Involvement of Calcium-Mediated Reactive Oxygen Species in Inductive GRP78 Expression by Geldanamycin in 9L Rat Brain Tumor Cells

Treatment with geldanamycin (GA) leads to an increase in [Ca²⁺]_c and the production of reactive oxygen species (ROS) in rat brain tumor 9L RBT cells. GA-exerted calcium signaling was blocked by BAPTA/AM and EGTA. The effect of GA on [Ca²⁺]_c was significantly reduced in the presence of thapsigargin (TG) and ruthenium red (RR). GA-induced GRP78 expression is significantly decreased in the presence of BAPTA/AM, EGTA and RR, suggesting that the calcium influx from the extracellular space and intracellular calcium store oscillations are contributed to by the calcium mobilization and GRP78 expression induced by GA. The induced GRP78 expression is sensitive to added {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 and Ro-31-8425, pinpointing the involvement of phospholipase C (PLC) and protein kinase C (PKC) in GA-induced endoplasmic reticulum (ER) stress. The antioxidants N-acetylcysteine (NAC), BAPTA/AM, EGTA and H7 also have significant inhibitory effects on ROS generation. Finally, neither H7 nor NAC was able to affect the calcium response elicited by GA. Our results suggest that the causal signaling cascade during GA-inducted GRP78 expression occurs via a pathway that connects PLC to cytoplasmic calcium increase, PKC activation and, then, finally, ROS generation. Our data provides new insights into the influence of GA on ER stress response in 9L RBT cells.     

Chitosan tablets for controlled release of theophylline: Effect of polymer—drug wet or dry blending and anionic—cationic interpolymer complex

Chitosan tablets containing theophylline were prepared by directly compressing the wet or dry blended polymer—drug powders. The effects of the viscosity and swelling ability on the release rates of drugs were examined. The theophylline releasing rates of tablets prepared by polymer—drug wet blending increase with a decrease in the viscosity of the blending chitosan solution. On the other hand, the swelling ability of the polymer greatly influences the release kinetics of the tablets prepared by polymer—drug dry blending. Tablets prepared by both polymer—drug wet and dry blending were acid-nonresisted. Tablets in simulated gastric fluid disintegrated quickly, and the drugs were released within four hours. To retard the disintegrated rate of chitosan tablets in acid medium, interpolymer complex of chitosan with anionic polyelectrolyte (alginate) is needed. By this treatment, the swelling and erosion rate of the chitosan tablets could be reduced, then controlling the release rate of the theophylline can be achieved. Drug release mechanism of the various tablets were investigated by the model of Peppas; in addition, a nuclear magnetic resonance imagine microscopy is also introduced to examine the swelling or diffusion mechanism of various tablets. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 2495–2505, 1997     

Multiple Sequence Alignment with Evolutionary Computation

In this paper we provide a brief review of current work in the area of multiple sequence alignment (MSA) for DNA and protein sequences using evolutionary computation (EC). We detail the strengths and weaknesses of EC techniques for MSA. In addition, we present two novel approaches for inferring MSA using genetic algorithms. Our first novel approach utilizes a GA to evolve an optimal guide tree in a progressive alignment algorithm and serves as an alternative to the more traditional heuristic techniques such as neighbor-joining. The second novel approach facilitates the optimization of a consensus sequence with a GA using a vertically scalable encoding scheme in which the number of iterations needed to find the optimal solution is approximately the same regardless the number of sequences being aligned. We compare both of our novel approaches to the popular progressive alignment program Clustal W. Experiments have confirmed that EC constitutes an attractive and promising alternative to traditional heuristic algorithms for MSA.     

Common-path optical heterodyne profilometer: a configuration

A novel configuration that combines a linearly polarized He-Ne laser and a birefringent lens to produce a common-path polarized optical heterodyne profilometer with respect to the heterodyned P and S waves has been set up. In this profilometer a linear polarized frequency-stabilized He-Ne laser was used with an acousto-optical modulator to replace the Zeeman laser as the light source that had two polarization eigenstates in different temporal frequencies. The proposed interferometer shows a more symmetric and ideal common-path structure than the conventional optical heterodyne profilometers with the Zeeman laser. The phase error aroused by the elliptical polarization and the nonorthogonality of the two eigenpolarization modes of the Zeeman laser can be reduced. The system's resolution in the vertical direction reaches 2 A, and in a 27-mum scanning range the repeatability of the surface profile measurements is shown to be 5 A.     

Biotransformation of irbesartan in man

The metabolism of irbesartan, a highly selective and potent nonpeptide angiotensin II receptor antagonist, has been investigated in humans. An aliquot of pooled urine from healthy subjects given a 50-mg oral dose of [14C]irbesartan was added as a tracer to urine from healthy subjects that received multiple, 900-mg nonradiolabeled doses of irbesartan. Urinary metabolites were isolated, and structures were elucidated by mass spectroscopy, proton NMR, and high-performance liquid chromatography (HPLC) retention times. Irbesartan and the following eight metabolites were identified in human urine: (1) a tetrazole N2-beta-glucuronide conjugate of irbesartan, (2) a monohydroxylated metabolite resulting from omega-1 oxidation of the butyl side chain, (3, 4) two different monohydroxylated metabolites resulting from oxidation of the spirocyclopentane ring, (5) a diol resulting from omega-1 oxidation of the butyl side chain and oxidation of the spirocyclopentane ring, (6) a keto metabolite resulting from further oxidation of the omega-1 monohydroxy metabolite, (7) a keto-alcohol resulting from further oxidation of the omega-1 hydroxyl of the diol, and (8) a carboxylic acid metabolite resulting from oxidation of the terminal methyl group of the butyl side chain. Biotransformation profiles of pooled urine, feces, and plasma samples from healthy male volunteers given doses of [14C]irbesartan were determined by HPLC. The predominant drug-related component in plasma was irbesartan (76-88% of the plasma radioactivity). None of the metabolites exceeded 9% of the plasma radioactivity. Radioactivity in urine accounted for about 20% of the radiolabeled dose. In urine, irbesartan and its glucuronide each accounted for about 5 to 10% of the urinary radioactivity. The predominant metabolite in urine was the omega-1 hydroxylated metabolite, which constituted about 25% of the urinary radioactivity. In feces, irbesartan was the predominant drug-related component (about 30% of the radioactivity), and the primary metabolites were monohydroxylated metabolites and the carboxylic acid metabolite. Irbesartan and these identified metabolites constituted 90% of the recovered urinary and fecal radioactivity from human subjects given oral doses of [14C]irbesartan.     

A method to reduce response times in prehospital care: the motorcycle experience

This study compared the response times of a motorcycle and a standard ambulance in a congested urban emergency medical services (EMS) setting. The study was performed in Taipei, Taiwan, a densely populated urban area. A basic life support (BLS) motorcycle (without defibrillation capability) and an advanced life support (ALS) ambulance were based at three study hospitals and simultaneously dispatched when there was a perceived need for ALS ambulance transport. Over a 3-month period, prehospital personnel evaluated 307 medical and trauma emergencies. Time data were insufficient for analysis in 33 cases, leaving a study population of 274. Response times of the motorcycle and the ambulance were prospectively assessed and compared. During rush hours, the response times of the motorcycle and ambulance were 4.9+/-3.0 minutes and 6.3+/-3.4 minutes (P < .05), respectively, and in non-rush hours, 4.2+/-2.1 minutes and 5.1+/-2.5 minutes (P < .05), respectively. Using motorcycles to transport EMTs to the emergency scene significantly reduced response time compared with a standard ambulance in a congested urban setting. Large prospective studies are required to determine the impact on patient outcome of shorter EMS response times using motorcycles. EMS motorcycles appear feasible and deserve consideration to help expedite prehospital care in other systems in densely populated cities.     

Lack of pharmacokinetic interaction between butorphanol nasal spray and cimetidine

To study the immune response within the subarachnoid space in patients with neurocysticercosis, we measured the cerebrospinal fluid contents of immunoglobulins A, E, G, and M in 38 patients and the contents of the proinflammatory cytokines TNF-alpha, IL-1b, IL-6 and IFN-gamma in 17 patients. The same measurements were made in 30 neurological patients without inflammatory or immune-mediated disorders. Each immunoglobulin and cytokine, including the gender and age of the patient, was compared by multiple regression analysis with the CSF contents of cells, protein and ELISA for cysticercal antigens. A direct correlation was found of IgM with cell content (p < 0.058) and with ELISA values (p < 0.027); of age with protein content (p < 0.006); of IL-6 with protein content (p < 0.018) and of IL-1b with ELISA values (p < 0.004). An inverse correlation was found of glucose with ELISA values (p < 0.008). A complex function of the immune response within the subarachnoid space was observed: mean values of IgG, IgM, IgE and interleukins 1b and 6 were increased, whereas values of IgA, TNF-alpha and IFN-gamma were similar to those of controls.     

Rule mining and classification in a situation assessment application: a belief-theoretic approach for handling data imperfections.

Management of data imprecision and uncertainty has become increasingly important, especially in situation awareness and assessment applications where reliability of the decision-making process is critical (e.g., in military battlefields). These applications require the following: 1) an effective methodology for modeling data imperfections and 2) procedures for enabling knowledge discovery and quantifying and propagating partial or incomplete knowledge throughout the decision-making process. In this paper, using a Dempster-Shafer belief-theoretic relational database (DS-DB) that can conveniently represent a wider class of data imperfections, an association rule mining (ARM)-based classification algorithm possessing the desirable functionality is proposed. For this purpose, various ARM-related notions are revisited so that they could be applied in the presence of data imperfections. A data structure called belief itemset tree is used to efficiently extract frequent itemsets and generate association rules from the proposed DS-DB. This set of rules is used as the basis on which an unknown data record, whose attributes are represented via belief functions, is classified. These algorithms are validated on a simplified situation assessment scenario where sensor observations may have caused data imperfections in both attribute values and class labels.