Measurement of tensor analyzing powers in deuteron photodisintegration

New accurate measurement of tensor analyzing powers T20, T21 and T22 in deuteron photodisintegration has been performed. Wide-aperture non-magnetic detectors allowed to cover broad kinematic ranges in a single setup: photon energy = 25 to 600 MeV, proton emission angle in CM = 24 to 48 deg. and 70 to 102 deg. New data provide a significant improvement of a few existing measurements. The angular dependency of the tensor asymmetries in deuteron photodisintegration is extracted for the first time.Comment: 4 pages, 5 figures, submitted to Phys. Rev. Let

Иммуномодулирующие свойства пробиотика на основе молочнокислых бактерий и растительного компонента

Визначено імуномодулювальну дію базової пробіотичної композиції молочнокислих бактерій на основі роду Lactobacillus, рослинного компонента карбюлози та комплексного пробіотика з карбюлозою на експериментальній моделі інтактних мишей. Встановлено, що введення до складу пробіотика карбюлози підвищувало функціональну активність клітин фагоцитарної системи, а саме поглинальну активність макрофагів (за показником фагоцитозу). Після введення інтактним мишам комплексного препарату на основі композиції молочнокислих бактерій з карбюлозою виявлено тенденцію до підвищення кількості CD19+ В-лімфоцитів, кількості CD25+-клітин у селезінці, до яких належать активовані Т- та В-лімфоцити, а також активовані макрофаги. Під впливом чистої карбюлози у селезінці дослідних мишей також підвищувалась кількість CD4+-клітин (на дев’яту добу) та CD25+-клітин (на третю та шосту добу). Отримані дані свідчать про потенційну здатність як базової композиції пробіотика, так і комплексного препарату з карбюлозою, направляти розвиток імунної відповіді по клітинному типу, важливому при захисті як від бактеріальних, так і вірусних патогенів.Purpose of this work was determination of the immunomodulatory effects of base probiotic composition of lactic acid bacteria based on genus Lactobacillus and the complex probiotic with carbyuloza on an experimental model of intact mice. It was found, that injection of carbyuloza in the probiotic composition increased functional activity of phagocytic system — namely, absorbing activity of macrophages. After injection of complex composition to intact mice, there was a tendency to increase the number of CD19+ B-lymphocytes, CD25+ cells in the spleen including activated T- and B-lymphocytes and activated macrophages. In addition, under the influence of net carbyuloza in spleens of mice the number of CD4+ cells (on 9th day), and CD25+ cells (at the third day and 6th) where up. The received data indicate the potential ability of a base composition of the probiotic and complex preparation with carbyuloza guide to the development of the immune response to cell type which is important in protecting against bacterial and viral pathogens.Определено иммуномодулирующее действие препаратов: базовой пробиотической композиции молочнокислых бактерий на основе рода Lactobacillus, растительного компонента карбюлозы и комплексного пробиотика с карбюлозой на экспериментальной модели интактных мышей. Установлено, что введение в состав пробиотика карбюлозы повышало функциональную активность клеток фагоцитарной системы, а именно поглощающую активность макрофагов (по показателю фагоцитоза). После введения интактным мышам комплексного препарата на основе композиции молочнокислых бактерий с карбюлозой выявленатенденция к увеличению количества CD19+ В-лимфоцитов, количества CD25+-клеток в селезенке, к которым относятся активированные Т- и В-лимфоциты, а также активированные макрофаги. Под влиянием чистой карбюлозы в селезенке мышей также повышалось количество CD4+-клеток (на девятые сутки)и CD25+-клеток (на третьи и шестые сутки). Полученные данные свидетельствуют о потенциальной способности как базовой композиции пробиотика, так и комплексного препарата с карбюлозой, направлять развитие иммунного ответа по клеточному типу, важном при защите как от бактериальных, так и вирусных патогенов

Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study

Abstract: Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC). Methods: Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5–26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions). Results: RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml). Conclusion: Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT

Bone Loss in Diabetes: Use of Antidiabetic Thiazolidinediones and Secondary Osteoporosis

Clinical evidence indicates that bone status is affected in patients with type 2 diabetes mellitus (T2DM). Regardless of normal or even high bone mineral density, T2DM patients have increased risk of fractures. One class of antidiabetic drugs, thiazolidinediones (TZDs), causes bone loss and further increases facture risk, placing TZDs in the category of drugs causing secondary osteoporosis. Risk factors for development of TZD-induced secondary osteoporosis are gender (women), age (elderly), and duration of treatment. TZDs exert their antidiabetic effects by activating peroxisome proliferator-activated receptor-γ (PPAR-γ) nuclear receptor, which controls glucose and fatty acid metabolism. In bone, PPAR-γ controls differentiation of cells of mesenchymal and hematopoietic lineages. PPAR-γ activation with TZDs leads to unbalanced bone remodeling: bone resorption increases and bone formation decreases. Laboratory research evidence points toward a possible separation of unwanted effects of PPAR-γ on bone from its beneficial antidiabetic effects by using selective PPAR-γ modulators. This review also discusses potential pharmacologic means to protect bone from detrimental effects of clinically used TZDs (pioglitazone and rosiglitazone) by using combinational therapy with approved antiosteoporotic drugs, or by using lower doses of TZDs in combination with other antidiabetic therapy. We also suggest a possible orthopedic complication, not yet supported by clinical studies, of delayed fracture healing in T2DM patients on TZD therapy

Роль цитокинов в патогенезе аутоиммунного диабета, вопросы иммуноинтервенции

The review devotes to studying the role of cytokines in development of autoimmune diabetes mellitus, latent autoimmune diabetes in adults included. Therapeutic approaches to prevent the loss of endogenous insulin secretion are discussed. There is review of clinical trials of immunosuppressive agents and modulators of immune tolerance in autoimmune diabetes mellitus.Рассмотрена роль цитокинов в патогенезе аутоиммунного сахарного диабета, включая латентный аутоиммунный диабет взрослых. Обсуждаются терапевтические подходы, направленные на предупреждение снижения секреции эндогенного инсулина. Приведен обзор клинических испытаний иммуносупрессивных средств и модуляторов иммунологической толерантности при аутоиммунном сахарном диабете (типа 1А)

Molecular modeling of a tandem two pore domain potassium channel reveals a putative binding Site for general anesthetics

[Image: see text] Anesthetics are thought to mediate a portion of their activity via binding to and modulation of potassium channels. In particular, tandem pore potassium channels (K2P) are transmembrane ion channels whose current is modulated by the presence of general anesthetics and whose genetic absence has been shown to confer a level of anesthetic resistance. While the exact molecular structure of all K2P forms remains unknown, significant progress has been made toward understanding their structure and interactions with anesthetics via the methods of molecular modeling, coupled with the recently released higher resolution structures of homologous potassium channels to act as templates. Such models reveal the convergence of amino acid regions that are known to modulate anesthetic activity onto a common three- dimensional cavity that forms a putative anesthetic binding site. The model successfully predicts additional important residues that are also involved in the putative binding site as validated by the results of suggested experimental mutations. Such a model can now be used to further predict other amino acid residues that may be intimately involved in the target-based structure–activity relationships that are necessary for anesthetic binding

A Subset of Osteoblasts Expressing High Endogenous Levels of PPARγ Switches Fate to Adipocytes in the Rat Calvaria Cell Culture Model

Understanding fate choice and fate switching between the osteoblast lineage (ObL) and adipocyte lineage (AdL) is important to understand both the developmental inter-relationships between osteoblasts and adipocytes and the impact of changes in fate allocation between the two lineages in normal aging and certain diseases. The goal of this study was to determine when during lineage progression ObL cells are susceptible to an AdL fate switch by activation of endogenous peroxisome proliferator-activated receptor (PPAR)gamma.Multiple rat calvaria cells within the ObL developmental hierarchy were isolated by either fractionation on the basis of expression of alkaline phosphatase or retrospective identification of single cell-derived colonies, and treated with BRL-49653 (BRL), a synthetic ligand for PPARgamma. About 30% of the total single cell-derived colonies expressed adipogenic potential (defined cytochemically) when BRL was present. Profiling of ObL and AdL markers by qRT-PCR on amplified cRNA from over 160 colonies revealed that BRL-dependent adipogenic potential correlated with endogenous PPARgamma mRNA levels. Unexpectedly, a significant subset of relatively mature ObL cells exhibited osteo-adipogenic bipotentiality. Western blotting and immunocytochemistry confirmed that ObL cells co-expressed multiple mesenchymal lineage determinants (runt-related transcription factor 2 (Runx2), PPARgamma, Sox9 and MyoD which localized in the cytoplasm initially, and only Runx2 translocated to the nucleus during ObL progression. Notably, however, some cells exhibited both PPARgamma and Runx2 nuclear labeling with concomitant upregulation of expression of their target genes with BRL treatment.We conclude that not only immature but a subset of relatively mature ObL cells characterized by relatively high levels of endogenous PPARgamma expression can be switched to the AdL. The fact that some ObL cells maintain capacity for adipogenic fate selection even at relatively mature developmental stages implies an unexpected plasticity with important implications in normal and pathological bone development

The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>Activation of peroxisome proliferator-activated receptor (PPAR)gamma is associated with bone loss and increased fracture risk, while PPARalpha activation seems to have positive skeletal effects. To further explore these effects we have examined the effect of the PPARalpha agonists fenofibrate and Wyeth 14643, and the PPARgamma agonist pioglitazone, on bone mineral density (BMD), bone architecture and biomechanical strength in ovariectomized rats.</p> <p>Methods</p> <p>Fifty-five female Sprague-Dawley rats were assigned to five groups. One group was sham-operated and given vehicle (methylcellulose), the other groups were ovariectomized and given vehicle, fenofibrate, Wyeth 14643 and pioglitazone, respectively, daily for four months. Whole body and femoral BMD were measured by dual X-ray absorptiometry (DXA), and biomechanical testing of femurs, and micro-computed tomography (microCT) of the femoral shaft and head, were performed.</p> <p>Results</p> <p>Whole body and femoral BMD were significantly higher in sham controls and ovariectomized animals given fenofibrate, compared to ovariectomized controls. Ovariectomized rats given Wyeth 14643, maintained whole body BMD at sham levels, while rats on pioglitazone had lower whole body and femoral BMD, impaired bone quality and less mechanical strength compared to sham and ovariectomized controls. In contrast, cortical volume, trabecular bone volume and thickness, and endocortical volume were maintained at sham levels in rats given fenofibrate.</p> <p>Conclusions</p> <p>The PPARalpha agonist fenofibrate, and to a lesser extent the PPARaplha agonist Wyeth 14643, maintained BMD and bone architecture at sham levels, while the PPARgamma agonist pioglitazone exaggerated bone loss and negatively affected bone architecture, in ovariectomized rats.</p