Intermittent opioid use and ischemic placental disease: Study quantifies risks, raises questions

Discomfort and, to a lesser extent, pain are common complaints during pregnancy, and some patients may turn to opioids for pain relief. Esposito and colleagues (Am J Epidemiol. 2021, in press) report associations between intermittent exposure to opioids during pregnancy and the risk of ischemic placental disease (IPD) – a syndrome that includes preeclampsia, placental abruption, small for gestational age (SGA) births, and preterm delivery. They found that early opioid exposure in pregnancy was associated with a modestly increased risk for abruption, SGA births, and preterm delivery, and both early and late exposure was associated with the greatest risk for these outcomes. Surprisingly, preeclampsia was not associated with opioid use. Through quantitative bias analysis, the authors cleverly tackle a number of biases to assess their roles in explaining the associations, including unmeasured confounding, outcome misclassification, and residual confounding; none exerted strong influences on the associations. Although the findings appear fairly robust on the surface, the lack of association between intermittent opioid use and preeclampsia, and important differences in characteristics of patients in the opioid exposed group compared to the unexposed group, suggest that further study is needed to clarify the relationship between intermittent opioid use, lifestyle factors, and IPD risk.

Antioxidant Additives versus Health Benefits of Brief/Intermittent Exposure to Potentially Toxic Physical or Chemical Agents

Although antioxidants can act locally to react with an oxidant, oral administration of “antioxidants” is quite useless in treating oxidative stress in tissues. Furthermore, it does not make sense to consider a vitamin as an antioxidant, but vitamin B3 leads to the in vivo formation of compounds that are essential for reducing this stress. A rigorous treatment of the subject indicates that to deal with oxidative stress, the most direct approach is to enhance the innate antioxidant mechanisms. The question is whether this is possible through daily activities. Diets can contain the necessary components for these mechanisms or may induce the expression of the genes involved in them. Another possibility is that pro-oxidant molecules in food increase the sensitivity and power of the detoxification pathways. This option is based on well-known DNA repair mechanisms after exposure to radiation (even from the Sun), or strong evidence of induction of antioxidant capacity after exposure to powerful pro-oxidants such as H2O2. More experimental work is required to test whether some molecules in food can increase the expression of antioxidant enzymes and/or improve antioxidant mechanisms. Identifying effective molecules to achieve such antioxidant power is critical to the food and nutraceutical industries. The potential of diet-based interventions to combat oxidative stress must be viewed from a new perspective.

Intermittent exposure to green and white light-at-night activates hepatic glycogenolytic and gluconeogenetic activities in male Wistar rats

Objectives Exposure to light-at-night (LAN) has been reported to impair blood glucose regulation. The liver modulates blood glucose through mechanisms influenced by several factors that include peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) and glucose-6-phosphatase (G6Pase). This study investigated the effect of intermittent exposure to green and white LAN on some hepatic glucose regulatory factors in male Wistar rats. Methods Animals were divided into three equal groups. Group I (control) was exposed to normal housing conditions. Groups II and III were each daily exposed to either green or white LAN for 2 h (7–9 pm) for 14 days. Body weight and blood glucose was monitored on days 0, 7, and 14. Thereafter, retro-orbital sinus blood was obtained after light thiopental anaesthesia and serum insulin was determined. Liver samples were also obtained and evaluated for glycogen, PGC-1α, and G6Pase activity. Insulin resistance was estimated using the HOMA-IR equation. Results Body weight and blood glucose on days 7 and 14 increased in groups II and III compared to control. Hepatic PGC-1α and G6Pase increased in group II (2.33 ± 0.31; 2.07 ± 0.22) and III (2.31 ± 0.20; 0.98 ± 0.23) compared to control (1.73 ± 0.21; 0.47 ± 0.11). Hepatic glycogen was 71.8 and 82.4% reduced in groups II and III compared to control. Insulin in group II increased (63.6%) whiles group III values reduced (27.3%) compared to control. Insulin resistance increased in group II (0.29 ± 0.09) compared to control (0.12 ± 0.03) and group III (0.11 ± 0.03), respectively. Conclusions Exposure to 2 h green and white LAN in the early dark phase increases hepatic glycogenolysis and gluconeogenetic activities resulting in increased blood glucose. In male Wistar rats, exposure to green but not white LAN may predispose to insulin resistance.

Transboundary air pollution and health: evidence from East Asia

Outdoor air pollution continues to be a challenging health issue, even as countries experience economic growth. By exploiting a unique transboundary setting in East Asia, we study the impact of an increase in particulate matter (PM) concentrations on fetal deaths. Due to the westerlies in the mid-latitudes, residents in South Korea at times experience intermittent exposure to high levels of air pollution. Using such atmospheric setting, we estimate a reduced-form impact of high PM events on fetal deaths, which captures in utero exposure to pollution. Controlling for local weather and pollution trends, regression results indicate that high PM events in Beijing lead to a significant increase in daily fetal mortality rates in Korea, by approximately 7.4 per cent. This research finding provides lower-bound estimates of not only negative spillovers manifested in fetal health but also the impact of pollution on the health of the Chinese population and calls for a need to tackle transboundary air pollution via international cooperation.

Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis

Osteoarthritis (OA) is a common cause of pain and disability. Local corticosteroid injections are effective in treating OA pain and inflammation but are short-acting. Prolonged intra-articular (IA) corticosteroid exposure may even lead to cartilage deterioration. The aim of this prospective study was to assess safety and provide proof-of-concept of IA-applied biodegradable polyesteramide-based microspheres (PEAMs) gradually releasing triamcinolone acetonide (TA). Mimicking continuous exposure associated with local drug delivery in canine articular chondrocytes cultured in the continuous presence of TA tissue regeneration was not affected, whereas intermittent exposure reduced proteoglycan production. In this respect, TA-PEAMs administered IA in a proof-of-concept study in 12 client-owned dogs with established OA also showed safety by radiographic examination, without changes in OA severity and in glycosaminoglycan synovial fluid levels. Treatment also resulted in clinical improvement in 10 out of 11 dogs during the two-month follow-up period, which persisted in 6 out of 10 dogs after 6 months, based on objective gait analysis and owner questionnaires. Synovial prostaglandin E2, a pro-inflammatory marker, was decreased two months after treatment. This study showed safety and proof-of-concept of IA-administered TA-PEAMs in dogs with OA, as a first step towards translation into the veterinary and human clinic.

Effects of radiofrequency radiation on colorectal cancer cell proliferation and inflammation

Objectives The aim of this study is to investigate the effects of radiofrequency radiation (RFR) on apoptosis, proliferation, stress response, and inflammation markers in colorectal cancer cells. Methods We tested the effects of intermittent exposure to RFR at different frequencies on two different colorectal cancer cell lines; HCT-116 and DLD-1. Protein levels were subsequently analyzed by ELISA. Results RFR led to a decrease in P53, p-P53, p-P38, and p-IkB levels in HCT-116 cells, while leading to an increase in BAD, p-BAD, p-STAT3,NF-κB levels. Two thousand one hundred Megahertz of RFR altered the P53, BAD, and NF-ΚB expression in HCT-116 cells. P53, p-P53, BAD, p-BAD, NF-κB, p-NF-κB, p-P38, p-SAPK/JNK, p-STAT3, and p-IkB levels increased after exposure to RFR at 900 and 2,100 MHz in DLD-1 cells. Unlike HCT-116 cells, 1,800 MHz of RFR was reported to have no effect on DLD1 cells. Conclusions RFR increased apoptosis and inflammatory response in HCT116 cells, while lowering the active P38 and active P53 levels, which are indicators of poor prognosis in several cancers. Genetic differences, such as P53 mutation (DLD-1), are critical to the cell response to RFR, which explains the reason why scientific studies on the effects of RFR yield contradictory results.

Induction of Artesunate Resistance in Plasmodium Falciparum 3D7 Strain Using Intermittent Exposure Method and Comparing P.fk13 Sequence between Susceptible and Resistant Strains

Background: Malaria is a major health issues in a number of countries in the world, especially tropical countries. Over the past 50 years, the resistance of Plasmodium falciparum has expanded against the antimalarial drugs that had been used to treat the disease. Recently resistance to some derivatives of artemisinin and the failure of artemisinin combination therapy (ACT) has threatened all major achievements in malaria control. Resistant strains are limited around the world, but it may spread very soon, hence the necessary to be prepared for any event regarding this matter, it is needed to organize more investigations about resistant strains and related genes. Preparation of a new resistant strain in the laboratory can provide opportunity to predict genes responsible for resistance. The aim of this study was to induce resistance to artesunate in Plasmodium falciparum 3D7 strain using intermittent exposure method and comparing P.fk13 gene sequence between susceptible and resistance strains.Methods: Plasmodium falciparum 3D7 strain was cultured according to Trager & Jensen method with some modifications. Serial concentrations between 10-2 mol/l, to 10-7mol/l were prepared, then P.falciparum 3D7 was exposed to each of the dilution to determine IC50 and lethal dose. After 24 hours exposure the rate of parasitemia and mean of growth inhibitory percent were evaluated. Sensitivity reduction process was started from the concentration of 10-7mol/l and ended at 10-2mol/l. Exposed parasites were collected after at least 27 days after cultivation in each drug concentration. DNA extraction, PCR and sequencing process were performed to investigate any possible mutations in the pfk13 gene sequence.Results: Effectiveness of 10-2mol/l concentration of artemisinin was found as a lethal dose. The resistant strain was provided in the lab, sequenced and registered in the gene bank as P.f Art -2, (accession number MH796123. 1). Alignment of this registered sample showed no mutation in P.f kelch13 gene in comparison with standard strain submitted in the Genebank. Conclusions: Results of this study showed that resistance to artesunate in malaria parasite may occur but with no mutation in the P.f kelch13 gene. Therefore, whole genome sequencing should be applied to determine mutations in resistant strains.