bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidative Effect of Vitamin D3 on Zinc‐Induced Oxidative Stress in CNS
Authors: LIN ANYA M. Y. , CHEN K B , CHAO P L
Published: July 2010

Abstract:Antioxidative mechanisms of vitamin D3 were evaluated bothin vitroandin vivo. A 4‐h incubation of brain homogenates at 37°C increased the formation of Schiff base fluorescent products of malonaldehyde, an indicator of lipid peroxidation. Incubation with vitamin D3 dose‐dependently suppressed auto‐oxidation. The antioxidative potency for inhibiting zinc‐induced lipid peroxidation was as follows: vitamin D3 > Trolox (a water‐soluble analogue of vitamin E) ≥β‐estradiol > melatonin. In the presence of high dose of desferrioxamine, a metal chelator, vitamin D3 attenuated auto‐oxidation. Thesein vitrodata indicate that vitamin D3 may act as a terminator of the lipid peroxidation chain reaction. The antioxidative effect of vitamin D3 on zinc‐induced oxidative injury was verified using local infusion of vitamin D3in vivo. Intranigral infusion of zinc elevated lipid peroxidation in the infused substantia nigra and depleted striatal dopamine content at 7 days after infusion. Furthermore, elevated cytosolic cytochrome c and DNA ladder, indicatives of apoptosis, were demonstrated in the infused substantia nigra. Simultaneous infusion of vitamin D3 and zinc prevented oxidative injury and apoptosis induced by zinc alone. The involvement of glia‐derived neurotrophic factor (GDNF) expression was excluded since vitamin D3 did not alter GDNF level in the infused substantia nigra at 24 h or 4 days after intranigral infusion of vitamin D3. Our results suggest that vitamin D3, independent of upregulation of GDNF expression, may acutely prevent zinc‐induced oxidative injuries via antioxidative mechanisms.
Antioxidant Effects ofN‐Acetylserotonin
Authors: OXENKRUG GREGORY
Published: July 2010

Abstract:This paper will review our recent data relevant to the antioxidant effects ofN‐acetylserotonin (NAS), the immediate precursor of melatonin, the pineal gland indole. Mechanisms of the antioxidant effects of NAS might involve interaction with melatonin type 3 receptors and nonreceptor mechanisms such as stimulation of glutathione peroxidase, an antioxidant enzyme; inhibition of lipid peroxidation; suppression of phospholipase A2 activation; attenuation of tumor necrosis factor‐α production; prevention of pathological opening of the mitochondrial permeability transition pores; and inhibition of sepiapterin reductase, the key enzyme of biosynthesis of tetrahydrobiopterin, the essential cofactor of nitric oxide synthase. NAS actions on some of these enzymes might be receptor‐mediated. Protective effects of NAS against oxidative damage are independent from the effect of melatonin and, depending on the model, are 5 to 20 times stronger than that of melatonin. Antioxidant effect of NAS might underpin its cognition‐enhancing, antiaging, antidepressant, antihypertensive, and antitumor effects. NAS and its derivatives might be useful in protection against oxidative stress‐related disorders (cell death, mutagenesis, aging) and diseases (sepsis, cancer, postischemic trauma, Alzheimer's disease, parkinsonism).
Acrylamide Stimulates Glutamine Uptake in Fischer 344 Rat Astrocytes by a Mechanism Involving Upregulation of the Amino Acid Transport System N
Authors: WU QI , SIDORYK MARTA , MUTKUS LYSETTE , ZIELIŃSKA MAGDALENA , ALBRECHT JAN , ASCHNER MICHAEL
Published: July 2010

Abstract: High demand of neoplastic tissues for glutamine (Gln) is met by its active transport across cell membranes. Chronic treatment with acrylamide in rodents is associated with an increased incidence of neoplasms, including astrocytomas. In this study, 24‐h acrylamide treatment significantly increased the initial rate of l‐[G‐3H]glutamine uptake in astrocyte cultures derived from the acrylamide‐sensitive Fischer 344 rat, and this effect could be fully inhibited by histidine, a model substrate for the amino acid transport system N. RT‐PCR analysis revealed that acrylamide treatment caused a significant increase in the astrocytic expression of the mRNA coding for the major system N protein, SNAT3, which is specifically overexpressed in malignant gliomas in situ. The acrylamide‐induced upregulation of astrocytic Gln transport via system N is likely to affect Gln homeostasis in these cells and may be causally related to the increased astrocytoma incidence observed in Fischer 344 rats.
Effects of Acrylamide on Primary Neonatal Rat Astrocyte Functions
Authors: ASCHNER MICHAEL , WU QI , FRIEDMAN MARVIN A.
Published: July 2010

Abstract: The present study assessed biochemical endpoints indicative of acrylamide toxicity in astrocyte cultures derived from neonatal rat pups. Given earlier reports on the possible ability of acrylamide to induce astrocytomas in the Fischer 344 rat, we performed studies in neonatal rat astrocyte cultures from the Fischer 344 to assess the ability of acrylamide to induce astrocytic proliferation. Measurements on astrocytic proliferation included [3H]‐leucine incorporation, [3H]‐thymidine incorporation, and changes in proliferating cell nuclear antigen (PCNA). Although acrylamide (0.1 and 1 mM for 7, 11, 15, or 20 days) did not significantly (P > 0.05) affect [3H]‐leucine or [3H]‐thymidine incorporation, it significantly (P < 0.05) increased PCNA protein expression in astrocytes exposed to acrylamide for 15 and 20 days. Additional studies revealed that this effect on PCNA protein expression was not associated with activation of dopamine‐2 (D2) receptors, given that quinpirole (10 μM added to cultures for the last hour of 7, 11, 15, or 20 days in culture), a selective D2 receptor agonist, did not produce results analogous to those seen with acrylamide treatment. Cotreatment of astrocytes with acrylamide (7, 11, 15, or 20 days) and the D2 receptor antagonist, sulpiride (1 μM for the last 6 h of exposure), also failed to reverse acrylamide's effect on PCNA protein induction. Taken together, these studies suggest that acrylamide promotes astrocytic cell proliferation in the CNS even though DNA synthesis did not appear stimulated.
Expression of Prostaglandin E2 Synthases in Mouse Postnatal Cortical Neurons
Authors: ECHEVERRIA VALENTINA , GREENBERG DAVID L. , DORÉ SYLVAIN
Published: July 2010

Abstract: Eicosanoids and the enzymes associated with their metabolism play an active role in the neuroinflammatory process that is often a hallmark of neurodegenerative disorders. Cerebral cortical neurons constitute a highly affected cell population in neurologic disorders. To obtain a cellular model to analyze prostaglandin action and metabolism in cortical neurons, we developed postnatal neuronal cultures from mouse cortex in a serum‐free medium. Cultured cortical cells were highly enriched in neurons containing only 5 ± 2% glial cells. The cultures were assayed for expression of several protein markers of neuronal maturity: synaptic markers (synapsin I and synaptophysin) and glutamate receptor subunits (NMDA receptor 1 and glutamate receptor 1). The protein expression of eicosanoid‐metabolizing enzymes, including cyclooxygenase‐2 and microsomal and cytosolic PGE2 synthases, was investigated as well. Postnatal neurons successfully survived for a long term (up to 40 days) in vitro in serum‐free media, as characterized by the expression of synapsin I, synaptophysin, and microtubule‐associated protein 2. Glutamate receptor subunit expression increased over time in cultures, with the highest levels at 15 days. Enzymes involved in the eicosanoid metabolism followed a distinct pattern of expression, suggesting potential regulation of PGE2 synthesis with time in cultures under basal conditions. Use of postnatal brain cultures offers several advantages, especially regarding degree of neuronal maturation, use of postnatal pups instead of pregnant mice, and potentially increased clinical relevance in models of neuroinflammation processes and prostanoid cellular neurobiology.
Manganese superoxide dismutase versus p53: the mitochondrial center
Authors: Holley Aaron K. , Dhar Sanjit K. , St. Clair Daret K.
Published: July 2010

Mitochondria are important sites of myriad metabolic activities. The actions of mitochondria must be carefully synchronized with other processes in the cell to maintain cellular homeostasis. Interorganellar communication between mitochondria and the nucleus is key for coordination of these cellular functions. Numerous signaling proteins and transcription factors are affected by reactive oxygen species and aid interorganellar communication. p53 is an important tumor suppressing protein that regulates many cellular activities, such as cell cycle regulation, DNA repair, and programmed cell death. p53 carries out these functions through both transcription‐dependent and transcription‐independent routes at mitochondria and the nucleus. Manganese superoxide dismutase (MnSOD), a p53‐regulated gene that is a vital antioxidant enzyme localized in the matrix of mitochondria, scavenges reactive oxygen species. Recent studies suggest that mitochondria can regulate p53 activity and that assaults on the cell that affect mitochondrial ROS production and mitochondrial function can influence p53 activity. Cross‐talk between mitochondria and p53 is important in normal cellular functions, and a breakdown in communication among mitochondria, p53, and the nucleus may have serious consequences in disease development.
A novel function of mtDNA: its involvement in metastasis
Authors: Ishikawa Kaori , Hayashi Jun‐Ichi
Published: July 2010

It has been controversial whether mtDNA mutations are responsible for oncogenic transformation (normal cells to develop tumors) and for malignant progression (tumor cells to develop metastases). To clarify this issue, we created transmitochondrial cybrids with mtDNA exchanged between mouse tumor cells that express different metastatic phenotypes. The G13997A mutation in the ND6 gene of mtDNA from high‐metastatic tumor cells reversibly controlled development of metastases by overproduction of reactive oxygen species (ROS). The mtDNA‐mediated reversible control of metastasis reveals a novel function of mtDNA, and suggests that ROS scavengers may be therapeutically effective in suppressing metastasis.
The NADH‐fumarate reductase system, a novel mitochondrial energy metabolism, is a new target for anticancer therapy in tumor microenvironments
Authors: Tomitsuka Eriko , Kita Kiyoshi , Esumi Hiroyasu
Published: July 2010

Since deficiencies of critical nutrients and hypoxia are observed in hypovascular tumors, glycolysis alone cannot explain how cancer cells maintain their required energy levels. To study energy metabolism in cancer cells within such tumor microenvironments, we examined the NADH‐fumarate reductase system, which is found in anaerobic organisms, such as parasitic helminthes. In human cancer cells cultured under tumor microenvironment‐mimicking conditions, mitochondrial NADH‐fumarate reductase activity increased in parallel with an increase in fumarate reductase activity, which is the reverse reaction of succinate‐ubiquinone reductase and is regulated by the phosphorylation of its subunit. Pyrvinium pamoate, an anthelmintic drug, has an anticancer effect within tumor‐mimicking microenvironments. We found that one of the biological mechanisms of pyrvinium is the inhibition of the NADH‐fumarate reductase system. Therefore, the NADH‐fumarate reductase system might be important for maintaining mitochondrial energy metabolism within the tumor microenvironments and might represent a novel target for anticancer therapies.
Animal and human studies with the mitochondria‐targeted antioxidant MitoQ
Authors: Smith Robin A.J. , Murphy Michael P.
Published: July 2010

As mitochondrial oxidative damage contributes to a wide range of human diseases, antioxidants designed to be accumulated by mitochondria in vivo have been developed. The most extensively studied of these mitochondria‐targeted antioxidants is MitoQ, which contains the antioxidant quinone moiety covalently attached to a lipophilic triphenylphosphonium cation. MitoQ has now been used in a range of in vivo studies in rats and mice and in two phase II human trials. Here, we review what has been learned from these animal and human studies with MitoQ.
Neuroprotective mechanisms of brain‐derived neurotrophic factor against 3‐nitropropionic acid toxicity: therapeutic implications for Huntington's disease
Authors: Wu Chia‐Lin , Hwang Chi‐Shin , Chen Shang‐Der , Yin Jiu‐Haw , Yang Ding‐I
Published: July 2010

3‐Nitropropionic acid (3‐NP) is an irreversible inhibitor of mitochondrial succinate dehydrogenase that has been used to explore the molecular mechanisms of cell death associated with mitochondrial dysfunction and neurodegeneration for Huntington's disease (HD). Brain‐derived neurotrophic factor (BDNF) is a neurotrophin that may regulate neuronal survival and differentiation. Experimental evidence derived from both clinical as well as basic research suggests a close association between BDNF deficiency and HD pathogenesis. In this review, we focus on recent progress in the molecular mechanisms responsible for the BDNF‐mediated neuroprotective effects against mitochondrial dysfunction induced by 3‐NP. Delineation of BDNF‐mediated neuroprotective actions against 3‐NP toxicity may add in the development of therapeutic intervention for HD where mitochondrial dysfunction is known to play a crucial role in pathogenesis of this devastating disease.
Bioenergetics and cell death
Authors: Kushnareva Yulia , Newmeyer Donald D.
Published: July 2010

Mitochondrial bioenergetic function is a key to cell life and death. Cells need energy not only to support their vital functions but also to die gracefully. Execution of an apoptotic program includes energy‐dependent steps, including kinase signaling, formation of the apoptosome, and effector caspase activation. Under conditions of bioenergetic collapse, cells are diverted toward necrotic demise. Mitochondrial outer membrane permeabilization (MOMP) is a decisive event in the execution of apoptosis. It is also causally linked to a decline in bioenergetic function via different mechanisms, not merely due to cytochrome c dispersion. MOMP‐induced bioenergetic deficiency is usually irreversible and commits cells to die, even when caspases are inactive. Here, we discuss the mechanisms by which MOMP impacts bioenergetics in different cell death paradigms.
Metabolic analysis of 13C‐labeled pyruvate for noninvasive assessment of mitochondrial function
Authors: Wu I‐Chien , Ohsawa Ikuroh , Fuku Noriyuki , Tanaka Masashi
Published: July 2010

Mitochondria may play important roles in metabolic diseases, neurodegeneration, and aging. Therefore, noninvasive methods to assess mitochondrial metabolic function in humans are urgently needed. We demonstrated that the 13C‐breath test using [1‐13C] acetate and [1‐13C] pyruvate holds great potential for assessing the metabolic status in mitochondria. The 13C‐breath test allows us to assess dynamic metabolic pathways noninvasively within 60 min. This test will not only facilitate clinical evaluation of patients but also provide huge opportunities for further understanding of these conditions. The potential of the 13C‐breath test using 13C‐labeled pyruvate in humans cannot be overemphasized.
Antioxidant Capacity and Antioxidant Content in Roots of 4 Sweetpotato Varieties
Authors: Rautenbach Fanie , Faber Mieke , Laurie Sunette , Laurie Robert
Published: July 2010

Abstract:  The antioxidant contents (β‐carotene, chlorogenic acid, and vitamin C) as well as the antioxidant capacity (ORAC, FRAP, and ABTS) of 4 sweetpotato varieties were measured in this study. The sweetpotato varieties were cultivated under different water regimes and also subjected to thermal processing. The results show that the 2 orange‐fleshed varieties (Resisto and W‐119) contain significant more β‐carotene, chlorogenic acid, and vitamin C than the 2 cream‐fleshed varieties (Bosbok and Ndou). Thermal processing decreased the carotenoid and vitamin C content of all the varieties but increased the chlorogenic acid content and antioxidant capacity. Drought stress appears to increase the β‐carotene, vitamin C, and chlorogenic acid contents as well as the antioxidant capacity of some of the sweetpotato varieties, especially W‐119.
Biochemical Changes during the Storage of High Hydrostatic Pressure Processed Avocado Paste
Authors: Jacobo‐Velázquez D.A. , Hernández‐Brenes C.
Published: July 2010

Abstract:  High hydrostatic pressure (HHP) processing improves the shelf life of avocado paste without a significant impact on flavor; however, scarce information is available on biochemical modifications during its extended storage period. The present study focused on the changes in oxidative enzyme activities of pressurized avocado paste (600 MPa for 3 min) during refrigerated storage (45 d at 4 °C). Aerobic plate counts (APC), lactic acid bacteria counts (LAB), pH, and instrumental color were also evaluated during storage.

 Processing with HHP caused a decrease in polyphenol oxidase (PPO) and lipoxygenase (LOX) activities, resulting in residual enzyme levels of 50.72% and 55.16%, respectively. Although instrumental color values didn't change significantly during the evaluated storage period, both enzymes (PPO and LOX) recuperated their activities at 10 to 15 d of storage, reached the original values observed in the fresh paste, and then started a declining phase until the end of the storage period. Pulp pH presented a consistent decline during the first 20 d of storage. LAB counts were very low during storage, discarding lactic acid production as responsible for the observed pH decline. Enzyme reactivation, cell disruption, and a gradual migration of intracellular components such as organic acids are herein proposed as the main mechanisms for the deterioration of HHP treated avocado paste during its refrigerated storage.

Practical Application:  At the present, HHP is the most effective commercial nonthermal technology to process avocado paste when compared to thermal and chemical alternatives. Although it has proven to be an excellent product‐technology match, little information is known on the biochemical changes that take place in the product during its refrigerated shelf life. Biochemical reactions during storage are important, since they can influence avocado paste nutritional and flavor qualities at the time of product consumption. The present study reports for the first time the re‐activation of PPO and LOX during storage of avocado paste under commercial and economically feasible processing conditions (600 MPa and 3 min). The reactivation of oxidative enzymes observed in the present study is relevant for future studies on the HHP stability of food systems in general, and it is considered an important finding for the food industry and researchers seeking to deliver products with superior nutritional and flavor characteristics.
Sensory Profile of a Model Energy Drink with Varying Levels of Functional Ingredients—Caffeine, Ginseng, and Taurine
Authors: Tamamoto Lauren C. , Schmidt Shelly J. , Lee Soo‐Yeun
Published: July 2010

Abstract:  Energy drinks have increased in popularity in recent years due to the claimed energy boost provided by functional ingredients. A multitude of functional ingredients have been utilized; however, there is limited research on their sensory effects in energy drink formulations. A 13‐member descriptive analysis panel was conducted to investigate the effects on the sensory and rheological properties of 3 common functional ingredients—caffeine, ginseng, and taurine—in a noncarbonated model energy drink solution. Combinations of these functional ingredients at 3 levels (low, medium, high) were added to create a total of 27 different solutions (3 × 3 × 3 factorial design). Analysis of variance was performed to evaluate the sensory effects of the varying concentrations of functional ingredients in solution. Principal component analysis (PCA) was performed to summarize the relationship among the attributes and solutions. In general, high levels of caffeine in solution resulted in low ratings of fruity attributes and high ratings of bitter tea and fruit bitter attributes. The high level of ginseng in solution was characterized by high ratings of bitter attributes. A horns effect was observed as the sweet, artificial lemon‐lime, pear, mango, and pineapple attributes were rated lower in intensity with increased ginseng levels. Taurine levels of up to 416 mg/100 mL had no significant effect on the sensory attribute ratings of the model energy drink solutions. These findings can be utilized to predict the changes in sensory characteristics when formulating energy drinks containing these popular functional ingredients.
Survival Analysis Applied to the Sensory Shelf‐Life Dating of High Hydrostatic Pressure Processed Avocado and Mango Pulps
Authors: Jacobo‐Velázquez D.A. , Ramos‐Parra P.A. , Hernández‐Brenes C.
Published: July 2010

Abstract:  High hydrostatic pressure (HHP) pasteurized and refrigerated avocado and mango pulps contain lower microbial counts and thus are safer and acceptable for human consumption for a longer period of time, when compared to fresh unprocessed pulps. However, during their commercial shelf life, changes in their sensory characteristics take place and eventually produce the rejection of these products by consumers. Therefore, in the present study, the use of sensory evaluation was proposed for the shelf‐life determinations of HHP‐processed avocado and mango pulps. The study focused on evaluating the feasibility of applying survival analysis methodology to the data generated by consumers in order to determine the sensory shelf lives of both HHP‐treated pulps of avocado and mango. Survival analysis proved to be an effective methodology for the estimation of the sensory shelf life of avocado and mango pulps processed with HHP, with potential application for other pressurized products.

Practical Application:  At present, HHP processing is one of the most effective alternatives for the commercial nonthermal pasteurization of fresh tropical fruits. HHP processing improves the microbial stability of the fruit pulps significantly; however, the products continue to deteriorate during their refrigerated storage mainly due to the action of residual detrimental enzymes. This article proposes the application of survival analysis methodology for the determination of the sensory shelf life of HHP‐treated avocado and mango pulps. Results demonstrated that the procedure appears to be simple and practical for the sensory shelf‐life determination of HHP‐treated foods when their main mode of failure is not caused by increases in microbiological counts that can affect human health.
Methylglyoxal Content in Drinking Coffee as a Cytotoxic Factor
Authors: Wang J. , Chang T.
Published: July 2010

Abstract:  A causal relationship between metabolic syndrome and methylglyoxal (MG) has been suggested. Consumption of coffee and other types of beverages has been known to produce MG, thus resulting in both nutritional and health concerns. The purpose of this study was to determine the ideal combination of coffee, cream, and sugar in order to minimize MG consumption. Four types of black coffee were tested: espresso, bold, mild, and a decaffeinated mild roast. Sugar and/or cream were added to the coffee samples to test whether MG levels were altered. Using high‐performance liquid chromatography, the concentration of MG in various coffee samples was determined. The espresso coffee sample was found to contain the highest level of MG at 230.9 μM. The bold coffee roast had the 2nd highest amount of MG, followed by the mild and decaffeinated varieties. Adding cream to bold coffee significantly reduced its MG level in comparison to the coffee sample without cream. On the other hand, the addition of sugar to the bold coffee did not further increase the MG level in the samples. The cellular damaging effect of MG was shown as there were decreased numbers of cultured HEK‐293 cells after 24 h of MG treatment (100 and 300 μM), which is consistent with an increased cell apoptosis induced by MG treatment (100 and 300 μM). Due to the overconsumption of exogenous MG, drinking an excess of any type of coffee poses health risks.
Two Endogenous Substrates for Polyphenoloxidase in Pericarp Tissues of Postharvest Rambutan Fruit
Authors: Sun Jian , Su Weiqiang , Peng Hongxiang , Zhu Jianhua , Xu Liangxiong , Bruñá Nuria Martí
Published: July 2010

Abstract:  The catalytic oxidation of phenolic substrates by polyphenoloxidase (PPO) causes pericarp browning of postharvest rambutan fruit. In the present study, PPO and its endogenous substrates were extracted from rambutan pericarp tissues (RPT). The substrate extracts were sequentially partitioned with ethyl acetate and n‐butanol. The analysis of total phenolic content showed that the most phenolic compounds were distributed in ethyl acetate fraction. By high‐performance liquid chromatography (HPLC), (−)‐epicatechin (EC) and proanthocyanidin A2 (PA2) were identified from this fraction. After reacting with rambutan PPO, EC turned brown rapidly within 10 min, indicating that it was a significant endogenous substrate. Although PA2 could also be oxidized by the PPO, it turned brown very slowly. In addition, because EC and PA2 were continually catalyzed into browning products by PPO during storage of the fruit at 4 and 25 °C, their contents in RPT gradually declined with the extended storage time. It was further observed that both substrate contents in rambutan fruit storing at 25 °C decreased more rapidly than that storing at 4 °C, suggesting that low temperature inhibited the catalytic oxidation of substrates so as to slow down pericarp browning.

Practical Application:  Pericarp browning is a serious problem to storage and transport of harvested rambutan fruit. A generally accepted opinion on the browning mechanism is the oxidation of phenolic substrates by PPO. Ascertaining PPO substrates will effectively help us to control enzymatic reaction by chemical methods so as to delay or even prevent pericarp browning of harvested rambutan fruit.
High lenticular tolerance to ultraviolet radiation‐B by pigmented guinea‐pig; application of a safety limit strategy for UVR‐induced cataract
Authors: Mody Jr Vino C. , Kakar Manoj , Söderberg Per G. , Löfgren Stefan
Published: July 2010

Purpose:  The purpose of this study was to determine a threshold measure, maximum tolerable dose (MTD), for avoidance of UVR‐B‐induced cataract in the pigmented guinea‐pig.

Methods:  Thirty pupil‐dilated anesthetized young female guinea‐pigs, divided into five equal groups, received between 0 and 84.9 kJ/m2 unilateral UVR‐B. Lens extraction and in vitro lens photography occurred 24 hr after exposure. Measurement of intensity of lens light scattering served as quantifying tool for the degree of cataract. Data analysis included regression, using a second order polynomial model. The applied MTD concept was based on the UVR‐B dose–response curve obtained for the pigmented guinea‐pig. A smaller number of pigmented guinea‐pigs, pigmented rats and albino rats underwent morphometric analysis of the anterior segment geometry.

Results:  All eyes exposed to UVR‐B developed cataract in the anterior subcapsular region. MTD for avoidance of UVR‐B‐induced cataract was 69.0 kJ/m2 in the pigmented guinea‐pig. Iris was considerably thicker in the guinea‐pig than in the rats. Lens blockage by the dilated iris was lowest in the guinea‐pig.

Conclusions:  Maximum tolerable dose for avoidance of UVR‐B‐induced cataract in the pigmented guinea‐pig was 69.0 kJ/m2, over 10‐fold higher than the threshold 5 kJ/m2 obtained by Pitts et al. in the pigmented rabbit. Maximum tolerable dose is an appropriate method for estimation of toxicity for UVR‐B‐induced cataract in the guinea‐pig. The pigmented guinea‐pig is significantly less sensitive to UVR‐B exposure than the pigmented rabbit and pigmented rat.
Selecting ribosomal protein genes for invertebrate phylogenetic inferences: how many genes to resolve the Mollusca?
Authors: Meyer Achim , Witek Alexander , Lieb Bernhard
Published: July 2010

1. Multi‐gene analyses are currently the gold standard in phylogenetics, despite limited taxon sampling. To facilitate broad taxon representation on an economically tolerable level, we optimize the gene selection for future PCR‐based sampling strategies.

2. Highly expressed ribosomal proteins (RP) were sampled chiefly for molluscs, the second largest metazoan phylum with largely unknown internal relationships. Thirty‐two new sequences forLepidochitona cinerea(Polyplacophora) were integrated into a data‐matrix of 79 RP genes, comprising 16 mollusc species (five classes). The resulting maximum likelihood tree was used to evaluate each single‐gene tree according to its topological fit. Genes were sorted in ascending order, successively concatenated and then evaluated.

3. The most efficient sub‐alignment consists of 18 selected genes. All analyses reveal the Mollusca as monophyletic. The phylogenetic utility of the selected and concatenated 18 ribosomal genes is comparable to results from phylogenomic analyses.

4. This optimized data set can be assembled using PCR methods and will allow expanding the taxon coverage in deep molluscan phylogeny far beyond the current sampling.
Involvement of kappa opioid receptors in the formalin-induced inhibition of analgesic tolerance to morphine via suppression of conventional protein kinase C activation
Authors: Fujita-Hamabe Wakako , Nagae Ryuji , Nawa Ayaka , Harada Shinichi , Nakamoto Kazuo , Tokuyama Shogo
Published: July 2010

Objectives

Repeated morphine treatment results in a decreased analgesic effect or the development of analgesic tolerance. However, we reported that some inflammatory chronic pain may inhibit morphine tolerance via kappa opioid receptor (KOR) activation. In this study, we further investigated the role of KOR in the inhibition of morphine tolerance in a chronic pain condition with a focus on the regulation of protein kinase C (PKC) activity.

Methods

Chronic pain was induced by formalin treatment into the dorsal part of the left hind paws of mice. The analgesic effect of morphine was measured by the tail flick method. We analysed the protein expression of PKC and its activity, and G-protein activity of mu opioid receptor (MOR) under repeated morphine treatment with or without formalin treatment.

Key findings

We found that conventional subtypes of PKC (cPKC) were up-regulated by repeated morphine treatment. Also, antisense oligonucleotide (AS-ODN) targeting cPKC completely suppressed the development of morphine tolerance. The disappearance of the repeated morphine-induced up-regulation of cPKC was completely reversed by treatment with AS-ODN targeting KOR. In addition, AS-ODN targeting KOR significantly reversed the chronic pain-induced down-regulation of PKC activity or up-regulation of MOR [35S]GTPγS binding activity after repeated morphine treatment.

Conclusions

These results indicate that KOR plays an important role in the inhibition of repeated morphine-induced cPKC up-regulation under chronic pain condition. Furthermore, this may result in the increase of MOR activity and in the inhibition of morphine tolerance under chronic pain condition.
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

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

Objectives

The 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.

Methods

The 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 findings

In 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.

Conclusions

These 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

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.
Contact Area and Static Friction of Rough Surfaces With High Plasticity Index
Authors: Li L. , Etsion I. , Talke F. E.
Published: July 2010

A model for the contact area and static friction of nominally flat rough surfaces and rough spherical surfaces is presented. The model extends previously published models, which are limited to plasticity index values below 8, to higher plasticity index values by accounting for fully plastically deformed asperities based on finite element results by Jackson and Green [2005, “A Finite Element Study of Elasto-Plastic Hemispherical Contact Against a Rigid Flat,” Trans. ASME, J. Tribol., 127, pp. 343–354]. The present model also corrects some deficiencies of the earlier models at very small plasticity index values below 0.5.
On the Prediction of Running-In Behavior in Mixed-Lubrication Line Contact
Authors: Akbarzadeh Saleh , Khonsari M. M.
Published: July 2010

A model is presented, which enables one to predict the running-in performance of the rolling/sliding surfaces subjected to mixed-lubrication line contact. The load-sharing concept was used, in which it is assumed that both the fluid film and the asperities contribute in carrying the imposed load. The plastic deformation of asperities during the running-in is taken into consideration. In the application of the load-sharing method, it is often assumed that asperity heights have a Gaussian distribution. This assumption has been relaxed in this model. Prediction results for the variation in the arithmetic average of asperity heights (Ra) during the running-in period for contact of two rollers are compared with published experimental data. Also presented are the results for the variation in wear volume, wear rate, and friction coefficient during the running-in period. The effect of surface pattern, speed, and load on the running-in behavior is studied. The steady-state wear rate for different surface patterns calculated from this model is compared with the wear rate predicted by the thermal desorption model, and the results are in agreement both in trend and magnitude. The effect of running-in on the Stribeck curve for different surface pattern is discussed.
Effect of Friction Modifiers and Antiwear Additives on the Tribological Performance of a Hydrogenated DLC Coating
Authors: Haque T. , Morina A. , Neville A.
Published: July 2010

There has been a lot of attention on the effect of lubricant additives on the friction at carbon coated surfaces. But only few papers have addressed the effect of additives on the durability of some diamondlike carbon DLC coatings. This paper presents a systematic study assessing the additive/additive and additive/surface interactions, and their influences on the durability of a low hydrogen-containing (15 at. % hydrogen) metal-free DLC coating (a-C:15H). In this study, lubricating oils containing a zinc dithiophosphate (ZDDP) antiwear additive and/or organomolybdenum friction modifiers (moly dimer and moly trimer) were used. Tribological tests were carried out in a pin-on-plate tribometer under boundary lubrication conditions. To understand the effect of additives, tribofilms formed on the wear tracks were analyzed using surface sensitive analytical techniques such as atomic force microscope, scanning electron microscopy, energy dispersive X-ray analysis, X-ray photoelectron spectroscopy, and Raman spectroscopy. Results showed that the ZDDP formed a zinc phosphate containing an ultrathin antiwear tribofilm, which offered excellent durability/wear protection to the a-C:15H coating. However, the antiwear performance of this additive was compromised when it was used with moly dimer or moly trimer. Surface analysis revealed that unlike steel surfaces, MoS2 formed on the DLC surfaces had negligible influence on friction, while the low friction DLC wear debris had strong influence on friction. Abrasive wear was found to be the dominating wear mechanism in the cases when additives showed poor wear protection on the a-C:15H coating.
Study of a Brittle Transparent Disk Under Dry RCF Conditions
Authors: Francisco Arthur , Abbouchi Houssein , Villechaise Bernard
Published: July 2010

Despite the numerous experimental works on rolling contact fatigue, dealing with two-disk contacts, some phenomena still remain badly understood. Most of the test benches, used for that purpose, impose the rotational speeds to the disks: global slipping occurs and the tangential force is measured. Even if this configuration is found in some mechanical contacts, it does not reflect situations, where only microslipping occurs with high tangential loads. For these reasons, an original bench has been designed: a specimen disk rotates a braked stainless steel disk under a normal load N. The tangential load T, due to the braked disk, is set below the global slipping value; the specimen disks are transparent for the cracks observation and brittle to avoid any plasticity complication. A typical run consists in carrying out a succession of steps of increasing the number of cycles. Each step ends with several measurements on the cracks: their counting and their width and depth measurements. The results are divided in two categories: general observations and quantitative results. The most evident observation concerns the crack shape since it propagates along an ellipse on the contact path. Furthermore, the direction of propagation inside the disk is perpendicular to the surface. Lastly, a regular primary network of well-defined cracks is observed with cracks less marked. Concerning the effects of varying loads, the higher the T, the faster the cracks initiate and propagate because of a higher tensile stress state. However, these effects can be partly overridden by N beneath the contact path. As the disk material is brittle, the crack behavior is quite similar to the one observed on metallic specimens. Even if the results are obtained in an epoxy resin, a reasonable transposition is possible. The disk transparency makes it possible to quantify the cracks growth and to propose original 3D photographs of the cracks.
Design and Evaluation of Damped Air Bearings at Head-Disk Interface
Authors: Li Jianhua , Xu Junguo , Shimizu Yuki , Honchi Masayuki , Ono Kyosuke , Kato Yukio
Published: July 2010

Perturbation and modal-analysis methods were employed to systematically study a damped slider’s dynamic characteristics, including an air-bearing slider’s stiffness, damping coefficient, frequency response to translation and wavy motion, natural frequencies, damping ratios, and modal shape-node line. We found that a design with grooves distributed on a trailing pad effectively improved the slider’s damping ratio in the second pitch mode; however, parametric studies revealed that the damping ratio was dependent on the number of grooves, their depth, location, width, length, distribution, orientation, and types. A higher damping ratio could be obtained by optimizing these parameters. The femto slider we designed with distributed damped grooves on a trailing pad had a higher damping ratio in the second pitch mode, and hence, its responses in the second pitch mode were greatly reduced, which were clarified through simulation and an experiment. Some issues on air-bearing stiffness reduction and negative damping at low frequency and contamination and lube pickup on the damped grooves were also evaluated in the experiment. No degradation could be found in the damped slider.
Closing the Scientific Loop: Bridging Correlation and Causality in the Petaflop Age
Authors: An Gary
Published: July 2010

Meeting the translational challenge presented by complex diseases and datasets requires the use of computer-augmented, high-throughput hypothesis evaluation within an evolutionary paradigm for the propagation of biomedical knowledge.
Comprehensive, Quantitative Mapping of T Cell Epitopes in Gluten in Celiac Disease
Authors: Tye-Din Jason A. , Stewart Jessica A. , Dromey James A. , Beissbarth Tim , van Heel David A. , Tatham Arthur , Henderson Kate , Mannering Stuart I. , Gianfrani Carmen , Jewell Derek P. , Hill Adrian V. S. , McCluskey James , Rossjohn Jamie , Anderson Robert P.
Published: July 2010

Three highly immunogenic peptides from gluten are primarily responsible for celiac disease, suggesting a rational immunotherapeutic approach that could replace the need for strict, lifelong dietary gluten avoidance.
The Skin(ny) on New β-Like Cells for Treating Diabetes
Authors: Bremer Andrew A.
Published: July 2010

Induced pluripotent stem cells derived from skin fibroblasts have β cell–like function and correct hyperglycemia in two mice models of diabetes.
Decoding Sudden Cardiac Death
Authors: Damani Samir
Published: July 2010

A genome association study has identified a genetic variant that is present in over half of individuals with ventricular fibrillation and confers a large increase in risk for this arrhythmia.
Don’t Worry, Be Happy
Authors: Ng Kenneth W.
Published: July 2010

The severity of osteoarthritis pain is associated with depression and mental health.
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

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
.