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R A Forse

Publications and source records attributed to R A Forse.

At least 37 records · Page 2Linked to original sources
PubMed1998

Metabolism of dietary alpha-linolenic acid vs. eicosapentaenoic acid in rat immune cell phospholipids during endotoxemia.

Short-term (i.e., 3 d) continuous enteral feeding of diets containing eicosapentaenoic (EPA) and gamma-linolenic (GLA) polyunsaturated fatty acids (PUFA) to endotoxemic rats reduces the levels of arachidonic acid (AA) and linoleic acid (LA) in alveolar macrophage (AM) and liver Kupffer and endothelial (K&E) cell phospholipids with attendant decreases in prostaglandin formation by these cells in vitro. Diets that contain alpha-linolenic acid (LNA) as a substrate for endogenous formation of EPA may not be as effective in facilitating these immune cell modifications given the limited activity of delta6 desaturase. In the present study we compared the effectiveness of an LNA-enriched diet vs. an (EPA + GLA)-enriched diet to displace phospholipid AA from AM and liver K&E cells in vivo in endotoxemic rats fed enterally for 3 or 6 d. We determined the fatty acid composition of AM and K&E cell phospholipids by gas chromatography. We found that AM and K&E cells from rats that had received the EPA + GLA diet for 3 d had significantly (P < 0.001) higher mole percentage of EPA and the GLA metabolite, dihomoGLA, than corresponding cells from rats given the LNA diet or a control diet enriched with LA. Rats given the LNA diet had relatively low levels of stearidonic acid, EPA and other n-3 PUFA, while rats given the LA diet had low levels of GLA and dihomoGLA. We conclude that diets enriched with LNA or LA may not be as effective as those enriched with EPA + GLA for purposes of fostering incorporation of EPA or dihomoGLA into and displacement of AA from macrophage phospholipids under pathophysiologic conditions commonly found in acutely septic patients.

Animals↗
PubMed1998

Increased production of TNF-alpha and decreased levels of dienoic eicosanoids, IL-6 and IL-10 in mice fed menhaden oil and juniper oil diets in response to an intraperitoneal lethal dose of LPS.

Eicosapentaenoic acid (EPA) and the non-methylene interrupted fatty acids (NMIFA) displace arachidonic acid (AA: 20:4omega6 -5,8,11,14) in the membrane phospholipids. Unlike EPA (20:5omega3 -5,8,11,14,17), the NMIFA (20:3omega6 -5,11,14 and 20:4omega3 -5,11,14,17) lacking the delta-8 double bond are not substrates for the formation of eicosanoids. For 20 days, the mice were fed diets containing 5wt% dietary fats from various sources. The magnitudes in the production of eicosanoids and cytokines produced in response to an intraperitoneal injection of endotoxin in mice fed menhaden fish oil (MO) diets enriched with EPA were compared with those maintained on juniper oil (JO) containing NMIFA or on safflower oil (SO), a major source of the AA precursor, linoleic acid. The levels of PGE2, 6-keto-PGF1alpha and TXB2 were markedly lower (P < 0.01) in animals fed either MO or JO diets compared to the controls. The plasma levels of tumor necrosis factor (TNF)-alpha were significantly higher (P < 0.05) with a concomitant decrease of interleukin (IL)-6 and of IL-10 in mice fed MO or JO diets (P < 0.01) compared to those fed SO diet. These data suggest that the effects of consuming NMIFA of JO despite their inability to form eicosanoids are similar to those of feeding EPA which forms biologically active alternate metabolites.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Dietary alpha-linolenic acid increases TNF-alpha, and decreases IL-6, IL-10 in response to LPS: effects of sesamin on the delta-5 desaturation of omega6 and omega3 fatty acids in mice.

Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. We investigated the effects of consumption of diets containing 0.25wt% sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha-linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets, the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) were elevated with a concomitant decrease of arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals fed LOSO diets with or without sesamin, an increase in the circulating levels of TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of differences in the levels of AA, the PGE2 levels were significantly lower in mice fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data suggest that irrespective of the availability of a specific fatty acid as a substrate, through regulating the PGE2 synthesis, the production of TNF-alpha could be modulated.

Animals↗
PubMed1998

Hemodynamic effects of the laparoscopic pneumoperitoneum during sepsis in a porcine endotoxic shock model.

OBJECTIVE: The authors compared the hemodynamic effects of laparoscopic intervention with conventional laparotomy in an endotoxic shock model in the pig. SUMMARY BACKGROUND DATA: Laparoscopic techniques are being applied more frequently to severely ill patients to evaluate potential abdominal sources of sepsis. Although hemodynamic effects of laparoscopy are minimal in healthy patients, recent studies have shown more significant changes in patients with chronic cardiopulmonary disease. It is unclear whether these effects are applicable to acutely septic patients. METHODS: Twelve domestic pigs received intravenous lipopolysaccharide (LPS) injection and underwent surgical abdominal exploration using either laparoscopy or conventional laparotomy. For baseline comparison, four pigs underwent exploratory laparoscopy without intravenous LPS injection. Hemodynamic measurements and blood gas analyses were obtained using Swan-Ganz and arterial catheters. RESULTS: After LPS exposure, animals undergoing laparoscopic evaluation were significantly more hypercarbic (p < 0.01) and acidotic (p < 0.01) than those undergoing conventional laparotomy. Their mean pulmonary arterial pressure and pulmonary vascular resistance were greater as well (not significant). The cardiac index (p < 0.05) and stroke volume (p < 0.05) were decreased in the laparoscopic group. Their oxygen delivery was decreased and oxygen consumption increased, although these were not significantly different from those of the laparotomy group. The degree of acidosis was highly correlated with the cardiac index (correlation coefficient, r = 0.82). CONCLUSIONS: Animals exposed to LPS tolerate laparoscopy but with significant hemodynamic compromise. Much of this effect seems to be mediated by a cardiodepressive effect of acidosis. This study suggests that laparoscopic intervention, when used in septic patients, should be used with caution.

Animals↗
PubMed1998

Nutrition support for patients after cardiopulmonary bypass: required modifications of the TPN solution.

OBJECTIVE: This study was designed to identify the unique metabolic characteristics of patients undergoing cardiopulmonary bypass (CPB) surgery who require postoperative parenteral nutrition. SUMMARY BACKGROUND DATA: Patients undergoing CPB surgery occasionally develop postoperative complications that result in the need for nutrition support. Although enteral nutrition is generally the preferred feeding route, symptomatic hyperlipasemia has been described in critically ill CPB patients receiving enteral nutrition proximal to the ligament of Treitz. In such instances, enteral feeding must be temporarily discontinued or severely curtailed, thereby necessitating the initiation of parenteral nutrition for full or partial support. METHODS: The period from 1988 through 1993 during which time 4091 CPB procedures were performed was reviewed. Data were retrospectively collected on 208 (5%) of the patients who underwent CPB who developed postoperative complications that necessitated the initiation of parenteral nutrition (PN) support. A random sample of 79 patients who underwent CPB who did not require PN were selected as controls. RESULTS: Patients requiring PN after CPB were significantly older and had a higher prevalence of diabetes and metabolic complications, specifically volume overload, hyponatremia, metabolic alkalosis, uremia, and hyperglycemia, than those patients who did not require PN after CPB. In addition, patients requiring PN after CPB were significantly more hypotensive and required more vasopressive drugs during the first 24 to 48 hours after surgery than control patients. CONCLUSIONS: In patients with postoperative complications after CPB, PN is often necessary to correct the metabolic characteristics of overhydration, hyponatremia, uremia, hyperglycemia, and alkalosis.

Aged↗
PubMed1997

The new dietary fats in health and disease.

Lipids are an integral part of the routine diet of patients and the general public. In this article, the physiologic properties of various dietary lipids are reviewed, beginning with those most commonly consumed-the long-chain triglycerides (LCTs) and extending to those with special purposes: the short- and medium-chain triglycerides. The nutritional dietary management of patients typically includes physical mixtures of lipids. Recently, structured triglycerides (STs), which combine advantages from conventional fats with those of special purposes, have become available. STs are currently developed by interesterifying a mixture of conventional fats and oils, usually with medium-chain triglycerides, to achieve a specific fatty acid profile. This results in a triglyceride containing combinations of short-, medium-, and long-chain fatty acids on a single glycerol backbone. They have unique chemical, physical, or physiologic properties that are not observed by simply blending mixtures of the starting fats and oils. A number of STs are under intense laboratory and clinical investigation in models of cancer, burns, and immune dysfunction. Much interest in the fatty acids resides in the sn-2 position on the glycerol molecule. This is because the fatty acid in the sn-2 position of triglycerides is preferentially absorbed as the 2-monoglyceride and serves as the template for reesterification by intestinal cells to re-form triglycerides. The sn-2 fatty acids are also preferentially preserved as components of chylomicrons and very-low-density lipoprotein particles for ultimate incorporation in tissue membranes. Technology is evolving to create STs with a selected fatty acid in this sn-2 position. For instance, incorporating linoleic, arachidonic, or eicosapentaenoic acid at the sn-2 position is being evaluated for the specific objective of modulating serum cholesterol concentrations and essential fatty acid absorption (a review of this work is included).

Absorption↗
PubMed1997

L-[1-(13)C] Phenylalanine oxidation as a measure of hepatocyte functional capacity in end-stage liver disease.

BACKGROUND: Liver disease is associated with impaired metabolism of these amino acids phenylalanine and tyrosine. Decreased metabolism of these amino acids leads to abnormal plasma elevations and impaired clearance rates. We have developed a noninvasive breath test that measures hepatic cytosolic enzyme activity. METHODS: The rate of hepatic phenylalanine metabolism was quantitatively calculated from the appearance of 13CO2 in the breath using the nonradioactive tracer L-[1-(13)C]phenylalanine. RESULTS: Normal controls (n = 47) oxidized phenylalanine more than twice that of end-stage liver disease patients (n = 117). Significant differences in the percent of phenylalanine oxidized per hour (mean +/- SEM) were found between controls (7.08% +/- 0.33%, 95% CI: 6.42%-7.74%) and Child Pugh classification patients, class A (4.96% +/- 0.69%, 95% CI: 3.50%-6.42%), class B (2.88% +/- 0.13, 95% CI: 2.39%-3.38%) and class C (1.75% +/- 0.13, 95% CI: 1.50%-2.01%). The phenylalanine breath test score significantly correlated with albumin levels, prothrombin time and total bilirubin. CONCLUSION: We have demonstrated that phenylalanine oxidation is significantly decreased with end-stage liver disease and is correlated with the best clinical measures of liver disease.

Adult↗
PubMed1997

Decreased production of interleukin-1-beta, prostaglandin-E2 and thromboxane-B2, and elevated levels of interleukin-6 and -10 are associated with increased survival during endotoxic shock in mice consuming diets enriched with sesame seed oil supplemented with Quil-A saponin.

Sesamin, present in sesame seed oil (SSO), can inhibit delta-5-desaturase activity and cause accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid, and subsequently decrease production of dienoic eicosanoids. The effects of diets containing both SSO and Quil A, a saponin that emulsifies fats and potentiates the immune responses, were also studied. A mixture of oils having a fatty-acid composition similar to that of SSO served as a control diet. The levels of docosapentaenoic acid in mice fed Quil-A-supplemented diets and of DGLA in those fed SSO diets were markedly higher in the liver. These changes were associated with a significant reduction in the plasma prostaglandin-E(1+2) and thromboxane-B2 levels in response to an intraperitoneal injection of a lethal dose of lipopolysaccharide (LPS) endotoxin (LD50 20 mg/kg). The levels of interleukin (IL-)6 were elevated and those of IL-1beta were decreased in mice consuming Quil-A-supplemented diets. The IL-10 levels that were elevated in all mice after LPS exposure, remained higher (even at 9 h) only in those fed Quil-A-supplemented diets, but declined rapidly in others. During a 48-hour observation period following LPS injection, all control animals died, and survival was 40% in the SSO group, and 27 and 50%, respectively, in those fed Quil-A-supplemented control and SSO diets. These data suggest that SSO and Quil A when present in the diet exerted cumulative effects that resulted in a decrease in the levels of dienoic eicosanoids with a reduction in IL-1beta and a concomitant elevation in the levels of IL-10 that were associated with a marked increase in survival in mice.

Animals↗
PubMed1996

n-3 fatty acids decrease colonic epithelial cell proliferation in high-risk bowel mucosa.

The n-3 fatty acids (C20:5, eicosapentaenoic acid; c22:6, docosahexaenoic acid) may be important in the development, growth, and metastasis of colon cancer, a leading cause of death in North America. Patients who have had a bowel neoplasm have a high risk of developing a second neoplasm, and this risk is associated with a high percentage of cells correspond to the S phase of bromodeoxyuridine (BrdUrd) labeling in mucosal epithelial cells. To determine the effect of n-3 fatty acid supplementation on DNA synthesis of rectal mucosa, patients with stage 1 or stage 2 colon carcinoma or adenomatous polyps were randomized to consume either 9 g/d n-3 fatty acid capsules or 9 g/d placebo capsules. Plasma phospholipid fatty acid analysis and proctoscopic mucosal biopsies were performed at baseline, 3, and 6 mon. Colonic crypts were isolated from the mucosa, disassociated with enzymes, and incubated with BrdUrd, and %S phase was measured by flow cytometry. The plasma phospholipid n-6/n-3 ratio was determined by gas chromatography. Supplement compliance was assessed by plasma phospholipid n-6/n-3 ratio. Mean capsule consumption in these two group was 82%. Prior to supplementation, there were no significant differences in the %S phase and the plasma n-6/n-3 ratio between these groups. Patients whose colonic epithelial cells indicated hyperproliferation at baseline showed a strongly positive correlation to the %S phase of BrdUrd uptake and the n-6/n-3 ratio. There was no significant change after n-3 treatment in patients with low baseline. Those in the placebo group showed no significant difference in n-6/n-3 ratio, although there was an increase in the %S phase of BrdUrd uptake at 6 mon. The n-3 group did not have significant side effects, and polyps were not found after completing 12 mon of n-3 fatty acid supplementation. This study suggests that n-3 fatty acid may be a useful chemopreventive agent in some patients as reflected in a plasma biomarker of colon tumor growth and metastasis. A low plasma phospholipid n-6/n-3 fatty acid ratio may serve as a nutritional marker that is associated with colonic epithelial cell hyperproliferation in the n-3-supplemented group as compared with the placebo group. Characteristics of mucosal proliferation at baseline may be a crucial factor for the effect of n-3 fatty acid supplementation.

Cell Division↗
PubMed1996

High-energy, high-protein, oral, liquid, nutrition supplementation in patients with HIV infection: effect on weight status in relation to incidence of secondary infection.

OBJECTIVE: to evaluate the use of high-energy, high-protein, oral, liquid, nutrition supplementation and nutrition counseling on the weight status of patients infected with the human immunodeficiency virus (HIV) with and without secondary infections. DESIGN: Prospective, descriptive, intervention trial. Follow-up clinic visits were scheduled every 1 to 3 weeks for at least 6 weeks to monitor weight, gastrointestinal symptoms, number of supplements consumed, and incidence of secondary infections. SUBJECTS/SETTING: Community-based, HIV-infected patients, with and without an acquired immunodeficiency syndrome (AIDS) defining illness, who were receiving outpatient medical care at Deaconess Hospital. Twenty-two patients enrolled; however, 4 dropped out and 1 died, so 17 were eligible for evaluation. INTERVENTION: Dietary counseling consisted of recommendations to consume a high-protein diet (1.5 g/kg ideal body weight); select foods that minimize gastrointestinal complications; and take at least one high-energy, high-protein, oral, liquid, nutrition supplement daily. MAIN OUTCOME MEASURES: Energy intake from the supplements and weight change over time in relation to whether a secondary infection occurred. STATISTICAL ANALYSIS: Means, standard deviations, and frequency. RESULTS: At the time of entry to the study, the patients with preexisting weight loss (16 of 17) were 14+/-8% below their usual body weight. On average, patients consumed 11+/-4 supplements per week for 6+/-3 weeks. The majority (12 of 17) were able to gain or maintain weight. Overall weight change was 1.1+/-2.2 kg. Only 5 of 17 patients lost weight, 4 of whom developed a secondary infection during the study (ie, after enrollment in the study). All of those who developed a secondary infection were classified as having AIDS and had lower mean CD4 counts at baseline than those who did not develop a secondary infection. Although those who developed a secondary infection had a higher incidence of weight loss, their consumption of oral supplements per week was greater than that of those without a secondary infection. APPLICATIONS/CONCLUSIONS: In patients with HIV infection and in the early stages of AIDS without a secondary infection, weight gain and/or maintenance was achievable with a high-energy, high-protein, oral, liquid, nutrition supplement in conjunction with nutrition counseling. The majority of the patients who developed a secondary infection, however, lost weight despite the use of supplements and counseling. Use of a high-energy, high-protein, oral, liquid, nutrition supplement, with intact nutrients, should be the first-line nutrition treatment for malnourished, HIV-infected patients without secondary infections.

AIDS-Related Opportunistic Infections↗
PubMed1996

Safety and long-term efficacy of revisional surgery in severe obesity.

BACKGROUND: A National Institutes of Health Consensus Conference in 1991 established gastric surgery as accepted therapy for the treatment of severe obesity. The increasing prevalence of obesity in the United States, and the increasing numbers of patients undergoing gastric surgery for severe obesity, result in substantial numbers of patients being considered for revisional surgery. The indications and efficacy of revisional surgery remain controversial. METHODS: Sixty-three patients were followed prospectively after undergoing revisional surgery for obesity between 1981 and 1994. All patients had previously undergone obesity operations. Weight data were recorded at the time of original obesity surgery, at revisional surgery, and at most current follow-up. Complications following revisional surgery were monitored. RESULTS: The follow-up in the group is 98%. Revisional surgery after obesity surgery was associated with a 0% mortality rate and a serious complication rate of 16%. Body mass index (BMI) at the time of original surgery was 50 +/- 10 kg/m2, at revisional surgery 39 + 9 kg/m2, and at recent follow-up 34 +/- 10 kg/m2 (P < 0.001 vs original BMI). Those patients whose original BMI was > 50 kg/m2 lost significantly more weight (P < 0.0001) than those with an original BMI < 50 kg/m2. CONCLUSIONS: Revisional gastric surgery is safe and does provide patients with the opportunity to achieve long-term weight control.

Body Mass Index↗
PubMed1996

Injury induces rapid changes in hepatocyte nuclear factor-1: DNA binding.

BACKGROUND: Transcriptional regulation in the liver plays a critical role in mediating the acute phase response to injury. The molecular mechanisms driving these transcriptional events, however, are poorly defined in vivo. The liver-specific transcription factor hepatocyte nuclear factor (HNF)-1 binds to the 5' upstream region of many acute phase genes. To explore the connection between injury and transcriptional regulatory mechanisms, we investigated the effect of injury on HNF-1 binding activity. METHODS: Liver nuclear extracts were prepared from animals after burn or anesthetized sham burn injury. HNF-1 binding activity, affinity, and off rate were assessed by electrophoretic mobility shift analysis. RESULTS: HNF-1 binding activity decreased by 28% 1 1/2 hours after injury. The dissociation constant for HNF-1 increased from 0.6 nm to 11.8 nm at 1 1/2 hours after burn injury partly because of an increase in off rate for the HNF-1: DNA complex. CONCLUSIONS: Burn injury leads to a significant decrease in HNF-1 binding activity as a result of decreased affinity of HNF-1 for DNA. These injury-induced alterations in binding of a liver-specific transcription factor for its DNA binding site represent a mechanism for rapidly modulating acute phase gene transcription in vivo.

Animals↗
PubMed1996

Rapid modulation of lung and liver macrophage phospholipid fatty acids in endotoxemic rats by continuous enteral feeding with n-3 and gamma-linolenic fatty acids.

Dienoic eicosanoids derived from phospholipid arachidonic acid (AA) in lung and liver macrophages promote leukosequestration, thrombosis, and tissue injury. Current enteral diets (diet A) are enriched with linoleic acid (LA), a precursor of AA. Novel diets low in LA and containing eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) foster formation of less inflammatory eicosanoids. The study objective was to assess the rapidity and extent of LA and AA displacement in vivo from alveolar macrophage (AM phi), lung, and liver Kupffer and endothelial (KE) cell phospholipids in rats fed enterally with diets enriched with 5.3% (by wt) EPA and either 1.2% or 4.6% GLA (diets B and C, respectively). After surgical placement of catheters, the rats were fed enterally and co-infused intravenously with either endotoxin or vehicle continuously for 3 or 6 d. Rats given either diet B or C had significantly lower (P < 0.01) relative percentages of AA and LA within the AM phi, lung, and KE cell phospholipids, and concomitantly higher percentages of EPA compared with rats infused with diet A after 3 d of enteral feeding irrespective of endotoxin co-infusion. Incorporation of dihomo-gamma-linolenic acid (DHGLA), the metabolite of GLA, into lung and KE phospholipids was significant in rats given diet C. Most of the changes in fatty acid composition occurred by day 3. The polyunsaturated fatty acid composition of AM phi, lung, and KE cell phospholipids can be rapidly modified by continuous short-term enteral feeding with EPA- and GLA-enriched diets irrespective of concurrent endotoxemia.

Animals↗
PubMed1995

The effect of dietary polyunsaturated fatty acids (PUFA) on acute rejection and cardiac allograft blood flow in rats.

For six weeks, recipient (Lewis RT11) and donor rats (LBNF11/n) were fed three diets that varied only in their lipid content. Diet A (MO) contained 19.5% menhaden oil and 0.5% safflower oil and was rich in omega 3 PUFA; diet B (SO) was 20% safflower oil rich in omega 6 PUFA; and diet C (BT) was 20% beef tallow rich in omega 9 monounsaturated fatty acids and saturated fat. In the first set of graft survival studies a group fed laboratory chow was included (CHOW). Heterotopic cardiac transplantation from donor to recipient animals was performed after the six-week feeding period. The effect of these diets on cardiac allograft survival, mixed lymphocyte response, and blood flow in the rejecting grafts was investigated. The median graft survival in days was significantly prolonged in the rats maintained on either MO (12 days) or SO (14.5 days) compared with the BT (8 days)-or lab chow (7.5 days)-fed animals (P < 0.05). Cyclosporine (CsA) administered at subtherapeutic levels further increased the differences between the PUFA-fed animals and the BT-fed group. The myocardial blood flow of the rejecting allografts was measured using an 85Sr-labeled microsphere technique on the fifth posttransplant day. Flow was greatest in the MO-fed group, and both MO and SO groups had significantly higher myocardial blood flow than BT-fed rats (P < 0.05) or those bearing isografts. The allogenic mixed lymphocyte responses of peripheral blood mononuclear cells (PBMC) and splenic lymphocytes were suppressed in MO- and SO-fed groups compared with BT-fed animals. The immunosuppressive effect of dietary PUFA warrants further investigation, and their use as a possible adjunctive treatment in organ transplantation should be considered.

Acute Disease↗
PubMed1995

Effect of membrane free fatty acid alterations on the adhesion of human colorectal carcinoma cells to liver macrophages and extracellular matrix proteins.

Epidemiologic studies have linked diets high in animal fat with colon carcinogenesis. A number of animal tumor models have shown that diets rich in omega-3 fatty acids inhibit colon carcinogenesis while diets rich in omega-6 fatty acids promote tumor growth. This study examines whether modification of the membrane fatty acid composition of both moderately (CX-1) and poorly differentiated (MIP-101 and Clone A) human colorectal carcinoma cells alters their interaction with Kupffer cells and extracellular matrix proteins (collagen type IV, fibronectin and laminin). The cells were treated with 15-16 micrograms/ml of docosahexanoic acid (22:6, omega 3) or linoleic acid (18:2,omega 6). Gas chromatography showed significant alterations in the membrane fatty acid composition of the human colorectal cancer cell lines. Binding assays were performed by measuring adherence of 51Cr-labelled tumor cells to Kupffer cell monolayers or to immobilized proteins. Omega-3 treatment significantly decreased the Kupffer cell binding of only the CX-1 line while omega-6 treatment decreased binding of all three cell lines. In contrast both omega-3 and omega-6 treatment of MIP-101 cells decreased binding to the extracellular matrix proteins with the omega-6 effect being more pronounced. These results indicate that the binding characteristics of the colon cancer cells to both Kupffer cells and extracellular matrix proteins may be determined in part by the membrane fatty acid composition. Decreased adherence to extracellular matrix proteins may lead to increased cell motility and invasiveness. Since Kupffer cell binding precedes tumor cell phagocytosis and killing, decreased binding may improve tumor cell survival.

Animals↗
PubMed1995

Lung preservation threshold in a compromised septic lung injury model.

BACKGROUND: Discrepancy between clinical and research works in lung transplantation could be due to differences between compromised clinical donor lungs and intact research lungs. The purpose of this laboratory study was to produce compromised lungs to compare with normal ones. METHODS: Sprague-Dawley rats were continuously infused with lipopolysaccharide (5 mg/kg) for 24 hours before organ harvest. Lungs were stored in University of Wisconsin solution at 4 degrees C for the following period: group 1: intact lungs, no storage (n = 12); group 2: septic lungs, no storage (n = 6); group 3: septic lungs for 6 hours (n = 5); and group 4: septic lungs for 12 hours (n = 5). All lungs were reperfused for 2 hours with venous blood using an isolated, pulsatile perfused lung system. RESULTS: Experimental variables were comparable between groups 1, 2, and 3. All septic lungs stored for 12 hours (group 4) failed within 1 hour of perfusion. CONCLUSIONS: These results indicate that compromised lungs with septic injury functioned at near control levels after 6 hours of preservation. Six hours may be a safe limit for human donor lungs, all of which are compromised in some way by the time of harvest.

Animals↗
PubMed1995

The role of gastric surgery in the multidisciplinary management of severe obesity.

Severe obesity affects the health and quality of life of 4 million Americans. The major cost of treating severe obesity and its associated comorbidities of hypertension, diabetes, cardiovascular disease, pulmonary insufficiency, cancer, and degenerative arthritis as well as the poor long-term results of medical, drug, and behavioral therapy has increased the numbers of patients being referred for surgical treatment. Gastric bypass and vertical banded gastroplasty are the two procedures recommended for severely obese patients. These operations currently have low morbidity and mortality. Surgery should be considered adjuvant therapy and must be part of a multidisciplinary approach. The significant long-term weight control resulting from the surgical therapy is associated with improvement and, often, resolution of comorbidities, including diabetes, hypertension, hyperlipidemia, and pulmonary insufficiency.

Combined Modality Therapy↗