bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensional relationships between perisynaptic astroglia and human hippocampal synapses
Authors: Witcher Mark R. , Park Yong D. , Lee Mark R. , Sharma Suash , Harris Kristen M. , Kirov Sergei A.
Published: November 2009

Perisynaptic astroglia are critical for normal synaptic development and function. Little is known, however, about perisynaptic astroglia in the human hippocampus. When mesial temporal lobe epilepsy (MTLE) is refractory to medication, surgical removal is required for seizure quiescence. To investigate perisynaptic astroglia in human hippocampus, we recovered slices for several hours in vitro from three surgical specimens and then quickly fixed them to achieve high‐quality ultrastructure. Histological samples from each case were found to have mesial temporal sclerosis with Blumcke Type 1a (mild, moderate) or 1b (severe) pathology. Quantitative analysis through serial section transmission electron microscopy in CA1 stratum radiatum revealed more synapses in the mild (10/10 μm3) than the moderate (5/10 μm3) or severe (1/10 μm3) cases. Normal spines occurred in mild and moderate cases, but a few multisynaptic spines were all that remained in the severe case. Like adult rat hippocampus, perisynaptic astroglial processes were preferentially associated with larger synapses in the mild and moderate cases, but rarely penetrated the cluster of axonal boutons surrounding multisynaptic spines. Synapse perimeters were only partially surrounded by astroglial processes such that all synapses had some access to substances in the extracellular space, similar to adult rat hippocampus. Junctions between astroglial processes were observed more frequently in moderate than mild case, but were obscured by densely packed intermediate filaments in astroglial processes of the severe case. These findings suggest that perisynaptic astroglial processes associate with synapses in human hippocampus in a manner similar to model systems and are disrupted by severe MTLE pathology. © 2009 Wiley‐Liss, Inc.
Leukotriene synthases and the receptors induced by peripheral nerve injury in the spinal cord contribute to the generation of neuropathic pain
Authors: Okubo Masamichi , Yamanaka Hiroki , Kobayashi Kimiko , Noguchi Koichi
Published: November 2009

Leukotrienes (LTs) belong to a large family of lipid mediators, termed eicosanoids, which are derived from arachidonic acids and released from the cell membrane by phospholipases. LTs are involved in the pathogenesis of inflammatory diseases, such as asthma, rheumatoid arthritis, and peripheral inflammatory pain. In the present study, we examined whether LTs were implicated in pathomechanism of neuropathic pain following peripheral nerve injury. Using the spared nerve injury (SNI) model in rats, we investigated the expression of LT synthases (5‐lipoxygenase; 5‐LO, Five lipoxygenase activating protein; FLAP, LTA4 hydrolase; LTA4h and LTC4 synthase; LTC4s) and receptors (BLT1, 2 and CysLT1, 2) mRNAs in the rat spinal cord. Semi‐quantitative RT‐PCR revealed that 5‐LO, FLAP, LTC4s, BLT1, and CysLT1 mRNAs increased following SNI, but not CysLT2 mRNAs. Using double labeling analysis of in situ hybridization with immunohistochemistry, we observed that 5‐LO, FLAP, and CysLT1 mRNAs were expressed in spinal microglia. LTA4h and LTC4s mRNAs were expressed in both spinal neurons and microglia. BLT1 mRNA was expressed in spinal neurons. The p38 mitogen‐activated protein kinase inhibitor, but not MEK inhibitor, reduced the increase in 5‐LO in spinal microglia. Continuous intrathecal administration of the 5‐LO inhibitor or BLT1 and CysLT1 receptor antagonists suppressed mechanical allodynia induced by SNI. Our findings suggest that the increase of LT synthesis in spinal microglia produced via p38 MAPK plays a role in the generation of neuropathic pain. © 2009 Wiley‐Liss, Inc.
Toll‐like receptor agonists as third signals for dendritic cell–tumor fusion vaccines
Authors: Cho Edward I. , Tan Chunrui , Koski Gary K. , Cohen Peter A. , Shu Suyu , Lee Walter T.
Published: November 2009

Background

The aim of the present study was to evaluate the therapeutic efficacy of dendritic cell (DC)–tumor fusion hybrids with Toll‐like receptor (TLR) agonists.

Methods

DC–tumor fusion hybrids were generated by electrofusion and injected into the inguinal lymph nodes of C57BL/6 mice with 3‐day established pulmonary metastases. Paired TLR agonists polyinosine:polycytadilic acid [poly(I:C)] and cytosine–phosphate–guanine (CpG) were then injected intraperitoneally. Enzyme‐linked immunosorbent assay (ELISA) was used to evaluate interleukin (IL)‐12 production from the DC–tumor fusion hybrids in vitro.

Results

Fusion + TLR agonists (60 metastases) had significantly fewer metastases than did the untreated control (262 metastases, p = .0001) and fusion alone (150 metastases, p = .02). ELISA showed that the DC–tumor fusion hybrids yielded 90 pg of IL‐12 after TLR stimulation compared with 1610 pg from dendritic cells alone.

Conclusions

CpG and poly(I:C) administered as a third signal with fusion hybrids as described significantly reduce melanoma metastasis compared with fusion hybrids alone. Fusion hybrids do not appear to be a significant source for IL‐12 secretion. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Widespread expression of prostate apoptosis response‐4 in nasopharyngeal carcinoma
Authors: Lee Jeng‐Woei , Hsiao Wei‐Ting , Lee Kuei‐Fang , Sheu Lai‐Fa , Hsu Hsue‐Yin , Hsu Lee‐Ping , Su Borcherng , Lee Moon‐Sing , Hsu Yih‐Chih , Chang Chung‐Hsing
Published: November 2009

Background.

Prostate apoptosis response‐4 (Par‐4) augments apoptosis in various tumors, either during apoptotic insult or by ectopic overexpression. However, investigation of Par‐4 expression in nasopharyngeal carcinoma (NPC) is lacking.

Methods.

Specimens from patients with NPC, hypopharyngeal carcinoma (HPC), or oral cavity cancer were examined for Par‐4 expression using immunohistochemistry. NPC cell proliferation and apoptosis were analyzed using immunohistochemical staining for Ki67, B‐cell lymphoma 2 (Bcl‐2), and in situ terminal deoxyribonucleotidyl transferase (TdT)–mediated biotin‐16‐dUTP nick end‐labeling (TUNEL) assay, respectively.

Results.

Par‐4 was ubiquitously expressed in NPC biopsies (96.2%, 25/26) and was significantly higher than in HPC (47.6%, 50/105, p < .0001) and oral cavity cancers (38.7%, 12/31, p < .0001). Remarkably, apoptosis of NPC cells was absent and Par‐4 expression was associated with obvious expression of Bcl‐2 and Ki67 in all patients tested with NPC.

Conclusions.

Immunohistochemistry results showed widespread expression of Par‐4 in NPC and revealed sustainable proliferation of NPC cells regardless of Par‐4 expression.© 2009 Wiley Periodicals, Inc. Head Neck, 2010
Cx3cl1 (Fractalkine): A Signpost for Biliary Inflammation in Primary Biliary Cirrhosis
Authors: Shimoda Shinji , Harada Kenichi , Niiro Hiroaki , Taketomi Akinobu , Maehara Yoshihiko , Tsuneyama Koichi , Kikuchi Kentaro , Nakanuma Yasuni , Mackay Ian R. , Gershwin Eric M. , Akashi Koichi
Published: November 2009

Improvements in the treatment of primary biliary cirrhosis (PBC) may depend upon dissection of mechanisms that determine recruitment of mononuclear cells to intralobular bile ducts, including the role of the chemokine-adhesion molecule CX3CL1 (fractalkine). We submit that there are unique interactions between intrahepatic biliary epithelial cells (BECs), endothelial cells (ECs), liver sinusoidal endothelial cells (LSECs), and liver-infiltrating mononuclear cells (LMCs), and that such interactions will in part dictate the biliary-specific inflammatory response. To address this, we studied fresh explanted livers from pretransplantation patients with PBC and with inflammatory liver disease due to viral infection (disease controls) and biopsy material from patients with a discrete liver tumor (normal controls). Using this clinical material, we isolated and stimulated BECs, ECs, LSECs, and LMCs with a panel of Toll-like receptor ligands. We also studied the interactions of these cell populations with LMCs with respect to adhesion capability and production of tumor necrosis factor α (TNF-α). Finally, we used fresh biopsy samples to evaluate mononuclear cells around intrahepatic biliary ductules using monoclonal antibodies specific to CD68 or CD154, markers for monocytes/macrophages, and activated T cells, respectively.

Conclusion:

There are common properties of ECs, LSECs, and BECs, whether derived from PBC or viral hepatitis, but there are also significant differences, particularly in the potential in PBC for LMCs to adhere to ECs and BECs and to produce TNF-α; such properties were associated with augmented CX3CL1 production by BEC from PBC liver. The processes defined herein suggest potential novel biotherapies for biliary specific inflammation. (Hepatology 2009.)
An event history approach to the evaluation of training, recruitment and employment programmes
Authors: Ridder G.
Published: November 2009

In this paper I evaluate a number of training, recruitment and employment programmes. The evaluation method is a combination of a quasi‐experimental design (a simple pre‐treatment‐post‐treatment design) and a stochastic process model to describe the response variables. I conclude that the programmes have no effect on older workers. Female and minority workers benefit most from the programmes. The training programmes are less effective than the recruitment programmes, which are in turn less effective than the employment programmes.
Exact inference in the inequality constrained normal linear regression model
Authors: Geweke John
Published: November 2009

Inference in the inequality constrained normal linear regression model is approached as a problem in Bayesian inference, using a prior that is the product of a conventional uninformative distribution and an indicator function representing the inequality constraints. The posterior distribution is calculated using Monte Carlo numerical integration, which leads directly to the evaluation of expected values of functions of interest. This approach is compared with others that have been proposed. Three empirical examples illustrate the utility of the proposed methods using an inexpensive 32‐bit microcomputer.
Forecasting with an econometric model: Some recent results using the national institute model
Authors: Hall S. G. , Henry S. G. B. , Johns C. B.
Published: November 2009

It is widely believed that the large econometric models cannot be used for forecasting without considerable intervention on the part of the forecaster. In this paper we challenge this view by reproducing a number of recent forecasts published by the National Institute but without the ad hoc interventions used at the time. We show that in no case would the forecast, produced by the model used mechanically, have been radically different from that actually published. Further, in an ex‐post comparison against actual out‐turns, the mechanical model forecast is not obviously dominated by the published version.
Commodity and asset demands with and without quantity constraints in the labour market
Authors: Bronsard Camille , Salvas‐Bronsard Lise
Published: November 2009

This paper reformulates the consumer's decision‐making problem in a temporary framework with and without quantity constraints in the labour market in such a way as to define a complete demand system which includes consumption, labour and saving. Then, based on American and Canadian data (1948–1980), this extended complete demand system is estimated using a priori theoretical properties. Quantity constraints in the labour market cannot be rejected, and marginal propensities to consume out of labour income are very different from the marginal propensities out of non‐labour income. Temporal separability is rejected and Slutsky conditions are preserved.
Capital utilization and capital accumulation: Theory and evidence
Authors: Shapiro Matthew D.
Published: November 2009

A firm may acquire additional capital input by purchasing new capital or by increasing the utilization of its current capital. The margin between capital accumulation and capital utilization is studied in a model of dynamic factor demand where the firm chooses capital, labour and their rates of utilization. A direct measure of capital utilization‐the work week of capital‐is incorporated into the theory and estimates. The estimates imply that capital stock is costly to adjust while the work week of capital is essentially costless to adjust. The estimated response of the capital stock to changes in its price and in the required rate of return is more rapid than found in other estimates.
Unemployment, disequilibrium and the short run phillips curve: An econometric approach
Authors: Quandt Richard E. , Rosen Harvey S.
Published: November 2009

The paper specifies a disequilibrium model for the aggregate labour market consisting of demand and supply functions for labour, an adjustment equation for wages as well as for prices, a transactions equation and, finally, an equation that relates measured unemployment to vacancies and to excess demand. The model has a more sophisticated treatment of dynamics than earlier disequilibrium models. The parameter estimates and the goodness‐of‐fit are satisfactory and the model's implications for the behaviour of several important variables are sensible. In particular, excess demand estimates computed in various ways are reasonable.
The role of fiscal policy in the St. Louis model: An evaluation and some new evidence
Authors: Raj Baldev , Siklos Pierre L.
Published: November 2009

This paper re‐examines the role of high employment budget expenditures (fiscal policy) in the St. Louis expenditure equation by using spectral analysis and the spectral estimates of a two‐sided distributed lag model. The analysis is undertaken with quarterly U.S. data from 1947:1 to 1984:IV in the rate of change form. A salient conclusion is that fiscal policy has statistically significant partial coherences with (nominal) income, with the latter leading the former over the business cycle. We find that income is jointly related to lead terms of fiscal policy in a two‐sided distributed lag model. Some explanations for these results are provided.
Postthaw clotting of peripheral blood stem cell products due to insufficient anticoagulant
Authors: Reich‐Slotky Ronit , Patel Nita , Dael Shatrina , Semidei‐Pomales Mildred , Stephens Hannah , Reich Michael , Schwartz Joseph
Published: November 2009

The amount of acid citrate dextrose formula A (ACD‐A), which is a commonly used anticoagulant in leukopheresis, has to ensure both the safety of the donor and guarantee the integrity of the peripheral blood stem cell (PBSC) product until its transplant. Two recent consecutive cases of postthaw PBSC product clotting initiated a look‐back investigation of the ACD‐A percentage in leukopheresis products collected in our facility. The data indicated a significant difference between the average amount of ACD‐A in prefreezing products collected during 2006 (11.4%) and in products collected during 2007 and 2008 (8.8% and 8.7%, respectively). These findings and the fact that the two clotted products had less than 7% ACD‐A indicated that insufficient amount of anticoagulant might contribute to their clotting. This investigation prompted us to modify our collection and thawing procedures to prevent similar events in the future. J. Clin. Apheresis 2009. © 2009 Wiley‐Liss, Inc.
Feasibility and safety of triple dose platelet collection by apheresis
Authors: Moog Rainer
Published: November 2009

Background:

Blood cell separators of the newest generation allow for the collection of high‐dose platelet concentrates. The aim of this study was to evaluate triple dose platelet collection with respect to feasibility and safety.

Materials and Methods:

Four hundred eighty plateletphereses were performed targeting to collect a triple platelet dose. Platelet counts were performed before and after apheresis and in platelet concentrates. Furthermore, donors were monitored for adverse events.

Results:

Triple dose platelet collection was achieved in 96% according to European and national guidelines. Mean donor platelet count before apheresis was 303 ± 64/nl and decreased to 195 ± 48/nl after plateletpheresis. The lowest platelet count after apheresis was 111/nl. Twenty‐one donor adverse events were observed (4.4%).

Conclusions:

Triple dose platelet collection is feasible and safe provided that donors are carefully checked for triple dose eligibility. J. Clin. Apheresis 2009. © 2009 Wiley‐Liss, Inc.
A dimensionless reaction coordinate for quantifying the lateness of transition states
Authors: Manz Thomas A. , Sholl David S.
Published: November 2009

The Hammond‐Leffler postulate asserts that transition states of exothermic reactions are reactant‐like (early), whereas transition states of endothermic reactions are product‐like (late). Related postulates have been proposed to describe the sensitivity of activation barriers for reactions occurring on catalytic surfaces to the catalyst structure. To evaluate the validity of these postulates for different chemical reactions, a general method for classifying transition states as either early or late is needed. One can envision a dimensionless reaction coordinate that changes continuously and monotonically from 0 to 1 along a minimum energy reaction pathway. The value of the dimensionless reaction coordinate for the transition state (WTS) classifies transition states as (a) early when WTS < 0.5, (b) late when WTS > 0.5, and (c) equidistant between reactants and products when WTS = 0.5. In this article, we derive such a dimensionless reaction coordinate and illustrate its usefulness for several different chemical reactions. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
A first‐order system least‐squares finite element method for the Poisson‐Boltzmann equation
Authors: Bond Stephen D. , Chaudhry Jehanzeb Hameed , Cyr Eric C. , Olson Luke N.
Published: November 2009

The Poisson‐Boltzmann equation is an important tool in modeling solvent in biomolecular systems. In this article, we focus on numerical approximations to the electrostatic potential expressed in the regularized linear Poisson‐Boltzmann equation. We expose the flux directly through a first‐order system form of the equation. Using this formulation, we propose a system that yields a tractable least‐squares finite element formulation and establish theory to support this approach. The least‐squares finite element approximation naturally provides an a posteriori error estimator and we present numerical evidence in support of the method. The computational results highlight optimality in the case of adaptive mesh refinement for a variety of molecular configurations. In particular, we show promising performance for the Born ion, Fasciculin 1, methanol, and a dipole, which highlights robustness of our approach. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
CC bond formation by radical cyclization: Facile syntheses of [6,6]pyranothiopyrans and [6,6]pyridothiopyrans
Authors: Majumdar K. C. , Sarkar S. , Pal P. , Muhuri S.
Published: November 2009

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4‐Chloromethylthiopyrano[3,2‐c][1]benzopyran‐5‐(2H)‐ones were refluxed with o‐bromophenols in acetone in the presence of anhydrous potassium carbonate and sodium iodide to afford a number of 4‐aryloxymethylthiopyrano[3,2‐c][1]benzopyan‐5‐(2H)‐ones in 72–79% yields. These compounds were refluxed with tri‐n‐butyltin hydride and azobisisobutyronitrile in dry benzene for 7–8 h to give [6,6]pyranothiopyrans in 76–84% yields with good diastereoselectivity. Similarly, [6,6]pyridothiopyrans were also synthesized in 70–75% yields with excellent diastereoselectivity. J. Heterocyclic Chem., (2009).
An efficient and clean synthesis of pyrido[2,3‐d]pyrimidine‐4,7‐dione derivatives in aqueous media
Authors: Shi Da‐Qing , Shi Jing‐Wen , Rong Shao‐Feng
Published: November 2009

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A series of 2‐amino‐5‐aryl‐5,6‐dihydropyrido[2,3‐d]pyrimidine‐4,7(3H,8H)‐dione derivatives were synthesized via the three‐component reaction of aromatic aldehyde, 2,6‐diaminopyrimidine‐ 4(3H)‐one, and Meldrum's acid in water in the presence of triethylbenzylammonium chloride (TEBAC). This protocol has the advantages of easier work‐up, milder reaction conditions, and environmentally benign procedure. J. Heterocyclic Chem., (2009).
Clean synthesis of furo[3,4‐e]pyrazolo[3,4‐b]pyridine‐5‐one derivatives in aqueous media
Authors: Shi Da‐Qing , Yao Hao
Published: November 2009

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A series of 4‐aryl‐3‐methyl‐1‐phenyl‐7H‐furo[3,4‐e]pyrazolo[3,4‐b]pyridine‐5‐ones were synthesizedviathe three‐component reaction of an aldehyde, 5‐amino‐3‐methyl‐1‐phenyl‐1H‐pyrazole and tetronic acid in aqueous media in the presence of triethylbenzylammonium chloride (TEBAC). This method has the advantages of easier work‐up, mild reaction conditions, high yields, and an environmentally benign procedure. J. Heterocyclic Chem., (2009).
Synthesis of novel annelated systems based on the interaction and reactivity estimation of amino‐1,5‐benzodiazepin‐2‐ones with dimethyl‐2‐oxoglutaconate
Authors: Janciene Regina , Stumbreviciute Zita , Vektariene Ausra , Kosychova Lidija , Klimavicius Algirdas , Palaima Algirdas , Puodziunaite Benedikta
Published: November 2009

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A number of substituted tetracyclic 4H‐[1,4]diazepino[3,2,1‐hi]pyrido[4,3,2‐cd]indole and tricyclic 1H‐[1,4]diazepino[2,3‐g] or [2,3‐h]quinoline derivatives were prepared from 7‐ (or 8, or 9)amino‐1,5‐benzodiazepin‐2‐ones by the Doebner–von Miller quinoline synthesis. The structure of the cyclized products depends on the position of the primary amino group and on the substituents of the diazepine ring of the starting compounds. The regiochemical outcome of the reaction was estimated by calculating average local ionization energies on the molecular surface at the Density Functional Theory (DFT) level of theory. J. Heterocyclic Chem., (2009).
A simple and practical method for the synthesis of 2‐amino‐5,6‐dihydro‐5,7‐diarylquinazolin‐4‐ols
Authors: Senguttuvan S. , Nagarajan Samuthira
Published: November 2009

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We report an efficient and new method of synthesis of 2‐amino‐5,6‐dihydro‐5,7‐diarylquinazolin‐4‐ols by the reaction of substituted cyclohexenones with guanidine hydrochloride in presence of NaOEt. The reactions are with 50–72% yield. All the synthesized compounds are characterized using IR, NMR and CHN analysis. J. Heterocyclic Chem., (2009).
A simple and expedient method for the synthesis of ethyl 3‐amino‐4,6‐diarylthieno[2,3‐b]pyridine‐2‐carboxylate
Authors: Shah Hetal C. , Shah Vaishali H. , Desai Nirmal D.
Published: November 2009

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2‐Chloro‐4,6‐diarylnicotinonitrile 1 was reacted with ethyl 2‐mercaptoacetate 2 to furnish ethyl 2‐(3‐cyano‐4,6‐diarylpyridin‐2‐ylthio)acetate 3 as intermediates. These intermediates were cyclized by Thorpe–Zeigler cyclization using solid–liquid phase‐transfer catalysis conditions to give ethyl 3‐amino‐4,6‐diarylthieno[2,3‐b]pyridine‐2‐carboxylate 4. One‐pot heterocyclization without isolating the intermediates was also achieved using solid–liquid phase transfer conditions. J. Heterocyclic Chem., (2009).
One‐pot synthesis of iimidazo[1,2‐c]quinazoline‐5(6H)‐thione and imidazo[1,2‐c]quinazolin‐5(6H)‐one with the aid of tin(II) chloride
Authors: Wang Man‐Man , Dou Guo‐Lan , Shi Da‐Qing
Published: November 2009

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An efficient, convenient, one‐pot synthesis of imidazo[1,2‐c]quinazoline‐5(6H)‐thione and imidazo[1,2‐c]quinazolin‐5(6H)‐one was accomplished in good yields via the novel reductive cyclization of 2‐(2‐nitrophenyl)‐1H‐imidazoles with isothiocyanates or isocyanates mediated by SnCl2·2H2O system. J. Heterocyclic Chem., (2009).
Synthesis of some heterocyclic imides and azomethine derivatives under solvent free condition and their anti‐inflammatory activity evaluation
Authors: Sondhi Sham M. , Rani Reshma , Diwvedi Amarendra Dhar , Roy Partha
Published: November 2009

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Condensation of various mono amines with various diacids gave heterocyclic imide derivatives and condensation of amines with various aldehydes gave azomethine derivatives in good yields under solvent free condition. Structures assigned to imide and azomethine derivatives are fully supported by spectral data. All these compounds were screened for anti‐inflammatory activity at a dose of 50 mg/kg p.o. Compound 8a (6‐((tetrahydrofuran‐2‐yl)methyl)‐6H‐pyrrolo[3,4]pyrazine‐5,7‐dione) exhibited anti‐inflammatory activity comparable to standard drug phenyl butazone which showed 37% activity at 50 mg/kg p.o. J. Heterocyclic Chem., 46, 1369, (2009).
Synthesis and antimicrobial activity of new tetrahydro‐naphthalene‐thiazolidinedione and thiohydantoine derivatives
Authors: Ates‐Alagoz Zeynep , Altanlar Nurten , Buyukbingol Erdem
Published: November 2009

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As part of an ongoing program aimed at recognizing novel antioxidant, antimicrobial, and anticancer molecules, herein we report the synthesis and biological evaluation of imidazolidin‐4‐one and thiazolidine‐2,4‐dione derivatives as antimicrobial agents. These compounds were prepared from 5,5,8,8‐tetramethyl‐5,6,7,8‐tetrahydro‐naphthalen‐2‐carboxaldehyde and 3‐substituted phenacyl‐2,4‐thiazolidinediones using Knoevenagel reaction. The structures of compounds were confirmed by 1H NMR, mass spectral data, and elemental analyses. The molecules were evaluated for in vitro antimicrobial activity against methicillin‐resistant Staphylococcus aureus (MRSA) (standard), methicillin‐resistant Staphylococcus aureus (isolated), Staphylococcus aureus (SA), Escherichia coli (EC), Bacillus subtilis (BS), and Candida albicans (CA). Compounds 3a, 3b, 3c, 3d, 3e, 3f, 3g and compound 4 showed equal and/or greater antimicrobial activity against MRSA and EC than ampicillin and sultamicillin. J. Heterocyclic Chem., (2009)
(4,4‐Difluoro‐4‐bora‐3a,4a,‐diaza‐s‐indacen‐3‐yl)acetaldehyde: Synthesis and chemical properties
Authors: Shandura Mykola P. , Yakubovskyi Viktor P. , Kovtun Yuriy P.
Published: November 2009

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A reaction of 3,5‐dimethylborondipyrromethene 3 with the DMF dimethylacetal gives rise to monoenamine 4. The latter is converted to the corresponding aldehyde 5. A considerable contribution of the enolic form of the aldehyde allows preparing numerous 3‐vinyl substituted borondipyrromethenes and some heterocyclic derivatives. A reaction of the aldehyde 5 with tertiary aliphatic amines and the consecutive Hofmann‐type decomposition of the intermediary quaternary salt give rise to the corresponding dialkylaminovinyl derivatives. J. Heterocyclic Chem., (2009).
Facile, efficient, and eco‐friendly synthesis of benzo[b]pyran‐2‐imines over MgO and transformation to the coumarin derivatives
Authors: Valizadeh Hassan , Fakhari Ashraf
Published: November 2009

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Room temperature synthesis of benzo[b]pyran‐2‐imine derivatives via the Knoevenagel condensation of malononitrile and cyanoacetates with salicylaldehyde derivatives over MgO and their transformation to the known coumarins is described. The satisfactory results were obtained with good yields, short reaction time, and simplicity in the experimental procedure. J. Heterocyclic Chem., (2009).
Application of 3‐methylthiopyrido[4,3‐e]‐1,4,2‐dithiazine 1,1‐dioxide to the synthesis of novel series of 4H‐pyrido[4,3‐e]‐1,2,4‐thiadiazine derivatives with potential biological activity
Authors: Brzozowski Zdzisław , Sławiński Jarosław , Kędzia Anna , Kwapisz Ewa , Gdaniec Maria
Published: November 2009

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Two series of 4H‐pyrido[4,3‐e]‐1,2,4‐thiadiazine derivatives 3, 4, 5 and 7, 8, 9, 10, 11, 12 were synthesized by the reactions of 3‐methylthiopyrido[4,3‐e]‐1,4,2‐dithiazine 1,1‐dioxide 1 with 2‐or 6‐hydrazinoazines and 2‐aminophenols or 2‐aminothiophenol, respectively. Aminolysis of 8 (R = Me, Y = O) afforded the corresponding 3‐(R‐amino)‐4‐(2‐hydroxy‐5‐methylphenyl)‐4H‐pyrido[4,3‐e]‐1,2,4‐thiadiazine 1,1‐dioxides 13, 14, 15, 16, 17, 18. The structures of these compounds were confirmed on the basis of elemental analysis, spectral data, and X‐ray crystallography. Compounds 3, 4, 5, 7, 8, 9, 10, 12, 13, 14, 15, and 17, 18 were screened in vitro for antibacterial activity. Moreover, preliminary in vitro anticancer assay was performed for compounds 3, 7, 10, 11, 12, 13, and 17, 18 at the National Cancer Institute (Bethesda, MD) at a single dose (10 μM) in the full NCI 60 cell panel. J. Heterocyclic Chem., (2009).
An evaluation of paper chromatography for measuring the levels of radiochemical impurities in 99mTc Medronate Injection
Authors: Millar Alistair M. , O'Brien Lesley M. , Beattie Lynn A. , Craig Fiona
Published: November 2009

Background: The European Pharmacopoeia specifies Instant Thin‐Layer Chromatography Silica Gel (ITLC‐SG) as the stationary phase for measuring radiochemical impurities in 99mTc Medronate. The Pall Corporation has stopped manufacturing ITLC‐SG. Aim: To investigate chromatography papers as alternatives to ITLC‐SG. Experimental: The resolution of the main 99mTc Medronate and impurity peaks were compared on five Whatman papers (1CHR, 31ET, 3MM, 4CHR and 54SFC) using the pharmacopoeial mobile phases: methyl ethyl ketone for detecting 99mTc pertechnetate impurity and sodium acetate solution (136 g/l) for detecting hydrolysed reduced and colloidal 99mTc impurities. The effects of three sample spot treatments (wet, hot dried and air dried) on the distribution of the radiochemical impurities were compared. The levels of radiochemical impurities measured in samples of 99mTc Medronate were compared. Results: The highest resolutions were obtained with 1CHR, 4CHR and 54SFC. Sample spot drying resulted in the measurement of artifactually high levels of 99mTc pertechnetate impurity. When analysing 99mTc Medronate, erroneously high levels of colloidal and 99mTc pertechnetate impurities were measured with 1CHR and 4CHR. Conclusions: 54SFC paper is a suitable alternative to ITLC‐SG for measuring radiochemical impurities in 99mTc Medronate. The sample spot should be wet when the paper strip is placed in the chromatography tank. Copyright © 2009 John Wiley & Sons, Ltd.
Differing in vitro survival dependency of mouse and rat NG2+ oligodendroglial progenitor cells
Authors: Horiuchi Makoto , Lindsten Tullia , Pleasure David , Itoh Takayuki
Published: November 2009

NG2 chondroitin sulfate proteoglycan is a surface marker of oligodendroglial progenitor cells (OPCs) in various species. In contrast to well‐studied rat OPCs, however, we found that purified mouse NG2 surface positive cells (NG2+ cells) require additional activation of cyclic AMP (cAMP) signaling for survival in a medium containing 30% B104 neuroblastoma conditioned medium supplemented with fibroblast growth factor‐2 (B104CM+FGF2), whereas B104CM+FGF2 alone is sufficient for survival and selective proliferation of rat OPCs. After induction of in vitro differentiation, more than 90% of mouse NG2+ cells became O4‐positive, and a majority expressed myelin basic protein by 5 day of differentiation, which confirmed the identity of isolated mouse NG2+ cells as OPCs. In comparison to rat OPCs, mouse OPCs in B104CM+FGF2 were less motile, and demonstrated lower basal phosphorylation levels of ERK1/2 and cAMP response element‐binding protein (CREB) and a higher incidence of apoptosis mediated by the intrinsic pathway. Transient up‐regulation of cAMP‐CREB signaling partially inhibited apoptosis of mouse OPCs independently of the ERK pathway. This study demonstrates a difference in trophic requirements between mouse and rat OPCs, with an essential role for cAMP signaling to preserve viability of mouse OPCs. © 2009 Wiley‐Liss, Inc.
Description of distributed features of the nestin‐containing cells in brains of adult mice: A potential source of neural precursor cells
Authors: Xu Renshi , Wu Chengsi , Tao Yuhui , Yi Juan , Yang Yunzhu , Yang Rongwei , Zhang Xiong , Zhang Yuhu , Liu Rugao
Published: November 2009

The distribution of neural precursor cells (NPCs) in adult mice brain has so far not been described. Therefore, we investigated the distribution of NPCs by analyzing the nestin‐containing cells (NCCs) in distinct brain regions of adult nestin second‐intron enhancer‐controlled LacZ reporter transgenic mice through LacZ staining. Results showed that NCCs existed in various regions of adult mouse brain. In cerebellum, the greatest number of NCCs existed in cortex of the simple lobule, followed by cortex of the cerebellar lobule. In olfactory bulb, NCCs were most numerous in the granular cell layer, followed by the mitral cell layer and the internal plexiform, glomerular, and external plexiform layers. In brain nuclei (nu), NCCs were most numerous in the marginal nu, followed by the brainstem and diencephalon nu. NCCs in sensory nu of brainstem were more numerous than in motor nu, and NCCs in the dorsal of sensory nu were more numerous than in the ventral part. In brain ventricle systems, NCCs were largely distributed in the center of and external to the lateral ventricle, the inferior part of the third ventricle, the dorsal and inferior parts of the fourth ventricle, and the gray matter around the cerebral aqueduct. NCCs in the left vs. right brain were not significantly different. These data collectively indicate that NCCs were extensively distributed in the cerebellum and olfactory bulb, the partial nu of the marginal system, the partial brain nu adjacent to brain ventricle systems, the subependymal zone, and the cerebral cortex around the marginal lobe and were a potential source of NPCs. © 2009 Wiley‐Liss, Inc.
CCAAT/enhancer binding protein delta in microglial activation
Authors: Ejarque‐Ortiz Aroa , Gresa‐Arribas Núria , Straccia Marco , Mancera Pilar , Solà Carme , Tusell Josep Maria , Serratosa Joan , Saura Josep
Published: November 2009

The transcription factor CCAAT/enhancer binding protein δ (C/EBPδ) regulates transcription of genes that play important roles in glial activation. Previous studies have shown the astroglial expression of C/EBPδ but the microglial expression of C/EBPδ remains virtually unexplored, with the exception of two microarray studies. In this report, using murine primary cultures and BV2 cells we clearly demonstrate that C/EBPδ is expressed by microglia and it is upregulated in microglial activation. Lipopolysaccharide upregulates C/EBPδ both in microglia and in astrocytes. This effect is time‐dependent, with a maximum effect at 3 hr at mRNA level and at 4–8 hr at protein level, and concentration‐dependent, with a maximum effect at 100 ng/mL. The lipopolysaccharide‐induced C/EBPδ upregulation in BV2 microglia is mimicked by agonists of the toll‐like receptors 2, 3 and 9 and can be prevented by an inhibitor of extracellular signal‐regulated kinase activation. C/EBPδ from activated BV2 microglia binds to the cyclooxygenase‐2 promoter and forms complexes with C/EBPβ isoforms. These results point to C/EBPδ as a putative key regulator of proinflammatory gene expression in microglial activation. © 2009 Wiley‐Liss, Inc.
Low levels of citrin (SLC25A13) expression in adult mouse brain restricted to neuronal clusters
Authors: Contreras Laura , Urbieta Almudena , Kobayashi Keiko , Saheki Takeyori , Satrústegui Jorgina
Published: November 2009

The mitochondrial aspartate‐glutamate carriers (AGC) aralar (SLC25A12) and citrin (SLC25A13) are components of the malate aspartate shuttle (MAS), a major intracellular pathway to transfer reducing equivalents from NADH to the mitochondrial matrix. Aralar is the main AGC isoform present in the adult brain, and it is expressed mainly in neurons. To search for the other AGC isoform, citrin, in brain glial cells, we used a citrin knockout mouse in which the lacZ gene was inserted into the citrin locus as reporter gene. In agreement with the low citrin levels known to be present in the adult mouse brain, β‐galactosidase expression was very low. Surprisingly, unlike the case with astroglial cultures that express citrin, no β‐galactosidase was found in brain glial cells. It was confined to neuronal cells within discrete neuronal clusters. Double‐immunolabelling experiments showed that β‐galactosidase colocalized not with glial cell markers but with the pan‐neuronal marker NeuN. The deep cerebellar nuclei and a few midbrain nuclei (reticular tegmental pontine nuclei; magnocellular red nuclei) were the regions where β‐galactosidase expression was highest, and it was up‐regulated in fasted mice, as was also the case for liver β‐galactosidase. The results support the notion that glial cells have much lower AGC levels and MAS activity than neurons. © 2009 Wiley‐Liss, Inc.
Tau hyperphosphorylation and axonal damage induced by N,N‐diethyldithiocarbamate (DEDTC) treatment along late postnatal development is followed by a rescue during adulthood
Authors: Utrera Juana , Junyent Felix , de Lemos Luisa , Pallàs Merce , Camins Antoni , Romero Rafael , Auladell Carme
Published: November 2009

Axonal degeneration has been described as the pathological hallmark of peripheral neuropathies induced by DEDTC. In addition, axonal damage has also been observed in the brain of mice treated daily with DEDTC along postnatal development, though with this experimental model there was observed to be axonal recovery after treatment, during the adulthood. To focus on this axonal dynamic activity, damage‐recovery, a key axonal protein, the microtubule associated protein tau, was analyzed in this DEDTC model. Tau is a phosphoprotein and its dynamic site‐specific phosphorylation is essential for its proper function; in fact, high levels are correlated with cell dysfunction. Furthermore, the levels of tau phosphorylation are associated with dynamic microtubules during periods of high plasticity. Thus, phosphorylated tau at two sites of phosphorylation, Ser199 and Ser396, were evaluated during the second week of postnatal development and throughout adulthood. The results obtained by Western blot made it evident that the levels of p‐tau Ser199 and p‐tau Ser396 were higher in treated mice than in controls. Interestingly, by immunohistochemistry there was shown to be an increase in p‐tau‐immunolabeling in neuronal soma together with axonal tract alterations in treated animals with respect to controls, and the analyses of GSK3β and cdk5 revealed an increase in its activity in DEDTC‐treated animals. Nevertheless, in the adult a general decline in p‐tau was observed together with a rescue of axonal tract. All these data support the idea that the axonal damage induced by DEDTC treatment along postnatal development is followed by an axonal rescue during adulthood. © 2009 Wiley‐Liss, Inc.
Peptides derived from the solvent‐exposed loops 3 and 4 of BDNF bind TrkB and p75NTR receptors and stimulate neurite outgrowth and survival
Authors: Fobian Kristina , Owczarek Sylwia , Budtz Christian , Bock Elisabeth , Berezin Vladimir , Pedersen Martin V.
Published: November 2009

Brain‐derived neurotrophic factor (BDNF) is critically involved in modeling the developing nervous system and is an important regulator of a variety of crucial functions in the mature CNS. BDNF exerts its action through interactions with two transmembrane receptors, either separately or in concert. BDNF has been implicated in several neurological disorders, and irregularities in BDNF function may have severe consequences. Administration of BDNF as a drug has thus far yielded few practicable results, and the potential side effects when using a multifunctional protein are substantial. In an effort to produce more specific compounds without side effects, small peptides mimicking protein function have been developed. The present study characterized two mimetic peptides, Betrofin 3 and Betrofin 4, derived from the BDNF sequence. Both Betrofins bound the cognate BDNF receptors, TrkB and p75NTR, and induced neurite outgrowth and enhanced neuronal survival, probably by inducing signaling through tha Akt and MAPK pathways. Distinct, charged residues within the Betrofin sequences were identified as important for generating the neuritogenic response, which was also inhibited when BDNF was added together with either Betrofin, indicating partial agonistic effects of the peptides. Thus, two peptides derived from BDNF induced neurite outgrowth and enhanced neuronal survival, probably through binding to BDNF receptors. © 2009 Wiley‐Liss, Inc.
Sonic hedgehog (SHH) promotes the differentiation of mouse cochlear neural progenitors via the Math1–Brn3.1 signaling pathway in vitro
Authors: Hu Xiaohua , Huang Jianmin , Feng Ling , Fukudome Shinji , Hamajima Yuki , Lin Jizhen
Published: November 2009

Sonic hedgehog (SHH) is essential for the development of the cochlear duct that harbors the organ of Corti. However, little is known about the molecular signaling pathway through which SHH promotes the development of the organ of Corti, especially cochlear sensory epithelial cells. In this study, we demonstrated that SHH contributes to the differentiation of cochlear neural progenitors (CNPs), which are derived from the postnatal day 1 organ of Corti in mice. Addition of SHH to CNPs increased the formation of epithelial cell islands, simultaneously activated the expression of Math1 that is a transcription factor for the initial differentiation of auditory hair cells. The increased expression of Math1 then regulated the promoter activity of Brn3.1, another transcription factor that controls the further differentiation and survival of auditory hair cells. Taken together, our data suggest that SHH plays an important role in the promotion of auditory hair cell differentiation via the Math1‐Brn3.1 signaling pathway. © 2009 Wiley‐Liss, Inc.
Maternal caffeine intake during gestation and lactation down‐regulates adenosine A1receptor in rat brain from mothers and neonates
Authors: Lorenzo A.M. , León D. , Castillo C.A. , Ruiz M.A. , Albasanz J.L. , Martín M.
Published: November 2009

Even though caffeine can be excreted in breast milk, few studies have analyzed the effect of maternal caffeine consumption during lactation on neonatal brain. In the present work pregnant rats were treated daily with 1 g/L of caffeine in their drinking water during pregnancy and/or lactation and the effect on adenosine A1receptor in brains from both lactating mothers and 15 days‐old neonates was assayed using radioligand binding and real time PCR assays. Mothers receiving caffeine during gestational period developed motor activation in gestational days 8–10 which was associated with a significant decrease of total adenosine A1receptor number (84%). A similar decrease was detected in mothers treated with caffeine during lactation (76%) and throughout gestation and lactation (73%); this was accompanied by a significant decrease in mRNA level coding adenosine A1receptor (28%). In male neonates, adenosine A1receptor was also decreased after chronic caffeine exposure during gestation (80%), lactation (76%) and gestation plus lactation (80%). In female neonates, adenosine A1receptor tended to decrease in response to caffeine exposure although no significant variations were found. No variation in the level of mRNA coding adenosine A1receptor was detected in neonates in any case. Concerning adenosine A2Areceptor, radioligand binding assays revealed that this receptor remains unaltered in maternal and neonatal brain in response to caffeine exposure. However, caffeine consumption during gestation and lactation evoked a significant decrease in mRNA level coding A2Areceptor (32%) in mothers' brain. © 2009 Wiley‐Liss, Inc.
Promoting directional axon growth from neural progenitors grafted into the injured spinal cord
Authors: Bonner Joseph F. , Blesch Armin , Neuhuber Birgit , Fischer Itzhak
Published: November 2009

Spinal cord injury (SCI) is a devastating condition characterized by disruption of axonal connections, failure of axonal regeneration, and loss of motor and sensory function. The therapeutic promise of neural stem cells has been focused on cell replacement, but many obstacles remain in obtaining neuronal integration following transplantation into the injured CNS. This study investigated the neurotransmitter identity and axonal growth potential of neural progenitors following grafting into adult rats with a dorsal column lesion. We found that using a combination of neuronal and glial restricted progenitors (NRP and GRP) produced graft‐derived glutamatergic and GABAergic neurons within the injury site, with minimal axonal extension. Administration of brain‐derived neurotrophic factor (BDNF) with the graft promoted modest axonal growth from grafted cells. In contrast, injecting a lentiviral vector expressing BDNF rostral into the injured area generated a neurotrophin gradient and promoted directional growth of axons for up to 9 mm. Animals injected with BDNF lentivirus (at 2.5 and 5.0 mm) showed significantly more axons and significantly longer axons than control animals injected with GFP lentivirus. However, only the 5.0‐mm‐BDNF group showed a preference for extension in the rostral direction. We concluded that NRP/GRP grafts can be used to produce excitatory and inhibitory neurons, and neurotrophin gradients can guide axonal growth from graft‐derived neurons toward putative targets. Together they can serve as a building block for neuronal cell replacement of local circuits and formation of neuronal relays. © 2009 Wiley‐Liss, Inc.
Balance dysfunction resulting from acute inner ear energy failure is caused primarily by vestibular hair cell damage
Authors: Mizutari Kunio , Fujioka Masato , Nakagawa Susumu , Fujii Masato , Ogawa Kaoru , Matsunaga Tatsuo
Published: November 2009

Inner ear energy failure is associated with disorders such as inner ear ischemia. Recently, we used the mitochondrial toxin 3‐nitropropionic acid (3‐NP) to establish an animal model of inner ear energy failure that presents with auditory dysfunction. Here we investigated the mechanisms underlying balance disorders in the 3‐NP animal model. Spontaneous nystagmus peaked 6 hr after treatment with either 300 mM or 500 mM 3‐NP. The nystagmus attenuated gradually and disappeared 3 days after 3‐NP treatment. A caloric test using ice water was performed to evaluate residual vestibular function 7 days after 3‐NP treatment. The response to caloric stimulation was reduced to ∼40% of the response of the untreated ear following 300 mM 3‐NP and was undetectable following 500 mM 3‐NP. Structural changes in the peripheral vestibular organs were analyzed by light and electron microscopy. Severe loss of stereocilia was observed following 500 mM 3‐NP, whereas disorganized and mildly reduced stereocilia were observed following 300 mM 3‐NP. There was severe loss and degeneration of vestibular hair cells following 500 mM 3‐NP but only slight loss and degeneration of hair cells following 300 mM 3‐NP. These results indicate that acute inner ear energy failure causes balance dysfunction mainly by damaging hair cells in the vestibule, which is distinct from the mechanism underlying auditory disorders. © 2009 Wiley‐Liss, Inc.