bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Maillard Hypothesis on Aging: Time to Focus on DNA
Authors: BAYNES JOHN W. 
Published: July 2010

AbstractAging is the outcome of the contest between chemistry and biology in living systems. Chronic, cumulative chemical modifications compromise the structure and function of biomolecules throughout the body. Proteins with long life spans serve as cumulators of exposure to chemical damage, which is detectable in the form of advanced glycation and lipoxidation end products (AGEs, ALEs); amino acids modified by reactive oxygen, chlorine, and nitrogen species; and deamidated and racemized amino acids. Not all of these modifications are oxidative in nature, although oxidative reactions are an important source of age‐related damage. Measurements of AGEs and ALEs in proteins are useful for assessing the rate and extent of Maillard reaction damage, but it is the damage to the genome that undoubtedly has the greatest effect on the viability of the organism. The extent of genomic damage represents a balance between the rate of modification and the rate and fidelity of repair. Damage to DNA accumulates not in the form of modified nucleic acids, but as chemically “silent” errors in repair—insertions, deletions, substitutions, transpositions, and inversions in DNA sequences—that affect the expression and structure of proteins. These mutations are random, vary from cell to cell, and are passed forward from one cell generation to another. Although they are not detectable in DNA by conventional analytical techniques, purines and pyrimidines modified by Maillard reaction intermediates may be detectable in urine, and studies on these compounds should provide insight into the role of Maillard reactions of DNA in aging and disease.
Alzheimer's Disease: Role of Aging in Pathogenesis
Authors: HARMAN DENHAM 
Published: July 2010

AbstractAlzheimer's disease (AD) is characterized by intraneuronal fibrillary tangles, plaques, and cell loss. Brain lesions in both sporadic AD (SAD) and familial AD (FAD) are the same, and in the same distribution pattern, as those in individuals with Down syndrome (DS) and in smaller numbers in nondemented older individuals. Dementia onset is around 40 years for DS, 40‐60 years for FAD, and usually over 60 years for SAD. The different categories of AD may be due to processes that augment to different degrees the innate cellular aging rate, that is, mitochondrial superoxide radical (SO) formation. Thus, they increase the rate of accumulation of AD lesions. This lowers the age of onset into the dementia ranges associated with DS, FAD, and SAD, and concomitantly shortens life spans. Faster aging lowers AD onset age by decreasing the onset age for neurofibrillary tangle formation and neuronal loss, and the age when brain intercellular H2O2can activate microglial cells. The early AD onset in DS is attributed to a defective mitochondrial complex 1. The proteins associated with FAD and their normal counterparts undergo proteolytic processing in the endoplasmic reticulum (ER). The mutated compounds increase the ratio of βA42to βA40and likely also down‐regulate the ER calcium (Ca2+) buffering activity. Decreases in ER Ca2+content should increase the mitochondrial Ca2+pool, thus enhancing SO formation. SAD may be due to increased SO formation caused by mutations in the approximately 1000 genes involved in mitochondrial biogenesis and function. The hypothesis suggests measures to prevent and treat.
Time to Talk SENS: Critiquing the Immutability of Human Aging
Authors: DE GREY AUBREY D. N. J. , AMES BRUCE N. , ANDERSEN JULIE K. , BARTKE ANDRZEJ , CAMPISI JUDITH , HEWARD CHRISTOPHER B. , McCARTER ROGER J. M. , STOCK GREGORY 
Published: July 2010

AbstractAging is a three‐stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus accumulates. This accumulating damage ultimately drives age‐related degeneration. Interventions can be designed at all three stages. However, intervention in metabolism can only modestly postpone pathology, because production of toxins is so intrinsic a property of metabolic processes that greatly reducing that production would entail fundamental redesign of those processes. Similarly, intervention in pathology is a “losing battle” if the damage that drives it is accumulating unabated. By contrast, intervention to remove the accumulating damage would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely. We survey the major categories of such damage and the ways in which, with current or foreseeable biotechnology, they could be reversed. Such ways exist in all cases, implying that indefinite postponement of aging—which we term “engineered negligible senescence”—may be within sight. Given the major demographic consequences if it came about, this possibility merits urgent debate.
The First Six Years at the National Institute for Longevity Sciences, Japan
Authors: KITANI KENICHI 
Published: July 2010

AbstractThe National Institute for Longevity Sciences (NILS) of Japan opened on July 7, 1995, 15 years after the Science Council of Japan recommended the establishment of the National Center for Aging and Geriatric Illnesses (the provisional name for NILS) in 1980. During the first four years of operation, 8 separate research departments, containing 21 laboratories, were established. NILS has both research departments for biomedical sciences, such as dementia research, molecular genetics, and geriatric research, and also departments of gerontechnology and the care of the elderly, which engage in research directed toward the comprehensive improvement of the health and well‐ being of the elderly. On July 9, 1995, the day of the opening ceremonies, NILS employed only three staff members, including the director general. At the end of fiscal year 2000 (March 31, 2001), the institute comprised a staff of more than 200 people, including 30 senior science staff and about 50 junior scientists. The Japanese government has recently decided to expand NILS to double its present size by the end of fiscal year 2004 (March 2005).
Mass Transfer and Nutrient Absorption in a Simulated Model of Small Intestine
Authors: Tharakan A. , Norton I.T. , Fryer P.J. , Bakalis S. 
Published: July 2010

Abstract:  There is an increasing need to understand how food formulations behave in vivo from both food and pharma industries. A number of models have been proposed for the stomach, but few are available for the other parts of the gastrointestinal tract. An experimental rig that simulates the segmentation motion occurring in the small intestine has been developed. The objective of developing such an experimental apparatus was to study mass transport phenomena occurring in the lumen and their potential effect on the concentration of species available for absorption. When segmentation motion was applied the mass transfer coefficient in the lumen side was increased up to a factor of 7. The viscosity of the lumen, as influenced by guar gum concentration, had a profound effect on the mass transfer coefficient. The experimental model was also used to demonstrate that glucose available for absorption, resulting from starch hydrolysis, can be significantly reduced by altering the lumen viscosity. Results suggest that absorption of nutrients could be controlled by mass transfer.Practical Application:  To address health‐related diseases such as obesity, novel foods that provide advanced functions are required. To achieve the full potential offered by the latest developments in the field of food material science, a fundamental understanding of the behavior of food structures in vivo is required. Using the developed gut model we have demonstrated that absorption of nutrients can be controlled by mass transfer limitations.
Lens opacity and refractive influences on the measurement of retinal vascular fractal dimension
Authors: Li Haitao , Mitchell Paul , Liew Gerald , Rochtchina Elena , Kifley Annette , Wong Tien Y. , Hsu Wynne , Lee Mong L. , Zhang Yong P. , Wang Jie J. 
Published: July 2010

Acta Ophthalmol. 2010: 88: e234–e240Abstract.Purpose:  To examine the influence of lens opacity and refraction on the measurement of retinal vascular fractal dimension (Df).Methods:  Optic disc photographs (right eyes) of 3654 baseline Blue Mountains Eye Study participants (aged 49–97 ) were digitized. Retinal vascular Df was quantified using a computer‐based program. Summated severity scores for nuclear, cortical and posterior subcapsular (PSC) cataract were assessed from lens photographs. Refraction data were converted to spherical equivalent refraction (SER), as sum spherical plus 0.5 cylinder power. Axial length was measured at 10‐year follow‐up examinations using an IOL master.Results:  Mean Df of the retinal vasculature was 1.444 ± 0.023 for 2859 eligible participants. Increasing lens opacity scores were associated with significant reduction in Df (β = −0.0030, p < 0.0001). Both cortical and PSC cataract involving central lens area were associated with reduced Df, after controlling for confounding factors (ptrend ≤ 0.0105). Increasing myopia severity was associated with reduced Df after adjusting for lens opacity scores and other confounders (ptrend < 0.0001). The slope of Df decrease per SER reduction was 0.0040 in eyes with SER ≤ −4D, compared to −0.0016 in eyes with SER > −4D. For axial length quintiles, there were no significant differences in mean Df in all groups except a reduction in the fifth quintile (axial length ≥24.15 mm) (all p < 0.05).Conclusion:  Ocular media opacity independently influenced retinal vascular Df measurement, but we found no evidence supporting any refractive axial magnification effect on this measure. Myopic refraction ≤−4D was associated with a reduction in Df, suggesting rarefaction of retinal vasculature associated with high myopia.
Quercetin and naringenin reduce abnormal development of mouse embryos produced by hydroxyurea
Authors: Pérez-Pastén Ricardo , Martínez-Galero Elizdath , Chamorro-Cevallos Germán 
Published: July 2010

Abstract

Objectives
There is limited evidence about the impact of quercetin and naringenin on embryonic development. The purpose of this work was to evaluate in vitro their direct teratogenic potential as well as their protective activity against teratogenesis mediated by oxidative damage on mouse embryos.

Methods
Quercetin and naringenin toxicity on whole mouse cultured embryos, as well as their ability to protect embryos against hydroxyurea-induced insult were evaluated.

Key findings
Quercetin 100 µm and naringenin 300 µm produced significant reduction of developmental and growth parameters, in comparison with those of the control group. Embryos exposed to the concurrent administration of quercetin or naringenin with hydroxyurea (2 µm, 2 h) were significantly protected from growth and developmental retardation, and abnormalities induced by hydroxyurea. Interestingly, embryos exposed to hydroxyurea and dimethyl sulfoxide 0.1%, the vehicle employed to dissolve flavonoids, also showed significant damage amelioration.

Conclusions
These results indicate that quercetin and naringenin have not only a minor toxic effect on development, but also a protective effect against hydroxyurea-induced embryonic damage.
Biological activity of the essential oil of Kadsura longipedunculata (Schisandraceae) and its major components
Authors: Mulyaningsih Sri , Youns Mahmoud , El-Readi Mahmoud Z , Ashour Mohamed L , Nibret Endalkachew , Sporer Frank , Herrmann Florian , Reichling Jürgen , Wink Michael 
Published: July 2010

Abstract

Objectives
The aim was to determine the chemical composition of the essential oil of Kadsura longipedunculata and the biological activity of the oil and its major components.

Methods
The essential oil from stem bark of Kadsura longipedunculata was analysed by capillary gas chromatography (GLC/FID) and gas chromatography–mass spectrometry (GLC/MS). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH•) was used to evaluate the antioxidant activity. Inhibition of both lipoxygenase and prostaglandin E2 was used to assess the anti-inflammatory activity. Antimicrobial activity was studied in vitro against a range of bacteria and fungi using diffusion and microdilution methods. Inhibition of trypanosome proliferation was assessed using resazurin as vital stain. The in-vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, MIA PaCa-2, HeLa, HL-60, MDA-MB-231 and SW-480) was examined using the MTT assay.

Key findings
Fifty compounds, representing 97.63% of total oil, were identified. δ-Cadinene (21.79%), camphene (7.27%), borneol (6.05%), cubenol (5.12%) and δ-cadinol (5.11%) were found to be the major components of the oil. The oil exerted a good antimicrobial activity against all Gram-positive bacteria tested, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. Streptococcus pyogenes and S. agalactiae were the most sensitive bacteria with a minimal inhibitory concentration (MIC) of 60 µg/ml oil. The essential oil showed a moderate fungicidal activity against yeasts, but it did not show any activity against Gram-negative bacteria. The essential oil showed a good trypanocidal activity in Trypanosoma b. brucei with an IC50 value of 50.52 ± 0.029 µg/ml. Radical scavenging activity had an IC50 value of 3.06 ± 0.79 mg/ml. 5-Lipoxygenase inhibition (IC50 = 38.58 µg/ml) and prostaglandin E2 production inhibition (28.82% at 25 µg/ml) accounted for anti-inflammatory activity of the oil. The oil exhibited some degree of cytotoxic activity against MIA PaCa-2, HepG-2 and SW-480 cell lines with IC50 values of 133.53, 136.96 and 136.62 µg/ml, respectively. The oil increased caspase 3/7 activity (an indicator of apoptosis) 2.5–4 fold in MIA Paca-2 cells. Camphene and borneol did not show antioxidant activity. However, both compounds exhibited some degree of antimicrobial, trypanocidal, anti-inflammatory and cytotoxic activity.

Conclusions
This investigation provided evidence for, and confirmed the efficacy of, K. longipedunculata, a traditionally used Chinese medicinal plant for the treatment of inflammation and infection.
The essential oil ofCroton nepetaefoliusselectively blocks histamine-augmented neuronal excitability in guinea-pig celiac ganglion
Authors: Leal-Cardoso José Henrique , Lahlou Saad , Weinreich Daniel , Caldas Magalhães Pedro Jorge 
Published: July 2010

AbstractObjectivesCroton nepetaefolius is a medicinal plant useful against intestinal disorders. In this study, we elucidate the effects of its essential oil (EOCN) on sympathetic neurons, with emphasis on the interaction of EOCN- and histamine-induced effects.MethodsThe effects of EOCN and histamine were studied in guinea-pig celiac ganglion in vitro.Key findingsHistamine significantly altered the resting potential (Em) and the input resistance (Ri) of phasic neurons (from −56.6 ± 1.78 mV and 88.6 ± 11.43 MΩ, to −52.9 ± 1.96 mV and 108.6 ± 11.00 MΩ, respectively). Em, Ri and the histamine-induced alterations of these parameters were not affected by 200 µg/ml EOCN. The number of action potentials produced by a 1-s (two-times threshold) depolarising current and the current threshold (Ith) for eliciting action potentials (rheobase) were evaluated. Number of action potentials and Ith were altered by histamine (from 2.6 ± 0.43 action potentials and 105.4 ± 11.15 pA to 6.2 ± 1.16 action potentials and 67.3 ± 8.21 pA, respectively). EOCN alone did not affect number of action potentials and Ith but it fully blocked the histamine-induced modifications of number of action potentials and Ith. All the effects produced by histamine were abolished by pyrilamine.ConclusionsEOCN selectively blocked histamine-induced modulation of active membrane properties.
Effect ofγ-glutamylcysteine ethylester on the levels ofc-fosmRNA expression, glutathione and reactive oxygen species formation in kainic acid excitotoxicity
Authors: Turunc Ezgi , Kanit Lutfiye , Yalcin Ayfer 
Published: July 2010

AbstractObjectivesThe aim of this study was to investigate the effect of γ-glutamylcysteine ethylester (GCEE), a precursor of glutathione biosynthesis, on the levels of glutathione, formation of reactive oxygen species and c-fos mRNA expression in rat hippocampus and cortex in kainic acid-induced excitotoxicity.MethodsSprague–Dawley rats were used and divided into four groups: control, kainic acid (10 mg/kg), GCEE (10 mg/kg) and kainic acid (10 mg/kg) + GCEE (10 mg/kg). Kainic acid and GCEE were administered to the rats intraperitoneally. The levels of glutathione and the expressions of c-fos mRNA in hippocampus and cortex tissues were determined using spectrophotometric and reverse transcription followed real-time PCR methods, respectively. Formation of reactive oxygen species was determined using dichlorofluorescin fluorescence in brain synaptosomes treated with kainic acid or GCEE in vitro.Key findingsKainic acid treatment significiantly upregulated the expression of c-fos mRNA in the hippocampus and cortex when compared to the control group. GCEE treatment significantly decreased the levels of c-fos mRNA in the cortex when compared to the kainic acid-treated group. GCEE treatment against kainic acid significantly increased the levels of glutathione in the cortex and hippocampus, and decreased the levels of formation of reactive oxygen species when compared to kainic acid-treated synaptosomes.ConclusionsThe increased levels of glutathione and the reduced levels of reactive oxygen species formation lead us to conclude that GCEE may be beneficial as a potential antioxidant against neurodegenerative processes where excitotoxicity is involved.
Suppression of tumour necrosis factor-αbySchizonepeta tenuifoliawater extract via inhibition of IκBαdegradation and Jun N-terminal kinase/stress-activated protein kinase activation
Authors: Kang Hee , Han Sang-Woo , Hong Joung-Woo , Sohn Nak-Won 
Published: July 2010

AbstractObjectivesThe anti-inflammatory effects of an aqueous extract of Schizonepeta tenuifolia on lipopolysaccharide (LPS)-induced tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in vivo and in vitro have been investigated.MethodsC57BL/6 mice were orally administered phosphate-buffered saline (control) or S. tenuifolia water extract (50, 200, 500 or 1000 mg/kg) for 10 days before intraperitoneal administration of LPS (1.3 mg/kg). Blood samples were obtained 1 h after LPS challenge, followed by determination of TNF-α and IL-6 levels. Peritoneal macrophages from thioglycollate-injected mice were obtained and stimulated with LPS and S. tenuifolia water extract for viability assay, cytokine analysis, real-time RT PCR and Western blotting.Key findingsOral administration of S. tenuifolia water extract to mice significantly reduced LPS-induced serum levels of TNF-α, but not IL-6. When peritoneal macrophages were treated in vitro with S. tenuifolia water extract, the inhibition of LPS-induced TNF-α was more pronounced than that of IL-6 at the level of secreted protein and mRNA. S. tenuifolia water extract reduced the degradation of IκBα and the nuclear relocation of p65 NF-κB, but the phosphorylation of IκBα was not affected. Inhibition of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) by S. tenuifolia water extract led secondarily to the inhibition of phospho-c-Jun and phospho-ATF-2.ConclusionsThese results indicated that the downregulation of TNF-α by S. tenuifolia water extract may have involved the inhibition of both IκBα degradation and activation of c-Jun and ATF-2 involving suppression of JNK/SAPK.
Thermodynamic Model of the Metallic Friction Process
Authors: Maciąg Maria 
Published: July 2010

Abstract
An energy model of stabilized friction and wear is presented. Heating of a definite mass of surface material to the flash point, in consideration of the mass’s specific heat and wear, is assumed to provide the basis for thermal processes. An energy balance is presented in the form of a first law of thermodynamics formula for open systems. Two new magnitudes, referred to as complex systemic constants C and D, are developed and their physical meaning is interpreted. These complex systemic constants are subsequently employed to describe the tribological system. Among other magnitudes in the model, density of thermal dissipation and enthalpy flux, power density of mechanical dissipation, wear severity, and specific work of wear are described. Friction and wear testing results [Ciecieląg, 1994, “Energy Conditions of Metal Resistance to Tribological Wear,” Ph.D. thesis, Świętokrzyska Technical University, Kielce; Żurowski, 1996, “Energy Aspect of Increasing Wear-Resistance of Metals in the Process of Engineering Dry Friction,” Ph.D. thesis, Świętokrzyska Technical University, Kielce; Sadowski and Żurowski, 1992, “Thermodynamic Aspects of Metals' Wear-Resistance,” Tribology and Lubrication Engineering, 3, pp. 152–159] are employed to describe, in quantitative terms, selected tribological systems on the basis of the presented thermodynamic model. A method of determining the complex systemic constants C and D is developed. Specific work of wear, wear severity, probability of emergence of a flux of tribological wear products, and relation of worn mass to heated mass and flash temperature as functions of temperature are defined. This paper concludes with application, significance, and advantages of the complex systemic constants C and D, and phenomena arising in frictional contact between two metals.
The association between radiographic knee osteoarthritis and knee symptoms, function and quality of life 10–15 years after anterior cruciate ligament reconstruction
Authors: Øiestad B E , Holm I , Engebretsen L , Risberg M A 
Published: July 2010

BackgroundThere are conflicting results in the literature regarding the association between radiographic knee osteoarthritis (OA) and symptoms and function in subjects with previous anterior cruciate ligament (ACL) reconstruction.AimTo investigate the associations between radiographic tibiofemoral knee OA and knee pain, symptoms, function and knee-related quality of life (QOL) 10–15 years after ACL reconstruction.Study designCross-sectional study.Material and methods258 subjects were consecutively included at the time of ACL reconstruction and followed up prospectively. The authors included the Knee Injury and Osteoarthritis Outcome Score to evaluate knee pain, other symptoms (symptoms), activities of daily living and sport and recreation (Sport/Rec) and QOL. The subjects underwent standing radiographs 10–15 years after the ACL reconstruction. The radiographs were graded with the Kellgren and Lawrence (K&L) classification (grade 0–4).Results210 subjects (81%) consented to participate in the 10–15-year follow-up. Radiographic knee OA (K&L ≥grade 2) was detected in 71%, and 24% showed moderate or severe radiographic knee OA (K&L grades 3 and 4). No significant associations were detected between radiographic knee OA (K&L grade ≥2) and pain, function or QOL, respectively, but subjects with radiographic knee OA showed significantly increased symptoms. Severe radiographic knee OA (K&L grade 4) was significantly associated with more pain, symptoms, impaired Sport/Rec and reduced QOL.ConclusionSubjects with radiographic knee OA showed significantly more symptoms than those without OA, and subjects with severe radiographic knee OA had significantly more pain, impaired function and reduced quality of life than those without radiographic knee OA 10–15 years after ACL reconstruction.