Valproic acid induces functional heat-shock protein 70 via Class I histone deacetylase inhibition in cortical neurons: a potential role of Sp1 acetylation.

Neuroprotective properties of the mood stabilizer valproic acid (VPA) are implicated in its therapeutic efficacy. Heat-shock protein 70 (HSP70) is a molecular chaperone, neuroprotective and anti-inflammatory agent. This study aimed to investigate underlying mechanisms and functional significance of HSP70 induction by VPA in rat cortical neurons. VPA treatment markedly up-regulated HSP70 protein levels, and this was accompanied by increased HSP70 mRNA levels and promoter hyperacetylation and activity. Other HDAC inhibitors--sodium butyrate, trichostatin A, and Class I HDAC-specific inhibitors MS-275 and apicidin, --all mimicked the ability of VPA to induce HSP70. Pre-treatment with phosphatidylinositol 3-kinase inhibitors or an Akt inhibitor attenuated HSP70 induction by VPA and other HDAC inhibitors. VPA treatment increased Sp1 acetylation, and a Sp1 inhibitor, mithramycin, abolished the induction of HSP70 by HDAC inhibitors. Moreover, VPA promoted the association of Sp1 with the histone acetyltransferases p300 and recruitment of p300 to the HSP70 promoter. Further, VPA-induced neuroprotection against glutamate excitotoxicity was prevented by blocking HSP70 induction. Taken together, the data suggest that the phosphatidylinositol 3-kinase/Akt pathway and Sp1 are likely involved in HSP70 induction by HDAC inhibitors, and induction of HSP70 by VPA in cortical neurons may contribute to its neuroprotective and therapeutic effects.

[OSCE improves medical student's BLS knowledge, but its long-term memory is not well maintained].

BACKGROUND: Objective structured clinical examination: OSCE is now widely used in educational scene in medical schools before medical students start their clinical training. However, the utility of OSCE on BLS education has not been confirmed yet. The effect of OSCE on BLS education was examined using questionnaires. METHODS: Questionnaires on knowledge of resuscitation were distributed to 166 medical school students (100 students in 1999 semester without OSCE, 66 in 2004 semester with OSCE). The questionnaire included 13 questions based on the 1992 or 2000 guidelines for cardiopulmonary resuscitation. Six out of 12 questions were defined as "skill related questions" and the student who correctly answered all these "skill related questions" were thought to be competent for providing adequate BLS. RESULTS: Competent student ratio was significantly higher in students with OSCE (48%, vs 20% without OSCE, P < 0.001). Thus OSCE was useful for medical student to establish BLS knowledge when compared with students without OSCE. However, this result also revealed that the acquired knowledge through OSCE did not last long. Although 98% of students actually passed OSCE, only half of them were competent on paper test during clinical training. CONCLUSIONS: OSCE improved medical students' knowledge of BLS, but did not contribute to prevent forgetting for a long time. Thus, reeducation in BLS is still necessary for students after passing OSCE.

[Anesthetic management of endovascular stent graft placement for thoracic aortic aneurysm using induction of transient cardiac asystole by ATP].

We experienced anesthetic management of endovascular stent graft placement for thoracic aortic aneurysm in a 69-year-old patient. Under general anesthesia, ATP 20 mg was administered intravenously. However, heart rate and blood pressure did not decrease sufficiently for placement of a stent graft. After additional injection of ATP 30 mg, heart rate and systolic blood pressure decreased to 20 bpm and 60-70 mmHg, respectively, enabling the placement of a self-expanded type stent graft in the proper site. No clinical complications related to this procedure were observed. Induction of transient cardiac asystole by ATP is an easy and safe procedure for placement of a stent graft in a patient with thoracic aortic aneurysm.

Atypical finding of brain Tc-99m-ECD SPECT imaging in herpes simplex encephalitis.

Lesions in acute herpes simplex encephalitis (HSE) have been reported to show decreased uptake of Tc-99m ethyl cysteinate dimer (ECD). A patient with acute HSE displaying a lesion in the left temporal lobe was evaluated by means of Tc-99m ECD single-photon emission computed tomography (SPECT). Dynamic SPECT images indicated regionally increased uptake of tracer in the ipsilateral temporal lobe in early phases, followed by slight washout of Tc-99m ECD from the lesion. Static SPECT images revealed increased tracer uptake in the same region. MRI later demonstrated that the HSE lesion involved the whole cortex of the temporal lobe on the affected side. These findings suggest that acute HSE lesions do not always exhibit hypoactivity on static Tc-99m ECD SPECT, and that dynamic Tc-99m ECD SPECT may help physicians diagnose acute HSE.

Very early and standard Tc-99m ethyl cysteinate dimer SPECT imaging in a patient with reperfusion hyperemia after acute cerebral embolism.

It has been reported that Tc-99m ethyl cysteinate dimer (ECD) SPECT imaging may not show reperfusion hyperemia in patients with subacute stroke. The authors describe a patient with embolic middle cerebral artery occlusion who was examined using xenon-133 and dynamic and standard Tc-99m ECD SPECT immediately after early recanalization. Standard Tc-99m ECD SPECT images revealed hypoactivity in the ipsilateral middle cerebral artery territory. In contrast, the dynamic Tc-99m ECD SPECT images from the first scan (very early images acquired 36 seconds after injection) showed hyperactivity in the same region and provided imaging contrast comparable to what would be obtained with xenon-133 tomography. Hemorrhagic transformation later developed in this region. These results indicate that images from very early dynamic Tc-99m ECD SPECT of areas with irreversible changes produced by acute stroke can reveal reflow hyperemia that standard Tc-99m ECD SPECT images fail to show.