bluuebunny/crossref_metadata_2025_split huggingface dataset:
High concentrations of cannabinoids activate apoptosis in human U373MG glioma cells
Authors: Widmer M. , Hanemann C.O. , Zajicek J. 
Published: July 2008

AbstractCannabinoids bind to two G‐protein‐coupled receptors, CB1 and CB2, expressed by neurons and cells of the immune system, respectively. Glioma cells (astrocyte‐derived brain tumor cells) express cannabinoid receptors, and numerous in vitro and in vivo studies performed in rodents have concluded that apoptosis could be induced by cannabinoids in these cells. Whether this also applies to human cells is controversial; we, therefore, assessed the effect of cannabinoids on human glioma cell viability with the human astrocytoma cell line U373MG. We report here that U373MG human glioma cells are sensitive only to high concentrations of cannabinoids (>5 μg/ml for Δ9‐THC). Similar concentrations of the compounds promoted a rapid activation of extracellular‐regulated kinase and c‐Jun NH2‐terminal kinase, suggesting that cannabinoid receptors are functional in U373MG cells. Nevertheless, these kinases are not involved in cannabinoid‐induced cell death in U373MG cells, insofar as blocking their activation with specific inhibitors does not reduce cell death. CB1 is expressed in U373MG cells and is involved in cannabinoid‐induced cell death, in that blocking its activation with a specific antagonist (AM251) almost totally prevented cell death following incubation of the cells with Δ9‐THC. In addition, as already reported, some cannabinoids may have modest proproliferative properties in U373MG cells. Human U373MG glioma cells are sensitive only to very high, pharmacologically irrelevant concentrations of cannabinoids, so it seems unlikely that cannabinoids would constitute promising molecules for treating malignant astrocytoma; they do not induce glioma cell death at doses that could be applied safely to humans. © 2008 Wiley‐Liss, Inc.
Okadaic acid increases autophagosomes in rat neurons: Implications for Alzheimer's disease
Authors: Yoon Seung Yong , Choi Jung Eun , Kweon Hee‐Seok , Choe Han , Kim Seong Who , Hwang Onyou , Lee Heuiran , Lee Joo‐Yong , Kim Dong Hou 
Published: July 2008

AbstractAutophagosomes are accumulated in Alzheimer's disease (AD), but the regulatory pathway of autophagy in AD remains largely unknown. By using electron microscopy, Western blotting, and immunocytochemistry, here we show that autophagosomes are accumulated in rat neurons by okadaic acid (OA), a protein phosphatase‐2A inhibitor known to enhance tau phosphorylation, β‐amyloid (Aβ) deposition, and neuronal death, which are the pathological hallmarks of AD. Autophagy can be generally induced via several distinct pathways, such as inhibition of mTOR or activation of beclin‐1. Interestingly, OA increased both mTOR and beclin‐1 pathways simultaneously, which suggests that autophagy in OA‐treated neurons is induced mainly via the beclin‐1 pathway, and less so via mTOR inhibition. Finally, inhibition of autophagy by 3MA reduced cytotoxicity in OA‐treated neurons. Our novel findings provide new insights into the pathology of and therapeutic intervention for AD. © 2008 Wiley‐Liss, Inc.
A technological platform to optimize combinatorial treatment design and discovery for chronic spinal cord injury
Authors: Guertin Pierre A. 
Published: July 2008

AbstractChronic spinal cord injury (SCI) is associated with the development of serious medical concerns. In fact, it is increasingly well documented that most SCI patients who survive the first 24 hr will rapidly develop, within a few months to a few years, cardiovascular problems, type II diabetes, muscle wasting, osteoporosis, immune deficiencies, and other life‐threatening problems. The cellular mechanisms underlying these so‐called secondary health complications remain unclear, and no drug or standard approach has been developed to specifically treat these complications. To investigate the cellular and metabolic changes associated with chronic SCI and functional recovery, work mainly from our laboratory recently has led to the characterization of a mouse model of chronic paraplegia. This review reports cellular, systemic, and metabolic changes (associated mainly with secondary health complications) occurring within a few days to a few weeks after SCI in low‐thoracic spinal cord–transected mice. We also describe our research platform developed to ease technological transfer and to accelerate drug‐screening studies in animals. A global understanding of the many chronic changes occurring after SCI together with efficient tools and approaches for testing new or existing drug candidates is likely to yield the design of innovative treatments against secondary complications that combine cellular plasticity–modulating agents, locomotor network–activating drugs, hormonal therapy, and exercise training. © 2008 Wiley‐Liss, Inc.
Dock4 regulates dendritic development in hippocampal neurons
Authors: Ueda Shuhei , Fujimoto Satoshi , Hiramoto Kiyo , Negishi Manabu , Katoh Hironori 
Published: July 2008

AbstractDendrite development is required for establishing proper neuronal connectivity. Rho‐family small GTPases have been reported to play important roles in the regulation of dendritic growth and morphology. However, the molecular mechanisms that control the activities of Rho GTPases in developing dendrites are not well understood. In the present study we found Dock4, an activator of the small GTPase Rac, to have a role in regulating dendritic growth and branching in rat hippocampal neurons. Dock4 is highly expressed in the developing rat brain, predominantly in hippocampal neurons. In dissociated cultured hippocampal neurons, the expression of Dock4 protein is up‐regulated after between 3 and 8 days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4 results in reduced dendritic growth and branching. Conversely, overexpression of Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and dendritic branches. These morphological effects elicited by Dock4 and ELMO2 require Rac activation and the C‐terminal Crk‐binding region of Dock4. Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons. © 2008 Wiley‐Liss, Inc.
Regeneration of nigrostriatal dopaminergic axons after transplantation of olfactory ensheathing cells and fibroblasts prevents fibrotic scar formation at the lesion site
Authors: Teng Xichuan , Nagata Isao , Li Hong‐Peng , Kimura‐Kuroda Junko , Sango Kazunori , Kawamura Koki , Raisman Geoffrey , Kawano Hitoshi 
Published: July 2008

AbstractThe fibrotic scar formed after central nervous system injury has been considered an obstacle to axonal regeneration. The present study was designed to examine whether cell transplantation into a damaged central nervous system can reduce fibrotic scar formation and promote axonal regeneration. Nigrostriatal dopaminergic axons were unilaterally transected in rats and cultures of olfactory‐ensheathing cells (OECs), and olfactory nerve fibroblasts were transplanted into the lesion site. In the absence of transplants, few tyrosine hydroxylase–immunoreactive axons extended across the lesion 2 weeks after the transection. Reactive astrocytes increased around the lesion, and a fibrotic scar containing type IV collagen deposits developed in the lesion center. The immunoreactivity of chondroitin sulfate side chains and core protein of NG2 proteoglycan increased in and around the lesion. One and 2 weeks after transection and simultaneous transplantation, dopaminergic axons regenerated across the transplanted tissues, which consisted of p75‐immunoreactive OECs and fibronectin‐immunoreactive fibroblasts. Reactive astrocytes and chondroitin sulfate immunoreactivity increased around the transplants, whereas the deposition of type IV collagen and fibrotic scar formation were completely prevented at the lesion site. Transplantation of meningeal fibroblasts similarly prevented the formation of the fibrotic scar, although its effect on regeneration was less potent than transplantation of OECs and olfactory nerve fibroblasts. The present results suggest that elimination of the inhibitory fibrotic scar is important for neural regeneration. © 2008 Wiley‐Liss, Inc.
Interaction of mitochondrial respiratory inhibitors and excitotoxins potentiates cell death in hippocampal slice cultures
Authors: Schuh Rosemary A. , Matthews Christopher C. , Fishman Paul S. 
Published: July 2008

AbstractThe broad‐spectrum insecticide rotenone, an inhibitor of complex I of the mitochondrial electron transport chain (ETC), gives rise to oxidative stress and bioenergetic failure. Pesticides including rotenone have been implicated in human neurodegenerative diseases, including Parkinson's disease. Another intensively investigated hypothesis of neurodegenerative disease involves the toxic action of the excitatory neurotransmitter glutamate. In the present study, we determined whether concomitant exposure of rotenone plus tetraethylammonium chloride (TEA) or the specific glutamate receptor agonists N‐methyl‐D‐aspartate (NMDA) or α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionic acid (AMPA) would cause greater cell death in organotypic hippocampal slice cultures than when given separately. Low, sublethal rotenone (100 nM), TEA (0.5–2.0 mM), NMDA (1.0–10 μM), and AMPA (1.0–10 μM) alone resulted in little cell death as determined by propidium iodide fluorescence. However, cell death was significantly to dramatically potentiated when the hippocampal slices were coincubated with comparable concentrations of rotenone plus TEA, NMDA, or AMPA. Similarly, in the presence of 10 μM NMDA, ETC inhibitors blocking other mitochondrial complexes also potentiated cell death. Immunohistochemical analysis using glial fibrillary acidic protein antibody determined that the cell death was preferentially neuronal. These results demonstrate that two different classes of toxicants can interact, resulting in potentiation of neurotoxicity, and further suggest that a combinatorial therapeutic approach may be required to ameliorate the potentiated cell death. © 2008 Wiley‐Liss, Inc.
Antioxidants partially restore glutamate transport defect in leber hereditary optic neuropathy cybrids
Authors: Sala Gessica , Trombin Federica , Beretta Simone , Tremolizzo Lucio , Presutto Paola , Montopoli Monica , Fantin Marianna , Martinuzzi Andrea , Carelli Valerio , Ferrarese Carlo 
Published: July 2008

AbstractLeber hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by visual loss resulting from retinal ganglion cell degeneration. Despite the important role of respiratory chain deficiency and oxidative stress induced by mtDNA point mutations affecting complex I, excitotoxic injury has been postulated as a concurrent pathogenic factor. We used transmitochondrial cybrid cell lines constructed using enucleated fibroblasts from three LHON probands carrying the most severe 3460/ND1 mutation and three controls as mitochondria donors, and the osteosarcoma‐derived mtDNA‐less cells, to study the possible efficacy of two selected antioxidant compounds in preventing glutamate uptake reduction previously observed in LHON cybrids. We demonstrated that two antioxidants, Trolox and decylubiquinone, partially restore glutamate transport impairment occurring in LHON cybrids. Rotenone, a classic complex I inhibitor, did not worsen the glutamate uptake defect present in LHON cybrids under basal conditions but significantly reduced glutamate transport in control cybrids. Furthermore, we observed that LHON cybrids showed an increased protein carbonylation under basal conditions, not further affected by rotenone and partially counteracted by antioxidants. Our findings strengthen the hypothesis that the complex I defect associated with LHON causes free radical overproduction, which is responsible for glutamate transport inhibition. We suggest that selected antioxidants may be clinically tested in LHON patients and relatives to restore glutamate uptake defect caused by LHON‐associated free radical overproduction. © 2008 Wiley‐Liss, Inc.
Antioxidant, antiinflammatory and antiapoptotic effects of dapsone in a model of brain ischemia/reperfusion in rats
Authors: Diaz‐Ruiz Araceli , Zavala Carlos , Montes Sergio , Ortiz‐Plata Alma , Salgado‐Ceballos Hermelinda , Orozco‐Suarez Sandra , Nava‐Ruiz Concepción , Pérez‐Neri Iván , Perez‐Severiano Francisca , Ríos Camilo 
Published: July 2008

AbstractAlthough dapsone (4,4′‐diaminodiphenylsulfone) has been described as a neuroprotective agent in occlusive focal ischemia in rats, its mechanism of action is still unknown. To explore this mechanism, oxidative, inflammatory and apoptotic processes were evaluated in the striatum of adult rats using a model of ischemia‐reperfusion (I/R), either with or without dapsone treatment. Male Wistar rats were submitted to transient middle cerebral artery occlusion for 2 hr, followed by reperfusion. Rats were dosed either with dapsone (12.5 mg/kg i.p.) or vehicle 30 min before or 30 min after the ischemia onset. Lipid peroxidation (LP) and nitrotyrosine contents were measured 22 hr after reperfusion, and myeloperoxidase activity was evaluated 46 hr after I/R. Different markers for apoptosis and necrosis were also evaluated both at 24 and 72 hr after I/R experimental procedure. LP increased by 37% in ischemic animals vs controls, and this effect was reversed by dapsone treatments. A similar effect was observed regarding nitrotyrosine striatal contents. Myeloperoxidase activity, a marker of inflammatory response, increased 3.7‐fold in ischemic animals vs. control rats, and dapsone treatment antagonized that effect. Although apoptosis was increased by the effect of ischemia at both evaluation times, dapsone antagonized that effect only at 72 hr after surgery. Dapsone antagonized all of the I/R end points measured, showing a remarkable ability to decrease markers of damage through antioxidant, antiinflammatory, and anti‐apoptotic effects. © 2008 Wiley‐Liss, Inc.
On the factors modulating the intensity of the tropical rainbelt over West Africa
Authors: Nicholson Sharon E. 
Published: July 2008

AbstractThis article presents a case study of a wet and a dry year over West Africa. These 2 years, 1955 and 1983, are characterized by rainfall anomalies of one sign throughout West Africa, including the Sahel and Guinea Coast (the no‐dipole cases defined in previous studies). The contrast in rainfall is related to a general weakening and intensification of the tropical rainbelt in the dry year (1983) and the wet year (1955), respectively. The study, limited to the month of August, examines the factors that modulate the intensity of the rainbelt. The more intense rainbelt of 1955 is associated with an anomalously strong tropical easterly jet (TEJ) and a slight northward displacement of the African easterly jet of the Northern Hemisphere (AEJ‐N). The link between the TEJ and rainfall is a causal one, with the strong TEJ enhancing rainfall by enhancing upper‐level divergence and sustaining a strong Hadley‐type overturning over West Africa, with strong vertical motion. In 1983, a weak TEJ and vertical alignment of the AEJ‐N and TEJ axes promote a weak rainbelt and ubiquitous drought. The factors that produce a rainfall dipole (i.e. an opposition in the sign of anomalies between the Sahel and the Guinea Coast) are notably different. The dipole results from meridional displacements of the circulation and rainbelt, rather than changes in rainbelt intensity. Although the strong TEJ is a prime factor, the development of the dipole requires the development of strong and vertically extensive equatorial westerlies. These are produced by strong surface pressure gradients over the Atlantic and West Africa. Copyright © 2008 Royal Meteorological Society
Analysis of a 27‐year rainfall data (1977–2003) in the Sultanate of Oman
Authors: Kwarteng Andy Y. , Dorvlo Atsu S. , Vijaya Kumar Ganiga T. 
Published: July 2008

AbstractAnalysis of variation of rainfall in space, time and amounts, and its attendant effect on the ecosystem is vital in arid and semi‐arid environments where the resource is scare, highly variable and unpredictable. In this study, we analyse the characteristics of rainfall in the Sultanate of Oman using data recorded between 1977 and 2003. The data is divided into six geomorphic compartments to represent the various topographic regions in Oman. The average yearly rainfall varies from a low of 76.9 mm in the interior region to a high of 181.9 mm in the Dhofar Mountains, with an average of 117.4 mm for the whole country. Mann–Kendall statistics show a negative but insignificant rainfall trends for the datasets. In northern Oman, the main rainfall season occurs between December and April and that accounts for 57.8–82.9% of the annual rainfall. February and March record the highest rainfall accounting for 35.3 to 42% of the yearly rainfall. The Dhofar Mountains and surrounding areas in southern Oman are dominated by the khareef season in July–August, which produces 44.3 to 67.5% of the rainfall in that area. The number of days of light rainfall (<10 mm per day) is the most dominant and accounts for 66–95% of the rain. Rain in excess of 50 mm per day is rare in Oman (0.4 and 2.9%), but when it does occur can result in serious consequences such as flash flooding, human catastrophes and land degradation. Rainfall records indicate that Muscat and surrounding areas are susceptible to tropical cyclones and catastrophic rainfall (>100 mm rainfall per day) approximately every 50 years. Copyright © 2008 Royal Meteorological Society
Characteristics of the leaf parts of some traditional Korean salad plants used for food
Authors: Chon Sang‐Uk , Heo Buk‐Gu , Park Yong‐Seo , Cho Ja‐Yong , Gorinstein Shela 
Published: July 2008

AbstractBACKGROUND: Total phenolics content, antioxidant activity and cytotoxicity of the methanol extracts from leaf parts of 13 Korean traditional salad plants were investigated in order to determine their properties.RESULTS: The highest phenolics content (mg ferulic acid equivalents kg−1 dry weight (d.w.), omit one) was found in methanol extracts from Polygonum aviculare, at 293.7 ± 6.0, followed by Euonymus alatus, at 250.7 ± 3.3, Saxifraga stolonifera, at 125.0 ± 8.1 and Ligularia fischeri, at 122.5 ± 5.9. The methanol plant extracts dose‐dependently increased free radical scavenging activity. Methanol extracts of Polygonum aviculare, Euonymus alatus and Saxifraga stolonifera, at 31 mg kg−1, exhibited the highest 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging activity (%) by 90.8 ± 4.2, 85.7 ± 3.9 and 64.1 ± 3.2, respectively. According to 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, the methanol extracts from Portulaca oleracea (IC50 < 25.0 µg mL−1) showed the highest cytotoxicity against Calu‐6, followed by Plantago asiatica (49.2 µg mL−1) and Osmunda japonica (89.6 µg mL−1).CONCLUSION: Total phenolics content of the tested plant extracts was correlated with the DPPH radical scavenging activity, suggesting the phenolics compounds are contributing to the antioxidant properties of Korean salad plants. The leaf parts of the 13 Korean traditional salad plants described here that are currently used as foods may also provide some benefit to human health, and research into their potential benefits as preventative and/or therapeutic agents is warranted. Copyright © 2008 Society of Chemical Industry
A modern regimen of pre‐operative concurrent chemo‐radiation therapy in locally advanced rectal cancer
Authors: Bazarbashi Shouki , el‐Bassiouni Mazen , Abdelsalam Mahmoud , Soudy Hussein , Sanea Nasser al , Jabbar Alaa Abdul , Manji Mohamed , Fagih Mosa , Ajarim Dahish 
Published: July 2008

AbstractPurposeTo evaluate the efficacy and toxicity of preoperative concurrent capecitabine and radiotherapy in the treatment of resectable locally advanced rectal cancer (LARC).Materials and MethodsWe conducted a phase II trial to assess pathological complete response, tumor downstaging, toxicity and survival of capecitabine (825 mg/m2 orally, twice daily) with radiotherapy (50.4 Gy/28 fractions) in 31 patients with LARC (cT3/T4 or N+) staged by endoscopic ultrasound (EUS).ResultsMedian age was 53 years; with M:F ratio of 1:1.58; 77.4% had Eastern Cooperative Oncology Group performance status of 1. EUS showed that 67.7% of tumors were T3, 19.4% were T4, and 58% were node positive. Of 30 patients who had surgery, 6.5% achieved pathological complete remission (pCR). Tumor and nodal downstaging were achieved in 53.9% and 50% of patients, respectively. Grade 3/4 toxicities were mainly diarrhea (35.5%) and proctitis (32.3%). Sphincter preservation was achieved in 4/21 (15%) of patients initially planned for abdominoperineal resection. The median follow‐up was 46 months (Range: 1.47–63.9), and the 3‐year disease‐free and overall survival were 59.8% and 76.6%, respectively.ConclusionCapecitabine given concurrently with radiation therapy is generally well tolerated, and proved to be an effective radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer, yielding results comparable to those reported with 5‐FU. J. Surg. Oncol. 2008;98:167–174. © 2008 Wiley‐Liss, Inc.
Using the Delphi method to assess the potential of Taiwan's hot springs tourism sector
Authors: Lee Cheng‐Fei , King Brian Edward 
Published: July 2008

AbstractThe purpose of the present study is to identify the various factors that influence the competitiveness of the hot springs tourism sector. The research draws on the models of Ritchie and Crouch, Dwyer and Kim, and Enright and Newton, who concluded that destination competitiveness is determined by three major components: resources and attractors, destination strategies and environments. The investigation produced both qualitative and quantitative data using the Delphi technique. An expert panel reached consensus about priorities for the development of Taiwan's hot springs tourism sector and provided written justifications for their responses. This paper reports on the qualitative findings of the three‐round Delphi survey and provides a supply‐side perspective on Taiwan's hot springs tourism sector. An examination of the expert comments concluded that the Taiwanese are increasingly concerned with good health and longevity. This emerging characteristic offers new business opportunities for the providers of hot springs tourism experiences to extend their appeal into health protection and medical treatments. However, if they are to achieve sustainable development and ensure high‐quality visitor experiences, hot springs proprietors will need to work closely with local governments and communities to promote sustainable use of natural hot springs and to conduct routine inspections of spa premises. Overall, the future of the hot springs tourism sector appears to be promising. Copyright © 2008 John Wiley and Sons, Ltd.
Concentration, productivity and profitability in the Italian commercial accommodation sector
Authors: Succurro Marianna 
Published: July 2008

AbstractThis study avails itself of the Aida data bank from which were taken the accounting data for the 2,518 limited companies active in the Italian accommodation sector in the years 2000–2006. The research aims at describing the structural characteristics and the competitive advantages of the Italian accommodation sector. The Italian position as leader would seem to be threatened by the entry into the market place of new‐comer countries. Understanding the sector's industrial organisation would appear to be a particularly important step towards the implementation of an effective policy for the industry. Copyright © 2008 John Wiley & Sons, Ltd.