bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction Between Finger Opposition Movements and Aftereffects of 1Hz-rTMS on Ipsilateral Motor Cortex
Authors: Avanzino Laura , Bove Marco , Tacchino Andrea , Trompetto Carlo , Ogliastro Carla , Abbruzzese Giovanni
Published: June 2008

One-hertz repetitive transcranial magnetic stimulation (1Hz-rTMS) over ipsilateral motor cortex is able to modify up to 30 min the motor performance of repetitive finger opposition movements paced with a metronome at 2 Hz. We investigated whether the long-lasting rTMS effect on motor behavior can be modulated by subsequent engagement of the contralateral sensorimotor system. Motor task was performed in different experimental conditions: immediately after rTMS, 30 min after rTMS, or when real rTMS was substituted with sham rTMS. Subjects performing the motor task immediately after rTMS showed modifications in motor behavior ≤30 min after rTMS. On the other hand, when real rTMS was substituted with sham stimulation or when subjects performed the motor task 30 min after the rTMS session, the effect was no longer present. These findings suggest that the combination of ipsilateral 1Hz-rTMS and voluntary movement is crucial to endure the effect of rTMS on the movement itself, probably acting on synaptic plasticity-like mechanism. This finding might provide some useful hints for neurorehabilitation protocols.
Notes on the Bees of Southern Maine: Anthophoridae,Halictoididae, Macropidae and Panurgidae
Authors: Lovell J. H. , Cockerell T. D. A.
Published: June 2008

The Anthophoridae, which are represented by numerous species in the Middle
States, become comparatively rare in northern New England. At Waldoboro in
southern Maine there have been taken as the result of much diligent collecting only
five species of Melissodes and one of Clisodon. With few exceptions, which will
be noted under the respective species, they are visitors in this locality of the Compositae
and fly during midsummer and early autumn. With the exception of Melissodes
desponsa Sm., which is rather common, they might easily escape the attention
of the general entomological collector.
Intelligent Hybrid Control Strategy for Trajectory Tracking of Robot Manipulators
Authors: Zuo Yi , Wang Yaonan , Huang Lihong , Li Chunsheng
Published: June 2008

We address the problem of robust tracking control using a PD‐plus‐feedforward
controller and an intelligent adaptive robust compensator for a rigid robotic manipulator with uncertain dynamics and external disturbances. A key feature of this scheme is that soft computer
methods are used to learn the upper bound of system uncertainties and adjust the width of the boundary layer base. In this way, the prior knowledge of the upper bound of the system uncertainties
does need not to be required. Moreover, chattering can be effectively eliminated, and asymptotic error convergence can be guaranteed. Numerical simulations and experiments of two‐DOF rigid robots are presented to show effectiveness of the proposed scheme.
Statistical Analysis of Efficient Unbalanced Factorial Designs for Two-Color Microarray Experiments
Authors: Tempelman Robert J.
Published: June 2008

Experimental designs that efficiently embed a fixed effects treatment structure within a random effects design structure typically require a mixed-model approach to data analyses. Although mixed model software tailored for the analysis of two-color microarray data is increasingly available, much of this software is generally not capable of correctly analyzing the elaborate incomplete block designs that are being increasingly proposed and used for factorial treatment structures. That is, optimized designs are generally unbalanced as it pertains to various treatment comparisons, with different specifications of experimental variability often required for different treatment factors. This paper uses a publicly available microarray dataset, as based upon an efficient experimental design, to demonstrate a proper mixed model analysis of a typical unbalanced factorial design characterized by incomplete blocks and hierarchical levels of variability.
Colonic Involvement in a Patient with Chronic Lymphocytic Leukaemia
Authors: Arkkila P. E. T. , Nuutinen H. , Ebeling F. , Elonen E. , Kärkkäinen P. , Karjalainen-Lindsberg M.-L.
Published: June 2008

Various gastrointestinal infiltrations have been described in patients with chronic lymphocytic leukaemia (CLL). Here, we report a 69-year-old man with CLL and anaemia in whom the macroscopic finding of colonoscopy was normal, but the histological specimens revealed lymphocytic leukemia in ileum and in colon. If a CLL patient has any symptoms suggesting a possible GI manifestation of the haematologic disease or anaemia not explained by bone marrow infiltration or hemolysis, the diagnostic evaluation should include endoscopies with adequate biopsies.
Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3
Authors: Kwon Mi-Kyung , Nam Ju-Ock , Park Rang-Woon , Lee Byung-Heon , Park Jae-Yong , Byun Young-Ro , Kim Sang-Yoon , Kwon Ick-Chan , Kim In-San
Published: June 2008

We have designed a novel peptide, TK3, composed of three functional domains, a protein transduction domain, a TAT followed by three tandem repeats of a proapoptotic peptide, and a caspase-3 cleavage site, (KLAKLAK)2-DEVD. TK3 was able to transduce into cells and then activate caspase-3, which in turn cleaved TK3 to release additional (KLAKLAK)2 peptides. (KLAKLAK)2 was well transduced by TAT into tumor cells and was able to induce apoptosis in vitro and in vivo. TK3 also induced apoptosis and inhibited angiogenesis in endothelial cells. Further, direct injection of TK3 into established B16F10 melanoma tumors in C57BL/6 mice resulted in almost complete inhibition of the tumor growth. These results suggest that TK3 could be beneficial for the treatment of accessible tumors and used as an adjuvant for cancer therapy. [Mol Cancer Ther 2008;7(6):1514–22]
Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor–induced angiogenesis
Authors: Singleton Patrick A. , Garcia Joe G.N. , Moss Jonathan
Published: June 2008

Many patients with cancer receive combinations of drug treatments that include 5-fluorouracil (5-FU) and bevacizumab. Therapeutic doses of 5-FU are often associated with unwanted side effects, and bevacizumab is costly. Therefore, we explored potential agents that can reduce the therapeutic concentration of these drugs. Our data indicate that methylnaltrexone (MNTX), a peripheral antagonist of the μ-opioid receptor, exerts a synergistic effect with 5-FU and bevacizumab on inhibition of vascular endothelial growth factor (VEGF)–induced human pulmonary microvascular endothelial cell (EC) proliferation and migration, two key components in cancer-associated angiogenesis. MNTX inhibited EC proliferation with an IC50 of ∼100 nmol/L. Adding 100 nmol/L MNTX to EC shifted the IC50 of 5-FU from ∼5 μmol/L to ∼7 nmol/L. Further, adding 50 ng/mL MNTX shifted the IC50 of bevacizumab on inhibition of EC migration from ∼25 to ∼6 ng/mL. These synergistic effects were not observed with naltrexone, a tertiary μ-opioid receptor antagonist. On a mechanistic level, we observed that treatment of human EC with MNTX, but not naltrexone, increased receptor protein tyrosine phosphatase μ activity, which was independent of μ-opioid receptor expression. Silencing receptor protein tyrosine phosphatase μ expression (small interfering RNA) in human EC inhibited both synergy between MNTX and bevacizumab or 5-FU and increased VEGF-induced tyrosine phosphorylation of Src and p190 RhoGAP with enhanced activation of Akt and the actin cytoskeletal regulatory protein, RhoA, whereas silencing Src, Akt, or RhoA blocked VEGF-induced angiogenic events. Therefore, addition of MNTX could potentially lower the therapeutic doses of 5-FU and bevacizumab, which could improve index. [Mol Cancer Ther 2008;7(6):1669–79]
Intrinsically lower AKT, mammalian target of rapamycin, and hypoxia-inducible factor activity correlates with increased sensitivity to 2-deoxy-d-glucose under hypoxia in lung cancer cell lines
Authors: Wangpaichitr Medhi , Savaraj Niramol , Maher Johnathan , Kurtoglu Metin , Lampidis Theodore J.
Published: June 2008

Down-regulation by small interfering RNA or absence of hypoxia-inducible factor (HIF-1α) has been shown to lead to increased sensitivity to glycolytic inhibitors in hypoxic tumor cells. In surveying a number of tumor types for differences in intrinsic levels of HIF under hypoxia, we find that the reduction of the upstream pathways of HIF, AKT, and mammalian target of rapamycin (mTOR) correlates with increased toxic effects of 2-deoxy-d-glucose (2-DG) in lung cancer cell lines when treated under hypoxia. Because HIF-1α translation is regulated by mTOR, we examined the effects of blocking mTOR under hypoxia with an analogue of rapamycin (CCI-779) in those cell lines that showed increased mTOR and AKT activity and found that HIF-1α down-regulation coincided with increased 2-DG killing. CCI-779, however, was ineffective in increasing 2-DG toxicity in cell lines that did not express HIF. These results support the hypothesis that although mTOR inhibition leads to the blockage of numerous downstream targets, CCI-779 increases the toxicity of 2-DG in hypoxic cells through down-regulation of HIF-1α. Overall, our findings show that CCI-779 hypersensitizes hypoxic tumor cells to 2-DG and suggests that the intrinsic expression of AKT, mTOR, and HIF in lung cancer, as well as other tumor types, may be important in dictating the decision on how best to use 2-DG alone or in combination with CCI-799 to kill hypoxic tumor cells clinically. [Mol Cancer Ther 2008;7(6):1506–13]
In vitro and in vivo targeting of hollow gold nanoshells directed at epidermal growth factor receptor for photothermal ablation therapy
Authors: Melancon Marites P. , Lu Wei , Yang Zhi , Zhang Rui , Cheng Zhi , Elliot Andrew M. , Stafford Jason , Olson Tammy , Zhang Jin Z. , Li Chun
Published: June 2008

Laser-induced phototherapy is a new therapeutic use of electromagnetic radiation for cancer treatment. The use of targeted plasmonic gold nanoparticles can reduce the laser energy necessary for selective tumor cell destruction. However, the ability for targeted delivery of the currently used gold nanoparticles to tumor cells is limited. Here, we describe a new class of molecular specific photothermal coupling agents based on hollow gold nanoshells (HAuNS; average diameter, ∼30 nm) covalently attached to monoclonal antibody directed at epidermal growth factor receptor (EGFR). The resulting anti-EGFR-HAuNS exhibited excellent colloidal stability and efficient photothermal effect in the near-infrared region. EGFR-mediated selective uptake of anti-EGFR-HAuNS in EGFR-positive A431 tumor cells but not IgG-HAuNS control was shown in vitro by imaging scattered light from the nanoshells. Irradiation of A431 cells treated with anti-EGFR-HAuNS with near-infrared laser resulted in selective destruction of these cells. In contrast, cells treated with anti-EGFR-HAuNS alone, laser alone, or IgG-HAuNS plus laser did not show observable effect on cell viability. Using 111In-labeled HAuNS, we showed that anti-EGFR-HAuNS could be delivered to EGFR-positive tumors at 6.8% ID/g, and the microscopic image of excised tumor with scattering signal from nanoshells confirmed preferential delivery to A431 tumor of anti-EGFR-HAuNS compared with IgG-HAuNS. The absence of silica core, the relatively small particle size and high tumor uptake, and the absence of cytotoxic surfactant required to stabilize other gold nanoparticles suggest that immuno-HAuNS have the potential to extend to in vivo molecular therapy. [Mol Cancer Ther 2008;7(6):1730–9]
5-Aminolaevulinic acid peptide prodrugs enhance photosensitization for photodynamic therapy
Authors: Bourré Ludovic , Giuntini Francesca , Eggleston Ian M. , Wilson Michael , MacRobert Alexander J.
Published: June 2008

Intracellular porphyrin generation following administration of 5-aminolaevulinic acid (ALA) has been widely used in photodynamic therapy for a range of malignant and nonmalignant lesions. However, ALA is relatively hydrophilic and lacks stability at physiologic pH, limiting its bioavailability. We have investigated more lipophilic, uncharged ALA-peptide prodrugs based on phenylalanyl-ALA conjugates, which are water soluble and chemically stable for improving ALA delivery. Pharmacokinetics of the induced protoporphyrin IX (PpIX) were studied in transformed PAM212 keratinocyte cells and pig skin explants. The intracellular porphyrin production was substantially increased with Ac-l-Phe-ALA-Me (compound 1) and Ac-l-Phe-ALA (compound 3) compared with equimolar ALA: after 6-h incubation, the PpIX fluorescence measured using 0.01 mmol/L of compound 1 was enhanced by a factor of 5 compared with ALA. Phototoxicity results showed good correlation with PpIX levels, giving a LD50 (2.5 J/cm2) of 25 μmol/L for ALA, 6 μmol/L for 5-aminolaevulinic hexyl ester, and 2.6 μmol/L for compound 1, which exhibited the highest phototoxicity. However, these results were stereospecific because the corresponding d-enantiomer, Ac-d-Phe-ALA-Me (compound 2), induced neither porphyrin synthesis nor phototoxicity. PpIX levels were considerably reduced when cells were incubated with compound 1 at low temperatures, consistent with active transport. In pig skin explants, compound 1 induced higher porphyrin fluorescence than ALA by a factor of 3. These results show that water-soluble peptide prodrugs of ALA can greatly increase its cellular uptake, generating more intracellular PpIX and improved tumor cell photosensitization. The derivatives are comparable in efficacy with 5-aminolaevulinic hexyl ester but less toxic and more stable at physiologic pH. [Mol Cancer Ther 2008;7(6):1720–9]
Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198
Authors: LaVallee Theresa M. , Burke Patricia A. , Swartz Glenn M. , Hamel Ernest , Agoston Gregory E. , Shah Jamshed , Suwandi Lita , Hanson Art D. , Fogler William E. , Sidor Carolyn F. , Treston Anthony M.
Published: June 2008

Clinical studies using the microtubule-targeting agent 2-methoxyestradiol (2ME2; Panzem) in cancer patients show that treatment is associated with clinical benefit, including prolonged stable disease, complete and partial responses, and an excellent safety profile. Studies have shown that 2ME2 is metabolized by conjugation at positions 3 and 17 and oxidation at position 17. To define structure-activity relationships for these positions of 2ME2 and to generate metabolically stable analogues with improved anti-tubulin properties, a series of analogues was generated and three lead analogues were selected, ENMD-1198, ENMD-1200, and ENMD-1237. These molecules showed improved metabolic stability with >65% remaining after 2-h incubation with hepatocytes. Pharmacokinetic studies showed that oral administration of the compounds resulted in increased plasma levels compared with 2ME2. All three analogues bind the colchicine binding site of tubulin, induce G2-M cell cycle arrest and apoptosis, and reduce hypoxia-inducible factor-1α levels. ENMD-1198 and ENMD-1200 showed improved in vitro antiproliferative activities. Significant reductions in tumor volumes compared with vehicle-treated mice were observed in an orthotopic breast carcinoma (MDA-MB-231) xenograft model following daily oral treatment with all compounds (ANOVA, P < 0.05). Significantly improved median survival time was observed with ENMD-1198 and ENMD-1237 (200 mg/kg/d) in a Lewis lung carcinoma metastatic model (P < 0.05). In both tumor models, the high-dose group of ENMD-1198 showed antitumor activity equivalent to that of cyclophosphamide. ENMD-1198 was selected as the lead molecule in this analogue series and is currently in a phase I clinical trial in patients with refractory solid tumors. [Mol Cancer Ther 2008;7(6):1472–82]
Reactivation of p53 by a specific MDM2 antagonist (MI-43) leads to p21-mediated cell cycle arrest and selective cell death in colon cancer
Authors: Shangary Sanjeev , Ding Ke , Qiu Su , Nikolovska-Coleska Zaneta , Bauer Joshua A. , Liu Meilan , Wang Guoping , Lu Yipin , McEachern Donna , Bernard Denzil , Bradford Carol R. , Carey Thomas E. , Wang Shaomeng
Published: June 2008

MDM2 oncoprotein binds directly to the p53 tumor suppressor and inhibits its function in cancers retaining wild-type p53. Blocking this interaction using small molecules is a promising approach to reactivate p53 function and is being pursued as a new anticancer strategy. The spiro-oxindole MI-43, a small-molecule inhibitor of the MDM2-p53 interaction, was designed and examined for its cellular mechanism of action and therapeutic potential in colon cancer. MI-43 binds to MDM2 protein with a Ki value of 18 nmol/L and is 300 times more potent than a native p53 peptide. MI-43 blocks the intracellular MDM2-p53 interaction and induces p53 accumulation in both normal and cancer cells, with wild-type p53 without causing p53 phosphorylation. Induction of p53 leads to modulation of the expression of p53 target genes, including up-regulation of p21 and MDM2 in normal primary human cells and in colon cancer cells with wild-type p53. Using HCT-116 isogenic colon cancer cell lines differing only in p53 status or RNA interference to knockdown expression of p53 in the RKO colon cancer cell line, we show that the cell growth inhibition and cell death induction by MI-43 is p53 dependent. Furthermore, induction of cell cycle arrest by MI-43 is dependent on p53 and p21. In normal cells, MI-43 induces cell cycle arrest but not apoptosis. This study suggests that p53 activation by a potent and specific spiro-oxindole MDM2 antagonist may represent a promising therapeutic strategy for the treatment of colon cancer and should be further evaluated in vivo and in the clinic. [Mol Cancer Ther 2008;7(6):1533–42]
Evaluation of a chemical library of small-molecule Dishevelled antagonists that suppress tumor growth by down-regulating T-cell factor–mediated transcription
Authors: You Liang , Xu Zhidong , Punchihewa Chandanamali , Jablons David M. , Fujii Naoaki
Published: June 2008

We describe the rational generation of small-molecule agents that suppress tumor cell growth by down-regulating canonical Wnt signaling. We first produced a chemical library of the derivatives of indole-2-ketones and carbinols; we then screened them by using scalable assays of biochemical antagonism of Dishevelled-1 PDZ domain interactions and cell-based assays of Dishevelled-1–driven T-cell factor–mediated transcription. Compounds showing parallel effects in these assays were tested for selective induction of apoptosis in cancer cells. A new compound (24) that met the criteria for high biochemical antagonism, T-cell factor–mediated transcription, and induction of tumor-selective apoptosis was found to significantly suppress the growth of tumor xenografts in mice. [Mol Cancer Ther 2008;7(6):1633–8]
Molecular mechanisms of the antiangiogenic and antitumor effects of mycophenolic acid
Authors: Domhan Sophie , Muschal Stefan , Schwager Christian , Morath Christian , Wirkner Ute , Ansorge Wilhelm , Maercker Christian , Zeier Martin , Huber Peter E. , Abdollahi Amir
Published: June 2008

The relative risk for the development of malignancies following solid organ transplantation seems to be decreased in patients treated with the immunosuppressive agent mycophenolic acid (MPA). However, the molecular mechanisms of the antineoplastic effects of MPA are not completely understood. Here, we report that human endothelial cells and fibroblasts are highly sensitive to MPA treatment. We found that U87 glioblastoma cells were resistant to MPA treatment in vitro. However, U87 tumor growth was markedly inhibited in vivo in BALB/c nude mice, suggesting that MPA exerted its antitumor effects via modulation of the tumor microenvironment. Accordingly, microvascular density and pericyte coverage were markedly reduced in MPA-treated tumors in vivo. Using functional in vitro assays, we showed that MPA potently inhibited endothelial cell and fibroblast proliferation, invasion/migration, and endothelial cell tube formation. To identify the genetic participants governing the antiangiogenic and antifibrotic effects of MPA, we performed genome-wide transcriptional analysis in U87, endothelial and fibroblast cells at 6 and 12 h after MPA treatment. Network analysis revealed a critical role for MYC signaling in endothelial cells treated with MPA. Moreover, we found that the antiangiogenic effects of MPA were organized by coordinated communications between MYC and NDRG1, YYI, HIF1A, HDAC2, CDC2, GSK3B, and PRKACB signaling. The regulation of these “hub nodes” was confirmed by real-time quantitative reverse transcription-PCR and protein analysis. The critical involvement of MYC in the antiangiogenic signaling of MPA was further shown by gene knockdown experiments. Together, these data provide a molecular basis for the antiangiogenic and antifibrotic effects of MPA, which warrants further clinical investigations. [Mol Cancer Ther 2008;7(6):1656–68]
The New Challenges of Inflation and External Imbalances Facing China
Authors: Yu Yongding
Published: June 2008

China is facing the threat of inflation, at the same time that the U.S. economy is in trouble. To maintain a sustainable growth rate, China must walk a tightrope. On one hand, China must tighten its monetary policy to bring inflation under control, which will slow down the growth rate of the Chinese economy. On the other hand, China also has to be ready to use expansionary fiscal policy to replace the weakened external demand to prevent its economy from falling into a “growth recession,” where the growth rate is below 8 percent, due to the double whammies of monetary tightening and a significant slowdown of the U.S. economy.
Poverty in Rural Cambodia: The Differentiated Impact of Linkages, Inputs, and Access to Land
Authors: Engvall Anders , Sjöberg Örjan , Sjöholm Fredrik
Published: June 2008

Cambodia has been growing rapidly over the past few years, but remains one of the poorest countries in East Asia. This paper analyzes rural poverty in Cambodia to identify the factors that explain its occurrence and persistence. The reduction of rural poverty in Cambodia requires (1) improvements in agricultural productivity and (2) the establishment of other income-earning opportunities for the rural population. Our econometric investigation of the 2004 Cambodian Socio-Economic Survey shows that the main causes of poverty differ between landowners and the landless, and between different regions. Increasing inputs to agriculture (e.g., fertilizers) is critical to increasing the welfare of landowning poor, and linkages with the rest of the economy are of vital importance to both landowners and the landless poor.
Supply-side Economics in the People's Republic of China's Regional Context: A Quantitative Investigation of Its VAT Reform
Authors: Zhai Fan , He Jianwu
Published: June 2008

The People's Republic of China (PRC) has now decided to shift its value-added tax (VAT) from production-based to consumption-based. This transition is currently piloted in the three provinces of the northeast PRC, and is expected to be extended to the whole country in the coming 2 or 3 years. Using a two-region dynamic general equilibrium model with overlapping generations, this paper investigates the macroeconomic and welfare effects of the VAT transition in PRC. The distribution effects between generations are also analyzed to get a sense of public opinion toward the reform. We put special emphasis on the pace of reform by analyzing the pre-announcement effects and the inter-regional impacts of tax reform that began in one pilot region. The simulation results suggest large welfare gains from the VAT transition. However, the pilot reform in the northeast provinces, which delays the national implementation of consumption-based VAT, would involve substantial transitional costs for the rest of the PRC.
Nonlinear Amygdala Response to Face Trustworthiness: Contributions of High and Low Spatial Frequency Information
Authors: Said Christopher P. , Baron Sean G. , Todorov Alexander
Published: June 2008

Previous neuroimaging research has shown amygdala sensitivity to the perceived trustworthiness of neutral faces, with greater responses to untrustworthy compared with trustworthy faces. This observation is consistent with the common view that the amygdala encodes fear and is preferentially responsive to negative stimuli. However, some studies have shown greater amygdala activation to positive compared with neutral stimuli. The first goal of this study was to more fully characterize the amygdala response to face trustworthiness by modeling its activation with both linear and nonlinear predictors. Using fMRI, we report a nonmonotonic response profile, such that the amygdala responds strongest to highly trustworthy and highly untrustworthy faces. This finding complicates future attempts to make inferences about mental states based on activation in the amygdala. The second goal of the study was to test for modulatory effects of image spatial frequency filtering on the amygdala response. We predicted greater amygdala sensitivity to face trustworthiness for low spatial frequency images compared with high spatial frequency images. Instead, we found that both frequency ranges provided sufficient information for the amygdala to differentiate faces on trustworthiness. This finding is consistent with behavioral results and suggests that trustworthiness information may reach the amygdala through pathways carrying both coarse and fine resolution visual signals.
Bowel Ischemia Following Pneumonia in Compromised Children
Authors: Kabre Rashmi , Katz Ben Z.
Published: June 2008

Two severely compromised children developed bowel necrosis in the context of severe pneumonia, presumably secondary to ischemia. No other obvious etiology for the abdominal pathology could be ascertained.
Two Cases Presenting With Pubertal Delay and Diagnosed as Celiac Disease
Authors: Abaci Ayhan , Esen Ihsan , Unuvar Tolga , Arslan Nur , Bober Ece
Published: June 2008

Pubertal delay may be due to underlying chronic diseases and primary endocrine diseases. Celiac disease, one of the common malabsorption disorders of childhood, may progress silently in some cases, and the cases diagnosed late present with growth failure or disturbance of pubertal development. Currently, due to the changing face of celiac disease, patients are being diagnosed in adolescence with atypical symptoms and findings. This study describes 2 patients aged 13 and 16 years who presented with pubertal delay and who were diagnosed with celiac disease, concluding that routine screening of celiac disease in the differential diagnosis of delayed puberty should be recommended.
The Limitations of the Discourse of Norms
Authors: Clarkson Jay
Published: June 2008

This article examines discourses of gay visibility in the online gay community of StraightActing.com. In this discourse the “flamer” and other “gay-acting” gender performers are frequently criticized for fear of their power to teach gay and straight people that one particular type of gay person is the norm. The author argues that this conceptualization of the term norm attributes gay visibility the power to construct a singular gay identity as preferred and positions gay men to fight among themselves for dominance over that one identity. It is essential we conceptualize the power of the visibility as able to produce multiple conventions of gay identity. The battle over control of a “gay norm” demonizes those who perform different degrees of transgression and impedes progress toward queer liberation.
Effect of acute tryptophan depletion on noradrenaline and dopamine in the rat brain
Authors: Ardis TC , Cahir M. , Elliott JJ , Bell R. , Reynolds GP , Cooper SJ
Published: June 2008

In human subjects, the acute tryptophan (TRP) depletion (ATD) paradigm has been shown to have effects on mood and cognition. It is assumed that these effects are mediated through the serotonin system. In this study, we have examined the effects of ATD on the central concentrations of the monoamine transmitters, noradrenaline (NA) and dopamine (DA) as well as on serotonin (5-HT). Effects on NA and DA could also affect mood and cognition. Following oral administration of TRP-containing (TRP+) and TRP-free (TRP−) amino acid mixtures, neurotransmitter concentrations and free plasma TRP concentrations were determined by High Performance Liquid Chromatography (HPLC) with electrochemical detection. Free plasma TRP was significantly and substantially reduced (79%) in rats given a TRP— amino acid mixture when compared with those given a TRP+ mixture. ATD also significantly decreased 5-HT and 5-hydroxyindolacetic acid in the frontal cortex, remaining cortex and hippocampus, but did not significantly reduce these in the striatum. Furthermore, ATD did not significantly alter the concentration of NA and DA in any brain region examined. This study demonstrates that the administration of a TRP− amino acid mixture in rats can reduce free plasma TRP to levels comparable to those reported in human studies. These results indicate that behavioural and cognitive changes produced by ATD in preclinical or clinical studies are likely to be due to specific effects on the serotonergic system.
Current and former ecstasy users report different sleep to matched controls: a web-based questionnaire study
Authors: Carhart-Harris RL , Nutt DJ , Munafò M , Wilson SJ
Published: June 2008

Abstract

This study sought to test the association between ecstasy-use and abnormal sleep. An anonymous web-based questionnaire containing questions on drug use and sleep was completed by 1035 individuals. From this large sample, a group of 89 ecstasy users were found who reported very little use of other drugs. This ”ecstasy-only“ group was further divided into two groups of 31 current users and 58 abstinent users. The subjective sleep of current and former ecstasy-only users was compared with that of matched controls. Patients were asked to rate their sleep according to: 1) sleep quality, 2) sleep latency, 3) night time awakenings and 4) total sleep time. Current ecstasy-only users reported significantly worse sleep quality ( P < 0.05) and a greater total sleep time ( P < 0.001) than controls. It was inferred that these differences might be due to recovery from the acute effects of the drug. Abstinent ecstasy-only users reported significantly more nighttime awakenings than controls ( P < 0.01). These subjective findings are in agreement with the objective findings of previous studies showing persistent sleep abnormalities in ecstasy users.
CCK-4-induced anxiety but not panic is associated with serum brain-derived neurotrophic factor in healthy subjects
Authors: Maron E , Tõru I , Mäemets K , Sepp S , Vasar V , Shlik J , Zharkovsky A
Published: June 2008

Abstract

Recent animal studies consistently confirm the involvement of brain-derived neurotrophic factor (BDNF) in the regulation of anxiety-related behaviours. The role of BDNF in human anxiety has been less investigated. The aim of our study was to examine the association between serum BDNF levels and panic/anxiety responses to cholecystokinin-tetrapeptide (CCK-4) challenge in healthy subjects. BDNF concentrations were detected in serum samples of 37 male and female volunteers before and 120 min after CCK-4 injection. The baseline levels of serum BDNF did not predict the occurrence of CCK-4-induced panic attacks or intensity of panic symptoms and did not significantly change 2 h after the challenge. BDNF serum concentrations 120 min after provocation did not differentiate panickers from non-panickers; however, the subjects reporting stronger anxiety response showed higher levels of BDNF than those with mild anxiety. The anxiety net increase on the Visual Analogue Scale, but not severity of panic symptoms, significantly and positively correlated with the change in BDNF concentration from baseline values. This is the first challenge study to demonstrate a possible impact of BDNF on human anxiety. Our findings suggest a general involvement of BDNF in the regulation of anxiety rather than a specific role of BDNF in disposition to panic attacks.
A comparison of the effects of a subtype selective and non-selective benzodiazepine receptor agonist in two CO2 models of experimental human anxiety
Authors: Bailey JE , Papadopoulos A , Seddon K , Nutt DJ
Published: June 2008

Abstract

Studies in human volunteers that can demonstrate proof of concept are attractive in that possible mechanisms and potential new drug treatments can be examined. We have been developing models of anxiety disorders using the inhalation of 7.5% CO2for 20 min to model generalised anxiety disorder, as well as using the previously reported 35% CO2as a model for panic anxiety. In a double-blind, placebo-controlled, three-way crossover study in 12 healthy volunteer subjects, we compared a full agonist at the benzodiazepine receptor that binds to four α-subtypes of the receptor (α-1,-2,-3,-5) (alprazolam 1 mg), with zolpidem (5 mg), an agonist selective for the α-1 subtype of the gamma amino butyric acid-receptor subtype A (GABA-A) receptor, which is a widely used hypnotic drug. Compared with placebo, both drugs significantly attenuated peak CO2-induced changes in subjective feelings after the inhalation of 7.5% CO2for 20 min. However, there were fewer significant differences after a single vital capacity inhalation of 35% CO2, where zolpidem was less efficacious than alprazolam at reducing CO2-induced symptoms. In conclusion, our results show that zolpidem shows some anxiolytic efficacy in the 7.5% CO2model, similar to alprazolam, and this is the first report of such an effect of zolpidem in a model of anxiety. These and other studies of benzodiazepines in clinical and volunteer studies suggest a definite role of the GABA-A receptor in CO2-induced anxiety, and it would be of interest to examine other GABA-A receptor subtype selective drugs, which are now in early phase clinical studies and are showing selective efficacy in pharmacodynamic studies.
Amisulpride doses and plasma levels in different age groups of patients with schizophrenia or schizoaffective disorder
Authors: Müller MJ , Eich FX , Regenbogen B , Sachse J , Härtter S , Hiemke C
Published: June 2008

Abstract

Because of a unique pharmacodynamic profile, amisulpride seems appropriate for treatment of elderly patients with schizophrenia. In a large-scale naturalistic therapeutic drug monitoring study, daily amisulpride dose, trough and dose-corrected amisulpride plasma levels, co-medication, clinical effectiveness (CGI) and side effects (UKU) were compared between age groups in 395 patients with schizophrenia or schizoaffective disorder (46% women; mean age 39.1 ± 14.2 years, range 18–83 years) under amisulpride therapy. Mean amisulpride doses (574 ± 269 mg/day), plasma levels (304 ± 274 ng/mL), dose-corrected amisulpride plasma levels (C/D ratios, 0.52 ± 0.41 ng/mL:mg), clinical response (at least moderate improvement, 71.6%), and side effects (any side effect, 32.2%; extrapyramidal symptoms, 14.9%) were comparable between age groups ( P > 0.25). At higher age, significantly more benzodiazepines ( P = 0.04), non-benzodiazepine hypnotics ( P = 0.004) and non-psychotropic medications ( P < 0.0001) were prescribed. The naturalistic study showed higher C/D ratios in women ( P = 0.019) and a slight increase of C/D ratios with age ( P = 0.026), but no substantial age-dependent effects on amisulpride doses or plasma levels. In patients above 60 years, clinical response was associated with lower amisulpride plasma levels ( P = 0.016) at comparable doses. Neither the age-dependent decrease of amisulpride clearance nor the significantly higher prevalence of co-morbidity and co-medication seem to be the reasons for definite clinical concerns against amisulpride treatment of elderly if contraindications are seriously taken.
Infusion of gliotoxins or a gap junction blocker in the prelimbic cortex increases alcohol preference in Wistar rats
Authors: Miguel-Hidalgo J , Shoyama Y , Wanzo V
Published: June 2008

Abstract

Postmortem research has revealed that there is a lower density of glial cells in regions of the prefrontal cortex (PFC) of uncomplicated alcoholics when compared with control subjects. Impairment of astrocyte function in the PFC may contribute to malfunction in circuits involved in emotion- and reward-related subcortical centers, heavily connected with the PFC and directly involved in the pathophysiology of addictive behaviours. The hypothesis was tested that infusion of gliotoxins known to injure astrocytes or of a gap junction blocker into the prelimbic area of the rat PFC results in increased preference for ethanol in rats exposed to free choice between water and 10% ethanol. Fluorocitric acid, L-α-aminoadipic acid (AAD) or the gap junction blocker 18-α-glycyrrhetinic acid (AGA) were bilaterally infused once into the rat prelimbic cortex and alcohol preference (ratio of 10% ethanol consumed to total liquid ingested) was measured before and after infusion. Infusion of AAD or AGA dissolved in their vehicles, but not of their vehicles alone, resulted in significant transient increase of preference for 10% ethanol. The present data suggest that impaired integrity of glial cells or the gap junctional communication between them in the rat PFC may contribute to changes in ethanol preference.
Catatonia, neuroleptics and brain damage – a case report
Authors: Chandran M , El-Shazly M
Published: June 2008

Abstract

Catatonia is a syndrome that encompasses multiple motor signs. It can be the only presenting clinical feature in a patient with underlying multiple neuropsychiatric syndromes. The authors present a case of amisulpiride-induced catatonia, further evaluation suggested neuroleptic malignant syndrome (NMS) and showed the occurrence of temporal lobe epilepsy (TLE) and underlying brain pathology with marked frontoparietal atrophy and periventricular white matter hyperintensities. The pathological substrate of catatonia and its complex association with neuropsychiatric syndromes are discussed.
Modafinil treatment of amphetamine abuse in adult ADHD
Authors: Mann N , Bitsios P
Published: June 2008

Abstract

Substance abuse is a frequent co-morbid condition of adult attention deficit hyperactivity disorder (ADHD). Treatment with conventional psychostimulants in adult ADHD with co-morbid stimulant abuse may be problematic. In this study, we report the case of a patient with adult ADHD with co-morbid amphetamine abuse who was treated successfully with the non-stimulant alertness-promoting drug modafinil. The drug resolved both the inattention/hyperactivity symptoms as well as the amphetamine abuse. Modafinil may be a suitable candidate treatment for adults with ADHD and stimulant abuse.
Risperidone-induced sexual dysfunction in a prepubertal child - a case report
Authors: Wadoo O , Chalhoub N
Published: June 2008

Abstract

We report on a child with attention deficit hyperactivity disorder and motor tics, who developed frequent penile erections during treatment with risperidone and atomoxetine. On discontinuation of risperidone, he recovered fully. Clinicians should be alert to the adverse effects of atypical antipsychotics, which are used to treat a wide variety of paediatric psychiatric disorders.
The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment
Authors: Wilffert B , Al Hadithy AFY , Sing VJ , Matroos G , Hoek HW , van Os J , Bruggeman R , Brouwers JRBJ , van Harten PN
Published: June 2008

Abstract

Tardive dyskinesia (TD) is associated with polymorphisms of the dopamine D3, serotonin 2A and 2C receptors (DRD3, HTR2A and HTR2C, respectively). This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), −1438G>A(HTR2A) and Cys23Ser (HTR2C) in African-Caribbean inpatients. One hundred and twenty-six patients under chronic antipsychotic treatment were genotyped. The assessment of TD was carried out with the abnormal involuntary movement scale (AIMS). The relationships between the carriership of the least frequent alleles and the respective orofaciolingual dyskinesia (TDof) (sum of the items 1-4 of the AIMS), limb-truncal dyskinesia (TDlt) (sum of items 5-7 of the AIMS) and TD (sum of items 1-7 of the AIMS) were analyzed with ANCOVA, comparing means with age as a covariate and stratification for carriers and non-carriers of the mutations. In addition, we conducted pre-planned t-tests to compare AIMS values of carriers of the combinations of alleles versus the corresponding non-carriers. In the study population, females with 9Ser carriership exhibited higher AIMS values than non-carriers. Male subjects with 9Ser carriership in combination with 23Ser or −1438A carriership exhibited higher AIMS values. In male patients also, the combination of 23Ser and −1438A carriership increased TD. The study clearly shows that the African-Carribean population differs from the Caucasian population with regard to the association of TD with the polymorphisms studied and suggests that the association of TD with the studied polymorphisms of the 5-HT2C and probably of the 5-HT2A receptor are the result of a changed susceptibility of the patients, independent of the action of the antipsychotics on these receptors.
Long-term effects of cannabis on oculomotor function in humans
Authors: Huestegge L , Radach R , Kunert HJ
Published: June 2008

Abstract

Cannabis is known to affect human cognitive and visuomotor skills directly after consumption. Some studies even point to rather long-lasting effects, especially after chronic tetrahydrocannabinol (THC) abuse. However, it is still unknown whether long-term effects on basic visual and oculomotor processing may exist. In the present study, the performance of 20 healthy long-term cannabis users without acute THC intoxication and 20 control subjects were examined in four basic visuomotor paradigms to search for specific long-term impairments. Subjects were asked to perform: 1) reflexive saccades to visual targets (prosaccades), including gap and overlap conditions, 2) voluntary antisaccades, 3) memory-guided saccades and 4) double-step saccades. Spatial and temporal parameters of the saccades were subsequently analysed. THC subjects exhibited a significant increase of latency in the prosaccade and antisaccade tasks, as well as prolonged saccade amplitudes in the antisaccade and memory-guided task, compared with the control subjects. The results point to substantial and specific long-term deficits in basic temporal processing of saccades and impaired visuo-spatial working memory. We suggest that these impairments are a major contributor to degraded performance of chronic users in a vital everyday task like visual search, and they might potentially also affect spatial navigation and reading.
Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression?
Authors: Ebinger M , Sievers C , Ivan D , Schneider HJ , Stalla GK
Published: June 2008

Abstract

Depression is a disease of growing incidence and economic burden worldwide. In view of increasing treatment resistance, new therapeutic approaches are urgently needed. In addition to its gonadal functions, testosterone has many effects on the central nervous system. An association between testosterone levels and depressive symptoms has been proposed. Many hormones and neurotransmitters are involved in the aetiology and the course of depression including serotonin, dopamine, noradrenaline, vasopressin and cortisol. Testosterone is known to interact with them. Preclinical data suggest that testosterone has antidepressant potential. However, the data from clinical studies have been inconsistent. This review provides a critical overview on the currently available preclinical and clinical literature and concludes with clinical recommendations.
An Optimization-Based System Model of Disturbance-Generated Forest Biomass Utilization
Authors: Curry Guy L. , Coulson Robert N. , Jianbang Gan  , Tchakerian Maria D. , Tattersall Smith C.
Published: June 2008

Disturbance-generated biomass results from endogenous and exogenous natural and cultural disturbances that affect the health and productivity of forest ecosystems. These disturbances can create large quantities of plant biomass on predictable cycles. A systems analysis model has been developed to quantify aspects of system capacities (harvest, transportation, and processing), spatial aspects of the biomass generation process, and deterioration impacts on biomass quality in the various inventory states (field stands, field-harvested inventories, transportation prepared inventories, and production facility inventories). Optimal decision alternatives can be used to guide responses to reclamation, utilization, mitigation, and control. This is particularly advantageous in insect and disease outbreaks, in which the process may last several years, with varying levels of intensity. The prescriptive system description, assuming capacities are fixed, results in a linear programming model. The time-dependent capacity decision model results in a mixed-integer programming model. The analytical model is developed in detail in this analysis.
Designing a Marketing Course With Field Site Visits
Authors: Van Doren Doris , Corrigan Hope Bober
Published: June 2008

A key goal of including field site visits in marketing courses is to give business students increased interaction with industry professionals and community leaders. Site visits give students a concrete idea of how different marketing disciplines work in the business world. Business students gain greater insight into a career in marketing from this type of course. Undergraduate students learn about careers in marketing early in their college education and graduate students realize new career opportunities. In this course, students prepared for and completed two experiential site visits to businesses in the local area to reach these goals. Significant benefits of this course included building stronger relationships between the Sellinger School of Business and Management and local companies and introducing students to prospective employers. This article describes the reasoning behind the course as well as practical strategies for faculty interested in implementing site visits as an experiential teaching approach. A pilot graduate course has been completed at Loyola College in Maryland with encouraging results, and an undergraduate course with site visits is planned. Early results indicate that it is possible to incorporate site visits into any marketing course.
Genotoxicity induced by pesticide mixtures: in-vitro studies on human peripheral blood lymphocytes
Authors: Das PP , Shaik AP , Jamil K
Published: June 2008

To assess the damage caused by pesticides and their mixtures on humans, we designed in-vitro experiments to evaluate their cytotoxicity and genotoxicity. Three equimolar pesticide mixtures were investigated for their capability to affect cultured human peripheral blood lymphocytes. The LC50 values for cytotoxicity, using standard trypan blue dye exclusion and calculated by probit analysis, were 4.18, 5.76, and 7.5 μM for endosulfan, carbofuran, and monocrotophos, respectively. When combined in equimolar concentrations, the LC50 values for cytotoxicity were 0.7, 0.9, and 1.0 μM for monocrotophos + carbofuran, endosulfan + monocrotophos, and endosulfan + carbofuran, respectively, using the method. DNA damage was estimated using chromosomal aberrations (chromatid breaks, fragments, gaps, aneuploidy, and satellite association) and comet assays using 1/10 of the LC50 concentrations. Using a standard alkaline comet assay procedure, high concentrations of individual pesticides (0.5–4.0 μM) caused significant DNA damage as indicated by visible tail lengths. Lower concentrations (0.05–0.5 μM) of their binary mixtures could cause the same effect. The results suggest that analysis of genotoxicity may serve as an important biomarker for occupational and household exposure to pesticides, especially mixtures of pesticides, with different modes of action.