bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia
Authors: Anagnostopoulou Katherine K , Kolovou Genovefa D , Kostakou Peggy M , Mihas Constantinos , Hatzigeorgiou Georgios , Marvaki Christina , Degiannis Dimitrios , Mikhailidis Dimitri P , Cokkinos Dennis V 
Published: June 2009

Abstract

Background
This study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia.

Methods
We selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h).

Results
In the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup.

Conclusion
In conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings.
Ozone and cardiovascular injury
Authors: Srebot Vera , Gianicolo Emilio AL , Rainaldi Giuseppe , Trivella Maria Giovanna , Sicari Rosa 
Published: June 2009

Abstract
Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular diseases in urban communities. The potential detrimental effects are both acute and chronic having a strong impact on morbidity and mortality. The acute exposure to pollutants has been linked to adverse cardiovascular events such as myocardial infarction, heart failure and life-threatening arrhythmias. The long-terms effects are related to the lifetime risk of death from cardiac causes. The WHO estimates that air pollution is responsible for 3 million premature deaths each year. The evidence supporting these data is very strong nonetheless, epidemiologic and observational data have the main limitation of imprecise measurements. Moreover, the lack of clinical experimental models makes it difficult to demonstrate the individual risk. The other limitation is related to the lack of a clear mechanism explaining the effects of pollution on cardiovascular mortality. In the present review we will explore the epidemiological, clinical and experimental evidence of the effects of ozone on cardiovascular diseases.
The pathophysiologic consequences of air pollutant exposures have been extensively investigated in pulmonary systems, and it is clear that some of the major components of air pollution (e.g. ozone and particulate matter) can initiate and exacerbate lung disease in humans [1]. It is possible that pulmonary oxidant stress mediated by particulate matter and/or ozone (O3) exposure can result in downstream perturbations in the cardiovasculature, as the pulmonary and cardiovascular systems are intricately associated, and it is well documented that specific environmental toxins (such as tobacco smoke [2]) introduced through the lungs can initiate and/or accelerate cardiovascular disease development. Indeed, several epidemiologic studies have proved that there is an association between PM and O3 and the increased incidence of cardiovascular morbidity and mortality [3]. Most of the evidence comes from studies of ambient particles concentrations. However, in Europe and elsewhere, the air pollution profile has gradually changed toward a more pronounced photochemical component. Ozone is one of the most toxic components of the photochemical air pollution mixture. Indeed, the biological basis for these observations has not been elucidated.
In the present review, the role of ozone as chemical molecule will be firstly considered. Secondly, pathogenetic mechanisms connecting the atmospheric ozone level and cardiovascular pathology will be examined. Thirdly, the literature relating hospitalization frequency, morbidity and mortality due to cardiovascular causes and ozone concentration will be studied. The correlation between ozone level and occurrence of acute myocardial infarction will be eventually discussed.
Akt finds its new path to regulate cell cycle through modulating Skp2 activity and its destruction by APC/Cdh1
Authors: Gao Daming , Inuzuka Hiroyuki , Tseng Alan , Wei Wenyi 
Published: June 2009

Abstract
Skp2 over-expression has been observed in many human cancers. However, the mechanisms underlying elevated Skp2 expression have remained elusive. We recently reported that Akt1, but not Akt2, directly controls Skp2 stability by interfering with its association with APC/Cdh1. As a result, Skp2 degradation is protected in cancer cells with elevated Akt activity. This finding expands our knowledge of how specific kinase cascades influence proteolysis governed by APC/Cdh1 complexes. However, it awaits further investigation to elucidate whether the PI3K/Akt circuit affects other APC/Cdh1 substrates. Our results further strengthen the argument that different Akt isoforms might have distinct, even opposing functions in the regulation of cell growth or migration. In addition, we noticed that Ser72 is localized in a putative Nuclear Localization Sequence (NLS), and that phosphorylation of Ser72 disrupts the NLS and thus promotes Skp2 cytoplasmic translocation. This finding links elevated Akt activity with the observed cytoplasmic Skp2 staining in aggressive breast and prostate cancer patients. Furthermore, it provides the rationale for the development of specific Akt1 inhibitors as efficient anti-cancer therapeutic agents.
Epidermal wound healing in severe sepsis and septic shock in humans
Authors: Koskela Marjo , Gäddnäs Fiia , Ala-Kokko Tero I , Laurila Jouko J , Saarnio Juha , Oikarinen Aarne , Koivukangas Vesa 
Published: June 2009

Abstract
Introduction
The effect of sepsis on epidermal wound healing has not been previously studied. It was hypothesised that epidermal wound healing is disturbed in severe sepsis.

Methods
Blister wounds were induced in 35 patients with severe sepsis and in 15 healthy controls. The healing of the wounds was followed up by measuring transepidermal water loss and blood flow in the wound, reflecting the restoration of the epidermal barrier function and inflammation, respectively. The first set of suction blisters (early wound) was made within 48 hours of the first sepsis-induced organ failure and the second set (late wound) four days after the first wound. In addition, measurements were made on the intact skin.

Results
The average age of the whole study population was 62 years (standard deviation [SD] 12). The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission was 25 (SD 8). The two most common causes of infections were peritonitis and pneumonia. Sixty-six percent of the patients developed multiple organ failure. The decrease in water evaporation from the wound during the first four days was lower in septic patients than in the control subjects (56 g/m2 per hour versus 124 g/m2 per hour, P = 0.004). On the fourth day, septic patients had significantly higher blood flow in the wound compared with the control subjects (septic patients 110 units versus control subjects 47 units, P = 0.001). No difference in transepidermal water loss from the intact skin was found between septic patients and controls. Septic patients had higher blood flow in the intact skin on the fourth and on the eighth day of study compared with the controls.

Conclusions
The restoration of the epidermal barrier function is delayed and wound blood flow is increased in patients with severe sepsis.
Transdermal Nitroglycerin Therapy May Not Prevent Early Postmenopausal Bone Loss
Authors: Wimalawansa Sunil J. , Grimes Julia P. , Wilson Alan C. , Hoover Donald R. 
Published: June 2009

Context: Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss.
Objective: The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss.
Design: This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial.
Setting: The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ).
Participants: Participants included 186 postmenopausal women aged 40–65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to −2.5.
Intervention: Women, stratified by lumbar T-score (&lt;−1.50 and ≥−1.50) and years since menopause (≤5 and &gt;5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements.
Measurements: BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes.
Results: After 36 months of therapy, changes of −2.1% in the active group (n = 88) and −2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval −1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P &lt; 0.001). Other adverse and serious adverse events were not different.
Conclusions: BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only ∼16 mg/d); a sub-therapeutic dose.
No substantial bone mineral density changes were observed between postmenopausal women receiving once-daily 22.5 mg of transdermal nitroglycerin, compared to calcium plus vitamin D (compliance adjusted dose = 16 mg/day).
The 26-Amino Acid ß-Motif of the Pit-1ß Transcription Factor Is a Dominant and Independent Repressor Domain
Authors: Jonsen Matthew D. , Duval Dawn L. , Gutierrez-Hartmann Arthur 
Published: June 2009

Abstract
The POU-homeodomain transcription factor Pit-1 governs the pituitary cell-specific expression of Pit-1, GH, prolactin (PRL), and TSHß genes. Alternative splicing generates Pit-1ß, which contains a 26-amino acid ß-domain inserted at amino acid 48, in the middle of the Pit-1 transcription activation domain (TAD). Pit-1ß represses GH, PRL, and TSHß promoters in a pituitary-specific manner, because Pit-1ß activates these same promoters in HeLa nonpituitary cells. Here we comprehensively analyze the role of ß-domain sequence, position, and context, to elucidate the mechanism of ß-dependent repression. Repositioning the ß-motif to the Pit-1 amino terminus, hinge, linker, and carboxyl terminus did not affect its ability to repress basal rat (r) PRL promoter activity in GH4 pituitary cells, but all lost the ability to repress Ras-induced rPRL promoter activity. To determine whether ß-domain repression is independent of Pit-1 protein and DNA binding sites, we generated Gal4-Pit-1TAD, Gal4-Pit-1ßTAD, and Gal4-ß-domain fusions and demonstrated that the ß-motif is sufficient to actively repress VP16-mediated transcription of a heterologous promoter. Moreover, ß-domain point mutants had the same effect whether fused to Gal4 or within the context of intact Pit-1ß. Surprisingly, Gal4-ß repression lost histone deacetylase sensitivity and pituitary specificity. Taken together, these results reveal that the ß-motif is a context-independent, modular, transferable, and dominant repressor domain, yet the ß-domain repressor activity within Pit-1ß contains cell type, promoter, and Pit-1 protein context dependence.
FGF-2 Stimulation of RANK Ligand Expression in Paget’s Disease of Bone
Authors: Sundaram Kumaran , Senn Joseph , Yuvaraj Sambandam , Rao D. Sudhaker , Reddy Sakamuri V. 
Published: June 2009

Abstract
Receptor activator for nuclear factor-κB ligand (RANKL), a critical osteoclastogenic factor expressed in marrow stromal/preosteoblast cells is up-regulated in Paget’s disease of bone (PDB). We previously demonstrated that heat-shock factor-2 (HSF-2) is a downstream target of fibroblast growth factor-2 (FGF-2) signaling to induce RANKL expression in bone marrow stromal/preosteoblast cells. In this study, we identified a 2.5-fold increase in serum FGF-2 levels in patients (n = 8) with PDB compared with normal subjects (n = 10). We showed that HSF-2 co-immunoprecipitates with heat-shock protein-27 (HSP-27) and that FGF-2 stimulation significantly increased phospho-HSP-27 levels in marrow stromal cells. Confocal microscopy revealed HSF-2 colocalization with HSP-27 in unstimulated cells and HSF-2 nuclear translocation upon FGF-2 stimulation. We further show that FGF-2 stimulation significantly increased the levels of phosphorylated signal transducers and activators of the transcription (p-STAT-1) in these cells. Western blot analysis confirmed that small interfering RNA suppression of STAT-1 significantly decreased (3.2-fold) RANKL expression and promoter activity in FGF-2-stimulated cells. Chromatin immunoprecipitation assay revealed STAT-1 binding to a putative motif located far upstream (−8 kb) in the hRANKL gene promoter region. These results suggest STAT-1 is a downstream effector of FGF-2 signaling and that elevated levels of FGF-2 stimulates RANKL expression in PDB.
Novel Regulators of Fgf23 Expression and Mineralization in Hyp Bone
Authors: Liu Shiguang , Tang Wen , Fang Jianwen , Ren Jinyu , Li Hua , Xiao Zhousheng , Quarles L. D. 
Published: June 2009

Abstract
We used gene array analysis of cortical bone to identify Phex-dependent gene transcripts associated with abnormal Fgf23 production and mineralization in Hyp mice. We found evidence that elevation of Fgf23 expression in osteocytes is associated with increments in Fgf1, Fgf7, and Egr2 and decrements in Sost, an inhibitor in the Wnt-signaling pathway, were observed in Hyp bone. β-Catenin levels were increased in Hyp cortical bone, and TOPflash luciferase reporter assay showed increased transcriptional activity in Hyp-derived osteoblasts, consistent with Wnt activation. Moreover, activation of Fgf and Wnt-signaling stimulated Fgf23 promoter activity in osteoblasts. We also observed reductions in Bmp1, a metalloproteinase that metabolizes the extracellular matrix protein Dmp1. Alterations were also found in enzymes regulating the posttranslational processing and stability of Fgf23, including decrements in the glycosyltransferase Galnt3 and the proprotein convertase Pcsk5. In addition, we found that the Pcsk5 and the glycosyltransferase Galnt3 were decreased in Hyp bone, suggesting that reduced posttranslational processing of FGF23 may also contribute to increased Fgf23 levels in Hyp mice. With regard to mineralization, we identified additional candidates to explain the intrinsic mineralization defect in Hyp osteoblasts, including increases in the mineralization inhibitors Mgp and Thbs4, as well as increases in local pH-altering factors, carbonic anhydrase 12 (Car12) and 3 (Car3) and the sodium-dependent citrate transporter (Slc13a5). These studies demonstrate the complexity of gene expression alterations in bone that accompanies inactivating Phex mutations and identify novel pathways that may coordinate Fgf23 expression and mineralization of extracellular matrix in Hyp bone.
Pectin-based microspheres for colon-specific delivery of vancomycin
Authors: Bigucci Federica , Luppi Barbara , Monaco Libera , Cerchiara Teresa , Zecchi Vittorio 
Published: June 2009

Abstract

Objectives
The aim of this study was to describe a colon-specific delivery system based on pectin hydrogels formed by complexation with chitosan.

Methods
Hydrogels were prepared at different weight ratios (4: 1, 7: 1, 10: 1; pectin/chitosan), loaded with vancomycin hydrochloride (2: 1, 4: 1; polymer/drug weight ratio) and collected by spray-drying. The microspheres obtained were characterized in terms of morphology, swelling behaviour, mucoadhesive properties and drug loading efficiency. The influence of different pectin/chitosan hydrogels on the release behaviour of microspheres at pH 2.0, 5.5 and 7.4 were evaluated in vitro with and without pectinolytic enzyme.

Key findings
The results showed that water uptake was increased by raising the environmental pH (from 2.0 to 7.4) and the pectin/chitosan weight ratio, while drug availability was increased by raising the environmental pH (from 2.0 to 7.4) and decreased by raising the pectin/chitosan weight ratio. In the presence of pectinase, the glycoside bonds of pectin were degraded and a considerable amount of drug was released in a short time.

Conclusions
This study suggested that pectin/chitosan microspheres were able to limit the release of vancomycin under acidic conditions and release it under simulated colonic conditions, confirming their potential for a colon-specific drug delivery system.
Post-prandial metabolic alkalosis in the seawater-acclimated trout: the alkaline tide comes in
Authors: Bucking Carol , Fitzpatrick John L. , Nadella Sunita R. , Wood Chris M. 
Published: June 2009

SUMMARYThe consequences of feeding and digestion on acid–base balance and regulation in a marine teleost (seawater-acclimated steelhead trout; Oncorhynchus mykiss) were investigated by tracking changes in blood pH and [HCO3–], as well as alterations in net acid or base excretion to the water following feeding. Additionally the role of the intestine in the regulation of acid–base balance during feeding was investigated with an in vitro gut sac technique. Feeding did not affect plasma glucose or urea concentrations, however, total plasma ammonia rose during feeding, peaking between 3 and 24 h following the ingestion of a meal, three-fold above resting control values (∼300 μmol ml–1). This increase in plasma ammonia was accompanied by an increase in net ammonia flux to the water (∼twofold higher in fed fish versus unfed fish). The arterial blood also became alkaline with increases in pH and plasma [HCO3–] between 3 and 12 h following feeding, representing the first measurement of an alkaline tide in a marine teleost. There was no evidence of respiratory compensation for the measured metabolic alkalosis, as PaCO2 remained unchanged throughout the post-feeding period. However, in contrast to an earlier study on freshwater-acclimated trout, fed fish did not exhibit a compensating increase in net base excretion, but rather took in additional base from the external seawater, amounting to ∼8490 μmol kg–1 over 48 h. In vitro experiments suggest that at least a portion of the alkaline tide was eliminated through increased HCO3– secretion coupled to Cl–absorption in the intestinal tract. This did not occur in the intestine of freshwater-acclimated trout. The marked effects of the external salinity(seawater versus freshwater) on different post-feeding patterns of acid–base balance are discussed.
Surviving the drought: burrowing frogs save energy by increasing mitochondrial coupling
Authors: Kayes Sara M. , Cramp Rebecca L. , Hudson Nicholas J. , Franklin Craig E. 
Published: June 2009

SUMMARY
During dormancy energy conservation is a key priority and as such dormant animals undergo a major metabolic depression to conserve their limited endogenous fuel supplies. Mitochondrial coupling efficiency, the efficiency with which mitochondria convert oxygen into ATP, significantly affects aerobic metabolism and thus to maximise energy savings during dormancy it has been hypothesised that coupling efficiency should increase. However, previous studies have shown coupling efficiency to be maintained or even to decrease. In this study we measured state 3 and state 4 mitochondrial respiration in the muscle of the burrowing frog, Cyclorana alboguttata and calculated the respiratory control ratio as a measure of coupling efficiency. After 7 months in aestivation, C. alboguttata significantly reduced oxygen consumption of isolated mitochondria by 83% and, unlike other dormant animals,the frogs appeared to decrease rates of proton leak to a greater extent than ATP synthesis, consistent with an increase in mitochondrial coupling efficiency. The significant energy savings observed at the mitochondrial level were reflected at higher levels of biological organisation, with tissue oxygen consumption depressed by as much as 81% and whole animal metabolic rate by 82%. Cyclorana alboguttata can survive in a dormant state for several years and we propose the hypothesis that energy efficiency is increased during aestivation.
Combustion and the design of future engine fuels
Authors: Bradley D 
Published: June 2009

The fast diminution of readily extractable sources of fossil fuels, particularly oil, and concerns about global warming are leading to the creation of many new potential fuels. Their practicability must be assessed in terms of a wide range of physico-chemical properties, in relation to the operational aerodynamics in different engines. This article concentrates on those properties related to combustion and these are discussed in detail for some fuels with contrasting properties. Intrinsic fuel properties include volumetric energy, vapour pressure, heat of reaction, latent enthalpy of vaporization, and the relative volumes of energy that engines can breathe. Important combustion properties include the minimum ignition energy, laminar burning velocity, Markstein numbers for strain and curvature, flame extinction stretch rates for positive and negative stretch, stretch factor for flame instability, turbulent flame burning and quenching, autoignition delay time, excitation time for autoignition heat release, research and motor octane numbers and cetane number (CN). Such properties are manifest in a variety of aerodynamic contexts: for example, the nature of autoignition depends on spatial reactivity gradients and the acoustic speed. Particular problems can arise in characterizing engine knock when operational regimes are outside those in which the octane and CNs are determined. The approach adopted in this article does not assume any unique alignment between fuels, mode of combustion, and power unit, and different possibilities are discussed.