Long-term perturbation of muscle iron homeostasis following hindlimb suspension in old rats is associated with high levels of oxidative stress and impaired recovery from atrophy

In the present study, we investigated the effects of 7 and 14 days of re-loading following 14-day muscle unweighting (hindlimb suspension, HS) on iron transport, non-heme iron levels and oxidative damage in the gastrocnemius muscle of young (6 months) and old (32 months) male Fischer 344 × Brown Norway rats. Our results demonstrated that old rats had lower muscle mass, higher levels of total non-heme iron and oxidative damage in skeletal muscle in comparison with young rats. Non-heme iron concentrations and total non-heme iron amounts were 3.4- and 2.3-fold higher in aged rats as compared with their young counterparts, respectively. Seven and 14 days of re-loading was associated with higher muscle weights in young animals as compared with age-matched HS rats, but there was no difference in muscle weights among aged HS, 7 and 14 days of re-loading rats, indicating that aged rats may have a lower adaptability to muscle disuse and a lower capacity to recover from muscle atrophy. Protein levels of cellular iron transporters, such as divalent metal transport-1 (DMT1), transferrin receptor-1 (TfR1), Zip14, and ferroportin (FPN), and their mRNA abundance were determined. TfR1 protein and mRNA levels were significantly lower in aged muscle. Seven and 14 days of re-loading were associated with higher TfR1 mRNA and protein levels in young animals in comparison with their age-matched HS counterparts, but there was no difference between cohorts in aged animals, suggesting adaptive responses in the old to cope with iron deregulation. The extremely low expression of FPN in skeletal muscle might lead to inefficient iron export in the presence of iron overload and play a critical role in age-related iron accumulation in skeletal muscle. Moreover, oxidative stress was much greater in the muscles of the older animals measured as 4-hydroxy-2-nonhenal (HNE)-modified proteins and 8-oxo-7,8-dihydroguanosine levels. These markers remained fairly constant with either HS or re-loading in young rats. In old rats, HNE-modified proteins and 8-oxo-7,8-dihydroguanosine levels were markedly higher in HS and were lower after 7 days of recovery. However, no difference was observed following 14 days of recovery between control and re-loading animals. In conclusion, advanced age is associated with disruption of muscle iron metabolism which is further perturbed by disuse and persists over a longer time period.     

In vitro characterisation of ultrasound-induced heating effects in the mother and fetus: A clinical perspective

IntroductionThe quantification of heating effects during exposure to ultrasound is usually based on laboratory experiments in water and is assessed using extrapolated parameters such as the thermal index. In our study, we have measured the temperature increase directly in a simulator of the maternal–fetal environment, the ‘ISUOG Phantom’, using clinically relevant ultrasound scanners, transducers and exposure conditions.MethodsThe study was carried out using an instrumented phantom designed to represent the pregnant maternal abdomen and which enabled temperature recordings at positions in tissue mimics which represented the skin surface, sub-surface, amniotic fluid and fetal bone interface. We tested four different transducers on a commercial diagnostic scanner. The effects of scan duration, presence of a circulating fluid, pre-set and power were recorded.ResultsThe highest temperature increase was always at the transducer–skin interface, where temperature increases between 1.4°C and 9.5°C were observed; lower temperature rises, between 0.1°C and 1.0°C, were observed deeper in tissue and at the bone interface. Doppler modes generated the highest temperature increases. Most of the heating occurred in the first 3 minutes of exposure, with the presence of a circulating fluid having a limited effect. The power setting affected the maximum temperature increase proportionally, with peak temperature increasing from 4.3°C to 6.7°C when power was increased from 63% to 100%.ConclusionsAlthough this phantom provides a crude mimic of the in vivo conditions, the overall results showed good repeatability and agreement with previously published experiments. All studies showed that the temperature rises observed fell within the recommendations of international regulatory bodies. However, it is important that the operator should be aware of factors affecting the temperature increase.     

A population-based study of causes of death after endometrial cancer according to major risk factors

ObjectiveTo identify the most common causes of death and potentially modifiable risk factors in endometrial cancer patients.Methods745 women diagnosed with incident endometrial cancer were enrolled in a population-based study from 1991 to 1994. Participants completed structured interviews about 1 year after diagnosis. Study files were linked with the National Death Index to identify dates and causes of death through 2016. Proportional hazards regression was used to estimate hazard rate ratios for cause of death adjusting for age and stage of disease. Hazard ratios were also examined according to comorbidities.ResultsOf the 745 women, 450 were deceased after a median of 19.9 years. The two most common causes of death were cardiovascular disease (N = 145, 32%) and any cancer (N = 135, 30%), with only 10% of women dying from endometrial cancer (N = 46). Obesity, diabetes and smoking increased risk of all-cause mortality (HRR 1.77, 95%CI 1.36–2.31; HRR 1.74, 95%CI 1.34–2.27; HRR 1.59, 95%CI 1.16–2.17). Diabetes also increased risk of cardiovascular disease-specific mortality (HRR 1.98, 95%CI 1.38–3.08), but not endometrial cancer mortality (HRR 0.55, 95%CI 0.21–1.48). Neither obesity nor smoking was associated with increased risk of cardiovascular disease-specific mortality (HRR 1.46, 95%CI 0.92–2.32; HRR 1.21, 95%CI 0.67–2.18) nor endometrial-cancer specific mortality (HRR 1.81, 95%CI 0.83–3.93; HRR 0.61, 95%CI 0.17–2.15).ConclusionsEndometrial cancer patients were 3 times more likely to die of cardiovascular disease than endometrial cancer. Obesity, smoking and diabetes increase the risk of death in these patients and are potentially modifiable. Clinical trials should be developed that incorporate counseling regarding these risk factors into survivorship care to determine impact on mortality.