Mdm2, but not Mdm4, protects terminally differentiated smooth muscle cells from p53-mediated caspase-3-independent cell death.

p53 is a potent inhibitor of cell growth and an inducer of apoptosis. During embryonic development, Mdm2 and Mdm4 inhibit the growth suppressive activities of p53. However, whether tight surveillance of p53 activity is required in quiescent cells is unknown. To test this, conditional inactivation of mdm2 and mdm4 was carried out in smooth muscle cells (SMCs). Upon SMC-specific inactivation of mdm2, and not of mdm4, mice rapidly became ill and died. Necropsy showed small intestinal dilation, and histological analyses indicated a severe reduction in the number of intestinal SMCs. Increased p53 levels and activity were detected in the remaining SMCs, and the phenotype was completely rescued on a p53-null background. Interestingly, intestinal SMCs are caspase-3-negative and therefore did not undergo caspase-3-dependent apoptotic cell death. Together, Mdm2, but not Mdm4, prevents accumulation of active p53 in quiescent SMCs and thereby the induction of p53-mediated caspase-3-independent cell death.

New developments in abdominal wall reconstruction after abdominal compartment syndrome decompression.

The acute abdominal compartment syndrome (ACS) is most often treated with surgical abdominal decompression. After the acute phase, primary closure of the abdominal wall may not be possible, due to tissue loss and retraction of the abdominal wall and its musculofascial components. This article gives an update of the reconstructive ladder for abdominal wall defects. Because of improved intensive care treatment and wound dressing, reconstruction can usually be delayed until infection and oedema have settled. Recent developments in bioprosthetics and new surgical techniques like component separation make better results with less donor site morbidity possible. However, there is still a place for local and distant flaps.

New developments in abdominal wall reconstruction after abdominal compartment syndrome decompression.

The acute abdominal compartment syndrome (ACS) is most often treated with surgical abdominal decompression. After the acute phase, primary closure of the abdominal wall may not be possible, due to tissue loss and retraction of the abdominal wall and its musculofascial components. This article gives an update of the reconstructive ladder for abdominal wall defects. Because of improved intensive care treatment and wound dressing, reconstruction can usually be delayed until infection and oedema have settled. Recent developments in bioprosthetics and new surgical techniques like component separation make better results with less donor site morbidity possible. However, there is still a place for local and distant flaps.

Efficacy of vaccination of pigs with different H1N1 swine influenza viruses using a recent challenge strain and different parameters of protection.

This study investigates whether antigenic evolution within H1N1 swine influenza viruses can compromise vaccine efficacy and, specifically, whether the A/New Jersey/8/76 strain in the commercial swine influenza vaccines needs to be updated. Pigs were vaccinated twice intramuscularly with experimental monovalent vaccines derived from different H1N1 strains (A/New Jersey/8/76, Sw/Belgium/1/83 or Sw/Belgium/1/98) or with a commercial bivalent vaccine based on A/New Jersey/8/76 (H1N1) and A/Port Chalmers/1/73 (H3N2). Experimental and commercial vaccines contained a different adjuvant. Two weeks after the second vaccination, all pigs were challenged intratracheally with Sw/Belgium/1/98. Mean pre-challenge haemagglutination inhibition (HI) antibody titres against the challenge virus were lower for the experimental A/New Jersey/8/76 vaccine than for the other vaccines. The reduction in mean virus titres in the lungs was highly significant for the latter vaccines, including the commercial New Jersey-derived vaccine, but not for the experimental A/New Jersey/8/76 vaccine. Clinical signs after challenge were negligible in all vaccinates. Post-challenge levels of interferon-alpha and tumor necrosis factor-alpha in bronchoalveolar lavage fluids were reduced in the vaccinates, while levels of interleukin-1 and neutrophils were less consistent. Though the A/New Jersey/8/76 strain is less effective in preventing infection by Sw/Belgium/1/98 than the homologous virus or than Sw/Belgium/1/83, all strains can protect completely if antibody titres against the challenge virus are sufficiently high. Apart from the vaccine strain, adjuvant and antigenic dose may play a crucial role in vaccine efficacy.