bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoaging and oxidative stress
Authors: Nishigori Chikako , Hattori Yukari , Arima Yaeno , Miyachi Yoshiki
Published: November 2003

Abstract Photoaging is significantly different from chronological aging in both clinical and histological appearance. It has been suggested that oxidative stress, generated by ultraviolet radiation (UVR), leads to photoaging over a long period. The presence of 8‐OHdG, and oxidatively modified proteins such as 4‐hydroxy‐2‐nonenal‐modified protein, 3‐l‐nitro‐tyrosine and N–ε(carboxymethyl)lysine in UV‐exposed skin specimens, supports this theory. The pathophysiology of photoaging of the skin caused by chronic inflammation after UVR is reviewed and discussed, with a focus on oxidative stress.
Tretinoin reverses upregulation of matrix metalloproteinase‐13 in human keloid‐derived fibroblasts
Authors: Uchida Gentaro , Yoshimura Kotaro , Kitano Yukie , Okazaki Mutsumi , Harii Kiyonori
Published: November 2003

Abstract Keloids are skin abnormalities that are characterized by excessive deposition of collagen bundles in the dermis. Patients with keloids complain not only about their cosmetic appearance, but also about continuous itching and/or tenderness associated with chronic inflammation. Degradation of extracellular matrix (ECM) may be upregulated, associated with the expansion of keloids into circumferential skin, and high metabolic activity of keloid tissues may be due to increased matrix metalloproteinase (MMP) activity. Based on these hypotheses, we examined differences in expression of MMP‐1, MMP‐8, and MMP‐13 between keloid‐derived and normal dermal fibroblasts. Since retinoids are potent inhibitors of MMPs in the treatment of photoaged skin and cancers, we also examined whether or not tretinoin affects MMP expression of keloid‐derived fibroblasts. The results of real‐time polymerase chain reaction and ELISA demonstrated significant upregulation of MMP‐13 and significant downregulation of MMP‐1 and MMP‐8 in keloid‐derived fibroblasts, at both mRNA and protein levels. MMP‐1 mRNA expression in the control group was significantly upregulated after the addition of tretinoin, whereas no significant change was observed in the keloid group. MMP‐8 mRNA expression in the control group was significantly upregulated by tretinoin, with the peak at 12 h, while no significant change was observed in the keloid‐derived fibroblasts. In contrast, the remarkably elevated MMP‐13 mRNA expression in the keloid group was significantly suppressed, with the peak suppression at 12 h after addition of tretinoin, while MMP‐13 mRNA expression in the control group was not significantly changed. The decrease in MMP‐1 and MMP‐8 may contribute to accumulation of type I and type III collagen in keloid tissues, and this mechanism may be modulated by molecular interaction with MMP‐13. Tretinoin appeared to reverse the abnormal expression profile of MMPs in keloid‐derived fibroblasts, such as markedly elevated expression of MMP‐13, partly through inactivation of AP‐1 pathway. The present results suggest that tretinoin may be clinically useful to improve the chronic inflammation seen in keloids and prevent expansion of keloid tissues into circumferential normal skin.
The inhibitory effect of glycolic acid and lactic acid on melanin synthesis in melanoma cells
Authors: Usuki Akiko , Ohashi Akiko , Sato Hirofumi , Ochiai Yasunobu , Ichihashi Masamitsu , Funasaka Yoko
Published: November 2003

Abstract α‐Hydroxy acids (AHAs) such as glycolic acid (GA) and lactic acid (LA) have been reported to be effective in treating pigmentary lesions such as melasma, solar lentigines, and postinflammatory hyperpigmentation. The mechanism of this effect might be due to epidermal remodeling and accelerated desquamation, which would result in quick pigment dispersion. However, the direct effect of AHAs on melanin synthesis has not yet been well studied. To elucidate such a direct effect of AHAs on melanogenesis, we performed melanin assays, growth curve determinations, Northern and Western blotting for melanogenic proteins [tyrosinase, tyrosinase related protein (TRP)‐1 and TRP‐2], and tyrosinase and, 4‐dihydroxyphenylalaninechrome tautomerase enzyme activity assays using mouse B16 and human melanoma cells. GA or LA (at doses of 300 or 500 μg/ml) inhibited melanin formation in similar dose‐dependent manner, without affecting cell growth. Although the mRNA and protein expression or molecular size of tyrosinase, TRP‐1 and TRP‐2 were not affected, tyrosinase activity was inhibited. To see whether GA and/or LA directly inhibit tyrosinase catalytic function, the effect of GA and LA on human tyrosinase purified from the melanosome‐rich large granule fraction of human melanoma cells was performed. GA or LA were shown to inhibit tyrosinase enzyme activity directly, but this effect was not due to the acidity of GA or LA, because adjusting the pH to 5.6 (the pH of GA and LA at concentrations of 2500 μg/ml), did not affect tyrosinase activity. Taken together, these results show that GA and LA suppress melanin formation by directly inhibiting tyrosinase activity, an effect independent of their acidic nature. GA and LA might work on pigmentary lesions not only by accelerating the turnover of the epidermis but also by directly inhibiting melanin formation in melanocytes.
Study of chlorination of nickel ferrite by gaseous chlorine and calcium chloride in the presence of active additives
Authors: Ilić Ilija , Stopić Srećko , Cerović Katarina , Kamberović Željko
Published: November 2003

Thermodynamic analysis and experimental research of the chlorination of nickel ferrite (NiFe2O4) by gaseous chlorine in the presence of added C, BaS, S and NaCl in the temperature range from 300 to 900°C are given in this paper. Nickel ferrite chlorination in the presence of BaS and CaCl2 was carried out in the temperature range from 750 to 950°C. The presence of added C, BaS, S and NaCl intensifies the chlorination process of nickel ferrite by gaseous chlorine and reduces the temperature the reaction begins at from 700 to 300°C. It is concluded that the process of nickel chlorination without additives is chemically controlled, whereas it is diffusion controlled in the presence of additives. The chlorination of nickel ferrite by calcium chloride, i.e., gaseous hydrochloric acid, is intensified in the presence of 7.5 mass % of CaCl2 and 2 mass % of BaS in nickel ferrite, and temperature range from 750 to 950°C. The results obtained in thermodynamic analysis are in good agreement with the experimental ones.
The strain‐rate dependence of flow stress and work‐hardening rate in three Al‐Mg alloys
Authors: Yao Xuexing , Zajac Stanislaw
Published: November 2003

Uniaxial compression tests have been carried out on Al‐0.5% Mg, Al‐1.0% Mg and Al‐3.0% Mg alloys at 265°C and at constant true strain‐rates in the range 10−3 to 10 s−1. Uniaxial compression tests with true strain‐rate sudden change from 1 to 10 s−1, which are applied at true strains of 0.1, 0.3 and 0.5, have been performed at 160, 365 and 520°C. The work‐hardening rate, θ  =  ∂σ/∂ε, has been evaluated at 265°C and found to exponentially decrease with increasing strain. The total strain‐rate exponent, mt, at 265°C and the instantaneous strain‐rate exponent, mi, at 160, 365 and 520°C are determined. It is found that mi is strain independent irrespective of temperature, while mt is less sensitive to strain when strain‐rates are high (10−1 to 10 s−1); however, it increases with strain when strain‐rates become low (10−3 to 10−1 s−1). The difference between mi and mt could be attributed to the strain‐rate dependence of the work‐hardening rate. The possible correlation between the strain‐rate exponents of flow stress (mi and mt) and the strain‐rate exponent of work‐hardening rate (mh) could be outlined as mt  =  αmi+mh, where α is a correlation coefficient.
Reduction smelting of bursa‐uludağ tungsten concentrates by the aluminothermic process
Authors: Yücel Onuralp , Özçelebi M. Abdülnafi
Published: November 2003

Tungsten is an important element for use in the production of some special steels and is added to steel as ferrotungsten alloys. Low carbon ferrotungsten is mostly produced by the metallothermic reduction process. The aim of this study was to determine ferrotungsten production parameters for the Etibank Scheelite concentrate containing 35% WO3 by an aluminothermic process. Although tungsten was recovered up to 95.4%, the tungsten content of alloy obtained was a maximum of 52.6% in the aluminothermic processing of tungsten calcine obtained by total oxidizing roasting of the concentrate. Therefore, pre‐roasting and magnetic separation treatments were applied to tungsten concentrate to enrich the tungsten content in the non‐magnetic part of the concentrate, and the tungsten recovery obtained was 92.5%. After applying total oxidizing roasting to the non‐magnetic part of the concentrate to decrease the sulfur content, a calcine containing 50.4% WO3 was obtained. By aluminothermic reduction of this calcine, tungsten could be recovered at 79.4% and concentrated as 75.4% in the ferroalloy.
Dissolution behavior of particulate graphite in Fe‐C melts
Authors: Sahajwalla V. , Khanna R.
Published: November 2003

A Monte Carlo simulation study has been carried out on the dissolution of a single graphite particle in Fe‐C (0–4 wt%) melts in the temperature range 1400°C to 1600°C. The aim of this study was to investigate the effect of the atomic nature of the interfacial region on the graphite dissolution behavior. Atoms in graphite and the melt were arranged on a rigid graphitic hexagonal lattice and the interactions were assumed to be pair‐wise and short ranged. Using canonical ensemble, simulations were carried out as a function of particle size, carbon content of the melt and temperature. Simulation results show that the dissolution of a graphite particle does not take place layer by layer. The C atoms in the basal plane dissolve preferentially from the edges while the atoms on a prismatic plane dissolve all across the particle surface. Iron liquid penetrates deep in the particle and leads to the formation of a broad interfacial region containing high concentrations of both C and Fe. The overall particle dissolution profile as a function of particle size, temperature and C concentration in the melt showed a good agreement with theoretical and experimental results.
Industrial application of a thermodynamical modelto predict inclusion composition
Authors: Madías Jorge , Genzano Cristian
Published: November 2003

A model to predict microinclusion volume and chemistry, based on thermodynamics and mass balance, was developed for aluminium‐killed calcium treated steels. The model turned out to be a useful tool in helping to solve many different problems at several steelworks. In this work, examples of such application are given, covering nozzle blockage by calcium sulphides in boron steels, macroinclusion formation by calcium attack on refractories, and chemical evolution of microinclusion with temperature.
On the hot working characteristics of INCONEL alloy MA 754 using processing maps
Authors: Murty S. V. S. Narayana , Rao B. Nageswara
Published: November 2003

Hot workability is concerned with the extent to which a material plastically deforms during shaping at high temperatures without the occurrence of flow localization or fracture. A simple condition for delineating the regions of unstable metal flow in the processing maps is suggested. The applicability of this criterion has been verified using the test data of INCONEL alloy MA 754 with microstructural observations. A hot workability map of this material is established for shop floor applications.
Investigation of the kinetics of reductionof manganese tungstate by hydrogen
Authors: Bustnes J. A. , Sichen Du , Seetharaman S.
Published: November 2003

The present work was carried out as a part of a research program studying the reduction kinetics of some transition metal tungstates. Manganese tungstate was reduced by hydrogen under isothermal conditions in the temperature range 883–1183 K. The reaction was found to take place in a single step with MnO and W as the solid products. The activation energy for the reduction of manganese tungstate was evaluated to be 92 kJ mol−1 using the initial reaction rates. This activation energy was compared with the activation energies of the other transition metal tungstates in the light of bond strength of the metal‐oxygen bonds.
Low reoxidation tundish metallurgy at Fundia Koverhar steel plant
Authors: Manninen Veikko , Lano Tomi , Holappa Lauri E. K.
Published: November 2003

Production of Al killed steel grades at Koverhar began in 1992 after revamping the casting machine no. 1. The refractories and equipment of caster no. 1 were planned to prevent reoxidation. However, nozzle clogging problems with impaired inclusion cleanliness were occasionally observed. In order to clarify the rôle of reoxidation in continuous casting, a research project was carried out with the Helsinki University of Technology. The whole casting sequences of 3 steel grades were scrutinized. The changes of steel composition from ladle to mold as well as tundish slag composition were systematically investigated. The starts of casting sequences, ladle changes and cast endings were especially examined. The effects of rice husk ash as the tundish cover and the carryover of ladle slag to the tundish were studied as well. The research project clearly revealed different reoxidation phenomena during the casting process. Exchange reactions between the steel and the tundish slag caused reduction of silicon and manganese oxides from the slag to the steel and oxidation of aluminium, eventually titanium, from the steel, respectively. These reactions, however, did not impair steel cleanliness, as oxide inclusions produced by the reactions were formed in the vicinity of the metal‐slag interface, and thus inclusions were readily removed to the slag. Nitrogen pick‐up was observed especially during the cast starts, indicating atmospheric reoxidation. It had, however, neither any notable influence on steel cleanliness nor on castability. Any tendency to clogging was not observed during the campaigns.
Study of chlorination of nickel silicate by gaseous chlorine and calcium chloride in the presence of active additives
Authors: Ilić Ilija , Stopić Srećko , Cerović Katarina , Kamberović Željko
Published: November 2003

The paper presents a thermodynamic analysis and experimental research on the kinetics of the chlorination of nickel silicate (2NiO×SiO2) by gaseous chlorine and calcium chloride without additives and in the presence of added C, BaS, S and NaCl, to intensify the process. The influence of temperature in the range from 673 up to 1223 K for various chlorination times has been studied. Additives increases the chlorination rate. The kinetics of the process were determined by the analysis of dependence of the nickel chlorination rate on time and temperature. It was established that nickel chlorination without additives is a chemically‐controlled reaction, and in the presence of added C, BaS, S and NaCl, a diffusion‐controlled reaction. As low‐grade ferrous nickel ores are of silicate type, the results obtained can find a significant applicable value in chlorination segregation treatments of given ores.
A study on the sulphide capacities of steelmaking slags
Authors: Nzotta M. M. , Andreasson M. , Jönsson P. , Seetharaman S.
Published: November 2003

This report is on the application of a mathematical model for the predictions of sulphide capacities of steelmaking slags. The model was verified earlier on laboratory scale. Predictions agreed well with experimental data. In this work, an attempt was made to calculate sulphide capacities from plant data (chemical analyses of steel and slag). Difficulty was encountered in determining the oxygen activity in the steel melt as well as the activity of alumina in the slag phase when calculating the sulphur distribution ratio. However, good agreement was obtained between predicted and experimentally determined sulphur distribution data, when the activity of oxygen in the metal phase was assumed to be 1×10−4 for the model calculations.
Thermodynamic analysis of inclusions in Ti‐deoxidised steels
Authors: Ruby‐Meyer Fabienne , Lehmann Jean , Gaye Henri
Published: November 2003

The precipitation of non‐metallic inclusions in Ti‐deoxidised steels is analysed with the multiphase equilibrium code CEQCSI which is based on the IRSID slag model. For that purpose, the slag model has been extended to systems containing titanium oxides, using data available in the literature, and validated with industrial results obtained on various steel grades. Applications concerning slag‐metal reactions in ladle metallurgy are described. 2 applications concerning inclusions in Ti‐deoxidised steels are also presented: (a) experimental study of the effect of steel contamination by magnesia refractory lining on the composition of oxide inclusions in a Ti‐deoxidised steel: there is a good correlation between analysed oxide compositions and compositions predicted by the model; (b) evaluation of the optimised steel composition to obtain Al2O3‐TiO2 inclusions during solidification for steels pertaining to the so‐called “metallurgy of oxides in steels”.
Effect of composition and thermomechanical processing on the ageing characteristic of copper‐bearing HSLA steel
Authors: Banerjee M. K. , Ghosh D. , Datta S.
Published: November 2003

3 alloys of copper‐bearing steels with or without boron have been studied in different thermomechanical controlled processing (TMCP) conditions. The influence of TMCP schedules onto the ageing behaviour in boron‐treated and boron‐free steels is examined. The structure property analysis of these steels is also carried out. It is found that when the finish rolling is carried out above Ar3, the steels direct cooled after TMCP are able to retain a higher amount of copper in solid, leading to higher ageing response. Boron is found to delay the precipitation of copper and the best ageing effect is recorded in B‐Cr steel.
Chloride removal from zinc ash
Authors: Şahin F. Çınar , Derin B. , Yücel O.
Published: November 2003

Zinc ash generated during the galvanising of steel and iron contains appreciable amount of zinc in the form of metallic zinc, zinc oxide, zinc chloride and zinc oxy‐chloride. The chloride removal from zinc ash is very important for producing zinc metal or zinc oxide. In this study, 3 different types of ash containing varying levels of chloride have been subjected, to 3 types of treatments. Various parameters, such as roasting temperature and time, alkali washing temperature and time, solid/liquid ratio and alkali addition, have been studied. Based on the laboratory‐scale experiments, large‐scale operations have been carried out for chloride removal from the zinc ash. The results indicate that pyrometallurgical roasting followed by alkali wash treatment with sodium carbonate of the ash will be useful in the removal of chloride from zinc ash.
Study of the effect of some process parameters on powder injection refining by a mathematical model
Authors: Koria Satish C. , Dutta Rajiv
Published: November 2003

Influence of some process parameters like carried‐over slag, top flux, bath stirring intensity and residence time of the flux on the refining ability of the injected flux by a mathematical model are studied. Refining is considered to occur both by transitory and permanent contact mechanisms. The differential equation is solved by the finite difference method for a wide range of amounts of carry‐over slag, composition and amounts of flux, bath stirring intensity and residence time of the flux. The refining curves and the separate contribution of transitory and permanent rate to total rate are presented and discussed as a function of the aforesaid parameters. The model is used to analyze the desulphurizing reaction in the presence of slag carried‐over from the previous steelmaking unit. It is found that for only the permanent contact desulphurizing reaction, the type, composition and amount of flux is less critical than stirring gas rate to achieve a high desulphurization % in the presence of carried‐over slag. For injection desulphurization, residence time of the flux, fraction of particles carried by the bubbles and the partition coefficient, are important parameters controlling the transitory contribution to the total rate in relation to type, composition and amount of flux. High desulphurization can be obtained both by permanent contact and injection method. It is asserted that the selection of any one method would depend more on locally available facilities like powder injection system, ladle free board height and availability of ladle with the stirring gas injection device.
High‐temperature meltdown characteristics of DRI‐flux mixture in a melter‐gasifier
Authors: Lee Young Jae , Cho Chong Min
Published: November 2003

The slag formation mechanism in the melter‐gasifier was examined by the meltdown test for DRI‐additive‐ash mixed bed under load and by analysis for the slag taken from the actual furnace of the two‐step ironmaking process. For the slag phase analyses, chemical analysis, SEM‐EDS and XRD pattern analysis were employed. The primary slag originated from the gangue in DRI was homogeneous. Partially‐melted secondary slag consisting of dicalcium silicate with dissolved FeO was formed under rather higher CaO/SiO2 basicity compared to that of tapped slag. Then, these slags reacted with bottom ash resulting in the homogeneous tertiary slag with the dissolved FeO. Finally, the final slag, similar to tapped slag, was collected on the top of the metal pool. The slag had CaO/SiO2 slightly greater than 1 in the hearth of the melter‐gasifier.
Theoretical and practical study of thermal stratification and drainage in ladles of different geometry
Authors: Grip Carl Erik , Jonsson Kjell Olof , Eriksson Sven , Jonsson Lage , Jönsson Pär , Pan Yuhua
Published: November 2003

SSAB Luleå, SSAB Oxelösund, MEFOS and Luleå University of Technology have cooperated in developing theoretical models for prediction of thermal stratification and drainage in steel ladles. Predicted results have been verified by measurements done in production ladles with heat weighs of 105 and 200 tonne as well as in a 7‐tonne pilot plant ladle. The thermal stratification was measured by thermocouples at different depths. The drainage flow was studied by means of tracer experiments. Numerical simulation models of the steel flow were developed for 7, 105 and 200 tonne steel ladles. The agreement between predictions and measurements was found to be good. The conclusion is that CFD simulation gives a good prediction of stratification and drainage flows in production ladles.
Deadman and hearth phenomena in the blast furnace
Authors: Raipala Kalevi
Published: November 2003

The deadman and hearth phenomena play key roles in hot metal quality. The condition of the deadman has a strong influence on hot metal temperature and composition. When hot metal can flow freely towards the tap hole and the deadman is a porous coke bed, then conditions are good for desulphurization and carbonization of hot metal. The deadman has also a significant effect on lining wear and campaign length by controlling hot metal flow in the hearth.

Particular observations of hearth behaviour have been made during the last six years. Data of blast furnace operation have been studied and compared with hearth condition, hot metal and slag properties. Several methods to control the dead man have been experienced in Koverhar. The best method so far is to use coarse coke with low reactivity and to control burden distribution with movable armour. Response times to hearth control actions are painfully long – four weeks or even more.

A set of indications about deadman condition have been collected. Hearth bottom temperatures are used to monitor the location of 1150°C isotherm. Rod tests have been used to sound the dead man hardness and to measure the length of the raceways.

Interesting dependence between deadman condition, reduction of iron, hot metal sulphur and carbon and hot metal temperature has been found. This knowledge has been practised resulting in remarkable improvement of hot metal quality and hearth condition.
Hydromechanical deep drawing
Authors: Damborg F. F. , Jensen M. R.
Published: November 2003

An experimental investigation on the control of process parameters for the hydromechanical deep drawing of mild steel and an aluminium alloy with special attention to control of the blank holder force (BHF) is carried out. The effect of the counter pressure in the hydromechanical deep drawing process is investigated in combination with different constant levels of the BHF. Differences in strains obtained for the conventional and hydromechanical deep drawing process as well as process limitations are presented. An attempt to improve partial quality by control of the packing effect between the blank and draw die by varying the blank holder force according to the punch force have been explored. A closed‐loop control for the BHF is implemented, but no significant effect could be found due to limitations of the BHF range and delayed response of the pneumatic‐based BHF system.
CFD analysis of the turbulent flow in ladles and the alloying process during tapping of steel furnaces
Authors: Laux Harald , Johansen Stein Tore , Berg Halvard , Klevan Ole Svein
Published: November 2003

Alloying of steel during tapping from BOF and EAF furnaces has recently been studied by computational fluid dynamics (CFD). The original paper has focused on the results of a comprehensive parameter study where alloy type, size, addition time, and other parameters were varied. The present work focuses on the CFD methodology that has been used to simulate the alloying process. In short, the CFD analysis of the dissolution process in the ladle combines a single‐phase turbulent flow field computation with the tracking of 1000 stochastic particle paths. In the original paper, the analysis was conducted in 2‐dimensional axisymmetric models of the ladle geometries, however, in the present work, the numerical analysis is extended to 3 dimensions. Comparisons are made between results for 3‐ and 2‐dimensional computations. It is shown that the analysis can be conducted in 2 dimensions with only small losses of accuracy. Moreover, it is shown that it is sufficient to obtain statistical averages from 1000 particle tracks. We discuss the simplifying assumptions of the previous work, where we focus on the gas that is entrained by the plunging steel jet. We show simulation results obtained from a CFD methodology that allows the computation of flow fields that include the effect of entrained gas bubbles. Finally, the CFD methodology that is presented and discussed in this work seems to be a useful tool to optimize the alloying process in a steelshop. It can help the steelmaker to decide how, when, and where to add what alloy particles. It also allows estimation of a feeding rate for optimal yield of the alloying particles.
Technology for an increased portion of fine ore in the COREX® process
Authors: Schenk J. L. , Wallner F. , Kepplinger W. L. , Shin M. K. , Cho M. Y. , Lee I. O.
Published: November 2003

COREX® is a smelting reduction process based on lumpy ore and coal. The fine‐ore portion in the ore burden charged into the reduction shaft is limited to about 5% to secure uniform gas penetration and stable operation of the reduction shaft. Fine‐ore injection into the COREX® process, as it has been developed jointly by VAI (VOEST‐ALPINE Industrieanlagenbau GmbH, Austria), RIST (Research Institute of Industrial Science and Technology, Korea) and POSCO (Pohang Iron and Steel Company Ltd., Korea) since 1992, offers the potential to use up to 25% of fine‐ore and iron‐containing fines in the COREX® process, which leads to an increased flexibility, to an enlarged capacity, and to improved economics of the COREX® process. Additionally, it allows the use of ore fines from material handling and the direct use of iron‐bearing fines of the metallurgical plant. Lab scale, cold and hot bench scale tests were used to assess the physical and the metallurgical behaviour of ore fines under process conditions. An industrial‐scale pilot plant designed according to the findings of these tests was attached to the COREX® C‐2000 plant of POSCO. The results of test campaigns on this plant are discussed and the economic benefits for the COREX® process are depicted.
Problems Associated with the Clinical Use of Proton Pump Inhibitors
Authors: Gillen Derek , McColl Kenneth E. L.
Published: November 2003

Abstract: Proton pump inhibitors have proven to be important in the treatment of acid/peptic diseases. However, their therapeutic uses have extended over time, which may alter their risk:benefit ratio. Significant rebound acid hypersecretion has been demonstrated, which persists for at least two months. Its clinical significance remains unknown. Enhanced oxyntic gastritis may be responsible for the increased acid suppressive effects of proton pump inhibitors in H. pylori‐infected patients. It remains unclear whether either H. pylori eradication or diminishing rates of infection in the developed world will therefore decrease the efficacy of proton pump inhibitors. Problems with carcinoids in rodents have not been found in man. However, the consequences of very long‐term use of proton pump inhibitors remain unknown. Similarly, the development of atrophic gastritis in H. pylori‐positive patients treated with proton pump inhibitors, with the long‐term concern of gastric carcinoma development, remains controversial.
Genotoxic Effects of the Alkaloids Harman and Harmine Assessed by Comet Assay and Chromosome Aberration Test in Mammalian Cells in vitro
Authors: Boeira Jane M. , Da Silva Juliana , Erdtmann Bernardo , Henriques João A. P.
Published: November 2003

Abstract: Harman and harmine are β‐carboline alkaloids which are present in plants widely used in medical practice, in beverages used for religious purposes in Brazil, as well as in tobacco smoke and over cooked food. In view of the controversial results observed in the literature about the mutagenic effects of these alkaloids, we studied their cytotoxic and genotoxic effects in V79 Chinese hamster lung fibroblasts in vitro using single‐cell gel assay, Comet assay, either in the presence or in absence of an exogenous metabolic activation system (S9‐mix), and by the chromosome aberration test without S9‐mix. Harmine was more cytotoxic than harman. Both harman and harmine increased aberrant cell frequency and induced DNA damage by the Comet assay. These results suggest that harman and harmine are genotoxic in V79 cells, probably as a consequence of their ability to induce DNA strand breaks.
Copper, Ceruloplasmin and Superoxide Dismutase (SOD1) in Patients with Down's Syndrome
Authors: Tórsdóttir Gudlaug , Kristinsson Jakob , Hreidarsson Stefán , Snaedal Jón , Jóhannesson Torkell
Published: November 2003

Abstract: The aim of this study was primarily to investigate whether similar signs of copper dyshomeostasis occur in dementia with age in Down's syndrome as previously found in Alzheimer's disease. Copper was accordingly determined in plasma, ceruloplasmin concentration in serum, ceruloplasmin oxidative activity and ceruloplasmin specific oxidative activity (activity related to mass) in serum, and superoxide dismutase (SOD1) in erythrocytes in 35 (27 males, 8 females) 18–53 years old (average 37 years) patients with Down's syndrome (Down's patients) and their age‐ and gender‐matched controls. SOD1 activity was on an average almost 50% higher in the patients than in their controls but the evidence of a causal relationship between increased SOD1 activity and Down's syndrome appears at best equivocal. Copper and ceruloplasmin levels and ceruloplasmin activities were similar in the patients and their controls. Ceruloplasmin and copper levels increased significantly with age in the patients but not in the controls. Ceruloplasmin activities or SOD1 activity did not change significantly with age, neither in the patients nor in the controls as whole groups. When SOD1 activity and ceruloplasmin activities of the oldest in the patients group (40 years or older) were compared with those of the younger patients, respectively, SOD1 activity and specific oxidative activity, but not ceruloplasmin oxidative activity were found to decrease significantly with age. The results thus suggest that development of dementia in Down's patients with age is paralleled with decrease in SOD1 activity and specific oxidative activity but not with decrease in ceruloplasmin oxidative activity itself as was also found in Alzheimer's patients.
Calcium Supplementation Efficiently Reduces Lead Absorption in Suckling Rats*
Authors: Varnai Veda Marija , Piasek Martina , Blanus˘a Maja , Sarić Marijana Matek , Šimić Diana , Kostial Krista
Published: November 2003

Abstract: The effect of calcium supplementation on tissue lead was evaluated in suckling Wistar rats. Such data are not yet available in the literature. The following artificial feeding regimen was used for calcium supplementation: cow's milk by addition of 1%, 3% or 6% Ca as CaHPO4×2H2O suspension to increase the daily calcium intake about 1.4, 2 or 3 times above control values. Artificial feeding was applied during 7 hr each day for nine consecutive days (from day 6 through 15 after birth). The effect of such treatment on lead absorption and elimination was evaluated in two separate experiments: calcium supplementation during oral lead exposure (as acetate; daily dose 2 mg Pb/kg body wt.; total Pb dose 18 mg/kg body wt.) or after a single intraperitoneal lead administration (5 mg/kg body wt.). At the end of experiments, lead in tissues (liver, kidneys, brain and carcass), and essential elements (Ca, Fe, Zn, Cu) were analysed by atomic absorption spectrometry. Calcium supplementation caused a statistically significant decrease of lead in all tissues of sucklings orally exposed to lead. This decrease was dose‐related being about 1.3, 1.5 and 2 times lower in groups supplemented with 1%, 3%, or 6% calcium compared to controls, respectively. Increased calcium intake had no effect on incorporated lead after parenteral lead exposure. Calcium supplementation increased carcass calcium and had no effect on trace elements in tissues, pups' general appearance and body weight gain. It is concluded that higher calcium intake might be a way of efficient reduction of lead absorption during the suckling period.
Prevention of Disease with Pharmaceuticals
Authors: Vainio Harri , Bianchini Franca
Published: November 2003

Abstract: The idea that diseases such as cardiovascular disease and cancer can be prevented by taking a ‘pill’ is attractive to many people. Chemoprevention is an established method in the primary and secondary prevention of cardiovascular disease such as myocardial infarct and stroke. Clinical trials have demonstrated beyond reasonable doubt that both fatal and non‐fatal coronary events and strokes can be prevented. Antihypertensive drugs have been shown to be effective through clinical trials in preventing myocardial infarctions, stroke and other cardiovascular morbidity and mortality. Statins are commonly used to lower the blood cholesterol concentration, and aspirin is widely used to prevent occlusive vascular disease. Aspirin and other non‐steroidal antiinflammatory agents have shown promise in the chemoprevention of colorectal cancer. While observational epidemiological studies have consistently suggested that diets rich in antioxidants such as β‐carotene might be useful in preventing coronary heart disease and cancer, the published reports of randomized trials clearly indicate that β‐carotene supplements are of no value in persons of high risk for such conditions. Although the chemoprevention of cancer is decades behind that of cardiovascular disease, there is no reason to believe that progress in cancer chemoprevention will differ substantially from that in cardiovascular disease. Better understanding of the molecular steps critical to carcinogenesis should open new avenues for cancer chemoprevention.
The Ototoxic Effects Induced in Rats by Treatment for 12 Weeks with 2‐Butenenitrile, 3‐Butenenitrile and cis‐2‐Pentenenitrile
Authors: Gagnaire François , Marignac Brigitte , Ban Masarin , Langlais Cristina
Published: November 2003

Abstract: Brainstem auditory and visual evoked‐potentials were studied in male Sprague‐Dawley rats during subchronic oral treatment with three unsaturated aliphatic nitriles. The rats were given, by gastric intubation, doses of 10, 20 and 40 mg  ·  kg−1 3‐butenenitrile (allyl cyanide) and 25, 50 and 100 mg  ·  kg−1 of either cis/trans‐2‐butenenitrile (crotononitrile) or cis‐2‐pentenenitrile once a day, 5 days per week for 12 weeks. Oral administration of the three unsaturated nitriles produced deafness and absence of reaction when the animals were subject to droptest. Rats in the high dosage groups exhibited a complete disappearance of the five waves of the auditory evoked‐potentials. There was a decrease in the amplitudes of the 2nd component of the auditory evoked‐potentials. Those changes were not reversible at the 8th week of the recovery period. A dose‐dependent effect on inner and outer hair cells was observed in the organ of Corti. The basal part of the cochlea was the most affected. Though no measurements were made of systemic exposure, a tentative ranking of decreasing ototoxicity of these three unsaturated nitriles might be proposed based on the electrophysiological deficiencies and histological losses observed: 3‐butenenitrile >cis‐2‐pentenenitrile >cis/trans‐2‐butenenitrile. Moreover, rats treated with those nitriles showed a corneal opacity as well as a decrease in the amplitude and lengthening of the peak latencies of the visual evoked‐potentials. These latter changes were reversible by the end of the 8th week of the recovery period and appeared to be related to the opacity of the cornea.
Immunolocalisation of Cytochrome P‐450 3A Enzymes in Human Breast Carcinoma: Relationship with Tumour Differentiation and Steroid Receptors
Authors: Galant Christine , Gala Jean‐Luc , Van Den Berge Véronique , Berlière Martine , Haumont Esther , Horsmans Yves
Published: November 2003

Abstract: Cytochrome P‐450 3A enzymes belong to the most abundant subfamily of the cytochrome P‐450 system. They are predominantly found in the liver where they metabolize numerous drugs and endogenous substances such as oestrogens. However, they are also expressed by normal and tumoural extrahepatic tissues. Accordingly, immunolocalization was assessed in malignant breast tumours (n=32) and normal counterparts, by using a monoclonal antibody that recognizes all human CYP3A proteins. We investigated a potential relation between expression of CYP3A protein expression, the degree of tumour differentiation assessed by the histological grade and the proliferation index assessed by Ki‐67 immunostaining. Immunodetection of CYP3A was observed in 27 of the 32 tumours analyzed (84%). A focal staining was also observed in the adjacent normal breast tissue in 33% of the samples, but expression was always fainter than in tumours. A significant negative association was found between CYP3A and the proliferation index, but there was no relation with receptor status or tumour differentiation. While CYP3A protein expression can be found in normal breast tissues, these data highlight higher and more frequent CYP3A in malignant breast cells. Such expression in malignant breast cells appears inversely related to the proliferation index whereas no relation is found with tumour differentiation.
Apomorphine‐Induced Aggressive Behaviour in para‐Chlorophenylalanine‐Treated Male Rats: Implications to Brain [3H]Ketanserin Binding and Monoamine Content
Authors: Matto Vallo , Vaarmann Annika , Allikmets Lembit
Published: November 2003

Abstract: The aim of this study was to investigate the role of serotoninergic neurotransmission and the effect of acute para‐chlorophenylalanine (350 mg/kg, intraperitoneally) treatment on apomorphine‐induced aggressive behaviour in adult male Wistar rats. In addition, [3H]ketanserin binding and monoamine content were studied. Repeated administration of apomorphine (1.0 mg/kg, subcutaneously, once daily for two weeks) gradually induced aggressive behaviour. Acute p‐chlorophenylalanine treatment down‐regulated the [3H]ketanserin binding and reduced over 90 per cent the content of serotonin and 5‐hydroxyindolacetic acid. In a half of the p‐chlorophenylalanine‐treated animals, the aggressive behaviour was suppressed, while there was no difference in [3H]ketanserin binding or monoamine content between the p‐chlorophenylalanine treated aggressive and non‐aggressive animals. In conclusion, the acute p‐chlorophenylalanine treatment attenuates the aggressiveness only in half of the animals, while the latter phenomenon is independent on the CNS monoamine content or [3H]ketanserin binding.
Effects of N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine (DSP4) on α2‐Adrenoceptors which Regulate the Synthesis and Release of Noradrenaline in the Rat Brain
Authors: Prieto Mónica , Giralt M. Teresa
Published: November 2003

Abstract: N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine (DSP4) induces a degeneration of noradrenergic axons originating in the locus coeruleus. The sensitivity of α2‐adrenoceptors which regulate the synthesis and release of noradrenaline was investigated in three brain regions which receive an unequal innervation from locus coeruleus, 21 days after DSP4 (50 mg/kg) administration. After giving treated rats a dopa decarboxylase inhibitor, the in vivo tyrosine hydroxylase activity and the tissue concentrations of noradrenaline were also evaluated. Relevant reductions of noradrenaline levels were found in hippocampus and parietal cortex (91% and 77.5%, respectively; P<0.001) together with a less pronounced reduction in hypothalamus (32%, P<0.01). The administration of the neurotoxin led to decreases of the basal tyrosine hydroxylase activity, determined as the accumulation of 3,4‐dihydroxyphenylalanine, in hippocampus and parietal cortex (75% and 50.5%, respectively; P<0.001), but not in hypothalamus. The inhibitory effect of clonidine on tyrosine hydroxylase activity was markedly reduced in hippocampus of rats treated with DSP4 (10±5% vs 57±3% in the control group, P<0.001) but was not changed in parietal cortex and hypothalamus. Moreover, in hippocampus, a lack of functionality of the α2‐adrenoceptors which regulate K+‐evoked [3H]noradrenaline release was determined. However, in cortical synaptosomes the concentration‐effect curve for the oxymetazoline shifted to the right. The administration of the neurotoxin did not modify the inhibitory effects of the agonist in hypothalamus. These results support the previously described selectivity of DSP4 for noradrenergic terminals arising from locus coeruleus and suggest a more severe lesioning of the hippocampus than the parietal cortex.
Low‐dose broad‐band UVA in morphea using a new method for evaluation
Authors: El‐Mofty M. , Zaher H. , Bosseila M. , Yousef R. , Saad B.
Published: November 2003

Until recently, various therapies for localized scleroderma have been used with limited success. Recently, phototherapy, with or without psoralen, was proposed as a successful treatment modality. The aim of this study was to evaluate the effect of broad‐band low‐dose ultraviolet A (UVA) phototherapy in patients with localized scleroderma, using a new method for evaluation. Twelve patients complaining of morphea were exposed to UVA irradiation at a dose of 20 J/cm2 3 times per week for 20 sessions. Selected covered plaques served as internal controls. The efficacy of therapy was judged clinically by sequential inspection and palpation. In biopsy specimens from exposed and covered plaques stained with hematoxylin and eosin (H & E) and Masson trichrome stains, the concentration of collagen per dermal surface area was measured with the use of a computerized image analyzer. All patients reported remarkable softening of skin lesions, confirmed by sequential palpatory assessment. A significant reduction in the mean concentration of collagen per surface area was detected in the plaques exposed to UVA (the P value being 0.007, P<0.01), whereas in the covered plaques the difference was not statistically significant (the P value being 0.10, P>0.05). The conclusion is that low‐dose broad‐band UVA phototherapy is a very effective and safe treatment modality for localized scleroderma.
Sunscreen application technique in photosensitive patients: a quantitative assessment of the effect of education
Authors: Azurdia R. M. , Pagliaro J. A. , Rhodes L. E.
Published: November 2003

Photosensitive patients are known to apply insufficient sunscreen and to neglect several prominently exposed skin sites. The aim of this study was to use fluorescence spectroscopy to assess the effect of education on sunscreen application technique in the short and longer term. Six patients with longstanding photosensitivity conditions were asked to apply an intrinsically fluorescent sunscreen to exposed skin, as they normally would on a sunny day. Detailed fluorescence measurements were taken from 70 sites on the head, neck and arms. Using the previously established dose‐response relationship for cream fluorescence, measurements were converted to equivalent thicknesses of cream. Patients were told the results of their sunscreen application assessment and deficiencies in technique were highlighted. Following education, application technique was reassessed twice, after intervals of 2 weeks and 6 months. Before education, sunscreen application was poor with inadequate amounts applied, and prominently exposed sites including ears, temples and neck often missed. At 2 weeks following education, improved application was seen at all sites, and the improvement was sustained at 6 months. Overall, education improved sunscreen application from a baseline median sunscreen thickness of 0.11 mg/cm2 to 0.82 mg/cm2 at 2 weeks and 1.13 mg/cm2 at 6 months (P<0.0001). Notably, median sunscreen thickness on the face improved from a baseline of 0.33 mg/cm2 to 1.51 mg/cm2 at 6 months. These findings demonstrate the importance of careful instruction to patients concerning sunscreen application technique; failure to do this may result in overconfidence in the ability of a sunscreen to protect. The next step is to assess a larger number of photosensitive patients with different diagnoses and to see whether improved technique correlates with improvement in clinical features.
The wrist is a reliable body site for personal dosimetry of ultraviolet radiation
Authors: Thieden E. , Ågren M. S. , Wulf H. C.
Published: November 2003

The purpose of this study was to investigate the reliability of measuring solar ultraviolet radiation (UVR) doses with personal UV dosimeters worn on the wrist. Individual solar UVR exposure was measured over one day under standardised conditions (One‐day Beach Study), and over an extended period of time with varying UV exposure and activities (Holiday Study). Dosimeters of a UV‐sensitive spore‐film filter type (VioSpor®) were placed on the right wrist and on the top of head of the test subjects. The wrist was chosen as being a practical position for personal dosimetry and the head position as an internal control for maximal personal UV doses. The One‐day Beach Study took place in the vicinity of Copenhagen in June 1998 over 5 h and included 11 subjects. The Holiday Study included 9 subjects during a period with a mean of 14 days in Scandinavia and Europe from June to September 1998. The head position received the highest UV dose in all subjects in both studies. In both studies, despite considerable individual variation, the mean wrist dose was the same (50%) of that received on the head, although the wrist dose correlated significantly with head dose (P<0.01) only in the Holiday Study. We conclude that the wrist position is a practical and convenient body site for personal dosimetry, yielding reliable results in group exposure studies.