Statins have pleiotropic effects that are considered beneficial in preventing cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). Many studies using statins have been performed but failed to show remarkable effects. We hypothesized that a long-acting statin would be more effective, due to a longer half-life and stronger pleiotropic effects. Patients with aSAH were randomly assigned to a pitavastatin group (4 mg daily; n = 54) and a placebo group ( n = 54) after repair of a ruptured aneurysm. The primary efficacy end point was vasospasm-related delayed ischemic neurological deficits (DIND), and the secondary end points were cerebral vasospasm evaluated by digital subtraction angiography (DSA), vasospasm-related new cerebral infarctions, and outcome at three months. Severe cerebral vasospasms on DSA were statistically fewer in the pitavastatin group than in the placebo group (14.8% vs. 33.3%; odds ratio, 0.32; 95% confidence interval, 0.11-0.87, p = 0.042); however, the occurrence of DIND and new infarctions and outcome showed no statistically significant differences between the groups. The present study is the first to prove the definite, statin-induced amelioration of cerebral vasospasm on DSA. However, administration of any type of statin at the acute phase of aSAH is not recommended.

Background: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. Methods: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. Results: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. Conclusions: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

The relatively high rate of post-operative recurrence in the treatment of chronic subdural hematoma (CSDH) is a significant problem. Goreisan is an herbal medicine that exhibits a hydragogue effect by inhibiting the expression of aquaporins, and its efficacy in preventing post-operative CSDH recurrence has been suggested by several case trials. This multi-center prospective randomized controlled trial was performed to investigate the preventative effect of goreisan on post-operative CSDH recurrence. Patients with symptomatic CSDH over 60 years old undergoing burr hole surgery were enrolled in this study. The patients were randomly allocated to the control group or the goreisan group, in which oral administration of goreisan (7.5 g daily) was continued for 12 weeks. The primary end-point was the post-operative recurrence rate at 12 weeks and the secondary end-point was hematoma volume reduction rates on computed tomography scan at 12 weeks. The analyses were performed not only on patients of all ages older than 60 years, but also on patients divided into those over or under 75 years old. One hundred and eighty patients were followed and analyzed (the control group, n = 88; the goreisan group, n = 92). The recurrence rates considering patients of all ages and patients under 75 years old were relatively low in the goreisan group but without a significant difference. The hematoma volume reduction rates showed no significant difference. Based on the results of the present study, a larger-scale study including more cases is necessary in future to confirm the efficacy of goreisan.

We previously reported that trehalose, a reduced disaccharide, was effective in the preservation of lungs. In this study, we investigated the possibility of prolonged cryopreservation of tracheas in a preservative solution containing trehalose. Five rings of cervical trachea were removed and immersed in the preservative solution. The harvested tracheas were then cryopreserved and stored in a deep freezer at -85 degrees C. One month later, five rings of mediastinal trachea were removed. The cryopreserved cervical tracheas were thawed and autotransplanted in place of the excised mediastinal trachea (n = 6). The anastomotic site and graft were then covered with an omental pedicle. All six animals survived for more than 6 months. All grafts survived without any evidence of atrophy or stenosis. Microscopic examination of the grafts showed that the integrity of the tracheal tissues was maintained. Our findings show that consistent cryopreservation of the trachea for 1 month is possible in a preservative solution containing trehalose.

The role of the Saccharomyces cerevisae peroxisomal acyl-coenzyme A (acyl-CoA) thioesterase (Pte1p) in fatty acid ␤-oxidation was studied by analyzing the in vitro kinetic activity of the purified protein as well as by measuring the carbon flux through the ␤-oxidation cycle in vivo using the synthesis of peroxisomal polyhydroxyalkanoate (PHA) from the polymerization of the 3-hydroxyacylCoAs as a marker. The amount of PHA synthesized from the degradation of 10-cis-heptadecenoic, tridecanoic, undecanoic, or nonanoic acids was equivalent or slightly reduced in the pte1⌬ strain compared with wild type. In contrast, a strong reduction in PHA synthesized from heptanoic acid and 8-methyl-nonanoic acid was observed for the pte1⌬ strain compared with wild type. The poor catabolism of 8-methyl-nonanoic acid via ␤-oxidation in pte1⌬ negatively impacted the degradation of 10-cis-heptadecenoic acid and reduced the ability of the cells to efficiently grow in medium containing such fatty acids. An increase in the proportion of the short chain 3-hydroxyacid monomers was observed in PHA synthesized in pte1⌬ cells grown on a variety of fatty acids, indicating a reduction in the metabolism of short chain acyl-CoAs in these cells. A purified histidine-tagged Pte1p showed high activity toward short and medium chain length acyl-CoAs, including butyryl-CoA, decanoyl-CoA and 8-methyl-nonanoyl-CoA. The kinetic parameters measured for the purified Pte1p fit well with the implication of this enzyme in the efficient metabolism of short straight and branched chain fatty acyl-CoAs by the ␤-oxidation cycle.