30 research outputs found

    Muscle-specific overexpression of AdipoR1 or AdipoR2 gives rise to common and discrete local effects whilst AdipoR2 promotes additional systemic effects

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    Hypoadiponectinemia and adiponectin resistance are implicated in the aetiology of obesity-related cardiometabolic disorders, hence represent a potential therapeutic axis. Here we characterised the effects of in vivo electrotransfer-mediated overexpression of the adiponectin receptors, AdipoR1 or AdipoR2, into tibialis anterior muscle (TAM) of lean or obese mice. In lean mice, TAM-specific overexpression of AdipoR1 (TAMR1) or AdipoR2 (TAMR2) increased phosphorylation of AMPK, AKT and ERK and expression of the insulin responsive glucose transporter glut4. In contrast, only TAMR2 increased pparα and a target gene acox1. These effects were decreased in obese mice despite no reduction in circulating adiponectin levels. TAMR2 also increased expression of adipoQ in TAM of lean and obese mice. Furthermore, in obese mice TAMR2 promoted systemic effects including; decreased weight gain; reduced epididymal fat mass and inflammation; increased epididymal adipoQ expression; increased circulating adiponectin. Collectively, these results demonstrate that AdipoR1 and AdipoR2 exhibit overlapping and distinct effects in skeletal muscle consistent with enhanced adiponectin sensitivity but these appear insufficient to ameliorate established obesity-induced adiponectin resistance. We also identify systemic effects upon TAMR2 in obese mice and postulate these are mediated by altered myokine production. Further studies are warranted to investigate this possibility which may reveal novel therapeutic approaches

    Interactions of Adiponectin and Lipopolysaccharide from Porphyromonas gingivalis on Human Oral Epithelial Cells

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    BACKGROUND: Periodontitis is an inflammatory disease caused by pathogenic microorganisms, such as Porphyromonas gingivalis, and characterized by the destruction of the periodontium. Obese individuals have an increased risk for periodontitis and show decreased serum levels of adiponectin. This in-vitro study was established to examine whether adiponectin modulates critical effects of lipopolysaccharide (LPS) from P. gingivalis on oral epithelial cells (OECs). METHODOLOGY/PRINCIPAL FINDINGS: The presence of adiponectin and its receptors in human gingival tissue samples and OECs was analyzed by immunohistochemistry and PCR. Furthermore, OECs were treated with LPS and/or adiponectin for up to 72 h, and the gene expression and protein synthesis of pro- and anti-inflammatory mediators, matrix metalloproteinases (MMPs) and growth factors were analyzed by real-time PCR and ELISA. Additionally, cell proliferation, differentiation and in-vitro wound healing were studied. The nuclear translocation of NFκB was investigated by immunofluorescence. Gingival tissue sections showed a strong synthesis of adiponectin and its receptors in the epithelial layer. In cell cultures, LPS induced a significant up-regulation of interleukin (IL) 1β, IL6, IL8, MMP1 and MMP3. Adiponectin abrogated significantly the stimulatory effects of LPS on these molecules. Similarly, adiponectin inhibited significantly the LPS-induced decrease in cell viability and increase in cell proliferation and differentiation. Adiponectin led to a time-dependent induction of the anti-inflammatory mediators IL10 and heme oxygenase 1, and blocked the LPS-stimulated NFκB nuclear translocation. CONCLUSIONS/SIGNIFICANCE: Adiponectin may counteract critical actions of P. gingivalis on oral epithelial cells. Low levels of adiponectin, as observed in obese individuals, may increase the risk for periodontal inflammation and destruction

    Undifferentiated carcinoma of the nasopharynx and leukemoid reaction: report of a case and literature review

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    A case of undifferentiated carcinoma of the nasopharynx presenting as a cervical mass associated with a paraneoplastic neutrophilic leukemoid reaction is reported. The diagnosis of undifferentiated nasopharyngeal carcinoma of the Regaud type was established by the presence of aggregates of epithelial neoplastic cells separated by areas of reactive lymphoid cells; the epithelial nature being confirmed by the positivity for epithelial markers (AE1/AE3, EMA). Serum IL-1a, GM-CSF and TNF alpha remained undetectable suggesting that these factors were not involved in the occurrence of the paraneoplastic leukemoid syndrome.Case ReportsJournal ArticleReviewSCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Intraoperative measurement of parathyroid hormone in minimally invasive surgery for parathyroid adenoma

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    INTRODUCTION: In the past bilateral neck exploration was the gold standard for successful surgical management of primary hyperparathyroidism. More restricted procedures have been introduced recently thanks to imaging techniques and intraoperative parathyroid hormone assay confirming eradication of hyperfunctioning tissue. METHODS: Thirty patients operated for parathyroid adenoma were submitted to intraoperative PTH determination with Quick Pack immunochemiluminescent assay (Nichols lab.) prior to excision and 5, 10 and 20 minutes after removal of the presumed hyperactive gland. Eleven patients were operated on by a minimally invasive procedure with videoassistance. RESULTS: Response to excision of the hyperfunctioning gland was evidenced by a significant decrease of PTH levels (50% of initial value) in 26 patients. Plasma PTH levels decreased by at least 80% of pre-excisional value after 20 minutes, 70% after 10 minutes and by 50% after 5 minutes. In 2 cases, significant decrease of PTH was obtained after 45 and 60 minutes respectively. In 2 other cases, the adenoma could not be found and there was no decrease of PTH even after extensive exploration of the neck. In the 11 patients who underwent minimal invasive surgery, 2 were converted to open neck surgery: in one case the adenoma was not accessible in the upper part of the neck, in the other case the hyperfunctioning gland remained undiscovered. CONCLUSION: intraoperative measurement of PTH should be considered a reliable and reproducible method for evaluation of the secreting activity of a parathyroid gland. The Quick Pack method has the advantage of confirming that the hyperactive gland has really been eradicated and consequently of considerably reducing operating time and avoiding extensive exploration of the neck.Journal Articleinfo:eu-repo/semantics/publishe

    Parameningeal rhabdomyosarcoma report of 19 cases

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    Parameningeal rhabdomyosarcoma. Parameningeal rhabdomyosarcomas are associated with a poor long term survival. This is due to the fact that they are aggressive tumours with early involvement of the skull base. The authors report a series of 19 cases between 1984 and 1995 with a relative proportion of children, male patients and tumours of embryonal type. Three patients were operated on and only one of them was found with tumour free margins. Systemic chemotherapy using the VAC-VAd protocol was administered in 18 patients and intrathecal chemotherapy was delivered in 5 patients with involvement of the skull base. Nine patients were irradiated with doses varying from 45 to 55 Gy. Twelve patients died from 20 days to 4 years after initial treatment; 6 were lost to follow up and only one patient is living without any evidence of disease after 11 years.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
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