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FOXO transcription factors are key regulators of DNA damage repair, proliferation and apoptosis in thyrocytes. Thyroid malignancies show impaired FOXO function. In this study, we investigated the transcriptional regulation of FOXO isoforms in thyroid epithelial cells. mRNA expression of FOXO isoforms (FOXO1, 3 and 4) was determined in FRTL-5 cells stimulated with different growth factors and H2O2. Furthermore, the impact of PI3K/AKT signalling on FOXO transcription was investigated in PI3K p110α mutant FRTL-5 cells and regulatory dependence of FOXO transcription on FOXO was studied in FRTL-5 cells with hFOXO3 overexpression. Finally, mRNA expression levels of FOXO isoforms were determined in human epithelial thyroid tumours. Growth factor deprivation induced transcription of FOXO1, 3 and 4, whereas insulin stimulation decreased FOXO1 and FOXO4 transcription in FRTL-5 cells. Inhibition of the PI3K/AKT cascade amplified FOXO1 and FOXO4 expression. In contrast, 2O2 and TSH did not influence FOXO transcription in thyrocytes. Overexpression of PI3K p110α inhibited FOXO3 and induced FOXO4 transcription. In human thyroid tumours, FOXO1 and FOXO3 mRNA levels were significantly downregulated in papillary thyroid carcinoma when compared to normal tissues. In contrast, follicular thyroid carcinomas showed significant upregulation of FOXO4 mRNA. In this paper, we demonstrate an influence of PI3K signalling on FOXO transcription in thyrocytes. Moreover, we show that thyroid cancers exhibit alterations in FOXO transcription besides the previously reported alterations in posttranslational FOXO3 regulation. These findings may add to the concept of targeting the PI3K pathway in advanced thyroid cancers. [ABSTRACT FROM AUTHOR]

Background Mastocytosis is frequently associated with mast cell-mediated symptoms which require relieving medication. While second generation antihistamines (sg AHs) are the first line therapeutic strategy to treat mast cell mediator-related symptoms, controlled clinical trials on how they improve quality of life have not been performed. Methods This randomized, double-blind, placebo-controlled, cross-over trial assessed rupatadine 20 mg daily in the treatment of mastocytosis symptoms in 30 adult patients. Symptoms were assessed by a visual analogue scale ( VAS) and symptom specific quality of life questionnaire ( Itchy Qo L). Results The mean Itchy Qo L total score and VAS symptom score were significantly improved in the rupatadine treatment phase compared with placebo. There were also significant reductions from placebo in the severity of itch, wheal and flare, flushing, tachycardia and headache but not gastrointestinal symptoms. Conclusions In this first comprehensive trial of a sg AH in mastocytosis, rupatadine 20 mg daily for 4 weeks significantly controlled symptoms and improved patients' quality of life. [ABSTRACT FROM AUTHOR]

Schnitzler's syndrome is characterized by recurrent urticarial rash and monoclonal gammopathy, associated with clinical and biological signs of inflammation and a long-term risk of AA amyloidosis and overt lymphoproliferation. An extensive literature review was performed, and the following questions were addressed during an expert meeting: In whom should Schnitzler's syndrome be suspected? How should the diagnosis of Schnitzler's syndrome be established? How should a patient with Schnitzler's syndrome be treated? How should a patient with Schnitzler's syndrome be followed up?. A diagnosis of Schnitzler's syndrome is considered definite in any patient with two obligate criteria: a recurrent urticarial rash and a monoclonal IgM gammopathy, and two of the following minor criteria: recurrent fever, objective signs of abnormal bone remodeling, elevated CRP level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. It is considered probable, if only 1 minor criterion is present. In patients with monoclonal IgG gammopathies, diagnosis is definite if three minor criteria are present and possible if two are present. First-line treatment in patients with significant alteration of quality of life or persistent elevation of markers of inflammation should be anakinra. Follow-up should include clinical evaluation, CBC and CRP every 3 months and MGUS as usually recommended. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aims to evaluate the feasibility, safety and complication rate of laparoscopic inguinal hernia repair for small babies weighing 3 kg or less. Methods: A retrospective analysis was performed on the surgical charts of 67 infants (47 boys and 20 girls) weighing 3 kg or less who underwent laparoscopic hernia repair in a 3-year period. A regular 5-mm scope was used for visualization, and 2 or 3-mm instruments were used for the closure of the inner inguinal ring using 3/0 non-absorbable suture. The median weight at surgery was 2,600 g (range 1,450-3,000 g). All except three were premature. Results: Of the 67 infants, 15 (22.3 %) presented with an irreducible hernia. In three cases of irreducible hernias, we also performed a transumbilical appendectomy at the end of the hernia repair. Minor problems related with anesthesia were noted in four cases. Hernia recurrence was observed in three patients (4.4 %). No cases of testicular atrophy occurred. In 10 boys, we observed 12 cases of high testes, only 4 testes requiring subsequent orchiopexy. Conclusions: Laparoscopic inguinal hernia repair for babies weighing 3 kg or less is feasible, safe and perhaps even less technically demanding than open inguinal herniotomy. [ABSTRACT FROM AUTHOR]

Background Schnitzler syndrome (SchS) is a rare disease with suspected autoinflammatory background that shares several clinical symptoms, including urticarial rash, fever episodes, arthralgia, and bone and muscle pain with cryopyrin-associated periodic syndromes ( CAPS). Cryopyrin-associated periodic syndromes respond to treatment with interleukin-1 antagonists, and single case reports of Schnitzler syndrome have shown improvement following treatment with the interleukin-1 blocker anakinra. This study evaluated the effects of the interleukin-1 antagonist rilonacept on the clinical signs and symptoms of SchS. Methods Eight patients with SchS were included in this prospective, single-center, open-label study. After a 3-week baseline, patients received a subcutaneous loading dose of rilonacept 320 mg followed by weekly subcutaneous doses of 160 mg for up to 1 year. Efficacy was determined by patient-based daily health assessment forms, physician's global assessment (PGA), and measurement of inflammatory markers including C-reactive protein ( CRP), serum amyloid A ( SAA), and S100 calcium-binding protein A12 (S100A12). Results Treatment with rilonacept resulted in a rapid clinical response as demonstrated by significant reductions in daily health assessment scores and PGA scores compared with baseline levels ( P < 0.05). These effects, which were accompanied by reductions in CRP and SAA, continued over the treatment duration. Rilonacept treatment was well tolerated. There were no treatment-related severe adverse events and no clinically significant changes in laboratory safety parameters. Conclusion Rilonacept was effective and well tolerated in patients with SchS and may represent a promising potential therapeutic option ( NCT01045772 [ Identifier]; Eudra CT #2006-004290-97). [ABSTRACT FROM AUTHOR]

The article presents a case study of a 48-year-old Caucasian woman who was successfully treated with anti-immunoglobulin E (IgE) therapy after developing severe urticaria factitia. It states that she was treated with nonsedating antihistamines after her skin produced massive pruritus and whealing but none of the treatments have resulted in sufficient symptom control. However, when the anti-IgE treatment was performed, complete protection from symptom development was achieved.