Biomedical subjects

Stephen J DeMichele

Publications and source records attributed to Stephen J DeMichele.

10 recordsLinked to original sources

PubMed2006

A nutritional strategy to improve oxygenation and decrease morbidity in patients who have acute respiratory distress syndrome.

Enteral nutrition is increasingly becoming the standard of care for critically ill patients with the goal of providing nutritional support that prevents nutritional deficiencies and reduces morbidity. Furthermore, the development of nutritional strategies that dampen inflammation is an encouraging advance in the management of patients who have acute respiratory distress syndrome. This article discusses evidence from randomized, controlled studies that the use of a specialized nutritional formula containing eicosapentaenoic acid plus gamma-linolenic acid and elevated antioxidants offer physiologic and anti-inflammatory benefits over standard formulas.

Animals↗

PubMed2006

Nutritional formula improved immune profiles of seniors living in nursing homes.

OBJECTIVES: To assess whether an experimental nutritional formula (EXP) supports immune function in seniors living in long-term care facilities. DESIGN: Prospective, randomized, double-blind, controlled trial conducted September 2002 through January 2003. SETTING: North central Florida nursing homes. PARTICIPANTS: Subjects aged 65 and older (n = 157). INTERVENTION: Subjects received 240 mL/d of EXP or standard liquid nutrition (CON) for 4 weeks before and 6 weeks after an influenza vaccination. MEASUREMENTS: Influenza vaccine antibody responses, immunophenotyping, lymphocyte activation, cytokines, and clinical measures (fever, number of prescribed antibiotics). RESULTS: Ninety-two subjects (n = 40, CON; n = 52, EXP) completed the study. Geometric mean antibody titers were similar between groups, yet the percentage of subjects with H1N1 antibody titers greater than 100 postvaccination was higher in the EXP group than in the CON group (43% vs 23%, P=.047). Similar trends were found for the percentage of subjects (intent to treat) with fourfold increases against the B/Hong Kong component (64% vs 46%, P = .09) or with H3N2 antibody titers of 40 or more (97% vs 89%, P=.06). EXP subjects had higher levels of influenza-activated lymphocytes (CD69+ and CD25+). Cytokine production after mitogen activation was lower in EXP than CON subjects (interleukin (IL)-6: 20+/-3 vs 29+/-3 ng/mL, P = .045; IL-10: 310+/-60 vs 603+/-140 pg/mL, P = .06). Fewer EXP subjects were treated for fever (5% vs 16%, P = .02) or prescribed antibiotics (7 vs 11 new antibiotics/100 days of study, P = .06). CONCLUSION: Seniors consuming the EXP formula demonstrated enhanced immune function, indicated by increased influenza vaccine response and lymphocyte activation, less fever, and fewer newly prescribed antibiotics than those consuming a standard ready-to-drink nutritional supplement.

Aged↗

PubMed2005

Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast cancer cells.

Many epidemiological studies have suggested that consumption of green tea may decrease the risk of cancer. The chemopreventive effect of green tea polyphenols (GTP) has been demonstrated through the inhibition of cell proliferation and angiogenesis in cell culture and animal models of breast cancer. Metastasis of breast cancer is the major reason for the high mortality of breast cancer patients and is directly linked to the invasive behavior of breast cancer cells. Cancer metastasis consists of several interdependent processes including cancer cell adhesion, cancer cell migration, and invasion of cancer cells. In this study, we evaluated the effect of GTP on human breast cancer cells, and we show that in addition to inhibiting cell growth, GTP also suppressed the invasive behavior of MDA-MB-231 cells. These anti-invasive effects of GTP were the result of the inhibition of constitutively active transcription factors AP-1 and NF-kappaB, which further suppressed secretion of urokinase plasminogen activator (uPA) from breast cancer cells. Based on these results, it can be hypothesized that GTP treatment resulted in the inhibition of formation of signaling complexes responsible for cell adhesion and migration (uPA, uPA receptor, vitronectin, integrin receptor) and cell invasion (uPA, uPA receptor). Our results indicate that GTP may contribute to the anticancer effects of green tea by inhibiting the invasive behavior of cancer cells.

Breast Neoplasms↗

PubMed2005

Novel nutritional immune formula maintains host defense mechanisms.

Military combat and training stress induce immune changes that increase the risk of infection and ultimately influence soldiers' performance and readiness. Strenuous military training/assessment provides a uniform stress and the opportunity to evaluate nutritional strategies to minimize stress-induced immune changes that predispose soldiers to infection. Immunological changes and effects of a novel nutritional immune formula (NNIF) were examined prospectively in a double-blind, controlled study of 200 soldiers attending Special Forces Assessment and Selection School. Immune function was measured by skin delayed-type hypersensitivity, lymphocyte phenotyping, mitogenic proliferative responses, and granulocyte function. Approximately 50% of soldiers completed the study (control, n = 57; NNIF, n = 50). Several stress-induced lymphocyte changes were observed (decreased mitogen-induced proliferation, T and total lymphocytes, and interferon-gamma-producing lymphocytes and increased percentage of neutrophils). NNIF modified several changes, including delayed-type hypersensitivity responses (NNIF, 78%; control, 59%; p < 0.05), increased proportions of helper T cells, activation of B cells, enhanced neutrophil phagocytosis, and attenuation of declines in certain functional subpopulations (i.e., cytotoxic/ suppressor lymphocytes). Soldiers who consumed NNIF experienced less stress-induced immune impairment, thereby lowering the risk of infection.

Adult↗

PubMed2004

Effect of long-term dietary supplementation of high-gamma-linolenic canola oil versus borage oil on growth, hematology, serum biochemistry, and N-6 fatty acid metabolism in rats.

Dietary supplementation of a high-gamma-linolenic acid canola oil (HGCO) containing approximately 36% (w/w) of gamma-linolenic acid (GLA, 18:3n-6) from the seeds of a genetically transformed canola strain, was assessed for its long-term biological effects. Growing Sprague-Dawley rats (n = 30) were fed a purified AIN93G diet containing 5, 10, or 15% (w/w) of HGCO as the fat source. For comparison, a separate group of rats (n = 10) was given the diet containing 15% (w/w) of borage oil (BO), which contained 22% (w/w) of GLA. After 12 weeks of feeding, the growth, relative organ weights, hematology, and serum biochemistry were found to be similar among rats fed the 5, 10, and 15% HGCO diets. The GLA levels in plasma and liver phospholipids (PL) were also similar. However, the levels of GLA in peripheral tissues (muscle PL and adipose triacylglycerols) were significantly higher in rats fed the 10 and 15% HGCO diets than those fed the 5% HGCO diet. When the above biologic parameters were compared between the 15% HGCO and 15% BO dietary groups, there were no significant differences except for lower final body weights and higher tissue levels of GLA, dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid (20:4n-6) in the 15% HGCO dietary group as compared with the 15% BO dietary group. This is due to a higher GLA content and possibly a more favorable stereospecific distribution of GLA in HGCO. Overall, long-term (12-week) feeding with diets containing up to 15% HGCO resulted in no adverse effects on growth, organ weight, hematology and serum biochemistry as compared to the diet containing 15% BO, suggesting that HGCO may be a safe alternative source of GLA.

Adipose Tissue↗

PubMed2004

The acute respiratory distress syndrome: role of nutritional modulation of inflammation through dietary lipids.

The acute respiratory distress syndrome (ARDS) is the most serious form of acute hypoxic respiratory failure. ARDS represents the expression of an acute, diffuse, inflammatory process in the lungs consequent to a variety of infectious and noninfectious conditions. It is characterized pathologically by damage to pulmonary epithelial and endothelial cells, with subsequent alveolar-capillary leak and exudative pulmonary edema. The main clinical features of ARDS include rapid onset of dyspnea, severe defects in gas exchange, and imaging studies demonstrating diffuse pulmonary infiltrates. The role of nutrition in the management of ARDS has traditionally been supportive. Recent research has demonstrated the potential of certain dietary oils (eg, fish oil, borage oil) to modulate pulmonary inflammation, thereby improving lung compliance and oxygenation, and reducing time on mechanical ventilation. This article reviews the alterations in the immune response that underlie ARDS, discusses the physiology of dietary oils as immunonutrients, summarizes animal and human studies that explore the therapeutic effects of dietary oils, and provides clinical recommendations for their use.

Journal Article↗

PubMed2003

Effects of high-gamma-linolenic acid canola oil compared with borage oil on reproduction, growth, and brain and behavioral development in mice.

Previous research in rats and mice has suggested that gamma-linolenic acid (GLA) derived from borage oil (BO: 23% GLA) may be an appropriate source for increasing levels of long-chain n-6 FA in the developing brain. Recently, transgenic technology has made available a highly enriched GLA seed oil from the canola plant (HGCO: 36% GLA). The first objective of this study was to compare the effects of diets containing equal levels of GLA (23%) from either BO or HGCO on reproduction, pup development, and pup brain FA composition in mice. The second objective was to compare the effects of the HGCO diluted to 23% GLA (GLA-23) with those of undiluted HGCO containing 36% GLA (GLA-36). The diets were fed to the dams prior to conception and throughout pregnancy and lactation, as well as to the pups after weaning. The behavioral development of the pups was measured 12 d after birth, and anxiety in the adult male offspring was assessed using the plus maze. The findings show that despite equivalent levels of GLA, GLA-23 differed from BO in that it reduced pup body weight and was associated with a slight increase in neonatal pup attrition. However, there were no significant effects on pup behavioral development or on performance in the plus maze. An increase in dietary GLA resulted in an increase in brain 20:4n-6 and 22:4n-6, with a corresponding decrease in 22:6n-3. Again, despite their similar levels of GLA, these effects tended to be larger in GLA-23 than in BO. In comparison with GLA-23, GLA-36 had larger effects on growth and brain FA composition but no differences with respect to effects on reproduction and behavioral development. These findings suggest that the HGCO can be used as an alternative source of GLA.

Animals↗

PubMed2003

Enteral nutrition with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome.

OBJECTIVE: Previously, we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants (EPA+GLA; Oxepa) had significantly reduced pulmonary inflammation, increased oxygenation, and improved clinical outcomes. In a subset of acute respiratory distress syndrome patients from this trial, we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4 that are responsible, in part, for pulmonary inflammation. DESIGN: Prospective, randomized, double-blind, controlled clinical trial. SETTING: Intensive Care Unit of the Ohio State University Medical Center. PATIENTS: A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome. INTERVENTIONS: A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous, isocaloric standard diet that was tube fed at a minimum caloric delivery of 75% of basal energy expenditure times 1.33 for at least 4 to 7 days. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage (BAL) was performed at baseline and study days 4 and 7 to obtain BAL fluid (BALF) for measurement of total protein, ceruloplasmin, and transferrin, total neutrophil count, IL-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4. Oxygenation, measured as Pao2/Fio2, was assessed before BAL. Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet. BALF levels of total protein, neutrophils, and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients. BALF levels of IL-6 declined similarly during the study in both groups. A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients. Significant improvements in oxygenation (Pao2/Fio2) occurred in EPA+GLA patients on study day 4 as compared with controls. Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability, IL-8, and leukotriene B4. CONCLUSIONS: This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support, in part, the potential mechanisms underlying the previously described clinical improvements with this diet. Additional controlled studies are needed to confirm these findings.

Antioxidants↗

PubMed2002

Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia.

BACKGROUND: Tocotrienols have been reported to lower LDL-cholesterol and fasting glucose concentrations and to have potent antioxidant effects, but the results are contradictory. OBJECTIVE: The objective was to study the relative effect of tocotrienol supplements of different compositions (mixed alpha- plus gamma-, high gamma-, or P25-complex tocotrienol) on blood lipids, fasting blood glucose, and the excretion of 8-iso-prostaglandin F(2alpha), a measure of oxidative stress, in healthy hypercholesterolemic men and women. DESIGN: This was a double-blind, randomized, parallel-design study in which subjects (n = 67 men and women) consumed 1 of 3 commercially available tocotrienol supplements or a safflower oil placebo for 28 d. Blood and urine samples were obtained before and after the 28-d supplementation phase for analysis of fasting blood lipids, glucose, tocotrienols and tocopherols, and 8-iso-prostaglandin F(2alpha). RESULTS: Overall, serum tocotrienols were increased in subjects who consumed tocotrienols, which showed that the putatively active components were absorbed. No significant differences in mean lipid or glucose concentrations were observed among the 4 treatment groups at the end of the 28-d supplementation phase. However, when the values were expressed as a percentage change from the concentrations during the presupplementation run-in phase, LDL cholesterol increased slightly (7 +/- 2%) but significantly (P < 0.05) in the group consuming the mixed alpha- plus gamma-tocotrienol supplement when compared with LDL cholesterol in the group consuming the P25-complex tocotrienol. Neither mean concentrations nor the percentage change in 8-iso-prostaglandin F(2alpha) differed significantly among treatments. CONCLUSION: Supplementation with 200 mg tocotrienols/d from 3 commercially available sources has no beneficial effect on key cardiovascular disease risk factors in highly compliant adults with elevated blood lipid concentrations.

Adult↗

PubMedDate not supplied

Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants on antioxidant status in patients with acute respiratory distress syndrome.

BACKGROUND: We previously showed that enteral feeding of a diet containing eicosapentaenoic acid, gamma-linolenic acid, and elevated antioxidants improved clinical outcomes compared with a control diet in acute respiratory distress syndrome (ARDS) patients. It has been suggested that oxidative stress may overwhelm endogenous antioxidant levels and allow free radicals to further damage lung tissue. Therefore, we determined whether these ARDS patients were under oxidative stress and whether the experimental diet could improve antioxidant status. METHODS: Ninety-eight ARDS patients received either the experimental or control diet (minimum of 75% of basal energy expenditure x 1.3) for at least 4 to 7 days. Total radical antioxidant potential (TRAP), lipid peroxide levels (LPO), and plasma antioxidant concentrations were determined at baseline and study days 4 and 7. Sixty-two normal individuals were assessed for reference values. RESULTS: At baseline, ARDS patients had significantly lower plasma beta-carotene, retinol, and alpha-tocopherol, lower TRAP, and higher LPO values compared with normals. After 4 days of feeding, beta-carotene and alpha-tocopherol levels were normalized and significantly increased in the experimental group compared with controls. TRAP and LPO were not significantly different between groups and study day 4 and 7 values were not different from baseline values. Retinol levels increased equally in both groups. CONCLUSIONS: Before treatment, ARDS patients were found to be in a state of oxidative stress and had reduced levels of antioxidants. Although enteral nutrition with the experimental diet for at least 4 to 7 days did not reduce oxidative stress as measured, it did restore plasma levels of beta-carotene and alpha-tocopherol to normal or higher levels and appeared to protect ARDS patients from further lipid peroxidation.

Adult↗