Cystathionine is a novel substrate of cystine/glutamate transporter: implications for immune function.

The cystine/glutamate transporter, designated as system xc(-), is important for maintaining intracellular glutathione levels and extracellular redox balance. The substrate-specific component of system xc(-), xCT, is strongly induced by various stimuli, including oxidative stress, whereas it is constitutively expressed only in specific brain regions and immune tissues, such as the thymus and spleen. Although cystine and glutamate are the well established substrates of system xc(-) and the knockout of xCT leads to alterations of extracellular redox balance, nothing is known about other potential substrates. We thus performed a comparative metabolite analysis of tissues from xCT-deficient and wild-type mice using capillary electrophoresis time-of-flight mass spectrometry. Although most of the analyzed metabolites did not show significant alterations between xCT-deficient and wild-type mice, cystathionine emerged as being absent specifically in the thymus and spleen of xCT-deficient mice. No expression of either cystathionine ß-synthase or cystathionine γ-lyase was observed in the thymus and spleen of mice. In embryonic fibroblasts derived from wild-type embryos, cystine uptake was significantly inhibited by cystathionine in a concentration-dependent manner. Wild-type cells showed an intracellular accumulation of cystathionine when incubated in cystathionine-containing buffer, which concomitantly stimulated an increased release of glutamate into the extracellular space. By contrast, none of these effects could be observed in xCT-deficient cells. Remarkably, unlike knock-out cells, wild-type cells could be rescued from cystine deprivation-induced cell death by cystathionine supplementation. We thus conclude that cystathionine is a novel physiological substrate of system xc(-) and that the accumulation of cystathionine in immune tissues is exclusively mediated by system xc(-).

Distinctiveness of prolonged grief disorder symptoms among survivors of the Great East Japan Earthquake and Tsunami.

Prolonged Grief Disorder (PGD) has been proposed for diagnostic classification as an independent psychiatric disorder. Previous research has investigated it in relation to other axis I disorders in order to determine whether it could be considered an independent nosological entity. The distinctiveness of this condition was apparent in cases of ordinary bereavement and in those following human-made disasters. However, this disorder may be expanded to include bereavement resulting from natural disasters. The present study aims to explore the differences between this disorder and posttraumatic stress disorder or major depressive disorder as experienced after the Great East Japan Earthquake and Tsunami. The subjects were 82 hospital workers. Each type of disorder was assessed by means of the Inventory of Complicated Grief, the Impact of Event Scale-Revised, and the Center for Epidemiological Studies Depression Scale. Exploratory factor analysis showed 3 dimensions, with PGD items independently clustering in the same dimension. Our findings support the uniqueness of PGD even in a post-natural disaster situation in a non-Western culture and warrant grief intervention for high-risk bereaved survivors.

[Efficacy of propofol in controlling myoclonus during rewarming in a brain hypothermia patient].

Propofol is an intravenous anaesthetic agent having anticonvulsant property. We report here a case in which propofol was effective in controlling myoclonus during rewarming in brain hypothermia patient. A 35-year-old male patient was admitted in a comatose state with right-sided hemiparesis, anisocoria and absence of bilateral light reflex. On admission, a head CT showed traumatic subarachnoid hemorrhage, left subdural hematoma, 10 mm midline shift and tentorial herniation with massive brain swelling together with extensive hypodensity in the frontal, temporal and occipital lobes bilaterally. Left decompressive hemicraniectomy, removal of hematoma and brain hypothermia therapy were started immediately. Postoperative head CT showed 15 mm midline shift. The temperature of the jugular bulb was maintained at 34 degrees C for 2 days together with sedation using midazolam under artificial ventilation. The patient was gradually rewarmed at a rate of 0.5 degree C per day from the third hospital day. Myoclonus of sudden onset developed on the patient's head and upper extremities on the third hospital day. An intravenous bolus injection of 10 mg midazolam and continued intravenous infusion of midazolam were given but they did not completely stop myoclonus. A bolus of propofol 60 mg was given intravenously and continuous intravenous infusion of propofol 2 mg.kg-1.hr-1 was started after which the progression of myoclonus disappeared. Myoclonus was kept controlled until the continuous intravenous infusion of midazolam and propofol was discontinued on the sixth hospital day, after which myoclonus occurred again after extubation on the seventh hospital day. The clinical course of this case suggests that propofol might be an alternative effective agent to suppress refractory myoclonus.