Search

Gout is an inflammatory disease triggered by deposition of monosodium urate (MSU) crystals in the joints, resulting in high neutrophil influx and pain. Here, we studied the role of the inhibitory receptor CD300a in the resolution process in a murine model of gout. We found increased CD300a expression on neutrophils emigrated to the joint. When compared to WT mice, CD300a(−/−) mice had persistent neutrophil influx till 24 hr after MSU injection. This was associated with increased concentration of IL‐1β and greater tissue damage in the joints of CD300a(−/−) mice. There was an increase in the percentage of apoptotic neutrophils in the synovial lavage of WT mice, as compared to CD300a(−/−) mice. This difference was reflected in the decline of efferocytic events in the synovial cavity of CD300a(−/−) mice 24 hr after MSU injection. A CD300a agonistic antibody was shown, for the first time, to increase apoptosis of human neutrophils, and this was associated with cleavage of caspase‐8. In conclusion, our results reveal an important role of CD300a in the control of leucocyte infiltration, IL‐1β production and caspase‐8 cleavage in neutrophils, contributing to the resolution of inflammation triggered by MSU injection.

Bioactive glasses (BGs) have shown great potential for tissue regeneration and their composition flexibility allows the incorporation of different ions with physiological activities and therapeutic properties in the glass network. Among the many ions that could be incorporated, cobalt (Co) is a significant one, as it mimics hypoxia, triggering the formation of new blood vessels by the vascular endothelial growth factor A (VEGFA), due to the stabilizing effect on the hypoxia inducible factor 1 subunit alpha (HIF1A), an activator of angiogenesis-related genes, and is therefore of great interest for tissue engineering applications. However, despite its promising properties, the effects of glasses incorporated with Co on angiogenesis, through human umbilical cord vein endothelial cells (HUVECs) studies, need to be further investigated. Therefore, this work aimed to evaluate the biocompatibility and angiogenic potential of a new sol-gel BG, derived from the SiO2 -CaO-P2 O5 -CoO system. The structural evaluation showed the predominance of an amorphous glass structure, and the homogeneous presence of cobalt in the samples was confirmed. in vitro experiments showed that Co-containing glasses did not affect the viability of HUVECs, stimulated the formation of tubes and the gene expression of HIF1A and VEGFA. in vivo experiments showed that Co-containing glasses stimulated VEGFA and HIF1A expression in blood vessels and cell nuclei, respectively, in the deep dermis layer of the dorsal region of rats, featuring considerable local stimulation of the angiogenesis process due to Co-release. Co-containing glasses showed therapeutic effect, and Co incorporation is a promising strategy for obtaining materials with superior angiogenesis properties for tissue engineering applications.

Streptococcus pneumoniae is a major cause of community-acquired pneumonia leading to high mortality rates. Inflammation triggered by pneumococcal infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Annexin A1 (AnxA1) mainly acts through Formyl Peptide Receptor 2 (FPR2) inducing the resolution of inflammation. Here, we have evaluated the role of AnxA1 and FPR2 during pneumococcal pneumonia in mice. For that, AnxA1, Fpr2/3 knockout (KO) mice and wild-type (WT) controls were infected intranasally with S pneumoniae. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals. Mechanistically, the absence of AnxA1 resulted in the loss of lung barrier integrity and increased neutrophil activation upon S pneumoniae stimulation. Importantly, treatment of WT or AnxA1 KO-infected mice with Ac2-26 decreased inflammation, lung damage, and bacterial burden in the airways by increasingStreptococcus pneumoniae is a major cause of community-acquired pneumonia leading to high mortality rates. Inflammation triggered by pneumococcal infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Annexin A1 (AnxA1) mainly acts through Formyl Peptide Receptor 2 (FPR2) inducing the resolution of inflammation. Here, we have evaluated the role of AnxA1 and FPR2 during pneumococcal pneumonia in mice. For that, AnxA1, Fpr2/3 knockout (KO) mice and wild-type (WT) controls were infected intranasally with S pneumoniae. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals. Mechanistically, the absence of AnxA1 resulted in the loss of lung barrier integrity and increased neutrophil activation upon S pneumoniae stimulation. Importantly, treatment of WT or AnxA1 KO-infected mice with Ac2-26 decreased inflammation, lung damage, and bacterial burden in the airways by increasing macrophage phagocytosis. Conversely, Ac2-26 peptide was ineffective to afford protection in Fpr2/3 KO mice during infection. Altogether, these findings show that AnxA1, via FPR2, controls inflammation and bacterial dissemination during pneumococcal pneumonia by promoting host defenses, suggesting AnxA1-based peptides as a novel therapeutic strategy to control pneumococcal pneumonia.

BACKGROUND Telomeres are specialized DNA structures that are critical to maintain cell homeostasis and to avoid genomic instability. Epidemiological studies have examined the association between leukocyte telomere length (LTL) and risk of cancers, but the findings remain conflicting. METHODS Mean LTL was measured by quantitative PCR in 97 patients with head and neck cancer (HNC) and 262 healthy controls. The association between LTL and patients' clinical status, such as smoke, alcoholism, and overall survival, were also evaluated. RESULTS The age-adjusted LTL was significantly shorter in patients with HNC in comparison to healthy controls (P = .0003). Patients with shortest LTL had an increased risk to develop HNC (P

Staphylococcus aureus is the main pathogen associated with septic arthritis. Upon infection, neutrophils are quickly recruited to the joint by different chemoattractants, especially CXCR1/2 binding chemokines. Although their excessive accumulation is associated with intense pain and permanent articular damage, neutrophils have an important function in controlling bacterial burden. This work aimed to study the role of CXCR2 in the control of infection, hypernociception and tissue damage in S. aureus-induced septic arthritis in mice. The kinetics of neutrophil recruitment correlated with the bacterial load recovered from inflamed joint after intra-articular injection of S. aureus. Treatment of mice from the start of infection with the non-competitive antagonist of CXCR1/2, DF2156A, reduced neutrophil accumulation, cytokine production in the tissue, joint hypernociception and articular damage. However, early DF2156A treatment increased the bacterial load locally. CXCR2 was important for neutrophil activation and clearance of bacteria in vitro and in vivo. Start of treatment with DF2156A 3 days after infection prevented increase in bacterial load and reduced the hypernociception in the following days, but did not improve tissue damage. In conclusion, treatment with DF2156A seems be effective in controlling tissue inflammation and dysfunction but its effects are highly dependent on the timing of the treatment start.

Gout is a self-limited inflammatory disease caused by deposition of monosodium urate (MSU) crystals in the joints. Resolution of inflammation is an active process leading to restoration of tissue homeostasis. Here, we studied the role of Annexin A1 (AnxA1), a glucocorticoid-regulated protein that has anti-inflammatory and proresolving actions, in resolution of acute gouty inflammation. Injection of MSU crystals in the knee joint of mice induced inflammation that was associated with expression of AnxA1 during the resolving phase of inflammation. Neutralization of AnxA1 with antiserum or blockade of its receptor with BOC-1 (nonselective) or WRW4 (selective) prevented the spontaneous resolution of gout. There was greater neutrophil infiltration after challenge with MSU crystals in AnxA1 knockout mice (AnxA1-/- ) and delayed resolution associated to decreased neutrophil apoptosis and efferocytosis. Pretreatment of mice with AnxA1-active N-terminal peptide (Ac2-26 ) decreased neutrophil influx, IL-1β, and CXCL1 production in periarticular joint. Posttreatment with Ac2-26 decreased neutrophil accumulation, IL-1β, and hypernociception, and improved the articular histopathological score. Importantly, the therapeutic effects of Ac2-26 were associated with increased neutrophils apoptosis and shortened resolution intervals. In conclusion, AnxA1 plays a crucial role in the context of acute gouty inflammation by promoting timely resolution of inflammation.

Pentachlorophenol (PCP) is globally dispersed and contamination of soil with this biocide adversely affects its functional biodiversity, particularly of fungi - key colonizers. Their functional role as a community is poorly understood, although a few pathways have been already elucidated in pure cultures. This constitutes here our main challenge - elucidate how fungi influence the pollutant mitigation processes in forest soils. Circumstantial evidence exists that cork oak forests in N. W. Tunisia - economically critical managed forests are likely to be contaminated with PCP, but the scientific evidence has previously been lacking. Our data illustrate significant forest contamination through the detection of undefined active sources of PCP. By solving the taxonomic diversity and the PCP-derived metabolomes of both the cultivable fungi and the fungal community, we demonstrate here that most strains (predominantly penicillia) participate in the pollutant biotic degradation. They form an array of degradation intermediates and by-products, including several hydroquinone, resorcinol and catechol derivatives, either chlorinated or not. The degradation pathway of the fungal community includes uncharacterized derivatives, e.g. tetrachloroguaiacol isomers. Our study highlights fungi key role in the mineralization and short lifetime of PCP in forest soils and provide novel tools to monitor its degradation in other fungi dominated food webs.

The purpose of this study was to evaluate the relationship between chemokines and dendritic cells (DCs) in human chronic periodontitis (CP).Gingival samples were obtained from 23 individuals with CP, and six samples of normal mucosa (NM) overlapping the third molar were used to control for the chemokine levels. Periodontal examination was conducted. Immunohistochemistry was performed for Factor XIIIa(+) and cluster of differentiation (CD)1a(+) immature DCs and CD83(+) mature DCs. Levels of the CC chemokine ligand (CCL)2, CCL3, CCL5, CCL19, CCL20, and CXC chemokine ligand (CXCL)8 were measured in gingival tissues using enzyme-linked immunosorbent assay. Inflammatory infiltrate, DCs, chemokines, classification of human CP, and clinical parameters were correlated and compared.The expression of CCL2 and CCL20 was positively correlated with increased densities of CD1a(+) DCs. CCL3 and CXCL8 were positively related to the clinical attachment level. CCL3, CCL5, CCL19, and CXCL8 levels increased in the gingival samples of patients with CP compared with NM, whereas CCL20 levels increased in advanced CP compared with mild-moderate CP.More CD1a(+) immature DCs are related to CCL2 and CCL20. CCL3 and CXCL8 chemokines are related to a greater severity of human CP.

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading. Type 1 diabetes results in bone remodeling, suggesting that this disease might affect orthodontic tooth movement. The present study investigated the effects of the diabetic state on orthodontic tooth movement. An orthodontic appliance was placed in normoglycemic (NG), streptozotocin-induced diabetes (DB), and insulin-treated DB (IT) C57BL6/J mice. Histomorphometric analysis and quantitative PCR of periodontium were performed. The DB mice exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphate (TRAP) -positive osteoclasts than NG mice. This was associated with increased expression of factors involved in osteoclast activity and recruitment (Rankl, Csf1, Ccl2, Ccl5, and Tnfa) in DB mice. The expression of osteoblastic markers (Runx2, Ocn, Col1, and Alp) was decreased in DB mice. Reversal of the diabetic state by insulin treatment resulted in morphological findings similar to those of NG mice. These results suggest that the diabetic state up-regulates osteoclast migration and activity and down-regulates osteoblast differentiation, resulting in greater orthodontic tooth movement.

Objectives: Solid caustic soda (CS) ingestion levels continue high in Brazil. The aggressiveness of a caustic agent depends, among other factors, on its concentration and time of contact with mucosa. However, the interdependence of these factors in the production of caustic lesion in the esophageal mucosa is not known, especially regarding CS as the strongest corrosive agent. We analyze the effects of concentration and time of contact on the aggressiveness of CS to the esophagus of live animals. Study Design/Methods: One milliliter of CS at concentrations between 1.83% and 73.33% was applied to rats. The solution was kept in contact with the mucosa for 10 to 120 minutes. Internal and external organ aspects were analyzed and the epithelium, submucosa, muscle layer, and adventitia were analyzed microscopically Results: Epithelial necrosis was observed at all concentrations. Among the necrotic layers, the submucosa was observed starting at the 7.33% concentration, and the muscular layer and adventitia were observed at 14.66% concentration. Damage to the pulmonary parenchyma and trachea occurred at 33.66% after 10 minutes, and perforation of the esophagus was observed only after 120 minutes. After 10 minutes, important corrosive lesions installed in the esophageal layers, expanding in depth and superficial extension. The use of heparin had no effect on the production of lesions. Conclusions: Ten minutes were sufficient to provoke necrosis, and longer contact increased the area of necrosis. Solution concentration levels were more important in damage production: 1.83% was sufficient for epithelial necrosis, 7.33% caused submucosal necrosis, and 14.66% muscle and adventitia necrosis; 33.66% solutions caused lung and trachea damage after 10 minutes and esophageal perforation after 120 minutes.

Background. There is considerable interest in the expression of cancer testis (CT) antigens in human cancers, because they may serve as the basis for diagnostic tests or an immunologic approach to therapy, or as prognostic markers. Methods. On this basis, we evaluated by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) the expression of genes that code for tumor antigens (melanoma antigen-1 [MAGE-1], MAGE-4, MAGE-10, MAGE-12, B melanoma antigen, CTL-recognized antigen melanoma antigen (CT antigen 2) [LAGE], New York esophageal squamous cell carcinoma antigen (CT antigen 1) [NYESO-1], and preferentially expressed antigen of melanoma [PRAME]) in surgical samples of the tumors, margins, and lymph nodes (when present) from patients with a diagnosis of head and neck carcinoma. The study was conducted on 33 patients (31 men and two women), aged 31 to 94 years (mean, 56 years), with squamous cell carcinomas located in the mouth (15 cases), larynx (14 cases), and pharynx (four cases). Results. The findings were compared with the clinical course and laboratory data. Expression of at least one antigen was observed in 66.6% of cases, with different rates of expression according to tumor staging (100% of T4, 57% of T3, 50% of T1 and T2) and smoking habit. There was a significantly higher expression of multiple genes (two or more) in tumors in advanced stages. Conclusions. We conclude that the tumor-specific antigen genes are expressed in variable frequencies and intensities in the primary lesions of head and neck squamous cell carcinomas and in their metastases, with expression of the PRAME gene being always present in the metastastatic lymph nodes. In primary lesions, gene expression correlated with smoking habit and with advanced tumors with a higher malignant potential, with the frequent expression of two or more of these genes. © 2006 Wiley Periodicals, Inc. Head Neck, 2006

The hypothesis that jugular thrombosis (JT) may cause a mass in the cervical region is usually overlooked. The objective of the present study was to identify the characteristics of neck masses resulting from JT in cancer patients and to analyze the possible reasons for their formation. A retrospective study was conducted on 8 patients with JT affected by 3 types of neoplasia, ie, carcinomas (3 cases), adenocarcinomas (3 cases), and lymphomas (2 cases) located in the breast, digestive apparatus, lymphatic system (2 cases each), lung and an undetermined site (1 case each), diagnosed over the last 12 years. The most frequent symptom of JT was the presence of a mass in the supraclavicular space (62.5% of cases) deeply located on the anterior margin of the sternocleidomastoid muscle and diagnosed by computed tomography and ultrasound. The masses were slightly hardened, with a clearly defined upper limit and an imprecise lower limit and with an irregular surface. The patients also presented with cough, hoarseness, pain during movements, facial edema, and collateral circulation. In one of the patients with a lung cancer, JT symptoms preceded the symptoms of cancer by 2 months. Hypercoagulation, compression, and invasion of a vessel possibly explain the occurrence of JT in these patients.

The lymphoid follicles at the base of the tongue can be detected when examining the pharynx of adults, but the presence of large follicles, denoted "severe" hypertrophy of the base of the tongue (HBT) is rare. The objective of the present study was to identify severe HBT cases and their symptoms and to correlate them with the presence of pharyngolaryngeal signs and esophageal symptoms of gastroesophageal reflux (GER) in patients seen at a laryngology clinic. Severe HBT was considered to be present when the follicles prevented the view of the epiglottis or were massively distributed through the pharynx and larynx. Five cases of severe HBT were detected among 306 patients submitted to videolaryngoscopy over a period of 2 years, corresponding to 1.6% (5/306) of the total sample studied. However, this index markedly increases to 4% (4/101) among patients with pharyngolaryngeal signs of GER and reached 7.5% (4/53) among patients presenting GER symptoms such as heartburn, regurgitation, retrosternal burning feeling, and dysphagia. The complaints due to severe HBT were noisy respiration, hoarseness, throat clearing, dry cough, globus pharyngeus, and nasal voice. We conclude that the frequency of hypertrophied follicles is increased in the presence of signs and symptoms of GER and those HBT symptoms are confused with those of GER, except for nasal voice and noisy respiration.

The reimplantation of a complete tracheal segment (CTS) as an autograft or homograft often results in total or partial necrosis of the CTS. However, previous experiments suggested that when the CTS is first vascularized by the sternohyoid muscle (SM) 21 days before the reimplantation, the CTS can be reimplanted without ischemia or stenosis. However, it is not clear if the CTS requires 21 days to attain full revascularization.This study aims to ascertain the minimum time necessary for revascularization of the 6 rings CTS by the SM allowing reimplantation free of ischemia.Fifteen mongrel dogs, divided into 3 groups were submitted to 2 sequential surgical procedures. In the first procedure, a SM flap was used to envelop 6 rings CTS in all dogs. After periods of 21 days (group 1, n = 5), 14 days (group 2, n = 5) and 7 days (group 3, n = 5), the compound flaps (CTS and SM) were neovascularized. Each CTS was transected and mobilized from the trachea and then replaced again in its original site, as an autoflap.After a period of at least 60 days, none of dogs presented any respiratory alteration. Macroscopic and microscopic analyses demonstrated adequate viability and no stenosis.Our findings suggest that it is possible to neovascularize the CTS using a SM flap within a period as short as 1 week.

The objective of this study was to determine a possible association between pharyngolaryngeal signs of gastroesophageal reflux (GER) and hypertrophy of the lymphoid follicles at the base of the tongue (HBT). For this purpose, 306 patients submitted to videolaryngoscopy were studied retrospectively and classified according to the presence and size of follicles on the base of the tongue. HBT was considered to be present when the follicles prevented the view of the vallecula. The patients were grouped according to the presence of videolaryngoscopic signs of GER and further subdivided according to the presence of esophageal, pharyngolaryngeal, and esophagopharyngolaryngeal symptoms, with an attempt made to relate these symptoms to the presence of HBT. HBT was detected in 62.4% (63/101) of the patients with signs of GER and in 29.3% (60/205) of patients with no signs of GER. When HBT incidence was studied according to the symptoms reported by the patient, the condition was found to be present in 57.2% (8/14) of patients with exclusively esophageal symptoms, in 63.6% (21/33) with esophagopharyngolaryngeal symptoms, and in 75% (15/20) with exclusively pharyngolaryngeal symptoms. We conclude therefore that HBT is associated with GER. (Otolaryngol Head Neck Surg 2000;122:607-10.)

Five children with Ewing's sarcoma, an uncommon neoplasm originating in the facial bones, were treated with chemotherapy, surgery, and radiotherapy. Younger children have poor prognoses. Children with tumors originating in the mandible appear to have better prognoses. Hematogenic metastases were the most frequent and those originating from maxillary tumors showed much faster growth and were resistant to the chemotherapy used.

Cervical trachea reconstruction with a non-stented platysma myocutaneous door flap (NPMCF) was studied in 23 dogs. Window defects involving 5, 10, or 15 rings and the whole anterior tracheal wall were produced in 3 different groups of animals. A segmentary defect involving the resection of 3 tracheal rings but preserving the posterior membranous wall was created in another group. The results were evaluated by clinical follow-up of up to 100 days, by tracheoscopy 1 week after surgery, and by macroscopic and microscopic examination after the animals' natural death or sacrifice. The NPMCF proved to be adequate for the reconstruction of window defects limited to 5 and 10 rings, with success rates of 100% and 75%, respectively. The use of the NPMCF for tracheal reconstruction had the following main advantages: 1. relatively simple, easy, and expeditious surgery; 2. use of a single operative field; 3. availability of large amounts of donor tissue; 4. adequate thickness; 5. reliable irrigation; 6. resistance to environmental exposure as evidenced by absence of infection; and 7. 100% take rate with no granulomas or scar stenosis at the suture lines. However, luminal occlusion due to flap collapse was a 100% fatal complication when the NPMCP was used either for reconstruction of larger window tracheal defects (15 rings—group 3) or segmentary defects (group 4); this was the main limitation of the method, followed by hair growth with accumulation of secretions, which can be easily dealt with. It can be anticipated that this method has a potential for application in well-selected patients.