Biomedical subjects

R A Forse

Publications and source records attributed to R A Forse.

At least 55 records · Page 3Linked to original sources

PubMed1995

An educational intervention in the surgical intensive care unit to improve ethical decisions.

BACKGROUND: The objective of this study was to determine whether an educational intervention on medical ethics offered during a surgical intensive care unit (SICU) rotation could effect meaningful change in a tertiary SICU. METHODS: A case-based education program was presented weekly to the surgical residents during their SICU rotation. Cases for study were designed to deal with specific ethical issues common to the SICU. Cases were studied with the residents in a group facilitated by a SICU attending physician and a nursing director. The effect of the course was monitored by case review and by the length of stay (LOS) assessment for patients who died in the SICU during 1990, the base year, through 1993. RESULTS: Discussions of an ethical nature occurred more regularly and earlier during these 4 years as determined by case reviews. For patients who died after being in the SICU a minimum of more than 30 days, a marked decrease occurred in the SICU LOS from 27.8 +/- 3.7 days in 1990 to 15.7 +/- 2.4 days in 1993 (p < 0.05). The number of deaths per year and the average acuity measured by the diagnosis related group score were similar during the 4 years. The LOS in the hospital for dying patients from non-SICU services remained similar during the same time frame. These changes resulted in the dying patients using 1003 SICU days in 1993, down from the 2028 days used in 1990 (p < 0.05). CONCLUSIONS: We conclude that through offering a clinical ethics program during the SICU portion of the residency training, residents increased knowledge and skill in addressing and integrating practical ethical issues into their surgical resident practice. In addition, patient care directly improved with an associated reduced SICU LOS and reduced cost.

Critical Care↗

PubMed1995

Generic enteral formulas: a new idea for the 1990s.

Generic equivalent enteral formulas are now commercially available. The purpose of this article is threefold: (1) to define generic equivalents and compare both their nutritional and monetary differences with brand name products, (2) to provide the clinician with factors to consider when evaluating generic formulas--the source and distribution of macronutrients and micronutrients, and patient tolerance, nutritional status and outcome--and (3) to provide information on how to incorporate generic enteral formulas onto an institution's enteral formulary. In today's environment of diminishing health care budgets, generic enteral formulas can play a role in cost containment without sacrificing quality nutritional care.

Aged↗

PubMed1995

Effects of prostaglandin E2, cholera toxin and 8-bromo-cyclic AMP on lipopolysaccharide-induced gene expression of cytokines in human macrophages.

Prostaglandin E2 (PGE2) appears to regulate macrophage cytokine production through the stimulatory GTP-binding protein (Gs protein)-mediated cyclic AMP (cAMP)-dependent transmembrane signal transduction pathway. In this study, we used PGE2, cholera toxin (CT; a direct G alpha s protein stimulator) and 8-bromo-cAMP (a membrane permeable cAMP analogue) to stimulate this pathway, and investigated their influence on cytokine gene expression in lipopolysaccharide (LPS)-activated human macrophages. The mRNA expression for interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 were determined employing reverse transcription polymerase chain reaction (RT-PCR) using specific primers. We demonstrated that PGE2, CT and 8-bromo-cAMP inhibited the LPS-induced gene activation of TNF-alpha and IL-1 alpha, and had no effect on the gene activation of IL-1 beta and IL-8. Further, our data indicate that PGE2 suppressed the gene activation of IL-6 following LPS stimulation, but neither CT nor 8-bromo-cAMP had an effect. These data suggest that PGE2 alters LPS-stimulated gene activation of only some of the early macrophage cytokines, and does so either by a Gs transmembrane cAMP-dependent or an independent system.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1994

Effects of continuous tube feeding of dietary fat emulsions on eicosanoid production and on fatty acid composition during an acute septic shock in rats.

The effects of a short-term (5 days) continuous intragastric tube feeding of diets containing n - 6 polyunsaturated fatty acids (PUFA) from safflower oil (SO) or n - 3 PUFA from menhaden oil (MO) on the production of proinflammatory mediators, and on the number of animals surviving after an intravenous injection of lipopolysaccharide (LPS) were investigated in rats. The phospholipid fatty acid composition of cell membranes from several organs and of plasma were also analyzed. No marked differences in the number of animals surviving or in the production of tumor necrosis factor-alpha were observed between the 2 groups of animals. However, 90 min after LPS exposure the plasma levels of prostaglandin (PG) E2 and 6-keto-PGF1 alpha decreased significantly (40% and 60%, respectively) for the group of rats fed MO diet compared to those fed SO diet (P < 0.05). Following continuous infusion of liquid MO diet, the amount of arachidonic acid (AA) detected was significantly lower in plasma (23%), spleen (43%), lungs (41%), and liver (38%), but was unchanged in the heart tissues. The percent of eicosapentaenoic acid (EPA) incorporated into phospholipids of plasma, spleen, lungs, liver, and heart were 7.6, 4.4, 2.1, 7.2, and 1.1%, respectively. These data indicate that after continuous MO feeding, a significant decrease in the production of proinflammatory eicosanoids was associated with a marked reduction in AA content. Further, these data suggest that nutritional intervention may have a therapeutic potential to ameliorate clinical symptoms due to excessive productions of eicosanoids during acute septic complications.

Animals↗

PubMed1994

A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients.

OBJECTIVE: To examine the safety and efficacy of multiple doses of PGG-glucan (poly-[1-6]-B-D-glucopyranosyl-[1-3]-B-D-glucopyranose) in high-risk patients undergoing major thoracic or abdominal surgery. DESIGN: An interventional, multicenter, double-blind, randomized, placebo-controlled study. SETTING: Four university-affiliated medical centers. PATIENTS: Sixty-seven high-risk patients undergoing major thoracic or abdominal surgery. INTERVENTION: Patients were randomized in a 1:1:1:1 ratio to receive saline placebo or PGG-glucan at a dose of 0.1 mg/kg, 0.5 mg/kg, and 1.0 mg/kg or 2.0 mg/kg. One dose was administered before surgery and three doses were administered after surgery. MAIN OUTCOME MEASURES: To examine the safety and efficacy of PGG-glucan infusion and to identify potentially important factors for a planned phase III study. RESULTS: A dose-response trend with regard to infection incidence among patients who received PGG-glucan was observed. Serious infections occurred in four patients who received placebo and in three patients who received PGG-glucan at a dose of 0.1 mg/kg. However, only one patient who received PGG-glucan at a high dose had a serious infection. The incidence and severity of adverse events was comparable in all groups. CONCLUSIONS: PGG-glucan was generally safe and well tolerated, may decrease postoperative infection rates, and warrants further investigation in a planned phase III trial.

Adjuvants, Immunologic↗

PubMed1994

Fatty acid composition of lung, macrophage and surfactant phospholipids after short-term enteral feeding with n-3 lipids.

Utilization of enteral feeding modalities may prove clinically relevant for rapid modulation of lung phospholipid polyunsaturated fatty acids (PUFA) that serve as substrates for the formation of vasoactive dienoic eicosanoids. We compared the effects of short-term enteral feeding with formulations enriched with either fish (n-3) or corn (n-6) oil PUFA on the fatty acid composition of rat lung, alveolar macrophage and surfactant phospholipids. The diets were infused continuously for 72 h through a surgically placed gastroduodenal feeding catheter by a syringe pump. The n-3 PUFA derived from the fish oil enriched diet were readily incorporated into the phospholipid membranes of the alveolar macrophages, lung tissue and pulmonary surfactant. The relative percentages of the n-3 PUFA were significantly higher and individual and total n-6 PUFA significantly lower in the macrophage, lung and surfactant phospholipids from the n-3-supplemented rats in comparison with those present in the rats infused enterally with the n-6 diet or untreated, chow-fed rats (baseline). In contrast, there was a significant increase in linoleic acid (18:2n-6) without modification of arachidonic acid (20:4n-6) in the alveolar macrophages, lung tissue and surfactant from rats enterally receiving the n-6 diet relative to levels measured in the rats at baseline. The results suggest that short-term continuous delivery of n-3-enriched enteral preparations can foster rapid modification of membrane phospholipid PUFA composition of lung tissue, alveolar macrophages and lung surfactant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Experience with enteral nutrition in a hospital population of acutely ill patients.

Enteral feeding has unique metabolic and immune advantages. This article describes the successful use of enteral nutrition, alone or in combination with parenteral feeding, in a tertiary-care hospital. Study participants were 89 patients who received enteral feeding during a 6-month period. These critically ill patients (ranging in age from 55 to 71 years) had severity of illness levels of 7 to 25 according to the Acute Physiologic and Chronic Health Evaluation (APACHE II) system and lengths of hospital stay from 27 to 73 days. Mortality was as high as 50% in patients with liver disease (nonmalignant), 35% in patients with cardiothoracic and vascular diseases, and 17% in patients with cancer and other diseases. Despite the severity of illness, patients met their energy and protein intake goals through enteral or combined feeding with total parenteral nutrition. Serial weights (ie, obtained weekly) and serum albumin concentrations did not improve during hospitalization. Complications related to enteral feeding were minimal (< 17% incidence). Differences were noted between survivors and nonsurvivors: nonsurvivors had lower serum albumin concentrations at the time of admission, had longer hospitalizations, and required total parenteral nutrition for more days than the survivors. Nonetheless, even with extremely sick patients, provision of enteral nutrition can be successful using the administration techniques we describe. Enteral nutrition could best be provided by beginning at a slow rate (10 c3/hour), inserting the feeding tube past the pylorus, and feeding according to sensible energy goals (25 kcal/kg of body weight), and using elemental then polymeric formulas.

Acute Disease↗

PubMed1994

Role of staging laparoscopy in the treatment of hepatic malignancy.

Despite current radiologic imaging capabilities, 40% to 70% of patients with primary or metastatic hepatic malignancies are found to have unresectable disease at the time of laparotomy. The present study evaluates the use of laparoscopy in the staging of hepatic malignancy. Twenty-nine patients underwent staging laparoscopy prior to a planned laparotomy for resection of a hepatic malignancy that was deemed resectable by computed axial tomographic scan and ultrasonography. Twelve patients had primary hepatic malignancies, and 17 had metastatic malignancies. Laparoscopy demonstrated evidence of unresectability in 48% (14 of 29) of patients studied. Four patients had unsuspected cirrhosis, and 10 had unresectable or extrahepatic metastatic disease. Patients who underwent laparoscopy alone had shorter mean hospital lengths of stay than historical controls who underwent laparotomy alone. We conclude that diagnostic laparoscopy should precede laparotomy for planned resection of hepatic malignancies.

Carcinoma, Hepatocellular↗

PubMed1994

Effect of prostaglandin E2 and other intracellular cyclic AMP elevating agents on the mitogen induced mouse splenocyte proliferation in a serum free culture condition.

Prostaglandins (PGs) play an important role in the regulation of the host's immune responses to infection and inflammation. However, the mechanisms through which the PGs regulate immune functions are not well known. In the present study, we investigated the T cell specific mitogen Concanavalin A (Con A) induced mouse splenocyte proliferation in a serum free condition in vitro in the presence of absence of different doses of PGE2, indomethacin, cholera toxin and forskolin. The Con A induced splenocyte proliferative responses were significantly inhibited following the addition of PGE2 and were markedly enhanced in the presence of indomethacin (PG synthase inhibitor). As with PGE2, both cholera toxin and forskolin, which increase intracellular cyclic AMP by activating stimulatory GTP binding protein (Gs protein) and adenylate cyclase respectively, inhibited splenocyte proliferation in a dose dependent manner. These data indicate that PGE2 down regulated mitogen induced splenocyte proliferation and that blocking the production of endogenous PGs potentiated T-cell mitogen response. Further, these findings suggest that PGE2 regulation of splenocyte proliferation is due to increasing intracellular cAMP through G protein transmembrane regulation of adenylate cyclase. This study also provided a defined experimental model to investigate mechanisms of the regulation of cellular function through the exogenous and endogenous mediators such as PGs and their intracellular signal transductions.

Adenylyl Cyclases↗

PubMed1994

Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients.

OBJECTIVE: The safety and efficacy of PGG-glucan in surgical patients at high risk for postoperative infection who underwent major thoracic or abdominal surgery were determined. SUMMARY BACKGROUND DATA: Recent studies have reported a 25% to 27% infectious complication rate in patients undergoing major surgery with an average cost per infected patient of $12,000. The efficacy of PGG-glucan pretreatment in prevention of sepsis has been demonstrated in rodent models for gram-negative and gram-positive bacterial and yeast infections. In vitro studies have demonstrated enhanced microbial killing by monocytes and neutrophils in healthy volunteers after PGG-glucan administration. Thus, PGG-glucan may play a role in decreasing the infectious complication rate in patients undergoing major surgery. METHODS: A double-blind, placebo-controlled randomized study was performed in 34 high-risk patients undergoing major abdominal or thoracic surgery. RESULTS: There were no adverse drug experiences associated with PGG-glucan infusion. Patients who received PGG-glucan had significantly fewer infectious complications (3.4 infections per infected patient vs. 1.4 infections per infected patient, p = 0.05), decreased intravenous antibiotic requirement (10.3 days vs. 0.4 days, p = 0.04) and shorter intensive care unit length of stay (3.3 days vs. 0.1 days, p = 0.03). CONCLUSIONS: PGG-glucan is safe and appears to be effective in the further reduction of the morbidity and cost of major surgery.

Abdomen↗

PubMed1994

Assessment of the cytokine response in liver donors at the time of organ procurement and association with allograft function after orthotopic transplantation.

BACKGROUND: The cause of allograft liver dysfunction after transplantation is unresolved. We tested the hypothesis that human donor liver may be predisposed to ischemia reperfusion injury, and graft dysfunction subsequent to ongoing inflammatory processes during donor hospitalization. STUDY DESIGN: A prospective study of organ donors and transplant recipients of allograft livers from these donors was conducted. Portal venous, inferior vena caval, and superior vena caval blood samples were obtained from 16 clinical organ donors at the time of organ procurement (one to 12 days post-trauma) to characterize the hepatic cytokine and acute phase protein response, to determine whether or not this response resulted from bacterial or endotoxin translocation to the portal circulation, and to assess whether or not transplant outcome was associated with plasma levels of cytokines in the donor. RESULTS: In comparison with systemic blood samples from ten healthy persons, all 16 donors exhibited significantly (p < 0.05) elevated plasma concentrations of interleukin-6, interleukin-8, soluble p55 tumor necrosis factor receptor type I (sTNFr-I), and C-reactive protein. No concentration differences existed among portal venous, inferior vena caval, and superior vena caval blood samples for any cytokine or acute phase protein measured. Donor levels of endotoxin, TNF-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobin were comparable with those in the healthy persons. Bacterial cultures of portal blood were negative. There was no association between the causation of donor trauma and either donor cytokine response or function and quality of the allograft liver after transplantation. Nor could an association between donor cytokine response and either early allograft function (less than 96 hours) or eventual transplant outcome in the recipients be detected. CONCLUSIONS: These results indicate that, although an ongoing inflammatory response to injury was evident in these donors at the time of organ procurement, there were no apparent adverse effects arising from these inflammatory processes on the function and quality of the donor liver after transplantation. Bacterial translocation does not seem to be a component of the pathogenesis of inflammation. Whether or not the presence of inflammation in the donor alters the metabolic responses of the allograft liver and recipient to transplant operation is unknown.

Acute-Phase Proteins↗

PubMed1994

Rapid modulation of liver-specific transcription factors after injury.

BACKGROUND: The reaction to injury is a well-orchestrated physiologic response involving the coordinated actions of multiple integrated systems. It initially occurs at the molecular level and involves changes in gene transcription. We hypothesized that the molecular mechanisms regulating the generation of an inflammatory response are similar to those orchestrating developmental and tissue-specific expression of proteins and, in the case of the acute phase response, occur through manipulation of liver-specific transcription factors and their binding activity. METHODS: Female BALB/c mice, 7 to 8 weeks old, were subjected to a 15% body surface area burn. Total and polyadenylated liver RNA was isolated, and Northern blot analysis was performed to determine the kinetics of the acute phase proteins albumin and fibrinogen and the liver-specific transcriptional factors CCAAT-enhancer binding protein (C/EBP) alpha, hepatocyte nuclear factor (HNF)-1 alpha, and HNF-4. RESULTS: Induction of the injury response was shown by an increase in fibrinogen messenger RNA levels and a decrease in albumin mRNA levels. The liver-specific transcription factor C/EBP alpha decreased after injury and remained significantly lower than control at 3 hours. HNF-4 mRNA levels fell more slowly, reaching significantly lower levels at 6 hours and remaining suppressed at 34 hours. HNF-1 alpha showed the most rapid fall in mRNA levels at 30 minutes after injury and remained significantly below control levels at 34 hours. CONCLUSIONS: The minimal burn injury model leads to the molecular induction of the acute phase response and induces significant and rapid changes in the liver-specific transcription factors C/EBP alpha, HNF-1 alpha, and HNF-4. These changes may represent a mechanism through which the organ-specific response to injury is mediated.

Animals↗

PubMed1994

Alterations in Ca2+ signal transduction in critically ill surgical patients.

BACKGROUND: Despite improvements in supportive care and pharmacologic therapies, sepsis and related disorders such as systemic inflammatory response syndrome (SIRS) continue to be a leading cause of death in the intensive care unit. We hypothesized that immune dysfunction in this setting may in part be mediated at the level of early signal transduction in monocytes and neutrophils as manifested by changes in intracellular free Ca2+. METHODS: Monocytes and neutrophils were isolated from patients in the intensive care unit who met the criteria for SIRS and from normal volunteers. Cells were loaded with the Ca(2+)-sensitive fluorescent dye Indo-1 and stimulated with the chemotactic peptide f-Met-Leu-Phe (fMLP). Changes in intracellular calcium ion concentration were measured by flow cytometry. RESULTS: Patient monocytes exhibited a decreased Ca2+ flux (43% +/- 3.1%) as compared with normal monocytes (63% +/- 2.5%) (p < 0.05). Patient neutrophils also exhibited a decreased Ca2+ flux in response to fMLP of 58% +/- 3.7% versus 69.3% +/- 3.1% for normal neutrophils (p < 0.05). Incubation of patient cells in normal plasma reversed this dysfunction and showed an improved Ca2+ flux to 60% +/- 2.7% for monocytes and 71% +/- 3.7% for neutrophils (p < 0.05). Conversely, calcium flux was decreased in both normal monocytes (42.3% +/- 3.1%) and normal neutrophils (55.4% +/- 3.8%) after incubation in SIRS patient plasma (p < 0.05). Incubation of normal monocytes and neutrophils in interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor, or lipopolysaccharide did not show a statistically significant alteration in calcium flux in response to fMLP. CONCLUSIONS: Patients with SIRS exhibit alterations in early signal transduction after stimulation with fMLP in monocytes and neutrophils. This effect appears to be mediated by a soluble factor because the defect in SIRS patient cells can be reversed by incubation in normal plasma and normal cells appear to acquire this defect after incubation in patient plasma. Further studies are underway to identify the factor or factors responsible for this functional defect.

Adult↗

PubMed1993

Regulation of cytokine mRNA expression in lipopolysaccharide-stimulated human macrophages.

One of the responses of the human macrophage to lipopolysaccharide (LPS) is the production of a number of cytokines. The regulation of these cytokines is still not clearly understood. To study this regulation, mRNA levels of interleukin 1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF-alpha), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-8/neutrophil chemotactic factor were determined in 10-day-old differentiated macrophages following stimulation with a low dose of LPS (0.001 to 10 ng/mL) with use of the polymerase chain reaction. Increased levels of mRNA for IL-8 were detectable after exposure to a very low dose of LPS (0.001 ng/mL) and levels of IL-1 beta and TNF-alpha were detectable only after stimulation with doses of 0.01 ng/mL. The mRNA for IL-8 was detected 30 minutes after the addition of LPS, while those for IL-1 beta and TNF-alpha were only measurable at 1 hour. The mRNAs for IL-1 alpha, IL-6, and GM-CSF were detectable only with a higher dose of lipopolysaccharide and only after a longer exposure time. In addition, the messages for IL-6 and GM-CSF were measurable for a short time, while those of IL-8 and of IL-1 beta were detectable for a longer time. The secretion of TNF-alpha and GM-CSF tightly followed gene activation, and that of IL-6 and IL-8 steadily increased even after the mRNA level of these cytokines returned to baseline. Secretion of IL-1 alpha and IL-1 beta was hardly detected, although their gene activation was obvious. These data indicate that cytokine mRNA levels following lipopolysaccharide stimulation are highly regulated. Individual cytokines show variable patterns of response. These responses are both dose and time dependent and are not necessarily associated with the secretion of protein.

Adult↗

PubMed1993

Results of the surgical treatment of obesity.

A prospective, randomized trial comparing vertical banded gastroplasty (VBG) and vertical gastric bypass (GB) for obesity was completed in 106 patients who did not differ in baseline body mass index (BMI = kg/m2) or length of follow-up. The goal of this surgery was to return patients to within 50% of their ideal weight, i.e., a body mass index less than 35 kg/m2, and to accomplish this while maintaining a low risk for malnutrition as well as other morbidity and mortality. Success was defined as a BMI less than 35 kg/m2 because the mortality risk increases rapidly above this degree of obesity. Surgical failures were encountered in 43% of the 54 patients in the VBG group, all of whom had division between the vertical staple lines. The main causes of failure were stenosis and enlargement of the gastroplasty orifice. Surgery failed in 23% of the GB-treated patients, due to perforation of the vertical staple line. An isolated gastric bypass (IGB) not dependent on staples was performed as the remedial operation for the failures of both VBG and GB. IGB was significantly better than VBG or GB, with a success rate of 83% compared with 39% for VBG and 58% for GB. Subsequent experience since completion of this randomized trial in 54 consecutive patients supports IGB for primary, as well as remedial, operations for the morbidly obese (BMI = 40 to 50 kg/m2), as well as for patients who are super obese (BMI greater than 50 kg/m2).

Adult↗

PubMed1993

Nutrition support and the human immunodeficiency virus (HIV).

Nutritional support of patients with HIV or acquired immune deficiency syndrome (AIDS) has many similarities to other disease states in that the same nutritional products and techniques are used. Some patients with HIV, and many with AIDS without secondary infection, experience a metabolic milieu similar to patients with cancer cachexia. In providing dietary counselling to the HIV patient, we encounter many of the obstacles that must be overcome to improve nutrition in cancer: anorexia, gastrointestinal discomfort, lethargy, and poor nutrient utilization, which limit the ability for nutritional repletion. When a secondary infection is superimposed on HIV, patients resemble more highly catabolic trauma patients or patients in the intensive care unit (ICU), where, despite aggressive efforts to feed, there is usually a net nitrogen wasting leading to the more rapid development of cachexia. However, even in this setting, feeding will limit substantially net catabolism when compared to total starvation. Because the nutritional needs of HIV patients vary greatly, individual strategies have to be designed as the patient moves through the stages of disease. Patients are generally able to consume adequate nutrition either as regular food or dietary supplements during the latency period of viral replication. Once secondary infections become prevalent, artificial diets administered by tube or by vein may be required during the period of active secondary infections, with dietary supplements often helpful during more quiescent periods. Patients with HIV are among the most challenging for clinicians providing nutritional support. Knowledge from treatment of patients with other diseases may be useful, but more data must be gathered on the unique aspects of aetiology and treatment of the anorexia, malabsorption, and ultimate wasting associated with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Hepatic utilization of exogenous nucleotide precursors for restoration of ATP after cold ischemia in rats.

The study objective was to assess hepatic utilization of exogenous adenosine or adenine to enhance ATP recovery in rat liver after cold ischemia. ATP was measured noninvasively by 31P nuclear magnetic resonance (NMR) in perfused livers before and after 18 h of cold ischemia. The hepatocellular concentration of ATP during the initial postischemic reperfusion without adenosine or adenine coinfusion was 60% of that in fresh liver. The ATP increased significantly (P < 0.001) to 139% and 82% of baseline in postischemic livers coinfused for 90 min with adenosine or adenine (final concentration, 1 mmol/L), respectively. Less than 0.5% of the excess adenosine was catabolized to uric acid. In conclusion, adenosine and, to a lesser extent, adenine are salvaged by liver after extended cold ischemia to enhance ATP restoration. Provision of these ATP precursors, as components of an enteral formulation may facilitate the repletion of liver ATP and foster early resumption of liver function after an ischemic insult.

Adenine↗

PubMed1993

Rapid incorporation of fish or olive oil fatty acids into rat hepatic sinusoidal cell phospholipids after continuous enteral feeding during endotoxemia.

Therapeutic modalities that downregulate macrophage and endothelial production of eicosanoid mediators by displacing membrane arachidonic acid (20:4 omega 6) may benefit patients at increased risk of septic complications. The objective of this study in rats was to assess the incorporation of fish or olive oil fatty acids into hepatic Kupffer and endothelial (K&E) cell phospholipids after 4 d of continuous enteral feeding during endotoxemia. Either endotoxin (ETX) (0.5-1 mg-1.day-1) or vehicle was infused intravenously during the last 72 h. Dietary fish and olive oil fatty acids were rapidly incorporated into both K&E and plasma phospholipids irrespective of ETX cotreatment. Rats infused with the fish oil-enriched diet had a significantly lower relative percent of both K&E linoleic acid (18:2 omega 6) and 20:4 omega 6, whereas rats infused with the olive oil-enriched diet only had a lower relative percent of 18:2 omega 6 compared with control rats receiving corn oil. Provision of specific dietary lipids by continuous enteral infusion may prove efficacious for the rapid modulation of hepatic sinusoidal cell membrane fatty acids under either normal or endotoxemic conditions.

Animals↗