ABSTRACT
Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are inflammatory diseases with different bone remodeling patterns. Fibroblast-like synoviocytes (FLS) are cells involved in the transition from an acute and reparable phase to a chronic and persistent stage in these diseases. The distinction of joint phenotypes involves inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and IL-22 directly or through key signaling pathways such as Wnt. To evaluate the role of FLS as the source of Wnt antagonists (sFRP3/FRZB and Dkk1) in the synovia, levels of TNF- α, IL-17, IL-22, Dkk1, and sFRP3 were measured by ELISA directly in the synovial fluid of patients with RA, PsA, or AS. Dkk1 and sFRP3 were also measured in the FLS culture supernatants after different inflammatory stimulus. sFRP3 and Dkk1 are constitutively expressed by FLS. IL-22 and sFRP3 were positively correlated (r=0.76; P<0.01) in synovial fluid. The stimulation of FLS with IL-22, but not TNF-alpha and IL-17, increased the production of sFRP3. No stimulus altered the basal expression of Dkk1. These results showed, for the first time, the ability of IL-22 to increase the expression of sFRP3/FRZB by human FLS in both in vitro and ex vivo models. This finding linked IL-22 to local inhibition of Wnt signaling and possibly to blockade of osteogenesis. Furthermore, FLS presented as a source of this inhibitor in synovial fluid, assigning to this cell a bone injury mechanism.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Interleukins/metabolism , Synoviocytes , Synovial Membrane , Cells, Cultured , Tumor Necrosis Factor-alpha , FibroblastsABSTRACT
Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals) and hypotensive resuscitation at 60 percent of baseline MAP (10 animals). Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg). Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1 percent), sham (95 ± 2.8 vs 59 ± 4.1 percent), and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1 percent). Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.
Subject(s)
Animals , Male , Rabbits , Fluid Therapy/methods , Resuscitation/methods , Shock, Hemorrhagic/therapy , Shock, Traumatic/therapy , Disease Models, Animal , Hematocrit , Shock, Hemorrhagic/blood , Shock, Hemorrhagic/etiology , Shock, Traumatic/blood , Shock, Traumatic/complicationsABSTRACT
Inquéritos flebotomínicos realizados em trës ecótopos distintos: Silvestre, ecótono e ambiente aberto. Foram realizados no período de um ano no Município de Santana do Deserto. Aplicando a metodología de captura com isca humana, coletamos 3.535 flebótomos pertenecentes a 14 espécies. Lutzomyia intermedia predominou, com preferencia aos ambientes aberto e ecótono, confirmando seu caráter euritópico nas áreas endemicas do sudeste e seu grau antropofilico. A segunda espécie mais frequente foi a Lutzomyia carreirai com maior densidade no ecótopo silvestre, onde demonstrou ser bastante antropofílica. As outras espécies compareceram com densidades reduzidas