bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel role for the δ‐opioid receptor in hypoxic preconditioning in rat retinas
Authors: Peng Pai‐Huei , Huang Ho‐Shiang , Lee Yih‐Jing , Chen Yih‐Sharng , Ma Ming‐Chieh 
Published: November 2008

Abstractδ‐Opioid receptor (DOR) is an oxygen‐sensitive protein whose function in the rat retina is unknown. We examined whether DOR is involved in hypoxic preconditioning (HPC)‐mediated retinoprotection following intraocular pressure (IOP) elevation. Rats were exposed to intermittent hypoxia (10% oxygen) to induce HPC. Unilateral retinal ischemia/reperfusion injury was induced by elevating IOP to 100 mmHg for 1 h. HPC attenuated the loss of neuronal marker expression and increased pro‐apoptotic caspase 3 activity in the IOP retina. Excess superoxide production and 8‐iso‐prostaglandin F2α accumulation caused by enhanced oxidant protein expression and reduced antioxidant enzyme level after IOP elevation were largely abrogated by HPC. HPC markedly increased the expression of hypoxia‐inducible factor‐1α (HIF‐1α) and DOR, but intravitreal administration of HIF‐1α‐specific small interfering RNA abrogated the up‐regulation of DOR. This suggested that DOR functions downstream of HIF‐1α. However, the endogenous content of leucine enkephalin in retinas was not affected by HPC or IOP. Treatment of retinas with the DOR antagonist naltrindole attenuated the HPC‐induced protection and activation of extracellular signal‐regulated kinase. These results suggest a novel mechanism of HPC‐mediated retinoprotection whereby HIF‐1α induces the expression of DOR, and DOR‐mediated activation of extracellular signal‐regulated kinase triggers cellular events that correct the redox imbalance in the post‐ischemic retina.
Hydrogen sulfide evokes neurite outgrowth and expression of high‐voltage‐activated Ca2+ currents in NG108‐15 cells: involvement of T‐type Ca2+ channels
Authors: Nagasawa Keita , Tarui Takeshi , Yoshida Shigeru , Sekiguchi Fumiko , Matsunami Maho , Ohi Ai , Fukami Kazuki , Ichida Seiji , Nishikawa Hiroyuki , Kawabata Atsufumi 
Published: November 2008

AbstractWe investigated if stimulation of T‐type Ca2+ channels with sodium hydrosulfide (NaHS), a donor of hydrogen sulfide (H2S), could cause neuronal differentiation of NG108‐15 cells. Like dibutyryl cyclic AMP (db‐cAMP), treatment with NaHS at 1.5–13.5 mM for 16 h enhanced neurite outgrowth in a concentration‐dependent manner. Synergistic neuritogenic effect was obtained in the cells stimulated with NaHS in combination with db‐cAMP at subeffective concentrations. Exposure to NaHS or db‐cAMP for 2 days resulted in enhancement of expression of high‐voltage‐activated currents consisting of N‐, P/Q‐, L‐ and also other types, but not of T‐type currents. Mibefradil, a pan‐T‐type channel blocker, abolished the neuritogenesis induced by NaHS, but not by db‐cAMP. The NaHS‐evoked neuritogenesis was also completely blocked by pretreatment with BAPTA/AM, a chelator of intracellular Ca2+, and by zinc chloride at a concentration known to selectively inhibit Cav3.2 isoform of T‐type Ca2+ channels, but not Cav3.1 or Cav3.3. Further, l‐ascorbate, recently proven to selectively inhibit Cav3.2, abolished the neuritogenic effect of NaHS, but not db‐cAMP. Our data thus demonstrate that NaHS/H2S is a novel inducer of neuronal differentiation in NG108‐15 cells, as characterized by neuritogenesis and expression of high‐voltage‐activated currents, and suggest the involvement of T‐type Ca2+ channels, especially Cav3.2.
Pancreas β‐cells morphology, liver antioxidant enzymes and liver oxidative parameters in alloxan‐resistant and alloxan‐susceptible Wistar rats: a viable model system for the study of concepts into reactive oxygen species
Authors: Behr Guilherme Antônio , Da Silva Evandro Gomes , Ferreira Amâncio Romanelli , Cerski Carlos Thadeu Schmidt , Dal‐Pizzol Felipe , Moreira José Cláudio Fonseca 
Published: November 2008

AbstractThe aim of this study was to investigate biochemical and antioxidant parameters in alloxan‐resistant (ALR) and alloxan‐susceptible (ALS) rats. Diabetes was induced in 60‐day‐old male Wistar rats by a single intraperitonial injection of alloxan (AL, 150 mg/kg). Ten days after induction, a group of rats showed a significant decrease in glycemia. This group was named alloxan‐resistant group. Susceptible rats showed a remarkable increase in the plasma lipid content, blood glucose and HbA1. Glycogen content in the liver decreased significantly in the ALS group (2.08 ± 0.41 mg%) compared with ALR group (4.22 ± 0.18). Aspartate aminotransferase and alanine aminotransferase activities were quantified in the plasma. Interestingly, ALR rats showed a decrease in both activities (42.1 ± 6.11 and 21.7 ± 5.54 U/mL) when compared with ALS rats (59.1 ± 6.55 and 58.1 ± 7.28 U/mL). The TBARS index was significantly increased in the ALS liver (0.38 ± 0.08 nm/mg protein) when compared with the ALR liver (0.18 ± 0.04). Superoxide dismutase and catalase activities in the ALR (230 ± 13 and 131 ± 15 U/mg protein) liver showed a marked increase when compared with the ALS liver (148 ± 13 and 68 ± 5 U/mg protein). The immunohistochemical and hematoxilin–eosin analysis also revealed that pancreatic islets of ALR rats display a different morphology amongst the groups. These results suggest an increased regenerative or recovery process in the ALR rat pancreatic islets and an increased hepatic antioxidant defenses in these group of alloxan‐resistant rats.
An insight on the neuropharmacological activity ofTelescopium telescopium– a mollusc from the Sunderban mangrove
Authors: Samanta S.K. , Manisenthil Kumar K.T. , Roy Amrita , Karmakar S. , Lahiri Shawon , Palit G. , Vedasiromoni J.R. , Sen T. 
Published: November 2008

AbstractThe present study was carried out to evaluate the biological properties of the tissue extract of a marine snailTelescopium telescopium, collected from the coastal regions of West Bengal India. On extensive pharmacological screening, it was found that the biological extract ofT. telescopium(TTE) produced significant central nervous system (CNS)‐depressant activity as observed from the reduced spontaneous motility, potentiation of pentobarbitone induced sleeping time, hypothermia and respiratory depression with transient apnoea. The extract significantly decreased both residual curiosity and also muscle coordination. The fraction, obtained following saturation with 60–80% ammonium sulphate (80S), was also found to demonstrate predominant CNS‐depressant activity. It was observed that both TTE and the 80S fraction significantly altered the brain noradrenaline and homovanillic acid levels without affecting the brain gamma amino butyric acid (GABA) concentration. Based on the present observations, it can be suggested that the CNS‐depressant effects produced by TTE and 80S could be attributable to modified catecholamine metabolism in the brain.
The Hill equation: a review of its capabilities in pharmacological modelling
Authors: Goutelle Sylvain , Maurin Michel , Rougier Florent , Barbaut Xavier , Bourguignon Laurent , Ducher Michel , Maire Pascal 
Published: November 2008

AbstractThe Hill equation was first introduced by A.V. Hill to describe the equilibrium relationship between oxygen tension and the saturation of haemoglobin. In pharmacology, the Hill equation has been extensively used to analyse quantitative drug–receptor relationships. Many pharmacokinetic–pharmacodynamic models have used the Hill equation to describe nonlinear drug dose–response relationships. Although the Hill equation is widely used, its many properties are not all well known. This article aims at reviewing the various properties of the Hill equation. The descriptive aspects of the Hill equation, in particular mathematical and graphical properties, are examined, and related to Hill’s original work. The mechanistic aspect of the Hill equation, involving a strong connection with the Guldberg and Waage law of mass action, is also described. Finally, a probabilistic view of the Hill equation is examined. Here, we provide some new calculation results, such as Fisher information and Shannon entropy, and we introduce multivariate probabilistic Hill equations. The main features and potential applications of this probabilistic approach are also discussed. Thus, within the same formalism, the Hill equation has many different properties which can be of great interest for those interested in mathematical modelling in pharmacology and biosciences.
Evaluation of chalcones – a flavonoid subclass, for, their anxiolytic effects in rats using elevated plus maze and open field behaviour tests
Authors: Jamal Huma , Ansari Wajid Hussain , Rizvi Shamim Jahan 
Published: November 2008

AbstractThe clinical applications of benzodiazepines as anxiolytics are limited because of their unwanted side effects. Therefore, the development of new pharmacological agents is well justified. Eight variably substituted chalcones were investigated for their effects on central nervous system if they have anxiolytic effects in rats. Anxiolytic effects of chalcones were also compared with standard anxiolytic drug (diazepam, DZP). Rats were injected intraperitoneally with chalcones, their derivatives and DZP for 3 days. Chalcones and their derivatives were injected at the dose of 25 mg/kg body weight and DZP was injected at the dose of 1 and 2 mg/kg body weight. Rats were then subjected to various anxiety paradigms including the open field behaviour and elevated plus maze tests. In addition, their effects on rota rod performance and grip strength were also examined. Variably substituted chalcones and DZP showed differential pattern of activities.
Can positron emission tomography facilitate paediatric drug development?
Authors: Zimmer Luc 
Published: November 2008

AbstractAdvances in paediatric clinical pharmacology are interdependent with a better understanding of the influence of growth on drug disposition and action. In this field, there is an increasing need for non‐invasive drug monitoring approaches. This paper aims to discuss the role of positron emission tomography in such practice. This molecular imaging technique enables the determination of the distribution of a drug radiolabelled with a positron‐emitting radionuclide. Able to directly assess both pharmacokinetic and pharmacodynamic events in humans, positron emission tomography provides a new perspective on paediatric drug research. Although placing this technique in a unique position to potentially contribute to the process of drug development and evaluation in paediatrics, several ethical and methodological aspects should be considered.
Muscle precursor cells isolated from aged rats exhibit an increased tumor necrosis factor‐α response
Authors: Lees Simon J. , Zwetsloot Kevin A. , Booth Frank W. 
Published: November 2008

SummaryImproving muscle precursor cell (MPC, muscle‐specific stem cells) function during aging has been implicated as a key therapeutic target for improving age‐related skeletal muscle loss. MPC dysfunction during aging can be attributed to both the aging MPC population and the changing environment in skeletal muscle. Previous reports have identified elevated levels of tumor necrosis factor‐α (TNF‐α) in aging, both circulating and locally in skeletal muscle. The purpose of the present study was to determine if age‐related differences exist between TNF‐α‐induced nuclear factor‐kappa B (NF‐κB) activation and expression of apoptotic gene targets. MPCs isolated from 32‐month‐old animals exhibited an increased NF‐κB activation in response to 1, 5, and 20 ng mL−1 TNF‐α, compared to MPCs isolated from 3‐month‐old animals. No age differences were observed in the rapid canonical signaling events leading to NF‐κB activation or in the increase in mRNA levels for TNF receptor 1, TNF receptor 2, TNF receptor‐associated factor 2 (TRAF2), or Fas (CD95) observed after 2 h of TNF‐α stimulation. Interestingly, mRNA levels for TRAF2 and the cell death‐inducing receptor, Fas (CD95), were persistently upregulated in response to 24 h TNF‐α treatment in MPCs isolated from 32‐month‐old animals, compared to 3‐month‐old animals. Our data indicate that age‐related differences may exist in the regulatory mechanisms responsible for NF‐κB inactivation, which may have an effect on TNF‐α‐induced apoptotic signaling. These findings improve our understanding of the interaction between aged MPCs and the changing environment associated with age, which is critical for the development of potential clinical interventions aimed at improving MPC function with age.
Molecular mechanisms of IL‐18BP regulation in DLD‐1 cells: pivotal direct action of the STAT1/GAS axis on the promoter level
Authors: Bachmann Malte , Paulukat Jens , Pfeilschifter Josef , Mühl Heiko 
Published: November 2008

AbstractInterleukin (IL)‐18, formerly known as interferon (IFN)‐γ‐inducing factor, is a crucial mediator of host defence and inflammation. Control of IL‐18 bioactivity by its endogenous antagonist IL‐18 binding protein (IL‐18BP) is a major objective of immunoregulation. IL‐18BP is strongly up‐regulated by IFN‐γ, thereby establishing a negative feedback mechanism detectable in cell culture and in vivo. Here we sought to investigate in D.L. Dexter (DLD) colon carcinoma cells molecular mechanisms of IL‐18BP induction under the influence of IFN‐γ. Mutational analysis revealed that a proximal γ‐activated sequence (GAS) at the IL‐18BP promoter is of pivotal importance for expression by IFN‐γ‐activated cells. Use of siRNA underscored the essential role of the signal transducer and activator of transcription (STAT)‐1 in this process. Indeed, electrophoretic mobility shift assay and chromatin immunoprecipitation analysis proved STAT1 binding to this particular GAS site. Maximal expression of IL‐18BP was dependent on de novo protein synthesis but unaffected by silencing of interferon regulatory factor‐1. Altogether, data presented herein indicate that direct action of STAT1 on the IL‐18BP promoter at the proximal GAS element is key to IL‐18BP expression by IFN‐γ‐stimulated DLD‐1 colon carcinoma cells.
Microbiological and Toxicological Effects of Perla Black Bean (Phaseolus vulgarisL.) Extracts:In VitroandIn VivoStudies
Authors: Lara‐Díaz Víctor Javier , Gaytán‐Ramos Ángel A. , Dávalos‐Balderas Alfredo José , Santos‐Guzmán Jesús , Mata‐Cárdenas Benito David , Vargas‐Villarreal Javier , Barbosa‐Quintana Alvaro , Sanson Misu , López‐Reyes Alberto Gabriel , Moreno‐Cuevas Jorge E. 
Published: November 2008

Abstract: We investigated the microbiological and toxicological effects of three Perla black bean extracts on the growth and culture of selected pathogenic microorganisms, the toxicity over Vero cell lines and anin vivorat model. Three different solvents were used to obtain Perla black bean extracts. All three Perla black bean extracts were tested for antibacterial and antiparasitic activity and further analysed for intrinsic cytotoxicity (IC50). Methanol Perla black bean extract was used for acute toxicity test in rats, with the up‐and‐down doping method. All Perla black bean extracts inhibited bacterial growth.Pseudomonas aeruginosa,Proteus vulgaris,Klebsiella oxytoca,Enterococcus faecalis,Staphylococcus aureus,Staphylococcus epidermidisandListeria monocytogenesshowed inhibition, whileEscherichia coliandEnterobacter aerogenesdid not. Acidified water and acetic acid Perla black bean extract were tested in parasites. The best IC50was observed forGiardia lamblia, while higher concentrations were active againstEntamoeba histolyticaandTrichomonas vaginalis. The Vero cells toxicity levels (IC50) for methanol, acidified water and acetic acid Perla black bean extract were [mean ± S.D. (95% CI)]: 275 ± 6.2 (267.9–282.0), 390 ± 4.6 (384.8–395.2) and 209 ± 3.39 (205.6–212.4) µg/ml, respectively.In vivoacute toxicity assays did not show changes in absolute organ weights, gross and histological examinations of selected tissues or functional tests. The acetic acid and methanol Perla black bean extract proved to exhibit strong antibacterial activity and the acidified water Perla black bean extract exerted parasiticidal effects againstGiardia lamblia,Entamoeba hystoliticaandTrichomonas vaginalis. The three Perla black bean extracts assayed over Vero cells showed very low toxicity and the methanol Perla black bean extractin vivodid not cause toxicity.
The minimum stellar metallicity observable in the Galaxy
Authors: Frebel Anna , Johnson Jarrett L. , Bromm Volker 
Published: November 2008

Abstract
The first stars fundamentally transformed the early Universe through their production of energetic radiation and the first heavy chemical elements. The impact on cosmic evolution sensitively depends on their initial mass function (IMF), which can be empirically constrained through the detailed studies of ancient, metal-poor halo stars in our Galaxy. We compare the lowest magnesium and iron abundances measured in Galactic halo stars with theoretical predictions for the minimum stellar enrichment provided by Population III stars under the assumption of a top-heavy IMF. To demonstrate that abundances measured in metal-poor stars reflect the chemical conditions at their formation, and that they can thus be used to derive constraints on the primordial IMF, we carry out a detailed kinematic analysis of a large sample of metal-poor stars drawn from the Sloan Digital Sky Survey. We assess whether interstellar accretion has altered their surface abundances. We find that the accretion is generally negligible, even at the extremely low levels where the primordial IMF can be tested. We conclude that the majority of the first stars were very massive, but had likely masses below ∼140 M⊙.
The Role of Fire Disturbance on Runoff and Erosion Processes – a Long‐Term Approach, Mt. Carmel Case Study, Israel
Authors: WITTENBERG LEA , INBAR MOSHE 
Published: November 2008

AbstractThe Mediterranean ecosystem of Mt. Carmel, Israel, is subjected to an increasing number of forest fires of various extents and severities. The impacts of forest fires on runoff and erosion are widely documented and include increased peak flows and soil loss until the return of a vegetation cover. Most studies, however, treat fire as a single event, whereas the present study is aimed at exploring the long‐term effects of repeated forest fires on eco‐geomorphic processes. The study integrates the results of plot‐based, detailed analysis of post‐fire runoff and erosion with vegetation recovery analysis, at a temporal‐spatial scale which includes the effect of reburning. Our results indicate that forest fires lead to a significant increase in runoff and sediment yields, particularly during the first two years following the disturbance, up to five orders of magnitude higher than from the adjacent unburnt control plots.
The Role of Land Management in Shaping Arid/Semi‐arid Landscapes: the Case of the Catholic Church (CICM) in Western Inner Mongolia from the 1870s (Late Qing Dynasty) to the 1940s (Republic of China)
Authors: ZHANG XIAOHONG , SUN TAO , ZHANG JINGSHU 
Published: November 2008

AbstractLand management has made a strong impact on the landscapes, especially in arid environments. Based on historical data, this paper evaluates the role of Catholic churches in the shaping of the Sanshenggong area in western China in the 1870s. Sanshenggong, an arid/semi‐arid region located in western Inner Mongolia, was an important Catholic region in the west Ordos Plateau after the 1870s. After the Congregation of the Immaculate Heart of Mary (Congregatio Immaculati Cordis Mariae) (CICM) obtained land from the Maharajah of Alashan Banner, the Belgian priests converted local Chinese (Hans) to Catholicism by lending land, houses and farm implements. By 1949 most people living there had been converted. As a result of intensive land management by the Catholic mission, the arid/semiarid landscape, formerly used as grazing lands, was changed to more intensive agricultural use. This case study exemplifies the practices and the important role an authoritarian religious organisation played in shaping oasis landscapes in arid and semiarid areas.
Uveal melanoma and macular degeneration: molecular biology and potential therapeutic applications
Authors: Economou Mario‐Alexander 
Published: November 2008

Abstract.Uveal melanoma is the most common primary intraocular malignant tumor in adults with 30% to 50% of patients that ultimately succumb to metastatic disease, mainly to the liver. (Shields et al. 1991) Although new diagnostic and therapeutic tools have been developed during the most recent years, only the eye conservation rate has been achieved, while the survival rate remains poor. The reason for this liver‐homing is largely unknown, but it is conceivable that hepatic environmental factors may be implicated in the growth, dissemination, and progression of this malignancy. The insulin‐like growth factor (IGF‐1) that binds to the IGF‐1 receptor (IGF‐1R) is mainly produced in the liver. It has been shown to be crucial for tumor transformation, maintenance of malignant phenotype, promotion of cell growth, and prevention of apoptosis. (Baserga 1995) The hepatocyte growth factor/scatter factor (HGF/SF) is another growth factor produced in the liver and exerts its biological effects through binding to the plasma membrane receptor c‐Met. The activation of this receptor by HGF/SF ligand can induce proliferation, motility, adhesion, and invasion of tumor cells. (Cruz et al. 2003) Metastasis is a process involving many components, including tumor cell adhesion, migration, extracellular matrix (ECM) proteolysis, and invasion. The tumor cells undergo intravasation, disperse via the vascular and the lymphatic systems, and finally extravasate to invade the secondary sites. In all these steps, proteolytic enzyme systems are involved, including the matrix metalloproteinase (MMP) system and the plasminogen activation system. The migration of a malignant cell through the ECM and the basement membrane requires proteolytic activities. (Stetler‐Stevenson et al. 1993). Efforts to target the IGF‐I system has been made with different types of cancer but not with uveal melanoma.
Investigation and recommendations concerning prevention and treatment of infectious diseases and promotion of hygiene in earthquake‐stricken areas
Authors: Zeng Guang 
Published: November 2008

AbstractIn order to identify all public hygiene problems in the Wenchuan quake‐affected areas, and also to provide relevant recommendations to local governments, the quake areas were entered for field investigation and consultation. The current situation and hidden dangers and problems of epidemic surveillance, planned immunization, drinking water hygiene, nutrition and food hygiene, environmental hygiene are discussed in the article. Some suggestions are also provided for government public hygiene policy: (i) launch a patriotic health campaign among the population; (ii) study on green agricultural policy of changing dung into manure; (iii) start from quake‐affected area to develop rural environmental hygiene work; (iv) prolong treatment of infectious diseases free of charge, and draw up a policy of free vaccination for earthquake victims; and (v) realize reform of the CDG funding system in the quake‐affected area. At last, meaning and judgment criteria of ‘no big epidemic after a great disaster’ are interpreted. The observation period is divided into three phases: forthcoming summer and autumn phase, forthcoming winter and next spring phase, and comprehensive recovery phase.