Effect of fentanyl on morphine levels in the brain in rats receiving intracerebroventricular injection of TNF-alpha.

Fentanyl citrate analgesia attenuates the excess nitrogen excretion in the urine and glucose production induced by trauma. On the other hand, intracerebroventricular injection of morphine stimulates excretion of stress hormones, such as catecholamines and corticosterone. Furthermore, morphine levels in the brain are increased during fasting and sepsis. The aims of this study were to determine whether intracerebroventricular injection of tumor necrosis factor-alpha (TNF-alpha) elevates morphine levels in the rat brain and whether prophylactic administration of fentanyl blocks metabolic responses induced by intracerebroventricular injection of TNF-alpha because of a reduction of morphine levels in the brain. Morphine levels in the brain were increased from 648 to 1,134 fmol/g at 30 min after intracerebroventricular injection of TNF-alpha (P < 0.05 vs. control). This increase was associated with an increase in stress hormones (corticosterone: 416.1 +/- 69.1 ng/ml, P < 0.05 vs. control; epinephrine: 3,778.3 +/- 681.3 pg/ml, P < 0.01 vs. control) and an enhancement of proteolysis (254.2 +/- 45.7 micromol Leu . kg-1 . h-1, P < 0.01 vs. control) and glucose production (7.5 +/- 0. 7 mg . kg-1 . min-1, P < 0.05 vs. control). Fentanyl reduced morphine levels in the brain to 624 fmol/g (not significant vs. control), resulting in a reduction of stress hormone levels in the plasma and blunted metabolic responses. In conclusion, prophylactic administration of fentanyl prevented an increase in morphine levels in the brain induced by intracerebroventricular injection of TNF-alpha, leading to a reduction in stress hormone levels and subsequent metabolic responses.

Effect of combination therapy with a methionine-mitomycin C conjugate and a methionine-deficient diet on tumor growth.

BACKGROUND: We investigated effects of a combination therapy of a methionine-mitomycin C conjugate (M-M conj) and methionine-free nutrition both in vitro and in vivo, compared to mitomycin C (MMC) administration alone. MATERIALS AND METHODS: The human esophageal cancer cell line, KE-3, incubated in either standard or methionine-free media, was treated with phosphate buffered saline (PBS), M-M conj in PBS, or MMC in PBS. The rate of cell survival was determined. The tumor bearing mice were maintained on either a standard or methionine-free diet (MFD) and treated with PBS, MMC, or M-M conj. RESULTS: The lowest tumor cell survival rate was found with the M-M conj plus methionine-free media at every dose tested (p < 0.05). Tumor weight was significantly lower with the M-M conj plus MFD than in any other group (p < 0.003). CONCLUSION: Methionine targets MMC to tumor during administration of MFD.

Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer.

OBJECTIVE: The objective of this study was to determine whether oral glutamine supplements can protect lymphocyte and gut barrier function in patients with advanced esophageal cancer undergoing radiochemotherapy. SUMMARY BACKGROUND DATA: Glutamine supplements improved protein metabolism in tumor bearing rats who underwent chemotherapy and reduced the toxicity of chemotherapy through an enhancement of glutathione production in rats. METHODS: Thirteen patients with esophageal cancer were randomly placed in either a control or a glutamine group. Glutamine was administered orally (30 g/day) at the start of radiochemotherapy and for the subsequent 28 days. All patients underwent mediastinal irradiation and chemotherapy consisting of 5-fluorouracil and cisplatin. The lymphocyte count was determined, and blast formation was assessed after stimulation with phytohemagglutinin and concanavalin A. Gut barrier function was assessed by measuring the total amount of phenolsulfonphthalein excreted in the urine after the oral administration of phenolsulfonphthalein. RESULTS: Glutamine supplements prevented a reduction in the lymphocyte count (control: 567 +/- 96/mm3 vs. glutamine: 1007 +/- 151, p < 0.05), and blast formation of lymphocyte (phytohemagglutinin, control: 19478 +/- 2121 dpm vs. glutamine: 33860 +/- 1433, p < 0.01, concanavalin A, control: 19177 +/- 1897 dpm vs. glutamine: 29473 +/- 2302, p < 0.01), and amount of phenolsulfonphthalein excretion in the urine was greater with control than with glutamine group (control: 15.4 +/- 2.4% vs. glutamine: 7.4 +/- 1.2, p < 0.05) 7 days after the initiation of radiochemotherapy. CONCLUSIONS: Oral glutamine supplementation protects lymphocytes and attenuates gut permeability in patients with esophageal cancer during radiochemotherapy.

Effect of methionine-free total parenteral nutrition and insulin-like growth factor I on tumor growth in rats.

The objectives of this study were to evaluate the effect of insulin-like growth factor I (IGF-I) on the fractional synthesis rate (FSR) of muscle and whole body protein breakdown rate (WPBR) during methionine-free total parenteral nutrition (MTPN). We also determined whether the inhibition of endogenous methionine availability reduced tumor protein synthesis. AH109A hepatoma cells were inoculated onto the backs of Donryu rats on day 0. On day 10, the rats were catheterized for TPN and assigned to one of four groups: 1) standard TPN (STPN), 2) STPN + IGF-I, 3) MTPN, or 4) MTPN + IGF-I. The addition of IGF-I to MTPN reduced the loss of body weight by both increasing muscle FSR and reducing WPBR. The tumor FSR did not differ between MTPN + IGF-I and MTPN. The methionine extraction ratio from the liver was negative with MTPN + IGF-I but positive in the other groups. We concluded that IGF-I blockage of endogenous methionine release from peripheral protein sites was associated with a shift to liver-derived methionine, with no change in tumor growth in MTPN-treated rats.

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 fentanyl citrate anesthesia on protein turnover in patients with esophagectomy.

The objectives of this study were to determine whether high doses of fentanyl anesthesia reduced the surgical stress level and to elucidate the effect of fentanyl anesthesia on protein turnover after esophagectomy. Seventeen male patients with esophageal cancer were divided into two groups, conventional anesthesia (CA) and fentanyl anesthesia (FA). The FA patients received 134.0 +/- 15.3 microg/kg fentanyl citrate and the CA patients 15.7 +/- 7.4 microg/kg fentanyl during the surgery. Protein turnover was measured by the method of bolus infusion of [15N]glycine (1 g). High dose of fentanyl anesthesia reduced cortisol levels during the surgery (CA 38.0 +/- 13.8 pg/ml vs FA 13.5 +/- 2.4, P < 0.05) and interleukin-6 levels in the plasma after the surgery (P < 0.02). The postoperative nitrogen retention was greater with fentanyl anesthesia than with conventional anesthesia. Both protein synthesis and breakdown rates were increased with fentanyl anesthesia, while they were unaltered in CA patients. Postoperative fibrinogen synthesis rate was greater with FA than with CA (CA 51.1 +/- 9.2%/day vs FA 100.9 +/- 14.0, P < 0.01). The protein turnover and fibrinogen synthesis data suggested a shorter duration of shock phase in FA patients than in CA patients. We concluded that a high dose of fentanyl anesthesia reduced surgical stress levels and shortened the postoperative shock phase, resulting in a nitrogen-sparing effect.

Effect of fentanyl citrate analgesia on glucose production following trauma in rats.

The postoperative hormonal milieu enhances glucose production. The objectives of this study were to determine whether fentanyl plus pentobarbital anesthesia reduced the excretion of stress hormones and whether this resulted in decreased glucose production following trauma. Male Sprague-Dawley rats were assigned into control and trauma. The trauma group was further subdivided into three groups according to the methods of anesthesia: T-1, pentobarbital (PB) alone; T-2, pentobarbital plus fentanyl (FE); and T-3, given PB during surgery and FE at the end of surgery. Glucose production was measured by a primed constant infusion of 3-3H-glucose. Fentanyl plus pentobarbital anesthesia prevented an increase in corticosterone levels in the plasma compared with in T-1 and T-3, 0.5 hr after the surgery. Fentanyl plus pentobarbital, anesthesia caused reductions of insulin and glucagon levels in the plasma and a decrease in catecholamines excretion in the urine. Glucose production was lower with FE+PB anesthesia than with PB alone (PB: 4.6 +/- 0.1 mg/kg/min vs PB+FE: 3.6 +/- 0.2 mg/kg/min, P < 0.05). However, fentanyl given at the end of surgery did not alter hormonal milieu and glucose production compared with pentobarbital alone. Blocking afferent neural stimuli from the wound and injury during the surgery is one approach to prevent an enhancement of postoperative glucose production.

A case report of rectal schwannoma.

We experienced a case of rectal schwannoma which was diagnosed before surgery. In this paper we have described this rare case and have discussed a number of similar cases reported in the literature.