Neutrophil-to-Lymphocyte Ratio as a Predictor of Short-Term Functional Outcomes in Acute Ischemic Stroke Patients.

Background: Neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory biomarker, has been associated with poorer outcomes in acute ischemic stroke patients. The present study was designed to expand these findings by investigating the association between NLR and short-term functional outcomes in acute ischemic stroke patients. Methods: This retrospective study evaluated patients within 7 days after the onset of acute ischemic stroke. Stroke severity on admission was measured using the National Institutes of Health Stroke Scale (NIHSS). The functional outcomes were assessed using the Berg Balance Scale (BBS), Manual Function Test (MFT), the Korean version of the modified Barthel Index (K-MBI), and the Korean Mini-Mental State Examination (K-MMSE) within 2 weeks of stroke onset. The modified Rankin Scale (mRS) was evaluated at discharge. Results: This study included 201 patients, who were grouped into three NLR tertiles (<1.84, 1.84−2.71, and >2.71) on admission. A multivariate analysis showed that the top tertile group (NLR > 2.71) had significantly higher risks of unfavorable outcomes on the K-MBI (p = 0.010) and K-MMSE (p = 0.029) than the bottom tertile group (NLR < 1.84). Based on the optimal cut-off values from a receiver operating characteristic curve analysis, a higher NLR was significantly associated with higher NIHSS scores (p = 0.011) and unfavorable outcomes on the K-MBI (p = 0.002) and K-MMSE (p = 0.001). Conclusions: A higher NLR is associated with poorer short-term functional outcomes in acute ischemic stroke patients.

Toxicity assessment of Gryllus bimaculatus (a type of cricket) glycosaminoglycan.

We performed general toxicity studies of Gryllus bimaculatus (two-spotted cricket) glycosaminoglycan (GbG), including a single, 4-week repeated oral dose toxicity test in ICR mice, and short-term genotoxicity tests. The mutagenic potential of the purified GbG was non-genotoxic when it was evaluated using short-term genotoxicity tests, namely Ames, chromosome aberration (CA), and micronuclei (MN) tests. In Salmonella typhimurium and Escherichia coli assays, GbG did not produce any mutagenic response in the absence or presence of S9 mix with five bacterial strains (TA98, TA100, TA1535, TA1537, and WP2uvrA). Chromosome aberration test showed that GbG had no significant effect on Chinese hamster ovary (CHO) cells. In mouse micronuclei tests after twice oral treatments per day for two days, no significant alteration in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice intraperitoneally administered with GbG at doses of 15.63, 31.25, or 62.50 mg/kg. These results indicate that GbG has no mutagenic potential in these in vitro and in vivo systems. After GbG was orally administered at doses of 20, 40, 80, and 160 mg/kg for a single oral dose toxicity study and at 0, 40, 80, and 160 mg/kg bw/day for 4-week oral dose toxicity study, there were no observed clinical signs or deaths related to treatment in any group tested. Therefore, the approximate lethal oral dose of GbG was considered to be higher than 160 mg/kg in mice. Throughout the administration period, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis), or gross pathology were detected. Microscopic examination did not identify any treatment-related histopathologic changes in organs of GbG-treated mice in the high dose group. These results indicate that the no-observed adverse effect level (NOAEL) of GbG is higher than 160 mg/kg bw/day in mice.

Rapid Disruption of Cellular Integrity of Zinc-treated Astroglia Is Regulated by p38 MAPK and Ca-dependent Mechanisms.

Cultured cortical primary astroglia treated with zinc died while rapidly detached from culture plates, a distinct part of zinc-treated astroglia. In the present study, we investigated the mechanism underlying the rapid change in the morphologic integrity of zinc-treated astroglia. Among the early cellular events occurring in zinc-treated astroglia, strong activation of p38 MAPK and JNK was evident. Although inhibitors of p38 (SB203580 and SB202190) or JNK (SP600125) did not protect zinc-insulted astroglia from cell death, the p38 inhibitors, but not the JNK inhibitor, suppressed actin filament and cell morphology disruption. The Ca(2+) ionophore, A23187, also suppressed actin filament and cell morphology disruption, but not cell death, of zinc-insulted astroglia. However, A23187 did not inhibit p38 MAPK activation in zinc-treated astroglia. Together these results suggest that zinc influx in astroglia results in rapid loss of the morphologic integrity via mechanisms regulated by p38 kinase and/or Ca(2+) signaling.

Determination of cytotoxicity attributed to multiwall carbon nanotubes (MWCNT) in normal human embryonic lung cell (WI-38) line.

Carbon nanotubes (CNT) possess beneficial physicochemical and mechanical properties; however, despite these advantages there are concerns regarding the adverse effects of CNT on lung and development of diseases, such as lung cancer and mesothelioma. According to fiber characteristics of length and diameter (aspect ratio), fibers with high aspect ratio (10-15 nm diameter and containing two different length distributions of 545 ± 230 and 10451 ± 8422 nm length) are more toxic to lung than low-aspect-ratio fibers (10-15 nm diameter and length of 192 nm). It was thus of interest to investigate the effects of multiwall carbon nanotubes (MWCNT) on the viability of normal human embryonic lung cells (WI-38) using trypan blue dye exclusion, the tetrazolium salt WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) assay, and lactate dehydrogenase (LDH) activity assay. MWCNT produced cell growth inhibition and death at 12.5-200 µg/ml after 24-72 h of incubation. In addition, high-aspect-ratio MWCNT were found to produce higher incidence of cytotoxicity than low-aspect-ratio fibers at 50-200 µg/ml concentration. In the presence of less than 10% trace element content such as iron in MWCNT, the trace element exerted no marked effect on cellular viability. Data indicate that MWCNT inhibited cell proliferation and triggered cell death, and it would appear that the MWCNT fiber characteristics rather than impurities play a predominant role in the observed the cytotoxicity attributed to MWCNT.

Morphogenetic lung defects of JSAP1-deficient embryos proceeds via the disruptions of the normal expressions of cytoskeletal and chaperone proteins.

Recent studies have shown that JNK/stress-activated protein kinase-associated protein 1 (JSAP1)-deficient mice die from respiratory failure shortly after birth. To understand the underlying mechanism, we investigated the histological appearances and cell type changes in developing jsap1(-/-) lungs between E12.5 and E18.5. At the light microscopic level, no overt abnormality was detected in jsap1(-/-) until E16.5. However, alveoli and airway formations that normally occur after E16.5 were poorly advanced in jsap1(-/-). Despite these morphological defects, surfactant secreting cells labeled by anti-SP-B or anti-SP-C were present in normal ranges in jsap1(-/-) lungs. Smooth muscle alpha-actin expressing cells were also developed in jsap1(-/-) lungs, although actin expression was decreased. The expressions of transcriptional factors, such as, nuclear factor Ib (Nfib), N-myc, and octamer transcriptional factor 1 (Oct-1), which play a critical role in lung morphogenesis, were found to be down-regulated, whereas signal transducer and activator of transcription 3 (Stat3), sonic hedgehog (Shh), and smoothened (Smo) were up-regulated, in jsap1(-/-) lungs at E17.5-E18.5 compared with those in jsap1(+/+) lungs. Proteomics analysis of E17.5 lung identified 39 proteins with altered expressions, which included actin, tropomyosin, myosin light chain, vimentin, heat shock protein (Hsp27), and Hsp84. These results suggest that JSAP1 is required for the normal expressions of cytoskeletal and chaperone proteins in the developing lung, and that impaired expressions of these proteins might cause morphogenetic defects observed in jsap1(-/-) lungs.