Local airways immune modifications induced by oral bacterial extracts in chronic bronchitis

Bacterial extracts can act as immune stimulants and in some instances have been used, rather empirically, to prevent recurrent infections in the nonimmunocompromised host. Some agents are administered via oral route with the goal to increase airways immune defenses. In animal models and in normal humans, gut-associated lymphoid tissue (GALT) stimulation is able to induce a generalized response by the whole mucosal-associated lymphoid tissue (MALT). The aim of this placebo-controlled, double-blind, parallel-group study was to evaluate whether the stimulation of the GALT through oral administration of a polyvalent bacterial extract (BE) could lead to significant immune modifications either systemically or locally in the respiratory tract in patients suffering from chronic bronchitis. We selected 20 subjects (5 nonsmokers, 6 smokers, and 9 ex-smokers) for at least 3 years. According to a balanced-block randomization method, ten patients received active treatment and ten received placebo. Either drug or placebo was to be taken as one capsule daily the first 10 days of 3 consecutive months. Each capsule of the active product contained 7 mg of a BE obtained from eight different bacterial strains. On entry (T0) and 90 days after beginning of treatment (T90), all patients underwent bronchoalveolar lavage (BAL) and peripheral blood withdrawal to assay BAL fluids and serum samples for immune parameters. The BAL recoveries, cellularity, cell differentials, and lymphocyte subsets (CD19, CD3, CD4, CD8) did not show significant differences. IgG/albumin and IgA/albumin values were not significantly different, but IgA/albumin was significantly increased in the treatment (T0 = 0.14, 0.01 to 0.27, median and range, T90 = 0.15, 0.08 to 0.45, p = 0.028) vs the placebo group when data from current smokers were excluded. Functional tests on alveolar macrophages (AM) (leading front stimulated motility and superoxide anion-O2(-)-release) showed a significant increase of random migration (T0 = 10.6, 7.0 to 23.6, T90 = 13.4, 8.1 to 28.8 microns, p = 0.02) and of stimulated motility after FMLP 10(-7) M (T0 = 13.2, 8.3 to 46.4, T90 = 18.3, 8.4 to 49.6 microns, p = 0.04), a significant increase of O2- release in basal conditions (T0 = 6.0, 1.7 to 30.5 nM/10(6) AM/10', T90 = 11.1, 5.5 to 24.5, p = 0.05) and after stimulation with opsonized zymosan (T0 = 17.7, 4.7 to 35.2, T90 = 22.1, 13.8 to 53.3, p = 0.009) in the treatment group only. Data were not significantly different in the placebo group between T0 and T90. No modifications in systemic immunity were ever observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Corandomization of fats improves absorption in rats

Human milk fat is well absorbed despite its large concentration of long-chain saturated fatty acids (LCSFA), particularly palmitic acid. The superior absorption has been ascribed in part to the uncommonly high proportion of the palmitic acid in the sn-2 position of the triglycerides, 70% in human milk triglycerides compared with 10-15% in the fats and oils commonly used in infant formula blends. Colipase-dependent pancreatic lipase selectively hydrolyzes the fatty acids at the sn-1 and 3 positions, yielding free fatty acids and the 2-monoglyceride, which are absorbable. Free palmitic acid, but not monopalmitin, can be lost as calcium soaps in the feces. The present study demonstrated that mixtures of coconut oil and palm olein are better absorbed by rats if the proportion of LCSFA in the sn-2 position is increased by the process of chemical randomization, in which the fatty acids of the native oils are redistributed equally to all three positions in the rearranged triglycerides. The fecal excretion of total fatty acids, essentially LCSFA, from the mixtures in which the oils were randomized together (corandomized) was 30 to 60% less than from the mixtures of native oils.     

Phenserine: a physostigmine derivative that is a long-acting inhibitor of cholinesterase and demonstrates a wide dose range for attenuating a scopolamine-induced learning impairment of rats in a 14-unit T-maze

Phenserine ((-)-N-phenylcarbamoyl eseroline), a carbamate analog of physostigmine (Phy), is a long-acting inhibitor of cholinesterase. We have assessed the potential clinical value of phenserine for cholinomimetic therapy of cognitive impairments associated with aging and Alzheimer's disease by evaluating its duration of in vivo activity against rat plasma acetylcholinesterase (AChE) and its effect on attenuating a scopolamine-induced impairment in learning performance of young rats in a shock-motivated 14-unit T-maze. Phenserine achieved maximum AChE inhibition of 73.5% at 5 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, 69, 3-month-old male Fischer-344 rats were pretrained in a straight runway to avoid electric footshock. On the following day, each animal received 15 trials in the 14-unit T-maze. Sixty minutes prior to the maze training, each rat received the first IP injection of either vehicle (Tween 80, ethanol and 0.9% NaCl) or phenserine at 1.5, 3.0, 4.0, 5.0, 7.5, or 10.0 mg/kg. Then 30 min prior to the training, each animal received a second IP injection of either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg; SCOP). Compared to the vehicle-SCOP group, all but the 7.5 mg/kg dose of phenserine significantly ameliorated error performance, runtime, shock frequency and shock duration in SCOP-treated rats at the final block of three trials. Appearing to have a long effect and a wide therapeutic window, phenserine deserves further study as a cognitive enhancer.     

Relationships between expectancies and adolescent dieting behaviors

Dieting expectancies are cognitive variables pertaining to anticipated outcomes individuals expect to obtain from dieting to lose weight. This investigation examined the factor structure of dieting expectancies in an adolescent population, age 10-18, and tested the ability of factors to distinguish among types of dieter, diet pill user, and vomiter groups. Emerging from a principal components analysis were five reliable expectancy factors: Social Confidence, Social Approval, Self-Worth, Positive Performance, and Negative Consequences. Results indicate dieting expectancies and gender are important in distinguishing among adolescents who engage in different dieting practices. Gender and Self-Worth were particularly important in distinguishing frequent dieters from nondieters. Social Approval was best at separating frequent dieters from occasional dieters, diet pills users from nonusers, and vomiters from nonvomiters.     

Double-strand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication

In wild-type diploid cells of Saccharomyces cerevisiae, an HO endonuclease-induced double-strand break (DSB) at the MAT locus can be efficiently repaired by gene conversion using the homologous chromosome sequences. Repair of the broken chromosome was nearly eliminated in rad52delta diploids; 99% lost the broken chromosome. However, in rad51delta diploids, the broken chromosomes were repaired approximately 35% of the time. None of these repair events were simple gene conversions or gene conversions with an associated crossover, instead, they created diploids homozygous for the MAT locus and all markers in the 100-kb region distal to the site of the DSB. In rad51delta diploids, the broken chromosome can apparently be inherited for several generations, as many of these repair events are found as sectored colonies, with one part being repaired and the other part being lost the broken chromosome. Similar events occur in about 2% of wild-type cells. We propose that a broken chromosome end can invade a homologous template in the absence of RAD51 and initiate DNA replication that may extend to the telomere, 100 or more kb away. Such break-induced replication appears to be similar to recombination-initiated replication in bacteria.     

Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands

The T lineage repertoire is shaped by T cell receptor (TCR)-dependent positive and negative thymic selection processes. Using TCR-transgenic (N15tg) beta2-microglobulin-deficient (beta2m-/-) RAG-2(-/-) H-2(b) mice specific for the VSV8 (RGYVYQGL) octapeptide bound to Kb, we identified a single weak agonist peptide variant V4L (L4) inducing phenotypic and functional T cell maturation. The cognate VSV8 peptide, in contrast, triggers negative selection. The crystal structure of L4/Kb was determined and refined to 2.1 A for comparison with the VSV8/Kb structure at similar resolution. Aside from changes on the p4 side chain of L4 and the resulting alteration of the exposed Kb Lys-66 side chain, these two structures are essentially identical. Hence, a given TCR recognizes subtle distinctions between highly related ligands, resulting in dramatically different selection outcomes. Based on these finding and the recent structural elucidation of the N15-VSV8/Kb complex, moreover, it appears that the germ-line Valpha repertoire contributes in a significant way to positive selection.     

Thresholds for ultrasonically induced lung hemorrhage in neonatal swine

The threshold for generation of lung hemorrhage in adult mice by pulsed ultrasound has been shown to be approximately 1 MPa at the surface of the lung (10-microseconds pulse and a carrier frequency of 2 MHz). This investigation used neonatal swine to determine if the findings for mice can be generalized to other species. After exploratory observations, the inverse sampling method was used in a primary study (22 animals, 88 exposure sites) to determine the threshold for lung hemorrhage in neonatal swine. The primary study was followed by a separate confirmation study (13 animals, 48 exposure sites), testing the conclusions of the first study and comparing damage at subthreshold levels with sham-exposed animals. A separate investigation explored the histological nature of tissue damage at suprathreshold levels. A 2.3-MHz focused transducer (10 microseconds at 100-Hz pulse-repetition frequency) was incremented vertically for a distance of 2 cm over the chest of the subject for a total exposure period of 16 min. Animals were euthanized and lungs were scored by visual inspection for numbers and areas of gross hemorrhages. The threshold level for hemorrhage was approximately 1.5 MPa peak positive pressure in water at the surface of the animal or, at the surface of the lung, 1.1 MPa peak positive pressure, 1 MPa fundamental pressure, 0.9 MPa maximum negative pressure, 25 W cm-2 pulse average intensity or a mechanical index of 0.6. These values are essentially the same as those reported for adult mice.