Association of intrapartum drugs to spontaneous intestinal perforation: A single center retrospective review

ABSTRACT Background: Spontaneous intestinal perforation (SIP) occurs commonly in extremely low gestational age newborns (ELGANs; < 30 weeks GA). Early, concurrent neonatal use of indomethacin (Neo_IN) and hydrocortisone (Neo_HC), is a known risk for SIP. Mothers in premature labor often receive indomethacin (Mat_IN) for tocolysis and steroids (Mat_S) for fetal maturation. Coincidentally, ELGANs may receive Neo_IN or Neo_HC within the first week of life. There is limited data on the effect of combined exposures to maternal and neonatal medications. We hypothesized that proximity exposure to these medications may increase the risk of SIP. Design: We reviewed the medical records of ELGANS from June 2014 to December 2019 at a single Level III NICU. We compared antenatal and postnatal indomethacin and steroid use between neonates with and without SIP. Chi-Square, Student’s t-test, Fisher’s Exact test, and Mann-Whitney U tests were used for analysis. Results: Among 417 ELGANs, SIP was diagnosed in 23; predominantly neonates <26 weeks GA (n = 21/126, 16.7%). Risk factors analysis focused on this GA cohort in which SIP was most prevalent. Mat_IN administration within two days of delivery increased SIP risk (OR 3.00, 95%Cl 1.25-7.94, p=0.036). Neo_HC was not independently associated with SIP (p=0.38). A higher proportion of SIP group had close temporal exposure of Mat_IN and Neo_HC compared to the non-SIP group, though not statistically significant (14% v. 7%, p=0.24). Conclusions: Peripartum Mat_IN was associated with increased risk for SIP in this small study sample. Larger studies are needed to further delineate SIP risk from the interaction of peripartum maternal medication with early postnatal therapies and disease pathophysiology.

Effect of single and combined exposures to UV-C and UV-A LEDs on the inactivation of Klebsiella pneumoniae and Escherichia coli in water disinfection

A system consisting of one UV-A (365 nm) and two UV-C (265 nm) light-emitting diodes (LEDs) was built to evaluate the effect of single and combined exposures to UV-A and UV-C LEDs on Klebsiella pneumoniae and Escherichia coli inactivation and subsequent reactivation. The dose was measured by actinometry using potassium ferrioxalate. Of laboratory prepared samples, 10 mL were irradiated for 20, 30, 45, 60 and 90 s. Logarithmic inactivation and percentages of photoreactivation and dark repair were calculated. E. coli and K. pneumoniae were reduced by more than 7 and 4 logs, respectively, at a dose of 21.5 mJ cm−2 using UV-C. No positive synergistic effect on the inactivation of the two bacteria was observed when using a simultaneous combination of UV-C and UV-A, probably due to a reactivation of the bacteria in the presence of UV-A light, which was not observed in irradiated samples under an individual exposure of 265 nm. For E. coli under 265 nm, the percentage of photoreactivation amounted to 10%, 3 h after irradiation. The results of this study demonstrated the capacity to inactivate E. coli and K. pneumoniae up to a considerable level and provide information for the application of UV LEDs in point-of-use systems.

Interactive toxicity effect of combined exposure to hematite and amorphous silicon dioxide nanoparticles in human A549 cell line

The study on the health effects of combined exposure to various contaminants has been recommended by many authors. The objective of the present study was to examine the effects of the co-exposure to hematite and amorphous silicon dioxide (A-SiO2) nanoparticles on the human lung A549 cell line. The A549 cell line was exposed to 10, 50, 100, and 250 µg/ml concentrations of hematite and A-SiO2 nanoparticles both independently and in combination. Their toxicity in both circumstances was investigated by MTT, intracellular reactive oxygen species, cell glutathione content, and mitochondrial membrane potential tests, and the type of interaction was investigated by statistical analysis using Statistical Package for Social Sciences (SPSS, v. 21). Results showed that the independent exposure to either hematite or A-SiO2 compared with the control group produced more toxic effects on the A549 cell line. The toxicity of combined exposure of the nanoparticles was lower compared with independent exposure, and antagonistic interactive effects were detected. The findings of this study could be useful in clarifying the present debate on the health effects of combined exposure of hematite and A-SiO2 nanoparticles. Because of the complexities of combined exposures, further studies of this kind are recommended.

Effect of Cadmium and Nickel Exposure on Early Development in Zebrafish (Danio rerio) Embryos

Exposure to even low concentrations of heavy metals can be toxic to aquatic organisms, especially during embryonic development. Thus, this study aimed to investigate the toxicity of nickel and cadmium in zebrafish (Danio rerio) embryos exposed to environmentally relevant concentrations of each metal alone or in combination from 4 h through to 72 h postfertilization. Neither metal altered survival, but individual and combined exposures decreased hatching rate. Whereas cadmium did not affect total body length, trunk area, eye diameter, or eye area, nickel alone and in combination with cadmium decreased each morphological parameter. Yolk sac area, an index of metabolic rate, was not affected by nickel, but was larger in embryos exposed to high cadmium concentrations or nickel and cadmium combined at high concentrations. Nickel decreased spontaneous movement, whereas cadmium alone or nickel and cadmium combined had no effect. Neither metal altered elicited movement, but nickel and cadmium combined decreased elicited movement. Myosin protein expression in skeletal muscle was not altered by cadmium exposure. However, exposure to nickel at low concentrations and combined exposure to nickel and cadmium decreased myosin expression. Overall, nickel was more toxic than cadmium. In conclusion, we observed that combined exposures had a greater effect on movement than gross morphology, and no significant additive or synergistic interactions were present. These results imply that nickel and cadmium are toxic to developing embryos, even at very low exposure concentrations, and that these metals act via different mechanisms.