bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carotenoid lutein protects rats from paracetamol-, carbon tetrachloride- and ethanol-induced hepatic damage
Authors: Sindhu Edakkadath R , Firdous Alikkunjhi P , Preethi Korengath C , Kuttan Ramadasan 
Published: July 2010

Abstract

Objectives
Carotenoids are a class of natural fat-soluble pigments that are found in many fruits and vegetables. Consumption of a diet rich in carotenoids has been epidemiologically correlated with a lower risk for several diseases. In the present study the carotenoid lutein (3,3′-dihydroxy-β,ε-carotene) was evaluated for its hepatoprotective activity in rats.

Methods
Paracetamol, 20% ethanol and carbon tetrachloride were used to induce liver toxicity.

Key findings
Levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase and alkaline phosphatases, which were increased in the serum, were found to be significantly reduced by the treatment of lutein in a dose-dependent manner, indicating that lutein may reduce the hepatotoxicity induced by these agents. Serum bilirubin was also significantly lower in lutein-treated groups compared with control. Increased lipid peroxidation, conjugated diene and hydroperoxides in the liver tissue produced by the administration of paracetamol were found to be reduced in the lutein-treated groups. Levels of antioxidant enzymes, like superoxide dismutase, catalase, glutathione peroxidase and glutathione, were found to be increased in lutein-treated groups compared with control group during alcohol- and CCl4-induced liver toxicity. Hydroxyproline, which is an indicator of fibrosis in liver tissue, was high in the ethanol-treated control group. Hydroxyproline levels were decreased by simultaneous lutein administration.

Conclusions
Histopathological evidence confirmed the protection offered by lutein from the tissue damage caused by hepatotoxins. The hepatoprotective action may be due to lutein's ability to scavenge reactive oxygen radicals.
Effects of the aqueous extract fromSalvia miltiorrhiza Bungeon caffeine pharmacokinetics and liver microsomal CYP1A2 activity in humans and rats
Authors: Wang Xin , Yeung John H K 
Published: July 2010

AbstractObjectivesThe effects of the aqueous extract of Salvia miltiorrhiza Bunge (Danshen) on metabolism/pharmacokinetics of caffeine and on liver microsomal CYP1A2 activity in humans and rats have been investigated.MethodsThe effects of Danshen aqueous extract on CYP1A2 activity were determined by metabolism of model substrates in the rat in vivo and in humans and rats in vitro. HPLC was used to determine model substrates and metabolites.Key findingsIn the rat, single dose Danshen aqueous extract treatment (100 or 200 mg/kg, i.p.) decreased metabolism of caffeine to paraxanthine, with overall decrease in caffeine clearance (6–20%), increase in area under the curve (AUC; 7–24%) and plasma half-life (t½ 14–16%). Fourteen-day Danshen aqueous extract treatment (100 mg/kg/day, i.p. or 200 mg/kg/day, p.o.) decreased caffeine clearance (16–26%), increased AUC (18–31%) and prolonged plasma t½ (8–10%). Aqueous extract of Danshen (125–2000 µg/ml) competitively inhibited human and rat liver microsomal CYP1A2 activity with inhibition constant (Ki) values at 190 and 360 µg/ml, respectively.ConclusionsThese studies demonstrated that Danshen aqueous extract affected the metabolism of CYP1A2 substrates through competitive inhibition and altered their clearance.
Effects of tesmilifene, a substrate of CYP3A and an inhibitor of P-glycoprotein, on the pharmacokinetics of intravenous and oral docetaxel in rats
Authors: Choi Young H , Suh Jung H , Lee Joo H , Cho Il H , Lee Myung G 
Published: July 2010

Abstract

Objectives
It has been reported that docetaxel is a P-glycoprotein substrate and is metabolized via the cytochrome P450 (CYP) 3A subfamily in rats. Tesmilifene is a substrate of the CYP3A subfamily and is an inhibitor of P-glycoprotein. Thus, the effects of various doses of tesmilifene on the pharmacokinetics of intravenous and orally administered docetaxel have been investigated in rats.

Methods
Docetaxel (20 mg/kg as base) was administered intravenously and orally without and with tesmilifene (5, 10, and 20 mg/kg) in rats.

Key findings
After intravenous administration of docetaxel with tesmilifene, the values of nonrenal clearance (CLNR) and area under the plasma concentration–time (AUC) for docetaxel were comparable with those without tesmilifene. Tesmilifene did not increase the values of AUC or of absolute oral bioavailability (F) for docetaxel after oral administration of docetaxel with tesmilifene.

Conclusions
The inhibition for the metabolism of docetaxel via hepatic and intestinal CYP3A subfamily, and inhibition of P-glycoprotein-mediated efflux of docetaxel in the intestine by tesmilifene were almost negligible. The extremely low value of F for docetaxel was due to the incomplete absorption from the gastrointestinal tract and considerable first-pass metabolism of docetaxel in rats.
Nature, Position, and Frequency of Mutations Made in a Single Cycle of HIV-1 Replication
Authors: Abram Michael E. , Ferris Andrea L. , Shao Wei , Alvord W. Gregory , Hughes Stephen H. 
Published: July 2010

ABSTRACT

There is considerable HIV-1 variation in patients. The extent of the variation is due to the high rate of viral replication, the high viral load, and the errors made during viral replication. Mutations can arise from errors made either by host DNA-dependent RNA polymerase II or by HIV-1 reverse transcriptase (RT), but the relative contributions of these two enzymes to the mutation rate are unknown. In addition, mutations in RT can affect its fidelity, but the effect of mutations in RT on the nature of the mutations that arise
in vivo
is poorly understood. We have developed an efficient system, based on existing technology, to analyze the mutations that arise in an HIV-1 vector in a single cycle of replication. A
lacZ
α reporter gene is used to identify viral DNAs that contain mutations which are analyzed by DNA sequencing. The forward mutation rate in this system is 1.4 × 10
−5
mutations/bp/cycle, equivalent to the retroviral average. This rate is about 3-fold lower than previously reported for HIV-1
in vivo
and is much lower than what has been reported for purified HIV-1 RT
in vitro
. Although the mutation rate was not affected by the orientation of
lacZ
α, the sites favored for mutations (hot spots) in
lacZ
α depended on which strand of
lacZ
α was present in the viral RNA. The pattern of hot spots seen in
lacZ
α
in vivo
did not match any of the published data obtained when purified RT was used to copy
lacZ
α
in vitro
.
Frozen shoulder: the effectiveness of conservative and surgical interventions—systematic review
Authors: Favejee M M , Huisstede B M A , Koes B W 
Published: July 2010

BackgroundA variety of therapeutic interventions is available for restoring motion and diminishing pain in patients with frozen shoulder. An overview article concerning the evidence for the effectiveness of these interventions is lacking.ObjectiveTo provide an evidence-based overview regarding the effectiveness of conservative and surgical interventions to treat the frozen shoulder.MethodsThe Cochrane Library, PubMed, Embase, Cinahl and Pedro were searched for relevant systematic reviews and randomised clinical trials (RCTs). Two reviewers independently selected relevant studies, assessed the methodological quality and extracted data. A best-evidence synthesis was used to summarise the results.ResultsFive Cochrane reviews and 18 RCTs were included studying the effectiveness of oral medication, injection therapy, physiotherapy, acupuncture, arthrographic distension and suprascapular nerve block (SSNB).ConclusionsWe found strong evidence for the effectiveness of steroid injections and laser therapy in short-term and moderate evidence for steroid injections in mid-term follow-up. Moderate evidence was found in favour of mobilisation techniques in the short and long term, for the effectiveness of arthrographic distension alone and as an addition to active physiotherapy in the short term, for the effectiveness of oral steroids compared with no treatment or placebo in the short term, and for the effectiveness of SSNB compared with acupuncture, placebo or steroid injections. For other commonly used interventions no or only limited evidence of effectiveness was found. Most of the included studies reported short-term results, whereas symptoms of frozen shoulder may last up to 4 years. High quality RCTs studying long-term results are clearly needed in this field.
Diagnosis of exercise-induced bronchoconstriction: eucapnic voluntary hyperpnoea challenges identify previously undiagnosed elite athletes with exercise-induced bronchoconstriction
Authors: Dickinson John , McConnell Alison , Whyte Greg 
Published: July 2010

BackgroundThere is increasing evidence to suggest many elite athletes fail to recognise and report symptoms of exercise-induced bronchoconstriction (EIB), supporting the contention that athletes should be screened routinely for EIB.PurposeTo screen elite British athletes for EIB using eucapnic voluntary hyperpnoea (EVH).Methods228 elite athletes provided written informed consent and completed an EVH challenge with maximal flow volume loops measured at baseline and 3, 5, 10 and 15 min following EVH. A fall of 10% in forced expiratory volume in 1 s (FEV1) from baseline was deemed positive. Two-way analysis of variance was conducted to compare FEV1at baseline and maximal change following EVH between EVH-positive and EVH-negative athletes who did and did not report a previous diagnosis of EIB. Significance was assumed if p≤0.05.ResultsFollowing the EVH challenge 78 athletes (34%) demonstrated EVH positive. 57 out of the 78 (73%) athletes who demonstrated EVH positive did not have a previous diagnosis of EIB. 30 athletes reported a previous diagnosis of asthma, nine (30%) of whom demonstrated EVH negative. There was no significant difference between the magnitude of the fall in FEV1between athletes who reported a previous diagnosis of EIB and demonstrated EVH positive, and those with no previous diagnosis of EIB who demonstrated EVH positive (mean±SD; −21.6±16.1% vs −17.1±9.7%; p=0.07).ConclusionThe high proportion of previously undiagnosed athletes who demonstrated EVH positive suggests that elite athletes should be screened routinely for EIB using a suitable bronchoprovocation challenge.
Are current back protectors suitable to prevent spinal injury in recreational snowboarders?
Authors: Schmitt Kai-Uwe , Liechti Bendicht , Michel Frank I , Stämpfli Rolf , Brühwiler Paul A 
Published: July 2010

ObjectiveBack protectors for snowboarders were analysed with respect to their potential to prevent spinal injury.DesignIn 20 Swiss skiing resorts, athletes were interviewed on the slope. In addition, an online survey was conducted. The performance of 12 commercially available back protectors was investigated by means of mechanical testing. A currently used drop test according to standard EN1621 (motorcycle protectors), testing energy damping was supplemented by penetration tests according to standard EN1077, which reflects snowsport safety concerns.Results6 out of 12 back protectors fulfilled the higher safety level defined in EN1621. Protectors making use of energy-absorbing layers performed particularly well. In contrast, hard shell protectors exhibited a higher potential to withstand the penetration test. The surveys confirmed that approximately 40–50% of snowboarders use a back protector. A large majority of users expect protection from severe spinal injury such as vertebral fractures or spinal cord injury.ConclusionsThe currently used test standards are fulfilled by many back protectors. Users, however, expect protectors to be efficient in impact scenarios that result in spinal injury, which are more severe than impacts as addressed in the current standards. This study highlights that there is a mismatch between the capabilities of current back protectors to prevent spinal injury in snowboarding and the expectations users have of these protectors.
DNA barcoding reveals multiple overlooked Australian species of the red algal order Rhodymeniales (Florideophyceae), with resurrection of Halopeltis J. Agardh and description of Pseudohalopeltis gen. nov.
Authors: Saunders Gary W. , McDonald Brian 
Published: July 2010

The DNA barcode (COI-5P) was used to investigate cryptic diversity among Rhodymenia spp. in southern Australia. Whereas eight species are currently recognized, we uncovered ca. 20 genetic species groups, phylogenetically assigned to four genera in two families. Procumbent specimens with molecular and anatomical signatures of the Fryeellaceae are assigned to Pseudohalopeltis tasmanensis gen. et sp. nov. Collections from Lord Howe Island recorded in the field as Rhodymenia / Fauchea sp. are assigned to the poorly known genus Microphyllum as Microphyllum robustum sp. nov. A cluster of species with distinct molecular and anatomical attributes is included in a resurrected Halopeltis J.G. Agardh, including Halopeltis australis (J. Agardh) comb. nov. (type species); Halopeltis austrina (Womersley) comb. nov.; Halopeltis cuneata (Harvey) comb. nov. [including Rhodymenia halymenioides (J. Agardh) Womersley]; Halopeltis gracilis sp. nov.; Halopeltis prostrata sp. nov.; and Halopeltis verrucosa (Womersley) comb. nov. Four additional species of Halopeltis from Lord Howe Island (LH1, LH2), Tasmania (TAS), and Western Australia are not characterized further. For Rhodymenia sensu stricto, similar levels of cryptic diversity were noted. Samples tentatively field-identified as “ Rhodymenia sonderi ,” but having affiliations to Rhodymenia rather than Halopeltis, are referred to Rhodymenia novahollandica sp. nov. Collections field-identified as R. obtusa are genetically distinct from that species and are assigned to Rhodymenia wilsonis (Sonder) comb. nov. Two highly divergent species currently identified as Rhodymenia leptophylla (LH from Lord Howe Island; TAS from Tasmania), as well as two additional cryptic previously unnamed taxa from South Australia (SA) and Victoria (VIC), are not characterized further.
Non-host resistance responses of Arabidopsis thaliana to the coffee leaf rust fungus (Hemileia vastatrix)
Authors: Gil Azinheira Helena , do Céu Silva Maria , Talhinhas Pedro , Medeira Clara , Maia Isabel , Petitot Anne-Sophie , Fernandez Diana 
Published: July 2010

Leaf rust, caused by Hemileia vastatrix Berk & Broome, is the most destructive fungal disease of coffee. In the absence of a suitable gene validation system in coffee, the objective of this study was to investigate whether the model plant Arabidopsis thaliana (L.) Heynh. may be used as a heterologous system for the molecular dissection of coffee responses to leaf rust. Histological examination of A. thaliana (Col-0) leaves inoculated with H. vastatrix (race II) showed that by 24 h after inoculation (hai), H. vastatrix uredospores differentiated appressoria and penetrated the stomata, but failed to form haustoria. Arabidopsis thaliana cellular resistance responses included hypersensitive-like response (HR) of stomata guard cells together with accumulation of phenolic compounds and callose deposition in walls of epidermal and mesophyll cells. Results indicate that H. vastatrix infection triggered the induction of a set of defence-related genes peaking at 18 and 42 hai. The non-host HR triggered by H. vastatrix in the model plant A. thaliana makes it usable to infer the function of coffee genes involved in pre-haustorial rust resistance.
Spaceflight-induced genetic and epigenetic changes in the rice (Oryza sativa L.) genome are independent of each other
Authors: Ou Xiufang , Long Likun , Wu Ying , Yu Yingjie , Lin Xiuyun , Qi Xin , Liu Bao 
Published: July 2010

An array of studies have reported that the spaceflight environment is mutagenic and may induce phenotypic and genetic changes in diverse organisms. We reported recently that in at least some plant species (e.g., rice) the spaceflight environment can be particularly potent in generating heritable epigenetic changes in the form of altered cytosine methylation patterns and activation of transposable elements. To further study the issue of spaceflight-induced genomic instability, and in particular to test whether the incurred genetic and epigenetic changes are connected or independent of each other, we performed the present study. We subjected seeds of the standard laboratory rice ( Oryza sativa L.) cultivar Nipponbare to a spaceflight in the spaceship Long March 2 for 18 days. We then investigated the genetic and DNA methylation stabilities of 11 randomly selected plants germinated from the spaceflown seeds by using two kinds of DNA markers, amplified fragment length polymorphism (AFLP) and methylation sensitive amplified polymorphism (MSAP). For AFLP, by using 15 primer combinations, we assessed 460 genomic loci and found that the frequencies of genetic changes across the 11 plants ranged from 0.7% to 6.7% with an average frequency of 3.5%. For MSAP, by using 14 primer combinations, we assessed 467 loci and detected the occurrence of four major types of cytosine methylation alterations at the CCGG sites, namely CG or CNG hypomethylation and CG or CNG hypermethylation. Collectively, the frequencies of the two kinds of hypermethylation, CG (1.95%) and CNG (1.44%), are about two times higher than those of the two kinds of hypomethylation, CG (0.76%) and CNG (0.80%), though different plants showed variable frequencies for each type of alteration. Further analysis suggested that both the genetic and cytosine methylation changes manifested apparent mutational bias towards specific genomic regions, but the two kinds of instabilities are independent of each other based on correlation analysis.
Design load of rigid footings on sand
Authors: Diaz Edgar G. , Rodríguez-Roa Fernando 
Published: July 2010

Experimental evidence has shown that most current methods are not able to predict design loads of footings on cohesionless soil with an acceptable degree of accuracy. In the present study, a simple and realistic settlement-based method is proposed to estimate the design load of rigid footings on sand subjected to static vertical loading. The design criterion based on restricting the end-of-construction settlement to 16 mm because of the inherent variability of the real soil deposits is herein adopted. A series of finite-element analyses based on an advanced constitutive model were carried out to study the load–settlement response of footings supported on 14 sandy soils. Routine design charts were developed to predict the net allowable soil pressure of footings on normally consolidated and overconsolidated sands. These charts consider footing shape, embedment depth, grain diameters D10and D60, particle shape, unit weight (or submerged unit weight for saturated sands), and indirect measurements of the shear strength derived from in situ tests, such as relative density, standard penetration test (SPT) or cone penetration test (CPT). As shown, the proposed charts match well with available experimental data.
Analysis of high-level S-layer protein secretion inCaulobacter crescentus
Authors: Lau Janny Ho Yu , Nomellini John F. , Smit John 
Published: July 2010

Caulobacter crescentus exhibits a hexagonally arranged protein layer on its outermost surface. RsaA, the sole protein of this “S-layer”, is secreted by a type I (ABC) transporter. Few type I transporters show high-level secretion, and few bacterial S-layers have been carefully examined for the amount of protein synthesis capacity needed to maintain cell coverage. Here we determined RsaA levels by quantitative immunoblotting methods, learned that very stable mRNA is a key factor in high-level secretion, and found that the transporter was capable of still higher secretion. A propensity for RsaA to aggregate was a barrier to quantitation, but with the use of S-layer shedding mutants and methods to keep RsaA soluble, we learned that ~31% of cell protein is RsaA. When multiple copies of rsaA were introduced, the level increased to ~51% of cell protein, a higher level than we are aware of for any protein in any bacterium. Unexpectedly, in comparing normal and S-layer shedding strains, an assembled S-layer was not a significant barrier to elevated secretion. The rsaA mRNA half-life was determined by real-time PCR to be 36 min, ranking with the most stable known in bacteria. A modification of the 5′ region resulted in a shorter half-life and a reduction in maximum protein synthesis levels. If secretion was prevented by knockout of type I transporter genes, RsaA levels dropped to 10% or less of normal, but with no significant reduction in rsaA mRNA. Overall, normal levels of RsaA were unexpectedly high, and still higher levels were not limited by transporter capability, the presence of an assembled S-layer, or the capacity of the cell’s physiology to produce large amounts of one protein. The normal upper limit of RsaA production appears to be controlled only by the level of an unusually stable message. Significant down-regulation is possible and is accomplished posttranscriptionally.
Glucose-induced endothelin-1 expression is regulated by ERK5 in the endothelial cells and retina of diabetic ratsThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Wu Yuexiu , Feng Biao , Chen Shali , Zuo Yufeng , Chakrabarti Subrata 
Published: July 2010

Upregulation of endothelin 1 (ET-1) causing blood flow alteration and increased extracellular matrix production are characteristic features of diabetic angiopathy. Several glucose-induced signaling mechanisms cause ET-1 upregulation in diabetic angiopathy. Extracellular signal-regulated kinase 5 (ERK5) is a member of the MAPK family, which plays a key role in cardiovascular development. ERK kinase (MEK) 5 is the specific MEK for ERK5 activation. In this study we examined the role of glucose-induced ERK5 signaling in mediating ET-1 expression in diabetic angiopathy. We investigated retinas from 1-month STZ-induced diabetic rats and human macro- and microvascular endothelial cells to study ERK5-dependent ET-1 alterations. Glucose (25 mmol/L) caused significant upregulation of ET-1 mRNA and downregulation of ERK5 and Kruppel-like factor 2 (KLF2) after 24 h treatment in the endothelial cells. Simultaneously, phospho-ERK5 proteins were reduced. Activation of ERK5 by constitutively active MEK5 (caMEK5) upregulated KLF2 and suppressed ET-1 expression in both cell lines, whereas ERK5 siRNA transfection resulted in decreased ERK5 and KLF2 and increased ET-1 mRNA expression. In addition, caMEK5 prevented glucose-induced upregulation of ET-1. Furthermore, 1 month of diabetes caused a significant increase in retinal ET-1 mRNA and decrease in ERK5 mRNA expression. These data indicate that ERK5 signaling regulates glucose-induced ET-1 expression in diabetes. The ERK5/ET-1 pathway may provide a potential novel target for the treatment of diabetic angiopathy.