Ιατρικά Άρθρα: 10/12/18

Παρασκευή 12 Οκτωβρίου 2018

Baclofen-Loaded Poly (d,l-Lactide-Co-Glycolic Acid) Nanoparticles for Neuropathic Pain Management: In Vitro and In Vivo Evaluation

Rejuvenation Research, Ahead of Print.

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Design and Application of 3D-Printed Photometers Controlled with an Arduino

3D Printing and Additive Manufacturing, Ahead of Print.

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Claudin‐1 expression decreases with increasing pathological grade in actinic keratosis and may be a marker of high‐risk actinic keratosis

Clinical and Experimental Dermatology, EarlyView.

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2018 Van Meter Lectureship presented by Carmelo Nucera, MD, PhD

Carmelo Nucera, MD, PhD

2018 Van Meter Lectureship "The role of a new thyroid-specific long non-coding RNA (lincRNA) in drug resistance and iodine metabolism in BRAFV600E thyroid cancer" presented by Carmelo Nucera, MD, PhD

October 11, 2018—The American Thyroid Association (ATA) announces with pleasure that the 2018 Van Meter Award has been presented to Dr. Carmelo Nucera, currently Assistant Professor in the Department of Pathology and at the Cancer Center and Cancer Research Institute of Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School. He is also an Associate Member at the Broad Institute of Harvard and MIT and Faculty member at the Center for Vascular Biology Research (CVBR) at BIDMC, which is dedicated to "improve human health by using genomics to advance our understanding of the biology and treatment of human disease, and to help lay the groundwork for a new generation of therapies."

The Van Meter Award recognizes outstanding contributions to research on the thyroid gland or related subjects by an investigator who is age 45 or under. Dr. Nucera has given the prestigious Van Meter Lecture on October 4 at 8:05 am, during this year's ATA Annual Meeting in Washington, DC from October 3 to 7. The award winner and the title of his lecture are kept secret until the time of the presentation. Dr. Nucera spoke on "The role of a new thyroid-specific long non-coding RNA (lincRNA) in drug resistance and iodine metabolism in BRAF^V600E thyroid cancer".

Dr. Nucera was born in Reggio Calabria (Italy), and received his MD summa cum laude in 2000 from the Medical and Surgery School at the University of Messina, Italy, where he also spent his residency in Endocrinology and Metabolic Diseases. During his residency he coordinated a local unit doing ultrasound screening of thyroid nodules, for the Ministry of Italian Scientific and Technological Research. He was also a Research Fellow and Coinvestigator at the Regina Elena Cancer Institute and Gemelli Medical School University Hospital in Rome, where he studied cloning techniques, molecular and cellular biology techniques, and transgenic mouse models for maternal thyroid hormone action during embryo-fetal development. At the Institute of Endocrinology of the University of Catania, he studied DNA automated sequencing and RNA extraction techniques for human thyroid tumors.

Dr. Nucera received his PhD in Experimental Endocrinology and Metabolic Diseases funded through the Italian Ministry of Scientific Research and Education, and completed his thesis on "novel mechanisms of BRAF^V600E-driven thyroid cancer progression" at the Division of Endocrine Surgery at Massachusetts General Hospital (MGH), and at BIDMC at Harvard Medical School.

He was also a post-doctoral research fellow at the same Division at MGH/Harvard. In the years following, Dr. Nucera acted as Attending Physician-Scientist at courses, workshops, and symposia, primarily at Harvard Medical School but also at the ATA.

His academic appointments have included Instructor in the Division of Cancer Biology and Angiogenesis in the Department of Pathology at BIDMC and, for the past five years, Assistant Professor in the Division of Experimental Pathology at the same institution at Harvard Medical School.

Dr. Nucera is primarily engaged in translational thyroid cancer research, as well as in teaching and tutoring medical students, post-docs, PhD students, and College students. He currently focuses on biomarker discovery such as regulatory long intergenic non-coding RNAs (LincRNA) and murine preclinical and co-clinical trials for targeted therapies for super-precision medicine. He is actively developing an independent research program at the BIDMC/Harvard, focused on a preclinical/translational model of patient-derived thyroid cancers and the role of the BRAF^V600E gene mutation in metastatic thyroid cancer. Since his residency, Dr. Nucera has investigated the cellular details of thyroid tumors. His goals have been, among others, to:

Determine the role of the BRAF gene mutation in human thyroid cancer microenvironment
Understand the autocrine and paracrine pathways by which BRAF^V600E (serine/threonine-protein kinase) and tyrosine kinase VEGFR2 (one of the vascular endothelial growth factors) promote aggressiveness in papillary thyroid cancer
Assess the role of stem-cell like pericytes in the mechanisms of drug resistance to targeted therapies in BRAF^V600E thyroid cancer
Unravel the clonal evolution of BRAF^V600E thyroid cancer treated with targeted therapies

Among the many mentees he has formally supervised are several post-doctoral research fellows, with whom he has collaborated on research studies and papers. For the past decade, Dr. Nucera has given presentations to his medical colleagues, nationally and internationally, concerning the details of his cellular research, thyroid cancer research, tumor modeling, targeted gene therapies, and clinical trials. As principal investigator (PI), he has successfully advanced many basic and clinical-translational projects and collaborations. His research expertise has been enhanced by his teaching experience at Harvard Medical School, resulting in his obtaining major grants as PI from the NIH and National Cancer Institute.

Dr. Nucera has served on the ATA Research and Internet Communications Committees and is a member of the Annual Thyroid Congress Program for the ATA. He has been recently nominated basic research Chair of the ATA Research Committee for 2018.

He is a reviewer for dozens of medical journals, including the New England Journal of Medicine, Frontiers in Oncology, the Journal of the National Cancer Institute, and the ATA's Thyroid. He is an Associate Editor for both Frontiers in Endocrinology and Discoveries. And he has received frequent honors and prizes for his research since medical school.

In his relatively brief career, Dr. Nucera has achieved much more in his research into thyroid oncology and gene therapy than many people over a lifetime. That commitment makes him a very worthy recipient for the prestigious 2018 Van Meter Award from the American Thyroid Association.

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The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international membership medical society with over 1,700 members from 43 countries around the world. Celebrating its 95^th anniversary, the ATA continues to deliver its mission of being devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health. These efforts are carried out via several key endeavors:

The publication of the highly regarded professional journals Thyroid, Clinical Thyroidology, and VideoEndocrinology
Annual scientific meetings
Biennial clinical and research symposia
Research grant programs for young investigators
Support of online professional, public, and patient educational programs
Development of guidelines for clinical management of thyroid disease and thyroid cancer

The ATA promotes thyroid awareness and information online through Clinical Thyroidology for the Public and extensive, authoritative explanations of thyroid disease and thyroid cancer in both English and Spanish. The ATA website serves as the clinical resource for patients and the public who look for reliable information on the Internet. Every fifth year, the American Thyroid Association joins with the Latin American Thyroid Society, the European Thyroid Association, and the Asia and Oceania Thyroid Association to cosponsor the International Thyroid Congress (ITC).

The post 2018 Van Meter Lectureship presented by Carmelo Nucera, MD, PhD appeared first on American Thyroid Association.

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Effect of TiF 4 varnish on microbiological changes and caries prevention: in situ and in vivo models

Abstract

Objective

The aim of this study was to evaluate microbiological changes, oral soft tissue toxicity, and caries-preventive effect of an experimental titanium tetrafluoride (TiF₄) varnish compared with a commercially available fluoride varnish (NaF), using in situ and in vivo models.

Materials and methods

The treatment groups were the following: TiF₄ varnish (experimental varnish), Duraphat® (fluoride positive control), placebo varnish (no fluoride), and no treatment (negative control). The varnishes were applied once over the enamel surface using a microbrush. For the in vivo study, 48 Wistar rats were infected with Streptococcus sobrinus 6715, received a treatment, and were submitted to a cariogenic challenge. After 4 weeks, S. sobrinus, oral soft tissue toxicity, presence, and severity of caries were evaluated. For the in situ study, 12 volunteers took part in this randomized crossover, double-blind study performed in four phases of 14 days each. They used intraoral appliances containing four enamel specimens that received the varnish according treatment group. After 24 h, the varnish was removed and plaque accumulation was allowed. A 20% sucrose solution was dripped over the enamel blocks (10×/day for 5 min each). Total streptococci, S. mutans, Lactobacillus, Candida spp. counts, and presence of white spot lesions were evaluated. Lesion depth was also quantified by micro-CT.

Results

For the in vivo study, the fluoride (F-varnishes) showed a statistically significant reduction in the percentage of S. sobrinus compared to the negative control (p < 0.05). Toxicological analysis revealed no abnormalities in oral tissues of rats from all groups, and both F-varnishes reduced the number and severity of caries lesions, without significant differences (p < 0.05). No statistical differences in microbiological counts were seen for the in situ experiment (p > 0.05). However, the specimens treated with TiF₄ exhibited lower percentage of white spot lesions and the lesion depth was significantly reduced by F-varnishes (p < 0.05).

Conclusions

F-varnishes showed reduction in the percentage of S. sobrinus in vivo, no oral soft tissue toxicity, and a caries-preventive effect in vivo and in situ.

Clinical relevance

NaF varnish is largely used due its capacity to form CaF₂-like layer on enamel. Therefore, development of studies focused on other fluoride compounds such as a TiF₄ varnish, which may have greater efficacy than NaF against tooth demineralization, is important.

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Penile bulb sparing in prostate cancer radiotherapy

Abstract

Objective

This study aimed to assess the reduction in dose to the penile bulb (PB) achieved by MRI-based contouring following drinking and endorectal balloon (ERB) instructions.

Patients and methods

A total of 17 prostate cancer patients were treated with intensity-modulated radiation therapy (IMRT) and interstitial brachytherapy (IBT). CT and MRI datasets were acquired back-to-back based on a 65 cm³ air-filled ERB and drinking instructions. After rigid co-registration of the imaging data, the CT-based planning target volume (PTV) used for treatment planning was retrospectively compared to an MRI-based adaptive PTV and the dose to the PB was determined in each case. The adapted PTV encompassed a caudally cropped CT-based PTV which was defined on the basis of the MRI-based prostate contour plus an additional 5 mm safety margin.

Results

In the seven-field IMRT treatment plans, the MRI-based adapted PTV achieved mean (D_mean) and maximum (D_max) doses to the PB which were significantly lower (by 7.6 Gy and 10.9 Gy, respectively; p <0.05) than those of the CT-contoured PTV. For 6 patients, the estimated PB D_max (seven-field IMRT and IBT) for the adapted PTV was <70 Gy, whereas only 1 patient fulfilled this criterium with the CT-based PTV.

Conclusion

MRI-based contouring and seven-field IMRT-based treatment planning achieved dose sparing to the PB. Whereas the comparison of MRI and CT contouring only relates to external beam radiotherapy (EBRT) sparing, considering EBRT and IBT shows the improvement in PB sparing for the total treatment.

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Dental radiographic findings in 18 individuals with SATB2 -associated syndrome

Abstract

Objective

To characterize the radiographic dental phenotype of individuals with SATB2-associated syndrome (SAS).

Materials and methods

Participants were evaluated by a multidisciplinary team during a concurrent clinic conducted during the 1st international SAS family meeting held in 2017 at a single institution. Whenever possible, panoramic and/or periapical radiographs were obtained in clinic or previously obtained and provided by the caregiver.

Results

Of the 37 individuals evaluated, 18 (12 males, median age 8.5 years) underwent radiographic examination. Dental radiographs revealed anomalies in all individuals starting at 2 years of age. The most consistent finding was delayed development of the mandibular second bicuspids (83%) with other common radiographic findings including delayed development of the roots of the permanent teeth (78%), severely rotated (56%) or malformed teeth (44%), and taurodontism (44%).

Conclusions

Dental anomalies are fully penetrant and can be documented radiographically in all individuals with SAS.

Clinical relevance

Dental radiographic findings of delayed second premolar development and delayed development of permanent root formation, especially concurrent with findings of taurodontism and malformed teeth, support a clinical suspicion for SAS and should help differentiate SAS from other neurodevelopmental syndromes.

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Left-shifting prism adaptation boosts reward-based learning

Publication date: Available online 12 October 2018

Source: Cortex

Author(s): S. Schintu, M. Freedberg, Z. Alam, S. Shomstein, E.M. Wassermann

Abstract

Visuospatial cognition has an inherent lateralized bias. Individual differences in the direction and magnitude of this bias are associated with asymmetrical D2/3 dopamine binding and dopamine system genotypes. Dopamine level affects feedback-based learning and dopamine signaling asymmetry is related to differential learning from reward and punishment. High D2 binding in the left hemisphere is associated with preference for reward. Prism adaptation (PA) is a simple sensorimotor technique, which modulates visuospatial bias according to the direction of the deviation. Left-deviating prism adaptation (LPA) induces rightward bias in healthy subjects, it is therefore possible that the right side of space increases in saliency along with left hemisphere dopaminergic activity. Right-deviating prism adaptation (RPA) has been used mainly as a control condition because it does not modulate behavior in healthy individuals. Since LPA induces a rightward visuospatial bias as a result of left hemisphere modulation, and higher dopaminergic activity in the left hemisphere is associated with preference for rewarding events we hypothesized that LPA would increase the preference for learning with reward. Healthy volunteers performed a computer-based probabilistic classification task before and after LPA or RPA. Consistent with our predictions, PA altered the preference for rewarded vs. punished learning, with the LPA group exhibiting increased learning from reward. These results suggest that PA modulates dopaminergic activity in a lateralized fashion.

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The hippocampus of birds in a view of evolutionary connectomics

Publication date: Available online 11 October 2018

Source: Cortex

Author(s): Christina Herold, Philipp Schlömer, Isabelle Mafoppa-Fomat, Julia Mehlhorn, Katrin Amunts, Markus Axer

Abstract

The avian brain displays a different brain architecture compared to mammals. This has led the first pioneers of comparative neuroanatomy to wrong conclusions about bird brain evolution by assuming that the avian telencephalon is a hypertrophied striatum. Based on growing evidence from divers analysis demonstrating that most of the avian forebrain is pallial in nature, this view has substantially changed during the past decades. Further, birds show cognitive abilities comparable to or even exceeding those of some mammals, even without a "six-layered" cortex. Beside higher associative regions, most of these cognitive functions include the processing of information in the hippocampal formation that shares a homologue structure in birds and mammals. Here we show with 3D polarized light imaging that the hippocampal formation of pigeons like the mammalian hippocampal formation shows regional specializations along the anterior-posterior axis in connectivity. In addition, different levels of adult neurogenesis were observed in the subdivisions of the hippocampal formation per se and in the most caudal regions pointing towards a functional specialization along the anterior-posterior axis. Taken together our results point to species specific morphologies but still conserved hippocampal characteristics of connectivity, cells and adult neurogenesis if compared to the mammalian situation. Here our data provides new aspects for the ongoing discussion on hippocampal evolution and mind.

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Processing inflectional morphology: ERP evidence for decomposition of complex words according to the affix structure

Publication date: Available online 11 October 2018

Source: Cortex

Author(s): Stefanie Regel, Andreas Opitz, Gereon Müller, Angela D. Friederici

Abstract

This study investigated the processing of inflectional morphology by registrating event-related brain potentials (ERPs) during sentence reading. In particular, we examined nouns combined with affixes that have distinct structural characteristics as proposed by morphological theory. Affixes were either complex consisting of functionally distinguishable subparts as occurring for German plural morphology, or simple consisting of one part only. To test possible differences in processing these affixes we compared grammatical nouns (e.g., Kartons (cartons)) to ungrammatical ones (e.g., *Kartonen) in two different syntactic contexts represented by a complex, or simple affix. The ERPs showed that ungrammatical nouns consisting of complex affixes elicited a left anterior negativity (LAN) reflecting enhanced morphosyntactic processing, which was absent for equivalent nouns consisting of simple affixes. This finding suggests that inflected words are decomposed dependent on the affix structure, whereby the affixes themselves seem to consist of morphological subparts in accordance with current morphological theories (Müller, 2007; Noyer, 1992). Moreover, ungrammatical nouns elicited early (reduced P200) and late (P600) ERP components relative to their grammatical equivalents, which implies an engagement of syntactic processes presumably based on intially enhanced pre-lexical processing of these irregularized nouns. The findings are discussed with respect to theoretical and neuropsychological accounts to inflectional morphology.

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Bi-cephalic Parietal and Cerebellar direct current stimulation interferes with early error correction in Prism Adaptation: toward a complex view of the neural mechanisms underlying visuomotor control

Publication date: Available online 11 October 2018

Source: Cortex

Author(s): Francesco Panico, Laura Sagliano, Dario Grossi, Luigi Trojano

Abstract

Prism Adaptation (PA) represents a valid tool to assess short-term visuomotor plasticity. Two adaptive processes are involved during PA: recalibration, contributing to early error compensation, and spatial realignment, contributing to after-effect development. Classical models on PA posit that adaptive mechanisms underlying PA rely on segregated regions in the brain. Indeed, they ascribe recalibration to the activity of the Posterior Parietal Cortex (PPC) and spatial realignment to the activity of the Cerebellum. The present experiment challenges the idea of a clear-cut separation of the role of the brain areas involved in PA, proposing an interpretation in terms of interrelated brain regions. To this purpose we interfered with the activity of the PPC and the Cerebellum by means of complementary protocols of stimulation.

Bi-cephalic transcranial Direct Current Stimulation was delivered simultaneously on the PPC and the Cerebellum during PA in two groups of participants receiving real stimulation with opposite polarities (anode on PPC and cathode on Cerebellum or vice-versa) and in a control group (Sham stimulation). Differences in mean errors between groups were analyzed. Results show that the two groups of real stimulation exhibited larger displacements in early error compensation compared to the Sham Group, but they did not differ from each other. No group difference was found in late error compensation and after-effect. In conclusion, the present findings provide the first direct evidence that a brain circuit connecting the PPC and the Cerebellum is involved in early stages of visuomotor adaptation, and pave the way for updating classical models of PA.

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Large-scale temporo-parieto-frontal networks for motor and cognitive motor functions in the primate brain

Publication date: Available online 11 October 2018

Source: Cortex

Author(s): Elena Borra, Giuseppe Luppino

Abstract

The extent to which neural circuits and mechanisms underlying sensory, motor, and cognitive cortical functions in the human brain are shared with those of other animals, especially non-human primates, is currently a key issue in the field of comparative neuroscience. Cortical functions result from the conjoint function of different, reciprocally connected areas working together as large-scale functionally specialized networks, which can be investigated in human subjects thanks to the development of non-invasive functional and connectional imaging techniques. In spite of their limitations in terms of spatial and temporal resolution, these techniques make it possible to address the issue of how and to what extent the neural mechanisms for different cortical functions differ from those of non-human primates. Indeed, 30 million years of independent evolution have resulted in significant differences between the brains of humans and macaques, which are the experimental model system phylogenetically closest to humans for obtaining highly detailed anatomical and functional information on the organization of cortical networks. In the macaque brain, architectonic, connectional, and functional data have provided evidence for functionally specialized large-scale cortical networks involving temporal, parietal, and frontal areas. These networks appear to play a primary role in controlling different aspects of motor and cognitive motor functions, such as hand action organization and recognition, or oculomotor behavior and gaze processing. In the present review, based on the comparison of these data with data from human studies, we will argue that there is clear evidence for human counterparts of these networks. These human and macaque putatively homolog networks appear to share phylogenetically older neural mechanisms, which, in the evolution of the human lineage, could have been exploited and differentiated, resulting in the emergence of human-specific higher-order cognitive functions. These considerations are fully in line with the notion of "neural reuse" in primate evolution.

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Primary motor cortex crucial for action prediction: a tDCS study

Publication date: Available online 11 October 2018

Source: Cortex

Author(s): Riccardo Paracampo, Mirella Montemurro, Manuel de Vega, Alessio Avenanti

Abstract

The neural network underlying action observation – i.e., the action observation network – forms an anticipatory representation of observed actions. Although correlational studies suggest that the motor cortex (M1) might be involved in this anticipatory coding, it is unclear whether M1 is also causally essential for making accurate predictions about observed actions. To test the functional relevance of M1 to action prediction, we used offline monopolar transcranial direct current stimulation (tDCS). In four tDCS groups of healthy participants, we administered 15 minutes of anodal or cathodal constant currents of 1 or 2 mA over the left M1 before participants performed two tasks requiring them to make predictions about the outcomes of reaching-grasping human actions (Action Prediction, AP) or non-human movements (Non-human Prediction, NP). In each group, participants received sham and active tDCS in two separate sessions. We found that 2mA cathodal tDCS (c-tDCS_2mA) selectively impaired accuracy in the AP task, but not in the NP task. No change in performance was found following anodal or 1-mA tDCS protocols. Additionally, no change was found following 2mA c-tDCS administered over a control site. These findings show task-, polarity-, intensity- and site-specific disruption of AP abilities following c-tDCS_2mA over M1. Thus, our study establishes specific tDCS parameters for effective M1 stimulation in AP and highlights the functional relevance of the motor system to making accurate predictions about the outcomes of human actions.

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Clinical characteristics and surgical outcome in USP8 -mutated human adrenocorticotropic hormone-secreting pituitary adenomas

Abstract

Purpose

somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been described in patients with Cushing's disease (CD). The aim of the study is to verify whether USP8 mutation may predict early and late outcome of pituitary surgery in patients with CD operated at a single institution.

Methods

We performed a retrospective genetic analysis of 92 adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Specimens were screened for USP8 hotspot mutations in the exon 14 with Sanger sequencing. Hormonal and surgical data were compared between USP8 variant carriers and wild-type tumors.

Results

USP8 variants were detected in 22 adenomas (23.9%) with higher prevalence in women (28.9% vs. 5.3% in men; p < 0.05). No significant difference in hormonal levels and tumoral features in relation to USP8 status was observed. Interestingly, USP8-variant carriers were more likely to achieve surgical remission than wild-type adenomas (100% vs. 75.7%; p = 0.01). Conversely, recurrence of CD occurred in 23% of USP8-mutated patients and in 13% of patients with wild-type adenoma. The recurrence-free survival did not differ significantly between the two groups (p = 0.42).

Conclusions

ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated by a single neurosurgeon. Recurrence rates are not related with USP8-variant status.

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Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells

Publication date: Available online 11 October 2018

Source: Journal of Autoimmunity

Author(s): Yuki Kagoya, Hiroshi Saijo, Yukiko Matsunaga, Tingxi Guo, Kayoko Saso, Mark Anczurowski, Chung-Hsi Wang, Kenji Sugata, Kenji Murata, Marcus O. Butler, Cheryl H. Arrowsmith, Naoto Hirano

Abstract

Forkhead box transcription factor 3 (FOXP3) plays a pivotal role in the suppressive function of regulatory T cells. In addition to mRNA levels, FOXP3 activity can also be controlled by posttranslational mechanisms, which have not been studied in a comprehensive manner. Through extensive screening using selective inhibitors, we demonstrate that the inhibition of type I protein arginine methytransferases (PRMTs) attenuates the suppressive functions of regulatory T cells. FOXP3 undergoes methylation on arginine residues at positions 48 and 51 by interacting with protein arginine methyltransferase 1 (PRMT1). The inhibition of arginine methylation confers gene expression profiles representing type I helper T cells to FOXP3⁺ T cells, which results in attenuated suppressive activity. A methylation-defective mutant of FOXP3 displays less potent activity to suppress xenogeneic graft-versus-host disease in vivo. These results elucidate an important role of arginine methylation to enhance FOXP3 functions and are potentially applicable to modulate regulatory T cell functions.

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Clinical characteristics and surgical outcome in USP8 -mutated human adrenocorticotropic hormone-secreting pituitary adenomas

Abstract

Purpose

Methods

Results

Conclusions

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Impact of chelation timing on gadolinium deposition in rats after contrast administration

Publication date: Available online 12 October 2018

Source: Magnetic Resonance Imaging

Author(s): John P. Prybylski, Carla Coste Sanchez, Michael Jay

Abstract

Objective

To determine if gadolinium (Gd) can be rechelated once released from Gd-based contrast agents (GBCAs) and deposited in vivo. Despite extensive research comparing GBCAs and GBCA formulations as well as the ongoing debate about their risks of deposition and the role of Gd release, it remains unknown if retained Gd can be eliminated by administering chelating agents.

Materials and methods

Rats were injected intravenously with 10 doses of 1 mmol/kg gadodiamide and treated with intravenous Zn-DTPA (30 μmol/kg) concomitantly or 1, 4 or 8 h after GBCA administration (N = 3 rats per group). After euthanization, tissues were harvested three days after the last dose of gadodiamide and tissue Gd concentrations were assessed by ICP-MS. Additionally, a simulation of a single 0.1 mmol/kg gadopentetate dose with 30 μmol/kg DTPA given either concomitantly or within the first 24 h after GBCA was run; simulated tissue Gd concentrations were compared with those observed in rats to determine if simulated trends were accurate.

Results

Concomitant DTPA did not produce a significant reduction in Gd concentration in any organ for rats. There was a time-dependent trend in liver Gd reduction. The 1 h timepoint was associated with a non-significant increase in kidney, brain and femur Gd relative to untreated controls. There were no significant deviations from the model-predicted Gd changes.

Discussion

Both the simulation and rat study did not identify major benefits for chelation at the doses given, despite the simulation assuming all Gd deposited in tissues is unchelated. The potential redistribution in the rat study provide a compelling result that may impact the clinical relevance of further work investigating rechelation of Gd. Future work should further describe the three-dimensional dose-time-response relationship for preventing Gd deposition, and how that relates to long-term Gd toxicities.

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Application of low-field, 1H/13C high-field solution and solid state NMR for characterisation of oil fractions responsible for wettability change in sandstones

Publication date: Available online 12 October 2018

Source: Magnetic Resonance Imaging

Author(s): Igor Shikhov, Donald S. Thomas, Aditya Rawal, Yin Yao, Bulat Gizatullin, James M. Hook, Siegfried Stapf, Christoph H. Arns

Abstract

Asphaltene adsorption on solid surfaces is a standing problem in petroleum industry. It has an adverse effect on reservoir production and development by changing rock wettability, plugging pore throats, and affects oil transport through pipelines. Asphaltene chemistry constitutes important part of the ageing process as part of petrophysical studies and core analysis. The mechanisms and contribution of various oil components to adsorption processes is not fully understood. To investigate the kinetics of the ageing process and address the relative contribution of different oil components, we prepared three sets of sandstone core plugs aged in different oil mixtures over various time intervals. Cores were then re-saturated with decane to evaluate their wetting state using low-field NMR relaxometry by monitoring a change of surface relaxivity. Adsorbed deposits were then extracted from cores for solution-state NMR analysis. Their ¹H and ¹H-¹³C correlation spectra obtained using heteronuclear single quantum coherence (HSQC) technique were matched to spectra of four SARA (saturates, aromatics, resins and asphaltenes) components of oil mixtures to deduce components of deposits and inter-component interactions. We notice that wettability reversal of rock is inversely proportional to initial asphaltene concentration. Analysis of deposits reveals an increase in their aliphatic content over ageing time, which is accompanied by a change of the morphology of the pore space due to cluster aggregates forming a network. Results suggest that the ageing process in respect to the wetting state of rock samples consists of three distinctive stages: (i) an early-time period, when the fraction of most polar asphaltenes creates a discontinuous layer corresponding to mixed-wet state; (ii) an intermediate-time interval, at which the full grain coverage may be achieved (at favourable chemical environment) corresponding to strong oil-wetting; (iii) a late-time stage, where intense macro-aggregates accumulation occurs, changing the pore space integrity. It is likely asphaltene-aliphatic interactions leading to growth of sub-micron size macro-aggregates.

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