bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackground:  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

AbstractThe 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

Abstract.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

Abstract.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

Abstract.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

Abstract.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

Abstract.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

Abstract.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

Abstract.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

Abstract.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

Abstract.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.