Lloyd W Mobley | PubMed Health

PubMedDate not supplied

Role of calcineurin in calcium-mediated hypoxic injury to white matter.

BACKGROUND CONTEXT: Calcium influx into cells is responsible for initiating the "final pathway" to cell death in neuronal tissue after traumatic or hypoxic injury. The specific pathways in this cascade are myriad and the importance each one plays is controversial. It is clear, though, that blocking individual pathways confers protection to these tissues. PURPOSE: In the present study we examined the role of Cyclosporin A (CsA), FK-506 and rapamycin in modulating the effects of Ca(2+) influx through their interactions with immunophilins and specifically the end result of calcineurin modulation. METHODS: Dorsal columns were isolated from the spinal cord of adult rats and injured by exposure to hypoxic conditions for 60 minutes. The samples were monitored electrophysiologically in an in vitro recording chamber (maintained at 37 C degrees ) during injury, and the compound action potential (CAP) was monitored with glass microelectrodes. The dorsal column was exposed to hypoxic Ringers solution alone or with the different immunosuppressants and compared with baseline readings. Functional recovery of the dorsal column was then assessed by recovery of the CAP. RESULTS: The mean CAP decreased to about 20% of baseline control levels during hypoxia and returned 53.8+/-7.6% of baseline (p<.05) after reoxygenation. CsA, an immunosuppressant known to inhibit calcineurin, promoted a significantly greater recovery of CAP amplitude to 76.8+/-5.2% and 72.1+/-13.2% of control (p<.05) after hypoxic injury and reoxygenation of dorsal column white matter when applied at concentrations of 1 microM and 10 microM, respectively. FK-506, which also inhibits calcineurin, was applied at a concentration of 0.1 microM, and promoted CAP amplitude recovery to 82.6+/-5.0% of control after hypoxic injury and reoxygenation of dorsal column white matter. The addition of rapamycin (1 microM), which binds to the same immunophilin as FK-506, to the FK-506 (0.1 microM) solution during hypoxic injury showed recovery of CAP amplitudes to only 56.9+/-6.7% of control. Electron microscopy revealed remarkable protection of axons and prevention of organelle disruption in segments treated with CsA and FK-506 during hypoxia when compared with hypoxic controls. CONCLUSION: In conclusion, both CsA and FK-506 confer in vitro protection to dorsal columns during hypoxic injury at physiological temperatures, and rapamycin blocks the protective effect of FK-506. Thus, calcineurin may play an important role in the physiology of neuronal injury.

Action Potentials↗

PubMedDate not supplied

Abdominal pseudocyst: predisposing factors and treatment algorithm.

Abdominal pseudocyst (APC) is an uncommon complication of ventriculoperitoneal shunts. Various predisposing factors have been attributed to it, including the presence of infection and multiple shunt revisions. We reviewed the records of shunt revisions performed over a 20-year period. During that time, 64 cases of APC were found in 36 patients. The records were then reviewed for the presence of infection, history of necrotizing enterocolitis, prior abdominal surgery, and treatment performed. Of the cases of APC, 46 were primary and 18 were recurrent. A history of prior abdominal surgery other than shunt revision was found in 47% of patients and a history of necrotizing enterocolitis was found in 19% of patients. The average number of prior shunt revisions was 4.1 per patient. Shunt infection as defined by positive cultures of either cerebrospinal fluid or abdominal fluid was present in only 23% of cases of APC. A history of prior shunt infection was present in 30% of patients. Infection was treated by shunt removal, external ventricular drainage, and appropriate antibiotics. After the infection was cleared or if no infection was present, treatment consisted of: (1) repositioning the distal catheter into the peritoneum, (2) repositioning the distal catheter into the pleural space, the atrium, or the gallbladder, (3) exploratory laparotomy with lysis of adhesions and repositioning the peritoneal catheter, (4) APC aspiration only, or (5) shunt removal or disconnection. Because of the complexity of APC management, we analyzed the outcomes of our cases and outlined an algorithm to simplify this process.

Abdomen↗