Clara Cell 10-kDa Protein Gene Transfection Inhibits NF-κB Activity in Airway Epithelial Cells

Clara cell 10-kDa protein (CC10) is a multifunctional protein with anti-inflammatory and immunomodulatory effects. Induction of CC10 expression by gene transfection may possess potential therapeutic effect. Nuclear factor κB (NF-κB) plays a key role in the inflammatory processes of airway diseases.To investigate potential therapeutic effect of CC10 gene transfection in controlling airway inflammation and the underlying intracellular mechanisms, in this study, we constructed CC10 plasmid and transfected it into bronchial epithelial cell line BEAS-2B cells and CC10 knockout mice. In BEAS-2B cells, CC10's effect on interleukin (IL)-1β induced IL-8 expression was explored by means of RT-PCR and ELISA and its effect on NF-κB classical signaling pathway was studied by luciferase reporter, western blot, and immunoprecipitation assay. The effect of endogenous CC10 on IL-1β evoked IL-8 expression was studied by means of nasal explant culture. In mice, CC10's effect on IL-1β induced IL-8 and nuclear p65 expression was examined by immunohistochemistry. First, we found that the CC10 gene transfer could inhibit IL-1β induced IL-8 expression in BEAS-2B cells. Furthermore, we found that CC10 repressed IL-1β induced NF-κB activation by inhibiting the phosphorylation of IκB-α but not IκB kinase-α/β in BEAS-2B cells. Nevertheless, we did not observe a direct interaction between CC10 and p65 subunit in BEAS-2B cells. In nasal explant culture, we found that IL-1β induced IL-8 expression was inversely correlated with CC10 levels in human sinonasal mucosa. In vivo study revealed that CC10 gene transfer could attenuate the increase of IL-8 and nuclear p65 staining in nasal epithelial cells in CC10 knockout mice evoked by IL-1β administration.These results indicate that CC10 gene transfer may inhibit airway inflammation through suppressing the activation of NF-κB, which may provide us a new consideration in the therapy of airway inflammation

JPN Guidelines for the management of acute pancreatitis:surgical management

Acute pancreatitis represents a spectrum of disease ranging from a mild, self-limited course to a rapidly progressive, severe illness. The mortality rate of severe acute pancreatitis exceeds 20%, and some patients diagnosed as mild to moderate acute pancreatitis at the onset of the disease may progress to a severe, life-threatening illness within 2–3 days. The Japanese (JPN) guidelines were designed to provide recommendations regarding the management of acute pancreatitis in patients having a diversity of clinical characteristics. This article sets forth the JPN guidelines for the surgical management of acute pancreatitis, excluding gallstone pancreatitis, by incorporating the latest evidence for the surgical management of severe pancreatitis in the Japanese-language version of the evidence-based Guidelines for the Management of Acute Pancreatitis published in 2003. Ten guidelines are proposed: (1) computed tomography-guided or ultrasound-guided fine-needle aspiration for bacteriology should be performed in patients suspected of having infected pancreatic necrosis; (2) infected pancreatic necrosis accompanied by signs of sepsis is an indication for surgical intervention; (3) patients with sterile pancreatic necrosis should be managed conservatively, and surgical intervention should be performed only in selected cases, such as those with persistent organ complications or severe clinical deterioration despite maximum intensive care; (4) early surgical intervention is not recommended for necrotizing pancreatitis; (5) necrosectomy is recommended as the surgical procedure for infected pancreatic necrosis; (6) simple drainage should be avoided after necrosectomy, and either continuous closed lavage or open drainage should be performed; (7) surgical or percutaneous drainage should be performed for pancreatic abscess; (8) pancreatic abscesses for which clinical findings are not improved by percutaneous drainage should be subjected to surgical drainage immediately; (9) pancreatic pseudocysts that produce symptoms and complications or the diameter of which increases should be drained percutaneously or endoscopically; and (10) pancreatic pseudocysts that do not tend to improve in response to percutaneous drainage or endoscopic drainage should be managed surgically

Analysis of malpractice claims: The Franco-Belgian "Cœlio Club" experience.

Malpractice claims are a regularly increasing concern in gastrointestinal surgery. The goal of this study was to compare the current status of claims in two different French-speaking communities by a retrospective descriptive study of surgeons' experiences, from the beginning of their practice up until December 31 2014. Data included the number, the reasons, and the results of medicolegal claims and their jurisdictions. Forty-three surgeons participated in this study. Two hundred medicolegal claims were analyzed. The mean number was 5.8 per surgeon. Bariatric surgery, colorectal surgery and parietal surgery were the most exposed. Forty-six (23%) faults were noted, while no fault was pronounced in 139 (69.5%) cases. The main reasons for lodging complaints were nosocomial infections, anastomotic leaks, poor postoperative care, hollow organ perforation, peripheral neurologic complication, and insufficient preoperative information. Forty-four percent of the complaints were analyzed by the conciliation and compensation commissions and 43.5% by the High Court. In the French-speaking group, there were 13 complaints, two of which gave rise to compensation. French surgeons are highly exposed to complaints: in French law, clumsiness or technical maladdress is considered as a fault. The patient should be informed preoperatively of all possible severe risks of a medical procedure. In Belgium, complications are exceptional and are considered random therapeutic events. Adhering to the recommendations emanating from the French High Authority of Health and Learned Societies as well as accreditation issued by the same High Authority should allow to decrease the number of undesirable events related to care and malpractice

Protein content in bronchoalveolar lavage fluid of patients with asthma and control subjects.

BACKGROUND: Secretory component (SC), Clara cell protein (CC10) and to some extent, IgM are proteins locally synthetized in airways. Albumin, alpha 2-macroglobulin and alpha 1-antitrypsin are mainly plasma proteins. In patients with asthma, blood proteins may occur in greater amounts in bronchoalveolar lavage fluid (BALF) than in control subjects because of plasma extravasation. These proteins were measured in BALF to define markers of local synthesis and plasma exudation. METHODS: Twenty-four patients with asthma (mean age, 40 +/- 3.1 years) and 24 control subjects (mean age, 29 +/- 11 years) were tested. Five aliquots of saline solution (50 ml) were instilled, and the recovered BALF was stored. Clara cell protein was measured by a sensitive immunoassay technique based on the agglutination of latex particles. SC, immunoglobulins, alpha 2-macroglobulin, alpha 1-antitrypsin, and albumin were measured by an immunoradiometric assay. Protein concentrations were normalized to albumin. RESULTS: In BALF from patients with asthma there was a significant increase in alpha 2-macroglobulin and IgM and a significant decrease of SC, alpha 1-antitrypsin, and Clara cell protein compared with control subjects. Also, the ratio to albumin was significantly increased for alpha 2-macroglobulin and IgM and decreased for SC. There was no correlation between the severity of asthma and the amount of proteins. CONCLUSIONS: BALF protein content is significantly different in patients with asthma and control subjects, for proteins produced locally and derived from plasma

Pharmacotherapy for ADHD in children and adolescents:A summary and overview of different European guidelines

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries. Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. What is Known: • There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents. • Pediatricians are often involved in assessment, diagnosis and management of children with ADHD. What is New: • Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents. • Discrepancies exist primarily in terms of selection and sequencing of different medications.</p

Pharmacotherapy for ADHD in children and adolescents:A summary and overview of different European guidelines

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries. Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. (Table presented.)</p