Co-Delivery of Renal Clearable Cerium Complex and Synergistic Antioxidant Iron Complex for Treating Sepsis.

The mononuclear phagocytic system clears the circulating inorganic nanomaterials from the bloodstream, which raises concerns about the chronic toxicity of the accumulated metal species. A better understanding of the behavior of each metal after systemic injection is thus required for clinical translations. This study investigates the significance of the metal-ligand interaction on the accumulation of cerium and demonstrates that only the form in which cerium is coordinated to a multidentate chelator with a strong binding affinity does not accumulate in major organs. Specifically, cerium complexed with diethylenetriamine pentaacetic acid (DTPA) forms renally excretable nanoparticles in vivo to circumvent the leaching of cerium ions, whereas weakly coordinated cerium-based nanomaterials produce insoluble precipitates upon encountering physiological phosphate anions. Ceria-based renally clearable nanoparticles (CRNs) derived from cerium-DTPA are utilized as the antioxidant pair with iron-DTPA, in which their combination leverages the Fenton reaction to synergistically scavenge hydrogen peroxide. This reduces the gene expression of pro-inflammatory factors in the macrophages activated with lipopolysaccharide as well as improves the survival rate of septic mice by alleviating the systemic inflammatory response and its downstream tissue injury in the liver, spleen, and kidneys. This study demonstrates that CRNs combined with iron-DTPA can be utilized as nonaccumulative nanomedicines for treating systemic inflammation, thereby overcoming the limitations of conventional ceria nanoparticle-based treatments.

Orally Deliverable Iron-Ceria Nanotablets for Treatment of Inflammatory Bowel Disease.

Ceria-based nanoparticles are versatile in treating various inflammatory diseases, but their feasibility in clinical translation is undermined by safety concerns and a limited delivery system. Meanwhile, the idiopathic nature of inflammatory bowel disease (IBD) calls for a wider variety of therapeutics via moderation of the intestinal immune system. In this regard, the synthesis and oral formulation of iron-ceria nanoparticles (CF NPs) with enhanced nanozymic activity and lower toxicity risk than conventional ceria-based nanoparticles are reported. CF NPs are clustered in calcium phosphate (CaP) and coated with a pH-responsive polymer to provide the enteric formulation of iron-ceria nanotablets (CFNT). CFNT exhibits a marked alleviative efficacy in the dextran sodium sulfate (DSS)-induced enterocolitis model in vivo by modulating the pro-inflammatory behavior of innate immune cells including macrophages and neutrophils, promoting anti-inflammatory cytokine profiles, and downregulating key transcription factors of inflammatory pathways.

Efficacy and Safety of Timely Urgent Superficial Temporal Artery-to-Middle Cerebral Artery Bypass Surgery in Patients with Acute Ischemic Stroke: A Single-Institutional Prospective Study and a Pooled Analysis.

BACKGROUND: Clinical outcome in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) is not satisfactory if reperfusion treatment fails or is not tried. AIMS: We aimed to assess the efficacy and safety of urgent superficial temporal-to-middle cerebral artery (STA-MCA) bypass surgery in selected patients. METHODS: Patients who were diagnosed with LVO-induced AIS in the anterior circulation but had a failed intra-arterial thrombectomy (IAT) or were not tried due to IAT contraindications were prospectively enrolled. Timely urgent STA-MCA bypass surgery was performed if they showed perfusion-diffusion mismatch or symptom-diffusion mismatch in the acute phase of disease. Clinical and radiological data of these patients were assessed to demonstrate the safety and efficacy of urgent bypass procedures. A pooled analysis of published data on urgent bypass surgery in acute stroke patients was conducted and analyzed. RESULTS: In 18 patients who underwent timely bypass, the National Institutes of Health Stroke Scale (NIHSS) score improved from 12.11 ± 4.84 to 9.89 ± 6.52, 1 week after surgery. Three-month and long-term (9.72 ± 5.00 months) favorable outcomes (modified Rankin Scale [mRS] scores 0-2) were achieved in 50 and 75% of the patients, respectively. The pooled analysis (117 patients from 10 articles, including ours) identified favorable mRS scores in 71.79% patients at 3 months. A significant NIHSS score improvement from 11.51 ± 4.89 to 7.59 ± 5.50 was observed after surgery with significance. Major complications occurred in 3 patients (2.6%, 3/117) without mortality. CONCLUSIONS: Urgent STA-MCA bypass surgery can be regarded as a safe optional treatment to prevent cerebral infarct expansion and to improve clinical and radiological outcomes in highly selected patients.

Stress-associated neurobiological activity is linked with acute plaque instability via enhanced macrophage activity: a prospective serial 18F-FDG-PET/CT imaging assessment.

AIMS: Emotional stress is associated with future cardiovascular events. However, the mechanistic linkage of brain emotional neural activity with acute plaque instability is not fully elucidated. We aimed to prospectively estimate the relationship between brain amygdalar activity (AmygA), arterial inflammation (AI), and macrophage haematopoiesis (HEMA) in acute myocardial infarction (AMI) as compared with controls. METHODS AND RESULTS: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging was performed within 45 days of the index episode in 62 patients (45 with AMI, mean 60.0 years, 84.4% male; 17 controls, mean 59.6 years, 76.4% male). In 10 patients of the AMI group, serial 18F-FDG-PET/CT imaging was performed after 6 months to estimate the temporal changes. The signals were compared using a customized 3D-rendered PET reconstruction. AmygA [target-to-background ratio (TBR), mean ± standard deviation: 0.65 ± 0.05 vs. 0.60 ± 0.05; P = 0.004], carotid AI (TBR: 2.04 ± 0.39 vs. 1.81 ± 0.25; P = 0.026), and HEMA (TBR: 2.60 ± 0.38 vs. 2.22 ± 0.28; P < 0.001) were significantly higher in AMI patients compared with controls. AmygA correlated significantly with those of the carotid artery (r = 0.350; P = 0.005), aorta (r = 0.471; P < 0.001), and bone marrow (r = 0.356; P = 0.005). Psychological stress scales (PHQ-9 and PSS-10) and AmygA assessed by PET/CT imaging correlated well (P < 0.001). Six-month after AMI, AmygA, carotid AI, and HEMA decreased to a level comparable with the controls. CONCLUSION: AmygA, AI, and HEMA were concordantly enhanced in patients with AMI, showing concurrent dynamic changes over time. These results raise the possibility that stress-associated neurobiological activity is linked with acute plaque instability via augmented macrophage activity and could be a potential therapeutic target for plaque inflammation in AMI.

Nonarteritic anterior ischemic optic neuropathy is associated with cerebral small vessel disease.

We investigated the presence of cerebral small vessel disease (SVD) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) compared to control subjects without NAION to identify the association between NAION and cerebral SVD. We retrospectively reviewed the cases of 63 patients with NAION and 2749 control subjects without any neurologic and ocular diseases including NAION who underwent careful medical interviews, ophthalmic examinations, and magnetic resonance imaging (MRI) studies of the brain. We assessed and compared the degree of cerebral SVD on the MRIs. The patients with NAION presented with cerebral SVD more frequently than controls (68% versus 37%, respectively, p<0.001), which was also observed after adjusting for age, sex, comorbid conditions including hypertension, diabetes, and dyslipidemia, and smoking using the standardized mortality ratio (68% vs. 37%, p<0.001). A multivariate logistic regression analysis showed that the odds of cerebral SVD were 4.86 (95% CI, 2.10 to 11.24, p<0.001) times higher in patients with NAION than in the controls. We found that there was an association between cerebral SVD and NAION even after adjusting for age, sex, and medical histories. Clinicians should consider brain MRI scans in patients with NAION to prevent neurological impairment after cerebral SVD.

Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage.

Background and Purpose- Despite early aneurysm repair and aggressive management for complications, subarachnoid hemorrhage (SAH) results in at least 25% mortality rate and 50% persistent neurological deficit. We investigated whether ceria nanoparticles which have potent antioxidative activities can protect against subarachnoid hemorrhage via attenuating fatal brain injuries. Methods- Uniform, 3 nm, water-dispersed ceria nanoparticles were prepared from short sol-gel reaction of cerium (III) ions with aminocaproic acid in aqueous phase. SAH was induced by endovascular perforation of middle cerebral artery of rats. A single dose of ceria nanoparticles (0.5 mg Ce/kg) or saline control was randomly administered intravenously at an hour post-SAH. Neuronal death, macrophage infiltration, SAH grade, and brain edema were evaluated at 72 hours. Mortality and neurological function were assessed for 14 days. Results- The obtained ceria nanoparticles with high Ce3+ to Ce4+ ratio demonstrated potent antioxidative, cytoprotective, and anti-inflammatory activities in vitro. In rodent SAH models, the severity of hemorrhage was comparable between the ceria nanoparticles- and saline-treated groups. However, ceria nanoparticles significantly reduced neuronal death, macrophage infiltration, and brain edema after SAH. Ceria nanoparticles successfully improved survival rates (88.2% in the ceria nanoparticles group versus 21.1% in the control group; P<0.001) and neurological outcomes (modified Garcia score: 12.1±0.5 in the ceria nanoparticles group versus 4.4±0.5 in the control group; P<0.001) of the animals with SAH. Conclusions- Ceria nanoparticles, totally synthesized in aqueous phase using aminocaproic acid, demonstrated promising results against SAH via potent antioxidative, neuroprotective and anti-inflammatory activities. Given the obvious limitations of current therapies for SAH, ceria nanoparticles can be a potential therapeutic agent which might result in a paradigm shift in SAH treatment.

Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage.

Nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which is composed of an NLRP3 domain, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC) domain, and procaspase-1, plays an important role in the immune pathophysiology of the secondary damage induced by intracerebral hemorrhage (ICH). This study aims to investigate whether pre-stroke treatment with fimasartan, an angiotensin II receptor blocker, has anti-inflammatory effects on ICH by inhibiting the activation of the NLRP3 inflammasome. Sprague-Dawley rats were divided into five groups: sham, vehicle, low-dose (0.5 mg/kg) and regular-doses (1.0 and 3.0 mg/kg) fimasartan. These rats were treated for 30 days before the induction of collagenase-induced ICH and continuously 3 days after surgery. The mean blood pressure (BP) in the low-dose fimasartan group was not significantly different from that of control, and BP in the regular-dose groups was decreased in a dose-dependent manner. Pretreatment with low-dose fimasartan attenuated ICH-induced edema and improved neurological functions. Activation of the NLRP3/ASC/caspase-1 and the NF-κB pathways after ICH was markedly reduced by low-dose fimasartan. The double immunofluorescence staining of brain cells showed a significant decrease in the co-localization of NLRP3 with Iba1 (microglia marker) positive cells by fimasartan treatment. Cultured microglia cells stimulated by hemolysate demonstrated significant activation of the inflammasome, which was reduced by fimasartan. Pretreatment with a low-dose fimasartan alleviated brain damage after acute ICH by inhibiting the NLRP3 inflammasome without lowering MBP. Our study suggests pre-stroke administration of fimasartan could potentially attenuate ICH-induced secondary brain injury by targeting the inflammasome.

Effect of Statins on Survival Following Stroke in Patients With Cancer.

The objective of this study was to investigate the potential benefits of statin therapy initiation in acute stroke in patients with active cancer. This study was conducted in two parts. First, data from patients who are presented with stroke and active cancer were obtained from prospectively collected multicenter hospital-based stroke registries. Patients were classified into statin user and non-user groups; the statin group was further divided into low-potency and high-potency statin subgroups. The primary outcome was time to mortality. Second, we obtained data from the Korean National Health Information Service-National Sample Cohort (NHIS-NSC) database for external validation and analyzed the effect of statins on mortality, taking compliance into consideration. For the stroke registry cohort, statin use was independently associated with reduced mortality in a multivariable model [hazard ratio (HR) = 0.675, 95% confidence interval (CI) = 0.457-0.996]. There was no interaction between statin use and cancer characteristics, vascular risk factors, or laboratory findings. A dose-dependent relationship between statin use and survival was also demonstrated. Analysis of the NHIS-NSC database found a similar association between statin therapy and reduced mortality (adjusted HR = 0.64, 95% CI = 0.45-0.90) and this effect persisted even after controlling for the adherence of statin use (HR = 0.60, 95% CI = 0.41-0.89). Statin therapy could be associated with reduced mortality in patients with acute stroke and active cancer.

Temporal changes in the neutrophil to lymphocyte ratio and the neurological progression in cryptogenic stroke with active cancer.

BACKGROUND: Ischemic stroke patients with active cancer frequently experience early neurological deterioration (END); however, the predictors of END are not well studied. The neutrophil to lymphocyte ratio (NLR) has recently been described as a predictor of poor outcomes in cancer and stroke. However, its role in cancer-related stroke has not been addressed. AIM: We aimed to evaluate the association between the NLR and END in cancer-related stroke patients. METHODS: We included 85 cryptogenic stroke patients with active cancer. END was defined as an increase ≥ 4 on the total National Institutes of Health Stroke Scale (NIHSS) score within 72 hours of admission. The NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. We obtained the NLR during the following three periods: at admission, 1-3 days after admission (D 1-3 NLR) and 4-7 days after admission (D 4-7 NLR). RESULTS: END occurred in 15 (18%) of the 85 patients. END was significantly associated with the initial NIHSS score, infarction volume, and the D 1-3 NLR. In multivariate analysis, a higher D 1-3 NLR, measured before END events, remained an independent predictor of END [adjusted odds ratio = 2.78, 95% confidence interval = 1.09-7.08, P = 0.032]. In terms of temporal changes in the NLR, the END group showed a tendency toward temporal increase in the NLR at D 1-3 (P = 0.061) with subsequent decrements in the D 4-7 NLR (P = 0.088), while the non-END group showed no significant changes in the NLR between periods. CONCLUSIONS: This study demonstrated that a higher NLR could predict END events in cryptogenic stroke patients with active cancer. However, the results should be confirmed in further large prospective studies.

Treatment of Cryptogenic Stroke with Active Cancer with a New Oral Anticoagulant.

BACKGROUND: Low-molecular weight heparin (LMWH) was shown to be effective and safe in treating venous thromboembolism, and generally used for stroke in cancer patients, but its effects on stroke are unclear. We compared clinical outcomes between LMWH and new oral anticoagulant (NOAC) in patients with cancer-related stroke. METHODS: We enrolled patients with cryptogenic ischemic stroke with active cancer who were treated with LMWH or NOAC between May 2012 and June 2015. The clinical outcomes, including early neurologic deterioration, early radiologic recurrence, 3-month modified Rankin scale score, 90-day mortality, cardio-cerebrovascular recurrence, and bleeding complications, were compared. RESULTS: Among 48 patients, 7 patients were treated with NOAC, and the remaining 41 patients with LMWH. Overall, the participants presented poor outcomes, including 20 (42%) early neurologic deteriorations, 28 (58%) early radiologic recurrences, 34 (71%) poor modified Rankin scale scores, 27 (56%) 90-day mortality events, 24 (50%) cardio-cerebrovascular recurrences, and 18 (38%) bleeding complications, that led to a change or temporary hold in medication in 12 cases. No statistical differences were found between the 2 groups in terms of demographic, clinical, or cardiovascular risk factors and clinical outcomes. CONCLUSIONS: NOAC showed the similar clinical outcomes and safety compared with LMWH in the treatment of cryptogenic ischemic stroke in active cancer patients.

Intravenous Thrombolysis in Acute Ischemic Stroke with Active Cancer.

Ischemic stroke patients with active cancer are known to have poor clinical outcomes. However, the efficacy and safety of intravenous alteplase (IV t-PA) in this group are still unclear. In this study, we aimed to evaluate whether stroke patients with cancer had poor clinical outcomes after use of IV t-PA. We reviewed ischemic stroke patients with active cancer treated with isolated IV t-PA between April 2010 and March 2015 at three national university hospitals from the registry for ischemic stroke in Korea. The clinical outcomes of early neurological deterioration (END), hemorrhagic transformation, in-hospital mortality, 3-month modified Rankin scale (mRS), the National Institutes of Health Stroke Scale (NIHSS) discharge score, and duration of hospitalization were compared. We enrolled a total of 12 patients, and the cohort showed poor outcomes including 4 (33%) END events, 7 (58%) hemorrhagic transformations, 3 (25%) in-hospital mortality cases, and 7 (58%) poor mRS (3-6) scores. Additionally, the cryptogenic stroke group (n = 6) more frequently had high mRS scores (P = 0.043) as well as tendencies for frequent END events, hemorrhagic transformations, in-hospital mortality cases, and higher discharge NIHSS scores without statistical significance. In conclusion, ischemic stroke patients with active cancer, especially those with a cryptogenic mechanism, showed poor clinical outcomes after use of IV t-PA.

Retinal Vein Occlusion as the Surrogate Marker for Premature Brain Aging in Young Patients.

Purpose: We investigated cerebral small vessel disease (SVD) in patients with incidental retinal vein occlusion (RVO). Methods: This retrospective, case-control, observational trial included 125 patients with RVO who underwent brain magnetic resonance imaging (MRI) and 1105 age-matched controls who underwent comprehensive medical interviews and MRI. Underlying cardiovascular diseases and MRI findings were investigated in the patients with RVO according to age (<60 or ≥60 years) and RVO occlusion level (central or branch). The characteristics of underlying cardiovascular disease and MRI findings were compared between the younger patients with RVO and age-matched controls. The cerebrovascular burden also was assessed in the younger patients with RVO. Results: The mean age of the patients with RVO was 63.9 ± 12.1 years and the predominant underlying disease was hypertension (72/125, 58%). The older RVO group had a longer history of hypertension and less smoking history. The prevalence of cerebral SVD in the RVO group was 54% (68/125), and was significantly higher in older than in younger patients with RVO (62% [53/86] vs. 38% [15/39], P = 0.016). However, the latter had a significantly higher prevalence of cerebral SVD than their age-matched controls (38% [15/39] vs. 4% [47/1105], P < 0.001). There was no difference in prevalence of cerebral SVD between the central and branch RVO groups (P = 0.478). Conclusions: Cerebral SVD presented frequently in patients with RVO and was magnified in young patients, suggesting that RVO is a surrogate marker for cerebral SVD.

Predictors of 30-day mortality and the risk of recurrent systemic thromboembolism in cancer patients suffering acute ischemic stroke.

BACKGROUND: Stroke in cancer patients is not rare but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. AIM: In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. METHODS: We included 210 ischemic stroke patients with active cancer. The 30-day mortality data were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. RESULTS: Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS scores, D-dimer levels, and CRP levels as well as frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46-3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. The initial NIHSS score (aOR = 1.07; 95% CI, 1.00-1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10-8.29, P = 0.032) were also significant independent of D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease in D-dimer levels, despite treatment, while the survivor group showed the opposite response. CONCLUSIONS: D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer.

Cystatin C is a useful predictor of early neurological deterioration following ischaemic stroke in elderly patients with normal renal function.

INTRODUCTION: Cystatin C has been suggested as a sensitive marker of renal function. A high level of cystatin C is related to cardiovascular disease and stroke in elderly patients. We investigated the relationship between levels of cystatin C and early neurological deterioration with acute ischaemic stroke in elderly patients without chronic kidney disease. PATIENTS AND METHODS: We evaluated a total of 771 elderly patients (mean age, 72.2; male, 59.0%) without chronic kidney disease who were admitted following acute ischaemic stroke between March 2010 and January 2015. The patients were divided into four groups based on the quartiles of serum cystatin C values. Early neurological deterioration was defined as an increase of ≥2 points from the baseline National Institutes of Health Stroke Scale score during the 7 days following onset. We compared the clinical characteristics and cystatin C concentrations between patients with and without early neurological deterioration. RESULTS: Eighty-six patients (11.2%) experienced early neurological deterioration. The percentage values of the higher (third and fourth) quartiles were significantly higher in the early neurological deterioration group (30.2% vs. 24.4% and 34.9% vs. 23.8%, P = 0.002). After adjustment for covariates, higher cystatin C levels were independently associated with a higher risk of early neurological deterioration: odds ratio (95% confidence interval) for second quartile 1.59 (0.70-3.58), third quartile 2.75 (1.25-6.04), fourth quartile 3.12 (1.36-7.16); P for trend 0.026. DISCUSSION AND CONCLUSIONS: This study demonstrated that cystatin C concentrations in elderly patients without chronic kidney disease were associated with early neurological deterioration following acute stroke. This suggests that cystatin C level could be a useful predictor for early neurological deterioration following acute stroke.

Cerebral Small Vessel Disease in Branch Retinal Artery Occlusion.

PURPOSE: We investigated the pathophysiology of branch retinal artery occlusion (BRAO) by evaluating the retina, brain, and carotid artery in patients with BRAO. METHODS: This study was a retrospective registry study. We used 46 eyes from 46 patients with acute BRAO and evaluated the medical history, including previous cardiovascular disease, and compared brain magnetic resonance images (MRI) and carotid artery stenosis state between the embolic BRAO group and nonembolic BRAO group. We measured differences in cerebrovascular characteristics, including brain MRI, according to the existence of retinal emboli. RESULTS: The embolic BRAO group tended to have a significantly higher likelihood of cardiovascular disease history, including ischemic heart disease and smoking history (P = 0.018 and P < 0.001, respectively). In addition, the embolic group had a higher frequency of acute cerebral infarctions and stenotic carotid arteries (P = 0.017 and P = 0.028, respectively). Although the overall frequency of cerebral small vessel disease (SVD) did not differ between embolic and nonembolic groups, the nonembolic BRAO group showed a significantly higher prevalence of cerebral SVD without large vessel pathology (P = 0.008). CONCLUSIONS: Patients with BRAO showed different cerebrovascular characteristics following retinal emboli, including brain MRI findings. The results suggest that we must consider SVD etiology as well as large vessel disease mechanisms in the pathophysiology of BRAO.

Anti-inflammatory effects of fimasartan via Akt, ERK, and NFκB pathways on astrocytes stimulated by hemolysate.

OBJECTIVE: The aim of this study was to investigate whether fimasartan, a novel angiotensin II receptor blocker, modulates hemolysate-induced inflammation in astrocytes. METHODS: We stimulated astrocytes with hemolysate to induce hemorrhagic inflammation in vitro. Astrocytes were pretreated with fimasartan and then incubated with hemolysate at different durations. Anti-inflammatory cell signaling molecules including Akt, extracellular signal regulated kinase (ERK), NFκB and cyclooxygenase-2 (COX-2) were assessed by western blotting. Pro-inflammatory mediators were evaluated by real-time RT-PCR and ELISA. RESULTS: The stimulation by hemolysate generated a robust activation of inflammatory signaling pathways in astrocytes. Hemolysate increased the phosphorylation of Akt at 1 h, and ERK1/2 at 20 min compared with the control group and promoted the degradation of IκBα. Pretreated fimasartan significantly decreased hemolysate-induced phosphorylation of Akt and ERK1/2. In addition, fimasartan also suppressed NFκB-related inflammatory pathways induced by hemolysate, including reduction of the gene expression of NFκB, and decreased nuclear translocation of NFκB and degradation of IκB. This reduction of inflammatory upstream pathways decreased the expression of inflammatory end-products: COX-2 and interleukin-1 (IL-1ß). Furthermore, the expression of COX-2 was attenuated by both Akt inhibitor (LY294002) and ERK inhibitor (U0126), and IκBα degradation was suppressed by LY294002. CONCLUSIONS: These results demonstrate that pretreatment with fimasartan to astrocytes suppresses the inflammatory responses induced by hemolysate. Akt, ERK and NFκB were associated with hemolysate-induced COX-2 and IL-1ß expression. Based on these mechanisms, fimasartan could be a candidate anti-inflammatory regulator for the treatment of intracerebral hemorrhage.

Recurrent intractable hiccups treated by cervical phrenic nerve block under electromyography: report of a case.

Intractable or persistent hiccups require intensive or invasive treatments. The use of a phrenic nerve block or destructive treatment for intractable hiccups has been reported to be a useful and discrete method that might be valuable to patients with this distressing problem and for whom diverse management efforts have failed. We herein report a successful treatment using a removable and adjustable ligature for the phrenic nerve in a patient with recurrent and intractable hiccups, which was employed under the guidance of electromyography.

Intrapulmonary recurrence after computed tomography-guided percutaneous needle biopsy of stage I lung cancer.

Tumor seeding, along the needle tract after percutaneous needle biopsy, is a rare condition and most of the reported cases are implantation metastasis, which occurred in the chest wall or the pleura. We present a case of implantation metastasis that occurred in the pulmonary parenchyma, after a computed tomography-guided percutaneous needle biopsy (CT-PNB) of stage I lung cancer.

Effects of human adipose-derived stem cells on the regeneration of damaged visceral pleural mesothelial cells: a morphological study in a rabbit model.

OBJECTIVES: Although an alveolar air leak (AAL) after pulmonary resection is a troublesome complication that diminishes a patient's quality of life and increases medical costs, current treatment and preventive methods for AAL are not effective. Therefore, we transplanted adipose-derived stem cells (ASCs) to the damaged visceral pleura to facilitate the regeneration of mesothelial cells and investigated the possibility of cell therapy as a treatment option for AAL. METHODS: Stem cells were isolated and cultured from discarded fat tissues that were collected after liposuction procedures. Flow cytometry analysis was performed to evaluate their suitability as mesenchymal stem cells. Cultured stem cells were seeded onto polyglycolic acid (PGA) sheets and incubated for 5 days. Under general anaesthesia, 10 New Zealand rabbits underwent thoracotomies. After the visceral pleura was damaged, PGA sheets containing ASCs were transplanted into 5 rabbits (ASC group) and PGA sheets without cells were transplanted into the other 5 rabbits (control group). Rethoracotomies were performed after 4 weeks, and the transplanted areas in the visceral pleura were excised for analysis. Haematoxylin and eosin and Azan staining were performed. In addition, electron microscopic examinations were performed to investigate the ultrastructure of the regenerating mesothelium. RESULTS: Cultured stem cells were positive for the surface proteins CD13, CD29, CD49d, CD90 and CD105, whereas they were negative for CD34, CD45 and human leukocyte antigen (HLA)-DR. The adhesions between the transplanted visceral pleura and parietal pleura were weaker in the ASC group than in the control group. On histological examination, the mesothelial cell monolayer of the visceral pleura was well preserved in the ASC group, whereas it was frequently lost in the control group. Electron microscopy demonstrated that the mesothelial cell monolayer and its abundant microvilli were well preserved in the ASC group, but were absent or disintegrated in the control group. CONCLUSIONS: Transplantation of ASCs to the damaged visceral pleura can contribute to the treatment and prevention of AAL by improving the regeneration of mesothelial cells.

Changes of cardiac troponin I and operative mortality of coronary artery bypass.

BACKGROUND: Recently, cardiac troponin I has been used to detect myocardial injury because of its superior cardiac specificity. However, there has been debate about the appropriate timing and cutoff level of cardiac troponin I to detect perioperative myocardial injury after coronary artery bypass grafting. The objective of this study was to define the relationship between operative mortality and changes in cardiac troponin I after isolated coronary artery bypass. PATIENTS AND METHODS: A retrospective analysis was carried out on data of 218 isolated coronary artery bypass patients who were operated on between June 2009 and February 2012. All patients followed an institutional perioperative management protocol that included 6 cardiac troponin I measurements (preoperatively and 0, 12, 24, 36, and 48 h after coronary artery bypass). According to the patterns of cardiac troponin I, the patient cohort was divided into 2 groups. Group 1 was patients in whom cardiac troponin I levels decreased 24 h after the operation, and group 2 comprised the patients with cardiac troponin I levels that did not decrease or even increased after 24 h. RESULTS: The operative mortality was 4.1% (9/218). Group 2 showed significantly higher mortality (5/25, 20%) than group 1 (4/193, 2.1%). CONCLUSION: An elevated cardiac troponin I level is common after coronary artery bypass. A persistently high level of cardiac troponin I after 24 h is an important predictor of operative mortality after coronary artery bypass surgery.