Gamma-Camera Direct Imaging of the Plasma and On/Intra Cellular Distribution of the 99mTc-DPD-Fe3O4 Dual-Modality Contrast Agent in Peripheral Human Blood.

The radiolabeled iron oxide nanoparticles constitute an attractive choice to be used as dual-modality contrast agents (DMCAs) in nuclear medical diagnosis, due to their ability to combine the benefits of two imaging modalities, for instance single photon emission computed tomography (SPECT) with magnetic resonance imaging (MRI). Before the use of any DMCA, the investigation of its plasma extra- and on/intra cellular distribution in peripheral human blood is of paramount importance. Here, we focus on the in vitro investigation of the distribution of 99mTc-DPD-Fe3O4 DMCA in donated peripheral human blood (the ligand 2-3-dicarboxypropane-1-1-diphosphonic-acid is denoted as DPD). Initially, we described the experimental methods we performed for the radiosynthesis of the 99mTc-DPD-Fe3O4, the preparation of whole blood and blood plasma samples, and their incubation conditions with 99mTc-DPD-Fe3O4. More importantly, we employed a gamma-camera apparatus for the direct imaging of the 99mTc-DPD-Fe3O4-loaded whole blood and blood plasma samples when subjected to specialized centrifugation protocols. The direct comparison of the gamma-camera data obtained at the exact same samples before and after their centrifugation enabled us to clearly identify the distribution of the 99mTc-DPD-Fe3O4 in the two components, plasma and cells, of peripheral human blood.

Optimization of radioprotective dose of Juglans nigra leaf extract using response surface methodology.

J. nigra leaf contains mixture of various pharmacologically active compounds and it is assumed that they may have the potential radioprotective effect. The purpose of this work was to predict radioprotective doses by correlating changes in organ distribution of radiopharmaceuticals with extract dose levels and rat body weight using response surface methodology (RSM) based on a second-order polynomial equation. The extract was administered daily by oral gavage to rats at dose of 6.9, 10.3, or 13.7 mg kg-1 body weight (bw) day-1 for 10 days. On the eleventh day, 0.1 ml of the one radiopharmaceutical (Na99mTcO4, 99mTc-dimercaptosuccinic acid and 99mTc-tin colloid) was injected into the tail vein. The statistical parameters: the coefficient of determination (0.81-0.95), the coefficient of variation (3.05-11.1), the adequate precision (8.82-19.12) and the mean relative percentage deviation (± 2.3-8.2) were indicated the precision and reliability of RSM. Using RSM, the predicted daily dose of leaf extract ranging from 11.19 to 11.99 mg kg-1 bw may be considered as an optimal daily radiopotective dose for protection of organs from radiation in cases of planned radiation exposures.

Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors.

As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiolabeled with Lutetium-177 (177Lu), generating 177Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by 177Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 µg/50 µL of 177Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 µg/50 µL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 µg/50 µL did not significantly benefit the therapy. Histopathology analysis revealed that the 177Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, 177Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy.

Quality Assessment of DIBR-Synthesized Views Based on Sparsity of Difference of Closings and Difference of Gaussians.

Images synthesized using depth-image-based-rendering (DIBR) techniques may suffer from complex structural distortions. The goal of the primary visual cortex and other parts of brain is to reduce redundancies of input visual signal in order to discover the intrinsic image structure, and thus create sparse image representation. Human visual system (HVS) treats images on several scales and several levels of resolution when perceiving the visual scene. With an attempt to emulate the properties of HVS, we have designed the no-reference model for the quality assessment of DIBR-synthesized views. To extract a higher-order structure of high curvature which corresponds to distortion of shapes to which the HVS is highly sensitive, we define a morphological oriented Difference of Closings (DoC) operator and use it at multiple scales and resolutions. DoC operator nonlinearly removes redundancies and extracts fine grained details, texture of an image local structure and contrast to which HVS is highly sensitive. We introduce a new feature based on sparsity of DoC band. To extract perceptually important low-order structural information (edges), we use the non-oriented Difference of Gaussians (DoG) operator at different scales and resolutions. Measure of sparsity is calculated for DoG bands to get scalar features. To model the relationship between the extracted features and subjective scores, the general regression neural network (GRNN) is used. Quality predictions by the proposed DoC-DoG-GRNN model show higher compatibility with perceptual quality scores in comparison to the tested state-of-the-art metrics when evaluated on four benchmark datasets with synthesized views, IRCCyN/IVC image/video dataset, MCL-3D stereoscopic image dataset and IST image dataset.

Gender-specific differences in hemodialysis patients: a multicenter longitudinal study from Serbia.

PURPOSE: The study was undertaken with the aim to determine gender-specific differences in incident hemodialysis (HD) patient and their changes over time. METHODS: The retrospective longitudinal closed cohort study involved 441 incident patients starting HD in 2014 and followed for 1-59 (median 43, IQR 40) months. Demographic, clinical data, treatment characteristics, laboratory findings and outcome were abstracted from the patients' medical records. RESULTS: The relative number of males on HD was about twice that of females throughout the five years investigated. At the beginning of the study, no significant differences were found in the main demographic and clinical characteristics except that diabetes was more often the underlying disease in men than in women. Systolic blood pressure decreased over time significantly more in females than in males. Throughout the study spKt/V was significantly higher in females than in males, but it increased in patients of both genders. There were no gender differences for comorbidities, vascular access and the majority of laboratory findings except for higher serum levels of creatinine and CRP in men than in women. Relatively more females were treated with erythropoiesis stimulating agents and phosphate binders than males. Age and malignancy were selected as significant predictors of mortality for both genders, and, in addition, polycystic kidney disease, serum level of albumin and CRP for men, but spKt/V for women. CONCLUSION: Some significant gender differences were observed throughout, while others appeared during the study but none of them were due to gender inequalities in the applied treatment.

Superficial Thrombophlebitis of the Breast (Mondor's Disease): An Uncommon Localization of Common Disease.

Mondor's disease (MD), or superficial thrombophlebitis of the anterolateral thoracoabdominal wall, is a rare disease that presents with a palpable cord-like induration beneath the skin. It is a benign, self-limiting condition with probably underestimated significance due to the fact it may be a rare manifestation of an underlying breast carcinoma. It can also resemble breast malignancy and, if physician is not familiar with clinical features of MD, it may lead to unnecessary biopsy. The diagnosis is straightforward in most cases and it may be based on a thorough history and physical examination and it can be ultrasonographically confirmed. Raising awareness of this condition may facilitate recognition and diagnosing MD and eventually limit unnecessary diagnostic procedures.

99mTc-bisphosphonate-coated magnetic nanoparticles as potential theranostic nanoagent.

Novel theranostic nanoplatform is expected to integrate imaging for guiding and monitoring of the tumor therapy with great therapeutic efficacy and fewer side effects. Here we describe the preparation of a multifunctional 99mTc-bisphosphonate-coated magnetic nanoparticles (MNPs) based on Fe3O4 and coated with two hydrophilic bisphosphonate ligands, i.e., methylene diphosphonate (MDP) and 1-hydroxyethane-1,1- diphosphonate (HEDP). The presence of the bisphosphonates on the MNPs surface, enabled their biocompatibility, colloidal stability and successful binding of the radionuclide. The morphology, size, structure, surface charge and magnetic properties of obtained bisphosphonate-coated Fe3O4 MNPs were characterized by transmission electron microscopy, X-ray powder diffraction, dynamic light scattering, laser Doppler electrophoresis, Fourier transform infrared spectroscopy and vibrating sample magnetometer. The specific power absorption values for Fe3O4-MDP and Fe3O4-HEDP were 113 W/g and 141 W/g, respectively, indicated their heating ability under applied magnetic field. Coated MNPs were radiolabeled with 99mTc using stannous chloride as the reducing agent in a reproducible high yield (95% for Fe3O4-MDP and 97% for Fe3O4-HEDP MNPs) and were remained stable in saline and human serum for 24 h. Ex vivo biodistribution studies presented significant liver and spleen uptake in healthy Wistar rats after intravenous administration at all examined time points due to the colloidal nature of both 99mTc-MNPs. Results of scintigraphy studies are in accordance with ex vivo biodistribution studies, demonstrating high in vivo stability of radiolabeled MNPs and therefore results of both methods were proved as accurate information on the biodistribution profile of investigated MNPs. Overall, in vitro and in vivo stability as well as heating ability, indicate that biocompatible radiolabeled bisphosphonate magnetic nanoparticles exhibit promising potential as a theranostic nanoagent.

Fast Blind Quality Assessment of DIBR-Synthesized Video Based on High-High Wavelet Subband.

Free-viewpoint video, as the development direction of the next-generation video technologies, uses the depth-image-based rendering (DIBR) technique for the synthesis of video sequences at viewpoints, where real captured videos are missing. As reference videos at multiple viewpoints are not available, a blind reliable real-time quality metric of the synthesized video is needed. Although no-reference quality metrics dedicated to synthesized views successfully evaluate synthesized images, they are not that effective when evaluating synthesized video due to additional temporal flicker distortion typical only for video. In this paper, a new fast no-reference quality metric of synthesized video with synthesis distortions is proposed. It is guided by the fact that the DIBR-synthesized images are characterized by increased high frequency content. The metric is designed under the assumption that the perceived quality of DIBR-synthesized video can be estimated by quantifying the selected areas in the high-high wavelet subband. The threshold is used to select the most important distortion sensitive regions. The proposed No-Reference Morphological Wavelet with Threshold (NR_MWT) metric is computationally extremely efficient, comparable to PSNR, as the morphological wavelet transformation uses very short filters and only integer arithmetic. It is completely blind, without using machine learning techniques. Tested on the publicly available dataset of synthesized video sequences characterized by synthesis distortions, the metric achieves better performances and higher computational efficiency than the state-of-the-art metrics dedicated to DIBR-synthesized images and videos.

Serum lipids and glucose disturbances at professional drivers exposed to occupational stressors.

The aim of this study is to find association between some groups of occupational stressors and serum lipids and glucose concentrations in professional drivers in road traffic. The study included 417 male professional drivers (162 inter city bus drivers, 36 suburban bus drivers, 33 city bus drivers, 81 truck drivers, 71 official car drivers and 34 professional taxi drivers). Occupational stressors were identified and total occupational stress index score was measured by standardized questionnaire authorized by Karen Belkic. Occupational stressors were divided into seven groups (underload, high demand, strictness, extrinsic time pressure, noxious exposures, avoidance and conflict). Serum glucose and lipids concentrations (total cholesterol, LDL cholesterol, HDL cholesterol and triacylglycerols) were measured in study group of drivers. Maximal total OSI values were achieved in group of professional truck drivers. The highest values of serum glucose, total cholesterol, LDL cholesterol and triacylglycerols and the lowest values of serum HDL cholesterol were found at professional truck drivers. With the increase of occupational stress index, there is an increase of the serum glucose, total cholesterol, LDL cholesterol and triacylglycerols concentration in the exposed group of drivers. Specific analytes thresholds' level of occupational stress index exists.

Design and preparation of 90Y-labeled imidodiphosphate- and inositol hexaphosphate-coated magnetic nanoparticles for possible medical applications.

Radiolabeled magnetic nanoparticles (MNPs) coated with hydrophilic phosphate ligands, i.e., imidodiphosphate (IDP) and inositol hexaphosphate (IHP), were developed as multifunctional agents to localize both radioactivity and magnetic energy at a tumor site. The coating of MNPs with phosphates made them biocompatible, increased their colloidal stability and allowed binding of the radionuclide 90Y to the available functional groups on the surface of the MNPs. IDP and IHP have not hitherto been used for the coating of MNPs and the results of this study of the functionalized MNPs showed that the phosphate groups influenced the modification of the surface of MNPs. Characterization of the MNPs was performed using X-ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering and laser Doppler electrophoresis. The specific power absorption values obtained for MNPs (46.95-80.76 W g-1) in different physiological media indicated their possible application in hyperthermia treatment. Both types of coated MNPs were 90Y-labeled in a reproducible high yield (>98%). In vitro studies of 90Y-MNPs in saline and human serum showed their high stability after 72 h. The biodistribution pattern of the MNPs after intravenous administration to healthy Wistar rats was followed by the radiotracer method, revealing that 90Y-Fe3O4-IDP and 90Y-Fe3O4-IHP MNPs were predominantly found in the liver (85.21% ID and 86.22% ID), followed by the spleen (9.23% ID and 8.82% ID) and the lungs (1.53% ID and 1.53% ID). The results of this comprehensive study showed that radiolabeled biocompatible phosphate magnetic complexes hold great promise for therapeutic uses combining magnetic hyperthermia and radiotherapy.

[Leiomyomas and massive digestive hemorrhages--case reports of patients diagnosed in 2004].

INTRODUCTION: During 2004, there were 6 patients with leiomyomas diagnosed and treated at the Department of Gastroenterology and Clinical Pathology of the Zemun Clinical Center. The most common location of these benign submucosal tumors is stomach, followed by small intestine and large intestine. CASE REPORT: The most common symptoms of these patients were massive intestinal hemorrhage, with haematemesis and melaena. Hemorrhages resulted from superficial lesions, caused by pressure of the tumour on the intestinal blood vessels. A significant contribution in reaching the final diagnosis and selecting appropriate therapeutic approach was provided by CT and arteriography. Most patients underwent surgical treatment, which provided precise diagnosis (based on histopathologicalfindings), and at the same time a definite therapeutic procedure. DISCUSSION AND CONCLUSION: According to the literature data, gastrointestinal leiomyomas account for 20%-30% of all types of gastrointestinal tumors. Our research revealed that the incidence of leiomyomas was significantly lower within our group of patients, accounting for 12% of all benign gastrointestinal tumors. They were also the main cause of hemodynamic instability in our patients having massive and recurrent intestinal hemorrhages, which is not often seen in practice. All of them originated either from muscularis propria or muscularis mucosae. These tumors are often an accidental finding at autopsy, especially if they are smaller than 3 centimeters and not followed by consequential complications. Presently, endoscopic ultrasonography is considered to be the the most accurate procedure in the diagnosis of leiomyoma, with a diagnostic specificity that is superior to other imaging techniques.

[Non-alcoholic fatty liver disease in obese persons with diabetes].

BACKGROUND: Obesity, diabetes and different lipid metabolic disorders are the most frequent risk factors for nonalcoholic fatty liver disease, presented with a high variability in clinical and histological findings. CASE REPORT: We presented a case of 37-year-old male, suffering from type 2 diabetes mellitus, grade III obesity (BMI 45 kg/m2) and multiple metabolic disorders. Abdominal ultrasound revealed hepatomegaly during the last six months. Laboratory diagnostics showed increased serum transaminase levels. Serologic markers for viral hepatitis B and C were negative. The patient denied significant alcohol consumption. Liver biopsy and pathohistologic finding revealed macro- (III grade) and microvesicular (I grade) fatty degeneration, as well as mixed-cell portal infiltration with moderate liver fibrosis, corresponding to the typical presentation of NASH (Non Alcoholic Steatohepatitis). CONCLUSION: NASH treatment options include the reduction of body mass and an adequate antidiabetic and dislipidemia treatment. The aim of all therapeutic measures was to stop the progression of the disease, to prevent the progression of fibrosis and the development of cirrhosis.

[Association of Helicobacter pylori infection with nodular antritis and follicular gastritis].

INTRODUCTION: Helicobacter pylori (H. pylori) infection is known to be the must common cause of chronic gastritis having some endoscopic and pathologic characteristies as determinated by the Sydney System for Gastritis Classification. The aim of our case report was to point out the relationship between an endoscopic finding of nodular antritis and the presence of H. pylori infection and active chronic gastritis. CASE REPORT: Our patient underwent upper gastrointestinal endoscopy for dyspeptic complaints and was diagnosed as having nodular antritis, but also underwent urease test and hystopathologic examination of antral mucosa, to determine the presence and density of H. pylori infection and the presence and severity of gastritis. After a course of anti H. pylori treatment, dyspepsia improved and new biopsy specimens obtained two months and six months afterwards revealed no pathological findings. CONCLUSION: The case report supported the association of H. pylori infection of lymphoid follicles with nodular gastric mucosis.