Ryuichi Katada

Postmortem computed tomography lung findings in fatal of hypothermia

To identify lung findings specific to fatal hypothermia on postmortem computed tomography (CT) imaging. Whole body CT scans were performed followed by full autopsy to investigate causes of death. There were 13 fatal hypothermia cases (group A) and 118 with other causes of death (group B). The chest cavity (CC), dead space including fluid/pneumothorax (DS), aerated lung volume (ALV), percentage aerated lung (%ALV), and tracheal aerated volume (ATV) were measured. Autopsy findings of groups A and B were compared. Receiver operating characteristics (ROC) curves were used to identify factors specific to fatal hypothermia. There were no differences in age, sex, number with emphysema, or time from death to CT examination between the 2 groups. CC, DS, ALV, %ALV, and ATV were 2601.0±247.4 (mL), 281.1±136.5 (mL), 1564.5±281.1 (mL), 62.1±6.2(%), and 21.8±2.7 (mL) in group A and 2339.2±67.7 (mL), 241.1±38.0 (mL), 739.9±67.0 (mL), 31.4±2.3(%), and 15.9±0.8 (mL) in group B, respectively. There were statistically significant differences between groups A and B in ALV, %ALV and ATV. The multiple comparison procedure revealed that ALV and %ALV differed significantly between fatal hypothermia and other causes of death (p<0.05). Using ROC evaluation, %ALV had the largest area under the curve (0.819). This study demonstrates that the %ALV is greater in fatal hypothermia cases than in those with other causes of death on postmortem CT chest imaging. Based on CT, hypothermia is very likely to be the cause of death if the %ALV is >70%.

Prior ethanol injection promotes brain edema after traumatic brain injury

Alcohol consumption prior to traumatic brain injury (TBI) promotes morbidity and mortality although the mechanisms involved remain unclear. The morbidity and mortality caused by TBI, especially brain contusion, are known to be closely associated with brain edema. Here we examined the effects of ethanol pretreatment on brain edema, inflammatory responses, and oxidative stress after brain contusion. Male Wistar rats were given 3 g/kg ethanol intraperitoneally and 1 h later were subjected to brain contusion. The ethanol-pretreated group had a significantly decreased survival rate. Magnetic resonance imaging showed ethanol pretreatment significantly augmented the volume of cytotoxic brain edema after contusion. In the ethanol-pretreated rat, the activities of NF-kappaB and AP-1 were reduced 6 h after contusion and COX-2 mRNA expression was increased 24 h after contusion. These findings suggest that ethanol augmented cerebral edema and mortality in rats with brain contusion, possibly through actions on cell survival pathways or COX-2 expression. In addition, antioxidant treatment at 3 h post-injury significantly attenuated some markers of oxidative stress, mortality, and volume of edema at 24 h after ethanol treatment and contusion.

Experimental rat model for alcohol‐induced osteonecrosis of the femoral head

Alcohol‐induced osteonecrosis of the femoral head (ONFH) is observed in alcohol abusers and patients with alcoholic fatty liver disease. It has been reported that Toll‐like receptor 4 (TLR4) signalling plays a crucial role in the pathogenesis of alcoholic fatty liver disease. We previously reported a corticosteroid‐induced ONFH rat model, and suggested that TLR4 signalling contributes to the pathogenesis of ONFH. Thus, it is thought that the pathogenesis of alcohol‐induced ONFH is probably similar to that of corticosteroid‐induced ONFH. The aim of this study was to develop a new animal model for alcohol‐induced ONFH and to evaluate the relationship between the pro‐inflammatory response via TLRs and the development of ONFH in rats. Male Wistar rats were fed a Lieber–DeCarli liquid diet containing 5% ethanol (experimental group) or dextran (control group) for 1–24 weeks. Histopathological and biochemical analyses were performed. Feeding the ethanol‐containing liquid diet resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction and hyperlipidaemia, whereas feeding the dextran‐containing diet did not cause ONFH. However, we could not recognize any relationship between the pro‐inflammatory response via TLR4 and the development of alcohol‐induced ONFH. Thus in this study we have developed a new rat model for alcohol‐induced ONFH based on the feeding of an ethanol liquid diet. ONFH was observed within seven days from the start of feeding with 5% ethanol‐containing liquid diet. Although this was linked to hepatic steatosis, a TLR4 association was not a feature of this model.

The suppression of TRIM21 and the accumulation of IFN- α play crucial roles in the pathogenesis of osteonecrosis of the femoral head

Osteonecrosis of the femoral head (ONFH), the pathogenesis of which remains unclear, has been observed in autoimmune disease patients treated with corticosteroids. Recently, it has been shown that anti-tripartite motif-containing 21 (TRIM21) autoantibodies, which are often present in patients with systemic lupus erythematosis and Sjögrens syndrome, inhibit the E3 ligase activity of TRIM21. TRIM21 negatively regulates nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs) 3 and 7, three downstream transcription factors, via toll-like receptor 4 signaling. The aim of this study was to clarify the role of TRIM21 in the pathogenesis of ONFH using an animal model. Male Wistar rats were injected with lipopolysaccharide (LPS) twice and with methylprednisolone (MPSL) or saline three times. N-acetyl cysteine (NAC) was administered either concurrently with MPSL or once daily for the 3 days following the last MPSL injection. The incidence of ONFH in the MPSL group was 23.5%. Co-treatment of NAC and MPSL increased the incidence of ONFH to 55.6%. MPSL treatment decreased the activity of NF-κB in the liver and significantly increased the activity of both IRF3 and IRF7. No significant differences were observed in the activity of any of these three transcription factors between the MPSL and the co-treatment groups. In the femoral head, co-treatment with NAC and MPSL significantly decreased the expression of TRIM21 at 3 h and significantly increased the expression of interferon (IFN)-α at 24 h when compared with the MPSL group. IFN-α is known to induce cell death. These findings suggest that the suppression of TRIM21 in the femoral head causes an accumulation of IFN-α, which in turn leads to the development of ONFH. In conclusion, the suppression of TRIM21 resulting from altered NF-κB and IRF homeostasis accelerates the ONFH in rats treated with corticosteroids following LPS administration.

Weight bearing does not contribute to the development of osteonecrosis of the femoral head

The hip joint is one of the major structures in the human body and the resultant force acting through the hip joint is 300% of body weight. Therefore, weight bearing, as a cause of ischaemia, may contribute to the development of non‐traumatic osteonecrosis of the femoral head (ONFH). However, it remains unclear whether weight bearing is related to the development of non‐traumatic ONFH. Therefore the aim of this study was to clarify the role of weight bearing in the development of non‐traumatic ONFH. Non‐weight‐bearing (NWB) rats were tail suspended to prevent any weight coming to bear on the hindlimbs from day 1 to the time of sacrifice. The weight‐bearing (WB) group rats were also housed individually, although without tail suspension. All rats were injected with lipopolysaccharide and methylprednisolone to promote the development of non‐traumatic ONFH. All animals were sacrificed three weeks after the final methylprednisolone injection. Histopathological analysis was performed. Osteonecrosis of the femoral head was observed not only in the NWB but also in the WB rats; however, no osteonecrosis of the humeral head was observed in either group. We confirmed that non‐traumatic ONFH developed in NWB rats, suggesting that weight bearing does not contribute to the development of non‐traumatic ONFH in rats.

The discrepant severity of external and internal injuries in a traffic accident: The cushioning effect via a human body against direct impact: Autopsy cases

Traffic accidents cause unexpectedly severe injuries of internal organs despite tiny injuries observed on the external body. A 51-year-old woman (subject 1) and a 54-year-old man (subject 2) were found dead on a road. Subject 1 had subcutaneous and intramuscular bleeding with décollement on the posterior aspect of her body, including upper cervical spine dislocation. Subject 2 did not exhibit any apparent findings on autopsy that were indicative of a direct injury by a motor vehicle, but had severe internal organ injuries, including the transection at the pontomedullary junction. We surmise that subjects 1 and 2 were walking in line with the vehicle which collided with them from behind, and then the body of subject 1 cushioned the direct impact of the vehicle against subject 2. This report illustrates the need of forensic autopsy for victims with no severe external injuries.

Effect of acute ethanol administration on histone acetylation in mouse brain

drugs, was shown to increase extracellular levels of 5HT in the nucleus accumbens (ACC), the frontal cortex, and the ventral hippocampus in rat. For elucidation of relationship between alcohol-addiction and 5HT system, we produced chronic alcohol treatment mice by the exposure to alcohol vapor for 20 days. C57BL/6J mice showed a significant increase in alcohol drinking behavior after alcohol exposure, whereas there was no significant difference in alcohol drinking of C3H/HeJ, another inbred strain. We then examined expression levels of 5HT receptor family and found that expression of 5HT2C receptor (5HT2CR) was significantly increased in the ACC and the dorsal raphe nucleus (DRN) by chronic alcohol exposure, suggesting that 5HT2CR might be involved in alcohol addiction. 5HT2CR was known to undergo premRNA editing at five sites (site A-E) within exon 5 by deaminating enzymes. As a result of RNA-editing, amino acid substitution occurs at three sites, which alters the ability of the receptor to activate phospholipase C. Here, we investigated RNA-editing changes in alcohol vapor inhalation mice. Either C57BL/6J or C3H/HeJ was exposed to alcohol vapor, followed by the determination of 5HT2CR isoform frequency. C57BL/6J mice exhibited a 1.5-fold increase in site D editing by exposure to alcohol vapor, resulting that 5HT2CR-VXV isoforms were 92% in the ACC. On the other hand, unedited INI-isoform was the most prevalent in C3H/HeJ mice, in spite of alcohol exposure. Furthermore, it was demonstrated that an increase of RNA-editing frequency by alcohol exposure was dependent on the expression level of ADAR1 and ADAR2, RNAediting enzymes. These findings suggest that difference in RNA-editing of 5HT2CR may be associated with alcohol-addiction and -response.