The effects of aging and nutritional state on hypoxia-reoxygenation injury in the perfused rat liver

During liver transplantation, donor livers are subject to hypoxia and reoxygenation. Recently, because of a shortage of suitable donors, the livers of older donors have been used for transplantation. In this study, we examined the influence of aging and nutritional state on hepatic intracellular pH (pH;) and the susceptibility of the rat liver to hypoxia-reoxygen-ation injury. Perfused livers from fasted and fed, young (2-3 months) and aged (24-28 months) male Wistar rats were compared during 30 min of nitrogen hypoxia followed by 20 min of reoxygenation. Under control conditions, pH; was significantly lower and glucose release higher in livers from fed young rats (7.24±0.04, 3.4±1.8 pmol/min/g) than in those from fasted young (7.33±0.04, 0.0±1.3), fasted aged (7.32± 0.03, -0.1 ±0.5), and fed aged rats (7.29±0.06, 0.9±1.0). In all groups, pH; fell by ~0.15 U during hypoxia. Lactate dehydrogenase (LDH) release from the livers of fed young livers was unaffected by hypoxia-reoxygen-ation as was that from the livers of fed aged rats, despite features that would be expected to predispose to injury (reduced glucosc output and more alkaline pH.). In contrast, livers from fasted young and aged rats had substantially increased LDH release and reduced bile flow during hypoxia. There were no age-related differences in these parameters, but, during reoxygenation, LDH release was significantly less in the aged livers. These results indicate that the livers of fed rats are resistant to hypoxia-reoxygenation injury and that aging does not increase the susceptibility of the liver to injury in the fasted state

Glucose transport and hypoxia-reoxygenation injury in the perfused rat liver

Abstract During liver transplantation, oxidative stress occurs during hypoxia and reoxygenation of the donor organ. Chemical oxidative stress impairs cell membrane transport. Therefore, in this study the influence of hypoxia and reoxygenation on hepatocellular membrane transport was investigated. Specifically, glucose transport was studied in the perfused rat liver using the multiple indicator‐dilution technique. First, it was observed that in normal rat livers, glucose transport was rapid but saturable (K48 ± 10 mmol/L and V9.4 ± 0.9 μmol/s per g of liver). To simulate hypoxia and reoxygenation, livers were perfused for 30 min with nitrogen‐saturated buffer and then with oxygen‐saturated buffer for 20 min. The livers from fed rats were protected from hypoxia‐reoxygenation injury whereas those from fasted rats were highly susceptible to injury as determined by lactate dehydrogenase release. After reoxygenation, the rate of glucose influx decreased significantly by ∼50% in the fasted livers (P < 0.001) but was unaffected in the fed livers. This impairment of the hepatocellular transport of glucose, which could be secondary to oxidative injury to the hepatocyte membrane, has implications for the function of donor livers that have sustained hypoxia‐reoxygenation (‘preservation') injury during transplantation. Copyrigh

Erratum: COVID-19 through the lens of gerontology

The previously published version of this article was incomplete. It has been replaced by a complete version, now with an updated title. The publisher apologizes for this error

The association between polymorphisms in the cytochrome P-450 2D6 gene and Parkinson's disease: A case-control study and meta-analysis

We performed a case-control study to investigate the association of the poor metaboliser genotype of the cytochrome P450 2D6 gene with Parkinson's disease (PD). Genotyping was determined by the polymerase chain reaction followed by digestion with restriction enzymes. The poor metaboliser genotype was more frequent in 112 patients with PD than in 206 matched controls (odds ratio 1.7, 95% CI: 0.94-2.45). A meta-analysis of these results together with ten other published studies gave a pooled odds ratio for the poor metaboliser genotype of 1.47 (95% CI: 1.18-1.96, P=0.01). Thus, the poor metaboliser genotype has a small but highly significant association with PD which would be easily missed in small studies. Research now should focus on the mechanism of this association

Pain, frailty and comorbidity on older men: the CHAMP study.

Intrusive pain is likely to have a serious impact on older people with limited ability to respond to additional stressors. Frailty is conceptualised as a functional and biological pattern of decline accumulating across multiple physiological systems, resulting in a decreased capacity to respond to additional stressors. We explored the relationship between intrusive pain, frailty and comorbid burden in 1705 community-dwelling men aged 70 or more who participated in the baseline phase of the CHAMP study, a large epidemiological study of healthy ageing based in Sydney, Australia. 9.4% of men in the study were frail (according to the commonly-used Cardiovascular Health Study frailty criteria).Using a combination of self-report and clinical measures, we found an association between frailty and intrusive pain that remained after accounting for demographic characteristics, number of comorbidities, self-reported depressed mood and arthritis (adjusted odds ratio 1.7 (95% confidence interval (CI) 1.1-2.7), p=0.0149). The finding that adjusting for depressed mood, but not a history of arthritis, attenuated the relationship between frailty and intrusive pain points to a key role for central mechanisms. Additionally, men with the highest overall health burden (frail plus high comorbid burden) were most likely to report intrusive pain (adjusted odds ratio 3.0 (95% CI 1.6-5.5), p=0.0004). These findings provide support for the concept that intrusive pain is an important challenge for older men with limited capacity to respond to additional physical stressors. To our knowledge, this is the first study to explore specifically the relationship between pain and frailty