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BACKGROUND: Various types of hydrogel compounds have recently been developed for controlling invasive and pest ants in a range of environmental settings including agricultural, urban and natural areas. The current study evaluated the potential of sodium polyacrylate (ACR) hydrogels to effectively deliver liquid baits to Argentine ants. RESULTS: Relative to standard polyacrylamide (PAM) hydrogels, individual ACR hydrogel particles were approximately five-fold heavier; this may affect how ants interact with the bait particles, and further influence bait uptake and efficacy. Additionally, ACR hydrogels had significantly higher water absorption capacity and significantly slower rate of water loss, especially during the first 2 h. The efficacy of ACR hydrogel bait containing 0.005% fipronil and various attractants was evaluated on laboratory colonies. Results demonstrated that ACR hydrogel acceptance is significantly increased by the addition of feeding attractants. In addition, a field trial was performed in a nature reserve invaded by Argentine ants to evaluate the efficacy of ACR hydrogel bait. The field trial demonstrated that ACR hydrogel bait containing 0.005% fipronil with various attractants is highly effective and that ant densities throughout the baited plots declined by >99% within 7 days. CONCLUSIONS: The results of this study demonstrate that: (i) fipronil is highly effective for Argentine ant control in natural areas when used in low concentrations (0.005%); (ii) ACR hydrogels are an effective tool for delivering liquid baits to Argentine ants; and (iii) hydrogel baits augmented with various attractants including salt, protein and pheromone are highly attractive to Argentine ants. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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The accumulation of crystal calcium oxalate (CaOx) in plants is linked to a type of stress-induced photosynthesis termed 'alarm photosynthesis', serving as a carbon reservoir when carbon dioxide (CO2) exchange is constrained. Colobanthus quitensis is an extremophyte found from southern Mexico to Antarctica, which thrives in high-altitude Andean regions. Growing under common garden conditions, C. quitensis from different latitudinal provenances display significant variations in CaOx crystal accumulation. This raises the following questions: are these differences maintained under natural conditions? And is the CaOx accumulation related to mesophyll conductance (gm) and net photosynthesis (AN) performed in situ? It is hypothesized that in provenances with lower gm, C. quitensis will exhibit an increase in the use of CaOx crystals, resulting in reduced crystal leaf abundance. Plants from Central Chile (33°), Patagonia (51°), and Antarctica (62°) were measured in situ and sampled to determine gas exchange and CaOx crystal accumulation, respectively. Both AN and gm decrease towards higher latitudes, correlating with increases in leaf mass area and leaf density. The crystal accumulation decreases at higher latitudes, correlating positively with AN and gm. Thus, in provenances where environmental conditions induce more xeric traits, the CO2 availability for photosynthesis decreases, making the activation of alarm photosynthesis feasible as an internal source of CO2.
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BACKGROUND: The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different rheumatic diseases in geriatric patients are scarce. OBJECTIVE: To describe the physical characteristics of geriatric SF and the prevalence of crystals in knee and other joint aspirates from patients with previously diagnosed joint disease. MATERIALS AND METHODS: A retrospective study was performed with a baseline of 517 SF samples between 2011 and 2023. White blood cell count was performed by Neubauer chamber and crystals were identified by polarized light microscopy. Descriptive statistical analysis was performed and prevalence was reported as a percentage. RESULTS: The mean age of the adults was 73.5±5.0 years, 54.4% were women and 45.6% were men. The mean SF volume was 6.3±9.5mL in older adults and 15.3±24.9mL in those younger than 65 years. The mean viscosity in older adults was 9.5±4.5mm and the mean leukocyte count was 7352±16,402leukocytes/mm3. Seventy percent of the older adults' SFs were referred to the laboratory for osteoarthritis (OA), with lower proportions for rheumatoid arthritis (RA) (14.6%) and gout (5.1%). Of the crystals observed in the geriatric population, 14.6% corresponded to monosodium urate crystals (CUM) and 18.9% to calcium pyrophosphate crystals (CPP). CONCLUSIONS: The characteristics of LS in older adults were smaller volume, increased viscosity, and non-inflammatory. The main diagnoses were OA, RA, and gout. The crystal content of the SF of the geriatric population corresponded mainly to CPP.
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Líquido Sinovial , Humanos , Líquido Sinovial/química , Idoso , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Gota/epidemiologia , Idoso de 80 Anos ou mais , Artrite Reumatoide , México/epidemiologia , Contagem de Leucócitos , Fatores EtáriosRESUMO
A 59-year-old male patient with long-standing tophaceous gout (more than 30 years) characterized by polyarticular involvement and recurrent disseminated tophi formation; his past medical history is relevant for poor adherence to urate-lowering medications, as well as persistent use of self-prescribed systemic glucocorticoids. Despite achieving therapeutic goals for serum uric acid levels, new tophi formation with an intradermal location in the form of "miliarial-type gout" was documented. Due to functional limitations, the patient underwent surgical resection of the olecranon bursa. This case illustrates a widespread and recurrent tophi formation associated with long-standing gout and regular and sustained glucocorticoid use, despite an adequate disease control based on serum urate levels and involving an intradermal location of tophi presenting as "miliarial-type" lesions. In addition, the coexistence of urate and cholesterol crystal deposition disease in olecranon gouty bursitis is presented. Finally, a sonographic extended field of view of lesions distributed along the patient's extremities is presented as a novel characterization of this condition.
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Artrite Gotosa , Gota , Masculino , Humanos , Pessoa de Meia-Idade , Ácido Úrico , Glucocorticoides/uso terapêutico , Gota/complicações , Gota/tratamento farmacológicoRESUMO
PyDDT is a free Python package of computer codes for exploiting X-ray dynamic multiple diffraction in single crystals. A wide range of tools are available for evaluating the usefulness of the method, planning feasible experiments, extracting phase information from experimental data and further improving model structures of known materials. Graphical tools are also useful in analytical methodologies related to the three-dimensional aspect of multiple diffraction. For general X-ray users, the PyDDT tutorials provide the insight needed to understand the principles of phase measurements and other related methodologies. Key points behind structure refinement using the current approach are presented, and the main features of PyDDT are illustrated for amino acid and filled skutterudite single crystals.
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In modeling systems of interacting particles, many-body terms beyond pairwise interactions are often overlooked. Nevertheless, in certain scenarios, even small contributions from three-body or higher-order terms can disrupt significant changes in their collective behavior. Here we investigate the effects of three-body interactions on the structure and stability of 2D, harmonically confined clusters. We consider clusters with three distinct pairwise interactions:logr,1/r, ande-κr/r, thus covering a wide range of condensed and soft matter systems, such as vortices in mesoscopic superconductors, charged colloids, and dusty plasma. In each case, we evaluate the energetics and normal mode spectra of equilibrium and metastable configurations as the intensity of an attractive, Gaussian three-body potential is varied. We demonstrate that, above a threshold value of the three-body energy strength, the cluster shrinks and eventually becomes self-sustained, that is, it remains cohesive after the confinement potential is shut down. Depending on the strengths of the two-body and three-body interaction terms, this compaction can be continuous or abrupt. The latter case is characterized by a discontinuous jump in the particle density and coexsitence of the compact and non-compact phases as metastable states, as in a first-order phase transition. For some values of the particle number, the compaction is preceded by one or more structural changes, resulting in configurations not usually seen in purely pairwise-additive clusters.
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The plastic phase of cyclohexane (polymorph I) was studied by Kahn and co-workers, without achieving a satisfactory determination of the atomic coord-inates [Kahn et al. (1973). Acta Cryst. B29, 131-138]. The positions of the C atoms cannot be determined directly as a consequence of the disorder in a high-symmetry space group, an inherent feature of plastic materials. Given this situation, the building of a polyhedron describing the disorder was the main tool for determining the molecular structure in the present work. Based on the shape of reflections {111}, {200} and {113} in space group Fm 3 m, we assumed that cyclohexane is disordered through the action of rotation group 432. The polyhedral cluster of disordered molecules is then a rhombic dodecahedron centred on the nodes of an fcc Bravais lattice. The vertices of this polyhedron are the positions of C atoms for the cyclohexane molecule, which is disordered over 24 positions. With such a model, the asymmetric unit is reduced to two C atoms placed on special positions, and an acceptable fit between the observed and calculated structure factors is obtained.
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Spatial branching processes are ubiquitous in nature, yet the mechanisms that drive their growth may vary significantly from one system to another. In soft matter physics, chiral nematic liquid crystals provide a controlled setting to study the emergence and growth dynamic of disordered branching patterns. Via an appropriate forcing, a cholesteric phase may nucleate in a chiral nematic liquid crystal, which self-organizes into an extended branching pattern. It is known that branching events take place when the rounded tips of cholesteric fingers swell, become unstable, and split into two new cholesteric tips. The origin of this interfacial instability and the mechanisms that drive the large-scale spatial organization of these cholesteric patterns remain unclear. In this work, we investigate experimentally the spatial and temporal organization of thermally driven branching patterns in chiral nematic liquid crystal cells. We describe the observations through a mean-field model and find that chirality is responsible for the creation of fingers, regulates their interactions, and controls the tip-splitting process. Furthermore, we show that the complex dynamics of the cholesteric pattern behaves as a probabilistic process of branching and inhibition of chiral tips that drives the large-scale topological organization. Our theoretical findings are in good agreement with the experimental observations.
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BACKGROUND: Guanine crystals are organic biogenic crystals found in many organisms. Due to their exceptionally high refractive index, they contribute to structural color and are responsible for the reflective effect in the skin and visual organs in animals such as fish, reptiles, and spiders. Occurrence of these crystals in animals has been known for many years, and they have also been observed in eukaryotic microorganisms, but not in prokaryotes. RESULTS: In this work, we report the discovery of extracellular crystals formed by bacteria and reveal that they are composed of guanine monohydrate. This composition differs from that of biogenic guanine crystals found in other organisms, mostly composed of ß anhydrous guanine. We demonstrate the formation of these crystals by Aeromonas and other bacteria and investigate the metabolic traits related to their synthesis. In all cases studied, the presence of the bacterial guanine crystals correlates with the absence of guanine deaminase, which could lead to guanine accumulation providing the substrate for crystal formation. CONCLUSIONS: Our finding of the hitherto unknown guanine crystal occurrence in prokaryotes extends the range of organisms that produce these crystals to a new domain of life. Bacteria constitute a novel and more accessible model to study the process of guanine crystal formation and assembly. This discovery opens countless chemical and biological questions, including those about the functional and adaptive significance of their production in these microorganisms. It also paves the road for the development of simple and convenient processes to obtain biogenic guanine crystals for diverse applications.
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Peixes , Guanina , Animais , Guanina/química , Pele , BactériasRESUMO
A female juvenile green turtle (Chelonia mydas), found alive in Guanabara Bay, Rio de Janeiro, Brazil, was weak, dehydrated and cachectic, with a healed fracture in the caudal portion of the carapace. Despite supportive treatment, the animal died after 9 days. At necropsy the main lesions were pallor of visceral organs, arthritis and deposits of whitish granular material in the wall of large arteries and the trachea. Histopathological analysis revealed mild to severe deposition of crystals, consistent with calcium oxalate, in both kidneys and the spleen, heart, small intestine, pancreas, thymus and salt gland, as well as bacterial meningitis, septic arthritis, spirorchidiasis and a fibropapilloma on the nictitating membrane. The main pathological findings were suggestive of septic shock, mainly due to the bacterial meningitis and septic arthritis, with systemic oxalosis and spirorchidiasis as contributing lesions. Although renal oxalosis has been described in green turtles as an incidental finding, presumably due to ingestion of oxalate-containing plants, this turtle had an unusual systemic deposition of oxalate crystals.
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Artrite Infecciosa , Hiperoxalúria , Tartarugas , Animais , Brasil , Hiperoxalúria/veterinária , Oxalatos , Artrite Infecciosa/veterináriaRESUMO
Liquid-crystalline systems are structures that represent an intermediate physical state between isotropic liquid and solid crystal. This particularity brings interesting characteristics of both states such as improved stability, molecular organization, high solubilization potential, diffusion control, and interaction with biological membranes, among others. This chapter describes the structure of liquid-crystalline systems, their classification according to the kind of molecular organization, the material that could be used for liquid crystal formation, the techniques that are applied for characterization, and the process of production. Moreover, the potential of nanostructured liquid-crystalline systems for the delivery of natural products, especially plant-based formulations, is discussed, highlighting the actual state of the art and examples from the literature. Finally, future prospectives for research and application of nanostructured liquid-crystalline systems as formulation of medicines and cosmetic products discussed.
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Abstract Objectives The deposition of monosodium urate (MSU) crystals within synovial joints and tissues is the initiating factor for gout arthritis. Thus, MSU crystals are a vital tool for studying gout's molecular mechanism in animal and cellular models. This study mainly compared the excellence and worseness of MSU crystals prepared by different processes and the degree of inflammation induced by MSU crystals. Methods MSU crystals were prepared using neutralization, alkali titration, and acid titration methods. The crystals' shape, length, quality, and uniformity were observed by polarized light microscopy and calculated by the software Image J. The foot pad and air pouch models were used to assess the different degrees of inflammation induced by the MSU crystals prepared by the three different methods at different time points. Paw swelling was evaluated by caliper. In air pouch lavage fluid, inflammatory cell recruitment was measured by hemocytometer, and the level of IL-1β TNF- α, and IL-18 by ELISA. Inflammatory cell infiltration was assayed by immunohistochemistry of air pouch synovial slices. Results For the preparation of MSU crystals with the same uric acid, the quantity acquired by the alkalization method was highest, followed by neutralization, with the acid titration method being the lowest. The crystals prepared by neutralization were the longest. The swelling index of the foot pad induced by MSU crystals prepared by acid titration was significantly lower than that of the other methods at 24 h. The inflammatory cell recruitment and level of 1-1β, TNF-α, and IL-18 in air pouch lavage fluid were lowest in animals with crystals prepared by acid titration. IL-1β secretion induced by MSU crystals prepared by acid titration was significantly lower than that of the other two groups, but there was no significant difference in IL-18 secretion between the three groups in THP-1 macrophages and BMDMs. Conclusions All three methods can successfully prepare MSU crystals, but the levels of inflammation induced by the crystals prepared by the three methods were not identical. The degree of inflammation induced by MSU crystals prepared by neutralization and alkalization is greater than by acid titration, but the quantity of MSU crystals obtained by the alkalization method is higher and less time-consuming. Apparently, the window of inflammation triggered by acid titration preparation is shorter compared to other forms of crystal preparation. Overall, MSU crystals prepared by the alkaline method should be recommended for studying the molecular mechanisms of gout in animal and cellular models.
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Background and Objectives: Deposits of monosodium urate (MSU) crystals due to increased levels of uric acid (UA) have been associated with bone formation and erosion, mainly in patients with chronic gout. The synovial membrane (SM) comprises several types of cells, including mesenchymal stem cells (SM-MSCs); however, it is unknown whether UA and MSU induce osteogenesis through SM-MSCs. Materials and Methods: Cultures of SM were immunotyped with CD44, CD69, CD90, CD166, CD105, CD34, and CD45 to identify MSCs. CD90+ cells were isolated by immunomagnetic separation (MACS), colony-forming units (CFU) were identified, and the cells were exposed to UA (3, 6.8, and 9 mg/dL) and MSU crystals (1, 5, and 10 µg/mL) for 3 weeks, and cellular morphological changes were evaluated. IL-1ß and IL-6 were determined by ELISA, mineralization was assessed by alizarin red, and the expression of Runx2 was assessed by Western blot. Results: Cells derived from SM and after immunomagnetic separation were positive for CD90 (53 ± 8%) and CD105 (52 ± 18%) antigens, with 53 ± 5 CFU identified. Long-term exposure to SM-MSCs by UA and MSU crystals did not cause morphological damage or affect cell viability, nor were indicators of inflammation detected. Mineralization was observed at doses of 6.8 mg/dL UA and 5 µg/mL MSU crystals; however, the differences were not significant with respect to the control. The highest dose of MSU crystals (10 µg/mL) induced significant Runx2 expression with respect to the control (1.4 times greater) and SM-MSCs cultured in the osteogenic medium. Conclusions: MSU crystals may modulate osteogenic differentiation of SM-MSCs through an increase in Runx2.
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Gota , Células-Tronco Mesenquimais , Humanos , Ácido Úrico/farmacologia , Osteogênese , Subunidade alfa 1 de Fator de Ligação ao Core , ProteínasRESUMO
Metamaterials are broadly defined as artificial, electromagnetically homogeneous structures that exhibit unusual physical properties that are not present in nature. They possess extraordinary capabilities to bend electromagnetic waves. Their size, shape and composition can be engineered to modify their characteristics, such as iridescence, color shift, absorbance at different wavelengths, etc., and harness them as biosensors. Metamaterial construction from biological sources such as carbohydrates, proteins and nucleic acids represents a low-cost alternative, rendering high quantities and yields. In addition, the malleability of these biomaterials makes it possible to fabricate an endless number of structured materials such as composited nanoparticles, biofilms, nanofibers, quantum dots, and many others, with very specific, invaluable and tremendously useful optical characteristics. The intrinsic characteristics observed in biomaterials make them suitable for biomedical applications. This review addresses the optical characteristics of metamaterials obtained from the major macromolecules found in nature: carbohydrates, proteins and DNA, highlighting their biosensor field use, and pointing out their physical properties and production paths.
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Técnicas Biossensoriais , Nanopartículas , Materiais Biocompatíveis , DNA , CarboidratosRESUMO
Calcium oxalate (CaOx) crystals in plants are formed in crystal idioblasts cells and have specific geometric shapes. Their proposed functions include calcium homeostasis and carbon source, among others. Amaranth is a plant that presents high tolerance to abiotic stresses and accumulates considerable amounts of CaOx crystals; however, few studies have focused on characterizing the crystals ultrastructure and none is related to identifying proteins bound to them. This information is of great interest to understand the mechanisms related to CaOx crystal formation and to support their proposed functions. Thus, this work aimed to characterize CaOx crystals in amaranth leaves. Crystals were purified and the proteins bound to them were isolated and identified by nLC-MS/MS. Leaf sections were analyzed by light and electron microscopy. The identified proteins were related to the chloroplast such as ATPb synthase, RuBisCO large subunit, and cell wall-related proteins, which were validated by immunohistochemistry and immunogold labeling. In addition, it was observed that CaOx crystal idioblasts were formed from parenchyma cells associated with mesophyll and veins, in which the thylakoid membranes of degraded chloroplasts turned into crystal chambers. These results significantly advance our understanding of the mechanisms of CaOx crystal formation and the potential function as an alternative carbon source in leaves.
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Oxalato de Cálcio , Cálcio , Oxalato de Cálcio/química , Carbono , Cloroplastos/metabolismo , Cristalização , Ribulose-Bifosfato Carboxilase , Espectrometria de Massas em TandemRESUMO
Almost half of orally administered active pharmaceutical ingredients (APIs) have low solubility, which affects their bioavailability. In the last two decades, several alternatives have been proposed to modify the crystalline structure of APIs to improve their solubility; these strategies consist of inducing supramolecular structural changes in the active pharmaceutical ingredients, such as the amorphization and preparation of co-crystals or polymorphs. Since many APIs are thermosensitive, non-thermal emerging alternative techniques, such as mechanical activation by milling, have become increasingly common as a preparation method for drug formulations. This review summarizes the recent research in preparing pharmaceutical formulations (co-amorphous, co-crystals, and polymorphs) through ball milling to enhance the physicochemical properties of active pharmaceutical ingredients. This report includes detailed experimental milling conditions (instrumentation, temperature, time, solvent, etc.), as well as solubility, bioavailability, structural, and thermal stability data. The results and description of characterization techniques to determine the structural modifications resulting from transforming a pure crystalline API into a co-crystal, polymorph, or co-amorphous system are presented. Additionally, the characterization methodologies and results of intermolecular interactions induced by mechanical activation are discussed to explain the properties of the pharmaceutical formulations obtained after the ball milling process.
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Although urinary crystals are habitual components, urolithiasis formation is always preceded by these concretions. We aimed to identify the change in the crystalline profile in sheep supplemented with ammonium chloride. Twenty-five male sheep aged three months, feedlot and randomly distributed into three groups were used: Control Group (CG) n = 5 did not receive Ammonium Chloride; G200 Group (n=10) (200mg/kg) of Ammonium Chloride for 56 consecutive days; G500 Group (n=10) (500mg/kg) of Ammonium Chloride for 56 consecutive days, administered daily orally. Sampling times and clinical evaluation were performed at seven days, with M0 (immediately before Ammonium Chloride), M1 (seven days after) until M8, totaling 70 days of feedlot. Urine samples were performed to identify the presence, type, and quantity of crystals. There was an increase in crystalluria in all groups in relation to time due to dietary influence, mainly in the CG, which presented more crystals of amorphous calcium phosphate and calcium oxalate. In addition, the G500 Group presented a higher presence of urate/uric acid crystals after urinary acidification, which are closely related to urinary pH.
Apesar de cristais urinários serem componentes habituais, a formação de urolitíase é sempre precedida dessas concreções. O presente estudo objetivou identificar a mudança do perfil cristalúrico em ovinos suplementados com cloreto de amônio. Foram utilizados 25 ovinos, machos, com idade de três meses, confinados e distribuídos aleatoriamente em três grupos: grupo controle (GC) (n=5) não recebeu cloreto de amônio; grupo G200 (n=10) (200mg/kg) recebeu cloreto de amônio por 56 dias consecutivos; grupo G500 (n=10) (500mg/kg) recebeu cloreto de amônio por 56 dias consecutivos, administrados diariamente por via oral. Os momentos (M) de colheita de amostras e avaliação clínica foram realizados com intervalo de sete dias, sendo M0 (imediatamente antes da administração do cloreto de amônio), M1 (sete dias após) até M8, totalizando 70 dias de confinamento. As amostras de urina foram analisadas para se identificar a presença, o tipo e a quantidade de cristais. Houve aumento da cristalúria em todos os grupos em relação ao tempo por influência dietética, principalmente no GC, que apresentou mais cristais de fosfato de cálcio amorfo e oxalato de cálcio. Além disso, o grupo G500 apresentou maior presença de cristais de urato/ácido úrico após acidificação urinária, estando esses intimamente relacionados ao pH urinário.
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Animais , Ovinos/urina , Cálculos Urinários/veterinária , Suplementos Nutricionais/efeitos adversos , Urolitíase/veterinária , Cloreto de Amônio , Doenças Urológicas/veterinária , Urinálise/veterináriaRESUMO
BACKGROUND: There is a growing search for therapeutic targets in the treatment of gout. The present study aimed to evaluate the analgesic and anti-inflammatory potential of angiotensin type 2 receptor (AT2R) antagonism in an acute gout attack mouse model. METHODS: Male wild-type (WT) C57BL/6 mice either with the AT2R antagonist, PD123319 (10 pmol/joint), or with vehicle injections, or AT2R KO mice, received intra-articular (IA) injection of monosodium urate (MSU) crystals (100 µg/joint), that induce the acute gout attack, and were tested for mechanical allodynia, thermal hyperalgesia, spontaneous nociception and ankle edema development at several times after the injections. To test an involvement of AT2R in joint pain, mice received an IA administration of angiotensin II (0.05-5 nmol/joint) with or without PD123319, and were also evaluated for pain and edema development. Ankle joint tissue samples from mice undergoing the above treatments were assessed for myeloperoxidase activity, IL-1ß release, mRNA expression analyses and nitrite/nitrate levels, 4 h after injections. RESULTS: AT2R antagonism has robust antinociceptive effects on mechanical allodynia (44% reduction) and spontaneous nociception (56%), as well as anti-inflammatory effects preventing edema formation (45%), reducing myeloperoxidase activity (54%) and IL-1ß levels (32%). Additionally, Agtr2tm1a mutant mice have largely reduced painful signs of gout. Angiotensin II administration causes pain and inflammation, which was prevented by AT2R antagonism, as observed in mechanical allodynia 4 h (100%), spontaneous nociception (46%), cold nociceptive response (54%), edema formation (83%), myeloperoxidase activity (48%), and IL-1ß levels (89%). PD123319 treatment also reduces NO concentrations (74%) and AT2R mRNA levels in comparison with MSU untreated mice. CONCLUSION: Our findings show that AT2R activation contributes to acute pain in experimental mouse models of gout. Therefore, the antagonism of AT2R may be a potential therapeutic option to manage gout arthritis.
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Dor Aguda , Artrite Gotosa , Gota , Camundongos , Masculino , Animais , Ácido Úrico , Hiperalgesia/tratamento farmacológico , Angiotensina II , Receptor Tipo 2 de Angiotensina , Peroxidase , Camundongos Endogâmicos C57BL , Gota/tratamento farmacológico , Gota/metabolismo , Artrite Gotosa/tratamento farmacológico , Bloqueadores do Receptor Tipo 2 de Angiotensina II/farmacologia , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Antioxidantes/uso terapêutico , Dor Aguda/tratamento farmacológico , RNA MensageiroRESUMO
Eosinophilic diseases, also termed eosinophil-associated diseases (EADs), are characterized by eosinophil-rich inflammatory infiltrates and extensive eosinophil degranulation with clinically relevant organ pathology. Recent evidence shows that eosinophil cytolytic degranulation, that is, the release of intact, membrane-delimited granules that arises from the eosinophil cytolysis, occurs mainly through ETosis, meaning death with a cytolytic profile and extrusion of nucleus-originated DNA extracellular traps (ETs). The ultrastructural features of eosinophil ETosis (EETosis) have been studied mostly in vitro after stimulation, but are still poorly understood in vivo. Here, we investigated in detail, by transmission electron microscopy (TEM), the ultrastructure of EETosis in selected human EADs affecting several tissues and organ systems. Biopsies of patients diagnosed with eosinophilic chronic rhinosinusitis/ECRS (frontal sinus), ulcerative colitis/UC (intestine), and hypereosinophilic syndrome/HES (skin) were processed for conventional TEM. First, we found that a large proportion of tissue-infiltrated eosinophils in all diseases (~45-65% of all eosinophils) were undergoing cytolysis with release of free extracellular granules (FEGs). Second, we compared the morphology of tissue inflammatory eosinophils with that shown by in vitro ETosis-stimulated eosinophils. By applying single-cell imaging analysis, we sought typical early and late EETosis events: chromatin decondensation; nuclear delobulation and rounding; expanded nuclear area; nuclear envelope alterations and disruption; and extracellular decondensed chromatin spread as ETs. We detected that 53% (ECRS), 37% (UC), and 82% (HES) of all tissue cytolytic eosinophils had ultrastructural features of ETosis in different degrees. Eosinophils in early ETosis significantly increased their nuclear area compared to non-cytolytic eosinophils due to excessive chromatin decondensation and expansion observed before nuclear envelope disruption. ETosis led not only to the deposition of intact granules, but also to the release of eosinophil sombrero vesicles (EoSVs) and Charcot-Leyden crystals (CLCs). Free intact EoSVs and CLCs were associated with FEGs and extracellular DNA nets. Interestingly, not all cytolytic eosinophils in the same microenvironment exhibited ultrastructure of ETosis, thus indicating that different populations of eosinophils might be selectively activated into this pathway. Altogether, our findings captured an ultrastructural signature of EETosis in vivo in prototypic EADs highlighting the importance of this event as a form of eosinophil degranulation and release of inflammatory markers (EoSVs and CLCs).
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Eosinófilos , Síndrome Hipereosinofílica , Cromatina/metabolismo , DNA/metabolismo , Eosinófilos/metabolismo , Humanos , Síndrome Hipereosinofílica/patologia , Microscopia Eletrônica de TransmissãoRESUMO
A 3-year-old male cockatiel (Nymphicus hollandicus) was diagnosed with joint arthritis due to hyperucemiasyndrome. The bird presented deposition of urate crystals on the synovial membrane with inflammation of joints and tendons (tufts), causing listlessness, anorexia and lameness, with difficulty in keeping perched or moving. Laboratory tests displayed an increase in uric acid and creatinine phosphokinase levels, and leukocytosis despite lymphopenia. Unsucessfully, the animal had been treated with allopathic medicine for 2 months, without a favorable response and still developing stressful reaction to handling.Methodology:High dilution therapy was attempted with 2 globules of Lycopodiumclavatum30 cH /bid and Arnica montana30 cH /bid /oral. The most expressive tufts were removed with daily cleaning of the affected area; a new diet was established and perches were removed, allowing the bird to remain on a flat surface until regression of symptoms. The medication was continued for 30 days. On the second appointment, although the caregiver reported episodes of probable pain, there was an improvement in behavior with normal appetite. Lyc30cH /sid was continued and Arn30cH /bid to qid, depending on pain episodes, for over 30 days. The tutor authorized the case report through a consent form. Results and discussion:Follow-up laboratory tests were performed everythree months for one year, reaching normal levels for uric acid (3.5-11 mg/dL) and CK (30-245mg/dL) on the third measurement. The bird presented no formation of new tufts along the second month of treatment. After 12 months, the animal ingests homeopathic globules spontaneously and presents stable clinical presentation (Lyc30cH / sid / 3 times a week) with no recurrence and without side effects nor stressful behavior. Conclusion: In view of these results, it is considered that homeopathic treatment is an option to be considered in the treatment of joint arthritis from hyperuricemia syndrome in birds.