bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Inflammatory Response to a Highly Selective PDE4 Inhibitor in the Rat and the Identification of Biomarkers that Correlate with Toxicity
Authors: Dietsch Gregory N. , Dipalma Chris R. , Eyre Russell J. , Pham Tuan Q. , Poole Karen M. , Pefaur Noah B. , Welch William D. , Trueblood Esther , Kerns William D. , Kanaly Suzanne T.
Published: March 2006

The primary toxicity associated with repeated oral administration of the PDE4 inhibitor IC542 to the rat is an inflammatory response leading to tissue damage primarily in the gastrointestinal tract and mesentery. Although necrotizing vasculitis is frequently seen with other PDE4 inhibitors, blood vessel injury was rare following IC542 administration and was always associated with inflammation in the surrounding tissue. The incidence and severity of the histologic changes in these studies correlated with elevated peripheral blood leukocytes, serum IL-6, haptoglobin, and fibrinogen, and with decreased serum albumin. By monitoring haptoglobin, fibrinogen and serum albumin changes in IC542-treated rats, it was possible to identify rats with early histologic changes that were reversible. Since PDE4 inhibition is generally associated with anti-inflammatory activity, extensive inflammation in multiple tissues was unexpected with IC542. Co-administration of dexamethasone completely blocked IC542-induced clinical and histologic changes in the rat, confirming the toxicity resulted from inflammatory response. In addition, IC542 augmented release of the proinflammatory cytokine IL-6 in LPS-activated whole blood from rats but not monkeys or humans. The effect of IC542 on IL-6 release from rat leukocytes in vitro is consistent with the proinflammatory response observed in vivo and demonstrates species differences to PDE4 inhibition.
Cardiac Hypertrophy: A Risk Factor for QT-Prolongation and Cardiac Sudden Death
Authors: Kang Y. James
Published: March 2006

Cardiac hypertrophy was viewed as a compensatory response to hemodynamic stress. However, cumulative evidence obtained from studies using more advanced technologies in human patients and animal models suggests that cardiac hypertrophy is a maladaptive process of the heart in response to intrinsic and extrinsic stimuli. Although hypertrophy can normalize wall tension, it is a risk factor for QT-prolongation and cardiac sudden death. Studies using molecular biology techniques such as transgenic and knockout mice have revealed many important molecules that are involved in the development of heart hypertrophy and have demonstrated signaling pathways leading to the pathogenesis. With the same approach, the consequence of heart hypertrophy has been examined. The significance of hypertrophy in the development of overt heart failure has been demonstrated and several critical molecular pathways involved in the process were revealed. A comprehensive understanding of the threats of heart hypertrophy to patients has helped to develop novel treatment strategies. The recognition of hypertrophy as a major risk factor for QT-prolongation and cardiac sudden death is an important advance in cardiac medicine. Cellular and molecular mechanisms of this risk aspect are currently under extensively exploring. These studies would lead to more comprehensive approaches to prevention of potential life threatening arrhythmia and cardiac sudden death. The adaptation of new approaches such as functional genomics and proteomics will further advance our knowledge of heart hypertrophy.
A Search to Predict Potential for Drug-Induced Cardiovascular Toxicity
Authors: Hamlin Robert L.
Published: March 2006

This is a brief review of properties of cardiovascular function that should be considered for interrogation in studies of toxicology and/or safety pharmacology for non-cardiologists and non-physiologists. Since concern over the rarely occurring, unusual, and drug-induced tachycardia, Torsade de pointes, is a leading cause for cessation of development of potential drugs and for removal of drugs from the market, therefore, the toxic manifestation of drugs will be emphasized. The putative origin of torsade de pointes, and the origin of the electrocardiogram and electrocardiographic features of ventricular arrhythmias will be discussed.
Magnetic resonance imaging in the assessment of cystic pancreatic lesions: differentiation of benign and malignant lesion status
Authors: Hänninen E. Lopez , Pech M. , Ricke J. , Denecke T. , Amthauer H. , Lehmkuhl L. , Böhmig M. , Röttgen R. , Pinkernelle J. , Felix R. , Langrehr J.
Published: March 2006

Purpose: To characterize cystic pancreatic lesions and tumors with magnetic resonance imaging (MRI), and to assess the value of morphological criteria in differentiating pseudocysts versus cystic tumors and benign versus malignant cystic tumors.

Material and Methods: Twenty-three patients with cystic pancreatic tumors or lesions underwent plain and contrast-material-enhanced MRI, including magnetic resonance cholangiopancreatography (MRCP). The MR findings were characterized and analyzed by two readers, and the role of various imaging criteria and combinations thereof for final lesion assignment were assessed. Final diagnoses were obtained from the results of open surgery ( n = 19) and/or biopsy ( n = 4).

Results: Final diagnoses included cystic tumors ( n = 11) and pseudocysts ( n = 12). The lesions were located in the head (56%) and body or tail (44%). Lesion diameters ranged from 7 to 50 mm. Various lesion contrast enhancement patterns were observed for both benign and malignant lesions. Serous cystadenomas were located in the head, they were lobulated, and had wall diameters⩽2 mm; with the combination of these characteristics all patients with serous cystadenoma could be identified, whereas in no other patient was this constellation observed.

Conclusion: MRI facilitated the diagnosis of serous cystadenomas, although no definite morphologic criterion for the differentiation between pseudocysts and mucinous cystadenomas was identified. In consideration of the substantial therapeutic consequences, either diagnostics in unclear cystic pancreatic lesions should comprise cyst fluid analysis if necessary, or eligible patients should be referred for surgical resection.
Primary cardiac burkett's type lymphoma: transthoracic echocardiography, multidetector computed tomography and magnetic resonance findings
Authors: De Filippo M. , Chernyschova N. , Maffei E. , Rovani C. , De Blasi M. , Beghi C. , Zompatori M.
Published: March 2006

Although primary cardiac lymphoma is an extremely rare disease and is associated with high mortality, it is treatable when diagnosed appropriately. We describe the transthoracic echocardiography, 16-row multidetector computed tomography (16-MDCT) and magnetic resonance findings of primary cardiac lymphoma in an immunocompromised patient and review of the literature.
Interventional procedures involving portal vein circulation: a review
Authors: Ćwikiel W.
Published: March 2006

Rapid development of diagnostic radiological methods during recent decades has been followed by development of new interventional procedures involving portal circulation. The majority of these interventions were developed for treatment of patients with symptoms secondary to portal hypertension (PH). Interventions involving portal vein circulation have an established position in the treatment of PH and other diseases, and further development of these methods can be expected.
Apparent diffusion coefficient maps of pediatric mass lesions with free-breathing diffusion-weighted magnetic resonance: feasibility study
Authors: Olsen Ø. E. , Sebire N. J.
Published: March 2006

Purpose: To assess the technical feasibility of apparent diffusion coefficient (ADC) mapping based on free-breathing diffusion-weighted magnetic resonance (DW-MR) outside the CNS in children.

Material and Methods: Twelve children with mass lesions of varied histopathology were scanned with short- tau inversion recovery (STIR), contrast-enhanced T1-weighted (CE-T1W), and diffusion-weighted (b = 0, 500 and 1000 s/mm2) sequences. ADC maps were calculated. Lesion-to-background signal intensity ratios were measured and compared between STIR/CE-T1W/ADC overall (Friedman test) and between viable embryonal tumors and other lesions (Kruskal-Wallis test).

Results: ADC maps clearly depicted all lesions. Lesion-to-background signal intensity ratios of STIR (median 3.7), CE-T1W (median 1.4), and ADC (median 1.6) showed no overall difference (chi-square = 3.846; P = 0.146), and there was no difference between viable embryonal tumors and other lesions within STIR/CE-T1W/ADC (chi-square 1.118/0.669/<0.001; P = 0.290/0.414/1.000, respectively).

Conclusion: ADC mapping is feasible in free-breathing imaging of pediatric mass lesions outside the CNS using standard clinical equipment.
Volumetric coronary angiography using the 256-detector row computed tomography scanner: comparison in vivo and in vitro with porcine models
Authors: Mori S. , Kondo C. , Suzuki N. , Hattori A. , Kusakabe M. , Endo M.
Published: March 2006

Purpose: To investigate the feasibility of volumetric cine imaging in human cardiac studies by comparing in vivo and in vitro coronary angiography using a 256-detector row computed tomography (CT) without ECG gating.

Material and Methods: The left and right coronary arteries of two domestic pigs were scanned in vivo and in vitro in cine mode using the 256-detector row CT. The device scanned approximately 100 mm in the cranio-caudal direction with one rotation, with a slice thickness of 0.5 mm.

Results: The coronary arteries could be observed to the third-degree branches in vitro, but could be visualized clearly only to the proximal portion (first-degree or second-degree branches) in vivo.

Conclusion: Application of cardiac volumetric cine imaging with 256-detector row CT may be a promising means of obtaining diagnostic information and has potential for adoption to human studies.
State Power, Linkage Mechanisms, and Diversion against Nonrivals
Authors: Foster Dennis M.
Published: March 2006

Mitchell and Prins (2004) have recently found that diversion from high levels of inflation is observed only among enduring rivals. However, neither this nor any other cross-national test of the relevance of opportunity to diversion has included a potentially important determinant of diversionary capacity : major power status. I contend that since militarily powerful states have both more extensive sets of international commitments and much greater physical capacities to divert against broader sets of opponents, they are less likely to limit their diversionary behavior to enduring rivals. Cross-national time series analyses of the association between inflation and militarized interstate dispute (MID) initiation for the period 1960—1999 reveal several differences between the diversionary activity of major powers and that of all other states. Models that account for the interaction between inflation and rivalry reveal that while nonmajor powers seemingly divert only against enduring rivals, major powers are marginally less likely to do so against rivals than they are against nonrivals. However, more detailed analyses indicate that these latter findings are being driven by the American case: While the United States is more likely to initiate MIDs against nonrivals than rivals at the highest levels of inflation, other major powers are more likely to initiate MIDs against rivals than nonrivals at all points. Moreover, the United States is, on average, more likely than all other states to initiate MIDs at all levels of inflation. At minimum, these findings imply that the United States is unique among major powers both in its capacity to divert from inflation and in its propensity to link diversion from inflation against nonrivals to its most important rivalries.
Induction of Apoptosis in Murine Fetal Thymocytes Following Perinatal Exposure to Diethylstilbestrol
Authors: Brown Nicole , Nagarkatti Mitzi , Nagarkatti Prakash S.
Published: March 2006

Perinatal exposure to diethylstilbestrol (DES) is known to cause thymic atrophy in mice, although the precise mechanism remains unclear. In the current study the authors investigated whether perinatal exposure to DES would trigger apoptosis in thymocytes. To this end, C57BL/6 pregnant mice were injected intraperitoneally (i.p.) on gestational day (gd)-15 and -16 with 5 μg/kg DES. Analysis of thymi harvested from mice on gd-17, gd-19 and postnatal day (PD)-1, showed a significant reduction in thymic cellularity on gd-17 only. Additionally, DES treatment significantly altered the proportion and absolute number of T-cell subsets, particularly on gd-17. Apoptosis was increased in DES-treated thymocytes when compared to the controls and was seen only on gd-17. Moreover, DES-treated gd-17 thymocytes had increased Asp-Glu-Val-Asp (DEVDase) activity. Microarray analysis of 96 apoptotic genes in gd-17 thymocytes revealed that exposure to DES increased the expression of several apoptotic genes primarily belonging to tumor necrosis factor (TNF) and TNF receptor (TNFR) family. Taken together, these results suggest that DES-induced thymic atrophy following perinatal exposure may result, at least in part, from increased apoptosis mediated by death receptor pathway involving TNF family members.
Cholesterol Interferes with the MTT Assay in Human Epithelial-Like (A549) and Endothelial (HLMVE and HCAE) Cells
Authors: Ahmad Shama , Ahmad Aftab , Schneider B. Kelly , White Carl W.
Published: March 2006

Metabolically active cells are able to convert the MTT [3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide] dye to blue formazan. This is the basis of the MTT assay, which is among the most widely used screening methods to evaluate cell viability and proliferation. When testing the effects of cholesterol products on the viability of human pulmonary epithelial-like A549 cells using trypan blue staining (cell numbers) and the MTT assay, results were inconsistent. The MTT assay indicated greater than 50% loss of viability with exposure of cells to cholesterol, whereas there was no decrease in viability indicated by trypan blue exclusion and propidium iodide uptake. A similar decrease in MTT reduction was obtained upon cholesterol treatment in human lung microvascular endothelial cells (HLMVECs) and human coronary artery endothelial cells (HCAECs) without loss of viability. This suggested a direct interference of cholesterol with the assay. However, using a cell-free system, there was no decrease in the reduction of MTT by ascorbic acid during incubation with a similar concentration of cholesterol. Light microscopy revealed enhanced exocytosis of formazan granules in presence of cholesterol. Incubation with apolipoprotein A-1 decreased cholesterol-mediated inhibition of MTT assay. These studies indicate decreased MTT reduction as a result of enhanced exocytosis of formazan due to cholesterol. A careful validation of viability assay procedures is therefore suggested in experiments where cholesterol is a constituent, to avoid a potential bias in concluding results of cytotoxicity studies.
Flow Cytometric Assessment of Peroxisome Proliferation from Frozen Liver of Fibrate-Treated Monkeys
Authors: Kwanyuen Puntipa , Witherspoon Sam M. , Creech Don R. , Colton Heidi M. , Falls J. Greg , Cariello Neal F.
Published: March 2006

Multiple methods currently exist for the assessment of peroxisome proliferation, including gene expression, enzyme activity, immunolabeling coupled with image analysis, and electron microscopy. This study describes a novel flow cytometric method to efficiently quantify peroxisome proliferation in cells from frozen livers. Frozen livers from cynomolgus monkeys treated with ciprofibrate at doses of 0, 3, 30, 150, and 400 mg/kg/day for 15 days were mechanically disaggregated using an automated dispersion method. The resulting cell suspensions were labeled using an allophycocyanin (APC)-conjugated antibody directed against peroxisomal membrane protein 70 (PMP70). Statistically significant increases in mean fluorescence intensity were observed from animals dosed at 30, 150, and 400 mg/kg/day compared to control. Parallel comparisons using electron microscopy and immunofluorescence microscopy suggest that flow cytometry may be an alternative to electron microscopy in determinations of peroxisome proliferation. Flow cytometric analysis of freshly isolated hepatocytes and frozen liver from rats treated with fenofibrate at 200 mg/kg/day for 10 days showed the flow cytometric method could detect peroxisome proliferation in both species. The research described here demonstrates the feasibility of applying flow cytometry for the detection of peroxisome proliferation.
A motor neuron disease–associated mutation in p150Glued perturbs dynactin function and induces protein aggregation
Authors: Levy Jennifer R. , Sumner Charlotte J. , Caviston Juliane P. , Tokito Mariko K. , Ranganathan Srikanth , Ligon Lee A. , Wallace Karen E. , LaMonte Bernadette H. , Harmison George G. , Puls Imke , Fischbeck Kenneth H. , Holzbaur Erika L.F.
Published: February 2006

The microtubule motor cytoplasmic dynein and its activator dynactin drive vesicular transport and mitotic spindle organization. Dynactin is ubiquitously expressed in eukaryotes, but a G59S mutation in the p150Glued subunit of dynactin results in the specific degeneration of motor neurons. This mutation in the conserved cytoskeleton-associated protein, glycine-rich (CAP-Gly) domain lowers the affinity of p150Glued for microtubules and EB1. Cell lines from patients are morphologically normal but show delayed recovery after nocodazole treatment, consistent with a subtle disruption of dynein/dynactin function. The G59S mutation disrupts the folding of the CAP-Gly domain, resulting in aggregation of the p150Glued protein both in vitro and in vivo, which is accompanied by an increase in cell death in a motor neuron cell line. Overexpression of the chaperone Hsp70 inhibits aggregate formation and prevents cell death. These data support a model in which a point mutation in p150Glued causes both loss of dynein/dynactin function and gain of toxic function, which together lead to motor neuron cell death.
Access of Extracellular Cations to their Binding Sites in Na,K-ATPase: Role of the Second Extracellular Loop of the α Subunit
Authors: Capendeguy Oihana , Chodanowski Pierre , Michielin Olivier , Horisberger Jean-Daniel
Published: February 2006

Na,K-ATPase, the main active transport system for monovalent cations in animal cells, is responsible for maintaining Na+ and K+ gradients across the plasma membrane. During its transport cycle it binds three cytoplasmic Na+ ions and releases them on the extracellular side of the membrane, and then binds two extracellular K+ ions and releases them into the cytoplasm. The fourth, fifth, and sixth transmembrane helices of the α subunit of Na,K-ATPase are known to be involved in Na+ and K+ binding sites, but the gating mechanisms that control the access of these ions to their binding sites are not yet fully understood. We have focused on the second extracellular loop linking transmembrane segments 3 and 4 and attempted to determine its role in gating. We replaced 13 residues of this loop in the rat α1 subunit, from E314 to G326, by cysteine, and then studied the function of these mutants using electrophysiological techniques. We analyzed the results using a structural model obtained by homology with SERCA, and ab initio calculations for the second extracellular loop. Four mutants were markedly modified by the sulfhydryl reagent MTSET, and we investigated them in detail. The substituted cysteines were more readily accessible to MTSET in the E1 conformation for the Y315C, W317C, and I322C mutants. Mutations or derivatization of the substituted cysteines in the second extracellular loop resulted in major increases in the apparent affinity for extracellular K+, and this was associated with a reduction in the maximum activity. The changes produced by the E314C mutation were reversed by MTSET treatment. In the W317C and I322C mutants, MTSET also induced a moderate shift of the E1/E2 equilibrium towards the E1(Na) conformation under Na/Na exchange conditions. These findings indicate that the second extracellular loop must be functionally linked to the gating mechanism that controls the access of K+ to its binding site.
Control of translation and mRNA degradation by miRNAs and siRNAs: Table 1.
Authors: Valencia-Sanchez Marco Antonio , Liu Jidong , Hannon Gregory J. , Parker Roy
Published: March 2006

The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro RNAs (miRNAs) and short interfering RNAs (siRNAs) and can affect mRNA degradation and translation, as well as chromatin structure, thereby having impacts on transcription rates. In this review, we discuss possible mechanisms by which miRNAs control translation and mRNA degradation. An emerging theme is that miRNAs, and siRNAs to some extent, target mRNAs to the general eukaryotic machinery for mRNA degradation and translation control.
Ligand-induced endocytosis of the pattern recognition receptor FLS2 in Arabidopsis
Authors: Robatzek Silke , Chinchilla Delphine , Boller Thomas
Published: March 2006

Pattern-recognition receptors (PRRs) trigger innate immune responses in animals and plants. One such PRR is the flagellin receptor FLS2 in Arabidopsis. Here, we demonstrate that a functional fusion of FLS2 to the green fluorescent protein (GFP) resides in cell membranes of most tissues. Stimulation with the flagellin epitope flg22 induces its transfer into intracellular mobile vesicles, followed by degradation. FLS2 internalization depends on cytoskeleton and proteasome functions, and receptor activation. A variant FLS2 mutated in Thr 867, a potential phosphorylation site, binds flg22 normally, but is impaired in flg22 responses and FLS2 endocytosis. We propose that plant cells regulate pathogen-associated molecular pattern (PAMP)-mediated PRR activities by subcellular compartmentalization.
Helping smokers to decide on the use of efficacious smoking cessation methods: a randomized controlled trial of a decision aid
Authors: Willemsen Marc C. , Wiebing Marieke , Van Emst Andrée , Zeeman Grieto
Published: February 2006

Aims  Most smokers attempt to stop smoking without using help. We evaluated the efficacy of a decision aid to motivate quitters to use efficacious treatment.

Setting and participants  A total of 1014 were recruited from a convenience sample of 3391 smokers who intended to quit smoking within 6 months.

Design and intervention  Smokers were assigned randomly to either receive the decision aid or no intervention. The decision aid was expected to motivate quitters to use efficacious cessation methods and contained neutral information on treatment methods, distinguishing between efficacious and non‐efficacious treatments.

Measurements  Baseline questionnaire and follow‐ups were used 2 weeks and 6 months after the start of the intervention. 

Findings  The decision aid increased knowledge of cessation methods and induced a more positive attitude towards these methods. Furthermore, 45% reported increased confidence about being able to quit and 43% said it helped them to choose between treatments. However, no clear effect on usage of treatment aids was found, but the intervention group had more quit attempts (OR = 1.52, 95% CI 1.14–2.02) and higher point prevalence abstinence at 6‐month follow‐up (20.2% versus 13.6%; OR = 1.51, 95% CI = 1.07–2.11).

Conclusions  An aid to help smokers decide to use efficacious treatment when attempting to quit smoking had a positive effect on smoking cessation, while failing to increase the usage of efficacious treatment. This finding lends support to the notion that the mere promotion of efficacious treatments for tobacco addiction might increase the number of quit attempts, irrespective of the actual usage of treatment.
HEX, PAX‐8 and TTF‐1 gene expression in human thyroid tissues: a comparative analysis with other genes involved in iodide metabolism
Authors: Lacroix Ludovic , Michiels Stefan , Mian Caterina , Arturi Franco , Caillou Bernard , Filetti Sebastiano , Schlumberger Martin , Bidart Jean‐Michel
Published: March 2006

Objective  Benign and malignant thyroid tumours are characterized by alterations of the expression level of thyroid‐specific genes involved in the iodide metabolism. Imbalance in the levels of transcription factors has been recognized as a critical molecular event in the development of neoplasm. The delineation of eventual correlations existing between the expression of transcription factors and of putative target genes in physiological and pathological conditions could be relevant to better understand tumorigenesis.

Patients and methods  We examined the expression levels of transcription factors involved in thyroid development [thyroid transcription factor 1 (TTF‐1), paired box gene 8 (PAX‐8) and haematopoietically expressed homeobox (HEX)] in 101 thyroid tissues, including 14 normal thyroid tissues, 13 hyperfunctioning tissues, 27 benign adenomas and 47 follicular or papillary carcinomas. Then, we compared their expression levels with those of thyroid‐specific genes involved in iodide metabolism.

Results  In benign tumours, PAX‐8 and TTF‐1 gene expression levels were not significantly different from the expression levels in normal tissues. However, a significant decrease was found in carcinomas. Interestingly, HEX gene expression was significantly decreased in both hyper‐ and hypofunctioning benign tissues and also in carcinomas. Expression levels of Pendred syndrome (PDS), natrium iodine symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO) and dual oxidase 1 or 2 (DUOX2) genes were significantly correlated with the expression of PAX‐8 and with that of HEX. Expression level of TTF‐1 was weakly correlated only with the expression levels of PDS and DUOX2.

Conclusion  Our findings suggest that alterations in the transcription factors PAX‐8, TTF‐1 and HEX gene expression, by acting individually or together, have a role in both thyroidal tumorigenesis and in the dedifferentiation process.
Effects of growth hormone on insulin resistance and atherosclerotic risk factors in obese type 2 diabetic patients with poor glycaemic control
Authors: Ahn Chul Woo , Kim Chul Sik , Nam Jae Hyun , Kim Hai Jin , Nam Ji Sun , Park Jong Suk , Kang Eun Seok , Cha Bong Soo , Lim Sung Kil , Kim Kyung Rae , Lee Hyun Chul , Huh Kap Bum
Published: March 2006

Objective  We aimed to evaluate the combined effects of GH treatment and diet restriction on lipolysis and anabolism, insulin resistance and atherosclerotic risk factors in obese patients with type 2 diabetes mellitus (T2DM).

Subjects  This randomized, double‐blind, placebo‐controlled study included 24 obese T2DM patients (male : female = 12 : 12, mean age 53·7 ± 7·2 years) with poor glycaemic control (fasting plasma glucose 10·673 ± 1·121 mmol/l, HbA1C 9·9 ± 2·3%). Sixteen of these patients were treated with recombinant human GH (1–1·5 units/day, 5 days/week) while undergoing diet restriction and exercise for 12 weeks.

Methods  Anthropometric and bioelectrical impedance measurements were undertaken to determine the lean body mass and total body fat. Computed tomography (CT) was performed to estimate visceral and subcutaneous fat distribution at the umbilicus level and the muscle area of the midthigh. Insulin resistance was measured by the insulin tolerance test (ITT) and by the homeostasis model assessment of insulin resistance (HOMA‐IR).

Results  The ratios VSR (visceral fat area/subcutaneous fat area) and VMR (visceral fat area/thigh muscle area) were significantly decreased in the GH‐treated group compared to the control group. An increase in lean body mass was observed in the GH‐treated group. Levels of total cholesterol, triglyceride, free fatty acid (FFA), fibrinogen, and plasminogen activator inhibitor‐1 (PAI‐1) were significantly decreased after GH treatment. Fasting glucose levels decreased similarly (P < 0·05 anova) in both groups during the treatment period. Fasting C‐peptide levels significantly increased, whereas insulin levels significantly decreased, in the GH‐treated group, but no changes were observed in the control group. The insulin sensitivity index (ISI) was significantly increased in the GH‐treated group (1·3 ± 1·4 vs. 1·9 ± 1·0%/min, P < 0·05).

Conclusions  GH treatment in obese T2DM patients with poor glycaemic control is beneficial in decreasing the amount of visceral fats, and may therefore result in improvements in insulin resistance, atherosclerotic risk factors and dyslipidaemia.
Hyperleptinaemia and hypoadiponectinaemia are associated with gallstone disease
Authors: Wang S. N. , Yeh Y. T. , Yu M. L. , Dai C. Y. , Chi W. C. , Chung W. L. , Lee K. T.
Published: February 2006

Background  Gallstone disease has been regarded as an obesity‐related disease. Therefore, we hypothesized that leptin and adiponectin, mainly produced by adipose tissue, may play roles in gallstone disease.

Patients and methods  The RIA method was used to analyze serum leptin and adiponectin levels of 90 gallstone patients and 91 healthy subjects.

Results  Our results showed that BMI, fasting glucose, serum AST and ALT, and leptin were significantly increased in the gallstone patients as compared with the healthy subjects (P < 0·001, P < 0·001, P < 0·001, P < 0·001, P < 0·001, and P = 0·013, respectively). Intriguingly, serum adiponectin was the only variable to be significantly decreased in the gallstone patients (P = 0·002). Furthermore, serum AST, leptin, and adiponectin were significantly associated with gallstone disease (P < 0·001, P = 0·021, and P = 0·006, respectively). Overweight (BMI ≥ 25 kg m−2), but not normal‐weight, gallstone patients had an increased serum leptin and a decreased serum adiponectin level as compared with matched healthy subjects (P < 0·001 and P = 0·024, respectively). In addition, serum leptin was positively correlated with BMI and serum cholesterol, while serum adiponectin was inversely correlated with serum triglyceride in the gallstone patients.

Conclusions  Our study indicated that hyperleptinaemia and hypoadiponectinaemia might be involved in the occurrence of gallstone disease. However, the causal relationship of hyperleptinaemia and hypoadiponectinaemia with gallstone disease might require further investigation.
Evidence for intestinal oxidative stress in patients with obstructive jaundice
Authors: Assimakopoulos S. F. , Thomopoulos K. C. , Patsoukis N. , Georgiou C. D. , Scopa C. D. , Nikolopoulou V. N. , Vagianos C. E.
Published: February 2006

Background  Obstructive jaundice results in failure of the intestinal barrier with consequent systemic endotoxemia associated with septic complications. We have recently shown that gut barrier failure in experimental obstructive jaundice is associated with high intestinal oxidative stress. This study was undertaken to investigate whether oxidative alterations occur in the intestinal mucosa of patients with obstructive jaundice.

Patients and methods  Fifteen patients with malignant biliary obstruction and no signs of cholangitis and 15 control patients were subjected to duodenal biopsy to assess intestinal oxidative stress, estimated by lipid peroxidation (malondialdehyde – MDA) and glutathione redox state [reduced glutathione (GSH), glutathione disulphide (GSSG) and GSH/GSSG ratio]. In addition, mucosal biopsies were examined histologically and intestinal mucosal protein content was determined biochemically as an index of intestinal trophic state.

Results  Patients with obstructive jaundice presented high levels of intestinal oxidative stress, with significantly increased lipid peroxidation (P < 0·001). Glutathione redox state was also suggestive of high intestinal oxidative stress in jaundiced patients, indicated by significantly decreased GSH (P = 0·001) and GSH/GSSG ratio (P = 0·006) and increased GSSG (P = 0·026). Histological examination showed a mild infiltration of the lamina propria by chronic inflammatory cells in obstructive jaundice, whereas duodenal architecture remained intact and epithelial continuity was retained. Duodenal mucosa was atrophic in jaundiced patients as indicated by a significant reduction of mucosal protein content compared with controls (P = 0·001). Among oxidative stress parameters, intestinal GSH exhibited a significant positive correlation with mucosal protein content (r = 0·588, P = 0·021).

Conclusions  Obstructive jaundice in humans induces intestinal oxidative stress, which may be a key factor contributing to intestinal barrier failure and the development of septic complications in this patient population.
The acquisition of stimulus equivalence in individuals with fragile X syndrome
Authors: Hall S. S. , DeBernardis G. M. , Reiss A. L.
Published: February 2006

Background  Few studies have employed stimulus equivalence procedures to teach individuals with intellectual disabilities (IDs) new skills. To date, no studies of stimulus equivalence have been conducted in individuals with fragile X syndrome (FXS), the most common known cause of inherited ID.

Method  Five adolescents with FXS were taught basic math and geography skills by using a computerized stimulus equivalence training programme administered over 2 days in 2‐h sessions.

Results  Four of the five participants learned the math relations, with one participant demonstrating stimulus equivalence at post‐test. Three of the five participants learned the geography relations, with all three of these participants demonstrating stimulus equivalence at post‐test.

Conclusions  These data indicate that computerized stimulus equivalence procedures, conducted in time‐limited sessions, may help individuals with FXS learn new skills. Hypotheses concerning the failure of some participants to learn the training relations and to demonstrate stimulus equivalence at post‐test are discussed.
Coronary heart disease risks in first‐ and second‐generation immigrants in Sweden: a follow‐up study
Authors: SUNDQUIST K. , LI X.
Published: February 2006

Objectives.  To analyse whether there is an association between country of birth in first‐generation immigrants and first hospitalization for or death from coronary heart disease (CHD) and to analyse whether this association remains in second‐generation immigrants.

Design.  In this follow‐up study, the MigMed database at the Karolinska Institute, Stockholm, was used to identify all hospital diagnoses of and deaths from incident CHD in first‐ and second‐generation immigrants in Sweden between 1 January 1987 and 31 December 2001. Incidence ratios standardized by age, geographical region and socio‐economic status were estimated by sex in first‐ and second‐generation immigrants; the reference group was Swedish‐born people whose parents were both born in Sweden.

Subjects.  The total Swedish population aged 25–69 years.

Results.  First‐generation immigrants from Finland, central European countries, other eastern European countries and Turkey had higher rates of CHD than men or women in the reference group. First‐generation immigrant women born in southern Europe, other western European countries and Baltic countries had lower CHD risks than the reference group. Sons of both male and female first‐generation immigrants showed CHD risks similar to or slightly higher than those of their parents. Amongst second‐generation women, only subjects with Finnish fathers or mothers had higher risks of developing CHD than the reference.

Conclusions.  Increased risks of CHD found in some first‐generation immigrant groups often persist in second‐generation immigrant men. Healthcare professionals and policy makers should take this into account when designing and undertaking measures to prevent CHD.
Mineral loss from bovine enamel by a 30% hydrogen peroxide solution
Authors: LEE K. H. , KIM H. I. , KIM K. H. , KWON Y. H.
Published: March 2006

summary  This study investigated the effect of a 30% hydrogen peroxide bleaching agent on bovine enamel in terms of mineral loss. Contents of mineral elements both in the teeth and bleaching agent were evaluated to estimate the effect of hydrogen peroxide on teeth. Finely polished non‐carious bovine incisors (n = 5) were immersed in a 30% hydrogen peroxide solution for 120 h. The amounts of concentrated elements in the bleaching agent (5 mL) were measured using inductively coupled plasma‐atomic emission spectrometer and ion chromatograph. The contents of mineral elements in the teeth were measured using an electron probe microanalyzer. The Ca/P ratio in the bleaching agent was approximately 1·99. The amount of Zn in the bleaching agent was below the detection limit. The total content of mineral elements of the unbleached enamel (90·75 ± 1·58) was slightly greater than that of the bleached enamel (87·44 ± 0·77). The Ca/P ratio of the bleached enamel was 2·06. The amount of Ca loss from the bleached enamels after 120 h was similar to the amount of Ca loss from teeth exposed to a soft drink or juice for a few minutes. Therefore, mineral loss caused by the bleaching process may not be a threatening factor to teeth.
Reproducibility of a method for analysis of morphological changes in perioral soft tissue in children using video cameras
Authors: MIYAKAWA T. , MORINUSHI T. , YAMASAKI Y.
Published: March 2006

summary  The purpose of the present study was to determine the appropriate reference facial expression and to examine the reproducibility of our system using two commercially available video cameras in consideration of functional diagnosis of perioral muscles. The following items were investigated: 1) influence of forward and backward movements and the experiment sequence from measurement to analysis, 2) usefulness of head fixation by a restraining device during video recording for evaluation of morphological changes in facial expression, 3) conditions for establishment of reference points for determination of movements of perioral soft tissue, and 4) reproducibility of perioral soft tissue movements as assessed by changes in landmarks. The results of this study showed that accurate static and dynamic evaluation of perioral soft tissue is possible by using our method of video recording with the subject's head restrained and our method of analysis. The results also showed that centric occlusion of the most appropriate reference facial expression as for measurement of perioral soft tissue movements and that protrusion of the lips and lateral extension of the angel of the mouth are facial expressions with high degrees of reproducibility.
Growth analysis of a patient with ectodermal dysplasia treated with endosseous implants: 6‐year follow‐up
Authors: ALCAN T. , BASA S. , KARGÜL B.
Published: March 2006

summary  The purpose of this article is to report the clinical course and 6‐year follow‐up of a child with ectodermal dysplasia who was treated with implants surgery very early. This article reports placement of mandibular endosseous implants in a 4‐year‐old patient with hypohidrotic ectodermal dysplasia and oligodontia. This congenital anomaly does not appear to retard healing and the osseointegration remains after 6 years and 3 months of loading. Mandibular and maxillary skeletal growth and development was normal. However, because of lack of alveolar growth, in time, patient's vertical growth pattern changed to low angle. This could be corrected by changing the vertical heights of the abutment and prosthesis. As a result, in ectodermal dysplasias cases with anadontia, early implant placement and fixed prosthesis could be a good multidisciplinary treatment option for poor cooperative child.
Antimicrobial activity of gallium against virulentRhodococcus equiin vitroandin vivo
Authors: HARRINGTON J. R. , MARTENS R. J. , COHEN N. D. , BERNSTEIN L. R.
Published: March 2006

Rhodococcus equi, a facultative intracellular bacterium, causes severe pneumonia in foals. Evidence suggests that most foals become infected very early in life, when they have immature or ineffective innate immune responses. This study evaluated the antimicrobial activity of gallium againstR. equi, as a potential chemoprophylactic and therapeutic agent.Rhodococcus equiwas grown in media with various concentrations of gallium nitrate (GN), with and without excess iron. GN significantly inhibited growth and killedR. equi, and these effects were abolished with excess iron. Antimicrobial effects of Ga appear to be related to its interference with iron metabolism. Mice were treated orally with gallium maltolate (GaM), 10 or 50 mg/kg BW, or distilled H2O prior to and after experimental infection withR. equi. Six days post‐infection, organs were harvested andR. equiconcentrations assessed, and serum gallium concentrations determined. GaM was absorbed in a dose‐dependent manner, andR. equitissue burdens were greater in control mice than in all GaM‐treated mice. GaM may aid in the control of disease by preventing development of overwhelmingR. equitissue burdens prior to the establishment of requisite innate and adaptive immune responses.
Is hepatitis C virus a risk factor for thyroid autoimmunity?
Authors: Floreani A. , Betterle C. , Carderi I. , Presotto F. , Pedini B. , Moscon A. , Di Andrea O. , Chiaramonte M. ,   Arsita‐one Research Group
Published: February 2006

Summary.  The role of hepatitis C virus (HCV) in inducing thyroid autoimmunity is still under discussion and to assess the prevalence of thyroid autoantibodies and thyroid disease in the general population and to analyse the role of HCV in inducing thyroid autoimmunity. We studied 697 subjects residing in Arsita (a small town in central Italy). Thyroid autoantibodies and nonorgan‐specific autoantibodies (NOSAs) were tested in each subject, who were also screened for anti‐HCV antibodies; all subjects found positive to HCV–RNA were considered as being HCV‐infected. Thyroid function tests were performed in all subjects positive for thyroid autoantibody. Seventy‐one subjects were found HCV‐positive; four of these (5.6%) were positive for at least one thyroid autoantibody, as opposed to 7 (4.9%) of the 142 sex‐ and age‐matched controls of the same population (P = n.s.). Thyroid dysfunction was found in 2/4 HCV‐positive, and in 1/7 HCV‐negative subjects with thyroid autoantibodies (P = n.s.). NOSAs were significantly more common in HCV‐positive than in HCV‐negative subjects (P < 0.0001). Hence HCV per se is not responsible for thyroid autoimmune dysfunction, whereas HCV does seem to induce NOSAs. It should be taken into account, however, that the phenotypic expression of autoimmune diseases is obviously influenced by a number of risk factors, including genetic predisposition, female sex and infectious agents, that could trigger the onset of the disease.
The Neutralizing Effects of Hyperimmune Antibodies Against Extracellular Fibrinogen‐Binding Protein, Efb, from Staphylococcus aureus
Authors: Shannon O. , Uekotter A. , Flock J.‐I.
Published: February 2006

Staphylococcus aureus is a significant cause of acute and chronic infection and boasts a diverse array of virulence factors. S. aureus produces and secretes a protein, extracellular fibrinogen (Fg)‐binding protein (Efb), which contributes to virulence in wound infection. Efb binds to both Fg and platelets and inhibits platelet function in vitro and in vivo. In this study, we have characterized the antibody response against Efb. Antibodies generated in response to immunization with Efb can neutralize the biological effects of Efb. Hyperimmune sheep immunoglobulin (Ig)G against Efb blocked the binding of Efb to Fg and prevented Efb‐mediated inhibition of platelet aggregation. Furthermore, these antibodies cross‐reacted with coagulase and blocked coagulase activity in plasma. Immunization of mice with Efb resulted in the generation of high titre specific antibodies. When subjected to a foreign‐body‐associated wound infection, the vaccinated animals developed significantly less severe wound infection than the unvaccinated controls. Also, human IgG against Efb was prepared from commercial IgG pools; however, the monospecific human anti‐Efb that was enriched was unable to neutralize Efb. We conclude that immunization with Efb is required in order to generate a protective antibody response to Efb from S. aureus.
Pollen‐food syndromes associated with weed pollinosis: an update from the molecular point of view
Authors: Egger M. , Mutschlechner S. , Wopfner N. , Gadermaier G. , Briza P. , Ferreira F.
Published: February 2006

Pollinosis patients often display adverse reactions upon the ingestion of plant‐derived foods as a result of immunoglobulin E (IgE) cross‐reactive structures shared by pollen and food allergen sources. The symptoms of such pollen‐food syndromes (PFS) or class 2 food allergies range from local oral allergy syndrome to severe systemic anaphylaxis. Two clinical syndromes, the celery‐mugwort‐spice syndrome and the mugwort‐mustard‐allergy syndrome have been described in association with weed pollinosis. However, other associations between weed pollinosis and hypersensitivity to certain kinds of food have also been observed, like the mugwort–peach, the ragweed–melon–banana, the plantain–melon, the pellitory–pistachio, the goosefoot–fruit, the Russian thistle–saffron, and the hop–celery association. The number of allergen sources involved, the allergens, and influencing factors including geography, diet, and food preparation contribute to the high clinical complexity of PFS. So far, known causative cross‐reactive allergens include profilins, lipid transfer proteins, and high‐molecular weight allergens and/or glycoallergens. The current usage of nonstandardized allergen extracts poses additional problems for both diagnosis and therapy of PFS patients. Further identification and characterization of involved allergens is inescapable for better understanding of PFS and vaccine development. Panels of recombinant allergens and/or hypo‐allergens are promising tools to improve both PFS diagnostics and therapy.
Can Wall Lizards Combine Chemical and Visual Cues to Discriminate Predatory from Non‐Predatory Snakes Inside Refuges?
Authors: Amo Luisa , López Pilar , Martín José
Published: March 2006

The ability to use multiple cues in assessing predation risk is especially important to prey animals exposed to multiple predators. Wall lizards, Podarcis muralis, respond to predatory attacks from birds in the open by hiding inside rock crevices, where they may encounter saurophagous ambush smooth snakes. Lizards should avoid refuges with these snakes, but in refuges lizards can also find non‐saurophagous viperine snakes, which lizards do not need to avoid. We investigated in the laboratory whether wall lizards used different predator cues to detect and discriminate between snake species within refuges. We simulated predatory attacks in the open to lizards, and compared their refuge use, and the variation in the responses after a repeated attack, between predator‐free refuges and refuges containing visual, chemical, or visual and chemical cues of saurophagous or non‐saurophagous snakes. Time to enter a refuge was not influenced by potential risk inside the refuge. In contrast, in a successive second attack, lizards sought cover faster and tended to increase time spent hidden in the refuge. This suggests a case of predator facilitation because persistent predators in the open may force lizards to hide faster and for longer in hazardous refuges. However, after hiding, lizards spent less time in refuges with both chemical and visual cues of snakes, or with chemical cues alone, than in predator‐free refuges or in refuges with snake visual cues alone, but there were no differences in response to the two snake species. Therefore, lizards could be overestimating predation risk inside refuges. We discuss which selection pressures might explain this lack of discrimination of predatory from similar non‐predatory snakes.