Background/Aims: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the ...complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.
Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.
Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).
Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs. (Clin Mol Hepatol 2021;27:186-196)
In order to clarify the risk of hematotoxicity of carboplatin, we inspected 19901 case reports of non-small cell lung cancer patients that were submitted to the FDA Adverse Event Reporting System ...(FAERS) between January 2004 and December 2015. These comprised 3907 cases which were treated with carboplatin and 15994 cases which were treated with other therapies in the absence of carboplatin. By comparison, carboplatin cases were significantly more likely to report anemia (OR = 2.27, 95% CI 1.85-2.78, P = 5.04×10-15), neutropenia (OR = 2.27, 95% CI 1.76-2.92, P = 2.39×10-10), and thrombocytopenia (OR = 2.38, 95% CI 1.84-3.08, P = 5.60×10-11). We further explored published evidences and found 205 human genes interacting with carboplatin. Functional analysis corroborated that these genes were significantly enriched in the biochemical pathway of hematopoietic cell lineage (adjusted P = 6.02×10-11). This indicated that carboplatin could profoundly affect the development of blood cells. Given the early awareness of the hematologic risks, great caution should be exercised in prescribing carboplatin to non-small cell lung cancer patients. And functional enrichment analysis on carboplatin-related genes warranted subsequent research with regard to the underlying toxicological mechanisms.
The conditions to determine geniposide and genipin using gradient liquid chromatography–tandem mass spectrometry (LC–MS/MS) via electrospray ionization were obtained using fractional factorial ...experimental design approaches, guided with Taguchi orthogonal arrays to enhance peak intensity. Geniposide, the major iridoid glycoside component of
Gardenia herbs, which has been recognized to have choleretic effects, is transformed to genipin in animals. In this paper, the gradient establishment times, ionization source temperatures, and the concentrations of volatile additive ammonium acetate were investigated under the guidance of experimental designs to obtain LC–MS/MS signals of the highest peak intensity. Using geniposide and genipin standards, the methods are validated at the concentration ranges of 0.5–1000
ng/mL and 10–5000
ng/mL using ammonium adducts. The correlation coefficients of geniposide and genipin standard curves are greater than 0.999. Compared with the sensitivities of previously published LC–MS/MS methods, the methods developed in this work provide 6-fold sensitivity improvement. The lowest concentrations of geniposide and genipin, 0.19 and 2
ng/mL, respectively, to generate detectable LC–MS/MS signal peaks are one order of magnitude lower than the repoered values in previous publications. The measurement accuracy and precision of geniposide are within 23% and 15%, respectively. The accuracy and precision of genipin are within 16% and 12.5%, respectively. When the validated calibration curves of geniposide and genipin are used to determine spiked control samples in rat blood dialysates, the geniposide determination errors are within 15% accuracy and within 5.8% precision, respectively, and the genipin determination errors are within 23% accuracy and within 3.6% precision, respectively.
The genetic control of Interleukin-10 (IL-10) and Tumour necrosis factor-alpha (TNF-alpha) production and the possible interaction between the two cytokines in influencing SLE susceptibility as well ...as clinical features has not been completely evaluated in the Taiwanese population.
We investigated the association of IL-10 and TNF-alpha promoter polymorphisms (-1082, -819 and -592 for IL-10 gene; -308 for TNF-alpha gene) with SLE in a total of 172 Taiwanese patients and 215 controls.
Our results indicate that IL-10 A/T/A-A/T/A genotype was associated with Taiwanese SLE, whereas no significance was observed between TNF-alpha genotype and SLE. Furthermore, the TNF-alpha G allele frequency of the polymorphism at -308 was significantly decreased in patients with oral ulcers. The combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly increased in SLE patients. In addition, the combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly decreased in patients with oral ulcers.
These results suggest a significant correlation of the combined IL-10 and TNF-alpha genetic polymorphisms contribute to SLE susceptibility and clinical features in the Taiwanese population.
Protective effects of asiaticoside on septic lung injury in mice Zhang, Li-na; Zheng, Jia-jia; Zhang, Li ...
Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie,
09/2011, Letnik:
63, Številka:
6
Journal Article
Recenzirano
Asiaticoside (AS), a major triterpenoid saponin component isolated from
Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities. The present study aimed to ...determine the protective effects and the underlying mechanisms of AS on septic lung injury induced by cecal ligation and puncture (CLP). Mice were pretreated with the AS (45
mg/kg) or AS as well as GW9662 at 1
h before CLP, the survival, lung injury, inflammatory mediators and signaling molecules, and Peroxisome proliferator-activated receptor-γ (PPAR-γ) were determined 24
h after CLP. The results showed that AS significantly decreased CLP-induced the mortality, lung pathological damage, the infiltration of mononuclear, polymorphonuclear (PMN) leucocytes and total proteins. Moreover, AS inhibited CLP-induced the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB), the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein in lung tissues, and the production of serum tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Interestingly, the expression of PPAR-γ protein in lung tissue was up-regulated by AS. Furthermore, GW9662 (the inhibitor of PPAR-γ) significantly reversed these beneficial effects of AS in septic mice. These findings suggest that AS could effectively protect from septic lung injury induced by CLP and the underlying mechanisms might be related to up-regulation of PPAR-γ expression to some extent, which inhibits MAPKs and NF-κB pathway.
The scorpion has been extensively used in various pharmacological profiles or as food supplies. The exploration of scorpion venom has been reported due to the presence of recombinant peptides. ...rBmalphaTX14 is an alpha-neurotoxin extracted from the venom gland of the East Asian scorpion Buthus martensii Karsch and can affect ion channel conductance. Here, we investigated the functions of rBmalphaTX14 using the Caenorhabditis elegans model. Using western blot analysis, rBmalphaTX14 was shown to be expressed both in the cytoplasm and inclusion bodies in the E.coli Rosetta (DE3) strain. Circular dichroism spectroscopy analysis demonstrated that purified rBmalphaTX14 retained its biological structures. Next, feeding nematodes with E.coli Rosetta (DE3) expressing rBmalphaTX14 caused extension of the life span and promoted the locomotion of the nematodes. In addition, we identified several genes that play various roles in the life span and locomotion of C. elegans through microarray analysis and quantitative real-time PCR. Furthermore, if the amino acid site H.sub.15 of rBmalphaTX14 was mutated, rBmalphaTX14 no longer promoted the C. elegans life span. In conclusion, the results not only demonstrated the functions and mechanism of rBmalphaTX14 in C. elegans, but also provided the new sight in the utility of recombinant peptides from scorpion venom.
By preparing 15 batches of substance benchmarks of Taohong Siwu Decoction, the methodology of the characteristic spectrums of substance benchmarks was established. The paste-forming rate range, the ...contents and the transfer rate range of the index components, hydroxy safflower yellow A, ferulic acid and paeoniflorin, the characteristic peaks and the similarity range of the characteristic spectrums of Taohong Siwu Decoction were determined to define key quality attributes of substance benchmarks of Taohong Siwu Decoction.In the 15 batches of substance benchmarks of Taohong Siwu Decoction, the similarity of characteristic spectrums was higher than 0.9. Furthermore, based on summarization of the characteristic peak information, there were 13 characteristic peaks in the whole decoction. Baishao had three characteristic peaks, Honghua had seven characteristic peaks, and Chuanxiong and Danggui had three characteristic peaks. The paste-forming rate of the 15 batches of substance benchmarks was controlled at 33.11%-4
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