Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog

Cachectin/tumor necrosis factor has been implicated as a mediator of lethal endotoxemia, but the metabolic and hemodynamic responses to this macrophage-derived peptide have been incompletely characterized. Cachectin was administered by intra-arterial infusion in two groups of beagle dogs at lethal (100 micrograms per kilogram) and sublethal (10 micrograms per kilogram) doses. The infusion produced serum cachectin levels (1 to 50 nanomoles per liter) similar to those achieved after experimental endotoxemia. The lethal response to cachectin was characterized by progressive hypotension, shock and death within three hours. Histopathologic findings included acute inflammation of the pulmonary interstitium, intravascular thrombosis with hemorrhagic necrosis, adrenal medullary necrosis and acute renal tubular necrosis. Cachectin infusion precipitated significant increases of plasma catecholamines, cortisol and glucagon in a dose response manner. Cachectin infused directly into the isolated hindlimb mediated reductions of skeletal muscle resting transmembrane potential and stimulated lactate efflux. Cachectin appears to occupy a crucial role in physiopathologic responses to infection, and likely participates in the mobilization of host energy stores, intravascular depletion and shock after lethal endotoxemia.     

Acquired immune deficiency syndrome (AIDS) and neoplasia

The acquired immune deficiency syndrome (AIDS) is a novel epidemic form of immunodeficiency that has been widely recognized within the last six years. AIDS is characterized by Kaposi's sarcoma, B cell lymphoma, and/or life-threatening opportunistic infections superimposed on an immune deficiency state which consists of lymphopenia with a selective depletion of the CD4 T cells. In addition, lymphocytes from AIDS patients show decreased responses to antigen or mitogen stimulation in vitro. Although the secondary infections and malignancies seen in these patients may be successfully treated, the underlying immune defect persists, leaving the patient susceptible to further complications.     

Apparent digestibility and glycaemic responses to an experimental induced viscosity dietary fibre incorporated into an enteral formula fed to dogs cannulated in the ileum.

The purpose of this study was to evaluate the apparent digestibility and postprandial glycaemic responses of ileal-cannulated dogs when fed an experimental induced viscosity dietary fibre (IVF) incorporated into a liquid enteral formula. Dietary treatments were: (1) control; (2) Glucerna; (3) Glytrol; (4) IVF; and (5) Jevity. Diets varied in concentrations of crude protein (CP), fat, starch and total dietary fibre (TDF). Dry matter and starch intakes by dogs fed the Glucerna and Glytrol treatments were lower (P<0.05) than for those consuming the other diets. However, daily intakes of CP and fat followed a reverse trend. Digestibility of nutrients at the ileum was high (>80%) for all dietary treatments. Mineral absorption proximal to the ileum and from the total tract was not significantly different among treatments. Mean incremental area under the serum glucose response curves for dogs fed Glytrol, Glucerna, and IVF treatments were lower (P<0.05) than the control treatment. Induced viscosity fibre appears to have no negative effects on nutrient digestion throughout the gastrointestinal tract. Its ability to moderate serum glucose concentrations would make it a potentially good choice for a diabetic liquid formula.     

The impact of commercial human infant formula on fecal attributes in a weanling pig model.

An experiment to assess the influence of commercially available infant formulas on characteristics of feces in a weanling piglet model was conducted. Seven commercial infant formulas [whey, whey+alpha-lactalbumin, whey+alpha-lactalbumin+oligofructose, whey+GOS+polyfructose, whey protein concentrate 1 (with 27.3% acid hydrolyzed fat), whey protein concentrate 2 (with 29.4% acid hydrolyzed fat), and enzymatically hydrolyzed whey protein concentrate] were offered to weanling piglets ad libitum for 14d. Fecal attributes that were assessed include: consistency, color, odor, dry matter, organic matter, pH, biogenic amines, short- and branched-chain fatty acids, phenols, indoles, and ammonia. Overall, there were very few differences among treatment groups in fecal attributes assessed. Minor differences in the concentrations of fecal acetate, valerate, putrescine, and cadaverine were observed in piglets fed GOS+polyfructose-containing formula. However, stool consistency, score, odor, pH, ammonia, phenols, and indoles were similar among treatment groups. Diet had an effect on fecal dry matter percentage, organic matter percentage, color, and 4 week body weights of the piglets. The results obtained in this experiment demonstrate that healthy gut function is prevalent in weanling piglets consuming the experimental treatments.     

Microcytosis in Hodgkin disease associated with unbalanced globin chain synthesis

A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemoglobin values [MCV] less than 80 fl). Three patients had iron deficiency, and one had beta-thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal alpha-to-beta-globin chain ratios (1.0 +/- 0.14). Seven patients with Hodgkin disease and MCV less than 80 fl had significantly lower alpha-to-beta chain ratios (0.66 +/- 0.05). Twelve normal controls and four with iron-deficiency anemia and MCV less than 80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal alpha-to-beta-chain ratio was corrected along with the anemia.     

Methods for Assessing the Biological Effects of Specific Plant Components

Until very recently, phytonutrient research was the province of natural product chemists and consisted of primarily anecdotal clinical references. In recent years, an extensive set of qualitative and semi-quantitative dietary epidemiologic data has been developed. This developing base of epidemiologic data is now being supplemented by biochemical, mechanistic, and genetic epidemiology of a more quantitative nature. As we seek to understand the mechanisms that explain a large body of epidemiologic evidence, newer laboratory methods continue to be developed. Though there is a continuing need for even more discriminating nutrition epidemiology to drive the basic research in this area forward, the focus of in vitro, animal and clinical (human) studies must continue to be refined, and appropriate biomarkers for chronic and acute (death) disease end-points must be developed.