bluuebunny/crossref_metadata_2025 huggingface dataset:
Tropospheric bromine chemistry and its impacts on ozone: A model study
Authors: Yang Xin , Cox Richard A. , Warwick Nicola J. , Pyle John A. , Carver Glenn D. , O'Connor Fiona M. , Savage Nick H.
Published: December 2005

An off‐line three‐dimensional tropospheric chemical transport model, parallel–Tropospheric Off‐Line Model of Chemistry and Transport (p‐TOMCAT), has been extended by incorporating a detailed bromine chemistry scheme that contains gas‐phase reactions and heterogeneous reactions on both cloud particles and background aerosols. Bromine emission from bromocarbon photo‐oxidation and from sea‐salt bromine depletion and bromine removal through dry and wet deposition are included. Using this model, tropospheric bromine chemistry and ozone budgets are studied. The zonal mean of the inorganic gas‐phase bromine compounds (Brx) is calculated to be high (4–8 pptv) in the lower troposphere of the midlatitudes to high latitudes in each hemisphere, with decreasing trends with altitude (down to ∼2–3 pptv in the upper troposphere). The lowest Brx (<2 pptv) is over low latitudes, corresponding to small sea‐salt Br emission and a high rate of precipitation scavenging. A mean lifetime of ∼5 days is obtained for the tropospheric Brx. Sea‐salt emission plays the dominant role in total Brx in the lower troposphere while organic Br‐containing compounds are important in upper layers. High daytime BrO mixing ratios (>1 pptv) are found over the high‐latitude ocean surface, corresponding to high tropospheric column BrO values of up to 1.6 × 1013 molecules/cm2 in the monthly mean. The addition of bromine chemistry to the model leads to a reduction in tropospheric ozone amounts by 4–6% in the Northern Hemisphere and up to ∼30% in the Southern Hemisphere high latitudes. The net ozone loss depends not only on total Brx, but also on solar irradiance, especially at high latitudes. The hydrolysis reaction of bromine nitrate, which occurs on cloud and aerosol surfaces (BrONO2 + H2Oaq → HOBr + HNO3), has a significant influence on ozone chemistry through its effect on NOx as well as on reactive BrO and Br.
Correlations and emission ratios among bromoform, dibromochloromethane, and dibromomethane in the atmosphere
Authors: Yokouchi Y. , Hasebe F. , Fujiwara M. , Takashima H. , Shiotani M. , Nishi N. , Kanaya Y. , Hashimoto S. , Fraser P. , Toom‐Sauntry D. , Mukai H. , Nojiri Y.
Published: December 2005

Bromoform (CHBr3), dibromochloromethane (CHBr2Cl), and dibromomethane (CH2Br2) in the atmosphere were measured at various sites, including tropical islands, the Arctic, and the open Pacific Ocean. Up to 40 ppt of bromoform was observed along the coasts of tropical islands under a sea breeze. Polybromomethane concentrations were highly correlated among the coastal samples, and the ratios CH2Br2/CHBr3 and CHBr2Cl/CHBr3 showed a clear tendency to decrease with increasing CHBr3 concentration. These findings are consistent with the observations that polybromomethanes are emitted mostly from macroalgae whose growth is highly localized to coastal areas and that CHBr3 has the shortest lifetime among these three compounds. The relationship between the concentration ratios CHBr3/CH2Br2 and CHBr2Cl/CH2Br2 suggested a large mixing/dilution effect on bromomethane ratios in coastal regions and yielded a rough estimate of 9 for the molar emission ratio of CHBr3/CH2Br2 and of 0.7 for that of CHBr2Cl/CH2Br2. Using these ratios and an global emission estimate for CH2Br2 (61 Gg/yr (Br)) calculated from its background concentration, the global emission rates of CHBr3 and CHBr2Cl were calculated to be approximately 820(±310) Gg/yr (Br) and 43(±16) Gg/yr (Br), respectively, assuming that the bromomethanes ratios measured in this study are global representative. The estimated CHBr3 emission is consistent with that estimated in a very recent study by integrating the sea‐to‐air flux database. Thus the contribution of CHBr3 and CHBr2Cl to inorganic Br in the atmosphere is likely to be more important than previously thought.
Activation of ERK1/2 by extracellular nucleotides in macrophages is mediated by multiple P2 receptors independently of P2X7‐associated pore or channel formation
Authors: Da Cruz Cristiane Monteiro , Ventura Ana Lúcia Marques , Schachter Julieta , Costa‐Junior Helio Miranda , Da Silva Souza Hercules Antonio , Gomes Fernanda Ramos , Coutinho‐Silva Robson , Ojcius David M , Persechini Pedro Muanis
Published: December 2005

Macrophages express several P2X and P2Y nucleotide receptors and display the phenomenon of ATP‐induced P2X7‐dependent membrane permeabilization, which occurs through a poorly understood mechanism. Several P2 receptors are known to be coupled to the activation of mitogen‐activated protein kinases (MAPKs) and Ca2+signaling.

Here, we use macrophages to investigate the phosphorylation of extracellular signal‐regulated kinases 1 and 2 (ERK1/2) by nucleotides and the involvement of MAPKs and intracellular Ca2+concentration in ATP‐induced membrane permeabilization.

Short‐term (5 min) pre‐exposure to oxidized ATP (oATP), a P2X7antagonist that does not inhibit P2X7‐associated inward currents or membrane permeabilization, inhibits the activation of ERK1/2 by ATP, ADP, the P2X7agonist 2′‐3′‐O‐(4‐benzoylbenzoyl)‐ATP (BzATP), but not by UTP and UDP. We conclude that macrophages display several P2Y receptors coupled to the ERK1/2 pathway and that oATP antagonizes the action of purine nucleotides, possibly binding to P2X7and/or other purine‐binding P2Y receptors.

We also show that BzATP and ATP activate ERK1/2 by two different pathways since ERK1/2 activation by BzATP, but not by ATP, is blocked by the tryrosine kinase inhibitor, genistein, and the Src protein kinase inhibitor, tyrphostin. However, the activation of ERK1/2 by ATP is blocked by the protein kinase C (PKC) inhibitor, chelerythrine chloride. Under the same conditions, membrane permeabilization is not blocked by genistein, tyrphostin, or chelerythrine chloride, indicating that tyrosine kinase, Src protein kinase, and PKC are not required for pore opening.

Membrane permeabilization is independent of ERK1/2 activation since chelerythrine, or short‐term exposure to oATP or PD98059, efficiently block ERK1/2 activation without inhibiting membrane permeabilization. In addition, membrane permeabilization is not inhibited by SB203580 and SB202190, two inhibitors of p38 MAPK, nor by intracellular BAPTA, which blocks ATP‐induced Ca2+signals.

These results suggest that multiple P2 receptors lead to ERK1/2 activation, that ligation of the same receptors by agonists with different affinities can lead to differential stimulation of separate pathways, and that MAPKs and intracellular Ca2+fluxes are independent of P2X7‐associated pore formation.

British Journal of Pharmacology(2006)147, 324–334. doi:10.1038/sj.bjp.0706559
Altered responsiveness of the guinea‐pig isolated ileum to smooth muscle stimulants and to electrical stimulation after in situ ischemia
Authors: Rodriguez Rodolfo , Ventura‐Martinez Rosa , Santiago‐Mejia Jacinto , Avila‐Costa Maria R , Fortoul Teresa I
Published: December 2005

We evaluated changes in contractility of the guinea‐pig isolated ileum, using intact segments and myenteric plexus‐longitudinal muscle (MPLM) preparations, after several times (5–160 min) of ischemia in situ.

Intestinal ischemia was produced by clamping the superior mesenteric artery. Ischemic and nonischemic segments, obtained from the same guinea‐pig, were mounted in organ baths containing Krebs‐bicarbonate (K‐B) solution, maintained at 37°C and gassed with 95% O2/5% CO2. The preparations were allowed to equilibrate for 60 min under continuous superfusion of warm K‐B solution and then electrically stimulated at 40 V (0.3 Hz, 3.0 ms). Thereafter, complete noncumulative concentration–response curves were constructed for acetylcholine (ACh), histamine (HIS), potassium chloride (KCl), and barium chloride (BaCl2). Mean Emax (maximal response) values were calculated for each drug.

Our study shows that alterations of chemically and electrically evoked contractions are dependent on ischemic periods. It also demonstrates that contractile responses of ischemic tissues to neurogenic stimulation decreases earlier and to a significantly greater extent than the non‐nerve mediated responses of the intestinal smooth muscle. Contractile responses to smooth muscle stimulants were all similarly affected by ischemia. Electron microscopy images indicated necrotic neuronal death. The decrease in reactivity of ischemic tissues to electrical stimulation was ameliorated by dexrazoxane, an antioxidant agent.

We consider the guinea‐pig isolated ileum as a useful model system to study the processes involved in neuronal ischemia, and we propose that the reduction in maximal responses to electrical stimulation is a useful parameter to study neuroprotection.

British Journal of Pharmacology (2006) 147, 371–378. doi:10.1038/sj.bjp.0706618
Adenosine‐ and hypoxia‐induced dilation of human coronary resistance arteries: evidence against the involvement of KATP channels
Authors: Lynch Fiona M , Austin Clare , Heagerty Anthony M , Izzard Ashley S
Published: December 2005

The ATP‐sensitive potassium (KATP) channel may be an important mediator of metabolic dilation in the human coronary circulation. As adenosine and hypoxia are considered to be major mediators of metabolic dilation in the coronary circulation, we investigated the effect of glibenclamide (a KATP channel blocker) on adenosine and hypoxic dilation of human coronary resistance arteries, with myogenic tone, in vitro.

Vessels were dissected from the atrial appendage from consenting patients and studied in vitro using a pressure arteriograph system. Segments of coronary resistance artery were pressurized to 60 mmHg and the vessels studied developed spontaneous myogenic tone.

The KATP opener pinacidil (final conc. 5 × 10−6 M) resulted in dilation, which was completely reversed by 5 × 10−6 glibenclamide (84±14 vs −10±9%, pinacidil and pinacidil plus glibenclamide, respectively, P=0.009, n=5).

Adenosine (final conc. 10−5 M) resulted in dilation, glibenclamide (5 × 10−6 and 10−5 M) was without effect (118±12 vs 104±16% adenosine and adenosine plus 10−5 glibenclamide, respectively, n.s., n=4).

Hypoxia (8±3 mmHg O2) resulted in a dilation that reversed when normoxic conditions were restored (60±9 vs 3±11% hypoxia and post‐hypoxia, respectively, P=0.014, n=3). The hypoxic dilation was not affected by glibenclamide (63±14 vs 55±6% hypoxia and hypoxia plus glibenclamide, respectively, n.s., n=4). In a further series of experiments, vessels were incubated with glibenclamide (5 × 10−6) prior to a hypoxic challenge; again, glibenclamide was without effect on the hypoxic dilation (−0.008±2 vs 95±3% glibenclamide and glibenclamide plus hypoxia, respectively, P=0.0005, n=3).

These data demonstrate that glibenclamide is without effect on both adenosine and hypoxic dilation of human coronary resistance arteries with myogenic tone, from the right atrial appendage in vitro. Our findings suggest that the KATP channel is unlikely to be a major mediator of metabolic dilation in these arteries.

British Journal of Pharmacology (2006) 147, 455–458. doi:10.1038/sj.bjp.0706622
Phylogeny and host associations of the fur-mite subgenus Listrophoroides (sensu stricto) Hirst (Acari:Atopomelidae) with an intriguing example of synhospitality on rats of the genus Maxomys
Authors: Bochkov Andre V. , OConnor Barry M.
Published: December 2005

Phylogenetic relationships among species of the parasitic mite subgenus Listrophoroides Hirst (Atopomelidae), fur-mites of Asian and African murine rodents, are reconstructed on the basis of parsimony analysis of morphological characters. This group is polyphyletic with respect to the outgroup, subgenera Marquesania Womersley and Paklistrophoroides Fain & Hyland. The mite phylogeny partially reflects the host phylogeny and several groups of closely related species associated with particular rodent groups are recognised. The rajah-group, with 34 species associated with rats of the genus Maxomys Sody, is most diverse. Most Maxomys species are parasitised by a single mite species but some of them harbour a complex of several species. Maxomys surifer (Miller), the most widespread species of the genus, hosts unique species combinations comprising 23 species in different parts of its range. This synhospitality is hypothesised to have originated during Pleistocene isolation of different host populations in multiple rain forest refugia. The current species complexes also reflect later host range expansions. These data are consistent with a hypothesis of Pliocene vicariance in some Sunda Shelf rodents and not with the traditional view of widespread migration across the Late Pleistocene Sunda Shelf. The rajah species-group is revised, 16 species are described as new and three are synonymised.
A revision of Herennia (Araneae:Nephilidae:Nephilinae), the Australasian 'coin spiders'
Authors: Kuntner Matjaž
Published: December 2005

The nephilid ‘coin spiders’ (Herennia Thorell) are known for their arboricolous ladder webs, extreme sexual size dimorphism and peculiar sexual biology. This paper revises Herennia taxonomy, systematics, biology and biogeography. The widespread Asian Herennia multipuncta (Doleschall) ( = H. sampitana Karsch, new synonymy; = H. mollis Thorell, new synonymy) is synanthropic and invasive, whereas the other 10 species are narrowly distributed Australasian island endemics: H. agnarssoni, sp. nov. is known from Solomon Islands; H. deelemanae, sp. nov. from northern Borneo; H. etruscilla, sp. nov. from Java; H. gagamba, sp. nov. from the Philippines; H. jernej, sp. nov. from Sumatra; H. milleri, sp. nov. from New Britain; H. oz, sp. nov. from Australia; H. papuana Thorell from New Guinea; H. sonja, sp. nov. from Kalimantan and Sulawesi; and H. tone, sp. nov. from the Philippines. A phylogenetic analysis of seven species of Herennia, six nephilid species and 15 outgroup taxa scored for 190 morphological and behavioural characters resulted in 10 equally parsimonious trees supporting the monophyly of Nephilidae, Herennia, Nephila, Nephilengys and Clitaetra, but the sister-clade to the nephilids is ambiguous. Coin spiders do not fit well established biogeographic lines (Wallace, Huxley) dividing Asian and Australian biotas, but the newly drawn ‘Herennia line’ suggests an all-Australasian speciation in Herennia. To explain the peculiar male sexual behaviour (palpal mutilation and severance) known in Herennia and Nephilengys, three specific hypotheses based on morphological and behavioural data are proposed: (1) broken embolic conductors function as mating plugs; (2) bulb severance following mutilation is advantageous for the male to avoid hemolymph leakage; and (3) the eunuch protects his parental investment by fighting off rival males.
Dysregulated Cytokine Metabolism, Altered Hepatic Methionine Metabolism and Proteasome Dysfunction in Alcoholic Liver Disease
Authors: McClain Craig , Barve Shirish , Joshi‐Barve Swati , Song Zhenyuan , Deaciuc Ion , Chen Theresa , Hill Daniell
Published: December 2005

Abstract: Alcoholic liver disease (ALD) remains an important complication and cause of morbidity and mortality from alcohol abuse. Major developments in our understanding of the mechanisms of ALD over the past decade are now being translated into new forms of therapy for this disease process which currently has no FDA approved treatment. Cytokines are low molecular weight mediators of cellular communication, and the pro‐inflammatory cytokine tumor necrosis factor (TNF) has been shown to play a pivotal role in the development of experimental ALD. Similarly, TNF levels are elevated in the serum of alcoholic hepatitis patients. Abnormal methionine metabolism is well documented in patients with ALD, with patients having elevated serum methionine levels, but low S‐adenosylmethionine levels in the liver. On the other hand, S‐adenosylhomocysteine and homocysteine levels are elevated in ALD. Recent studies have documented potential interactions between homocysteine and S‐adenosylhomocysteine with TNF in the development of ALD. Altered proteasome function also is now well documented in ALD, and decreased proteasome function can cause hepatocyte apoptosis. Recently it has been shown that decreased proteasome function can also act synergistically to enhance TNF hepatotoxicity. Hepatocytes dying of proteasome dysfunction release pro‐inflammatory cytokines such as Interleukin‐8 to cause sustained inflammation. This article reviews the interactions of cytokines, altered methionine metabolism, and proteasome dysfunction in the development of ALD.
Relation of Endotoxin, Endotoxin Binding Proteins and Macrophages to Severe Alcoholic Liver Injury and Multiple Organ Failure
Authors: Fukui Hiroshi
Published: December 2005

Abstract:Our retrospective analysis of 105 patients with alcoholic liver injury confirmed that patients with severe alcoholic hepatitis (SAH) showed severe hyperbilirubinemia, reduced hepatic biosynthetic capacity, and marked acute inflammatory reactions, and developed multiple organ failure (MOF). Multivariate analysis using the Cox proportional hazards model showed serum C‐reactive protein and DIC as significant independent prognostic factors among SAH, LC+AH, and AH groups. Improved assay showed an increase of plasma endotoxin with the progression of alcoholic liver injury. In most survivors, plasma Et levels decreased in the recovery phase. Serum interleukin (IL)‐6 and IL‐8 levels in the acute phase were high in patients with AH and LC+AH, especially in non‐survivors and in patients with SAH. In the recovery phase, these cytokine levels in survivors tended to decrease, but in non‐survivors, IL‐6 remained high, and IL‐8 further increased. Serum levels of HDL and albumin, which are protective against endotoxicity by inhibiting endotoxin uptake and TNF production by macrophages, were decreased with the progression of alcoholic liver injury. Animal experiments supported that the increase in endotoxin‐binding capacity of HDL and albumin may serve as a protective mechanism against endotoxin in chronic ethanol‐loaded rats and that an addition of high‐dose ethanol to these rats may lead to impaired binding and inactivation of endotoxin. Lipopolysaccharide‐binding protein (LBP) which enhances endotoxin uptake and TNF production by macrophages, was generally increased in patients with alcoholic liver injury. This imbalance among endotoxin binding proteins in the blood may induce overproduction of cytokines by macrophages in patients with severe alcoholic liver injury. Our animal experiments further revealed that an additional administration of a high‐dose ethanol to chronic alcohol‐fed rats led to decrease of endotoxin clearance, increased extrahepatic accumulation of endotoxin and elevation of plasma TNF. The splenic macrophages and pulmonary alveolar macrophages are demonstrated to be important for endotoxin uptake, and excessive production of TNF in rats given large amounts of alcohol. Anin vitroculture experiment in the presence of rat LBP suggested a role of these macrophages in excessive production of TNF‐α. When the functions of various macrophages were compared in rats given alcohol, maximum TNF‐α secretion was noted in alveolar macrophages, In conclusion, endotoxemia and its effects on extrahepatic macrophages may play key roles in the progression of severe alcoholic liver injury and MOF.
Activation of the Innate Immune System and Alcoholic Liver Disease: Effects of Ethanol per se or Enhanced Intestinal Translocation of Bacterial Toxins Induced by Ethanol?
Authors: Bode Christiane , Bode J Christian
Published: December 2005

Abstract: It is generally accepted that activation of the innate immune system and increased release of pro‐inflammatory cytokines and other mediators plays an important role in the development of alcoholic liver disease (ALD). The mechanisms involved in the ethanol‐induced activation of monocytes/macrophages (including Kupffer cells) are however, still a matter of debate. The brief review will summarize the published data from the literature on the two main pathomechanisms discussed until now: I) Gut‐derived bacterial toxins, specially endotoxin; and II) metabolic changes induced by alcohol oxidation (independent of mechanism I). For pathomechanism I, clear evidence has been published from numerous groups: Alcohol induces mucosal injury in the upper gastrointestinal tract and leads to marked increase in the permeability of the gut mucosa to macromolecules such as endotoxin. The resulting endotoxemia then leads to activation of Kupffer cells and other macrophages. The increased release of pro‐inflammatory mediators (e.g., TNF‐α, Il‐1, reacting oxygen species) and infiltration of other inflammatory cells (e.g., neutrophils) finally causes liver damage. Regarding the second pathomechanism it has repeatedly been argued that the metabolic alterations which are induced by chronic administration of ethanol to rats or mice might increase the sensitivity of monocytes/macrophages to secrete TNF‐α and other pro‐inflammatory mediators thereby increasing the susceptibility to ethanol‐induced liver injury. However, in all feeding experiments the effect of ethanol on intestinal permeability and enhanced translocation of bacterial toxins (endotoxin) is likely to occur (or at least cannot be excluded). The latter holds true also for experiments using isolated macrophages/Kupffer cells from ethanol fed animals. Therefore, to clarify whether or not alterations related to ethanol metabolism (“direct” effects of ethanol) contribute to the activation of the innate immune system studies using germ‐free animals are needed to exclude the “indirect” effect of ethanol via gut‐derived bacterial toxins.
Ceramide, Tumor Necrosis Factor and Alcohol‐Induced Liver Disease
Authors: Fernandez‐Checa José C. , Colell Anna , Mari Montserrat , García‐Ruiz Carmen
Published: December 2005

Abstract: Background: The pathogenesis of alcohol‐induced liver disease (ALD) is incompletely known. One of the key processes mediating the progression of ALD involved the overproduction of tumor necrosis factor (TNF) and the susceptibility of hepatocytes to TNF‐induced apoptosis by alcohol intake.

Methods: Analyze the apoptotic signaling of TNF resulting in the targeting and subsequent recruitment of mitochondria to death pathways.

Results: Studies in experimental animal models of the disease have provided evidence for the role of ceramide generated from acidic sphingomyelinase in the apoptotic signaling of TNF through recruitment of mitochondria. The mitochondrial pool of glutathione (mGSH) is a vital line of defense against oxidative stress by precluding the accumulation peroxides generated endogenously within mitochondria and as a cofactor of mitochondrial antioxidant enzymes. The depletion of mGSH by alcohol has been described to determine the susceptibility of hepatocytes to TNF‐mediated cell death.

Conclusions: The level of mGSH determines the fate of hepatocytes to acidic sphingomyelinase activation by TNF and hence strategies aimed to replenish mGSH or to antagonize the generation of ceramide from acidic sphingomyelinase may be of therapeutic value for ALD.
Ethanol‐Induced Liver Injury: Potential Roles for Egr‐1
Authors: Pritchard M T. , Nagy L E.
Published: December 2005

Abstract: Chronic ethanol‐induced liver injury follows a typical progression from its earliest stage of steatosis to more advanced injury, characterized by the development of inflammation, hepatocyte necrosis/apoptosis, fibrosis and finally cirrhosis. Kupffer cells, the resident macrophage in the liver, play a critical role in the progression of liver injury. Increased exposure of Kupffer cells to lipopolysaccharide (LPS) during chronic ethanol exposure leads to the production of a number of inflammatory mediators, including tumor necrosis factor α (TNF‐α). Recent evidence indicates that in addition to increased exposure to LPS, Kupffer cells also develop an enhanced sensitivity to LPS after chronic ethanol feeding. We have recently identified early growth response‐1 (Egr‐1), an immediate‐early gene transcription factor, as an important contributor to increased LPS‐stimulated TNF‐α secretion by Kupffer cells after chronic ethanol exposure. In other models of tissue injury, such as ischemia‐reperfusion in the lung, Egr‐1 acts as a coordinator of the complex response to stress. Here we review the literature regarding the role of EGR‐1 in regulation of a number of genes implicated in each of the stages of chronic ethanol‐induced liver injury.

In addition to the critical role of Egr‐1 in generating maximal LPS‐stimulated TNF‐α expression, Egr‐1 also controls the expression of a number of inflammatory mediators, including intercellular adhesion molecule (ICAM)‐1, monocyte chemotactic protein (MCP)‐1 and macrophage inflammatory protein (MIP)‐2, as well as genes contributing to fibrosis, such as transforming growth factor (TFG)‐β1, platelet‐derived growth factor PDGF‐A chain and fibroblast growth factor (FGF). Understanding the contribution of Egr‐1 to the expression of genes involved in the development of chronic ethanol‐induced liver injury may lead to the development of improved therapies designed to prevent and/or reverse alcohol‐induced liver injury.
Oxidative Stress and Signal Transduction Pathways in Alcoholic Liver Disease
Authors: Zima Tomáš , Kalousová Marta
Published: December 2005

Abstract:Ethanol is linked to several pathologies like alcohol liver injury, neurotoxicity, cardiomyopathy, fetal alcoholic syndrome or cancer. It is generally accepted that oxidative stress plays a central role in their pathogenesis. After chronic and excessive consumption, alcohol may accelerate oxidative mechanisms both directly via increased production of reactive oxygen species and indirectly by impairing protective mechanisms against them. Ethanol, its metabolites arising during its metabolic degradation as well as novel compounds formed via ethanol induced oxidative stress, especially during the action of the ethanol inducible microsomal cytochrome CYP2E1, may apart from direct damage to biological structures affect signal transduction pathways thus modulating and potentiating damage. Alteration of the redox status of cells following chronic ethanol misuse may have profound effects on cellular function and viability and lead to cell death and tissue damage. These changes linked to pathologic processes in the organism, are related to alteration of intracellular signaling pathways associated with protein kinases and transcription factor activation. Mainly mitogen activated protein kinase (MAPK) family, transcription factors–nuclear factor κB (NF‐κB) and activating protein 1 (AP‐1) are involved in the deterioration of cells and organs. The response is cell‐type specific and depends on the dose of ethanol. Oxido‐reduction balance, regulatory disturbances and signal transduction cascades responsible for alcoholic damage have been partially described, nevertheless, further studies are required to allow future novel diagnostic and therapeutical strategies. We are only at the beginning …
Sesamin Ingestion Regulates the Transcription Levels of Hepatic Metabolizing Enzymes for Alcohol and Lipids in Rats
Authors: Kiso Yoshinobu , Tsuruoka Nobuo , Kidokoro Ayako , Matsumoto Ichiro , Abe Keiko
Published: December 2005

Abstract: Background: Sesamin, a major lignan in sesame seeds, has multiple functions such as stimulation effect of ethanol metabolism in mice and human, and prevention of ethanol‐induced fatty liver in rats. However, the mechanism has not been clarified yet.

Methods: The changes of gene expression were investigated in rats given 250 mg/kg of sesamin (sesamin rats) or vehicle (control rats) for three days by using a DNA microarray analysis. At 4 hr after the final ingestion, the profiles of gene expression in rat livers were compared.

Results: The analysis showed that 38 transcripts were up‐regulated with a significant change of more than two‐fold and eight transcripts were down‐regulated with a significant change to less than half in the livers of sesamin rats versus control rats. The gene expression levels of the early stage enzymes of β‐oxidation including long‐chain acyl‐CoA synthetase, very long‐chain acyl‐CoA synthetase and carnitine palmitoyltransferase were not changed, however, those of the late stage enzymes of β‐oxidation including trifunctional enzyme in mitochondria, and acyl‐CoA oxidase, bifunctional enzyme and 3‐ketoacyl‐CoA thiolase in peroxisomes, were significantly increased by sesamin ingestion. Also, in sesamin rats, the gene expression of aldehyde dehydrogenase was increased about three‐fold, whereas alcohol dehydrogenase, liver catalase and CYP2E1 were not changed. Changes in the gene expression of alcohol‐ and aldehyde‐metabolizing enzymes observed in a DNA microarray were also confirmed by a real‐time PCR method.

Conclusions: These results suggested that sesamin ingestion regulated the transcription levels of hepatic metabolizing enzymes for alcohol and lipids.
Expression patterns of hair and epithelial keratins and transcription factors HOXC13, LEF1, and β‐catenin in a malignant pilomatricoma: a histological and immunohistochemical study
Authors: Cribier Bernard , Worret Wolf‐Ingo , Braun‐Falco Markus , Peltre Bernard , Langbein Lutz , Schweizer Jürgen
Published: December 2005

Background:  We have previously shown that benign pilomatricomas not only maintain the sequential expression of the hair matrix and precortex keratins hHa5 and hHa1 of normal hair follicles in their transitional cell compartment, but also preserve the association of hHa5 expression with that of its regulatory homeoprotein HOXC13 in the lower transitional cell compartment. In contrast, hHa1 expression in the upper transitional cell compartment is uncoupled from the nuclear co‐expression of the LEF1/β‐catenin complex seen in normal hair follicles (Cribier et al., J Invest Dermatol 2004; 122: 1078).

Methods:  Formalin‐fixed paraffin sections of the tumor were examined using a panel of mono‐ and polyclonal hair and epithelial keratin antibodies as well as antibodies against HOXC13, LEF1, and β‐catenin.

Results:  Morphologically, the malignant pilomatricoma investigated here clearly deviated from the described major tumor type by a large number of differently sized parakeratotic squamoid whorls emerging within the mass of basaloid cells and surrounded by cells remembering transitional cells, but only rarely containing shadow cells and signs of calcification. We show that hHa5/HOXC13 co‐expression was maintained in transitional cell areas, in which hHa1 expression was much stronger than in benign pilomatricomas, but again uncoupled from concomitant nuclear LEF1/β‐catenin expression. Surprisingly, however, and in clear contrast to benign pilomatricomas, these transitional cells co‐expressed the epithelial keratins K5, K14, and K17, with the latter being as strongly expressed as hHa1, both also staining the entire inner mass of the parakeratotic whorls.

Conclusions:  Although the malignant pilomatricoma investigated here was distinctive in that it contained a multitude of parakeratinizing whorls and no signs of calcification, it shared both hHa5/HOXC13 co‐expression and disrupted hHa1/β‐catenin–LEF1 expression in its transitional cell compartment around the whorls with benign pilomatricomas. However, in clear contrast to the latter, transitional cells of the malignant tumor also strongly expressed the epithelial keratins K5, K14, and K17. We speculate that the observed dominance of the epithelial differentiation pathway over the competing conventional shadow cell differentiation pathway may prevent massive calcification of the tumor.
Macrophage‐rich epithelioid angiosarcoma mimicking malignant melanoma
Authors: Brightman Lori A. , Demierre Marie‐France , Byers H. Randolph
Published: December 2005

Background:  Cutaneous epithelioid angiosarcoma is a type of cutaneous angiosarcoma and usually arise both on the head or neck of the elderly.

Case report:  An 86‐year‐old male with an epithelioid angiosarcoma of the scalp that mimicked malignant melanoma.

Results:  A large irregular dark grey‐blue plaque with an adjacent speckled tan nodule was suggestive of a primary cutaneous malignant melanoma with adjacent in‐transit metastasis. Both had a well‐circumscribed growth pattern and were composed of numerous large epithelioid cells with scattered severe atypia and mitoses. The tumor was positive for S‐100 protein and vimentin and negative for low‐ and high‐molecular weight cytokeratins. However, at high power, the epithelioid cells with severe atypia were negative for S‐100 protein, and abundant large epithelioid macrophages were responsible for the S‐100 protein positivity. The malignant tumor cells were negative for HMB‐45, positive for CD31 and Factor VIII‐related antigen, and focally positive for CD34. A focus of infiltrative, classical angiosarcoma with irregular vascular channels lined with plump, anaplastic endothelial cells was then found deep to the epithelioid tumor.

Conclusions:  Macrophage‐rich epithelioid angiosarcoma demonstrates abundant S‐100 protein‐positive epithelioid macrophages. This subset of epithelioid angiosarcoma may mimic malignant melanoma and may present as a pitfall in diagnosis.
Adenosis tumor of anogenital mammary‐like glands: a case report and demonstration of clonality by HUMARA assay
Authors: Kazakov Dmitry V. , Bisceglia Michele , Sima Radek , Michal Michal
Published: December 2005

Abstract:  In mammary pathology, adenosis tumor is defined as a clinically recognizable lesion that histologically primarily consists of adenosis, but also exhibits various combinations of diverse epithelial changes seen in other benign breast diseases. A lesion that occurred in the anogenital area of a 46‐year‐old woman and apparently arose in anogenital mammary‐like glands is described and which, in our opinion, is best classified as adenosis tumor. A biopsy revealed a well‐demarcated, unencapsulated lesion surrounded by compressed fibrous tissue forming a pseudocapsule. Several histological patterns within the same tumor mass were recognizable: sclerosing adenosis‐like changes, variably sized microcysts and cysts, some with rare short papillary projections having hyalinized cores, rare tubular structures exhibiting epithelial features reminiscent of simple ductal hyperplasia, areas with oxyphilic (apocrine) metaplasia, and clear cell epithelial changes resembling mucinous metaplasia. Decapitation secretion was notable in many lumens. Rare lumens were filled with foamy macrophages. There were also focal clear cell changes of myoepithelial cells. The stroma was paucicellular and sclerotic in some foci and composed of myofibroblasts and myxoid in others. Calponin, actins, and p63 stained myoepithelial cells. The cells in the oxyphilic (apocrine) metaplasia areas stained for mitochondrial antigen and Bcl‐2. Antibodies to progesterone and estrogen receptor stained approximately 50 and 20% of the epithelial cell population, respectively. Human androgen receptor gene analysis yielded a monoclonal pattern. As our case exhibited a number of patterns identical to those seen in diverse benign breast diseases, its classification as adenosis tumor seems justifiable. This cutaneous perianal lesion is indistinguishable microscopically from its mammary analogue and was clinically detectable.
Pure sclerotic neurofibroma: a neurofibroma mimicking sclerotic fibroma
Authors: González‐Vela M. Carmen , Val‐Bernal J. Fernando , González‐López Marcos A. , Drake Marta , Fernández‐Llaca J. Héctor
Published: December 2005

Background:  Neurofibroma (NF) is a benign tumor of the nerve sheath. Several variants of NF have been described.

Purpose:  We report a case of NF with sclerotic changes resembling sclerotic fibroma (SF).

Methods and Results:  The patient was a 61‐year‐old man who had an asymptomatic cutaneous lesion on the right scapular region. Physical examination revealed a pedunculated, white‐to‐pinkish nodule that had a firm consistency, spherical morphology, and smooth surface. Microscopically, the nodule showed a well‐circumscribed, nonencapsulated dermal tumor composed of scant cells and thick collagen bundles with prominent clefts. The tumor cells were immunoreactive for vimentin and S100 protein. The patient was diagnosed as having pure sclerotic NF. To our knowledge, only five cases of NF with SF‐like pattern have been previously published, and in two this pattern was pure.

Conclusion:  It is important to recognize this exceptional type of NF because it may be easily confused with SF, as well as with a wide variety of neoplasms or hamartomatous conditions containing similar sclerotic pattern.
Expression of retinoid receptors in sebaceous cell carcinoma
Authors: Chakravarti Nitin , El‐Naggar Adel K. , Lotan Reuben , Anderson James , Diwan Abdul H. , Saadati Hossein G. , Diba Roxana , Prieto Victor G. , Esmaeli Bita
Published: December 2005

Purpose:  The aim of this study is to investigate whether there are any abnormalities in the in vivo expression of retinoid acid receptors (RAR‐α, RAR‐β and RAR‐γ) and retinoid X receptors (RXR‐α, RXR‐β and RXR‐γ) in sebaceous cell carcinoma.

Methods:  Expression of retinoid receptors in paired specimens of cancerous tissues (n = 10) and adjacent normal tissues (n = 10) from 10 patients with sebaceous cell carcinoma was studied immunohistochemically by using anti‐retinoid receptor antibodies.

Results:  In eight of the 10 normal tissue samples, all six receptors were expressed. In the other two samples, all receptors were expressed except RAR‐γ (one sample) or RXR‐γ (two samples). Five tumours (50%) lacked RAR‐α; RAR‐α expression was lower in tumours than in normal tissues in eight of 10 cases. RAR‐β was expressed in the cytoplasm of nine of 10 tumours; RAR‐β expression was at least as high in tumours as in normal tissue in eight of 10 cases. Two tumours lacked RAR‐γ; three tumours had lower RAR‐γ expression than paired normal epithelium; four had the same RAR‐γ expression, and one had higher RAR‐γ expression. RXR‐α expression was strong in all normal tissues and tumour samples. Ten tumours lacked RXR‐β and all 10 tumours lacked RXR‐γ expression.

Conclusions:  Diminished RXR‐β and RXR‐γ expression might be related to the development of sebaceous cell carcinoma. Additional studies are required to establish whether the defects in RAR expression in sebaceous cell carcinoma might affect the potential response of this tumour to treatment with retinoids.
Multiple cellular neurothekeomas – a case report and review on the role of immunohistochemistry as a histologic adjunct
Authors: Mahalingam M. , Alter J. N. , Bhawan J.
Published: December 2005

Background:  Cellular neurothekeoma is a relatively rare, benign cutaneous neoplasm, which usually presents as a solitary papule or nodule involving the head and neck area of young adults. Multiple neurothekeomas have not, to date, been known to occur.

Methods:  We report a 30‐year‐old, otherwise healthy, male who presented with multiple neurothekeomas (15) in the head and neck area over a period of 12 years.

Results:  While the unifying feature of all biopsied (10 of 15) lesions was the presence of epithelioid cells – the lesions differed in their cellularity and the degree of sclerosis of the stromal component. Antigenic profiling of the lesional cells revealed expression of vimentin, NKI/C3, PGP 9.5, factor XIIIa and CD68 but not S100, HMB45, MelanA, EMA, MSA, desmin, CD57 or NGF‐R.

Conclusions:  This case report is the first to document the occurrence of multiple cellular neurothekeomas. An unusual histologic feature of some of the biopsied lesions was the presence of a markedly sclerotic stroma.
Expression of c‐kit (CD117) in Spitz nevus and malignant melanoma
Authors: Isabel Zhu Y. , Fitzpatrick James E.
Published: December 2005

Background:  CD117, the receptor for kit‐ligand, which is a growth factor for melanocyte migration and proliferation, has shown differential staining in various benign and malignant melanocytic lesions. The purpose of this study is to compare CD117 immunohistological staining in Spitz nevus versus malignant melanoma, to determine whether CD117 can aid in the diagnosis of these two lesions.

Methods:  CD‐117 immunohistological staining was performed in 22 clinically and pathologically diagnosed pigmented lesions including 9 cases of Spitz nevus, 10 cases of primary MM and 3 cases of metastatic melanoma.

Results:  There was no significant difference in CD117 staining in either epidermis or dermis between Spitz nevi and primary melanomas. However staining of metastatic melanomas is less than dermal staining of primary MM and Spitz nevus.

Conclusions:  CD117 is unlikely a useful diagnostic tool in differentiating Spitz nevus from primary MM. On the other hand, CD 117 may be useful in differentiating metastatic melanoma from primary melanoma in patients who had a history of melanoma and who present with new dermal lesions.
Flavour encapsulation and controlled release – a review
Authors: Madene Atmane , Jacquot Muriel , Scher Joël , Desobry Stéphane
Published: December 2005

Flavours can be among the most valuable ingredients in any food formula. Even small amounts of some aroma substance can be expensive, and because they are usually delicate and volatile, preserving them is often a top concern of food manufacturers. Encapsulation describes different processes to cover an active compound with a protective wall material and it can be employed to treat flavours so as to impart some degree of protection against evaporation, reaction, or migration in a food. Encapsulation of flavours has been attempted and commercialized using many different methods such as spray drying, spray chilling or spray cooling, extrusion, freeze drying, coacervation and molecular inclusion. The choice of appropriate microencapsulation technique depends upon the end use of the product and the processing conditions involved in the manufacturing product. This overview describes each method cited above in terms of the basic chemical and/or physical principles involved and covers mechanisms of flavour release from food matrices.
The broader usage of sugars and fillers in milk chocolate made possible by the new EC cocoa directive
Authors: Bolenz Siegfried , Amtsberg Kristina , Schäpe Rita
Published: December 2005

The European Community directive 2000/36/EC now allows the addition of any sugar to chocolate and also adding up to 40% (w/w) of any foodstuff. Milk chocolates with lactose‐replacing sucrose and also with added fillers were tested for physical and sensory properties. Helianthus tuberosus flour, pea and oat fibres made the taste of the chocolate unacceptable. The addition of cellulose and wheat fibre at low dosages resulted in tolerable flavour; however, fat absorption of fibres caused worse flow properties and toughness made particle sizes to increase. Sugar beet fibres introduced bitter and cereal notes. The three products mentioned above would be useable only after modifications to the upstream process. Lupin gave a higher yield value because of its lecithin content but otherwise showed positive impact and could be used to supplement milk ingredients after adjustments to the recipe. As inulin improved the flow and sensory characteristics, it could be recommended both for its physical and nutritional properties. Lactose was not detectable up to 20%, but had some negative effects at higher levels in a low‐fat formulation and could require refining modifications. Further development seems worthwhile.
Effect of rotation on the heat penetration characteristics of thermally processed tuna in oil in retort pouches
Authors: Ansar Ali Ameer , Sudhir Balaraman , Srinivasa Gopal Teralandur Krishnaswamy
Published: December 2005

Tuna in oil was processed in retort pouches (20 × 17 cm) to a, F0 value of 10. Heat penetration characteristics were determined using a rotary retort to an F0 value of 10 and the results compared with a stationary retort. For studying the changes in heat penetration during rotation, tuna in oil was packed into retort pouches, subjected to different rotation speeds (2, 4 and 6 r.p.m.) and thermally processed to the same F0 value. For the same F0 value of 10, although there was a reduction in process time with increasing rotation speed up to 6 r.p.m., the magnitude of the reduction in processing time decreased with increase in speed of rotation. However up to 2 r.p.m. there was a considerable reduction in process time.
Sensory, physical, chemical and microbiological changes in European sea bass (Dicentrarchus labrax) fillets packed under modified atmosphere/air or prepared from whole fish stored in ice
Authors: Poli Bianca Maria , Messini Anna , Parisi Giuliana , Scappini Federico , Vigiani Valentina , Giorgi Gianluca , Vincenzini Massimo
Published: December 2005

Quality changes and shelf‐life in European sea bass fillets packed under 40% CO2: 60% N2 (MAP) and air (AIR) or prepared from the whole ungutted fish stored in ice (ROUND) were compared. Raw and cooked sensory scores, pH, colour, expressible water, malonaldehyde, total viable count, Pseudomonas spp., H2S‐producing bacteria, Lactobacillus spp., Streptococcus spp., Staphylococcus spp., coliforms and proteolytic counts, were determined until AIR and MAP raw fillet spoilage. Raw ROUND fillets had the best quality and shelf‐life (10 vs. 8 vs. 7 days after slaughtering in ROUND, MAP and AIR, respectively), while the MAP fillets had better sensorial scores, lower pH values and better microbiological counts, but greater lightness values than the corresponding AIR fillets. MAP fillets also had the highest malonaldehyde levels. The higher correlation between Streptococcus spp. and odour scores (r = −0.971, P < 0.01) compared to the other species could suggest that it is a specific spoilage organism in the MAP condition used.
Atypical growth of Renibacterium salmoninarum in subclinical infections
Authors: Hirvelä‐Koski V , Pohjanvirta T , Koski P , Sukura A
Published: December 2005

Two growth types of Renibacterium salmoninarum were isolated from subclinically infected rainbow trout, one producing the smooth colonies typical of R. salmoninarum and the other forming a thin film on the surface of the agar with no separate colonies. The atypical growth was present on kidney disease medium agar in primary cultures of the kidney but not on selective kidney disease medium (SKDM). Fluorescent antibody staining of the fresh isolate and polymerase chain reaction amplification were the most reliable techniques to identify the atypical growth of R. salmoninarum. The condition was reversible, with growth reverting from atypical to the smooth colony form in experimentally infected rainbow trout and under laboratory conditions. There was no mortality, or any clinical signs of bacterial kidney disease (BKD) in the fish challenged with the atypical growth, although small numbers of smooth colonies of R. salmoninarum were isolated from 8% of these fish. The atypical growth reported here may explain some of the failures of culture, when SKDM agar alone is used for the detection of BKD in subclinically infected fish.