Radiation-Detoxified Form of Endotoxin Effectively Activates Th1 Responses and Attenuates Ragweed-Induced Th2-Type Airway Inflammation in Mice.

Urbanization with reduced microbial exposure is associated with an increased burden of asthma and atopic symptoms. Conversely, environmental exposure to endotoxins in childhood can protect against the development of allergies. Our study aimed to investigate whether the renaturation of the indoor environment with aerosolized radiation-detoxified lipopolysaccharide (RD-LPS) has a preventative effect against the development of ragweed-induced Th2-type airway inflammation. To explore this, cages of six-week-old BALB/c mice were treated daily with aerosolized native LPS (N-LPS) or RD-LPS. After a 10-week treatment period, mice were sensitized and challenged with ragweed pollen extract, and inflammatory cell infiltration into the airways was observed. As dendritic cells (DCs) play a crucial role in the polarization of T-cell responses, in our in vitro experiments, the effects of N-LPS and RD-LPS were compared on human monocyte-derived DCs (moDCs). Mice in RD-LPS-rich milieu developed significantly less allergic airway inflammation than mice in N-LPS-rich or common environments. The results of our in vitro experiments demonstrate that RD-LPS-exposed moDCs have a higher Th1-polarizing capacity than moDCs exposed to N-LPS. Consequently, we suppose that the aerosolized, non-toxic RD-LPS applied in early life for the renaturation of urban indoors may be suitable for the prevention of Th2-mediated allergies in childhood.

Fructose, glucose and fat interrelationships with metabolic pathway regulation and effects on the gut microbiota.

The purpose of this 30-day feeding study was to elucidate the changes, correlations, and mechanisms caused by the replacement of the starch content of the AIN-93G diet (St) with glucose (G), fructose (F) or lard (L) in body and organ weights, metabolic changes and caecal microbiota composition in rats (Wistar, SPF). The body weight gain of rats on the F diet was 12% less (P = 0.12) than in the St group. Rats on the L diet consumed 18.6% less feed, 31% more energy and gained 58.4% more than the animals on the St diet, indicating that, in addition to higher energy intake, better feed utilisation is a key factor in the obesogenic effect of diets of high nutrient and energy density. The G, F and L diets significantly increased the lipid content of the liver (St: 7.01 ± 1.48; G: 14.53 ± 8.77; F: 16.73 ± 8.77; L: 19.86 ± 4.92% of DM), suggesting that lipid accumulation in the liver is not a fructose-specific process. Relative to the St control, specific glucose effects were the decreasing serum glucagon (-41%) concentrations and glucagon/leptin ratio and the increasing serum leptin concentrations (+26%); specific fructose effects were the increased weights of the kidney, spleen, epididymal fat and the decreased weight of retroperitoneal fat and the lower immune response, as well as the increased insulin (+26%), glucagon (+26%) and decreased leptin (-25%) levels. This suggests a mild insulin resistance and catabolic metabolism in F rats. Specific lard effects were the decreased insulin (-9.14%) and increased glucagon (+40.44%) and leptin (+44.92%) levels. Relative to St, all diets increased the operational taxonomic units of the phylum Bacteroidetes. G and L decreased, while F increased the proportion of Firmicutes. F and L diets decreased the proportions of Actinobacteria, Proteobacteria and Verrucomicrobia. Correlation and centrality analyses were conducted to ascertain the positive and negative correlations and relative weights of the 32 parameters studied in the metabolic network. These correlations and the underlying potential mechanisms are discussed.

Real-World Massage Therapy Produces Meaningful Effectiveness Signal for Primary Care Patients with Chronic Low Back Pain: Results of a Repeated Measures Cohort Study.

OBJECTIVE: While efficacy of massage and other nonpharmacological treatments for chronic low back pain is established, stakeholders have called for pragmatic studies of effectiveness in "real-world" primary health care. The Kentucky Pain Research and Outcomes Study evaluated massage impact on pain, disability, and health-related quality of life for primary care patients with chronic low back pain. We report effectiveness and feasibility results, and make comparisons with established minimal clinically important differences. METHODS: Primary care providers referred eligible patients for 10 massage sessions with community practicing licensed massage therapists. Oswestry Disability Index and SF-36v2 measures obtained at baseline and postintervention at 12 and 24 weeks were analyzed with mixed linear models and Tukey's tests. Additional analyses examined clinically significant improvement and predictive patient characteristics. RESULTS: Of 104 enrolled patients, 85 and 76 completed 12 and 24 weeks of data collection, respectively. Group means improved at 12 weeks for all outcomes and at 24 weeks for SF-36v2's Physical Component Summary and Bodily Pain Domain. Of those with clinically improved disability at 12 weeks, 75% were still clinically improved at 24 weeks ( P < 0.01). For SF-36v2 Physical and Mental Component Summaries, 55.4% and 43.4%, respectively, showed clinically meaningful improvement at 12 weeks, 46.1% and 30.3% at 24 weeks. For Bodily Pain Domain, 49.4% were clinically improved at 12 weeks, 40% at 24 weeks. Adults older than age 49 years had better pain and disability outcomes than younger adults. CONCLUSIONS: Results provide a meaningful signal of massage effect for primary care patients with chronic low back pain and call for further research in practice settings using pragmatic designs with control groups.

Comparison of endotoxin levels in cow's milk samples derived from farms and shops.

The observations on the protective effect of bacterial endotoxin in farm-derived cow's milk on childhood asthma and allergy are contradictory. The aim of this study was to determine the endotoxin levels in 'farm-derived whole raw' and 'processed shop' sources of cow's milk, and to test how the temperature and storing conditions might alter their endotoxin concentrations. Milk was collected from farms and shops. The level of endotoxin was measured by micro (gel-clot) Limulus amebocyte lysate test expressed as EU/ml. The concentration ranges of endotoxin were much higher and more widely scattered in the samples of whole raw farm milk than in the processed shop milk. Cold storage or heating increased the endotoxin concentrations in all samples of farm milk, but not in the processed shop milk. These results show that elevated levels of endotoxin in raw farm milk samples can occur from the cowshed or be formed during storage. In processed shop milk, storage does not cause any changes in the amount of endotoxin. Therefore, it is consistent that the handling and storage of raw milk alters the endotoxin concentrations, which may explain previous contradictory findings regarding the beneficial modulating effects on innate immunity toward allergy prevention in early childhood.

The immunomodulatory role of bile acids.

Enzymatic oxidation of cholesterol generates numerous distinct bile acids which function both as detergents that facilitate the digestion and absorption of dietary lipids and as hormones that activate five distinct receptors. Activation of these receptors alters gene expression in multiple tissues, leading to changes not only in bile acid metabolism but also in glucose homeostasis, lipid and lipoprotein metabolism, energy expenditure, intestinal motility, bacterial growth, inflammation, and in the liver-gut axis. This review focuses on the present knowledge regarding the physiologic and pathologic role of bile acids and their immunomodulatory role, with particular attention to bacterial lipopolysaccharides (endotoxins) and bile acid and immunological disorders. The specific role that bile acids play in the regulation of innate immunity, various systemic inflammations, inflammatory bowel diseases, allergy, psoriasis, cholestasis, obesity, metabolic syndrome, alcoholic liver disease, and colon cancer will be reviewed.

Nutrition intervention to decrease symptoms in patients with advanced heart failure.

For a majority of patients with advanced heart failure, there is a need for complementary, non-pharmacologic interventions that could be easily implemented by health care providers to provide palliative care. Three major pathologic pathways underlying heart failure symptoms have been identified: fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic pathways. Therefore, the purposes of this study are to test the effects of a 6-month nutrition intervention of dietary sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure symptoms, health-related quality of life, and time to heart failure rehospitalization or all-cause death. The aims of this double blind-placebo controlled study are (1) to determine the effects of a 6-month nutrition intervention on symptom burden (edema, shortness of air, and fatigue) and health-related quality of life at 3 and 6 months, and time to heart failure rehospitalization or all-cause death over 12 months from baseline; (2) compare dietary sodium intake, inflammation, and markers of oxidative stress between the nutrition intervention group and a placebo group at 3 and 6 months; and (3) compare body weight, serum lycopene, and erythrocyte omega-3 index between the nutrition intervention group and a placebo group at 3 and 6 months. A total of 175 patients with advanced heart failure will be randomized to either the nutrition intervention or placebo group.

Role of oil vehicle on hepatic cell proliferation in PCB-treated rats.

We report the role of dietary glycine and the type of oil used as a vehicle in the hepatotoxicity of control rats and rats treated with 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153). In our first experiment, glycine or valine (as control) was fed in an unrefined diet at 5% for the entire study duration (5 days) to inhibit Kupffer cell activity. PCB-153 (100 or 300 µmol/kg) dissolved in medium chain triglyceride (MCT) oil, was injected intraperitoneally 2 days before euthanasia; the peroxisome proliferator Wy-14,643 was included as a positive control. MCT oil decreased cell proliferation by approximately 50%. PCB-153 slightly increased hepatic cell proliferation, but dietary glycine did not reduce cell proliferation. Because of the inhibition of cell proliferation in rats receiving MCT oil compared with rats receiving no injection, we hypothesized that MCT oil may have been inhibiting the hepatocyte proliferation in PCB-153-treated rats. We therefore performed another experiment using 3 types of oil as a vehicle for PCB-153: MCT oil, corn oil, and olive oil. Rats were injected with PCB-153 (300 µmol/kg) or one of the vehicles, again 2 days before euthanasia. MCT oil again decreased the hepatocyte proliferation by approximately 50%. In rats receiving PCB-153, hepatocyte proliferation was slightly higher than their respective vehicle controls for corn oil and olive oil but not for MCT oil. These studies show that the oil vehicle is important in cell proliferation after PCB exposure, with MCT oil appearing to be protective.

Impact of two types of Internet-based information on medical students' performance in an Objective Structured Clinical Exam (OSCE).

OBJECTIVES: Internet-based information has potential to impact physician-patient relationships. This study examined medical students' interpretation and response to such information presented during an objective clinical examination. METHOD: Ninety-three medical students who had received training for a patient centered response to inquiries about alternative treatments completed a comprehensive examination in their third year. In 1 of 12 objective structured clinical exams, a SP presented Internet-based information on l-theanine - an amino acid available as a supplement. In Condition A, materials were from commercial websites; in Condition B, materials were from the PubMed website. RESULTS: Analyses revealed no significant differences between Conditions in student performance or patient (SP) satisfaction. Students in Condition A rated the information less compelling than students in Condition B (z=-1.78, p=.037), and attributed less of the treatment's action to real vs. placebo effects (z=-1.61, p=.053). CONCLUSIONS: Students trained in a patient centered response to inquiries about alternative treatment perceived the credibility of the two types of Internet-based information differently but were able to respond to the patient without jeopardizing patient satisfaction. Approach to information was superficial. Training in information evaluation may be warranted.

Isoflavone-rich soy isolate reduces lipid peroxidation in mouse liver.

The purpose of this study was to determine if an isoflavone-rich soy isolate affords protection against peroxidative damage in vivo. Weanling C57BL6 male mice were fed a basal diet (AIN-93G) supplemented with either nothing or 1.08 gram isoflavone-rich soy isolate/kg diet for 60 days. The soy isolate contained 400 mg/g isoflavone aglycones (226 mg/g genistein and 174 mg/g daidzein). Immediately following sacrifice liver was processed for measuring the levels of lipid peroxidation products, malondialdehyde (MDA) and conjugated dienes, and the levels of alpha-tocopherol, glutathione (GSH), and ascorbic acid, as well as the activities of catalase, selenium-dependent glutathione peroxidase (Se-GPx), selenium-nondependent glutathione peroxidase (non-Se-GPx), and superoxide dismutase (SOD). Compared with the control group, mice fed the diet supplemented with soy isolate had significantly (p<0.05) lower hepatic levels of MDA and conjugated dienes. The activities of catalase and SOD were significantly increased (p<0.05) in the liver of soy isolate-supplemented mice. The levels of vitamin E, GSH, and ascorbic acid and the activities of Se-GPx and non-Se-GPx were not significantly altered by the soy isolate. The results obtained provide experimental evidence that isoflavone supplementation confers protection against peroxidative damage to membrane lipids in vivo, possibly through enhancing the activities of the antioxidant enzymes catalase and SOD.

Innovations in integrative healthcare education: a healing journey for cancer patients in ontario and an online interdisciplinary CAM course for allied health students in Kentucky.

Content on integrative healthcare and complementary and alternative medicine (CAM) is being taught in hundreds of educational programs across the country. Nursing, medical, osteopathic, chiropractic, acupuncture, naturopathic, and other programs are finding creative and innovative ways to include these approaches in new models of education and practice. This column spotlights such innovations in integrative healthcare and CAM education and presents readers with specific educational interventions they can adapt into new or ongoing educational efforts at their institution or programs. We invite readers to submit brief descriptions of efforts in their institutions that reflect the creativity, diversity, and interdisciplinary nature of the field.

Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites.

Several lines of evidence suggest that rutin, flavonoid in fruits and vegetables, or one of its metabolites may effectively modulate advanced glycation end product (AGE) formation. Following ingestion, rutin forms metabolites that include 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3,4-dihydroxytoluene (3,4-DHT), m-hydroxyphenylacetic acid (m-HPAA), 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA) and 3,5,7,3',5'-pentahydroxyflavonol (quercetin). We studied the effects of rutin and its metabolites on the formation of AGE biomarkers such as pentosidine, collagen-linked fluorescence, N(epsilon)-carboxymethyllysine (CML) adducts, glucose autoxidation and collagen glycation, using an in vitro model where collagen I was incubated with glucose. Rutin metabolites containing vicinyl dihydroxyl groups, i.e., 3,4-DHT, 3,4-DHPAA and quercetin, inhibited the formation of pentosidine and fluorescent adducts, glucose autoxidation and glycation of collagen I in a dose-dependent manner, whereas non-vicinyl dihydroxyl group-containing metabolites, i.e., HVA and m-HPAA, were much less effective. All five metabolites of rutin effectively inhibited CML formation. In contrast, during the initial stages of glycation and fluorescent AGE product accumulation, only vicinyl hydroxyl group-containing rutin metabolites were effective. These studies demonstrate that rutin and circulating metabolites of rutin can inhibit early glycation product formation, including both fluorescent and nonfluorescent AGEs induced by glucose glycation of collagen I in vitro. These effects likely contribute to the beneficial health effects associated with rutin consumption.

Adenosine inhibits the release of interleukin-1beta in activated human peripheral mononuclear cells.

The effects of adenosine and subtype-specific activators of adenosine receptors (A1, A2A, A2B and A3) were studied on the release of interleukin-1beta (IL-1beta) from peripheral mononuclear cells, monocytes and lymphocytes. In the cells activated by the protein kinase C specific phorbol ester (phorbol 12-myristate 13-acetate) and Ca(2+) ionophore (A23187) both adenosine and the subtype-specific receptor agonists, CPA (A1), CGS 21680 (A2A) and IB-MECA (A3) induced a concentration-dependent inhibition of IL-1beta release. The rank order of potency in the inhibition of IL-1beta release was CPA=CGS 21680>IB-MECA>adenosine>NECA (in the presence of A1, A2A and A3 receptor inhibitors). The inhibitory actions of CPA, CGS 21680 or IB-MECA were significantly reduced in the presence of DPCPX, ZM 243185 or MRS 1191 as subtype-specific antagonists on A1, A2A and A3 adenosine receptors, respectively. It can be concluded that adenosine inhibits the release of IL-1beta from the activated human peripheral mononuclear cells. In this process A1, A2A and A3 receptors are involved.

Large doses of zinc oxide increases the activity of hydrolases in rats.

The effect of pharmacological doses of zinc oxide (1000; 2500; 5000 mg per kg diet) and two levels of dietary protein on pancreatic and intestinal hydrolase activity in rats were studied. It was hypothesized that ZnO would increase intestinal and pancreatic hydrolase enzyme activity. Male Wistar rats, averaging 64 g body weight, were randomly allocated to dietary treatments (chow diets- meeting all NRC requirements) containing 10% or 15% protein supplemented with additional ZnO (above 100 mg/kg ZnSO(4)) as follows: 0.0; 0.1; 0.25; 0.5% w/w. Water and food were provided ad libitum. Animals were fed the diets for 10 days and body weights were recorded; after decapitation blood and organ samples were collected. Amylase, lipase, trypsin, and total protease activity of pancreatic homogenates and small intestinal contents were determined. ZnO supplementation dose dependently increased the plasma Zn concentration and significantly increased amylase, lipase, trypsin and total protease activity in pancreatic homogenates and small intestinal contents. The statistical analysis showed significant protein and ZnO interaction on the activity of amylase in the pancreas, and amylase, trypsin and total-protease in the small intestinal content. Therefore ZnO at high dietary concentration may influence the digestion of nutrients via increased hydrolase activity.

Effects of carnitine and taurine on fatty acid metabolism and lipid accumulation in the liver of cats during weight gain and weight loss.

OBJECTIVE: To determine the effects of carnitine (Ca) or taurine (Ta) supplementation on prevention of lipid accumulation in the liver of cats. ANIMALS: 24 adult cats. PROCEDURE: Cats were fed a weight-gaining diet sufficient in n-6 polyunsaturated fatty acids (PUFAs), low in long-chain n-3 PUFAs (n-3 LPUFA), and containing corn gluten for 20 weeks. Cats gained at least 30% in body weight and were assigned to 4 weight-reduction diets (6 cats/diet) for 7 to 10 weeks (control diet, control plus Ca, control plus Ta, and control plus Ca and Ta). RESULTS: Hepatic lipids accumulated significantly during weight gain and weight loss but were not altered by Ca orTa after weight loss. Carnitine significantly increased n-3 and n-6 LPUFAs in hepatic triglycerides, decreased incorporation of 13C palmitate into very-low-density lipoprotein and hepatic triglycerides, and increased plasma ketone bodies. Carnitine also significantly increased weight loss but without altering the fat to lean body mass ratio. Taurine did not significantly affect any variables. Diets low in n-3 LPUFAs predisposed cats to hepatic lipidosis during weight gain, which was further exacerbated during weight loss. Mitochondrial numbers decreased during weight gain and weight loss but were not affected by treatment. Carnitine improved fatty acid oxidation and glucose utilization during weight loss without correcting hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: The primary mechanism leading to hepatic lipidosis in cats appears to be decreased fatty acid oxidation. Carnitine may improve fatty acid oxidation but will not ameliorate hepatic lipidosis in cats fed a diet low in n-3 fatty acids.

Effect of dietary protein quality and essential fatty acids on fatty acid composition in the liver and adipose tissue after rapid weight loss in overweight cats.

OBJECTIVE: To examine effects of dietary protein quality (casein [CA] vs corn gluten [CG]) and dietary lipids (corn oil [CO] vs oil blend [OB] rich in long-chain polyunsaturated fatty acids [LCPUFAs]) on fatty acid composition in liver and adipose tissue after weight loss in overweight cats. ANIMALS: 24 ovariohysterectomized adult cats. PROCEDURE: Cats were allowed ad libitum access to a high-quality diet until they weighed 30% more than their ideal body weight. Cats were then randomly assigned to 1 of 4 weight-reduction diets (6 cats/diet) and were fed 25% of maintenance energy requirements per day. Diets consisted of CG-CO, CA-CO, CG-OB, and CA-OB, respectively, and were fed until cats lost weight and returned to their original lean body mass. Liver biopsy specimens and samples of perirenal, subcutaneous, and abdominal fat were obtained and analyzed for fatty acid content. RESULTS: Following weight loss, fatty acid composition of the liver and adipose tissue was primarily affected by protein quality in that cats fed CA had significantly higher percentages of 20:4(n-6) and 22:6(n-3) fatty acids than those fed CG. Cats fed the CG-CO diet had the lowest concentrations of LCPUFAs, suggesting that dietary lipids and protein quality each influence fatty acid composition in tissues. CONCLUSIONS AND CLINICAL RELEVANCE: These data provide direct evidence that dietary protein quality alters fatty acid composition of tissues during weight loss in cats. The fatty acid patterns observed suggest that protein quality may alter fatty acid composition through modulation of desaturase activity.

The effects of fish oil and isoflavones on delayed onset muscle soreness.

INTRODUCTION/PURPOSE: Fish oils (FO) have been shown to modulate the inflammatory response through alteration of the eicosanoid pathway. Isoflavones (ISO) appear to reduce the inflammatory pathway through their role as a tyrosine kinase inhibitor. Delayed onset muscle soreness (DOMS) develops after intense exercise and has been associated with an inflammatory response. Therefore, we hypothesized that physical parameters associated with DOMS could be decreased via the modulation of the inflammatory response by supplementing subjects with either FO or ISO. METHODS: 22 subjects were recruited and randomly assigned to one of three treatment groups: FO (1.8 g of omega-3 fatty acids x d(-1)), ISO (120 mg soy isolate x d(-1)), or placebo (PL) (Western fat blend and/or wheat flour). All treatment groups received 100-IU vitamin E x d(-1) to minimize lipid peroxidation of more highly unsaturated fatty acids. Subjects were supplemented 30 d before the exercise and during the week of testing and were instructed to refrain from unusual exercise. DOMS was induced by 50 maximal isokinetic eccentric elbow flexion contractions. Strength parameters, pain, arm circumference, and relaxed arm angle (RANG) were measured at 48, 72, and 168 h post exercise. Cortisol, creatine kinase (CK), interleukin-6 (IL-6), tumor necrosis factor (TNFalpha), malondialdehyde (MDA), and serum iron were measured before supplementation, after supplementation, and post exercise. RESULTS: Significant decreases were observed in RANG and strength 48 h postexercise among all groups, and there were significant increases in pain and arm circumference. There were no significant changes among all groups from baseline at 168 h (7 d) post exercise. There were no significant treatment effects between groups for the physical parameters or for cortisol, CK, IL-6, TNFalpha, MDA, or serum iron. CONCLUSION: These data indicate FO or ISO, at the doses supplemented, were not effective in ameliorating DOMS with the above-cited protocol.