Alleviation of mortality induced by salicylate and stress

Protection from the deleterious effects of the interaction of environmental stress and salicylate by calcium supplement was investigated in 96 pigmented rats. Within a 2×2×4 factorial design, rats were assigned to groups defined by:A) ad lib access to 1) plain tap water, or 2) 50 mM calcium chloride solution;B) exposure to stressors consisting of daily 10 h periods of 1) 98 dB SPL noise, or 2) confinement precluding movements;C) daily injections of 233, 350, or 410 mg/kg of sodium salicylate or the saline vehicle. For subjects maintained on tap water, weight loss and mortality increased with salicylate levels, with all subjects dying in the group drinking water and injected with 410 mg/kg. Calcium protected all of the subjects in the noise stress group but not in the confined group.     

Effects of salicylate on the electrical properties of the proximal convoluted tubule of Necturus maculosus]

The effects of peritubular salicylate for chloride substitution were studied in the isolated perfused Necturus kidney. This substitution resulted in changes of cell membrane p.d., varying from tubule to tubule; the withdrawal of the test-anion invariably produced a steep and prolonged depolarization. Exposure of the tissue to salicylate brought about, in addition, electrical uncoupling of junctional membranes, which was not related to concomitant changes of membrane p.d.     

On the limitations of comparing mean square forecast errors

Linear models are invariant under non-singular, scale-preserving linear transformations, whereas mean square forecast errors (MSFEs) are not. Different rankings may result across models or methods from choosing alternative yet isomorphic representations of a process. One approach can dominate others for comparisons in levels, yet lose to another for differences, to a second for cointegrating vectors and to a third for combinations of variables. The potential for switches in ranking is related to criticisms of the inadequacy of MSFE against encompassing criteria, which are invariant under linear transforms and entail MSFE dominance. An invariant evaluation criterion which avoids misleading outcomes is examined in a Monte Carlo study of forecasting methods.     

Entropy measures of signal in the presence of noise: evidence for ‘byte’ versus ‘bit’ processing in the nervous system

Summary A method for detecting signal in the presence of noise in a highly specific was is described. Using action potential interval data from 12 neurons in rat cerebellum, we have demonstrated that the sequential ordering of spike intervals contains both noise and signal. We have identified and quantified the magnitude of relative entropy (uncertainty) for specified sets of interval patterns, ranging in length from 3–5 successive intervals. Some of these sets have exceptionally low entropy and thus seem to be especially meaningful as a set (word) to the brain.     

The sedative effects of nicotinamide on gerbil wheel-running activity

Summary The activity of 5 groups of gerbils was monitored over 22 days. 3 of the groups received daily injections of nicotinamide (125, 250 or 500 mg/kg) and a 4th group received saline. The 5th group was untreated. The results indicated that both the 250 and 500 mg/kg nicotinamide administrations greatly reduced the activity levels of the gerbils.This work was supported in part by Faculty Research Grant No. 82-6209 from the University of Alabama in Birmingham to J.M.B.     

Inactivation of yeast glucose-6-P dehydrogenase by aspirin

Summary Glucose-6-P dehydrogenase is irreversibly inactivated by treatment with Na salts of aspirin. Kinetic data show that 1 molecule of aspirin reacts with each active unit when the enzyme is inactivated. The rate of inactivation is enhanced with increasing pH but is reduced in the presence of glucose-6-P or NADP⁺. Na salicylate fails to inactivate the enzyme.This work was supported by grant RR-8006 from the General Research Branch, Division of Research Resources, NIH (USA).     

Potentiation of immunologic memory by Corynebacterium parvum and its mechanism]

Immune response to bovine serum albumin (BSA) at dose of 2,50 mg/kg which is rather a weak immunogen in Rabbits, when given intravenous was highly potentiated when the animals received a previous single intravenous infection of 2 mg/kg of C. parvum, followed by subsequent BSA anamnestic challenges for several months. Thus, the antibody amounts synthesized following the 1st anamnestic injection (3 weeks) were 0,260 mg/ml in the control versus, 0,800 mg/ml in the C. parvum pretreated groups; following the 2nd anamnestic challenge (12 weeks afterwards) 1 mg/ml in the control versus, 2,50 mg/ml in the treated groups following the 3rd anamnestic challenge (28 weeks afterwards) 1,3 mg/ml in the control versus 5 mg/ml in the C. parvum pretreated groups; following the 4th anamnestic challenge (52 weeks afterwards) 0,300 mg/ml in the control versus 0,800 mg/ml in the C. parvum treated groups. On the whole for the four first anamnestic challenges the differences at peak levels between the control and C. parvum treated groups were about to 4. Furthermore, the antibody molecules synthesized by the C. parvum treated animals were found to belong to IgG class. The results suggest that the immunological mechanisms mobilized are peculiar to C. parvum since they could not be reproduced either by BCG or by Freun'd adjuvant under similar conditions.     

超临界CO2在制备PCL/水杨酸甲酯控释体系中的应用研究

本文利用超临界二氧化碳（SCCO2）对生物可降解材料--聚己内酯（PCL）进行溶胀和塑化,进而将其作为携带剂,将水杨酸甲酯嵌入到PCL中,制备含有水杨酸甲酯的PCL多孔材料,即PCL/水杨酸甲酯控释体系,并研究超临界流体条件下水杨酸甲酯的插嵌规律.研究结果表明,PCL对水杨酸甲酯有很好的吸附能力,通过测定所制备的多孔材料PCL/水杨酸甲酯体系的缓释行为,表明其多孔结构对药物分子具有一定的缓释功能,药物分子释放时间最长可达18 h以上.     

Expression of the anti-apoptotic gene survivin correlates with taxol resistance in human ovarian cancer

Stable transfection of human ovarian carcinoma cells with survivin cDNA caused a four- to sixfold increase in cell resistance to taxotere and taxol (two-sided Student's t test, p < 0.05), with a concomitant reduction in the apoptotic response to taxol, but did not affect cell sensitivity to cisplatin or oxaliplatin. Such findings were indirectly supported by similar observations obtained with clinical tumours. In fact, high levels of survivin protein expression (>30% positive cells), detected by immunohistochemistry in 90/124 (73%) advanced ovarian carcinomas, were significantly associated with clinical resistance to a taxol/platinum-based regimen but unrelated to tumour shrinkage following cisplatin-including combinations (non-taxol based). In the 95 patients receiving a taxol/platinum-based regimen, survivin overexpression correlated with a lower clinical or pathologic complete remission rate than absent/low protein expression (43 vs 75%, p = 0.0058 by logistic regression adjusted for tumour stage, histological grade and p53 expression). Conversely, in the 29 cases treated with cisplatin-containing regimens (not taxol based), survivin expression was unrelated to tumour response. Cellular studies and clinical data suggest a direct link between survivin expression and tumour cell susceptibility to taxol.     

Sleep disturbance due to transportation noise: ear plugs vs oral drugs

Conclusion Sleep is not only the output of an EEG machine but a global phenomenon with unique physiological, environmental and psychological features occurring in a given individual. There is no question that statistical evaluation of noise-induced sleep disturbances in non homogeneous groups of subjects has resulted in the construction of a magnificent neurophysiological edifice by assembling a few individual bricks. In this respect, whether subjectively disturbed or not, we now know that when we sleep in noisy areas our delta sleep is reduced, our heart rate fails to habituate to individual noises, and we are more likely to develop psychic disturbances than residents in quiet areas. Data from these studies are however interspersed with results from a number of experiments during which the subject has been looked upon as nothing but a sleeper, i.e., experiments in which day-time stresses and noises were considered as irrelevant for the night-time study. It seems important therefore that future studies should gather more longitudinal data based on a limited number of subjects selected according to their day-time habits and psychological (e.g., extroverts/introverts) and physiological (e.g., short or long sleepers) characteristics. The knowledge about these situational factors and personality traits might provide new insights into individual biological strategies developed to cope with noise stress. The difficulties in assessing the effect of noise on sleep are particularly obvious if we consider another finding: deaf subjects spend significantly less time in delta sleep than do control subjects⁴⁷ and they present sleep pattern alterations remarkably similar to those which are most consistently described in noisy conditions.Research by the authors has been supported by grants from the Ministère de la Qualité de la Vie et de l'Environnement (France) and Commission of European Communities.     

Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications

Polyamines are aliphatic cations with multiple functions and are essential for life. Cellular polyamine levels are regulated by multiple pathways such as synthesis from amino acid precursors, cellular uptake mechanisms that salvage polyamines from diet and intestinal microorganisms, as well as stepwise degradation and efflux. Investigations using polyamine biosynthetic inhibitors indicate that alterations in cellular polyamine levels modulate normal and cancer cell growth. Studies using transgenic mice overexpressing polyamine biosynthetic enzymes support a role of polyamines in carcinogenesis. Many, if not all, signal transduction pathways intersect with polyamine biosynthetic pathways and the regulation of intracellular polyamine levels. Direct binding of polyamines to DNA and their ability to modulate DNA-protein interactions appear to be important in the molecular mechanisms of polyamine action in cell proliferation. Consistent with the role of polyamines as facilitators of cell growth, several studies have shown their ability to protect cells from apoptosis. However, polyamines also have a role in facilitating cell death. The basis of these diverse cellular responses is currently not known. Cell death response might be partly mediated by the production of hydrogen peroxide during polyamine catabolism. In addition, the ability of polyamines to alter DNA-protein and protein-protein interactions might be disruptive to cellular functions, when abnormally high levels are accumulated due to defects in polyamine catabolic or efflux pathways. A large body of data indicates that polyamine pathway can be a molecular target for therapeutic intervention in several types cancers. Inhibitors of biosynthesis, polyamine analogues as well as oligonucleotide/polyamine analogue combinations are promising drug candidates for chemoprevention and/or treatment of cancer.     

Interaction of cortisol and epinephrine in the regulation of leucine kinetics in man

To assess the interaction of the two major stress hormones epinephrine and cortisol in the regulation of leucine kinetics in man, epinephrine (50 ng/kg/min) was infused either alone or in combination with cortisol (2 micrograms/kg/min) into two groups of 6 postabsorptive normal male subjects during 180 min. Plasma leucine concentrations decreased by 28% (p less than 0.05) from baseline during epinephrine treatment (plasma levels 515 pg/ml); this was due to a decrease of leucine appearance (determined by 1-13C-leucine infusions) by 23% (p less than 0.025); leucine oxidation decreased by 29% (p less than 0.05). However, when plasma cortisol concentrations were elevated to supraphysiological levels (16.3 mumol/l) during epinephrine administration, the decreases of leucine plasma concentrations, appearance and oxidation were abolished. Plasma glucose and FFA concentrations were similarly elevated during both kinds of treatment. Since leucine appearance represents a measurement of total body protein breakdown and leucine disappearance into non-oxidative pathways reflects protein synthesis, the data indicate that plasma epinephrine concentrations during severe stress exert a protein anabolic effect in man which may counteract catabolic properties of elevated plasma cortisol.     

Noise and "pedagogic efficiency" in school activities.

A group of 8 pupils born in 1962 and a group of 8 future teachers between 25 and 40 years of age, were submitted in 1975 to two types of tests in the presence of environment noises at various levels (45 to 75 dBa), in order to assess the influence of this nuisance on the pedagogic efficiency. The results show a nocivity threshold for the pupils at around 55 dBA and for the teachers at aroung 65 dBA. Furthermore, backward pupils suffer more in this context from the interference of noise than the advanced ones.     

The effects of salicylate and aspirin on the activity of phosphorylase a in perfused hearts of rats

Summary Sodium salicylate and aspirin are known to have a glycogenolytic effect as judged by either the glycogen level or lactate production in perfused hearts of rats. In this work it was possible to demonstrate that phosphorylase a level was increased in the hearts subjected to the action of these drugs.     

Essais d'inhibition de l'action inflammatoire cutanée du chloroforme chez le rat

Summary (1)—In the rat, total extracts of cortex, cortisone and A.C.T.H. do not retard the fixation of a vital colorant at the level of a cutaneous zone irritated by chloroform.(2)—Phenergan prolongs the delay in the appearance of the blue.(3)—Sodium salicylate selectively inhibits the inflammatory cutaneous action of chloroform, even after adrenalectomy.     

Messenger RNA differential display strategies in birds and amphibians

As an inroad to the discovery of genes involved in important biological activities, various techniques have been developed for detecting genes based on their expression levels. Arbitrary amplification of different messenger RNA (mRNA) populations and their comparison on display autoradiograms made mRNA differential display one of the most straightforward approaches to identification of differentially regulated mRNAs. Over the past decade this strategy has been employed in many in vitro and in vivo systems. The use of the method in bird and amphibian model systems is reviewed here, emphasizing several unique combinations of model system and design of differential display screen.     

The sedative effects of nicotinamide on gerbil wheel-running activity.

The activity of 5 groups of gerbils was monitored over 22 days. 3 of the groups received daily injections of nicotinamide (125, 250 or 500 mg/kg) and a 4th group received saline. The 5th group was untreated. The results indicated that both the 250 and 500 mg/kg nicotinamide administrations greatly reduced the activity levels of the gerbils.     

Effect of human serum on alkaline phosphatase induction in cultured human tumor cells

The continuous cell lines T 24 and HT-29, derived from human bladder and colon carcinomas, produce term-placental and intestinal alkaline phosphatase, respectively. Growth in hyperosmolar medium or exposure to prednisolone or sodium butyrate induces increased enzyme levels, and combinations of inducers elicit synergistic activity increases. The effect of the inducing agents is strikingly diminished when cells are grown in the presence of high concentrations of human serum, and the synergistic increases are essentially abolished. Major human serum protein fractions do not affect alkaline phosphatase induction.     

Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells

The influence of the proinflammatory cytokine interleukin (IL)-17 on inducible nitric oxide (NO) synthase (iNOS)-mediated NO release was investigated in the mouse insulinoma cell line MIN6 and mouse pancreatic islets. IL-17 markedly augmented iNOS mRNA/protein expression and subsequent NO production induced in MIN6 cells or pancreatic islets by different combinations of interferon-γ, tumor necrosis factor-α, and IL-1β. The induction of iNOS by IL-17 was preceded by phosphorylation of p38 mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK activation completely abolished IL-17-stimulated NO release. IL-17 enhanced the NO-dependent toxicity of proinflammatory cytokines toward MIN6 cells, while IL-17-specific neutralizing antibody partially reduced the NO production and rescued insulinoma cells and pancreatic islets from NO-dependent damage induced by activated T cells. Finally, a significant increase in blood IL-17 levels was observed in a multiple low-dose streptozotocin model of diabetes, suggesting that T cell-derived IL-17 might be involved in NO-dependent damage of beta cells in this disease. Received 14 June 2005; received after revision 17 September 2005; accepted 21 September 2005