Toshihiro Noake

Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats

BACKGROUND Since tumor-bearing rats are deficient in glutamine, we investigated whether (1) glutamine and glutathione deficiency occur in tumor-bearing rats, (2) glutamine supplementation caused an increase of glutathione levels in host tissues and tumor, (3) glutamine enhances protein synthesis in host tissues, and (4) glutamine stimulated the tumor to synthesize protein and DNA. METHODS Male Donryu rats were randomized into four groups: (1) non-tumor-bearing rat (NTB) + standard total parenteral nutrition (STPN); (2) NTB + glutamine-supplemented TPN (GTPN); (3) tumor-bearing rat (TB) + STPN; (4) TB + GTPN. On day 0 AH109A rat hepatoma cells were subcutaneously injected into the backs of rats to induce tumor. The animals were maintained on TPN for 6 days from day 10 through day 15. On day 15, 1-14C-leucine was given by a 5-hour continuous infusion (2.0 microCi/h per rat) to determine the fractional synthesis rate and endogenous leucine production. The levels of glutamine and glutathione were measured by HPLC. the tumor DNA synthesis was estimated by bromodeoxyuridine labeling index. RESULTS Tumor development led to a significant weight loss, but this weight loss was significantly lessened by glutamine supplementation because of an increase in muscle protein synthesis. Glutamine did not enhance tumor weight, protein, and DNA synthesis in the tumor. Tumor development caused a significant reduction of glutathione in the muscle, jejunum, and liver, but supplemented glutamine increased the levels of glutathione in the jejunum. CONCLUSION Glutamine supplementation is beneficial in preventing deficiencies of glutamine and glutathione and in improving protein metabolism in tumor-bearing rats.

Perianal Paget's disease treated with a wide excision and gluteal fold flap reconstruction guided by photodynamic diagnosis: report of a case.

P erianal extramammary Paget’s disease is a malignant tumor of the skin invading the epidermis, and the first-choice treatment is a wide excision of the skin. In many cases, however, it is very difficult to know whether the disease is localized or extends to the anus. Photodynamic diagnosis (PDD) is a method more convenient and less invasive than biopsy for the detection of cutaneous infiltration before surgical incision. We present here a case of perianal Paget’s disease in which PDD was used to delineate the skin to be excised before preservation of the anal sphincter, wide skin excision, and reconstruction with gluteal fold flap and a full-thickness pedicle flap and which had a favorable postoperative course without any anal stenosis.

Perianal Paget’s Disease Treated With a Wide Excision and Gluteal Fold Flap Reconstruction Guided by Photodynamic Diagnosis

P erianal extramammary Paget’s disease is a malignant tumor of the skin invading the epidermis, and the first-choice treatment is a wide excision of the skin. In many cases, however, it is very difficult to know whether the disease is localized or extends to the anus. Photodynamic diagnosis (PDD) is a method more convenient and less invasive than biopsy for the detection of cutaneous infiltration before surgical incision. We present here a case of perianal Paget’s disease in which PDD was used to delineate the skin to be excised before preservation of the anal sphincter, wide skin excision, and reconstruction with gluteal fold flap and a full-thickness pedicle flap and which had a favorable postoperative course without any anal stenosis.

Leukocytapheresis for the treatment of active pouchitis: a pilot study

BackgroundPouchitis is a major long-term complication of ileal pouch-anal anastomosis for ulcerative colitis. The aim of this study is to investigate the efficacy of leukocytapheresis for the treatment of active pouchitis.MethodsEight patients with active pouchitis received leukocytapheresis weekly for 5 weeks in an open-label treatment protocol together with baseline therapy.ResultsPatients showed significant improvement in their pouchitis disease activity index scores, from 9.5 (range, 8–10) to 4.0 (range, 2–8) (P < 0.05). Six (75%) of the 8 treated patients achieved remission. No adverse events were observed.ConclusionsLeukocytapheresis therapy could be a new therapeutic strategy for patients with pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. These encouraging results lead us to propose a randomized controlled trial.

Glutamine and arginine metabolism in tumor-bearing rats receiving total parenteral nutrition

Arginine supplementation increases glutamine levels in muscle and plasma. Since glutamine production is increased in catabolic states, these observations prompted us to investigate whether the flux of arginine to glutamine was increased in tumor-bearing (TB) rats, and we measured the synthesis rate of glutamine from arginine in control versus TB rats receiving standard total parenteral nutrition (TPN) solution. Male Donryu rats (N = 36; body weight, 200 to 225 g) were divided into two groups, control and TB rats. Yoshida sarcoma cells (1 x 10(6)) were inoculated into the back of the rats (n = 18) subcutaneously on day 0. The rats were given free access to water and rat chow. On day 5, all animals, including non-TB rats (n = 18), were catheterized at the jugular vein and TPN was begun. On day 10, TPN solution containing either U-14C-glutamine (2.0 microCi/h) or U-14C-arginine (2.0 microCi/h) was infused as a 6-hour constant infusion. At the end of the isotope infusion, plasma was collected to determine the glutamine production rate in rats receiving U-14C-glutamine, and the ratio of specific activity of glutamine to specific activity of arginine was measured in rats receiving U-14C-arginine. Only 2 g tumor caused a decrease in glutamine levels and an increase in glutamine and arginine production. The low flux rate of arginine to glutamine was observed in control rats (Arg to Gln, 41.0 +/- 11.9 mumol/kg/h). On the other hand, TB caused a significant increase in Arg to Gln compared with the control (213.3 +/- 66.1 mumol/kg/h, P < .01 v control). An increase in the flux rate of Arg to Gln was associated with an enhancement in the ratio of specific activity of ornithine to specific activity of arginine in TB rats (control 51.5% +/- 10.9% v 77.4% +/- 8.9%, P < .05). We conclude that (1) glutamine and arginine metabolism is altered with very small tumors, (2) although the flux of Arg to Gln was increased in TB and rats, the small increase in Arg to Gln cannot explain the observed large increase in Gln production.

Effect of methionine-deprived total parenteral nutrition on tumor protein turnover in rats

Background. Previous studies have shown that a methionine‐lacking diet inhibited tumor growth in rats. The aim of this study was to determine how methionine free total parenteral nutrition (MTPN) can result in the inhibition of tumor growth on tumor protein metabolism in rats.