Distribution of parabens and 4-HB in human blood.

Human blood has been commonly and routinely analyzed to determine internal human exposure to parabens. However, data on the occurrence of parabens and their common metabolite, p-hydroxybenzoic acid (4-HB), in different human blood matrixes is still limited. In this study, 139 pairs of serum and whole blood samples were collected from Chinese adults, and then analyzed them for 5 parabens and 4-HB. Methylparaben (MeP) and propylparaben (PrP) were consistently the predominant parabens in human serum (mean 2.3 and 2.1 ng/mL, respectively) and whole blood (1.9 and 1.3 ng/mL, respectively). Mean concentrations of 4-HB in human serum and whole blood were 7.7 and 12 ng/mL, respectively. Concentrations of parabens, except benzylparaben (BzP), and 4-HB in human serum were significantly (p < 0.01) correlated with that in whole blood. Distribution pattern of parabens and 4-HB in human blood was evaluated, for the first time, based on their partitioning between human serum and whole blood (Kp). Mean Kp values of parabens, except BzP, increased with the alkyl chain length from 0.83 to 1.6. BzP (mean 1.4) had a comparable mean Kp value to PrP (mean 1.4). Among target analytes, 4-HB had the lowest mean Kp value (0.75). These data are important to select appropriate blood matrixes for conducting human exposure assessment and epidemiological studies on parabens.

Occurrence of p-phenylenediamine antioxidants in human urine.

General populations are widely exposed to various p-phenylenediamine antioxidants (PPDs). N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a typical p-phenylenediamine antioxidant, has been detected in human urine samples. However, the occurrence of other widely used PPDs in human urine is still unclear. This study comprehensively characterized the occurrence of 9 PPDs in human urine from 151 Chinese adults. Our results showed that all target PPDs were detected in human urine samples, with the total concentrations of PPDs ranging from 0.41 to 38 ng/mL. PPDs in human urine was dominated by 6PPD (mean 1.2 ng/mL, range < LOD - 3.8 ng/mL), followed by N-phenyl-N'-cyclohexyl-p-phenylenediamine (CPPD; 0.85 ng/mL,

Signal mining study of severe cutaneous adverse events of valaciclovir or acyclovir based on the FAERS database.

OBJECTIVE: This study aimed to explore a comprehensive empirical investigation and assess SCARs related to valaciclovir or acyclovir based on FAERS database from FDA, thus providing a theoretical foundation for the rational application of drugs in clinic. METHODS: SCARs reports relevant to valaciclovir or acyclovir were searched in FAERS database from the 2004 Q1 to 2023 Q2. These data were further mined by a proportional analysis and Bayesian approach to detect signals of SCARs caused by two drugs. Meanwhile, the clinical characteristics, onset time, correlation, and stratification analysis of the two drugs in SCARs were analyzed. RESULTS: Both drugs exhibited positive signals for drug reaction with DRESS, AGEP, TEN, SJS-TEN overlap and SJS. The median onset time of SCARs caused by valaciclovir or acyclovir was 30 days vs 10 day for DRESS, 11 days vs 9 days for AGEP, 17 days vs 12 days (TEN) and 12 days vs 8 days (SJS). Excluding the effect of combinational drugs, there was an association between the two antiviral drugs and SCARs. CONCLUSION: By analyzing the FAERS database, the risk trends of SCARs caused by valaciclovir or acyclovir have been identified, providing valuable insights to recognize various types of SCARs in clinics.

Associations between urinary parabens and lung cancer.

Parabens are a family of endocrine-disrupting chemicals. Environmental estrogens may play a vital role in the development of lung cancer. To date, the association between parabens and lung cancer is unknown. Based on the 189 cases and 198 controls recruited between 2018 and 2021 in Quzhou, China, we measured 5 urinary parabens concentrations and examined the association between urinary concentrations of parabens and lung cancer risk. Cases showed significantly higher median concentrations of methyl-paraben (MeP) (2.1 versus 1.8 ng/mL), ethyl-paraben (0.98 versus 0.66 ng/mL), propyl-paraben (PrP) (2.2 versus 1.4 ng/mL), and butyl-paraben (0.33 versus 0.16 ng/mL) than controls. The detection rates of benzyl-paraben were only 8 and 6% in the control and case groups, respectively. Therefore, the compound was not considered in the further analysis. The significant correlation between urinary concentrations of PrP and the risk of lung cancer (odds ratio (OR)adjusted = 2.22, 95% confidence interval (CI): 1.76, 2.75; Ptrend < 0.001) was identified in the adjusted model. In the stratification analysis, we found that urinary concentrations of MeP were significantly associated with lung cancer risk (OR = 1.16, 95% CI: 1.01, 1.27 for the highest quartile group). Besides, comparing the second, third, and fourth quartile groups with the lowest group of PrP, we also observed urinary PrP concentrations associated with lung cancer risk, with the adjusted OR of 1.52 (95% CI: 1.29, 1.65, Ptrend = 0.007), 1.39 (95% CI: 1.15, 1.60, Ptrend = 0.010), and 1.85 (95% CI: 1.53, 2.30, Ptrend = 0.001), respectively. MeP and PrP exposure, reflected in urinary concentrations of parabens, may be positively associated with the risk of lung cancer in adults.

The effect of intravenous immunoglobulin passive immunotherapy on unexplained recurrent spontaneous abortion: a meta-analysis.

The aim of this study was to investigate the effect of passive immunotherapy using intravenous immunoglobulin (IVIG) on unexplained recurrent spontaneous abortion (RSA). Live birth rates were analysed and binary data were calculated using risk ratio and 95% confidence interval. Meta-analysis of 11 studies showed that the difference in the live birth rate between the IVIG treatment and placebo groups was on the margin of significance (RR = 1.25, 95% CI 1.00 to 1.56, P = 0.05). Both cumulative and trial sequential meta-analyses indicated potential beneficial effect of IVIG but the evidence was inconclusive. Subgroup analysis showed that the live birth rate in primary (RR = 0.88, 95% CI 0.71 to 1.07) and secondary (RR = 1.26, 95% CI 0.99 to 1.61) RSA patients was not significantly different between the IVIG and placebo groups. Live birth rate was significantly different when IVIG was administered before conception (RR = 1.67, 95% CI 1.30 to 2.14, P < 0.0001) but not after implantation (RR = 1.10, 95% CI 0.93 to 1.29). Evidence is insufficient to support the beneficial effects of IVIG on an unexplained RSA. Further high quality studies are needed to elucidate the effectiveness of IVIG.