bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic tractography recovers a rostrocaudal trajectory of connectivity variability in the human insular cortex
Authors: Cerliani Leonardo , Thomas Rajat M. , Jbabdi Saad , Siero Jeroen C.W. , Nanetti Luca , Crippa Alessandro , Gazzola Valeria , D'Arceuil Helen , Keysers Christian
Published: July 2011

The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet been investigated in vivo. In the present work, we used in vivo probabilistic white‐matter tractography and Laplacian eigenmaps (LE) to study the variation of connectivity patterns across insular territories in humans. In each subject and hemisphere, we recovered a rostrocaudal trajectory of connectivity variation ranging from the anterior dorsal and ventral insula to the dorsal caudal part of the long insular gyri. LE suggested that regional transitions among tractography patterns in the insula occur more gradually than in other brain regions. In particular, the change in tractography patterns was more gradual in the insula than in the medial premotor region, where a sharp transition between different tractography patterns was found. The recovered trajectory of connectivity variation in the insula suggests a relation between connectivity and cytoarchitecture in humans resembling that previously found in macaques: tractography seeds from the anterior insula were mainly found in limbic and paralimbic regions and in anterior parts of the inferior frontal gyrus, while seeds from caudal insular territories mostly reached parietal and posterior temporal cortices. Regions in the putative dysgranular insula displayed more heterogeneous connectivity patterns, with regional differences related to the proximity with either putative granular or agranular regions. Hum Brain Mapp 33:2005–2034, 2012. © 2011 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.
Functional dissociation of the left and right fusiform gyrus in self‐face recognition
Authors: Ma Yina , Han Shihui
Published: July 2011

It is well known that the fusiform gyrus is engaged in face perception, such as the processes of face familiarity and identity. However, the functional role of the fusiform gyrus in face processing related to high‐level social cognition remains unclear. The current study assessed the functional role of individually defined fusiform face area (FFA) in the processing of self‐face physical properties and self‐face identity. We used functional magnetic resonance imaging to monitor neural responses to rapidly presented face stimuli drawn from morph continua between self‐face (Morph 100%) and a gender‐matched friend's face (Morph 0%) in a face recognition task. Contrasting Morph 100% versus Morph 60% that differed in self‐face physical properties but were both recognized as the self uncovered neural activity sensitive to self‐face physical properties in the left FFA. Contrasting Morphs 50% that were recognized as the self versus a friend on different trials revealed neural modulations associated with self‐face identity in the right FFA. Moreover, the right FFA activity correlated with the frequency of recognizing Morphs 50% as the self. Our results provide evidence for functional dissociations of the left and right FFAs in the representations of self‐face physical properties and self‐face identity. Hum Brain Mapp 33:2255–2267, 2012. © 2011 Wiley Periodicals, Inc.
Event‐related potential activity in the basal ganglia differentiates rewards from nonrewards: Response to commentary
Authors: Foti Dan , Weinberg Anna , Dien Joseph , Hajcak Greg
Published: July 2011

We recently demonstrated that the feedback negativity may be better understood as a reward‐related positivity that is absent on nonreward trials, and source localization revealed that this reward response may reflect activity in the striatum. In a commentary on our report, Cohen et al. argue against this latter finding, claiming it is unlikely that the striatum contributes to the scalp‐recorded event‐related potential. We disagree with the line of reasoning presented by Cohen et al., and we respond here to each of their points. Based on all the available evidence, we argue that the striatum is a plausible generator of a reward‐related response observed at the scalp, and this possibility warrants further investigation. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.
Nitroglycerin Improves the Hemodynamic Response to Vasopressin in Portal Hypertension
Authors: Groszmann Roberto J. , Kravetz David , Bosch Jaime , Glickman Mortom , Bruix Jordi , Bredfeldt James , Conn Harold O. , Rodes Juan , Storer Edward H.
Published: July 2011

This study was designed to investigate whether the addition of nitroglycerin to vasopressin infusion could avoid the deleterious systemic effects of vasopressin while maintaining or enhancing the therapeutic benefits of portal pressure reduction. The effect of nitroglycerin on splanchnic and systemic hemodynamics was studied in cirrhotic patients and portal hypertensive dogs receiving i.v. vasopressin. During i.v. vasopressin infusion (0.4 units per min), the cardiac output decreased in patients by 14% from 7.6 ± 0.9 (mean ± S.E.) to 6.5 ± 0.7 liters per min, p < 0.01, the mean arterial pressure increased 21% from 87 ± 2 to 105 ± 4, p < 0.01, and the heart rate decreased 11% from 79 ± 3 to 71 ± 3, p < 0.01. The administration of sublingual nitroglycerin (0.4 mg) returned all the systemic hemodynamic parameters to baseline values. In dogs, vasopressin infusion significantly reduced portal pressure and flow while increasing portal venous resistance. Nitroglycerin when added to the vasopressin infusion reduced portal venous resistance and further decreased portal pressure in dogs. In patients, vasopressin reduced the hepatic blood flow (44%), wedged hepatic venous pressure (11%), and the gradient between wedged and free hepatic venous pressures (23%). Nitroglycerin administration caused a further reduction of the wedged hepatic venous pressure (23.6 ± 2.3 to 21.1 ± 2.0, 11%, p < 0.01). There was a small but not significant further decline (7%) in the hepatic venous pressure gradient. These results provide evidence that the addition of nitroglycerin to an i.v. infusion of vasopressin reversed the detrimental effects of vasopressin while preserving the beneficial effects.
A Study of Bile Canalicular Contractions in Isolated Hepatocytes
Authors: Phillips James M. , Oshio Chikara , Miyairi Mamoru , Katz Hart , Smith Charles R.
Published: July 2011

Living hepatocytes observed under standard methods of cell isolation and culture show frequent active contractions of bile canaliculi when viewed by time–lapse cinephotomicrography. This report gives details of the methods used to show the contractions. In addition, the characteristics of the contraction pattern are defined and analyzed. The contractions are regular, canalicular contraction time (systole) lasts 60 sec, and the most probable interval between contractions is 5 1/2 min. The finding of a regular pattern of contraction suggests an ordered, programmed, and integrated mechanism which entails a high degree of communication and functional coordination between neighboring hepatocytes.
Uptake and Intracellular Disposition of Iga by Rat Hepatocytes in Monolayer Culture
Authors: Jones Albert L. , Huling Sandra , Hradek Gary T. , Gaines Henry S. , Christiansen William D. , Underdown Brian J.
Published: July 2011

It is well documented that the liver provides an important source of secretory immunoglobulin A (sIgA) in the gut fluid. In the rat, liver parenchymal cells can actively sequester the dimeric form of IgA (dIgA) from plasma and transfer it attached to its receptor, secretory component (SC), via vesicles into the bile. In the present investigation, isolated rat hepatocytes in monolayer culture were studied using quantitative electron microscopic autoradiography to determine if the previous reported specific binding of dIgA by isolated cells would result in internalization of the ligand and, if so, whether its distribution within the cultured hepatocytes would be similar to that found in vivo. The specificity of the process for receptor (SC) availability was evaluated utilizing sIgA and by blocking the receptor with rabbit IgG anti–rat SC antibody. For these studies, purified dIgA and sIgA were iodinated with [125I] and added to fresh culture medium 24 hr following the isolation of the hepatocytes. After 3, 30, and 60 min of incubation with the isotope, the cells were washed, fixed, and processed for light and electron microscopic autoradiography. Binding of dlgA to the cells occurred by 3 min, and the number of autoradiographic grains per unit membrane length remained constant throughout the 60–min time period. With time, there was a progressive increase in the per cent of internalized grains. As in the previous in vivo studies, the majority of these internalized grains were localized to vesicles and smooth surface endoplasmic reticulum. There was no evidence of binding or uptake of sIgA at any time period and pretreatment with anti–SC reduced binding and internalization of dIgA to 16% of the control value.

These data provide new evidence that isolated hepatocytes in monolayer culture appear functionally intact with regard to dIgA uptake and demonstrate their usefulness as an in vitro system for future studies of IgA metabolism.
Adenine Arabinoside 5′–Monophosphate Treatment of Chronic Type B Hepatitis
Authors: Hoofnagle Jay H. , Minuk Gerald Y. , Dusheiko Geoffrey M. , Schafer Daniel F. , Johnson Rodney , Straus Stephen , Jones Anthony E. , Gerin John L. , Ishak Kamal
Published: July 2011

Six patients with chronic type B hepatitis were treated with adenine arabinoside 5′–monophosphate at a dosage of 10 to 15 mg per kg per day for 10 days. All demonstrated an immediate and marked decrease in serum hepatitis B virus DNA and DNA polymerase, and 5 of the 6 became negative for both markers by the end of the period of therapy. One patient remained negative for hepatitis B virus DNA and DNA polymerase when therapy was discontinued. This patient subsequently exhibited clinical, serum biochemical, and histological remission in disease activity concurrent with seroconversion from hepatitis B e antigen to antibody. In the remaining five patients, serum hepatitis B virus DNA and DNA polymerase returned to pretreatment values soon after therapy was stopped, and these patients demonstrated no significant changes in clinical, biochemical, serological, or histological features of the disease. Side effects of the therapy were mild and transient. These results suggest that a 10–day course of adenine arabinoside 5′–monophosphate is not adequate to induce permanent amelioration of infection and disease activity in the majority of patients with chronic type B hepatitis.
Interferon Production by Peripheral Lymphocytes in Hbsag–Positive Liver Diseases
Authors: Kato Yasuhiro , Nakagawa Hirohito , Kobayashi Kenichi , Hattori Nobu , Hatano Kiichi
Published: July 2011

Interferon production by lymphocytes was normal in HBsAg carriers with normal liver function tests and normal liver histology, whereas it was significantly decreased in HBsAg–positive patients with chronic active hepatitis and cirrhosis. It is possible that an impaired interferon system is causally related to the development of chronic liver disease in hepatitis B virus infection.
Spontaneous Disappearance of Viral Replication and Liver Cell Inflammation in Hbsag–Positive Chronic Active Hepatitis: Results of A Placebo Vs. Interferon Trial
Authors: Schalm Solko W. , Heijtink Rudolf A.
Published: July 2011

In 20 patients with HBsAg–and HBeAg–positive chronic active hepatitis, we determined the long–term effect of human leukocyte interferon as well as placebo treatment. During the 2–year follow–up period, HBsAg remained present in all patients, but the Dane particle markers HBeAg and DNA polymerase disappeared in two of 10 patients who had received interferon, and in 4 of 10 patients from the placebo group.

Patients with loss of HBeAg initially had HBs antigenemia for a longer period as well as a lower serum concentration of both HBsAg and DNA polymerase, fewer HBcAg–containing hepatocyte nuclei, and higher serum transaminase levels than did the patients in whom HBeAg persisted. Disappearance of Dane particle markers was associated with a decrease in HBsAg titer, appearance of anti–HBe, normalization of the serum transaminases, and morphological transition to inactive chronic hepatitis.

We conclude that, in HBsAg– and HBeAg–positive chronic active hepatitis, disappearance of Dane particle markers occurs in approximately 30% of the patients within a 2–year period and that arrest of active viral replication is associated with loss of activity of chronic hepatitis. Treatment with human leukocyte interferon in the doses used in this study did not change the natural course of the disease.
The Significance of Igm Antibodies to Hepatitis B Core Antigen in Hepatitis B Carriers and Hepatitis B–Associated Chronic Liver Disease
Authors: Feinman Victor S. , Overby Lacy R. , Berris Barnet , Chau Kurt , Schable Charles A. , Maynard James E.
Published: July 2011

IgM antibody to hepatitis B core antigen (IgM anti–HBc) was determined in 60 patients whose serum was positive for hepatitis B surface antigen (HBsAg) and 18 patients whose serum was negative for HBsAg, but positive for antibody to hepatitis B core antigen (anti–HBc). Two radioimmunoassays were done utilizing either anti–u antibody to capture IgM or Staphylococcus A protein to separate IgG and IgM. Both methods failed to detect IgM anti–HBc in 30 healthy carriers, 5 HBsAg–positive cirrhotics, 2 patients with HBsAg–positive hepatocellular carcinoma, and 18 HBsAg–negative anti–HBc–positive patients. IgM anti–HBc was present in all 4 patients with acute hepatitis B and in 4 of 8 patients with HBsAg–positive chronic active hepatitis. In patients with chronic active hepatitis, IgM anti–HBc was positive in those with the most intense infiltrate of mononuclear cells on liver biopsy. There was no correlation with the presence of hepatitis B e antigen or anti–HBe. Three of 11 patients with HBsAg–positive chronic persistent hepatitis were intermittently positive by the Staphylococcus A method but all were negative by the u–capture method when a low sensitivity cutoff was employed. The sensitivity of the test can be adjusted at will by the manufacturers and, therefore, introduction of interchangeable controls and standards will enable clinical application of this testing system with meaningful results.

Testing for IgM anti–HBc may help the clinician in differentiating healthy HBsAg carriers from patients with HBsAg–positive acute and chronic hepatitis. It is also of value in differentiating patients with acute hepatitis B from HBsAg carriers who develop acute hepatitis of different etiology. Accumulation of more data and correlations with the intensity and nature of the mononuclear infiltrates in chronic hepatitis will increase understanding of the mechanism of switchover from IgM to IgG anti–HBc response and factors favoring chronicity in hepatitis B.
The Mechanism of Biliary Excretion of α1–Acid Glycoprotein in the Rat: Evidence for A Molecular Weight–Dependent, Nonreceptor–Mediated Pathway
Authors: Thomas Peter , Toth Carol A. , Zamcheck Norman
Published: July 2011

The transport of human α1–acid glycoprotein from the circulation to the bile has been studied in the rat. Biliary excretion was proportional to the i.v. injected dose, and the percentage excreted remained constant. The amount excreted in the bile (over 4 hr) was inversely related to the rate of hepatic (hepatocyte) uptake and the galactose receptor which is specific for asialo glycoproteins was not involved. Reinjection of the glycoprotein excreted in bile resulted in a similar proportion of the dose being reexcreted, suggesting that a subset of the glycoprotein is not selected for excretion in bile. Transit times from blood to bile for glucagon, insulin, α1–acid glycoprotein, fetuin, albumin, and carcinoembryonic antigen were directly related to their molecular weights. Removal of sialic acid from the asialo glycoproteins did not affect these transit times. Possible mechanisms for the biliary excretion of α1–acid glycoprotein are discussed.
The Effect of Tauroursodeoxycholic Acid and Taurine Supplementation on Biliary Bile Acid Composition
Authors: Batta Ashok K. , Salen Gerald , Shefer Sarah , Tint Steven G. , Dayal Bishambar
Published: July 2011

The biliary bile acid conjugation patterns were determined by high–performance liquid chromatography in five subjects after 6 months of 500 mg per day of free ursodeoxycholic acid feeding. Prior to bile acid therapy, approximately 35% of the biliary bile acids were conjugated with taurine and approximately 65% were glycine conjugated, and ursodeoxycholic acid was either absent or, when present, accounted for less than 5% as the glycine conjugate. After 6 months, ursodeoxycholic acid became the major biliary bile acid and approximately 90% of it was present as the glycine conjugate and approximately 10% as the taurine conjugate. In another experiment, in seven patients, 1 gm per day of sodium tauroursodeoxycholate (equivalent to approximately 750 mg per day of free ursodeoxycholic acid and approximately 250 mg per day of taurine) was administered for 10 days. The proportion of tauroursodeoxycholic acid rose to 41% of the total biliary ursodeoxycholic acid but 59% still remained conjugated with glycine. When three patients were fed 1.5 gm per day of taurine together with 750 mg per day of free ursodeoxycholic acid for 10 days, the taurine conjugation of ursodeoxycholic acid and other bile acids increased to 29 to 40%. These studies show that the administration of free ursodeoxycholic acid results in the increased formation of glycour–sodeoxycholic acid while the administration of 1 gm per day of tauroursodeoxycholic acid or 1.5 gm per day of taurine together with 750 mg per day of free ursodeoxycholic acid increases the excretion of tauroursodeoxycholic acid in the bile only to about 40% of the total biliary ursodeoxycholic acid. Thus, the taurine of tauroursodeoxycholic acid is partially lost during its enterohepatic circulation while the free taurine during taurine supplementation is only partially available for conjugation.
Demonstration of Albumin Receptors Onisolated Human Hepatocytes by Light and Scanning Electron Microscopy
Authors: Trevisan Alessandro , Gudat Fred , Guggenheim Richard , Krey Gunthild , Dürmüller Ursula , Lüond Guido , Düggelin Marcel , Landmann Jonas , Tondelli Pietro , Bianchi Leonardo
Published: July 2011

The presence of albumin receptors on the plasma membrane of isolated human hepatocytes was investigated employing albumin–coupled latex minibeads. Hepatocyte–latex reaction was visualized by phase contrast and scanning electron microscopy.

The experiments demonstrate that hepatocytes exhibit binding activity for polymeric and monomelic forms of glutaraldehyde–treated albumin. Additionally, the reaction was shown to be species–nonspecific.

These findings support the hypothesis that polymerized albumin may act as a bridge between receptors on hepatitis B virus and human hepatocytes.
Human Liver Plasma Membrane Ca–Atpase: Identification and Sensitivity to Calcium Antagonists
Authors: Lotersztajn Sophie , Mavier Philippe , Clergue Jeanne , Dhumeaux Daniel , Pecker Françoise
Published: July 2011

A high–affinity calcium–stimulated ATPase (Ca–ATPase) was identified in a plasma membrane subcellular fraction from human liver. The subcellular distribution of the enzyme corresponds to that of classical plasma membrane markers, and its kinetic parameters are identical to those of the Ca–ATPase identified in rat liver plasma membranes in that: (i) calcium activation of ATPase activity followed a cooperative mechanism (Hill number = 1.2), half–maximal activation occurring at 4.5 ± 2.0 nm free calcium; (ii) K0.5 of the enzyme for ATP was 54 ± 5 μM, and kinetic studies indicated that two interacting sites were involved; (iii) micromolar concentrations of MgCl2 had an inhibitory effect on enzyme activity, and (iv) the enzyme did not require potassium for activation by calcium and was not sensitive to ouabain or oligomycin. These properties are characteristic of Ca–ATPases coupled to calcium pumps in plasma membranes. The effects of the local anesthetic, tetracaine, and three calcium antagonists bepridil, verapamil, nifedipine, were investigated. Bepridil at 50 μM caused 75% inhibition of Ca–ATPase activity by decreasing the maximal velocity of the enzyme reaction; its action was immediate and reversible. Verapamil (0.5 μM) also induced 75% inhibition of the Ca–ATPase, but its affinity for the system was a third of that of bepridil. The enzyme was much less sensitive to nifedipine and tetracaine. The method described in the present paper for measuring Ca–ATPase activity in small human liver biopsies will permit the study of this enzyme during the course of hepatic disorders.
Immunofluorescence of Phenobarbital Inducible Cytochrome P–450 in the Hepatic Lobule of Normal and Phenobarbital–Treated Rats
Authors: Ohnishi Kunihiko , Mishima Akihiko , Okuda Kunio
Published: July 2011

The localization of the form of cytochrome P–450 that is induced by phenobarbital was studied by direct immunofluorescence in the hepatocytes of rats pretreated with phenobarbital in comparison with saline–treated rats. Specific fluorescence was seen in the hepatocyte cytoplasm in saline– and phenobarbital–treated rats; a more concentrated halo of fluorescence was detected surrounding the nuclei in the centrilobular zones after phenobarbital treatment. In the saline–treated rats, fluorescence was barely discernible but slightly more intense in the centrilobular than perilobular zones. In phenobarbital–treated rats, fluorescence was much more intense, with a similar but much greater difference between the centrilobular and perilobular zones. The tissue distribution and induction site of this component of the cytochrome P–450–dependent microsomal system may be relevant to the site of drug toxicity and the development of chemical carcinogenesis.
Valproate–Induced Hepatic Steatogenesis in Rats
Authors: Lewis James H. , Zimmerman Hyman J. , Garrett Carlton T. , Rosenberg Elliot
Published: July 2011

The administration of high–dose valproic acid (VPA) (750 mg per kg) consistently produced significant microvesicular steatosis in mature Sprague–Dawley rats after 48 hr. Similar changes occurred in animals pretreated with phenobarbital which received a lower dose of VPA (350 mg per kg), but no steatosis was seen in animals treated with the low–dose VPA alone. The steatogenic effect of VPA is most likely mediated by a toxic metabolite. It can also be speculated that phenobarbital, by enhancing the inducing effects of the hepatic mixed–function oxidase system, may lead to increased conversion of VPA to a toxic metabolite. Young and weanling rats appeared to be resistant to the steatogenic effects of VPA. Reproduction of microvesicular steatosis in this experimental model may permit exploration of factors that enhance or inhibit VPA–induced hepatic injury.
Highly Acylated 3,4‐Secograyanane Diterpenoids from the Fruits of Pieris formosa
Authors: Wu Zhao‐Yuan , Li Hong‐Mei , Li Yuan‐Dan , Li Hai‐Zhou , Li Rong‐Tao
Published: July 2011

From the fruits of Pieris formosa, four new highly acylated 3,4‐secograyanane diterpenoids, secorhodomollolides E–H (1–4, resp.), along with two known ones, secorhodomollolides C and D (5 and 6, resp.), were obtained. Their structures were established mainly by spectroscopic methods, including 1D‐ and 2D‐NMR spectroscopy, and mass spectrometry.
Drug delivery by red blood cells
Authors: Biagiotti Sara , Paoletti Maria Filomena , Fraternale Alessandra , Rossi Luigia , Magnani Mauro
Published: July 2011

Drug delivery is a growing field of interdisciplinary activities that combine the use of new materials with the biochemical properties of selected drugs, with the aim of improving their therapeutic action and reducing their toxicity. In few cases, proper medical devices have been also realized to implement new drug delivery modalities. In this article, we have summarized available information and our experience on the use of autologous Red Blood Cells as carriers for drugs to be released within the vascular system. This is not a comprehensive review, but it focusses on the mechanisms that are available to distribute drugs in circulation by carrier red blood cells and provide illustrative examples on how this is currently obtained. We have not included a summary of clinical data collected in recent years using this technology but simply provided proper references for the interested readers. Finally, a special attention is devoted to the possibility of entrapping, into autologous red blood cells, recombinant drug‐binding proteins. This new strategy is opening the way at a new modality to influence the vascular distribution of drugs by realizing a dynamic circulating container (the engineered red cell) capable of reversible binding and transportation of one or more drugs of interest selected on the bases of the red cell entrapped target proteins. This new modality is not yet fully developed and explored but will certainly provide a technical solution to the problem of stabilizing drug concentration in circulation improving drug efficacy and reducing drug toxicity. © 2011 IUBMB IUBMB Life, 2011
Delivery of nanoparticle‐complexed drugs across the vascular endothelial barrier via caveolae
Authors: Wang Zhenjia , Tiruppathi Chinnaswamy , Cho Jaehyung , Minshall Richard D. , Malik Asrar B.
Published: July 2011

The endothelial cell monolayer lining the vessel wall forms a size‐selective, semi‐permeable barrier between the blood and tissue that must be crossed by blood borne therapeutic agents to reach diseased extravascular tissue. Nanoparticles engineered to carry drugs present an opportunity to enhance the specificity and efficacy of drug delivery. Therefore, an understanding of how these engineered nanoparticles are transported across the vessel wall will help us to more fully exploit this powerful therapeutic technology. Vascular endothelial cells are rich in caveolae, cell surface invaginations 50–100 nm in diameter that mediate endocytosis of lipids, proteins, and viruses. Caveolar invaginations pinch off to form intracellular vesicles that can transport cargo across the cell and release the cargo into the extravascular space via exocytosis. Here, we will review the current concepts and state of development for delivering engineered nanoparticles across the endothelium via the caveolae‐mediated pathway. © 2011 IUBMB IUBMB Life, 2011
Drug carriers for vascular drug delivery
Authors: Koren Erez , Torchilin Vladimir P.
Published: July 2011

The currently used drug carriers for vascular drug delivery are reviewed. The human vascular system possesses unique physiological features that can be exploited for enhanced and effective targeted drug delivery. Although the thin layer of endothelial cells (EC) lines the interior surface of blood vessels forming an interface between circulating blood in the lumen and the tissue beyond the vessel wall, it can also function as a target for drugs to EC in different vascular areas. ECs overexpress specific cell‐surface molecules under various pathological conditions (tumor neovasculature, inflammation, oxidative stress, and thrombosis), which are absent or barely detectable in established normal blood vessels. By coupling unique endothelial surface markers, such as antibodies, specific peptides, and growth factors to a variety of drug carriers, effective active vascular‐targeted drug delivery systems can be achieved. This review focuses on the recent advances and strategies for effective targeted vascular drug delivery using a variety of drug‐loaded carriers along with new targeting approaches that can be used in the design and optimization of such carriers. © 2011 IUBMB IUBMB Life, 2011
Macroeconomic forecasting and structural change
Authors: D'Agostino Antonello , Gambetti Luca , Giannone Domenico
Published: July 2011

The aim of this paper is to assess whether modeling structural change can help improving the accuracy of macroeconomic forecasts. We conduct a simulated real‐time out‐of‐sample exercise using a time‐varying coefficients vector autoregression (VAR) with stochastic volatility to predict the inflation rate, unemployment rate and interest rate in the USA. The model generates accurate predictions for the three variables. In particular, the forecasts of inflation are much more accurate than those obtained with any other competing model, including fixed coefficients VARs, time‐varying autoregressions and the naïve random walk model. The results hold true also after the mid 1980s, a period in which forecasting inflation was particularly hard. Copyright © 2011 John Wiley & Sons, Ltd.
Influence of low‐level laser associated with osteogenic proteins recombinant human BMP‐2 and Hevea brasiliensis on bone repair in Wistar rats
Authors: Iyomasa Mamie Mizusaki , Mardegan Issa João Paulo , de Queiróz Tavares Mirella Lemos , Lara Pereira Yamba Carla , Sasso Stuani Maria Bernadete , Mishima Fabíola , Coutinho‐Netto Joaquim , Sebald Walter
Published: July 2011

This study analyzed the newly formed bone tissue after application of recombinant human BMP‐2 (rhBMP‐2) and P‐1 (extracted from Hevea brasiliensis) proteins, 2 weeks after the creation of a critical bone defect in male Wistar rats treated or not with a low‐intensity laser (GaAlAs 780 nm, 60 mW of power, and energy density dose of 30 J/cm2). The animals were divided into two major groups: (1) bone defect plus low‐intensity laser treatment and (2) bone defect without laser irradiation. The following subgroups were also analyzed: (a) 5 μg of pure rhBMP‐2; (b) 5 μg of pure P‐1 fraction; (c) 5 μg of rhBMP‐2/monoolein gel; (d) 5 μg of P‐1 fraction/monoolein gel; (e) pure monoolein gel. Comparisons of the groups receiving laser treatment with those that did not receive laser irradiation show differences in the areas of new bone tissue. The group treated with 5 μg of rhBMP‐2 and laser irradiation was not significantly different (P >0.05) than the nonirradiated group that received the same treatment. The irradiated, rhBMP‐2/monoolein gel treatment group showed a lower area of bone formation than the nonirradiated, rhBMP‐2/gel monoolein treatment group (P < 0.001). The area of new bone tissue in the other nonirradiated and irradiated groups was not significantly different (P > 0.05). Furthermore, the group that received the 5 μg of rhBMP‐2 application showed the greatest bone formation. We conclude that the laser treatment did not interfere with the area of new bone tissue growth and that the greatest stimulus for bone formation involved application of the rhBMP‐2 protein. Microsc. Res. Tech. 2011. © 2011 Wiley Periodicals, Inc.
Study of the osteoconductive capacity of hydroxyapatite implanted into the femur of ovariectomized rats
Authors: Do Prado Ribeiro Daniele Cristina , de Abreu Figueira Luanda , Mardegan Issa JoÃO Paulo , Dias Vecina Cesar Adriano , JosÉDias Fernando , Da Cunha Marcelo Rodrigues
Published: July 2011

Osteoporosis is a global public health that affects postmenopausal women due to the deficiency of estrogen, a hormone that plays an important role in the microarchitecture of bone tissue. Osteoporosis predisposes to pathological bone fracture that can be repaired by conventional methods. However, depending on the severity and quantity of bone loss, the use of autogenous grafts or biomaterials such as hydroxyapatite might be necessary. The latter has received increasing attention in the medical field because of its good biological properties such as osteoconductivity and biocompatibility with bone tissue. The objective of this study was to evaluate using histologic and radiographic analyses, the osteogenic capacity of hydroxyapatite implanted into the femur of rats with ovariectomy‐induced osteoporosis. Eighteen rats were divided into three groups with six animals in each: group nonovariectomized, bilaterally ovariectomized not receiving estrogen replacement therapy, and bilaterally ovariectomized submitted to estrogen replacement therapy. Defects were created experimentally in the distal epiphysis of the femur with a surgical drill and filled with porous hydroxyapatite granules. The animals were sacrificed 8 weeks after surgery. The volume of newly formed bone in the implant area was quantified by morphometrical methods. The results were analyzed by ANOVA followed by the Tukey test (P < 0.05). The hydroxyapatite granules showed good radiopacity. Histological analysis revealed less quantity of newly formed bone in the ovariectomized group not submitted to hormone replacement therapy. In conclusion, bone neoformation can be expected even in bones compromised by estrogen deficiency, but the quantity and velocity of bone formation are lower. Microsc. Res. Tech., 2011. © 2011 Wiley Periodicals, Inc.
Bone repair investigation using rhBMP‐2 and angiogenic protein extracted from latex
Authors: Issa JoÃO Paulo Mardegan , Defino Helton Luiz Aparecido , Pereira Yamba Carla Lara , Netto Joaquim Coutinho , Sebald Walter , Bentley Maria VitÓRia L.B. , Iyomasa Mamie Mizusaki , Ervolino Edilson
Published: July 2011

Background: The aim of this work was to study the new bone tissue formation after bone morphogenetic protein type 2 (rhBMP‐2) and P‐1 application, using 5 and 10 μg of each, combined to a material carrier, in critical bone defects. Methods: It was used 70 Wistar rats (male, ∼250 g) that were divided in 10 groups with seven animals on each. Groups are the following: critical bone defect only, pure monoolein gel, 5 μg of pure P‐1, 5 μg of pure rhBMP‐2, 5 μg of P‐1/monoolein gel, 5 μg of rhBMP‐2/monoolein gel, 10 μg of pure P‐1, 10 μg of pure rhBMP‐2, 10 μg of P‐1/monoolein gel, 10 μg of rhBMP‐2/monoolein gel. Animals were sacrificed after 4 weeks of the surgical procedure and the bone samples were submitted to histological, histomorphometrical, and immunohistochemical evaluations. Results: Animals treated with pure P‐1 protein, in both situations with 5 μg and 10 μg, had no significant difference (P > 0.05) for new bone formation; other groups treated with 10 μg were statistically significant (P < 0.05) among themselves and when compared with groups in which it was inserted the monoolein gel or critical bone defect only (P < 0.05). In the group involving the 10 μg rhBMP‐2/monoolein gel association, it was observed an extensive bone formation, even when compared with the same treatment without the gel carrier. Conclusion: Using this experimental animal model, more new bone tissue was found when it was inserted the rhBMP‐2, especially when this protein was combined to the vehicle, and this process seems to be dose dependent. Microsc. Res. Tech., 2011.© 2011 Wiley Periodicals, Inc.
Changes in the amount of kidney pigmented macrophage aggregates throughout the breeding cycle of female Ohrid trout, Salmo letnica Kar. (Teleostei, Salmonidae)
Authors: Jordanova Maja , Rocha Maria João , Rebok Katerina , Rocha Eduardo
Published: July 2011

Changes in fish macrophages (Macs) are useful indicators of environmental pressures, but responses due to chemical and nonchemical stresses may be confounded by natural sources of variability. These may include sex and gonadal stage. In this study, we start addressing the following question: is the seasonally dependent ovary stage a factor to consider when using kidney Macs as biomarkers? To tackle this problem, the relative amount of pigmented Macs in kidney (head, trunk, and tail portions) was stereologically estimated in Ohrid trout, and related with the breeding status. The amount of Macs significantly increased from pre vitellogenesis to late vitellogenesis and showed a decreasing trend then after, with lower values noted after spawning in the head (1.9% versus 7.5% versus 2.0%), trunk (1.8% versus 7.5% versus 2.5%), and tail (2.5% versus 6.7% versus 2.9%) kidney. The decrease seen at spawning was significant in head and trunk kidney, and at post spawning it was significant for all kidney portions. The amounts of Macs were positively correlated with the ovary relative weights and plasma estradiol levels. We proved for the first time that fish kidney pigmented Macs can vary in amount during the breeding cycle. Our data, combined with literature, strongly support that the sex‐steroid profile and kidney status‐seasonal remodeling both influence the Macs pool; likely not only in female trout. So, while increases in Macs may warn of ecosystem problems, we show that using kidney Macs for biomonitoring should also take into account seasonally, particularly that related with ovary maturation. Microsc. Res. Tech. 2011. © 2011 Wiley Periodicals, Inc.
Ultrashort echo time MRI of cortical bone at 7 tesla field strength: A feasibility study
Authors: Krug Roland , Larson Peder Eric Zufall , Wang Chunsheng , Burghardt Andrew J. , Kelley Douglas A.C. , Link Thomas M. , Zhang Xiaoliang , Vigneron Daniel B. , Majumdar Sharmila
Published: July 2011

Purpose:

To implement and examine the feasibility of a three‐dimensional (3D) ultrashort TE (UTE) sequence on a 7 Tesla (T) clinical MR scanner in comparison with 3T MRI at high isotropic resolution.

Materials and Methods:

Using an in‐house built saddle coil at both field strengths we have imaged mid‐diaphysial sections of five fresh cadaveric specimens of the distal tibia. An additional in vivo scan was performed at 7 Tesla using a quadrature knee coil.

Results:

Using the same type of saddle coil at both field strengths, a significant increase in SNR at 7T compared with 3T (factor 1.7) was found. Significantly shorter T2* values were found at the higher field strength (T2* = 552.2 ± 126 μs at 7T versus T2* = 1163 ± 391 μs at 3T).

Conclusion:

UHF MRI at 7T has great potential for imaging tissues with short T2. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults
Authors: Bouilleret Viviane , Cardamone Lisa , Liu Cyril , Koe Amelia S. , Fang Ke , Williams John P. , Myers Damian E. , O'Brien Terence J. , Jones Nigel C.
Published: July 2011

Purpose:

To examine the long‐term consequences of manganese exposure due to the use of manganese‐enhanced magnetic resonance imaging (MEMRI) in a model of closed head injury, the fluid‐percussion injury (FPI) model.

Materials and Methods:

Two groups of adult male Wistar rats (n = 72) were studied with either MEMRI, whereby rats receive MnCl2 (100 mg/kg intraperitoneally) 24 hours prior to scanning, or standard MRI (sMRI) with no contrast agent. Rats from both groups underwent FPI or sham injury and were longitudinally assessed for 6 months for neurological toxicity using behavioral tests, EEG recording, and MRI scanning.

Results:

Regardless of whether they received FPI, MEMRI animals showed progressive signs of cerebral toxicity compared with sMRI rats, including significantly reduced weight gain, progressive brain volume decrease, and increased anxiety and depressive‐like behaviors.

Conclusion:

Long‐term structural and functional consequences of using manganese as a contrast agent for MRI can confound experimental outcomes and must be taken into account when designing longitudinal imaging studies using manganese‐enhanced MRI. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Coronary MR angiography using citrate‐coated very small superparamagnetic iron oxide particles as blood‐pool contrast agent: Initial experience in humans
Authors: Wagner Moritz , Wagner Susanne , Schnorr Jörg , Schellenberger Eyk , Kivelitz Dietmar , Krug Lasse , Dewey Marc , Laule Michael , Hamm Bernd , Taupitz Matthias
Published: July 2011

Purpose:

To evaluate very small superparamagnetic iron oxide particles (VSOP‐C184) as blood‐pool contrast agent for coronary MR angiography (CMRA) in humans.

Materials and Methods:

Six healthy volunteers and 14 patients with suspected coronary artery disease underwent CMRA after administration of VSOP‐C184 at the following doses: 20 μmol Fe/kg (4 patients), 40 μmol Fe/kg (5 patients), 45 μmol Fe/kg (6 healthy volunteers), and 60 μmol Fe/kg (5 patients). In healthy volunteers, contrast‐to‐noise ratio (CNR), signal‐to‐noise ratio (SNR), and vessel edge definition (VED) of contrast‐enhanced CMRA were compared with non–contrast‐enhanced CMRA. In patients, a per‐segment intention‐to‐diagnose evaluation of contrast‐enhanced CMRA for detection of significant coronary stenosis (≥50%) was performed.

Results:

Three healthy volunteers (45 μmol Fe/kg VSOP‐C184) and two patients (60 μmol Fe/kg VSOP‐C184) had adverse events of mild or moderate intensity. VSOP‐C184 significantly increased CNR (15.1 ± 4.6 versus 6.9 ± 1.9; P = 0.010), SNR (21.7 ± 5.3 versus 15.4 ± 1.6; P = 0.048), and VED (2.3 ± 0.6 versus 1.2 ± 0.2; P < 0.001) compared with non–contrast‐enhanced CMRA. In patients, contrast‐enhanced CMRA yielded sensitivity, specificity, and diagnostic accuracy for detection of significant coronary stenosis of 86.7%, 71.0%, 73.1%, respectively.

Conclusion:

CMRA using VSOP‐C184 was feasible and yielded moderate diagnostic accuracy for detection of significant coronary stenosis within this proof‐of‐concept setting. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Cortical calcification in sturge–weber syndrome on MRI‐SWI: Relation to brain perfusion status and seizure severity
Authors: Wu Jianlin , Tarabishy Bisher , Hu Jiani , Miao Yanwei , Cai Zhaocheng , Xuan Yang , Behen Michael , Li Meng , Ye Yongquan , Shoskey Richard , Haacke E. Mark , Juhász Csaba
Published: July 2011

Purpose:

To determine the relationship between calcified cortex and perfusion status of white matter and seizure severity in patients with Sturge–Weber Syndrome (SWS), a sporadic neurocutaneous disorder characterized by a leptomeningeal angioma, progressive brain ischemia, and a high incidence of seizures using susceptibility weighted imaging (SWI) and dynamic susceptibility contrast‐enhanced perfusion weighted imaging (DSC‐PWI).

Materials and Methods:

Fifteen children (ages: 0.9–10 years) with unilateral SWS prospectively underwent magnetic resonance imaging (MRI). The degree of cortical calcification was assessed using SWI while perfusion status was quantified using DSC‐PWI images (asymmetries of various perfusion parameters). Comparisons between calcification, perfusion status, and seizure variables were performed.

Results:

Patients with severely calcified cortex demonstrated significantly lower perfusion in the ipsilateral white matter (mean asymmetry: −0.52 ± 0.22) as compared to patients with only mildly calcified cortex or no calcification (mean asymmetry: 0.08 ± 0.25). Patients with severely calcified cortex also suffered from a higher seizure burden (a composite measure of seizure frequency and epilepsy duration; P = 0.01) and a trend for earlier seizure onset and longer epilepsy duration.

Conclusion:

Severe calcification in the affected hemisphere is related to severely decreased perfusion in underlying white matter and is associated with more severe epilepsy in SWS patients. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Dynamic phantom with heart, lung, and blood motion for initial validation of MRI techniques
Authors: Swailes Nolan E. , MacDonald Matthew Ethan , Frayne Richard
Published: July 2011

Purpose:

To develop an anthropomorphic phantom to simulate heart, lung, and blood motion. Magnetic resonance imaging (MRI) is sensitive to image distortion and artifacts caused by motion. Imaging phantoms are used to test new sequences, but generally, these phantoms lack physiological motion. For the validation of new MR‐based endovascular interventional and other techniques, we developed a dynamic motion phantom that is suitable for initial in vitro and more realistic validation studies that should occur before animal experiments.

Materials and Methods:

An anthropomorphic phantom was constructed to model the thoracic cavity, including respiratory and cardiac motions, and moving blood. Several MRI methods were used to validate the phantom performance: anatomical scanning, rapid temporal imaging, digital subtraction angiography, and endovascular tracking. The quality and nature of the motion artifact in these images were compared with in vivo images.

Results:

The closed‐loop motion phantom correctly represented key features in the thorax, was MR‐compatible, and was able to reproduce similar motion artifacts and effects as seen in in vivo images. The phantom provided enough physiological realism that it was able to ensure a suitable challenge in an in vitro catheter tracking experiment.

Conclusion:

A phantom was created and used for testing interventional catheter guiding. The images produced had similar qualities to those found in vivo. This phantom had a high degree of appropriate anthropomorphic and physiological qualities. Ethically, use of this phantom is highly appropriate when first testing new MRI techniques prior to conducting animal studies. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
T1‐weighted 3D dynamic contrast‐enhanced MRI of the breast using a dual‐echo dixon technique at 3 T
Authors: Dogan Basak E. , Ma Jingfei , Hwang Ken , Liu Ping , Yang Wei Tse
Published: July 2011

Purpose:

To evaluate a single‐pass fast spoiled gradient echo (FSPGR) two‐point Dixon sequence and a gradient echo sequence with spectral fat suppression in their performance at 3 T for fat suppressed contrast‐enhanced bilateral breast imaging.

Materials and Methods:

Twenty patients were prospectively enrolled in an imaging protocol that included axial Dixon and 3D FSPGR with spectrally selective fat saturation sequences as part of patient care in this study. Qualitative analysis was performed retrospectively by two readers who scored the images for homogeneity and degree of fat saturation, severity of artifacts, and quality of normal anatomical structures. Enhancing lesions were scored according to the confidence with which American College of Radiology (ACR) BI‐RADS magnetic resonance imaging (MRI) features were identified.

Results:

The Dixon sequence showed superior fat saturation homogeneity, quality of posterior anatomical structures, and decreased artifact severity that were statistically significant (P < 0.0001). The degree of fat saturation was scored higher in the Dixon sequence, although the difference did not reach statistical significance. There were no significant differences between the 3D T1‐weighted FSPGR and Dixon groups for assessing lesion features.

Conclusion:

Our findings suggest that the Dixon technique is an effective fat suppression method for contrast‐enhanced breast MRI. The Dixon technique also seemed to provide better anatomical definition of posterior structures and improvement in severity of artifacts. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.