The role of ATP in the differential ability of Sr2+ to trigger Ca2+ oscillations in mouse and human eggs.

At fertilization in mice and humans, the activation of the egg is caused by a series of repetitive Ca2+ oscillations which are initiated by phospholipase-C(zeta)ζ that generates inositol-1,4,5-trisphophate (InsP3). Ca2+ oscillations and egg activation can be triggered in mature mouse eggs by incubation in Sr2+ containing medium, but this does not appear to be effective in human eggs. Here, we have investigated the reason for this apparent difference using mouse eggs, and human eggs that failed to fertilize after IVF or ICSI. Mouse eggs incubated in Ca2+-free, Sr2+-containing medium immediately underwent Ca2+ oscillations but human eggs consistently failed to undergo Ca2+ oscillations in the same Sr2+ medium. We tested the InsP3-receptor (IP3R) sensitivity directly by photo-release of caged InsP3 and found that mouse eggs were about 10 times more sensitive to InsP3 than human eggs. There were no major differences in the Ca2+ store content between mouse and human eggs. However, we found that the ATP concentration was consistently higher in mouse compared to human eggs. When ATP levels were lowered in mouse eggs by incubation in pyruvate-free medium, Sr2+ failed to cause Ca2+ oscillations. When pyruvate was added back to these eggs, the ATP levels increased and Ca2+ oscillations were induced. This suggests that ATP modulates the ability of Sr2+ to stimulate IP3R-induced Ca2+ release in eggs. We suggest that human eggs may be unresponsive to Sr2+ medium because they have a lower level of cytosolic ATP.

Native valve infective endocarditis due to Achromobacter xylosoxidans in an apparently immunocompetent individual.

A 79-year-old woman presented with fever, lethargy and weight loss. Clinically, the patient was confused, frail and had a systolic murmur. Her temperature was 38 °C and she remained persistently febrile. Initial investigations revealed neutrophilia with an elevated C reactive protein level. Multiple peripheral blood cultures grew Achromobacter xylosoxidans, a Gram-negative rod, which is a very rare cause of infection in patients who are immunocompetent. Subsequent transoesophageal echocardiography confirmed endocarditis with obvious vegetations on the mitral valve. The patient was treated with intravenous meropenem and cotrimoxazole in line with microbiology guidance. Surgical intervention in the form of mitral valve replacement was considered, but the patient was felt to be at prohibitive risk. After 6 weeks of intravenous antibiotics, a repeat transoesophageal echocardiogram showed no improvement in the mitral valve vegetation, which had increased in size. At this stage, her clinical course was complicated by major upper gastrointestinal bleeding requiring transfusion, multiorgan failure and ultimately death.