bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant polyphenols: How to translate their in vitro antioxidant actions to in vivo conditions
Authors: Fraga Cesar G. 
Published: July 2007

AbstractEpidemiological evidence demonstrates that diets rich in fruit and vegetables promote health, and attenuate, or delay, the onset of various diseases, including cardiovascular disease, diabetes, certain cancers, and several other age‐related degenerative disorders. The chemical components and the physiological and molecular mechanisms by which fruit and vegetables reduce the risk for these pathophysiological conditions are matters of intense investigation. Regarding plant components, polyphenols are a group of phytochemicals that are gaining acceptance as responsible for the health benefits offered by fruit and vegetables. Because of their chemical structure, plant polyphenols are able to scavenge free radicals and inactivate other pro‐oxidants. The connection of these chemical properties to a physiological antioxidant action has triggered extensive research aimed to relate the consumption of plant polyphenols with human health. Although significant progress has been made, there are still some critical areas that need to be elucidated to arrive at definitive conclusions on the mechanisms linking plant polyphenol consumption, reduction in oxidative damage, and health improvement. Some of these topics will be discussed in this review of alternative molecular mechanisms, based on polyphenol‐membranes and polyphenol‐proteins interactions that develop in an antioxidant protection but are not directly related to free radical scavenging or metal chelating.
IUBMB Life, 59: 308‐315, 2007
Synaptotoxicity in Alzheimer's Disease: The Wnt Signaling Pathway as a Molecular Target
Authors: Inestrosa Nibaldo C. , Varela‐Nallar Lorena , Grabowski Catalina P. , Colombres Marcela 
Published: July 2007

AbstractRecent evidence supports a role of the Wnt pathway in neurodegenerative disorders such as Alzheimer's disease (AD). A relationship between amyloid‐β‐peptide (Aβ)‐induced neurotoxicity and a decrease in the cytoplasmatic levels of β‐catenin has been proposed. Also, the inhibition of glycogen synthase kinase (GSK‐3β), a central modulator of the pathway, protects rat hippocampal neurons from Aβ‐induced damage. Interestingly, during the progression of AD, it has been described that active GSK‐3β is found in neuronal cell bodies and neurites, co‐localizing with pre‐neurofibrillary tangles observed in disease brains. Since Aβ oligomers are associated with the post‐synaptic region and we have found that the non‐canonical Wnt signaling modulates PSD‐95 and glutamate receptors, we propose that the synaptic target for Aβ oligomers in AD is the postsynaptic region and at the molecular level is the non‐canonical Wnt signaling pathway. Altogether, our evidence suggests that a sustained loss of Wnt signaling function may be involved in the Aβ‐dependent neurodegeneration observed in AD brains and that the activation of this signaling pathway could be of therapeutic interest in AD.
H+‐PPases: yesterday, today and tomorrow
Authors: Serrano Aurelio , Pérez‐Castiñeira José R. , Baltscheffsky Margareta , Baltscheffsky Herrick 
Published: July 2007

AbstractSuggestions by Calvin about a role of inorganic pyrophosphate (PPi) in early photosynthesis and by Lipmann that PPi may have been the original energy‐rich phosphate donor in biological energy conversion, were followed in the mid‐1960s by experimental results with isolated chromatophore membranes from the purple photosynthetic bacterium Rhodospirillum rubrum. PPi was shown to be hydrolysed in an uncoupler stimulated reaction by a membrane‐bound inorganic pyrophosphatase (PPase), to be formed at the expense of light energy in photophosphorylation and to be utilized as an energy donor for various energy‐requiring reactions, as a first known alternative to ATP. This direct link between PPi and photosynthesis led to increasing attention concerning the role of PPi in both early and present biological energy transfer. In the 1970s, the PPase was shown to be a proton pump and to be present also in higher plants. In the 1990s, sequences of H+‐PPase genes were obtained from plants, protists, bacteria and archaea and two classes of H+‐PPases differing in K+ sensitivity were established. Over 200 H+‐PPase sequences have now been determined. Recent biochemical and biophysical results have led to new progress and questions regarding the H+‐PPase family, as well as the families of soluble PPases and the inorganic polyphosphatases, which hydrolyse inorganic linear high‐molecular‐weight polyphosphates (HMW‐polyP). Here we will focus attention on the H+‐PPases, their evolution and putative active site motifs, response to monovalent cations, genetic regulation and some very recent results, based on new methods for obtaining large quantities of purified protein, about their tertiary and quaternary structures.
IUBMB Life, 59: 76‐83, 2007
Regulation of glucose transporter type 4 isoform gene expression in muscle and adipocytes
Authors: Im Seung‐Soon , Kwon Sool‐Ki , Kim Tae‐Hyun , Kim Ha‐il , Ahn Yong‐Ho 
Published: July 2007

AbstractThe gene expression of glucose transporter type 4 isoform (GLUT4) is known to be controlled by metabolic, nutritional, or hormonal status. Understanding the molecular mechanisms governing GLUT4 gene expression is critical, because glucose disposal in the body depends on the activities of GLUT4 in the muscle and adipocytes. The GLUT4 activities are regulated by a variety of mechanisms. One of them is transcriptional regulation. GLUT4 gene expression is regulated by a variety of transcriptional factors in muscle and adipose tissue. These data are accumulating regarding the transcriptional factors regulating GLUT4 gene expression. These include MyoD, MEF2A, GEF, TNF‐α, TR‐1α, KLF15, SREBP‐1c, C/EBP‐α, O/E‐1, free fatty acids, PAPRγ, LXRα, NF‐1, etc. These factors are involved in the positive or negative regulation of GLUT4 gene expression. In addition, there is a complex interplay between these factors in transactivating GLUT4 promoter activity. Understanding the mechanisms controlling GLUT4 gene transcription in these tissues will greatly promote the potential therapeutic drug development for obesity and T2DM.
IUBMB Life, 59: 134‐145, 2007
The mAKAP signalosome and cardiac myocyte hypertrophy
Authors: Bauman Andrea L. , Michel Jennifer J. Carlisle , Henson Edward , Dodge‐Kafka Kimberly L. , Kapiloff Michael S. 
Published: July 2007

AbstractCardiac hypertrophy is regulated by a large intracellular signal transduction network. Each of the many signaling pathways in this network contributes uniquely to the control of cell growth. In the last few years, it has become apparent that multimolecular signaling complexes or 'signalosomes' are important for mediating crosstalk between different signaling pathways. These complexes integrate upstream signals and control downstream effectors. In the cardiac myocyte, the protein mAKAPβ serves as a scaffold for a large signalosome that is responsive to upstream cAMP, Ca2+, and mitogen‐activated protein kinase signaling. The mAKAPβ signalosome is important for the control of NFATc transcription factor activity and for the overall induction of myocyte hypertrophy.
IUBMB Life, 59: 163‐169, 2007
The pathogenesis of transaldolase deficiency
Authors: Perl Andras 
Published: July 2007

AbstractThe signaling networks that mediate cell growth, differentiation, and survival are dependent on complex metabolic and redox pathways. Metabolism of glucose through the pentose phosphate pathway (PPP) fulfills two unique functions: formation of ribose 5‐phosphate for the synthesis of nucleotides, RNA, and DNA in support cell growth and formation of NADPH for biosynthetic reactions and neutralization of reactive oxygen intermediates (ROI). Balancing of NADPH and ROI levels by the PPP enzyme transaldolase (TAL) regulates the mitochondrial trans‐membrane potential (Δψm), a critical checkpoint of ATP synthesis and cell survival. While complete deficiency of glucose 6‐phosphate dehydrogenase (G6PD) or transketolase (TK) is lethal, TAL‐deficient mice developed normally with the exception of male sterility due to structural and functional damage of sperm cell mitochondria. Recently, two cases of complete TAL deficiency have been reported in patients with liver cirrhosis which results from increased cell death of hepatocytes. Delineation of the cell type‐specific role that TAL plays in the PPP and cell death signal processing will be critical for understanding the pathogenesis of TAL deficiency.
iubmb Life, 59: 1‐9, 2007
Conformational stability and thermodynamic characterization of homotetrameric Plasmodium falciparum β‐ketoacyl‐ACP reductase
Authors: Karmodiya Krishanpal , Sajad Syed , Sinha Sharmistha , Maity Koustav , Suguna Kaza , Surolia Namita 
Published: July 2007

AbstractThe conformational stability of the homotetrameric Plasmodium falciparumβ‐ketoacyl‐ACP reductase (FabG) was determined by guanidinium chloride‐induced isothermal and thermal denaturation. The reversible unfolding transitions were monitored by intrinsic fluorescence, circular dichroism (CD) spectroscopy and by measuring the enzyme activity of FabG. The denaturation profiles were analyzed to obtain the thermodynamic parameters associated with unfolding of the protein. The data confirm the simple A4 ↔ 4A model of unfolding, based on the corroboration of CD data by fluorescence transition and similar ΔG estimation for denaturation curves obtained at four different concentration of the FabG. Denaturation is well described by the linear extrapolation model for denaturant‐protein interactions. In addition, the conformational stability (ΔGs) as well as the ΔCp for the protein unfolding is quite high, 22.68 kcal/mole and 5.83 kcal/(mole K), respectively, which may be a reflection of the relatively large size of the tetrameric molecule (Mr 120, 000) and a large buried hydrophobic core in the folded protein. This study provides a prototype for determining conformational stability of other members of the short‐chain alcohol dehydrogenase/reductase superfamily of proteins to which PfFabG belongs.
iubmb Life, 59: 441‐449, 2007
Reducing the catch of small shrimps in the Gulf of Maine pink shrimp fishery with a size-sorting grid device
Authors: He Pingguo , Balzano Vincent 
Published: July 2007

Abstract
He, P., and Balzano, V. 2007. Reducing the catch of small shrimps in the Gulf of Maine pink shrimp fishery with a size-sorting grid device. – ICES Journal of Marine Science, 64: 1551–1557. Since implementation of the Nordmøre grid in the Gulf of Maine pink shrimp (Pandalus borealis) trawl fishery in the early 1990s, fish bycatch has been reduced drastically. However, the Nordmøre grid does not reduce the amount of small shrimps landed when the shrimps are on the fishing grounds. This paper reports on two designs of a new size-sorting grid system, one with a funnel and one without. The designs' main feature is the size-sorting grid's position, installed in front of the main Nordmøre grid. They were tested in the flume tank and at sea. Parallel tows involving two vessels and alternating tows using one vessel were made to compare the size-sorting grid system. Both size-sorting designs reduced the number of small shrimps in the catch significantly, by 38 and 45 kg−1 of catch, respectively. There was some reduction in shrimp catch rates, presumably from the release of small shrimps. There were no significant differences in the number or quantity of major bycatch species for the commercial grid and the two experimental grid designs. The designs were practical to operate and easy to install. Their application could reduce the catch of small shrimps in the pink shrimp fishery in the Gulf of Maine and in other areas.
Pharmacokinetics of lamivudine in subjects receiving peritoneal dialysis in end‐stage renal failure
Authors: Asari Ashwin , Iles‐Smith Heather , Chen Ya‐Chi , Naderer Odin J. , Johnson Mark A. , Yuen Geoffrey J. , Otto Vicky , Dunn John A. , Gokal Ram 
Published: July 2007

What is already known about this subject • Prior to the conduct of this study, information on the pharmacokinetics of lamivudine in subjects with renal impairment was limited to patients on haemodialysis. (Br J Clin Pharmacol 1998; 46: 21–7).• No pharmacokinetic data were available on subjects receiving lamivudine who were concurrently receiving peritoneal dialysis.• With increasing numbers of individuals opting for peritoneal dialysis, the need to establish if dose modification was necessary in this setting was important to ensure efficacious and safe drug exposures were being obtained. What this study adds • This study demonstrated that similar to patients receiving haemodialysis, dose modifications based on reductions in renal function (i.e. decreased CLCR), also applied to subjects on peritoneal dialysis.AimsTo establish whether peritoneal dialysis (PD) requires dosing modification from the CLCR‐corrected lamivudine dose in end‐stage renal failure subjects.MethodsThis was an open‐label cohort study. A total of 12 subjects undergoing PD, six continuous ambulatory peritoneal dialysis (CAPD) and six automated peritoneal dialysis (APD), for at least 3 months received lamivudine 10 mg (5 mg ml −1 × 2 ml) daily for 8 consecutive days, followed by an intensive pharmacokinetic assessment. Urine and dialysate were collected from 0 to 24 h postdose on day 8 where possible. Pharmacokinetic parameters were calculated using noncompartmental techniques.ResultsThe plasma pharmacokinetic results demonstrated that peritoneal dialysis clearance (CLD) of lamivudine was similar between APD and CAPD patients with median (range) of 0.19 l h−1 (0.14–0.25) and 0.1 l h−1 (0.09–0.25), respectively. CLD was approximately 1/15th to 1/30th of plasma clearance, demonstrating that peritoneal dialysis does not contribute significantly to overall lamivudine clearance in this patient population. The AUC(0,24 h) of lamivudine given 10 mg daily to APD and CAPD patients was 3430 ng ml−1 h and 3469 ng ml−1 h, respectively, similar to historical data obtained in patients with normal renal function administered at the normal dose of 100 mg daily (3781 ng ml−1 h). There were no clinically significant changes in any safety assessments that were attributable to lamivudine.ConclusionsESRD patients who receive CAPD or APD require no supplemental dosing. These patients should follow the standard dosing reduction for patients infected with HIV or HBV with renal dysfunction.
Pharmacokinetic and pharmacodynamic properties of oral L‐citrulline and L‐arginine: impact on nitric oxide metabolism
Authors: Schwedhelm Edzard , Maas Renke , Freese Ralf , Jung Donald , Lukacs Zoltan , Jambrecina Alen , Spickler William , Schulze Friedrich , Böger Rainer H. 
Published: July 2007

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • L‐Arginine is a semiessential amino acid that is converted to nitric oxide (NO) by NO synthase (NOS).• NO improves endothelial function by elevating cyclic guanosine monophosphate.• However, oral L‐arginine treatment in humans is hampered by extensive metabolism. WHAT THIS STUDY ADDS • Oral L‐citrulline supplementation raises plasma L‐arginine concentration and augments NO‐dependent signalling in a dose‐dependent manner.• L‐Citrulline may thus be an alternative to L‐arginine in patients with impaired NOS activity.AIMSOral L‐arginine supplementation has been used in several studies to improve endothelium‐dependent, nitric oxide (NO)‐mediated vasodilation. L‐Arginine treatment is hampered by extensive presystemic elimination due to intestinal arginase activity. In contrast, L‐citrulline is readily absorbed and at least in part converted to L‐arginine. The aim of our study was to assess this metabolic conversion and its subsequent pharmacodynamic effects.METHODSIn a double‐blind, randomized, placebo‐controlled cross‐over study, 20 healthy volunteers received six different dosing regimes of placebo, citrulline, and arginine. Pharmacokinetic parameters (Cmax, Tmax, Cmin, AUC) were calculated after 1 week of oral supplementation. The ratio of plasma L‐arginine over asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase (arginine/ADMA ratio), urinary cyclic guanosine monophosphate (cGMP) and nitrate excretion rates, and flow‐mediated vasodilation (FMD) was measured to assess pharmacodynamic effects.RESULTSL‐Citrulline dose‐dependently increased AUC and Cmax of plasma L‐arginine concentration more effectively than L‐arginine (P < 0.01). The highest dose of citrulline (3 g bid) increased the Cmin of plasma L‐arginine and improved the L‐arginine/ADMA ratio from 186 ± 8 (baseline) to 278 ± 14 [P < 0.01, 95% confidence interval (CI) 66, 121]. Moreover, urinary nitrate and cGMP were increased from 92 ± 10 to 125 ± 15 µmol mmol−1 creatinine (P = 0.01, 95% CI 8, 58) and from 38 ± 3.3 to 50 ± 6.7 nmol mmol−1 creatinine (P = 0.04, 95% CI 0.4, 24), respectively. No treatment improved FMD over baseline. However, pooled analysis of all FMD data revealed a correlation between the increase of arginine/ADMA ratio and improvement of FMD.CONCLUSIONOur data show for the first time that oral L‐citrulline supplementation raises plasma L‐arginine concentration and augments NO‐dependent signalling in a dose‐dependent manner.
Developmental pharmacokinetics of ciclosporin – a population pharmacokinetic study in paediatric renal transplant candidates
Authors: Fanta S. , Jönsson S. , Backman J. T. , Karlsson M. O. , Hoppu K. 
Published: July 2007

What is already known about this subject • Ciclosporin is an immunosuppressant drug with a narrow therapeutic index and large variability in pharmacokinetics.• It is likely that the inter‐ and intraindividual variability in ciclosporin pharmacokinetics and dose requirements is even larger in children than in adults as a result of variation in biological maturation status.• However, data on the developmental pharmacokinetics of ciclosporin, as well as other CYP3A4 substrate drugs, in children are scarce. What this study adds • Adult CYP3A4 activity seems to be reached by the age of 6–12 months, and allometrically scaled body weight is a good predictor of the hepatic clearance of ciclosporin, a CYP3A4 substrate.• Ciclosporin oral bioavailability, known previously to display large interindividual variability, is not influenced by age.• These conclusions were reached using a robust modelling approach (NONMEM) with rich paediatric pharmacokinetic data collected after full i.v. and p.o. profiles.AimsTo use population pharmacokinetic modelling to characterize the influence of developmental and demographic factors on the pharmacokinetic variability of ciclosporin.MethodsPharmacokinetic modelling was performed in NONMEM using a dataset comprising 162 pretransplant children, aged 0.36–17.5 years. Ciclosporin was given intravenously (3 mg kg−1) and orally (10 mg kg−1) on separate occasions followed by blood sampling for 24 h.ResultsA three‐compartment model with first‐order absorption without lag‐time best described the pharmacokinetics of ciclosporin. The most important covariate affecting systemic clearance (CL) and distribution volume (V) was body weight (BW; scaled allometrically), responsible for a fourfold difference in uncorrected ciclosporin CL and a sixfold difference in ciclosporin V. The other significant covariates, haematocrit, plasma cholesterol and creatinine, were estimated to explain 20–30% of interindividual differences in CL and V of ciclosporin. No age‐related changes in oral bioavailability or in BW‐normalized V were seen. The BW‐normalized CL (CL/BW) declined with age and prepubertal children (<8 years) had an approximately 25% higher CL/BW than did older children. Normalization of CL for allometric BW (BW3/4) removed its relationship to age.ConclusionThe relationship between CL and allometric BW is consistent with a gradual reduction in relative liver size, until adult values, and a relatively constant CYP3A4 content in the liver from about 6–12 months of age to adulthood. Ciclosporin oral bioavailability, known previously to display large interindividual variability, is not influenced by age. These findings can enable better individualization of ciclosporin dosing in infants, children and adolescents.
Recommendations for the management of the haematological and onco‐haematological aspects of Gaucher disease1
Authors: Hughes Derralynn , Cappellini Maria Domenica , Berger Marc , Droogenbroeck Jan Van , De Fost Maaike , Janic Dragana , Marinakis Theodore , Rosenbaum Hanna , Villarubia Jesús , Zhukovskaya Elena , Hollak Carla 
Published: July 2007

SummaryCurrent knowledge of the haematological and onco‐haematological complications of type 1 Gaucher disease has been reviewed with the aim of identifying best clinical practice for treatment and disease management. It was concluded that: (i) Awareness of typical patterns of cytopenia can help clinicians distinguish haematological co‐morbidities. (ii) Red blood cell studies and complete iron metabolism evaluation at baseline are recommended. (iii) Haemoglobin levels defining anaemia should be raised and used in Gaucher disease treatment and monitoring. (iv) Surgeons should be aware of potential bleeding complications during surgery in Gaucher patients.The higher incidence of multiple myeloma in Gaucher disease suggests that Gaucher patients should have their immunoglobulin profile determined at diagnosis and monitored every 2 years (patients <50 years) or every year (patients >50 years). If monoclonal gammopathy of undetermined significance (MGUS) is found, general MGUS guidelines should be followed. Future studies should focus on the utility of early treatment to prevent immunoglobulin abnormalities and multiple myeloma.
Suppression of the asthmatic phenotype by ultraviolet B‐induced, antigen‐specific regulatory cells
Authors: McGlade J. P. , Gorman S. , Zosky G. R. , Larcombe A. N. , Sly P. D. , Finlay‐Jones J. J. , Turner D. J. , Hart P. H. 
Published: July 2007

SummaryBackground
Over recent decades, there has been a significant global increase in the prevalence of asthma, an inflammatory disease of the respiratory system. While ultraviolet radiation (UV) has been used successfully in the treatment of inflammatory conditions such as psoriasis, studies of UV‐induced regulation of allergic respiratory responses have been rare, and have not analysed in vivo measurements of airway hyperresponsiveness (AHR) or the antigen specificity of the UV‐induced effects.Objective
To investigate the regulatory properties of erythemal ultraviolet B (UVB) irradiation of the skin and the induction of allergen‐induced airway immunity in a murine asthma model, and to examine the mechanisms involved.Methods
BALB/c mice were exposed to a single erythemal dose of UV 3 days before intraperitonial sensitization (day 0) and boost (day 14) with the antigen, ovalbumin (OVA). Airway‐associated, asthma‐like responses to aerosolized OVA at day 21 were analysed including (a) AHR measured in vivo, (b) OVA‐specific proliferative responses and cytokine production by cells from the lung‐draining lymph nodes (LDLN), and (c) inflammatory cells and cytokines in the bronchoalveolar lavage fluid. To determine UVB‐induced mechanisms of regulation, LDLN cells from UVB irradiated, OVA‐sensitized mice were adoptively transferred into naïve BALB/c mice that were subsequently sensitized and challenged with OVA, or a non‐specific antigen.Results
UVB irradiation of skin significantly suppressed AHR to methacholine and OVA‐specific responses in the LDLN and in the lung compartment. Reduced OVA‐specific responses by LDLN cells from both UVB irradiated mice and mice that received 5 × 106 LDLN cells from UVB irradiated, but not from non‐irradiated, OVA‐sensitized mice suggested that UVB‐induced regulatory cells are responsible for many of the asthma‐reducing effects of dorsal UVB exposure.Conclusion
UVB irradiation of skin suppresses AHR and cellular responses of the airways to respiratory allergens. Further, this study implicates UVB or its downstream mediators as a potential approach to reducing the severity of asthma.