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Several drugs have recently been reported to induce rapid antidepressant effects in clinical trials and rodent models. Although the cellular mechanisms involved remain unclear, reports suggest that increased glutamate transmission contributes to these effects. Here, we demonstrate that the antidepressant-like efficacy of three unique drugs, with reported rapid onset antidepressant properties, is coupled with a rapid transient rise in glutamate cycling in the medial prefronal cortex (mPFC) of awake rats as measured by ex vivo1H-[13C]-nuclear magnetic resonance spectroscopy. Rats were acutely pretreated by intraperitoneal injection with a single dose of ketamine (1, 3, 10, 30 and 80 mg kg−1), Ro 25-6981 (1, 3 and 10 mg kg−1), scopolamine (5, 25 and 100 μg kg−1) or vehicle (controls). At fixed times after drug injection, animals received an intravenous infusion of [1,6-13C2]glucose for 8 min to enrich the amino-acid pools of the brain with 13C, followed by rapid euthanasia. The mPFC was dissected, extracted with ethanol and metabolite 13C enrichments were measured. We found a clear dose-dependent effect of ketamine and Ro 25-6981 on behavior and the percentage of 13C enrichment of glutamate, glutamine and GABA (γ-aminobutyric acid). Further, we also found an effect of scopolamine on both cycling and behavior. These studies demonstrate that three pharmacologically distinct classes of drugs, clinically related through their reported rapid antidepressant actions, share the common ability to rapidly stimulate glutamate cycling at doses pertinent for their antidepressant-like efficacy. We conclude that increased cycling precedes the antidepressant action at behaviorally effective doses and suggest that the rapid change in cycling could be used to predict efficacy of novel agents or identify doses with antidepressant activity.

ABSTRACTAnalysis of 1,180 diarrheal stool samples in Zanzibar detected 247 Vibrio choleraeO1, Ogawa strains in 2009. Phenotypic traits and PCR-based detection of rstR, rtxC, and tcpAalleles showed that they belonged to the El Tor biotype. Genetic analysis of ctxBof these strains revealed that they were classical type, and production of classical cholera toxin B (CTB) was confirmed by Western blotting. These strains produced more CT than the prototype El Tor and formed a separate cluster by pulsed-field gel electrophoresis (PFGE) analysis.

ABSTRACTThe incidence of Vibrio choleraenon-O1, non-O139 strains from hospitalized patients with acute diarrhea constituted 27.4% (n= 54) of the total 197 V. choleraestrains isolated from patients in Kolkata, India, in 2003. Of 197 strains, 135 were identified as O1 serotype Ogawa and 2 were identified as O139. In the same time period, six O1 background rough strains that possessed all known virulence factors were identified. Serotype analysis of the non-O1, non-O139 strains placed 42 strains into 19 serogroups, while 12 remained O nontypeable (ONT); the existing serotyping scheme involved antisera to 206 serogroups. Detection of a good number of ONT strains suggested that additional serogroups have arisen that need to be added to the current serotyping scheme. The non-O1, non-O139 strains were nontoxigenic except for an O36 strain (SC124), which regulated expression of cholera toxin as O1 classical strains did. Additionally, strain SC124 carried alleles of tcpAand toxTthat were different from those of the O1 counterpart, and these were also found in five clonally related strains belonging to different serogroups. Strains carrying tcpAexhibited higher colonization in an animal model compared to those lacking tcpA. PCR-based analyses revealed remarkable variations in the distribution of other virulence factors, including hlyA, rtxA, Vibrioseventh pandemic island I (VSP-I), VSP-II, and type III secretion system (TTSS). Most strains contained hlyA(87%) and rtxA(81.5%) and secreted cytotoxic factors when grown in vitro. Approximately one-third of the strains (31.5%) contained the TTSS gene cluster, and most of these strains were more motile and hemolytic against rabbit erythrocytes. Partial nucleotide sequence analysis of the TTSS-containing strains revealed silent nucleotide mutations within vcsN2(type III secretion cytoplasmic ATPase), indicating functional conservation of the TTSS apparatus.

The compound 3-amino-2-quinoxalinecarbonitrile 1,4-dioxide (4) displays potent hypoxia-selective cytotoxicity in cell culture. This compound is structurally similar to the known hypoxia-selective DNA-damaging agent tirapazamine (1, TPZ), but the ability of 4 to cause DNA damage under low-oxygen conditions has not previously been characterized. The results presented here provide the first evidence that 4 causes reductively activated DNA damage under hypoxic conditions. The findings indicate that one-electron reduction of 4 by NADPH:cytochrome P450 reductase yields an oxygen-sensitive intermediate (5). This activated intermediate is rapidly destroyed by reaction with O2 under aerobic conditions, but goes forward to cause DNA damage under low-oxygen conditions. Analysis of the DNA damage indicates that reductive activation of 4 leads to production of a highly reactive, freely diffusible oxidizing radical that causes sequence-independent cleavage of the deoxyribose backbone and oxidative damage to the heterocyclic bases in duplex DNA. On the basis of the experiments reported here, the chemical nature of the DNA damage caused by redox-activated 4 is analogous to that reported previously for TPZ.

Polyethersulfone (PES) ultrafiltration (UF) membranes with and without surface-modifying macromolecules (SMMs) were prepared and characterized in terms of the mean pore size and pore-size distribution, surface porosity, and pore density. The results demonstrated that both the mean pore size and the molecular weight cutoff (MWCO) of the SMM-modified membranes are lower than those of the corresponding unmodified ones. Membrane fouling tests with humic acid as the foulant indicated that the permeate flux reduction of the SMM-modified membranes was much less than that of the unmodified ones. Therefore, fouling was more severe for the unmodified membranes. Moreover, the dry weight of the humic acid deposited on the membrane surface was considerably higher for the unmodified membranes. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 3132–3138, 2003

Surface modifying macromolecules (SMM) were synthesized and blended into the casting solution of poly(ether sulfone). The solution was cast to films with thickness of 0.12 and 0.24 mm. The cast films were placed in an oven with forced air circulation for periods of 3, 5, 7, and 2000 min to remove the solvent, before being immersed into water at 4 °C for gelation. The membranes so prepared were further dried and subjected to contact angle measurement and XPS (X-ray photoelectron spectroscopy) analysis. It was found that the contact angle increased as the solvent evaporation period increased. The increase in contact angle was faster when the membrane was thinner. According to the XPS analysis, after an initial time lag the surface fluorine content increased as the evaporation time increased and finally leveled off. The increase in surface fluorine content was also faster when the membrane was thinner. A kinetic model was established for the SMM surface migration.

Integrally skinned asymmetric flat sheet membranes were prepared from poly(2,6-dimethyl 1,4-phenylene oxide)(PPO) for CO2–CH4 separation. Various experiments were carried out to identify PPO membranes, which have good mechanical strength and gas separation abilities. Membrane strength and selectivity depend on the interplay of the rate of precipitation and the rate of crystallization of the PPO. The effects of major variables involved in the membrane formation and performance, including the concentration of the polymer, solvent, and additive, the casting thickness, the evaporation time before gelation, and the temperature of the polymer solution, were investigated. Factorial design experiments were carried out to identify the factor effects. The membrane performance was modelled and optimized to approach preset values for high CO2 permeance and a high CO2 : CH4 permeance ratio. Membranes were prepared based on the optimum conditions identified by the model. Essentially, defect-free membranes were prepared at these conditions, which resulted in a pure gas permeance of 9.2 × 10⁻⁹ mol/m² s Pa for CO2 and a permeance ratio of 19.2 for CO2 : CH4. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1601–1610, 1999

Heparin inhibitable lectins are physiologically important because of their interactions with extracellular matrix and with other cell surface glycoconjugates. However, due to the unstable nature of these animal lectins, it becomes necessary to purify them in the shortest possible time. In the present study, a chromatographic procedure was developed to separate heparin inhibitable lectin activity.Lectin activities from human foetal brain were separated on a Q-Sepharose column employing different equilibration conditions. When proteins were loaded on to a phosphate-buffered saline (PBS) equilibrated column and eluted with salt gradient, only one lectin peak was obtained. However, when proteins were loaded on to a hypotonic equilibrated column and eluted with a salt gradient, four lectin peaks were obtained.The lectin peak obtained from the PBS equilibrated column was characterized as heparin inhibitable lectin. On SDS–PAGE analysis, it gave a single band of 29 kDa. For optimum lectin activity, a pH of around 7.0 was required. Lectin activity was stimulated by Mn++; amino acid composition was different from other known lectins. The lectin was particularly rich in acidic amino acids.Regional distribution of 29 kDa lectin in different foetal brain regions gave the highest content in the cerebral cortex, showing a caudoroastral distribution. Determination of the subcellular distribution of the lectin in the foetal cerebral cortex gave the highest value with a mitochondrial fraction.

Attempts were made to spin hollow-fiber membranes from poly(vinylidene fluoride) (PVDF) material by the dry–wet phase inversion method. Hollow fibers so prepared were characterized for various parameters and by electron microscopic techniques. Membranes were also tested for the separation of water/1-propanol mixtures in vapor phase. It was found that the hollow fibers were water selective despite the fact that PVDF material is hydrophobic. Intrinsically organic selective property of PVDF material was proved by coating a porous polyetherimide membrane with a PVDF layer, which resulted in enhancement of 1-propanol permeation while suppressing the permeation of water. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 65:1263–1270, 1997

The commercial application of polymer blends is undoubtedly the result of extensive research in this field. However, sometimes poor performance results from incompatibility of components in the blends, which in turn affects processibility. Processing is in large part simply flow and forming of compounds. A major problem often encountered in industry is batch-to-batch variation of viscosity and elastic memory of the compound, two characteristics which largely determine the compound's processability and dimensional stability. Efficient and quality production require reproducibility in the processing stages [1-4]. If a polymer melt is sheared mechanically, it can then be processed in a less elastic and less viscous state provided that the recovery of a more fully entangled, equilibrium state is not too fast [5]. Mechanical shear may reduce entanglement density r6-81. Shear modifications are manifested in changes in viscosities, die swell, die entrance pressure losses, melt fracture, etc. Various methods have also been developed over the years for rheological characterisation of polymer melts (9-17).

Membrane separation characteristics in the nanofiltration (NF) and reverse osmosis (RO) regions of the filtration spectrum are governed by a complex combination of both steric hindrance and surface force interactions. NF and RO membranes having surface charges show unusual selectivity behavior not predicted on the basis of physical pore size alone. Hence, practical characterizations should employ techniques to gain insight on membrane function. In this work, the separation characteristics of an anionically charged modified polyvinyl alcohol (PVA) thin-film composite membrane under different operating pressures were investigated. A qualitative measurement of the surface force interactions between solutes and membrane polymer was conducted using liquid chromatography technique. An attempt was also made to study the chlorine resistance of the composite membrane.

Ein Verfahren zur raschen Bestimmung von Mangan im Bereich von 4–24 mg/50 ml wird beschrieben. Es beruht auf der quantitativen Oxydation von Mn(II) zu Mn(III) mit Dichromat in 8,0–9,0 M phosphorsaurer Lösung bei Raumtemperatur. Die Störmöglichkeiten sind geringer als bei sonst üblichen Methoden. Das Verfahren wurde mit Erfolg zur Manganbestimmung in Erzen und Legierungen angewendet und gute Übereinstimmung mit Standardmethoden erzielt. Es wird für die schnelle Routineanalyse empfohlen.