Pathological consequences of low atmospheric pressure stunning in broiler chickens

Low atmospheric pressure stunning (LAPS) is a novel approach to pre-slaughter stunning of chickens using progressive hypobaric hypoxia by the application of gradual decompression (280s cycle) according to a set of prescribed pressure curves. Low atmospheric pressure stunning produces a non-recovery state. Concerns have been raised relating to the possible pathological and welfare consequences of expansion of air in the body during LAPS. In a randomised trial, we compared the gross pathology of broilers exposed to LAPS with a control group euthanised by intravenous injection of pentobarbital sodium (60 mixed sex broilers per treatment). The birds were exposed to each treatment in triplets and all birds were subject to necropsy examination to detect and score (1 to 5, minimal to severe) haemorrhagic lesions or congestion for all major organs and cavities (e.g. air sacs, joints, ears and heart) as well as external assessment for product quality (e.g. wing tips). Behavioural data (latency to loss of posture and motionless) and chamber cycle data (temperature, humidity, pressure and oxygen availability) confirmed that LAPS had been applied in a manner representative of the commercial process. All of the organs observed were structurally intact for both treatment groups. No lesions were observed in the external ears, oral cavity, tracheal lumen, crop and air sacs of birds from either treatment group. There was no difference between treatments in the wingtips, nasal turbinates, thymus, biceps femoralis and colon. Haemorrhagic lesions were observed in the calvaria, brains, hearts and lungs of both treatment groups, but lesions in these areas were more severe in the LAPS treatment group. It was not possible to distinguish between pathological changes induced by decompression or recompression. In the barbiturate group, more severe haemorrhagic lesions were observed in the superficial pectoral muscles as well as greater congestion of the infraorbital sinuses, liver, spleens, duodenum, kidneys and gonads. These findings provide evidence that LAPS did not result in distension of the intestines and air sacs sufficient to cause changes, which were grossly visible on postmortem examination. There was also no evidence of barotrauma in the ears and sinuses. The pathological changes observed in the barbiturate treatment were as expected based on barbiturate toxicity. Low atmospheric pressure stunning appears to produce pathological changes by a variety of well-established mechanisms, and while these pathological data have limited value as welfare indicators, the results confirm that organ integrity was not compromised by the process.     

Hypoxia-based strategies for angiogenic induction

Therapeutic angiogenesis promises to aid the healing and regeneration of tissues suffering from a compromised vascular supply. Ischaemia therapy has so far primarily focused on delivering isolated angiogenic growth factors. The limited success of these strategies in clinical trials, however, is increasingly forcing researchers to recognize the difficulties associated with trying to mimic the angiogenic process, due to its natural complexity. Instead, a new school of thought is gradually emerging, focusing on how to induce angiogenesis at its onset, by utilizing hypoxia, the primary angiogenic stimulus in physiological, as well pathological states. This shift in therapeutic approach is underlined by the realization of the importance of depressed HIF-1 α-mediated gene programming in non-healing ischemic tissues, which could explain their apparent habituation to chronic hypoxic stress and the limited capacity to generate adaptive angiogenesis. Hypoxia-based strategies, then effectively aim to override the habituated angiogenic cellular response, re-start the regenerative process and drive it to completion. Here we make a distinction between those strategies that utilize hypoxia in vitro as a preconditioning tool to optimize the angiogenic potential of tissue/cells before transplantation, vs. strategies that aim to induce hypoxia-induced signaling in vivo, directly, through pharmacological means or gene transfer. We then discuss possible future directions for the field, as it moves into the phase of clinical trials.     

The relationship between iron status and lead absorption in rats

The absorption of lead from loops of small intestinein situ was investigated in rats in which iron absorption was increased by stimuli varying in type, intensity, or duration. Lead absorption was increased by a short period of severe iron restriction before any change in hematological indices became apparent. A period of hypoxia, which markedly increased iron absorption, did not influence absorption of lead. An extended period of moderate iron restriction resulted in a marked reduction in liver iron stores and increased iron absorption throughout the 17-wk experiment. Under these conditions lead absorption was initially also increased, but after 12 wk, when iron intake had become adequate to meet essential requirements, lead absorption was similar to that in iron-supplemented rats. These results are discussed in the light of evidence for a receptor-mediated absorption process for iron.     

The Shc protein Rai enhances T-cell survival under hypoxia

Hypoxia occurs in physiological and pathological conditions. T cells experience hypoxia in pathological and physiological conditions as well as in lymphoid organs. Indeed, hypoxia-inducible factor 1α (HIF-1α) affects T cell survival and functions. Rai, an Shc family protein member, exerts pro-survival effects in hypoxic neuroblastoma cells. Since Rai is also expressed in T cells, we here investigated its role in hypoxic T cells. In this work, hypoxia differently affected cell survival, proapoptotic, and metabolic programs in T cells, depending upon Rai expression. By using Jurkat cells stably expressing Rai and splenocytes from Rai^−/−mice, we demonstrated that Rai promotes T cell survival and affects cell metabolism under hypoxia. Upon exposure to hypoxia, Jurkat T cells expressing Rai show (a) higher HIF-1α protein levels; (b) a decreased cell death and increased Akt/extracellular-signal-regulated kinase phosphorylation; (c) a decreased expression of proapoptotic markers, including caspase activities and poly(ADP-ribose) polymerase cleavage; (d) an increased glucose and lactate metabolism; (e) an increased activation of nuclear factor-kB pathway. The opposite effects were observed in hypoxic splenocytes from Rai^−/−mice. Thus, Rai plays an important role in hypoxic signaling and may be relevant in the protection of T cells against hypoxia.