The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma

AbstractTo test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity

Microlensing Detections of Planets in Binary Stellar Systems

We demonstrate that microlensing can be used for detecting planets in binary stellar systems. This is possible because in the geometry of planetary binary systems where the planet orbits one of the binary component and the other binary star is located at a large distance, both planet and secondary companion produce perturbations at a common region around the planet-hosting binary star and thus the signatures of both planet and binary companion can be detected in the light curves of high-magnification lensing events. We find that identifying planets in binary systems is optimized when the secondary is located in a certain range which depends on the type of the planet. The proposed method can detect planets with masses down to one tenth of the Jupiter mass in binaries with separations <~ 100 AU. These ranges of planet mass and binary separation are not covered by other methods and thus microlensing would be able to make the planetary binary sample richer.Comment: 5 pages, two figures in JPG forma

Clinical Comparison of the Auditory Steady-State Response with the Click Auditory Brainstem Response in Infants

ObjectivesOur goal was to determine the effectiveness of using the auditory steady state response (ASSR) as a measure of hearing thresholds in infants who are suspected of having significant hearing loss, as compared with using the click-auditory brainstem response (C-ABR).MethodsWe retrospectively analyzed the audiologic profiles of 76 infants (46 boys and 30 girls, a total of 151 ears) who ranged in age from 1 to 12 months (average age: 5.7 months). The auditory evaluations in 76 infants who were suspected of having hearing loss were done via the C-ABR and ASSR. In addition, for reference, the mean ASSR thresholds were compared to those of 39 ears of infants and 39 ears of adults with normal hearing at 0.5, 1, 2, and 4 kHz.ResultsThe highest correlation between the C-ABR and ASSR thresholds was observed at an average of 2-4 kHz (r=0.94). On comparison between the hearing of infants and adults at 0.5, 1, 2, and 4 kHz, the mean ASSR threshold in infants was 12, 7, 8, and 7 dB higher, respectively, than that in adults.ConclusionASSR testing may provide additional audiometric information for accurately predicting the hearing sensitivity, and this is essential for the management of infants with severe to profound hearing loss

The impact of sagittal balance on clinical results after posterior interbody fusion for patients with degenerative spondylolisthesis: A Pilot study

<p>Abstract</p> <p>Background</p> <p>Comparatively little is known about the relation between the sagittal vertical axis and clinical outcome in cases of degenerative lumbar spondylolisthesis. The objective of this study was to determine whether lumbar sagittal balance affects clinical outcomes after posterior interbody fusion. This series suggests that consideration of sagittal balance during posterior interbody fusion for degenerative spondylolisthesis can yield high levels of patient satisfaction and restore spinal balance</p> <p>Methods</p> <p>A retrospective study of clinical outcomes and a radiological review was performed on 18 patients with one or two level degenerative spondylolisthesis. Patients were divided into two groups: the patients without improvement in pelvic tilt, postoperatively (Group A; n = 10) and the patients with improvement in pelvic tilt postoperatively (Group B; n = 8). Pre- and postoperative clinical outcome surveys were administered to determine Visual Analogue Pain Scores (VAS) and Oswestry disability index (ODI). In addition, we evaluated full spine radiographic films for pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), sacrofemoral distance (SFD), and sacro C7 plumb line distance (SC7D)</p> <p>Results</p> <p>All 18 patients underwent surgery principally for the relief of radicular leg pain and back pain. In groups A and B, mean preoperative VAS were 6.85 and 6.81, respectively, and these improved to 3.20 and 1.63 at last follow-up. Mean preoperative ODI were 43.2 and 50.4, respectively, and these improved to 23.6 and 18.9 at last follow-up. In spinopelvic parameters, no significant difference was found between preoperative and follow up variables except PT in Group A. However, significant difference was found between the preoperative and follows up values of PT, SS, TK, LL, and SFD/SC7D in Group B. Between parameters of group A and B, there is borderline significance on preoperative PT, preoperative LL and last follow up SS.</p> <p>Correlation analysis revealed the VAS improvements in Group A were significantly related to postoperative lumbar lordosis (Pearson's coefficient = -0.829; p = 0.003). Similarly, ODI improvements were also associated with postoperative lumbar lordosis (Pearson's coefficient = -0.700; p = 0.024). However, in Group B, VAS and ODI improvements were not found to be related to postoperative lumbar lordosis and to spinopelvic parameters.</p> <p>Conclusion</p> <p>In the current series, patients improving PT after fusion were found to achieve good clinical outcomes in degenerative spondylolisthesis. Overall, our findings show that it is important to quantify sagittal spinopelvic parameters and promote sagittal balance when performing lumbar fusion for degenerative spondylolisthesis.</p

Analysis of the predictive role and new proposal for surgical strategies based on the modified Tomita and Tokuhashi scoring systems for spinal metastasis

BACKGROUND: We sought to identify preoperative factors significantly correlated with survival. We also aimed to evaluate the validity of the prognostic scores in the Tomita and Tokuhashi systems and discuss several aspects to improve the predictive accuracy of these systems. Moreover, we suggest modified criteria for selecting treatment strategies. METHODS: In total, the outcomes of 112 patients with spinal metastasis who underwent surgery between January 2006 and June 2011 were retrospectively reviewed. The validity of the prognostic scores was assessed on the basis of their correlation with survival. For various primary malignancies, new scoring criteria were applied in each system according to the survival results obtained in this study. Each revised scoring system was adjusted with a similar principle of scoring as described previously. Patient survival according to each preoperative factor was analyzed by the Kaplan-Meier method. The predictive value of each scoring system was evaluated by the log-rank test and Cox regression analysis. RESULTS: The interval from the diagnosis of the primary malignancy to that of spinal metastasis (p = 0.023) and the interval from the diagnosis of spinal metastasis to surgery (p = 0.039) were significantly correlated with survival. Regarding Tokuhashi scores, the correlation coefficient was 0.790 before adjustment (p = 0.001) and 0.853 after adjustment (p < 0.001). For Tomita scores, the correlation coefficient was -0.994 (p < 0.001) both before and after adjustment. CONCLUSIONS: Tomita scores more accurately predicted survival than Tokuhashi scores. It is helpful to evaluate both scoring systems with adjustment for primary malignancy depending on the clinical setting. Patients with Tomita scores less than or equal to 8 and Tokuhashi scores greater than or equal to 6 are recommended to undergo surgical management

Targeted delivery of bleomycin to the brain using photo-chemical internalization of Clostridium perfringens epsilon prototoxin

Cells infiltrating into normal brain from malignant brain tumors are protected by the blood brain barrier (BBB) which prevents the delivery and limits the effects of anti-tumor agents. We have evaluated the ability of photochemical internalization (PCI) to limit the effects of an agent known to broadly open the BBB to a target region of the brain. The PCI-based relocation and activation of macromolecules into the cell cytosol has the advantage of minimal side effects since the effect is localized to the area exposed to light, allowing the access of chemotherapeutic agents only to these regions. Non tumor bearing inbred Fisher rats were treated with photosesitizer, and a nontoxic intraperitoneal dose of Clostridium perfringens epsilon prototoxin (ETXp) followed by light exposure. Post-contrast T1 MRI scans were used to monitor the degree BBB disruption. F98 tumor cells were implanted into the brains of other animals that were subsequently treated 24 h later with ETXp-PCI BBB opening followed by the i.p. administration of bleomycin (BLM). PCI delivery of ETXp at low fluence levels demonstrated significant MRI enhancement. No effect on the BBB was observed if photosesitizer and light was given in the absence ETXp. The survival of animals implanted with F98 tumor cells was significantly extended following ETXp-PCI BBB opening and BLM therapy compared to controls. PCI delivered ETXp was effective in opening the BBB in a limited region of the brain. ETXp-PCI mediated BBB opening clearly increased the efficacy of BLM therapy

Kinematics and excitation of the ram pressure stripped ionized gas filaments in the Coma cluster of galaxies

We present the results of deep imaging and spectroscopic observations of very extended ionized gas (EIG) around four member galaxies of the Coma cluster of galaxies: RB199, IC4040, GMP2923 and GMP3071. The EIGs were serendipitously found in an H-alpha narrow band imaging survey of the central region of the Coma cluster. The relative radial velocities of the EIGs with respect to the systemic velocities of the parent galaxies from which they emanate increase almost monotonically with the distance from the nucleus of the respective galaxies, reaching -400 - -800 km/s at around 40 - 80 kpc from the galaxies. The one-sided morphologies and the velocity fields of the EIGs are consistent with the predictions of numerical simulations of ram pressure stripping. We found a very low-velocity filament (v_rel = -1300 km/s) at the southeastern edge of the disk of IC4040. Some bright compact knots in the EIGs of RB199 and IC4040 exhibit blue continuum and strong H-alpha emission. The equivalent widths of the H-alpha emission exceed 200 A, and are greater than 1000 A for some knots. The emission line intensity ratios of the knots are basically consistent with those of sub-solar abundance HII regions. These facts indicate that intensive star formation occurs in the knots. Some filaments, including the low velocity filament of the IC4040 EIG, exhibit shock-like emission line spectra, suggesting that shock heating plays an important role in ionization and excitation of the EIGs.Comment: Accepted for publication in The Astrophysical Journal. 14 pages, 23 figures, emulateapj forma

Little Response of Cerebral Metastasis from Hepatocellular Carcinoma to Any Treatments

Objective : We retrospectively evaluated the survival outcome of patients with brain metastasis from hepatocellular carcinoma (HCC). Methods : Between 1991 and 2007, a total of 20 patients were diagnosed as having brain metastasis from HCC. The mean age of the patients was 55 +/- 13 years, and 17(85.0%) were men. Seventeen (85.0%) patients had already extracranial metastases. The median time from diagnosis of HCC to brain metastasis was 18.5 months. Fourteen (70.0%) patients had stroke-like presentation due to intracerebral hemorrhage (ICH). Ten (50.0%) patients had single or solitary brain metastasis. Among a total of 34 brain lesions, 31 (91.2%) lesions had the hemorrhagic components. Results : The median survival time was 8 weeks (95% Cl, 5.08-10.92), and the actuarial survival rates were 85.0%, 45.0%, 22.5%, and 8.4% at 4, 12, 24, and 54 weeks. Age < 60 years, treatment of the primary and/or extracranial lesions, and recurrent ICH were the possible prognostic factors (p = 0.044, p < 0.001, and p = 0.111, respectively). The median progression-free survival (PFS) time was 3 months (95% Cl, 0.95-5.05). Conclusion : The overall survival of the patients with brain metastasis from HCC was very poor with median survival time being only 8 weeks. However, the younger patients less than 60 years and/or no extracranial metastases seem to be a positive prognostic factor.Choi HJ, 2009, J NEURO-ONCOL, V91, P307, DOI 10.1007/s11060-008-9713-3Kim SR, 2006, WORLD J GASTROENTERO, V12, P6727Seinfeld J, 2006, J NEURO-ONCOL, V76, P93, DOI 10.1007/s11060-005-4175-3Cho DC, 2005, J CLIN NEUROSCI, V12, P699, DOI 10.1016/j.jocn.2004.08.026Chang L, 2004, SURG NEUROL, V62, P172, DOI 10.1016/j.surneu.2003.10.002Del Ben M, 2003, J EXP CLIN CANC RES, V22, P641El-Serag HB, 2002, J CLIN GASTROENTEROL, V35, pS72SALVATI M, 2002, J NEUROSURG SCI, V46, P77McIver JI, 2001, NEUROSURGERY, V49, P447Hayashi K, 2000, SURG NEUROL, V53, P379El-Serag HB, 1999, NEW ENGL J MED, V340, P745Peres MFP, 1998, ARQ NEURO-PSIQUIAT, V56, P658Deuffic S, 1998, LANCET, V351, P214Kim M, 1998, J NEURO-ONCOL, V36, P85TaylorRobinson SD, 1997, LANCET, V350, P1142Gaspar L, 1997, INT J RADIAT ONCOL, V37, P745LUCEY MR, 1997, LIVER TRANSPLANT SUR, V3, P628Murakami K, 1996, NEURORADIOLOGY, V38, pS31PATCHELL RA, 1990, NEW ENGL J MED, V322, P494OTSUKA S, 1987, NEUROL MED CHIR TOKY, V27, P654OKEN MM, 1982, AM J CLIN ONCOL-CANC, V5, P649PUGH RNH, 1973, BRIT J SURG, V60, P646