bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Loss of Inner Hair Cells and Type‐I Ganglion Neurons in Carboplatin‐Treated Chinchillas: Mechanisms of Damage and Protection
Authors: DING D.‐L. , WANG J. , SALVI R. , HENDERSON D. , HU B.‐H. , McFADDEN S. L. , MUELLER M.
Published: February 2006

Abstract: Carboplatin preferentially destroys inner hair cells (IHCs) and type‐I spiral ganglion neurons while sparing outer hair cells (OHCs). Loss of IHCs and type‐I ganglion cells is associated with a significant reduction of the compound action potential (CAP). However, the cochlear microphonic (CM) potential and distortion product otoacoustic emissions (DPOAEs) remain normal, indicating that the OHCs are functionally intact. In the vestibular system, carboplatin selectively destroys type‐I hair cells and their afferent neurons. Damage of type‐I vestibular hair cells and their afferent terminals is associated with significant depression of nystagmus induced by cold, caloric stimulation. Histochemical studies revealed a rapid decrease in succinate dehydrogenase (SDH) staining in IHCs soon after carboplatin treatment, and staining intensity remained depressed in surviving IHCs for at least 1 month after carboplatin treatment. These results suggest that carboplatin depresses the metabolic function in surviving IHCs. Several lines of evidence suggest that free radicals may contribute to carboplatin‐induced sensory cell damage. Intracochlear infusion of l‐buthionine‐[S,R]‐sulfoximine (BSO), which depletes intracellular glutathione (GSH), increases IHC and OHC loss. Previous in vitro studies have shown that neurotrophin 4/5 (NT‐4/5) promotes the survival of spiral ganglion neurons from cisplatin ototoxicity. In vivo perfusion of NT‐4/5 promoted the survival of spiral ganglion neurons, but did not protect the hair cells.
A Radical Demise: Toxins and Trauma Share Common Pathways in Hair Cell Death
Authors: KOPKE RICHARD , ALLEN KEITH A. , HENDERSON DONALD , HOFFER MICHAEL , FRENZ DOROTHY , VAN DE WATER THOMAS
Published: February 2006

ABSTRACT: The pathologic similarities noted after ototoxic and/or traumatic injury to the cochlea as well as the key features of the cochlea that make it susceptible to reactive oxygen species (ROS) damage are reviewed. Recent evidence linking ROS to cochlear damage associated with both ototoxins and/or trauma are presented. Mechanisms of generation of ROS in the cochlea and how these metabolites damage the cochlea and impair function are also reviewed. Finally, examples of novel therapeutic strategies to prevent and reverse hearing loss due to noise and/or ototoxins are presented to illustrate the clinical relevance of these new findings.
Protection and Spontaneous Recovery from Cisplatin‐Induced Hearing Loss
Authors: SMOORENBURG GUIDO F. , DE GROOT JOHN C. M. J. , HAMERS FRANK P. T. , KLIS SJAAK F. L.
Published: February 2006

ABSTRACT: Cisplatin [cis‐diamminechloroplatinum(II)] has proved itself as a potent antineoplastic agent. However, nephrotoxicity, neurotoxicity, gastrointestinal toxicity, myelosuppression, and ototoxicity interfere with its therapeutical efficacy. Forced diuresis reduces nephrotoxicity, effectively leaving neurotoxicity and ototoxicity as the major side effects of concern, and gastrointestinal toxicity and myelosuppression as the secondary side effects.

So far, attempts to reduce these side effects by developing equally potent platinum analogs have been unsuccessful. Some success has been achieved, however, by cotreatment with protective agents. Nearly all these agents are sulfuror sulfhydryl‐containing compounds (thio compounds), known as antioxidants and potent heavy metal chelators. These thio compounds may provide protection from cisplatin toxicity either (1) by direct interaction between the cisplatin and the thio moiety, (2) by displacing platinum from its site of toxic action, (3) by preventing platinum from interfering with superoxide dismutase, or (4) by scavenging of cisplatin‐induced free radicals. In particular the first two protective mechanisms bear the risk of reducing the antineoplastic activity of cisplatin.

Since nephrotoxicity can be controlled effectively by forced diuresis, a more specific approach of coping with ototoxicity by focusing on protection at the sensorineural level was chosen. Being familiar with the neuroprotective and neurotrophic properties of ACTH‐related neuropeptides, specifically against cisplatin‐induced peripheral neuropathies, it was judged expedient to test for a possible otoprotective action of these neuropeptides. The results were positive, although tainted with high interanimal variability.

When testing for the possibility that the neuropeptides would merely delay cisplatin‐induced ototoxicity rather than reduce it, it was discovered in control series without neuropeptide cotreatment that the ear can recover spontaneously from cisplatin‐induced hearing loss. This was found both electrophysiologically and in outer hair cell (OHC) counts. Although these preliminary findings require further investigation, they strongly suggest that spontaneous recovery of cochlear injury can occur in the mature mammalian cochlea. Moreover, the otoprotective action of the ACTH‐related neuropeptides suggests that it may be possible to stimulate recovery from acute hearing loss using neuropeptides.
Mechanisms of Alterations in the Microcirculation of the Cochlea
Authors: SEIDMAN MICHAEL D. , QUIRK WAYNE S. , SHIRWANY NAJEEB A.
Published: February 2006

ABSTRACT: Labyrinthine function is tightly coupled to proper homeostasis. This includes appropriate blood flow that is under strict autoregulatory control. Perturbations in labyrinthine microcirculation can lead to significant cochlear and vestibular dysfunction. The etiology of many otologic disorders, including sudden sensorineural hearing loss, presbyacusis, noise‐induced hearing loss, and certain vestibulopathies, are suspected of being related to alterations in blood flow. Some of the mechanisms responsible for hypoperfusion and possibly ischemia, within the cochlea, are addressed, with emphasis on the possibility that both noise and age contribute to localized low blood‐flow states and stasis. This reduction in blood supply to the cochlea is likely, in part, responsible for reduced auditory sensitivity associated with chronic noise exposure and aging.
Successful Treatment of Noise‐Induced Cochlear Ischemia, Hypoxia, and Hearing Loss
Authors: LAMM KERSTIN , ARNOLD WOLFGANG
Published: February 2006

ABSTRACT: Cochlear blood flow (CoBF), perilymphatic partial pressure of oxygen (PL‐pO2), cochlear microphonics (CMs), compound action potentials of the auditory nerve (CAPs), and auditory brainstem responses (ABRs) were studied in noise‐exposed guinea pigs during and after the following treatments: intravenous infusion of isotonic saline (placebo); blood flow promoting drugs (hydroxyethyl starch = HES, pentoxifylline, betahistine, gingko biloba, naftidrofuryl); antiinflammatory agents (prednisolone, diclofenac sodium, histamine H1‐receptor antagonist); isobaric oxygenation (IBO); and hyperbaric oxygenation (HBO) with and without supplements (simultaneous infusion of isotonic saline, pentoxifylline, prednisolone, or HES). It was found that PL‐pO2 declined simultaneously with deterioration of CM, CAP, and ABR amplitudes after exposure to broad‐band noise (bandwidth 1–12 kHz, 30 min, 106‐dB SPL). CoBF decreased only 30 min after cessation of broad‐band noise and progressed with cochlear hypoxia, while the hearing loss showed no further signs of deterioration and no recovery up to 3 h after exposure. Treatment (60 min) started 60 min after cessation of noise and was studied for a further 60 min. Isotonic saline did not influence the measuring parameters. Noise‐induced cochlear hypoxia was compensated by IBO and more effectively by HBO with and without supplements, while other treatments had no sustained effect. A sustained therapeutic effect on noise‐induced cochlear ischemia was achieved only by HES, HBO+HES, and pentoxifylline. However, the best therapeutic effect on noise‐induced hearing loss was achieved with a combination of HBO and prednisolone, followed by monotherapy with prednisolone or HES with the result that not only did the CAPs and ABRs completely recover, the CMs also showed significant improvement, although full recovery did not occur. All other therapies were significantly less effective or did not improve noise‐induced reduction of auditory evoked potentials.
Recovery of Kainic Acid Excitotoxicity in Chinchilla Cochlea
Authors: ZHENG XIANG YANG , SALVI RICHARD J. , McFADDEN SANDRA L. , DING DA LIAN , HENDERSON DONALD
Published: February 2006

ABSTRACT: The present study examines the recovery of the inner hair cell (IHC)/auditory nerve synapse following cochlear excitotoxicity induced by kainic acid (KA). Three hours after KA treatment, there was massive swelling of type I afferent endings under the IHCs. Five to ten days later, the pattern of IHC innervation appeared to be normal. Distortion‐product otoacoustic emissions were normal during the whole experiment. The amplitude of the auditory nerve compound action potential (CAP) was significantly reduced immediately after KA treatment and then recovered over a 30‐day period. However, it only took five days for the evoked response from the inferior colliculus (IC) to recover from a substantial depression. In contrast to amplitudes, thresholds for the CAP and IC recovered at the same rate and returned to normal within 5 days after KA. Single auditory nerve fibers were also assessed at various times after the KA treatment. Ten days after KA, these fibers had almost normal thresholds, tuning, spontaneous, and driven discharge rates. The results indicate that (1) excitotoxically damaged cochlear afferent neurons can rapidly regenerate and establish viable synapses with the IHCs, and (2) the central auditory system recovers more rapidly than the periphery.
Neurotrophic Factors in the Auditory Periphery
Authors: QUN LIANG XING , PIRVOLA ULLA , SAARMA MART , YLIKOSKI1 JUKKA
Published: February 2006

ABSTRACT:Many of the neurotrophic factors promote the survival of developing peripheral sensory neurons, and they might be useful as therapeutic agents in the adult neuronal systems. During development, neurotrophin‐3 (NT‐3) and brain‐derived neurotrophic factor (BDNF) mRNAs are expressed in the auditory sensory epithelium, which composes the peripheral target field of the cochlear (spiral) neurons. NT‐3 mRNA is also expressed in the inner hair cells of the mature organ of Corti. mRNAs encoding their signal‐transducing receptors, TrkC and TrkB, respectively, are expressed in the cochlear neurons. In addition to neurotrophins, which seem to have an important role during development, another neurotrophic factor, glial cell‐line‐derived neurotrophic factor (GDNF), seems to be involved in the maintenance of postnatal auditory neurons. In the present work, the cellular distribution of neurotrophins and GDNF in the developing and adult rat inner ear are compared. The effects of recombinant neurotrophins and GDNF on dissociated cochlear neuronsin vitroare also compared. Recently, NT‐3 and BDNF were usedin vivoas therapeutic agents to protect guinea pig cochlear neurons from aminoglycoside‐induced degeneration and GDNF from noise‐induced degeneration. These data demonstrate that NT‐3, BDNF, and GDNF might be potential candidates for prevention of degeneration of the auditory nerve in man.
Rescue and Regrowth of Sensory Nerves Following Deafferentation by Neurotrophic Factors
Authors: ALTSCHULER R. A. , CHO Y. , YLIKOSKI J. , PIRVOLA U. , MAGAL E. , MILLER J. M.
Published: February 2006

ABSTRACT: Trauma and loss of cochlear inner hair cells causes a series of events that result first in the retraction of the peripheral processes of the auditory nerve, scar formation in the organ of Corti, and over the course of weeks to months (depending on the species) the loss of auditory nerve cell bodies (spiral ganglion cells). Neurotrophic factors play an important role in the mature nervous system as survival factors for maintenance and protection and also can play a role in regrowth. Studies in the cochlea now show that application of exogenous neurotrophic factors can enhance survival of spiral ganglion cells after deafness and induce regrowth of peripheral processes, perhaps by replacing lost endogenous factors. Combinations of factors may be most effective for achieving greatest survival and regrowth. Our studies find that brain‐derived neurotrophic factor (BDNF) and glial‐line‐derived neurotrophic factor (GDNF) are very effective at enhancing spiral ganglion cell survival following deafness from ototoxic drugs or noise. It has also been found that BDNF plus fibroblast growth factor (FGF) is very effective at inducing process regrowth. Electrical stimulation also acts to enhance spiral ganglion cell survival, and the combination of electrical stimulation and neurotrophic factors could prove a most effective intervention.
Gene Therapy in the Inner Ear: Mechanisms and Clinical Implications
Authors: VAN DE WATER THOMAS R. , STAECKER HINRICH , HALTERMAN MARC W. , FEDEROFF HOWARD J.
Published: February 2006

ABSTRACT: The application of gene therapy to the inner ear is an emerging field of study. Most studies report the expression of marker genes (e.g., galactosidase) within the tissues of the cochlea. The first biologic response of an inner ear tissue (i.e., auditory neurons) to transduction by a gene therapy vector expressing a therapeutic gene (a herpes amplicon vector containing a BDNF gene) was observed in spiral explants obtained from early postnatal rat cochleae. This study was important because it demonstrated the feasibility of a gene augmentation approach to treat traumatized cochleae. Long‐term expression of transduced or transfected genes in cochlear tissues have been obtained with adenovirus, adeno‐associated virus, and herpes amplicon vectors. The herpes amplicon vector (i.e., HSVbdnflac) that evoked a biologic response in vitro has also been successfully used to support the survival of auditory neurons in vivo following loss of the auditory hair cells (i.e., loss of trophic factor). Gene therapy has been successfully applied to the cochlea of a laboratory animal, and future studies will define the types of vectors and therapeutic genes that will work best for the treatment of inner ear diseases in the clinic.
The Role of Antioxidants in Protection from Impulse Noise
Authors: HENDERSON D. , MCFADDEN S. L. , LIU C. C. , HIGHT N. , ZHENG X. Y.
Published: February 2006

ABSTRACT: The hearing loss from exposure to noise and ototoxic drugs share a number of audiological and pathological similarities. Recent research has shown that reactive oxygen species (ROS) may be a common factor in both noise‐ and drug‐induced hearing loss. This review describes three experiments that point to ROS as a causative factor in both noise‐ and drug‐induced hearing loss and antioxidants as a protective agent. In the first experiment, the ears of chinchillas were treated with R‐N6‐phenylisopropyladenoisine (R‐PIA) and exposed to 150‐dB impulse noise. The treated ears developed substantially less permanent hearing loss (PTS) and hair cell loss than the untreated ears. One interpretation of this experiment is that R‐PIA increases the availability of glutathione (GSH). In the second experiment, the role of GSH was specifically examined. The ears of chinchillas were treated with glutathione monoethylester (GEE), a pro‐GSH drug that has been shown to readily cross cell membranes and increase GSH levels. The GEE‐treated ears had significantly less PTS and hair‐cell loss than the nontreated ear. Previous research has shown that moderate levels of noise exposure can increase a subject's resistance to noise, and also increase the availability of antioxidant enzymes in the cochlea. In the third experiment, chinchillas were given a series of “toughening” exposures (i.e., 6 h of a 0.5‐kHz OB noise at 95 dB for 10 days). After the series of “toughening” exposures, the subjects were treated with carboplatin, a drug that causes massive inner‐hair‐cell lesions in the chinchilla. The animals receiving the 10‐day toughening exposure developed less PTS and hair‐cell loss than the control animals.
Gender‐Specific Effects of Drugs on Hearing Levels of Older Persons
Authors: MILLS JOHN H. , MATTHEWS LOIS J. , LEE FU‐SHING , DUBNO JUDY R. , SCHULTE BRADLEY A. , WEBER PETER C.
Published: February 2006

ABSTRACT: As part of a study of human presbyacusis, a questionnaire on medicinal drug usage was given to 357 subjects (184 females, 173 males). Previous results from 211 subjects showed gender effects, that is, for males, none of the drugs had any measurable effects on hearing, whereas women taking calcium channel blockers (CCBs) had hearing levels 12 dB better than women not taking them; women taking β adrenergic medication had hearing levels 20 dB poorer, and women taking antihistamine/cold preparations had hearing levels 9 dB poorer. Results from the original 211 subjects were confirmed when the sample size was increased from 211 to 357 subjects only for the β adrenergic medications. Results for antihistamine/cold preparation medications showed small effects only for female subjects. Data from 13 additional female subjects who used CCBs showed hearing levels 10–14 dB poorer than predicted from the original data. Male data were consistent in both samples. The inconsistency for females could reflect sampling error. A more likely possibility is that since the original 10 subjects using CCBs had a mean age of 72 yr and the second sample of 13 had a mean age of 79.5 yr, poorer hearing levels might be anticipated because of the difference in chronological age and possibly duration of drug usage.
Cellular Mechanisms of Risk and Transformation
Authors: AUGENLICHT LEONARD H. , BORDONARO MICHAEL , HEERDT BARBARA G. , MARIADASON JOHN , VELCICH ANNA
Published: February 2006

ABSTRACT Our early work using the first array and imaging methods for the quantitative analysis of the expression of 4000 cDNA sequences suggested that modulation of mitochondrial gene expression was a factor in determining whether colonic epithelial cells displayed a differentiated or transformed phenotype. We have since dissected a pathway in which mitochondrial function is a key element in determining the probability of cells undergoing cell‐cycle arrest, lineage‐specific differentiation, and cell death. Moreover, this pathway is linked to signaling through β‐catenin‐Tcf, but in a manner that is independent of effects of the APC gene on β‐catenin‐Tcf activity. Utilization of unique mouse genetic models of intestinal tumorigenesis has confirmed that mitochondrial function is an important element in generation of apoptotic cells in the colon in vivo and has demonstrated that modulation of cell death may be involved in intestinal tumor progression rather than initiation. Normal spatial and temporal patterns of cell proliferation, differentiation, and apoptosis in the colonic mucosa are determined by developmentally programmed genetic signals and external signals generated by homo‐ and heterotypic cell interactions, humoral agents, and lumenal contents. Mitochondrial function may play a pivotal role in integrating these signals and in determining probability of cells entering different maturation pathways. How this is accomplished is under investigation using high‐density cDNA microarrays.
Oncogenic Activating Mutations in the neu/erbB‐2 Oncogene Are Involved in the Induction of Mammary Tumors
Authors: CHAN RICHARD , MULLER WILLIAM J. , SIEGEL PETER M.
Published: February 2006

ABSTRACT Amplification and overexpression of erbB‐2/neu is an important determinant in the initiation and progression of human breast cancer. Indeed, transgenic mice that overexpress the neu proto‐oncogene heritably develop mammary adenocarcinomas. Tumorigenesis in these transgenic strains is associated with activation of the intrinsic catalytic activity of Neu. In many of these tumors, activation of Neu occurs as a result of somatic mutations located within the transgene itself. Examination of the altered neu transcripts revealed the presence of in‐frame deletions that encode aberrant Neu receptors lacking 5 to 12 amino acids within the extracellular domain proximal to the transmembrane region of Neu. In addition to these deletion mutants we have also detected single point mutations within this juxtatransmembrane region. The majority of the mutations analyzed affect the one of several conserved cysteine residues present within this region. Introduction of these activating mutations into the wild‐type neu cDNA results in its oncogenic conversion. Taken together, these observations suggest that this cysteine‐rich region plays an important role in regulating the catalytic activity of Neu.
Inhibition of Cyclooxygenase‐2 Expression: An Approach to Preventing Head and Neck Cancer
Authors: MESTRE JUAN R. , CHAN GEORGETTE , ZHANG FAN , YANG EUN K. , SACKS PETER G. , BOYLE JAY O. , SHAH JATIN P. , EDELSTEIN DAVID , SUBBARAMAIAH KOTHA , DANNENBERG ANDREW J.
Published: February 2006

ABSTRACT Cyclooxygenase (COX) catalyzes the formation of prostaglandins (PG) from arachidonic acid. A large body of evidence has accumulated to suggest that COX‐2, the inducible form of COX, is important in carcinogenesis. In this study, we determined whether (1) COX‐2 was overexpressed in squamous cell carcinoma of the head and neck (HNSCC) and whether (2) retinoids, a class of chemopreventive agents, blocked epidermal growth factor (EGF)‐mediated activation of COX‐2 expression. Levels of COX‐2 mRNA were determined in 15 cases of HNSCC and 10 cases of normal oral mucosa. Nearly a 100‐fold increase in amounts of COX‐2 mRNA was detected in HNSCC. By immunoblot analysis, COX‐2 protein was detected in 6 of 6 cases of HNSCC but was undetectable in normal mucosa. Because retinoids protect against oral cavity cancer, we investigated whether retinoids could suppress EGF‐mediated induction of COX‐2 in cultured oral squamous carcinoma cells. Treatment with EGF led to increased levels of COX‐2 mRNA, COX‐2 protein, and synthesis of PG. These effects were suppressed by a variety of retinoids. Based on the results of this study, it will be important to establish whether newly developed selective COX‐2 inhibitors are useful in preventing or treating HNSCC. Moreover, the anticancer properties of retinoids may be due, in part, to inhibition of COX‐2 expression. Combining a retinoid with a selective COX‐2 inhibitor may be more effective than either agent alone in preventing cancer of the upper aerodigestive tract.
The Role of COX‐2 in Intestinal Cancer
Authors: WILLIAMS CHRISTOPHER , SHATTUCK‐BRANDT REBECCA L. , DuBOIS RAYMOND N.
Published: February 2006

ABSTRACT Cyclooxygenase (COX), the key regulatory enzyme for prostaglandin synthesis is transcribed from two distinct genes. COX‐1 is expressed constitutively in most tissues, and COX‐2 is induced by a wide variety of stimuli and was initially identified as an immediate‐early growth response gene. In addition, COX‐2 expression is markedly increased in 85–90% of human colorectal adenocarcinomas, whereas COX‐1 levels remain unchanged. Several epidemiological studies have reported a 40–50% reduction in the risk of developing colorectal cancer in persons who chronically take such nonsteroidal anti‐inflammatory drugs (NSAIDs) as aspirin, which are classic inhibitors of cyclooxygenase. Genetic evidence also supports a role for COX‐2, since mice null for COX‐2 have an 86% reduction in tumor multiplicity in a background containing a mutated APC allele. These results strongly suggest that COX‐2 contributes to the development of intestinal tumors and that inhibition of COX is chemopreventative.
Calcium and Vitamin D: Their Potential Roles in Colon and Breast Cancer Prevention
Authors: GARLAND CEDRIC F. , GARLAND FRANK C. , GORHAM EDWARD D.
Published: February 2006

The geographic distribution of colon cancer is similar to the historical geographic distribution of rickets. The highest death rates from colon cancer occur in areas that had high prevalence rates of rickets‐regions with winter ultraviolet radiation deficiency, generally due to a combination of high or moderately high latitude, high‐sulfur content air pollution (acid haze), higher than average stratospheric ozone thickness, and persistently thick winter cloud cover. The geographic distribution of colon cancer mortality rates reveals significantly low death rates at low latitudes in the United States and significantly high rates in the industrialized Northeast. The Northeast has a combination of latitude, climate, and air pollution that prevents any synthesis of vitamin D during a five‐month vitamin D winter. Breast cancer death rates in white women also rise with distance from the equator and are highest in areas with long vitamin D winters. Colon cancer incidence rates also have been shown to be inversely proportional to intake of calcium. These findings, which are consistent with laboratory results, indicate that most cases of colon cancer may be prevented with regular intake of calcium in the range of 1,800 mg per day, in a dietary context that includes 800 IU per day (20 μg) of vitamin D3. (In women, an intake of approximately 1,000 mg of calcium per 1,000 kcal of energy with 800 IU of vitamin D would be sufficient.) In observational studies, the source of approximately 90% of the calcium intake was vitamin D‐fortified milk. Vitamin D may also be obtained from fatty fish. In addition to reduction of incidence and mortality rates from colon cancer, epidemiological data suggest that intake of 800 IU/day of vitamin D may be associated with enhanced survival rates among breast cancer cases.
Preclinical and Early Human Studies of Calcium and Colon Cancer Prevention
Authors: LIPKIN MARTIN
Published: February 2006

ABSTRACT Colorectal cancer continues to be a major cause of tumor mortality in the United States and other countries; despite attempts to improve the screening of high‐risk populaitons, the incidence of this disease is still very high. Therefore, chemoprevention continues to be an important goal for the primary prevention of colorectal cancer. Among recent chemopreventive approaches, the administration of calcium and vitamin D continue to be evaluated in both preclinical and clinical studies. Many experimental findings described below have indicated associations between high calcium and vitamin D intake and decreased risk for colorectal cancer.
European Trials on Dietary Supplementation for Cancer Prevention
Authors: BIASCO GUIDO , PAGANELLI GIAN MARIA
Published: February 2006

ABSTRACT European institutions aimed at cancer research and control are spending sizable resources to develop preclinical and clinical chemoprevention trials. Pilot studies showed positive effect on colorectal cell proliferation from supplementation with calcium; vitamins A, C, and E; Ω‐3 fatty acids; and folic acid. A significant reduction in adenoma recurrence after polypectomy was found in patients randomly assigned to take vitamin A, C, and E supplementation or, to a lesser extent, lactulose. Although first reports showed a disquieting higher incidence of lung cancer in male smokers who took β‐carotene supplementation, the European Organization of Research and Treatment of Cancer (EORTC) planned a chemoprevention study on the prevention of second primary tumors in patients with curatively treated head and neck or lung cancer (EUROSCAN). Retinol palmitate or N‐acetylcysteine or both are given for two years. The European Cancer Prevention Organization (ECP) is carrying out a clinical trial in patients with previous adenomas of the large bowel, to test the efficacy of calcium or fiber supplementation on adenoma recurrence. ECP in collaboration with EURONUT has also started a multinational intervention study of the effect of H. pylori eradication and/or dietary supplementation with vitamin C on intestinal metaplasia.
Update from Asia: Asian Studies on Cancer Chemoprevention
Authors: YUN TAIK‐KOO
Published: February 2006

ABSTRACT In Asia, nontoxic dietary products are considered desirable primary prevention vehicles for conquering cancer. As early as 1978, investigators in Korea carried out extensive long‐term anticarcinogenicity experiments using the mouse lung tumor model and observed an anticarcinogenic effect of Panax ginseng C.A. Meyer extract in 1980. The results showed that natural products can provide hope for human cancer prevention. A newly established nine‐week medium‐term model using mouse lung tumors (Yun's Model) could confirm the anticarcinogenicity of ginseng that varies according to its type and age. Subsequently, the ginseng was shown by epidemiological studies to be a nonorgan‐specific cancer preventive agent associated with a dose‐response relationship. The anticarcinogenic effects of vegetarian foods common at every dining table in Korea and some synthetics were also studied using Yun's nine‐week model. In brief, ascorbic acid, soybean lecithin, capsaicin, biochanin A, Ganoderma lucidum, caffeine, and a novel synthetic 2‐(allylthio)pyrazine decrease the incidence of mouse lung tumors, whereas fresh ginseng (4 years old), carrot, spinach, Sesamum Indicum, β‐carotene, and 13‐cis retinoic acid do not. This result regarding beta‐carotene is consistent with the ineffective findings of the ATBC trial, the CARET trial, and the Physicians' Health Study. In 1983, a cancer chemoprevention study group was first established in Japan. subsequently, (‐)‐epigallocatechin gallate, cryptoporic acid E, and sarcophytol A from natural products, and synthetic acyclic retinoid and canventol were shown to be anticarcinogenic or chemopreventive in human subjects. despite the frequent consumption of tea wordwide as a beverage and current experimental evidence of anticarcinogenesis, including controversial results of epidemiological studies, more systematic clinical trials for confirmation of preventive activity of tea against cancer are needed. Placebo‐controlled intervention trials of dietary fiber are under study in Japan. In the past decade, new triterpenoids were isolated from various natural sources, and its biological activities were investigated in Asia. In the late 1970s a comprehensive chemoprevention program was established at the Institute of Materia Medica, Chinese Academy of Medical Sciences. Since then, many retinoid compounds have been synthesized and screened in the search for chemopreventive cancer agents. The National Cancer Institute (USA) and China are jointly engaged in the two‐nutrition intervention in Linxian, China. The results of joint study of the general population and of dysplasia in china should stimulate further research to clarify the potential benefits of micronutrient supplements. We need to clarify if there is a connection between the lower rates of cancer mortality in Korea and the frequent consumption of anticarcinogenic vegetables or traditional foods, including ginseng and Ganoderma lucidum. The constituents of the nontoxic stable dietary products promise to be the future hope for conquering cancers in the coming years.
Multifunctional Aspects of the Action of Indole‐3‐Carbinol as an Antitumor Agent
Authors: BRADLOW H. LEON , SEPKOVIC DANIEL W. , TELANG NITIN T. , OSBORNE MICHAEL P.
Published: February 2006

ABSTRACT Previous studies from this laboratory have suggested that 2‐hydroxyestrone is protective against breast cancer, whereas the other principal metabolite, 16α‐hydroxyestrone, and the lesser metabolite quantitatively, 4‐hydroxyestrone, are potent carcinogens. Attempts to directly decrease the formation of the 16‐hydroxylated metabolite were either unsuccessful or required such high levels of the therapeutic agent as to be impractical. On the other hand the concentration of the protective metabolite, 2‐hydroxyestrone, proved to be readily modulated by a variety of agents, both in the direction of increased protection and the opposite direction, increased risk by a variety of agents and activities. We have focussed our attention on indole‐3‐carbinol, a compound found in cruciferous vegetables, and its further metabolites in the body, diindolylmethane (DIM) and indolylcarbazole (ICZ), because of its relative safty and multifaceted activities. It has been shown that it induces CyP4501A1, increasing 2‐hydroxylation of estrogens, leading to the protective 2‐OHE1, and also decreases CyP1B1 sharply, inhibiting 4‐hydroxylation of estradiol, thereby decreasing the formation of the carcinogenic 4‐OHE1. In addition to these indirect effects as a result of altered estrogen metabolism, indole‐3‐carbinol has been shown to have direct effects on apoptosis and cyclin D, resulting in blockage of the cell cycle. In addition to its antitumor activity in animals, it has also been shown to be effective against HPV‐mediated tumors in human patients. All of these responses make the study of its behavior as a therapeutic agent of considerable interest.
Resveratrol Inhibits Cyclooxygenase‐2 Transcription in Human Mammary Epithelial Cells
Authors: SUBBARAMAIAH KOTHA , MICHALUART PEDRO , CHUNG WEN JING , TANABE TADASHI , TELANG NITIN , DANNENBERG ANDREW J.
Published: February 2006

ABSTRACT A large body of evidence suggests that inhibiting cyclooxygenase‐2 (COX‐2), the inducible form of COX, will be an important strategy for preventing cancer. In this study, we investigated whether resveratrol, a chemopreventive agent found in grapes, could suppress phorbol ester (PMA)‐mediated induction of COX‐2 in human mammary and oral epithelial cells. Treatment of cells with PMA induced COX‐2 mRNA, COX‐2 protein, and prostaglandin synthesis. These effects were inhibited by resveratrol. Nuclear runoffs revealed increased rates of COX‐2 transcription after treatment with PMA, an effect that was inhibited by resveratrol. Resveratrol inhibited PMA‐mediated activation of protein kinase C and the induction of COX‐2 promoter activity by c‐Jun. Phorbol ester‐mediated induction of AP‐1 activity was blocked by resveratrol. These data are likely to be important for understanding the anticancer and anti‐inflammatory properties of resveratrol.
Arc Modeling
Authors: LOWKE J. J. , SANSONNENS L. , HAIDAR J.
Published: February 2006

ABSTRACT: This paper is an account of how arc modeling has increased our predictive capability of properties of arc plasmas. Basic material functions of, for example, thermal and electrical conductivities, can be calculated for any plasma, given the component elements of the plasma. Then solution of conservation equations gives properties of the plasma. Examples are given of successes of arc modeling. (1) A one dimensional calculation for an arc confined in a cylindrical tube gives the principal electrical properties of an arc lamp. (2) Two dimensional calculations including the arc and the electrodes gives an explanation of the transition from globular to spray modes of metal transfer in arc welding. (3) Also predictions of plasma and electrode temperatures in tungsten arc welding are in good agreement with experiment. (4) Time dependent calculations of the development of electron avalanches in lightning, explain the development of the stepped leader.
Properties of Electric Arc Stabilized by Mixture of Water with Ethanola
Authors: HRABOVSKÝ MILAN , KONRÁD MILOŠ , KOPECKÝ VLADIMÍR , SEMBER VIKTOR
Published: February 2006

ABSTRACT:Plasma torch with liquid stabilized (Gerdien) are was investigated experimentally. Mixture of water and ethanol was used as a stabilizing medium. Volt‐ampere characteristics and power balance of the arc were measured. Radial profiles of temperature at the torch exit and composition of plasma in generated plasma jet were found by methods of emission spectroscopy. Exit plasma velocity and total mass flow rate, which is given by the evaporation rate from the stabilizing liquid, were determined from the measured data. The results of experiments show substantial effect of addition of small amount of ethanol into water on basic arc characteristics and properties of plasma jet.
Measurements of Heat Flux in an Atmosphere‐ and Temperature‐Controlled Plasma Spray Process.
Authors: MEILLOT ERICK , FROMENTIN JEAN PIERRE
Published: February 2006

ABSTRACT: The C.E.A. (the French Atomic Energy Agency) has developed the A.T.C. plasma spray process (Atmosphere‐and Temperature‐Controlled process): a classical inert plasma spraying system is coupled with a cryogenic cooling of the substrate by liquefied gas atomization. This process alternately supplies positive and negative heat fluxes to the substrate. In order to quantify these fluxes, and to better control the process, a heat flux measurement system has been developed: under industrial conditions, several multi‐layer sensors measure the flux received by the substrate. This paper presents the diagnostic apparatus and the first results measured in A.T.C. plasma spraying conditions. These results were obtained in dynamic operating conditions.
Effect of Anode Attachment on Flow Structure in Plasma Jet Generated in DC Arc Torcha
Authors: HRABOVSKÝ MILAN , KONRÁD MILOŠ , KOPECKÝ VLADIMÍR , SEMBER VIKTOR
Published: February 2006

ABSTRACT: Effect of an arc anode attachment on stability of plasma jet was studied in a plasma torch with dc electric arc stabilized by water. The torch was equipped with an external anode and thus direct observation of interaction of the anode attachment with the plasma jet was possible. High speed photography of the anode region and the jet was synchronized with voltage measurements. Different modes of the anode attachment were distinguished and movement of the attachment along the anode surface was photographed. Formation of an anode jet was observed. An interaction of the anode jet with the main jet produce strong instability of plasma flow in the jet which rapidly develops into jet whipping and fluttering. It is shown that momentum flux in the anode jet is comparable with the one in the main jet and thus a formation of the anode jet is principal cause of a plasma jet instability. Results of spectroscopic diagnostics of the anode region indicate strong entrainment of ambient air into the anode jet.
Plasma Destruction of Gaseous and Liquid Wastes
Authors: MURPHY A. B.
Published: February 2006

ABSTRACT: The current status of waste destruction using thermal plasmas is reviewed. The Australian PLASCONTM system is described and its current commercial implementations are listed. An overview is given of the research and development program that was required for the PLASCON system to reach its current status. The program included experimental trials to determine optimum conditions for destruction, materials and component testing, and a theoretical component consisting of thermochemical, chemical kinetic and fluid dynamic modelling. The application of PLASCON to the destruction of ozone‐depleting substances such as chlorofluorocarbons and halons is discussed as an example. The conversion of the input ozone‐depleting substance to CF3Cl (CFC‐13), a more stable ozone‐depleting substance, is an example of a problem that was successfully addressed in this case. This and other successes of the research and development program are discussed.
Manufacturing of Solid Oxide Fuel Cells ‐ A Challenge for DC and RF Plasma Deposition Processes ‐ 1, 2
Authors: HENNE RUDOLF H. , LANG MICHAEL , MÜLLER MATTHIAS , RUCKDÄSCHEL ROBERT , SCHILLER GÜNTER
Published: February 2006

ABSTRACT: It is expected that fuel cells and particularly solid oxide fuel cells (SOFC) as direct converters of chemical energy into electrical energy will gain an important position in future stationary electric power generation. SOFCs of present development state operate in a temperature range of around 900 °C. Their efficiency is considerably higher and their operation less burdened by wastes and environmental problems compared to presently applied systems. Therefore, there exists great interest to make such SOFC units available in a technical scale. A main precondition for a wide spread application of SOFCs is particularly a considerable reduction of the production costs. Besides the improvement of presently used methods mainly basing on sintering techniques, also new technologies have been under consideration and development. In this connection DC and RF plasma deposition processes became attractive for producing components or even entire cells. But further process improvements are needed to meet the special quality and economic demands of the SOFCs.
INDUSTRIAL 2,5‐TONS PLASMA‐INDUCTION FURNACE
Authors: MIHOVSKY M. , TZONEV TZ. , LUCHEVA B.
Published: February 2006

ABSTRACT:A 2,5‐tons induction furnace at Kremikovtzi Ltd. in Bulgaria was reconstructed into a plasma‐induction one by PLASMALAB project. It is in regular operation now. The main purposes of this actual work are to develop a metallurgical technology for copper and copper alloys fine scrap (turnings) melting, to determine the rate of the oxidation of the alloying elements in the charge and to find the optimum relation between plasma and induction power in order to obtained a maximum yield and a minimum power consumption.
CONTROL ON LINE OF LEAD AND ZINC EVAPORATION IN THE TREATMENT BY TRANSFERRED ARC OF FLY ASHES FROM WASTE INCINERATORS
Authors: Bernard S. , Fauchais P. , Jarrige J. , Lecompte J. P. , Denoirjean P.
Published: February 2006

ABSTRACT: This study is about the destruction of fly ashes from waste incinerators. It was performed in a laboratory sized plasma reactor where the wastes were treated by a transferred arc stabilized by an argon flow. The concentration of the different evaporated elements, especially those of heavy metals, in the exhaust gases was followed on‐line by an ICP analysis system which allows to caracterize the evaporation rate for lead, zinc and chlorine. The analysis of the inert glass formed after plasma treatment was made by X‐rays fluorescence which allowed measuring the conversion efficiency of the process. For an argon plasma, the type of the lead or zinc anion salts, the are current, the arc length, and the additives to reduce the viscosity of the slag were the parameters of this study.
Plasma Decontamination Of Depleted Uranium Oxide From Stainless Steel Surfacesa
Authors: VEILLEUX JOHN M. , EL‐GENK MOHAMED S. , CHAMBERLIN E. P. , MUNSON C. , FITZPATRICK J.
Published: February 2006

ABSTRACT: A series of single effect, RF plasma, glow discharge experiments were conducted using NF3 gas to decontaminate depleted uranium dioxide from stainless‐steel substrates. In the experiments, the plasma absorbed power was varied from 25 to 210 W, the pressure from ∼10 to 40 Pa, and the NF3 flow rate from 3 to 18.5 SCCM. Results demonstrated that UO2 can be completely removed from stainless‐steel substrates after several minutes processing at under 100 W with initial etch rates ranging from 0.2 to 7.4 μm/min. A primary etch mechanism is proposed in which F atoms created in the plasma diffuse to the surface UO2 and react to form successive intermediates of uranium fluorides and/or oxyfluorides with reactions continuing to form the volatile UF6 which desorbs into the gas phase to be pumped away. Ions created in the plasma are too low in concentration to be the primary etch mechanism, yet they can deliver enough energy to enhance the reaction process. UO2 etching is a self‐limiting process due to the formation of non‐volatile uranium oxyfluorides and fluorides which form over the UO2, slowing or completely blocking the reaction to UF6.
Thermal Cutting of Concrete and Related Materialsa
Authors: DZUR BIRGER , ROTHER WOLFGANG , NUTSCH GABRIELE , SCHILLING JOACHIM , SCHWARZE AXEL
Published: February 2006

ABSTRACT: A large number of techniques in the construction industry are dealing with the mixture, reinforcement and use of concrete and related materials. But this is contrasted by only a few technologies for the destruction of old construction substance. Especially strongly steel reinforced concrete poses problems for breaking it apart with conventional means. In this paper some thermodynamical properties of concrete and some theoretical considerations about its melting are given. The development of a new technology for thermal cutting and the destruction of steel reinforced concrete and related materials by using a DC‐plasma torch with non‐transferred arc is described. Such a torch is well known from thermal spraying applications. It was modified and optimized to cut and drill concrete with a nitrogen plasma jet, as it is shown in some examples.
The Repair of Railway Frogs Using Plasma Sprayed Coating.
Authors: ISAKAEV EMIN , YABLONSKY ALEXANDER , KOGAN ALEXANDER , KATARZHIS VLADIMIR , KUTNOV VICTOR , IVANOV PETER
Published: February 2006

ABSTRACT: A new technological process for railway frogs repair is developed by specialists from Associated Institute for High Temperatures on the base of plasma sprayed coating, ensuring the high quality defectless coating, which is less sensitive to operator errors, is more automated and has greater productivity compared with existing ones. Repaired frogs have passed successfully heavy field testing on the Experimental Ring of All Russia Research Institute for Railway Transport.
Modelling and Measurements of Particle in‐flight Characteristics of Atmospheric Plasma Sprayed Yttria Stabilised Zirconia
Authors: NYLEN PER , BOLOT RODOLPHE , HANSBO ANITA , CODDET CHRISTIAN
Published: February 2006

ABSTRACT: Stabilised ZrO2 particle in flight characteristics in an Ar‐H2 atmospheric plasma jet have been studied using analytical and experimental techniques. A commercial code was used to simulate the plasma flow. A standard k‐ɛ turbulence model was used. Powder particle velocity, temperature history and trajectory were calculated using a stochastic discrete particle model and compared with measurements. A good correlation was found between predictions and measurements. Relationships between the sprayed particle velocity, temperature and size were investigated and a clear correlation was found. The method presented here seems to be a powerful and cost‐effective tool, which could be used to optimise spray parameters off‐line.