Regulating of LncRNA2264/miR-20b-5p/IL17RD axis on hydrogen sulfide exposure-induced inflammation in broiler thymus by activating MYD88/NF-κB pathway.

Hydrogen sulfide (H2S) is an environmental pollutant. Chronic exposure to H2S can damage the immune system of birds, but the detailed mechanisms of H2S-induced thymus toxicity have not been determined. Competitive endogenous RNA (ceRNA) mechanism participates in many pathophysiological processes by regulating gene expression, including environmental pollutant-induced injury. Therefore, we investigate the specific mechanisms of ceRNA in the process of H2S-induced thymic immune damage in broiler chickens. In the current study, 120 one-day-old male Ross 308 broilers were randomly divided into two groups (n = 60 chickens/group), raising in the control chamber (0.5 ± 0.5 ppm) or H2S-exposed chamber (4.0 ± 0.5 ppm at 0-3 weeks of age and 20.0 ± 0.5 ppm at 4-6 weeks of age groups) to replicate the H2S-exposed broilers. NaHS (3 mM or 6 mM) was used to treat chicken macrophages (HD11) to establish an in vitro. Histopathology and ultrastructural changes of thymus were assessed by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). Gene expression profiles were analyzed by using transcriptomics. The underlying mechanisms of thymic injury were further revealed by dual luciferase reporter gene assay, qRT-PCR and Western blotting. Research results showed that H2S exposure induced an inflammatory response in thymus, with the expression of LncRNA2264 was significantly down-regulated. LncRNA2264 could competitively bind to miR-20b-5p and caused downregulation of the IL17RD. H2S could activate inflammatory factors through the LncRNA2264/miR-20b-5p/IL17RD axis. In summary, this study suggested that LncRNA2264 acted as a miR-20b-5p molecular sponge to regulate the expression of IL17RD involved in H2S exposure-induced thymic inflammation, which has positive implications for guiding the prevention and control of H2S gas poisoning in livestock housing and ensuring animal welfare.

Thymus-Pineal Gland Axis: Revisiting Its Role in Human Life and Ageing.

For years the thymus gland (TG) and the pineal gland (PG) have been subject of increasingly in-depth studies, but only recently a link that can associate the activities of the two organs has been identified. Considering, on the one hand, the well-known immune activity of thymus and, on the other, the increasingly emerging immunological roles of circadian oscillators and the rhythmically secreted main pineal product, melatonin, many studies aimed to analyse the possible existence of an interaction between these two systems. Moreover, data confirmed that the immune system is functionally associated with the nervous and endocrine systems determining an integrated dynamic network. In addition, recent researches showed a similar, characteristic involution process both in TG and PG. Since the second half of the 20th century, evidence led to the definition of an effectively interacting thymus-pineal axis (TG-PG axis), but much has to be done. In this sense, the aim of this review is to summarize what is actually known about this topic, focusing on the impact of the TG-PG axis on human life and ageing. We would like to give more emphasis to the implications of this dynamical interaction in a possible therapeutic strategy for human health. Moreover, we focused on all the products of TG and PG in order to collect what is known about the role of peptides other than melatonin. The results available today are often unclear and not linear. These peptides have not been well studied and defined over the years. In this review we hope to awake the interest of the scientific community in them and in their future pharmacological applications.

Immunofluorescent characterization of innervation and nerve-immune cell neighborhood in mouse thymus.

The central nervous system impacts the immune system mainly by regulating the systemic concentration of humoral substances, whereas the peripheral nervous system (PNS) communicates with the immune system specifically according to local "hardwiring" of sympathetic/parasympathetic (efferent) and sensory (afferent) nerves to the primary and secondary lymphoid tissue/organs (e.g., thymus spleen and lymph nodes). In the present study, we use immunofluorescent staining of neurofilament-heavy to reveal the distribution of nerve fibers and the nerve-immune cell neighborhood inside the mouse thymus. Our results demonstrate (a) the presence of an extensive meshwork of nerve fibers in all thymic compartments, including the capsule, subcapsular region, cortex, cortico-medullary junction and medulla; (b) close associations of nerve fibers with blood vessels (including the postcapillary venules), indicating the neural control of blood circulation and immune cell dynamics inside the thymus; (c) the close proximity of nerve fibers to various subsets of thymocytes (e.g., CD4+, CD8+ and CD4+CD8+), dendritic cells (e.g., B220+, CD4+, CD8+ and F4/80+), macrophages (Mac1+ and F4/80+) and B cells. Our novel findings concerning thymic innervation and the nerve-immune cell neighborhood in situ should facilitate the understanding of bi-directional communications between the PNS and primary lymphoid organs. Since the innervation of lymphoid organs, including the thymus, may play essential roles in the pathogenesis and progression of some neuroimmune, infectious and autoimmune diseases, better knowledge of PNS-immune system crosstalk should benefit the development of potential therapies for these diseases.

ULTRASTRUCTURAL CHANGES IN THE ORGANS OF THE IMMUNE SYSTEM UNDER THE INFLUENCE OF XENOBIOTICS.

Nowadays scientific achievements in various areas of lives have caused the creation of more and more «foreign body substances¼ known as xenobiotics. As it is widely accepted that human health is a product of both genetics and the environment; and premise that also holds true for the immune system with unclear morphogenetic aspect, so we selected the purpose of our work as detection of ultrastructural changes in the spleen and thymus under the influence of tryglycidyl ether of polyoxypropylenetriol (TEPPT) and propylene glycol (PP). Subacute experiment has been performed on the matured male rat's with administration of 1/10 LD50 and 1/100 LD50 of TEPPT and PP during 7 days, 15 days, 30 days and 45 days. Obtained materials of spleen and thymus have been investigated with ultramicroscopic and histological examination. Detection of cellular density has been performed. On the base of obtained results we can conclude that structure of spleen and thymus is susceptible to influence of TEPPT and PP. Ultrastructural changes in those organs of the immune system are characterized by margination of chromatin in nuclei, appearance of pronounced invaginations of karyolemma till fragmentation of nuclei; condensed, wrinkled cytoplasm, dilatation of mitochondria, vacuolization of cytoplasm. Such changes are manifestation of hydropic dystrophy and apoptosis development with resulting in reducing of cellular density in 45 days more pronounced under TEPPT influence with 1/10 LD50 dose: in mantle zone of spleen follicle from 171.1±4.1to 123.7±10.8 cells/104 µm2, in marginal zone of spleen follicle from 104.6±3.8 to 79.4±9.7, in cortical zone of thymus from 180.1±3.9 to 128.3±9.1, in medullar zone of thymus from 137.4±3.7 to 98.6±8.3.

Immunofluorescent Localization of Non-myelinating Schwann Cells and Their Interactions With Immune Cells in Mouse Thymus.

The thymus is innervated by sympathetic/parasympathetic nerve fibers from the peripheral nervous system (PNS), suggesting a neural regulation of thymic function including T-cell development. Despite some published studies, data on the innervation and nerve-immune interaction inside the thymus remain limited. In the present study, we used immunofluorescent staining of glial fibrillary acidic protein (GFAP) coupled with confocal microscopy/three-dimensional (3D) reconstruction to reveal the distribution of non-myelinating Schwann cells (NMSC) and their interactions with immune cells inside mouse thymus. Our results demonstrate (1) the presence of an extensive network of NMSC processes in all compartments of the thymus including the capsule, subcapsular region, cortex, cortico-medullary junction, and medulla; (2) close associations/interactions of NMSC processes with blood vessels, indicating the neural control of blood flow inside the thymus; (3) the close "synapse-like" association of NMSC processes with various subsets of dendritic cells (DC; e.g., B220+ DCs, CD4+ DCs, and CD8+ DCs), and lymphocytes (B cells, CD4+/CD8+ thymocytes). Our novel findings concerning the distribution of NMSCs and the associations of NMSCs and immune cells inside mouse thymus should help us understand the anatomical basis and the mechanisms through which the PNS affects T-cell development and thymic endocrine function in health and disease.

What do we know about the structure of human thymic Hassall's corpuscles? A histochemical, immunohistochemical, and electron microscopic study.

Hassall's corpuscles are the most prominent structures in the human thymus. However, relatively few analyses have been performed to determine their function and cellular origins during development. In this study, we evaluated the cellular microenvironment of human thymic Hassall's corpuscles using histochemistry, immunohistochemistry, and transmission electron microscopy. We examined 95 human thymic tissue samples, which were perioperatively obtained from children undergoing cardiac surgery. To characterize the complex cellular microenvironment of human thymic corpuscles, we used a panel of 14 different antibodies to identify discrete cell types. We also utilized various histochemical methods (PAS reaction, alcian blue staining, alkaline phosphatase and acid phosphatase activity staining, von Kossa staining of calcified particles) and transmission electron microscopy to visualize these structures. Considerable variation in the sizes, shapes, and numbers of Hassall's corpuscles was observed, even amongst children of the same age. Inside the largest Hassall's corpuscles, cystic dilatation with an accumulation of cellular debris was found. These morphological observations might be associated with disruptions in the formation, migration, or differentiation of cardiac neural crest cells, which are essential for heart and thymus development. Immunohistochemical staining and electron microscopy revealed that Hassall's corpuscles resemble other types of stratified squamous epithelia. Most Hassall's corpuscles are heterocellular, consisting of thymic epithelial cells, macrophages, interdigitating dendritic cells, myoid cells, and, occasionally, mast cells and lymphocytes. To explore the potential functions of Hassall's corpuscles, we found that the concentrations of B-lymphocytes and BCL2-positive lymphocytes suggested a role in regulation of lymphopoiesis. We also found that these structures do not originate from the perivascular epithelium as previously proposed, nor could we identify blood or lymph endothelial cells in close proximity. This leaves the origins of Hassall's corpuscles an open question.

Histology and ultrastructure of the thymus during development in tilapia, Oreochromis niloticus.

The thymus in teleost fishes plays an important role in producing functionally competent T-lymphocytes. However, the thymus in tilapia is not well known, which greatly hampers investigations into the immune responses of tilapia infected by aquatic pathogens. The histological structure and ultrastructure of the thymus in Oreochromis niloticus, including embryos and larvae at different developmental stages, juveniles, and adult fish, were systematically investigated using whole mount in situ hybridization (WISH), and light and transmission electron microscopy (TEM). The position of the thymus primordium was first labeled in the embryo at 2 days post-fertilization (dpf) with the thymus marker gene recombination activating gene 1 (Rag1), when the water temperature was 27 °C. Obvious structures of the thymus were easily observed in 4-dpf embryos. At this stage, the thymus was filled with stem cells. At 6 dpf, the thymus differentiated into the cortex and medulla. The shape of the thymus was 'broad bean'-like during the early stages from 4 to 10 dpf, and became wedge-shaped in fish larvae at 20 dpf. At 6 months post-fertilization (mpf), the thymus differentiated into the peripheral zone, central zone, and inner zone. During this stage, myoid cells and adipocytes appeared in the inner zone following thymus degeneration. Then, the thymus displayed more advanced degeneration by 1 year post-fertilization (ypf), and the separation of cortex and medulla was not observed at this stage. The thymic trabecula and lobule were absent during the entire course of development. However, the typical Hassall's corpuscle was present and underwent degeneration. Additionally, TEM showed that the thymic tissues contained a wide variety of cell types, namely lymphocytes, macrophages, epithelial cells, fibroblasts, and mastocytes.

[Transplantation of bone marrow mesenchymal stem cell improves antioxidant capacity and immune activity of aging model rats ].

Objective: To investigate the impact of bone marrow mesenchymal stem cell( BMSC) transplantation on the antioxidant capacity and immune activity of aging rats induced by D-galactose. Methods: Ten healthy male SD rats served as a control group( aged 2 months). To establish aging models,healthy SD rats were daily injected subcutaneously with D-galactose( 400 mg / kg). Then the aging model rats were randomized into aging model group and BMSC group( ten rats in each group). The BMSC group was injected with 3 × 106 BMSCs via tail vein. And rats in the control and model groups were injected with the same amount of normal saline. Blood samples were taken from the rats of the three groups to detect the content of malonaldehyde( MDA) and the activities of superoxide dismutase( SOD). The thymic mass was weighed and the indexes of thymus were calculated; thymus lymphocyte transforming index was measured with MTT assay; the levels of IL-2and IL-10 in the thymus were detected by ELISA; and the ultrastructural changes of the thymus in each group were observed under a transmission electron microscope. Results: BMSC transplantation can increase the activity of SOD,decrease the level of MDA. Compared with the model group,the indexes of thymus as well as thymus lymphocyte transforming index significantly increased in the BMSC group. And in the BMSC group,the level of IL-2 was higher,and the level of IL-10 was distinctly lower. The thymus cells were arranged loosely,some nuclei presented with characteristic changes of pyknosis or apoptosis,and adipose tissues increased in the aging model group. BMSC could protect the ultrastructures of thymus cells,reticulo-epithelial cells,and the cell organelles were abundant and complete. Conclusion: BMSC transplantation can improve antioxidant capacity and immune activity of aging rats,thus postponing immunosenescence.

Reaction of Lymphoid Organs to Injection of Iron-Carbon Nanoparticles.

The distribution of iron-carbon nanoparticles in FeC-DSPE-PEG-2000 modification (micellar particles with structure (Fe) core-carbon shell; PEG-based coating) is studied. The greater part of the nanoparticles accumulated in the spleen and liver, a small amount in the lungs, and the minimum amount in the thymus. The structural changes in the lymphoid organs were minor and involved only the microcirculatory bed. Analysis of the peripheral blood showed manifest anemia, thrombocytopenia, and leukocytosis.

Preferential Use of Public TCR during Autoimmune Encephalomyelitis.

How the TCR repertoire, in concert with risk-associated MHC, imposes susceptibility for autoimmune diseases is incompletely resolved. Due largely to recombinatorial biases, a small fraction of TCRα or ß-chains are shared by most individuals, or public. If public TCR chains modulate a TCRαß heterodimer's likelihood of productively engaging autoantigen, because they are pervasive and often high frequency, they could also broadly influence disease risk and progression. Prior data, using low-resolution techniques, have identified the heavy use of select public TCR in some autoimmune models. In this study, we assess public repertoire representation in mice with experimental autoimmune encephalomyelitis at high resolution. Saturation sequencing was used to identify >18 × 10(6) TCRß sequences from the CNSs, periphery, and thymi of mice at different stages of autoimmune encephalomyelitis and healthy controls. Analyses indicated the prominent representation of a highly diverse public TCRß repertoire in the disease response. Preferential formation of public TCR implicated in autoimmunity was identified in preselection thymocytes, and, consistently, public, disease-associated TCRß were observed to be commonly oligoclonal. Increased TCR sharing and a focusing of the public TCR response was seen with disease progression. Critically, comparisons of peripheral and CNS repertoires and repertoires from preimmune and diseased mice demonstrated that public TCR were preferentially deployed relative to nonshared, or private, sequences. Our findings implicate public TCR in skewing repertoire response during autoimmunity and suggest that subsets of public TCR sequences may serve as disease-specific biomarkers or influence disease susceptibility or progression.

Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling.

BACKGROUND/AIMS: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation-induced T cell imbalance, and on immune dysfunction induced by gamma-rays. METHODS: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro-apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4+ and CD8+ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. RESULTS: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-α and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro-inflammatory cytokine (TNF-α and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. CONCLUSIONS: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity.

Optimization of Single- and Dual-Color Immunofluorescence Protocols for Formalin-Fixed, Paraffin-Embedded Archival Tissues.

Performance of immunofluorescence staining on archival formalin-fixed paraffin-embedded human tissues is generally not considered to be feasible, primarily due to problems with tissue quality and autofluorescence. We report the development and application of procedures that allowed for the study of a unique archive of thymus tissues derived from autopsies of individuals exposed to atomic bomb radiation in Hiroshima, Japan in 1945. Multiple independent treatments were used to minimize autofluorescence and maximize fluorescent antibody signals. Treatments with NH3/EtOH and Sudan Black B were particularly useful in decreasing autofluorescent moieties present in the tissue. Deconvolution microscopy was used to further enhance the signal-to-noise ratios. Together, these techniques provide high-quality single- and dual-color fluorescent images with low background and high contrast from paraffin blocks of thymus tissue that were prepared up to 60 years ago. The resulting high-quality images allow the application of a variety of image analyses to thymus tissues that previously were not accessible. Whereas the procedures presented remain to be tested for other tissue types and archival conditions, the approach described may facilitate greater utilization of older paraffin block archives for modern immunofluorescence studies.

Effects of dietary n-6/n-3 polyunsaturated fatty acid ratios on the mass, and histological and ultrastructures of liver, spleen and thymus of 70-day-old Yangzhou goslings.

The objective of this study was to determine the effects of dietary n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on the organ indexes, and histological and ultrastructures of organs including liver, spleen and thymus in 70-day-old Yangzhou goslings. One-hundred and sixty 21-day-old Yangzhou goslings were randomly divided into 4 groups and fed 4 diets varying in the n-6/n-3 PUFA ratio from 3:1 up to 12:1. After 1-week acclimation, the feeding experiment lasted for 6 weeks. At the end of the experimental period, goslings were slaughtered and the liver, spleen and thymus were weighed, and their histological and ultrastructures were examined. The results showed that the organ indices in the 3:1 group were remarkably higher than in the other three groups, whereas the mitochondrial square did not differ among four groups. The histological and ultrastructures of the liver, spleen and thymus were not affected by the diets with the lower n-6/n-3 PUFA ratios (3:1 and 6:1). However, feeding diets with the higher n-6/n-3 PUFA ratios (9:1 and 12:1), the nuclear chromatin was concentrated and marginalized; the cell membrane was contracted inwardly and disrupted; the mitochondrial membrane was damaged to some degree. In conclusion, the diet containing higher content of n-3 PUFA might improve immune capacity of goslings the animal by accelerating the growth and maintaining cellular structures of organs like liver, spleen and thymus.

[Ginkgo biloba extract enhances the immune function of spleen and thymus in SD rats].

OBJECTIVE: To study the effect of Ginkgo biloba extract (GBE) on the immune function of spleen and thymus in SD rats. METHODS: Forty SD rats were randomly divided into four groups (10 rats each group). Three experimental groups were given GBE daily by gavage in doses of 40, 120, 360 mg/(kg.d), respectively. Animals in the control group were fed the same amount of PBS. After 28 days, the rats were sacrificed by chloral hydrate anesthesia. The spleen and thymus were harvested to determine the organ index first. MTT assay was used to detect the concanavalin A (ConA)-induced splenic lymphocyte proliferation and transformation. Neutral red assay was performed to measure the rat peritoneal macrophage phagocytosis. The ultrastructural changes of spleen and thymus were observed under scanning electron microscope. RESULTS: Administration of GBE in the rats increased the mass indexes of rat thymus and spleen, dose-dependently elevated the lymphocyte proliferative responses and enhanced the peritoneal macrophage phagocytosis. In experimental groups, the numbers of mature spleen and thymus lymphocytes were significantly raised in comparison with the control rats. CONCLUSION: GBE plays a regulatory role in immune function of the rat by increasing the mass of immune organs, increasing the number of mature T lymphocytes as well as their proliferative responses, and enhancing the phagocytic capacity of peritoneal macrophages.

[Age-related peculiarities of thymus reaction to the exposure to helium-neon laser and injured muscle alloplasty with the muscle tissue from the animals of the same age].

Histological, cytological and morphometric changes in the thymus of 1 month-old, adult (3-4 months-old) and old (24-30 months-old) rats (24 animals in each group) were studied during muscle regeneration after the alloplasty of the injured area with the muscle tissue from the animal of the same age. Muscles of the donor or recipient were subjected to the course of preliminary irradiation with He-Ne laser (dose: 4.5-5.4 J/cm2 for each extremity; total dose of 9.0-10.8 J/cm2 per animal). It was shown that the exposure of gastrocnemius muscles that were prepared for the operation to He-Ne laser radiation decreased morpho-functional activity of the thymus in young, adult and old recipient rats the before surgery. This was demonstrated by its weaker reaction to the allograft during the early time intervals after surgery. The observed effect was more pronounced with the increasing age of an animal.

Array tomography: characterizing FAC-sorted populations of zebrafish immune cells by their 3D ultrastructure.

For 3D reconstructions of whole immune cells from zebrafish, isolated from adult animals by FAC-sorting we employed array tomography on hundreds of serial sections deposited on silicon wafers. Image stacks were either recorded manually or automatically with the newly released ZEISS Atlas 5 Array Tomography platform on a Zeiss FEGSEM. To characterize different populations of immune cells, organelle inventories were created by segmenting individual cells. In addition, arrays were used for quantification of cell populations with respect to the various cell types they contained. The detection of immunological synapses in cocultures of cell populations from thymus or WKM with cancer cells helped to identify the cytotoxic nature of these cells. Our results demonstrate the practicality and benefit of AT for high-throughput ultrastructural imaging of substantial volumes.

A novel aspect of the structure of the avian thymic medulla.

We provide evidence for the compartmentalization of the avian thymic medulla and identify the avian thymic dendritic cell. The thymic anlage develops from an epithelial cord of the branchial endoderm. Branches of the cord are separated by primary septae of neural crest origin. The dilation of the primary septae produces the keratin-negative area (KNA) of the thymic medulla and fills the gaps of the keratin-positive network (KPN). Morphometric analysis indicates that the KNA takes up about half of the volume of the thymic medulla, which has reticular connective tissue, like peripheral lymphoid organs. The KNA receives blood vessels and in addition to pericytes, the myoid cells of striated muscle structure occupy this area. The myoid cells are of branchial arch or prechordal plate origin providing indirect evidence for the neural crest origin of the KNA. The marginal epithelial cells of the KPN co-express keratin and vimentin intermediate filaments, which indicate their functional peculiarity. The basal lamina of the primary septum is discontinuous on the surface of the KPN providing histological evidence for the loss of the blood-thymus barrier in the medulla. In the center of the KNA, the dendritic cells lie in close association with blood vessels, whereas the B-cells accumulate along the KPN. The organization of the KPN and KNA increases the "surface" of the so-called cortico-medullary border, thereby contributing to the efficacy of central tolerance.

The Idealized Brazilian Health System versus the real one: contributions from the nursing field / O Sistema Único de Saúde idealizado versus o realizado: contribuições da Enfermagem / El Sistema Único de Salud idealizado versus el realizado: contribuciones de la Enfermería

OBJECTIVE: to identify the perceptions of professionals working in a facility connected with the Brazilian Unified Health System - SUS in regard to what they know, think and talk about public health policy. METHOD: this exploratory-descriptive study with a qualitative nature was conducted with 28 professionals working in a facility connected with the SUS. Data were collected through interviews with guiding questions and analyzed through the thematic content analysis technique. RESULTS: coded and interpreted data resulted in three thematic axes: The SUS - perfect web that does not work in practice; The recurrent habit of complaining about the SUS; The need to rethink the way of thinking about, acting in and managing the SUS. CONCLUSION: the professionals working for the SUS are aware of the principles and guidelines that govern the Brazilian health system, however, they reproduce a dichotomous and linear model of conception and practice strongly linked to the thinking of society in general. .

OBJETIVO: conhecer a percepção de profissionais que atuam em uma instituição conveniada com o Sistema Único de Saúde sobre o que sabem, pensam e falam dessa política pública de saúde. MÉTODO: trata-se de estudo exploratório-descritivo, de caráter qualitativo, realizado com 28 profissionais que atuam em uma instituição conveniada com o Sistema Único de Saúde. Os dados foram coletados por meio de entrevistas com questões norteadoras e analisados pela técnica de análise de conteúdo temática. RESULTADOS: os dados codificados e interpretados resultaram em três eixos temáticos: Sistema Único de Saúde - teia perfeita que não funciona na prática; o recorrente hábito de reclamar do Sistema Único de Saúde; a necessidade de repensar o modo de pensar, atuar e gerir o Sistema Único de Saúde. CONCLUSÃO: os profissionais que atuam no Sistema Único de Saúde têm conhecimento dos princípios e diretrizes que regem o sistema de saúde nacional, no entanto, reproduzem um modelo de concepção e atuação dicotômico, pontual e linear ainda fortemente vigente no pensar da sociedade em geral. .

OBJETIVO: conocer la percepción de profesionales que actúan en una institución que tiene convenio con el Sistema Único de Salud - SUS sobre lo que saben, piensan y hablan de esta política pública de salud. MÉTODO: se trata de un estudio exploratorio descriptivo, de carácter cualitativo, realizado con 28 profesionales que actúan en una institución que tiene convenio con el SUS. Los datos fueron recolectados por medio de entrevistas con preguntas orientadoras y analizados con la técnica de análisis de contenido temático. RESULTADOS: los datos codificados y interpretados resultaron en tres ejes temáticos: SUS - red perfecta que no funciona en la práctica; el recurrente hábito de reclamar del SUS; y la necesidad de repensar el modo de pensar, actuar y administrar el SUS. CONCLUSIÓN: los profesionales que actúan en el SUS tienen conocimiento de los principios y directrices que gobiernan el sistema de salud nacional, sin embargo, reproducen un modelo de concepción y actuación dicotómico, puntual, linear y además fuertemente vigente en el pensar de la sociedad en general. .

Response of thymus lymphocytes to streptozotocin-induced diabetes and exogenous vitamin C administration in rats.

Diabetes causes oxidative stress, which in turn generates excessive free radicals resulting in cellular damage. Vitamin C is an antioxidant that protects tissues and organs from oxidative stress. The thymus is one of the most important lymphoid organs, which regulates T-lymphocyte proliferation and maturation. The aim of this study is to investigate the protective effects of vitamin C on the thymus of streptozotocin (STZ)-induced diabetic rats. The mitotic activity and cell integrity of thymic lymphocytes were explored. Wistar Albino rats were divided into three groups: control (Group 1), STZ-diabetes (Group 2) and vitamin C-treated STZ-diabetics (Group 3). Rats received a single intraperitoneal injection of 45 mg/kg STZ to induce diabetes. Vitamin C (20 mg/kg) was administered intragastrically. Semithin and ultrathin sections were examined under a light or an electron microscope, respectively. Considerable numbers of mitotic lymphocytes were observed in the thymus of control rats. In the diabetic rats, however, numbers of mitotic lymphocytes decreased to ∼57% of controls, and cell division abnormalities were observed. Additionally, diabetic rats showed degeneration in the structure of the thymus including trabecular thickening, accumulation of lipid vacuoles, heterochromatic nuclei and loss of mitochondrial cristae. Degradation of medullar and cortical integrity was also detected. In the vitamin C-treated STZ-diabetic group, the structure of the thymus and mitotic activity of the lymphocytes were similar to the control group. These results suggest that vitamin C protects the thymus against injury caused by diabetes and restores thymocyte mitotic activity.

Proteasome inhibition with bortezomib depletes plasma cells and specific autoantibody production in primary thymic cell cultures from early-onset myasthenia gravis patients.

Bortezomib is a potent inhibitor of proteasomes currently used to eliminate malignant plasma cells in multiple myeloma patients. It is also effective in depleting both alloreactive plasma cells in acute Ab-mediated transplant rejection and their autoreactive counterparts in animal models of lupus and myasthenia gravis (MG). In this study, we demonstrate that bortezomib at 10 nM or higher concentrations killed long-lived plasma cells in cultured thymus cells from nine early-onset MG patients and consistently halted their spontaneous production not only of autoantibodies against the acetylcholine receptor but also of total IgG. Surprisingly, lenalidomide and dexamethasone had little effect on plasma cells. After bortezomib treatment, they showed ultrastructural changes characteristic of endoplasmic reticulum stress after 8 h and were no longer detectable at 24 h. Bortezomib therefore appears promising for treating MG and possibly other Ab-mediated autoimmune or allergic disorders, especially when given in short courses at modest doses before the standard immunosuppressive drugs have taken effect.