Chronic exercise and the pro-inflammatory response to endotoxin in the serum and heart.

Purpose: To examine the effects of moderate intensity chronic exercise on tumor necrosis factor-alpha (TNFalpha) and inducible nitric oxide synthase (iNOS) responses to endotoxin in female Sprague-Dawley rats.

Methods: Rats were divided into two groups, exercise (n=17) and sedentary (n=24). Exercise (Ex) rats completed 12 weeks of motorized treadmill running 3 days/week for 15-25 min at 22-25 m/min, while sedentary (Sed) rats remained in their cages.

Ischemia/reperfusion-induced disruption of rat small intestine transit is reversed by total enteral nutrition.

Objectives: A reduced blood flow to the gut is a consistent event after traumatic shock. Enteral nutrition support has been shown to reduce the septic morbidity after major trauma. We evaluated the effects of a transient ischemia followed by reperfusion (I/R) and an enteral nutrition support regimen on the motility of the small intestine of the rat.

Influence of the ward colon tumor on the innate and endotoxin-induced inflammatory response of the rat.

Cachexia, a depressed immune function, and an increased infection rate are recurring problems for cancer patients; the response of the host to an infection may also be increased. We have reported that the transplantable Ward colon tumor (WCT) enhanced the lethality of endotoxin (lipopolysaccharide [LPS]) to the host. The mechanism of this increased LPS lethality and the effect of the presence of the WCT on the host inflammatory response, however, have not been reported.

Organ heavy-metal accumulation during parenteral nutrition is associated with pathologic abnormalities in rats.

Objectives: Metabolic bone disease, hepatic abnormalities, splenic insufficiency, and nephropathy have been associated with long-term total parenteral nutrition (TPN). We determined the heavy-metal contamination in TPN solutions and investigated whether it was associated with organ deposition and pathologic organ damage.

Methods: Five representative TPN solutions (two adult standard solutions, one renal solution, and one standard pediatric solution to reflect clinical practice) and 28 TPN components were analyzed with inductively coupled plasma mass spectrometry.

Temporal expression of tumor necrosis factor-alpha and nitric oxide synthase 2 in rat small intestine after endotoxin.

Temporal changes in tumor necrosis factor-alpha (TNF-alpha) and nitric oxide synthase 2 (NOS 2) were evaluated in segments of duodenum, jejunum, and ileum removed from male Sprague-Dawley rats 30, 60, 120, 180, and 240 min after lipopolysaccharide (LPS), 5 mg/kg, intraperitoneally. Plasma was assayed for TNF-alpha and for nitrate/nitrite (NOx). Intestinal and plasma TNF-alpha were elevated by 60 min after LPS and were back to control levels by 180 min.

Effect of ornithine in parenteral nutrition regimens on difluoromethylornithine-induced platelet suppression and changes in tumor polyamine content.

We have demonstrated that DFMO-induced thrombocytopenia can be ameliorated with concomitant ornithine (Orn) in chow-fed rats; a reversal in DFMO-associated tumor polyamine reduction and antitumor activity, however, was also evident. To determine the effect of Orn in total parenteral nutrition (TPN) regimens on DFMO-induced thrombocytopenia and changes in tumor polyamine concentrations, Ward-colon-tumor-bearing (WCT) rats were given TPN with arginine (ENA) or with ornithine substituted for arginine (ENO) alone or with DFMO (1.5 g/day) added directly to the infusate.

Influence of the Ward colon tumor on the host response to endotoxin.

Cachexia and a decreased immune function are negative prognostic factors for cancer patients. While the decreased immunity results in a greater susceptibility to bacterial infection, the response of the host to the resulting infection is not clear. The experiments reported here were designed to evaluate the toxicity of endotoxin to rats with a transplantable Ward colon tumor (WCT) and to evaluate the mechanism of the observed increase in lethal toxicity.

A parenteral nutrition regimen with ornithine substituted for arginine alters the amino acid, but not polyamine, content of the ward colon tumor.

Substituting ornithine for arginine in total parenteral nutrition (TPN) regimens eliminates the TPN-enhanced growth of the Ward colon tumor. Plasma arginine was increased when tumor growth was increased, suggesting a role for this amino acid. The erythrocyte polyamine content, however, was elevated in rats receiving both TPN regimens, indicating an increased synthesis and availability for tumors receiving arginine- and ornithine-containing regimens.

Reduced tissue ornithine increases the cytotoxicity of difluoromethylornithine.

Background: Polyamines are low molecular weight cations that are essential for the growth of all cells. The polyamine inhibitor difluoromethylornithine (DFMO) will decrease tumor growth when administered parenterally; thrombocytopenia is the major dose-limiting toxicity. Since an essential amino acid-based total parenteral nutrition (TPN) regimen was shown to reduce the ornithine and polyamine content of a transplantable sarcoma in preliminary studies, the effect of the amino acid content of TPN on the antitumor activity of DFMO was evaluated.

Nutritional support for adaptation to radiation-induced suppression of mucosal immunity in the intestine of the rat.

Appropriate enteral nutrition provided immediately after injury or trauma to the gastrointestinal tract may limit or reverse damage to the mucosal barrier. In this regard, diets containing amino acids, such as arginine and glutamine, or fish oil have been identified as beneficial. This report assesses the role of amino acids as "essential nutrients" in the repair of intestinal mucosa damaged by gamma radiation.

Citrulline and arginine increase the growth of the Ward colon tumor in parenterally fed rats.

Arginine is considered a necessary component of parenteral regimens because of the high nitrogen intake. The effect of arginine on tumor growth, however, is controversial. Our results suggest that substituting ornithine for arginine in parenteral regimens will ameliorate an arginine-related increase in growth of a Ward colon tumor.

Effect of intralipid infusion on serum high- and low-density lipoprotein cholesterol, lecithin:cholesterol acyltransferase, and lipoprotein lipase in tumor-bearing rats.

We compared the effects of 0.45% normal saline (NS), 5% Intralipid (IL), and 16.7% glucose (Glu) infusions on total serum triglycerides and cholesterol, serum high-(HDL-c) and low-density lipoprotein cholesterol (LDL-c), and activity of serum lecithin:cholesterol acyltransferase (LCAT), and serum lipoprotein lipase (LPL) in rats implanted with a fibrosarcoma.

Concentrations in serum and distribution in tissue of free and liposomal amphotericin B in rats during continuous intralipid infusion.

The influences of Intralipid (IL) and 0.45% normal-saline infusions on the concentration in serum and distribution in tissue of amphotericin B (AmpB) and liposomal amphotericin B (L-AmpB) in rats were compared. In animals receiving a continuous IL infusion, concentrations of AmpB in kidneys and lungs were significantly higher, but the concentration of AmpB in serum was significantly lower in animals administered AmpB versus those given L-AmpB.

Effects of intralipid infusion on rat serum lipoproteins.

The purpose of this investigation was to study the effects of continuous Intralipid infusions on serum HDL and LDL levels in the rat. Male Fischer 344 rats were infused continuously via central venous catheter with 10% Intralipid for 96 h and 5, or 2.5% Intralipid for 14 days.

Glutamine stability in biological tissues evaluated by fluorometric analysis.

Although glutamine has been considered unstable during storage and therefore difficult to quantitate, recent results suggest this amino acid is stable at low pH ranges. We evaluated the stability of glutamine in plasma and tissue extracts, using fluorometric analysis. The measured concentration of glutamine detected varied linearly up to 0.

Substituting ornithine for arginine in total parenteral nutrition eliminates enhanced tumor growth.

Total parenteral nutrition (TPN) may enhance the growth of some tumors: this enhanced growth is associated with an increase in the erythrocyte polyamine levels. The effect of arginine in TPN on tumor growth was compared with ornithine using rats with a transplantable Ward colon tumor. The relationship of circulating arginine, ornithine, glutamine, and polyamines with tumor growth was investigated.

Amelioration of thrombocytopenia with concomitant ornithine in sarcoma-bearing rats receiving high dose difluoromethylornithine.

The dose limiting toxicity of difluoromethylornithine (DFMO), when administered by continuous infusion, is thrombocytopenia. DFMO-induced antitumor activity and thrombocytopenia were time- and dose-dependent up to 1700 mg/kg/d when administered continuously for 12 days. Concomitant ornithine administration (at selected molar ratios to DFMO) ameliorated thrombocytopenia induced by DFMO at a dose of 2000 mg/kg/day without adversely affecting its antitumor activity.

Colorectal ornithine decarboxylase activity in human mucosa and tumors: elevation of enzymatic activity in distal mucosa.

To examine the value of ornithine decarboxylase (ODC) assay as a biological marker of potential malignancy in large bowel, we harvested 43 colorectal carcinoma, 7 adenoma, 6 polyps, and 77 normal-appearing mucosa at surgery from patients with colorectal carcinoma. In addition, 13 normal rectal mucosa were obtained at biopsy from patients with benign diseases or diseases unrelated to colorectal carcinoma as normal control. ODC activity was significantly higher in polyps and adenocarcinomas than in normal-appearing mucosa from patients with colorectal carcinoma.

Evaluation of continuous-infusion alpha-difluoromethylornithine therapy for colorectal carcinoma.

A total of 32 evaluable patients with measurable advanced colorectal carcinoma were treated with continuous-infusion alpha-difluoromethylornithine (DFMO) at a median daily dose of 8 g/m2 (range, 6-14 g/m2). DFMO was infused over 24 h daily for 28 days, followed by a rest period of 7 days. Of the 32 patients, 14 had received no prior chemotherapy.

Differential effects of parenteral nutrition on tumor growth and erythrocyte polyamine levels in the rat.

The influence of total parenteral nutrition (TPN) on tumor growth and erythrocyte polyamine levels was evaluated in rats with a transplantable fibrosarcoma or a Ward colon tumor. During the experimental periods the fibrosarcoma grows exponentially when rats are fed chow ad libitum while the colon tumor reaches a plateau of its Gompertzian growth curve. A 12-day regimen of TPN resulted in an increased growth of the colon tumor but not the fibrosarcoma.

Alterations in polyamine metabolism during continuous intravenous infusion of alpha-difluoromethylornithine showing correlation of thrombocytopenia with alpha-difluoromethylornithine plasma levels.

Polyamine biosynthesis is important for cell proliferation and growth. The purpose of this study was to determine the biochemical and pharmacological parameters associated with host toxicity from a continuous infusion of alpha-difluoromethylornithine (DFMO). Twenty-five patients with metastatic carcinoma of the colon or rectum received continuous infusion of DFMO at a median dose of 8 g/m2/day (range, 6-14) for 28 days.

Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity.

The purpose of this study was to evaluate the effect of a concomitant infusion of ornithine on the difluoromethylornithine (DFMO)-induced thrombocytopenia and antitumor activity. Male Fischer 344 rats with either a transplantable fibrosarcoma or Ward colon tumor were given a 12-day continuous infusion of DFMO (2000 mg/kg/day) alone or with ornithine. The dose of ornithine was defined as the molar ratio to DFMO.

Influence of total parenteral nutrition on tumor growth and polyamine biosynthesis of fibrosarcoma-bearing rats after induced cachexia.

The effect of a protein-free diet (PF) or a restricted intake of chow (RI) and subsequent host repletion with total parenteral nutrition (PF-TPN, RI-TPN) on tumor growth and polyamine metabolism of fibrosarcoma-bearing rats was examined. Host weight was significantly reduced by PF and RI. Tumor growth was reduced in malnourished rats with the PF regimen resulting in the greatest decrease.