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ABSTRACTNanometer-sized Cu-enriched solute clusters containing Mn, Ni, and Si atoms are considered as the primary embrittling feature in reactor pressure vessel steels. In order to understand the effects of solute atoms Mn, Ni, and Si on hardening and cluster formation, reactor pressure vessel model alloys FeCu, FeCuSi, FeCuNi, and FeCuNiMn were irradiated at 290 °C in a research reactor. Thermal ageing at 450 °C was also carried out to compare with the results in the neutron irradiation. The addition of Mn resulted in larger hardening and higher cluster number density in both thermal ageing and neutron irradiation. In FeCu0.8NiMn alloy, the size distribution of Cu-enriched clusters formed in 62-h thermal ageing (almost peak hardening) was very similar to that formed in the neutron irradiation, indicating they are on a similar growing stage. But the average Ni and Mn composition in clusters formed in neutron irradiation was higher. A good linear relationship between hardening and the square root of cluster volume fraction for both neutron irradiation and thermal ageing data was found.

After central nervous system (CNS) injury, reactive astrocytes display opposing functions, inducing neural repair and axonal regeneration via the release of growth factors, or forming a glial scar which acts as a barrier to axonal regeneration. Endogenous neural stem/progenitor cells have also recently been identified at the site of CNS injury, where they have been shown to differentiate into mature neurons in an animal model of ischemia. However, the pathophysiological mechanisms underpinning the contribution of reactive astrocytes and neural stem/progenitor cells to neural repair are still to be fully elucidated. Pituitary adenylate cyclase activating polypeptide (PACAP) is widely expressed in the CNS, where it has been shown to exert numerous biological effects. This review will summarize the current state of knowledge regarding the expression of PACAP and its receptors during neural development, as well as the involvement of PACAP in astrocytes and neural stem/progenitor cell biology. In addition, we will also discuss emerging evidence that implicates PACAP in neurogenesis and neural repair in response to brain pathophysiology.

Lipid peroxidation is caused by reactive oxygen species (ROS) and is involved in traumatic brain injury (TBI). Consequently, a therapeutic strategy for TBI may be to control lipid peroxidation. The only drug approved to date for blocking lipid peroxidation is edaravone (MCI-186), a novel free-radical scavenger shown to exert neuroprotective effects in acute ischemic stroke. Although edaravone scavenges hydroxyl and nitric oxide radicals, its effect on alkoxyl radicals (OR–), which also contribute to lipid peroxidation, is unknown. To date, the study of free radicals in blood has been severely hampered by technical difficulties in their detection. We used an in vitro and ex vivo electron spin resonance (ESR) method employing 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap to investigate whether edaravone can scavenge OR–. By mixing either methemoglobin or human blood with tert-butyl hydroperoxide, we found that this technique can detect OR– generated in vitro. We also found that generated OR– can be completely absorbed by administration of edaravone in vitro (400 µM). Analysis of jugular venous blood collected from 17 TBI patients immediately before and 20 minutes after the administration of edaravone (30 mg, i.v.) revealed higher OR– levels in the untreated patients blood than in normal control blood samples. However, treatment with edaravone suppressed these OR– levels by 24.6% (radical intensity = 71.1 ± 5.2—53.6 ± 5.2; p < 0.01). Thus, edaravone can scavenge OR– and significantly reduce levels of these radicals in TBI patients. The novel ex vivo ESR method described here provides a valuable clinical measure of oxidative stress.

The deformation behavior and initiation mechanisms of intergranular (IG) and transgranular (TG) cracks in irradiated 304L stainless steel were studied by slow-strain-rate tensile tests in inert gas and simulated BWR water environments, followed by fractographic and microstructural examinations. Neutron irradiation was made in test reactors to fluences of up to 6.2x1020n/cm2(E>1 MeV). Intergranular cracking occurred in water above a critical neutron fluence of around 1 × 1020n/cm2, based on the results of the SSRT tests and SEM fractography. That critical fluence is mechanistically supported by irradiated, deformed microstructures exhibiting dislocation channeling at that fluence, while radiation-induced Cr depletion at the grain boundaries was minor. Transgranular cracking of the irradiated material occurred in water below the critical fluence, initiating in the non-uniformly strained surface region of the test bar in the later stages of plastic deformation. The initiation of TG cracking is hypothesized to be related to a high density of deformation twins. Intergranular cracking is proposed to have initiated where localized slip bands terminated at grain boundaries, while TG cracking is inferred to have initiated at deformation twin boundaries. High stress and strain concentrations at grain/twin boundaries would be the common cause of non-ductile crack initiation.

The cytokine interleukin‐1 (IL‐1) has been implicated in ischemic brain damage, because the IL‐1 receptor antagonist markedly inhibits experimentally induced neuronal loss. However, to date, no studies have demonstrated the involvement of endogenous IL‐1α and IL‐ 1β in neurodegeneration. We report here, for the first time, that mice lacking IL‐1α/β (double knockout) exhibit markedly reduced neuronal loss and apoptotic cell death when exposed to transient cardiac arrest. Furthermore, we show that, despite the reduced neuronal loss, phosphorylation of JNK/SAPK (c‐Jun NH2‐ terminal protein kinase/stress activated protein kinase) and p38 enzymes remain elevated in IL‐1 knockout mice. In contrast, the inducible nitric oxide (iNOS) immunoreactivity after global ischemia was reduced in IL‐1 knockout mice as compared with wild‐type mice. The levels of nitrite (NO2−) and nitrate (NO3−) in the hippocampus of wild‐type mice were increased with time after ischemia‐reperfusion, whereas the increase was significantly inhibited in IL‐1 knockout mice. These observations strongly suggest that endogenous IL‐1 contributes to ischemic brain damage, and this influence may act through the release of nitric oxide by iNOS. J. Comp. Neurol. 448:203–216, 2002. © 2002 Wiley‐Liss, Inc.

Displaced rib fractures can injure intercostal vessels leading to chest wall hematomas. As the bleeding occurs within the vessel, compression of the vessel wall helps in preventing further bleeding. Therefore, chest wall hematomas rarely result in shock. A thin 78-year-old man transferred to the emergency department with complaints of left dorsal pain due to an injury. He had a history of hypertension and aorta dissection. He arrived at the ED in a state of shock and presented with a large left dorsal wall mass. Subsequent imaging using computed tomography angiography revealed a large hyperdense hematoma at the left dorsal-flank wall along with rib fracture (11th intercostal artery). Moreover, a large fusiform aneurysm was detected from the abdominal aorta to the iliac arteries. Extravasation of the contrast agent was detected at the branch of the 11th intercostal artery, and hence, embolization was performed. The dermis, which comprises collagen and elastin fibers, plays an important role in vessel compression to prevent bleeding. The aortic media also comprises collagen and elastin fibers. Cell turnover, loss of collagen, and excessive elastolysis are associated with the formation of abdominal aortic aneurysms. The systemic degeneration of connecting tissue (collagen and elastin fiber) appears to be progress in patients with an aortic aneurysms and history of aortic dissection compared with other healthy older individuals. Physicians should be cognizant of the potential unexpected large hematoma complications if a risk of systemic connecting tissue degradation exists, as seen in patients with aortic aneurysm or aortic dissection.

We have demonstrated that the ischemia-induced apoptosis of neurons in the CA1 region of the rat hippocampus was prevented by either intracerebroventricular or intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP). However, the molecular mechanisms underlying the anti-apoptotic effect of PACAP remain to be determined. Within 3-6 h after ischemia, the activities of members of the mitogen-activated protein (MAP) kinase family, including extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK)stress-activated protein kinase (SAPK), and p38 were increased in the hippocampus. The ischemic stress had a potent influence on the MAP kinase family, especially on JNKSAPK. PACAP inhibited the activation of JNKSAPK after ischemic stress. Secretion of interleukin-6 (IL-6) into the cerebrospinal fluid was intensely stimulated after PACAP infusion. IL-6 inhibited the activation of JNKSAPK, while it activated ERK. These observations suggest that PACAP and IL-6 act to inhibit the JNKSAPK signaling pathway, thereby protecting neurons against apoptosis.