Inhibition of AXUD1 attenuates compression-dependent apoptosis of cementoblasts.

OBJECTIVES: Root resorptions are common undesirable side effects of orthodontic treatment. In most patients, these defects are repaired by cementoblasts. However, in 1-5 % of patients, the repair fails. The repair mechanism is not well understood. Apoptosis of cementoblasts might contribute to an impaired repair of root resorptions induced by orthodontic forces. MATERIALS AND METHODS: To gain insight into putative molecular pathways leading to compression-induced apoptosis of human primary cementoblasts (HPCBs), three independent cell populations were subjected to compressive loading at 5, 20, and 30 g/cm2 for 1, 6, and 10 h. The mRNA expression of AXUD1, a novel pro-apoptotic gene, was monitored by quantitative reverse transcription PCR (qRT-PCR). To identify a possible function in compression-dependent apoptosis, AXUD1 was silenced in cementoblasts using an siRNA approach. Apoptosis of cementoblasts was measured by annexin V staining and flow cytometry. The phosphorylation of c-Jun-N-terminal kinases (JNKs) was investigated by Western blotting. RESULTS: AXUD1 was significantly induced in a time- and force-dependent manner. The rate of apoptotic HPCBs increased by 20-40 % after 10 h of compression (30 g/cm2). Phosphorylation of JNKs was detected after 10 h at 30 g/cm2. SiRNA-mediated knockdown of AXUD1 led to decreased phosphorylation of JNKs and reduced apoptosis rates in compressed HPCBs. CONCLUSIONS: Compression-induced apoptosis of HPCBs is mediated by AXUD1 via a JNK-dependent pathway. CLINICAL RELEVANCE: AXUD1-dependent apoptosis of human cementoblasts might contribute to an impaired repair of root resorptions during orthodontic tooth movement. Further studies are needed to develop treatment strategies aiming to minimize root resorption during orthodontic tooth movement.

Adenovirus infection and treatment with cidofovir in children after liver transplantation.

In a retrospective study, serum samples from 21 pediatric liver transplant recipients were analysed by quantitative real-time PCR for ADV infection up to 24 wk after Tx. ADV DNA was detected in serum of eight children after Tx, one of whom developed life-threatening fulminant hepatitis and sepsis. None of these children were symptomatic at the time of first detection of ADV DNA in serum after Tx. Seven children with positive ADV PCR had low adenoviral loads, showed no increase in viral load and remained clinically asymptomatic in the follow-up period of 24 wk. After 10 wk under immunosuppression one child presented clinically with adenoviral sepsis and severe necrotizing hepatitis. This patient revealed a dramatic increase of ADV from baseline titers up to 1.3 x 10(9 )copies/mL serum within 10 wk after Tx. ADV was also detected in a liver biopsy of this child at 1.2 x 10(4) copies/cell and typed by sequence analysis as human ADV species C, type 6, a rarely detected ADV type and first described in a liver transplant patient. Immunosuppression was reduced in this patient immediately and the antiviral drug cidofovir administered intravenously followed by viral suppression and clinical improvement of the child.

Sudden death of an immunocompetent young adult caused by novel (swine origin) influenza A/H1N1-associated myocarditis.

The main cause of death from novel (swine origin) influenza A/H1N1 infection is acute respiratory distress syndrome. Most fatal cases are immunocompromised patients or patients with a severe underlying disease. Here, we report a fatal case of acute interstitial myocarditis associated with novel influenza A/H1N1 infection in an immunocompetent young woman. A previously healthy 18-year-old woman experienced malaise, diarrhea, and fever for several days prior to a sudden collapse at home. Autopsy revealed a predominantly lymphocytic myocarditis in the absence of a significant respiratory tract infection. Infection with novel (swine origin) influenza A/H1N1 was confirmed by PCR analysis of blood as well as myocardial tissue. Influenza-caused diarrhea with consecutive hypokalemia potentially contributed to the fatal outcome of the myocarditis, characterized by ventricular fibrillation. In conclusion, sudden death by myocarditis may be a rare complication of novel influenza A/H1N1 infection in otherwise healthy individuals, even in the absence of significant respiratory tract infection.