Intermittent binge-like ethanol exposure during adolescence attenuates the febrile response by reducing brown adipose tissue thermogenesis in rats.

Ethanol (EtOH) consumption is a primary health risk worldwide, which generally starts during adolescence in a binge pattern (i.e., the episodic consumption of high amounts). Binge EtOH consumption can lead to modifications of the innate and adaptive immune responses, including fever. The present study evaluated the febrile response that was induced by lipopolysaccharide (LPS) and prostaglandins E2 (PGE2) and the mechanisms of thermoregulation in adolescent rats that were exposed to EtOH in a binge-like pattern. Male Wistar rats were treated with an intraperitoneal (i.p.) injection of EtOH or saline on postnatal days (PND) 25, 26, 29, 30, 33, 34, 37, and 38. On PND 51, they received a pyrogenic challenge with LPS (i.p.) or PGE2 (intracerebroventricular) to induce a febrile response. Interscapular brown adipose tissue (BAT) mass and uncoupling protein (UCP) activity in isolated mitochondria were evaluated on PND 51. The rats were then subjected to cold challenges to analyze adaptive thermogenesis. Intermittent EtOH exposure during adolescence impaired the LPS- and PGE2-induced febrile response 12 days after the end of EtOH exposure. Ethanol exposure decreased interscapular BAT mass, oxygen consumption, and UCP activity in isolated mitochondria, resulting in an impairment in thermogenesis at 5 °C. No morphological changes in BAT were observed. These findings indicate that binge-like EtOH exposure during adolescence impairs thermoregulation by reducing BAT mass and function. This reduction may last for a prolonged period of time after the cessation of EtOH exposure and may affect both cold defenses and the febrile response during the development of infectious diseases.

Cold stress on Araucaria angustifolia embryogenic cells results in oxidative stress and induces adaptation: implications for conservation and propagation.

Araucaria angustifolia (Bert.) O. Kuntze is a species critically endangered of extinction and its development and propagation is strongly affected by abiotic stress. We have previously shown the activation of uncoupling protein in A. angustifolia embryogenic stem cells subjected to cold stress. Now, we have furthered those studies by exposing these cells to cold stress (4 ± 1 °C for either 24 or 48 h) and evaluating parameters associated with oxidative stress and alterations in the cellular and mitochondrial responses. Cold stress affect the H2O2 levels and lipid peroxidation increased after both stress condition, an effect associated with the decrease in the activities of peroxidases, catalase and ascorbate/dehydroascorbate ratio. On the other hand, the activities of ascorbate peroxidase, monodehydroascorbate and dehydroascorbate reductases increased as an indication of adaptation. Another important impact of cold stress conditions was the decrease of external alternative NAD(P)H dehydrogenases activity and the increase of mitochondrial mass. These results show that cold stress induces oxidative stress in A. angustifolia embryogenic cells, which results in activation of the glutathione-ascorbate cycle as a compensation for the decrease in the activities of catalase, peroxidases, and external NAD(P)H dehydrogenases. Our results contribute to the understanding of the pathways that gymnosperms employ to overcome oxidative stress, which must be explored in order to improve the methods of conservation and propagation of A. angustifolia.

Plasma kinetics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.

Low-density lipoprotein (LDL) could be used as a carrier of chemotherapeutic agents to neoplastic cells that overexpress LDL receptors (rLDL), but LDL is difficult to obtain and handle. Recently, it was observed that a protein-free emulsion resembling the lipid portion of LDL (LDE) behave like native LDL when injected into the bloodstream. In this study, the evidence that LDE is taken up by rLDL was expanded by comparing LDL and LDE plasma decay curves in rabbits and by competition experiments with lymphocytes. To verify whether LDE could be removed from the plasma by neoplastic cells with increased rLDL, LDE labeled with 14Ccholesteryl ester was injected into 14 patients with acute myeloid leukemia (AML) and into 7 with acute lymphocytic leukemia (ALL). In AML rLDL expression is increased but in ALL it is normal. LDE plasma fractional clearance rate (FCR, in h-1) was calculated from the remaining radioactivity measured in plasma samples collected during 24 h following injection. LDE FCR was 3-fold greater in AML than in ALL patients 0.192 +/- 0.210 (SD) and 0.066 +/- 0.033 h-1, respectively, P < 0.035. When LDE injection was repeated in 9 AML patients in hematological remission, LDE FCR diminished 66% compared to the pretreatment values (from 0.192 +/- 0.210 to 0.065 +/- 0.038 h-1, P < 0.02), so that it could be estimated that nearly 66% of the emulsion was taken up by AML cells and only 34% by the normal tissues. As expected, LDE FCR was unchanged in 4 patients with ALL in hematological remission (0.069 +/- 0.044 h-1). Gamma camera images obtained 6 h after the injection of 99mTc-label LDE into one patient with ALL showed biodistribution similar to that of LDL. In one AML patient LDE was comparatively more concentrated over the areas corresponding to the bone marrow infiltrated by AML cells. Our results indicate that LDE FCR is increased in a disease known to contain malignant cells that overexpress rLDL, suggesting that LDE is taken up by malignant cells with increased rLDL.

Effect of MI-D, a new mesoionic compound, on energy-linked functions of rat liver mitochondria.

MI-D (4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylami ne chloride), a new mesoionic compound, depressed the phosphorylation efficiency of liver mitochondria as deduced from an accentuated decrease of the respiratory control coefficient and ADP/O ratio. Analysis of segments of the respiratory chain suggested that the MI-D inhibition site is further on than complex I and between complexes II and III. The transmembrane electrical potential (delta psi) was collapsed dependent on MI-D concentration. ATPase activity was dramatically increased by MI-D in intact mitochondria, but inhibited in carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled mitochondria. These results suggest that MI-D acts as an uncoupler agent, a property closely related to its structural characteristics.

Cardiovascular disease risk factors and diet of Fulani pastoralists of northern Nigeria.

BACKGROUND: The Fulani of northern Nigeria are seminomadic pastoralists who consume a diet rich in saturated fats, do not use tobacco, are lean, and have an active lifestyle. Little is known about their serum lipid profiles and corresponding risk of cardiovascular disease. OBJECTIVE: We measured serum lipid, homocysteine, folate, and vitamin B-12 concentrations in Fulani men and women and assessed the nutrient content of their diet. DESIGN: Blood samples from 42 men (18-64 y old) and 79 women (15-77 y old) living in the Jos Plateau of Nigeria were analyzed for cholesterol (total, HDL, and LDL), triacylglycerol, homocysteine, folate, and vitamin B-12 serum concentrations. Body composition was determined by bioelectrical impedance analysis. Dietary information was obtained with use of a 7-d dietary recall and a food-frequency questionnaire. Results were compared with US referent ranges. RESULTS: The mean energy content of the Fulani diet was relatively low (men, 6980 kJ; women, 6213 kJ) and the mean protein content was high (men, 20% of energy; women, 16% of energy). Nearly one-half of energy was provided by fat, and one-half of that was derived from saturated fatty acids. The diet provided marginal to adequate amounts of vitamins B-12, B-6, and C but only one-third of the US recommended dietary allowance for folate. The mean total cholesterol, HDL-cholesterol, and triacylglycerol concentrations of Fulani adults were within the referent ranges; the mean LDL-cholesterol concentration of Fulani adults below the range; and the mean serum homocysteine concentration of Fulani men above the range. Homocysteine and folate concentrations were inversely correlated for both men and women. CONCLUSIONS: Despite a diet high in saturated fat, Fulani adults have a lipid profile indicative of a low risk of cardiovascular disease. This finding is likely due to their high activity level and their low total energy intake.