Abstract Background: Pandemic influenza virus is a public health issue, and the neuraminidase inhibitors (NIs) “Oseltamivir” and “Zanamivir” are effective treatments. While teenagers use NIs, there ...are concerns regarding neuropsychiatric adverse events (NPAEs). Aim: We aimed to use the Taiwan National Health Insurance Research Database to identify the correlation between NPAEs and NIs use in teenagers aged 13–19 years. Methods: The final population between 2000 and 2015 included in this study was 3698 individuals, with 2287 individuals having received “Oseltamivir” and “Zanamivir” (study cohort group) and 9148 individuals not receiving “Oseltamivir” and “Zanamivir” (comparison cohort group). We initially used a multivariate Cox regression analysis during the tracking period to determine the cumulative incidence of NPAEs. Results: Our findings revealed no significant increase in the likelihood of developing NPAEs in the study group. The Kaplan–Meier survival curve demonstrated that individuals who received “Oseltamivir” and “Zanamivir” were not associated with statistically significantly increased NPAEs compared with controls (log-rank test, P = 0.724). Conclusion: No more risk in comparison of the normal population in our study, and the safety of “Oseltamivir” and “Zanamivir” is established treatments for influenza.
Background: Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D ...and inflammatory cytokines are debated. Our objective was to investigate whether supplemental interferons are associated with longitudinal change of vitamin D status in humans. Methods: A total of 48 patients with 24 or 48 weeks of pegylated interferon-alpha plus ribavirin therapy were examined for serum 25-hydroxyvitamin D (25OHD) level before treatment, at the end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in the Gene Expression Omnibus. Findings: The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH)D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly at end-of-treatment and decreased markedly by the end of the 24-week follow-up period. In the non-SVR group, this treatment-dependent change was lost. In gene expression analysis, the vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders but not in poor responders. Conclusion: In the aggregate, these data suggest that interferons have a regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs. Keywords: cytokines, interferon-alpha, PBMCs, VDR signaling, vitamin D
Drug-eluting beads transarterial chemoembolization (DEB-TACE) is an alternative to conventional lipiodol-based TACE (cTACE) to treat hepatocellular carcinoma (HCC). With the advancement in ...pharmacology, small-caliber DEB-TACE (<100 μm) has been introduced since 2016. For the treatment of hepatic neoplasms or HCC, there is a tendency to use smaller beads by DEB-TACE to achieve more extensive tumor necrosis and a significant reduction in liver toxicity in comparison with that caused by cTACE. However, the indications and potential complications of small-caliber DEB-TACE remain uncertain and have not been well established, due to lack of randomized phase III clinical trials. Instead of systematic or meta-analysis review, this narrative review article describes the suggested indications and contraindications of DEB-TACE with small DEBs, benefit of super-selective embolization of the feeding arteries and the recommended selection of small-caliber DEB. This review was approved by the institutional review board (File Number: 1-105-05-158).
Abstract
Background & Aims
Gilbert's syndrome causes pharmacological variation in drug glucuronidation and unexpected toxicity from therapeutic agents. The two common genotypes of Gilbert's syndrome ...are a dinucleotide polymorphism (
TA
)
7
in
TATA
‐Box as well as the 211G>A mutation in the coding exon 1, particularly in Asians, of human
UGT
1A1
gene. In this study, we aimed to establish an effective method to detect the 211G>A mutation.
Methods
The coding exon 1 sequence of human
UGT
1A1
gene was analysed by Vector
NTI
software. The 211G>A mutation in the coding exon 1 of
UGT
1A1
gene was determined by restriction fragment length polymorphism (
RFLP
) method. Serum total bilirubin level was measured as well.
Results
A newly identified Bsm
BI
site was located in the coding exon 1 of
UGT
1A1
gene. The 211G>A mutation in the coding exon 1 of
UGT
1A1
gene was determined by
DNA RFLP
. Furthermore, we reported our present work on genetic analysis of mutations of
UGT
1A1
gene, and the correlation of
UGT
1A1
mutations with serum total bilirubin levels in Taiwanese population. The results showed that 15 subjects carried 211G>A mutation in 23 subjects related with Gilbert's syndrome. The homozygous 211G>A mutant as well as simultaneously heterozygous mutants both in
TATA
‐Box and 211G>A significantly increased the risk of Gilbert's syndrome similar to subjects carrying homozygous
TATA
‐Box mutant.
Conclusions
Bsm
BI RFLP
is an effective method to detect 211G>A mutation in the coding exon 1 of
UGT
1A1
gene. The common 211G>A mutation is one of the causes of Gilbert's syndrome in Taiwanese population.
Neural induction is the process that occurs during embryogenesis whereby ectoderm is converted into neural tissue. However, the cellular and molecular mechanisms that govern this process are still ...not completely understood. For instance, in Xenopus, calcium signalling is known to play a pivotal role in neural induction but whether a similar mechanism occurs in mammals is unknown. As part of a wider study on genes regulating neural stem cell (NSC) development, we have discovered a novel role for Neuronatin (Nnaf), a regulator of intracellular Ca2+ concentration. In my thesis, I describe the use of a mouse embryonic stem cell (ESC)-derived neural differentiation model to dissect the function of Nnat in neural development. Using gain- and loss-of function experiments I show that ESCs in which Nnat expression had been knocked-down have a dramatically decreased ability to generate NSCs, and subsequently neurons, while ESCs that over-expressed Nnat generate an excess of NSCs and neurons. I reveal that Nnat interacts directly with the sarcoendoplasmic reticulum Ca2+-ATPase 2 (Apt2a2/SERCA2), and that Apt2a/SERCA inhibitors cause an increase in cytosolic calcium levels rescuing the ability of Nnat knockdown cells to generate neural cell-types. From these experiments I conclude that Apt2a/SERCA inhibition mimics the function of Nnat and, via the increase of cytosolic calcium, causes neural induction in Nnat knocked-down ESCs. I go on to show that this increase in cytosolic Ca2+, caused by inhibiting Apt2a/SERCA, activates Erk signalling and that inhibition of Erk signalling dramatically reduces the ability of ESCs to generate NSC. Together these results suggest that Nnat functions by increasing cytosolic Ca2+ levels, which in turn causes activation of Erk signalling leading to neural induction. In line with this, the expression of BMP4, which is an inhibitor of neural induction, was found to be up-regulated by Nnat knocked-down.
Neural induction is the process that occurs during embryogenesis whereby ectoderm is converted into neural tissue. However, the cellular and molecular mechanisms that govern this process are still ...not completely understood. For instance, in Xenopus, calcium signalling is known to play a pivotal role in neural induction but whether a similar mechanism occurs in mammals is unknown. As part of a wider study on genes regulating neural stem cell (NSC) development, we have discovered a novel role for Neuronatin (Nnaf), a regulator of intracellular Ca2+ concentration. In my thesis, I describe the use of a mouse embryonic stem cell (ESC)-derived neural differentiation model to dissect the function of Nnat in neural development. Using gain- and loss-of function experiments I show that ESCs in which Nnat expression had been knocked-down have a dramatically decreased ability to generate NSCs, and subsequently neurons, while ESCs that over-expressed Nnat generate an excess of NSCs and neurons. I reveal that Nnat interacts directly with the sarcoendoplasmic reticulum Ca2+-ATPase 2 (Apt2a2/SERCA2), and that Apt2a/SERCA inhibitors cause an increase in cytosolic calcium levels rescuing the ability of Nnat knockdown cells to generate neural cell-types. From these experiments I conclude that Apt2a/SERCA inhibition mimics the function of Nnat and, via the increase of cytosolic calcium, causes neural induction in Nnat knocked-down ESCs. I go on to show that this increase in cytosolic Ca2+, caused by inhibiting Apt2a/SERCA, activates Erk signalling and that inhibition of Erk signalling dramatically reduces the ability of ESCs to generate NSC. Together these results suggest that Nnat functions by increasing cytosolic Ca2+ levels, which in turn causes activation of Erk signalling leading to neural induction. In line with this, the expression of BMP4, which is an inhibitor of neural induction, was found to be up-regulated by Nnat knocked-down.
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