bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropil and neuronal changes in hippocampal NADPH‐diaphorase histochemistry in the ME7 model of murine prion disease
Authors: Picanço‐Diniz C. W. , Boche D. , Gomes‐Leal W. , Perry V. H. , Cunningham C.
Published: December 2004

Nitric oxide (NO) has been implicated in neurotoxicity and cerebral blood flow changes in chronic neurodegeneration, but its activity in the mammalian prion diseases has not been studied in detail. Nicotine adenine dinucleotide phosphate (NADPH)‐diaphorase (NADPH‐d) histochemistry is a simple and robust histochemical procedure that allows localization of the tissue distribution of NO synthases. The aim of the present study is to assess whether NADPH‐d histochemical activity is altered in the hippocampus in the ME7 model of prion disease in C57BL/6J mice. At early and late stages after the initiation of the disease we assessed features of the NADPH‐d positive cells and the neuropil histochemical activity in CA1 and dentate gyrus using densitometric analysis. In C57BL/6J mice 13 weeks postinjection of the prion agent ME7, when behavioural changes first become apparent, neuropil NADPH‐d histochemical staining increases, whereas at late stages it decreases dramatically. Both type I and type II NADPH‐d positive cells were found to survive throughout the hippocampal formation into the late stages of the disease, but diaphorase activity was reduced in dendritic branches and abnormal varicosities were present in both dendritic and axonal processes of NADPH‐d positive type I cells. The pathophysiological implications of the results remain to be investigated but both blood flow alteration and NO neurotoxicity may be features of the disease.
Degeneration of the central vestibular system in spinocerebellar ataxia type 3 (SCA3) patients and its possible clinical significance
Authors: Rüb U. , Brunt E. R. , De Vos R. A. I. , Del Turco D. , Del Tredici K. , Gierga K. , Schultz C. , Ghebremedhin E. , Bürk K. , Auburger G. , Braak H.
Published: December 2004

Although the vestibular complex represents an important component of the neural circuits crucial for the maintenance of truncal and postural stability, and it is integrated into specialized oculomotor circuits, knowledge regarding the extent of the involvement of its nuclei and associated fibre tracts in cases with spinocerebellar ataxia type 3 (SCA3) is incomplete. Accordingly, we performed a pathoanatomical analysis of the vestibular complex and its associated fibre tracts in four clinically diagnosed and genetically confirmed SCA3 patients with the aim of providing more exact information as to the involvement of the vestibular system in this disorder. By means of unconventionally thick serial sections through the vestibular nuclei stained for lipofuscin pigment and Nissl material, we could show that all five nuclei of this complex (interstitial, lateral, medial, spinal, and superior vestibular nuclei) are subject to neurodegenerative processes in SCA3, whereby examination of thick serial sections stained for myelin revealed that all associated fibre tracts (ascending tract of Deiters, juxtarestiform body, lateral and medial vestibulospinal tracts, medial longitudinal fascicle, vestibular portion of the eighth cranial nerve) underwent atrophy and demyelinization in all four of the patients studied. The reported lesions can help to explain the truncal and postural instability as well as the impaired optokinetic nystagmus, vestibulo‐ocular reaction, and horizontal gaze‐holding present in SCA3 cases.
Evaluation of clinical and immunological effects of inactivated influenza vaccine in children with asthma
Authors: Chiu Wen‐Jen , Kuo Ming‐Ling , Chen Li‐Chen , Tsao Ching‐Hsiung , Yeh Kuo‐Wei , Yao Tsung‐Chieh , Huang Jing‐Long
Published: December 2004

Although annual influenza vaccinations are recommended by many authorities, some doctors may be reluctant to vaccinate asthmatic children because of the risk of inducing bronchial reactivity and exacerbating the asthma. In this study, the effect of split influenza vaccine on clinical symptoms, airway responsiveness and its influence on T lymphocytes was evaluated. Twenty‐one asthmatic children with stable asthma were recruited and divided into two groups. Eleven patients who received the influenza vaccine formed the vaccination group and 10 patients who received a placebo formed the placebo group. Forced expiratory volume in 1 s (FEV1), airway response (PC20 methacholine, PC20 = provocation concentration causing a 20% fall in FEV1) and the T lymphocyte subset ratio (Th1/Th2) were recorded on day 1 pre‐vaccination and day 14 post‐vaccination. Patients were also asked to record their peak expiratory flow (PEF) every morning and evening and to complete daily symptom scores over the period of 2 weeks. There were no significant changes in PC20, FEV1, PEF variability, symptom scores and the Th1/Th2 ratio between the vaccination and placebo groups between day 1 pre‐vaccination and day 14 post‐vaccination. Similar results of PEF variability and asthma symptom score were obtained when the analysis was restricted to the day 1 pre‐vaccination and day 3 post‐vaccination. Immunization with split influenza vaccine does not exacerbate asthma in children either with a clinical or immunological effect. These results suggest that children with stable asthma can safely be immunized with a split influenza vaccine.
T‐lymphocyte subsets, thymic size and breastfeeding in infancy
Authors: Jeppesen Dorthe L. , Hasselbalch Helle , Lisse Ida M. , Ersbøll Annette K. , Engelmann Mads D. M.
Published: December 2004

We followed the changes in concentration of T‐lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4+ and CD8+ cells. Two different populations of infants between birth and 1 year of age were examined. Study Group I: infants with a variable duration of breastfeeding. Study Group II: long‐term breastfed infants. In both groups a correlation was found between CD8+ cells and the thymic index at 10 months of age. In Group I, infants still breastfed at the 8‐month examination had a higher CD8% than formula‐fed infants (p = 0.05), and infants breastfed at the 4‐month examination had a higher CD4% at 10 months of age (p= 0.03). Group II showed an increase in the absolute number of CD4+ and CD8+ cells from 8 to 10 months of age; and a positive correlation between the number of breastfeedings per day at 8 months of age, and an increase in CD4+ cells from 8 to 10 months of age (p <0.01). In conclusion, a correlation was found between thymus size and CD8+ cells. Breastfeeding might have both a current and long‐term immune‐modulating effect on the developing cellular immune system.
Treatment of perennial allergic rhinitis with lactic acid bacteria
Authors: Wang Ming Fuu , Lin Hsiao Chuan , Wang Ying Yu , Hsu Ching Hsiang
Published: December 2004

Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases via modifying the gut ecosystem. The aim of this study was to assess whether ingestion of fermented milk containing Lactobacillus paracasei‐33 (LP‐33), a strain newly isolated from the human intestinal tract, can improve the quality of life of patients with perennial allergic rhinitis. In a randomized, double‐blind, placebo‐controlled trial, we gave patients fermented milk with (n = 60) or without (n = 20) the addition of LP‐33 (2 × 109 colony‐forming units per bottle) for 30 days. A modified questionnaire concerning pediatric rhinoconjunctivitis quality of life was administered to all subjects or their parents at each clinical visit. Scores for the overall quality of life significantly decreased in the LP‐33 group as compared with the placebo group, in both frequency (−16.02 ± 2.14 vs. −7.27 ± 3.55, respectively; p = 0.037) and level of bother (−16.35 ± 2.33 vs. −6.20 ± 3.13, respectively; p = 0.022) after the 30‐day treatment. Subjects reported no severe adverse effects such as fever, abdominal pain, or diarrhea. The results suggest that ingestion of LP‐33‐fortified fermented milk for 30 days can effectively and safely improve the quality of life of patients with allergic rhinitis, and may serve as an alternative treatment for allergic rhinitis.
Modelling the establishment and spread of autotetraploid plants in a spatially heterogeneous environment
Authors: Li B.-H. , Xu X.-M. , Ridout M. S.
Published: December 2004

The establishment and spread of autotetraploids from an original diploid population in a heterogeneous environment were studied using a stochastic simulation model. Specifically, we investigated the effects of heterogeneous habitats and nonrandom pollen/seed dispersal on the critical value (μ) of unreduced 2n gamete production necessary for the establishment of autotetraploids as predicted by deterministic models. Introduction of a heterogeneous environment with random pollen/seed dispersal had little effect on the μ value. In contrast, incorporating nonrandom pollen/seed dispersal into a homogeneous environment considerably reduced the μ value. Incorporating both heterogeneous habitats and nonrandom pollen/seed dispersal may lead either to an increase or to a decrease in the μ value compared to that with random dispersal, indicating that the two factors interact in a complex way.
Trade-offs between sexual and clonal reproduction in an aquatic plant: experimental manipulations vs. phenotypic correlations
Authors: Thompson F. L. , Eckert C. G.
Published: December 2004

That trade-offs result from the allocation of limited resources is a central concept of life history evolution. We quantified trade-offs between sexual and clonal reproduction in the aquatic plant, Butomus umbellatus, by experimentally manipulating sexual investment in two distinct nutrient environments. Increasing seed production caused a significant but nonlinear trade-off. Pollinating half of all flowers strongly reduced clonal bulbil production, but pollinating the remaining flowers did not cause any further trade-off. Trade-offs were not stronger under low nutrient conditions that clearly limited plant growth. Experimentally induced trade-offs were not reflected in negative phenotypic correlations between sexual and clonal allocation among plants within eight populations grown in a uniform greenhouse environment. Diminishing effects of increased sexual allocation plus a lack of accord between experimental manipulations and phenotypic correlations suggest that trade-offs between sexual and clonal reproduction are unlikely to constrain the evolution of reproductive strategy in this species.
Variable selection in Platanthera bifolia (Orchidaceae): phenotypic selection differed between sex functions in a drought year
Authors: Maad J. , Alexandersson R.
Published: December 2004

We estimated selection on three morphological characters in the hermaphroditic, hawkmoth-pollinated orchid Platanthera bifolia and explored selection surfaces through male and female function. The work was carried out in northern Sweden during two flowering seasons (1994 and 1995) in one natural population and one season (1995) in another natural population. Fitness was estimated as number of pollinia removed (male function) and number of fruits produced (female function). We detected directional selection towards larger inflorescence size (flower number) through both sex functions in both populations in 1995. In 1994, with an unusually dry growing season, 78% of the individuals failed to set any fruit, and there was selection for larger inflorescences only through male function. In this year, there was selection towards longer flower spurs, which could be a direct or indirect effect of spurs being shortened by drought. The results demonstrate that selection patterns may vary temporally and spatially, and that the ‘male function hypothesis’ may be applicable as female function is more resource dependent than male function.
Parasites make male pipefish careless
Authors: Mazzi D.
Published: December 2004

Parasite-mediated sexual selection is expected to favour the avoidance of matings with infected individuals. However, the extent to which the costs and benefits of discriminating against parasitized mates trade off may depend upon numerous factors. I investigated the effects of sex and infection status on choosiness in sex-role reversed deep-snouted pipefish (Syngnathus typhle L.) that were either artificially infected with the trematode parasite Cryptocotyle sp. or sham-infected. Sham-infected males were significantly more likely to associate with a sham-infected female rather than with a Cryptocotyle-infected female. Infected males failed to discriminate against infected potential partners. Males were choosier the larger they were relative to the females available for choice. Females were not discriminatory, regardless of their infection status. Given an inverse relation between female fecundity and parasite load, choosy unparasitized males may gain enhanced reproductive success from their choice decisions. In contrast, more heavily infected wild-caught males gave birth to slightly fewer, but not smaller offspring than did uninfected or lightly infected males, suggesting only a low direct premium on choosy females. The detrimental effects of parasitism on male choosiness, and the lack of female discrimination against infected males likely have profound repercussions on the strength of sexual selection acting on the two sexes and on the dynamics of host–parasite interactions in this system.
Effects of egg yolk testosterone on growth and immunity in a precocial bird
Authors: Andersson S. , Uller T. , Lõhmus M. , Sundström F.
Published: December 2004

In oviparous vertebrates, maternal steroid allocation to eggs can have important fitness consequences for the offspring. However, elevated testosterone levels are not only associated with beneficial postnatal effects, such as enhanced growth and high social status, but may also entail costs by suppressing the immune system. In this study, testosterone levels in eggs of Chinese painted quail (Coturnix chinensis) were experimentally manipulated to evaluate its effects on growth and immunocompetence. Testosterone did not affect embryonic development, body size or growth during the first 20 days. However, elevated testosterone levels during embryonic development were immunosuppressive for chicks with inherently higher growth rate. Adaptive scenarios where only beneficial effects of increased testosterone levels are considered may therefore need to be re-evaluated.
Plant-like mating in an animal: sexual compatibility and allocation trade-offs in a simultaneous hermaphrodite with remote transfer of sperm
Authors: Pemberton A. J. , Sommerfeldt A. D. , Wood C. A. , Flint H. C. , Noble L. R. , Clarke K. R. , Bishop J. D. D.
Published: December 2004

The importance of sexual compatibility between mates has only recently been realized in zoological research into sexual selection, yet its study has been central to botanical research for many decades. The reproductive characteristics of remote mating, an absence of precopulatory mate screening, internal fertilization and embryonic brooding are shared between passively pollinated plants and a phylogenetically diverse group of sessile aquatic invertebrates. Here, we further characterize the sexual compatibility system of one such invertebrate, the colonial ascidian Diplosoma listerianum. All 66 reciprocal pairings of 12 genetic individuals were carried out. Fecundities of crosses varied widely and suggested a continuous scale of sexual compatibility. Of the 11 animals from the same population c. 40% of crosses were completely incompatible with a further c. 20% having obvious partial compatibility (reduced fecundity). We are unaware of other studies documenting such high levels of sexual incompatibility in unrelated individuals. RAPD fingerprinting was used to estimate relatedness among the 12 individuals after a known pedigree was successfully reconstructed to validate the technique. In contrast to previous results, no correlation between genetic similarity and sexual compatibility was detected. The blocking of many genotypes of sperm is expected to severely modify realized paternity away from ‘fair raffle’ expectations and probably reduce levels of intra-brood genetic diversity in this obligatorily promiscuous mating system. One adaptive benefit may be to reduce the bombardment of the female reproductive system by outcrossed sperm with conflicting evolutionary interests, so as to maintain female control of somatic : gametic investment.
Between-year variation of MHC allele frequencies in great reed warblers: selection or drift?
Authors: Westerdahl H. , Hansson B. , Bensch S. , Hasselquist D.
Published: December 2004

The major histocompatibility complex (MHC) genes are extremely polymorphic and this variation is assumed to be maintained by balancing selection. Cyclic interactions between pathogens and their hosts could generate such selection, and specific MHC alleles or heterozygosity at certain MHC loci have been shown to confer resistance against particular pathogens. Here we compare the temporal variation in allele frequencies of 23 MHC class I alleles with that of 23 neutral microsatellite markers in adult great reed warblers (a passerine bird) in nine successive cohorts. Overall, the MHC alleles showed a significantly higher variation in allele frequencies between cohorts than the microsatellite alleles, using a multi-variate genetic analysis (amova). The frequency of two specific MHC alleles, A3e (P = 0.046) and B4b (P = 0.0018), varied more between cohorts than expected from random, whereas none of the microsatellite alleles showed fluctuations exceeding the expectation from stochastic variation. These results imply that the variation in MHC allele frequencies between cohorts is not a result of demographic events, but rather an effect of selection favouring different MHC alleles in different years.
Microbial Threat – the Copenhagen Recommendations Initiative of the EU
Authors: Frimodt‐Møller N.
Published: December 2004

The Microbial Threat was the name of an invitational EU conference held in Copenhagen in 1998, which for the first time made antibiotic resistance an official EU issue. The initiative resulted in a set of conclusions, which together with a summary of the conference was published as The Copenhagen Recommendations. This was soon followed by an EU Council Recommendation in 2001 exhorting the member states to follow and enact the recommendations from the Copenhagen meeting. Funding from EU research funds was later provided for projects monitoring resistance as well as antibiotic use, both of which have been lacking in most EU countries until now. The initiative is a good example of a major health issue being lifted by a concerted and official EU action.
Spread of Resistant Bacteria and Resistance Genes from Animals to Humans – The Public Health Consequences
Authors: Mølbak K.
Published: December 2004

The paper reviews the lines of evidence which link the use of antimicrobial drugs for food animals with the emergence of antimicrobial drug resistance in bacteria pathogenic to humans, with a particular focus on the public health aspects. Deductions from the epidemiology of food‐borne infections, ecological studies, outbreak investigations, typing studies and direct epidemiological observations show that resistant bacteria are transferred from food animals to man. In addition to transfer in the food chain, exchange of mobile genetic elements among commensal and pathogenic bacteria contributes to the emergence of drug resistance. There is growing evidence that this has measurable consequences for human public health. One consequence is increased transmission supported by unrelated use of anti‐microbials in humans. Other consequences are related to reduced efficacy of early empirical treatment, limitations in the choices for treatment after confirmed microbiological diagnosis, and finally a possible coselection of virulence traits. Recent epidemiological studies have measured these consequences in terms of excess mortality associated with resistance, increased duration of illness, and increased risk of invasive illness or hospitalization following infections with resistant Salmonella.
Evidence of an Association Between Use of Anti‐microbial Agents in Food Animals and Anti‐microbial Resistance Among Bacteria Isolated from Humans and the Human Health Consequences of Such Resistance
Authors: Angulo F. J. , Nargund V. N. , Chiller T. C.
Published: December 2004

Several lines of evidence indicate that the use of anti‐microbial agents in food animals is associated with anti‐microbial resistance among bacteria isolated from humans. The use of anti‐microbial agents in food animals is most clearly associated with anti‐microbial resistance among Salmonella and Campylobacter isolated from humans, but also appears likely among enterococci, Escherichia coli and other bacteria. Evidence is also accumulating that the anti‐microbial resistance among bacteria isolated from humans could be the result of using anti‐microbial agents in food animals and is leading to human health consequences. These human health consequences include: (i) infections that would not have otherwise occurred and (ii) increased frequency of treatment failures and increased severity of infection. Increased severity of infection includes longer duration of illness, increased frequency of bloodstream infections, increased hospitalization and increased mortality. Continued work and research efforts will provide more evidence to explain the connection between the use of anti‐microbial agents in food animals and anti‐microbial‐resistant infections in humans. One particular focus, which would solidify this connection, is to understand the factors that dictate spread of resistance determinants, especially resistant genes. With continued efforts on the part of the medical, veterinary and public health community, such research may contribute to more precise guidelines on the use of anti‐microbials in food animals.
Antimicrobial Resistance in Bacteria from Food‐producing Animals. Risk Management Tools and Strategies
Authors: Grugel C. , Wallmann J.
Published: December 2004

The application of antimicrobial agents has proved to be the main risk factor for development, selection and spread of antimicrobial resistance. This link applies to the use of antimicrobial agents in human and in veterinary medicine. Furthermore, antimicrobial‐resistant bacteria and resistant genes can be transmitted from animals to humans either by direct contact or via the food chain. In this context, risk management has to be discussed regarding prevention and control of the already existing antimicrobial resistance. One of the primary risk management measures in order to control the development and spread of antimicrobial resistances is by regulating the use of antimicrobial agents and subjecting their use to guidelines. Thereby, the occurrence of antimicrobial resistant bacteria in the human and veterinary habitat can be controlled to a certain degree. There is little information about past attempts to prevent the development of resistances or to control them, and even less is known about the effectiveness or the cost intensiveness of such efforts. Most of the strategies focus on preventing and controlling antimicrobial resistance by means of the reduction or limitation of the use of antimicrobial agents in food‐producing animals.
Onychomycosis in Denmark: prevalence of fungal nail infection in general practice
Authors: Svejgaard E. L. , Nilsson J.
Published: December 2004

The study was initiated in order to get knowledge of the frequency of onychomycosis in patients visiting general practitioners in Denmark. A study design was using a display showing photos of abnormal nails including fungal infection, a clinical examination and a questionnaire. The practitioners obtained nail material. Direct microscopy and culture as well as histopathology, were carried out blindly in two different mycological laboratories. A number of 8546 patients were seen during the 6 months of the study, 5755 (67.3%) took part in the investigation. Clinical abnormal nails were observed in 948 (16.5%) patients, 52% males and 48% females, aged 18–92, mean 55 years old. Onychomycosis caused by dermatophytes were found in 238 (4.1%) and by Candida albicans in 45 (0.8%). Trichosporon cutaneum and Scopulariopsis brevicaulis were isolated each in 15 cases as single cultures. Onychomycosis, was typically seen in toenails as the distal‐lateral type in males more than 40 years old. Predisposing factors were familiar dermatophytosis (22%), trauma (16.9%), diabetes mellitus (6.7%) and peripheral circulatory insufficiency (5.9%).
Prevalence of Candida dubliniensis among germ tube‐positive yeasts recovered from the respiratory specimens in HIV‐negative patients
Authors: Fotedar R. , Al Hedaithy S. S. A.
Published: December 2004

The present investigation was conducted to identify Candida dubliniensis, from respiratory specimens, recovered from HIV‐negative patients. Over a 7‐month period, 75 germ tube and chlamydospore‐positive yeasts were screened for C. dubliniensis, using a variety of phenotypic characteristics. Their identification was based on sugar assimilation reactions using API 20 C Aux. A total of seven (9%) isolates recovered from sputum, bronchial lavage and nasopharyngeal aspirate were identified as C. dubliniensis. All the isolates were susceptible to amphotericin B. One isolate each showed resistance to fluconazole and ketoconazole, and two were resistant to itraconazole. A significantly high percentage (43%) of C. dubliniensis showed resistance to flucytosine.
Immune response in mouse experimental cholangitis associated with colitis induced by dextran sulfate sodium
Authors: NUMATA YOSHIHIRO , TAZUMA SUSUMU , NISHIOKA TOMOJI , UENO YOSHITAKA , CHAYAMA KAZUAKI
Published: December 2004

Background and Aim:  Primary sclerosing cholangitis is frequently complicated by inflammatory bowel disease. Although many colitis models have been reported, little information has been obtained about complicated cholangitis. The aim of the present study was to determine whether hepatobiliary disorders occur in mice experimental colitis, and to clarify the underlying mechanisms.

Methods:  The CD‐1 mice were fed standard chow with or without dextran sulfate sodium in the drinking water, followed by histological examination of the liver and colon. Mononuclear cells were isolated from these organs, and cytokine production was assessed. The CD4/CD8 ratio and the population of natural killer T (NKT) cells were analyzed by flow cytometry.

Results:  Inflammatory cell infiltration and focal necrosis in the liver were found in 33% of treated mice. In treated mice, the CD4/CD8 ratio increased in the liver, whereas no such change was found in the colon. Also an increase of interferon‐γ and a decrease of interleukin‐4 production were observed. The NKT cell population showed transient changes in the liver and colon.

Conclusions:  Hepatobiliary disorders were complicated with experimental colitis in CD‐1 mice. Immunological findings indicate a T‐helper‐1‐dominant underlying mechanism, and NKT cells may play a pathogenic role in this model. This model may help to elucidate the relationship between hepatic and colonic inflammations.

© 2004 Blackwell Publishing Asia Pty Ltd
Hepatocellular carcinoma in Saudi Arabia: Role of hepatitis B and C infection
Authors: AYOOLA EPHRAIM A , GADOUR MOHAMMED OEH
Published: December 2004

Background and Aim:  To estimate the risk of hepatocellular carcinoma (HCC) in non‐alcoholic patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, 118 patients who were admitted to a regional hospital in Saudi Arabia were compared with 118 age‐ and sex‐matched healthy individuals.

Results:  The prevalence of HBsAg in HCC patients (67%; 95% confidence interval (CI): 57.7–75.3) was significantly higher than the rate (6.7%; 95%CI: 3.0–12.9) in the controls (OR: 28.4; 95%CI: 12.6–63.9; P < 0.001). There was a high risk of HCC in the presence of HBsAg alone (OR: 34.3; 95%CI: 14.8–79.1, P < 0.001) and anti‐HCV alone (OR: 12.2; 95%CI: 3.2–47.2; P < 0.001). Although HBV and HCV were independent risk factors in the development of HCC, there was no interactive relationship between the two viruses. Dual infections occurred in only 3.4% and were associated with only a moderate increase in the risk of HCC (OR: 14.6; 95%CI: 1.57–135.9). In 24.6% of the cases no virus was identified as the etiologic factor.

Conclusion:  Hepatitis B virus constitutes a major risk factor and HCV contributes a less significant role in the development of HCC. The ongoing program of HBV vaccination may significantly decrease the prevalence of HBV‐associated HCC in this population.
Insulin resistance and C‐reactive protein as independent risk factors for non‐alcoholic fatty liver disease in non‐obese Asian men
Authors: PARK SEUNG HA , KIM BYUNG IK , YUN JUNG WON , KIM JEONG WOOK , PARK DONG IL , CHO YONG KYUN , SUNG IN KYUNG , PARK CHANG YOUNG , SOHN CHONG IL , JEON WOO KYU , KIM HYANG , RHEE EUN JUNG , LEE WON YOUNG , KIM SUN WOO
Published: December 2004

Background and Aim:  Although insulin resistance is often considered the link between obesity and non‐alcoholic fatty liver disease (NAFLD), the role of insulin resistance, independent of obesity, as a NAFLD risk factor in non‐obese men has been less well established. Systemic inflammation may be accompanied by insulin resistance in healthy subjects. The goal of the present study was to examine if insulin resistance and systemic inflammatory markers are independent predictors of NAFLD in non‐obese men.

Methods:  The authors conducted a cross‐sectional survey of 120 patients with NAFLD and 240 controls matched by age and body mass index. Controls had no evidence of alcohol abuse, hepatitis B or C, obesity, or previous history of diabetes, fasting hyperglycemia or hypertension. Diagnosis of NAFLD was based on an elevated alanine aminotransferase level and sonographic evidence of a fatty liver. Insulin resistance was determined using a homeostasis model assessment (HOMA‐IR).

Results:  The age‐adjusted risk of developing NAFLD was strongly associated with the elevated levels in measurements of uric acid, fasting blood sugar, triglycerides, apolipoprotein B, C‐reactive protein (CRP) and HOMA‐IR, and decreased levels of high density lipoprotein cholesterol and apolipoprotein A‐I. Multivariate analysis based on univariate analysis indicated that an increase in CRP (odds ratio [OR] = 1.37; 95% confidence interval [CI]: 1.06–1.77) per 1 SD (1.48 mg/L) and HOMA‐IR (OR = 2.28; 95% CI: 1.67–3.11) per 1 SD (0.63) were independent risk factors for NAFLD.

Conclusion:  Insulin resistance and systemic inflammatory response are of key importance for inducing NAFLD, particularly in apparently healthy non‐obese men.
Small bowel bacterial overgrowth is a common cause of chronic diarrhea
Authors: TEO MARCUS , CHUNG STEPHEN , CHITTI LAURI , TRAN CUONG , KRITAS STAMATIKI , BUTLER ROSS , CUMMINS ADRIAN
Published: December 2004

Background and Aims:  Often a cause for chronic non‐specific diarrhea (≥3 stools per day for more than 4 weeks) is not identified. Small bowel bacterial overgrowth (SBO) can occur without morphological damage and remains difficult to diagnose. Often diarrhea is treated empirically with antibiotics with a good response. The aims of the present study were first to investigate the prevalence of SBO in a consecutive series of patients with chronic diarrhea and second to compare the utility of duodenal fluid culture and 14C‐d‐xylose breath/lactulose test in diagnosing SBO.

Methods:  In the first study, the cause of chronic diarrhea was prospectively diagnosed in 87 subjects. In the second study, tests of SBO were compared in 18 subjects with chronic diarrhea and 15 subjects with reflux oesophagitis used as control subjects. Duodenal fluid was aspirated at endoscopy and cultured and later a 14C‐d‐xylose breath/lactulose test was performed.

Results:  In the first study, SBO was present in 48% of those with chronic diarrhea. In the second study, the diarrhea group had an average (range) stool frequency of 5.5 (3–10) per day and had normal duodenal biopsies. A total of 33%, 50%, 67% of subjects had SBO by duodenal culture alone, by a 14C‐d‐xylose breath/lactulose test alone and by a combination of both tests, respectively. In the control group, 0%, 13% and 13% had SBO by duodenal culture alone, by 14C‐d‐xylose breath/lactulose test alone and by combination of tests, respectively.

Conclusion:  Small bowel bacterial overgrowth is a common (33–67%) cause of chronic diarrhea.

© 2004 Blackwell Publishing Asia Pty Ltd
Combined supplementation of vanadium and beta‐carotene suppresses placental glutathione S‐transferase‐positive foci and enhances antioxidant functions during the inhibition of diethylnitrosamine‐induced rat liver carcinogenesis
Authors: CHATTOPADHYAY MITALI BASU , CB MAHENDRA KUMAR , KANNA P SURESH , RAY RAJARSHI SANKAR , ROY SOUVIK , CHATTERJEE MALAY
Published: December 2004

Background and Aim:  The present study was designed to investigate the chemopreventive effects of combined vanadium (V; 0.5 p.p.m.) and beta‐carotene (BC; 120 mg/kg of basal diet) on diethylnitrosoamine (DEN)‐induced and phenobarbital (PB)‐promoted rat hepatocarcinogenesis.

Methods:  All rats were subjected to two‐thirds partial hepatectomy (PH) at the fourth week. After PH they were administered either trioctanoin alone (groups A′, B′, C′ and D′) or a single injection of DEN in trioctanoin at a dose of 10 mg/kg of body weight (groups A, B, C and D). Two weeks after the DEN treatment PB was administered (0.05% in basal diet) to all the DEN‐treated rats and continued until the end of the experiment. Supplementation of V (groups B and B′), BC (groups C and C′) or both V and BC (groups D and D′) at the doses stated previously were started 4 weeks before DEN administration (at week 0) and continued until the 16th week.

Results:  It was observed that in the DEN‐treated and PB‐promoted group (group A) the expression of the numbers and areas of the placental form of glutathione S‐transferase (GST‐P)‐positive altered hepatic foci (AHF) was maximum. Treatment with V (group B) and BC (group C) significantly reduced the expression of GST‐P‐positive AHF by 29.5% and 42.8%, respectively. An additive protection action (65.7%) was noticed in group D, which received both V and BC for the entire period of the experiment. It was also observed that supplementation of V and BC for the entire period of the experiment significantly reduced the number and size of the hyperplastic nodules, while the combination treatment worked as an additive effect, reducing the number and size of the hyperplastic nodules to 22% from 89%. Moreover, a significantly reduced level of cytosolic glutathione (P < 0.001) and glutathione‐S‐transferase (P < 0.001) activity and stabilization of aerobic metabolism and hepatic architecture of the cells as compared with carcinogen control were observed in the V + BC‐treated group.

Conclusion:  The present study suggests that V, an essential trace element, may be useful in combination with BC, an antioxidant, in the inhibition of experimentally induced rat hepatocarcinogenesis.
Prevalence of immune disturbances and chronic liver disease in family members of patients with primary biliary cirrhosis
Authors: BITTENCOURT PAULO LISBOA , FARIAS ALBERTO QUEIROZ , ABRANTES‐LEMOS CLARICE PIRES , GONCALVES LUCIANA LOFEGO , GONCALVES PATRICIA LOFEGO , MAGALHÃES EMILIA PEREIRA , CARRILHO FLAIR JOSÉ , LAUDANNA ANTONIO ATÍLIO , CANÇADO EDUARDO LUIZ RACHID
Published: December 2004

Background and Aims:  Primary biliary cirrhosis (PBC) has been reported in up to 4–6% of first degree relatives of patients with the disease. In addition, immune abnormalities, including hypergammaglobulinemia, autoantibodies and increased frequency of autoimmune disorders, were reported in family members of PBC patients. The aim of the present study was to investigate the prevalence of PBC in relatives of patients with PBC, and to investigate the occurrence of chronic liver disease (CLD) and immune abnormalities in these subjects.

Methods:  One‐hundred first degree relatives of 26 patients with PBC were interviewed and submitted to physical examination and determination of liver enzymes, γ‐globulin, bilirubin and auto‐antibodies, including antinuclear (ANA), antismooth muscle (SMA), antimitochondrial antibodies (AMA) by indirect immunofluorescence (IIF) and anti‐M2 antibody by immunoblotting (IB).

Results:  Immune disturbances were rarely observed in relatives of PBC patients. Higher γ‐globulin levels, SMA and ANA were detected in four, eight and two family members, respectively. In most subjects, these autoantibodies were either in low titers or associated with concurrent diseases. Only four relatives had extrahepatic autoimmune diseases and another eight exhibited other CLD. Primary biliary cirrhosis was detected in a sister of one patient. Additionally, two other relatives of PBC patients who tested negative for AMA by IIF showed reactivity for anti‐M2 by IB.

Conclusions:  Immune disturbances, including ANA and SMA, are uncommon in family members of PBC patients. Conversely, anti‐M2 antibodies and overt PBC do occur in relatives of PBC patients, even in Brazil where the disease is quite rare.
Induction of a 72‐kDa heat shock protein and protection against lipopolysaccharide‐induced liver injury in cirrhotic rats
Authors: MIKAMI KEN‐ICHIRO , OTAKA MICHIRO , GOTO TAKASHI , MIURA KOUICHI , OHSHIMA SHIGETOSHI , YONEYAMA KAZUO , LIN JIUN‐GUEY , WATANABE DAISUKE , SEGAWA DAISUKE , KATAOKA EI , ODASHIMA MASARU , WATANABE SUMIO
Published: December 2004

Background and Aim:  A 70‐kDa heat shock protein (stress‐inducible HSP70, HSP72) has been reported to be a cytoprotectant in a variety of organs. It has been reported that HSP72 protected non‐cirrhotic rats against endotoxemia. However, its cytoprotective effect against endotoxemia in cirrhotic rats has not yet been studied. In this study, we investigated the cytoprotective effect of HSP72 on lipopolysaccharide (LPS)‐induced liver injury in carbon tetrachloride (CCl4)‐induced cirrhotic rats.

Methods:  Liver cirrhosis was produced by an 8‐week intraperitoneal injection of CCl4 in male Sprague–Dawley rats. Expression of HSP72 was investigated using western blot analysis. Cirrhotic rats were given an intraperitoneal injection of LPS (10 mg/kg) with or without hyperthermia (42.5°C, 15 min) preconditioning. Liver injury was assessed biochemically (aspartate transaminase, alanine transaminase, bilirubin, lactate dehydrogenase, creatinine) and histologically. The plasma tumor necrosis factor (TNF)‐α level was determined.

Results:  Hyperthermia preconditioning induced a 4‐fold increase in HSP72 in the cirrhotic rat liver. Pre‐induction of HSP72 prevented LPS‐induced liver injury, as evaluated using serum biochemical parameters and histology with reduced TNF‐α response.

Conclusion:  These findings suggest that pre‐induction of HSP72 may provide therapeutic strategies for Gram‐negative sepsis‐induced liver injury in liver cirrhosis.
Kupffer cell depletion attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide treatment
Authors: FUKUDA MASAHIKO , YOKOYAMA HIROKAZU , MIZUKAMI TAKESHI , OHGO HIDEKI , OKAMURA YUKISHIGE , KAMEGAYA YOSHITAKA , HORIE YOSHINORI , KATO SHINZO , ISHII HIROMASA
Published: December 2004

Background and Aim:  The mechanisms involved in the beneficial effect of gadolinium chloride against endotoxin‐induced liver damage were studied.

Methods:  Superoxide anions released into the hepatic sinusoids were examined in a liver perfusion model using the cytochrome C method.

Results:  Gadolinium chloride treatment fully depleted ED2‐positive cells from the liver and significantly attenuated superoxide anion release after a lipopolysaccharide or tumor necrosis factor‐α (TNF‐α) challenge. Moreover, gadolinium chloride treatment resulted in a significant decline in endothelial cell damage in the hepatic sinusoids as assessed by the purine nucleoside phosphorylase/glutamic–pyruvic transaminase ratio in the liver perfusate. Although gadolinium chloride treatment did not affect the level of serum TNF‐α, it significantly reduced that of interleukin (IL)‐8 and neutrophil migration in the hepatic sinusoids after the lipopolysaccharide challenge.

Conclusion:  These data suggest that a reduction of the superoxide anion level in the hepatic sinusoids in acute endotoxemia and subsequent reduction of neutrophil migration into the liver may indicate that gadolinium chloride treatment suppresses the progression of liver damage in acute endotoxemia.
Apoptotic pathway related to oval cell proliferation
Authors: YANO YOSHIHIKO , HAYASHI YOSHITAKE , TERAMOTO TADAHISA , NAKAJI MIYUKI , NAGY PETER , NINOMIYA TOSHIAKI , WADA ATSUSHI , HIRAI MIDORI , KIM SOO RYANG , SEO YASUSHI , YOON SEITETSU , KASUGA MASATO
Published: December 2004

Background and Aim:  Oval cells, liver stem cell‐derived cells, are generated from the liver periportal region and spread into the parenchyma by an autocrine signaling pathway. The mechanism behind how oval cells take their place among packed silent hepatocytes, however, is not well understood. We hypothesized that apoptosis involves a decrease in hepatocytes surrounding oval cells.

Methods:  Male Fisher rats were treated using the AAF/PH protocol to induce oval cells in the liver. Apoptosis was assessed by measuring the activity of caspase‐3, ‐8 and ‐9, and apoptosis‐related molecules such as caspase‐3, Fas, Fas‐L and Bax were also assessed by immunohistochemical analysis and reverse transcriptase‐polymerase chain reaction (RT–PCR). Apoptosis was confirmed by TUNEL staining. Regarding antiapoptotic factors, nuclear factor‐κB (NF‐κB) DNA binding activity and proliferating cell nuclear antigen (PCNA) expression were examined.

Results:  NF‐κB elevated at the early stage of oval cell proliferation. Conversely, caspase activity increased after NF‐κB elevation. The mRNA of caspase‐3, Fas, Fas‐L and Bax was induced during and after AAF/PH treatment. Immunohistochemically, oval cells lacked the expression of these proteins, whereas the hepatocytes, particularly those surrounding oval cells, expressed strongly.

Conclusions:  The present study suggests that the apoptosis in hepatocytes through both extrinsic and intrinsic pathways mediates oval cell proliferation.
Expression of the HFE hemochromatosis gene in a community‐based population of elderly women
Authors: ROSSI ENRICO , KUEK CONCHITA , BEILBY JOHN P , JEFFREY GARY P , DEVINE AMANDA , PRINCE RICHARD L
Published: December 2004

Background and Aim:  Recent studies suggest that the clinical penetrance of associated hereditary hemochromatosis, defined as either the C282Y homozygote or compound heterozygote HFE genotype status, is much lower than previously thought.

Methods:  We investigated the clinical penetrance and phenotypic expression of HFE‐associated hereditary hemochromatosis in a community‐based population of 1352 elderly female subjects with a mean age of 75 years. Serum transferrin saturation and ferritin levels were determined on all subjects bearing a C282Y mutation and a subset of wild‐type C282Y subjects.

Results:  The prevalences of the C282Y homozygous and compound heterozygous HFE genotypes were 0.15% (2/1352) and 2.0% (27/1352), respectively. The observed prevalence of 0.15% for C282Y homozygotes borders on significance (P = 0.054) for deviation from the Hardy–Weinberg population equilibrium calculations, which predict a prevalence of 0.49%, whereas the observed and predicted compound heterozygote prevalences were not significantly different. Clinical symptoms of hemochromatosis were absent in both the C282Y homozygote subjects. Of the compound heterozygous subjects, 2/27 (7%) had elevated serum transferrin saturation and ferritin values; however, clinical symptoms of hemochromatosis were absent in both. Considered as a whole, the compound heterozygous subjects had markedly elevated means for serum iron (19.4 vs 16.0 µmol/L, P = 0.0008), transferrin saturation (34.8% vs 25.2%, P < 0.0001) and ferritin (157 vs 92 µg/L, P = 0.002) compared with the wild‐type subjects.

Conclusion:  The C282Y homozygous HFE hereditary hemochromatosis genotype was under‐represented in this elderly cohort, whereas the compound heterozygous genotype was not. None of the homozygous or compound heterozygous subjects expressed the phenotype of iron overload disease.

© 2004 Blackwell Publishing Asia Pty Ltd
Risk behaviors and antibody hepatitis B and C prevalence among injecting drug users in south‐western Sydney, Australia
Authors: MAHER LISA , CHANT KERRY , JALALUDIN BIN , SARGENT PENNY
Published: December 2004

Background and Aim:  Hepatitis C virus (HCV) infection is now the leading notifiable disease in Australia. The current study aimed to determine the prevalence of HCV and hepatitis B virus (HBV) infection and associated risk behaviors among injecting drug users (IDUs) screened in south‐western Sydney as part of a multisite prospective cohort study.

Methods:  Using a combination of snowball sampling and word‐of‐mouth recruitment strategies, 377 IDUs were interviewed using a structured questionnaire and tested for exposure to HCV and HBV. Entry criteria were injecting drug use in the previous 6 months and antibody HCV serostatus not known to be positive.

Results:  More than one‐third (36.6%) tested HCV antibody positive and one‐quarter (28%) had been exposed to HBV. Independent predictors of HCV seropositivity were HBV core antibody positive serostatus, incarceration in the past year, injecting in public, Asian ethnicity and duration of injecting. Individual risk behaviors, including sharing needles and syringes, sharing other injecting equipment and being injected by others, were not significant in either bivariate or multivariate models.

Conclusions:  Results indicate an urgent need for structural interventions designed to reduce the exposure of IDUs, particularly indigenous Australian and Asian injectors, to risk environments. Structural interventions, including population‐based hepatitis B immunization, expanded access to needle and syringe programs and drug treatment, prison diversion programs and medically supervised injecting facilities, should be incorporated into existing blood‐borne virus prevention efforts.
Argon plasma coagulation as first‐line treatment for chronic radiation proctopathy
Authors: SEBASTIAN SHAJI , O'CONNOR HUMPHREY , O'MORAIN COLM , BUCKLEY MARTIN
Published: December 2004

Background and Aim:  Chronic radiation proctopathy is a troublesome complication of radiotherapy to the pelvis, for which current treatment modalities are unsatisfactory. The present prospective study was designed to determine the usefulness and safety of argon plasma coagulation in the management of chronic radiation proctopathy.

Methods:  Twenty‐five consecutive patients (M:F 24:1, mean age: 69 years) with radiation proctopathy were prospectively included. All patients received argon plasma coagulation by a standard protocol. Response to treatment was assessed by symptom response, bleeding severity score, hematological parameters and transfusion requirements over a median 14‐month follow up.

Results:  Patients received a median of one treatment session with argon plasma coagulation. There was significant improvement in rectal bleeding in all patients, with complete cessation of bleeding in 21 (81%) of the patients. The median bleeding severity score fell from 3 to 0 (P < 0.0005). The mean hemoglobin level rose from 10.05 ± 2.21 g/dL before treatment to 12.44 ± 1.09 g/dL at 6 months following treatment (P < 0.002). There was also improvement in other symptoms such as urgency and diarrhea. Over the period of follow up, there was no recurrence of anemia and no complications were noted.

Conclusion:  These results suggest that argon plasma coagulation is a safe and effective modality in the treatment of chronic radiation proctopathy.

© 2004 Blackwell Publishing Asia Pty Ltd