Urinary biomarkers of kidney tubule injury, risk of acute kidney injury, and mortality in patients with acute ischaemic stroke treated at a stroke care unit.

BACKGROUND AND PURPOSE: Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI). The aim of this study was to investigate whether kidney tubule injury is associated with the development of AKI and mortality in patients with acute ischaemic stroke. METHODS: Acute ischaemic stroke patients hospitalized in the stroke care unit (SCU) within 24 h after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Baseline urinary L-FABP was measured on admission. We evaluated the associations among urinary L-FABP, incidence of AKI, and 90-day mortality adjusted for renal function, albuminuria and other potentially predictive variables, using multivariable analysis. RESULTS: In total, 527 acute ischaemic stroke patients (342 men, median age 74 years) were enrolled in the study. Twenty-seven patients (5.1%) experienced AKI within 7 days of admission. In the univariate analysis, high urinary L-FABP level had positive associations with AKI [53.8 µg/g creatinine (Cr) vs. 3.9 µg/g Cr; P < 0.001] and 90-day mortality (15.5 µg/g Cr vs. 4.0 µg/g Cr; P < 0.001). In the multivariate analysis, elevated urinary L-FABP level (per 10-µg/g Cr increase) was independently associated with AKI (odds ratio 1.225, 95% confidence interval (CI) 1.083-1.454; P = 0.003) and 90-day mortality (hazard ratio 1.091, 95% CI 1.045-1.138; P < 0.001). CONCLUSION: Urinary biomarkers of kidney tubule injury are independently associated with the development of AKI and 90-day mortality in patients with acute ischaemic stroke treated at the SCU.

Application of the Self- Assembling Peptide P11-4 for Prevention of Acidic Erosion.

The aim of this study was to use ultrasonography to evaluate the effect of the self-assembling peptide P11-4 on acid erosion prevention. Curodont Repair (CR), which includes peptide P11-4, was used. Rectangular prisms of bovine enamel (4×1×1 mm) were immersed in pure orange juice for a period of 5 minutes six times per day for 28 days. These samples were divided into four groups of six specimens each and treated differently for an additional period of 28 days: 1) baseline group specimens were stored in artificial saliva; 2) CR group specimens were exposed to curodont without acid challenge; 3) NCRA (no curodont+acid challenge) specimens were treated with orange juice without curodont exposure; and 4) CRA (CR+acid challenge) specimens were treated with curodont before treatment with orange juice. The propagation time of longitudinal ultrasonic velocity (UV) was measured. Ultrastructural observation of each tested enamel surface was carried out using field-emission scanning electron microscopy (SEM). The UV data were analyzed using two-way analysis of variance with time and treatment as confounding factors. Post hoc pairwise tests among groups were performed using the Tukey honestly significant difference test. The average UV in intact bovine enamel for the baseline group ranged from 4,483 to 4,549 m/s and did not vary significantly within the test period. The average ultrasonic velocity (UV) in all samples decreased after the initial erosion. The UV in NCRA decreased further over time. Increased UVs were found for CR and CRA. For CR and CRA, there was no significant difference in UV at the end of the experiment from the initial value before erosion. In the results of SEM observation, the CR and CRA groups had similar morphologic features in that etching patterns were not clearly due to precipitation between the enamel rods. From the results of this in vitro study, it might be concluded that applying enamel matrix derivatives and self-assembling peptides on erosive lesions can improve remineralization.

Polymerization Behavior and Mechanical Properties of High-Viscosity Bulk Fill and Low Shrinkage Resin Composites.

The present study determined the mechanical properties and volumetric polymerization shrinkage of different categories of resin composite. Three high viscosity bulk fill resin composites were tested: Tetric EvoCeram Bulk Fill (TB, Ivoclar Vivadent), Filtek Bulk Fill posterior restorative (FB, 3M ESPE), and Sonic Fill (SF, Kerr Corp). Two low-shrinkage resin composites, Kalore (KL, GC Corp) and Filtek LS Posterior (LS, 3M ESPE), were used. Three conventional resin composites, Herculite Ultra (HU, Kerr Corp), Estelite ∑ Quick (EQ, Tokuyama Dental), and Filtek Supreme Ultra (SU, 3M ESPE), were used as comparison materials. Following ISO Specification 4049, six specimens for each resin composite were used to determine flexural strength, elastic modulus, and resilience. Volumetric polymerization shrinkage was determined using a water-filled dilatometer. Data were evaluated using analysis of variance followed by Tukey's honestly significant difference test (α=0.05). The flexural strength of the resin composites ranged from 115.4 to 148.1 MPa, the elastic modulus ranged from 5.6 to 13.4 GPa, and the resilience ranged from 0.70 to 1.0 MJ/m3. There were significant differences in flexural properties between the materials but no clear outliers. Volumetric changes as a function of time over a duration of 180 seconds depended on the type of resin composite. However, for all the resin composites, apart from LS, volumetric shrinkage began soon after the start of light irradiation, and a rapid decrease in volume during light irradiation followed by a slower decrease was observed. The low shrinkage resin composites KL and LS showed significantly lower volumetric shrinkage than the other tested materials at the measuring point of 180 seconds. In contrast, the three bulk fill resin composites showed higher volumetric change than the other resin composites. The findings from this study provide clinicians with valuable information regarding the mechanical properties and polymerization kinetics of these categories of current resin composite.

The relationship between stroke severity and prior direct oral anticoagulant therapy in patients with acute ischaemic stroke and non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: Anticoagulant treatment with a vitamin K antagonist (VKA) has been reported to reduce stroke severity when patients with atrial fibrillation (AF) suffer acute ischaemic stroke (AIS). Direct oral anticoagulant (DOAC) therapy also has the potential to reduce the initial severity of AIS. However, the effect of DOAC therapy on the severity of AIS is not well known. The aim of the present study was to investigate the effect of DOACs on initial stroke severity in patients with AIS and non-valvular AF. METHODS: From March 2011 to July 2016, consecutive patients with AIS having non-valvular AF were recruited. The effects of prior DOAC treatment on severity were assessed by multivariate logistic regression analyses. RESULTS: A total of 484 patients [208 women; median age 79 (interquartile range, 71-85) years; National Institutes of Health Stroke Scale (NIHSS) score 9 (interquartile range, 3-20)] were enrolled. Of these, 352 (73%) were on no anticoagulant medication, 54 (11%) were undertreated with a VKA, 35 (7%) were sufficiently treated (admission prothrombin time-international normalized ratio: ≥2.0 for patients <70 years old and ≥1.6 for ≥70 years old) with a VKA and 43 (9%) were on a DOAC. The initial NIHSS score (median 10 in patients with no anticoagulation, 13 in undertreated VKA, 7 in sufficient VKA and 6 in DOAC, P = 0.018) was different among the groups. Multivariate analysis showed that DOAC was independently and negatively associated with severe (initial NIHSS score ≥ 10) stroke (odds ratio, 0.39; P = 0.041), compared with no anticoagulant therapy. CONCLUSIONS: Direct oral anticoagulant treatment prior to the event should reduce initial stroke severity in patients with AIS and non-valvular AF.

The novel G-quadruplex-containing long non-coding RNA GSEC antagonizes DHX36 and modulates colon cancer cell migration.

Long non-coding RNAs (lncRNAs) are frequently dysregulated in a variety of human cancers. However, their biological roles in these cancers remain incompletely understood. In this study, we analyze the gene expression profiles of colon cancer tissues and identify a previously unannotated lncRNA, FLJ39051, that we term GSEC (G-quadruplex-forming sequence containing lncRNA), as a lncRNA that is upregulated in colorectal cancer. We further demonstrate that knockdown of GSEC results in the reduction of colon cancer cell motility. We also show that GSEC binds to the DEAH box polypeptide 36 (DHX36) RNA helicase via its G-quadruplex-forming sequence and inhibits DHX36 G-quadruplex unwinding activity. Moreover, knockdown of DHX36 restores the reduced migratory activity of colon cancer cells caused by GSEC knockdown. These results suggest that GSEC plays an important role in colon cancer cell migration by inhibiting the function of DHX36 via its G-quadruplex structure.

Valproic acid enhances the effect of bone marrow-derived mononuclear cells in a rat ischemic stroke model.

Bone marrow derived mononuclear cell (MNC) transplantation is a potential therapy for ischemic stroke. Here, we hypothesized that valproic acid (VPA) would modulate transplantation effects of MNCs in a rat ischemic stroke model. Male Sprague-Dawley rats were subjected to transient 90min middle cerebral artery occlusion. Infarct volume, neurological outcome, and immunohistological assessments were performed 7 days after ischemia. MNCs injected 6 or 24h but not 48 or 72h after ischemia significantly reduced infarct volume and improved neurological deficits. We then tested whether the therapeutic window of MNC transplantation could be expanded through combination therapy with VPA. MNC transplantation at 48h combined with VPA injection three times at 47, 53, and 72h after ischemia significantly ameliorated infarct volume and neurological deficits compared to a vehicle group. Combination therapy reduced the number of myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1-positive cells, tumor necrosis factor-α-positive cells, and von Willebrand factor-positive cells in the ischemic boundary zone. The number of engrafted MNCs that were fluorescently labeled with PKH 26, on day 7, was significantly higher after combination therapy than after that MNC transplantation alone. Our results demonstrated that combination therapy with VPA enhanced the anti-inflammatory and vasculo-protective effects against endothelial damage following ischemia, and increased the survival of transplanted cells, leading to expansion of the therapeutic time window for MNC transplantation. Together, these findings suggest that VPA may be an appropriate partner for cell-based treatment of ischemic stroke.

Pharmacoresistant convulsions and visual hallucinations around two weeks after selegiline overdose: a case report.

A case of pharmacoresistant convulsions after selegiline overdose is reported. A 50-year-old male having been suffering from bipolar II disorder for 16 years attempted suicide by taking an overdose of 195 mg selegiline with other psychotropics. He developed recurrent pharmacoresistant seizure from 12th day to 19th day after selegiline overdose. He also had visual hallucinations and temporary high blood pressure. The authors suspect that the catecholamine-influenced convulsions and visual hallucinations that manifested during the period increased by the MAO-inhibiting action of selegiline which lasts about 2 weeks.

Searching for very early precursors of autism spectrum disorders: the Hamamatsu Birth Cohort for Mothers and Children (HBC).

Autism spectrum disorders (ASD) are life-long neurodevelopmental conditions. The pathophysiology is poorly understood, and the clinical diagnosis can only be made through behavioural assessments. The prevalence of ASD has increased eight-fold over the last three decades. Paralleling this rise, research interest in the disorder has been accumulating, centering on two aspects: risk factors that would explain the increase in prevalence, and precursors that could predict an emergence of ASD prior to 2 years of age. As regard factors responsible for the increased prevalence, an increasing trend of low birthweight (4.2% in 1980 v. 9.6% in 2006 at Japan) and advanced paternal age at birth are potentially implicated. To explore these issues, and to yield an early diagnostic algorithm for ASD, the authors initiated the ongoing Hamamatsu Birth Cohort for Mothers and Children (HBC) in 2007. The strengths of the HBC include frequent, direct face-to-face assessments of all the participating mothers and children during the first 4 years of life (12 assessments); this depth of assessments will disclose subtle changes in the developmental domains of individuals with ASD, which might otherwise be overlooked. A total of 1200 pregnant women are to be recruited by the end of 2010. Assembled information comprises a range of variables related to the mother's characteristics and child development. The comprehensiveness of the HBC will provide an informative data source that will elucidate early trajectories of children with ASD in addition to revealing detailed, developmental properties of typically developing children.

Serum levels of P-selectin in men with high-functioning autism.

Immune dysfunction has been proposed as a mechanism for the pathophysiology of autistic-spectrum disorders. The selectin family of adhesion molecules plays a prominent role in immune/inflammatory responses. We determined the serum levels of three types of soluble-form selectin (sP, sL and sE) in 15 men with high-functioning autism and 22 age-matched healthy controls by enzyme-linked immunosorbent assay. Levels of sP-selectin and sL-selectin were significantly lower in patients than in controls. Furthermore, sP-selectin levels were negatively correlated with impaired social development during early childhood.

Electroconvulsive therapy for burning mouth syndrome.

OBJECTIVE: Burning mouth syndrome (BMS) is an orofacial pain disorder characterized by a chronic, idiopathic burning sensation of the oral mucosa that mostly affects middle-aged women. Although both psychological and neuropathological factors have been postulated to underlie BMS, the pathogenic mechanism of the condition remains controversial, as do the treatment strategies. METHOD: A single case was reported. RESULTS: Ms A, a 66-year-old woman with BMS type 1, which is characterized by daily burning pain associated with circadian variation, underwent electroconvulsive therapy (ECT). After the completion of 12 ECTs, the pain markedly diminished and the pronounced ECT effect persisted over the subsequent 24-week period of observation. CONCLUSION: To our knowledge, this is the first clinical report on the efficacy of ECT for treating pain associated with BMS. ECT can be considered to be an option for treating individuals with enduring and intractable intraoral burning pain.

Reduced low-density-lipoprotein cholesterol causing low serum cholesterol levels in gastrointestinal cancer: a case control study.

Several epidemiological studies suggested an inverse relation between serum cholesterol level and cancer mortality. We analyzed the relation between gastrointestinal cancers and serum cholesterol levels. A total of 631 patients were recruited as cancer-bearing cases, comprising 181 esophageal cancers, 251 gastric cancers and 199 colorectal cancers. A case-control analysis was conducted on the serum TC, HDL-C, LDL-C and TG levels. TC and LDL-C were significantly lower in cancer-bearers by approximately 15 mg/dl. Furthermore, analyses by cancer site also showed significantly lower TC and LDL-C levels in cancer-bearers than in controls for all three sites. In this analysis, early stage cancer-bearers showed a significant decrease in TC levels by approximately 11 mg/dl compared with controls, and also a similar decrease in LDL-C levels. These results suggest that low TC levels are not related to cancer stage. Furthermore, findings of no significant differences in HDL-C and TG between cancer-bearing cases and controls in addition to a specific decrease in LDL-C in cancer-bearers suggest that hypocholesterolemia observed in these cases stems from low LDL-C. However, cancer-bearers and controls showed a similar distribution of TC and LDL-C levels. We should be aware that latent cancer bearers may be present among subjects with hypocholesterolemia.

Comparison of stent placement and colostomy as palliative treatment for inoperable malignant colorectal obstruction.

BACKGROUND: Stent placement is a useful palliative treatment for inoperable acute malignant colorectal obstruction. However, data comparing stent placement with colostomy are scarce. METHODS: We compared the clinical outcome of 18 patients who had stent placement and 17 patients who underwent only colostomy. RESULTS: The postoperative hospital stay was 22.3 days for stent placement compared with 47.4 days for colostomy (p = 0.016). The duration to readmission was 129.2 days for stent placement and 188.4 days for colostomy. The estimated duration of primary stent patency was 106 days. Mean survival period was 134 days in patients with stent placement and 191 days in patients with colostomy. CONCLUSION: Postoperative hospital stay was shorter in patients with stent placement but duration to readmission and survival were longer in patients with colostomy. However, stent placement increases the option of palliative treatment and is an effective treatment contributing to improving quality of life.

[A case of pneumonectomy for lung cancer associated with scleroderma].

A 60-year-old female, diagnosed as scleroderma, was referred to our hospital because of symptoms of common cold and abnormal findings on a chest X-ray. The chest X-ray and CT scan revealed a mass in the left upper field, suspected to invade left anterior chest wall. Moreover, fibrotic changes were observed in the lung field. Cytology by bronchofiberscopy showed squamous cell carcinoma. Evaluation of pulmonary function, including unilateral pulmonary artery occlusion test (UPAO), revealed possibility of lung resection. Subsequently, pneumonectomy with combined resection of left 1st rib was performed. Postoperative course was uneventful and she was discharged. She was admitted again four months after the operation with appetite loss and body weight loss. Further examinations revealed arrhythmia, renal failure, pancreatitis and liver metastasis. Her general conditions grew worse and she died five months after the operation. In conclusion, UPAO was a useful method to determine the functional lung resectability for the case with scleroderma. However, effects of surgical stress for the development of scleroderma remain to be elucidated.

A proposal for the unification of five species of the cyanobacterial genus Microcystis Kützing ex Lemmermann 1907 under the rules of the Bacteriological Code.

Genomic DNA homologies were examined from six Microcystis (cyanobacteria) strains, including five different species, Microcystis aeruginosa, Microcystis ichthyoblabe, Microcystis novacekii, Microcystis viridis and Microcystis wesenbergii. All DNA-DNA reassociation values between two strains of M. aeruginosa and the other four species exceeded 70%, which is considered high enough for them to be classified within the same bacterial species. It is proposed to unify these five species into M. aeruginosa under the Rules of the Bacteriological Code and NIES843T (= IAM M-247T) is proposed as the type strain. Two other species, Microcystis flos-aquae and Microcystis pseudofilamentosa, should be regarded as morphological variations of this unified M. aeruginosa. The current taxonomy of cyanobacteria depends too much upon morphological characteristics and must be reviewed by means of bacteriological methods as well as traditional botanical methods.

The effects of bisoprolol, a selective beta1-blocker, on glucose metabolism by long-term administration in essential hypertension.

Bisoprolol, a beta1-selective beta-blocker, was administered to 13 patients with mild to moderate essential hypertension once daily at doses of 5-10 mg for 24 weeks, and its long-term effects on blood pressure and glucose metabolism were investigated. The systolic, diastolic and mean blood pressures were significantly reduced. At the end of the treatment period, the blood glucose level and hemoglobin A1c were not significantly different from those at baseline. In the glucose tolerance test at the end of the treatment period, the blood glucose and plasma insulin levels after a glucose load of 75 g were not significantly different at any time point, and the sums of each were not significantly different from their baseline levels. Based on these results, bisoprolol appears to be a beta1-selective beta-blocker possessing a satisfactory hypotensive effect without any adverse effects on glucose metabolism for long-term use, and is therefore a safe and useful drug for the treatment of essential hypertension.

Bisphenol A inhibits testicular functions and increases luteinizing hormone secretion in adult male rats.

Effects of a xenobiotic estrogen, bisphenol A (BPA), on reproductive functions were investigated using adult male rats. BPA was dissolved into sesame oil and injected s.c. every day (1 mg/rat) for 14 days. Animals were killed by decapitation after the final administration of BPA, and the trunk blood, pituitary, and testes were collected. Plasma concentrations of prolactin were dramatically increased and pituitary contents of prolactin were slightly increased in the BPA group compared to the control group. Plasma concentrations of testosterone were decreased and plasma concentrations of LH were increased in BPA-treated rats compared to control rats. Testicular contents of inhibin were decreased in BPA-treated rats compared to control rats, although plasma concentrations of inhibin were not changed after administration of BPA. The testicular response to hCG for progesterone and testosterone release was decreased in BPA-treated rats. Administration of BPA did not change the pituitary response to luteinizing hormone-releasing hormone (LH-RH) in castrated male rats treated with testosterone. Male sexual behavior also was not changed as a result of BPA treatment. These results suggest that BPA directly inhibits testicular functions and the increased level of plasma LH is probably due to a reduction in the negative feedback regulation by testosterone. The testis is probably a more sensitive site for BPA action than the hypothalamus-pituitary axis.

Regulation of calcitonin receptor by glucocorticoid in human osteoclast-like cells prepared in vitro using receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor.

Using mouse osteoclast-like cells (OCs), we have shown that treatment with glucocorticoids (GCs) resulted in an increase in calcitonin (CT) binding by enhancing CT receptor (CTR) gene transcription. Additionally, treatment with GCs demonstrated increased sensitivity to CT. There is, however, scant information on the effects of GC or CTR regulation by GCs in human osteoclasts. In this study we examined CTR regulation by GCs and the effects of GCs and CT together in human OCs. OCs were prepared by treatment of peripheral blood mononuclear cells in vitro with soluble receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor. Treatment of mature OCs with dexamethasone (Dex) resulted in a dose- and time-dependent increase in [(125)I]salmon CT (sCT) binding capacity. Treatment with Dex enhanced CTR messenger RNA (mRNA) expression, suggesting that CTR up-regulation is at least partly due to an increase in de novo CTR synthesis. Triamcinolone and prednisolone reproduced the Dex effect on [(125)I]sCT-specific binding and CTR mRNA expression, but 17beta-estradiol, progesterone, dehydroepiandrosterone, and aldosterone did not. A Scatchard plot analysis showed that Dex enhanced CTR number with a minimal change in the affinity to sCT. Autoradiographic studies using [(125)I]sCT showed that Dex enhanced the CTR density on individual multinuclear OCs. Up-regulation of [(125)I]sCT-specific binding and CTR mRNA expression was seen even in the presence of sCT, but the enhancement diminished subsequently at later times (36-48 h after sCT removal), which was consistent with our previous observation in mouse OCs. This suggests that GCs and CTs act on CTR expression differently, consistent with our previous work using mouse OCs, in which we found that GCs increased transcription of CTR gene expression, whereas CT reduced CTR mRNA stability. The results obtained in this study show that GC increased CTR expression and sensitivity to CT in cells of the human osteoclast lineage and provide the basis for understanding the beneficial effects of combination treatment with GCs and CTs in malignancy-associated hypercalcemia.