Influence of novel resin monomer on viability of L-929 mouse fibroblasts in vitro

We have previously synthesized a novel acrylic resin monomer, methacryloyloxyethyl methyl succinate (TA). The aim of this in vitro study, therefore, was to examine its influence on cell viability using L-929 mouse fibroblasts and then compare the results with MMA, EMA, and LMA. Medium containing each monomer was changed every 15 minutes as some monomers were volatile. After one hour of exposure, these mediums were replaced with a normal medium and cells were further incubated for 72 hours. IC50 value for each monomer was determined, and chronological cell viability and cytomorphologic observation were evaluated. Viability was impaired in a dose-dependent manner. All monomers, except TA, tended to correlate between molecular weight and cell viability. On the other hand, TA showed excellent viability and did not impair growth abruptly. These results thus demonstrated that cellular damage by TA was much lower than that by other monomers.     

Fluoride release from newly developed dental adhesives

This study compared fluoride release from three fluoride-releasing dental adhesives (Trial KBF Bond, One-up Bond F, Reactmer Bond) and one conventional dental adhesive (Clearfil SE Bond) for 70 days in vitro. From each material, five disk-shaped specimens (diameter: 9.0 mm, height: 1.5 mm) were prepared and immersed in 5 ml of 10 mM phosphate buffered solution (pH 7.0). After 1, 3, 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70 days, the samples were transferred into new solutions. The fluoride content was determined with a combined fluoride sensitive electrode attached to an ion analyzer. Data were statistically analyzed with ANOVA, followed by Scheffé's test. Reactmer Bond showed the greatest fluoride release over 70 days (280.2 +/- 10.1 micrograms/cm2) among the materials tested. The values for One-up Bond F and Trial KBF Bond were 83.4 +/- 5.3 micrograms/cm2 and 58.6 +/- 1.5 micrograms/cm2, respectively. The values were significantly different among the four groups (p < 0.0001). Clearfil SE Bond showed almost no fluoride release over 70 days.     

Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis: report of five cases.

To minimize the adverse effects of high-dose administration of steroids and cyclophosphamide in patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA), granulocytapheresis (GCAP) or leukocytapheresis (LCAP) was performed to reduce inflammation. Four patients with rapidly progressive glomerulonephritis (RPGN) and one patient with pulmonary hemorrhage due to MPO-ANCA-associated vasculitis were treated by cytapheresis. The prednisolone (PSL) dose was 0.28 +/- 0.15 mg/kg/day (mean +/- SD) (range 0.18-0.50 g/kg/day). In the 4 RPGN patients, the peak serum creatinine level was 3.7 +/- 1.9 mg/dl (range 1.7 to 5.6 mg/dl). GCAP was performed in 3 RPGN patients and in 1 pulmonary hemorrhage patient. LCAP was performed in 1 RPGN patient. In the 4 RPGN patients, renal function improved after combined therapy with cytapheresis and corticosteroids. In the pulmonary hemorrhage patient, evidence of pulmonary hemorrhage on chest computed tomography scanning diminished after combined therapy with cytapheresis and corticosteroids. Cytapheresis, when combined with a low-dose or intermediate-dose PSL regimen, is effective in the treatment of ANCA-associated vasculitis.     

Pharmacokinetic analysis based on dynamic contrast-enhanced MRI for evaluating tumor response to preoperative therapy for oral cancer

Purpose:

To evaluate whether a pharmacokinetic analysis is useful for monitoring the response of oral cancer to chemoradiotherapy (CRT).

Materials and Methods:

Twenty‐nine patients were included. They underwent dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) before and after CRT. The DCE‐MRI data were analyzed using a Tofts and Kermode (TK) model. The histological evaluation of the effects of CRT was performed according to Ohboshi and Shimosato's classification.

Results:

None of the pre‐CRT parameters were significantly different between the responders and nonresponders. The post‐CRT volume of the extravascular extracellular space (EES) per unit volume of tissue (v_e) of responders (0.397 ± 0.080) was higher than that of nonresponders (0.281 ± 0.076) (P = 0.01). The change of the v_e between the pre‐ and post‐CRT of the responders (0.154 ± 0.093) was larger than that of the nonresponders (0.033 ± 0.073) (P = 0.001). Therefore, the increase in the v_e strongly suggested a good tumor response to CRT, which reflected an increase of the EES secondary to the destruction of the cancer nest. The changes in the volume transfer constant (K^trans) were significantly different between the responders and nonresponders (P = 0.018).

Conclusion:

Both the increase of the v_e and the elevation of permeability (K^trans) were indicative of a good tumor response to CRT. The pharmacokinetic analysis had potential for monitoring the histopathological response to CRT. J. Magn. Reson. Imaging 2012;36:589–597. © 2012 Wiley Periodicals, Inc.     

Receptor binding, behavioral, and electrophysiological profiles of nonpeptide corticotropin-releasing factor subtype 1 receptor antagonists CRA1000 and CRA1001

Receptor binding, behavioral, and electrophysiological profiles of 2-[N-(2-methylthio-4-isopropylphenyl)-N-ethylamino]-4-[4-(3-flu orophe nyl)-1,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine (CRA1000) and 2-[N-(2-bromo-4-isopropylphenyl)-N-ethylamino]-4-[4-(3-fluoropheny l)- 1,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine (CRA1001), putative novel and selective antagonists for corticotropin-releasing factor1 (CRF1) receptor were examined. Both CRA1000 and CRA1001 inhibited 125I-ovine CRF binding to membranes of rat frontal cortex with IC50 values of 20.6 and 22.3 nM, respectively. Likewise, CRA1000 and CRA1001 inhibited 125I-ovine CRF binding to membranes of rat pituitary. In contrast, both CRA1000 and CRA1001 were without affinity for the CRF2beta receptor when examined using rat heart. In mice orally administered CRA1000 and CRA1001 reversed the swim stress-induced reduction of the time spent in the light area in the light/dark exploration task. In nonstress conditions, CRA1000 and CRA1001 were without effect on the time spent in the light area in the same task in mice. Orally administered CRA1000 and CRA1001 dose dependently reversed the effects of i.c.v. infusion of CRF on time spent in the open arms in the elevated plus-maze in rats. Lesioning of olfactory bulbs induced hyperemotionality, and this effect was inhibited by either acute or chronic oral administration of CRA1000 and CRA1001 in rats. The firing rate of locus coeruleus neurons was increased by i.c.v.-infused CRF. This excitation of locus coeruleus neurons was significantly blocked by pretreatment with i.v. administration of CRA1000 and CRA1001. CRA1000 and CRA1001 had no effects on the hexobarbital-induced anesthesia in mice, the rotarod test in mice, the spontaneous locomotor activity in mice, and a passive avoidance task in rats. These observations indicate that both CRA1000 and CRA1001 are selective and competitive CRF1 receptor antagonists with potent anxiolytic- and antidepressant-like properties in various experimental animal models, perhaps through inhibition of CRF1 receptors. CRA1000 and CRA1001 may prove effective for treating subjects with depression- and/or anxiety-related disorders without the side effects seen in the related currently prescribed medications.     

ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)^H46R rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins—inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1^H46R rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1^H46R rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.