bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐Term Ethanol Feeding Enhances Susceptibility of the Liver to Orally Administered Lipopolysaccharides in Rats
Authors: Tamai Hironao , Horie Yoshineri , Kato Shinzo , Yokoyama Hirokazu , Ishii Hiromasa
Published: April 2006

Background Endotoxin has been implicated in the pathogenesis and progression of alcoholic liver disease. However, it is still unclear how long‐term ethanol feeding affects absorption of endotoxin from the intestine and susceptibility of the liver to gut‐derived endotoxin. The object of this study was to determine the effect of long‐term ethanol feeding on hepatic susceptibility to orally administered endotoxin.

Methods Male Wistar rats that weighed approximately 150 g were pair‐fed with an ethanol‐containing liquid diet or a control diet for 35 days. In some experiments, 0, 10, or 20 mg/kg of lipopolysaccharides (LPS) was added to the liquid diet for 7 days beginning on day 29. On day 36, the animals were killed for blood biochemistry and histologic examination of the liver. We also determined plasma endotoxin levels after 20 mg/kg of LPS administration using a gastric tube. In another set of experiments, we determined intestinal permeability using FD4 (fluorescein isothiocyanate‐labeled dextran with an average molecular weight of 4000 D).

Results With 10 mg/kg of LPS, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels were significantly increased in the ethanol‐fed rats but not in controls. After 20 mg/kg of LPS administration, more substantial increases in serum ALT and ALP levels were observed in ethanol‐fed rats as compared with control diet‐fed rats. Plasma endotoxin levels in long‐term ethanol‐fed rats were higher than those in control rats after intragastric administration of high‐dose endotoxin (20 mg/kg). Furthermore, intestinal permeability to FD4 was increased by long‐term ethanol administration.

Conclusions Long‐term ethanol feeding increases intestinal permeability to and absorption of endotoxin, which can sequentially enhance hepatic susceptibility to orally administered endotoxin. This model has potential as a subclinical experimental model for the study of alcoholic liver disease.
Significant Correlation Between Insulin Resistance and Serum Gamma‐Glutamyl Transpeptidase (γ‐GTP) Activity in Non‐Drinkers
Authors: Yokoyama Hirokazu , Hirose Hiroshi , Moriya Susumu , Saito Ikuo
Published: April 2006

To understand the significance of elevated serum γ‐GTP levels, factors relevant to the serum γ‐GTP level were studied using data of health check‐ups for the employees of a Japanese corporation. The γ‐GTP level was positively correlated with levels of various liver function tests including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Except for them, the γ‐GTP level was positively correlated with levels of insulin resistance, uric acid, total cholesterol, triglyceride, and body mass index. The correlation between the γ‐GTP level and LDL cholesterol was also observed only when subjects who drank more than 5 times a week were selectively studied. When non‐drinkers and opportunity drinkers were selectively studied, 63.6% of subjects whose γ‐GTP level was more than 120 IU/liter showed elevated insulin resistance levels. Multiple factors including insulin resistance may affect serum γ‐GTP activity in clinical subjects.
Are Relations Between Parental History of Alcohol Problems and Changes in Drinking Moderated by Positive Expectancies?
Authors: VanVoorst Wendy A. , Quirk Stuart W.
Published: April 2006

Background: Risk factors of alcohol abuse generally have been examined for their additive or direct effects on the development of alcohol‐related problems. This study was designed to assess the interaction between two important predictors: parental history of alcohol problems and positive expectancies regarding alcohol consumption.

Methods: The positive expectancies, reported parental alcohol problems, and alcohol use and problems of 169 first‐year college students were assessed at their entrance to college, and their alcohol use and problems were assessed again approximately 3 months later. The main effects of positive family history and expectancies as well as their interaction in predicting changes in alcohol use and problems were examined in hierarchical regression analyses.

Results: A parental history of alcohol‐related problems was related to greater alcohol problems at the two assessment times, and positive expectancies for the effects of alcohol were related to both alcohol problems and alcohol use. The parental history × positive expectancies term significantly added to the prediction of changes in alcohol problems (8% incremental increase in explained variance) even after baseline problems were entered in a prior step in the equation. Follow‐up exploration revealed that the interaction was accounted for by high levels of alcohol problems at time 2 being reported by those high in positive expectancies and reporting high parental alcohol problems. The parental history × positive expectancies interaction term also added slightly to the prediction of changes in alcohol use amounts but accounted for a modest 1% incremental variance.

Conclusions: Reported parental history and positive alcohol expectancies interacted to predict increases in alcohol problems over the course of the first semester of college. These results suggest that risk factors for alcohol problems may conjointly interact to confer heightened risk. Such interactive models may further assist in identifying at risk young adults. Limitations such as the reliance on self‐report measures and the predominantly female sample are discussed.
Financial Costs of Alcoholism Treatment Programs: A Longitudinal and Comparative Evaluation Among Four Specialized Centers
Authors: Nalpas B. , Combescure C. , Pierre B. , Ledent T. , Gillet C. , Playoust D. , Danel T. , Bozonnat M. C. , Martin S. , Balmès J. L. , Daurès J. P.
Published: April 2006

Background: Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow‐up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification.

Methods: We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service.

Results: The mean cost of hospitalization ranged from €1326 to €1917 (p= 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow‐up per patient ranged from €419 to €1704 (p= 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately €500/month in three centers and €658 in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p= 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost.

Conclusions: This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost‐efficient, and beneficial for patients and the public health office economy.
Effect of Type of Alcoholic Beverages on Carbohydrate‐Deficient Transferrin, Sialic Acid, and Liver Enzymes
Authors: Sillanaukee P. , van der Gaag M. S. , Sierksma A. , Hendriks H. F. J. , Strid N. , Pönniö M. , Nikkari S. T.
Published: April 2006

Background: There are only limited data obtained under well controlled conditions on the effects of moderate drinking on markers of alcohol use disorders. The aim of this study was to investigate the effects of moderate intake of different alcoholic beverages on these markers, including carbohydrate‐deficient transferrin (CDT), sialic acid (SA), and the liver enzymes γ‐glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase.

Methods: Eleven apparently healthy, nonsmoking middle‐aged men were included in a 12‐week randomized, diet‐controlled crossover trial according to a 4 × 4 Latin‐square design. Changes in CDT, SA, γ‐glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase were analyzed after 3 weeks of daily intake of four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or water (control).

Results: After 3 weeks’ daily consumption of red wine, a significant decrease of serum CDT concentration was observed compared with water consumption. There was no effect of any alcoholic beverage on the other outcome measures.

Conclusions: Daily consumption of 40 g of alcohol from different types of alcoholic beverages with dinner did not affect SA or liver enzymes. Further investigations to explore the mechanisms for the red wine–induced decreases of CDT, including changes in iron metabolism, are clearly needed.
Validity of Brief Alcohol Screening Tests Among Adolescents: A Comparison of the AUDIT, POSIT, CAGE, and CRAFFT
Authors: Knight John R. , Sherritt Lon , Harris Sion Kim , Gates Elizabeth C. , Chang Grace
Published: April 2006

Background: Adolescents should be screened for alcohol misuse as part of routine care. The objective of this study was to compare the criterion validity of the Alcohol Use Disorders Identification Test (AUDIT), the Problem Oriented Screening Instrument for Teenagers substance use/abuse scale (POSIT), and the CAGE and CRAFFT questions among adolescents.

Methods: Fourteen‐ to 18‐year‐old patients arriving for routine healthcare at a large, hospital‐based adolescent clinic completed the four screens and the criterion standard Adolescent Diagnostic Interview, which yields DSM‐IV diagnoses of alcohol abuse and dependence. Receiver operating characteristic (ROC) curves were plotted to determine optimal cut‐points. Areas under the ROC curves of the four screens were compared, and sensitivities and specificities were calculated.

Results: Participants’ past 12‐month alcohol diagnostic classifications were as follows: no use (58.6%), nonproblem use (13.0%), problem use (20.8%), abuse (5.4%), and dependence (2.2%). Optimal cut‐points associated with problem use or higher were 2 for AUDIT, 1 for POSIT, 1 for CAGE, and 1 for CRAFFT. ROC curve area of the CAGE was significantly lower compared with areas of all other screens. Sensitivities (95% confidence intervals) were AUDIT 0.88 (0.83–0.93), POSIT 0.84 (0.79–0.90), CAGE 0.37 (0.29–0.44), and CRAFFT 0.92 (0.88‐0.96); specificities were AUDIT 0.81 (0.77–0.85), POSIT 0.89 (0.86–0.92), CAGE 0.96 (0.94–0.98), and CRAFFT 0.64 (0.59–0.69).

Conclusions: The AUDIT, POSIT, and CRAFFT have acceptable sensitivity for identifying alcohol problems or disorders in this age group. The CAGE is not recommended for use among adolescents.
Inhibition of Alcohol‐Associated Colonic Hyperregeneration by α‐Tocopherol in the Rat
Authors: Vincon P. , Wunderer J. , Simanowski U. A. , Koll M. , Preedy V. R. , Peters T. J. , Werner J. , Waldherr R. , Seitz H. K.
Published: April 2006

Background: Chronic alcohol consumption results in colorectal mucosal hyperregeneration, a condition associated with an increased risk for colorectal cancer. Possible mechanisms may involve the effects of acetaldehyde and/or free radicals generated during alcohol metabolism. Vitamin E is part of the antioxidative defense system, and its concentration is decreased or its metabolic utilization increased in various tissues after chronic alcohol consumption. We wondered whether α‐tocopherol supplementation may prevent ethanol‐induced colorectal cell cycle behavior and whether these changes were related to alterations in protein synthesis.

Methods: Five groups of male Wistar rats, each consisting of 14 animals, received liquid diets as follows: group 1, alcohol; group 2, alcohol +α‐tocopherol; group 3, control (i.e., isocaloric glucose); group 4; control (i.e., isocaloric glucose) +α‐tocopherol. Group 5 was fed a solid chow diet ad libitum. After 4 weeks of feeding, immunohistology was performed with anti‐proliferating cell nuclear antigen (PCNA) or anti‐BCL2 antibodies. Fractional (ks) and absolute (Vs) rates of protein synthesis and rates of protein synthesis relative to RNA (kRNA) and DNA (kDNA) were measured with a flooding dose of L‐[4‐3H] phenylalanine with complementary analysis of protein and nucleic acid composition.

Results: The PCNA index was increased significantly in the colon after ethanol administration compared with controls (ethanol, 10.3 ± 2.3 vs. control, 6.51 ± 1.6% PCNA positive cells, p < 0.05), although neither the protein, RNA, and DNA concentrations nor ks, kRNA, kDNA, and Vs were affected. This increase in PCNA index was significantly diminished by coadministration of α‐tocopherol (ethanol +α‐ tocopherol, 7.86 ± 1.71% PCNA positive cells, p < 0.05) without significant alterations in protein synthetic parameters. A similar result was obtained for the PCNA index in the rectal mucosa (ethanol, 14.6 ± 4.4 vs. control, 12.1 ± 4.2% PCNA positive cell), although this did not reach statistical significance. Neither ethanol nor α‐ tocopherol feeding had any significant effect on BCL‐2 expression in the colorectal mucosa. As with the colon, protein synthetic parameters in the mucosa were not affected by alcohol feeding at 4 weeks. These effects on colonic cell turnover without corresponding changes in protein synthesis thus represent a specific localized phenomenon rather than a general increase in anabolic processes in the tissue and reaffirm the hyperregenerative properties of chronic alcohol consumption.

Conclusions: Alcohol‐associated hyperproliferation could be prevented, at least in part, by supplementation with α‐tocopherol. This may support the hypothesis that free radicals are involved in the pathogenesis of alcohol‐associated colorectal hyperproliferation.
Zinc Supplementation at the Time of Ethanol Exposure Ameliorates Teratogenicity in Mice
Authors: Carey Luke C. , Coyle Peter , Philcox Jeffrey C. , Rofe Allan M.
Published: April 2006

Background: We have previously demonstrated that ethanol teratogenicity in mice is related to the maternal expression of metallothionein (MT), a zinc (Zn)‐binding protein. Ethanol induces maternal liver MT, which causes plasma Zn concentrations to decrease as Zn moves into the liver. During pregnancy it is suggested that this change decreases fetal Zn supply and contributes to abnormal development. Here we investigated whether maternal Zn supplementation at the time of ethanol exposure reduces teratogenicity.

Methods: Mice were injected with 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hr) and ZnSO4 (2.5 μgZn/g subcutaneously at 0 hr) and were killed over 16 hr to ascertain changes in plasma Zn. Plasma Zn concentrations peaked at 2 hr, where levels were 5‐fold normal and then returned toward normal over 14 hr. Pregnant mice were treated in a similar manner on gestation day 8 with saline, saline + Zn, ethanol + Zn, or ethanol alone, and fetal abnormalities were assessed on gestation day 18.

Results: External abnormalities were most prevalent in offspring from dams treated with ethanol. Zn treatment at the time of ethanol exposure reduced the incidence of fetal abnormalities to basal levels. Litters from dams treated with ethanol + Zn contained more fetuses and fewer fetal resorption sites compared with those from ethanol‐treated dams.

Conclusions: These findings demonstrate that Zn supplementation at the time of ethanol exposure significantly negates the deleterious effects of ethanol on the fetus.
Disuse Exaggerates the Detrimental Effects of Alcohol on Cortical Bone
Authors: Hefferan Theresa E. , Kennedy Angela M. , Evans Glenda L. , Turner Russell T.
Published: April 2006

Background: Alcohol abuse is associated with an increased risk for osteoporosis. However, comorbidity factors may play an important role in the pathogenesis of alcohol‐related bone fractures. Suboptimal mechanical loading of the skeleton, an established risk factor for bone loss, may occur in some alcohol abusers due to reduced physical activity, muscle atrophy, or both. The effect of alcohol consumption and reduced physical activity on bone metabolism has not been well studied. The purpose of this study was to determine whether mechanical disuse alters bone metabolism in a rat model for chronic alcohol abuse.

Methods: Alcohol was administered in the diet (35% caloric intake) of 6‐month‐old male rats for 4 weeks. Rats were hindlimb‐unloaded the final 2 weeks of the experiment to prevent dynamic weight bearing. Afterward, cortical bone histomorphometry was evaluated at the tibia‐fibula synostosis.

Results: At the periosteal surface of the tibial diaphysis, alcohol and hindlimb unloading independently decreased the mineralizing perimeter, mineral apposition rate, and bone formation rate. In addition, alcohol, but not hindlimb unloading, increased endocortical bone resorption. The respective detrimental effects of alcohol and hindlimb unloading to inhibit bone formation were additive; there was no interaction between the two variables.

Conclusions: Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.
Alcohol, But Not Lipopolysaccharide‐Induced Liver Apoptosis Involves Changes in Intracellular Compartmentalization of Apoptotic Regulators
Authors: Deaciuc Ion V. , D'Souza Nympha B. , Burikhanov Ravshan , Nasser Munira S. , Voskresensky Igor V. , de Villiers Willem J. S. , McClain Craig J.
Published: April 2006

Abstract: Background: While alcohol‐induced augmentation of liver apoptosis has been demonstrated in humans and laboratory animals, the underlying mechanisms are not fully elucidated. This study addresses the question whether alcohol and bacterial lipopolysaccharide (LPS), a putative mediator of alcohol effects on the liver, induce augmentation of liver apoptosis by intrinsic or extrinsic signaling pathways. This information may prove important for future design of therapies for alcoholic liver disease.

Methods: Male rats were fed either an alcohol‐containing liquid diet or an isocaloric, control diet for 15–16 weeks. At the end of feeding period, the rats were treated with LPS (0.8 mg·kg−1 body weight) or sterile saline and killed 3 and 24 hr later. The liver and blood were sampled for histology and biochemical assays. Hepatocytes were isolated by collagenase perfusion and fractionated to yield mitochondria and cytoplasm. The propensity of mitochondria to undergo permeability transition in the presence of a Ca2+ overload was determined along with distribution of various apoptotic regulators (AIF, Smac2, Bax, cytochrome c, Bcl‐XL, Bfl‐1, and caspase‐2) between mitochondria and cytoplasmic fractions.

Results: Increased liver apoptosis in alcohol‐treated rats was associated with translocation of several apoptotic regulators between mitochondria and cytoplasm in a manner suggesting that alcohol induces augmentation of apoptosis by recruiting intrinsic apoptotic signals. LPS treatment of rats counteracted alcohol‐induced changes in intracellular compartmentalization of apoptotic regulators despite an increased rate of apoptosis. LPS may, therefore, recruit extrinsic apoptotic signals, such as proinflammatory cytokines.

Conclusions: Hepatocytes are to be able to mount an apoptotic response to both intrinsic and extrinsic signals. Alcohol increases liver apoptosis predominantly through an intrinsic signaling pathway while LPS recruits extrinsic signaling pathways.
ALDH2/ADH2 Polymorphism Associated with Vasculopathy and Neuropathy in Type 2 Diabetes
Authors: Suzuki Yoshihiko , Taniyama Matsuo , Muramatsu Taro , Higuchi Susumu , Ohta Shigeo , Atsumi Yoshihito , Matsuoka Kempei
Published: April 2006

In the history of diabetes, chlorpropamide alcohol flushing test (CPAF) was a big topic in the 1970s to 1980s. Alcohol tolerance after chlorpropamide has prognostic significance, with the intolerant group (CPAF‐positive group) being less prone to develop vascular complication than the tolerant group (CPAF‐negative group). A mechanism of CPAF has been regarded as the inhibition of aldehyde dehydrogenase 2 (ALDH2) by an N1‐alkyl‐substituted derivative of chlorpropamide, and the expression of these mutations of ALDH2 and alcohol dehydrogenase 2 (ADH2) could determine the alcohol tolerance among the Japanese population. Therefore, we hypothesized that expression of different ALDH2 and ADH2 polymorphisms may induce differences in vascular complications in diabetes and conducted two studies. The first study (study 1) was to determine the association of ALDH2/AHD2 polymorphism with diabetic complications. To know the association of ALDH2/AHD2 polymorphism with diabetic vasculopathy and neuropathy, a total of 158 patients with type 2 diabetes were divided into four groups on the basis of ALDH2 “activity” and ADH2 “superactivity.” The frequency of proteinuria and the percentage of proliferative retinopathy among the patients with retinopathy was higher in those with active ALDH2 and superactive ADH2. We speculated that protein kinase C isoforms up‐regulated by 4‐hydroxynonenal that was detoxified by ALDH2 and ADH2 may account for the long‐term development of diabetic nephropathy and severe retinopathy. As for neuropathy, the frequency of symptomatic neuropathy was higher in patients with inactive ALDH2 and usual ADH2. We speculate that increased tissue levels of toxic aldehyde could result from inactive ALDH2 and usual ADH2 expression, which results in the increased level of reactive aldehyde in sensory neuron pathway, thereby causing symptomatic polyneuropathy.
Comparative Analyses of Four Different Methods of Genotyping ALDH2
Authors: Itoga Sakae , Nanmoku Toru , Uchimoto Takayuki , Sunaga Masahiko , Nezu Masahiko , Tomonaga Takeshi , Harada Shoji , Nomura Fumio
Published: April 2006

Background: A number of methods of genotyping single nucleotide polymorphisms (SNPs) are currently available, ranging from the traditional restriction fragment length polymorphism (RFLP) and single‐stranded conformational polymorphism (SSCP) to more sophisticated technologies. We determined the utility of three novel methods by genotyping aldehyde dehydrogenase‐2 (ALDH2).

Methods: DNA was isolated from blood samples of 241 control subjects and 74 patients with esophageal cancer. The utility of three novel genotyping methods—melting curve analysis using a LightCycler, SNaPshot analysis using an ABI PRISM 310 genetic analyzer, and denaturing high‐performance liquid chromatography using a WAVE DNA fragment analysis system—were compared with that of conventional fluorescent‐based polymerase chain reaction (PCR)‐SSCP using an ALF express DNA sequencer.

Results: The frequency of the mutant ALDH2*2 allele was significantly higher in patients with esophageal cancer (27.7%) than in control subjects (16.2%; p < 0.01; habitual alcohol drinkers). The melting curve analysis was accurate, more rapid, and easier to use than the SNaPshot analysis or denaturing high‐performance liquid chromatography analysis. Fluorescent‐based PCR‐SSCP proved useful for analyzing a large number of samples.

Conclusion: Melting curve analysis using the LightCycler is suitable for the genotyping of small numbers of samples in a routine clinical setting; fluorescent‐based PCR‐SSCP analysis using the ALF express DNA sequencer can be used for large‐scale genotyping in epidemiologic studies.
Isolation of Stimulants of Gastrointestinal Motility in Beer
Authors: Yokoo Yoshiaki , Fujii Wataru , Hori Hisako , Nagao Koji , Suwa Yoshihide , Taniyama Kohtaro , Tsuji Kuniro , Yoshida Toshiyuki , Nukaya Haruo
Published: April 2006

Background: Among various alcoholic beverages, it has reported that beer has a potent activity to stimulate gastric emptying. Our previous studies showed that beer congener stimulated gastrointestinal motility by directly stimulating muscarinic M3 receptor, present in smooth muscles of the gastrointestinal tract. However, active components that account for the action have yet to be identified. We attempted to isolate the stimulant(s) of gastrointestinal motility in beer.

Methods: Beer congener was prepared from beer and used to separate and purify active components by a series of liquid chromatography using affinity to muscarinic M3 receptor as an index. Gastrointestinal motility‐stimulating activity was evaluated using a test for activity that causes contraction of longitudinal muscles in guinea pig ileum and a test for gastric emptying activity in mice.

Results: The active components (compounds A and B) were purified and isolated from beer by four liquid chromatography steps. The IC50 values of two active isolates to muscarinic M3 receptor were 0.65 × 10−6 g/ml and 2.30 × 10−6 g/ml, respectively. The concentrations of compounds A and B contained in beer were sufficient to explain most of the muscarinic M3 receptor binding activity of beer. The active fraction that contained both compounds A and B (which was 10 times as active as beer congener in muscarinic M3 receptor binding activity) dose‐dependently contracted the longitudinal muscles of guinea pig ileum with an activity that was 20 times as potent as that of beer congener. The same active fraction significantly stimulated gastric emptying in mice with an activity 20 times as potent as that of beer congener.

Conclusions: Two active components (compounds A and B) were isolated as gastrointestinal motility stimulants (muscarinic M3 agonists) in beer. These results suggest that the two isolated active components are the active entities of the gastrointestinal motility‐stimulating effect of beer.
Pioglitazone Prevents Acute Liver Injury Induced by Ethanol and Lipopolysaccharide Through the Suppression of Tumor Necrosis Factor‐α
Authors: Ohata Mitsuru , Suzuki Hideaki , Sakamoto Kazuhiko , Hashimoto Kenichi , Nakajima Hisato , Yamauchi Masayoshi , Hokkyo Ken , Yamada Hisashi , Toda Gotaro
Published: April 2006

Background: Peroxisome proliferator–activated receptor‐γ (PPAR‐γ), which is a ligand‐dependent transcriptional factor, forms a heterodimer with retinoid X receptor (RXR) and controls many genes that are relevant to the regulation of lipid metabolism and insulin sensitization. Recent studies have shown that stimulation of PPAR‐γ inhibits the production of inflammatory cytokines in monocytes and macrophages. Alcohol and lipopolysaccharide (LPS) have already been shown to induce liver injury through the activation of many inflammatory cytokines. Thus, the activation of PPAR‐γ by its ligand may represent a potential effect causing liver injury. In this study, we investigated the effects of pioglitazone, a ligand for PPAR‐γ, on acute liver injury induced by ethanol and LPS.

Methods: Female Sprague‐Dawley rats that weighed 300 g were given ethanol (5 g/kg body weight) intragastrically and received an intraperitoneal injection of LPS 24 hr later. Subsequently, pioglitazone (1 mg/kg body weight) or vehicle alone was injected intraperitoneally 10 min and 24 hr after ethanol administration. Plasma levels of aspartate transaminase and alanine aminotransferase were measured by spectrophotometer. Plasma levels of tumor necrosis factor‐α (TNF‐α) were also determined using an enzyme‐linked immunosorbent assay. Plasma and hepatic levels of lipid peroxide were measured, and the histologic findings of the liver were examined. Reverse transcription–polymerase reaction analysis of TNF‐α, PPAR‐γ, RXR‐α, and β‐actin mRNA was performed. Western blot analysis using the p65 subunit of NF‐κB was also performed.

Results: Pioglitazone prevented increase in plasma aspartate transaminase, alanine aminotransferase, and TNF‐α levels but had no effect on plasma and hepatic levels of lipid peroxide. Pioglitazone also prevented hepatic inflammation and necrosis induced by ethanol and LPS. Ethanol and LPS induction of TNF‐α mRNA in the liver was blunted by pioglitazone; however, RXR‐α mRNA was not affected. PPAR‐γ mRNA levels were suppressed by ethanol and LPS but recaptured by pioglitazone. Western blot analysis showed that pioglitazone did not inhibit translocation of NF‐κB to nuclei.

Conclusion: These results suggest that pioglitazone may prevent liver injury induced by ethanol and LPS through the suppression of TNF‐α.
The Phosphodiesterase III Inhibitor Olprinone Decreases Sensitivity of Rat Kupffer Cells to Endotoxin
Authors: Enomoto Nobuyuki , Takei Yoshiyuki , Hirose Miyoko , Yamashina Shunhei , Ikejima Kenichi , Kitamura Tsuneo , Sato Nobuhiro
Published: April 2006

Background: Sensitivity of Kupffer cells to endotoxin [lipopolysaccharide (LPS)] and overproduction of tumor necrosis factor‐α (TNF‐α) are critical for progression of alcoholic liver injury. Therefore, suppression of TNF‐α should prove useful for treatment of alcoholic liver injury. However, a transient increase of intracellular calcium ([Ca2+]i) is required for LPS‐induced TNF‐α production by the macrophage cell line. The phosphodiesterase III inhibitor olprinone has been shown to suppress [Ca2+]i level in vascular smooth muscle cells. Accordingly, the purpose of this study was to determine whether olprinone could prevent sensitization of Kupffer cells to endotoxin.

Methods: Kupffer cells were isolated by collagenase digestion and differential centrifugation. LPS was added to Kupffer cells 24 hr after incubation with or without olprinone (0.1 μmol/liter). After addition of LPS (10 μg/ml) to culture media, [Ca2+]i was measured using a fluorescent indicator, fura‐2.

Results: LPS increased [Ca2+]i of Kupffer cells in control rats from basal levels (28 ± 4 nmol/liter) to 280 ± 14 nmol/liter. This increase was blunted by olprinone (91 ± 8 nmol/liter). Similarly, olprinone diminished the LPS (1 μg/ml)‐induced TNF‐α production by Kupffer cells by 30% (2220 ± 116 vs. 1386 ± 199 pg/ml; p < 0.05).

Conclusions: These results indicate that olprinone decreases sensitivity of Kupffer cells to endotoxin.
Associations Between Serum Leptin Levels and Transaminase Activities and the Status of Lifestyle in Japanese Workers
Authors: Yokoyama Hirokazu , Hirose Hiroshi , Ohgo Hideki , Saito Ikuo
Published: April 2006

Background: Leptin has been implicated in the pathogenesis of various liver diseases. In this study, associations between serum leptin levels and serum transaminase activities and the statuses of various lifestyles, including that of ethanol consumption, were studied.

Methods: Associations between these factors were statistically examined in 122 Japanese men on the basis of the data taken from their health checkups. Individuals with cirrhosis, hepatitis virus infection, and autoimmune liver diseases were excluded.

Results: Spearman's simple regression analyses demonstrated that serum leptin levels correlated with serum activities of aspartate aminotransferase (r= 0.174, p= 0.0382) and alanine aminotransferase (ALT; r= 0.336, p < 0.0001) but not with serum γ‐glutamyl transpeptidase activity (r= 0.155, p= 0.0656). In multiple regression analysis in which subjects’ age, levels of serum triglyceride, and insulin resistance index were adjusted, the logarithmic serum leptin level was significantly associated with logarithmic ALT activity (p= 0.004) but not with logarithmic aspartate aminotransferase activity (p= 0.134). ANOVA showed no significant association between serum leptin levels and total lifestyle status assessed by Breslow's index. Multiple logistic regression analysis showed that normal body mass index and proper exercise were factors accounting for maintaining a normal leptin level, whereas the ethanol consumption level did not affect the serum leptin level. No significant association between ethanol consumption and serum leptin level was confirmed by single regression analysis as well as by Spearman's simple regression test.

Conclusion: Increased serum leptin is related to morbid conditions increasing ALT. Because the association between the degree of ethanol consumption and the serum leptin level was not significant, the reported association between the serum leptin level and alcoholic liver disease should, at least, not be a feature of its early stage.
Alcohol Use and Suicidal Behavior in Women: Longitudinal Patterns in a U.S. National Sample
Authors: Wilsnack Sharon C. , Wilsnack Richard W. , Kristjanson Arlinda F. , Vogeltanz‐Holm Nancy D. , Windle Michael
Published: April 2006

Abstract: Background: Much of the research on suicidality has focused on adolescents and completed suicides, with less attention to types of suicidal behavior (ideation and attempts) that are more common among women. Research has associated women's suicidality with hazardous drinking, adverse childhood experiences, relationship problems, depression, and earlier suicidal behavior. The longitudinal analyses here examine long‐term antecedents of suicidal ideation among women in the U.S. general population.

Methods: We used 1981 and 1991 survey data to predict post‐1991 suicidal ideation in a 1996 national sample of 709 women aged 26 to 54 (538 current drinkers). Predictors included 1991 measures of hazardous drinking, depressive episodes, illicit drug use, general health, children at home, interaction with partner, and previous suicidal ideation. Predictors from childhood included recalled parental drinking, parental love or rejection, early drinking and sexual intercourse, and sexual abuse. Demographic predictors included age, education, and ethnicity. A three‐stage structural equation model that included these variables was evaluated with Mplus for women who were drinkers in 1991 and/or 1996.

Results: Almost all women who attempted suicide also reported suicidal ideation. Among women drinkers, suicidal ideation before 1991 was more common in the following groups: Latinas, women who believed that their parents had rejected them, and women who reported childhood sexual abuse. Hazardous drinking and poorer health in 1991, childhood histories of sexual abuse and early drinking, and previous suicidal ideation predicted suicidal ideation after 1991. Domestic stressors in 1991 (inability to share feelings with a partner and having four or more young children at home) also predicted subsequent suicidal ideation, but depressive episodes did not. Suicidal ideation was less likely among women drinkers who reported past illicit drug use.

Conclusions: Suicidal ideation among women drinkers was largely predictable from previous suicidal ideation, hazardous drinking, adverse childhood experiences, and domestic stressors. Higher rates of pre‐1991 suicidal ideation among Latinas indicate a need for further study of ethnic influences on suicidality. Reduced suicidal ideation among women with past illicit drug use suggests that conclusions about such use from shorter‐term studies may be oversimplified. Understanding women's suicidal ideation, as a precursor to suicidal actions, requires more detailed research on pathways by which hazardous drinking as well as combined distress from childhood experiences and adult domestic environments may increase women's despair and thoughts of suicide.
Valuation and Performance of Reacquisitions Following Equity Carve‐Outs
Authors: Gleason Kimberly , Madura Jeff , Pennathur Anita K.
Published: April 2006

While existing literature reports a positive market reaction to parent companies conducting carve‐outs, we find that the response to carve‐outs that are ultimately reacquired is negative or insignificant. Reacquired units perform considerably worse than those that are not reacquired. Thus, parents may perceive that the market does not recognize the potential of these poorly performing units, and reacquires them to capitalize on the parents' private information. The reacquisition announcement results in a favorable market reaction for the parents and the units. However, parents experience negative long‐term buy‐and‐hold abnormal returns when they reacquire less than 100% of units' shares.
Contact dermatitis in a spinal injuries centre
Authors: Walshe Margaret M.
Published: April 2006

A routine patch testing survey earned out on 122 patients in the National Spinal Injuries Centre at Stoke Mandeville Hospital showed that 40.1 % of the patients studied gave positive patch test results to medicaments and other topical applications. The incidence of positive results was higher in patients with a history of pressure sores (45.1 %) than in those who had never had sores (33.3 %). The significance of these results is discussed.
Cross‐sensitization patterns in acrylate allergies
Authors: Jordan William P.
Published: April 2006

Five subjects developed allergic contact dermatitis to one or more acrylate components used in a commercial adhesive tape. Patch testing to acrylic monomers was performed to examine their cross‐reaction patterns. Two subjects with broad cross‐reactions to acrylates did not react to methyl methacrylate or the alkyl methacrylate that corresponded to the acrylate which induced the sensitization. Methyl methacrylate may not be adequate as a screen for many acrylates used commercially.
Occupational dermatoses among foresters
Authors: Siregar R. S.
Published: April 2006

The incidence of occupational dermatoses among the forest workers of a limber company has been investigated. In the survey 73.69% of the occupational dermatoses observed were contact dermatitis, predominantly due to sawdust and sap. Insect bites, mycotic infections and staphylococcal and streptococcal infections were seen. The results of the survey and preventive measures are discussed.
Preventive dermatology: A point of view and a challenge
Authors: Burry John N.
Published: April 2006

The implications of “subliminal toxicology a term which has been coined by Dr. L. Goldberg, the editor of Food and Cosmetics Taxicology, are discussed and related In the practice of dermatology. It is argued that only legislation proposed by dermatologists and instituted by Government Authorities can fully protect the public against unnecessary exposure to medicinal and industrial chemicals.
Chlorocresol sensitivity
Authors: Burry John N. , Kirk John , Reid John G. , Turner Tom
Published: April 2006

Contact allergic sensitivity may follow the use of chlorocresol incorporated us a preservative in to both betamethasone cream and aqueous cream, which are commonly prescribed as a mixture in South Australia. In several cases, although the clinical courses indicated sensitivity to chlorocresol, patch test reactions to this chemical were negative. In these cases positive patch lest reactions to chloroxylenol, a chemical closely related to chlorocresol, confirmed the diagnoses.
Aroma chemicals Reference sources for perfume and flavour ingredients with special reference to cinnamic aldehyde
Authors: Collins F. W. , Mitchell J. C.
Published: April 2006

Bibliographic sources for the complex subject of aroma chemicals are reviewed. The references ore not comprehensive but are those which we found to be of value in finding out some of the opportunities for contact with a sensitizing chemical compound, cinnamic aldehyde.
Cinnamic aldehyde in toothpaste. 1. Clinical aspects and patch tests
Authors: Magnusson B. , Wilkinson D. S.
Published: April 2006

Although cinnamon is known to cause dermatitis in bakers and confectioners, it has only rarely been reported as causing trouble in food or cosmetics. A newly‐formulated ‘spicy’ toothpaste containing cinnamon as a flavouring agent was the cause of oral symptoms in eight patients referred to clinics in Buckinghamshire and in Malmo and in a further eight patients discovered Subsequently.

Similar symptoms and patch test results were observed independently at both centres. Positive reactions were obtained with 1 % cinnamic aldehyde in 15 out of 16 patients tested. Only one patient reacted to a standard sample of balsam of Peru (25 % in petrolatum).
Contact dermatitis in patients with leg ulcers
Authors: Angruni G. , Rantucio F. , Meneghini C. L.
Published: April 2006

The incidence of contact allergy to 63 substances, including active principles and excipients used in n variety of topical preparations, has been studied by patch testing in 306 patients being treated conservatively for stasis dermatitis with or without ulceration. Positive reactions to one or more test compounds were recorded in 177 patients. The main offenders among drugs were neomycin, sulphonamide and promethazine; among the excipients, they were parabens, lanolins and benzoyl peroxide. Frequent, reactions were observed to certain substances of the ‘para’ group, benzocaine, diaminodiphenylmethane, aniline and paruphenylendiamine, with the first three acting mainly as indicators of cross‐sensitization. The extension and spread of allergic dermatitis can also he produced by drugs administered systematically. Recognition of the allergens responsible for allergic contact dermatitis arising at the lower leg site is a necessary condition if chronicity and Spread of the dermatitis are to be prevented. For the same reason it is important to restrict topical applications to non‐allergic substances.
The histopathology of fiberglass dermatitis in relation to von Hebra's concept of eczema
Authors: Cuypers J. M. C. , Hoedemaeker J. , Nater J. P. , de Jong M. C. J. M.
Published: April 2006

A group of 36 normal control persons was patch‐tested with glass fibers. The tested filaments had a length of about 3 to 5 mm and a length of 9 to 13 μM. The glass fibers were obtained from the normal production process. They were coated with cured epoxy resin. A group of 29 normal control persons was tested with the Mime type of fibers from which the epoxy finish had been burned off. Another group of 36 persons was patch‐tested with ultrasmall glass globes with a diameter of 10 to 15 μM. Coated and uncoated glass globules were tested. On every person 5 patch tests with the same material were done. They were removed after 1, 5, 24, 48 and 72 h. On coated fiber, 12 of 36 tested people reacted with either a + or a ++ reaction. On the uncoated fibers a reaction could be noted in 10 out of 29 persons.

The patch tests with coated as well as uncoated glass globules were all negative. A total of 60 biopsies was performed in those cases where + or ++ reactions were noted. The histological examination of the biopsies showed no differences between the reactions on coaled and uncoated fibers. The skin reactions to glass fiber showed, besides microtraumatic changes, several histological characteristics of an eczematous reaction, tike spongiosis and perivascular lymphocytic infiltration. The importance of these findings is discussed. It is emphasized that histological alterations are only one of the six points which must be taken into account when the diagnosis of eczema is considered.
The angry back syndrome: eczema creates eczema
Authors: Mitchell J. C.
Published: April 2006

False positive patch test reactions are common when the skin of the back is hyper‐reactive, Such reactions can obscure or invalidate observations of multiple specific sensitivity and of cross‐sensitivity to contactants. The pathogenesis of the hyper‐reactive skin (‘angry back’) is discussed and a mechanism postulated for the notion that eczema at certain sites can provoke an eczematous tendency at other sites.
Contact hypersensitivity to some perfume materials
Authors: Mitchell J. C.
Published: April 2006

Some recent publications concerning perfume contact sensitivity are briefly reviewed. Japanese workers have identified some perfume sensitizers and have devised an allergen replacement system. Costus absolute of perfumery has been found to sensitize guinea‐pig and man; sesquiterpene lactones are responsible for cross‐sensitivity with some other plant products. Balsam of Peru is a useful screen for perfume sensitivity; terpenoids of balsams require study.
Legislation on prevention of occupational dermatoses
Authors: Behrbohm Peter
Published: April 2006

Legislation is one way to eliminate sensitizers und irritants. Purity requirements, declaration and labelling, industrial health codes and pre‐employment occupational aptitude examinations are useful in combating occupational and contact dermatitis by drugs and products of daily use. Chromium compounds, turpentine, balsam of Peru, benzocaine and others can be eliminated by administration and legislation.
Para‐chloro‐meta‐xylenol allergic contact dermatitis in seven individuals
Authors: Storrs Frances J.
Published: April 2006

Seven individuals are discussed who developed allergic contact dermatitis following sensitization to the antibacterial agent parachlorometaxylenol (chloroxylenol, PCMX) contained in either medicated Vaseline or in electro‐cardiogram paste. The hazard of PCMX sensitization is great in that this chemical is present in over 30 “across the counter” products. PCMX sensitive people may cross‐react to chlorocresol.
Allergic “contact” dermatitis from disulfiram implants.
Authors: Lachapelle J. M.
Published: April 2006

Two cases of allergic “contact” dermatitis to implanted disulfiram (tetraethylthiuramdisulfide or TETD) pellets are described. This side effect has never been reported before. Other local complications from disulfiram implantations are reviewed.
Acute laryngeal obstruction presumed secondary to thiomersal (merthiolate) delayed hypersensitivity
Authors: Maibach Howard
Published: April 2006

A patient treated his slight sore‐throat with a thiomersal first aid spray. The next day, because of continued discomfort, he repealed its use. Laryngeal obstruction followed within hours. Emergency tracheostomy produced prompt improvement. Patch testing revealed an extreme spreading reaction to thiomersal. It is our interpretation that the acute laryngeal obstruction was delayed hypersensitivity to this first aid spray.
Updating the maximization test for identifying contact allergens
Authors: Kligman Albert M. , Epstein William
Published: April 2006

The maximization test for detecting contact allergens has proved to possess both sensitivity and specificity. However, modifications have become necessary because of excessive irritancy reactions to sodium lauryl sulfate. Fewer exposures are now recommended during induction and lower concentrations for challenge patch testing. Pre‐testing of each subject in the panel is now standard procedure. The problem of interpreting challenge patch tests is discussed in detail.
Contact dermatitis from pyrrolnitrin (an antimycotic agent)*
Authors: Meneghini C. L. , Angelini G.
Published: April 2006

Two cases are described of acute contact dermatitis from an antifungal cream, containing pyrrolnitrin, employed for the treatment of tinea cruris. Positive reactions to pyrrolnitrin and to a chemically related substance, 1‐chloro‐2,4 dinitrobenzene, were put into evidence.
Contact sensitivity to Irgasan DP 300
Authors: Roed‐Petersen Jytte , Auken Gunnar , Hjorth Niels
Published: April 2006

Two persons had allergic contact dermatitis caused by Irgasan 0.2 % in a deodorant foot‐powder and 0.12 % in a deodorant stick respectively. Both had positive patch test reactions to Irgasan 2 % pet. One patient was further tested with Irgasan 1 % pet, and 0.5 % pet. She had positive reactions to these dilutions. In a blind half‐sided usage test, a soap bar containing 0.5 % Irgasan caused mild itching and a perceptible erythema, although the use of this soap was otherwise tolerated for one month. The soap bar without Irgasan caused no reactions.

Although primary sensitization from Irgasan toilet soaps has not been reported, a previously sensitized person may react to the use of Irgasan in soaps.