Slc25a39 and Slc25a40 Expression in Mice with Bile Duct Ligation or Lipopolysaccharide Treatment.

SLC25A39/40, involved in mitochondrial GSH (mGSH) import from the cytoplasm, is essential for protection against oxidative stress and mitochondrial dysfunction. We examined the effects of cholestasis, through bile duct ligation (BDL) and lipopolysaccharide (LPS)-induced inflammation in mice, on Slc25a39/40 expression. Additionally, we used human clear cell renal carcinoma (KMRC-1) cells to elucidate the mechanism of regulation of SLC25A39/40 expression in the kidneys after LPS treatment. BDL resulted in a decrease in Slc25a39 mRNA in the liver and a decrease in Slc25a39/40 mRNA and protein in the kidneys. Consequently, there was a significant decrease in mGSH levels in the kidneys of BDL mice compared with those in sham mice. LPS treatment resulted in increased Slc25a40 expression in the kidneys. In KMRC-1 cells, the combination treatment of LPS-RS or FPS-ZM1 with LPS suppressed the LPS-induced increase in SLC25A40, suggesting that SLC25A40 expression could be regulated by the signaling pathway via toll-like receptor 4 and the receptor for advanced glycation end products, respectively. Our findings contribute to understanding the role of mGSH in the maintenance of the mitochondrial redox state. To the best of our knowledge, this is the first study that demonstrates the changes in Slc25a39/40 expression in mice with cholestasis-associated renal injury and LPS-induced inflammation.

Early diagnosis of Cryptococcus neoformans var. grubii meningitis using multiplex PCR assay in an immunocompetent patient.

Cryptococcosis is an invasive fungal infection that mainly affects the lungs and central nervous system. While patients with cell-mediated immunodeficiency are at high risk of developing cryptococcosis, there have been increasing reports of cryptococcosis in immunocompetent individuals with no underlying conditions. Herein, we report a case of cryptococcal meningitis in a 55-year-old apparently immunocompetent man with a history of heavy alcohol consumption. Although the patient was initially treated for tuberculous meningitis and varicella-zoster virus induced vasculopathy due to a history of exposure to tuberculosis and a presence of stroke, a multiplex polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) identified Cryptococcus species unexpectedly, enabling swift treatment and a favorable clinical outcome. The multiplex PCR assay, which can identify multiple pathogens simultaneously and instantly, may lead to early diagnosis and treatment by detecting unanticipated pathogens. Furthermore, the strain was identified through multilocus sequence typing (MLST) analysis as Cryptococcus neoformans var. grubii, Sequence Type 5, molecular type: VNI. Although simplified microbial identification techniques such as mass spectrometry have recently been developed, molecular biological assays are still essential for the accurate identification of infectious strains.

The Effect of Goreisan on the Prevention of Chronic Subdural Hematoma Recurrence: Multi-Center Randomized Controlled Study.

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.

Intra-arterial oxidative stress correlates negatively with cognitive function and positively with postoperative ischemic lesions in carotid artery stenosis stenting.

BACKGROUND AND PURPOSE: Carotid plaque contains biologically active substances released into the blood during carotid artery stenting (CAS). The main purpose of this prospective study was to analyse sequential changes in oxidative stress during CAS and their relationship to clinical factors. METHODS: Twenty-two consecutive CAS procedures were performed between May 2014 and April 2016. Arterial blood was collected four times: (1) after the sheath insertion without edaravone; (2) pre-angioplasty with edaravone from the carotid artery; (3) after post-stenting angioplasty from an occluded carotid artery; and (4) before sheath removal. Derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured photometrically. The relationship between d-ROMs or BAP and preoperatively investigated biochemical parameters, cognitive function, and number of diffusion-weighted image (DWI) high spot lesions was analysed using one-way ANOVA and the Tukey-Kramer HSD test. RESULTS: The d-ROM values for CAS were 355±58.8 Carratelli Units at sheath insertion, 315±57.2 after edaravone infusion, 328±56.8 after post-stenting angioplasty, and 315±53.0 just before sheath removal. The d-ROM values were reduced significantly after edaravone infusion (P<0.05). The BAP at sheath insertion was reduced significantly according to age (P<0.05). The d-ROMs at sheath insertion correlated negatively with the dementia scale and positively with the post-CAS DWI high spots (1.00±1.07; P<0.05). Other biochemical parameters did not correlate with the d-ROM values or BAP. CONCLUSION: Oxidative stress is correlated negatively with cognitive function and positively with postoperative ischemic lesions. Antioxidant potential decreases with ageing.

Regression of atherosclerosis with apple procyanidins by activating the ATP-binding cassette subfamily A member 1 in a rabbit model.

BACKGROUND AND AIMS: Apple polyphenol contains abundant procyanidins, which have been associated with an anti-atherosclerosis and cholesterol-lowering effect. The aim of this study was to investigate whether apple procyanidins (APCs) feature therapeutic efficacy in terms of regressing atherosclerosis and whether this efficacy is due to mechanisms other than a cholesterol-lowering effect. METHODS: After eight weeks on an atherogenic diet, rabbits were given a normal diet for another eight weeks to normalize the increased serum lipids level. The rabbits in the baseline group were sacrificed at this stage. The control group was subsequently fed a normal diet for eight weeks, while the APCs group was administrated 50 mg/kg/day of APCs in addition to the normal diet. Serum lipids and aortic intimal-medial thickness (IMT) were serially examined, and the resected aorta was examined histologically and through molecular biology. RESULTS: Aortic IMT on ultrasonography and the lipid accumulation area examined using Sudan IV staining were significantly reduced in the APCs group as compared to the control group. Serum lipid profiles were not different between the groups. Immunohistochemistry showed significantly decreased staining of an oxidative stress marker and significantly increased staining of ATP-binding cassette subfamily A member 1 (ABCA1) in the APCs group. Western blotting and RT-PCR also showed increased expression of ABCA1 mRNA and its protein in the APCs group. CONCLUSIONS: This study revealed that APCs administration causes a regression of atherosclerosis. APCs might hold promise as an anti-atherosclerotic agent.

Safety of preprocedural antiplatelet medication in coil embolization of ruptured cerebral aneurysms at the acute stage.

Preoperative antiplatelet medication for aneurysm coil embolization during acute subarachnoid hemorrhage (SAH) is not common. However, recent advances in neurointerventional devices make antiplatelet medication necessary for SAH surgery. We tested the hypothesis that preprocedural antiplatelet therapy in the acute stage of SAH prevents complications due to ischemia or induced bleeding. We retrospectively reviewed 35 consecutive ruptured cerebral saccular aneurysms that underwent coiling at our institute. Two hundred milligrams of aspirin and 150 mg of clopidogrel were administered to the patients at least two hours before coiling. Systemic heparinization was given after sheath insertion. Procedure-related thrombus formation on digital subtraction angiography, and clinical evidence of ischemia and procedure-related stroke on CT were reviewed. The median patient age was 69 years. Five males and 30 females were included. Seventy-seven percent of patients were Hunt-Hess grades 1 to 3. Assist techniques were used in 20 cases (57%). We inserted one extracranial internal carotid artery stent, but no intracranial stent. Intraoperative thrombosis occurred in one case (2.9%), with no clinical symptoms. Postoperative cerebrospinal fluid drainage was done in three cases, but we experienced no bleeding complications. Preoperative antiplatelet therapy leads to a low rate of thromboembolic events in coiling during acute stage SAH, and this strategy had no adverse influence on bleeding complications.

Role of oxidized LDL and lectin-like oxidized LDL receptor-1 in cerebral vasospasm after subarachnoid hemorrhage.

OBJECT: Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a serious complication. Free radicals derived from subarachnoid clotting are recognized to play an important role. Oxidized low-density lipoprotein (ox-LDL) and lectin-like oxidized LDL receptor-1 (LOX-1) have been shown to be related to the pathogenesis of atherosclerosis and may increase in cerebral arteries after SAH, due to the action of free radicals derived from a subarachnoid clot. These molecules may also affect the pathogenesis of vasospasm, generating intracellular reactive oxygen species and downregulating the expression of endothelial NO synthase (eNOS). If so, apple polyphenol might be effective in the prevention of vasospasm due to an abundant content of procyanidins, which exhibit strong radical scavenging effects, and the ability to suppress ox-LDL and LOX-1. The purposes of this study were to investigate changes in levels of ox-LDL and LOX-1 after SAH and whether administering apple polyphenol can modify cerebral vasospasm. METHODS: Forty Japanese white rabbits were assigned randomly to 4 groups: an SAH group (n = 10); a shamoperation group (n = 10), which underwent intracisternal saline injection; a low-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 10 mg/kg per day from Day 0 to Day 3; and a high-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 50 mg/kg per day. At Day 4, the basilar artery and brain was excised from each rabbit. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar artery, and the expression of ox-LDL, LOX-1, and eNOS was examined for each basilar artery by immunohistochemical staining and reverse transcriptase polymerase chain reaction. In addition, neuronal apoptosis in the cerebral cortex was evaluated by TUNEL. RESULTS: Compared with the sham group, the expression of ox-LDL and LOX-1 in the basilar arterial wall was significantly increased in the SAH group, the expression of eNOS was significantly decreased, and the cross-sectional area of basilar artery was significantly decreased. Compared with the SAH group, the cross-sectional area of basilar artery was increased in the polyphenol groups, together with the decreased expression of ox-LDL and LOX-1 and the increased expression of eNOS. In the high-dose polyphenol group, those changes were statistically significant compared with the SAH group. In the low-dose polyphenol group, those changes were smaller than in the high-dose polyphenol group. No apoptosis and no changes were seen in the cerebral cortex in all groups. CONCLUSIONS: This is the first study suggesting that ox-LDL and LOX-1 increase due to SAH and that they may play a role in the pathogenesis of vasospasm. It is assumed that procyanidins in apple polyphenol may inhibit a vicious cycle of ox-LDL, LOX-1, and ROS in a dose-dependent manner. Apple polyphenol is a candidate for preventive treatment of cerebral vasospasm.

Early ambulation produces favorable outcome and nondemential state in aneurysmal subarachnoid hemorrhage patients older than 70 years of age.

BACKGROUND: We analyzed consecutive subarachnoid hemorrhage (SAH) cases in patients older than 70 years of age who underwent aneurysm surgery. We report the influence of early ambulation on outcome in advanced-age SAH. METHODS: From 2005 through 2010, 71 aneurysmal SAH cases whose Hunt-Hess grades ranged from 1 to 3 were included. All cases underwent clip ligation or coil embolization. Male to female ratio was 8/63; median age was 76 years (range, 70-87). We routinely have patients become ambulatory the day after surgery. The ambulation date was used to determine four groupings: 0-5 days, 6-10 days, 11-15 days, and 16 days and longer. We analyzed the relationship between ambulation date and the Glasgow Outcome Scale (GOS) or dementia at 30 days after the SAH. Favorable outcome was defined as good recovery and moderate disability according to the GOS. Dementia was screened by use of the revised-Hasegawa dementia scale. The chi-square test was used and a P < 0.05 was considered statistically significant. RESULTS: Mean days to ambulation was 10.7 ± 9.3 SD days. Forty-eight cases (66%) achieved favorable outcome, and 27 cases (38%) reached a nondemential state. Early ambulation positively correlated with favorable GOS and postoperative nondemential state. CONCLUSIONS: Elderly SAH patients with good Hunt-Hess grades should have a clip ligation or endovascular coiling. Early ambulation produces favorable outcome and a nondemential state in elderly SAH patients.

A rare case of primary bone xanthoma of the clivus.

Primary bone xanthoma is a rare type of tumor, and those developing primarily within the skull are even more unusual. In this case, a primary bone xanthoma of the clivus without endocrine or metabolic complications represents the first of this type to be reported. The patient, a 24-year-old woman, initially experienced frequent headaches. Subsequent skull tomography and bone-window computed tomography (CT) revealed a clearly demarcated osteolytic lesion in the clivus. T1-weighted magnetic resonance imaging (MRI) exhibited low intensity, and T2-weighted MRI showed iso-high intensity and a heterogeneously faint contrast effect. The tumor was completely resected, after which the patient's headaches disappeared completely. Because xanthoma is devoid of neoplastic features, it does not necessarily require aggressive therapy. Therefore, it is very important to understand the characteristics of its clinical symptoms and to give due consideration to differential diagnosis based on pathological presentations and imaging features. This study introduces information regarding a bone xanthoma originating within the skull, together with a review of bone xanthoma literature.

Novel rat middle cerebral artery occlusion model: Trans-femoral artery approach combined with preservation of the external carotid artery.

We developed a novel trans-femoral artery approach to the rat middle cerebral artery occlusion model (TF-MCAO) without sacrificing the external carotid artery (ECA) with/without the pterygopalatine artery, which is important for chewing food. To make the TF-MCAO we first dissect the left common carotid artery (CCA), ECA, and internal carotid artery (ICA). Transient occlusion clips are applied to the proximal ECA and the pterygopalatine artery; we never sacrifice the ECA branch. A 24-gage catheter is inserted into the left femoral artery. We insert a slightly bent 0.014in. hydrophilically coated guide wire via a haemostasis valve. Anatomically, the left common carotid artery is located rostral to the descending aorta, permitting a straight-forward, blind approach to the CCA. The guide wire is gently advanced about 17mm from the bifurcation of the CCA until slight resistance is encountered. The guide wire and temporary occlusion clips are withdrawn after 90min. Rats were sacrificed 24h after reperfusion. Eleven rats were examined. One rat died before occlusion due to deep anesthesia. The success rate for producing infarction was 80%. The mean infarction volume of the basal ganglia was 94.4mm(3)+/-9.4 se and mean infarction volume of the cerebral cortex was 124.2mm(3)+/-21.6 se. No rat died due to cerebral infarction and no rat suffered subarachnoid hemorrhage. We conclude that TF-MCAO was useful for producing a cerebral infarction.