Holdergamble3552

OBJECTIVE TNF-α, which acts directly on osteoclastogenesis, may modify bone turnover. Thus, the objective of this study was to evaluate the influence of infliximab on extraction socket healing. MATERIAL AND METHODS Eighty-four Wistar rats were randomized into two groups (infliximab EV 5 mg / kg or saline EV 1 ml / kg) and submitted to lower first molar extraction protocol. The animals were sacrificed 1, 3, 7, 14, 21 and 28 days after surgery. The jaws were subjected to radiographic, histomorphometric, histochemical (picrosirius red) and immunohistochemical (TNF-α, RANKL and OPG) analysis. RESULTS No differences were observed between the groups in surgical difficulty parameters mass of teeth, number of root fractures and surgical time. Lower area filling with bone as well as increased amounts of remaining cicatricial tissue were observed in the infliximab group at 14 days (p less then 0.001). Lower scores for polymorphonuclear neutrophils were seen at 3 (p less then 0.01) and 7 days (p less then 0.001), lower mononuclear counts at 7 days (p less then 0.01) and lower osteoclast counts at 7 and 14 days (p less then 0.01 and p less then 0.001, respectively). Additionally, reduced TNF-α, RANKL and OPG immunoreactivity were observed, especially at 7 days (p less then 0.05). CONCLUSION TNF-α inhibitor may alter the bone repair capacity after tooth extraction, especially in the initial repair periods, by lower expression of TNF α, RANKL and OPG. Thus, additional caution may be needed in patients who use this class of medication after dental extraction. INTRODUCTION This study retrospectively evaluated outcomes and adverse radiation effects (AREs) associated with stereotactic body radiation therapy (SBRT) for canine heart base tumors (HBTs). A secondary aim was to identify any demographic or echocardiographic factors that might determine which dogs would most benefit from SBRT. ANIMALS Twenty-six dogs that received SBRT for an imaging-based diagnosis of a HBT were evaluated. METHODS Twenty-three dogs were treated with three fractions of 10 Gy delivered daily or every other day. The remaining 3 dogs received variable protocols of one to five fractions. Demographic, echocardiographic, and radiographic information, AREs, and treatment responses were collected. Correlations of these data with survival time were evaluated. RESULTS The median overall survival time was 404 days (95% confidence interval 239-554 days). The majority of dogs experienced a partial response (25%) or stable disease (60%) for a median duration of 333 days (95% confidence interval 94-526 days). Three dogs had progressive disease within six months of SBRT. Radiographic pneumonitis was identified in 7 of 23 dogs, and clinical pneumonitis was identified in 4 dogs. WM-1119 No other AREs were noted. The rate of distant metastasis was 13%. On multivariate analysis, it was found that vena caval obstruction, supraventricular and ventricular arrhythmias, clinical signs, and enlarged locoregional lymph nodes at presentation were negatively associated with survival time. CONCLUSIONS Stereotactic body radiation therapy was delivered with a low rate and degree of normal tissue complications. Asymptomatic dogs with confirmed, progressive growth of a HBT may most likely benefit from SBRT. BACKGROUND Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent episodes of subcutaneous/submucosal edema, which may be preceded by erythema marginatum (EM) as a prodromal symptom. Our aim was to analyze the changes occurring in the parameters of the coagulation system during the development of EM and HAE attacks. MATERIALS AND METHODS Eight C1-INH-HAE patients (1 male, 7 females, median age 41.7 years) were studied. Blood samples were obtained from all patients (during symptom-free periods, EM, and HAE attacks), as well as from 20 sex- and age-matched healthy controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, Factor V, Factor VII, Factor X, Factor XI, and Factor XII levels were measured. RESULTS D-dimer levels were significantly lower, whereas aPTT was significantly prolonged in healthy controls vs. the values measured during the symptom-free period (p = 0.0497; p = 0.0043), in the presence of EM (p = 0.002; p = 0.0002), or during HAE attacks (p  less then  0.0001; p = 0.0002). We observed the following differences between samples taken during HAE attacks vs. in symptom-free periods D-dimer levels were significantly elevated (p = 0.0391), while aPTT was significantly shorter during HAE attacks (p = 0.0159). D-dimer levels were significantly higher during EM than in symptom-free periods (p = 0.0078). Comparing the samples drawn during EM or during HAE attacks, there were no significant differences in the study parameters. CONCLUSIONS D-dimer levels were elevated during EM and this suggests that EM may be part of the HAE attack. Nevertheless, further research into the complement and kinin-kallikrein systems is needed in more patients for a better understanding of the pathomechanism of EM. Small molecule inhibitors have proven useful in the treatment of a variety of tumors, but they are often limited by unsustainable benefits and confer resistance quickly. Immunotherapy can result in durable clinical responses, but activity only occurs in a minority of patients. The unfavorable tumor microenvironment (TME) is an important factor limiting immunotherapy. An appropriate understanding of how small molecule inhibitors modulate the TME may optimize the combination of targeted treatment and immunotherapy in managing tumors. In this study, we found that transient treatment with sunitinib malate inhibited the disorganized extension of tumor vessels, pericytes and collagen IV but increased the relative ratio of pericyte-wrapping blood vessels with alleviated hypoxia in tumors, which resulted from tumor vascular normalization. Sunitinib malate increased infiltration of CD8+ T cells and decreased regulatory T cells (Tregs), accompanied by inhibited expression of TGF-β1 and IL-10 and increased CCL-28, IFN-γ and IL-12, but no significant inhibition of myeloid-derived suppressor cells (MDSCs) was observed.