Spinal N-methyl-D-aspartate receptor 2B subunit (NR2B)-increased expression plays an important role in the facilitation and maintenance of the persistent pain state due to peripheral nerve injury. A vaccination strategy to reduce the expression of brain protein is feasible and may have therapeutic potential for neurological disorders. Thus, we investigated the effect of oral immunization with recombinant adenovirus serotype 5-mediated NR2B gene transfer (rAd5/NR2B) for the modulation of neuropathic pain. After peroral administration of the rAd5/NR2B vaccine, transgene NR2B expression persisted for at least a week and was associated with the induction of high serum titers of NR2B-specific antibodies. Following the occurrence of mechanical allodynia due to peripheral nerve injury, NR2B-specific antibodies could pass the blood-brain barrier, transport and subsequently bind to the spinal NR2B protein. The humoral immunoresponse results in the strong antiallodynia in the spared nerve injury animal model. These data proved the feasibility of oral immunization with rAd5/NR2B for the prevention of neuropathic pain.
Major efforts have been made in the development of a system that takes the reviewer step-by-step by the use of the developmental toxicity and exposure assessment data to a recommended risk assessment and risk management position. Thereupon a set of regulatory decisions can be arrived at that are backed up by sound scientific analysis. Examples of pesticides that have been found to be teratogenic in animal testing are provided to demonstrate the process of use of exposure data in making risk assessment and management decisions.
This study compared the use of a new type of peritoneocentesis trocar with conventional laparotomy for the placement of the distal catheter in the treatment of hydrocephalus with ventriculoperitoneal shunt. A total of 376 patients with hydrocephalus were recruited to the study and were assigned randomly to undergo insertion of the distal catheter by conventional laparotomy (n = 195) or using the new peritoneal trocar (n = 181). The time taken for the surgical procedure and the complication rate over the following 1-year period were compared between the two groups. The mean length of the procedure to place the distal catheter was significantly shorter in the trocar group compared with the laparotomy group. Infection and obstruction rates were significantly higher in the laparotomy group than in the trocar group. In conclusion, the use of the new trocar was associated with lower rates of surgically induced trauma and complications compared with conventional laparotomy.
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