Expression of the cystine-glutamate exchanger (xc-) in retinal ganglion cells and regulation by nitric oxide and oxidative stress.

The cystine-glutamate exchanger, system x(c)(-), mediates the Na(+)-independent exchange of cystine into cells, coupled to the efflux of intracellular glutamate. System x(c)(-) plays a critical role in glutathione homeostasis. Early studies of brain suggested that system x(c)(-) was present primarily in astrocytes but not neurons. More recent work indicates that certain brain neurons have an active system x(c)(-). In the retina, system x(c)(-) has been demonstrated in Müller and retinal pigment epithelial cells. We have recently suggested that two protein components of system x(c)(-), xCT and 4F2hc, are present in ganglion cells of the intact retina. Here, we have used (1) molecular and immunohistochemical assays to determine whether system x(c)(-) is present in primary ganglion cells isolated from neonatal mouse retinas and (2) functional assays to determine whether its activity is regulated by oxidative stress in a retinal ganglion cell line (RGC-5). Primary mouse ganglion cells and RGC-5 cells express xCT and 4F2hc. RGC-5 cells take up [(3)H]glutamate in the absence of Na(+), and this uptake is blocked by known substrates of system x(c)(-) (glutamate, cysteine, cystine, quisqualic acid). Treatment of RGC-5 cells with NO and reactive oxygen species donors leads to increased activity of system x(c)(-) associated with an increase in the maximal velocity of the transporter with no significant change in the substrate affinity. This is the first report of system x(c)(-) in primary retinal ganglion cells and RGC-5 cells. Oxidative stress upregulates this transport system in RGC-5 cells, and the process is associated with an increase in xCT mRNA and protein but no change in 4F2hc mRNA or protein.

Is laparoscopic resection of colorectal polyps beneficial?

BACKGROUND: We set out to compare the results of laparoscopic and open resections of colorectal polyps. METHODS: Forty-five consecutive patients who underwent operation by a single surgeon for endoscopically irretrievable colonic polyps between April 1992 and March 1996 were classified into the following two groups: group I, laparoscopic procedures for colonic polyps (n = 23); and group II, open procedures for colonic polyps (n = 22). RESULTS: No significant differences were seen between the groups relative to age [71.7 +/- 10.7 versus 70.6 +/- 13.7 years], gender [male:female = 10:13 versus 13:9], history of previous abdominal operation (eight of 23 [34.8%] versus 10 of 22 [45.5%]), type of pathology (villous: seven of 23 [30.4%] versus four of 22 [18.1%], tubulovillous: nine of 23 [39.1%] versus six of 22 [27.2%], tubular: three of 23 [13.0%] versus seven of 22 [31.8%]), size of polyps (2.6 +/- 1.7 cm versus 2.7 +/- 1.5 cm), or type of procedures (right hemicolectomy: 15 of 23 [65.2%] versus 11 of 22 [50%], sigmoid colectomy: five of 23 [21.7%] versus six of 22 [27.3%], left hemicolectomy: two of 23 [8.7%] versus two of 22 [9.1%]). There was no mortality and no difference in the incidence of postoperative complications (four of 23 [17.4%] versus seven of 22 [31.8%]), blood loss (167 cc versus 243 cc), number of retrieved lymph nodes (7.1 +/- 5 versus 6.6 +/- 4), incidence of carcinoma in polyps (two of 23 [13.0%] versus four of 22 [18.2%]), or medical cost ($22,840 versus $18,420), respectively, between the two groups. There were statistically significant differences in length of ileus (3.5 +/- 1.0 days versus 5.5 +/- 1.8 days), postoperative pain (2.3 +/- 1.4 versus 3.7 +/- 1.9 on postoperative day 1 [patient pain rating scale 1-10]), length of hospital stay (6. 5 +/- 2.0 days versus 9.4 +/- 2.7 days), and return to normal activity (5.2 +/- 4.2 weeks versus 9.3 +/- 12.1 weeks) in group I compared to group II, respectively. However, patients in group II had a longer mean specimen length (18.5 +/- 6.4 cm versus 29.1 +/- 22.7 cm) and a shorter mean operative time (177.6 +/- 52.7 min versus 143 +/- 51.4 min) than patients in group I. CONCLUSIONS: Laparoscopic colectomy for colonic polyps has definite advantages over traditional open surgery, including less postoperative pain, earlier return of bowel function, and earlier return to normal activity. Conversely, its disadvantages include longer operative time and a shorter specimen.