bluuebunny/crossref_metadata_2025 huggingface dataset:
Bovine Serum Albumin Antibodies as a Disease Marker for Hepatitis EVirus Infection
Authors: Haroun Medhat
Published: December 2005

This report evaluates the significance of antibody/bovine serum albumin
(BSA) interactions as a risk factor for the diagnosis of acute hepatitis E. Serum samples
from 40 patients with acute hepatitis E and from 40 age/sex matched healthy adult subjects
were tested for IgA, IgG, and IgM by ELISA and by turbidimetric assay. BSA was used as a
target to characterize changes in levels of interacting immunoglobulins. Initial results
obtained before removal of antibodies that interacted with BSA suggested that HEV
patients had increased levels of IgM in their sera. It was found
that normal individuals had mean IgA, IgG, and IgM levels of 2.55 mg/mL, 9.80 mg/mL, and 1.73 mg/mL, respectively while HEV patients had mean levels of 2.66 mg/mL, 10.04 mg/mL, and 2.01 mg/mL (P < .26, P < .32, and P < .0004). However, the mean level of IgM in HEV‐infected sera after purification from
antibodies that interacted with BSA was determined to be 1.72 mg/mL indicating that there was no significant difference in IgM level
in HEV patients compared to normal individuals (P < .6). The presence of antibodies that interact with BSA might serve as a
diagnostic tool for detection of high‐risk patients.
Molecular Bases of β‐Thalassemia in the Eastern Province of Saudi Arabia
Authors: Al-Ali Amein K. , Al-Ateeq Suad , Imamwerdi Burhan W. , Al-Sowayan Saleh , Al-Madan Mohammed , Al-Muhanna Fahad , Bashaweri Laila , Qaw Foad
Published: December 2005

β‐thalassemia is a group of heterogeneous recessive
disorders common in many parts of the world. Al‐Qatif and Al‐Hassa
oases in the Eastern Province of Saudi Arabia are regions known
for high frequency of these disorders. Using two molecular
methods, based on multiplexing‐amplification refractory system and
reverse hybridization principles, the spectrum of β‐thalassemia in the region was studied. Sixty‐nine subjects with known
β‐thalassemia disease and volunteers with high hemoglobin
A2(HbA2) and low mean corpuscular volume (MCV) were included in this study.
Ten mutations were detected in 91% of the subjects under study. Six of these
mutations had previously been observed while the other four mutations are reported
here for the first time. In addition, four of the mutations accounted for 76.8% of the subjects studied. IVSII‐1 (G > A), IVSI‐5 (G > A), and codon 39 (C > T) mutations were found to be the most frequent. However, the
frequencies of different mutations reported here are slightly
different from those reported earlier. A number of these mutations
were also found in the neighboring countries, which can be
explained in terms of gene flow.
Health Considerations Regarding Horizontal Transfer of MicrobialTransgenes Present in Genetically Modified Crops
Authors: Kleter Gijs A. , Peijnenburg Ad A. C. M. , Aarts Henk J. M.
Published: December 2005

The potential effects of horizontal gene transfer on human health
are an important item in the safety assessment of genetically
modified organisms. Horizontal gene transfer from genetically
modified crops to gut microflora most likely occurs with
transgenes of microbial origin. The characteristics of microbial
transgenes other than antibiotic‐resistance genes in
market‐approved genetically modified crops are reviewed. These
characteristics include the microbial source, natural function,
function in genetically modified crops, natural prevalence,
geographical distribution, similarity to other microbial genes,
known horizontal transfer activity, selective conditions and
environments for horizontally transferred genes, and potential
contribution to pathogenicity and virulence in humans and animals.
The assessment of this set of data for each of the microbial genes
reviewed does not give rise to health concerns. We recommend
including the above‐mentioned items into the premarket safety
assessment of genetically modified crops carrying transgenes other
than those reviewed in the present study.
Effects of Extracellular Matrix on the Morphology andBehaviour of Rabbit Auricular Chondrocytes in Culture
Authors: Villar-Suárez Vega , Colaço B. , Calles-Venal I. , Bravo I. G. , Fernández-Álvarez J. G. , Fernández-Caso M. , Villar-Lacilla J. M.
Published: December 2005

Isolated chondrocytes dedifferentiate to a fibroblast‐like shape on plastic
substrata and proliferate extensively, but rarely form nodules. However, when dissociation
is not complete and some cartilage remnants are included in the
culture, proliferation decreases and cells grow in a reticular
pattern with numerous nodules, which occasionally form small
cartilage‐like fragments. In an attempt to reproduce this stable
chondrogenic state, we added a cartilage protein extract, a sugar
extract, and hyaluronan to the medium of previously
dedifferentiated chondrocytes. When protein extract was added,
many cartilaginous nodules appeared. Hyaluronan produced changes
in cell phenotype and behaviour, but not nodule formation. Protein
extract has positive effects on the differentiation of previously
proliferated chondrocytes and permits nodule formation and the
extensive production of type‐II collagen. A comparison with
incompletely dissociated chondrocyte cultures suggests that the
presence of some living cells anchored to their natural
extracellular matrix provides some important additional factors
for the phenotypical stability of chondrocytes on plastic
surfaces. In order to elucidate if it is possible that the
incidence of apoptosis is related to the results, we also
characterized the molecular traits of apoptosis.
Levels of Cytokines (IL‐1β, IL‐2, IL‐6, IL‐8, TNF‐α) and Trace Elements (Zn, Cu) in Breast Milk From Mothers of Preterm and Term Infants
Authors: Ustundag Bilal , Yilmaz Erdal , Dogan Yasar , Akarsu Saadet , Canatan Halit , Halifeoglu Ihsan , Cikim Gurkan , Aygun A. Denizmen
Published: December 2005

It has been well documented that human milk contains several
immunomodulator components which are important during infant
period when the newborn′s immune system is still under
development. In this study, we aim at examining levels of
cytokines, zinc (Zn), and copper (Cu) in milk from
mothers of premature and mature infants, and comparing changes
during lactation periods consequently. Milk was collected from
total of 40 mothers (group M: mothers of mature infants, n = 20;
group PM: mothers of premature infants, n = 20) from four
lactation stages: colostrum (0–7 days), transitional (7–14
days), mature milk (21 days), and mature milk (2nd month). Levels
of cytokines (interleukin [IL]‐lβ, IL‐2, IL‐6, IL‐8, tumor
necrosis factor‐alpha [TNF‐α]) were determined by
chemiluminesence method, whereas atomic absorption
spectrophotometer was used for the determination of Zn and
Cu levels. Cytokine levels were determined to be
high in colostrum and transient milk from mothers of full‐term
infants, whereas their levels were reduced drastically in the 21st
day and the 2nd month milk (P < .01, P < .001). Similar
trends were observed in milk from mothers of premature infants,
but cytokine levels were significantly lower in colostrum compared
to colostrum from mothers of mature infants (P < .01). The
differences in cytokine levels were continuous in transient milk
(P < .05) and mature milk (21 days) (P < .05), whereas there was
no statistically significant differences between milk from both
groups of mothers in the 2nd month (P > .05). Zn levels in
milk from mothers of premature infants were significantly lower
compared to the ones from mothers of mature infants (P < .01) and
these differences continued through the 2nd month. Although
Cu levels were lower in milk from mothers of premature
infants, there was no statistically significant difference except
colostrum (P > .05). Our results clearly demonstrate that the
level of immunomodulating agents such as cytokines and trace
elements in milk from mothers of premature infants is less than
the level of the same agents in milk from mothers of full‐term
infants. Although there are commercially available products for
infant feeding, human milk is still the best natural nutrient for
newborns. Therefore, when premature infants are breastfed,
necessary precautions such as supplemantary diets must be
considered for possible infections and risks related with immune
system deficiency.
Low‐Grade Systemic Inflammation Profile, Unrelated toHomocysteinemia, in Obese Children
Authors: Economou Emanuel V. , Malamitsi-Puchner Ariadne V. , Pitsavos Christos P. , Kouskouni Evangelia E. , Magaziotou-Elefsinioti Ioanna , Creatsas George
Published: December 2005

To investigate in prepubertal obese children (POC) the
profile of chronic low‐grade systemic inflammation (CLGSI) and
its relation to homocysteinemia, 72 POC were evaluated for serum
C‐reactive protein (CRP) and amyloid A (SAA) levels, both markers
of CLGSI, and plasma levels of total homocysteine (tHcy), an
independent risk factor for adult atherosclerosis, in comparison
to 42 prepubertal lean children (PLC). The main observations in
POC were higher CRP levels compared to PLC, positive association
of SAA levels to CRP levels, no association of CRP or SAA levels
to tHcy levels. Thus, in POC, positively interrelated to each
other, elevated CRP and unaltered SAA levels reveal a unique
profile of the CLGSI, not explaining homocysteinemia‐induced risk
for future atherosclerosis.
Crotalus durissus terrificus Venom Interferes WithMorphological, Functional, and Biochemical Changes in Murine Macrophage
Authors: Cruz Anselmo Hernández , Mendonça Ronaldo Z. , Petricevich Vera L.
Published: December 2005

Crotalus durissus terrificus venom (Cdt) is toxic for a
variety of eukaryotic cells, especially at high concentrations.
However its effects on host immune cells are not well known. The
purpose of this study was to determine the effect of Cdt on
functional status and the mediators production in peritoneal
macrophages. The effects of Cdt were analyzed in vitro and were
detected using functional status of macrophages as
determined by the H2O2 release, spreading percentage,
phagocytic index, vacuole formation, and mediators production.
Several functional bioassays were employed: cytotoxicity was
determined by taking the lyses percentage and the presence of
hydrogen peroxide (H2O2) in macrophages, using the
horseradish peroxidase‐dependent oxidation of phenol red and
nitric oxide (NO) in the supernatants of macrophages by the
Griess reaction. The tumor necrosis factor (TNF) activity was
detected by measuring its cytotoxic activity on L929 cells, and
the production the level of other cytokines was assayed
using enzyme‐linked immunosorbent assay. In vitro studies revealed
that Cdt produced (a) a discrete increase in the release of
H2O2 and vacuole formation; (b) a decrease in spreading
percentage and in the phagocytic index; and (c) an increment in
the mediators production. More pronounced increments of IL‐6 and
TNF were observed after 24 and 48 hours, respectively. Maximum
levels of IFN‐γ
and NO were observed after 96
hours. Interestingly, levels of all mediators presented a discreet
decrease, as the amount of Cdt was increased. In contrast, the
IL‐10 levels observed for all doses studied here did not alter.
The IL‐6/IL‐10 ratio may possibly reflect the balance of pro‐ and
anti‐inflammatory cytokines in macrophages, which may be
manifested in the inflammatory status during the envenoming
processes. Taken together, these data indicate that Cdt have a
differential effect on macrophage activation and that this venom
is a potent inhibitor of anti‐inflammatory response.
The Imbalance Between Metalloproteinases and Their Tissue InhibitorsIs Involved in the Pathogenesis of Dermatitis Herpetiformis
Authors: Zebrowska Agnieszka , Narbutt Joanna , Sysa-Jedrzejowska Anna , Kobos Jozef , Waszczykowska Elzbieta
Published: December 2005

Dermatitis herpetiformis (DH) is a subepidermal autoimmune
disease characterized by skin and intestinal lesions consistent
with coeliac disease. There are also some data that
metalloproteinases (MMPs) are involved in the development of skin
lesions in DH, however their exact role in this process is not
fully understood. The aim of the study was to investigate whether
MMPs and their inhibitors are involved in pathogenesis of DH. Skin
biopsies were taken from 13 patients with active DH and from 10
healthy subjects. The localization and expression of MMPs and
TIMPs were examined by immunohistochemistry. MMPs expression was
detected in basal keratinocytes and in the whole epidermis in all
of the DH subjects. Neutrophils in microabscesses and in blister fluid
were also positive for MMPs. Expression of TIMPs was moderate or
weak in all examined biopsies. Our results allow us to conclude
that imbalance between these enzymes takes an important role in
the pathogenesis of DH.
Oxidative Stress in Patients With Acne Vulgaris
Authors: Arican Ozer , Kurutas Ergul Belge , Sasmaz Sezai
Published: December 2005

Acne vulgaris is one of the common dermatological
diseases and its pathogenesis is multifactorial. In this study, we
aim to determine the effects of oxidative stress in acne vulgaris.
Forty‐three consecutive acne
patients and 46 controls were enrolled. The parameters of
oxidative stress such as catalase (CAT), glucose‐6‐phosphate
dehydrogenase (G6PD), superoxide dismutase (SOD), and
malondialdehyde (MDA) in the venous blood of cases were measured
spectrophotometrically. The values compared with control group,
the relation between the severity and distribution of acne, and
the correlation of each enzyme level were researched.
CAT and G6PD levels in patients were found to be
statistically decreased, and SOD and MDA levels were found to be
statistically increased (P < .001). However, any statistical
difference and correlation could not be found between the severity
and distribution of lesions and the mean levels of enzymes. In
addition, we found that each enzyme is correlated with one another.
Our findings show that oxidative stress
exists in the acne patients. It will be useful to apply at least
one antioxidant featured drug along with the combined acne
treatment.
Effects of Antioxidant Therapy on Leukocyte Myeloperoxidase andCu/Zn‐Superoxide Dismutase and Plasma Malondialdehyde Levels in ExperimentalColitis
Authors: Kurutas Ergul Belge , Cetinkaya Ali , Bulbuloglu Ertan , Kantarceken Bulent
Published: December 2005

The aim of the present study was to evaluate the effects of
N‐acetylcysteine (NAC) and L‐carnitine (LCAR) supplementations on
polymorphonuclear leukocytes myeloperoxidase (MPO) and
Cu/Zn‐superoxide dismutase (Cu/Zn‐SOD) and plasma malondialdehyde
(MDA) in acetic acid (AA)‐induced ulcerative colitis model. The
mean polymorphonuclear leukocyte MPO and Cu/Zn‐SOD activity was
significantly higher in the colitis group than in the control
group. Both NAC and LCAR pretreatment markedly decreased MPO and
Cu/Zn‐SOD activity compared to colitis group. AA administration
significantly increased the levels of plasma MDA in comparison
with controls. However, NAC and LCAR administration to the
AA‐treated rats significantly reduced the MDA levels compared to
colitis group. In conclusion NAC and LCAR could be beneficial
agents in restoring the circulating proinflammatory mediators.
The Development of Strategic Thinking: Learning to Impact Human Systems in a Youth Activism Program
Authors: Larson Reed , Hansen David
Published: December 2005

Human systems, including institutional systems and informal social networks, are a major arena of modern life. We argue that distinct forms of pragmatic reasoning or ’strategic thinking‘ are required to exercise agency withinsuch systems. This article explores the development of strategic thinking in a youth activism program in which young people worked for social change. These youth came to understand different human systems, the school board, teachers, and students, and they learned to employ three strategic modes of reasoning: seeking strategic information, framing communications to the audience, and sequential contingency thinking. Although youth described themselves as agents of their development, adults played important roles in supporting their experience of a cycle of experiential learning. These findings suggest how the new cognitive potentials of adolescence allow youth to develop modes of reasoning that expand their capacity to exercise agency over a longer arc of time and across a wider interpersonal space.
Competency-Based Occupational Standards: Influences on Australian Speech Pathology Education
Authors: Ferguson Alison
Published: December 2005

Speech Pathology Australia developed competency-based occupational standards in response to a national government initiative across all professions and these standards have formed the basis for the accreditation process of speech pathology education programmes in Australia since 1994. This paper presents a critical appraisal of the contribution of a competency framework to curricular design, focussing on both content coverage and teaching methodologies. Also, the assessment of learning promoted through a competency-based framework is considered in relation to models of critical thinking.
US Doctoral Education: Critical Shortages and Plans for Reshaping the Future
Authors: Gallagher Tanya M.
Published: December 2005

The paper describes the major features of doctoral curricula in the United States for speech-language pathology, speech, language, hearing science and the AUD degree in audiology. Critical shortages in doctoral personnel in the United States, factors that are considered to be contributing to the problem of shortages and actions that have been recommended for reshaping the future of doctoral education are also discussed.
Education in Logopaedics in the Maltese Islands
Authors: Grech Helen
Published: December 2005

The Communication Therapy (CT) Division of the University of Malta is relatively small and young and is the only local training establishment of speech-language pathologists (SLPs) in the Maltese Islands. It aims to achieve a distinctive profile of excellence and international standing in the education and training of caring, accountable and autonomous SLPs. Various strategies are adopted by the CT Division in order to reach its goals and to overcome its limitations and challenges. These include running its own Teaching and Research Clinic, engaging in European staff/student exchange and conducting research projects with other organizations to develop scientific data and tools for use with the Maltese communication-disordered population.
Education for Practice in the UK and Ireland: Implementing Problem-Based Learning
Authors: Leahy M.M. , Dodd B.J. , Walsh I.P. , Murphy K.
Published: December 2005

Objective: This paper outlines the education of speech and language therapists in the UK and Ireland, and presents a preliminary study of student therapists’ perceptions of problem-based learning (PBL) as a learning strategy in preparation for clinical work. PBL has been used extensively in medical and dental education in Europe, in Canada, and in the Middle East, and has been applied to speech and language therapist education in Sweden and in Australia. Its implementation in the UK and Ireland is relatively new. Methods: A survey questionnaire was circulated to students in two centres via e-mail. Questions posed included student impressions of the most and least useful elements of PBL in their preparation for clinical practice, as well as how they considered improvements could be made; student reflections regarding PBL were also sought. Results and Conclusions: Findings support the implementation of PBL in the education of speech and language therapists, with more experienced students showing more positive support for PBL. Issues raised by the study include emphasis on clinical relevance of problems, particularly in the early years of the course. The majority of students regarded PBL as directly relevant for clinical preparation.
Education of Speech-Language Pathologists around the World: The Scandinavian Experience
Authors: Söderpalm Ewa
Published: December 2005

The object of this paper is to give an overview of the education and training programmes in logopedics offered in the Scandinavian/Nordic countries and to provide some information about the development of the programmes in Scandinavia since their foundation in the 1920s. In order to collect information about the various programmes, a questionnaire comprising 12 questions was sent to representatives for education programmes and national societies affiliated to the IALP. In the past all the countries used to provide possibilities for teachers to continue their education with courses in logopedics to become ‘special teachers’. These programmes no longer exist except in Norway. Degree programmes at bachelor’s and/or master’s level are now offered in all the Nordic countries. It can be concluded that the education and training in logopedics have developed into university degree programmes, with few exceptions, in the Nordic countries.
The Development of the Toronto Structured Interview for Alexithymia: Item Selection, Factor Structure, Reliability and Concurrent Validity
Authors: Bagby R. Michael , Taylor Graeme J. , Parker James D.A. , Dickens Susan E.
Published: December 2005

Background: Assessments of personality constructs increasingly use self-report and structured interview instruments, which allow for a multimethod measurement approach and decrease specific measurement method bias. The aim of this study was to develop a valid and reliable structured interview for assessing the alexithymia construct. Methods: Sixty interview questions were written initially, each with a set of scoring criteria and prompts and probes to elicit information assisting in the scoring of the respondents’ answers. Results: After pilot testing, the number of questions was reduced to 43, which were administered to 136 community participants and 97 psychiatric outpatients. A series of item and scale analyses further reduced the item pool to 24 items. Principal component analysis and confirmatory factor analysis of these 24 items revealed preliminary evidence of a hierarchical, four-factor structure, with four lower factors nested within two higher-order latent factors. This structural configuration resulted in the Toronto Structured Interview for Alexithymia (TSIA) with two domain scales and four facet scales. The TSIA and its six scales demonstrated acceptable levels of interrater, internal, and retest reliability. The TSIA and its scales correlated modestly but significantly with the 20-item Toronto Alexithymia Scale and its three factor scales, providing some support for the concurrent validity of this interview. Conclusion: The TSIA appears to be a promising structured interview for assessing alexithymia.
Dissociation as a Predictor of Cognitive Behavior Therapy Outcome in Patients with Obsessive-Compulsive Disorder
Authors: Rufer Michael , Held Dada , Cremer Julia , Fricke Susanne , Moritz Steffen , Peter Helmut , Hand Iver
Published: December 2005

Background: Previous studies have found a strong association between dissociation and obsessive-compulsive disorder (OCD). The purpose of the present study was to evaluate whether dissociation is a predictor of cognitive behavior therapy (CBT) outcome in patients with OCD. Methods: Fifty-two patients with OCD were assessed using the Dissociative Experience Scale (DES), the Yale-Brown Obsessive-Compulsive Scale and the Beck Depression Inventory. CBT lasted on average 9.5 weeks and included exposure therapy. Results: Patients who dropped out due to noncompliance had higher baseline DES scores and depression scores compared to the 43 patients (83%) who completed the study. Significant OCD symptom reduction at posttreatment was observed in study completers with a large effect size (d = 1.7). More severe OCD symptoms at posttreatment were associated with higher DES scores at baseline, and treatment nonresponders had significantly higher baseline DES scores compared to responders. These associations with outcome were mainly due to the DES subfactor absorption-imaginative involvement. In regression analyses, higher absorption-imaginative involvement scores at baseline predicted poorer CBT outcome, even after controlling for depressive symptoms, comorbid axis I disorders and concomitant psychotropic drugs. Conclusions: Results from this preliminary study suggest that higher levels of dissociation (particularly absorption-imaginative involvement) in patients with OCD might predict poorer CBT outcome. If our results can be replicated, treatment outcome might be improved by additional interventions for those patients with OCD who indicate high levels of dissociation, for example by using interventions aimed at improving coping with emotionally stressful situations.
Effect of Anti-OprF-OprI Immunoglobulin on APACHE II Score in a Porcine Two-Hit Model of Hemorrhagic Shock/Resuscitation and Pseudomonas aeruginosa Sepsis
Authors: Haberstroh J. , Gilleland Jr. H.E. , von Specht B.-U.
Published: December 2005

Background: Up to now, randomized clinical trials of treatment of bacterial sepsis with immunoglobulins show conflicting results. This paper investigates the effect of prophylactic immunization with anti-OprF-OprI antiserum on the APACHE II score in a clinically relevant two-hit model of hemorrhagic shock/resuscitation followed by Pseudomonas aeruginosa sepsis in pigs. Methods: Twenty-three German Landrace-Hybrid pigs underwent chronic implantation of vascular catheters (internal and external jugular vein, carotic and pulmonary artery), hemorrhagic shock (mean blood loss 40% of estimated blood volume) for 45 min, followed by resuscitation with crystalloid, colloid, and shed blood. Randomization was to a control group (no immunization, n = 6), an F-I group (50 mg/kg i.p. anti-OprF-OprI immunoglobulin, n = 6), an S group (50 mg/kg i.p. unspecific porcine immunoglobulins, n = 6), and a PS group (50 mg/kg i.p. immunoglobulin against the antigens of heat-killed P. aeruginosa, n = 5). After at least 18 h for recovery from anesthesia, the pigs underwent a continuous intravenous infusion of P. aeruginosa for 48 h. Thereafter, the animals were monitored for another 48 h and then dissected. Results: The APACHE II score significantly increased from baseline value in all groups during bacterial challenge. However, there were no between-group differences in APACHE II score. In contrast, pigs of the F-I and PS groups showed significant lower lung concentrations of P. aeruginosa (p < 0.05 vs. control group) at autopsy. Conclusion: These experimental data suggest that under comparable clinical conditions, a prophylactic immunization with anti-OprF-OprI immunoglobulin would not have an overall benefit to patients with P. aeruginosa sepsis.
Neutrophil Elastase Inhibitor Ameliorates Reperfusion Injury in a Canine Model of Lung Transplantation
Authors: Aoki T. , Tsuchida M. , Takekubo M. , Saito M. , Sato K. , Hayashi J.
Published: December 2005

Background: We investigated the effects of neutrophil elastase inhibitor ONO-5046 Na on lung ischemia-reperfusion injury in a canine model of single lung transplantation. Methods: 24 mongrel dogs, 12 donors and 12 recipients, were used for single lung transplantation. Lung grafts were preserved for 18 h by cold ischemia then transplanted into the left thoracic cavity of recipients. In 6 recipients (ONO group), a bolus of ONO-5046 Na (10 mg/kg) was introduced before reperfusion and followed by continuous infusion (10 mg/kg/h). The remaining 6 recipients (control group) did not receive ONO-5046 Na and thus served as controls. We evaluated lung function and respiratory parameters over 240 min. Results: The total cell number in bronchoalveolar lavage fluid increased significantly in the control group in comparison to that in the ONO group. Histologic scores after 4 h of reperfusion and myeloperoxidase activity were significantly lower in the ONO group than in the control group. Conclusion: Neutrophil elastase inhibitor ONO-5046 Na may be useful in ameliorating lung reperfusion injury after transplantation.
Kupffer Cells Infiltrate Liver Tissue Early after Ischemia-Reperfusion and Partial Hepatectomy
Authors: Baier P.K. , Baumgartner U. , Hempel S. , Wolff-Vorbeck G. , von Dobschuetz E. , Hopt U.T.
Published: December 2005

Kupffer cells, ED2+ macrophages of the liver, play an important role in liver damage and regeneration. It is proposed that Kupffer cells are stationary and regenerate after acute liver trauma by local proliferation. We analyzed their kinetics in three surgically relevant murine models of acute liver injury: partial liver resection, ischemia with reperfusion and sepsis. We found an early increase in ED2+ cells after 0.5 h and a maximum after 12 h. These results suggest an infiltration of the cells early after the injury and a later local proliferation. These ED2+ macrophages are localized predominantly periportally; nearly no macrophages are found pericentrally, except in the sepsis model. Therefore, a shifting of macrophages from portal to central seems to be unlikely, suggesting a hepatic zonation of homing factors.
New Surgical Technique for Portal Venous Port System in Swine
Authors: Kaiser G.M. , Frühauf N.R. , Broelsch C.E.
Published: December 2005

The need for serial blood sampling and continuous infusion using the portal vein for experimental surgery and pharmacological studies is evident. As suitable animal models are rare, we established a new technique to implant a permanent vascular access device to the portal vein in swine. All operations in study animals (n = 8) were technically feasible due to a regularly detected side branch of the portal vein within the inferior pancreatic region; complications did not occur. Mean operation time was 48 ± 17 min. This study clearly shows that the portal venous access is feasible and can be achieved safely using the inferior pancreatic vein for a permanent vascular access port system.
Pitavastatin Prevents Bacterial Translocation after Nonpulsatile/Low-Pressure Blood Flow in Early Atherosclerotic Rat: Inhibition of Small Intestine Inducible Nitric Oxide Synthase
Authors: Tsunooka N. , Nakagawa H. , Doi T. , Yukumi S. , Sato K. , Horiuchi A. , Miyauchi K. , Watanabe Y. , Imagawa H. , Kawachi K.
Published: December 2005

Background: Cardiopulmonary bypass decreases intestinal mucosal blood flow because of nonpulsatile and low-pressure blood flow resulting in bacterial translocation (BT) and atherosclerosis also has peripheral blood flow deficiency. The risk of nonpulsatile and low-pressure blood flow for atherosclerotic animals and the effect of statin administration, which has pleiotropic effects, were studied. Methods: Wistar rats were divided into four groups: group N (normal diet), group C (high-cholesterol diet), group S (group C plus pitavastatin therapy), and group I [group C plus inducible nitric oxide (iNOS) inhibitor therapy]. First of all, vascular responses were measured. Then the rats underwent nonpulsatile/low-pressure blood flow in the intestine, and the serum peptidoglycan concentration as a parameter of BT, the small intestinal PO2 ratio (intestinal PO2/PaO2) as a parameter of mucosal blood flow, and NO concentrations were measured before surgery (T0), at the end of 90 min of stenosis (T1), and 90 min after the release of stenosis (T2). Immunostaining for nitrotyrosine was also performed at T2. Results: Group C had vascular endothelial dysfunction without histological changes, which indicated early atherosclerosis. The serum peptidoglycan concentration increased significantly at T2 only in group C. The intestinal PO2 ratio was decreased at T1 in all the groups, and retuned to baseline at T2 in group N and group S, but not in group C or group I. Jejunal NO only in group C was significantly higher at all time points and ileal NO production at T1 and T2. There tended to be a positive stain for nitrotyrosine along the mucosal epithelium in group C. Conclusion: In the setting of early atherosclerosis, intestinal blood flow does not only improve after nonpulsatile/low-pressure blood flow but causes BT because of a large amount of NO from high enzymatic intestinal iNOS activity, and pitavastatin treatment can prevent BT by improving both issues.
Stapled Haemorrhoidopexy for Haemorrhoids in Combination with Lateral Internal Sphincterotomy for Fissure-in-Ano
Authors: Kanellos I. , Angelopoulos S. , Zacharakis E. , Kanellos D. , Pramateftakis M.G. , Blouhos K. , Betsis D.
Published: December 2005

The aim of this prospective study is to describe the combined technique and results of stapled haemorrhoidopexy and lateral internal sphincterotomy for patients suffering from prolapsing 3rd-degree haemorrhoids and chronic fissure-in-ano. During the period from 1999 to 2004, 26 patients underwent combined surgical treatment for anal fissure and prolapsing symptomatic haemorrhoids. Preoperative and postoperative clinical evaluation and the patient’s degree of satisfaction were recorded. Early complications included faecal urgency (3 patients) and pain (2 patients). Complete continence was restored within 10 weeks in all patients except 1 who had persisting incontinence to flatus. All fissures healed completely within 4 weeks. No haemorrhoidal or fissure recurrence has been observed during follow-up. The combination of stapled haemorrhoidopexy and lateral internal sphincterotomy is a safe and effective procedure for the treatment of prolapsing 3rd-degree haemorrhoids and chronic anal fissures.
Cortical and Subcapsular Cataracts: Significance of Physical Forces
Authors: Pau Hans
Published: December 2005

Cortical cataracts usually begin with either sharp limited clear fluid clefts, resulting in opaque spokes, or clear lamellar separations, resulting in cuneiform opacities. They do not commence prior to 45 years of age. From this age on an increase in lens nuclei hardening can be detected. Therefore, during disaccommodation in older lenses, mechanical shear stresses must develop between the soft remaining cortices and the harder nuclei. These shear stresses are significant regarding the different cortical ruptures in predisposed lenses: in a privileged radial direction (according to zonular traction) of the sharp limited cortical spokes, or in parallel microridges at the commencement of lamellar separations, as observed when a rubber surface slides against a harder object. In pure cortical cataracts the ion pump (K+ > Na+) and investigated metabolic parameters remain largely intact. Therefore, it is not surprising that, in contrast to subcapsular cataracts, subcapsular opacities do not occur. Subcapsular cataracts are known to be caused by a variety of factors: aging, diabetes, corticosteroids, iridocyclitis, or X-ray, among many others. In contrast to cortical cataracts, subcapsular cataracts were found to be closely associated with ion pump damage (Na+ > K+) and a variety of metabolic activity alterations. In subcapsular cataracts passive fluids (from the vitreous and camera anterior) enter externally through the lens capsule. This initially forms numerous free clear, secondary grey, subcapsular fluid vacuoles. If the ion pump (metabolic barrier) is more severely damaged fluids may also enter the lens nucleus (secondary grey nuclear cataract), which rarely results in intumescent cataract. In cortical and subcapsular cataracts and lens perforations the main cause of grey opalescence appears to be the result of lens proteins (water-soluble crystalline) coming into direct contact with free fluids (water). In cortical cataracts this happens in the area of sharp limited mechanical cortical ruptures (fluid clefts), and in subcapsular cataracts during passive, external fluid entry, resulting in subcapsular fluid vacuoles and opacities, and also later grey-white nuclear opacities. The importance of water contact with water-soluble lens crystallines in behalf of light scattering and turbidness also has been investigated experimentally.
Confirmation of the Adult-Onset Primary Open Angle Glaucoma Locus GLC1B at 2cen-q13 in an Australian Family
Authors: Charlesworth Jac C. , Stankovich James M. , Mackey David A. , Craig Jamie E. , Haybittel Michael , Westmore Rodney N. , Sale Michèle M.
Published: December 2005

Primary open-angle glaucoma (POAG) is genetically heterogeneous, with 6 named POAG loci GLC1A-F mapped and genes myocilin (MYOC) and optineurin (OPTN) identified at 2 of the loci. Using penetrance-model-free methods, we screened the POAG loci GLC1A-F in an extended Australian pedigree, using 3–5 markers within each locus. p values of less than 0.05 were obtained empirically using SimWalk2 and exactly using Genehunter for 2 markers within the GLC1B region on chromosome 2. Fine mapping of this region produced pvalues of 0.01 or less at 5 markers flanked by D2S1897 and D2S2269. The 9 cM haplotype of interest overlaps the original GLC1B region. These results provide supportive evidence for the GLC1B locus on chromosome 2cen-q13 and verify the existence of POAG susceptibility gene in this region, increasing the likelihood of gene identification.
Retinal Angiomatous Proliferation: Association with Clinical and Angiographic Features
Authors: Donati Maria Carla , Carifi Gianluca , Virgili Gianni , Menchini Ugo
Published: December 2005

Aim: It was the aim of this study to evaluate the frequency of retinal angiomatous proliferation (RAP) and its association with specific clinical and angiographic characteristics in age-related macular degeneration (AMD). Methods: A consecutive series of 126 newly diagnosed patients with exudative AMD was reviewed retrospectively. All underwent a complete ophthalmic examination, a red-free photograph and fluorescein angiography. Most patients (85/126) underwent indocyanine green choroidal angiography (ICGA). RAP was diagnosed when a connection between the retinal vasculature and the neovascular complex was recognized angiographically. Results: Out of 126 patients with recent neovascular AMD, 17 had RAP (13.5%; 95% CI 8.1–20.7). The study eye of patients with RAP had more frequent hemorrhages (88.2 vs. 59.6%; p = 0.027), hard exudates (82.4 vs. 26.6%; p < 0.001), pigment epithelium detachment (64.7 vs. 23.8%; p = 0.001) and a hot spot in ICGA (70.6 vs. 22.1%; p < 0.001) with respect to the other forms of exudative AMD. Hemorrhages were more frequently superficial, multiple and within the edge of the lesion in the RAP group. Bilateral AMD was more common in the RAP group (70.6 vs. 38.0%; p = 0.011). No statistically significant differences were found regarding sex, age and visual acuity. Conclusion: RAP represents a common lesion in patients with neovascular AMD referred to a tertiary care clinic. The recognition of hemorrhages, hard exudates, pigment epithelium detachment or a hot spot in ICGA can assist a correct diagnosis.
Oxidative Damage to Lens in Culture: Reversibility by Pyruvate and Ethyl Pyruvate
Authors: Varma S.D. , Hegde K.R. , Kovtun S.
Published: December 2005

It is generally believed that prophylactic intake of antioxidants is beneficial in delaying the onset of some aging manifestations such as cataract. However, whether such a supplementation will also be effective if the pathophysiogical process has already set in remains a largely open question. We examined this possibility with lens changes leading to cataract formation, since cataract genesis is intimately related to a continued generation of reactive oxygen species (ROS) in the aqueous humor. Since the formation of cataract is a well-defined progressive disease, starting with an early refractive change and leading to gradual enhancement of opacification, we hypothesized that even a belated start with an appropriate anti-oxidant could halt the pathological process and delay cataract maturation and vision impairment. Using lens cultures, we tested this hypothesis with pyruvate, known to be an effective and highly potent ROS scavenger. Adding pyruvate to the culture medium after lenses had sustained a 50% damage was significantly effective in preventing progress. This was apparent by better maintenance of the active rubidium transport activity in these lenses compared to controls without pyruvate treatment. Glutathione levels were also higher in the pyruvate group.
Keratectasia after Laser in situ Keratomileusis
Authors: Kim Hyojin , Song In Kyung , Joo Choun-Ki
Published: December 2005

Purpose: To describe the morphological features of a prominent ectasia of the cornea after laser in situ keratomileusis (LASIK). Methods: The morphology of the ectatic corneas was examined using corneal topography, light microscopy and transmission electron microscopy in 2 cases who underwent penetrating keratoplasty due to poor visual acuity induced by progressive corneal ectasia after LASIK. Results: On topographic examination, the apex of the corneal surface was observed within the central 3-mm zone, and the smallest thickness was 0.116 and 0.271 mm in each case. On histological examination, the epithelial layer became thinner and detached easily. Bowman’s membrane was broken down and folded. An irregular arrangement of the stromal lamellae with fibroblastic keratocytes was found. The fulled fiber cell, a transformed epithelial cell, was visible in a plane on Bowman’s layer in the central region. In contrast, the corneal endothelium was intact, and no abnormality was found in both cases. Conclusion: On morphological examination of 2 cases with corneal ectasia, a forward protrusion of both the anterior and posterior corneal surfaces occurred, and epithelial detachment, Bowman’s membrane breakage and folding and irregular lamellae were found. The 2 cases had greatly thinned and protruding corneas, yet there was no abnormality in the corneal endothelium.
Expression of Cochlin in the Vestibular Organ of Rats
Authors: Ikezono Tetsuo , Shindo Susumu , Ishizaki Masamichi , Li Lishu , Tomiyama Shunichi , Takumida Masaya , Pawankar Ruby , Watanabe Atsushi , Saito Akihiko , Yagi Toshiaki
Published: December 2005

The COCH gene mutated in autosomal dominant sensorineural deafness (DFNA9) encodes cochlin, a major constituent of the inner ear extracellular matrix. Cochlin constitutes 70% of the inner ear protein and cochlin isoforms can be classified into three subgroups, p63s, p44s and p40s. Symptoms of some DFNA9 patients are consistent with those of Ménière’s disease. Here, we report the expression of cochlin in the vestibular organ of rats using isoform-specific antibodies that recognize all three isoforms. Cochlin is highly expressed in the stromata of the maculae of otolithic organs and cristae of semicircular canals, and in the channels in the bony labyrinth that transmit the dendritic innervation to the cristae and maculae. Cochlin cannot be detected in the sensory cells, dark cells, nor in the acellular structures, otolithic membrane or in the cupula. These findings support the theory that deposition of acidophilic substance in the inner ear caused by mutation of cochlin can induce a secondary retrograde dendritic degeneration of the vestibular nerves.
CGRP Expression in the Vestibular Periphery after Transient Blockage of Bilateral Vestibular Input
Authors: Hara Hirotaka , Takeno Kenji , Shimogori Hiroaki , Yamashita Hiroshi
Published: December 2005

This study aimed to establish an animal model of reversible bilateral vestibular disorders that is suitable for examining the mechanisms of vestibular plasticity, and to observe the changes in the plasticity of vestibular efferent systems. Tetrodotoxin (TTX) was infused continuously for 7 days into the bilateral perilymph of guinea pig cochlea. We assessed the vestibulo-ocular reflex (VOR) for evaluating the vestibular function. We also investigated the changes in calcitonin gene-related peptide (CGRP) immunoreactivity in vestibular end organs to observe the changes in the plasticity of vestibular systems. The VOR was completely eliminated by TTX administration and returned to the preoperative levels within 120 h after TTX discontinuation. An obvious increase in the number of CGRP-immunoreactive fibers was observed within the neurosensory epithelia of the maculae and cristae. An animal model of reversible bilateral vestibular disorders was established and used for investigating the plasticity of the vestibular nervous system.
A New Method for Drug Application to the Inner Ear
Authors: Ito Juichi , Endo Tsuyoshi , Nakagawa Takayuki , Kita Tomoko , Kim Tae-Soo , Iguchi Fukuichiro
Published: December 2005

Inner ear sensory cells are very susceptible to injuries and recovery after damage is very difficult. Recently several drugs including neurotrophic factors have been reported to protect against inner ear injury. The purpose of this experimental study is to find new methods for applying drugs to the inner ear that effectively protect against inner ear damage. Biodegradable hydrogel was used as a carrier for application of brain-derived neurotrophic factor (BDNF) into the inner ear of guinea pigs through the round window membrane. After application of BDNF the number of surviving spiral ganglion neurons increased following injury of inner ear hair cells and spiral ganglion neurons by ototoxic treatment. This result indicates that BDNF provides effective protection against inner ear damage and that biodegradable hydrogel is useful for application of drugs to the inner ear.
Microarray Analysis of Stress-Related Gene Expression in Patients with Ménière’s Disease
Authors: Sekine Kazunori , Morita Kyoko , Masuda Kiyoshi , Sato Go , Rokutan Kazuhito , Takeda Noriaki
Published: December 2005

We developed an original microarray carrying 1,467 cDNAs of stress-related genes for the assessment of stress responses. In this study, we used microarray analysis to assess the stress-related gene expression profiles in peripheral leukocytes in 2 patients with definite Ménière’s disease. In the attack and active phases, mRNA expression levels of 57 genes and 163 genes were either up-regulated more than twofold or down-regulated by less than half in patient 1 and patient 2, respectively. Patient 1 had sporadic episodes of vertigo attack, while patient 2 had an intractable course with frequent vertigo attacks, suggesting that the magnitude of changes in gene expression is correlated with the severity of the disorder in Ménière’s disease. The expression of a total of 26 genes commonly changed in both patients in the attack and active phases and returned to the baseline levels in the remission phase, suggesting the involvement of the distinct group of stress-related genes in the development of vertigo attacks in Ménière’s disease. We then examined the effects of caloric stimulation on the stress-related gene expression profiles in peripheral leukocytes in 5 healthy volunteers. Although unilateral caloric stimulation with cold water caused acute vertigo with nystagmus, the expression profiles of stress-related genes did not significantly change after this experiment. This finding indicated that the up- or down-regulated genes in the attack and active phases in patients with Ménière’s disease are not secondary to vertigo or vertigo-associated anxiety. All these findings suggested that the distinct group of stress-related genes contributed to the development of vertigo attacks of Ménière’s disease and that stress-related gene expression profiles in peripheral leukocytes can be a predictive and therapeutic tool for episodic vertigo attacks in patients with Ménière’s disease.
Epidemiologic Characteristics of Definite Ménière’s Disease in Japan
Authors: Shojaku Hideo , Watanabe Yukio , Fujisaka Michiro , Tsubota Masahito , Kobayashi Kenji , Yasumura Satsuki , Mizukoshi Kanemasa
Published: December 2005

To identify epidemiologic characteristics of definite cases of Ménière’s disease (DMD), we conducted retrospective surveys of the period 1990–2004 of the Nishikubiki district and of the period 1980–2004 of Toyama Medical and Pharmaceutical University. Three hundred and seventy-five patients (50 from Nishikubiki, 325 from Toyama) were diagnosed with DMD according to the diagnostic criteria proposed by the Japanese Society for Equilibrium Research. There was a slight increase in the prevalence of DMD during the period 1990–2004. However, incidence did not change significantly over time. The average annual prevalence and incidence were 34.5 and 5.0, respectively, per 100,000 population. Incidence and prevalence predominated in females. With respect to age at disease, the incidence in elderly patients was increased when we corrected for age distribution in the overall population.