bluuebunny/crossref_metadata_2025 huggingface dataset:
Testosterone Regulates Androgen Receptor Immunoreactivity in the Copulatory, but not Courtship, Neuromuscular System in Adult Male Green Anoles
Authors: Holmes M. M. , Wade J.
Published: August 2005

Androgens regulate the expression of male reproductive behaviour in diverse vertebrate species, often acting on androgen receptors (AR) to induce structural or functional changes in the nervous system and periphery. Male green anoles possess two sexually dimorphic neuromuscular systems, one controlling throat fan (dewlap) extension, which occurs during courtship, and the other mediating copulatory organ function. Although androgens are required for behavioural activation in both systems, testosterone has differential effects on the neuromuscular morphology. It increases the size of copulatory muscle fibres during the breeding season, but significant effects on dewlap muscle fibre size and motoneurone soma size in either system have not been detected. Corresponding to the lack of testosterone‐induced morphological effects in the courtship system, relatively low levels of AR are expressed in the associated motoneurones. The present experiment had two goals, aiming to determine whether: (i) the other courtship and copulatory neuromuscular tissues express AR and (ii) testosterone and/or seasonal environmental changes regulate AR expression. The percentage of AR+ nuclei was evaluated in both the breeding and nonbreeding seasons in gonadally intact adult males (Experiment 1) and in castrated males treated with either testosterone or vehicle (Experiment 2). AR was extensively expressed in the dewlap and copulatory muscles, and in a high percentage of the copulatory motoneurones, but immunoreactivity did not vary across season. Testosterone increased the percentage of AR+ nuclei in the copulatory muscles of both breeding and nonbreeding males but not in the dewlap muscle or copulatory motoneurones. Finally, the target structures for both systems (cartilages and hemipenes) expressed AR in all animals. Therefore, the effects of testosterone on AR immunoreactivity suggest that up‐regulation of the receptors may be important for morphological change. However, because all structures investigated in the present experiment expressed AR, the data also indicate that the receptors are involved with other functions.
Ghrelin‐Induced Stimulation of Colonic Propulsion is Dependent on Hypothalamic Neuropeptide Y1‐ and Corticotrophin‐Releasing Factor 1 Receptor Activation
Authors: Tebbe J. J. , Mronga S. , Tebbe C. G. , Ortmann E. , Arnold R. , Schäfer M. K.‐H.
Published: August 2005

Peptides participating in the hypothalamic control of feeding behaviour are also involved in the central autonomic control of gastrointestinal functions, such as secretion and motility. An anatomical interaction and functional relationship in the central nervous system between the feeding‐related peptides neuropeptide Y and ghrelin is well documented. Furthermore, it has been shown that feeding‐related peptides can influence digestive function via central corticotrophin‐releasing factor (CRF) pathways. In the present study, we investigated the role of ghrelin in the central autonomic control of colonic motility. Furthermore, we addressed the hypothesis that ghrelin is involved in the hypothalamic control of colonic motor function, utilizing central neuropeptide Y receptors and hypothalamic CRF pathways. Ghrelin (0.03, 0.06 and 0.12 nmol) bilaterally microinjected into the paraventricular nucleus (PVN) induced a significant stimulation of colonic propulsion. In particular, the colonic transit time decreased from 312 ± 7 min to 198 ± 12 min. Microinjection of the neuropeptide Y1 receptor antagonist, BIBP‐3226 (200 pmol), or the nonselective CRF receptor antagonist, astressin (30 pmol), into the PVN abolished the stimulatory effect of ghrelin injected into the PVN on colonic transit time, whereas pretreatment with the selective CRF2 receptor, antisauvagine‐30 (28 pmol), failed to affect the effect of PVN‐ghrelin injection on colonic propulsion. These results suggest that ghrelin can act as central modulator of gastrointestinal motor functions at the level of the PVN via neuropeptide Y1‐ and CRF1 receptor‐dependent mechanisms.
Effect of Calcitonin Gene‐Related Peptide on Gonadotrophin‐Releasing Hormone mRNA Expression in GT1‐7 Cells
Authors: Kinsey‐Jones J. S. , Li X. F. , Bowe J. E. , Brain S. D. , Lightman S. L. , O'Byrne K. T.
Published: August 2005

Recent evidence has shown calcitonin gene‐related peptide (CGRP) to be a key mediator of stress‐induced suppression of the gonadotrophin‐releasing hormone (GnRH) pulse generator, although little is known about the neural pathways involved. In the present study, we investigated the potential direct action of CGRP on GnRH neurones using GT1‐7 cells, an established GnRH cell line. First, we detected expression of the CGRP receptor subunits, calcitonin receptor‐like receptor and receptor activity‐modifying protein‐1 in the GT1‐7 cells by reverse transcriptase‐polymerase chain reaction. Second, we have shown that CGRP inhibits GnRH mRNA expression in the GT1‐7 cells, which was effectively reversed by the CGRP receptor antagonist, CGRP8‐37. These results suggest that CGRP down regulates expression of GnRH mRNA, via CGRP receptors in the GT1‐7 cell, thus implying that a potential direct action of CGRP may mediate a suppressive effect on the GnRH neural network.
Cannabinoids Modulate Synaptic Activity in the Rat Supraoptic Nucleus
Authors: Soya A. , Serino R. , Fujihara H. , Onaka T. , Ozaki Y. , Saito T. , Nakamura J. , Ueta Y.
Published: August 2005

In the present study, we investigated the effects of the cannabinoid receptor agonist CP55,940 on excitatory and inhibitory synaptic transmission in the rat supraoptic nucleus. Whole‐cell patch clamp recordings were performed on supraoptic neurones in in vitro brain slice preparations. CP55,940 significantly reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents in a concentration‐dependent manner. These changes were potently reversed by the CB1 receptor antagonist AM251. The results indicate that cannabinoids modulate the activity of magnocellular neurosecretory neurones by presynaptic inhibition of both excitatory and inhibitory synaptic transmission.
Efficacy of a posterior implant support for extra shortened dental arches: a biomechanical model analysis
Authors: MAEDA Y. , SOGO M. , TSUTSUMI S.
Published: August 2005

summary  The purpose of this study was to test the efficacy of utilizing implants underneath distal free‐end denture bases to establish a stable occlusal support for extreme shortened dental arches (ESDA). The authors constructed a two‐dimensional finite element model of the ESDA where only lower anterior teeth remain. Posterior occlusal support was provided by a fixed partial denture with an osseointegrated implant (IFPD), fixed cantilever partial denture (CFPD), or a removable partial denture with or without an implant underneath (IRPD and RPD). A dentate mandible model was the control. When muscle vectors simulating clenching force were applied, stress levels on the temporal bone surface area under each configuration were compared, to evaluate the efficacy in establishing the occlusal support. The largest stress increase in temporal bone was found in the ESDA situation followed by the RPD. The least amount of stress increase was found with the IFPD followed by IRPD when the implant was placed in the molar region. The stress increase with IRPD was about 20–45% of the amount with RPD. Our results suggest that IFPD provides most favourable and stable occlusal support, however, IRPD with a single posterior implant also provide stable occlusal support with reducing the stress levels in the temporomandibular joint
Effect of APF gel on micromorphology of resin modified glass–ionomer cements and flowable compomers
Authors: BENDERLI Y. , GÖKÇE K. , KAZAK M.
Published: August 2005

summary  The purpose of this study was to evaluate the surface micromorphology of resin modified glass–ionomer cements and flowable compomers. In the study two resin modified glass–ionomers and two flowable compomers were used to prepare standardized 20 cylinderic samples. Samples were divided into four groups. Surface treatments with APF gel for experimental groups (group B,C,D) or distilled water as a control (group A) were performed four times. In group B, only APF gel was applied. In group C, after the APF gel application, the samples were immersed into the demineralizing and remineralizing solutions. In group D, before the APF gel application, the buffer solution was applied. The examinations of the surface micromorphology of the materials were made by using scanning electron microscope (SEM). Results showed that in group B all of the materials except Compoglass Flow, and in group C all of the materials showed erratic behaviours. In group D, severe erratic effect (score 2) was obtained on the surfaces of Vivaglassliner and Dyract Flow, and for the others score 1 signals were found. The moderate degradation was obtained by applying of only APF gel on the surfaces of both material groups. The addition of pH circulation caused increasing of micromorphologic changes on the surfaces of all materials. The effect of application of buffer solution on the surfaces before APF gel changed according to the materials. If acidulated fluoride gel is preferred for prophylactic therapy in patients’ mouth, for the success, either buffer or neutral fluoride have to be applied on the restored teeth by resin based materials before acidulated fluoride application.
Morphological Characterization of Receptor Activator of NFκB Ligand (RANKL) and IL‐1β Expression in Rodent Collagen‐Induced Arthritis
Authors: Weiss R. J. , Harris H. Erlandsson , Wick M. C. , Wretenberg P. , Stark A. , Palmblad K.
Published: August 2005

Bone loss represents a major unsolved problem in rheumatoid arthritis (RA). The receptor activator of nuclear factor‐κB ligand (RANKL) is essential for the development and activation of osteoclasts, which are key mediators of bone erosions. This study was performed to determine temporal and spatial expression of RANKL compared with the potentially destructive cytokine interleukin‐1β (IL‐1β), related to progression of synovitis and joint destruction in collagen‐induced arthritis (CIA), a model of RA. CIA was induced in dark agouti (DA) rats, and tissue specimens were obtained for immunohistochemical analyses at various time points before and after disease onset. Arthritis was monitored visually, and joint pathology was examined histologically. No disease‐preceding expression of RANKL was detected. However, a marked increase of both RANKL‐ and IL‐1β‐expressing cells correlated with the progression of synovial inflammation and clinical disease severity. Abundant and concomitant expression of these cytokines was detected at sites of bone erosion, where a co‐localization by osteoclast‐like multinuclear tartrate‐resistant acid phosphatase (TRAP)+ cells was noted. In contrast to the paucity of RANKL expression in cartilage, an abundant expression of IL‐1β was demonstrated, particularly in superficial cartilage layers. These data support the hypothesis that RANKL and IL‐1β are central contributors to joint destruction in CIA.
Whole influenza virus vaccine is more immunogenic than split influenza virus vaccine and induces primarily an IgG2a response in BALB/cmice
Authors: Hovden A.‐O. , Cox R. J. , Haaheim L. R.
Published: August 2005

The aim of this study was to compare the kinetics and the magnitude of the humoral immune response to two different influenza vaccine formulations, whole and split virus vaccines. BALB/cmice were immunized intramuscularly with one or two doses (3 weeks apart) of 7.5, 15 or 30 µg of haemagglutinin of monovalent A/Panama/2007/99 (H3N2) split or whole virus vaccine. The two vaccine formulations induced similar kinetics of the antibody‐secreting cells response; however, differences in the magnitude were observed in the spleen and bone marrow. Vaccination with whole virus vaccine generally elicited a quicker and higher neutralizing antibody response, particularly after the first dose of vaccine. The two vaccine formulations gave different immunoglobulin G (IgG) subclass profiles. Split virus vaccine stimulated both IgG1 and IgG2a antibodies suggestive of mixed T‐helper 1 (Th1) and Th2 response, whereas whole virus vaccine induced mainly an IgG2a antibody response, which is indicative of a dominant Th1 response. The increased immunogenicity of whole virus vaccine in a naïve population could reduce the vaccine concentration needed to provide protective immunity.
Enhanced Maturation and Functional Capacity of Dendritic Cells Induced by Mannosylated L2 Domain of ErbB2 Receptor
Authors: Zhong G. , Wang J. , Xu M. , Xie Z. , Yu M. , Wang J. , Zhou T. , Gong W. , Sun Y. , Hu M. , Zhang X. , Shen B. , Guo N.
Published: August 2005

The nature of antigens and functional state of dendritic cells (DC) are important in antigen presentation. The ability of DC for the induction of T‐cell responses is promoted by maturation. It has been confirmed that mannose receptors mediate highly efficient endocytosis and presentation of mannosylated proteins. In the present study, L2 domain of ErbB2 ectodomain was expressed in Escherichia coli, purified and mannosylated. The maturation and functional capacity of DC induced by mannosylated L2 (mL2) protein were investigated. The results showed that L2 protein could induce DC maturation, which was accompanied by elevated expression of MHC and co‐stimulatory molecules. The effect of mL2 protein on DC maturation was more remarkable than that of non‐mL2 proteins. Uptake of mL2 antigens by DC was more efficient. Furthermore, the T cells can be stimulated to proliferate in vitro and secrete Th1 and Th2 cytokines. Higher levels of both IFN‐γ and IL‐10 were detected from the T cells stimulated by mL2‐pulsed DC, suggesting a concurrent activation of CD4+ and CD8+ T cells. The results demonstrated that L2 domain of ErbB2 receptor is an immunodominant molecule. The mL2 domain of ErbB2 can induce an enhanced maturation and functional capacity of DC. It may become an effective strategy to induce anti‐ErbB2 response.
Aspirin Downregulates Homocysteine Formation in Stimulated Human Peripheral Blood Mononuclear Cells
Authors: Schroecksnadel K. , Frick B. , Winkler C. , Wirleitner B. , Schennach H. , Fuchs D.
Published: August 2005

Moderate hyperhomocysteinaemia is established as an independent risk factor for atherosclerosis, thrombosis, stroke and dementia. Hyperhomocysteinaemia is mostly caused by the deficiency of B‐vitamins folate and vitamin B12, which are essential cofactors in the remethylation of homocysteine to methionine. Interestingly, moderate hyperhomocysteinaemia is also often observed in chronic diseases, in which also elevated immune activation markers such as neopterin or sTNFR‐II are found. In order to simulate immune activation in vitro, human peripheral blood mononuclear cells (PBMC) were stimulated with mitogens. Stimulation significantly increased homocysteine production in comparison with unstimulated PBMC; in parallel also neopterin formation was induced. Homocysteine formation was due to cell proliferation, proliferating T lymphocytes, and also the myelomonocytic cell line U‐937 produced homocysteine. Treatment with the anti‐inflammatory drug aspirin dose‐dependently inhibited homocysteine production and also neopterin formation in human PBMC. Treatment with salicylic acid showed similar effects as aspirin; FACS analysis showed that both compounds inhibited cell proliferation by arresting cells in the G0/G1‐phase. In U‐937, both compounds also slightly induced apoptosis at 5 mm. Proliferation‐induced homocysteine formation and in parallel also monocyte activation can be suppressed effectively by aspirin and salicylic acid in vitro, suggesting that also in vivo aspirin may downregulate not only inflammation but also formation of homocysteine.
Tumor cell dissociation score highly correlates with lymph node metastasis in superficial esophageal carcinoma
Authors: CHIBANA YOKO , FUJII SHIGEHIKO , ICHIKAWA KAZUHITO , FUJITA MIKIO , ONO YUKO , TOMITA SHIGEKI , IMURA JOHJI , KAWAMATA HITOSHI , TERANO AKIRA , FUJIMORI TAKAHIRO
Published: August 2005

Background:  It is still not clear which parameters are important for predicting the metastatic potential of superficial esophageal squamous cell carcinoma (SESCC). The purpose of the present paper was thus to investigate tumor cell dissociation (TCD) in SESCC as a predictive factor of lymph node metastasis.

Methods:  Thirty‐three SESCC were classified into four groups based on the depth of tumor invasion. Carcinomas not invading as far as the muscularis mucosa were classified as group A; carcinomas invading to the muscularis mucosa or less than one‐third of the upper submucosa were classified as group B; those invading to the middle layer of the submucosa were classified as group C; and those invading one‐third of the lower submucosa were classified as group D. The TCD score was calculated by dividing the length of the TCD region by the maximal longitudinal length of the area of invasion into or beyond the lamina  propria,  and  multiplying  by  100.  E‐cadherin  expression  of  the  carcinomas  was  investigated  in  the TCD area and the successive area of mucosal invasive carcinoma (SAM).

Results:  The incidence of lymph node metastasis was 0% in group A, 10% in group B, 36.4% in group C and 57.1% in group D. The mean TCD scores (±SEM) of SESCC with lymph node metastasis were higher than that without (85.3 ± 5.7, 16.3 ± 3.9, respectively; P < 0.001). In group C, the TCD score of cases with lymph node metastases was higher than in those without lymph node metastasis (P < 0.001). E‐cadherin expression was significantly reduced in the area of TCD compared with the SAM located over the TCD area (P < 0.001).

Conclusions:  The TCD score is an important predictive marker for lymph node metastasis in SESCC. Clinical evaluation of TCD scores in endoscopic mucosal resection (EMR) specimens would enable accurate prediction of lymph node metastasis and extend the indication of EMR treatment for SESCC.
Prevalence of Helicobacter pylori infection, endoscopic gastric findings and dyspeptic symptoms among a young Japanese population born in the 1970s
Authors: SHIMATANI TOMOHIKO , INOUE MASAKI , IWAMOTO KEIKO , HYOGO HIDEYUKI , YOKOZAKI MICHIYA , SAEKI TOSHINARI , TAZUMA SUSUMU , HORIKAWA YOKO
Published: August 2005

Background:  With the prevalence of Helicobacter pylori (H. pylori) infection rapidly decreasing in Japan, endoscopic findings and dyspeptic symptoms need to be re‐evaluated.

Methods:  In a health check‐up program, endoscopy was performed on 530 young Japanese subjects (371 men and 159 women) born in the 1970s. Helicobacter pylori infection was evaluated using serology and a rapid urease test. Endoscopic gastritis was classified according to the Sydney classification system, in addition to nodular gastritis. Dyspeptic symptoms were also recorded before endoscopy.

Results:  Of the 530 subjects, 87 (16.4%) were H. pylori positive. Of the 443 H. pylori‐negative subjects, 349 (78.8%) were considered to have endoscopically normal gastric mucosa. However, of the 87 H. pylori‐positive subjects, only 19 (21.8%) tested normal (P < 0.001). The prevalence of several types of gastritis was significantly higher in H. pylori‐positive subjects compared with H. pylori‐negative subjects: atrophic gastritis (37.9% vs 1.1%, P < 0.001), flat erosive gastritis (29.9% vs 7.2%, P < 0.001), rugal hyperplastic gastritis (12.6% vs 0.0%, P < 0.001), and nodular gastritis (13.8% vs 0.0%, P < 0.001). Other types of gastritis were not related to H. pylori status. The prevalence of subjects with dyspeptic symptoms was significantly higher in H. pylori‐positive subjects compared with H. pylori‐negative ones (28.7% vs 6.5%, P < 0.001).

Conclusion:  It is suggested that in consideration of its recent low prevalence and the slow increase in its infection, the prevalence of H. pylori‐related gastritis will gradually decrease in Japan. Further studies will be required to ascertain if there is a need for H. pylori eradication in this young population.

© 2005 Blackwell Publishing Asia Pty Ltd
Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non‐alcoholic fatty liver disease
Authors: GULSEN MUSTAFA , YESILOVA ZEKI , BAGCI SAIT , UYGUN AHMET , OZCAN AYHAN , ERCIN C NURI , ERDIL AHMET , SANISOGLU S YAVUZ , CAKIR ERDINÇ , ATES YUKSEL , ERBIL M KEMAL , KARAEREN NECMETTIN , DAGALP KEMAL
Published: August 2005

Background:  Although steatosis is common in patients with severe hyperhomocysteinemia due to deficiency of cystathionine β‐synthase, there are no satisfactory data on homocysteine concentrations in patients with non‐alcoholic fatty liver disease. The main aim of the present study was to evaluate the clinical significance of plasma homocysteine concentrations in patients with non‐alcoholic fatty liver disease.

Methods:  Seventy‐one non‐alcoholic fatty liver disease patients, 36 patients with chronic viral hepatitis and 30 healthy persons were enrolled in the study. Homocysteine levels were measured by high‐performance liquid chromatography. Insulin, folate, vitamin B12 and lipoprotein levels were also determined in all groups.

Results:  Homocysteine in the non‐alcoholic fatty liver disease group was found to be significantly higher than other groups. Homocysteine was found to be significantly higher in the non‐alcoholic steatohepatitis group when compared with simple steatosis group. A positive correlation was found between homocysteine and triglyceride, very‐low‐density‐lipoprotein (VLDL) cholesterol, insulin, and index of insulin resistance in the non‐alcoholic fatty liver disease group, and a negative correlation was found between homocysteine and folate, or vitamin B12 in all groups. The homocysteine threshold for the prediction of steatohepatitis was 11.935 ng/mL. Furthermore; plasma homocysteine was a statistically significant predictor for severity of necroinflammatory activity in non‐alcoholic steatohepatitis.

Conclusions:  The plasma homocysteine concentrations were significiantly higher in patients with non‐alcoholic fatty liver disease, while the concentrations were not affected by chronic viral hepatitis. Plasma homocysteine is a parameter for discriminating steatohepatitis from simple steatosis. Determining the plasma homocysteine concentrations may facilitate selection of steatosis patients in whom a liver biopsy should be performed.

© 2005 Blackwell Publishing Asia Pty Ltd
Hepatitis C virus infection facilitates gallstone formation
Authors: CHANG TE‐SHENG , LO SING KAI , SHYR HUEIH‐YUAN , FANG JI‐TSENG , LEE WEI‐CHEN , TAI DAR‐IN , SHEEN I‐SHYAN , LIN DENG‐YN , CHU CHIA‐MING , LIAW YUN‐FAN
Published: August 2005

Background:  Bile duct damage and hepatic steatosis are two characteristic histological findings in hepatitis C virus infection; and high prevalence of hepatitis C antibody is noted in patients with cholangiocarcinoma. The purpose of the present study was to examine the relationship between biliary diseases and hepatitis C virus infection.

Methods:  Persons who received a general checkup in Chang Gung Memorial Hospital between 2000 and 2002 were included. All of them had hemogram, serum biochemistry, hepatitis B surface antigen, hepatitis C antibody and ultrasonography studies. The prevalence of gallbladder stone, bile duct stone and gallbladder polyp/cholesterolosis were compared in different viral infection groups.

Results:  Of the 28 486 persons, 22 967 were negative for both hepatitis B surface antigen and hepatitis C antibody (group NBNC), 4152 were hepatitis B surface antigen carriers (broup B), 1195 were positive for hepatitis C antibody (group C), and 172 were positive for both markers. The 379 persons (1.3%) having had cholecystectomy were considered to have gallbladder stone at the time when cholecystectomy was done. Gallbladder stone was found in 6.0% persons of group NBNC, 5.4% in group B and 11.7% in group C. The prevalence of gallbladder stone in group C was found especially high for age groups 31–40 years and 61–70 years. The prevalence of bile duct stone was higher in group C (0.4%) than in group NBNC or B (both 0.1%). Stepwise logistic regression analysis showed that age, liver cirrhosis, body mass index, hepatitis C virus infection and gender were independent factors associated with gallbladder stone.

Conclusions:  Hepatitis C virus infection facilitates gallstone formation.

© 2005 Blackwell Publishing Asia Pty Ltd
Alteration of the expression of adenosine triphosphate‐binding cassette transporters associated with bile acid and cholesterol transport in the rat liver and intestine during cholestasis
Authors: KAMISAKO TOSHINORI , OGAWA HIROSHI
Published: August 2005

Background and Aim:  Multidrug resistance protein 2 (Mrp2), Mrp3, adenosine triphosphate‐binding cassette transporter g5 (Abcg5) and adenosine triphosphate‐binding cassette transporter g8 (Abcg8) have been identified as bile acid or cholesterol transporter in the enterocytes as well as hepatocytes. The purpose of the present study was to evaluate intestinal and hepatic adenosine triphosphate‐binding cassette transporter expressions during cholestasis.

Methods:  Experiment 1: Rats were subjected to bile duct ligation or sham operation. Blood, liver and small intestines were obtained 24 and 72 h after operation. Experiment 2: Rats were divided into four groups as follows: (i) control group; (ii) diosgenin group (fed with diosgenin in diet [1%(wt/wt)] for 7 days); (iii) ethinyl estradiol group (recieved ethinyl estradiol [5 mg/kg daily] for 5 days); and (iv) diosgenin‐ethinyl estradiol group (received ethinyl estradiol and diosgenin). After treatment, blood, bile, liver and intestines were obtained. The mRNA related to lipid and bile acid metabolism was analyzed by reverse transcription polymerase chain reaction.

Results:  Intestinal Mrp2 and Abcg5/Abcg8 mRNA expression remarkably decreased 24 h after bile duct ligation (43% and 61%/54% of sham operation) and recovered 72 h after bile duct ligation (103% and 95%/83% of sham operation). Intestinal Mrp3 mRNA expression did not change after bile duct ligation. Intestinal Mrp2 mRNA expression was remarkably increased in diosgenin and diosgenin‐ethinyl estradiol groups in comparison with the control group. There were no significant differences in intestinal Mrp3 mRNA expression among the four groups. Hepatic Mrp3 mRNA expression was remarkably increased in the D, EE and DE groups in comparison with the control group (531%, 321% and 1160% of control, respectively, P < 0.01). Hepatic Abcg5 and Abcg8 mRNA expression decreased in ethinyl estradiol and diosgenin‐ethinyl estradiol groups compared with the control group and there were no differences in intestinal Abcg5 and Abcg8 mRNA expressions among the four groups.

Conclusion:  Bile duct ligation affects not only hepatic but also the intestinal Mrp2 and Abcg5 and Abcg8 expressions. Intestinal Mrp2 mRNA level was regulated by factor in the lumen (e.g. diosgenin feeding). Cholestasis by ethinyl estradiol treatment was enhanced by diosgenin and the increase in hepatic Mrp3 mRNA level might affect the enhancement.

© 2005 Blackwell Publishing Asia Pty Ltd
Hepatocellular carcinoma and octreotide: Treatment results in prospectively assigned patients with advanced tumor and cirrhosis stage
Authors: PLENTZ RUBEN R , TILLMANN HANS L , KUBICKA STEFAN , BLECK JÖRG S , GEBEL MICHAEL , MANNS MICHAEL P , RUDOLPH KARL L
Published: August 2005

Background and Aim:  Treatment of inoperable hepatocellular carcinoma (HCC) remains a major clinical problem. The only efficient treatment options are percutaneous ethanol injection (PEI), radiofrequency ablation (RF) and transarterial chemoembolization (TACE), but these therapies are only applicable to patients with limited tumor spread and sufficient liver function. For patients with advanced tumor and poor liver function a systemic therapy is required. Octreotide, a somatostatin analog with antimitotic activity, is a controversial treatment option.

Methods:  In the current study we prospectively assigned a group of 41 HCC patients with advanced HCC and cirrhosis stage to treatment with octreotide. The clinical and laboratory parameters were monitored and survival was analyzed using a Cox regression model.

Results:  The medium survival in the group of all patients was 571 days. Using the Cox regression there was a significant difference in survival for alpha‐fetoprotein (P = 0.026) and Quick's test (P = 0.009) in consideration of the tumor dimension compared to the other characteristics. The tumor remained stable in 26 patients over a mean follow‐up of 21 months and progressed in 14 patients. One patient showed a partial response. There was no incidence of severe side‐effects (WHO grade 3–4). During the follow‐up time, 14 patients died because of their underlying disease.

Conclusions:  Treatment with octreotide appears safe and patients show similar survival compared to a group of patients with advanced HCC treated with TACE. Further studies are necessary to investigate somatostatin receptor subtypes or receptor mutations of patients with advanced HCC in relation to their response.

© 2005 Blackwell Publishing Asia Pty Ltd
Oral refeeding in patients with mild acute pancreatitis: Prevalence and risk factors of relapsing abdominal pain
Authors: CHEBLI JULIO MARIA FONSECA , GABURRI PEDRO DUARTE , DE SOUZA AÉCIO FLÁVIO MEIRELLES , JUNIOR ELSON VIDAL MARTINS , GABURRI ANA KARLA , FELGA GUILHERME EDUARDO GONÇALVES , DE PAULA ELIANE APARECIDA , FORN CECÍLIA GANIMI , DE ALMEIDA GERUSA VILELA , DE CASTRO NEHME FLAVIA
Published: August 2005

Background and Aim:  In acute pancreatitis (AP), oral refeeding may stimulate pancreatic secretion, increasing the inflammation of the glandular tissue causing relapse of abdominal pain or even exacerbation of the disease. This study aimed to assess the prevalence and risk factors of abdominal pain relapse over oral refeeding in patients convalescing with AP as well as the impact of pain recurrence on the hospital stay.

Methods:  Inclusion criteria were AP confirmed by biochemical and/or radiological data in the absence of severe disease or extensive necrosis. The same diet was offered to all patients during oral refeeding. Demographic, clinical, biochemical and radiological data were prospectively recorded and analyzed.

Results:  A total of 130 patients were included. During the oral refeeding period, 32 (24.6%) patients had pain relapse, which was more common on days 1 (68.8%) and 2 (28.1%). Pain relapse was related to higher serum levels of lipase on the day before refeeding, higher serum levels of C‐reactive protein on the fourth day, and presence of peripancreatic fluid collections (P < 0.01). Pain relapse significantly increased total hospital stay (P < 0.01).

Conclusions:  In patients with mild AP, pain relapse during oral refeeding was relatively high (24.6%), particularly on the first or second day. Their risk appeared be associated with more intense or persistent pancreatic inflammation on the day before refeeding, and presence of peripancreatic fluid collections. Pain relapse increased hospital stay, and likely overall costs on disease treatment.
Hepatic steatosis and the risk of hepatocellular carcinoma in chronic hepatitis C
Authors: KUMAR DINESH , FARRELL GEOFFREY C , KENCH JAMES , GEORGE JACOB
Published: August 2005

Background and Aim:  Obesity associated hepatic steatosis has been suggested to have a premalignant potential. We determined whether hepatic steatosis predisposes to liver cancer in persons with chronic hepatitis C virus (HCV) infection.

Methods:  We compared the histological severity of steatosis in the index liver biopsies of 25 patients with chronic hepatitis C who subsequently developed hepatocellular carcinoma (HCC) with matched controls who did not. Cases were aged (mean) 54.7 years, 84% males, 76% genotype 1, and 64% fibrosis stage 4; and controls were matched for these characteristics. Those with a sustained virologic response to antiviral therapy were excluded.

Results:  Duration of HCV infection, concomitant alcohol intake, body mass index and indices of past hepatitis B virus (HBV) infection were comparable between the groups. Controls were followed for a longer period after the index liver biopsy than were cases (113 months vs 55 months, P < 0.001). As determined by percentage area of biopsy core occupied by steatosis on computer assisted morphometric evaluation, and graded by semiquantitative histological assessment, steatosis was comparable among cases and controls. The odds of developing HCC among those with steatosis grades 1 and 2 did not differ significantly from those without steatosis. There was no association between increasing morphometric percentage area occupied by steatosis and the subsequent development of HCC. Neither steatosis grade or percent area of steatosis on biopsy were selected in multivariate regression analysis as independent predictors for the development of HCC.

Conclusions:  Hepatic steatosis does not augment the risk of hepatocarcinogenesis in patients with chronic HCV infection.

© 2005 Blackwell Publishing Asia Pty Ltd
Comparison between coefficient of R‐R interval variation and gastric emptying in type 2 diabetes mellitus patients
Authors: ASAKAWA HIDEKI , ONISHI MAKI , HAYASHI ISAO , FUKUDA AYUMI , TOKUNAGA KATSUO
Published: August 2005

Background:  Autonomic neuropathy is a common complication of diabetes mellitus (DM).

Method:  To clarify the relationship between cardiovascular autonomic function and gastric emptying rate, we investigated the gastric emptying and coefficient of R‐R interval variation (CVRR) of 84 type 2 diabetic patients: 28 cases without peripheral neuropathy and 56 cases with peripheral neuropathy. All patients were subjected to a gastric emptying test according to the marker method (administration of a capsule containing 20 pieces of radiopaque marker during breakfast, followed by abdominal X‐ray imaging 3 and 5 h later). Patients had their CVRR assessed at rest and during deep breathing.

Results:  Gastric emptying scores were significantly correlated with CVRR during deep breathing and with the duration of DM, but neither age nor CVRR at rest in all patients. Gastric emptying scores and CVRR at rest and during deep breathing in patients with peripheral neuropathy were significantly deteriorated than those in patients without peripheral neuropathy. A significant correlation between gastric emptying and CVRR during deep breathing could be observed in the patients with peripheral neuropathy, but not in those without it.

Conclusions:  These findings showed that CVRR during deep breathing might be a good indicator of diabetic gastropathy and that peripheral neuropathy was closely related with cardiac and gastric autonomic neuropathy in the type 2 diabetic patients.

© 2005 Blackwell Publishing Asia Pty Ltd
Silent substitution S‐cone electroretinogram in subjects with diabetes mellitus
Authors: Mortlock Katharine E. , Chiti Zohreh , Drasdo Neville , Owens David R. , North Rachel V.
Published: August 2005

A defect in the blue sensitive mechanism has been reported in certain ocular and systemic diseases. For example, tritanopic colour vision defects and changes to the S‐cone electroretinogram (ERG) have been demonstrated in glaucoma and diabetes mellitus. Electrophysiological methods of eliciting the S‐cone ERG, however, often result in considerable L‐ and M‐cone intrusion. We report the findings of a study employing the silent substitution S‐cone ERG technique, which is thought to represent an almost pure S‐cone signal, and the L'Anthony desaturated D15 colour vision test in subjects with Type 1 or 2 diabetes mellitus with no or minimal background retinopathy. The results of this study show a significantly increased S‐cone ERG b‐wave implicit time and significantly worse colour vision in those with background retinopathy compared with those with no diabetic retinopathy. This suggests that S‐cone pathway dysfunction may be responsible for the deterioration in colour vision found in diabetes mellitus.
The effect of strabismus on a young child's selection of a playmate
Authors: Johns Heather A. , Manny Ruth E. , Fern Karen D. , Hu Ying‐Sheng
Published: August 2005

Purpose:  This study investigated the effect of strabismus on a child's playmate selection.

Methods:  Photographs of orthotropic children aged 3–6 years were altered to simulate various magnitudes of strabismus. The pictures were arranged in pairs, one orthotropic child and one with strabismus. One hundred children aged 3–8 years viewed the photographs and were asked to select a playmate from each pair.

Results:  Chi‐squared analysis found 23 children showed evidence that strabismus influenced their choices (p < 0.07). Of these 23, 12 preferred playmates with strabismus and 11 preferred orthotropic playmates. Chi‐squared analysis of all subjects combined found decisions were not based on the magnitude or direction of strabismus.

Conclusions:  As only 11% of the children consistently selected against playmates with strabismus, and about the same percentage preferred playmates with strabismus (12%), the presence of strabismus does not appear to be a significant factor in peer acceptance in this age group.
Comparison of the ICare® rebound tonometer with the Goldmann tonometer in a normal population
Authors: Fernandes P. , Díaz‐Rey J. A. , Queirós A. , Gonzalez‐Meijome J. M. , Jorge J.
Published: August 2005

The aim of this study was to evaluate the accuracy of measurement of intraocular pressure (IOP) using a new induction/impact rebound tonometer (ICare®) in comparison with the Goldmann applanation tonometer (AT).

The left eyes of 46 university students were assessed with the two tonometers, with induction tonometry being performed first. The ICare® was handled by an optometrist and the Goldmann tonometer by an ophthalmologist.

In this study, statistically significant differences were found when comparing the ICare® rebound tonometer with applanation tonometry (AT) (p < 0.05). The mean difference between the two tonometers was 1.34 ± 2.03 mmHg (mean ± S.D.) and the 95% limits of agreement were ±3.98 mmHg. A frequency distribution of the differences demonstrated that in more than 80% of cases the IOP readings differed by <3 mmHg between the ICare® and the AT.

In the present population the ICare® overestimates the IOP value by 1.34 mmHg on average when compared with Goldmann tonometer. Nevertheless, the ICare® tonometer may be helpful as a screening tool when Goldmann applanation tonometry is not applicable or not recommended, as it is able to estimate IOP within a range of ±3.00 mmHg in more than 80% of the population.
Simian immunodeficiency virus disrupts extended lengths of the blood–brain barrier
Authors: MacLean A.G. , Belenchia G.E. , Bieniemy D.N. , Moroney‐Rasmussen T.A. , Lackner A.A.
Published: August 2005

Abstract:  It is known that there is disruption of the blood–brain barrier during terminal AIDS encephalitis in both human immunodeficiency virus (HIV)‐infected humans and simian immunodeficiency virus (SIV)‐infected rhesus macaques. Much, although by no means all, of the neuropathological findings of HIV and SIV infection involves accumulation of monocytes/macrophages that have likely crossed the blood–brain barrier (BBB). There is no convincing, rigorous, demonstration of HIV (or SIV) infecting endothelial cells in vivo. However, this is not to say that HIV infection would not have any effects on the physiology of microvascular brain endothelial cells. Because of the elaborate nature of cerebral microvessels, previous studies of cerebral endothelial cells have been constrained by sectioning artifacts. Examination of freshly isolated cerebral microvessels allows investigation of extended lengths of vessels (>150 μm) without sectioning artifacts. These studies determine the changes in the expression of the tight junction protein zo‐1 protein on the endothelial cells of cerebral capillaries at terminal acquired immune deficiency syndrome, demonstrating that there is a decreased expression of zo‐1 protein over extended lengths of microvessels.
Naturally SIV‐infected sooty mangabeys: are we closer to understanding why they do not develop AIDS?
Authors: Silvestri Guido
Published: August 2005

Abstract:  Simian immunodeficiency viruses (SIV) infection of sooty mangabey (SM) monkeys (Cercocebus atys), a natural host species, does not induce CD4+ T cell depletion and acquired immunodeficiency syndrome (AIDS) despite chronic high levels of virus replication. In contrast, SIV infection of non‐natural host species, such as rhesus macaques (RM), induces a disease that closely resembles AIDS in humans. The mechanisms underlying the lack of disease progression in SIV‐infected SMs are incompletely understood, but certainly reflect a complex evolutionary adaptation whereby the host immune system is not significantly damaged by the highly replicating virus. It is now widely recognized that a better understanding of these mechanisms may provide clues to the pathogenesis of immunodeficiency in HIV‐infected humans. In this article I discuss five different hypotheses that may account for the non‐pathogenic course of infection in SIV‐infected SMs and briefly review the available data supporting each of these hypotheses.
Infection with a molecularly cloned SIVsm virus elicits high titer homologous neutralizing antibodies with heterologous neutralizing activity
Authors: Mahalanabis M. , Hirsch V.M. , Haigwood N.L.
Published: August 2005

Abstract:  We have evaluated the homologous and heterologous neutralizing antibody response in a cohort of six Macaca nemestrina infected with the cloned virus SIVsm62d that showed different levels of envelope diversification. Two progressor macaques developed AIDS by 1.5 years post‐inoculation and four non‐progressors were asymptomatic for 3 years of follow‐up. All macaques developed high titers of neutralizing antibodies against homologous SIVsm viruses and intermediate titers against SIVsmB670. Heterologous virus neutralization of SIVmac, SIVmne, and HIV‐2 was detected at much lower levels in both progressor macaques; only one of four non‐progressors had evidence for broader neutralizing antibody activity. We noted changes in potential N‐linked glycosylation (PNG) sites in V1/V2, C2, and V4 that were common to multiple macaques. These results support a model for viral neutralization where heterologous neutralization is, in part, driven by a strong homologous response and may be coupled to changes in PNG sites in envelope.
Immune mechanisms associated with protection from vaginal SIV challenge in rhesus monkeys infected with virulence‐attenuated SHIV 89.6
Authors: Miller Christopher J. , Abel Kristina
Published: August 2005

Abstract:  Although live‐attenuated human immunodeficiency virus‐1 (HIV) vaccines may never be used clinically, these vaccines have provided the most durable protection from intravenous (IV) challenge in the simian immunodeficiency virus (SIV)/rhesus macaque model. Systemic infection with virulence attenuated‐simian–human immunodeficiency virus (SHIV) 89.6 provides protection against vaginal SIV challenge. This paper reviews the findings related to the innate and adaptive immune responses and the role of inflammation associated with protection in the SHIV 89.6/SIVmac239 model. By an as yet undefined mechanism, most monkeys vaccinated with live‐attenuated SHIV 89.6 mounted effective anti‐viral CD8+ T cell responses while avoiding the self‐destructive inflammatory cycle found in the lymphoid tissues of unprotected and unvaccinated monkeys.
Early virological events in various tissues of newborn monkeys after intrarectal infection with pathogenic simian human immunodeficiency virus
Authors: Miyake Ariko , Ibuki Kentaro , Suzuki Hajime , Horiuchi Reii , Saito Naoki , Motohara Makiko , Hayami Masanori , Miura Tomoyuki
Published: August 2005

Abstract:  Children infected with human immunodeficiency virus type 1 often have higher viral loads and progress to acquired immunodeficiency syndrome more rapidly than adults. In our previous study of simian–human immunodeficiency virus (SHIV)‐infected adult monkeys, immature CD4CD8 double‐positive T cells in the thymus and jejunum decreased faster than mature CD4 single‐positive T cells. Here, we examined the effect of virus replication on immature T cells from the same SHIV‐inoculated newborn monkeys having more immature T cells than adults. The infectious viruses were more abundantly detected in the thymus than in other tissues at both 13 and 26 days post‐infection (dpi). However, mature CD4+ T cells in the thymus declined after 13 dpi and immature CD3− CD4 single‐positive T cells remained at 26 dpi. These results suggested that many immature CD4+ T cells in the thymus of newborns support the production of infectious viruses even after the depletion of mature CD4+ T cells.
Caveolae: Stable Membrane Domains with a Potential for Internalization
Authors: Hommelgaard Anette M. , Roepstorff Kirstine , Vilhardt Frederik , Torgersen Maria L. , Sandvig Kirsten , van Deurs Bo
Published: August 2005

The role of caveolae in endocytosis is hotly debated. Here, we argue that most caveolae are stable microdomains at the cell surface. Only a small fraction of caveolae is constitutively internalized, leading to a quantitatively minor uptake of ligands and receptors. In addition, we suggest that a more pronounced downregulation of caveolae from the plasma membrane can occur, presumably stimulated by receptor cross‐linking and clustering in caveolae. Finally, we propose that future studies dealing with internalization of caveolae should actually document such internalization and include kinetic data.
The Role of ARF1 and Rab GTPases in Polarization of the Golgi Stack
Authors: Bannykh Serguei I. , Plutner Helen , Matteson Jeanne , Balch William E.
Published: August 2005

The organization and sorting of proteins within the Golgi stack to establish and maintain its cis to trans polarization remains an enigma. The function of Golgi compartments involves coat assemblages that facilitate vesicle traffic, Rab‐tether‐SNAP receptor (SNARE) machineries that dictate membrane identity, as well as matrix components that maintain structure. We have investigated how the Golgi complex achieves compartmentalization in response to a key component of the coat complex I (COPI) coat assembly pathway, the ARF1 GTPase, in relationship to GTPases‐regulating endoplasmic reticulum (ER) exit (Sar1) and targeting fusion (Rab1). Following collapse of the Golgi into the ER in response to inhibition of activation of ARF1 by Brefeldin A, we found that Sar1‐ and Rab1‐dependent Golgi reformation took place at multiple peripheral and perinuclear ER exit sites. These rapidly converged into immature Golgi that appeared as onion‐like structures composed of multiple concentrically arrayed cisternae of mixed enzyme composition. During clustering to the perinuclear region, Golgi enzymes were sorted to achieve the degree of polarization within the stack found in mature Golgi. Surprisingly, we found that sorting of Golgi enzymes into their subcompartments was insensitive to the dominant negative GTP‐restricted ARF1 mutant, a potent inhibitor of COPI coat disassembly and vesicular traffic. We suggest that a COPI‐independent, Rab‐dependent mechanism is involved in the rapid reorganization of resident enzymes within the Golgi stack following synchronized release from the ER, suggesting an important role for Rab hubs in directing Golgi polarization.