bluuebunny/crossref_metadata_2025 huggingface dataset:
The body and doing gender: the relations between doctors and nurses in hospital work
Authors: Davies Karen
Published: November 2003

Abstract This article attempts to show how the concept of the body – as it has been applied in feminist thought – can be utilised in trying to understand the changing and at times problematic working relations between doctors and nurses in Sweden. Three approaches are applied with respect to the body: (1) Doctors and nurses belong to two differentcollective bodieswhich embody historical constructions of masculinity and femininity – which in turn have influenced how members of each corps have seen and worked with the other and how they approach each other even in the present day. (2)Gender is inscribed on the body. It is contended that in social encounters we never interact with each other as genderless beings, although we may very well take gender for granted and its importance may possibly be most salient in initial encounters. A nurse, then, never just interacts with a doctor – it is a female doctor or a male doctor and this makes a difference. ‘Doing gender’ is accomplished in these practices. (3) There is the question ofsituatedness– where (hospital staff) bodies find themselves on the ward and in the hospital in the daily run of things. Space and place are not neutral but are linked to relations of power and gender and class. How doing dominance and doing deference are accomplished – but also changed – in hospital work is addressed.
Family stories and the use of heuristics: women from suspected hereditary breast and ovarian cancer (HBOC) families
Authors: Kenen Regina , Ardern‐Jones Audrey , Eeles Rosalind
Published: November 2003

Abstract The practice of medicine will increasingly be medicine of the family rather than the traditional physician/patient dyad, especially where a genetic condition is involved. This study explores how clients from suspected hereditary breast and ovarian cancer (HBOC) families seeking cancer genetics risk counselling are influenced by family stories and the use of heuristics (inferential shortcuts used to make sense of complicated information) in interpreting and applying genetic information they receive, and suggests ways in which genetic counsellors can integrate family context into their traditional counselling practices. We conducted an exploratory, qualitative study at a major clinical and research cancer centre in the United Kingdom from January to June 2000 which was reviewed by the hospital clinical research and ethics committees. Twenty‐one semi‐structured, in‐depth interviews were conducted using a purposive sample of women coming to the cancer genetics clinic for the first time, supplemented by five months of clinical observation at weekly clinics. In addition to many family stories based on the number and outcomes of the cancers in their families, we noted: (1) fragments of stories, (2) secret stories, (3) emerging explanations and (4) misconceptions. We did not find widespread intergenerational family myths. The women used three main heuristics in interpreting their breast/ovarian cancer risk: (1) representativeness, (2) availability and (3) illusion of control, as well as what Kahneman refers to as the Peak and End rule. Recent psychological research indicates that illusions of control may have positive affects on both physical and mental health. This may pose a future ethical issue for genetic counsellors in determining how to balance the benefit of positive illusions with the delivery of statistical probabilities of risk.
The historiography of French economic growth in the nineteenth century
Authors: Crouzet François
Published: November 2003

There has been a long‐standing debate about French nineteenth‐century economic growth. After 1945 the ‘retardation—stagnation’ thesis dominated. From the 1960s ‘revisionists’ painted a more optimistic view. Recently, ‘anti‐revisionism’ has revived gloomy ideas. New research has been primarily responsible for changes of view. National income estimates, and later cliometric studies, bolstered the revisionist argument. Work on the ‘great depression’ stimulated anti‐revisionism. Scholars have also been influenced by the economic and political state of France at the time they were writing and the debate has been somewhat politicized. The article ends by surveying the ‘moderate revisionism’ which now prevails.
Modulation of L‐type voltage‐gated calcium channels by recombinant prion protein
Authors: Korte Stefan , Vassallo Neville , Kramer Michael L. , Kretzschmar Hans A. , Herms Jochen
Published: November 2003

The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies. Here we analysed in detail the effect of recombinant PrPC and N‐ and C‐terminal fragments of PrPC on the whole‐cell current amplitude through voltage‐gated calcium channels (VGCCs) of cultured wild‐type cerebellar granule cells. With the application of full‐length recombinant PrPC (50–500 nm), a highly significant reduction of the whole‐cell current amplitude was observed in a dose‐dependent manner. Amplitude reduction was abolished when cells were pre‐incubated with nifedipine, a specific blocker of voltage‐gated L‐type calcium channels. N‐terminal PrP fragments also led to a dose‐dependent reduction of the maximal current amplitude, whereas a C‐terminal fragment did not affect the current amplitude. These data demonstrate that nanomolar concentrations of PrPC modulate L‐type VGCCs in mouse cerebellar granule cells, an effect that is dependent upon the copper‐binding amino‐terminal domain of PrPC.
Quality assessment of frying oils and fats from 63 restaurants in Athens, Greece
Authors: Andrikopoulos Nikolaos K. , Boskou George , Dedoussis George V. Z. , Chiou Antonia , Tzamtzis Vassilios A. , Papathanasiou Assimina
Published: November 2003

Samples of used frying oils and fats from 63 restaurants and fast‐food outlets, from the inner and outer suburbs of Athens, were randomly collected during a 1‐month period. Sampling was performed after deep‐frying or pan‐frying of several foods, of both vegetable and animal origin, in different frying oils or fats (sunflower oil, cottonseed oil, corn oil, palm oil, palm kernel oil, soybean oil, vegetable shortening oil, vegetable cooking oils and fats). Sunflower oil was the most widely used frying medium and deep‐fried potatoes (French fries) were the most common fried food. Sixteen samples (approximately 25%) were found with polymerized triglycerides (PTG) over the 12% limit of rejection, while 11 of them (approximately 17%) with total polar materials (TPM) over the 25% limit of rejection. From the above ‘over‐limit’ samples, only one was from the pan‐frying process. The higher TPM and PTG mean values were found in low‐unsaturated vegetable frying oils and cooking fats, with the highest values observed when food of animal origin was fried. Vitamin E content of the fried samples examined was lower than that of the respective fresh samples (28% mean loss), but in most cases in relatively high levels.
A longitudinal study of vergence adaptation in incipient presbyopia
Authors: Baker Fiona J. , Gilmartin Bernard
Published: November 2003

Background:  To investigate vergence adaptation during the incipient phase of presbyopia, when the amplitude of accommodation approaches the level where the first reading addition is required. The study aimed to assess the ability of the vergence system to counteract changes in the component contributions to the overall vergence response with the decline in the amplitude of accommodation in presbyopia, although previous reports on the nature of changes in accommodative, tonic and proximal vergence are equivocal.

Methods:  Using a ‘flashed’ Maddox rod technique, an assessment of vergence adaptation to 6Δ base‐out and 6Δ base‐in prism was made for 28 subjects (aged 35–45 years at the commencement of the study). The measurements were taken four times over a 2‐year period.

Results:  Using a repeated measures analysis of variance, the results show that with the decline in amplitude of accommodation, there is a statistically significant reduction in the magnitude of vergence adaptation to both base‐out (p < 0.05) and base‐in prism (p < 0.01).

Conclusions:  This study shows that with ageing, there is a decrease in the ability of the slow vergence mechanism to overcome a change in fusional vergence demand and would suggest that either the fast component of fusional vergence must cope with any change in fusional vergence demand or that the sum of the accommodative, tonic and proximal vergence responses are virtually stable with age.
The assessment of automated measures of hydrogel contact lens refractive index
Authors: Nichols Jason J. , Berntsen David A.
Published: November 2003

Purpose:  To investigate within‐ and between‐operator reliability and validity of refractive index measures of hydrogel lenses.

Methods:  Twenty‐three lenses of various nominal water contents were examined by two operators on two occasions separated by 1 h. An automated refractometer (CLR 12‐70, Index Instruments, Cambridge, UK) was used for refractive index measures. Lenses were presented in a random order to each operator by a third party, and operators were masked to any potential lens identifiers. Intraclass correlation coefficients (ICC), 95% limits of agreement (LoA), and paired t‐tests were used to characterize the within‐ and between‐operator reliability and validity of lens refractive index measures.

Results:  The mean (±S.D.) difference between sessions was 0.0001 ± 0.0011, which did not significantly differ from zero (p = 0.64). Within‐operator reliability was excellent (ICC = 0.9990, 95% LoA = −0.0021 to 0.0024). The mean (±S.D.) difference between‐operators was 0.0002 ± 0.0010, which was not significantly different from zero (p = 0.54). Between‐operator reliability was also excellent (ICC = 0.9984, 95% LoA = −0.0026 to 0.0029). The mean difference between the nominally reported refractive index and our refractive index measures was −0.0009 ± 0.082, which did not differ statistically from zero (p = 0.52); the 95% LoA for this difference was −0.0152 to 0.0169.

Conclusion:  There is good reliability within‐ and between‐operators in measuring the refractive index of hydrogel lenses using the CLR 12‐70 automated refractometer.
Effect of gestational nicotine treatment on newborn rat retina: a histopathological and morphometric analysis
Authors: Evereklioglu Cem , Özkiriş Abdullah , Alaşehirli Belgin , Sari Ibrahim , Güldür Emin , Cengiz Beyhan , Kontaş Olgun
Published: November 2003

Background:  Smoking is a significant risk factor in several debilitating and fatal diseases. It has been implicated in bilateral tobacco‐toxic and Leber's hereditary optic neuropathies. Although it has been demonstrated that smoking has a cumulative effect on retinal and optic nerve functions and causes diffuse and localised retinal sensitivity decrease in healthy chronic heavy smokers, the affected retinal layer has not been identified and there is no experimental study investigating the effect of nicotine exposure during gestation on the newborn rat retina.

Purpose:  This experimental investigation evaluated histologically the influence in vivo of maternal nicotine treatment during pregnancy on the newborn rat retina. Different dosages of the test compound simulated the range of low, moderate, and heavy smokers in humans.

Methods:  Experimentally naive, adult female Wistar‐albino rats weighing 200–250 g were mated with adult male rats over 2 days for copulation in the proportion of two females for every male animal. After confirming pregnancy with vaginal smear method, 40 gravid rats (dams) were then randomly assigned into four equal groups (three experimental and one control; n = 10 in each). On day 9 of gestation, groups 1, 2, and 3 experimental dams were treated with intraperitoneal (i.p.) (–)‐nicotine tartrate at doses of 0.5, 1, and 2 mg kg body weight−1 day−1, respectively during pregnancy from gestational day 9–21. Group 4 control dams were given i.p. saline solution daily for the same period. After normal delivery, the newborn litters were sacrificed at postnatal day 1 or day 30. The eyes were enucleated for histopathologic and morphometric analysis of the retinas. Nicotine‐induced neuronal changes were measured by morphometric analyses on cell counts of ganglion cell layer (linear cell density in number per unit length of retina) and thickness of the various retinal layers.

Results:  The litters in control group 4, and experimental groups 1 and 2 had normal retinal findings. On the other hand, morphometric analysis of retinal sections in experimental group 3 eyes demonstrated a 20.7% decrease in the number of surviving ganglion cells (40.7 ± 2.0) compared with controls (51.3 ± 1.1; p < 0.001). The thickness of whole retina (126.6 ± 5.4 μm) was also reduced by 13.5% compared with controls (146.3 ± 4.5 μm; p = 0.007). The main site of retinal atrophy was the inner plexiform layer (30.1 ± 1.6 μm vs 43.5 ± 1.3 μm; p < 0.001) with almost no change in the other retinal layers.

Conclusions:  Gestational nicotine treatment induces marked changes in the organisation of the developing retina in newborn rats histopathologically. Quantitative morphometric analysis clearly demonstrated that the two most affected structures were the retinal ganglion cells and the inner plexiform layer, both of which are supplied by central retinal artery.
Learning effect, normal range, and test–retest variability of Frequency Doubling Perimetry as a function of age, perimetric experience, and the presence or absence of glaucoma
Authors: Heeg Govert P. , Ponsioen Theodorus L. , Jansonius Nomdo M.
Published: November 2003

The learning effect for several different Frequency Doubling Perimetry parameters was studied in full threshold mode in a large group of patients (n = 342) of various ages, with and without perimetric experience, and with and without glaucoma. A significant learning effect was only found for the mean deviation (MD) in aged normals without perimetric experience. The median of MD increased for both OD (from +0.2 to +1.0 dB) and for OS (from +0.5 to +1.3 dB). The effect disappeared largely during a third visit (median OD +1.2 dB, OS +1.3 dB). The normal range and the test–retest variability were measured in the same dataset. The learning effect for MD (1 dB or less) appeared to be small as compared with both the normal range (about 12 dB) and the test–retest variability (about 3 dB).
Effects of Growth Hormone Overexpression and Growth Hormone Resistance on Neuroendocrine and Reproductive Functions in Transgenic and Knock‐Out Mice2
Authors: Bartke Andrzej , Chandrashekar Varadaraj , Turyn Daniel , Steger Richard W. , Debeljuk Luciano , Winters Todd A. , Mattison Julie A. , Danilovich Natalia A. , Croson William , Wernsing Danyel R. , Kopchick John J.
Published: November 2003

Transgenic mice overexpressing growth hormone (GH) exhibit alterations in the function of the hypothalamic‐pituitary‐gonadal (HPG) axis and the H‐P‐adrenal axis. Alterations in the turnover of hypothalamic neurotransmitters, in plasma hormone levels, and in regulation of their release are associated with reproductive deficits, particularly in females. Results reported after publication of our minireview on this subject provided evidence that GH‐transgenic mice have increased binding of GH to GH binding proteins in plasma, are hyperinsulinemic and insulin resistant, and have major alterations in energy budgets with increased allocation to growth. Reduced life span and fertility of these animals may be related to insufficient allocation of energy to reproduction and maintenance. Growth hormone resistance induced by transgenic expression of an antagonistic bGH analog or by targeted disruption (knock‐out, KO) of the GH receptor (GH‐R) gene leads to dramatic suppression of plasma levels of insulin‐like growth factor‐1 (IGF‐1), and dwarf phenotype due to reduced growth and increased adiposity. In both models of GH resistance, there are marked reproductive deficits in females, decline of breeding performance of males, and alterations in the function of the HPG axis. In GH‐R‐KO females, puberty is delayed, and litter size is reduced. Fetal weights are reduced whereas placental weights are increased, and the weight of newborn pups is reduced despite an increase in the length of gestation. In GH‐R‐KO males, copulatory behavior and fertility are reduced, plasma PRL is elevated, and responses to lutenizing hormone releasing hormone (LHRH) in vivo and to LH in vitro are suppressed. However, reproductive deficits in GH‐R‐KO mice are very mild when compared to those described previously in IGF‐KO animals. Apparently, the amounts of IGF‐1 that may be produced locally in the absence of GH stimulation are sufficient for sexual maturation and fertility in both sexes, whereas quantitative deficits in reproductive function reflect absence of GH‐dependent IGF‐1 production and other consequences of eliminating GH signaling. The reproduction phenotype of the GH‐R‐KO mice is also mild when compared to dwarf mice that lack GH, prolactin (PRL), and thyroid stimulating hormone (TSH). This is presumably related to the presence of redundant mechanisms in the stimulatory control of the gonads by the pituitary and the ability of animals capable of producing PRL and TSH to compensate partially for the absence of GH signaling.
Role of Integrins in Cancer: Survey of Expression Patterns
Authors: Mizejewski Gerald J.
Published: November 2003

Tumor cells are characterized by uncontrolled growth, invasion to surrounding tissues, and metastatic spread to distant sites. Mortality from cancer is often due to metastasis since surgical removal of tumors can enhance and prolong survival. The integrins constitute a family of transmembrane receptor proteins composed of heterodimeric complexes of noncovalently linked α and β chains. Integrins function in cell‐to‐cell and cell‐to‐extracellular matrix (ECM) adhesive interactions and transduce signals from the ECM to the cell interior and vice versa. Hence, the integrins mediate the ECM influence on cell growth and differentiation. Since these properties implicate integrin involvement in cell migration, invasion, intra‐ and extra‐vasation, and platelet interaction, a role for integrins in tumor growth and metastasis is obvious. These findings are underpinned by observations that the integrins are linked to the actin cytoskeleton involving talin, vinculin, and α‐actinin as intermediaries. Such cytoskeletal changes can be manifested by rounded cell morphology, which is often coincident with tumor transformation via decreased or increased integrin expression patterns. For the various types of cancers, different changes in integrin expression are further associated with tumor growth and metastasis. Tumor progression leading to metastasis appears to involve equipping cancer cells with the appropriate adhesive (integrin) phenotype for interaction with the ECM. Therapies directed at influencing integrin cell expression and function are presently being explored for inhibition of tumor growth, metastasis, and angiogenesis. Such therapeutic strategies include anti‐integrin monoclonal antibodies, peptidic inhibitors (cyclic and linear), calcium‐binding protein antagonists, proline analogs, apoptosis promotors, and antisense oligonucleotides. Moreover, platelet aggregation induced by tumor cells, which facilitates metastatic spread, can be inhibited by the disintegrins, a family of viper venom–like peptides. Therefore, adhesion molecules from the integrin family and components of angiogenesis might be useful as tumor progression markers for prognostic and for diagnostic purposes. Development of integrin cell expression profiles for individual tumors may have further potential in identifying a cell surface signature for a specific tumor type and/or stage. Thus, recent advances in elucidating the structure, function, ECM binding, and signaling pathways of the integrins have led to new and exciting modalities for cancer therapeutics and diagnoses.
Immortalized Dopamine Neurons: A Model to Study Neurotoxicity and Neuroprotection
Authors: Clarkson Edward D. , Edwards‐Prasad Judith , Freed Curt R. , Prasad Kedar N.
Published: November 2003

6‐Hydroxydopamine (6‐OHDA) causes selective degeneration of dopaminergic neurons in the rat brain and has been used to produce an animal model of Parkinsonism. Recently, a clonal line of immortalized dopamine (DA) neurons (1RB3AN27), which expresses varying levels of tyrosine hydroxylase, dopamine transporter, neuron specific enolase, and nestin, was established. These DA neurons reduce behavioral deficits in 6‐OHDA–lesioned rats. The relative sensitivity of fetal and adult neurons to potential neurotoxins is not well defined. The availability of immortalized DA neurons provides a unique opportunity to compare the relative neurotoxicity of 6‐OHDA in differentiated and undifferentiated DA neurons in vitro and identify neuroprotective agents. Our results showed that 6‐OHDA treatment for 24 hr decreased the viability of undifferentiated and differentiated immortalized DA neurons in vitro, as determined by the MTT assay, and increased the rate of apoptosis in differentiated DA neurons. The differentiated DA neurons (IC50 = 33 μM) were about 2‐fold more sensitive to 6‐OHDA than undifferentiated DA neurons (IC50 = 75 μM) in cell culture. Similarly, the differentiated DA neurons were more sensitive to another neurotoxin, 1‐methyl‐4‐phenylpyridinium (MPP+), which is commonly used to induce Parkinsonism in animal models, than were the undifferentiated DA neurons in culture. Among growth factors tested, only glial cell line–derived neurotrophic factor (GDNF) partially protected differentiated DA neurons against 6‐OHDA–induced toxicity. These results suggest that undifferentiated and differentiated immortalized DA neurons can be a useful experimental model to study relative sensitivity to neurotoxins and neuroprotective agents that could have relevance to fetal and adult neurons.
Cellular Glutathione Peroxidase Protects Mice Against Lethal Oxidative Stress Induced by Various Doses of Diquat
Authors: Fu Yangxin , Cheng Wen‐Hsing , Ross Deborah A. , Lei Xin gen
Published: November 2003

This study was to determine if cellular glutathione peroxidase (GPX1) protects against acute oxidative stress induced by diquat. Lethality and hepatic biochemical indicators in GPX1 knockout mice [GPX1(–/–)] were compared with those of wild‐type mice (WT) after an intraperitoneal injection of diquat at 6, 12, 24, or 48 mg/kg of body weight. Although the WT survived all the doses, the GPX1(–/–) survived only 6 mg diquat/kg and were killed by 12, 24, and 48 mg diquat/kg at 52, 4.4 and 3.9 hr, respectively. Compared with those of surviving mice that were sacrificed on Day 7, the dead GPX1(–/–) had diquat dose‐dependent increases (P < 0.05) in plasma alanine aminotransferase (ALT) activities. The GPX1(–/–) also had higher (P < 0.05) liver carbonyl contents than those of the WT, but the differences were irrespective of diquat doses. Whereas hepatic total GPX and phospholipid hydroperoxide glutathione peroxidase activities or hepatic GPX1 protein was not significantly affected by the diquat treatment, liver thioredoxin reductase and catalase activities were lower (P < 0.05) in the GPX1(–/–) injected with 12 mg diquat/kg than those of other groups. In conclusion, normal GPX1 expression is necessary to protect mice against the lethality, hepatic protein oxidation, and elevation of plasma ALT activity induced by 12–48 mg diquat/kg.
Antioxidants, NFκB Activation, and Diabetogenesis
Authors: Ho Emily , Bray Tammy M.
Published: November 2003

Although many risk factors can trigger the development of insulin‐dependent diabetes (IDDM), it is likely that reactive oxygen species (ROS) play a central role in β‐cell death and disease progression. This review will focus on the role of antioxidant defense systems in the susceptibility to IDDM and on ROS as cellular messengers that regulate the expression of genes leading to β‐cell death. Accumulating evidence indicates that increased antioxidant defense systems reduce the susceptibility to IDDM in animal models or in human study. It is suggested that pancreas‐specific ROS productions play a critical role in signaling the cellular autoimmune/inflammatory response by activating the transcription factor, NFκB. Various diabetogenic factors may lead to an increase in ROS production, which activates the redox‐sensitive NFκB. This may be the initial event for the expression of cytokines and chemotactic agents involved in the autoimmune/inflammatory response. It is believed that this cascade results in a cyclic amplification of ROS and eventually leads to apoptosis and/or necrosis of β cells. The specificity of antioxidants to inhibit NFκB activation and the hyperglycemic response emphasizes the importance of selectivity in antioxidant therapy. Research in this area will contribute significantly to our understanding of the cellular and mechanistic role of ROS in the etiology of IDDM and will lead to the development of better prevention strategies.
Antioxidants, Oxidative Stress, and Degenerative Neurological Disorders
Authors: Floyd Robert A.
Published: November 2003

Recently, clinical trials of several neurodegenerative diseases have increasingly targeted the evaluation of the effectiveness of various antioxidants. The results so far are encouraging but variable and thus confusing. Rationale for the possible clinical effectiveness of antioxidants in several degenerative conditions has arisen out of the many years of basic science generally showing that reactive oxygen species (ROS) and oxidative damage are important factors in the processes involved. Aging is one of the most significant risk factors for degenerative neurological disorders. Basic science efforts in our laboratory have centered on exploring the role of ROS and oxidative stress in neurodegenerative processes. The present review brings together some of the basic concepts we have learned by following this approach for the last 20 years and specifically the results we have obtained by following up on our serendipitous findings that a nitrone‐based free radical trap, α‐phenyl‐tert‐butylnitrone (PBN), has neuroprotective activity in several experimental neurodegenerative models. The mechanistic basis of the neuroprotective activity of PBN does not appear to rely on its general free radical trapping or antioxidant activity per se, but its activity in mediating the suppression of genes induced by pro‐inflammatory cytokines and other mediators associated with enhanced neuroinflammatory processes. Neuroinflammatory processes, induced in part by pro‐inflammatory cytokines, yield enhanced ROS and reactive nitric oxide species (RNS) as well as other unknown components that have neurotoxic properties. Neurotoxic amounts of RNS are formed by the activity of inducible nitric oxide synthase (iNOS). The demonstration of enhanced 3‐nitro‐tyrosine formation in affected regions of the Alzheimer's brain, in comparison to age‐matched controls, reinforces the importance of neuroinflammatory processes. iNOS induction involves activation by phosphorylation of the MAP kinase p38 and can be induced in cultured astrocytes by IL‐1β or H2O2. The action of PBN and N‐acetyl cysteine to suppress the activation of p38 was demonstrated in cultured astrocytes. The demonstration of activated p38 in neurons surrounding amyloid plaques in affected regions of the Alzheimer's brain attest to enhanced signal transduction processes in this neurodegenerative condition. The major themes of ROS and RNS formation associated with neuroinflammation processes and the suppression of these processes by antioxidants and PBN continue to yield promising leads for new therapies. Outcomes of clinical trials on antioxidants will become less confusing as more knowledge is amassed on the basic processes involved.
Antioxidants and Oxidative Stress in Exercise
Authors: Ji Li Li
Published: November 2003

Strenuous exercise increases oxygen consumption and causes disturbance of intracellular pro‐oxidant–antioxidant homeostasis. The mitochondrial electron transport chain, polymorphoneutrophil, and xanthine oxidase have been identified as major sources of intracellular free radical generation during exercise. Reactive oxygen species pose a serious threat to the cellular antioxidant defense system, such as diminished reserve of antioxidant vitamins and glutathione, and increased tissue susceptibility to oxidative damage. However, enzymatic and nonenzymatic antioxidants have demonstrated great adaptation to acute and chronic exercise. The delicate balance between pro‐oxidants and antioxidants suggests that supplementation of antioxidants may be desirable for physically active individuals under certain physiological conditions by providing a larger protective margin.
Aging: Is Oxidative Stress a Marker or Is It Causal?
Authors: Fukagawa Naomi K.
Published: November 2003

Rapid developments in free radical biology and molecular technology have permitted exploration of the free radical theory of aging. Oxidative stress has also been implicated in the pathogenesis of a number of diseases. Studies have found evidence of oxidative damage to macromolecules (DNA, lipids, protein), and data in transgenic Drosophila melanogaster support the hypothesis that oxidative injury might directly cause the aging process. Additional links between oxidative stress and aging focus on mitochondria, leading to development of the mitochondrial theory of aging. However, despite the number of studies describing the association of markers of oxidative damage with advancing age, few, if any definitively link oxidative injury to altered energy production or cellular function. Although a causal role for oxidative stress in the aging process has not been clearly established, this does not preclude attempts to reduce oxidative injury as a means to reduce morbidity and perhaps increase the healthy, useful life span of an individual. This review highlights studies demonstrating enhanced oxidative stress with advancing age and stresses the importance of the balance between oxidants as mediators of disease and important components of signal transduction pathways.
Heme Oxygenase: Who Needs It?
Authors: Galbraith Richard
Published: November 2003

Heme is a molecule that is synthesized by the sequential actions of eight enzymes and is ubiquitous throughout nature. For many years it has been known that heme is also catabolized to yield biliverdin (which is subsequently reduced to bilirubin), one atom of iron, and one molecule of carbon monoxide. There has been a recent explosion of interest in this degradative process that is catalyzed by the rate‐limiting enzyme, heme oxygenase. In particular, there has been a special interest in the potential physiological and pathological roles that may be played by these breakdown products. This minireview will examine some of these potential functional correlates, with special emphasis on potential oxidant and antioxidant effects of the bilirubin, carbon monoxide, and iron that result from the activity of heme oxygenase.
Ethanol's Effect on Rat Pituitary Adrenal Axis is Prevented by Purine Metabolic Pathway Inhibitors
Authors: Szabó Jozsef , Bruckner Geza , Medveczky Istvan , Kósa Emma , Balogh Adam
Published: November 2003

This study investigated the in vitro dose effects of ethanol (EtOH), adenosine (ADO), and urate (URA) on the basal and CRF stimulated ACTH production of pituitary tissue culture (PTC). Furthermore, the effects of low (LE = 0.5 g/kg bodyweight) and high (HE = 2.5 g/kg bodyweight) concentrations of EtOH were tested in rats on plasma ACTH and corticosterone concentration (PCC), with or without the following ADO metabolic pathway inhibitors: 6‐mercaptopurine (6MP) (salvage pathway) and purpurogallin (PPG) (xanthine dehydrogenase).

EtOH at 0–50 mM does not increase the in vitro basal or CRF (10−7M) stimulated ACTH secretion in PTC; in fact doses up to 20 mM tended to be inhibitory. ADO significantly increased only basal ACTH secretion whereas URA increased both basal and CRF‐stimulated ACTH secretion.

Pretreatment with PPG or 6MP + PPG significantly increased both in vivo ACTH and PCC over control values in rats. HE versus LE significantly increased ACTH and PCC in the control (H2O) and 6MP pretreated groups whereas in the PPG pretreated animals, only ACTH was increased significantly by HE. However, combined pretreatment with 6MP + PPG prevented the effect of HE on ACTH and PCC. The current experiment suggests that purine metabolism is involved in ethanol's effect on the hypothalamic‐pituitary‐adrenal axis.
Membrane‐Initiated Steroid Actions and theProteins that Mediate Them
Authors: Watson Cheryl S. , Gametchu Bahiru
Published: November 2003

Membrane‐initiated or nongenomic activities of steroids contribute to the effects of steroids on a wide variety of target organs, including those with low receptor numbers, recently discovered due to the increased sensitivity of new measurement techniques. Membrane‐initiated responses are the cell's rapid and first response to steroids. The responses that emanate from the membrane can have direct functional consequences, such as secretion of other peptide hormones or rapid behavioral changes. Other rapid responses are prerequisites for subsequent genomic responses. The wide variety of signal transduction schemes employed by various tissues and hormones are summarized and discussed in terms of the identity of proteins that mediate these responses. Probable mixed binding systems for steroids in plasma membranes are compared to similar multiple hormone–binding protein systems in extracellular fluids and inside cells. These issues are related to steroid‐dependent tumor growth, developmental and therapeutic apoptosis, and the actions of endocrine disrupters. The integration of membrane‐initiated effects with genomic mechanisms results in the complete cellular response to steroids.
Survival and Lung Pathology of Mouse Models of Hermansky‐ Pudlak Syndrome and Chediak‐Higashi Syndrome
Authors: MCGARRY MICHAEL P. , REDDINGTON MADONNA , NOVAK EDWARD K. , SWANK RICHARD T.
Published: November 2003

Hermansky‐Pudlak Syndrome (HPS), a recessively inherited disease in humans, affects the biosynthesis/processing of the related intracellular organelles: lysosomes, melanosomes, and platelet dense granules. The disease is multigenic in both humans and mice where 14 separate genes have been demonstrated to be causative. Patients often die prematurely with severe lung abnormalities. Patients with the related Chediak‐Higashi Syndrome (CHS) likewise have significantly reduced life spans. Long‐term survival and lung histomorphology were analyzed in a pilot experiment involving several genetically defined singly and doubly mutant mouse HPS mutants and the beige CHS mutant to determine whether these parameters are altered in the mouse models. The mutants differed widely in both longevity and lung architecture. Mice doubly homozygous for the pale ear and ruby eye or for the muted and pearl genes had the shortest life spans with none surviving the two‐year experimental duration. Life spans were similarly severely reduced in the beige and gunmetal mutants. Intermediate life spans were apparent in the pearl, pallid, and cocoa mutants whereas minimal effects were noted in ruby eye, muted, light ear, and cocoa mutants. Enlarged air spaces were noted in histologic sections of lungs of several of the mutants. For the most part, the severity of lung abnormalities was inversely proportional to the long‐term survival of these various mutants, suggesting that lung pathology may contribute to mortality, as has been suggested for human HPS patients.
Antitumor Effect of Vitamin D‐Binding Protein‐Derived Macrophage Activating Factor on Ehrlich Ascites Tumor‐Bearing Mice
Authors: Koga Yoshihiko , Naraparaju Venkateswara R. , Yamamoto Nobuto
Published: November 2003

Cancerous cells secrete α‐N‐acetylgalactosaminidase (NaGalase) into the blood stream, resulting in deglycosylation of serum vitamin D3‐binding protein (known as Gc protein), which is a precursor for macrophage activating factor (MAF). Incubation of Gc protein with immobilized β‐galactosidase and sialidase generates the most potent macrophage activating factor (designated GcMAF). Administration of GcMAF to cancer‐bearing hosts can bypass the inactivated MAF precursor and act directly on macrophages for efficient activation. Therapeutic effects of GcMAF on Ehrlich ascites tumor‐bearing mice were assessed by survival time and serum NaGalase activity, because serum NaGalase activity was proportional to tumor burden. A single administration of GcMAF (100 pg/mouse) to eight mice on the same day after transplantation of the tumor (5 × 105 cells) showed a mean survival time of 21 ± 3 days for seven mice, with one mouse surviving more than 60 days, whereas tumor‐bearing controls had a mean survival time of 13 ± 2 days. Six of the eight mice that received two GcMAF administrations, at Day 0 and Day 4 after transplantation, survived up to 31 ± 4 days whereas, the remaining two mice survived for more than 60 days. Further, six of the eight mice that received three GcMAF administrations with 4‐day intervals showed an extended survival of at least 60 days, and serum NaGalase levels were as low as those of control mice throughout the survival period. The cure with subthreshold GcMAF‐treatments (administered once or twice) of tumor‐bearing mice appeared to be a consequence of sustained macrophage activation by inflammation resulting from the macrophage‐mediated tumoricidal process. Therefore, a protracted macrophage activation induced by a few administrations of minute amounts of GcMAF eradicated the murine ascites tumor.
Tea Flavonols in Cardiovascular Disease and Cancer Epidemiology
Authors: Hollman Peter C. H. , Feskens Edith J. M. , Katan Martijn B.
Published: November 2003

Tea is an important dietary source of flavonols in countries such as the Netherlands, the United Kingdom and Japan. Flavonols may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumor development in animal studies. The association between flavonol intake and cancer risk was investigated in three prospective studies (Zutphen Elderly Study in the Netherlands, a Finnish cohort, and the Netherlands Cohort Study). Only one study (Finnish cohort) showed an inverse association with cancer mortality. The intake of flavonols with subsequent cardiovascular disease was studied in six prospective epidemiological studies. In some populations (Seven Countries Study, Zutphen Elderly Study, a Finnish cohort) a clear protective effect was observed. In a large US cohort, a protective effect was only found in a subgroup with previous history of coronary heart disease, whereas in Welsh men, flavonol intake, mainly from tea, was associated with an increased risk of coronary heart disease. These conflicting results may be due to confounding by coronary risk factors associated with tea consumption. The question of whether flavonols protect against cardiovascular disease remains still open; a protective effect of flavonols against cancer is less likely.
Plasma and Lipoprotein Levels of Tea Catechins Following Repeated Tea Consumption
Authors: Van Het Hof Karin H. , Wiseman Sheila A. , Yang Chung S. , Tijburg Lilian B. M.
Published: November 2003

Epidemiological studies suggest that antioxidant flavonoids in tea may reduce the risk of cardiovascular disease, possibly via protection of low‐density lipoproteins (LDL) against oxidation. However, the extent of absorption of tea flavonoids and their accumulation in LDL during regular consumption of tea is not clear. Therefore we investigated plasma and lipoprotein levels of catechins during tea consumption and the impact on LDL oxidizability ex vivo. Eighteen healthy adults consumed, in an incomplete balanced cross‐over design, green tea, black tea, black tea with milk or water, one cup every 2 hr (eight cups/day) for three days. Blood samples were obtained in the mornings and evenings of each day. Plasma total catechin concentration was determined in all blood samples, and the distribution of catechins among lipoproteins was determined at the end of the third day (t = 60 hr). The resistance of LDL to copper‐induced oxidation ex vivo was assessed before tea consumption and at t = 60 hr. Repeated tea consumption during the day rapidly increased plasma total catechin levels whereas they declined overnight when no tea was consumed. There was a gradual increase in plasma levels in the mornings (respectively, 0.08 μM vs. 0.20 μM on first and last day of black tea consumption) and evenings (respectively, 0.29 μM vs. 0.34 μM on first and last day of black tea consumption). Green tea catechins were mainly found in the protein‐rich fraction of plasma (60%) and in high‐density lipoproteins (23%). Although present in LDL, the concentration of catechins in LDL was not sufficient to enhance the resistance of LDL to oxidation ex vivo. Addition of milk to black tea did not affect any of the parameters measured. In conclusion, the present study shows that catechin levels in blood rapidly increase upon repeated tea consumption. The accumulation of catechins in LDL particles is not sufficient to improve the intrinsic resistance of LDL to oxidation ex vivo.
The Effect of Tea Consumption on Oxidative Stress in Smokers and Nonsmokers
Authors: Klaunig James E. , Xu Yong , Han Chi , Kamendulis Lisa M. , Chen Junshi , Heiser Carla , Gordon Michael S. , Mohler III Emile R.
Published: November 2003

While the anticarcinogenic effects of tea in animal models have been reported by several groups, human epidemiological studies examining tea consumption and cancer prevention have produced equivocal results. The beneficial properties of tea to human health may be related to the antioxidant properties of tea components. However, little evidence has been provided that tea consumption can either increase the antioxidant capacity or decrease oxidative stress in humans. In the present study, the effects of tea treatment (green tea) on biomarkers of oxidative stress were investigated in smokers and nonsmokers in two volunteer study groups (one in China and the other in United States). Green tea consumption in both study groups decreased oxidative DNA damage (8‐OHdG in white blood cells and urine), lipid peroxidation (MDA in urine), and free radical generation (2, 3‐DHBA in urine) in smokers. Nonsmokers (US study group) also exhibited a decrease in overall oxidative stress.
Antioxidant Capacity and Polyphenolic Components of Teas: Implications for Altering In Vivo Antioxidant Status1
Authors: Prior Ronald L. , Cao Guohua
Published: November 2003

The Oxygen Radical Absorbance Capacity (ORAC) assay was used to determine the total antioxidant capacity of tea. Green and black teas (n = 18) had a mean antioxidant capacity of 761.1 ± 85.3 μmol Trolox Equivalents (TE) per g dry matter. However, their antioxidant capacity varied from 235 μmol to over 1526 μmol Trolox equivalents (TE)/g dry matter, and total phenolics ranged from 32 to 147 mg/g in different commercial teas. One tea phenolics extract had an antioxidant capacity of 4796 μmol TE/g dry matter and 625 mg total phenolics/g. On a dry matter basis, an antioxidant capacity of 761 μmol TE/g is considerably higher than any of the other fruits and vegetables measured in our laboratory. However, since dry tea is not consumed directly, brewing conditions may influence the final antioxidant capacity in the tea as consumed. We tested both green and black teas by placing one tea bag (1.95 g) in 150 ml (5 oz.) of boiling water. In the first brewed cup, approximately 84% of the total antioxidant activity was solubilized within the first 5 min of brewing. An additional 13% of the antioxidant activity was extracted into the second glass of 150 ml with an additional 5 min of brewing. At the dilutions obtained after the first brewing, the tea as consumed would contain approximately 8.31 μmol TE per ml. This total antioxidant capacity compares to other drinks from fruits and vegetables that had antioxidant capacity values ranging from 1.6 to 15 μmol TE/ml. At these antioxidant levels, consumption of 150 ml of tea could make a significant contribution to the total daily antioxidant capacity intake. (−)‐Epicatechin and (+)‐catechin, two components from tea, had an antioxidant capacity of 2.36 and 2.49 μmol/μmol or 8.13 and 8.58 μmol/mg, respectively. In 16 tea samples we observed a mean of 10.0 ± 0.6 μmol TE/mg total phenolics. Tea can be an important source of what has been referred to as “non‐nutrient” antioxidant phytochemicals. However, with the variation that exists in antioxidant capacity with various tea preparations, measures of antioxidant capacity intake are critical to the study of intake and health outcomes and/or biomarkers of health outcomes.
Tea and Health: The Underlying Mechanisms
Authors: Weisburger John H.
Published: November 2003

Detailed multidisciplinary research on the effect of tea and the associated tea polyphenols has led to major advances on the underlying mechanisms. In most studies, green and black tea have similar effects, four of which are reviewed in this paper. 1) Tea polyphenols are powerful antioxidants that may play a role in lowering the oxidation of LDL‐cholesterol, with a consequent decreased risk of heart disease, and also diminish the formation of oxidized metabolites of DNA, with an associated lower risk of specific types of cancer. 2) Tea and tea polyphenols selectively induce Phase I and Phase II metabolic enzymes that increase the formation and excretion of detoxified metabolites of carcinogens. 3) Tea lowers the rate of cell replication and thus the growth and development of neoplasms. 4) Tea modifies the intestinal microflora, reducing undesirable bacteria and increasing beneficial bacteria. The accumulated knowledge suggests that regular tea intake by humans might provide an approach to decrease the incidence of and mortality from major chronic diseases.
Developmental Regulation of Hepatic Ceruloplasmin mRNA and Serum Activity by Exogenous Thyroxine and Dexamethasone
Authors: Fitch Cheryl A. , Song Ying , Levenson Cathy W.
Published: November 2003

Ceruloplasmin (Cp) is a copper‐dependent oxidase with roles that include the regulation of iron metabolism, participation in the acute‐phase response to inflammation, and antioxidant systems. Although developmental increases in hepatic Cp gene expression and serum activity have been described, the molecular mechanisms that are responsible for this regulation are not fully understood. The studies described here explored the possible role of glucocorticoids and thyroxine (T4) in the early neonatal development of Cp by the administration of these hormones on postnatal Day 1 (24 hr after birth), and the measurement of both hepatic Cp mRNA and serum activity through postnatal Day 10. Administration of the synthetic glucocorticoid hormone, dexamethasone (2 μg/g body wt), resulted in an increase in Cp mRNA on Days 3–7 that was accompanied by an increase in serum Cp activity that reached statistical significance at Day 10. Exogenous T4 (2 μg/g body wt) significantly increased Cp mRNA 24 hr after administration. Serum Cp activity was also significantly elevated by the early neonatal administration of T4. Furthermore, gestational hypothyroidism resulted in a significant decrease in Cp activity after postnatal Day 3. These data suggest a role for thyroid hormone and possibly glucocorticoids in the normal developmental regulation of Cp.