低剂量γ射线辐照对血清一氧化氮及一氧化氮合酶水平的影响

目的：观察低剂量γ射线照射人离体外周血对血清中一氧化氮（NO）和一氧化氮合酶（NOS）水平的影响。方法：采集10份健康献血员全血，肝素抗凝，然后采用γ射线照射，照射剂量率为17Gy／min，总吸收剂量为1Gy，分别于照射前及照射后1h，2h采用分光光度法检测血清中NO含量和NOS活性。结果：经γ射线照射1h后，血清中NO及NOS水平与照射前比较明显升高（P〈0.01）；照射后2h，血清中NOS水平与照射后1h比较无统计学差异（P〉0、05），但是还明显高于照射前的水平（P〈0．01）；在照射后2h，血清中NO含量与照射后1h比较明显降低（P〈0.01），但仍明显高于照射前水平（P〈0．01）。结论：采用剂量为1Gy的γ射线照射外周血，可引起血清中NO水平及NOS活性的显著升高．从而为低剂量辐照自体血回输对肿瘤的辅助治疗提供了理论支持。     

Effect of temporal and spatial temperature gradients on the ampullae of Lorenzini

Summary Afferent single fiber impulses were recorded from isolated ampullae of Lorenzini of dogfishes (Scyliorhinus canicula). The ampullae were placed between two thermodes, each of which could be circulated separately with water at 12°, 18° and 24° C, thus allowing cooling and warming with various combinations of spatial temperature gradients. At constant temperature, there was a static discharge in the ampullary fibers. Cooling elicited a dynamic overshoot in frequency, followed by adaptation to a new steady state, whereas warming led to a transient inhibition. Within the limits of error the direction and slope of the spatial temperature gradient had no influence whatsoever on the static and dynamic responses of the ampullae, the only effective parameters being the temperature at the site of the receptor and the rate of temperature change with time.About 13% of the single fibers responded with bursts of impulses, interrupted by silent intervals, and 10% showed an inversed dynamic response, i.e. dynamic overshoot on warming and transient inhibition on cooling. It is possible that these patterns of activity are anomalous responses.This work was supported by the Deutsche Forschungsgemeinschaft.     

Effect of various doses of palm vitamin E and tocopherol on aspirin-induced gastric lesions in rats

This study examined the effects of vitamin E on the prevention of aspirin-induced gastric lesions. The study was divided into two phases. Phase 1 determined the effects of various doses of palm vitamin E on the factors affecting mucosal integrity. Thirty-two male rats of the Sprague-Dawley strain (200-250 g) were randomly divided into four groups. Group I was fed a normal diet (control), Groups II, III and IV were fed a diet supplemented with palm vitamin E in a dose of 60 mg/kg food, 100 mg/kg food and 150 mg/kg food, respectively. The rats were killed after 4 weeks of feeding for the determination of gastric malondialdehyde (MDA), acid and mucus content. There was a significant decrease in gastric MDA and gastric acid in all the palm vitamin E supplemented groups compared to control. However, these doses of palm vitamin E had no significant effect on gastric mucus. The phase 2 study determined the effect of multiple doses of palm vitamin E and tocopherol on the prevention of aspirin-induced gastric lesions. Fifty rats of the same weight and strain were randomized into seven groups. Group I was fed a normal diet; groups II to IV were fed with a palm vitamin E enriched diet in doses of 60 mg, 100 mg and 150 mg/kg food, respectively; groups V to VII were fed with a tocopherol-enriched diet in doses of 20 mg, 30 mg and 50 mg/kg food, respectively. After 4 weeks of feeding with the respective diets the rats were challenged with a single intra-gastric dose of 400 mg/kg body weight aspirin suspended in propylene glycol. The rats were killed 6 h post-aspirin exposure for the determination of gastric lesion index and gastric parameters as mentioned in the phase I study. The gastric lesions index was significantly lower in all the vitamin E groups compared to control. The lowest ulcer index was observed in the groups that received 100 mg of palm vitamin E and 30 mg tocopherol in the diet. However, there was no significant difference in ulcer indices between palm vitamin E and tocopherol-treated groups. The lower ulcer index was only accompanied by lower gastric MDA content. We conclude that both palm vitamin E in doses of 60 mg, 100 mg and 150 mg/kg food as well as tocopherol in doses of 20 mg, 30 mg and 50 mg/kg food are equally effective in preventing aspirin-induced gastric lesions. The most probable mechanism is through their ability in limiting the lipid peroxidation that is involved in aspirin-induced gastric lesions.     

Fluconazole induces genotoxicity in cultured human peripheral blood mononuclear cells via immunomodulation of TNF-α, IL-6, and IL-10: new challenges for safe therapeutic regimens

Context: Fluconazole (FNZ) is a drug used in antifungal therapy. However, the minimum FNZ dose to interfering with immune responses or inducing DNA damage is still unknown.

Objective: This study investigated the toxicological profile of FNZ on cultured human peripheral blood mononuclear cells (PBMCs) treated with different concentrations of this azole.

Materials and methods: Cultured PBMCs were exposed to FNZ (6, 12, 30, 60 and 120?μg/mL) and the toxicological profile was assessed by the following parameters: cytotoxic and nuclear division index (necrotic, apoptotic and viable cells), DNA damage (alkaline comet test), mutagenic potential (micronucleus test), cytokine modulation (IL-1, IL-6, IL-10, TNF-α, IFN-γ), and predictive toxicity (Osiris^® and LAZAR^® programs).

Results: Our results demonstrated that FNZ induced cellular DNA damage and mutagenicity at concentrations above the plasma peak (>30?μg/mL) and 6?μg/mL, respectively, which was associated with increased TNF-α, and decrease IL-6 and IL-10 concentrations. These effects may be related to increased apoptosis and cytotoxic nuclear division index in the cultured PBMCs. In silico results indicated potential mutagenic, tumorigenic, irritant, and carcinogenic effects, which were partially confirmed by the above assays.

Discussion and conclusions: Together, these findings suggest the need to rationalize the use of FNZ, especially if it is used for long periods or with concomitant pathologies requiring azole therapy that may increase FNZ's plasma concentration.     

Direct measurement of the thermal responses of nude resting men in dry environments

Summary Two nude resting men were exposed for two-hour periods to each of 25 dry environments, with air temperatures ranging between 12.8° C and 49.1° C and wind speeds between 0.67 m/sec and 4.94 m/sec. The mean radiant temperature of the surroundings was kept equal to the air temperature. Rates of radiant and convective heat exchange were measured directly, separately and continuously. The men had reached a thermal steady state after 105 min in the warm environments, but not in the cold environments. Graphs are presented to show the effect of ambient temperature and wind speed on the radiation and convection rates attained after 105 min, as well as on metabolic rate, sweat evaporation rate, rectal temperature and mean skin temperature. These graphs revealed some important aspects of the behaviour of man's thermal control system. In particular the physiological conductance increased with increasing ambient temperature and then saturated at an ambient temperature near 35° C. This saturation resulted in a constant difference between rectal temperature and mean skin temperature irrespective of the environmental conditions.Published with the permission of the Chamber of Mines of South Africa.     

Time course of the increase in airway responsiveness associated with late asthmatic reactions to toluene diisocyanate in sensitized subjects

To understand better the mechanism of the increase in airway responsiveness associated with late asthmatic reactions, we determined the time course of toluene diisocyanate (TDI) effect on airway responsiveness in six sensitized subjects who exhibited a late asthmatic response after TDI exposure (0.018 +/- 0.005 ppm, 30 min) in the laboratory. Airway responsiveness was assessed before TDI exposure and then at 8 hr, 1 day, 1 wk, and 1 mo after TDI exposure. To assess responsiveness we determined the provocative dose of methacholine causing a decrease in FEV1 of 20% (PD20FEV1). The methacholine PD20 decreased from 0.50 mg geometric standard error of the mean (GSEM = 1.54) to 0.06 mg (GSEM = 1.55) (p less than 0.001) at 8 hr after exposure to TDI, was still decreased to 0.15 mg (GSEM = 1.93) (p less than 0.05) at 1 day, returned to 0.26 mg (GSEM = 1.91) (p greater than 0.05) at 1 wk, and returned to 0.43 mg (GSEM = 1.71) at 1 mo, indicating that full recovery occurred within 1 to 4 wk. These results demonstrate that TDI-induced late asthmatic response is associated with a reversible increase in airway responsiveness to methacholine and suggest that the TDI effect is linked to an acute inflammatory response in the airways.     

Noise characteristics of stainless-steel surface electrodes

Bioelectric events measured with surface electrodes are subject to noise components which may be significant in comparison with low-level biological signals such as evoked neuroelectric potentials, and myoelectric potentials. In an effort to better understand noise arising from these electrodes, electrode and measurement system noise is modelled. The effect of electrode surface area on electrode impedance and noise is studied using circular stainless-steel electrodes of varying diameters. The main contributions of the work are the development of a model for stainless-steel electrode noise as a function of electrode area, and demonstrating that, for the band-width of interest to evoked neuroelectric and myoelectric signals (8–10 000 Hz), the primary noise components are thermal and amplifier current generated. The magnitudes of both of these depend on the electrode impedance magnitude. Electrode impedance is shown to be a power function of both electrode diameter and frequency, consistent with a capacitive electrode model.     

Thermal pleasantness sensation: an indicator of thermal stress

Summary The degree of pleasantness or unpleasantness of thermal sensation aroused by a particular peripheral thermal stimulus has been shown to be an indicator of thermal state of the body in relation to the thermoregulatory set point. This phenomenon is known as thermal alliesthesia. The quantification of thermal alliesthesia was possible using two methods: (1) A set of temperature stimuli (15, 20, 25, 30, 35, and 38 C) was applied, by means of a Peltier thermode 5.5×2.7 cm², on the back of the hand, the forehead, and the back of the neck. When each stimulus had been applied for 5 s the subjects voted their degree of thermal pleasantness/unpleasantness on a psychophysical scale ranging from +2.0 for very pleasant to –2.0 for very unpleasant. (2) The subjects were also asked to adjust the Peltier thermode temperature, without looking at the temperature scale, such that the temperature (on the back of the neck) was maintained at the level the subjects considered most pleasant. The subjects also rated their general thermal comfort sensation on a five point scale ranging from +2.0 for very comfortable to –2.0 for very uncomfortable. Rectal temperature and skin temperature at eight locations were continuously recorded. Passive thermal exposures (54) were made with nine passive subjects and 42 exposures were done with working (50 watt) subjects. All exposures were carried out in a climatic chamber at a constant temperature, relative humidity (45%), and air speed (0.3 m/s). Each subject underwent 6 exposures at six room temperatures of 15, 20, 25, 30, 35, and 40 C. The results of work exposures confirmed the findings of previous studies; namely, the effect of core temperature change overrides any effect due to mean skin temperature on alliesthesial response. A mathematical function to predict the mean slope of the thermal pleasantness rating/stimulus line (a measure of the alliesthesial response) was derived using the data obtained from the passive thermal exposures. The results indicate that alliesthesial response can be used as a quantitative indicator of thermal stress.Supported by the European Coal and Steel Community, Luxembourg     

Heat and water vapour transfer of protective clothing systems in a cold environment,measured with a newly developed sweating thermal manikin

A moveable sweating thermal manikin has recently been developed. Thermal and water-vapour resistances of three kinds of cold-protective clothing ensembles, laminated with polytetrafluoroethylene, polyurethane and without a laminate were measured, with the aid of the manikin in a cold environment of 5°C with a relative humidity of 70% and an air velocity of around 1.5 m s^–1. Two sweating rates of 65 and 130 g m^–2 h^–1 were employed. Supplied heat fluxes in both of the sweat rates ranged from 350 W m^–2 to 400 W m^–2. To maintain a comfortable condition, the skin wettedness (w) (mean weighted value) had to be kept at 0.6. The measurements obtained from the manikin when testing the three ensembles were w=0.3 (approximately) for the low sweat rate and w0.6 for the high sweat rate, irrespective of the property differences among the ensembles. In addition, the condensation in the ensembles in comparison with those calculated from an analytical equation is discussed. Condensation mass fluxes in the ensembles obtained byexperiment and those from the calculation agreed sufficiently well. Thus, distribution of the condensation in the ensembles was estimated using the equation.     

Aspirin-Interleukin-3 Interrelationships in Patients With Anti-Phospholipid Syndrome

PROBLEM: Previously we reported on the generation of experimental anti-phospholipid syndrome (APS) in mice. These models were employed to evaluate the efficacy of various novel therapeutic modalities including interleukin-3 (IL-3) and low dose aspirin. The efficacy of the latter was found to be interrelated. Low dose aspirin is capable of inhibiting the activity of the enzyme cyclooxygenase which is responsible for the metabolism of arachidonic acid towards the production of prostaglandins. This shifts the metabolism of arachidonic acid to the other pathway and leads to an overproduction of leukotrienes. The leukotrienes act as stimulators of IL-3 production, a positive cytokine in pregnancy which enhances placental and fetal development. In the current study we evaluated the IL-3 levels in pregnant women with APS and expanded our knowledge on the interrelationships between aspirin, arachidonic acid metabolites and IL-3 in the human system. METHODS: IL-3 levels were recorded in the serum of pregnant women with APS and compared to a control pregnant group. In addition peripheral blood mononuclear cells from healthy subjects were incubated with different concentrations of aspirin or with arachidonic acid metabolites (Leukotriene B4, C4 or PGE₂), and IL-3 production in the culture fluids was evaluated. RESULTS: Serum level of IL-3 in pregnant patients with primary APS, APS secondary to SLE and SLE was lower in comparison to the control group. The in vitro studies revealed that only low dose aspirin (10 mg/μl) stimulated IL-3 production while higher doses of the drug failed to induce the cytokine generation. Leukotriene B4 and C4 were stimulatory whereas PGE₂ acted as inhibitor of IL-3 production. CONCLUSIONS: The serum level of IL-3 is decreased to pregnant women with primary or secondary APS. Low dose aspirin is capable of stimulating EL-3 production in vitro most probably through an elevation of leukotriene production, which may explain its beneficial activity in preventing the manifestations of APS.