bleeding (OR = 1.24, 95% CI = 1.14–1.35). While in patients who didn't take other anticoagulation agents or aspirin, warfarin use was not associated with all-cause mortality (OR = 0.90, 95% CI = 0.78–1.04), or any stroke (OR = 1.00, 95% CI = 0.71–1.40). Its use was associated with significantly decreased risk of ischemic stroke (OR = 0.71, 95% CI = 0.60–0.85), but not associated with hemorrhagic stroke (OR = 1.45, 95% CI = 0.83–2.55). Besides, another subgroup analysis showed that warfarin therapy didn't exert a protective role in patients with normal serum lipid levels (OR = 1.04, 95% CI = 0.85–1.26), but seemed to decrease the risk of ischemic stroke in patients with hyperlipidemia (OR = 0.38, 95% CI = 0.11–1.29).Conclusion: Our results suggested that it was necessary to prescribe warfarin for the prevention of ischemic events in hemodialysis patients with atrial fibrillation, but if these patients were already prescribed with other anticoagulants for the treatment of other co-existing diseases, then warfarin was not recommended.